Unit 4 Knowledge Check 3

Table of Contents
PATHOLOGIES
• Multiple Sclerosis ✓
• Ataxia ✓
• Facial Nerve Palsy ✓
• Amyotrophic Lateral Sclerosis ✓
• Peripheral Nervous System Injury ✓
• Neuromuscular Conditions
NEUROSCIENCE
• Vestibular System ✓
• Development of Nervous System ✓
• Electrical Principles of Cells & Synaptic Transmission ✓
• Neuroplasticity ✓
• Motor Learning ✓
• Cranial Nerves & Muscle Tone & Blood Supply ✓
• Functional Electrical Stimulation
• Neural Control of Locomotion ✓
PAIN / MISCELLANEOUS
• Peripheral Neuropathic Pain ✓
• Complex Regional Pain Syndrome ✓
DIAGRAMS
 PATHOLOGIES
Multiple Sclerosis
• Cathy Aten – primary progressive multiple sclerosis
o Have to make multiple micro-adjustments of body in order to feel safe
o Blog to chronicle lift with MS
o Takeaways: life and art has been “edited down” to what is necessary only/what is needed
o Having more difficulty with transfers and walking
• Questions:
o What is multiple sclerosis/MS?
o How is someone diagnosed?
o Are there different types of MS?
o Is Cathy’s presentation typical for someone with MS? Are her symptoms typical for MS?
o Will she get better? What can physiotherapy do?
• Multiple sclerosis: progressive autoimmune disease characterized by inflammation & demyelination
• Abnormal immune-mediated response triggers immune cell activation (e.g. helper T-cells) that cross the blood-
brain barrier
o Starts “damaging inflammatory cascade of events” w/ demyelination/myelin damage in the brain, spinal
cord, optic nerves; oligodendrocyte loss; axonal damage
o Acute inflammatory attack on myelin subsides contributing to common pattern of relapses (worsening)
& remissions (without disease progression, partial/complete Sx recovery)
o Some remyelination can occur in early MS but as oligodendrocytes become damaged, myelin repair
doesn’t occur
o Lesions or plaques in the CNS as a result of inflammation, myelin destruction, scarring
• Two-stage process:
o 1st: inflammatory damage with demyelination and some axonal damage
o 2nd: degenerative changes including axonal and oligodendrocyte destruction
o Recently suggested that neuroinflamm. + neurodegen. occur simultaneously
• Epidemiology: more commonly affects young adults between 20-49
o Affects F > M (2-3x more likely to be diagnosed with MS)
o More common in higher latitudes (further from equator) – Canada has one of highest MS rates in the
world
o Environmental and genetic factors can increase risk:
▪ Low vitamin D
▪ Smoking
▪ Epstein-Barr virus
▪ Obesity
• MS types: variable and unpredictable between and within people
o [1] Relapsing-Remitting MS (RRMS)
o [2] Secondary Progressive MS (SPMS)
o [3] Primary-Progressive MS [PPMS]
o [4] Clinically Isolated Syndrome [CIS] – single episode of neurological symptoms that may suggest MS
(added 2013)
• Relapsing-remitting MS (RRMS): most common, affects ~85% of those with MS
o Unpredictable, defined relapses (attacks or flare-ups) where new Sx appear, or existing ones worsen –
followed by remissions
 o MS relapse: new or worsening of MS symptom(s) lasting >24 hours – can last days, weeks, or months
o Most of those with RRMS eventually transition to secondary progressive MS
• Secondary-progressive MS (SPMS): begins with RRMS, progresses to relapses while remissions are less apparent
with steady worsening of function
o Progressively worsens but can have occasional relapses/minor remissions/plateaus
o ~50% of RRMS patients develop SPMS within 10-20 years of initial diagnosis
• Primary-progressive MS: least common MS, in 15% of MS population
o Progressive worsening from the onset with no relapses or remissions in general
• Diagnosis: no definitive diagnostic test for MS
o Neurologist diagnosis: combination of MHx, neurological exam to rule out other conditions, lab tests
(esp. MRI)
o MRI is highly sensitive for detecting MS plaques/lesions
• Clinical presentation: depends on location of CNS demyelination
o Numbness and tingling in the hands and feat
o Weakness
o Decreased coordination
o Intention tremor
o Vision problems
o Uhthoff’s phenomena – body overheats
o Fatigue
o https://mssociety.ca/about-ms/symptoms
o Symptoms listed on MS Society:
▪ Balance/dizziness
▪ Bladder dysfunction
▪ Bowel dysfunction
▪ Cognitive impairment
▪ Depression
▪ Fatigue
▪ Gait (difficulty in walking)
▪ Optic neuritis
▪ Pain
▪ Paroxysmal symptoms
▪ Sensory impairment, numbness/tingling
▪ Sexual dysfunction
▪ Spasticity
▪ Tremor
▪ Uhthoff’s phenomena (heat intolerance)
▪ Weakness
▪ Other: dysarthria (difficulty speaking), dysphagia (difficulty swallowing), dry mouth, hormonal
influences (women), inappropriate affect (pseudo bulbar affect, emotional incontinence,
involuntary emotional expression disorder IEED), poor coordination/incoordination, mood
lability/bipolar affective disorder
• Additional symptom: ataxia → MS symptoms “include sensory loss, visual disturbance, double vision, muscle
weakness, ataxia and impaired balance, which may considerably reduce the QOL in affected individuals”
• Medical management: 3 categories
o [1] Management of acute relapses
 ▪ Corticosteroids shorten the length & severity of relapses; these drugs don’t modify course of
disease
o [2] Disease-modifying therapies (DMT)
▪ Slow progression of disease and reduce relapses; generally target inflammatory process
▪ MS Society: 17 approved DMTs for RRMS and 1 approved DMT for early PPMS
▪ Different DMTs are recommended for each type of MS
o [3] Management of symptoms
▪ Ease MS-related symptoms like fatigue, spasticity, pain, tremor, etc.
▪ Prescribed medications depend on the symptoms
• Physiotherapy management: depends on clinical presentation
o Evaluate and address body’s ability to move and function, particular emphasis on walking, strength,
balance, posture, fatigue, pain
o Stretching, ROM and strengthening exercises, gait training, training with mobility aids (canes, crutches,
scooters, wheelchairs) and other assistive devices
o Goal to achieve and maintain optimal function; prevent deconditioning, muscle weakness from lack of
mobility, muscle contractures
• Exercise: profound and prevalent physical inactivity in those with PD & MS that could initiate a cycle of
deconditioning and worsening of disease consequences, independent of latent disease processes
o Cycle of deconditioning:
Primary Impairments:
e.g. weakness – fatigue – tremor – increased
tone

Decreased Activity/Exercise

Secondary Impairments:
e.g. increased weakness, more fatigue, stiffness,
low mood and energy, sleep disturbances
o
o Exercise breaks the cycle of deconditioning
▪ Increasing activity and exercise will help break the deconditioning cycle and reduce secondary
impairments
• Canadian physical activity guidelines for adults w/ MS:
o Adults (18-64) with mild to moderate disability:
▪ 30 min moderate intensity aerobic activity, 2x/week
▪ Strength training exercises for major muscle groups, 2x/week
▪ Meeting guidelines may reduce fatigue, improve mobility, enhance elements of health related
QOL
• Role of PT in MS, breaking the deconditioning cycle:
o Exercise (e.g. endurance training, muscle strengthening, task-oriented training)
o Behavioural interventions
o Health promotion
o Self-management
o Education
 o Provide community resources, assist to navigate the system
o Advocate for more options in the community
• Fill in the blanks:
o Multiple sclerosis (MS) is a progressive autoimmune disease. It is the result of immune cells attacking
the myelin sheaths in the brain, spinal cord, and optic nerve. Women are more likely to get MS than
men. There are 3/4 types of MS. The most common type is relapsing-remitting MS (RRMS) and the most
severe type is primary progressive MS (PPMS). MS is diagnosed by a neurologist who will likely require
an MRI to confirm the diagnosis.
- What best describes MS?
o An autoimmune disease
o A genetic disease
o An infectious disease
o A metabolic disease
- What is attacked in MS?
o Blood vessels
o Neurotransmitters
o T-cells
o Myelin
- Based on the prevalence of MS, who is most likely to be diagnosed with MS?
o 28 yo male
o 60 yo male
o 22 yo female
o 55 yo female
- Penelope reports recent blurred vision, tingling in her hands and feet and fatigue. Her doctor thinks she may
have MS> What tests may her doctor complete?
o MRI
o ECG
o Cerebral angiography
o Ultrasound
- Penelope was diagnosed with relapse-remitting MS> She started taking disease-modifying medications. What is
the benefit of disease-modifying mechanisms?
o Stop the progression
o Increase inflammation
o Reduce relapses
o Decrease spasticity
- Kameela has primary progressive MS. What types of medications may be useful for her?
o Medications for thinning blood
o Medications for fatigue
o Medications for freezing in gait
o Medications for a resting tremor
Ataxia
• Ataxia: incoordination of movement that is not the result of muscle weakness; neurological symptom (not a
condition)
o Involves insufficient postural control and incoordination of multi-joint movements
o Mobility without stability
• Causes:
o Multiple sclerosis
o Cerebellar damage (e.g. stroke, tumour, TBI, hypoxia at birth, hydrocephalus, infection, metabolic
disease, drug and alcohol intoxication, exposure to other toxins)
o Hereditary conditions
1. Friedreich’s ataxia (recessive disorder)
2. Spinocerebellar ataxia (autosomal dominant disorder)
• Types:
o Cerebellar ataxia: result of damage or dysfunction to the cerebellum
o Sensory ataxia: dysfunction of proprioceptive input from the periphery and ascending systems
▪ Issue in proprioception with more noticeable Sx when eyes are closed
▪ May not be responsive to management described in these notes
o Type of ataxia may not be differentiated clinically; focus on cerebellar ataxia as it’s more common
• Role of the cerebellum: compares actual motor output to intended movement & adjusts the operation of motor
centres as necessary
o Damage to cerebellum = inability to fine tune and respond to sensory & motor information; affects
spatial accuracy and timing of voluntary movements

Actual motor output compares Intended movement

Adjusts operation of
motor centres
o
• Clinical presentation: “may result in range of f(x)al difficulties involving balance and walking; reaching; grasping
and manipulation; eye movement; swallowing; speech intelligibility
o Disorders of functional mobility:
▪ Bracing segments (e.g. use thighs against bed to stand)
▪ Locking joints
▪ Wide BOS
▪ Increased reliance on vision
o Disorders of gait:
▪ Unsteady, irregular and staggering with lateral deviations from line of progression
▪ High risk of falling
o Disorders of balance:
▪ Increased postural sway
▪ Poor anticipatory postural control
▪ Abnormal balance reactions
o Disorders of eye movement:
▪ Difficulties in accurate fixation of vision
• Clinical features:
o Dysmetria: inability to judge distance/range leading to over- and under-shooting errors
 o Dysdiadochokinesis: difficulty with movement reversal leading to the inability to perform rapid
alternating movement
o Dyssynergia: compensation strategy in which movement is separated into series of components, in a
sequence of steps, rather than as a single, smooth activity
o Rebound phenomenon: loss of “check reflex” which functions to halt forceful, active movements
o Intention tremor: involuntary oscillatory movement resulting from alternate contractions of opposing
muscle groups present with active movement
o Postural tremor: involuntary oscillatory movement resulting from alternate contractions of opposing
muscle groups of the proximal muscles
o Dysarthria: disorder of motor component of speech articulation caused by a lack of coordination of oral
musculature and breathing
o Impaired control of eye movement
o Disorders of functional mobility and gait
• Assessments of ataxia: most common → faster mvmts generally amplify difficulties
o Finger-nose
o Heel-shin
o Rapid alternating movement
o Rebound test
o Position holding
o Functional reach
o Nine-hole peg test (NHPT)
o Rhomberg
o Sharpened Rhomberg
o Berg balance scale
o Timed up and go (TUG)
o Tandem walking
• Match assessment to clinical feature you would be most likely to observe
o Finger-nose → dysmetria
o Rapid alternating movement → dysdiadochokinesis
o Position holding → postural tremor
• Ataxia-specific outcome measure – e.g. Scale for Assessment and Rating of Ataxia (SARA)
o Can help to compare pre and post ability, communicate findings
• Ataxia management goal: to improve the functional level of the patient through restorative techniques – when
this is not possible, use compensatory strategies to make the patient as independent as possible within the
present functional level
o Previously, ataxia was only managed with compensatory approaches
• PT management:
o Altering the conditions in which movement is occurring
▪ Add sensory input – enhance kinesthetic awareness and possibly stimulate co-contraction of
stabilizing muscle around the joint to reduce tremor
• Joint compression: provide light compression of joint during f(x)al activity
• Light resistance provided during f(x)al mvmt
• Distal stabilization: primarily the arm via manual support or supportive surface
▪ Decrease speed
▪ Visualization/conscious control – might include self-talk to relax and visualize smooth mvmt
▪ Change target size e.g. larger target when reaching for items, progress to smaller items
 ▪ Reduce range of reaching – might start with reaching activities closer to body as outer range
(further from body) is more difficult to control than inner range
o Promote proximal stability
▪ Rhythmical stabilizations – alternating isometric contractions against resistance without
intention of movement; can be used in different positions to build trunk co-contraction for
stability
▪ Facilitate good alignment
▪ Progress activities from larger base of support to smaller base of support (e.g. progress from
using development sequence – prone → prone on elbows → 4 point kneeling → 2 point
kneeling → half kneeling → stand)
o Balance exercises
o Compensation (e.g. weights applied on limbs and/or body or on piece of equipment as a form of
compression or resistance)
• Example exercises for ataxia – Ilg et al. (2009), 4-week course of intensive training with 3 sessions of 1
hour/week
o Static balance
▪ Quadruped standing: stabilize the trunk, lift one arm
o Dynamic balance
▪ Kneeling: put one foot in front and back alternately
o Whole body movements
▪ Quadruped standing (i.e. 4 point kneeling): lift one arm and leg of the other side → flex arm, leg,
and trunk → extend arm, leg, and trunk alternately
▪ Kneeling: sit beside heel on right side → kneeling → side beside heel on left side alternately
o Steps to prevent falling and falling strategies:
▪ Standing – bend trunk and knees to touch the floor; erect the body alternately
▪ Standing – bend the trunk and knees to touch the floor and go down to quadruped standing
Facial Nerve Palsy
• Facial nerve palsy: PNS injury
o Peripheral nervous system: nerves leading to and exiting from CNS including the cranial nerves exiting
the brain stem and the spinal nerves exiting the spinal cord
o Olfactory and optic nerves are within the skull

o Yellow = CNS; blue = PNS

• Facial nerve: cranial nerve 7, mixed cranial nerve
o Innervates ipsilateral muscles of facial expression, the digastric and stylohyoid muscle and stapedius
muscle of middle ear
o Innervates salivary and lacrimal glands
o Transmits sensation from anterior 2/3 of tongue
• FNP: reduced or absent nerve conduction of facial nerve due to trauma or damage
o Most common cause is Bell’s palsy – acute onset of idiopathic FNP typically progressing over 72hrs
o Can also be caused by infection, tumour, fracture, surgery
o Incidence: 20-30 cases per 100 000 people, more prevalent in older adults
• Symptoms:
o Complete or partial hemifacial paresis
o Incomplete eye closure
o Decreased taste in 2/3rds of anterior tongue
o Dryness of eye or mouth
o Increase sensitivity to sounds
o Difficulty with speech, eating, and/or drinking
• Red flags: a key red flag to rule out is paralysis due to stroke (UMN lesion)
o Medical attention recommended to determine cause of paralysis which may require medical care
o UMN lesion results in contralateral weakness to lower side of face
o LMN lesion results in ipsilateral weakness of upper and lower side of face
 o
o Determine if UMN or LMN lesion: ask patient to smile and raise eyebrows – raise both eyebrows means
it’s an UMN lesion; cannot raise both eyebrows means it’s a LMN lesion

Medical Management:
- Involves diagnosing and determining cause of FNP
- Further medical management is related to the cause of the FNP
- Management can include:
o Corticosteroids w/ or w/o antiviral meds and eye care such as meds to keep the eye moist and applying
tape to close the eye
o Referral to PT

PT Assessment:
- Subjective history
- History of present illness
- Facial movement
o Raise eyebrows
o Close eyes
o Smile
o Blow air into one cheek
- Facial sensation
- Screening cranial nerves
- Goals

Recovery:
- Depends on the cause and extent of FNP
- Better for ppl with incomplete paralysis than complete
- 30-41% of individuals with FNP will have a cause of that palsy which requires specific management and is often
associated with a poorer prognosis
- Reports of recovery from Bell’s palsy vary, but generally most patients with Bell’s palsy have some recovery
without intervention within 2-3 weeks after onset of symptoms and complete recovery within 3-6 months
- Severe cases of Bell’s palsy may see ongoing changes in facial function for 12-18 months following onset
- ~70% of individuals with Bell’s palsy will fully recover
o Other 30% will have varying degrees of recovery which may include continued symptoms of partial
motor recovery, hemifacial spasms and synkinesis
Synkinesis:
- Abnormal involuntary movement that occurs with voluntary movement
 - Can occur with or following recovery from FNP
- Aberrant regeneration is thought to be one of the main causes of synkinesis
- Example of synkinesis:
o Eye involuntarily closing when the person smiles
- Systematic review indicated that PT alone had an impact in synkinesis symptomatic improvement and can be an
effective and independent treatment
o Methods of PT mentioned in review include:
▪ Visual feedback and/or electro myography (EMG) during prescribed facial expressions (e.g.
combinations of snarling, smiling, lip puckering, pursing lips, baring teeth and puffing cheeks)
▪ Taping
▪ Manual stretching
▪ Massage

PT Management:
- Education; explaining condition, recovery, eye care, and self-management strategies
- Soft tissues massage, may also be included
- Facial neuromuscular training
o Facilitating the intended facial movement patterns and eliminating or decreasing unwanted patterns
o Exercises include: wrinkle forehead, smile, snarl, lip pucker at various amplitudes and speeds
- Functional retraining
- Biofeedback
- Electrotherapy
- Taping
- Acupuncture

Exploring the Evidence:

- The clinical practice guideline released by the Canadian Medical Association Journal made the following
recommendations regarding PT:
o No recommendations regarding use of exercise PT for acute Bell’s Palsy for any severity
o Suggest exercise PT for patients with persistent weakness
o Suggest against the use of electrostimulation

YouTube Video 1
• Provides innervation to muscles for facial expression except for those that elevate eyelids (oculomotor nerve)
• Mainly motor nerve but there is a sensory division
o Sensory division can be called the nervus intermedius/glossopalatine nerve
• Anterior 2/3 of tongue and reflex function involving corneal reflex + glabellar reflex
• May be affected in cerebral infarction, Parkinson’s
o Results in facial palsy
• Examine patient's face - may be apparent by asymmetries
o Flattening of naso-labial groove
o Can show as UMN or LMN lesion
▪ UMN: forehead muscles are spare
• UPPER
o Ask patient to look up and raise eyebrows
▪ Look for even wrinkling of eyebrows
 ▪ Ask patient to close eyes tightly while PT tries to force them open
• LOWER
o Ask patient to show teeth, smile, puff out cheeks while PT palpates cheek for even muscle tone
o Paresis/paralysis of all ipsilateral facial muscles including the forehead
• Glabellar reflex: patient has to keep eyes open
o PT gives a series of taps to forehead with finger
o Normal reaction: no blinking
o Abnormal reaction: repeated blinking when forehead is tapped

YouTube Video 2
• Exercises for Bell's palsy
• Weakness of muscles on one side of face
• Need to make a lot of facial expressions
• Do it in front of mirror
• Start by raising both eyebrows (doing both sides encourages weaker side to lift up)
o Use finger on top of affected eyebrow to help with raising eyebrow
o 10x to start off with since it's weak
• Bring eyebrows in together (scrunch) - can use finger again to bring eyebrow into centre
• Flare nose - either out or down, use finger on the crease of the nose to help
o 10x
• Mouth smile - use finger to help pull the corner of the mouth up
o Don't hold at the start - later, try to hold for 3s
ALS (Amyotrophic Lateral Sclerosis)
History:
• Progressive degeneration and loss of motor neurons in spinal cord and brainstem (LMNs) and motor cortex &
UMNs)
• Course is inexorably progressive → >60% of individuals die within 3 years of onset, usually of resp failure
• Level of disability changes over timescale of months, not years
• Heterogeneity in phenotype, cause, and genetic predisposition – suggests ALS is a syndrome rather than a single
disease

Epidemiology:
• Prevalence is ~2-6/100,000, incidence had been increasing over past few decades, latest US date says not
• Prevalence 50X greater in Pacific Rim (e.g., Guam, Honshu Island in Japan), otherwise similar incidence and
prevalence worldwide
• More common in certain occupations --> Italian soccer players and military
• Lifetime risk is ~1/600 to 1/2000
• More common in males (male:female = 1.2-1.6:1), this difference is decreasing

Risk Factors:
• Age:
o Risk peaks between 50-75 years – ALS is not a disease of aging
o Median age of onset – 55 yrs
o Juvenile onset ALS (genetic condition) - prolonged survival
• Family history:
o 5-10% have family history of ALS – autosomal dominant inheritance, autosomal recessive and X-linked
forms have been described
• Environmental factors --> findings inconclusive (smoking, pesticides, lead, toxins etc)

Etiology & Pathogenesis:

• Familial ALS: >15 FALS-associated gene variants identified
• Pathogenic process not well understood, likely multifactorial
• Possible causes:
o Oxidative stress – imbalance b/w production and removal of reactive oxygen species (ROS) or decreased
ability to repair ROS damage, results in structural damage
▪ Individuals with familial ALS have mutations in superoxide dismutase 1 (SOD1) - gene that
encodes enzymes that eliminate oxygen free radicals
▪ An accumulation of free radicals causes cell damage
o Mitochondrial dysfunction – abnormalities in intracellular energy production, calcium homeostasis and
apoptosis
o Defective glutamate metabolism – increase levels of glutamate in CSF; this is neurotoxic (disrupts
intracellular calcium homeostasis, mitochondrial function & ATP production), excess glutamate leads to
cell death
o Protein aggregation in cell body and proximal axon – a cardinal, histopathological feature of ALS
o Impaired axonal transport – delivery of essential components, such as RNA, proteins and organelles to
the axonal compartment is disrupted
o Dysregulated endosomal trafficking
 o Autoimmune and inflammatory processes – less evidence to support this proposed pathogenesis
o Persistent viral infection – less evidence to support this proposed pathogenesis

Motor Neuron Vulnerability:

• ALS is a multisystem disorder
• Motor neurons affected earliest and & most severely
o Large cell size and long axon means high metabolic demands and reliance on axonal transport
mechanisms, which are impaired
o Needs optimal mitochondrial function, which is impaired
o High intrinsic oxidative stress
o Vulnerable to excitotoxicity and dysregulation of intracellular calcium homeostasis
• Motor neurons more resistant to ALS
o Fast fatigue resistant motor neurons in the spinal cord
o Oculomotor neurons in the brainstem
o Neurons in Onuf’s nucleus (sacral motor neurons)

Diagnosis:
• No specific diagnosis test for ALS
• Diagnosis reached after observing clinical signs associated with ALS & ruling out other pathologies with lab tests
&/or imaging
• Disease progression must be seen for diagnosis of ALS (“mimic syndromes do not progress as rapidly)
• Objective sensory findings (impaired sensation) incompatible with diagnosis of ALS (unless resulting from a co-
morbidity)
• Diagnosis of ALS likely accurate in ~95% of cases
• Typical time from symptom onset to diagnosis is ~9-15 months

El Escorial Criteria:
• Definitive diagnosis of ALS requires:
o Evidence of LMN degeneration by clinical or electrophysiological exam
o Evidence of UMN degeneration by clinical exam
o Progressive spread of symptoms/signs within a region or to other regions (determined by history or
exam)
• Along with absence of:
o Electrophysiological and pathological evidence of other diseases that might explains signs of LMN/UMN
degeneration
o Neuroimaging evidence of other diseases

General Clinical Course:

• Onset:
o Gradual, over months
o Asymmetrical
o First symptoms are often UMN & LMN sign in 1 limb that spread to other areas
▪ UMN: spasticity, hyperreflexia, clonus
▪ LMN: atrophy, weakness, fasciculations
o Initial weakness usually in isolated muscles, often distally
o Sensory exam usually normal
 o Preservation of oculomotor, bowel and bladder functions
• Disease phenotype categorized by site of onset:
o Bulbar-onset – 20-30% of patients
▪ Dysarthria/dysphagia
▪ LMN: bulbar palsy – weakness of facial muscles, weakness & fascisculation of tongue, decreased
palatal movement and atrophy
▪ UMN: pseudobulbar palsy – brisk jaw jerk, emotional lability (I.e. pathological laughing or crying)
tongue spasticity
▪ More frequent in women and in late-onset disease
o Cervical-onset & Lumbar-onset – 65-80% of patients
▪ Cervical and lumbar onset occur in equal proportions
• In one ALS study, 35.5% of patients had cervical onset and 34.9% had lumbar onset
▪ Lumbar-onset signs and symptoms:
• LMN signs in legs (e.g. foot drop, proximal weakness manifested as difficulty
ascending/descending stairs)
• UMN signs often follow (hyperreflexia, clonus)
• Degeneration of anterior horn cells in lumbar enlargement
▪ Cervical onset of sign and symptoms:
• Bilateral or unilateral UE symptoms:
o Proximal weakness (e..g shoulder abduction)
o Distal weakness (e.g. pincer grip)
o UMN (e..g hyperreflexia) &/or LMN signs (atrophy, fasciculations)
o Respiratory-onset (5% of patients)
▪ Dyspnea – attacks can cause anxiety
▪ Respiratory muscle weakness
▪ Chronic nocturnal hypoventilation
• Leads to disordered sleep and daytime fatigue
• Can occur months or years before respiratory failure
• Significantly decreases QOL
▪ Thick mucus secretions from decreased fluid intake and decreased coughing pressure
▪ Pneumonia common
• As the disease progresses, individual present with these signs and symptoms:
o Swallowing/speech
▪ Dysphagia
• Choking risk, change of diet consistency, may progress to needing percutaneous
endoscopic gastronomy (PEG)
• Weight loss and malnutrition
▪ Dysarthria
• Can progress to complete loss of oral communication
• Speech therapy helpful in early stage if progression slow
o Respiratory muscle weakness:
▪ Respiratory insufficiency/failure results from diaphragm weakness and motor unit loss in
intercostal and axial muscles
▪ Signs of respiratory muscle weakness:
• Abdominal paradox
• Use of accessory muscles for breathing
 o Pain:
▪ Some sources report no pain with ALS
▪ Not a prominent feature of ALS
▪ 73% of individuals with ALS experience pain
• MSK pain in later stages due to atrophy and altered tone around joints, muscle
contractures and joint stiffness
o Cognitive impairment
▪ Up to 50% have some cognitive impairment
▪ Frontotemporal dementia (FTD) in 15% of patients
• Personality changes
• Irritability
• Poor insight
• Impaired executive function
• Impaired working memory
▪ Those with neuropsychiatric & cognitive changes show significant cortical atrophy (motor and
somatosensory areas, expanding to other frontal and temporal areas in FTD)
o Affect:
▪ Pathological laughing &/or crying in up to 50% of individuals with ALS – can impact participation
in social situations
▪ After diagnosis, many experience reactive depression
• ~10% experience major depression, but self-reported depressive symptoms in 44-75% of
individuals
o Quality of life:
▪ Self-assessed QOL usually doesn’t decrease significantly
• Psychological response shift --> Response shift refers to a change in the meaning of
one’s self-evaluation of a target construct because of (a) a change in the respondent’s
internal standards of measurement (scale recalibration), (b) a change in the
respondent’s values (reprioritization), or (c) a redefinition of the target construct
(reconceptualization).
▪ Passive coping style associated with decreased quality of life for patients and caregivers
▪ Like patients, next of kin show greater anxiety and depression and poorer scores on SF-36 than
general population

Terminal Phase:
• >60% die within 3 yrs of diagnosis, out of the remaining, 10% live for >8yrs
• >90% of patients die peacefully in sleep
• 20% of individuals in Netherlands with ALS died through euthanasia or physician assisted suicide
• Patients should be counseled on the terminal phase
o In the event of terminal respiratory failure, how do they want care to proceed?
o Care decisions should be reviewed regularly bc preferences for life sustaining treatments can change
with time
Prognosis:

Medical Management:
• Disease modifying treatment:
o Health Canada approved drugs:
▪ Riluzole
• Inhibits presynaptic release of glutamate (decreases toxic effect of excessive glutamate)
• Increases lifespan by a median of 11-14 months
▪ Edaravone
• Antioxidant and free radical scavenger
o Focus on symptom control, maintaining quality of life and palliative care

General – PT Management of ALS:

• Traditional PT approach beneficial in early stages
• Rapid and progressive decline in physical and functional ability requires unique PT approach – rehabilitation in
reverse
o e.g. transfer training proceeds in the reverse order from that seen in traditional PT (standby assistance
→ moderate or max assist → mechanical lift)
o Treatment frequency varies with rate of loss of physical function
• PT care plan typically includes:
o Education
o Mobility training
o Cardiorespiratory PT
o ROM exercises
o Strengthening exercises
o Prevention of secondary complications (e.g. prevent contractures, maintain respiratory health)
o Reduction of pain, spasticity
• When direct patient care is not required, PT visits should occur every 1-2 months to:
o Modify PT care plan
 o Update home exercise program
o Review/modify instructions for caregiver
o Prevent complications
o Assess need for direct PT care
• Goal setting:
o Focus on optimizing independence, QOL & comfort
o STG revised weekly/monthly
o LTG reflect the significant disability and care needs of ALS and end of life concerns

PT ASSESSMENT:
• Assessment tools used by PT, with #1-3 important for tracking disease progression:
o MMT or handheld dynamometry
o FVC – measure this at diagnosis and every 3 months after
o ALS functioning rating scale, revised ALS functional rating scale
o Quality of life
▪ Disease specific questionnaires exist:
• ALS specific questionnaire
• ALS assessment questionnaire 40 (ALSAQ40)
o Scores correlate well with scores on functional rating scales
▪ Generic QOL instruments can also be used:
• SF-36 has been validated in the ALS population
• ALS Functional Rating Scale (ALSFRS):
o 10-item ordinal rating scale
o For each task, 0=unable to attempt task, 4 = normal function
o High test-retest reliability & good construct validity
o ALSFRS scores declined in parallel w/ declines in measures of motor and pulmonary function, i.e.
sensitive to change
• ALS Functional Rating Scale Revised (ALSFRS-R):
o Revised version created as original scale gave less weight to breathing compared with bulbar and limb
function
o Breathing item replaced by 3 items assessing dyspnea, orthopnea, need for ventilation
o Total score ranges from 0 (max disability) to 48 (normal function)
o Decline in ALSFRS-R score is a predictor of decreased survival

PT MANAGEMENT:
• Education:
o Safe mobility, fall prevention
o Energy conservation
o Positioning/pressure relief
o ROM exercises to prevent contractures and MSK pain
o Prevention of pulmonary complications
o Environment modifications
o Adaptive equipment
o Community resources
o Disease progression – what to expect
• ROM
 o AROM exercises
o Transition to AAROM as strength declines
o PROM exercises important in later stages of disease
▪ Prevent contractures that can limit caregiver’s ability to assist with mobility (e.g. ankle DF
needed for weight bearing during transfers) or personal care (e.g. hip or shoulder abduction for
bathing)
o ROM with joint mobilization to reduce joint pain that results from immobility
• Exercise & ALS:
o Programs:
▪ Strengthening
▪ Flexibility/ROM
▪ Walking
▪ CV training
▪ Balance
o Engaging in exercise has been controversial in the past:
▪ Some thought individuals with ALS should avoid exercise to:
• Preserve strength
• Prevent overwork muscle damage
o Intense exercise facilitates some pathogenic mechanisms
• Research regarding how ppl with neuromuscular diseases respond to physical activity is
lacking
o Perform exercise to:
▪ Decrease spasticity, MSK pain, contractures, and joint stiffness
▪ Increase QOL
▪ Increase activity to prevent deconditioning and disuse weakness
▪ May have potential to slow loss of strength
▪ No controlled studies have reported overwork weakness
▪ Exercise tailored to individual’s exercise capacity should prevent overload of nervous, muscular,
and respiratory systems
▪ Moderate exercise promotes neural plasticity
▪ Use objective measurements to document disease progression for each patient
▪ Consider patient’s response to exercise when determining what exercises are appropriate and
safe and when program should be adjusted
▪ Exercise in early stages of disease when patients have sufficient strength, respiratory function
and endurance to exercise without excessive fatigue
▪ Re-evaluate patient’s abilities every few months to adjust exercise program
▪ In later stages of ALS, when respiratory capacity and functional ability is poor, approach exercise
with caution
▪ Use technology to optimize exercise regimes
o Two studies that can guide decision making concerning exercise:
▪ Dal Bello-Haas et al. 2007
• Investigated effects of resistance exercise on function (ALSFRS), fatigue, QOL(SF-36)
• Participants did either home program or stretching, or moderate intensity resistance exs
3x/week
• Results:
o No adverse effects
 o No neg effects on maximal voluntary isometric contraction (MVIC) or FVC
o After 6 months of exercise, resistance group showed greater ALS-FRS & SF-36
scores and showed less decline in leg strength
▪ Sanjak et al. 2010
• May be difficult for individuals with ALS to participate in regular exercise of a high
enough dosage to achieve CV conditioning, neuroplasticity
• Feasibility of assisted treadmill walking for ambulatory patients with ALS (n=9)
• Active assisted, mild-moderate intensity, treadmill walking
• Inclusion: ambulate 25 ft ≤1 min with gait aid; FVC ≥50% of predicted value (based on
age/sex)
• 60 min [6 x (5 min walking + 5 min rest)], up to 40% body weight supported; RPE kept to
max of 12 or 13 on modified Borg, adjust treadmill speed as needed, monitor SpO2
• Results: low to moderate intensity treadmill exercise was feasible, tolerable, safe for ALS
• Pulmonary complications mgmt.:
o Pulmonary impairment can go unnoticed in early stages – due to limb weakness, patients won’t exert
themselves ∴ won’t experience respiratory Sx (dyspnea)
▪ ALS patients w/o dyspnea shown to have FVC as low as 38% of predicted values
o Dysphagia: leads to malnutrition, dehydration, aspiration pneumonia
▪ Insertion of PEG tube recommended when FVC >50% of predicted value; early use of PEG tube
associated with prolonged survival (1-4 months)
o Poor secretion removal: due to weak expiratory muscles, ineffective cough
▪ Treatment: suction, assisted cough, chest percs, postural drainage
▪ Non-invasive methods don’t work = tracheostomy for tracheal suctioning
o Non-invasive positive pressure ventilation (NIPPV) is preferred method of ventilatory support
▪ May prolong survival more than other treatments
▪ Early prescription (before respiratory failure signs, FVC >50% of predicted) correlates with
increased survival, increased QOL
• 2020 guidelines: FVC threshold >65% of predicted as earlier initiation of oxygen
improves survival
▪ Not all patients can tolerate NIPPV (bulbar-onset patients have more difficulty)
• Candidates: mild progression, mild bulbar involvement, good communication skills, high
motivation, supportive family
o Respiratory muscle training – train inspiratory muscles to delay decline in respiratory function
▪ Limb muscle training applied to respiratory muscle training
o Pinto et al. (2012): 26 early-stage ALS patients, inspiratory muscle training
▪ Study onset – normal respiratory function (FVC >70%, max inspiratory and expiratory pressures
were >50% of predicted values)
▪ Intervention: active inspiratory muscle training – 10 minutes/session, 2 sessions/day
▪ Threshold inspiratory muscle trainer, threshold load set to 30-40% of max inspiratory pressure
Peripheral Nervous System Injury
 Laceration Carpal Tunnel Syndrome GBS

Type(s) of Peroneal nerve is cut Compression of median nerve Demyelination of peripheral

injury nerves

Classificatio Neurotmesis (5th degree) Neuropraxia Polyneuropathy (immune

n Mononeuropathy (can become mediated)
more severe) (Acute inflammatory
demyelinating
Polyneuropathy)

Expected Weeks to years Pain can be managed with
recovery physiotherapy for less severe cases,
but more severe cases may require
surgery which then takes around 6-
8 weeks to fully recover from.
No loss of structural function (will
recover)
3-12 months
Symptoms stop progressing
within the first 4 weeks. 80-
90% of patients will recover
with little or no disability
within a few weeks to a year.

Expected -Foot drop Numbness Tingling and pins-needles in

clinical Paralysis of dorsiflexors,
presentatio evertors, and toe extensors
n Sensory loss on
anterolateral leg and
dorsum of foot.
Tingling
Pain in thumb, index finger, middle
finger, and medial half of ring finger
Tinel and Phalen signs
Pain and paresthesia at wrist, may
travel up
feet with assoc back pain.
Then weakness in legs
predominantly. Muscle stretch
reflexes are lost

Prognosis Partial recovery possible
after surgery.
Complete recovery is
unlikely.
Good functional outcome
indicated by: younger age,
early repair, end to end
repair, distal injury to the
nerve
If not treated, it can lead to
irreversible median damage with
loss of hand function
Anoxia or ionic imbalances - will
recover quicker
Poor prognosis or can have
prolonged recovery time. Can
include rapidly progressive
weakness and potential need
for mechanical ventilation. 5-
10% mortality rate. 80-90% of
patients recover with little or
no disability with appropriate
care and rehabilitation.

Potential Ankle foot orthosis, surgical Avoid repetitive wrist activities Intravenous gammaglobulin or
managemen interventions to repair Neutral wrist splint plasmapheresis.
t nerve If conservative measures above fail, In the acute phase:
can have lidocaine and positioning of the patient to
methylprednisolone injections or avoid contractures and
 surgical sectioning of transverse
carpal ligament
musculoskeletal pain is
important. Once stable: ROM
exercises to keep the joints
free as well as to activate
proprioceptors and produce
afferent input to the brain will
start.
As soon as volitional activity
restarts, motor performance
will be trained, gradually
increasing training intensity
adapted to the course of
recovery. Splinting of hands,
fingers, and ankle is important
as contractures develop
quickly. Depending on the
severity crutches and walking
splints (peroneal splint) have
to be provided; also
intermittent wheelchair use
may be necessary. TENS and
electrical muscle stimulation
may be applied if needed.
EMG biofeedback training was
shown to improve muscle
performance of the upper
extremity

Any Neuropathic pain is likely as Neuropathic pain can occur Yes, damage to schwann cells
neuropathic there is damage to the • Changes to nerve function in myelin is a cause of
pain? How peripheral nerve. Clinical signs: peripheral neuropathic pain.
would you • Changes to nerve • Hyperalgesia • Changes to nerve
know and function • Allodynia function
address? Clinical signs: • Area of sensory loss Clinical signs:
• Hyperalgesia • Region makes • Hyperalgesia
• Allodynia neuroanatomical sense • Allodynia
• Area of sensory loss Treatment: • Area of sensory loss
• Region makes • Self management • Region makes
neuroanatomical • Exercise, relaxation neuroanatomical
sense (descending inhibition) sense
Treatment: Treatment:
• Self management • Self management
• Exercise, relaxation • Exercise, relaxation
(descending (descending inhibition)
inhibition)
 Note: motor nerves more
affected, less likely to get NP
pain

Group 5, 8, 9, 4, 6, 12, 13,3, Summary of PNI

Type(s) of injury Motor neuropathy

Sensory neuropathy
Autonomic nerve neuropathy
Combination neuropathies

Laceration, Traction, Compression, autoimmune, stretch,

contusion, diabetic

Classification Neurapraxia (Type 1)

Axonotmesis (Type 2-4)
Neurotmesis (Type 5)
Mononeuropathy
Multiple Mononeuropathy
Polyneuropathy
Sensory vs Motor
Seddon’s classification (Neurapraxia (Type 1);
Axonotmesis (Type 2-4); Neurotmesis (Type 5))
(based on type of injury, extent of damage, how many
nerves are injured etc.)

Expected recovery Variable based on degree of injury, age of patient, time

elapsed since injury,

Fifth degree unlikely to recover - requires surgical

intervention

We expect some recovery

Expected clinical presentation Variable based on degree of injury. Combination of
sensory, motor (weakness, paralysis, reflexes,
coordination), pain symptoms.

Prognosis Variable based on degree of injury/type of injury.

Additional factors affecting prognosis may include; age,
lifestyle factors, rehabilitation adherence.

Potential management Education re: pain, positioning, clinical course, additional

healthcare professions
Bracing/splints
Pain management (TENS, descending modulation,
exercise, medication, etc.)
Strengthening
Maintain ROM
Surgery
LE - gait retraining, balance, coordination

Treatment focus for most nerve injuries:

• Pain Management
• Muscle Weakness
• Functional deficits
• Sensory deficits
• Balance deficits
• Psychosocial/Emotional
Any neuropathic pain? How would you know and
address?
Pain characteristics through subjective assessment
Look for key features:
• Sensory loss or decrease
• Spontaneous pain
• be radiating, burning, stabbing, sharp/pricking
• Hyperalgesia and allodynia
• Neuroanatomically plausible
PT Management of Neuropathic Pain:
• Understanding the pain – teaching about pain
and neuroplasticity
• Mind-body strategies to calm nervous system
• Goal oriented physical activity – to change pain
and other general effects of physical activity and
exercise
• Sleep training
• Cognitive and behavioral strategies to cope with
stigma
• Support network
• Active coping
Neuromuscular Conditions
• NM condition: impacts motor unit (anterior horn cells, peripheral nerve, neuromuscular junction, muscle)
o Many are progressive in nature so knowing diagnosis is important b/c different natural history,
weakness pattern, prognosis, appropriate treatment
o Specific diagnosis has specific weakness pattern
• SPINAL MUSCULAR ATROPHY (SMA)
o Autosomal recessive; mutation or lack of survival motor neuron gene (SMN1); 1 in 10 000 live births
o Anterior horn cells of spinal cord are affected
o Scoliosis is very common – muscle weakness leads to it
▪ Efficacy of spinal bracing unclear; can interfere with respiration, rib cage development
▪ Many require spinal fusion – consider alignment, positioning 24hrs/day
▪ Therapies: more drug treatments in the work; increasing PT demand (type 1 SMA = 60%)
o Gene-modifying therapies: spinraza (nusinersen), zolgensma (onasemnogene abeparvovec), risdiplam
(evrysdi)
▪ Zolgensma: gene therapy for <2 years old, one-time injection; approved by Health Canada in
2021
▪ Risdiplam: similar mechanism to spinraza – oral medication
▪ New “types” – non-sitters (those unable to sit unsupported); sitters (those who can sit
unsupported); walkers (those who are unable to walk)
o Significant contractions impacting mobility (hips, knees, elbows, fingers)
o Need to be proactive to maintain ROM (muscle imbalance leads to contractures – can develop quickly)
o SMA classification

▪
o Exercise is indicated but be mindful of fatigue; keep spine flexible, supported
o Manage contractures to promote function
o Strengthening is indicated – consider different envts to help with active assisted mvmts (sling, pool)
o Equipment provision to promote life participation
• DUCHENNE MUSCULAR DYSTROPHY
o Muscle is affected
▪ Gower’s sign, toe walking, drop falls
o Genetic disorder, defect in gene coding for dystrophin (shock absorber for muscle cells)
o Progressive muscle weakness, degeneration leads to loss of function
o Cannot regenerate damage muscle – impacts all muscles of body including heart, respiratory
o Treat with Deflazacort (corticosteroid) has altered natural history of DMD, can live into early 30s
 ▪
o Gower’s sign: hands and knees position, climbs to stand by walking hands up legs
o Toe walk is safest way to walk; drop fall due to hip extensor, quad weakness
o High risk of fractures – low bone mineral density, weak muscles pull on bone = poor development, less
weight-bearing; steroids also cause weak bones
o NO WALKERS – arms too weak to support body, can fall on walker and fracture, lead to risk of fatty
embolism syndrome
o Strength training contraindicated in muscular dystrophies; may be appropriate with low reps and low
resistance in some neuromuscular conditions

o
o Overnight AFOs, contracture prevention, energy conservation
 o
• CHARCOT MARIE-TOOTH
o Most common inherited peripheral neuropathy
o Slowly progressive deterioration of peripheral nerves (sensory + motor nerves affected)
▪ Progressive muscle atrophy and muscle weakness
▪ Sensory changes
▪ Many types of CMT – most common is CMT 1A
o Symptoms: drop foot in gait, problems with balance, decrease sensation, fatigue, scoliosis and/or
kyphosis, foot abnormalities, problems with hand function
o Treatment goals: maintain Achilles length, maintain stable + flexible + pain-free foot, prevent disuse
atrophy, stay active
• Pediatric exercise recommendations: 1 hr/day, 3d/week, moderate intensity
o Focus: balance exercises, aerobic exercises, bone and muscle strengthening
▪ Bike riding, games of catch, swimming, resistance exercises, video exercise games, low impact
martial arts
• Adult exercise recommendations: 2.5hrs/week of aerobic exercise, 10 minutes bursts spread throughout the
week
o Low impact – monitor fatigue; swimming, yoga, bike, elliptical
o Bone and muscle strengthening at least 2d/week
▪ Low weight, higher reps
▪ Don’t exercise to fatigue
▪ Frequent rests
▪ Exercise bands and machines rather than free weights

•
 NEUROSCIENCE
Vestibular System
• Vestibular system contributes to: [broad role]
o Sensory info about head movement and head position relative to gravity
o Gaze stabilization (control eye movement when head moves) – keep visual input stable
o Balance
o Autonomic function
o Consciousness
• Vestibular function: periphery and central
o Periphery: vestibular receptors & vestibular nerve (cranial nerve axon)
o Central: brainstem vestibular nuclei (at junction of pons and medulla) & cerebral cortex

Peripheral Vestibular System

• Vestibular apparatus:
o Bony labyrinth
o Membranous labyrinth
o Hair cells – do the signalling/are the sensory receptors
• Bony labyrinth: inner ear; close to temporal bone → vestibular apparatus is attached to cochlea
o Cochlea – part of the auditory system
o Vestibular apparatus = 3 SCC + 2 OO
o 3 semicircular canals
o 2 otolith organs – saccule and utricle

o
• Semicircular canals: 3 hollow rings that are perpendicular to each other (acceleration measured in 3 planes of
motion)
o Superior/anterior; posterior; horizontal
o Open at both ends into the utricle; otolith organs are at the bottom
o Ampulla: contains crista; the swelling at the end of the canal (both ends)
 o

Bony labyrinth

Perilymph

Membranous
labyrinth

Endolymph

Hair cells

o
▪ Bony labyrinth
▪ Perilymph: fluid separating membranous labyrinth from bony labyrinth
▪ Membranous labyrinth: thin layer of tissue suspended inside bony labyrinth; hollow
▪ Endolymph: fluid inside membranous labyrinth – plays a role in signalling within vestibular
system
▪ Hair cells: receptors inside membranous labyrinth
• Crista and hair cells:
o Crista: supporting cells & sensory hair cells
o Hair cells embedded in cupula
o Endolymph fluid moves within the semicircular canal → causes cupula to move/bend → deforms the
hair cells embedded within → depolarize and fire/signal the movement → information carried by
vestibular nerve to the brainstem

o
• SCC – signal rotational accel/decel: movements like nodding yes, shaking no, or lateral side bend of head
o The hair cells have a baseline firing rate that increases or decreases depending on the movement
direction
 inertia hair cell
causes fluid bend hair firing rate ↑
head rotates bend cupula
in canal to cells or ↓ beyond
lag behind baseline rate

o
o Pairs – signal head movement
▪ Each canal works in concert with a partner on the other side of the head
▪ Pairs: 2 canals with maximal endolymph flow during rotation in a single plane (in one direction
only)

L anterior + R posterior
Axis of rotation for L posterior + R anterior
horizontal canal L horizontal + R horizontal

▪
▪ Left and right canals are paired based on whether they have maximal flow; preferentially
activated
▪ Produce reciprocal signals – increased firing in one canal and decreased firing in the other
(Figure B)
▪ E.g. L horizontal canal (LHC) & R horizontal canal (RHC) – rotate head to the right; hair cells in
LHC ↓ firing, hair cells in RHC ↑ firing
▪ Shaking head no → semicircular canals, not the saccule/utricle (but might stimulate both types)
• Otolith organs: see earlier picture for saccule & utricle
o Membranous sacs; macula is parallel structure to cupula (signal sensory receptors)
o Respond to head position relative to gravity & linear acceleration, deceleration (e.g. walking or in car)
o Each contains a macula made up of hair cells & gelatinous mass (hair cells are embedded within the GM)
▪ Calcium carbonate crystals (otoconia) are on top of GM
▪ Density differences between structures impact the ability to detect head position WRT gravity
o Otoconia density > gelatinous mass density ∴ causes otoconia to displace the GM so hair cells get bent

o Note the entire structure/image is a macula

 otoconia hair cell
change
tilt displace bend hair firing
head
macula gelatinous cells frequency
position
mass ↑ or ↓

o
• Otoliths – signal head position; distinguish between what movements they will be sensitive to (different in their
orientation ∴ detect motion in different directions)
Utricle Saccule
Macula orientation Horizontal Vertical
Responds to Head tilt starting from head in Moves up from laterally flexed position (e.g.
upright position (e.g. bend forward from side-lying to standing)
to pick something up off the floor) Linear acceleration/deceleration
o Otoliths detect linear acceleration ∴ detect movement while walking (impt for directing balance
responses)
• Vestibular apparatus primary role:
Semicircular Canals Otoliths
Stabilize vision (keep eye on target when head Affects spinal cord activity in lower motor neuron
moves) [track where head is rotating in space] to postural muscles [linear accel. WRT gravity]
• Vestibular nerve:
Pons & Medulla
Inner Ear
Vestibular Nuclei
Otolith Organs
Vestibular Nerve
Cerebellum
Semicircular Canals
Flocculonodular Lobe

o
o Hair cells signal and info is carried by vestibular nerve from periphery to CNS
o Information either goes: [1] directly to cerebellum into flocculonodular lobe (part of
vestibulocerebellum) or [2] vestibular nuclei in pons & medulla (however, usually don’t move in one
plane so utricle + saccule will probably both be stimulated to a certain extent)

Central Vestibular System

• Components: 4 nuclei in brainstem, 6 pathways; vestibulocerebellum and vestibular cortex
• Vestibular nuclei: bilateral set on LS & RS of brainstem, located at junction of pons & medulla near 4th ventricle
o Receive vestibular input along with vision, proprioception, cutaneous/tactile, auditory
 o
• Vestibular pathways: highlighted = need to know the names
Name Connects To Purpose/Influences
Medial longitudinal fasciculus Extraocular nuclei Eye & head movements
Vestibulospinal tracts (medial & Lower motor Posture
lateral) neurons
Vestibulocollic CN 11 nucleus Head position
Vestibulothalamocortical Thalamus & PIVC Conscious awareness of head position
(parieto-insular mvmt
vestibular cortex)
Vestibulocerebellar Vestibulocerebellum Magnitude of responses to vestibular
info (e.g. vestibulo-ocular reflex)
Vestibuloreticular Reticular formation Reticularspinal tracts
Autonomic centres for nausea &
vomitting
o Eye and head movement:
▪ Medial longitudinal fasciculus
▪ Vestibulocollic
o Conscious awareness
▪ Vestibulothalamocortical
o Balance & posture (+ alignment against gravity)
▪ Vestibulospinal
▪ Vestibulocerebellar
o Other (related to level of consciousness)
▪ Vestibuloreticular
 Parieto-insular
vestibular cortex (PIVC)

o Information is divergent (going to many places)

▪ Information from vestibular apparatus is diverted into cerebellum, does not synapse on
vestibular nuclei (doesn’t reach consciousness)
• Vestibulocerebellum
INPUT
CEREBELLAR OUTPUT FUNCTION
- vestibular apparatus & LOBE/DIVISION - vestibular nuclei - eye movements
vestibular nuclei
- flocculonodular lobe - vestibulospinal tracts - balance & equilibrium
- visual cortex
o
o Information doesn’t reach consciousness if it’s coming from vestibular apparatus & nuclei
o Input into flocculonodular lobe of cerebellum and sends output through nuclei, vestibulospinal tracts in
order to govern eye movements, balance, equilibrium
• Primary vestibular cortex: located at posterior end of insular cortex (buried under temporal and parietal lobes;
can see it if you pry apart the lobes along the lateral sulcus)
o Roles: multisensory integration & orientation/position in space WRT gravity
▪ Receives info from different sensations ∴ performs integration function + processing position in
space with respect to gravity (makes us consciously aware of it)
o Info that we become consciously aware of
o In animals, called parieto-insular vestibular cortex (PIVC); hard to study, you can’t do imaging since it’s
active w/ movement
• Falling asleep in a car (motion somnolence) + feeling carsick – same issue
o Conflict between sensory influences (e.g. vestibular system – stimulated by motion;
visual/kinesthetic/somatosensory systems – different info)
o E.g. flies on a rotating disk felt drowsy with slow rotation speeds; cxn btwn vestibular system & reticular
formation
• Important in PT with virtual reality as patients can get motion sickness (outcome measure is available)

Vestibular Role in Motor Control

• 2 primary roles in motor control (along with providing sensory info about head movement, position)
o Gaze stabilisation
o Postural/balance adjustments
• Role in motor control: inputs and outputs; describes how vestibular input is used in motor control
 STIMULI RECEPTORS CENTRAL PROCESSING OUTPUT
Angular acceleration of
the head Vestibular cerebral Perception of head
Semicircular orientation
cortex
canals
Linear acceleration of Vestibular nuclei and
the head vestibulocerebellum Oculomotor nuclei
Eye movements
Saccule and
Head position relative to Spinal cord
utricle Postural control
gravity

Sensory Motor Sensory & Motor

o Info detected by apparatus is fed into vestibular nuclei and vestibulocerebellum; central processing
integrates with other inputs and sends outputs to various targets (e.g. area resp. for perception aka
PIVC)
• Role in motor control: connections
SENSATIONS RECEPTORS CENTRAL PROCESSING OUTPUT

Vestibular information Vestibular cortex Conscious

Thalamus
awareness of head
Vision Vestibular Extraocular nuclei position and mvmt
nuclei
Proprioception Superior colliculus Eye movements
Accessory nerve
Tactile information
Cerebral cortex Head movement
Auditory information Cerebellum Spinal cord
Reticular Posture of head
formation and body

Sensory Motor Sensory & Motor Reticular

formation Nausea and

vomitting

Altered
consciousness

o Outputs are related to sensation and motor control; vestibular info is integrated with info from other
systems

Clinical Applications
• Vestibular conditions:
o Peripheral: benign paroxysmal positional vertigo (BPPV) (not caused by tumour; sudden onset of Sx
depending on head position)
o Central: postural vertical disorder

BPPV
• Symptoms: rapid change in head position → dizziness and nystagmus
o Subsides in <2 minutes (even if provoking head position is maintained) – the movement causes Sx
o Provoking activities: get in/out of bed, turning in bed, reaching above head, bending over to look/reach
low down
 o
• Cause: displacement of otoliths/otoconia from macula into the semicircular canal (canalithiasis)
o Trauma, infection, spontaneous (in older adults)
o Posterior semicircular canal most affected (when sitting upright, it’s the one that’s most gravity-
dependent
• Pathophysiology:
1.
Unilateral
Loose Mismatch
Vestibular signal in
otoliths/ signals
Head Otoliths fall Abnormal nerve fires absence of
otoconia at Cupula elicits
moves into new flow of even after head
lowest bends nystagmus
quickly position endolymph head stops movement
point of and
moving 2. Other
canal dizziness
side stops
signalling
o
o Disruption of flow w/ foreign body in SCC = vestibular nerve continues to fire after head stops moving
o Only one side fires (other side doesn’t) b/c otoconia causes firing ∴ conflict, mismatched signal causes
nystagmus and dizziness
• Diagnostic test & treatment:
o Ax = Dix-Hallpike maneuver: cause otoliths to move to new gravity-dependent position, eliciting Sx
o Tx = Modified Epley maneuver: move otoliths out of SCC into the vestibule; immediately resolves BPPV
in 75-80% patients
• YouTube 1 – diagnostic test and treatment
o Patient is sitting, PT turns patient’s head to one side quickly (patient should try to keep eyes open at all
times)
o Contraindications: neck pain, recent surgery on neck
o Patient long sitting on plinth, PT grabs patient head to turn 45° to one side and then lower patient into
supine position “quickly” while ensuring head hangs over the bed 30° below horizontal plane
o Observe for nystagmus for at least 30s
o Should repeat on both sides (L & R lateral positions) → if DH is positive, perform Epley to treat BPPV
o Epley: head hangs over plinth, turn patient’s head 90° and maintain for 30s → patient turns onto their
side (side-lie) → rotate patient’s head so they look directly towards floor → maintain position for 30-60s
→ sit patient up sideways (go upright) while maintaining head rotation → once sitting upright, re-align
head to midline and flex neck, maintain for 30s
• YouTube 2 – nystagmus during Dix-Hallpike → PT is behind patient instead of beside (might be a better position)
o Goggles measure eye movement – “beating/oscillation” of the eyes (looks like eyeball is
pulsing/twitching)
o Nystagmus subsides after patient has been in one position for enough time
• YouTube 3 – otoconia movement during Hallpike & Epley
o Sit upright
 o Turn head 45° to the left
o Lie back into left Hallpike position
o Wait 60s
o Turn head 90° to the right
o Turn a further 90° into a nose down position
o Return to upright position

Postural Vertical Disorder [umbrella term]

• Symptoms
o Misperception of postural vertical
o Misaligns body relative to gravity
o Strongly resists passive correction of alignment (feels like they’re being pushed over)
o Named for direction of pushing/pulsion
o Lateropulsion: push away from less affected side (aka pushing syndrome)
▪ E.g. image – left side affected ∴ use unaffected right side to push over to affected side
▪ Therapist is trying to correct him
▪ Occurs in ~63% of people after a stroke; usually resolves by 6 months but can delay recovery
esp. as there is an increased potential for falls
• Pathophysiology: highlighted = potential sites of stroke-related damage

Vestibular Parieto-insular
Posterior Postural
Otolith organs nuclei vestibular
thalamus vertical
(medulla/pons) cortex
o
Development of Nervous System
• Genetic and environmental factors influence cells throughout development
o Development is a process of:
▪ Cell growth, migration, differentiation
▪ Cell death
▪ Axonal retraction
o Certain processes are completed in utero (while fetus develops in the uterus); some processes continue
after birth (pediatric development)

Developmental Stages in Utero

• 3 stages – there is variability in the timeline for stages
Fetal Stage
Pre-Embryonic Stage Embryonic Stage
Beginning of Week 9 to
Conception to Day 14 Day 15 to End of Week 8
Birth
o
• PRE-EMBRYONIC STAGE: fertilization to day 14

•Fertilized ovum [A]

•Cell division as ovum moves down uterine tube [B]

•Solid sphere of cells [C]

•Cavity opens in sphere [D]

•Sphere implants endomentrium of uterus

•Inner cell mass develops into embryonic disk [E]
•3rd (mesoderm) cell layer develops between other 2
A – fertilized ovum (single cell)
B – four cell stage
C – solid sphere of cells
D – hollow sphere of cells (ICM becomes ED)
E – two layered ED; L cross-section, R above

o
▪Egg is fertilized
▪Travels down uterine tube towards uterus & cells divide
▪Solid sphere of cells develops, and a cavity starts to form inside the sphere
▪Outer layer of cells: fetal contribution to placenta
• Inner layer of cells: differentiate incl. becoming the NS; ICM develops into embryo
▪ Once cell mass reaches uterus it implants into the lining and leads to more ICM development
▪ ICM develops into embryonic disc which initially has 2 layers (ectoderm, endoderm) –
mesoderm forms later on → ED is important as it gives rise to all other components of the
embryo
o Fertilized egg → cell division → cell mass achieved, cavity forms → outer layer becomes placenta, inner
layer becomes embryo → differentiates into embryonic disc → 2 layers → mesoderm layer forms in
between (3rd layer)
• EMBRYONIC STAGE: day 15 to end of week 8
 Ectoderm Mesoderm Endoderm
• Sensory organs • Dermis • Gut
• Epidermis • Muscles • Liver
• Nervous system* • Skeleton • Pancreas
• Excretory system • Respiratory system
• Circulatory system
• FETAL STAGE: week 9 to birth
o Major organs and body systems continue to grow and mature
o Capacity to move limbs
o Majority of growth in weight and length
o Nervous system develops more fully, and myelination begins* (myelination will continue after birth)

Formation of Nervous System

Stages
• Zoom in/further breakdown of the embryonic stage: can be divided into 2 stages
Stage 1 - Day 18 to 26
Stage 2 - Day 28 to 56
Ectoderm forms neural Ends of neural tube close
Brain forms
tube (neurulation)
o
o Embryonic stage is where a lot of changes in the NS development occurs
o Closing of neural tube ends signals the next stage (where the brain forms)

Neural Tube

Left – bird’s eye view (above the embryo)

Right – cross-section through the embryo
• A – day 16
• B – day 18 → midline section of neural plate
moves toward the interior of the embryo,
creating a neural groove
• C – day 21 → folds of neural plate meet,
forming neural tube; neural crest separates
from tube and remaining ectoderm
• D – open ends of neural tube are neuropores;
neural tube differentiates into inner and
outer layer

•
 •Neural plate forms [A]

•Neural groove forms [B]

•Folds of groove touch (day 21) [C]

•Neural crest separates [C]

•Groove zips closed (open ends = neuropores) [D left]

•Neural tube & crest move inside the embryo

•Overlying ectoderm closes over top

•Tube differentiates into 2 concentric rings (day 26) [D right]

•Neuropores close (superior - day 27; inferior - day 30)

•
o First – thickening occurs in ectoderm to form neural plate (in purple)
▪ Mesoderm in middle, endoderm and ectoderm on top
▪ Neural plate forms as a thickening in the layer
o After neural plate forms, there is an indentation (neural groove) that forms in the middle towards the
mesoderm layer
▪ 2 folds of roof grow together, touch, and close off
▪ A piece pinches off called the neural crest (on either side)
o Once neural groove is formed and folds initially touch, the neural tube will zip closed from the middle
and proceed outwards to the front and back (caudal and rostral) – forming a neural tube
o Neural tube is closed with two open ends – superior and inferior neuropores
o Once neural tube formed, it moves down inside the embryo
▪ Overlying ectoderm forms a layer over top of it
▪ Neural crest is still present
o Neural tube differentiates into 2 concentric rings
▪ Inner layer becomes gray matter (cell bodies/somas)
▪ Outer layer becomes white matter (axons)
o Neuropores eventually close with superior pore closing before inferior pore
• YouTube video:
o By day 16: 3 layers (ectoderm, mesoderm, endoderm) – ectoderm becomes NS
o Neurulation: first stage of process, process of neural plate becoming neural tube
o Day 18: part of ectoderm begins to thicken – neural plate
▪ Between cranial end of embryo and primitive node
o Day 19: neural plate begins to buckle in midline to form neural folds and neural groove
 ▪
▪ Folds progress towards each other, begin to fuse ~day 21
▪ Form hollow cylinder – neural tube
o Fusion continues towards caudal and cranial ends
o Unfused ends – caudal neuropore, cranial neuropore → cranial closes ~day 24, caudal ~day 26
o Peaks of neural folds have neural crest cells which form a layer over the top of the closed neural tube →
develops into most of peripheral nervous system
o Neurulation starts in centre and goes to both ends; CNS develops from neural tube
o Fetus will start to curl into fetus position by day 21
• Somites: spherical clusters of cells – divide from adjacent mesoderm as the neural tube closes

o
o 3 parts that become different sections
Dermatome – becomes dermis
Sclerotome – becomes vertebra and skull
Dorsal root Myotome – become skeletal muscle

Dorsal root ganglion

Ventral root

o
o Neural tube: inner layer proliferates – cell division
▪ Grooves form on each side – separate tube into ventral & dorsal
▪ Ventral section: motor/basal plate → axons grow out and innervate myotome next to it (send
projections)
▪ Dorsal section: association/alar plate → form interneurons (w/ SC) and projection neurons (w/
brain)
o Neural crest: separates into 2 columns, one on each side of neural tube
▪ Breaks up into segments corresponding with somites
▪ Neural crest forms: peripheral sensory neurons, myelin cells, autonomic neurons
▪ Cells develop into peripheral sensory neurons
 ▪ 2 processes grown: 1 connects to spinal cord, 1 innervates dermatome section of somite
(primary afferent) [central and peripheral axons ∴ pseudounipolar neuron]
▪ Cell body of neuron is a dorsal root ganglion and it develops outside of neural crest/tube
• Spinal cord vs. spinal column: spinal cord corresponds with vertebra correctly in fetus up to 3 months → aligned
somites cause nerves to project out laterally
o Spinal cord shorter than vertebral column
o Spinal column growth has faster rate than spinal cord growth (column/bone > cord/nerves)
o Lower motor neurons come from neural tube; primary afferent connecting spinal cord to dermatome
develops from neural crest

Recap of In-Utero Development

• 3 stages: pre-embryonic, embryonic, fetal
o PE: fertilized egg develops → divides into mass of cells → gives rise to embryonic disc (3 layers)
• ED layers: ectoderm – nervous system; mesoderm – muscles, skin, skeleton and somites (break off to form
muscles, skin, and skeleton)
o Ectoderm thickens to form neural plate → neural groove → neural tube
▪ Neural tube closes off and sinks into the embryo, differentiating into outer layer (white matter)
and inner layer (grey matter)
o Somites and neural crest develop, eventually connect to form primary afferent
▪ Primary afferent grows central and peripheral processes to connect the dermatome to the
association plate of the neural tube
▪ Axons grow out of motor plate of neural tube to innervate myotome of the somite
o Dermatomes and myotomes of somite develop into the representative myotomes & dermatomes
assessed in a person

Brain
• Begins on day 28 when the superior neuropore closes
o Superior end becomes the brain → expands to form 3 enlargements
o Hindbrain, midbrain, forebrain
• The enlargements are hollow as it becomes the ventricles (for CSF) [figure A]
 •
• Hindbrain → medulla, pons cerebellum; cavity → 4th ventricle
• Midbrain → midbrain; cavity → cerebral aqueduct
• Forebrain (posterior) → thalamus and hypothalamus (diencephalon)
• Forebrain (anterior) → telencephalon; cavity → lateral ventricles
o Telencephalon becomes cerebral hemispheres
o Expand extensively to envelop diencephalon
o Contains: deep nuclei (basal ganglia), white matter, cortex
• Hemispheres expand ventrolaterally to form temporal lobe
o Develop C shape – ventricles & caudate nucleus adopt C shape too
o Lateral aspect doesn’t grow as much so other regions cover the insula
• Eventually, edges of cortex cover over the insula to form lateral sulcus
o Surface of cerebral & cerebellar hemispheres being to fold and create sulci & gyri

Recap of Brain Development

• https://www.youtube.com/watch?v=tA1Gv3oyotA
• From conception to birth
• First 4 weeks after conception, neural plate forms in outermost layer of embryonic cells
o Folds to become neural groove and then curls to become neural tube which differentiates into
forebrain, midbrain, hindbrain, spinal cord
• Forebrain - cerebral cortex; translate sensory stimulation, control complex
behaviours/thoughts/memories/problem solving + motor learning
• Midbrain - neural relay station to send info from body to different parts of brain
• Hindbrain - control most basic physiological processes (breathing, heart rate)
o Spinal cord is pathway for conveying info between brain and rest of body
• Weeks 4-8: embryo grows rapidly, start to look more human (face)
o Eyes on side of head start to migrate forward
o 2 distinct cerebral cortex hemispheres emerge
 • Weeks 8-26 in fetal stage: cerebral cortex grows to cover midbrain by week 28
• Weeks 28-40 in fetal stage - fill brain with gyri and sulci; cortex expands in surface area and become folded
beginning at week 28
o Cerebral folds + wrinkles create vast neural network
• By week 8 the brain structures are in place but brain tissue is rapidly increases as new nerve cells form -
neurogenesis/neural migration
• New nerve cells migrate from innermost layers of tissue outwards - guided by fibres of glial cells (glial cells form
underlying structure of nervous system)
• Later formed cells move further away from starting point so brain grows, more layers
o Once cell reaches destination, it will specialize/get characteristics specific to that area
o Will sprout extensions needed to communicate with other neurons - dendrites and axons
o Dendrites - receive incoming signals; axons carry outgoing signals
• Synaptogenesis - synaptic proliferation
o Point of communication between dendrite and axon - "exuberant synaptogenesis"
o Continues into first year of life

Cellular-Level Development
• Equilibrium of progressive and regressive processes – some things might be created while others are pruned
back

- cell proliferation, - neuronal death

migration, and - axon retraction
growth
- axon extension
- synapse formation
- myelination
o
o Axon extension – form connections
o Axon retraction – cells don’t survive so when axons reach out to make connections & are unsuccessful,
they retract

Progressive Processes
• Cell migration: 2 mechanisms
o Cells of neural tube are stem cells (don’t have function yet) – will divide and move to where they need
to go
o Can divide into neurons or glia (supporting cells)
o Mechanism 1: send slender process to brain surface and pull itself along
o Mechanism 2: climb along radial glial (cells which stretch from centre of brain to the surface); use a
“supporting bridge” that has created a process
• Cell differentiation: e.g. neural tube develops into anterior or posterior / motor and association plate
respectively
o Reach final location and differentiate – become specific type of cell or specific type of function (e.g.
become primary afferent or autonomic nerve or motor axon)
o Neuron function isn’t genetically determined but depends on the area it migrated to
o Cues in environment, chemical factors, receptors, etc. which help it differentiate and become function
it’s supposed to serve → ∴ determined by environment and surrounding factors
• Axon extension/growth: once the neuron reaches the site, how does it make connections with other things?
How does the cell in the motor plate send out its axon to eventually innervate the correct myotome of the
somite?
o Done through growth cone (process emerging from neuron) – enlarged end of the axon

o
o Axon process emerges from neuron cell body – forward end of process expands to form growth cone
▪ Growth cone samples the environment
▪ GC also makes contact with other cells and chemical cues
▪ Chemical cues are secreted – axon is either attracted or repelled by the cues thus guiding
growth to eventually make contact

o
▪ Growth cone bends towards positive/attractive cues and moves away from negative/repelling
cues
▪ Axon is being projected or grown
o E.g. frog embryonic brain cells – neurons from eye extend axons to connect to midbrain targets
▪ GC extends and retracts thin processes called filopodia & veil-like processes called lamellipodia
▪ Frequent changes in shape/direction as GC responds to attractive, repulsive extracellular cues
▪ Axons might cross paths as they probe environment and cues; once they reach the midbrain
(optic tectum) they will slow down and grow processes to sample target neurons & establish
synaptic connections
▪ 6 hours to reach target that is <1mm distance away
• Synapse formation:
o Target cell reached [A] → synaptic vesicles form [B] → neurotransmitters are released [C&D] → post-
synaptic cell develops receptors [E&F]
 o
o Once axon reaches target cell via growth cone, the GC will recede
o Some of the structures that provided support for GC will contribute to synapse formation
o Target cell reached by axon and then start to form synaptic vesicles (holding NT)
o Once contact is made, NT is released (test/build up cxn)
▪ Axons sent out to NT to stimulate the target/contact cell
▪ In response, the post-synaptic cell/target cell develops receptors
▪ If conditions are right, cxns are formed; if enough NT are released & enough receptors develop,
the synapse is formed
o This suggests activity within the NS also determines what synapses are formed
• Myelination: myelin sheath is made of lipid & protein which wrap around axons; formed by the glial cells
o Begins in the 4th fetal month and is complete by 3 years of age
o Different rates of myelination in different brain regions
▪ Motor roots develop from neural tube to motor plate, later innervate myotome → myelinated
in the 4th fetal month, complete at 1 month of age
▪ Descending tracts coming down from brain (UMN makes contact with LMN) – myelination
continues until 2 years of age

Regressive Processes
• Neuronal death: up to 50% of neurons formed in development die; fetus develops a lot of neurons that won’t
survive
o Reasons: failed to establish optimal connections w/ target cells; too inactive to maintain connections
(not enough communication across new synapse in order to firm it up and make it a permanent
connection; not enough activity to keep it stimulated ∴ dies off)
• Axon retraction: surviving neurons will retract axons from certain target cells while other connections are left
intact
o Certain neurons survive, but axons don’t remain intact
o Send out processes that didn’t make contact – might retract
o Synesthesia in central somatosensory system → theory is that there is less neuronal death or less axonal
retraction during nervous system development which leads to extra connections that normal people
don’t have
Electrical Principles of Cells & Synaptic Transmission
• Electrical currents (communication btwn neurons) occur through movement of charged particles
o Body function depends on chemical and electrical cell interactions
• Neuron parts

o
Dendrites Branchlike extensions
Receive info from other neurons
Input site
Soma (cell body) Contains organelles
Axon Process extending from soma
Sends information to other neurons or cells
Output site
Axon hillock Specialized region of soma
Where action potential starts
Presynaptic terminal Transmit information to presynaptic cell
Contain vesicles with NT
o Bipolar (retina); pseudounipolar (dorsal root ganglion); multipolar (hippocampus, Purkinje)

o
• Neuron cell membrane – plasma membrane (like all cells)
o Separates outside and inside/ECF, ICF; has specialized ion channels that can generate electrical current
o Ions: move away from areas of high concentration to areas of low concentration
• Electrochemical gradient is combination of concentration gradient + electrical field gradient
o Ions move down gradient to reach equilibrium but membrane prevents this – gated channels
o Stimulus causes gated channels to open (embedded in membrane)
o Ion channels: voltage-gated, ligand-gated, modality-gated (e.g. stretch), Na+-K+ pump, leak channels
• Electrical potential – mV, potential energy source – ions flow when channel opens = kinetic energy (current)
o Resting membrane potential
o Local potential
o Action potential
• RMP: difference in charge between interior and exterior of neuron (voltage); steady state no net flow of ions
o Voltmeter measure: both electroces inserted in ECF – 0mV
 o 1 in ECF, one in ICF – RMP = -70 mV (range -60 to -80 mV)
o Maintain RMP: passive ion diffusion via leak channels (mostly K+), Na/K pumps, anions trapped inside
o Na/K pump: maintain concentration gradient
▪ Use energy/active transport of ions (ATP) against the gradient – 3 Na+ out, 2 K+ in
o Depolarize – become less negative
o Hyperpolarize – become more negative
o Two types of RMP changes – local potentials, action potentials
• Local potentials: localize change in membrane potential
o Occur at post-synaptic membrane (ligand-gated) synaptic potentials; sensory receptors (modality-gated)
receptor potentials
o Depolarize or hyperpolarize – graded in amplitude or duration
o Steps
▪ Stimulus (NT, modality e.g. stretch, chemical, light)
▪ Activate ion channel (ligand or modality gated)
▪ Ions flow across neuron membrane
▪ Change in RMP (hyperpolarize or depolarize)
o Temporal summation – combined effect; local potential changes within milliseconds (same location of
membrane)
o Spatial summation – combined effect; local potentials generated at adjacent regions of membrane
within ms
o Significance of summation: summation of local potentials → action potential
• AP: signal carrying info to nervous system
o Large change in voltage across neuron membrane
▪ Depolarized/less negative
▪ All or none
▪ Travel long distances
o Mediated by voltage-gated channels
o Threshold: firing level, ~ at -55mV (need to bring MP to this value for an action potential to occur)
• Absolute refractory period: membrane unresponsive, Na+ channels remain closed for fixed period of time ~1ms
following AP initiation
• Relative refractory period: membrane potential more (-) than RMP, Na+ channels can open as it requires a
stronger stimulus, approximately 3ms following ARP
• AP features
o All-or-none: once started, it goes to completion (amplitude always the same – 30 mV)
o Propagation: passive = ion flows to adjacent neuron membrane; active = generate new AP at adjacent
membrane
▪ Conduction velocity 0.5-120 m/s
▪ Affected by axon diameter (increased diameter = greater current flow, less time required to
change electrical potential across adjacent membrane) and myelin (insulation, limit AP
dissipation)
o Continuous vs. saltatory conduction:
▪ Continuous: AP generated at each spot along axon
▪ Saltatory: myelin prevents current dissipation, AP only regenerates at gaps in myelin along axon
(nodes of Ranvier)
•
• Synapses: neural communication site between neuron and post-synaptic cell
o AP reaches presynaptic terminal
o Change in electrical potential at membrane (depolarizes) – VG Ca2+ channels open, calcium enters
presynaptic terminal
o Calcium binds to docking proteins, connects vesicles with NT to presynaptic terminal membrane
o Vesicle fuses w/ presynaptic terminal membrane, NT released into cleft
o NT diffuses across cleft, binds to receptors on post-synaptic cell membrane
o Binding of receptor leads to either opening of ion channel or activation of intracellular messengers
• Convergence: multiple inputs form different cells terminate on 1 neuron
• Divergence: single axon has many branches terminating on different cells
o Synaptic contacts:

•
• Post-synaptic potentials: local potential, occurs due to change in ion concentration across post-synaptic
membrane
 o Depolarizing – excitatory post-synaptic potential (EPSP)
o Hyperpolarizing – inhibitory postsynaptic potential (IPSP)
• EPSP: NT binds to post-synaptic ligand-gated sodium channel -> sodium flows into cell -> depolarize (more +ve)
• IPSP: NT binds to receptor on ligand-gated channel -> chlorine flows in or potassium flows out -> hyperpolarize
(more -ve)
• Presynaptic facilitation & inhibition
o Only at axoaxonic synapses
o Neuron influences amount of NT released by presynaptic neuron
o Influences effectiveness of synapse between presynaptic and postsynaptic neurons
• Glia cells: number of glia is around the same number of neurons
o Critical support network for neurons
o Involve din a number of diseases’ pathogenesis
o Core functions: signalling/cleaning/nourishing, myelinating, defending
o Types: astrocytes, oligodendrocytes & Schwann cells, microglia
• Astrocytes: star-shaped cells in CNS; f(x) – clean up, nutrient transport, signalling
o Clean up: take up extra potassium in EC envt, remove NT from synaptic cleft and clean up debris
o Nutrient transport: end-feet connect neurons to capillaries; highly active neurons need more blood flow
so astrocytes facilitate nutrient supply between capillary & neuron
o End feet
o Signalling: stimulate astrocytes send waves of calcium to neighbouring astrocytes via gap junctions;
bidirectional signalling, regulates communication at synapse between neurons
• Oligodendrocytes & Schwann cells: form myelin sheath (lipids, proteins)
o Oligodendrocytes in CNS – each one myelinates part of several axons of different neurons
o Schwann cells in PNS – each only myelinates 1 axon; unmyelinated peripheral axons aren’t completely
bare (not wrapped in myelin but surrounded by Schwann cell membrane)
• Microglia
o Phagocytes
o CNS immune system
o Stimulated abnormally by disease (PD, AD, stroke, HIV/AIDS)
Neuroplasticity
• Neuroplasticity: ability of neuron to change function, chemical profile, structure
• Hebb’s Rule: when cell A and cell B repeatedly fire at the same time chemical changes occurring both cells so
that the connection b/w the two cells is made stronger (more efficient)
MECHANISMS OF NEUROPLASTICITY:
HABITUATION:
- Short term:
o Lasts <30 mins
o Due to pre-synaptic changes
- Long term:
o Lasting days to weeks
o Changes in postsynaptic receptors and protein synthesis
- Gill withdrawal reflex in sea slug:
o Tactile stim to siphon
o Sensory neuron generates EPSP in interneurons and motor neurons
o Motor neuron fires
o Withdrawal of gill
o Short term habituation:
▪ Repeated stim
▪ Decreased NT vesicles released from sensory neuron
▪ Decreased amplitude of PSPs in interneurons and motor neurons
▪ Result: motor neuron fires less briskly and reflex response diminishes
o Long term habituation:
▪ 4 sessions of 10 stimuli (separated by hrs to days) = habitation for 3 weeks
• Structure changes
• Control: 90% of sensory neurons synapse with gill motor neurons
• Long term habituated: 30% of sensory neurons synapse with gill motor neurons
EXPERIENCE DEPENDENT PLASTICITY:
- Long term potentiation:
o Silent synapse --> active synapse by highly correlated pre-synaptic and postsynaptic firing
o A) silent synapses lack functional glutamate receptors (AMPA)
o NMDA receptor binds glutamate and Ca enters cell
o AMPA receptors floating in cytoplasm insert into the membrane
o With repeated stim, post synaptic membrane generates new dendritic spine
o Presynaptic cell undergoes structural changes
 - Long term depression
o Active synapse --> silent synapse
o AMPA receptors removed form the postsynaptic membrane
o Postsynaptic membrane likely to depolarized when glutamate released

- Astrocyte contribution to experience dependent plasticity:

o Astrocytes release gliotransmitters
▪ Modulate neuronal activity
▪ Modulate synaptic transmission
• Modulate NT release and receptor expression
• Take up NT from the cleft
▪ Contribute to synaptogenesis and axonal remodelling

PLASTICITY WITH TRAINING:

- Study investigates changes in cerebellar cortex with diff. types of activity
- 38 rats in 4 groups: AC, FX, VX, IC
o Rats in AC: demonstrated improved motor skill
▪ Increased 25% number of synapses per Purkinje cell
o Rats in FX+VX mastered the exercise wheel on first day
▪ VX: increased density of capillaries (bc more physical activity)
 - 2 different patterns of adaptation to environmental demands:
o Synaptogenesis: need for skilled movements
o Angiogenesis: reps of simple well practiced movements
INACTIVE AND ALONE:
- Stroke patients and older adults do not walk enough and are isolated too much to be able to have
neuroplasticity

RECOVERY/PLASTICITY AFTER INJURY:

Excitotoxicity:
- Oxygen deprivation --> neuronal death
- Excitotoxicity = cell death caused by overexcitation of neurons
o Adds more damage and loss of neurons
o Glutamate (excitatory NT) in large quantities is toxic to neurons --> several destructive consequences
o Increased Ca leads to K+ out of cell
▪ Na/K pump attempts to restore the gradient
▪ This requires energy (glycolysis) leads to lactic acid build up and damage to cell membrane
o High intracellular Ca
▪ Activates enzymes = proteases
▪ Break down cellular proteins
▪ Produce oxygen free radicals
▪ Damages mitochondria
o The flow of ions across the membrane
▪ Causes water to enter the cell
▪ Cell edema

Axonal Injury and Sprouting:

- Axon terminal degenerates
- Myelin breaks down and forms debris
- Cell body undergoes metabolic changes
- Presynaptic terminal retract from dying cell body
- Postsynaptic cells degenerate
Axonal Injury and Plasticity:
- Regeneration of axons occurs more in PNS >CNS bc of:
o NGF produced by Schwan cells
o More effective clearing of debris
o Residual Schwann cells guide axonal growth
- Recovery rate is slow
o 1-3mm growth/day or 1-3 inches/month
- Regeneration may be increased by
o Exercise
o Electrical stim
o Both
- SPROUTING:
o Collateral sprouting:
▪ Denervated target is reinnervated by branches of intact axons of neighbouring neurons

o Regenerative sprouting:
▪ Axon and target cell are damaged
▪ Injured axon sends out sprouts to a new target

- CNS:
o Sprouting from spared and injured axons can occur
o Functional regeneration of axons doesn’t occur in CNS bc of:
▪ Glial scars (formed by astrocytes and microglia)
 ▪ Limited NGF
▪ Growth inhibiting actors released by glia e.g. NOGO

SYNAPTIC CHANGES:
- Injuries may cause degeneration but not cell death
- Conversely injuries that destroy cell body of neuron lead to cell death
- Several mechanisms to overcome this type pf CNS damage (III-v)
o Synaptic changes
o Functional reorganization
o Changes to NT release
- Recovery of synaptic effectiveness:
o Local edema after injury
o Interferes with microvascular function
o Which interferes with synthesis and transport of NT -> synapse inactive
o When edema is resolved, effectiveness is restored

- Denervation hypersensitivity:
o Presynaptic axon terminals destroyed
o Postsynaptic cell creates new receptor sites
o NT released from nearby spared axons --> increased/hypersensitive response occurs

- Synaptic hyper-effectiveness
o Presynaptic neuron – only some branches are damaged
o NT is redistributed to the remaining axon branches
o Larger than normal amounts of NT released onto postsynaptic receptors

- Unmasking silent synapses:

o Redundant, unused synapses exist in the CNS
o May become active when other pathways have been injured

FUNCTIONAL REORGANIZATION OF CORTEX:

 - Cortical representation (maps/homunculus) can be modified by
o Sensory input
o Experience
o Learning
o Peripheral injury
o Brain injury
- e.g. expert violin players have enlarged area of somatosensory cortex representing fingers of left hand
- Genetics can influence plasticity of the brain
o Brain derived neurotrophic factor (BDNF) important for plasticity and repair
o Ppl with mutation of gene BDNF exhibit poorer recovery
▪ Decreased motor map reorganization after training
▪ Altered patterns of brain activity associated with reduced motor learning
CLINICAL APPLICATIONS:

CLINICAL APPLICATIONS: HABITUATION

- Children with tactile defensiveness (reactive to stimulation to skin)
o Gentle repetitive stimulation of skin
o Gradually increase intensity to stimulation
CLINICAL APPLICATIONS: EXPERIENCE DEPENDENT PLASTICITY
- CIMT – constrain induced movement therapy
- Restrain unaffected limb 90% of waking hours
- Train 5 days/week, 2 weeks, 6 hours/day
- CIMT eligibility criteria:
o 10x10x10
▪ 10º active wrist ext
▪ 10º active thumb abd
▪ 10º active extension of any other 2 digits
o Also suggested:
▪ Limited spasticity according ot modified Ashworth
▪ 45º shoulder flex and abd
▪ 90º elbow flex and ext
o Adequate balance
o Minimal cognitive dysfunction
- CIMT: CORTICAL REORGANIZATION
o Some evidence suggests that CIMT might increase cortical activation patterns
Motor Learning
• Set of processes associate with practice/experience lead to relatively permanent change in skilled behaviour
capability
• Process:
o Acquisition: practice skill, performance improves – impacted by mood, motivation, fatigue
o Consolidation: no practice between session 1 & 2, continued changes in brain activity
o Retention: performed learned motor skill; gains in performance compared to performance at end of
session 1
• Stages:
o Cognitive/novice: understand the task, variable performance, highly cognitive, inefficient, not adaptable,
large improvements
o Associative/advanced: refine skill, less variable performance, less cognitive, increased coordination,
more adaptable, slower improvement
o Autonomous/expert: automatic performance, low attention, focus on other aspects (e.g. 2nd task), most
efficient and coordinated
• CNS structures involved: learn finger movement sequences, fMRI – motor cortex, basal ganglia, cerebellum had
increased blood flow (increased activity)
o With lots of practice, gradual and specific change sin motor cortex that represent learned movement
sequence
o Cerebellum involved in early/fast learning phase when establishing initial motor routine
o Basal ganglia & striatum – when sequence is well-learned/automatic execution, distributed neural
networks includes motor cortex and basal ganglia – can retain and produce movement
• Structures involved in motor learning

o
o GREEN – CORTICO-STRIATO-THALAMO-CORTICAL LOOP (cortex, basal ganglia, thalamus)
▪ Well-learned/execution automatic
▪ Distributed neural system (striatum & motor cortices) produce, retain learned behaviour
▪ Level of activity doesn’t change with extended practice
▪ LT storage of learned movement
o BLUE – CORTICO-CEREBELLO-THALAMO-CORTICAL LOOP (cortex, cerebellum, thalamus)
▪ Cerebellum involved in early/fast learning phase when initial motor routine est.
▪ Activity decreases with practice
• Framework for applying motor learning to neuro rehab

o
 o Forms of learning: both implicit and explicit involved in ML; continuum
IMPLICIT EXPLICIT
Provide/use very little verbal info Conscious learning, individual acquires verbal
Less aware of details of motor learning knowledge about mvmt
Refine coordination/calibration of Involved in learning goals/objectives of movement
movement
o Therapy elements:
ELEMENT ML PRINCIPLES DETAILS
Organization Envt and task to be learned Blocked vs. random practice
Adaptive vs. part vs whole
task
Instructions Info about how to perform task, objective/goal of Internal vs. external focus of
task attention
Mode & content
Feedback Info available to patient after movement Type & content of feedback
performed Feedback frequency
▪ Random practice is superior (better retention) – trials A, B, C presented randomly
• Blocked – all A trials, then all B trials, then all C trials
• Elaborative processing hypothesis – effortful, meaningful processing promoting
compare/contrast analysis of actions
• Forgetting & reconstructing hypothesis – ST forgetting of action plan when different task
performed, forcing action reconstruction each time a task is performed again
▪ Adaptive – practice simple version of whole task and increase complexity
▪ Part task – subdivided into parts, practiced as pre-training for whole task (carryover evidence
lacking)
▪ External focus is superior (keep red markers at same height – internal = keep feet at same
height)
▪ Mode of delivery: verbal instructions, visual demo, manual guidance
▪ Content: # of steps in instruction
▪ Intrinsic feedback: naturally available from one’s own senses (vision, somatosensory,
proprioception)
▪ Extrinsic feedback supplements naturally available info, shouldn’t be redundant
▪ Knowledge of results (KR) – info of outcome; knowledge of performance – info of how skill was
performed
• Type/content: mainly motivational, reinforcing, physios talked more than patients
▪ Frequency: KR feedback given less often is better
• Too much feedback creates dependency, don’t learn to use intrinsic feedback to guide
movement (more complex tasks need more feedback)
• Average feedback: give KR of average performance after several trials
• Faded feedback: high rate of feedback and then reduce it
• Bandwidth feedback: feedback when performance outside predetermined acceptable
limit/band
• Motor learning in PD:
o If you give more feedback to a PD patient there is better retention
o Controls training under 20% KR were better than controls under 100% KR
o Patients under 100% KR were better than patients under 20% KR
• Gait symmetry post-stroke – display B influenced understanding
o TGA – temporal gait asymmetry (want it to be closer to 1)

o
Cranial Nerves & Muscle Tone & Blood Supply
Cranial nerves:
• Exchange info between PNS & CNS
• 12 pairs
• Originate from cerebrum and brainstem
• Innervate structures in head and neck (except CN 10 – vagus that innervates structures in thoracic and
abdominal viscera)
• Axons and receptors outside of skull
o Part of PNS
o Myelinated by Schwann cells
• CN 1 & 2 entirely within skull (no peripheral component)
o Myelinated by oligodendrocytes
• Cranial nerve cell bodies:
o Sensory CN:
▪ Ganglia outside brainstem (similar to DRG)
▪ Except neurons with proprioceptive info from face – cell bodies inside brainstem
o Motor CN:
▪ Nuclei inside brainstem (similar to LMN in ventral horn)
• Specialization: some carry only motor signals, carry only sensory signals, carry sensory + motor signals, unique
special sensory function (visual, auditory, vestibular), some also have autonomic function
• Cranial Functions:
o Motor innervation to muscles of face, eyes, tongue, jaw, superficial neck muscles
o Transmit somatosensory info from skin and muscles of face and temporomandibular joint
o Transmit special sensory info (visual, auditory, vestibular, taste, olfactory)
o Parasympathetic regulation of pupil size, eye tear glands, HR, BP, breathing, digestion

Number Name Related Function Connection to Brain

1 Olfactory
2 Optic
3 Oculomotor
4 Trochlear
5 Trigeminal
6 Abducens
7 Facial
8 Vestibulo-
cochlear
Smell Inferior frontal lobe
Vision; afferents for pupillary and accommodation reflexes Diencephalon
Moves eye up and down, medially; raises upper eyelid, Midbrain (anterior)
efferent for vestibulo-ocular reflex
Constricts pupil, adjusts the shape of the lens of eye,
efferent for pupillary and accommodation reflexes
Moves eye medially and down efferent for vestibulo-ocular Midbrain (posterior)
reflex
Somatosensation from the face, temporomandibular joint, Pons
eyebal; afferent for corneal reflex
Chewing
Abducts eye; efferent for vestibulo-ocular reflex Between pons and medulla
Facial expression; closes eye, protects hearing; efferent for Between pons and medulla
corneal reflex
Taste
Tears, salivation
Sensation of head position relative to gravity and head Between pons and medulla
movement; afferent for vestibulo-ocular reflex; hearing
 9 Glosso- Sensation from pharynx, posterior tongue, middle ear, Medulla
pharyngeal afferent for gag and swallowing reflexes, taste
Constricts pharynx
BP and chemistry from carotid artery
Salivation
10 Vagus Sensation from pharynx, larynx, skin in external ear canal
Regulates swallowing and speech, efferent for gag and
swallowing reflexes
Afferents from viscera
Regulates viscera
11 Accessory Elevates shoulders, turns head Spinal cord
12 Hypo-glossal Moves tongue Medulla

Conscious sensation
Motor efferents
Autonomic afferents
Parasympathetic efferents

OH OH OH TO TOUCH AND FEEL VERY GOOD VELVET AH HEAVEN

SOME SAY MARRY MONEY BUT MY BROTHER SAYS BIG BOOBS MATTER MOST

CN 1: OLFACTORY
Category Special sensory
Function Afferents for olfaction
Other Info travels in olfactory tract to:
- Primary olfactory cortex
(insula)
- Amygdala
- Parahippocampal gyrus

CN 2, 3, 4 & 6: OPTIC, OCULOMOTOR, TROCHLEAR, ABDUCENS

- Vision and eye movement
o CN2: carries vision info to primary visual cortex
o CN3: muscles move the eye, lift eyelid, constrict pupil, increase curvature of lens (inferior oblique,
superior rectus, medial rectus, inferior rectus, levator palpebrae superioris, constrictor pupillae, ciliary
muscles)
o CN4 & CN6 – each innervate one muscle that moves the eye (superior oblique – CN4; lateral rectus –
CN6)
CN 5: TRIGEMINAL
Category Mixed – sensory + motor
Function: - Sensory information from face, eyeball, tongue,
temporomandibular joint (all branches)
- Innervate muscles for chewing
- Afferent limb of the corneal blink reflex
o Corneal blink reflex – ophthalmic neurons of CN5 –
afferent limb
o Cornea touched
o Information relayed by ophthalmic neurons of CN 5
o Synapse in spinal trigeminal nucleus (medulla)
o Interneurons relay signal bilaterally
o Facial nerve CN 7
o Close both eyelids
Other 3 branches; ophthalmic, maxillary, mandibular

CN 7: FACIAL
Category Mixed: sensory + motor + parasympathetic
Function Taste from anterior tongue
Touch, nociceptive and pressure info from tongue, pharynx and
ear canal
Innervate muscles to close eye, move lips and facial expressions
Innervate salivary, nasal and lacrimal (tear) glands
Efferent limb of corneal blink reflex
Other Cell bodies for LMN in facial nerve nucleus – divided into upper
and lower halves
- Corticobrainstem track --> bilateral signals --> upper ½
nucleus -> upper facial muscles
- Corticobrainstem track --> contralateral signals -->
lower ½ nucleus --> lower facial muscles

CN 8: VESTIBULOCOCHLEAR
Category Special sensory
Function Head movement and position
Hearing
Orient head and eyes towards sound (inferior colliculus)
Increases activity level throughout CNS (reticular formation)
Conscious awareness and recognition of sounds (thalamus -->
primary auditory cortex)
 Other - 2 branches: vestibular and cochlear
- Info sent to:
o Reticular formation
o Inferior colliculus
o Medial geniculate nuclei (thalamus) --> primary
auditory cortex
Cochlea converts sound to neural signals:
- Snail shell shaped organ
- Fluid filled spiraling tube
- 2 chambers divided by a membrane
- Organ of Corti – within cochlea – hair cells convert
sound to neural signals
- Longer cells vibrate at lower frequency
- Shorter cells vibrate at higher frequency

CN 9: GLOSSOPHARYNGEAL
Category Mixed: sensory + motor + autonomic
Function Taste from posterior tongue
Sensation from soft palate, tongue, pharynx, ear
Innervates muscle of pharynx
BP and chemical info from carotid artery
Innervates parotid gland (salivary gland in front of ears)
Afferent limb of gag and swallow reflex
Other Reflex pathways involve same CN
Touch pharynx/stimulate palate --> signal by CN 9 --> medulla -->
interneurons --> CN 10 --> pharyngeal muscles contract

CN 10: VAGUS
Category Mixed: sensory + motor + autonomic
Function Somatosensation & nociception from pharynx, larynx, ear
Innervate muscles of pharynx and larynx
Afferent information from viscera in thorax and abdomen
Extensive innervation of thoracic and abdominal viscera
Reduce HR, constrict bronchi, stimulate digestion
Efferent limb of gag and swallowing reflexes
Other

CN 11: ACCESSORY
Category Motor
Function Innervates trapezius and SCM muscles
 Other

CN 12: HYPOGLOSSAL
Category Motor
Function Innervating tongue muscles
Other

NEUROPHYSIOLOGY OF MUSCLE TONE

- Terminology: muscle tone
o Tone = resistance to passive stretch while the patient is attempting to maintain a relaxed state of muscle
activity
o Muscle tone is a continuum (flaccidity – hypotonia – normal – hypertonia)
o Hypertonia: abnormally increased resistance to externally imposed movement about a joint
▪ May be caused by spasticity, dystonia, rigidity or a combination

CONTRIBUTIONS TO MUSCLE TONE:

- Titin
o Sarcomere: composed of 2 types of proteins
▪ Contractile:
• Myosin (thick)
• Actin (thin)
• (tropomyosin, troponin)
▪ Structural:
• Z line
• M line
• Titin
- Weak cross-bridge binding
o Formed when myosin attaches to actin but heads don’t swivel

▪
o No muscle contraction
o Sarcomere stays the same length
o But resistance to stretch generated by these bonds
o Real life examples:
▪ Grasp pen tight for 30 seconds, slowly open hand, consciously aware of increased resistance to
hand opening
▪ Sitting for long period of time, getting up feel increased resistance to stretch
- Connective tissue
 - Proprioceptive information (including reflexes)
o Frequently implicated in muscle tone
o But in an intact nervous system there is minimal change in muscle electrical activity during a slow
stretch
o With neurological injury or disease reflexes become altered
▪ Hypersensitive muscle spindle stretch receptors
▪ Decreased threshold of the alpha LMNs
▪ Increased number of acetylcholine receptors – release of ACh causes muscles to contract
▪ Denervation, hypersensitivity, collateral axonal sprouting
- Descending motor commands
o Reflex modulation
▪ Intact NS has descending commands (e.g. CST corticospinal tract) modulating the circuitry
involved in spinal reflexes
▪ Balance between excitatory and inhibitory
o Several mechanisms of modulation:
▪ e.g. presynaptic facilitation and inhibition
o Potential to modulate the reflex circuitry at several points
▪ Presynaptic terminals of afferent neurons, interneurons, alpha motor neurons
BLOOD SUPPLY:
- Brain:
o 2 pairs of arteries supply blood to the brain
▪ Vertebral arteries --> supply occipital and inferior temporal lobes, brainstem, cerebellum
• Vertebral arteries join --> form basilar artery
o At junction of pons and medulla
• Basilar artery + branches supply pons and cerebellum
• At junction of pons and midbrain basilar artery divides --> posterior cerebral arteries
▪ Internal carotid arteries --> supply most of cerebrum
• 3 cerebral arteries supply different territories
• Internal carotid arteries branch -->
o Anterior cerebral arteries
o Middle cerebral arteries
• Basilar artery branches -->
o Posterior cerebral artery

o
- Circle of Willis:
o Anastomotic ring of 9 arteries
o Supplies all the blood to cerebral hemispheres
o 3 pairs of large arteries + 3 small communicating arteries
▪ Large arteries and communicating arteries
 • 2 anterior cerebral arteries (branches of internal carotid) joined by 1-anterior
communicating artery
• 1 internal carotid artery join to 1-posterior cerebral artery by 1 posterior communicating
artery – REPEAT ON OTHER SIDE
o 2 posterior cerebral arteries

o
Functional Electrical Stimulation
fdaf
Neural Control of Locomotion
• Locomotion: any form of rhythmic and alternating activity involving multiple degrees of freedom (e.g.
swimming, crawling, walking, flight, hopping)
o Common: rhythmic & alternating movements
o Can be stereotypical (controlled at low levels of CNS) and not stereotypical (adapt to changing envt,
need higher levels of CNS control)
• Studied with animal models, 4 types of preparations + human evidence
Animal Preparation Location of What is Intact What is Not Intact
Cut/Preparation
Intact N/A Everything N/A
Spinal (reduction) Spinal cord (lower Spinal segments Brainstem, cerebellum,
thoracic) controlling hind limb cerebral cortex
muscles
Decerebrate (reduction) Brainstem either (1) above +/- midbrain, pons, Cerebral cortex, midbrain
or (2) below midbrain medulla, spinal segments (if cut below)
Deafferented Dorsal roots Motor neuron activity and No afferent/sensory info
muscle activity
Immobilized (& spinal) Neuromuscular junction Sensory information, No muscle activity
(fictive locomotion) (paralyze muscles with motor neuron discharge (reflexes)
ACh inhibitor)
• Early evidence that locomotion governed by spinal cord

o
o Evidence (rhythmic stepping without supraspinal or sensory input) →
▪ Hypothesis (rhythmic pattern produced independently in spinal cord) →
• Model (central pattern generator)
• Central pattern generator (CPG): reciprocal neuronal network in spinal cord, capable of generating rhythmic
(complex temporal) pattern of motor activity in absence of/independent of phasic (rhythmic) sensory input from
peripheral receptors
o Half-centre theory: contractions in flexors and extensors of a limb are controlled by two groups of
neurons (CPG) – each limb controlled by separate CPG
o Each CPG has 2 groups of excitatory interneurons/half-centres – directly project and control activity of
flexor, extensor motor neurons with mutual inhibitory interconnections between to ensure only 1 half
centre is active at a time
o Fatigue process reduces excitation of active half centre → phase switching occurs when reduction in
excitability falls below critical value → opposing centre released from inhibition
 o
o CPG in ~L6 of invertebrates and lower vertebrates; humans – lumbosacral regions
o CPGs are highly modifiable and receive inputs form afferent pathways & descending commands
• Sensory inputs to CPG – input adjusts and regulates basic motor pattern; proprioceptive inputs regulate timing,
somatosensory inputs adjust stepping to external stimuli
o Somatosensory input from muscle
▪ Spinal & decerebrate cats – increase treadmill speed can increase step rate; afferent input
regulates stance duration
▪ Passively and rhythmically move hip – knee flexor burst just as hip reaches peak extension
▪ Hip flexors: stretch at terminal stance, signal swing transition coming from spindles in flexor
muscles
▪ Extensors: stimulate Ib afferents in ankle extensors and inhibit ipsilateral flexors, prolonged
burst in ipsilateral extensors ∴ delay swing or extend stance phase
• Stimulate GTOs to prolong stance phase; opposite of usual GTO action
• Phase dependent reflex reversal
• If there is perturbation in stance, want to reinforce it and stay stable
o Somatosensory input from skin
▪ Spinalized cat – stimulus to paw in swing phases causes flexion withdrawal reflex
▪ Stimulus to paw in stance phases causes flexors to inhibit, extensors to activate – maintain
weight-earing on stance limb (again, phase-dependent reflex reversal)
o Visual input (supraspinal)
▪ Fine control of stepping modulated by higher cortical centres (brainstem, cerebellum, motor
cortex)
▪ 3 primary functions: activate spinal system to control overall speed; refine motor pattern in
response to feedback from limbs; guide limb movement in response to visual input
▪ Gait initiation and speed control: decerebrate prep evidence in comparing intact and non-intact
midbrain – mesencephalic locomotor region (MLR) is key
▪ MLR stimulation initiates stepping; stimulus intensity proportional to walking speed &
transitions – does not influence limb coordination (done by spinal network)
• MLR doesn’t directly project to spinal cord but goes to medial reticular formation
• MRF project to spinal cord (reticulospinal pathway)
 ▪
o (Vestibular apparatus)
o Decerebrate animals can do simple walking but no tasks requiring advanced coordination
• Cortical involvement in gait – intact cat on treadmill with obstacles
o Motor cortex, foreleg muscles all fire
o Firing rate of M1 increases
o Increased cortical activity associated with enhanced EMG activity
o Role in adjusting EMG (CPG) activity to meet task requirements
• Cerebellar contribution to gait: lesion in cerebellum = ataxia (poorly coordinated stepping)
o Spinocerebellar divisions involved in CPG regulation – receives input from limbs via spinal cord

o
• CPGs in humans: recovery of walking function; evidence -case reports; clonidine studies; developmental studies
o Case report:

▪
▪ Spontaneous leg mmovements: alterante flexoin and ext. of hips, knee,s ankles
• Smooth and rhythmic and more forceful than voluntary; couldn’t stop by voluntary
effort, rolling onto side and flexing hip/nee stopped the movement
o Clonidine studies: drugs that mimic noradrenaline can stimulate walking in mammals (noradrenergic
agonist)
▪ Administered to people with incomplete SCI (oral, intrathecal)
▪ Measured gait on treadmill (TM) with body weight support (BWS)
▪ EMG activity in legs more regulate and walking speed increased
o Infant stepping: infants produce stepping motions immediately after birth when upright, suggesting
basic circuits for walking are established genetically
▪ Stepping is free from descending control in first year of life (immature neocortex, descending
tracks)
 ▪ 3-6 months, take more steps when moving treadmill – proprioceptive input from moving belt is
impt
▪ More steps/min when baby supports more of its weight
• Clinical applications:
o Use dependent plasticity in spinal cord, patterns of sensory input are critical
o BWS TM TRAINING
▪ Clinically complete SCI – increased weight bearing capacity, rhythmic patterns of activity
produced
▪ Clinically incomplete SCI – improved gait control
▪ Sensory cues and continued training is impt
o PHARMACOLOGIC THERAPIES
▪ Noradrenergic (clonidine) agonists facilitate stepping
▪ GABA & glycine antagonist reduce inhibition at SC level after lesion to allow network to be more
active
o COMBINATION
▪ Most potent is pharmacology with training – set spinal cord state to prime optimal conditions
for training
▪ Partial BWS engage sensory cues; FES + robotics
o Neuro Recovery Network (NRN): intensive activity-based therapies – high intensity, high volume
o Robotics & exoskeletons: wearable devices, Lokomat
• Pediatric case study: non-ambulatory 4.5 year old – incomplete cervical SCI, baseline was only crawling with
arms
o By session 33, child could take first independent steps without physical cues or manual assistance
▪ After locomotor training, kids could walk independently with rolling walker
▪ No lower limb muscle strength changes
• SUMMARY: basic control mechanism for locomotor patterns is in SC; more sophisticated organism = greater
involvement of higher-level structures; might be “harness” to recover walking function in the future
 PAIN/MISCELLANEOUS
Peripheral Neuropathic Pain
Definitions & Meaning of Damage to a Nociceptor
• Neuropathic pain: pain caused by lesion or disease of the somatosensory nervous system
o Previous definition: pain initiated or caused by primary lesion or dysfunction in the nervous system
o Change to acknowledge the mechanism, more specific (sensory system)
o Dysfunction without neuron damage is nociplastic pain
• Neuropathic pain is divided into central and peripheral
o Central neuropathic pain: pain caused by lesion or disease of central somatosensory nervous system
o Peripheral neuropathic pain: pain caused by lesion/disease of peripheral somatosensory nervous system
o A clinical description – requires demonstrable lesion or disease to satisfy established neurological
diagnostic criteria
o Lesion – diagnostic test show abnormality or trauma
o Disease – known underlying cause of lesion (stroke, vasculitis, diabetes mellitus, genetic abnormality)
• These are clinical descriptions – don’t imply underlying nociceptive mechanism
o Neuralgia: pain in distribution of nerve or nerves
o Radicular pain: clinical description of distribution of pain or other sensory symptoms, doesn’t necessarily
imply mechanism
o Neuropathy: disturbance of function or pathological change in a nerve; implies nerve damage or disease
▪ Mononeuropathy: in one nerve
▪ Mononeuropathy multiplex: in several nerves
▪ Polyneuropathy: diffuse and bilateral
• Injuries to peripheral neurons – damage or disease
o Trauma:
▪ Nerve injured by force (e.g. trauma, amputation, surgical trauma)
▪ Nerve compression (e.g. carpal tunnel, entrapment, ischemic)
o Diseases:
▪ Diabetes, tumours, radiation-induced, anti-retroviral-induced, B12 deficiency, chemotherapy-
induced, toxins & alcohol, infection, immune, idiopathic small-fibre neuropathy, chronic
inflammatory demyelinating neuropathy

o
o PNI – neuron lives if damage to neuron is distal to cell body (won’t function as well but it can bring
abnormal sensory input into SC) → topic of this lecture
▪ Deafferentation injury: deafferentation of second order neuron
▪ PNI – injury distal to DRG (cell body – black dot)
▪ Nociceptive primary afferent enters SC, synapse at dorsal horn
o Proximal damage relative to cell body – can’t bring in any input to SC; deafferentation injury, causing
central neuropathic pain
• Pathological pain: neuropathic pain from non-tissue source; from neuron and response to nerve damage
o Weak stimulus-response relationship, pain in area doesn’t mean tissue is damaged in the area
o Pathological and low threshold pain – pain can even come on its own
 o
• Characteristics: peripheral neuropathic pain = nerve damage or disease
o Key features:
▪ Location of sensory Sx make neuroanatomical sense (i.e. correspond to known anatomical nerve
or nerve root distribution)
▪ Usually an area of sensory loss or decrease
▪ History of injury/disease that could affect NS
o Signs & symptoms:
▪ Spontaneous pain ++ can be radiating, burning, stabbing, sharp/pricking; can be sudden and
severe “electric shock” (depends on lesion)
▪ Evoked: hyperalgesia & allodynia
o Key is sensory loss and sensory gain – damage to neuron changes how it functions (numbness & pain in
the same body location)
• Loss of meaningful activation by receptors at distal end of neuron
o Neuron damage disconnects it from normal receptor site ∴ don’t respond to environmental normal
stimulus
o Damage to nociceptive neuron changes how it functions → damaged neuron can still send signals if
depolarized but the signals are meaningless/don’t encode stimulus
o Does not “truthfully” signal what is going on in the environment
• Nerves are not passive conductors of information – neuron and axon transmit info from one area of body to
another
o Rather than being a telephone cable where both ends’ signals will fall silent
o Chemicals are transmitted up and down from nucleus to parts of neuron where the chemicals are
needed
o When transmission of chemicals is interrupted, the neuron changes how it behaves
o Ion channels, transducer molecules, receptors are synthesized and transported down the axon
▪ Afferent has a lot of jobs e.g. conducting protein to and from
▪ Will attempt to maintain cell in normal circumstances but will also heal & change cell when it’s
attacked

Mechanisms – Effect of Damage to Nociceptor

• Peripheral nerve injury induces extensive molecular changes t/o primary sensory neuron
o From periphery to cell bodies in DRG, to terminals in SC
o Induces changes in SC itself
• Nerve damage results in chronic pain through multiple routes
 o
o Neuropathic pain is difficult to treat b/c there are so many mechanisms that can contribute with
different percentages for each patient; peripheral nerve damage can result in chronic neuropathic pain
in multiple routes
o Changes to peripheral portion of injured nerves – more sensitive, fires spontaneously (ectopic)
o Changes in cell body of injured neuron (DRG) – more excitable, spontaneous firing
▪ Response in synapse in dorsal horn with induced changes even though original damage is in the
peripheral nerve
▪ Neuron and immune changes cause synapse to fire abnormally/more sensitive
o Changes in brain – change in central processing, central sensitization
• Changes in function of neuron after injury:
o ST: inflammation from injury sensitizes the nerve at the injury site and the entire neuron (cell body +
CNS connections)
o LT: triggers metabolic and functional changes in neuron itself
• Immune cells respond to nerve injury: Wallerian degeneration
o Injured neuron responds, tries to grow/heal
o [A] injury to nerve or neuron
o [B] injury has brought immune cells to site (T lymphocyte, macrophage, mast cell)
▪ Schwann cells proliferate & dedifferentiate – form guiding tubes for regenerating axons/neurons
▪ Regeneration doesn’t always happen

▪
• Immune response affects neuron
o Immune cell aids in nerve inflammation, repair, regrowth – neuronal injury affects inflammation &
repair
▪ Schwann cells release chemicals – neurotrophic factors, cytokines, prostaglandins
▪ Neurons take in these chemicals (has receptors)
 ▪
o Inflammation & repair affects neuron (neurotrophic factors)
▪ Takes in chemicals, goes up to cell body and alter gene expression & how injured nerve behaves

▪
• Neurotrophic factors (NTF) from EC envt signal nucleus – cell membrane of axon for injured neuron has NTF
receptors
o When receptors are activated, chemical messengers move inside cell to nucleus and signal protein
production
o Injury to myelin sheath and Schwann cells – NTF released to start this signalling
o Neurotrophic factors present after injury
o Taken up by neurons
o Travel to nucleus to signal up/down regulation of transcription

o
• Nucleus signalled to make specific proteins
o New proteins transported back down (ion channels & receptor molecules inserted in cell membrane to
change how it functions)
o New concentration of ion channels and receptors – membrane remodelling
o Phenotypic changes/phenotypic switch: neuron has new response characteristics/responds differently
o This is what makes neuropathic pain unique

o
• Remember nerve is composed of axons from many neurons – bundles of neurons inside the nerve
o Within each bundle there are individual axons/fibres of individual neurons (thousands of neurons in
peripheral nerve)
o We are describing the level of injury to an individual neuron, not the whole nerve
 o Whole nerve injury e.g. amputation or cut to whole nerve → usually it’s only individual neurons within
the nerve that are injured

▪
• Chemicals from Wallerian degeneration affect other neurons in same nerve
o Injury/disease may affect some neurons in nerve and not others BUT undamaged neurons in the nerve
are still affected
o Peripheral changes in primary afferent nociceptive neuron after partial nerve lesion - #1 & #3 axons are
damaged, #2 & #4 axons are intact

o
o Expression of Na+ channels increased in neuron #3 due to lesion
o Myelin disruption and release of neurotrophic factors trigger expression of channels and receptors on
uninjured nociceptive fibres → changes excitability of uninjured fibre
• Effects of membrane remodelling: more ion channels and new α-adrenoceptors (respond to noradrenaline)
o More ion channels: increased responsiveness (hyperalgesia) and abnormal spontaneous activity (ectopic
discharges/impulses)
o New receptors: nucleus will transcribe proteins it doesn’t usually make + normally somatic nerves don’t
respond to noradrenaline
▪ After some injury, neurons start production of receptor for nor-adrenaline
▪ When sympathetic post-ganglionic fibre is active & releases nor-adrenaline, the body
fibre/somatic fibre/nociceptor responds
• Extensive molecular changes to primary nociceptor from periphery to cell body in DRG, SC
o Peripheral sensitization from injury
o Neural-immune interaction
o Change in neurotrophic factor signalling cell to change phenotype
o Coupling btwn sympathetic efferent & sensory afferent fibres esp. in DRG are linked to abnormal
excitation (long-term)
• Injury discharge can induce central changes – bombardment of activity induces central sensitization (CS)
o Injured nerve has unique discharge sending specific message to CNS
o Ongoing spontaneous fibre firing and ectopia also sends abnormal info into CNS
▪ Responsible for immediate pain
▪ Bombardment of activity induces central sensitization through activity-dependent central
sensitization
o Glial cell activation – immune response within SC, can also cause long-term changes
• Central changes in spinal cord connections
o Activity dependent central sensitization
 o Long-term learning of synapse in dorsal horn
o Neuro-immune-glial cell activation causing sensitization – loss of normal GABAergic inhibition; activation
of microglia in SC in response to injury
o Changes in descending inhibition/facilitation
o Cortical remodelling – may have to do with perception in ongoing neuropathic pain
▪ Changes peripherally and centrally when a nerve has injury/disease (reason for definition
change)

Clinical Assessment, Recognition, and Management of Neuropathic Pain

• Neuropathic pain is unique from other pain types b/c of injury or disease
o Nerve injury/disease trigger molecular intracellular processes – result in range of metabolic and
functional responses (neuroplasticity) in sensory cell body & CNS
o LT changes in NS function and structure of neuron – trigger molecular intracellular processes
• Changes affect treatment & prognosis
o Damaged nociceptive neurons are functionally changed, behave differently from undamaged neurons
o Changes in neuron function stimulate central sensitization
o Several candidate mechanisms – need to learn more about neuroimmune interactions
▪ Hard to treat impairment/pain itself
o Mgmt: interventions aimed at disability, result from living with long-term condition of neuropathic pain
• Recognizing neuropathic pain: important to understand if component of pain is neuropathic – can aim treatment
o Example case: shoulder pain is nociceptive (MSK, mechanical signs, from surgery trauma and tissue
injury); chest pain is neuropathic (has no mechanical signs, hypersensitive to touch/pinprick, can
increase for no reason, not worse in morning/evening, not worse with activity/better with rest, worse
when tired or has a chill)
o Findings from subjective Ax:
▪ Possible nociceptive pain sources
▪ Characteristics that cause you to consider nociceptive pain
▪ Possible neuropathic pain sources
▪ Signs/symptoms to make you think of neuropathic pain
▪ What to do next
• Screening – look for key clinical signs of neuropathic pain
o Almost always area of sensory deficit
▪ Area of max pain within area of sensory deficit
o Spontaneous pain (none to severe) with no mechanical trigger/component
▪ Ongoing or spontaneous shooting, electric shock – pain happening for no reason
o Evoked pain – exaggerated pain to stimulus
▪ Allodynia, hyperalgesia, and/or hyperpathia
▪ Often no clear stimulus/response relationship
▪ No 24-hour pattern, often not related to location or response intensity
o Quality
▪ Commonly a burning and/or shooting quality, unusual dysesthesia (tingling, etc.)
o Location of Sx make neuroanatomical sense – use pattern of signs to understand where lesion is
• Peripheral neuropathic pain – nerve damage or disease recap – see above “Characteristics: peripheral
neuropathic pain = nerve damage or disease”
• Neuropathic pain current guidelines for clinical decision: no clinical test to tell you if someone has neuropathic
pain
 o Diagnostic algorithm designed 2016 – help understand new definition
o Mechanism falls under nerve damage or lesion; yes to both Qs means person potentially has
neuropathic pain
o [1] Look at history – is there a neurological lesion or disease that can lead to neuropathic pain (diabetes,
injury, accident, etc.)
o [2] Is the distribution of pain neuroanatomically plausible? What is location of Sx? Does it follow a
peripheral nerve or nerve root or spinal cord distribution or brain distribution?

o
▪ Neuroanatomically plausible distribution of symptoms: symptoms make sense based on lesion
location

▪
o Clinical examination & objective findings – apply sensory testing lab to peripheral nerve root lesion, back
pain, diabetic neuropathy
▪ Map out sensory loss (decreased sensation) & sensory gain (pain/hyperalgesia/allodynia)
▪ What is the pattern of the symptoms? Is it neuroanatomically plausible?
▪ If it’s plausible, suspect clinical neuropathic pain
o “Definite neuropathic pain” – reserved for when confirmatory test exists (diagnostic imaging)
▪ Location and nature of lesion can explain the pain
▪ Doesn’t occur most of the time, often operate on “probable neuropathic pain” level
• Standardized tests for neuropathic pain:
o Gold standard is clinical examination
o Standardized/screening tests for neuropathic pain: LANSS (Leeds assessment of neuropathic symptoms
& signs), PDQ (pain detect questionnaire), DN4 (douleur neuropathique)
• DN4 (douleur neuropathique)
o Short, good, easy to score
o 7 interview questions + 3 examination questions – cut off score = 4/10 (83% sensitivity, 90% specificity)

o
o Consolidate what was told to determine if someone has neuropathic pain
▪ Q1 – pain characteristics
▪ Q2 – sensory symptoms (paraesthesia, dysesthesia, anesthesia)
▪ Q3 – loss or hypoesthesia
▪ Q4 – hyperalgesia after brushing
• Treatment of neuropathic pain: unique from other pains as mechanisms are different
o When will neuropathic pain be seen? Everywhere – might not be main reason but is a part of the clinical
picture
▪ Injury to somatosensory system
• MSK injury (after trauma, surgery, amputation)
• Neurological injury
• Peripheral nerve injuries
▪ Diseases involving somatosensory system
• Diabetes, tumours, HIV, radiation, metabolic diseases
• Neurological diseases (stroke, MS, peripheral nerve diseases)
• Medication-induced neuropathies (e.g. treat HIV or cancers)
o Neuropathic pain is a chronic condition (long-term pathology) – no single pharmacological/non-
pharmacological treatment to cure it
▪ Often need combination of treatments to address different mechanisms (pharm + non-pharm)
▪ Meds only control ~30% of pain
▪ Management of chronic health condition
▪ PT, OT have key roles in teaching strategies/tools to manage and function with life
• Living with neuropathic pain: pain is at the centre of the patient’s life like a bicycle wheel
o Frustration over no cure, lack of control over pain with poorer mental health, increased disability
o Sleep disruption, stigmatization (why not better?), financial losses & increased costs, decreased QOL
▪ Lower QOL than even cancer, HIV/AIDs, other medical problems
▪ Biopsychosocial nature of chronic pain and effect on lives
▪ When there is no drug that substantially impacts pain
 o Can work on sequalae (things that pain does in broader sense of life) → pain can become central factor
in someone’s life
o Difficulties in biological, psychological, and social spheres
▪ Functional capacity is reduced ∴ less ability to do what they want to do → can lead to
depression/sadness
▪ Factors can all affect each other
▪ PTs manage factors to manage pain, live well with their pain ∴ reduced in the long run

Less time
with
friends
Depression
Do less
(sadness)

Always
PAIN Stress
tired

Less self-
Poor sleep
confidence
Anxiety
(worry)

o
• Multiple mechanisms and targets for treatment [things PTs can do]

o
o Peripheral mechanisms (ectopic firing):
▪ Topicals
▪ Nerve blocks
▪ NGF inhibitors
▪ Cytokine inhibitors
o Ascending input: calm down the synapse/stop ectopic firing of neuron
▪ C-TENS
▪ Anticonvulsants (e.g. gabapentin)
 ▪ SNRIs
▪ Opioids
▪ NMDA blockers (e.g. ketamine)
▪ SC stimulation
Cytokine inhibitors (aimed at neuroglial immune link)
o Descending modulation:
▪ Cognitive behavioural therapy (CBT)
▪ Antidepressants
▪ Acupuncture
▪ Cannabinoids
▪ Brain stimulation
▪ Pain science education
▪ Physical activity/exercise
▪ A-TENS
o Cortex: where pain is perceived – integrate cognitive strategies & commitment therapy strategies
▪ CBT
▪ Placebo
▪ Motor cortex stimulation
▪ Distraction
▪ Education
▪ Retraining maladaptive connections – cognitive functional therapy
• Self-management: give patient the resources to master situation
o Understand the pain – teach about pain, pain processing, neuroplasticity
o Mind-body strategies to calm nervous system
o Goal-oriented physical activity – change the pain, other general effects of physical activity/exercise (e.g.
impact sleep and mental health)
o Sleep training
o Cognitive/behavioural strategies to cope with stigma and pain
o Support network importance
o Active coping strategies
Complex Regional Pain Syndrome
Background
• Specific pain diagnosis
• Case study: Sara – 13-year-old female, left lower extremity after dodgeball 4 months ago
o Ruled out fracture in ED, followed up with ortho clinic to wear air cast for 2 weeks due to persistent pain
– suspected minor soft tissue injury
o After air cast discharge, pain gradually worsened and other symptoms became apparent – swelling,
discolouration, sensitive to touch – told she may have CRPS 6 weeks at follow up with ortho clinic
• Complex (multifactorial, poorly understood) regional (distal region of limb) pain (severe, disabling) syndrome
(pain + associated symptoms e.g. change in colour, swelling, temperature, etc.)
• CRPS: pain in regional distribution that usually starts distally in an extremity after trauma and is disproportionate
in magnitude or duration to the typical course (of pain) after similar tissue trauma – specifically about
somatosensory nervous system
o Type 1: without associated nerve damage (>95% of cases)
o Type 2: with associated nerve damage

o
o Can vary from person to person – images represent more severe cases
o Colour changes – purple blue, purple red
o [A] – shiny skin, toenails look different; [B] – motor changes where index finger is in flexed position; [C] –
swollen and foot dystonia (abnormal posture with flexed inverted position)
• Epidemiology – considered rare disease in children, female to male ratio is characteristically 3-4:1
Pediatric (Canadian data) Adult (US data)
Incidence 1.14 / 100 000 children 5.46 – 26.2 / 100 000 person
years
Prevalence Not reported 20.56 / 100 000
Female to male ratio 4:1 3-4:1
Highest incidence age/sex Females >12 years Females 50-59 years
Mean age at diagnosis 12.2 ± 2.4 years 46.9 ± 16 years
o Incidence – number of new cases per year/per person year
o Prevalence – at any given time
• Uni-dimensional pain classification
Classification System Examples
Pain diagnoses (ICD-11) Chronic primary pain, chronic secondary pain e.g. fibromyalgia, headache
Temporal Acute pain, chronic pain
Physiological mechanism Nociceptive, neuropathic, nociplastic
Body site or organ system Low-back pain, visceral pain
Etiology Post-traumatic pain, post-surgical pain, cancer-related pain, idiopathic
• ICD-11 diagnoses – pain is a disease by itself, not secondary to tissue damage/disease
o CRPS is a specific diagnosis and a type of chronic primary pain

o
• Pathophysiology: complex = multifactorial (biological, genetic, envt, psychosocial), not completely understood
o Body has abnormal response to injury
o Might have genetic predisposition – increased risk of developing CRPS if known family member had it
o Inflammatory changes & maladaptive changes to PNS, CNS to maintain pain – minor tissue trauma
triggers inflammatory process which influences peripheral sensitization
▪ Can change CNS structurally & functionally
▪ Changes can occur independently ∴ some ppl have some symptoms, others don’t
o Biological pathways trigger associated symptoms

o
• Dominant pain mechanism = nociplastic pain
o CRPS type 2 is associated with direct damage to NS, but CRPS overall is associated with nociplastic pain
(dysfunction of nervous system)
• Biopsychosocial model contributing factors – if they develop pain, how they experience pain, how they respond
to Tx
o No specific factors thought to cause CRPS, but these factors are more prevalent in ppl with CRPS
 Psychological
Factors
Biological Factors - perceived control
- self-efficacy
- genetics
- catastrophic
- physiology thinking
- neurochemistry - hypervigilance
- tissue health - depression
- anxiety
- anger

Social Factors
- socioeconomic status
- social
- skepticism
- operant
- social learning
- social support

o
• Fear avoidance model: not specific to CRPS
o Start with an injury which leads to pain experience – most people follow right side path
o Left side path – catastrophizing pain
▪ Feel helplessness, negative thoughts about pain, ruminate/think about pain constantly, magnify
the pain
▪ Leads to pain-related fear → fear of movement ∴ avoid activities/mvmts that might cause pain
▪ Cause disuse, change moods and develop physical/social/psychological disabilities
o Can go round and round (increase pain, go through cycle all over again)

Clinical Features
• Associated symptoms – can vary between and within people (e.g. over time as disease progresses)
o Sensory: hyperalgesia (pin prick sensitivity), allodynia (sensitivity to light touch)
o Vasomotor (temperature or skin colour changes)
o Sudomotor/edema: edema/swelling, changes in sweating (more or less)
o Motor: decreased ROM and/or motor dysfunction (weakness, tremor, dystonia)
o Trophic: hair (more hair growth), nail, skin changes (looks shiny) – more severe disease
▪ Every patient has different clinical presentation ∴ grouped into categories
▪ Temperature changes – is objective (e.g. can measure with thermometer a 1 or few degrees
difference)
• Triggering event: patterns in triggering event that lead to onset of symptoms; informs where you might
encounter someone with CRPS (e.g. at fracture clinic or specialty surgery clinic)
o Classified triggering event in 1000 patients for type 1 and type 2 (type 2 was much less common; 904 vs.
125 ppl)
o Diverse list e.g. spontaneous/insidious, sharp trauma/laceration, carpal tunnel syndrome
o Most common in type 1: fracture & blunt trauma
o Most common in type 2: CTS & surgery
 o
• Pain location: primarily in UE (~70% of cases) and more common in distal area of the extremity (hand or foot)
o Widespread or proximal areas represented much smaller % of cases

o
• Pain intensity: McGill pain questionnaire
o Multi-dimensional self-report tool to measure intensity, quality, affective components of pain
o Compare scores of pain in different conditions – CRPS has higher/worse scores
o “One of the most severely painful conditions that exist, followed closely by trigeminal neuralgia”
o Average score of 40/50 for CRPS/causalgia

Assessment
• Diagnostic criteria: no valid radiological, genetic, laboratory, or electrical diagnostic test (no true gold standard)
∴ clinical criteria is used instead (lots of potential Sx with variability = difficult) → use criteria with caution & with
clinical expertise
o IASP officially endorses Valencia Criteria – minor modification to previous Budapest Criteria
o Budapest Criteria validity: sensitivity 45-99%, specificity 68-85% ∴ can have false +ve/-ve
o Limitations:
▪ Poor quality of diagnostic studies
▪ May not capture early phase of disease – criteria only applies in advanced stage/when severe
▪ Not validated in pediatrics
▪ Difficult to compare between studies using different criteria (can’t compare to gold standard)
• Valencia diagnostic criteria:
1. Chronic pain in a limb (persistent or recurrent >3 months) is present
 2. Pain is associated with at least one symptom in 3 of 4 categories
3. Must display at least one sign at time of evaluation in ≥2 categories
4. Pain is associate with at least one of the following: [a] emotional distress or [b] interference with daily
life activities & social participation
5. Pain is not better explained by another chronic pain condition
o Categories:
▪ Sensory: hyperalgesia and/or allodynia
▪ Vasomotor: temperature asymmetry and/or skin colour changes and/or asymmetry
▪ Sudomotor/edema: edema and/or sweating changes and/or sweating asymmetry
▪ Motor/trophic: decrease ROM and/or motor dysfunction (weakness, tremor, dystonia) and/or
trophic change (hair, nail, skin)
• Differential diagnoses
Orthopedic disorders Fracture, sprain, bone contusion, bursitis, apophysitis, ligamentous injury,
muscle injury
Neurologic disorders Peripheral neuropathy, cervical/lumbosacral radiculopathy, diabetic
neuropathy, neuroma, nerve entrapment, complex migraine, spinal cord
trauma/tumour, transverse myelitis, syrinx, demyelinated disorders,
poliomyelitis, Guillain-Barre syndrome
Rheumatologic Rheumatoid arthritis, juvenile rheumatoid arthritis, osteoporosis, sarcoidosis
disorders
Infectious disorders Systemic fungal/bacterial/viral infections, osteomyelitis, Lyme disease
Vascular disorders Vasculitis, arterial insufficiency, Raynaud phenomenon
Miscellaneous Toxic exposure to heavy metals (lead) or chemotherapeutic agents (vinca
alkaloids), porphyria, B12 deficiency, thiamine deficiency, Fabry disease,
somatoform disorder
o Cannot have another pain diagnosis to be diagnosed with CRPS – most challenging criteria to satisfy
o Often patients with CRPS have been on a long journey to conclude they have CRPS
o Can lead to more severe pain & disability, mistrust of healthcare system b/c of frustrating journey
• E.g. subjective pain history
o Provocation – moving ankle, wearing socks, putting pressure [aggravated by movement, touch, weight-
bearing]
o Quality – burning, on fire, shooting, throbbing, aching, miserable, uncomfortable [many quality
descriptors]
o Region – entire left foot up to the knee [distal extremity in sock/glove pattern]
o Severity – average pain intensity 9/10, pain spikes t/o the day 10/10 [high pain intensity]
o Timing – constant pain throughout the day, pain spikes can be provoked or at random [constant, can
spike at random or if provoked]
o Pain history – associated symptoms: “hurts to touch foot or put sock on” “can’t move toes or ankle”
“always looks purple or blue”
• E.g. physical exam
o Observation – associated symptoms (colour changes, swelling, hair/skin/nail changes)
o Temperature – temperature difference from L/R via infrared thermometer
o ROM – ankle/knee ROM comparison – focus on AROM as PROM is painful to touch
▪ Left foot tremors, cannot go all the way up in DF
▪ Might be limited by pain or motor control (tremor)
▪ Might not have tissue-based restriction but there may be contractures or tissue factors
o Sensation – be mindful of how much pain patient is in; balance between Ax and tolerance
 o Weight-bearing – through the extremity, put foot on scale to measure force applied
o Functional assessment – sit to stand, gait, mobility devices, stairs (impt for day to day life)
• E.g. uni-dimensional pain classification; can also use MSK clinical translation framework (non-mechanical pain,
high degree of sensitization)
o Chronic primary pain (acute onset that becomes chronic over time)
o Dominant physiological mechanism is nociplastic (NS dysfunction); a small component of type 2 is
neuropathic
o Hand and feet are most affected; UE more common in adults, LE more common in kids
o No known etiology but triggering events exist

Treatment
• 2013 review: no high-quality evidence treatments
o Common medications have low quality evidence; ketamine, bisphosphonates and calcitonin may
effectively reduce pain when compared to placebo in short term
▪ Ketamine – via infusion
▪ Bisphosphonates – target bone stimulation for extended limb disuse
▪ Topical agents – numb area (DMSO did not improve scores more than N-acetylcysteine)
o Look at non-pharmacological evidence
o Spinal cord stimulation was more effective eat reducing pain with PT than just PT alone (implant in the
spine)
o No sure-fire way to treat pain, disability in CRPS
• 2016 review: 18 RCTs with primary endpoints of pain and function/disability
o Few interventions were tested in multiple trials
o Limitations: small study sizes, various diagnostic criteria, high risk of bias in study design – difficulties in
blinding patient and providers to interventions being delivered
o Exercise
▪ Multi-modal PT can provide small, LT functional improvements (low quality evidence LQE)
▪ Graded motor imagery may provide medium & long-term improvements in pain & disability
(LQE)
▪ Mirror therapy can provide LT improvements in pain and function in post-stroke CRPS (very LQE)
▪ Virtual body swapping & tactile discrimination do not provide ST benefits in pain (very LQE)
o Electrotherapy: mixed evidence, low to very low quality evidence
▪ Stellate ganglion block via ultrasound (SGBVU) combined with conventional treatment not
superior to placebo ultrasound for pain & hand function
▪ SGBVU
▪ PEMF therapy
▪ Laser therapy
▪ CO2 bath therapy
• Physical treatments: multi-modal or 3P approach to treating pain; most common are GMI & desensitization
o Pain neuroscience education
o Physical activity & activity pacing
o Passive treatments – TENS, heat, electrotherapy, ice, cooing
o Graded motor imagery
o Desensitization
• GMI theory: changes in somatosensory and motor cortex, changes in organization & size of cortical map
 o “Smudging of the brain” – areas that are painful become larger, borders become smudged, reason for
widespread sensory changes
o Stimulate motor cortex through imagining motor movements (less painful and feared)
o Goal: normalize motor movements & re-map the brain
• GMI application: three phases of graded approach, 2 weeks per therapy
o [1] Laterality – left/right discrimination, think of affected body part (e.g. app – see a series of image,
answer if it’s the right or left limb as thinking of it activates the motor cortex)
o [2] Explicit motor imagery – imagined motor movements (e.g. like dancers/athletes thinking abut their
routine activates cortex); guide patient through task and hear a script, think about using their body part
o [3] Implicit motor imagery – mirror therapy (trick the brain in seeing a functional leg)
• Desensitization theory: changes in somatosensory and motor cortex; localized sensory changes (sensitivity to
light touch/allodynia & increased sensitivity to painful touch/hyperalgesia)
o Stimulate the nervous system with stimuli that aren’t normally painful; reduce fear of touch via graded
exposure
o Goal: normalize sensation, re-map the brain/retrain to interpret sensory stimuli as normal/non-
threatening
• Desensitization application:
o Traditional: rub (non-painful/non-threatening) texture on painful area for 3-6 minutes, repeat with 5
textures
▪ Mind-body strategies and graded approach (5 min → 10 min → 15 min)
▪ Relaxation, deep breathing, distraction
▪ Lighter textures before heavier textures
o Functional: apply sensory stimuli to painful area t/o day as per normal routines
▪ Normalize socks, gloves, shoes
▪ Gradually work towards normal footwear/clothing
▪ Bathing – patients will avoid water on area ∴ goal is to towel dry it off, normalize sensation
• Virtual reality: games – e.g. patient has CRPS on foot so avoids weight-bearing and uses crutches
o Game of squishing fruit to make juice – forced use by eliminating UE movements and putting the fruit in
visual field of affected side (e.g. only on right side)
o Distracting for pain management, game reward system; provides embodiment as CRPS patients have
limb neglect/don’t feel ownership of their limb → amplify movements with software to seem like they
have full range

Other Considerations
• Prognosis:
o Pediatric: 68% of adults w/ CRPS in childhood reported pain in adulthood; 32% report pain spread to
other locations (lasts a long time, high rates of reoccurrence)
o Adults: discolouration, temperature, sweating changes, edema are most likely Sx to resolve within 6-13
months
▪ Motor symptoms more likely to persist (weakness, reduced ROM) > 1 year
▪ Subset of patients – symptoms are long-term (several years)
▪ Implies functional limitations are chronic
o Meet a CRPS patient, expect long time course – think of symptom-based treatment
• Impact of CRPS on overall life
o Higher rates of co-morbid mental health diagnoses
▪ Depression, anxiety, somatization, psychological distress, suicidal ideation
 ▪ *Not a cause or predictor of CRPS
o Poor QOL, disability
▪ Self-care – 50% of patients reported significant interference in ability to care for self
▪ Activities
▪ Work
▪ Gait aid - >1/3 of patients used gait aid for mobility
o 75% of patients reported significant interference with activities, mood, work, recreational
Polypharmacy
Defining Polypharmacy
• Polypharmacy: the use of multiple medications by a patient (≥5) with or without a documented indication, or
the use of more medications than clinical necessary or effective for patient’s condition
• Canada, 2022: polypharmacy was common among adults – 21% use ≥5 prescription medications, 21% use ≥5
non-prescription medications, 16% use at least 3 prescription and 3 non-prescription concurrently
• Impact on rehabilitation: a factor in
o Falls
o Heart failure
o Hospitalization
o Increased healthcare costs
o Malnutrition
o Impaired cognition
• Demographic & clinical risk factors:
o Age: more common in older Canadians (65+)
o Gender: higher use of non-prescription meds in women
o Complexity: more common in pre-frail & frail adults; rising rates of multimorbidity in Canadians
▪ Multimorbid person has multiple HCPs ∴ different treatment plans, there might be a lack of
communication
▪ Leads to prescription cascades
• Prescription cascades: waterfall of meds, new medical condition due to initial drug therapy so more therapy
prescribed
o Due to multi-morbidity and subsequent side effects

Neurological Conditions
• Stroke: commonly found among older patients undergoing stroke rehab
o Increased # of meds during stroke recovery negatively associate with improvements in daily living, home
discharge
• TBI: those with ≥6 drugs on admission had lower Bethel Index (BI) (measure of ability to perform ADLs)
efficiency, lower BI gain, longer length of stay
• Parkinson’s disease: overall prevalence of polypharmacy and hyperpolypharmacy (10+ medications) was 40%
and 18%; polypharmacy associate with higher rates of rehospitalization and cognitive decline
• Multiple sclerosis: polypharmacy rates range from 15-65%; correlate with comorbidities, fatigue, increased
disability, cognitive deficits, increased hospitalizations, higher relapse rate, lower QOL (younger population;
understudied)
• SUMMARY: higher prevalence and impact in neurological conditions
Effects of Polypharmacy
• Common medications in Canadians:
o Analgesics (36.3%)
o Vitamins
o Anti-inflammatories
o Lipid-modifying gents
o ACE inhibitors (CV agent) (19.6%)
o Antacids
o Antithrombotic agents
o Psychoanaleptics (antidepressants, psychostimulants, antidementia) (11.1%)
o Antidiabetics (9.9%)
o Psycholeptics (antipsychotics anxiolytics, hypnotic and sedatives) (8.3%)
o Diuretics (CV agent) (6.2%)
• Fall-risk increasing drugs (FRIDs): commonly found in Canadians at risk of polypharmacy
o Cardiovascular agents (α-blockers, β-blockers, calcium channel blockers, diuretics, angiotensin-
converting enzyme inhibitors, angiotensin receptor antagonists, vasodilators)
o CNS drugs (antipsychotics, sedative-hypnotics, benzodiazepines, antidepressants, antiparkinsonians)
o Analgesics (NSAIDs)
o Thyroid drugs
o Antidiabetics (biguanides, sulfonylureas, other oral hypoglycemics, insulin)
• Impact on gait and balance
o Gait requires coordination of various systems (CNS, PNS, CR, MSK, etc.)
o Many common meds affect systems in older populations, negatively impact domains of cognition that
are critical for controlling gait/balance – attention, processing speed, executive function
o Increase use of meds is associated with decreased gait speed & increased gait variability (established
falls risk markers)
o FRIDs in stroke populations – contributed to increased risk of falls post-stroke, explain only a small
amount of variation observed in gait speed, BBS scores
• Common impacts on rehab:
o Multiple medications contribute to increased risk of falls → fractures lea to decline in physical function,
cognitive decline, depression, reduced QOL
o Increased risk of potentially inappropriate medications → drugs are implicated as common cause of
aspiration pneumonia
o Drug-induced parkinsonism usually occurs within 1-3 months after the start of antipsychotic treatment
→ in rehab settings, undernutrition found in 14-65% of hospitalize patients – drug induced malnutrition
should be monitored

Addressing Polypharmacy
• Some medications may be potentially inappropriate
o Can cause confusion
o Potentially lethal with severe infection – metformin + moderate-severe kidney failure
o Combination of meds can enhance effect – timolol (glaucoma) & metoprolol (for high BP) – lowers heart
rate and blood pressure (risk of hypotension)
• Key stakeholders in medication management
o Caregiver(s), pharmacist, prescribing physician, patient
 • Optimize medications during rehab – work w/ prescribers/pharmacists to address any issues that may arise due
to adverse drug reactions during rehab

o
• PT care team integration: integration of physiotherapists into PHC would be enhanced, GPs identified inclusion
of working diagnosis, treatment summary, likely LT outcomes as key components to effective communication
o PT will enhance access, optimize clinical outcomes, deliver patient centred care, reduce unnecessary
hospitalizations, avoid catastrophe and unwarranted costs

Discussion
n/a