NEUROLOGICAL CONDITIONS

MULTIPLE SCLEROSIS PATHOPHYSIOLOGY

CONTENTS 1. Immune response triggers activation of immune cells that

cross the blood-brain barrier
1. Related Anatomy 2. Phagocytic activities may contribute to demyelination
2. Basic Pathophysiology / Pathomechanics causing disruption of function (conduction block)
3. Common Causes / Etiology of the Disease Condition 3. Acute inflammatory event emerges further slowing nerve
4. Description of the Disease Condition / Associated conduction
Problems 4. Early stages: oligodendrocytes survive
5. Differential Diagnosis Chronic stages: oligodendrocytes repair cannot occur
5. Demyelinated areas are filled with fibrous astrocytes and
RELATED ANATOMY undergo gliosis (Main cause of permanent neurologic
disability)
CENTRAL NERVOUS SYSTEM 6. In advanced cases: Acute and Degenerative Lesions of
varying size scattered throughout the CNS
- Brain & spinal cord are the main centers where
Hallmark
correlation and integration of information occurs
- Presence of multifocal plaques (lesions) of demyelination
in the cerebral hemispheres, optic nerves, brain stem, and
GRAY MATTER
spinal cord
- Consists of nerve cells/dendrites embedded in neuroglia
- Function: Information processing
Myelin
- Serves as an insulator, speeding up the conduction along
WHITE MATTER
nerve fibers from one node of Ranvier to another (Saltatory
- Consists of nerve fibers/axons embedded in the neuroglia
Conduction)
- Colored white due to the presence of lipid material in
myelin sheaths of nerve fibers
- Function: Transmission of information over long distances COURSE OF DISEASE

Note: Benign MS
 Brain -> Gray Matter outside, White matter inside - Disease in which the patient remains fully functional in all
(information processing hub) neurological systems 15 years after onset
 Spinal cord -> Gray Matter inside, White matter outside
(connection of PNS to the brain) Malignant MS (Marburg disease)
- Relatively rare characterized by rapid onset and almost
ASCENDING AND DESCENDING TRACTS continual progression leading to significant disability or
death within a relatively short time after onset
ASCENDING TRACTS (AFFERENT) FOUR MAJOR CLINICAL SUBTYPES OF MS
TRACT FUNCTION 1. Relapsing-remitting MS (RRMS)
Lateral Spinothalamic Pain and temperature - Most common course, characterized by discrete attacks or
Anterior Spinothalamic Light touch and pressure relapses, defined as periods of acute worsening of
Fasciculus gracilis and Discriminative touch and vibratory neurological function, followed by remissions, defined as
cuneatus (DCML) sense periods without disease progression and partial or complete
Anterior Spinocerebellar Unconscious muscle and joints of abatement of signs and symptoms
trunk and LE
Posterior Spinocerebellar Unconscious muscle and joints of 2. Secondary-Progressive MS (SPMS)
trunk and UE - Developed before the advent of disease-modifying
medications
DESCENDING TRACTS (EFFERENT) - Begins with a relapsing-remitting course followed by
TRACT FUNCTION progression to steadily and irreversible decline with or
Anterior Corticospinal Controls the voluntary control of without occasional acute attacks
axial muscles (trunk)
Lateral Corticospinal Controls the voluntary control of 3. Primary-Progressive MS (PPMS)
limb muscles (extremities) - Rare, characterized by a nearly continuous worsening of the
Rubrospinal Facilitates flexor muscles disease from the onset without distinct attacks. Patient may
Vestibulospinal Facilitates extensor muscles experience modest fluctuations
Tectospinal Reflex movements concerning
sight 4. Progressive-Relapsing MS (PRMS)
- Begins with a progressive disease course from onset and
steady deterioration (similar to PPMS), but with occasional
acute attacks

BASIC PATHOPHYSIOLOGY/PATHOMECHANICS
 DESCRIPTION OF CONDITION & ASSOCATED INJURIES

MULTIPLE SCLEROSIS

Multiple Sclerosis (MS)

- “An autoimmune disease characterized by inflammation,
selective demyelination, and gliosis. It causes both acute
and chronic symptoms and can result in significant
disability and impaired quality of life.”
- Dr. Jean Charcot first defined it (1868) by its clinical and
pathological characteristics:
o Paralysis and the cardinal symptoms of intention
tremor, scanning speech, and nystagmus
(Charcot’s triad)
- Using autopsy studies, he identified areas of hardened
plaques (sclerosis in plaques)

Snell Neuroanatomy 8th Edition

- Characterized by the appearance of patches of
demyelination in CNS white matter, generally starting in
the optic nerve, spinal cord, or cerebellum

ETIOLOGY ASSOCIATED DEMYELINATING DISORDERS

COMMON CAUSES OPTIC NEURITIS (ON)

- Sudden unilateral loss of vision, can vary from a slight
1. Genetic central scotoma to complete loss of light perception
2. Vitamin D deficiency - Patients with clinical isolated syndromes (CIS) have shown
3. Smoking they are at higher risk of progressing to clinical MS within
1 to 2 years
Molecule Mimicry
- Persons with genetic susceptibility when exposed to a viral TRANSVERSE MYELITIS ™
agent, their immune system responds with activated - An inflammatory disorder of the spinal cord
myelin-reactive lymphocytes - May present after an infection
- The viruses may be retained in the body resulting in self- - TM patients who develop MS present with asymmetric and
perpetuating autoimmune process incomplete motor or sensory symptoms
- Pure TM not converting to MS have symmetric findings
Onset: and more profound disability
 Ages 20-40 years
DEVIC’S DISEASE (NEUORMYELITIS OPTICA)
 Rare in children and adults >50 years
- The traditional concept consists of the subacute
 Common in women by a ratio of 2:1-3:1
combination of relatively severe ON and TM with sparing
 Prevalent in white population of the brain
- New research – Patients have a combination of ON and
MECHANISMS TM, both of which can be severe, with initial relative
sparing of brain involvement
1. Autoimmunity - Lesions tend to be longer (3+ segments) than typical MS
2. Infection lesions (usually 1 segment)
3. Genetics
4. Environment DIFFERENTIAL DIAGNOSIS
5. B Cells
6. Microbiome
 Neuromyelitis optica  Rheumatoid arthritis
7. Progressive MS
8. Autoantigen  Acute disseminated  Lyme disease
encephalomyelitis
 Transverse myelitis  Systematic lupus
CO-MORBIDITIES
erythematosus
 Neurosyphilis  Sjögren’s syndrome
CO-MORBIDITY EXAMPLES
 Cerebral autosomal  Carcinoma
Autoimmune Inflammatory bowel disease, Thyroid dominant arteriopathy
disease, Uveitis, Arthritis, Systemic lupus with subcortical infarcts
erythematosus and leukoencephalopathy
Physical Hypertension, Hyperlipidemia, Heard  Behçet disease  Wegener granulomatosis
disease, Chronic lung disease,
 Neurosarcoidosis  Hypercoagulable state
Osteopenia/Osteoporosis
 B12 deficiency  Migraine history
Behavioral Anxiety, depression, sleep disorders,
alcohol use, obesity  Folate deficiency  Hypertension
Less common Kidney and liver disease, asthma, cancer  Vasculitis process  Mitochondrial disorders
  Mixed connective tissue  Normal Bladder Spastic or flaccid bladder, Dyssynergic bladder,
disease incontinence
 Neurosarcoidosis Sexual Impotence, decreased libido, impaired ability to
achieve orgasm
VITAMINS Mnemonic (NMSS):
CLASSIFICATI DIFFERENTIAL DIAGNOSIS
ON
Vascular Multiple lacunar infarcts; CADISIL; spinal
arteriovenous malformation
Infectious Lyme disease; HIV myelopathy; PML;
HTLV-1 myelopathy
Traumatic Spondylitis myelopathy
Autoimmune NMO; Acute disseminated
encephalomyelitis; CNS vasculitis; Behçet
syndrome; sarcoidosis; SLE
Metabolic/Toxic Central pontine myelinolysis; vitamin B12
deficiency; vitamin B6 deficiency;
radiation; hypoxia
Idiopathic/Genetic Spinocerebellar degeneration; Friedreich
ataxia; Arnold-Chiari malformation;
adrenoleukodystrophy
Neoplastic CNS lymphoma; glioma; paraneoplastic
encephalomyelitis; metastatic cord
compression
pSychiatric Conversion disorder

CLINICAL PRESENTATION

EARLY SYMPTOMS
 Numbness and weakness in one or several limbs
progressing from paresthesias
 Visual disturbances such as double vision, atrophy of one
optic nerve
 Impaired ocular movement
 Fatigue is typically the early symptoms that will present
with MS

Pattern of Symptoms
- Varies greatly from person to person
- Varies over time in each individual affected
- First symptoms usually transient; typically sensory and
visual
- Diagnosis involves evidence of damage occurring in at
least two separate areas of CNS and at two separate points
in time at least one month apart (Dissemination of lesions
in space and time)

COMMON SYMPTOMS
SYMPTOM CAUSE
Sensory Hypoesthesia, numbness, paresthesia
Pain Paroxysmal limb pain, dysesthesia, headache,
chronic neuropathic pain, Lhermitte’s sign,
hyperpathia, optic or trigeminal neuritis
Visual Blurred or double vision (diplopia), diminished
acuity/loss of vision, scotoma, nystagmus, lateral
gaze palsy
Cognitive Short-term memory deficits, diminished
executive function, diminished attention or
concentration, diminished information
processing, diminished visual-spatial abilities
Bowel Constipation, diarrhoea, incontinence
Affective Depression, anxiety, pseudobulbar affect
Motor Paresis or paralysis, fatigue, spasticity, spasms,
ataxia (incoordination, intention tremor),
postural tremor, impaired balance and gait
Speech and Dysarthria, diminished verbal fluency,
Swallowing dysphonia, dysphagia
 PT MANAGEMENT
GOALS
SUBJECTIVE
 To achieve maximum level of functional independence
 Facilitate neurological recovery
SUBJECTIVE  Minimize disability
 Successfully reintegrate back into home, family, and
GLASGOW COMA SCALE community
 Re-establish a meaningful and gratifying life
OBJECTIVE

OBJECTIVE

DISEASE SPECIFIC OUTCOME MEASURES

SCALE NAME DIMENSION MODE OF
S ASSESSED ADMINISTRATION
Expanded Disability Impairments / Standardized neurological
Status Scale (EDSS) Ambulation examination / observation of
walking performance
Incapacity Status Disability Observation of performance /
Scale (ISS) interview of patient and/or
caregiver
Environmental Handicap Interview of patient and/or
Status Scale caregiver
Multiple Sclerosis Impairment / Three simple tests (Timed 25-
Functional Disability Foot Walk, Nine-Hole Peg Test,
Composite (MSFC) Paced Auditory Serial Addition
Test – 3 min)
Neuroperformance Impairment / Quantitative neurologic tests
Testing (NPT) Disability
Scripps Impairment / Standardized neurologic
Neurological Rating Disability examination
Scale (SNRS)
Ambulation Index Walking Observation of gait performance
(AI) performance on 25 ft
Multiple Sclerosis Patient Survey
Impact Scale-29
items (MSIS-29)
Multiple Sclerosis Patient- Patient survey
Walking Scale-12 reported
items (MSWS) walking
performance
Multiple Sclerosis Patient- Patient survey
Quality of Life reported
Inventory (MSQLI) health status
and symptom
severity
Multiple Sclerosis Patient- Patient Survey
Quality of Life-54 reported
(MSQOL-54) health status
and symptom
severity

TESTS TO BE PERFORMED
 Pupillary ex

ASSESSMENT

OBJECTIVE
PLAN

EARLY/MILD
COMMON IMPAIRMENTS AND ACTIVITY LIMITATIONS INTERVENTION STRATEGIES
 Few/minimal impairments and activity limitations with Preventive and Restorative
independence maintained  Regular exercise
 Motor symptoms present but do not interfere with daily activities
 Symptoms for RRMS are more variable and do not progress at the
same rate as PPMS or PRMS
 SPMS initially presents with relapsing-remitting course (RRMS)
followed by a more progressive course