Spastic paraparesis (UMN bilat LL)

Approach  Approach
1. Sensation abnormal: spinal cord
a) Sensory level: spinal cord - compression or causes of myelitis!
- Dorsal column: SADC, tabes dorsalis, as above
- Dissociated sensory: syringomyelia, anterior spinal artery thrombosis
- Patchy sensory loss: Chronic myelopathy, concomitant peripheral neuropathy
b) Glove and stocking: chronic myelopathy, medical myelopathy E.g. vit B12
2. Sensation normal: MND, brain (subcortical or cortical), exceptions in spinal cord
a) MND
b) Subcortial: Binswanger, multiple infarcts
c) Cortical: parasagittal lesions, cerebral palsy
d) Exceptions: hereditary spastic paraplegia, tabes dorsalis can have no sensory loss.

 Combined LMN and UMN i.e. absent ankle jerks!!

1. Subacute combined degeneration
2. Tabes dorsalis
3. Friederich's ataxia
4. MND
5. Cervical myelopathy + DM peripheral neuropathy
O/E  Examine:
1. Usual neuro LL PE (tone reflexes sensation)
2. Back: scars, deformity, spinal tenderness
3. UL: pronator, wasting
4. Cerebellar for dysmetria
5. Complete exam: complete neuro exam, DRE for anal tone/saddle anaesthesia, gait assessment

 Present:
1. This pt has a spastic paraparesis with/without a sensory deficit
2. This is evidenced by an upper motor neuron pattern of weakness in bilateral lower limbs, with
hypertonia, hyperreflexia, upgoing plantars and weakness with power 3/5 bilaterally
3. Describe sensation:
a) There is a sensory level at the level of ____, vs glove and stocking loss of sensation
- with loss of pinprick, vibration, or proprioception
b) OR there is no sensory deficit
4. There are markers of chronicity including wasting, but no Charcot's joint or trophic ulcers
5. The likely neuro-localization is:
a) With sensory loss: spinal cord
b) No sensory loss: MND, brain (subcortical or cortical), exceptions in spinal cord (HSP, tabes dorsalis)
c) With cerebellar: MS, spinocerebellar degeneration, syringomyelia
6. The likely etiology is:
a) If in spinal cord, causes of myelitis or compression. Differentiate further depending on whether
affecting dorsal column, patchy sensory loss or dissociated sensory.
b) If in brain, usual stroke, abscess, tumour, MS/NMO/ADEM
7. In summary:
a) This pt has spastic paraparesis with/without sensory level
b) Functionally he required __ for ambulation
c) With no complications of chronicity
Causes  Causes of cord compression:
1. Extramedullary:
a) Vertebral: spondylosis, trauma/fractures, PID, bone tumour
b) Extradural: abscess, mets
c) Intradural: meningioma, neurofibroma
2. Intramedullary: Syringomyelia, tumour (glioma)

 Causes of myelitis: see other notes. Demyelinating, non-demyelinating, compressive non-

compressive
Invx for  I would like to divide by investigations into serological and radiological tests
ALL neuro 1. My priority would be to perform imaging of the spine/brain including a dedicated MRI, to exclude
a structural cause
2. Serological tests to assess for underlying etiology: usually FBC B12/folate, renal panel and
electrolytes, TFT, LFT, fasting glucose, VDRL, +/- copper, genetic testing
3. Electrophysiological studies:
a) EMG to differentiate between a muscular, nerve or AHC cause
- Muscle: fibrillations, positive waves and fasciculations
- Nerve, axonal: decreased amplitudes
- Nerve, demyelinating: decreased velocity and prolonged latency
b) Nerve conduction studies to look for demyelination
4. Take a thorough drug history

 Invx for spastic paraparesis:

1. My priority would be to perform imaging of the spine/brain including a dedicated MRI, to exclude
a structural cause causing spinal cord compression
2. Bloods: B12, VDRL, electrolytes
Mgt for 1. Multidisciplinary approach involving education and counselling, PTOT for rehab and equipment
ALL neuro (ankle foot orthoses, splint, walking aid), ST, lifestyle changes including avoidance of causative
drugs/toxins
2. Manage complications of immobility including pressure sore, DVT, pneumonia
3. Medications for symptom control
Individual causes of spastic paraparesis
Mixed  Cervical myelopathy:
LMN and 1. Spastic paraparesis with mild sensory deficit
UMN - most commonly C5-6 spondylosis
- often no sensory loss but may have pseudoathetosis with loss of proprioception and vibration
2. Associated with
a) Wasting and weakness of small muscles of the hand
b) inverted supinator jerk, grip-release
c) Passive abduction of the little finger

 MND
1. Signs = mixed upper and lower motor neuron lesion
a) Fasciculations
b) Spastic paraparesis with upgoing plantar response, but absent ankle reflexes and LL wasting
c) Pseudobulbar palsy
d) No sensory, ocular and cerebellar involvement
 2. Definition: progressive degeneration of corticospinal tracts, anterior horn cells, bulbar motor
nuclei
a) AMLS: both UMN and LMN
b) Primary lateral sclerosis: UMN only, best prognosis
c) Progressive muscular atrophy: LMN only
d) Progressive bulbar palsy: LMN only of face, reflexes preserved
e) Pseudobulbar palsy: UMN ony of face
3. Invx: clinical diagnosis!!
Tests to rule out ddx:
a) NCS: no axonal/demyelination
b) EMG: fibrillation, positive waves, fasciculations
c) MRI: to rule out structural etiologies
d) Bloods: FBC, CMP, CK, TFT
4. Mgt:
a) Counselling and education - end of life discussion
b) Multidisciplinary approach involving PTOT, ST
c) Manage complications of immobility including pressure sore, DVT, pneumonia
d) Medications for symptom control (4): baclofen for spasticity, quinine/phenytoin for cramps,
anticholinergics like hyoscine, amitryptyline/fluvoxamine for pseudobulbar palsy
Dorsal  Subacute combined degeneration
column 1. Definition: vit B12 deficiency affecting mainly the dorsal column and corticospinal tract
2. Causes: diet, drugs (metformin, PPI), pernicious anemia, gastrectomy, small intestine (Crohns,
Celiac, bacterial overgrowth)
3. Signs:
a) Spastic paraparesis with sensory deficit - UMN with upgoing plantas
b) Brisk knee jerk but absent ankle jerk
c) Dorsal column signs: decreased light touch, vibration sense and proprioception
d) Associated with: anemia, previous gastrectomy scars
4. Invx:
a) Bloods: macrocytic anemia, hypersegmented PMN on PBF, anti-parietal and anti-intrinsic factor,
homocysteine/methylmalonic acid are elevated in early
b) MRI spine shows degeneration of the lateral and dorsal columns

 Tabes dorsalis:
1. Definition: demyelination of nerves primarily in dorsal column due to tertiary lewitic disease
2. Signs:
a) Spastic paraparesis with sensory deficit primarily affecting dorsal column
b) Gait: Rhomberg, sensory ataxia
c) Associated with:
- Chronicity: Charcots joints, trophic ulcers, incontinence
- Argyll Robertsons pupils
3. Neuro manifestations of syphilis (5):
a) Acute: syphilitic meningitis, transvers myelitis
b) Meningovascular disease -> young stroke
c) Tabes dorsalis: 3 stages - pre-ataxia, ataxia, paresis
d) Generalized paresis of the insane i.e. chronic meningoencephalitis
e) Gummata in the CNS
4. Ix: specific treponemal: TPPA, TPHA, EIA. Non-specific: VDRL is marker of treatment efficacy, RPR
 5. Mgt:
a) Multidisc approach involving ID physician and PT
b) IV penicillin +/- steroids to prevent Jarisch-Herxheimer reaction
Flaccid paraparesis (Bilat LL LMN)
Approach  General LMN approach:
1. Proximal, no sensory loss: AHC, NMJ, muscle
2. Proximal, sensory loss: root, plexus
3. Distal, no sensory loss: AHC, pure motor polyneuropathy, distal myopathy
4. Distal, sensory loss: radiculopathy/plexopathy, mononeuritis multiplex, or symmetrical length-
dependent polyneuropathy

 Causes:
Approach to flaccid paraparesis is SAME as LMN approach except distal causes more common than
proximal causes!!
1. Distal with no sensory loss (4): AHC, pure motor polyneuropathy, distal myopathy +/- NMJ
a) AHC (fasciculation): MND, SMA, polio
b) Pure motor polyneuropathy: MMN (multifocal motor neuropathy), some AIDP/CIDP, porphyria,
heavy metal
c) Distal myopathy/myelopathy: myotonia dystrophica, Welanders distal myopathy (rare)
2. For Distal with sensory loss (3):
a) Dermatomal sensory deficit: radiculopathy/plexopathy. Specific causes include cauda equina,
spina bifida
b) Glove and stocking sensory deficit: symmetrical length dependent polyneuropathy.
Causes are ABCD+HUT: alcohol, B12, CIDP/AIDP, DM, drugs + HSMN, uremia, thyroid
c) Single peripheral nerve deficit: mononeuritis multiplex
Present  Offer (3):
1. Complete a full neuro exam
2. Gait. High steppage suggests sensory ataxia
3. DRE for anal tone/saddle anaesthesia

 This pt has flaccid paraparesis, as evidenced by:

1. A lower motor neuron pattern of weakness, with hypotonia, decreased reflexes and downgoing
plantars, and weakness more prominent proximally OR distally
2. This is not associated with sensory loss. OR this is associated with patchy or symmetrical sensory
loss in a glove and stocking distribution, predominantly affecting pinprick (small fibre) vs
vibration/proprioception (large fibre)
3. Other associated findings include: muscle wasting, tongue fasciculations, pseudohypertrophy,
fatiguability
4. There are signs of chronicity: pes cavus, trophic ulcers, bedside aids
5. The likely neurolocalization is: use LMN approach!!
6. The likely etiology is___
Common  Poliomyelitis:
causes 1. Pathophysio: 3 serotypes of enterovirus. Replicate in nasopharynx and GIT -> hemato spread ->
predilection to AHC causing flaccid paralysis, and brainstem causing bulbar palsy
2. Clinical manifestations (4):
a) Inapparent infection
b) Abortive: nausea, vomiting, abdo pain
 c) Non-paralytic: above plus meningeal irritation
d) Paralytic: paralysis and wasting of bulbar and spinal distribution
3. Ix: viral cuture of stool/CSF/pharynx, CSF analysis (increased protein and lymphocytosis), MRI
spinal cord shows AHC abnormalities
4. No cure, supportive treatment.

 Spina bifida:
1. Definition: birth defect from abnormal neuralation during first 4 weeks of embryogenesis
2. Etiology: folate deficiency, antenatal exposure to valproic acid/carbamazepine or isotretinoin
3. Signs:
a) LMN LL with dermatomal sensory loss!
b) Bladder involvement - neurogenic
c) Skin changes over spine: scars, tuft of hair, dimple, sinus, naevus, lipom
d) A/w Chiari II malformation, hydrocephalus, lymphedema, erectile dysfunction
4. Ix: antenatal testing for amniotic AFB, maternal serum AFB, US
5. Mgt is supportive with mgt of neurogenic bladder, erectile dysfunction, high-dose folic
supplementation

 Spinal muscular atrophy:

1. Definition: neuromuscular disease characterised by degeneration of AHC in spinal cord and motor
nuclei in lower brainstem. 4 types, type 4 is adult-onset with normal life expectancy
2. Invx:
a) Genetic testing: homozygous deletion of exon 7 and 8 in SMI1 gene, or point mutation
b) EMG: fibrillation, positive sharp waves
c) Muscle biopsy: mixture of atrophy and compensatory hypertrophy of muscle fibres
d) CK is normal, unlike in muscular dystrophy!
3. Mgt is supportive
Peripheral neuropathy
Present 1. Complete exam: full neuro exam, assess gait (high steppage gait suggesting sensory ataxia), urine
dipstick for glycosuria, drug history (meds, alcohol)
2.This pt has a lower motor neuro lesion suggestive of a mixed motor and sensory peripheral
neuropathy as evidenced by:
a) Distal motor deficits from the level of the___ with (3): wasting of the lower limbs, decreased tone
and reflexes with downgoing plantars, and decreased power of grade ___
b) Sensory loss in a glove and stocking distribution
- small fibre: loss of pinprick and light touch
- large fibre: impairment of vibration and joint position sense
3. With regards to underlying etiology: ABCDEFGHI+U
- Alcohol
- B12 deficinecy
- Cancer / paraneoplastic
- Drugs
- Endocrine: DM, hypothyroid
- Familial: HSMN with pes cavus
- GBS: AIP/CIDP
- HIV
- Infection: leprosy - thickened, diphtheria, lyme
- Uremia
 4. With regards to function, I note:
a) Assistive aids, orthoses (for footdrop)
b) Charcots joint
c) Amputation, ulceration
Causes  Approach to polyneuropathy:
1. Involvement: motor, sensory, sensorimotor
2. Pathology: axonal, demyelinating, mixed
3. Presentation: acute, chronic

 Classification based on sensory and motor:

1. Pure motor:
a) Metabolic: MMN (multifocal motor neuropathy), acute intermittent porphyria
b) Drugs: lead, dapsone
c) Infx: diphtheria
2. Sensory:
a) Metabolic: alcohol, DM, hypothyroid, B12, uremia
b) Drugs: isoniazid, metronidazole, hydralazine, disulfiram, colchicine
c) Infx: leprosy, lyme, HIV
3. Mixed sensorimotor:
a) Metabolic: alcohol, DM, hypothyroid
b) Drugs: lithium, vincristine/platinum, amiodarone, gold, allopurinol
c) infx: AIDP/CIDP, HSMN
Invx 1. Basic bloods to assess for common etiology: FBC RP, B12, fasting glucose, HIV, TFT
2. Nerve conduction study if diagnosis is unclear
- only can test large myelinated nerve fibres
a) Axonal: decreased amplitudes
b) Demyelinating: decreased velocity and prolonged latency
3. EMG: can show acute axonal damage - presence of spontaneous muscle fibre activity at rest
occuring as a result of denervation
4. Nerve biopsy
Mgt 1. PT: ankle-foot orthoses, splint, waking aid
2. Lifestyle: reduce exposure to underlying cause E.g. alcohol, DM, toxin
3. Pharmaco: gabapentin or TCA for symptom control
Common 1. Common sites of thickened nerves: ulnar nerve at elbow, common peroneal nerve at head of
qns fibula, greater auricular nerve in neck
2. Causes of thickened nerves:
a) HSMN, neurofibromatosis, Refsums (retinitish pigmentosa)
b) Amyloidosis, acromeg, leprosy
3. Causes of painful peripheral neuropathy:
a) Alcohol, DM, B12 deficiency
b) Cancer, porphyria, arsenic
4. Types of neuropathy in DM:
a) Symmetrical sensory neuropathy
b) Mixed sensorimotor
c) Predominantly motor, asymmetrical - diabetic amyotrophy
d) Mononeuritis multiplex
e) Autonomic neuropathy
 5. Others: GBS, causes of mononeuritis multiplex
HSMN /  Present:
Charcot 1. Motor-sensory periperal neuropathy: LMN pattern of weakness with decreased tone/reflexes and
Marie absent ankle jerks, BILAT FOOT DROP (weakness of dorsiflexion)
Tooth 2. If generalized, wasted hands
(common 3. Ther is mild sensory loss in a glove and stocking distribution, vibration > pain
test!!) 4. This is seen in association with:
- pes cavus, clawing of toes, trophic ulcers/calluses
- inverted champagne bottle appearance due to distal wasting with preserved thigh muscles
- thickened nerves esp lateral popliteal/greater auricular
5. Functionally, he walks with aids and I not a foot orthosis at the bed side
6. In summary, he has a motor-sensory peripheral neuropathy. Common underlying etiologies
include DM, vit B12 deficiency, alcohol. However in view of the pt’s young age and presence of
deformity, I offer the main differential of hereditary sensory-motor neuropathy

 Definition: heterogeneous group of hereditary chronic motor/sensory neuropathy

1. Type 1 demyelinating: AD chr 17. Palpable nerves, absent reflex
2. Type 2 axonal: late presentation/mild, AD. No palpable nerves, intact reflex
3. Type 3 demyelinating hypertrophic neuropathy of infancy (derjerine-Sottas): AR, palpable nerve
with absent reflex

 Invx:
1. Rule out other causes of peripheral neuropathy
2. EMG/NCS: showing demyelination with decreased conduction velocity
3. Genetic testing for chr 17 PMP-22 gene

 Common questions:
1. Why are there thickened nerves: in response to demyelination, schwann cells proliferate and form
concentric arrays of re-myelination, resulting in “onion bulb” appearance on histo
2. Pathophysio of pes cavus: high-arch foot that does not flatten when pt weightbears, as a result of
imbalance in muscles whereby anterior tibialis/peroneus is weaker than the posterior
tibialis/peroneus
3. Ddx: friederich ataxia, cerebral palsy, spinal dysraphism
Footdrop  Extra things to test:
1. Hip abduction, IR -> weak means L5 radiculopathy
2. Knee flexion and ankle plantarflexion -> weak means sciatic
3. Ankle inversion, eversion -> weak means either L5 or sciatic
4. Ankle jerk -> decreased means sciatic

 Approach for LMN footdrop:

1. L5 radiculopathy (highest):
- Causes: disc herniation, spinal stenosis
a) Weak hip abduction and internal rotation
b) Normal knee flexion and ankle plantarflexion
c) Normal ankle jerk
2. Sciatic neuropathy:
- Causes: hip surgery, injection, injury
a) Normal hip abduction and internal rotation
 b) Weak knee flexion and ankle plantarflexion
c) Decreased ankle jerk
3. Peroneal:
- Causes: compression E.g. weightloss, periop, trauma
a) Everything normal except ankle dorsiflexion and eversion
- compared to L5 and sciatic, ankle inversion is not weak
Hemiparesis
Present 1. This pt has an upper motor neuron type of weakness on the X side, as evidenced by hypertonia,
hyperreflexia, upgoing plantars and power 3/5 on the X side
2. With or without sensory loss
3. This is associated with:
a) Facial droop involving the frontalis muscle on the opposite side, suggesting a lower motor neuron
lesion of CN7
b) Facial droop not involving the frontalis muscle on the same side, suggesting an upper motor
neuron lesion of CN7
c) OR there is no cranial nerve involvement
4. I did not note any cortical signs such as gaze preference, aphasia, neglect, or sensory extinction +/-
homonymous hemianopia (difficult to test)
5. The likely neurolocalisation is in the brainstem, specifically ___medullary syndrome, vs subcortical
6. The likely etiology is: infarct, tumour, abscess, MS/ADEM/NMO
Cerebellum
O/E  Basic examination:
1. Cranial nerves:
a) Nystagmus:
- gaze evoked nystagmus
- ocular dysmetria, broken persuits
b) INO, RAPD
c) Cerebellar dysarthria: British constitution (slurred, staccato)
d) Others: gingival hypertrophy, telengiectasia, parotid enlargement
2. UL:
a) Pronator drift and Holmes rebound
b) Dysmetria with intention tremor
c) Dysdiadochokinesia
3. Sit/trunk
a) truncal ataxia
b) Test pendular reflex at side of the bed
4. Gait:
a) Rhombergs: for concomitant sensory ataxia
b) Normal gait: fall towards side of lesion
c) Tandem gait
5. Complete exam:
a) Fundoscopy: optic atrophy suggestive of demyelinating disease
b) Full neuro exam
c) If bilat:
- mouth: gingival hypertrophy, macroglossia, telengiectasia
- alcohol: dupuytrens, parotid, CLD
  Associated findings:
1. CN:
a) CPA: 5-8, ipsilat cerebellar
b) Lateral medullary (PICA): ipsilat 5-11, Horners, cerebellar, controlat loss of pain and temperature
c) Jugular foramen (Arnold Chiari): CN9-11
d) Northnagel: ipsilat CN3, contralat cerebellat
2. With hemiparesis: ataxic hemiparesis (lacunar infarct)
3. Demyelination/MS
4. Spastic paraparesis: friederich's ataxia, Arnold Chiari malformation, MS, tabes dorsalis
Present 1. This pt has a cerebellar syndrome
2. As evidenced by dysmetria and dysdiadochokinesia bilaterally / on X side
3. This is associated with:
a) UMN lesion affecting one side or both sides of the body
b) Cranial nerves are grossly intact, with no nystagmus/INO/RAPD
4. There is truncal ataxia / gait impairment, and Rhombergs is negative
5. In summary, this pt has bilateral or unilateral cerebellar disease with a possible underlying etiology
of ____.
Causes  Localization:
1. Limb ataxia: cerebellar lobes
2. Gait ataxia: anterior vermis
3. Truncal ataxia: posterior vermis

 Causes of bilat cerebellar disease:

1. Alcohol
2. Vascular: bilat CVA
3. Degenerative: multisystem atrophy
4. Demyelination: MS
5. Metabolic: Wilsons, hypothyroid
6. Drug: phenytoin, lithium
7. Infection
8. Malignancy: paraneoplastic (ovarian, breast, SCC, Hodgkins), bilat CPA tumour in NF2
9. Hereditary: ataxic telangiectasia, friederich's

 Causes of Unilat cerebellar disease:

1. Vascular: cerebellar, lacunar or brainstem infarcts
2. Malignancy: SOL - medulloblastoma or astrocytoma
3. Infection/abscess
Common  Friederich ataxia:
cases 1. Definition:
a) AR spinocerebellar ataxia resulting from gene mutation with trinucleotide repeat GAA in the
fraxatin gene on chromosome 9, onset before 25 years old
b) Clinical: triad of neuro (cerebellar, spinothalamic, dorsal column, peripheral nerve), CMP and DM!!
2. Presentation:
a) Complete exam (5): complete neuro exam, test hearing for sensorineural deafness, CVS for HOCM,
fundoscopy for optic atrophy, urine dipstick for glycosuria
 b) This pt has a blat cerebellar aaxia associated with spastic paraparesis:
- bilat cerebellar sings
- UMN pattern of weakness with upgoing plantar response
- absent knee and ankle reflex
- dorsal column sensory loss (proprioception/vibration), Rhomberg +
- Chronicity: pes cavus, distal wsting of hands/legs, bedside aids
c) This is seen in a/w DM dermopathy, cardiomegaly
d) In summary this pt has a cerebellar syndrome with upper motor pattern of weakness and
peripheral neuropathy suggesting a unifying diagnosis of Friederich's ataxia

 Ataxic telangiectasia:
1. Definition: neurodegenerative disease with hallmark features of ataxia and telangiectasia. Due to
defect in ATM gene which serves to recognize double stranded breaks -> increased risk of infection
and malignancy
2. Clinical:
a) Telangiectasia - if ocular, can be confused with conjunctivitis
b) Ataxia
c) Choreoathetosis
d) Recurrent sino-pulmonary infections
e) Malignancy esp lymphoma, leukemia
3. Invx:
a) Supportive with raised AFP, immunoglobunin, low lymphocyte count
b) MRI brain showing cerebellar atrophy
c) Diagnostic: PCR for ATM deficiency
Parkinson’s disease
O/E  Steps:
1. Inspect: resting tremor, paucity of facial expression, decreased blink rte +/- monotonous speech
2. Bradykinesia, see which side is slower
3. UL: Pronator drift, tone, reflexes, power
4. Cerebellum!!
5. Eye EOM tro PSP, brush teeth/comb hair tro CBD
6. Gait (6): hesitation and slowness of initiation, shuffling, decreased arm swing, stooped posture,
turning in numbers +/- retropulsion

 Offer (5):
1. Gait if not done so, consider other PD tests like gabellar tap or retropulsion
2. Postural BP!
3. Complete drug history, family history for genetic parkinsonism
4. AMT or MMSE tro LBD or parkinson’s-associated dementia
5. Assess swallowing, bADLs
Present 1. This pt has features of parkinsonism, which are asymmetrical involving the R > L
a) Resting tremor, paucity of facial expression, decreased blink rate +/- monotonous speech
b) Bradykinesia (paucity and decreased amplitude of movt), more prominent on the R/L
c) Cogwheel +/- leadpipe rigidity
d) Characteristic gait with (5): stooped posture, difficulty in initiation, shuffling with festination, lack
of arm swing, turning in numbers
3. With regards to likely etiology:
 a) No pronator drift or hyperreflexia suggestive of vascular parkinsonism
b) No gaze palsy suggestive of progressive supranuclear palsy (impaired down -> up-> horizontal)
c) No extrapyramidal features or cerebellar signs suggestive of multi-system atrophy
d) Cortico-basal degeneration: limb apraxia or dystonic arm
4. Disability:
a) Features of immobility: pressure sores, contractures
b) AFO, back brace, walking aids
c) Functional deficits: writing, fine movts
5. In summary, this pt has parkinsonism features without any clinical signs of parkinsons plus
syndrome. Functional he was still able to ambulate unaided.
Define  Definition:
1. Neurodegenerative disease with 2 out of 3 of:
a) Resting tremor 3-5Hz
b) Bradykinesia
c) Rigidity
2. Pathologically it is defined by degeneration of dopaminergic nigrostriatal neurons

 Hohen and Yahr staging

1. Stage 1: unilat and mild
2. Stage 2: bilat with minimal disability
3. Stage 3: significant bradykinesia and gait impairment
4. Stage 4: significant rigidity and limited walking
5. Stage 5: completely bedbound/invalid
Causes 1. Parkinsons disease
2. Parkinsons plus syndromes: poorer prognosis and poor response to dopaminergic therapy
a) Supranuclear gaze palsy: down then up then horizontal gaze palsy, postural instability and axial
rigidity with falls, frontal lobe signs
- other eye signs: slow pursuits, saccadic eye movts
b) MSA: A (Shy Drager), C (Olivopontocerebellar atrophy), P (striatonigral degeneration)
c) CBD: limb apraxia/alien limb syndrome, dystonia
d) LBD: dementia, parkinsonism, hallucination
3. Secondary parkinsonisM:
a) Drugs: antipsychotics (risperidone, haloperidone), maxolon, methyldopa
b) Toxins: magnesium, mercury, carbon monoxide, methanol
c) Viral encephalitis E.g. west nile
d) Wilsons disease
e) Paraneoplastic syndrome
Invx  Intro:
1. Parkinson's disease is a clinical diagnosis
2. However, I would like to investigate for underlying etiology with radiological and serological tests

 Invx:
1. Radiological
a) MRI brain to rule out structural cause especially if pt is elderly. Looking for:
- basal ganglia pathology such as tumour, inflammation and infection
- infarcts suggestive of vascular parkinsonism
- if no lesion seen, this would suggest idiopathic parkinsons disease
 b) I would also consider functional brain imaging showing decreased basal ganglia pre-synaptic
dopamine uptake
2. Serological tests:
a) Electrolytes looking for low CMP
b) LFT and RP to rule out ESRF and liver failure, which can also cause tremors
c) TFT to rule out hypothyroidism, which could account for slowness and bradykinesia
d) If pt is young, rule out Wilsons disease with slit-lamp examination and serum caeruloplasmin and
24-hr urinary copper
d) Take a complete drug history, looking for antipsychotics like haloperidol, prokinetics like
metoclopramide, and toxins like carbon monoxide/manganese
Mgt  Intro:
1. Parkinson's disease is a progressive disease with functional implications, hence a multi-disciplinary
approach involving the physio, occupational, speech therapist and neurologist is required
2. I would divide my mgt into pharmacological, management of complications, and possibly even
look into surgical modalities

 Pharmaco:
1. First-line Levodopa + peripheral decarboxylase inhibitor (benserazide/carbidopa)
a) MoA: levodopa is a natural chemical converted into dopamine in the brain, while carbidopa
prevents levodopa from being converted peripherally
b) Madopar: levodopar + benserazide
c) SE: nausea, postural hypotension, somnolence, motor fluctuations, dyskinesia from
overstimulation of dopamine receptors
d) Why not start levodopa immediately in young pt: increased risk of developing dyskinesia and
insensitivity to treatment
e) Absolute CI for L-dopa: melanoma!!
2. Dopamine-based agents early in the disease course or in younger pts:
a) Dopamine agonist:
- Ergot: bromocriptine, perfolide, lisuride
- Non-ergolide: pramipexole, ropinerole
b) MAO-B inhibitor: selegiline, rasagiline
3. COMT inhibitor:
a) Entacapone, tolcapone
b) decrease GI breakdown of levodopa, and hence can prolong duration of dopaminergic
supplementation (maximise interval)
c) SE: may increase dyskinesia
4. Treatment of tremors:
a) Amantadine: NMDA antagonist that reduced peak dose dyskinesia
b) Anticholinergics: benzhexol, procyclidine, orphenadrine. Benzhexol can worsen hallucinations!

 Mgt of complications:
1. Complications of immobility such as pressure sore, pneumonia, DVT
2. Management of autonomic dysfunction leading to postural instability, constipation,
insomnia/depression/anxiety
 Surgical:
1. Deep brain stimulation for tremors!
2. Thalomotomy: tremors
3. Pallidotomy: for all features
  How to diff tremor in PD from essential tremors:
1. Essential tremors: symmetrical, worse with voluntary movt
2. Writing: micrographia in PD, large and irregular script in essential tremors as tremor is
exacerbated by writing
Myasthenia Gravis
Present 1. Complete exam (3): forced vital capacity (15ml/kg = mechanical ventilation), swallowing
assessment, lung examination
2. This pt has myasthenia gravis:
a) Ocular: complex opthalmoplegia
b) Limb: proximal myopathy
c) Bulbar involvement
d) Fatiguability
3.This is seen in association with:
a) Midline sternotomy scar: Thymus surgery
b) RA: penicillamine-induced
c) Previous treatment: central line
d) Cachexia/LN - suggest ddx of Lambert-Eaton
4. Functionally, this pt has impaired swallowing with PEG/NG feeding
5. In summary, this pt has evidence of myasthenia gravis with ocular and limb involvement
Define  Definition:
1. Chronic autoimmune disorder of the post-synaptic membrane at the neuromuscular junction in
skeletal muscles
2. Characterized by muscle weakness which fatigues and improves on rest

 Presentations:
1. Age distribution:
a) Female 20-30 years old
b) Male >50 years old
2. 3 Clinical presentations:
a) Ocular: ptosis, diplopia
b) Oropharyngeal: dysarthria, difficulty swallowing
c) Generalized: weakness, reduced exercise tolerance

 Grading severity of weakness: MG Foundation of America

1. Grade 1: ocular only
2. Grade 2: muscles other than ocular
a) 2A: limb and axial
b) 2B: respiratory and bulbar muscles
3. Grade 3 moderate weakness, grade 4 severe, grade 5 intubation required
Invx 1. MG is a clinical diagnosis supported by serological and electrophysiological tests
2. Serology:
a) Anti-acetylcholine receptor (anti-AchR) antibody assay: 80% of generalized MG pts, 50% of ocular.
Titres do not correlate with severity
b) Anti-muscle specific kinase antibodies: 70% of AchR seronegative MG pts
3. Electrophysiological testing:
a) Repetitive nerve stimulation (RNS): >10% decline in compound muscle action potential (CMAP)
 amplitude btw the first and fourth potential in a train of 10 stimulations i.e. decreased response with
repetitive nerve stimulation
b) Single fibre nerve electromyography: evidence of neuromuscular blockade with increased jitter
4. Imaging:
a) CXR: anterior mediastinal mass, aspiration pneumonia
b) CT chest: 15% thymoma, 75% thymic hyperplasia
Mgt  Mgt of stable disease
1. Immunosuppressant: steroids (may have paradoxical worsening) +
azathioprine/cyclophosphamide
2. Anti-cholinesterase pyridostigmine
3. Thymomectomy

 Medical emergencies:
1. Myasthenic crisis: defined as an exacerbation requiring mechanical ventilation
a) FVC 15ml/kg or less (normal >/=60ml/kg)
b) Negative inspiratory force (NIF) 20 cm H2O or less (normal >/=70 cmH2O)
c) Ppt: non-compliance to meds, infection, stressor (pregnancy, postpartum, surgery), medications
(aminoglycosides, procainamide, phenytoin)
2. Cholinergic crisis: weakness due to overtreatment with anti-cholinesterase. Flaccid paralysis with
cholinergic effect - diarrhoea, salivation, miosis
3. Mgt:
a) Secure airway with intubation and mechanical ventilation
b) Withdraw anti-cholinesterase meds
c) Plasma exchange or IVIG
Lambert 1. Autoimmune disorder of neuromuscular junction occuring either as paraneoplastic condition
Eaton (small cell) or without cancer
2. Invx: anti-P/Q voltage-gated calcium channel antibodies
Nerve conduction studies show doubling of CMAP post-exercise