Neurology JC023: Unsteady Gait: Cerebellar Lesions, Movement Disorders, Parkinsonism Flashcards

1
Q

Physiology of gait

A

3 levels of gait control:
1. Upper level (**Gait execution)
- Premotor cortex
- Motor cortex
- Regulatory system: **
Extrapyramidal system (e.g. Basal ganglia)

  1. Middle level (Subcortical centres: **Synergy of gait)
    - Midbrain locomotor region (MLR)
    - Spinal locomotor network (SLN)
    - Regulatory system: **
    Cerebellar system
  2. Lower level (Force production)
    - Peripheral nervous system
    - Musculoskeletal system
    - Regulatory system: Spinal reflex pathways (
    Vestibular + ***Proprioceptive inputs)

Regulatory system: **Postural control + **Balance

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2
Q

Gait disorders

A
  1. Apraxic gait
    - **Motor cortex + Extrapyramidal system affected (Diffuse problem)
    - **
    Difficulty initiating walking, 行行下唔行
  2. Parkinsonian gait
    - ***Extrapyramidal system affected
    - Hypokinetic gait, Small steps, Turn slowly
  3. Ataxic gait
    - **Cerebellar system + Spinal reflex pathways affected
    - **
    Wide based, Truncal unsteadiness
  4. Hemiplegic / Diplegic / Spastic gait
    - Upper level of gait centre affected (e.g. Stroke)
  5. Antalgic gait
    - Musculoskeletal system affected (∵ pain)
  6. Waddling gait
    - Musculoskeletal system affected
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3
Q

Causes of Gait disorders

A
  1. Motor deficits
    - UMN (spasticity)
    - LMN (amytrophy = muscular wasting)
    - Muscular disorders
  2. Movement disorders (Extrapyramidal disease)
  3. Sensory ataxia
  4. Cerebellar ataxia
  5. Vestibular disorders
  6. Parkinsonian syndromes
  7. Normo-pressure hydrocephalus
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4
Q

Revision: Cerebellum

A

Cerebellum:
- Coordination / Fine-tuning of voluntary movements
- Control of equilibrium + muscle tone
- Responsible for ***ipsilateral side

Vermis / Other paramedian structures:
- **Truncal stability
- **
Gaze fixation
- ***Gait
—> rely on integration of Sensory (Vision) + Vestibular + Motor (Proprioception) signals input

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5
Q

Cerebellar disorders

A

Ataxia (共濟失調症):
- ***loss of coordination
- irregularity / disorderliness
- may result from:
1. Cerebellar disorders
2. Impaired sensory feedback (Sensory ataxia)

  1. Limb ataxia / Ataxic gait
    - Dysmetria + Tremor + Dysdiadochokinesia
    - hard to test if weakness / sensory impairment
    - muscle tone is reduced but often not apparent
  2. Scanning dysarthria (***specific for cerebellar disorder)
    - Explosive dysarthria (incoordination of speech / respiration —> speech volume / rate vary from word to word) + Cerebellar speech (slow + slurred)
  3. Nystagmus
    - vestibulocerebellar pathway affected —> Ocular Dysmetria (jerkiness of smooth-pursuit eye-movements with disrupted fixation)
    - **Gaze-evoked + **Horizontal
    - unilateral lesion: fast-phase of nystagmus is towards the ***affected side
  4. Dysmetria
    - errors in range + force of movements —> under / over-shooting of target: Finger-nose, Heel-shin test
  5. Dysdiadochokinesia
    - decomposition of fine repetitive movements
    - NOT specific for cerebellar disorders
    - can be seen in ALL neurological conditions affecting motor control of limb
  6. Hypotonia
  7. Intention / Kinetic tremor
    - exaggerated by maximising range of movement tested
  8. ***Pendular tendon reflexes
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6
Q

Etiologies of Cerebellar disorders

A

Children:
- Congenital maldevelopment (Arnold-Chiari malformation, Dandy-Walker syndrome)
- Metabolic disorders
- **Infections (Chicken pox encephalitis)
- **
Tumours (Medulloblastoma, Cystic astrocytoma)
- Hereditary degenerative disorders

Adult:
- Hereditary degenerative disorders (AD Spinocerebellar ataxias, Recessive Friedreich’s ataxia)
- Alcoholism
- **Cerebrovascular disease
- **
Multiple sclerosis
- **Metabolic disorders (e.g. Hypothyroidism)
- **
Drug overdose (e.g. Anticonvulsant, Antihistamine)
- ***Tumours (direct involvement / paraneoplastic syndrome)

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7
Q

Ataxic gait

A

Result of Incoordination of movements + Unsteady balance of trunk

Features:
- **Wide based (to maintain balance)
- **
Truncal unsteadiness (when asked to walk tandem)
- **Tendency to Jerk sideway
- **
Walk relatively quickly
- Irregular length / synergy
- Greatly exacerbated during rapid postural adjustments e.g. Turning corners
- may combine with other gait disorders (e.g. Spastic gait in MS, High-stepping gait in Tabes dorsalis)

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8
Q

Hemiplegic gait

A
  • Arm adducted
  • Internally rotated at shoulder
  • ***Flexed at elbow
  • Pronation of forearm
  • ***Flexion of wrist and fingers
  • Leg slightly flexed at hip
  • ***Extended at knee
  • Plantar flexion
  • ***Inversion at foot
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9
Q

Apraxic gait / Gait apraxia

A
  • ***Difficulty initiating walking
  • Disorganised walking skills
  • ***Shuffling small steps
  • BUT ***arm swing and posture are normal (vs PD: reduced arm swing, stooping posture)
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10
Q

Cerebellum vs Basal ganglia

A

Cerebellum: Rapid (ballistic movement)

Basal ganglia: Slow (ramp, smooth movement)
1. Caudate nucleus
2. Putamen
3. Globus pallidum
4. Substantia nigra

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11
Q

Extrapyramidal disorders (aka Movement disorders)

A

Disorders of Basal ganglia:
- affect slow (ramp) rather than rapid (ballistic) movements

Basal ganglia motor loop:
- complex network consisting of multiple nuclei
- D1: excitatory pathway
- D2: inhibition pathway
- normally balance out each other, imbalance: Movement disorders

Dyskinesia / Hyperkinetic disorders (Defect in D2 inhibition pathway)
- Chorea (舞蹈症)
- Ballismus (芭蕾舞症)
- Athetosis (手足徐動症), Choreoathetosis
- Dystonia (肌張力不全症)
- Tremor (顫抖症)
- Myoclonus (肌躍症)
- Tics (肌抽搐症)

Akinesia / Hypokinetic disorders (Defect in D1 excitatory pathway)
- Parkinsonism

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12
Q

Chorea (舞蹈症)

A

Lesion in Striatum / related structures

Features:
- **Irregularity + **Randomness + Excessive + **Spontaneous + Jerky + Non-repetitive
- At different parts of body in random sequence
- **
No weakness
- Gait: Tendency to sway + jerk
- ***Muscle tone ↓
- Patient may mask it by Quasi-purposive (seemingly on purpose)
- Irregular + Explosive speech

Causes:
- Huntington’s disease
- Cerebral palsy
- **
Kernicterus (excessive bilirubin)
- Rheumatic fever (
Sydenham’s chorea, reactivate as **Chorea gravidarum during pregnancy)
- SLE
- Structural lesions (e.g. Tumour, AV malformation)
- ***Wilson’s disease
(- Can be secondary to PD due to high Levodopa dose)

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13
Q

Hemiballismus (單側芭蕾舞症) / Ballismus (芭蕾舞症)

A

Exaggerated form of Chorea / Proximal chorea

Etiology:
- Stroke —> Lesion affect **Contralateral Basal ganglia / Subthalamic nucleus unilaterally —> **Contralateral Hemiballismus

Features:
- Irregular, Non-repetitive
- ***Violent excursions of affected limbs (∵ proximal muscles affected)

Treatment:
- ***Tetrabenazine (block Dopamine reuptake)

Prognosis:
- usually disappear several weeks after onset

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14
Q

Athetosis (手足徐動症)

A

Etiology:
- **Neonatal cerebral hypoxia
- **
Kernicterus

Features:
1. ***Abnormal limb posturing
- Shoulder: Adducted + Internally rotated
- Elbow: Semi-flexed
- Wrist / MCP joints: Flexed
- IP joints: Extended

  1. ***Slow, coarse, twisting writhing movements of extremities
    - Flexion / Extension of wrist, fingers, elbow
    - Retraction, Internal rotation at shoulder
  2. Patient may grasp affected limb with normal hand to ***restrain movement
  3. UMN signs may present
  4. Lower limb less affected
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15
Q

Dystonia (肌張力不全症)

A

Frozen Athetosis
***Abnormal posturing

Etiology (reversible):
- Focal brain lesion (involving Basal ganglia, Rostral midbrain)
- Wilson’s disease
- Drug-induced dystonia

Features:
- **Excessive muscular tone + contraction of antagonistic muscle groups
—> Sustained postural distortion of limbs + trunk (扭麻花, painful)
—> may be distorted by Repetitive spasmodic twisting movements
- **
Posture / Action / Task-specific
- Sporadic / Familial

Types:
1. Focal Dystonia (more common)
- **Cervical dystonia (Spasmodic torticollis)
- **
Blepharospasm
- Foot dystonia
- Writer’s cramp

  1. Generalised dystonia

Treatment:
- **Anticholinergics
- Levodopa
- **
Benzodiazepines
- Botox local injection

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16
Q

Tremor (顫抖症)

A
  • ***Rhythmic oscillating movement of a segment of limb / head
  • ***Alternating / Synchronous contraction of antagonistic pair muscles —> Rhythmic oscillating movement
  • Fixed periodicity
  • Waveforms / Amplitudes can vary

3 types:
1. Resting tremor (esp. Parkinsonian)
2. Postural tremor
3. Intention / Kinetic tremor (esp. Cerebellar)
(4. Essential tremor)

Parkinsonian tremor:
- 4-6Hz
- in relaxed + supported limb
- occur when affected body parts are **at rest
- **
subside with action

Postural tremor:
- enhanced physiologic (8-12 Hz) tremor on outstretched hand:
—> anxiety, exercises, sleep deprivation, drugs, alcohol, thyrotoxicosis, heavy metal poisoning

Cerebellar Kinetic tremor:
- ***3-6 Hz
- Terminal accentuation / Terminal dysmetria: ↑ in tremor towards target
- Past-pointing
- Treatment: No
- Pathology in Red nucleus: Severe Resting + Kinetic tremor

Physiological tremor:
- 8-12 Hz
- more obvious with old age, anxiety, thyrotoxicosis

Essential tremor:
- 5-10 Hz
- **action-induced
- resemble **
exaggerated physiological tremor
- **not well-defined etiology
- worsen by stress / age
- some have positive family history (Benign essential tremor)
- alcohol can improve transiently
- Treatment: **
β-blocker, ***Primidone (barbiturate)

17
Q

Myoclonus (肌躍症)

A

Very wide DDx

Features:
- **Sudden, Brief shock-like muscle contractions
- Variable intensity
- Repetitive / Paroxysmal jerk
- **
Simple movement (not complex e.g. chorea / athetosis)
- ***Less rhythmic + Visible pauses (vs Tremor)

Types:
1. Focal (involving only a few muscles)
- Basal ganglia disorders (neck, arm, shoulder)

  1. Generalised
    - types:
  2. Physiological (nocturnal, hiccups)
  3. Essential
  4. ***Epileptic
  5. Symptomatic
    - Abnormal Cerebral cortex activities
    —> Epilepsy syndromes
    —> Neurodegenerative diseases e.g. AD, CJD
    —> Mitochondrial diseases
    —> Cerebral anoxia
    - Spinal cord disorders

Treatment:
- Depend on etiological diagnosis / specific disease syndrome
- **Benzodiazepines
- Piracetam
- **
Anticonvulsant e.g. Na Valproate

18
Q

Differentials of myoclonus

A
  • ***Epilepsy with myoclonus seizures
  • ***Secondary myoclonus
  • ***Dystonia myoclonus / chorea-related
  • Basal ganglia disorders
  • Stiff-person syndrome
  • Essential myoclonus
  • Periodic movements of sleep
  • Brainstem, spinal myoclonus
19
Q

Tics (肌抽搐症)

A

Etiology:
- **Gilles de la Tourette’s syndrome
- **
Compulsive behaviour
- Obsessive ruminations
- ADHD

Features
- **Brief, Rapid
- **
Coordinated movements, **Stereotypic (vs Chorea: irregular, random)
- Repeated at irregular intervals
- Ability of **
voluntary suppression, but ***inner urge to make movement (vs Chorea: involuntary)
- Can be trivial
- Not uncommon

Persistent multiple simple tics:
- begin before 15 yo
- associated with vocal tics
- complete remission can occur in adulthood

Chronic multiple motor + vocal tics:
- Gilles de la Tourette’s syndrome
- **Male
- Treatment: **
Clonidine (α2 agonist), ***Haloperidol (typical antipsychotic)

Prognosis:
- Symptoms begin in childhood, Worst during late adolescence
- Resolve spontaneously after 20 yo (majority)

20
Q

Drug-induced movement disorders

A
  1. Acute dystonic reactions
    - ***Anti-dopaminergic drugs (in young patients after a few hours) (Prochloperazine, Metoclopramide)
    - Cranial, Cervical, Axial muscles
    - Oculogyric crisis

Treatment:
- **IV Anticholinergics (Procyclidine, Benztropine, Diphenhydramine)
- **
Benzodiazepines

  1. Tardive dyskinesia:
    - Elderly taking long-term antipsychotic
    - may be due to Dopamine receptor ***hypersensitivity
    - Continuous stereotypic oro-lingual movements
    —> Lip-smacking
    —> Chewing
    —> Rolling of tongue in mouth, pushing against cheek, periodic protrusion
    - Gait unaffected

Treatment:
- Difficult
- Withdrawal (abruptly may paradoxically cause Tardive dyskinesia)

(Extrapyrimidal symptoms of Anti-psychotics:
1. Akathisia
2. Dystonia
3. Parkinsonism
4. Tardive dyskinesia)

21
Q

Parkinson’s disease

A

A Clinicopathological entity

Etiology:
- Mostly **Sporadic (only a few Familial)
- Idiopathic degeneration of **
Substantia nigra
- Presence of Intraneuronal ***Lewy bodies on microscopy

Parkinsonism:
- Clinical features of PD (reflecting loss of dopaminergic neurons)

Pathology:
- Loss of neurons in Substantia nigra (Melanin-containing, Dopaminergic)
- Loss of neurons in Brainstem, Pallidum, Putamen
- Lewy bodies inclusions (PD)

Parkinsonian syndromes:
- big family of syndromes that present with Parkinsonism
- PD one of them (but commonest Parkinsonian syndrome)

22
Q

Other causes of Parkinsonism

A
  1. Secondary parkinsonism
    - **Antipsychotic (i.e. Neuroleptics e.g. Phenothiazine) / Other dopamine-depleting drugs (e.g. Metoclopramide)
    - **
    Wilson’s disease (must be excluded in early-onset Parkinsonism)
    - Lithium
    - Toxins: MPTP, CO poisoning, Cu, Mn
    - Trauma (e.g. Punch drunk syndrome)
    - Microvascular disease (HT, Atherosclerotic)
    - **Normal pressure hydrocephalus
    - Post-encephalitis lethargica
    - AD, **
    Lewy body dementia, CJD
    - Leucodystrophies
    - Hallevorden-Spatz disease
    - Westphal variant of Huntington’s disease
    - Denatao-rubro-pallido-luysian atrophy
    - Guam variant of motor neuron disease
  2. Other neurodegenerative disease involving Basal ganglia
    - **Diffuse Lewy body disease
    - **
    Progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome)
    - ***Multiple system atrophy
    - Corticobasal ganglionic degeneration
    —> called Parkinsonism “Plus” syndromes (have other features apart from Parkinsonism ∵ more widespread disease process)
23
Q

Epidemiology of PD

A
  • 80% of Parkinsonian syndromes
  • Prevalance: 160/100,000 population
  • Incidence: 20/100,000 per year
  • 1% population >65 yo
  • Onset: 40-70 yo, peak in ***6th decade
  • Onset before 30 yo: ~1%
  • Onset before 50 yo: ~10%
  • M:F = 3:2
24
Q

Natural history of PD

A
  • Degenerative condition
  • Insidious onset
  • Gradual progression
  • Average survival from onset ***13 years
  • Mortality rate 2-5x of age-matched population

***“Hoehn and Yahr” staging
Stage 1: Unilateral (3 years)
Stage 2: Bilateral (6 years)
Stage 3: Bilateral + Postural imbalance (7 years)
Stage 4: Severe, need help (9 years)
Stage 5: Chair / Bedbound (14 years)

25
Q

Risk factors of PD

A

Likely multi-factorial
1. Aging
- Nigral cells 425,000 reduced to 200,000 by 80 yo (30% of age-matched subject to start with —> early emergence of motor dysfunction)

  1. Genetics
    - family history
    - specific mutation
  2. Environment (less clear)
26
Q

***Clinical features of PD

A

Parkinsonism (TRAP):
1. Resting Tremor
- Resting (↓ with action, ↑ with rest)
- Begins in hand / foot
- Flexion + Extension of **fingers (usually little movement above wrists)
- Exacerbated by stress
- **
Coarse (4-6 Hz)
- ***“Pill-rolling”

  1. Rigidity
    - ↑ Resistance to passive movements (Lead-pipe / Cogwheel) (vs Spasticity: distribution + velocity-dependent)
    - ↑ Muscle tone equal in flexor / extensor
    - Uniform throughout range of movement
    - **Cogwheel rigidity (combination of Tremor + Hypertonia)
    - **
    Fatigue, muscle ache (∵ sustained muscle contraction)
  2. Akinesia / Bradykinesia
    - Slowness in voluntary movements
    - **
    ↓ Automatic movements (e.g. Arm swinging)
    - Gait disturbance
    —> Flexed, Stooping posture
    —> Slow
    —> **
    ↓ Arm swing
    —> Poor foot clearance
    —> Poor gait initiation
    —> **Small steps, Shuffling (Marche a petit)
    —> Turning difficulty
    —> Falls
    —> Difficulty in initiation —> then advances rapidly with small steps to catch up with shift in centre of gravity (
    Festinating gait)
    - Lack of facial expression + blinking (
    Facial amimia)
    - Clumsiness in rapid repetitive movements (
    Dysdiadochokinesia)
    - Blepharospasm, sustained blink responses (
    Myerson’s sign)
    - Small hand writing (
    **Micrographia)
    - ***↓ Voice, monotonous speech
  3. Postural instability
    - Tendency to fall backwards (***Retropulsion)

Other S/S apart from Motor symptoms:
1. Psychiatric
- Panic, Anxiety
- Depression
- Paranoia, Hallucinations (more prone to SE of anti-parkinsonian drugs)

  1. Sensory
    - Paresthesia
    - Pain
  2. Autonomic dysfunction
    - Tachycardia
    - Sweating
    - Constipation
    - Belching
    - SOB
    - Postural hypotension
    - ***Detrusor instability
  3. Cognitive decline
    - Slowness in thought
    - Poor memory
    - Lack of motivation
27
Q

Clinical red flags to differentiate Parkinsonism Plus vs PD

A
  1. ***Rapid progression, early instability and falls
  2. ***Poor treatment response to Levodopa (PD has excellent response to Levodopa)
  3. ***Early + prominent dementia
  4. **Pyramidal signs, Cerebellar signs, Autonomic dysfunction, **Gaze palsy
  5. Young onset with strong family history
28
Q

Diagnosis of PD

A

Clinical diagnosis:
- **Klawans principle: Presence of S/S of PD + without S/S not consistent with PD
- ∵ **
NO reliable in-life markers

UK PD Society Brain Bank Clinical Diagnostic Criteria
Step 1: Diagnosis of Parkinsonian syndrome (S/S of PD)
- Bradykinesia
- >=1 of following
—> Muscle rigidity
—> 4-6 Hz rest tremor
—> Postural instability not caused by primary visual, vestibular, cerebellar, proprioceptive dysfunction

Step 2: Exclusion criteria for PD (without S/S not consistent with PD)
- S/S with Parkinsonism Plus syndrome

Step 3: Supportive prospective positive criteria for PD (only 80% specificity)
- Progressive disorder
- Persistent asymmetry affect side of onset most
- Excellent response (70-100%) to Levodopa
- Severe Levodopa-induced chorea
- Levodopa response >=5 years
- Clinical course of >=10 years

Other investigations:
1. DaT (Dopamine transporter) scan (123I-β-CIT and 123I-FP-CIT SPECT)
2. 18F-dopa, 11C-Raclopride PET scan
—> can still be positive in Parkinsonism Plus syndromes

  1. TC-US midbrain for Fe deposition in SNc (substantia nigra pars compacta)
  2. MRI (DWI, DTI, ADC map)
29
Q

Genetics of PD

A
  • Sporadic
  • Positive family Hx: Double risk of PD
  • > 10 genetic loci implicated in Parkinsonian syndromes: PARK, SNCA, LRRK etc. (although most of them related to Parkinsonism Plus syndromes)
  • Gene mutation: **α-synuclein, **Parkin
  • ***LRRK2 associated with
    1. Familial PD
    2. Sporadic late-onset cases (0.5-2%)
30
Q

Treatment of PD

A

NOT exist in PD:
1. Restorative therapy (reverse disease process)
2. Neuroprotective therapy (arrest / slow down disease progression)

Only available in PD:
3. Symptomatic / Palliative therapy
- Dopaminergic (replenish dopamine deficiency from Nigral cell degeneration)
- Anti-inhibitory

Drug therapy:
- ***Levodopa + Carbidopa (peripheral DOPA decarboxylase inhibitor) (Gold standard)

Early stage:
- **Anticholinergic (Benzhexol)
- **
MAO-BI (Selegiline)

Adjunct:
- **Dopamine agonists (Bromocriptine, Ropinirole, Apomorphine, Pergolide)
- **
COMT inhibitor (Entacapone, Tolcapone)
- Amantadine

Surgery:
- **Pallidotomy
- **
Thalamotomy
- ***Deep brain stimulation
- Cell transplantation

Others:
- Physical therapy
- Daily living aid

31
Q

***Dopaminergic therapy

A
  1. Levodopa
    - converted to Dopamine in remaining Nigral cell
    - combined with peripheral Dopa-decarboxylase inhibitor / Transferase inhibitor —> achieve higher CNS concentration
    - Problems with long term use:
    —> **Loss of efficacy (only for ~5 years, ∵ gradual loss of dopaminergic terminals)
    —> Drug-induced **
    Choreiform Dyskinesia (Motor fluctuations, End-of-dose wearing off, Unpredictable on-off response)
    —> **Psychiatric complications (Hallucinations, Psychosis)
    —> Can add **
    Atypical antipsychotics with low propensity for inducing extrapyramidal SE (e.g. Clozapine, Olanzepine, Quetiapine)
  2. MAOI (Monoamine oxidase B inhibitor)
    - ↓ breakdown of dopamine
  3. Dopamine receptor agonist
    - ↑ sensitivity of dopamine receptor
32
Q

Anti-inhibitory therapy

A

Surgical treatment
1. Lesioning specific D2 nuclei e.g. Pallidotomy, Thalamotomy
- Down-regulate D2 inhibitory pathway

  1. Deep brain stimulation (current)
    - Overdrive pacing of STN (subthalamic nucleus) with electrodes —> blockade effect
33
Q

Treatment flow of PD

A

Early disease, impaired ADL
—> **Tremor predominant: Selegiline, Anticholinergic, Levodopa
—> **
Other features dominant: Selegiline, Amantadine, Dopamine agonist, Levodopa

—> Good response: Lowest dose that maintains control
—> Poor / No response: ↑ Dose, Consider other diagnosis

Moderate impairment of ADL
—> Levodopa
—> Wearing off: Smaller + more frequent doses, Carbidopa Levodopa, Add Dopamine agonist, COMT inhibitor (Entacapone)
—> **Dyskinesia: ↓ Dose, Add Amantadine
—> **
Non-motor adverse effects: ↓ Dose, Add Quetiapine, Clozapine

Consider surgical options for severe, pharmacologically unaddressable detriments

34
Q

Other structures affected by PD

A

Apart form Substantia nigra pars compacta

  1. Ventral tegmental area
  2. Locus ceruleus
  3. Raphe nuclei
  4. Substantia innominate
  5. Intermediolateral column
  6. Olfactory bulb
35
Q

Parkinsonism

A
  • Occurs in all ethnicities groups
  • related to aging
  • clinical signs
36
Q

Other notes

A

Other notes

37
Q

Huntington’s disease

A
  • Manifest 30-50 yo
  • Chorea —> Dementia

Pathophysiology:
- Neuronal loss in **Striatum + **Cerebral cortex

Genetics:
- **Autosomal dominant
- **
Chromosome 4, repeat GAG

Behavioural problems:
- personality change
- affective disorders
- frank psychosis

Prevalence: 5-10 / 100,000

MRI / CT:
- Cortical + Caudate atrophy

Treatment:
- No cure
- ***Symptomatic (Haloperidol: atypical antipsychotic)

Clinical features:
- Marching the knee reflex

Prognosis:
- Death within 10-12 years

38
Q

Wilson’s disease (Hepatolenticular degeneration)

A
  • ***Autosomal recessive
  • Defect in copper-transporting ATPase coded on chromosome 13 (ATP7B gene) + Low Ceruloplasmin / Cannot incorporate Cu
    —> **Cu accumulation in Liver + **Basal ganglia
    —> Neurological manifestations in childhood / young adulthood
    —> Dyskinesia / Parkinsonism / Psychiatric problems

Features:
- Kayser-Fleischer rings (Cerebral involvement)

Prognosis:
- Untreated: die from **Cirrhosis / **Neurological complications within 10 years

Treatment:
- ***Penicillamine (Cu chelation)
- Liver transplantation (Cu removal)

Prevention:
- Family screening to detect presymptomatic cases —> treat with ZnSO4