JC23 (Medicine) - Cerebellar Lesions and Gait Disorders Flashcards
Outline the anatomical components to control normal gait
□ Higher control: premotor cortex, motor cortex >> Pyramidal tract
□ Pattern generator:
Midbrain locomotor region (MLR) generates drive
Spinal locomotor network (SLN) allows rhythm generation and pattern formation
>> Reticulospinal tract
□ Effector: spinal reflex pathways to PNS/ motor unit
□ Regulation: Extrapyramidal system → upper level (initiation) Cerebellar system → middle level (synergy) Spinal reflex pathways → lower level (effector)
Anatomical components that control initiation, pattern, rhythm and end of normal gait?
Initiation:
- Premotor
- Motor cortices
Synergy: subcortical centres
- Mesencephalic/ Midbrain locomotor region (MLR)
- Spinal locomotor network (SLN)
Anatomical components that control posture and balance of normal gait
Regulatory:
- Basal ganglia
- Cerebellum
- Vestibular/proprioceptive apparatus
List 7 types of gait disorders
Ataxic gait
Parkinsonian gait
Hemiplegic/ diplegic/ spastic gait
Apraxic gait
Antalgic gait
LMN gait: Myopathic Waddling gait, Neuropathic steppage gait
Features of hemiplegic gait
unilateral arm + leg paralysis
Features: mimicks ancient reflexive gait
Arm: adducted and internally rotated at shoulder, flexed at elbow, pronation of forearm, flexion of wrist and fingers
Leg:
- Abduction and circumduction at hip to prevent dragging
- Knee extended, foot plantarflexed and inversion at foot
Features of paraplegic gait
spastic paraplegia
□ Features: scissor-like posture due to adductor spasm + extensor tightness
→ Strong adduction at hips
→ Two legs perform circumduction
Features of Parkinsonian gait
Features:
□ Flexed, stooping posture
□ Bradykinesia: hesitation in starting, freezing
□ Festination: initial hesitance
→ leans forward to initiate walking
→ hurries in shuffling steps to ‘catch-up’ on himself
Features of apraxic gait
Cause: bilateral frontal lobe or hemispheric diseases
Features:
□ Wide-based gait
□ Poor initiation – leg appear stuck to the floor
□ Tendency to fall backwards
Features of ataxic gait (cerebellar or sensory ataxia)
Cerebellar ataxia: ‘drunken’ gait
- Wide-based (shoulder-wide) Jerk and unsure steps varying in size
- Trunk sways forward
- May only be detectable in tandem gait in mild cases
Sensory ataxia: ‘stomping’ gait
- Gait appear normal with eyes open
- Feet appear to ‘stomp’ on ground → to enhance proprioceptive input
Features of neuropathic gait
□ Cause: LMN weakness of pretibial and peroneal muscles (dorsiflexors)
□ Features:
→ Leg lifted high for toe clearance
→ Toes touch ground before heels
Features of myopathic gait
□ Cause: proximal myopathy → bilateral hip adductor weakness → inability to fix pelvis during walking
□ Features: ‘waddling gait’
→ Bilateral dropping of pelvis
→ Appears as swaying buttocks
Features of antalgic gait
□ Cause: pain with weight bearing
□ Feature:
→ Shortened stance relative to swing phase
7 types of hyperkinetic disorders
Chorea
Ballismus
Athetosis/ Choreoathetosis
Dystonia
Tremor
Myoclonus
Tics
Define tremor
alternating contractions of antagonistic muscle groups causing involuntary rhythmic oscillation of body parts
3 major types of tremor
□ Rest tremor: occurs in supported body parts w/o ms activation
□ Postural tremor: occurs when maintaining certain posture
□ Kinetic tremor: occurs during voluntary movement
→ Simple kinetic tremor
→ Intention tremor
→ Task-specific tremor e.g. writing
1 Example of rest tremor
Features
Parkinsonian tremor:
Coarse, low-frequency (3-4Hz) tremor
Typically starts at unilateral UL and spread to other limbs
Associated with rigidity and bradykinesia
2 examples of kinetic tremor
Features
Essential tremor
- Variable amplitude, high-frequency (8-10Hz) tremor
- Postural and kinetic tremor, NOT at rest
- Typically affects bilateral arms (not LL) and head
Cerebellar tremor
- Coarse, low-frequency (4-6Hz) tremor
- Intention tremor
1 example of postural tremor
Features
Physiological tremor
Low-amplitude, high frequency (10-12Hz) tremor
Symmetrical and distal in distribution
Not evident in normal circumstances
Triggers of physiological tremor
- anxiety,
- emotional stress,
- drugs (eg. β2-agonist and other catecholaminergic drugs, lithium, antidepressants),
- alcohol/opioid withdrawal,
- thyrotoxicosis,
- fever
Describe chorea movement
sudden, unpredictable/ Random**
quasipurposive
involuntary fidgety/jerky movement
Describe Athetosis movement
slower, coarser, more writhing movement, esp affecting distal parts of limbs
Describe Ballism movement
involuntary movement that are proximal and large amplitude with a flinging/kicking character
□ Most often unilateral (hemiballism)
□ Classically a/w contralateral subthalamic nucleus stroke
Causes of choreiform movements
disruption in basal ganglia circuitry resulting in imbalance between indirect and direct pathways
□ Inherited: Huntington’s disease, Wilson’s disease, neuro-acanthocytosis…
□ Vascular: basal ganglia stroke
□ Inflammatory: Sydenham chorea, SLE, vasculitis
□ Neoplastic: Basal ganglia tumours, paraneoplastic chorea
□ Drugs: neuroleptics, levodopa, DA, antihistamines, amphetamines, digoxin, OC pills
□ Infectious: AIDS, neurosyphilis, cerebral malaria…
□ Metabolic: kernicterus, polycythaemia vera, hypoparathyroidism, chorea gravidorum (in pregnancy)
Diagnosis and management of choreiform movement disorders
Diagnosis: Hx, neurological/CVS exam + slit-lamp examination
Mx: tetrabenazine and clonazepam for symptomatic
Tics
- Describe
- Types
- Control?
abrupt stereotyped repetitive movements involving discrete muscle groups
□ Can mimic normal coordinated movements, vary in intensity and lack rhythm
→ Motor tics, eg. eye-blinks, shoulder shrugs, facial grimaces…
→ Phonic tics, eg. barks, grunts, swearing…
□ May be temporarily inhibited by will power and usually disappear by sleep
Causes of primary tics (-)
2 types of primary tics
no underlying structural lesions, usually onset in childhood and resolves after 20y
→ Transient tic disorder: last <1y, occurs in normal children
→ Gilles de la Tourette syndrome: otherwise unexplained motor + phonic tics with onset <21y
Causes of secondary tics (-)
tics begin abruptly, are persistent or are problematic
→ Eg. dopaminergic drugs, stimulants, neuroleptics, other inherited diseases
Management of tics (-)
Behavioural Tx (eg. habit reversal treatment) as mainstay
Drugs:
□ D2 blockers: haloperidol, pimozole, aripiprazole → risk of tardive dyskinesia → ↓use nowadays
□ Dopamine depleters: tetrabenazine → usually 1st choice nowadays after failure of behavioural Tx
□ α-agonists: guanfacine, clonidine → used if concomitant ADHD + Tourette syndrome
Describe Myoclonus
brief, repetitive, involuntary sudden ‘shock-like’ jerks of muscle groups
Results from focal discharge from cortex (majority), subcortical or spinal cords
Causes of myoclonus (-)
□ Physiological: hypnic (during sleep transitions), anxiety-related, exercise-related
□ Essential myoclonus
□ Epileptic myoclonus: a/w seizure syndrome, eg. juvenile myoclonic epilepsy
□ Symptomatic (secondary) myoclonus:
→ Focal CNS lesions, eg. post-stroke, CNS tumour
→ Metabolic and toxic encephalopathies
→ Neurodegenerative diseases, eg. CJD, Alzheimer’s disease, CBD
→ Metabolic storage diseases
→ Progressive myoclonic epilepsy (with progressive cognitive decline, seizures, ataxia and death)
Describe Dystonia
Sustained/intermittent involuntary muscle contractions in antagonistic muscle groups causing abnormal movements or distorted postures
Dystonic movements are typically patterned, twisting and may be tremulous, i.e. dystonic tremor
Types of Dystonia (-)
□ Focal: a group of muscles, eg. blepharospasm, oromandibular dystonia, cervical dystonia
□ Segmental: contiguous groups of muscles, eg. craniobrachial dystonia, Meige syndrome
□ Multifocal: ≥2 non-contiguous groups of muscles
□ Generalized, eg. idiopathic torsion dystonia
Dystonia (-)
- Exacerbating factors
- Relieving factors
- Extent of limb involvement
Exacerbating factors: voluntary action, fatigue, stress and emotional states
Relieving factors: sensory tricks (geste antagoniste, eg. touching face), sleep and relaxation
Extent of limb involvement: LL onset in early onset vs facial, neck or UL onset in late onset
3 causes of dystonia (-)
Idiopathic torsion dystonia:
→ Hereditary: early onset (<21y), LL focal onset becoming generalized
→ Sporadic: adult onset (>21y), UL, facial or cervical onset w/o generalization
Secondary dystonia
→ Brain injury, eg. cerebral palsy, head injury
→ Neurodegenerative diseases, eg. Parkinsonism, spinocerebellar ataxia, Huntington’s disease
→ Drug-induced, eg. anticonvulsants, CCB, DA-agonist, levodopa, neuroleptics
Treatment of dystonia (-)
Pharmacotherapy:
levodopa (if young-onset), anticholinergic/BZD (if adult-onset)
Botox injection
3 Anatomical divisions of cerebellum
3 Functional divisions of cerebellum
Anatomical: Anterior lobe, Posterior lobe, Flocculonodular lobe
Functional:
- Vestibulocerebellum - flocculonodular lobe for vestibular reflexes
- Spinocerebellum - Vermis and intermediate zone for error-detection of truncal and distal muscles
- Cerebrocerebellum - hemisphere for motor planning, rapidly alternating movement
Clinical features of midline cerebellar lesion
Spinocerebellum - Vermis and intermediate zone for error-detection of truncal and distal muscles
□ Nystagmus: horizontal or vertical nystagmus
□ Truncal ataxia: wide-based cerebellar gait, Romberg –ve
□ LL dysmetria: heel-shin test
Clinical features of hemispheric cerebellar lesions
Cerebrocerebellum - hemisphere for motor planning, rapidly alternating movement
abnormalities in limb coordination
□ Limb ataxia: UL dysmetria, intention tremor, dysdiadochokinesia, rebound, gait ataxia
□ Scanning dysarthria: same emphasis put on each syllable
Acute causes of cerebellar signs
Vascular
Cerebellar ischaemia
Cerebellar haemorrhage
Drugs and toxins*
Antiepileptics, eg. phenytoin
Chemo, eg. cytarabine, 5FU
Alcohol
Infectious
Meningoencephalitis
ADEM
Subacute causes of cerebellar signs (-)
Autoimmune*
Multiple sclerosis
Miller-Fisher syndrome
SLE, Behcet’s, coeliac…
Paraneoplastic degeneration*
SCLC, gyne, breast, lymphoma
Neoplastic, esp CPA tumours
Metabolic*
Chronic alcoholism
Wernicke encephalopathy (vitamin B1 deficiency)
Vitamin E deficiency
Hypothyroidism
Chronic progressive causes of cerebellar signs (-)
Congenital
Chiari malformation
Dandy-Walker syndrome
Cerebellar agenesis
Hereditary*
Spinocerebellar ataxia (AD) - SCA
Friedreich’s ataxia (AR) - FA
Ataxia-telangiectasia (AR) - AT
Wilson’s disease (AR)
Mitochondrial diseases
Neurodegenerative*
Multiple system atrophy (MSA)
Progressive supranuclear palsy (PSP)
Cerebellar degeneration
Define Parkinson’s disease
idiopathic degeneration of substantia nigra with intraneuronal Lewy bodies
Classic symptoms of parkinonism
Extrapyramidal symptoms:
- Tremor: develops early unilaterally, 4-6Hz, decrease in late stage due to bradykinesia and rigidity
- Rigidity: ‘Cogwheel’ or ‘lead-pipe’ rigidity, flexed/stooped posture
- Akinesia or bradykinesia: slowness, hesitance, motor arrest
- Postural instability: imbalance and falls, propulsion/ retropulsion when standing
Examples of bradykinesia due to Parkinson’s
Loss of finger dexterity
Shuffling gait
Masked face
Monotonous speech
Drooling saliva (slow swallowing)
Ddx Parkinson’s disease
Idiopathic Parkinsonism (Parkinson’s disease, PD): commonest, 80% of cases
Parkinsonian-plus syndromes:
□ Multisystem atrophy (MSA)
□ Progressive supranuclear palsy (PSP, Steele-Richardson-Olzewski syndrome)
□ Corticobasal degeneration (CBD)
Secondary (symptomatic) parkinsonism:
□ Post-encephalitic, eg. encephalitis lethargica
□ Drug-induced, eg. dopamine-depleting/anti-dopaminergic drugs, lithium, antihistamines
□ Chronic head trauma, eg. ‘punch-drunk’ syndrome
□ Neoplastic, eg. parasagittal meningioma
Inherited neurodegenerative diseases:
□ Wilson’s disease
□ Hallervorden-Spatz syndrome
Pseudoparkinsonism:
□ Cerebral arteriosclerotic disease
Essential tremor, Cerebellar tremor (intention), Akinetic Huntington’s chorea
Pathophysiology of Parkinson’s disease
□ Motor symptoms: Depletion of dopaminergic neurons, degeneration of nigrostriatal pathway → ↓dopamine input to striatum → balance shifted towards indirect pathway → bradykinesia, rigidity
□ Cognitive symptoms: degeneration of mesocortical/mesolimbic dopaminergic pathways
□ Autonomic dysfunction: dopamine depletion in hypothalamus
□ Dementia: degeneration of cholinergic nucleus (spread of Lewy Bodies to cortex)
List non-motor symptoms of Parkinson’s disease
Neuropsychiatric:
- Depression
- Anxiety
- PD-psychosis: common in late stages, can be due to levodopa
PD-Dementia
Autonomic dysfunction:
- Postural hypotension
- Constipation
- Sweating
Miscellaneous: fatigue, pain, sleep disturbance, sexual disturbance, anosmia
Severity staging of Parkinson’s Disease
Clinical red flags of parkinsonism
Presentation:
* Young onset with strong family history
* Rapid progression
* Early instability and falls
* Early and prominent dementia
Extent:
* Pyramidal/ cerebellar signs
* Autonomic dysfunction
Treatment:
* Poor response to Levodopa
Outline Clinical Diagnostic criteria of Parkinson’s disease ***
UKPD Society Brain Bank Clinical Diagnostic Criteria
Clinical features: Bradykinesia + at least one of:
- Muscular rigidity,
- 4-6Hz rest tremor,
- postural instability without primary visual, vestibular, cerebellar or proprioceptive_dysfunction
Exclusion criteria: exclude other diseases
Supportive prospective positive criteria: 3+ for def. dx
Unilateral onset
Rest tremor present
Progressive, persistent asymmetrical involvement
excellent response to levodopa for 5 years or more
Severe levodopa induced chorea
clinical course of ten years or more
S/S that indicate alternative diagnosis to Parkinson’s disease (-)
□ Onset/course: sudden onset, rapid progression, young onset with strong FHx of other ds
□ Clinical pattern: early and prominent dementia, early frequent falls, early incontinence, no tremor in presence of significant bradykinesia
□ S/S of other causes: pyramidal/cerebellar signs/autonomic dysfx (MSA), gaze palsy (PSP), cortical signs/alien hand syndrome (CBD)
□ Retrospective: poor treatment response to levodopa (PD usually excellent response)
Specific imaging for Parkinson’s disease
CT/MRI to rule out alternative causes
Dopaminergic SPECT/PET: ↓dopamine activity in basal ganglia: examples:
- DaT scan (SPECT)
- 18F-Dopa Scan, 11C- Raclopride PET scan
- MRI - DTI, DWI, ADC mapping
Treatment outline for PD
Initial treatment: Levodopa
Adjunctive treatment for dyskinesia or motor fluctuation
Options: dopamine agonist, MAO-B inhibitor, COMT inhibitor
Surgical Tx considered for pharmacologically refractory cases
Examples of levodopa-based treatment for PD
eg. Sinemet (levodopa + carbidopa), Madopar (levodopa + beserazide)
MoA of levodopa + carbidopa/ beserazide (-)
MoA:
Levodopa is precursor of dopamine → decarboxylated into dopamine → replenishes inadequate dopamine in striatum
Carbidopa/ Beserazide: Peripheral DOPA decarboxylase inhibitor cannot pass BBB → Decrease peripheral decoration of levodopa → Decrease peripheral side effects, Increase central availability
Levodopa S/E
→ Nausea, vomiting, orthostatic hypotension
→ Confusion and visual hallucinations
→ Impulse control disorders: eg. compulsive cleaning, gambling, hypersexuality
→ Dopamine dysregulation syndrome/ Addiction: compulsive use of dopaminergic drug (addiction)
Outline treatment plan for PD by: (-)
- Tremor predominant or not
- Good response to therapy or not
- Impairment of ADL or not
Long term Dopamine therapy complications *
- Loss of efficacy
- Motor fluctuations: unpredictable response to levodopa with On and Off episodes
- Dyskinesia: Chorea and dystonia in peak-dose or diphasic
- Psychiatric complications
Adjunct therapy to levodopa for PD
Dopamine agonist (DA), eg. rotigotine (skin patch), pramipexole, ropinirole, apomorphine
MAO-B inhibitor (MAOI), eg. selegiline, rasagiline
□ MoA: inhibitor of monoamine oxidase → decrease DA breakdown
Catechol-O-methyltransferase (COMT) inhibitor, eg. entacapone
□ MoA: ↓methylation of dopamine and levodopa → increase duration of action of levodopa
Salvage therapy for long-term levodopa use
Amantadine:
□ MoA: unknown, likely a/w NMDA receptor blockade
□ Use: treatment of LD-induced dyskinesias
Anticholinergics, eg. orphenidrine, benzhexol (Artane), benztropine
□ MoA: inhibitor muscarinic cholinergic fibres in striatum → ↓inhibition
□ Use: initial therapy in young-onset pt w/ prominent dystonia and tremor
2 surgical options for PD
Destructive neurosurgery:
→ Thalamotomy for control of medically intractable tremor
→ Pallidotomy for control of LD-induced dyskinesias, rigidity, bradykinesia, tremor
Deep brain stimulation (DBS): medically refractory tremor or motor fluctuation
Management options for non-motor symptoms of PD
Psychosis: antipsychotics (eg. quetiapine, clozapine, pimavanserin)
PD-Dementia: cholinesterase inhibitor
Depression: desipramine (TCA) and citalopram (Refute most SSRIs)
(SSRIs can interact with MAOI (5HT syndrome) and a/w risk of ↑motor symptoms)
