Cerebellar Disorders and Movement Disorders

Question 1

What is cerebellar responsible for?

Answer 1

Cerebellum modulates Coordination and Learned Movement patterns rather than speed
Cerebellum receives afferents from Proprioceptive receptors (Inferior Cerebellar
Peduncles), Vestibular Nuclei, Basal Ganglia, Corticospinal System and Olivary Nuclei; Its
Effects leave (Mostly via Superior Cerebellar
Peduncles) to Red Nuclei, Vestibular Nuclei,
Basal Ganglia and Corticospinal System

Question 2

What does the lateral cerebellar lobe do

Answer 2

Lateral Cerebellar Lobe (Cerebrocerebellum)

coordinates movement of Ipsilateral Limbs;

Question 3

What does the vermis do?

Answer 3

Vermis (Spinocerebellum) concerned with

Maintenance of Axial Posture and Balance;

Question 4

What does the flocculonodular lobe do?

Answer 4

Flocculonodular Lobe (Vestibulocerebellum)
regulates Balance and Eye Movements

Question 5

What causes cerebellar lesions?

Answer 5

Cerebellar Lesions can be caused by Obstructive Hydrocephalus; Severe Pressure Headaches, Vomiting and Papilloedema; Alternatively, Coning of Cerebellar Tonsils leads to Respiratory Arrest due to compression of the Brainstem

Question 6

Lateral Cerebellar Hemisphere Lesions

Answer 6

• Disruption of Ipsilateral Normal Sequence of Movements (Dyssynergia); Rebound upward
overshoot; Gait becomes Broad and Ataxic faltering towards side of lesion
• Movement is imprecise in Direction, Force and Distance (Dysmetria); Dysdiadochokinesis
occurs; Intention Tremor and Past-Pointing; Speed of fine movements is preserved
• Nystagmus – Coarse Horizontal Nystagmus; Fast component moves towards side of lesion
• Dysarthria – Halting, Jerking, “Scanning” speech
• Titubation (Rhythmic head movements); Hypotonia and Hyporeflexia

Question 7

Midline Cerebellar Lesions

Answer 7

• Difficulty standing and sitting unsupported (Truncal Ataxia) with a Rolling, Broad, Ataxic Gait
• Lesions of the Flocculonodular Node can cause Vertigo and Vomiting with Gait Ataxia

Question 8

Physiological tremors

Answer 8

Physiologically normal 8-12Hz; Increased with Anxiety, Caffeine, Hyperthyroidism and Drugs; Occurs in Mercury poisoning

Question 9

Coarse Postural Tremor

Answer 9

seen in Benign Essential Tremor (5-8Hz) and in ETOH XS

Question 10

Intention Tremor

Answer 10

Exacerbated by Action; Associated with Past-pointing and Dysdiadochokinesis; Occurs in Cerebellar Lobe disease and Lesions of Cerebellar Peduncles;
Titubation and Nystagmus might be present

Question 11

Rest Tremor

Answer 11

Seen typically in Parkinson’s Disease; Worse at rest; 4-7 Hz (Pill-rolling Tremor)

Question 12

Coarse Tremors

Answer 12

can be seen in Red Nuclei lesions and rarely Frontal Lesions

Question 13

Who gets idiopathic parkinsons disease?

Answer 13

Prevalence 150 in 100,000; Prevalence increases sharply with Age (1 in 200 of 80+yrs); 1.5× more common in Men; Small increased risk in Rural living and Well Water consumption; Pesticide induced (i.e. MPTP related) causes severe Parkinsonism; Non-smokers have a higher
risk of developing Parkinson’s Disease

Question 14

Genetic Aetiology of IPD

Answer 14

• Significant genetic component; Gene Loci PARK 1-11; Rare but together account for large proportion of Early Onset and Familial Parkinson’s Disease

Question 15

Pathophysiology of Parkinson’s Disease

Answer 15

Presence of Neuronal Inclusions (Lewy Bodies) and Loss of Dopaminergic Neurones in Substantia Nigra Pars Compacta
o Lewy Bodies contain tangles of α-Synuclein and Ubiquiti; Becomes more widespread as PD progresses, spreading to Lower Brainstem, Midbrain and Cortex
o Degeneration of other Basal Ganglia Nuclei; Degree of Nigrostriatal Dopaminergic Cell Loss correlates with severity of Akinesia
o Average of 70% lost by time of first presentation

Question 16

Presentation of Parkinson’s Disease: Motor Symptoms

Answer 16

• Tremor – Starts in Fingers and Hands; Unilateral initially, spreading to leg on same side then opposite Arm; Present at rest and reduces when hand is in motion; Pill-rolling tremor pattern;
• Rigidity – Lead Pipe Rigidity; Not dependent on speed of movement (C/f Clasp Knife); Stiffness
+ Tremor = Cogwheel Rigidity
• Bradykinesia distinguished from Slowness of movements is progressive Fatiguing and
Decrement in Amplitude of repetitive movements; Difficulty initiating movement (usually Upper Limb); Rapid Dexterous movements impaired, Impassive Face (Serpentine Stare)
• Postural Instability – Stooped posture; Gait becomes shuffling with Small Stride, Slow Turns, Freezing and Reduced Arm Swing; May lead to falls although occurs late
• Micrographia (Writing becomes progressively smaller); Speech becomes Quiet, Indistinct and
Flat; Drooling and Dysphagia might feature; Leads to Aspiration Pneumonia

Question 17

Presentation of Parkinson’s Disease: Non Motor

Answer 17

• Anosmia (90% of patients) – Dopamine transmission required for Olfaction
• Depression/Anxiety (50%), Aches/Pains, REM Sleep Behaviour Disorder, Autonomic Features
(Urinary Urgency, Hypotension), Constipation, Restless Leg Syndrome
• Cognitive – Common in late stage PD (80%), develop into Dementia; Depression is common due to involvement of Serotonergic and Adrenergic Systems; Anxiety is also comorbid

Question 18

Progression of Parkinson’s

Answer 18

• PD progressively deteriorates; Most patients respond well to treatment but might become treatment unresponsive when Cognitive Impairment, Dysphagia and Postural Instability/Falls start to develop by mid-70s
• Death commonly resulting from Bronchopneumonia (Infective, Aspiration) and Immobility

Question 19

Diagnosis of Parkinson’s Disease

Answer 19

• Clinical Diagnosis; rule out other Parkinsonian Syndromes
• MRI Head would be normal; Dopamine Transporter (DaT)
imaging to access Nigrostriatal Cell Loss; Cannot distinguish between PD and other Akinetic-Rigid
Syndromes but can rule out Drug Induced Parkinsonism

Question 20

Treatment of Parkinson’s Disease

Answer 20

Dopamine Replacement is not always needed in Early-stage PD; Only started in disability;
Treatment of Non-Motor Symptoms E.g. Depression, Constipation, Pain and Sleep disorders
• Levodopa – Most effective form of treatment; Combined with DOPA Decarboxylase Inhibitor (e.g. Benserazide in Co-Beneldopa or Carbidopa in Co-Careldopa) to reduce Peripheral side
effects (Nausea, Hypotension)

Question 21

Pharmacology of Parkinson’s treatment

Answer 21

• Dopamine Agonists – Used in combination with Levodopa or Initial Monotherapy in patients
65-70; Fewer motor complications but less effective and less tolerated then Levodopa
o Non-Ergot derived e.g. Pramipexole, Ropinirole used in preference to Ergot-derived, which are associated with fibrotic reactions (e.g. Valvular Fibrosis)

• Selegiline and Rasagiline (MAOB Inhibitors), Amantadine (? MOA), Anticholinergics (Rarely
used; Causes confusion in older patients), Apomorphine (Potent short acting Dopamine Agonist used as a rescue or maintenance by infusion pump for Advanced PD)

Question 22

How does medical therapy change as PD develops

Answer 22

• Medical therapy becomes more difficult as disease progresses; Approximately 10% of patients per year develop complications from therapy (Wearing off, Dyskinesia/Choreiform
movements, On/Off Phenomenon);

Question 23

What are strategies for managing motor complications?

Answer 23

o Dose Fractionation of Levodopa
o COMT Inhibitors (Entacapone) to prolong duration of Levodopa
o Slow release Levodopa; Mostly used for overnight
o Avoid protein rich meals; Taking doses at least 40 minutes prior to
meals
o Apomorphine Continuous
Infusion, Deep Brain Stimulation, Levodopa intestinal gel

Question 24

Neurosurgery in Parkinson’s

Answer 24

• Deep Brain Stimulation – Stereotactic insertion of Electrodes into the Basal
Ganglia/Thalamus; Usually for patients <70yrs; Subthalamic Nucleus, Globus
Pallidus (Improves Dyskinesia only),

Question 25

Other therapies in managing Parkinson's

Answer 25

PT and OT – Walking Aids, SALT, Falls prevention, External Cueing Techniques

Question 26

Drug Induced Parkinsonism

Answer 26

• Dopamine Blockage/Depletion by drugs e.g. Neuroleptics (except Clozapine) induce Parkinsonism, or worsen symptoms in affected patients; May precipitate symptoms

Question 27

Atypical Parkinsonism

Answer 27

• Other Neurodegenerative Diseases which affect the Basal Ganglia; Progressive, although might respond to Levodopa; Usually causes death within a decade o Red Flags – Symmetrical initial response, Absence of Tremor, Levodopa unresponsiveness, Early falls (within first year) and Wheelchair use

Question 28

Progressive Supranuclear Palsy

Answer 28

(Steele-Richardson-Olszewski) – Parkinsonism, Postural Instability with Early Falls, Vertical Supranuclear Gaze Palsy, Pseudobulbar Palsy and Dementia; Associated with Tau Deposition o Affects Basal Ganglia, Brainstem, Cerebral Cortex (Especially Frontal), Dentate Nucleus of Cerebellum and Spinal Cord (might affect Continence)

Question 29

Multiple System Atrophy

Answer 29

Parkinsonism with Autonomic Symptoms and Ataxia; Associated with α-Synuclein Glial Cytoplasmic Inclusions; Neuron loss and Gliosis

Question 30

Corticobasal Degeneration

Answer 30

Alien Limb Phenomena, Myoclonus and Dementia

Question 31

Wilson's Disease

Answer 31

• Disorder of Copper Metabolism; Deposition into Basal Ganglia, Cornea and Liver causing Cirrhosis; Should be considered in patients <50yrs with Akinetic-Rigid Syndrome or any Hyperkinetic Movement Disorder with Liver Cirrhosis • Investigations include Serum Copper and Caeruloplasmin • Intellectual Impairment develops; Neurological damage reversible with early treatment • Treat with Chelating Agent (e.g. Penicillamine)

Question 32

Hyperkinetic Movement Disorders

Answer 32

• Tremor (Rhythmic Oscillation), Chorea (Excessive Irregular Movements Fitting from one body part to another), Myoclonus (Brief Electric shock-like Jerks), Tics (Stereotyped movements or Vocalisations) and Dystonia (Sustained muscle spasms causing twisting movements and abnormal posturing)

Question 33

Essential Tremor

Answer 33

* Inherited in Autosomal Dominant manner; Bilateral, Fast low amplitude tremor mainly in Upper Limbs; Head and Voice occasionally involved * Tremor is postural; Starts at any age but usually early in life; Slowly progressive but rarely causes severe disability, exacerbated by Anxiety * Treatment is unnecessary and mostly unhelpful; Small amounts of Alcohol, Propranolol, Primidone or Gabapentin might help * Stereotactic Thalamotomy and DBS used in severe cases

Question 34

Hemiballismus

Answer 34

• Infarction/Haemorrhage of Contralateral Subthalamic Nucleus leads to Violent Swinging Movements due to loss of Indirect Pathway (Basal Ganglia loop involved in Inhibition) • Acute Chorea-Hemiballismus can also occur after Diabetic HONK; Osmotic shift causing Myelinolysis seen in CT/MRI imaging of the Basal Ganglia

Question 35

Causes of Chorea

Answer 35

* Causes include Thyrotoxicosis, SLE, Antiphospholipid Syndrome, Polycythaemia * Genetic causes – Huntington’s Disease, Neuroacanthocytosis, Benign Hereditary Chorea * Structural disorders of Basal Ganglia, Drugs (Levodopa, Oral Contraceptives), Pregnancy * Post-Infective – Sydenham’s Chorea Post Streptococcus or Acute Rheumatic Fever * Dopamine Blockade (Phenothiazines) or Depleting (Tetrabenazine) drugs

Question 36

Huntington's Disease Presentation

Answer 36

• Usually presenting in Middle age; Subtle fidgeting followed by Progressive Psychiatric and Cognitive symptoms; Prevalence worldwide of 5 per 100,000

Question 37

Huntington's Disease Genetics

Answer 37

• Due to CAG repeat expansion; Translation of expanded Polyglutamine repeat sequence in Huntingtin; Thought to be toxic gain-of-function protein • Repeat length inversely related to age at onset (Juvenile patients have over 60 repeats); Anticipation – Successive generations have Earlier Onset and more Severe disease o Expansion of CAG repeats occurs during Meiosis especially in Spermatogenesis

Question 38

Huntington's Treatment

Answer 38

Autosomal Dominant with Complete Penetrance; No disease modifying treatment; Chorea improved with Dopaminergic Blockade/Depletion although Progressive Neurodegeneration leads to Dementia and ultimately death after 10-20yrs

Question 39

Myoclonus

Answer 39

* Cortical Myoclonus – Distal presentation (Hands and Fingers) and Stimulus Sensitive (Spontaneous or Triggered by Touch/Loud noises) * Spinal/Brainstem Myoclonus – Localised lesions

Question 40

Primary Myoclonus

Answer 40

Physiologically normal Nocturnal Myoclonus (Commonly feeling of falling); Startle response is a form of Brainstem Myoclonus

Question 41

Myoclonic Dystonia

Answer 41

Rare Autosomal Dominant disorder due to mutations in ε-Sarcoglycan Gene (DYT11); Allelic with Benign Essential Myoclonus o Sarcoglycan involved in connecting the Muscle fibre cytoskeleton with ECM

Question 42

Secondary Myoclonus

Answer 42

• Seen in wide variety of Metabolic Disorders including Hepatic/Renal Failure (Asterixis = Liver Flap), Part of Dementias and Neurodegenerative Disorders, Encephalitis • Post-Anoxic Myoclonus secondary to Severe Cerebral Anoxia

Question 43

Progressive Myoclonic Epilepsy Ataxia Syndromes

Answer 43

* Rare conditions of Genetic and Metabolic Disorders; Myoclonus accompanying Progressive Epilepsy, Cognitive Decline and Ataxia * E.g. Lafora Body Disease, Neuronal Ceroid Lipofuscinosis, Unverricht-Lundborg disease

Question 44

Tics

Answer 44

• 15% Lifetime prevalence; Brief stereotyped movements affecting Face and Neck; Might also affect any other body part (e.g. Vocal Tics); Can be suppressed, leading to build up of Anxiety and Overflow leading to release • Simple transient Tics – Blinking, Sniffing, Facial Grimacing are common in childhood • Adult Onset Tics are rare; Usually secondary cause

Question 45

Tourette's

Answer 45

Commonest cause of Tics; Multiple Motor Tics and at least one Vocal Tic starting in Childhood and persisting longer than 1yr; 3× more common in Boys • Coexists with Behavioural problems including ADHD, OCD; Major cause of disability • Explosive Barking, Grunting of Obscenities (Coprolalia), Gestures (Copropraxia) and Copying what other people say (Echolalia) • Thought to be complex problem regarding Histaminergic Neurotransmission

Question 46

Primary Dystonia

Answer 46

Only or Main Clinical Manifestation; Usually Genetic

Question 47

Secondary Dystonia

Answer 47

Due to Brain Injury, Cerebral Palsy or Drugs

Question 48

Heredo-degenerative dystonia

Answer 48

Wider Neurodegenerative Disorder

Question 49

Paroxysmal Dystonia

Answer 49

Rare, mostly genetic attacks of Chorea and Dystonia

Question 50

Young Onset Primary Dystonia

Answer 50

* Mutations in DYT1 Gene causes Limb-Onset Dystonia in Adolescence * Most patients have GAG Deletion in TorsinA ER ATPase protein; Autosomal Dominant, Low Penetrance, Variable Phenotype that can progress to Generalised Dystonia * Cognitive function is intact; Definitive treatment of severe disease by DBS

Question 51

Adult Onset Primary Dystonia

Answer 51

* Much more common; Onset around 55yrs; Focal; Affects Head and Neck mostly * Treatment by Targeted injection of Botulinum Toxin into affected muscles for all Focal Dystonias; Antimuscarinics (e.g. Trihexyphenidyl) sometimes helpful

Question 52

Torticollis

Answer 52

Dystonic spasms in Neck Muscles causing head turning or drawn backwards; Jerky Head Tremor might be present; Sensory Trick (Geste) might relieve spasm temporarily

Question 53

Writer's Cramp/ Task Specific Dystonia

Answer 53

Specific inability to perform previously Highly-developed Repetitive Skilled Movement, instead provoking Dystonic posturing; Other functions remain normal o Overuse may lead to Task-specific Dystonias e.g. Musicians, Typists

Question 54

Blepharospasm and Oromandibular Dystonia

Answer 54

Spasms of forced blinking, Involuntary movement of the Mouth/Tongue; Speech might be affected

Question 55

DOPA-Responsive Dystonia (DRD)

Answer 55

Typically Dystonic Walking begins in Childhood; Resemble Spastic Paraparesis/Cerebral Palsy o Dominantly Inherited Mutations in GTP Cyclohydrolase Gene; Codes for protein needed for Dopamine Synthesis Patients with Dystonic Gaits sometimes given Levodopa trials

Question 56

Drug Induced Dystonia

Answer 56

``` Drug Induced (Neuroleptics) causing Akathisia (Restless, Repetitive, Irresistible need to move), Parkinsonism (D1 and D2 Receptor Blockade), Acute Dystonic reactions (Spasmodic Torticollis, Trismus and Oculogyric Crises (Episodic Sustained Upward gaze) o ```

Question 57

Tardive Dyskinesia

Answer 57

Tardive Dyskinesia – Mouthing and Lip-Smacking Grimaces after years of Neuroleptic use; Temporarily worsens when drug stopped/reduced; Atypical Neuroleptics less prone to cause