Cerebellar Disorders and Movement Disorders Flashcards
What is cerebellar responsible for?
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
What does the lateral cerebellar lobe do
Lateral Cerebellar Lobe (Cerebrocerebellum)
coordinates movement of Ipsilateral Limbs;
What does the vermis do?
Vermis (Spinocerebellum) concerned with
Maintenance of Axial Posture and Balance;
What does the flocculonodular lobe do?
Flocculonodular Lobe (Vestibulocerebellum) regulates Balance and Eye Movements
What causes cerebellar lesions?
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
Lateral Cerebellar Hemisphere Lesions
• 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
Midline Cerebellar Lesions
- 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
Physiological tremors
Physiologically normal 8-12Hz; Increased with Anxiety, Caffeine, Hyperthyroidism and Drugs; Occurs in Mercury poisoning
Coarse Postural Tremor
seen in Benign Essential Tremor (5-8Hz) and in ETOH XS
Intention Tremor
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
Rest Tremor
Seen typically in Parkinson’s Disease; Worse at rest; 4-7 Hz (Pill-rolling Tremor)
Coarse Tremors
can be seen in Red Nuclei lesions and rarely Frontal Lesions
Who gets idiopathic parkinsons disease?
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
Genetic Aetiology of IPD
• Significant genetic component; Gene Loci PARK 1-11; Rare but together account for large proportion of Early Onset and Familial Parkinson’s Disease
Pathophysiology of Parkinson’s Disease
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
Presentation of Parkinson’s Disease: Motor Symptoms
• 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
Presentation of Parkinson’s Disease: Non Motor
• 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
Progression of Parkinson’s
- 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
Diagnosis of Parkinson’s Disease
• 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
Treatment of Parkinson’s Disease
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)
Pharmacology of Parkinson’s treatment
• 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)
How does medical therapy change as PD develops
• 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);
What are strategies for managing motor complications?
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
Neurosurgery in Parkinson’s
• Deep Brain Stimulation – Stereotactic insertion of Electrodes into the Basal
Ganglia/Thalamus; Usually for patients <70yrs; Subthalamic Nucleus, Globus
Pallidus (Improves Dyskinesia only),
Other therapies in managing Parkinson’s
PT and OT – Walking Aids, SALT, Falls prevention, External Cueing Techniques
Drug Induced Parkinsonism
• Dopamine Blockage/Depletion by drugs e.g. Neuroleptics (except Clozapine) induce
Parkinsonism, or worsen symptoms in affected patients; May precipitate symptoms
Atypical Parkinsonism
• 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
Progressive Supranuclear Palsy
(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)
Multiple System Atrophy
Parkinsonism with Autonomic Symptoms and Ataxia; Associated with α-Synuclein Glial Cytoplasmic Inclusions; Neuron loss and Gliosis
Corticobasal Degeneration
Alien Limb Phenomena, Myoclonus and Dementia
Wilson’s Disease
• 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)
Hyperkinetic Movement Disorders
• 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)
Essential Tremor
- 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
Hemiballismus
• 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
Causes of Chorea
- 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
Huntington’s Disease Presentation
• Usually presenting in Middle age; Subtle fidgeting followed by Progressive Psychiatric and Cognitive symptoms; Prevalence worldwide of 5 per 100,000
Huntington’s Disease Genetics
• 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
Huntington’s Treatment
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
Myoclonus
- Cortical Myoclonus – Distal presentation (Hands and Fingers) and Stimulus Sensitive (Spontaneous or Triggered by Touch/Loud noises)
- Spinal/Brainstem Myoclonus – Localised lesions
Primary Myoclonus
Physiologically normal Nocturnal Myoclonus (Commonly feeling of falling); Startle response is
a form of Brainstem Myoclonus
Myoclonic Dystonia
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
Secondary Myoclonus
• 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
Progressive Myoclonic Epilepsy Ataxia Syndromes
- 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
Tics
• 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
Tourette’s
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
Primary Dystonia
Only or Main Clinical Manifestation; Usually Genetic
Secondary Dystonia
Due to Brain Injury, Cerebral Palsy or Drugs
Heredo-degenerative dystonia
Wider Neurodegenerative Disorder
Paroxysmal Dystonia
Rare, mostly genetic attacks of Chorea and Dystonia
Young Onset Primary Dystonia
- 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
Adult Onset Primary Dystonia
- 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
Torticollis
Dystonic spasms in Neck Muscles causing head turning or drawn backwards; Jerky Head Tremor might be present; Sensory Trick (Geste) might relieve spasm temporarily
Writer’s Cramp/ Task Specific Dystonia
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
Blepharospasm and Oromandibular Dystonia
Spasms of forced blinking, Involuntary movement of the Mouth/Tongue; Speech might be affected
DOPA-Responsive Dystonia (DRD)
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
Drug Induced Dystonia
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
Tardive Dyskinesia
Tardive Dyskinesia – Mouthing and Lip-Smacking Grimaces after years of Neuroleptic use; Temporarily worsens when drug stopped/reduced; Atypical Neuroleptics less
prone to cause
