5 Movement and Neurodegenerative Disorders 5.1 Approach to Movement Disorders 5.1.1 Approach to Abnormal Movements Ref: Davidson Ch26, Neurology in Practice Ch8, JC23, JC Teaching clinic, Maudsley’s guidelines Ch2 Movement disorders are divided into: □ Hyperkinetic disorders: tremor, chorea/choreoathetosis, tics, ballismus, myoclonus, dystonia, stiff-person syndrome □ Hypokinetic disorders: Parkinsonism, catatonia Note that functional movement disorders (common) may mimic any syndrome patterns A. Tremor Tremor: alternating contractions of antagonistic muscle groups causing involuntary rhythmic oscillation of body parts Types of tremor: □ Rest tremor: occurs in supported body parts w/o ms activation Test: observe with body part supported, ↑by mov’t in other body parts and ↓by its own mov’t □ Postural tremor: occurs when maintaining certain posture Test: observe by extending UL horizontally, pointing at objects, sitting erect w/o support, standing, protruding tongue □ Kinetic tremor: occurs during voluntary movement → Simple kinetic tremor: tremor roughly the same throughout course of a voluntary movement → Intention tremor: crescendo increase as affected body part approaches its target → Task-specific tremor: occurs during specific task, eg. primary writing tremor Example Features Comments - Low-amplitude, high frequency (10-12Hz) tremor - Not evident in normal circumstances - Exacerbation of physiologic tremor Physiological - Postural tremor, occurs upon maintaining posture is the commonest cause of action - Symmetrical and distal in distribution tremor tremor - Should seek a primary medical - ↑ by anxiety, emotional stress, drugs (eg. β2-agonist and other catecholaminergic drugs, lithium, antidepressants), cause first in action tremor alcohol/opioid withdrawal, thyrotoxicosis, fever - Variable amplitude, high-frequency (8-10Hz) tremor - Prev 300/100k (up to 5%) - 30-70% FHx +ve, AD inheritance Essential - Postural and kinetic tremor, NOT at rest - Typically affects bilateral arms (not LL) and head - Usually a/w insidious onset tremor - May be alleviated by alcohol but not ↑ by caffeine - Mx: propranolol, primidone, benzodiazepine (1st line), DBS of - NOT a/w other Parkinsonian and cerebellar features ventromedial nucleus of thalamus - Coarse, low-frequency (3-4Hz) tremor - May be first manifestation of Parkinsonian - Resting tremor, dampened during volition idiopathic PD - Typically starts at unilateral UL and spread to other limbs - Anticholinergics may be used as tremor - Classically described as ‘pill-rolling’ tremor initial Tx in tremor-dominant PD in - Associated with rigidity and bradykinesia young pt Cerebellar - Coarse, low-frequency (4-6Hz) tremor - Intention tremor, maximal approaching end of movement / tremor - Associated with other cerebellar features - Page 94 of 179 - B. Choreiform Movements Chorea: sudden, unpredictable quasipurposive involuntary fidgety/jerky movement □ ↑ by voluntary movement, stress, anxiety; ↓ during sleep Athetosis: slower, coarser, more writhing movement, esp affecting distal parts of limbs □ Often occurs together with athetosis (choreoathetosis) Ballism: involuntary movement that are proximal and large amplitude with a flinging/kicking character □ Most often unilateral (hemiballism) □ Classically a/w contralateral subthalamic nucleus stroke Aetiology: all choreiform movements result from a disruption in basal ganglia circuitry resulting in imbalance between indirect and direct pathways → localizes to basal ganglia □ Inherited: Huntington’s disease, Wilson’s disease, neuro-acanthocytosis... □ Vascular: basal ganglia stroke □ Inflammatory: Sydenham chorea, SLE, vasculitis □ Neoplastic: BG 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: Hx, neurological/CVS exam + slit-lamp examination Mx: tetrabenazine and clonazepam for symptomatic Tx C. Tics Tics: abrupt stereotyped repetitive movements involving discrete muscle groups □ Can mimic normal coordinated movements, vary in intensity and lack rhythm → Motor tics, eg. eye-blinks, head tossing, shoulder shrugs, facial grimaces → Phonic tics, eg. barks, grunts, throat-clearing noises □ May be temporarily inhibited by will power and usually disappear by sleep Causes: □ 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 □ Secondary tics should be suspected if tics begin abruptly, are persistent or are problematic → Eg. dopaminergic drugs, stimulants, neuroleptics, other inherited diseases Mx: behavioural Tx as mainstay (response to drug Tx unsatisfactory in general) - Page 95 of 179 - D. Myoclonus Myoclonus: brief, repetitive, involuntary sudden ‘shock-like’ jerks of muscle groups □ Results from focal discharge from cortex (majority), subcortical or spinal cords Causes: □ Physiological: hypnic (during sleep transitions), anxiety-related, exercise-related □ Essential myoclonus: myoclonus as primary symptom, non-progressive Hx □ 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, eg. due to cerebral anoxia, organ failure, hypoNa, hypoGly → Neurodegenerative diseases, eg. CJD, Alzheimer’s disease, CBD → Metabolic storage diseases → Progressive myoclonic epilepsy (with progressive cognitive decline, seizures, ataxia and death) Mx: clonazepam, piracetam, sodium valproate as symptomatic relief E. Dystonia 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 Classification: □ 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 Clinical features: □ Context: initiated/worsened by voluntary action, fatigue, stress and emotional states → occurs at rest in late stages □ Alleviation by sensory tricks (geste antagoniste, eg. touching face), sleep and relaxation □ Hypertrophy of involved muscles progressing into fixed muscle contractures in late stages □ Involvement: LL onset in early onset vs facial, neck or UL onset in late onset Aetiology: pathogenesis unknown, probably involve dopaminergic and cholinergic systems □ Idiopathic torsion dystonia: dystonia as only feature w/o other neurological deficits → Hereditary: early onset (<21y), LL focal onset becoming generalized, eg. DYT1-TOR1A → Sporadic: adult onset (>21y), UL, facial or cervical onset w/o generalization □ Secondary dystonia, esp when a/w ↓cognition, pyramidal/extrapyramidal features, cerebellar ataxia, sensory loss → Brain injury, eg. cerebral palsy, head injury → Neurodegenerative diseases, eg. Parkinsonism, spinocerebellar ataxia, Huntington’s disease → Drug-induced, eg. anticonvulsants, CCB, Das, levodopa, neuroleptics □ Pseudodystonia, eg. AAJ subluxation, stiff-person syndrome, bone/ligamentous injury, posterior fossa tumour, psychogenic dystonia Dx: clinical + r/o alternative causes, esp when a/w atypical features Mx: treat underlying cause + symptomatic Tx □ Pharmacotherapy: levodopa (if young-onset), anticholinergic/BZD (if adult-onset) □ Botox injection: Tx of choice for focal dystonia, combined w/ Rx in systemic/segmental dystonia → MoA: IM injection → presynaptic NMJ blockage → ↓ACh release → ‘chemodenervation’ → S/E: injection site reaction, muscle atrophy, ptosis, lower facial weakness, ↑lacrimation (generally reversible) - Page 96 of 179 - F. Neuroleptic-induced Movement Disorders Type Features Treatment Subjectively unpleasant state of inner restlessness A/w strong desire/compulsion to move ↓ or change antipsychotic Propranolol Akathisia Stereotypic motor behaviours, eg. constant crossing/uncrossing leg, foot stamping when seated, rocking Benztropine motion of trunk, wrining of hands Benzodiazepine Occurs in 25% pt within hours-weeks Involuntary contractions of major muscle groups Anticholinergics, eg. Acute eg. oculogyric crisis (eyes rolling upwards), torticollis (H&N benztropine, diphenhydramine dystonia twisted to the side), dysphagia, laryngospasm (rare) Change antipsychotics Occurs in 10% pt (esp children/young M) within hours Botox injection Drug-induced Tremor, rigidity and bradykinesia ↓ or change antipsychotic Parkinsonism Occurs in ~20% pt within days-weeks Benztropine Delayed onset of abnormal movements Eg. bucco-lingual-masticatory dyskinesia ↓ or change antipsychotic Tardive (commonest) i.e. complex chewing/tongue popping mov’t STOP anticholinergics64 dyskinesia Eg. piano-playing fingers, body rocking Eg. torticollis (i.e. tardive dystonia) Tetrabenazine Occurs in 5% pt/yr within months-years 5.1.2 Approach to Abnormal Gait Ref: Neurology and Neurosurgery Illustrated P. 192, JC23 A. Physiology of Gait Normal gait depends on: □ Normal muscles: hip flexion, knee flexion, ankle dorsiflexion □ Corodination to ensure fluidity □ Antigravity reflexes