Neurology

Movement Disorders

Idiopathic Parkinson's disease (IPD)

Introduction

  • First described by James Parkinson in 1817 in an essay on the "shaking palsy" and later named after him by Charcot

Aetiology

  • Degenerative disease of the substantia nigra resulting in impaired function of the normal neural extrapyramidal motor circuits producing a classical clinical picture.
  • Presents when 80% Degeneration of the substantia nigra with loss of dopamine releasing neurones
  • Eosinophilic intracellular Lewy bodies which contain alpha synuclein
  • Often asymmetrical pathological signs and clinical signs
  • Agricultural chemicals - seen more commonly in farmers.
  • Genetic forms due to mutations in the Parkin gene family
  • Less common in smokers
  • A toxin MPTP caused a Parkinson's disease like syndrome in those who took the drug and is used as an experimental model of IPD
  • Common Prevalence is 150 in 100,
  • Incidence 20/100, Equal occurrence in males and females.

Clinical

  • TRAP Tremor - at rest reduced by movement, rhythmic, hands, legs, tongue even lips
  • Rigidity throughout full range of movement (lead pipe or cog wheel if tremor)
  • Asymmetry makes IPD more likely
  • Akinesia - mask face and slow blink, quiet monotone speech, slow dysarthric speech, unable to turn in bed, freezing at doorways
  • Postural instability
  • Others - constipation, siallorhoea (reduced swallow), Hypophonia, Micrographia
  • Dementia, Positive Glabellar tap (rarely done) slow shuffling gait.
  • Depression - common and should be treated
  • Reduced sense of smell is an early finding
  • Test functionality - doing up buttons, assessing gait.

Investigations

  • Diagnosis is mainly clinical. CT may be done to exclude other causes e.g stroke, tumours
  • Flourodopa scan can show altered metabolism in basal ganglia but not useful enough to be diagnostic

Management

  • The main issue is that the most effective drug Levodopa over the years then tends to cause extra movements - so called dyskinesias as well as becoming less effective
  • On-off phenomenon are also seen when patients suddenly lose all function
  • Has been improved slightly with COMT inhibitors
  • Levodopa + peripheral decarboxylase inhibitor e.g. sinemet or madopar
  • Start small dose giving up to 3 to 5 doses per day as symptoms need
  • Also long acting preparations useful
  • L-Dopa MAOB inhibitor e.g. selegiline or rasagiline may help
  • Dopamine agonists e.g. ropinirole can be tried either as initial therapy or add on to above
  • Anticholinergics - e.g. benzhexol can help tremor but best avoided in over 60s as can cause delirium
  • Levodopa + COMT inhibitors such as entacapone is popular
  • Treat depression if present
  • Surgery - deep brain stimulation, Specialist nurse support, Occupational therapy and physiotherapy

Parkinsonism

Introduction

  • A clinical syndrome similar to IPD characterised by Tremor, Rigidity and Akinesia.
  • Different causes and response to treatment than IPD

Differentiate from IPD - Causes

  • Idiopathic PD, Stroke, Drug induced MPTP
  • Neuroleptics
  • Dopamine blockers, Reserpine, Carbon monoxide poisoning
  • Manganese, Wilson's disease (copper overload)
  • Repeated trauma - boxers, Post encephalitis lethargica

Clinical

  • Patients may have additional features suggesting another cause other than IPD
  • Postural instability, eye signs -suggests PSP, Symmetry at presentation goes against IPD
  • Failure of response to L-Dopa - not typical for IPD
  • Early falls, Autonomic, Cerebellar and pyramidal and autonomic signs - consider Multiple system atrophy.

Investigations

  • Diagnosis is mainly clinical
  • CT may be done to exclude other causes e.g stroke, tumours
  • Consider Copper studies in young
  • Drug history

Management

  • Stop any offending drug
  • Trial of Levodopa + peripheral decarboxylase inhibitor
  • Trial of anticholinergic

Restless legs syndrome

Introduction

  • Associations with pregnancy and Iron deficiency anaemia and renal disease

Clinical

  • Commoner than reported
  • Urge to get out of bed and move limbs
  • Worse in evening and with rest
  • Limb movements in sleep, family history.

Investigations

  • Check Hb and ferritin

Management

  • Cautiously stop Antidepressants (??), caffeine, calcium antagonists.
  • Try Dopamine agonists, Opiate, Gabapentin, Clonazepam

Benign Essential tremor

Introduction

  • Familial - autosomal dominant

Clinical

  • Rather benign in most but can be disabling and socially embarrassing
  • Main focus is not to be misdiagnosed as Parkinson's disease.
  • Tremor in anxious situations classically helped by alcohol
  • Head nodding - titubation, Voice tremor

Management

  • Treatment not usually needed
  • Reassurance that its not PD
  • In some who are badly affected Beta Blockers or Primidone may be used

Sydenham's chorea

Introduction

  • Seen with acute rheumatic fever
  • antibodies to streptococci cross react with epitopes in the basal ganglia to produce the clinical effects.

Clinical

  • Choreiform movements tend to resolve after several months
  • But it is well recognised that triggers in later life can cause re occurrence of the movement disorder.
  • Such triggers include pregnancy (chorea gravidarum), oral contraceptives, digoxin and phenytoin

Investigations

  • ASO titres
  • Check major and minor criteria for rheumatic fever
  • FBC, Autoantibodies to exclude SLE

Management

  • None in particular

Progressive supranuclear palsy

Introduction

  • Abundant neurofibrillary tangles - Tauopathy
  • Neuronal depletion in substantia nigra and basophilic neurofibrillary tangles seen in neurons of basal ganglia, brainstem, frontal cortex and cerebellum

Clinical

  • Parkinsonism, Postural instability, Vertical gaze supranuclear palsy, Dementia, Elderly patients >
  • Symmetrical akinetic rigidity, Extensor rigidity, Erect posture, neck hyperextension, Reptilian stare - reduced blink rate
  • Impaired downward gazes, Rest tremor uncommon, Postural instability - falls back
  • Brainstem signs Blepharospasm with associated dysarthria and dysphagia
  • Deep growling voice
  • Tremor less likely than PD, Reptilian stare, Axial rigidity, Falls and Postural instability, Preserved Doll's head movement of eyes
  • Gaze palsy eye signs may appear late and can delay the diagnosis
  • Associated frontolimbic dementia
  • Rocket sign - rapidly rises out of chair
  • Autonomic function normal

Investigations

  • MRI Midbrain shows appearance of "Mickey mouse ears"
  • Enlarged IIIrd ventricle and interpeduncular cistern
  • Degeneration of basal ganglia and brainstem
  • Abnormal anal sphincter EMG (MSA and PSP)

Management

  • Classically there is a poor response to Levodopa
  • Death occurring at a median of six years after onset

Multiple system atrophy (MSA)

Aetiology

  • Common features are Glial cell cytoplasmic inclusions (GCIs) which are Alpha-synuclein positive

Clinical

  • The parkinsonism is more likely to be bilateral and response to L-Dopa is variable and fluctuates
  • Cognitive function better preserved than Idiopathic PD
  • MSA (P) Pyridamal : commonest and do worst Minority respond to L-Dopa transiently
  • MSA (C)-Cerebellar ataxia : 20% Nonspecific features in both Corticospinal signs e.g. extensor plantars and hyperreflexia
  • MSA Autonomic (A) Postural instability and late falls, Autonomic dysfunction with both e.g. postural hypotension, erectile dysfunction, bladder

Investigations

  • Abnormal anal sphincter EMG with signs of degeneration
  • MRI abnormalities in the striatum, putamen, pons, and cerebellum are highly suggestive
  • MRI DWI may help differentiate MSA-P from IPD

Management

  • There may be some responsiveness to L-Dopa and so worth trying
  • Increase dose to 1000 mg daily over 3 months
  • Rapidly progressive and Management is symptomatic and palliative
  • Survival about 9 years on average

Corticobasal degeneration

Aetiology

  • Tauopathy which Affects nigrostriatal tracts and subcortical structures e.g. thalamus, subthalamic nuclei, pallidum, red nucleus, dentate nucleus

Clinical

  • An initially unilateral parkinsonism + cortical signs and Alien limb phenomenon where the hand makes involuntary complex movements
  • Basal ganglia : Asymmetrical akinetic-rigid syndrome, jerky dystonias, Myoclonus, supranuclear gaze palsy in horizontal and lateral directions
  • Cortical - Apraxias, Dysphasias, Alien limb phenomenon, disinhibition, depression, dementia

Investigations

  • MRI - Frontoparietal cortical degeneration may be seen

Management

  • Variable response to L-Dopa
  • Dystonias - anticholinergics, baclofen, botulinum toxin, benzodiazepines

Wilson's disease

Aetiology

  • Autosomal recessive
  • Copper metabolism defect.
  • Gene is that for ATP7B a copper transporting P-type ATP
  • Leads to a failure to excrete copper normally

Clinical

  • Wing beating tremor, Parkinsonism, choreoathetoid movements, Cirrhosis and liver failure
  • Kayser-Fleischer ring seen at slit lamp examination, Drooling smiling appearance, Osteoporosis

Investigations

  • Low serum copper and caeruloplasmin, Increased urinary copper, Liver biopsy to assess copper content
  • MRI scan may show abnormalities in basal ganglia

Management

  • Chelating agents e.g. Pencillamine and Trientine.
  • Zinc sulphate
  • Early treatment can prevent damage

Drug induced movement disorders

Aetiology

  • Drugs may cross the blood brain barrier with affects on the basal ganglia, cerebellum and adjacent areas

Clinical

  • Tremor : Lithium, Beta agonists
  • Parkinsonism :neuroleptics block dopamine
  • Choreoathetosis : L-Dopa and DA agonists.
  • Acute dystonia : Phenothiazines, Haloperidol, Metoclopramide.
  • Tardive dyskinesias : Prolonged phenothiazine usage.
  • Ataxia : Anticonvulsants - Check drug level as needed

Management

  • Stop drug if possible
  • Anticholinergic for acute dystonia

Chorea

Aetiology

  • Possibly dopamine > Ach in basal ganglia and associated circuits

Causes

  • OCP, SLE, Sydenham's chorea, Wilson's disease, Antiparkinsonism therapy, Huntington's chorea
  • Rare - Choreoacanthocytosis, Spinocerebelar ataxia, Friedreich's ataxia
  • Olivopentocerebellar atrophy, Dentorubral pallidoluysian atrophy

Management

  • Tetrabenazine depletes dopamine and can be useful.
  • Haloperidol may also be used
  • Start small doses of either.

Myoclonic jerks

Causes

  • Creuzfeldt-Jakob disease, Uraemia, Hypocalcaemia and tetany
  • Liver failure, Hypoxic brain damage, Subacute sclerosing panencephalitis
  • Juvenile Myoclonic epilepsy, Alzheimer's disease

Management

  • Sodium valproate, Lamotrigine

Stiff Person Syndrome

Aetiology

  • Rarely paraneoplastic variant associated with breast cancer and antineuronal antibody to GAD
  • GAD converts Glutamic acid to GABA an inhibitory neurotransmitter

Clinical

  • Middle aged with progressive onset
  • Falls may be seen
  • Hyperextended posture
  • Episodic stiffness in axial muscles and proximal legs with associated painful spasms in response to touch, noise/ Labile blood pressure.
  • 30% have Diabetes Mellitus and autoimmune disease - thyroiditis, pernicious anaemia, vitiligo

Investigations

  • 60% have antibodies to GAD-65kd isoform (Glutamic acid decarboxylase)

Management

  • Use IVIG, Plasma exchange, High dose Steroids, Baclofen, Diazepam

Choreo acanthocytosis

Aetiology

  • Commonest cause is Bassen-Kornzweig disease (Abetalipoproteinemia) which is Autosomal recessive
  • Other rare forms exist with different characteristics.

Clinical

  • Childhood onset of mild chorea, tics, ataxia, parkinsonism and dystonia, seizures
  • Subcortical dementia, peripheral axonal neuropathy

Investigations

  • A minority have acanthocytes (red cells with spiny projections) seen on blood film which may be transient
  • Elevated CK, Low vitamin E level, high cholesterol level, and abnormal lipoprotein electrophoresis.
  • CT/MRI - atrophy of caudate and putamen

Management

  • High dose Vitamin E helps
  • Supportive and symptomatic treatment for the movement disorders.