Idiopathic Parkinson's disease (IPD)
- First described by James Parkinson in 1817 in an essay on the "shaking palsy" and later named after him by Charcot
- 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.
- 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.
- 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
- 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
- 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
- Dopamine blockers, Reserpine, Carbon monoxide poisoning
- Manganese, Wilson's disease (copper overload)
- Repeated trauma - boxers, Post encephalitis lethargica
- 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.
- Diagnosis is mainly clinical
- CT may be done to exclude other causes e.g stroke, tumours
- Consider Copper studies in young
- Drug history
- Stop any offending drug
- Trial of Levodopa + peripheral decarboxylase inhibitor
- Trial of anticholinergic
Restless legs syndrome
- Associations with pregnancy and Iron deficiency anaemia and renal disease
- Commoner than reported
- Urge to get out of bed and move limbs
- Worse in evening and with rest
- Limb movements in sleep, family history.
- Check Hb and ferritin
- Cautiously stop Antidepressants (??), caffeine, calcium antagonists.
- Try Dopamine agonists, Opiate, Gabapentin, Clonazepam
Benign Essential tremor
- Familial - autosomal dominant
- 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
- Treatment not usually needed
- Reassurance that its not PD
- In some who are badly affected Beta Blockers or Primidone may be used
- Seen with acute rheumatic fever
- antibodies to streptococci cross react with epitopes in the basal ganglia to produce the clinical effects.
- 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
- ASO titres
- Check major and minor criteria for rheumatic fever
- FBC, Autoantibodies to exclude SLE
- None in particular
Progressive supranuclear palsy
- Abundant neurofibrillary tangles - Tauopathy
- Neuronal depletion in substantia nigra and basophilic neurofibrillary tangles seen in neurons of basal ganglia, brainstem, frontal cortex and cerebellum
- 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
- 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)
- Classically there is a poor response to Levodopa
- Death occurring at a median of six years after onset
Multiple system atrophy (MSA)
- Common features are Glial cell cytoplasmic inclusions (GCIs) which are Alpha-synuclein positive
- 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
- 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
- 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
- Tauopathy which Affects nigrostriatal tracts and subcortical structures e.g. thalamus, subthalamic nuclei, pallidum, red nucleus, dentate nucleus
- 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
- MRI - Frontoparietal cortical degeneration may be seen
- Variable response to L-Dopa
- Dystonias - anticholinergics, baclofen, botulinum toxin, benzodiazepines
- Autosomal recessive
- Copper metabolism defect.
- Gene is that for ATP7B a copper transporting P-type ATP
- Leads to a failure to excrete copper normally
- Wing beating tremor, Parkinsonism, choreoathetoid movements, Cirrhosis and liver failure
- Kayser-Fleischer ring seen at slit lamp examination, Drooling smiling appearance, Osteoporosis
- Low serum copper and caeruloplasmin, Increased urinary copper, Liver biopsy to assess copper content
- MRI scan may show abnormalities in basal ganglia
- Chelating agents e.g. Pencillamine and Trientine.
- Zinc sulphate
- Early treatment can prevent damage
Drug induced movement disorders
- Drugs may cross the blood brain barrier with affects on the basal ganglia, cerebellum and adjacent areas
- 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
- Stop drug if possible
- Anticholinergic for acute dystonia
- Possibly dopamine > Ach in basal ganglia and associated circuits
- 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
- Tetrabenazine depletes dopamine and can be useful.
- Haloperidol may also be used
- Start small doses of either.
- Creuzfeldt-Jakob disease, Uraemia, Hypocalcaemia and tetany
- Liver failure, Hypoxic brain damage, Subacute sclerosing panencephalitis
- Juvenile Myoclonic epilepsy, Alzheimer's disease
- Sodium valproate, Lamotrigine
Stiff Person Syndrome
- Rarely paraneoplastic variant associated with breast cancer and antineuronal antibody to GAD
- GAD converts Glutamic acid to GABA an inhibitory neurotransmitter
- 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
- 60% have antibodies to GAD-65kd isoform (Glutamic acid decarboxylase)
- Use IVIG, Plasma exchange, High dose Steroids, Baclofen, Diazepam
- Commonest cause is Bassen-Kornzweig disease (Abetalipoproteinemia) which is Autosomal recessive
- Other rare forms exist with different characteristics.
- Childhood onset of mild chorea, tics, ataxia, parkinsonism and dystonia, seizures
- Subcortical dementia, peripheral axonal neuropathy
- 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
- High dose Vitamin E helps
- Supportive and symptomatic treatment for the movement disorders.