Bradykinesia – slowness of movement initiation with progressive reduction in speed and amplitude of repetitive actions. This results in paucity of movement - expressionless face, decreased blink rate, monotonous hypophonic speech and micrographia and a gradual change in gait – reduced arm swing, festinance (shuffling steps) and freezing at obstacles and doors.
Tremor – worse at rest, pill rolling action (thumbs rolls over the fingers) and 4-6 cycles/second.
Rigidity – increased tone – superimposed tremor leads to characteristic cog-wheeling tremor.
Idiopathic Parkinson’s disease, Parkinson’s-plus syndromes, multiple cerebral infarcts, post-encephalopathy, drug induced e.g. by neuroleptics, prochlorperazine or metoclopramide, toxin induced e.g. MPTP (illicit narcotic), manganese or copper (Wilson’s disease) or trauma.
PD - epidemiology
The mean age of onset is 65 years of age and the prevalence is 1.6% in Europe.
PD - presentation
Syndrome of bradykinesia plus one of the following – resting tremor, muscular rigidity or postural instability without another cause – the onset is usually asymmetric which is persistent.
- Non-motor features – depression, dementia, visual hallucinations, anosmia, dribbling saliva, mild urinary frequency and urgency, REM behavioural sleep disorder and L-dopa side effects.
PD - pathophysiology
Degeneration of dopaminergic neurones in the substantia nigra and associated development of Lewy bodies causes decreased striatal dopamine levels.
PD Mx - Levodopa
Used in combination with a dopa-decarboxylase inhibitor as Madopar or Sinemet. Initial side effects of nausea and vomiting can be treated with domperidone. Efficacy reduces over time, requiring larger and more frequent dosing, with worsening side effects – dyskinesia, painful dystonias and response fluctuations such as unpredictable freezing and end of dose reduced responses. Non-motor side effects include psychosis and visual hallucinations.
PD Mx - dopamine agonists
Such as Ropinirole and Pramipexole are used as monotherapy to delay starting L-dopa in the early stages of PD or as an adjunct to a lower dose of L-dopa as PD progresses. Rotigotine transdermal patches are also available as mono or adjunct therapy. Side effects – drowsiness, nausea, hallucinations or compulsive behaviour.
PD Mx - MAO-B inhibitors
Such as rasagiline or selegiline are an alternative to dopamine agoinsts in the early stages of PD. Side effects include atrial fibrillation and postural hypotension.
PD Mx - COMT inhibitors
Entacapone or tolcapone can be used to lessen the ‘off’ time in those with end of dose wearing off. Tolcapone is more effective but LFTs need to be monitored.
PD Mx - future therapies
Istradefylline – an adenosine A2X receptor blocker that acts in the basal ganglia and can be used to potentiate the response to low dose L-dopa and reduce the ‘off’ time.
Parkinson plus - PSP
Progressive supranuclear palsy – early postural instability and falls, vertical gaze palsy, rigidity of the trunk > limbs, symmetrical onset, speech and swallowing problems and tremor is unusual.
Parkinson plus - MSA
Multiple system atrophy – early autonomic features (e.g. postural hypotension and bladder dysfunction), cerebellar and pyramidal signs (PD signs) and rigidity is worse than tremor.
Parkinson plus - CBD
Cortico-basal degeneration – akinetic rigidity involving one limb, cortical sensory loss and apraxia – in the extreme there is automatous interfering activity of the affected limb – ‘the alien limb’.
Parkinson plus - lewy body dementia
Early dementia with fluctuating cognition and visual hallucinations.
Parkinson plus - vascular parkinsonism
Parkinsonism is worse in the legs and gait abnormality is prominent.
Multiple sclerosis - definition
Discrete plaques of demyelination occur at sites throughout the CNS caused by a T cell mediated immune response - the trigger is unknown. Demyelination heals incompletely resulting in a relapsing and remitting symptoms. Prolonged demyelination causes axonal loss and progressive symptoms.
MS - epidemiology
Mean age of onset is 30 years of age and the female to male ratio is 3:1. MS is more common in colder areas – prevalence is 42 in 100,000 in England and 200 in 100,000 in Scotland but rarer in the black African and Asian populations. Adults carry risk with them but children develop risk.
MS - presentation
Usually monosymptomatic – unilateral optic neuritis (pain on eye movement or rapid decline in central vision), numbness or tingling of the limbs, leg weakness, brainstem or cerebellar signs (e.g. diplopia or ataxia). Symptoms usually worsen with heat e.g. after a hot bath or during exercise.
MS - clinical features
General – malaise, nausea, positional vertigo, seizures, aphasia, meningism, high temperature.
Sensory – dysaesthesia, pins and needles, decreased vibration sense and trigeminal neuralgia.
Motor – spastic weakness and transverse myelitis (spinal cord inflammation) – causes loss of motor, sensory, autonomic, reflex and sphincter function below the level of the lesion.
Cerebellum – trunk and limb ataxia, intention tremor, monotonous speech and increased falls.
Eyes – diplopia, hemianopia, optic neuritis – decreased visual acuity and phenomena below.
Gastrointestinal – swallowing disorders and constipation.
Genitourinary – erectile dysfunction, anorgasmia, urinary retention and incontinence.
Cognitive – amnesia, mood disturbances (up or down) and decreased executive functioning.
MS - eponyms
Devic’s syndrome – aka neuromyelitis optica (NMO) is an MS variant with transverse myelitis and optic atrophy – distinguishable from MS by the presence of NMO-IgG antibodies.
Lhermitte’s sign – neck flexion causes electric shocks in the trunk and limbs. Also positive in cervical spondylosis, spinal cord tumours and subacute combined degeneration of the cord.
Uhthoff’s phenomenon – vision worsens after exercise and after a hot meal or bath.
Pulfrich effect – latencies between the eyes are unequal leading to disorientation.
MS - progression
In early stages relapses (which can be stress induced) may be followed by a full recovery. With time remissions are incomplete so disability accumulates. However in some patients steady progression of disability from onset occurs.
Poor prognostic features – diagnosis in an older man, motor signs at the onset, many relapses early in the disease, multiple MRI lesions and axonal loss.
MS - diagnosis
Clinical as no test is pathognomonic. It requires demonstration of lesions disseminated in time and space, attributable to another cause. Early diagnosis reduces relapse rates and disability.
- Macdonald criteria (see below)
- MRI – sensitive but not specific for plaque detection – can produce evidence of lesions disseminated in time. Can also be used to exclude other causes e.g. cord compression.
- CSF – oligoclonal bands of IgG on electrophoresis suggests CNS inflammation.
- Evoked potentials – visual, auditory and somatosensory evoked potentials may all be delayed.
MS - Macdonald criteria
Attacks Lesions Additional criteria
- 2 or more attacks, 2 or more lesions and additional criteria - none – clinical evidence is sufficient.
- 2 or more attacks, 1 lesion and additional criteria - disseminated in space on MRI or further attack.
- 1 attack, 2 or more lesions and additional criteria - disseminated in time on MRI or further attack.
- 1 attack, 1 lesion and additional criteria - disseminated in space and time or further attack.
- 0 attacks or lesions and additional criteria - 1 year of progression plus 2 of – positive brain or spine MRI or CSF.
MS - specific management
Methylprednisolone – 1g/24 hours IV or PO for 3 days shortens relapses but should be used sparingly – max twice per year due to steroid side effects. It does not affect overall prognosis.
Interferon 1α and 1β – reduces relapses by 30% and results in decreased lesion accumulation on MRI but effect on disability is modest. Side effects – flu like symptoms or depression.
Monoclonal antibodies: Natalizumab – acts against the VLA-4 receptor that allows immune cells to adhere to and cross the blood brain barrier. It reduces relapses by 70% and MRI lesions by 90%.
Monocloncal antibodies: Alemtuzumab – acts against T cells and is 2nd line in relapsing remitting MS.
Azathioprine – may be as effective as interferon for relapsing remitting and 20 times cheaper.
MS - symptom control
Spasticity – start at a low dose and build up at weekly intervals e.g. diazepam 5mg OD to TDS.
Urgency or frequency – if post-micturation residual volume is less than 100mL give oxybutynin 2.5mg TDS or tolterodine but if the volume is more than >100mL teach self-catheterisation.
Space occupying lesions - signs
Raised ICP – drowsiness, irritability, falling pulse, rising blood pressure (Cushing’s response), Cheyne-Stokes respiration (deep and fast breathing), pupil changes and decreased visual acuity.
Headache – worse on waking up in the morning, lying down, bending forwards and coughing.
- Seizures – seen in 50% -more likely if focal or with localising aura or post-ictal weakness.
- Focal neurology – raised ICP causes false localising signs – most commonly 6th nerve palsy.
- Personality changes – lack of application to tasks or initiative or inappropriate behaviour.
- Later signs – nausea and vomiting, papilloedema and a decreased GCS are worrying signs.