Parkinsons, MS and space occupying lesions

Question 2

Parkinsonism triad

Answer 2

• 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.

Question 3

Parkinsonism causes

Answer 3

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.

Question 4

PD - epidemiology

Answer 4

The mean age of onset is 65 years of age and the prevalence is 1.6% in Europe.

Question 5

PD - presentation

Answer 5

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.

Question 6

PD - pathophysiology

Answer 6

Degeneration of dopaminergic neurones in the substantia nigra and associated development of Lewy bodies causes decreased striatal dopamine levels.

Question 7

PD Mx - Levodopa

Answer 7

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.

Question 8

PD Mx - dopamine agonists

Answer 8

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.

Question 9

PD Mx - MAO-B inhibitors

Answer 9

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.

Question 10

PD Mx - COMT inhibitors

Answer 10

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.

Question 11

PD Mx - future therapies

Answer 11

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.

Question 12

Parkinson plus - PSP

Answer 12

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.

Question 13

Parkinson plus - MSA

Answer 13

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.

Question 14

Parkinson plus - CBD

Answer 14

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’.

Question 15

Parkinson plus - lewy body dementia

Answer 15

Early dementia with fluctuating cognition and visual hallucinations.

Question 16

Parkinson plus - vascular parkinsonism

Answer 16

Parkinsonism is worse in the legs and gait abnormality is prominent.

Question 17

Multiple sclerosis - definition

Answer 17

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.

Question 18

MS - epidemiology

Answer 18

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.

Question 19

MS - presentation

Answer 19

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.

Question 20

MS - clinical features

Answer 20

• 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.

Question 21

MS - eponyms

Answer 21

• 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.

Question 22

MS - progression

Answer 22

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.

Question 23

MS - diagnosis

Answer 23

• 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. Use Macdonald criteria.
• 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.

Question 24

MS - specific management

Answer 24

• 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%. 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.

Question 25

MS - symptom control

Answer 25

• 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.

Question 26

Space occupying lesions - signs

Answer 26

• 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.

Question 27

SOL - causes

Answer 27

Tumours, aneurysm, abscess, subdural haematoma, granuloma (e.g. tuberculoma) or cyst.

Question 28

SOL - tumours

Answer 28

Primary tumours include astrocytoma, glioblastoma, oligodendroglioma, ependymoma, meingoma, lymphoma or haemangioblastoma. 30% are metastatic e.g. from breast, lung or melanoma.

Question 29

SOL - differential diagnosis

Answer 29

Stroke, head injury, venous sinus thrombosis, vasculitis (e.g. SLE, PAN or giant cell arteritis), MS, encephalitis, post-ictal Todd’s paralysis, metabolic or Us and Es disturbance.

Question 30

SOL - investigations

Answer 30

CT ± MRI and consider a biopsy (avoid lumber puncture prior to CNS imaging)

Question 31

Brain tumour management

Answer 31

• Benign – these should be removed where possible however some may be inaccessible.
• Malignant – if a tumour is inaccessible but causing hydrocephalus a ventriculo-peritoneal shunt can be inserted. Chemo-radiotherapy can be used post-surgery or as monotherapy.
• Symptom control – seizure prophylaxis e.g. with phenytoin is important but often fails and headaches can be treated with codeine 60mg QDS. Cerebral oedema should be treated with dexamethasone 4mg TDS or if intracranial pressure is acutely raised give mannitol.

Question 32

Idiopathic intracranial hypertension - definition

Answer 32

aka pseudotumor cerebri should be considered in those presenting with a space occupying lesion (headache, raised ICP, papilloedema) when none is found. Typical patients are obese women with blurred vision ± diplopia, VIth nerve palsy and an enlarged blind spot if papilloedema is present. Consciousness and cognition are always preserved.

Question 33

IIH - causes

Answer 33

Often unknown or secondary to venous sinus thrombosis or drugs e.g. tetracycline.

Question 34

IIH - management and prognosis

Answer 34

• Management – weight loss, acetazolamide, loop diuretics and prednisolone may reverse papilloedema. If drugs fail consider optic nerve sheath fenestration or lumbar peritoneal shunt.
• Prognosis – often self-limiting but permanent visual loss occurs in up to 10% of patients.