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5 Parkinsons Disease

4th Year Neurology Teaching Handbook Parkinson’s Disease Parkinsonism = Tremor, bradykinesia, rigidity and postural instability Background • Aetiology − Idiopathic – most common ⇒ Parkinson’s disease − Drug/toxin induced – phenothiazines, metoclopramide, reserpine can cause reversible parkinsonism, although symptoms may take months to resolve. • PD pathology -­‐ Dopamine depletion in the nigrostriatal system. Lewy bodies Clinical features 1.
Tremor – coarse tremor, 3-­‐5Hz Rigidity -­‐ Causes flexed posture Bradykinesia – masklike facies, hypophonia, impairment of rapidly alternating movement. Abnormal gait and postural instability -­‐ small, shuffling steps, loss of arm swing, unsteadiness turning, festinating gait. Differential diagnosis • Essential tremor – early age of onset, FHx of tremor, postural tremor, improves with alcohol intake. Commonly affects the head (nod/headshake) -­‐ PD commonly affects the face and lower jaw. • Lewy body dementia – progressive neurobehaviour changes, dementia and hallucinations. • Depression – expressionless face, poorly modulated voice, ↓ voluntary activity. Can coexist. • Wilson’s disease – important differential for younger patients Parkinson plus syndromes Tend to respond less well to treatment and have a worse prognosis than idiopathic PD • Progressive supranuclear palsy – commonest. Supranuclear gaze palsy (impaired upward gaze) with early falls secondary to loss of postural reflexes. Associated axial rigidity. • Mulitple system atrophy – Autonomic failure leading to incontinence, orthostatic hypotension, cold peripheries, cerebellar signs • Corticobasal degeneration – rarest and the worstprognosis. Alien limb/hand syndrome, apraxia (secondary to cortical degeneration), asymmetrical limb movement, aphasia • Striatonigral degeneration – rare. Neuronal loss in putament, GP, caudate nucleus. presents with bradykinesia and rigidity. Investigations Diagnosis is often clinical, investigations will depend upon differential •
Isotope DATA scan can show deficiencies in DA pathways. •
MRI/CT depending upon differential Management NICE guidelines First line Adjuvant Late disease with bad Levodopa e.g. sinemet Dopamine agonists eg pramiprexole MAO-­‐B inhibitors eg selegiline Dopamine releasing agents eg amantadine Anticholinergics eg benztropine COMT inhibitors eg entacapone Apomorphine Lisa Blundell and Thomas Williams 4th Year Neurology Teaching Handbook dyskinesia Modified release levodopa Refractory to drug treatment Deep brain stimulation Treatment can minimise symptoms/disability but does not alter underlying progression of the disease. Drugs & Treatments Dopamine agonist • Ergot derivatives e.g. bromocriptine. • Non-­‐ergot -­‐ ↓ S/e Pramipexol, ropinirole and apomorphine hydrochloride used in early PD. − Apomorphine can be injected to rescue on-­‐off Sx in late disease Levodopa • Particularly helpful against bradykinesia. • Formulation -­‐ Combined with carbidopa in sinemet, modified -­‐release – may ↓ fluctuations. • Side effects – N+ V, hypotension, abnormal movement (dykinesias), restlessness, and confusion. Late dyskinesias and behavioural changes are often dose-­‐related. Confusion and psychotic mental disturbances can be alleviated by using olanzepine/risperidone (do not affect the dopamine transmission). Also wearing-­‐off effect before next dose ⇒ on-­‐off phenomenon. • Contraindications – narrow-­‐angle glaucoma, psychotic illness, MAOI. Caution with peptic ulcers. MAO-­‐B inhibitors -­‐ Selegiline and Rasagiline •
Inhibit the breakdown of dopamine and thus enhance the anti-­‐parkinsonian effect of levodopa. Amantadine •
mild PD in combination with anticholinergic. Anticholinergics – Benzotropine, hexyphenidyl •
Very effective at relieving tremor and rigidity (less so for bradykinesia) − Best avoided in elderly because of S/E – dry mouth, constipation, urinary retention. − Titrate until benefit is reached or s/e limit further increments. Catechol-­‐O-­‐methyltransferase inhibitors -­‐ e.g. entacapone •
Can ↓ dose requirements of levodopa by ↑ transport into blood and across BBB. Deep brain stimulation • High frequency stimulation of the globus pallidus or STN • Benefits over surgery (thalamotomy or pallidotomy)– reversible, lower morbidity and causes minimal damage. Parkinson’s Disease examination You have been instructed to ‘examine this patient with Parkinson’s Disease’ WIPE (Wash hands, introduce, permission, explain/expose) Inspection •
Around the bed – walking aids (postural instability), medications •
Patient o Voice (when asking the patient permission to examine) -­‐ quite with little intonation. o Face – mask-­‐like facies o Tremor Gait •
Ask the patient if they are able to walk – take care as patient may be at risk of falls. •
Loss of arm swing, small shuffling steps, difficulty intiating, stopping, turning, hunched posture, freezing/cueing) •
DDx – apraxic gait e.g. in normal pressure hydrocephalus/small vessel disease Ask the patient to sit down again Upper limb •
Tremor -­‐ look for nature, symmetry o Ask patient to count back from 20 (distraction – can bring out tremor) Lisa Blundell and Thomas Williams 4th Year Neurology Teaching Handbook Ask patient to tap hand on knee, one hand at a time and watch for tremor in resting hand. (synkinesis) Rigidity – ask about pain o Take the patient’s hand in yours and test each upper limb for cogwheel rigidity (=rigidity+tremor). Ask patient to count back from 20; this should bring out the tremor. o Assess tone at elbow – lead pipe rigidity. Bradykinesia – o Ask patient to hold arms up and make large rapid opposing movements between fingers and thumb. Look for diminuition of affected side. o
Face •
Glabellar tap test – Offer test, stand behind the patient tap on the forehead multiple times, normally patients stop blinking after a couple of tap. In PD the patient continues tapping. Functional assessment Can help with the differential but also give a sense of how the patient might function in ADLs. • Ask the patient to do up a button • Ask to write a sentence. Look for small and spidery writing (micrographia) • Draw a spiral and ask them to copy it (Archimedes spiral). In PD the spiral is typically small and wobbly. DDx -­‐ essential tremor: normal size and spacing of the lines, but wobbly. Parkinson’s plus syndrome • Eye movements (loss of downgaze in PSP, nystagmus in MSA) • Feel the temperature of the peripheries (autonomic disruption in MSA) • Check for postural hypotension (autonomic disruption in MSA) • Test for other signs of cerebellar lesions (because cerebellar disease is a differential and because there are cerebellar signs in MSA) • Examine speech (aphasia in corticobasal degeneration, may also have sensory inattention, alien limb, myoclonus) • On inspection – dystonic arm (held in a strange position – may be seen in CBD) • Cognitive assessment (Lewy body dementia or dementia as part of idiopathic parkinson’s disease) Remember the patient may be is on treatment and my have dyskinesias or very few symptoms rather than the classical symptoms. Case A 61-­‐year-­‐old right-­‐handed man presents with ‘involuntary twitches’ of his left hand. 6 months ago he noticed that when he is at rest, his left hand shakes. He can stop the shaking by looking at his hand and concentrating. The shaking does not impair his activities in any way. He has no trouble holding a glass of water. There is no tremor in his right hand, and his lower extremities are not affected. He has had no trouble walking, and there have been no falls. There have been no behavioral or language changes. On examination, a left hand tremor is evident when the man is distracted. His handwriting is mildly tremulous. He has bilateral cogwheel rigidity with contralateral activation, which is worse on the left. His rapid alternating movements are bradykinetic on the left. 1.
What is the differential diagnosis and what is the most likely diagnosis? What would be the first line treatment options? Which brain structures are primarily affected? What are the characteristic histological features? Which brain structures are targeted for deep brain stimulation? If his disease progresses, what other clinical features may you expect to find on examination? Even though the physiologic deficiency in Parkinson’s disease is of dopamine, L-­‐dopa rather than dopamine is given to patients. Why? 7. What is the role of carbidopa? Lisa Blundell and Thomas Williams 4th Year Neurology Teaching Handbook 8. After several years of successful anti-­‐Parkinsonian treatment, he abruptly develops acute episodes of profound bradykinesia and rigidity. Remission of these signs occurs as abruptly as the onset. What is name of this clinical phenomenon? Lisa Blundell and Thomas Williams