Movement Disorders — Written Clinical Reasoning

SAQ 1 — Advanced Parkinson's Disease with Motor Complications, Psychosis and Cognitive Decline (20 marks, 30 minutes)

Prompt: Outline your integrated management plan for this patient, addressing the wearing off, the peak-dose dyskinesia, the visual hallucinations, the freezing of gait and falls, and the cognitive decline. Justify each decision with reference to evidence and guideline recommendations. [1]

Model Answer

Problem list (4 marks): [1]

1. Wearing off (end-of-dose deterioration) — each levodopa dose now lasts only 2 hours; off-time is causing functional impairment.
2. Peak-dose dyskinesia — choreiform movements 1 hour after each dose, reported as more disabling than the off periods.
3. Visual hallucinations — formed, detailed, with retained insight; early feature of PD psychosis, may herald cognitive decline.
4. Freezing of gait with falls — a levodopa-resistant axial symptom and major falls risk; three falls in a month is a red flag.
5. Cognitive decline — MoCA 24/30 is at the threshold for mild cognitive impairment; the hallucinations and gait freezing suggest non-dopaminergic (Braak stage 4 to 6) disease progression.
6. Polypharmacy — he is on four dopaminergic agents from three drug classes, increasing the risk of hallucinations and orthostatic hypotension. [1]

Management of wearing off and dyskinesia (5 marks): [1]

The central principle here is that dyskinesia is the dominant complaint and must drive the strategy — chasing the off-time with more levodopa would worsen the dyskinesia. My approach: [1]

• Reduce the size of each levodopa/carbidopa dose and increase the frequency — for example, switch from 100/25 six times daily to 75/18.75 (three-quarter tablet) every 2 hours while awake, smoothing the plasma levodopa profile. This lowers the peaks (reducing dyskinesia) while maintaining total daily dopaminergic stimulation (reducing off-time).
• Add amantadine 100 mg once or twice daily — the only oral agent with good evidence for reducing levodopa-induced dyskinesia (Snow et al, PMID 10803797). Extended-release amantadine 274 mg once nightly is specifically approved for dyskinesia and off-time reduction. I would monitor for confusion and hallucinations, which may limit use in this patient who already has cognitive change.
• Consider reducing or weaning the dopamine agonist (ropinirole) — agonists contribute to dyskinesia and are the highest-risk class for hallucinations in this cognitively changing patient. I would wean ropinirole slowly (over weeks) to avoid dopamine agonist withdrawal syndrome, transferring the dopaminergic load to levodopa. The rasagiline may be continued or also weaned if hallucinations persist.
• If oral optimisation fails to control both the dyskinesia and the off-time, I would escalate to device-aided therapy: levodopa-carbidopa intestinal gel (LCIG) via PEG-J, continuous subcutaneous apomorphine infusion, or deep brain stimulation. Given his cognitive decline (MoCA 24) and hallucinations, GPi-DBS would be preferred over STN-DBS (better neuropsychiatric profile, Follett PMID 20519680), and a formal neuropsychological assessment would be mandatory before any surgical referral. Cognitive decline and active psychosis are relative contraindications to DBS and would need careful multidisciplinary discussion. [1]

Management of visual hallucinations (4 marks): [1]

Visual hallucinations in PD reflect a combination of dopaminergic therapy (especially agonists), disease progression (Braak limbic and cortical stages), visual pathway dysfunction, and emerging cognitive impairment. My approach, in order: [1]

1. Exclude delirium and treat reversible contributors — check for infection (urine, chest), check electrolytes, review all medications for anticholinergic load, and assess sleep. Many 'PD hallucinations' in clinic are unmasked delirium.
2. Reduce and simplify dopaminergic therapy — wean and stop the dopamine agonist (ropinirole) first, as it carries the highest neuropsychiatric risk; reduce anticholinergics and amantadine if present; minimise levodopa to the lowest effective dose (accepting some worsening of motor function — a difficult but necessary trade-off). The rule is: reduce agonists before reducing levodopa, because levodopa has the lowest neuropsychiatric burden.
3. Add a cholinesterase inhibitor — rivastigmine (licensed for PD dementia) or donepezil, which improve both cognitive function and psychotic features, particularly in patients with co-existing cognitive impairment as this man has.
4. If an antipsychotic is unavoidable — the only evidence-based options are pimavanserin (a selective 5-HT2A inverse agonist, Cummings PMID 24183563, FDA-approved for PD psychosis; not available in ANZ/UK) or low-dose quetiapine (12.5 to 25 mg at night, off-label, with caution). I must explicitly avoid haloperidol, chlorpromazine, risperidone and olanzapine, which can cause catastrophic worsening of parkinsonism and, in patients with underlying DLB, fatal neuroleptic sensitivity. I would counsel the patient and family about the residual risk of quetiapine and document the discussion. [1]

Management of freezing of gait and falls (4 marks): [1]

Freezing of gait (FOG) is largely levodopa-resistant and reflects non-dopaminergic disease progression; escalating dopaminergic therapy will not help and may worsen cognition and orthostatic hypotension. My approach: [1]

• Optimise the on-state first — ensure the patient is not under-treated for off-period freezing (which DOES respond to levodopa). A structured motor diary and adjustment of dosing intervals is the first step.
• Cueing strategies — visual cues (lines on the floor, a laser-cane projecting a line to step over), auditory cues (marching to a metronome set at the patient's preferred cadence, counting 'one-two-three-go'), and attentional strategies (consciously shifting weight, rocking before stepping). These are taught by a PD-specialist physiotherapist and are the most effective intervention for FOG.
• Physiotherapy — PD-specific exercise programmes (LSVT BIG, PDSAFE) improve balance and reduce falls.
• Falls risk assessment — review orthostatic hypotension (check lying and standing blood pressure; reduce causative medications; consider compression stockings, fludrocortisone or midodrine), review vision, review the home environment (occupational therapy for grab rails, removal of rugs), and consider a walker or rollator (though freezing can paradoxically worsen with a frame — a laser-walker is preferred).
• Address the cognitive contribution — FOG has a strong fronto-executive component; cognitive impairment worsens FOG, so the cholinesterase inhibitor may help both problems. [1]

Management of cognitive decline and overall integration (3 marks): [1]

A MoCA of 24/30 in the setting of PD of 11 years' duration, with hallucinations and gait freezing, is consistent with PD mild cognitive impairment progressing toward PD dementia. I would: [1]

• Establish a baseline with serial MoCA (6 to 12 monthly).
• Refer for formal neuropsychological assessment to characterise the cognitive profile (frontal-executive vs posterior-cortical).
• Add a cholinesterase inhibitor (rivastigmine) for both the cognitive and psychotic features.
• Screen for and treat depression, which is common and worsens cognitive performance.
• Initiate advance care planning — discuss goals of care, appoint a substitute decision-maker, document preferences around hospitalisation, feeding (PEG placement in advanced PD dysphagia does not improve outcomes and increases aspiration risk), and palliative care input for end-stage disease.
• Multidisciplinary review: neurology, PD nurse specialist, physiotherapy, occupational therapy, speech pathology (for voice and swallow assessment), dietetics, and social work. [1]

SAQ 2 — Young Patient with a Movement Disorder: Wilson Disease (10 marks, 15 minutes)

Prompt: A 24-year-old man presents with a 4-month history of progressive tremor, slurred speech and behavioural change. On examination he has a coarse irregular tremor, mild rigidity, a slow ataxic gait and a yellow-brown corneal discolouration at the limbus. The liver edge is palpable. Outline the diagnostic workup and the principles of initial management. [1]

Model Answer

Diagnostic approach (the rule, 2 marks): [1]

A movement or psychiatric disorder in a patient under 40 is Wilson disease until proven otherwise. The diagnosis is clinical-biochemical and uses the Leipzig scoring system (Ferenci 2003, PMID 12955875), which integrates clinical, biochemical and genetic data. The principle is that early diagnosis and treatment transform a fatal disease into a manageable one. [1]

Investigations (5 marks): [1]

1. Serum ceruloplasmin — typically low (under 0.2 g/L) in 85 to 95 percent of neurological Wilson disease. A normal ceruloplasmin does NOT exclude Wilson disease — it is an acute-phase reactant, raised in inflammation, pregnancy and oestrogen therapy. A low level is supportive but not diagnostic alone.
2. 24-hour urinary copper — the most useful single biochemical test. Elevated above 100 micrograms/24 hours is highly suggestive; above 40 micrograms warrants further testing. Always collected in an acid-washed container to avoid contamination.
3. Slit-lamp examination for Kayser-Fleischer rings — golden-brown copper deposits in Descemet's membrane of the cornea, present in 95 percent of neurological Wilson disease (less often in hepatic presentations). Pathognomonic when present.
4. Liver function tests and liver biopsy hepatic copper — abnormal LFTs are expected; hepatic copper quantification on liver biopsy (over 250 micrograms/g dry weight is diagnostic; normal is under 50) remains the gold standard for hepatic Wilson disease and provides staging of cirrhosis.
5. ATP7B genetic testing — full gene sequencing of the ATP7B gene on chromosome 13 is now first-line confirmatory in many centres, particularly in patients with intermediate Leipzig scores.
6. Brain MRI — may show signal change in the basal ganglia (putamen, globus pallidus) and the characteristic 'face of the giant panda' sign in the midbrain in established neurological disease; supportive but non-diagnostic.
7. Family screening — all first-degree relatives must be screened with ceruloplasmin, 24-hour urinary copper, slit-lamp examination, LFTs and ATP7B testing, because pre-symptomatic treatment prevents disease. [1]

Initial management principles (3 marks): [1]

1. Lifelong chelation therapy is the cornerstone — never stop once started, even after liver transplant. First-line is trientine (250 to 500 mg four times daily, better tolerated and increasingly preferred) or penicillamine (250 to 500 mg four times daily, copper chelator but with a high rate of adverse effects — initial neurological deterioration in 20 to 50 percent, nephrotic syndrome, bone marrow suppression, skin changes; requires pyridoxine 25 to 50 mg daily supplementation). I would use trientine first-line and reserve penicillamine for specific indications. Zinc acetate 50 mg three times daily impairs intestinal copper absorption and is used for maintenance therapy and for pre-symptomatic patients identified on family screening.
2. Dietary copper restriction — avoid copper-rich foods (shellfish, liver, nuts, chocolate, mushrooms) during the initial treatment phase.
3. Monitor response — clinical and biochemical monitoring (24-hour urinary copper to confirm effective chelation — target 200 to 500 micrograms/24 hours on chelation, falling to 100 to 200 on long-term maintenance; LFTs; neurological examination). Initially every 1 to 3 months, then 6 to 12 monthly.
4. Liver transplantation for decompensated liver disease or fulminant hepatic failure — curative for the hepatic disease and stabilises neurological disease. Less effective for established neurological damage.
5. Multidisciplinary input — hepatology, neurology, psychiatry, clinical genetics (for the family), dietetics, and social work. Pregnancy requires pre-conception counselling and continuation of chelation (switch penicillamine to zinc, reduce trientine). [1]