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IM19.1-8 | Movement Disorders — PBL Case

CLINICAL SETTING

Dr Rajan is the General Medicine registrar at a tertiary teaching hospital in Chennai. He is supervising a final-year MBBS student, Aravind, during a General Medicine outpatient clinic. The next patient is Mr Krishnamurthy, a 68-year-old retired school headmaster, accompanied by his daughter. She does the talking: 'Appa has been having this shaking in his right hand for the last three years. It started small — just when he was resting — but now it is there all the time. He is also very slow. Getting dressed takes him an hour. His handwriting has become tiny. And recently he started having these sudden wild movements of his arms after his morning tablet, which frighten the whole family.' She places a tablet strip on the table: levodopa-carbidopa 100/25 mg, prescribed at a district hospital two years ago. 'He takes it three times a day.' Mr Krishnamurthy sits quietly, with a fixed, inexpressive face. His right hand is resting on his thigh, with a coarse tremor visible. Aravind opens his notebook and writes: 'Chief complaint: tremor — [classification?].'

Trigger 1: First Encounter — Characterising the Movement Disorder

Dr Rajan begins by observing Mr Krishnamurthy from across the desk before touching him. He notes: mask-like face with reduced blinking, right-hand rest tremor at approximately 4–5 Hz, slightly stooped posture, and reduced right arm swing on casual observation. He asks Mr Krishnamurthy to reach for a glass of water on the desk. As Krishnamurthy extends his arm, the tremor momentarily diminishes. He then asks him to write his name — the signature is in tiny micrographic script. On formal examination: cogwheel rigidity of the right arm, mild rigidity of the left arm, bradykinesia on right-hand finger-tapping (reduced amplitude and speed by the fourth tap), and a mildly hypophonic voice. His gait: small shuffling steps, reduced right arm swing, and he turns in three to four small steps rather than pivoting. There is no cerebellar sign. Cranial nerves are intact. DAT-SPECT done six months ago shows asymmetrically reduced uptake in the right putamen.

DISCUSSION POINTS

  • Classify Mr Krishnamurthy's tremor using the activation-condition framework (rest, postural, kinetic, intention). What does its disappearance during voluntary reach tell you about its origin?
  • The examination shows bradykinesia, cogwheel rigidity, rest tremor, and micrographia. Name the clinical syndrome, state the minimum diagnostic criteria required to make this diagnosis, and identify which physical finding Dr Rajan used as his mandatory criterion.
  • What does the DAT-SPECT finding of asymmetrically reduced putaminal uptake indicate, and why is this pattern asymmetric at onset in this condition?
Click to reveal Trigger 2: The Second Problem — 'Wild Movements After the Morning Tablet' (discuss previous trigger first!)

Trigger 2: The Second Problem — 'Wild Movements After the Morning Tablet'

Dr Rajan asks the daughter to describe the 'wild movements' in detail. She says: 'About an hour after he takes his morning tablet — the levodopa one — his arms and sometimes his face start moving on their own. Like dancing. It lasts for about 30 to 40 minutes and then goes away on its own. He doesn't fall but it is distressing. It has been happening for the last 4 months.' Dr Rajan asks Mr Krishnamurthy about his day: he describes that in the morning before his tablet he is stiff and slow (bad), then after about 45 minutes the tablet 'kicks in' and he feels much better (good), but then the 'dancing' starts (bad again), and by lunchtime he is slow again until his next tablet. Aravind sketches a timeline on his notepad. Dr Rajan reviews the prescription: levodopa-carbidopa 100/25 mg three times daily — the same dose since it was started two years ago. He has not been reviewed by a neurologist. He is also on metformin 500 mg twice daily for type 2 diabetes.

DISCUSSION POINTS

  • Draw (or describe) the motor fluctuation pattern for a single dosing interval based on Mr Krishnamurthy's description. Name the two distinct motor complications he is experiencing and their relationship to plasma levodopa levels.
  • What is the pathophysiological mechanism responsible for the 'dancing movements' 1 hour after the morning levodopa dose? At which stage of Parkinson's disease treatment are these most likely to develop, and what factors accelerate their onset?
  • What adjustments to the current levodopa regimen, or what additional pharmacological options, would you consider for managing motor fluctuations and dyskinesias? Name a specific drug from at least two different drug classes with their mechanisms of action.
Click to reveal Trigger 3: The Daughter's Worry — Is It Really Parkinson's? (discuss previous trigger first!)

Trigger 3: The Daughter's Worry — Is It Really Parkinson's?

The daughter leans forward: 'Doctor, I read on the internet that there are several conditions that look like Parkinson's but are worse — Parkinson's-plus they call it. My uncle was told he had Parkinson's but then we found out he had something different because he started falling and his eyes stopped moving properly.' Dr Rajan considers this. He performs two additional examinations: (1) asking Mr Krishnamurthy to follow a moving finger vertically — his vertical pursuit eye movements are full and smooth; (2) asking him to perform a rapid heel-toe test bilaterally — no cerebellar signs. He also notes: no severe orthostatic hypotension on standing (no lightheadedness, BP change < 15 mmHg systolic). He recalls that Mr Krishnamurthy has had a sustained, significant response to levodopa for two years, with onset of symptoms at age 65 and asymmetric right-sided onset of rest tremor. He tells the daughter: 'The combination of features here strongly favours idiopathic Parkinson's disease rather than a Parkinson-plus syndrome.'

DISCUSSION POINTS

  • The daughter mentions an uncle who had vertical gaze palsy and early falls. Which Parkinson-plus syndrome does this describe, and how does its pathology differ from idiopathic Parkinson's disease?
  • Dr Rajan checked vertical eye movements and orthostatic hypotension specifically. Which Parkinson-plus syndromes would these findings help exclude, and what are the defining clinical features of each?
  • What features in Mr Krishnamurthy's history support a diagnosis of idiopathic Parkinson's disease over Parkinson-plus? Use the IPMDS 2015 clinical diagnostic criteria framework to make your argument.
Click to reveal Trigger 4: The Young Cousin in the Waiting Room (discuss previous trigger first!)

Trigger 4: The Young Cousin in the Waiting Room

While writing up the plan for Mr Krishnamurthy, a nurse comes in and says: 'Doctor, there is a young man — 24 years — waiting outside. His family brought him saying he was fine last month but suddenly developed tremor, problems walking, and his behaviour changed. His school results have been deteriorating for a year. The family mentions a brother who had liver disease at age 19.' Dr Rajan asks the nurse to bring him in to see Aravind first as a teaching case. Aravind examines the young man and finds: a coarse wing-beating tremor of both arms on outstretching, dysarthria, mild dystonic posturing of the left hand, and an anxious, labile affect. There are no cerebellar signs. Blood tests from an outside lab show serum ceruloplasmin 9 mg/dL (reference 20–40 mg/dL). Dr Rajan requests an urgent slit-lamp examination.

DISCUSSION POINTS

  • What is the most likely diagnosis in this 24-year-old, and what is the significance of the low serum ceruloplasmin combined with the family history of early-onset liver disease in a sibling?
  • Describe the diagnostic triad of this condition. What would you expect to see on slit-lamp examination, on MRI brain, and on 24-hour urinary copper?
  • What is the first-line pharmacological treatment for this condition, and why does early treatment matter? If untreated, what neurological and systemic complications would you anticipate?

Group Task Assignments

  • Using the motor fluctuation timeline described by Mr Krishnamurthy, construct a labelled diagram showing plasma levodopa levels across a single dosing interval and map 'off' (wearing off), 'on' (therapeutic), and 'on with dyskinesia' (peak-dose) states onto the curve. Explain how COMT inhibition and dopamine agonist addition would alter this curve.
  • Draft an evidence-based pharmacological management plan for Mr Krishnamurthy to address: (a) his motor fluctuations (wearing off), and (b) his peak-dose dyskinesias. For each drug you add or adjust, state the mechanism, dose class, key side effects, and one drug interaction relevant to his concurrent metformin use.
  • Debate the proposition: 'DAT-SPECT should be performed in all patients presenting with a suspected movement disorder before commencing levodopa therapy.' Consider the diagnostic utility, cost-effectiveness, and clinical scenarios where it would and would not change management.
  • Construct a differential diagnosis table for the 24-year-old with low ceruloplasmin, comparing Wilson's disease with other causes of young-onset movement disorder (juvenile PD, Huntington's disease, drug-induced, structural). For each, state the confirmatory investigation and the treatment.

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [IM19.2] How are movement disorders classified by phenomenology — specifically, what are the defining features that distinguish rest tremor from postural and intention tremor, and how does this classification predict the anatomical substrate?
  2. [IM19.4] What are the components of a structured neurological examination for movement disorders, and what do UPDRS/MDS-UPDRS scores measure in the assessment of Parkinson's disease severity?
  3. [IM19.6] What are the IPMDS 2015 clinical diagnostic criteria for idiopathic Parkinson's disease, and what clinical features constitute absolute exclusion criteria (i.e., features that rule out idiopathic PD in favour of a Parkinson-plus syndrome)?
  4. [IM19.8] What are the six major drug classes used in Parkinson's disease pharmacotherapy, what is the mechanism of each, and what are the principal long-term motor complications of levodopa therapy (wearing off, peak-dose dyskinesias, on-off fluctuations) and their management?
  5. [IM19.7] What is DAT-SPECT, what does it image, and in which clinical scenarios is it the investigation of choice for differentiating causes of parkinsonism? Why is it normal in drug-induced parkinsonism and essential tremor?
  6. [IM19.5] What are the diagnostic criteria for Wilson's disease (hepatolenticular degeneration), how is the diagnosis confirmed biochemically and by imaging, and what is the first-line treatment?