Provisional Diagnosis: Parkinsonism-Hyperpyrexia Syndrome (PHS)
The provisional diagnosis for a patient presenting with severe parkinsonian symptoms following dopaminergic medication withdrawal is Parkinsonism-Hyperpyrexia Syndrome (PHS), a rare but potentially fatal neurological emergency that mimics neuroleptic malignant syndrome. 1, 2
Core Diagnostic Features
PHS presents with a characteristic tetrad that must be recognized immediately:
- Hyperthermia (fever, potentially up to 41°C or higher) 3, 1
- Severe worsening of parkinsonian rigidity ("lead pipe" rigidity, muscle stiffness) 3, 2
- Altered mental status (ranging from confusion and reduced consciousness to delirium, stupor, or coma) 3, 2
- Autonomic instability (tachycardia, blood pressure fluctuations, diaphoresis, tachypnea) 3, 2
Critical Triggering Factor
The most important diagnostic clue is the temporal relationship to dopaminergic medication withdrawal or dose reduction, particularly levodopa. 1, 2, 4 This syndrome occurs when there is abrupt cessation or significant reduction of antiparkinsonian medications, creating a state of dopamine deficiency in the central nervous system. 3, 2
Key Distinguishing Features from Other Syndromes
PHS must be differentiated from neuroleptic malignant syndrome (NMS), though they share similar presentations:
- PHS: Triggered by withdrawal of dopaminergic drugs (creating dopamine deficiency) 2, 4
- NMS: Triggered by dopamine antagonist exposure (antipsychotic medications) 3
- Onset timing: PHS typically develops over days following medication withdrawal, while NMS usually occurs within 1-7 days of antipsychotic exposure 3
Supporting Laboratory Findings
While no pathognomonic tests exist, expect to find:
- Markedly elevated creatine kinase (CK) due to muscle breakdown 3, 2
- Leukocytosis (typically 15,000-30,000 cells/mm³) 3
- Metabolic acidosis 3, 2
- Elevated liver enzymes (transaminases, alkaline phosphatase, LDH) 3
- Myoglobinuria (indicating rhabdomyolysis) 3
Critical Complications to Monitor
PHS carries significant morbidity and mortality (up to 4% mortality, with an additional one-third having permanent sequelae): 2
- Acute renal failure (from rhabdomyolysis and myoglobinuria) 2
- Aspiration pneumonia 2
- Deep venous thrombosis/pulmonary embolism 2
- Disseminated intravascular coagulation (DIC) 2
- Cardiac arrhythmias 1
Differential Diagnosis to Exclude
Before confirming PHS, systematically rule out other acute illnesses that can present similarly: 1
- Sepsis/systemic infection (PHS mimics septic presentation with fever and altered mental status) 5, 6
- Pneumonia 1
- Central anticholinergic toxicity 1
- Heat stroke 1
- Primary CNS pathology (stroke, encephalitis, meningitis) 1
- Serotonin syndrome (if patient on serotonergic medications; distinguished by myoclonus, hyperreflexia, and clonus rather than rigidity) 3
Common Pitfall to Avoid
The most dangerous pitfall is mistaking PHS for sepsis and delaying reinstitution of dopaminergic therapy. 5, 6 While both conditions present with fever, altered mental status, and systemic inflammatory response, the presence of severe parkinsonian rigidity and recent medication withdrawal should immediately raise suspicion for PHS. 5, 2
Documentation Requirements
Your provisional diagnosis should include:
- Specific history of dopaminergic medication withdrawal (timing, which medications, dosage changes) 2, 4
- Presence of all four cardinal features (hyperthermia, rigidity, altered consciousness, autonomic instability) 3, 2
- Baseline parkinsonian status before the acute deterioration 2
- Exclusion of infectious/metabolic causes 1
Special Consideration for DBS Patients
In patients with deep brain stimulators (DBS), battery depletion or device malfunction can trigger PHS even without medication changes. 5, 6, 7 This represents an additional mechanism of dopamine deficiency that must be considered in the differential diagnosis. 6, 7