Parkinsonism–hyperpyrexia syndrome

Related Subjects: Acute Kidney Injury |Acute Rhabdomyolysis |Hyperkalaemia |Neuroleptic Malignant Syndrome |Malignant Hyperpyrexia (Malignant Hyperthermia) |Parkinsonism–hyperpyrexia syndrome |Serotonin syndrome |Cholinergic crisis-syndrome |Anticholinergic syndrome

🧠 Parkinsonism–Hyperpyrexia Syndrome (PHS) is a rare but life-threatening emergency seen in patients with Parkinson’s disease. It most often follows abrupt withdrawal, dose reduction, delayed administration, or poor absorption of dopaminergic medication, especially 💊 levodopa. It may also occur during intercurrent illness, surgery, trauma, dehydration, or deep brain stimulator malfunction.

⚡ Pathophysiology: sudden central dopamine deficiency → severe motor decompensation, rigidity, hyperthermia and autonomic instability. Clinically, it resembles neuroleptic malignant syndrome (NMS), but PHS is usually due to dopaminergic failure rather than dopamine receptor blockade.

🔥 Key Clinical Features

• 🌡️ Hyperthermia: Fever or hyperpyrexia, often with systemic deterioration.
• ⚡ Severe rigidity: Marked worsening of baseline Parkinsonism, bradykinesia or akinesia.
• 💓 Autonomic instability: Sweating, tachycardia, labile blood pressure and dehydration.
• 🧩 Neurological features: Confusion, delirium, dysphagia, stupor or coma in severe cases.
• 🩸 Rhabdomyolysis and AKI: Raised CK, myoglobinuria and risk of renal failure.

⚠️ Common Triggers

• ❌ Sudden withdrawal, reduction or delayed administration of levodopa or dopamine agonists.
• 🚫 Poor absorption due to vomiting, ileus, bowel obstruction or being nil by mouth.
• 🤒 Intercurrent infection such as pneumonia, aspiration pneumonia or UTI.
• 🩺 Surgery, trauma, dehydration, metabolic stress or acute hospital admission.
• 💊 Dopamine-blocking drugs such as haloperidol, metoclopramide or prochlorperazine.
• 🔋 Deep brain stimulator battery failure, malfunction or accidental switching off.

🧪 Investigations

• 📈 Creatine kinase: often raised due to rigidity and rhabdomyolysis.
• 🧪 U&E, creatinine, LFTs, FBC, CRP, glucose, calcium, magnesium and phosphate.
• 💧 Look for dehydration, hypernatraemia, AKI and electrolyte disturbance.
• 🧫 Blood cultures, urine culture and CXR if infection or sepsis is possible.
• 💊 Full medication review: check exact Parkinson’s drug timings, omissions and recent changes.
• 🔋 If the patient has deep brain stimulation, check device function urgently.

🔍 Differential Diagnosis

• Neuroleptic malignant syndrome: recent antipsychotic or dopamine-blocking antiemetic exposure.
• Sepsis: infection causing fever, delirium and systemic deterioration.
• Serotonin syndrome: serotonergic drugs, clonus, hyperreflexia and diarrhoea.
• Malignant hyperthermia: peri-anaesthetic trigger, severe hypercapnia and rigidity.
• Heat stroke: environmental exposure with failure of thermoregulation.

🚨 Complications

• 🩸 Rhabdomyolysis and acute kidney injury.
• 🫁 Aspiration pneumonia and respiratory failure.
• 🧬 Disseminated intravascular coagulation.
• 🛌 Pressure injury, venous thromboembolism and prolonged immobility.
• ⚰️ Death if untreated or recognised late.

💊 Management

• 📞 Treat as a medical emergency; involve neurology, acute medicine, pharmacy and critical care early.
• 💊 Restart dopaminergic therapy urgently, especially levodopa, using the patient’s usual dose and exact timing where possible.
• 🧃 If unable to swallow, give dispersible levodopa via NG tube where appropriate.
• 🩹 If enteral treatment is not possible, consider specialist alternatives such as rotigotine patch or apomorphine under neurology/pharmacy guidance.
• 💧 Give IV fluids, correct electrolytes and monitor urine output, renal function and CK.
• ❄️ Use active cooling for significant hyperthermia; antipyretics alone are usually insufficient.
• 🦠 Treat infection, aspiration, dehydration or other precipitating causes.
• 🚫 Stop and avoid dopamine-blocking drugs such as haloperidol, metoclopramide and prochlorperazine.
• 🏥 Consider ICU/HDU care if severe hyperthermia, respiratory failure, AKI, shock or reduced consciousness.
• 💪 Dantrolene, bromocriptine or amantadine have been reported in severe cases, but should be used only with specialist advice.
• 🕊️ In advanced or end-stage Parkinson’s disease, consider ceilings of care and palliation if the patient fails to respond to an appropriate trial of active treatment.

⏰ UK hospital safety point: Parkinson’s medication is time-critical. Levodopa should be given at the patient’s usual individually prescribed times, not simply at standard drug-round times. NICE states that adults with Parkinson’s disease in hospital or care homes should receive levodopa within 30 minutes of their individually prescribed administration time.

💡 Exam Tip:
PHS = Parkinson’s patient + missed, stopped or poorly absorbed dopaminergic medication.
NMS = dopamine receptor blockade, usually after antipsychotic or dopamine-blocking antiemetic exposure.
Always check the drug chart in any Parkinson’s patient with acute fever, rigidity, delirium or immobility.