Parkinson’s disease in the ED: a potpourri of hyperpyrexia, dyskinesias, psychosis, and autonomic dysfunction
- Jan 22nd, 2018
- Matthew Baluzy
Authors: Matthew Baluzy, DO (EM Resident Physician, LAC+USC Emergency Medicine Residency) and Jeff Riddell, MD (Assistant Professor of Clinical Emergency Medicine, LAC+USC Emergency Medicine Residency) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)
A 60-year-old male with history of hypertension and Parkinson’s disease is brought to your emergency department from the local jail for altered mental status. Per EMS, the patient was arrested four days ago and since his arrival in jail has not been started on his home medications including hydrochlorothiazide and carbidopa/levodopa 25mg/250mg TID.
On arrival, the patient’s vital signs include: Temp 40 degrees Celsius, HR 125, BP 160/100, RR 24, SaO2 of 96% on 2L NC.
Exam reveals an ill-appearing male speaking one to two-word sentences of inappropriate and slow, mumbled words. His extremities are rigid with an asymmetric tremor. ECG shows sinus tachycardia. CXR and CT head are negative. Labs show a leukocytosis of 15,000, CK of 3,000, creatinine of 2.2, normal urine studies, and normal CSF studies.
What is going on with this patient?
A brief refresher on the basal ganglia can make it easier to remember the pathology, presentation, and treatment of Parkinson’s disease. Two important structures within the basal ganglia include the substantia nigra pars compacta and the striatum. Dopaminergic signals from the substantia nigra pars compacta have a net excitatory effect while acetylcholine in the striatum tends to have a net inhibitory effect.1
The loss of dopaminergic neurons in the substantia nigra pars compacta and formation of intraneuronal Lewy bodies are the hallmark of Parkinson’s disease.2 Strategies to treat the disease often involve increasing excitatory signals with dopamine or decreasing inhibitory signals with anticholinergic agents targeting the striatum.
Initially, most patients will have a characteristic triad of motor symptoms: Resting tremor, Bradykinesia, and Cogwheel rigidity.1
This is often accompanied by postural instability leading to an unsteady, shuffling gait. Many patients also demonstrate en-bloc turning (turns without twisting the torso) and anteropulsion or retropulsion (needing to take numerous steps with small forward or backward disturbances). The onset of the disease is between 40 and 70 years of age, and the progression is insidious, typically occurring over 5-15 years.1 The disease of often classified by four stages:
- Diagnosis: recognition of signs and symptoms
- Maintenance: on medications without significant postural instability
- Complex: increasing disability and decreased medication efficacy
- Palliative: inability to tolerate medications or significant disability
Disease progression leads to disability and death from complications including traumatic falls, infections such as aspiration pneumonia, and immobility leading to thromboembolic disease.3
Drug-induced parkinsonism (DIP) is the second-most-common form of parkinsonism and is often mistaken for Parkinson’s disease. Studies have found that nearly 7% of patients diagnosed with Parkinson’s disease are later reclassified as having DIP.4 Offending agents are those that cause dopaminergic receptor blockade in the basal ganglia. Common drugs include:
- Typical antipsychotics: haloperidol, chlorpromazine, prochlorperazine, fluphenazine, and promethazine
- Atypical antipsychotics: risperidone, olanzapine, aripiprazole, and ziprasidone
- Antiemetics: metoclopramide
- Calcium channel blockers: verapamil
Classically, DIP presents with symmetric symptoms and lack of tremor in comparison to the asymmetric features and resting tremor seen in Parkinson’s disease.4 In the emergency department, prompt recognition of DIP can prevent future morbidity from motor symptoms. Treatment includes cessation of the offending drug. Full resolution of symptoms may take weeks to months.
Early in the disease course, patients with Parkinson’s disease have a smooth and predictable response to dopaminergic medications. As the disease progresses the response to medications becomes variable and associated with motor fluctuations. Additionally, dyskinesias are abnormal movements that can result from chronic use of levodopa or other dopamine agonist. They can present as dystonia, ballismus, or choreas.5
ED evaluation and management of motor fluctuations and dyskinesias involve searching for precipitating illnesses and treatment of complications.6 One study found that acute akinesias were precipitated by gastrointestinal disturbances such as peptic ulcer disease and volvulus, systemic infections or recent surgical procedures.7 Complications of motor fluctuations and dyskinesias include dehydration and thromboembolism from prolonged periods of immobility. Persistent movements can cause rhabdomyolysis, myoglobinuria, and renal injury. Respiratory muscle dyskinesias may result in aspiration and respiratory failure requiring airway management. Benzodiazepines may be helpful in lessening the severity of dyskinesias.6 Alteration of Parkinson’s medications can be done in concert with a neurologist as dyskinesias and motor fluctuations are managed differently.
Acute psychosis is a frequently encountered complication later in the disease course and can be difficult to manage. Psychosis can result from disease progression, medication side-effects, or an underlying illness.6 The workup is similar to most patients with a new presentation of psychosis: a complete medication history, a search for occult causes and infections such as UTI or pneumonia, blood glucose, ECG, thyroid studies, a metabolic panel, and neuroimaging.
If the work-up is unrevealing, then the psychosis may be the result of the dopaminergic properties of Parkinson’s medications. In consult with a neurologist, severe psychosis may respond to down-titration of medications. Antipsychotics may be used, and the most frequently favored medications include quetiapine and clozapine.8 Medications such as haloperidol, olanzapine, and risperidone are avoided, as they may significantly worsen motor symptoms.6 Emergent management of psychosis with agitation should focus on benzodiazepines rather than antipsychotics in the ED.
Autonomic dysfunction in Parkinson’s disease is common and presents as constipation, urinary retention, and orthostatic hypotension. These findings often worsen with age, disease severity, and increased medication use.9 Constipation and urinary retention can be managed by usual measures and are rarely associated with fecal impaction, bowel obstruction, bowel perforation, or renal failure. Orthostatic hypotension is a frequent cause of syncope in this patient population.6 It results both from the disease itself and from dopaminergic medications. High risk patients for severe orthostatic hypotension include those initiating medications or in patients taking high doses. ED evaluation includes ruling-out other causes of syncope (ie, arrhythmia, PE, sepsis) and searching for secondary trauma. Acute management includes fluid administration and treatment of reversible causes. At discharge, the patient’s neurologist may recommend salt supplementation, compression stockings or down-titration of dopaminergic medications. Other pharmacologic options include volume expanders and vasopressors such as fludrocortisone and midodrine.10
If this was your diagnosis to the case presentation at the beginning of the post, then well done! Parkinsonism-hyperpyrexia syndrome (PHS) is a rare complication of Parkinson’s disease that closely resembles neuroleptic malignant syndrome.11 It results from sudden withdrawal of dopaminergic medications and/or the addition of dopamine-blocking medications. Medication noncompliance or abrupt dose changes may lead to PHS. Other cases have resulted from the addition of neuroleptics or from medication changes seen after deep brain stimulator implantation.12 Patients often present with fever, altered mental status, autonomic instability, and worsening parkinsonism. Like NMS, complications may include rhabdomyolysis, renal failure, electrolyte derangements, respiratory failure, and cardiovascular collapse.11
Treatment involves both supportive measures and reinstitution of dopaminergic medications. Cooling is essential using conductive or evaporative techniques, with additional benzodiazepines and paralytics as needed. Fluid administration is often required and antibiotics may be empirically started. If the precipitating factor was the removal of a dopaminergic drug such as levodopa, it should be reinstituted as soon as possible via PO or NG route if needed at the dose used prior to the onset of symptoms.11 Additional medications include bromocriptine and dantrolene. Bromocriptine can be used to restore dopaminergic tone and is dosed at 2.5 mg PO/NG TID initially and can be titrated to effect with a max dose of 40 mg/day. Dantrolene, a skeletal muscle relaxant, can be used to treat both hyperthermia and rigidity. It is often dosed at 1-2.5 mg/kg IV and can be repeated TID-QID up to a max dose of 10 mg/kg/day. It should be avoided in patients with underlying liver disease due to risk of hepatotoxicity.12 Admission to an ICU setting and early consultation with neurology is recommended.
-Drug-induced parkinsonism may result from the use of anti-dopaminergic agents. These include neuroleptics and antiemetics. Cessation of these medications can produce significant improvement in the patient’s motor symptoms.
-Motor fluctuations and dyskinesias are common. Search for underlying causes including infections, GI disorders, metabolic disturbances, or recent stressors such as surgery. Complications include rhabdomyolysis, thromboembolic disease and respiratory failure. Benzodiazepines may help acutely and the patient’s home medications will need to be adjusted.
-The evaluation of acute psychosis also involves searching for precipitating causes but may be secondary to the disease process itself and the use of dopaminergic medications. Benzodiazepines should be used for psychosis with agitation because neuroleptics may worsen motor symptoms. Dosage adjustments can improve symptoms but should be done with a neurologist. If neuroleptics are required, quetiapine and clozapine are recommended.
-Autonomic dysfunction includes urinary retention, constipation, and orthostatic hypotension. All are treated with usual measures, but persistent or severe orthostatic hypotension may require further treatment with volume expanders or vasopressors.
-Parkinsonism-hyperpyrexia syndrome is a rare complication that is caused by acute dopamine withdrawal. It presents similarly to NMS with fever, altered mental status, autonomic instability, and worsening parkinsonism. Treatment includes supportive care, reinstitution of dopamine agonist, and adjunctive medications such as bromocriptine and dantrolene.
References / Further Reading
- Blumenfeld H. Neuroanatomy through clinical cases. 2nd ed. Sunderland, MA: Sinauer Associates, Inc. Publishers; 2014.
- Massano J, Bhatia KP. Clinical Approach to Parkinson’s Disease: Features, Diagnosis, and Principles of Management. Cold Spring Harbor Perspectives in Medicine. 2012;2(6). doi:10.1101/cshperspect.a008870.
- Sloan E, Handel D, Gaines S. Chronic Neurological Disorders. In: Tintinalli, J. E. (2011). Emergency medicine: a comprehensive study guide. New York: McGraw-Hill.
- Shin HW, Chung SJ. Drug-Induced Parkinsonism. Journal of Clinical Neurology. 2012;8(1):15-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325428/. Accessed December 11, 2017.
- Quinn N. Drug treatment of Parkinson’s disease. The BMJ. 1995;310:575-579. https://www-ncbi-nlm-nih-gov.libproxy1.usc.edu/pmc/articles/PMC2548944/pdf/bmj00582-0039.pdf. Accessed December 11, 2017.
- Factor SA, Molho ES. Emergency department presentations of patients with Parkinson’s disease. The American Journal of Emergency Medicine. 2000;18(2):209-215. doi:10.1016/s0735-6757(00)90023-8.
- Thomas A, Iacono D, Luciano AL, Armellino K, Onofrj M. Acute akinesia or akinetic crisis in Parkinson’s disease. Neurological Sciences. 2003;24(3):219-220. doi:10.1007/s10072-003-01396.
- Friedman JH. Parkinson Disease Psychosis: Update. Behavioural Neurology. 2013;27(4):469-477. doi:10.1155/2013/645429.
- Verbaan D, Marinus J, Visser M, Rooden SMV, Stiggelbout AM, Hilten JJV. Patient-reported autonomic symptoms in Parkinson disease. Neurology. 2007;69(4):333-341.doi:10.1212/01. wnl.0000266593.50534.e8.
- Berger MJ, Kimpinski K. A Practical Guide to the Treatment of Neurogenic Orthostatic Hypotension. Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques. 2014;41(02):156-163. doi:10.1017/s0317167100016528.
- Newman, E.J., Grosset, D.G. & Kennedy, P.G.E. The Parkisonism-Hyperpyrexia Syndrome. Neurocrit Care (2009) 10: 136. https://doi-org.libproxy1.usc.edu /10.1007/s12028-008-9125-4
- Frucht SJ. Movement Disorder Emergencies Diagnosis and Treatment. Totowa, NJ: Humana Press; 2013. https://books.google.com/books?hl=en&lr=&id=dEhIiVp2l_MC&oi=fnd&pg= PA29&ots=vMBbq0Ik6R&sig=ubSgCL_tw2-758QdISbiXFcnlw0#v=onepage&q&f=false. Accessed December 11, 2017.