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August 2016

Enteroviral Postencephalitic Parkinsonism With Evidence of Impaired Presynaptic Dopaminergic Function

Author Affiliations
  • 1Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 2Department of Neurology, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, England
JAMA Neurol. 2016;73(8):1023-1025. doi:10.1001/jamaneurol.2016.1043

Postencephalitic parkinsonism is reported following infection with certain viruses such as Japanese B encephalitis virus, St Louis encephalitis virus, western equine encephalitis virus, eastern equine encephalitis virus, West Nile virus, Epstein-Barr virus, influenza A virus, and certain enteroviruses such as coxsackievirus B and echoviruses.1 These viruses affect the cortex, thalamus, brainstem, and spine, but preferential involvement of the substantia nigra (SN) has been reported.1,2 Postencephalitic parkinsonism with SN involvement has also been reported in cases of encephalitis lethargica (EL; von Economo disease),3,4 which occurred in epidemic form between 1915 and 1928. To our knowledge, although a viral etiology has long been suspected in EL, no infectious agent has ever been isolated.

The mechanism underlying viral SN tropism is not known. Nonetheless, collectively these cases support the hypothesis that viral infection of the SN can produce parkinsonism, and some have argued that viruses may be one of many environmental causes of nigrostriatal degeneration resulting in the subsequent development of idiopathic Parkinson disease.1,2

Report of a Case

A previously healthy woman in her 30s with no recent travel history presented to an outside facility with a 6-day history of left otalgia, headache, fever, and neck stiffness. Her body temperature was 38.9°C, but her neurologic examination results were reportedly normal. Cerebrospinal fluid analysis revealed an elevated protein level with associated lymphocytic pleocytosis; polymerase chain reaction results were positive for enterovirus (Table). Four days following admission, she developed progressive asymmetric (left > right) quadriparesis with rigidity and a fluctuating level of alertness. Magnetic resonance imaging (MRI) of the brain demonstrated symmetrical T2 signal change extending from the midbrain caudally to the dorsal pons (Figure). Given continued deterioration in the intervening days, transfer to our institution was recommended. Six days prior to transfer, she was treated with a course of intravenous immunoglobulins and began treatment with carbidopa, 12.5 mg, and levodopa, 50 mg, 3 times daily.

Table.  Laboratory Investigation Results
Laboratory Investigation Results
Figure.  Magnetic Resonance Imaging (MRI) and Dopamine Transporter Scan Imaging
Magnetic Resonance Imaging (MRI) and Dopamine Transporter Scan Imaging

A, Coronal fluid-attenuated inversion recovery MRI 3 days after presentation showing signal change extending caudally from the midbrain to the pons. B, T2-weighted axial MRI 15 days later showing overall improvement and maturation of signal in the substantia nigra (SN), right (arrowhead) greater than left. C, T2-weighted axial MRI at 1 year demonstrating gliotic changes in the SN, right (arrowhead) greater than left. D, T2-weighted axial MRI demonstrating subtle signal abnormality in the bilateral basal ganglia at presentation. E, T2-weighted axial MRI showing no appreciable evolution or radiologic evidence of tissue destruction at 1 year. F and G, Dopamine transporter scan 3 weeks (F) and 1 year (G) after presentation showing reduced uptake in the right putamen and in the right greater than left putamen, respectively.

At transfer 2 weeks after initial presentation, the patient was alert but her speech was hypokinetic. She had ocular flutter and marked rigidity, left greater than right, in all 4 limbs. Repeated MRI showed overall improvement but interval maturation of the signal change in the SN, right greater than left (Figure). Dopamine transporter scan demonstrated reduced tracer uptake in the right striatum (Figure). Ongoing levodopa therapy resulted in near resolution of her parkinsonism and was discontinued a few months after discharge.

Evaluation at 1 year revealed cogwheel rigidity, bradykinesia, and rest tremor in her left upper extremity. She also reported intermittent dystonic posturing of her left foot. Repeated MRI showed gliotic changes in the right SN (Figure). Dopamine transporter scan demonstrated reduced uptake in the putamen, right greater than left (Figure). She is currently undergoing a treatment trial with ropinirole hydrochloride.


To our knowledge, this is the first report of viral postencephalitic parkinsonism demonstrating radiographic evidence of impaired dopaminergic presynaptic function. Positron emission tomography with fluorine F 18–labeled fluorodopa has been performed on patients with both pandemic-associated and sporadic EL, with results comparable to those of patients with Parkinson disease.5 Although diagnostic criteria exist for EL, the scope of the disorder remains ill defined and it is unclear whether all cases of EL share the same etiology or even whether EL is a distinct nosological entity.5,6 Consequently, the role of infection in this disorder remains hypothetical.

The patient presented with levodopa-responsive parkinsonism in the setting of enteroviral encephalitis. Initial MRI showed diffuse brainstem signal change, but repeated imaging over a year demonstrated asymmetrical destructive changes in the SN (right > left). Functional imaging showed persistent changes in the striatum. Although the patient’s parkinsonism is currently static, it remains to be seen whether it progresses along the lines of Parkinson disease.

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Article Information

Corresponding Author: Michel Toledano, MD, Department of Neurology, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, Fulham Palace Road, London W6 8RF, England (michel.toledano@imperial.nhs.uk).

Published Online: June 27, 2016. doi:10.1001/jamaneurol.2016.1043.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

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