Abstract
Article abstract A 33-year-old woman admitted for meningoencephalitis had features of encephalitis lethargica develop on her third day of illness. She had ophthalmoplegia, akinetic mutism, and prominent extrapyramidal signs consisting of lip and hand tremors, cogwheel rigidity, and facial bradykinesia.
Encephalitis lethargica is a rare disorder, with only sporadic cases mentioned in the medical literature after 1921.1-5 The diagnosis is clinical but is complicated by the lack of distinguishing factors.6,7 Howard and Lees8 proposed seven major diagnostic criteria for encephalitis lethargica, defining it as an acute or subacute encephalitic illness with at least three of the following criteria: 1) signs of basal ganglia involvement; 2) oculogyric crises; 3) ophthalmoplegia; 4) obsessive-compulsive behavior; 5) akinetic mutism; 6) central respiratory irregularities; and 7) somnolence or sleep inversion or both. Our patient presented herein fulfilled these criteria as she had parkinsonian features, ophthalmoplegia, and akinetic mutism.
Case report.
A 33-year-old woman with an upper respiratory tract infection was admitted for fever, headache, vertigo, and vomiting. Three days later, she had slowing of mentation and neck stiffness, with photophobia and blurred vision develop. At the same time, she had extrapyramidal features of slurred speech, facial bradykinesia, and cogwheel rigidity. CSF examination revealed a pleocytosis: cells 1350/mm3 (polymorphs 80%, lymphocytes 20%, erythrocytes occasional); globulins positive; total proteins, 1.95 g/L (0.1–0.4); chloride, 121 mmol/L (120–130); glucose, 2.2 mmol/L (2.5–5.5); blood glucose, 8.6 mmol/L. CSF cultures for bacteria, mycobacteria, fungi, and viruses (herpes simplex, measles, mumps, Flavivirus) were negative.
She was treated for bacterial meningitis and responded within 1 week, with the repeat CSF showing a reduction of cells of 76 (lymphocytes 90%, polymorphs 10%, erythrocytes occasional) and proteins of 0.8 g/L.
However, she continued to be slow in mentation, and the facial bradykinesia and cogwheel rigidity worsened, until she was bedbound 15 days into her admission. Coarse tremors of her tongue, lips, and upper limbs developed. Her speech became increasingly slurred until there was complete absence of voluntary tongue movements. There was a sixth-nerve palsy with failure of abduction of the left eye.
The patient was diagnosed as having encephalitis lethargica, a postmeningoencephalitic syndrome associated with extrapyramidal dysfunction, ophthalmoplegia, and akinetic mutism. She responded to treatment with madopar (Roche, Basel, Switzerland) 375 mg/day, selegiline 10 mg/day, and bromocriptine 30 mg/day and was able to walk 1 month into her admission. Her mental state and speech returned to normal, and her ophthalmoplegia resolved 3 months later. At this time, the patient had her madopar reduced to 187.5 mg/day, and the selegiline and bromocriptine were gradually tapered off.
The MRI on the tenth day of her admission showed hyperintense lesions in the substantia nigra bilaterally on T2-weighted images (figure 1A). The T1-weighted scan was normal other than for mild leptomeningeal enhancement at the cerebellar folia (figure 1B), a finding supportive of the clinical picture of meningoencephalitis. The second scan 3 weeks later showed better definition of the same lesions: hyperintense on T2- (figure 2A) and hypointense with rim high signal on T1-weighted images (figure 2B). At 3 months, when the patient was almost fully recovered except for residual facial bradykinesia, a third follow-up scan with additional isotropic diffusion-weighted imaging was performed. It showed the same bilateral symmetric substantial nigral abnormalities, which were isointense to cerebrospinal fluid on the T2- and diffusion-weighted scans (figure 3).
Figure 1. (A) T2-weighted image on tenth day of admission shows bilateral hyperintense lesions in the substantia nigra (arrow). (B) Contrast-enhanced T1-weighted image on 10th day of admission shows leptomeningeal enhancement at the cerebellar folia.
Figure 2. (A) Follow-up T2-weighted image 3 weeks later shows better definition of the bilateral substantia nigra abnormalities (arrow). (B) Follow-up unenhanced T1-weighted image 3 weeks later of bilateral substantia nigra abnormalities, which are hypointense with rim high signal (arrow).
Figure 3. Follow-up diffusion-weighted image at 3 months with the patient almost fully recovered shows complete suppression of signal and isointensity to cerebrospinal fluid in the substantia nigra abnormalities (white arrow).
The brainstem auditory-evoked response showed a reversal of the wave-V/wave-I amplitude on the left side, whereas the visual and somatosensory study results were normal. Electroencephalographic and polysomnographic study results were normal. Investigation results to exclude treatable causes of parkinsonism, including ceruloplasmin, copper, and heavy metals, were normal.
Discussion.
The MRI lesions illustrate several interesting points. First, they show that patients with encephalitis lethargica have a radiologic correlate. Although depigmentation of the substantia nigra has been described previously in pathologic specimens,9 this is the first report of a patient showing bilateral substantia nigra lesions on MRI. It will assist physicians in diagnosing this complicated syndrome. Second, the MRI lesions were well-localized to the substantia nigra and bilateral. They correlated well with the extrapyramidal signs in this patient. In a normal individual, the substantia nigra, a part of the basal ganglia that connects with the striatum (caudate nucleus and globus pallidus), consists of black pigmented cells and produces dopamine, a chemical transmitter. The basal ganglia, through the action of dopamine, is responsible for planning and controlling automatic movements of the body via the corticobasal ganglia-thalamic pathway. Dopamine depletion from bilateral substantia nigra disease, as in this patient, interrupts this pathway and produces bradykinesia and rigidity. However, it is unclear why the substantia nigra is selectively involved in meningoencephalitis. Unfortunately, we could not isolate the etiologic agent as both the bacterial and viral cultures from the cerebrospinal fluid were negative. Third, the MRI lesions show the rapid nature and subsequent progression of the disease. The first MRI 10 days into her admission revealed changes in the substantia nigra bilaterally, suggesting a fairly acute process. The second MRI 3 weeks later showed unusual hypointense lesions with rim high signal on T1-weighted images. The cause of the rim high signal is unclear but may represent paramagnetic ion trapping. These changes were still present 3 months later, suggesting that they were likely to represent areas of focal damage with subsequent cystic encephalomalacia. In conclusion, although depigmentation of the substantia nigra has been described previously in pathologic specimens of patients with encephalitis lethargica, this is the first case of a patient showing bilateral substantia nigra changes on MRI.
- Received December 30, 1998.
- Accepted July 29, 1999.
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