Movement Disorders Vol. 10, No. 2, 1995,.pp. 215-219 0 1995 Movement Disorder Society

Brief Report

Reversible Parkinsonian Syndrome Complicating Cy sticercus Midbrain Encephalitis

Ashok Verma, Joseph R. Berger, "Brian C. Bowen, and Juan Sanchez-Ramos

Departments of Neurology and *Radiology, the University of Miami School of Medicine, Miami, Florida, U.S.A.

Summary: We describe a clinical picture similar to Parkinson's disease in a patient with midbrain encephalitis due to cysticercosis. The clinical, radio- graphic, and cerebrospinal fluid findings suggested an inflammatory reaction to a dying cyst that involved midbrain structures. The encephalopathy appeared to worsen temporarily after the institution of anticysticercus therapy. A dis- cordance between worsening parkinsonian symptoms and improving pyrami- dal features was noted. Virtually a complete clinical recovery eventually en- sued. Key Words: Parkinson syndrome-Neurocysticercosis-Encephalitis- Praziquantel .

Neurocysticercosis (NCC), a parasitic disease caused by the encysted larvae of the tapeworm, Taenia solium, is endemic in Asia, Eastern Europe, and South America (1). In United states, NCC, with rare exception (2), is seen only in the immigrant population (3-5). NCC produces a highly variable clinical picture depending on the number and site of the lesions, host immune response against the par- asite, and the sequelae of the previous infestations (1-8). A potentially serious brain reaction (cysticer- cotic encephalitis) to the released antigens of dying cysts may occur as either a spontaneous phenome- non or during anticysticercosis therapy (7-8). We report a case of parkinsonism complicating cys- ticercus midbrain encephalitis. The extrapyramidal features resolved completely with recovery of the encephalitic illness.

A videotape segment accompanies this article. Accepted September 6, 1994. Address correspondence and reprint requests to Dr. J.

Sanchez-Ramos at Department of Neurology, University of Mi- ami School of Medicine, 1501 N.W. 9th Avenue, Miami, FL 33136. U.S.A.

CASE REPORT

A 31-year-old woman from Nicaragua had gener- alized tonic-clonic seizures for 5 years. The previ- ous investigations included two brain computed to- mographic scans that showed multiple intraparen- chymal calcified lesions compatible with a diagnosis of neurocysticercosis. Her seizures were well con- trolled on a daily dose of 300 mg phenytoin. On February 15, 1993, she presented with a low-grade fever, increasing lethargy, and intermittent diplopia for 2 days. She denied headache, vomiting, or re- currence of seizures. General physical examination was unremarkable except for a temperature of 99°F. No subcutaneous nodules, muscle tenderness, or nuchal rigidity was observed. She was drowsy but arousable and, when aroused, answered questions appropriately. Corectopia with 3-mm pupils and light-near dissociation were noted. She had a verti- cal gaze palsy and a slight skew deviation with left hypertropia. There was no papilledema. The cranial nerves were otherwise normal. Motor examination revealed normal strength and coordination. Muscle

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216 A . VERMA ET AL.

stretch reflexes were brisk in the left upper extrem- ity. Plantar responses were flexor bilaterally.

Laboratory investigations including complete blood count, differential leukocyte count, platelets, serum electrolytes, and blood chemistry were nor- mal. Other normal laboratory tests included rapid plasma reagin, fluorescent treponemal antibody as- say, prothrombin time, activated partial thro- moplastin time, antithrombin 111, fibrinogen, pro- tein C, protein s, lupus anticoagulant, rheumatoid factor, and antinuclear antibody assay.

The erythrocyte sedimentation rate was 48 mm/h. Toxicology screen was negative and serum phenyt- oin level was 18.2 ng/ml. A chest radiograph and electrocardiogram were normal. Brain computed tomography (CT) scan with and without contrast enhancement showed diffuse, scattered calcifica- tion with slight ventricular asymmetry, with the right ventricle larger than the left (Fig. 1). Lumbar puncture revealed clear cerebrospinal fluid with an opening pressure of 280 mm of water, cells 120/dl (98% monocytes), protein 54 mgldl, and glucose 57.7 mg/dl (blood glucose 95 mg/dl). A cerebrospi- nal fluid (CSF) gram stain, India ink preparation, serological test for cryptococcal antigen, and acid- fast bacillus stain were all negative. No microbial growth was seen on CSF cultures. A tuberculin (pu- rified protein derivative) skin test was 22 mm after 48 h.

Praziquantel (50 mg/kg weightlday in divided doses) therapy was started. Her clinical condition was monitored in a neurointensive care unit and she received intravenous dexamethasone (4 mg every 6 h) in addition to continued phenytoin and support- ive measures. During the next 2 days, her drowsi-

ness progressed to stupor; new ophthalmological findings included central ptosis, restriction of hori- zontal gaze, and left fourth cranial nerve palsy. She developed bilateral hemiparesis that was greater on the left side. Her temperature rose to 101°F with a concomitant leukocytosis (maximum 23.4 x lo3). A repeat brain CT scan on February 20, 1993 was un- changed. An electroencephalogram showed diffuse slowing of background without epileptiform activ- ity. A CT scan of the head revealed multiple calci- fied and cystic lesions. A cranial magnetic reso- nance image showed a large cyst in the outflow tract of the fourth ventricle, and the midbrain tectal area showed an enhancing cysticercus lesion (9) that in- volved the periaqueductal gray (Fig. 2). A second, less intense, area of enhancement was seen in the medial ventral midbrain (left greater than right).

On February 25, 1993, her fever subsided and her level of consciousness improved. She exhibited a moderate right-sided weakness and dense left hemi- plegia. On March 1, resting tremor of the right arm at -4-5 Hz was noted. The following day she had features of right hemiparkinsonism with cogwheel rigidity and the absence of tremor in the left arm. The rigidity and tremors increased further and per- sisted during the next week, while her hemiparesis continued to improve. Seven days later, she was conscious and responsive, but was not able to am- bulate because of mixed symptoms of parkinsonism (predominantly right sided) and hemiparesis (mainly left side). Praziquantel therapy was contin- ued for 21 days followed by rapid tapering of corti- costeroid drugs. On March 11, her left-sided weak- ness was only mild with improvement in parkinso- nian symptoms. The extrapyramidal features

FIG. 1. Computed tomography of the brain (February 15) shows diffuse scat- tered calcification with slight ventricular asymmetry. Level of basal ganglia (A) and level of the body of the lateral ven- tricles (B).

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PARKINSONISM COMPLICATING NEUROCYSTICERCOSIS 217

A-C

FIG. 2. Cranial magnetic resonance scan (February 18). A A postgadolinium axial T1-weighted image shows enhancement in the periaqueductal gray matter (long arrow) and the medial ventral midbrain (short arrow). B A midsagittal section reveals contiguous areas of nodular (short arrow) and peripheral, cyst-like enhancement in the fourth ventricle. The enhancement in the periaqueductal region (long arrow) and ventral mesencephalon is also seen. C: An axial section through the medulla shows the cystic lesion within the fourth ventricle.

continued to improve in the following days. Soon before her discharge to a rehabilitation facility, her parkinsonism had markedly improved (see video- tape) and she could walk a few steps with assis- tance.

On a follow-up visit (July 15, 1993) she was asymptomatic. She displayed a restriction of up and down gaze and small corectopic pupils with light- near dissociation. She had no other neurological deficit. She continues to receive phenytoin and a daily 300 mg isoniazid for 6 months for antituber- culous prophylaxis.

DISCUSSION Symptomatic or secondary parkinsonism can oc-

cur in an encyclopedic number of disease states (10). Most of these syndromes are irreversible, al- though in some cases with metabolic ( I l ) , “trau- matic” (12), vascular (13), toxic (14), or drug- in- duced (10) parkinsonism, the symptoms may be self-limiting or reversible after removal of the caus- ative factor. Reversible parkinsonism occurring in cysticercotic midbrain encephalitis has not been previously described.

Unlike idiopathic Parkinson’s disease, the ex- trapyramidal symptoms of secondary parkinsonism are often combined with additional neurological or systemic features that provide the etiological diag- nosis. In our case, the clinical picture, CSF find- ings, and brain images indicated an acute inflamma- tory response to degenerating cysticercus cysts in-

volving critical brainstem structures. The eye findings can be explained by the enhancing lesion in the lining of the cerebral aqueduct extending to pe- riaqueductal gray and tectal structures. The altered state of consciousness was likely due to involve- ment of the reticular activating system in the mid- brain tegmentum. The bilateral and asymmetrical motor manifestations suggested involvement of cor- ticospinal tracts of the cerebral peduncles and sub- stantia nigra. The inflammatory reactions to degen- erating cysticercus lesions appeared to be aggra- vated by the antiparasitic praziquantel therapy resulting in clinical signs of parkinsonism and hemi- plegia of greater magnitude than the visible extent of the enhancing midbrain lesions would suggest. The cause of the dense left hemiplegia is difficult to explain without neuroimaging evidence of inflam- mation or edema in corticospinal pathways coursing through the right cerebral peduncle. The asymme- try of the clinical expression of parkinsonism was probably a consequence of greater involvement of substantia nigra in the left midbrain (as visualized in the magnetic resonance scan) and perhaps involve- ment of the corticospinal pathway higher up in the region of the right internal capsule. However, neu- roimaging did not reveals lesions in the striatum or internal capsule. The nodular cysticercus lesion within the caudal fourth ventricle did not result in obstructive hydrocephalus and does little to explain the clinical features of the case. The mild enlarge- ment of the right lateral ventricle, due perhaps to

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218 A . VERMA ET AL.

partial obstruction of the right foramen of Monroe, was of insufficient magnitude to have an impact on corticospinal pathways or basal ganglia function. The reversibility of the motor symptoms in this case suggests that edema related to inflammation initi- ated by the degenerating cyst(s), rather than a de- structive process, was responsible for the clinical features.

Several disease states with variable but predom- inantly midbrain lesions and parkinsonism have been described. The clinical features of postenceph- alitis parkinsonism (PEP) (15,16), namely, acute en- cephalitic illness with lethargy, oculomotor signs, and pyramidal and extrapyramidal features some- what resemble this case. The midbrain is the dom- inant site of neuronal destruction in PEP (15). How- ever, classic PEP follows viral encephalitis and the symptoms are not reversible (15). Occasional cases of transient parkinsonism occurring with encepha- litis due to arboviruses, measles, and varicella- zoster virus have been described (15,17). Neuro- syphilis, Creutzfeldt-Jakob disease, and the ac- quired immunodeficiency syndrome are other infectious diseases that may result in midbrain dys- function, including parkinsonism (10).

Acute-onset parkinsonism may result from vas- cular insult to the basal ganglia (10,13,18-22), and this can be reversible in clinical course (13,19,20). Tolosa and Santamaria (19) reported three patients who developed subacute parkinsonism with CT ev- idence of basal ganglia infarction. There were no other major clinical signs, and the patients sponta- neously improved. Friedman et al. (13) reported acute-onset parkinsonism after a stroke in a young patient. A brain CT scan showed bilateral basal gan- glia infarcts. The symptoms reversed over 10 days without any specific antiparkinsonian therapy. However, infarction of the basal ganglia frequently has been seen without evidence of associated par- kinsonism. One obvious explanation could be that these patients have additional deficits severe enough to obliterate the underlying parkinsonian symptoms. For example, a pyramidal tract lesion would mask bradykinesia and tremor, as was evi- dent in our case. Parkinsonism can be experimen- tally produced in monkeys by isolated structural le- sions of the substantia nigra (23). The existence of parkinsonism as a consequence of lacunar strokes in the striatum and midbrain has been described (18,22) by some, but refuted by others (24). The symptoms in “arteriosclerotic” parkinsonism are not reversible (18,21,22).

In summary, cysticercus cysts located within the midbrain may result in parkinsonism. Although the neurological symptoms are alarming, they are po- tentially reversible. NCC should be added to the list of infectious diseases known to cause parkinsonian symptoms.

Acknowledgment: This study was supported in part by the National Parkinson Foundation, Miami, Florida.

LEGENDS TO THE VIDEOTAPE Segment 1. Illustration of features of parkinson-

ism (during phase of improvement): Masked facies, decreased blinking, tremor of right upper extremity (evident at rest and in certain postures), bradykine- sia bilaterally (but right much worse than left), cog- wheel rigidity of the right upper extremity, and marked rigidity of the neck. In addition, nonparkin- sonian features can be noted: difficulties with con- jugate gaze, skew deviation, and increased deep tendon reflexes.

Segment 2. This was filmed several days before discharge and demonstrates significant improve- ment in signs of parkinsonism, but persistent masked facies.

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