A 41-year-old male Caucasian, who has lived in the city of Sao Paulo for the last 22 years came to the emergency room with an 8-day history of continuous, intense, bilateral occipital headache associated with photophobia, nausea, and vomiting. Three days after the initial symptoms, he had fever, myalgia, and vertigo. In the following days he developed slurred speech, marked gait instability, and imbalance. His past medical history was uneventful (he denied the occurrence of oral or genital ulcers, arthritis, or any skin lesions preceding the recent symptoms). He was not on any medication and denied alcoholism, smoking, use of illicit drugs, or neurologic complaints in the past. He had no familial history of neurologic disease. He has six cats that are well maintained and regularly vaccinated. He denied traveling during the last 2 years, but used to go camping between the age of 27 and 31 to a region where there were tick infestations.
At the emergency room, the remarkable physical findings included an ataxic gait, which worsened with the Tandem maneuver, dysarthric speech, and nystagmus to the right. Brain computed tomography (CT) was normal, and the analysis of cerebral spinal fluid (CSF) revealed lymphocytic pleocytosis with 528 cells/mm3 (91% of lymphocytes, 8% monocytes, and 1% neutrophils), protein was 76.3 mg/dL (reference value [RV]: <40 mg/dL), glucose was 50 mg/dL (plasma glucose 94 mg/dL, RV: >2/3 plasma glucose). Chloride and lactate values were in the reference range. Gram stain, China ink, cultures for acid-fast bacilli, fungus, and usual bacteria were all negative. Although the clinical course was not characteristic for herpetic meningoencephalitis, intravenous acyclovir was started.
On the third day of hospitalization, despite the maintenance of normal mental status, the patient presented involuntary, fast, arrhythmic, conjugated, multidirectional eye movements preventing him from fixing his gaze (opsoclonus) [video]. He also developed generalized rhythmic resting and action tremors associated with myoclonic jerks at postural fixation, and volitional limb movements, particularly in the right side. The cerebellar signs worsened, appearing as marked truncal-limb dyssynergia, bilateral limb dysmetria, dysdiadochokinesia, and cerebellar ataxia, which progressed to astasia and abasia. The motor and sensory examination (deep and superficial sensations) was unremarkable, as were all the deep tendon reflexes. The autonomic function and cranial nerves examinations were also unremarkable, except for hearing loss. The patient was unable to stand and walk, and became completely dependent for daily activities, such as eating, brushing teeth, shaving, and bathing.
Based on these neurological signs, the diagnosis of opsoclonus-myoclonus-ataxia syndrome (OMAS) was raised and a wide diagnostic workup was carried out to identify unusual infectious agents and immune dysfunction, the more common cause of this syndrome in adults. Sodium valproate was prescribed for the relief of myoclonic movements. Ampicillin was empirically started in consideration of the diagnostic possibility of Listeria rhomboencephalitis and acyclovir was withdrawn. A new CSF test confirmed the lymphocytic pleocytosis with 210 cells/mm3 (99% lymphocytes, 1% neutrophils), protein was 84.7 mg/dL, glucose was 51 mg/dL, lactate and chloride values were within normal limits, adenosine deaminase was 3.05 UI/L (RV: 9 UI/L). In spite of the partial decrease in CSF cellularity, the patient's neurological deficits were unchanged. Methylprednisolone (1g/day/5 days) regimen was administered followed by a 5-day course of intravenous immunoglobulin (400 mg/kg/day) with mild clinical improvement.
Cranial magnetic resonance imaging (MRI) showed a tenuous, poorly defined, oval-shaped hyper signal lesion in fluid-attenuated inversion-recovery (FLAIR) and T2-weighted sequences, measuring 1.5 cm, with no diffusion restriction or enhancement after contrast infusion, in the left thalamus. No abnormal signs were found in the brainstem, cerebellum, or cranial nerves (Figure 1).
The electroencephalogram was normal. At the brainstem auditory evoked potential test, delay was registered in all wave latencies for the right ear, and in waves III and V for the left ear. However, all interpeak latencies were normal on both sides, indicating a distal cochlear nerve dysfunction in the right ear with preservation of intra-brainstem auditory pathways.
Contrast abdominal, thoracic, and pelvic CT, as well as testicular ultrasonography, failed to demonstrate any abnormalities suggestive of neoplasia. Prostate-specific antigen determination was within normal limits.
Renal and liver function tests, electrolytes, hepatic enzymes, blood cell count, lactic dehydrogenase (LDH), free-thyroxin, thyroid stimulating hormone (TSH), immunoglobulin dosage and protein electrophoresis were all non-contributory. Laboratory exams for systemic inflammatory activity disclosed C-reactive protein maximum value of 30 mg/L (RV: <5 mg/L) and erythrocyte sedimentation rate of 30 mm in the first hour (RV <15 mm in the first hour). ANA tested by indirect immunofluorescence with Hep-2 cells was unremarkable as was the test for rheumatoid factor.
Syphilis test results were negative in blood and CSF as well as cultures for fungus and bacteria. A polymerase chain reaction assay for Herpes virus 1, 2, and 6, Varicella zoster virus, cytomegalovirus, and Mycobacterium tuberculosis in the CSF were all negative. Immunological tests for HIV were negative in blood and CSF, and the immunological window was ruled out by a negative viral load count. Serological tests for Dengue virus, Hepatitis B and C virus, Leptospira sp. were negative. Serology for Epstein Barr virus, toxoplasmosis, and rubella showed positivity for IgG but negativity for IgM.
In the meantime, the immunologic reaction (IgM) for Borrelia burgdorferi was positive in the CSF by enzyme-linked immunosorbent assay (ELISA) but negative in the serum (ELISA and Western Blott) performed in the Brazilian Lyme Disease Reference Laboratory1. With this result, the diagnosis of neuroborreliosis was highly considered and ceftriaxone (2 g/day) therapy was instituted for 3 weeks, followed by doxycycline 100 mg twice daily for 2 months. After 7 days of use of ceftriaxone, the cerebellar signs and opsoclonus improved [video 2], the myoclonic jerks disappeared, and the patient was able to stand up and walk with assistance.