In November 2016, a 44-year-old man presented to the neurology clinic with progressive gait and balance deterioration, slurred speech, and incoordination. The patient first noticed symptoms in the summer of 2015: he reported stumbling, feeling of balance, and shuffling when walking. A few months later, he noticed he was mumbling when speaking and had to repeat himself often in order to be understood. By 2016, all his symptoms had progressed. He started falling and noticed a left hand tremor. Family and personal history were unremarkable. The patient reported moderately alcohol consumption of approximately 8 drinks/day on weekends for about 20 years. Although he completely ceased alcohol consumption a year before presenting to the clinic, shortly after noticing the gait change, motor symptoms continued to progress. Initial neurological examination in our clinic revealed a wide-based gait and inability to perform tandem gait or stance (Video S1 in Supplementary Material). Saccadic dysmetria, and downbeat nystagmus was noted during upgaze but the remainder of cranial nerves were normal. Speech was dysarthric. He was hyporeflexic throughout but strength, tone, and sensation were normal. Remainder of the physical exam and mental status were without deficits. Initial brain magnetic resonance imaging scan (MRI) showed cerebellar vermian atrophy (Figure 1A).
Due to the progression of ataxia despite alcohol cessation, investigation for other acquired causes of cerebellar ataxia was initiated which included comprehensive metabolic tests, infectious disease serologies (Coccidioides, cryptococcal, HIV, Histoplasma, Lyme disease, Tropheryma whipplei, VDRL), paraneoplastic panel, toxicology (including alcohol levels), and vitamin (including thiamin levels:151 nmol\L) level screens. All tests were normal except for slightly elevated vitamin B6 and B12 levels. A whole body computerized tomography (CT) scan was obtained searching for potential neoplasm causing paraneoplastic ataxia. Neither chest nor abdominopelvic CT showed suspicious neoplastic lesions; however, the presence of pulmonary nodules of up to 0.3 cm prompted a Quantiferon TB gold test which was positive. Latent tuberculosis treatment was initiated with isoniazid.
Lumbar puncture revealed three nucleated cells, normal protein and normal glucose, but IgG index of 1.19 MML (normal <0.85 MML), IgG synthesis rate of 17.84 mg (normal <=12 mg/24 h), 8 IgG oligoclonal bands (normal <4 bands) suggesting abnormal intrathecal IgG synthesis from an infectious, inflammatory, or immune-mediated process. Comprehensive cerebrospinal fluid (CSF) and serum infectious, paraneoplastic and autoimmune encephalopathy panels (NMDA receptor Ab, Neuronal VGK Ab, Glutamic acid decarb 65 Ab, GAbA B receptor Ab, AMPA receptor Ab, ANNA 1-3 Ab, Antiglial neuronal nuclear Ab, Purkinje type 1-2\TR Ab, Amphiphysin Ab, N\P\Q Type Ca channel Ab, ACHR binding Ab, ACHR ganglionic Neuronal Ab, Camp5 titer, Striated muscle Ab), all results were normal including germ cell tumor-related anti-Ma2 and small cell lung carcinoma-associated antineuronal-nuclear 1 antibodies. Serum tumor markers for testicular cancer (alpha fetoprotein, lactate dehydrogenase, and human chorionic gonadotropin) were normal. A decision to infuse intravenous (IV) immunoglobulin for a potential remote immune-mediated neurological disorder was made. IV steroids were avoided due to latent tuberculosis. Scrotal ultrasound to evaluate for occult testicular malignancy and body positron emission tomography (PET) scan to look for occult visceral malignancy were scheduled.
While awaiting outstanding diagnostic studies, 2 months after the initial consultation, the patient was admitted to hospital due to rapid alteration in mental status over 1-2 days and generalized tonic-clonic seizures. An electroencephalogram showed right temporal seizures. He was stabilized and treated effectively with antiepileptic drugs until seizures resolved. Brain MRI showed non-enhancing hyperintensity and swelling of right amygdala as well as hyperintensity in the periaqueductal gray area (Figure 1B). Although these findings are nonspecific and can be seen in disorders such as Wernicke's encephalopathy, given the rapid occurrence of global encephalopathy, seizures, and abnormal CSF findings, the primary concern was limbic encephalitis from a potential paraneoplastic syndrome. Therefore, a 5-day course of plasma apheresis was initiated at the end of which his neurological course remained stable.
A testicular ultrasound done in hospital showed a worrisome mass measuring 9 mm x 7 mm in the right testicle (Figure 1C). A right inguinal radical orchiectomy was performed, with pathological findings showing a 1.3 cm scar tissue with fibrosis and microcalcifications without sign of viable tumor or intratubular germ cell neoplasia in situ (Figure 2A). Although these findings were deemed nonspecific, a regressed germ cell tumor remained a concern.
Although a previous CT of the body was normal, given the concern for occult malignancy, an F18-FDG PET/CT scan was pursued which revealed a 1.4-cm x 0.9-cm solitary hypermetabolic lymph node in the interaortocaval distribution, worrisome for metastatic disease but not amenable to percutaneous biopsy (Figure 1D). A robotic retroperitoneal lymph node dissection was performed and pathology revealed a CD117 positive metastatic seminoma:stage IIA (Figures 2B-D) most probably secondary to a primary testicular "burned out" tumor. Four cycles of Etoposide and Cisplatin were initiated and completed. After completion of chemotherapy, the patient demonstrated no evidence of malignant disease. To date (Video S1 in Supplementary Material), with 1 year of follow-up after completion of therapy ataxia persisted although with some gradual improvement, the patient is currently able to walk with a cane although still suffers from occasional falls, speech and fine motor skills have slightly improved as well, no new seizures were reported.