Paraneoplastic Syndrome Associated with Kelch-Like Protein 11 Antibodies Presenting with Progressive Ataxia and Tremor.

Abstract

Kelch-like protein 11 antibodies have recently been isolated in the context of a novel, progressive paraneoplastic syndrome.1 Although the initial cohort was composed exclusively of men with testicular germ cell tumors presenting with ataxia and rhombencephalitis, the oncological and phenotypic associations have subsequently broadened.2, 3 Here, we present the case of a 33-year-old man who developed a progressive neurologic paraneoplastic syndrome associated with Kelch-like protein 11 antibodies, even after remission of his malignancy. The patient had a history of stage 1 testicular seminoma for which he underwent orchiectomy 5 years before presentation. He was seen in our clinic for a slowly progressive postural tremor in the upper extremities in addition to subtle tremor involving trunk, legs, and lips. The tremor improved slightly with alcohol but had no response to low dose propranolol (10 mg 3 times daily). He also had 2 years of progressive dysarthria and slowing of speech, subtle decline in coordination and fine motor skills in his hands, and a sensation of being off-balance with rare vertigo. He noted that he was always clumsy as a young child. A paternal uncle had Parkinson's disease, but there was no family history of ataxia. Exam (Video 1) was notable for normal cognition, saccadic visual pursuit, dysarthria, high frequency, low amplitude postural tremor in the hands, dysrhythmic and clumsy finger taps and toe taps, subtle dysdiadochokinesia, and mildly impaired tandem gait with normal pull test. Muscle tone, sensory exam, and reflexes were normal, except for a crossed adductor sign on the right. Magnetic resonance imaging showed pan-cerebellar atrophy with normal brainstem morphology and no signal abnormality (Fig. 1). Vitamin B12 level was borderline decreased (238 ng/L), although he had no clinical change after vitamin B12 replacement. Copper, ceruloplasmin, vitamin E, Angiotensin Converting Enzyme (ACE), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and tissue transglumatinase, gliadin Immunoglobulin A (IgA)/Immunoglobulin G (IgG), dsDNA, GQ1B, Anti-smith antibody (Sm), and Sjogren syndrome A (SSA) and Sjogren syndrome B (SSB) Abs were normal/negative. There was no evidence of recurrent malignancy in the remaining testicle and no evidence of metastatic disease per annual surveillance scans and serum tumor markers. Lumbar Puncture (LP) showed cerebrospinal fluid (CSF) with normal cell count, protein, glucose, and negative cytology, but positive oligo-clonal bands (10 distinct bands) and elevated IgG index. Extensive paraneoplastic antibody testing in serum and CSF was negative, including anti-MaTa Abs. A comprehensive genetic ataxia panel was negative. CSF was evaluated at Mayo Clinic laboratories where the staining pattern on rodent brain slices was concordant with the newly described paraneoplastic syndrome associated with Kelch-like protein 11 antibodies.1 He had initial minimal response to intravenous solumedrol, but subsequent worsening in gait ataxia, not helped with intravenous immunoglobulin. He is currently receiving rituximab and reports subjective slowing in his neurologic decline. Knowledge of this newly described paraneoplastic syndrome is important to disseminate as prevalence is estimated at 1.4 cases per 100,000 population, which is higher than that of other typical paraneoplastic antibodies associated with autoimmune encephalitis (eg, Anti-Ri [ANNA2] Abs with prevalence 0.6 per 100,000 population).1 In this case, his elevated CSF oligoclonal bands prompted further testing for a paraneoplastic syndrome despite the absence of a recurrent malignancy. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. P.P.: 1A, 1B, 1C, 2A, 2B I.O.B.: 1A, 1B, 1C, 2A, 2B No institutional review board approval was needed for this case report. The authors confirm that a formal informed written consent was obtained. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. There was no specific funding received for this work. The authors declare that there are no conflicts of interest relevant to this work. I.O.B. is on the advisory boards of Biogen Inc., Boston Scientific, Accorda, and Amneal Pharmaceuticals and is a consultant for LEK Consulting, Ideo Inc., and Humancraft. P.P. has no disclosures.