Objective: To describe a paraneoplastic cerebellar syndrome with Holmes tremor secondary to a novel antibody.

Background: Holmes tremor is a large amplitude, 3-4 Hz tremor present at rest and enhanced with action and posture[1]. Multiple structural, traumatic, inflammatory or paraneoplastic lesions to the nigrostriatal and cerebellar outflow pathways are responsible for this tremor phenomenology[1]. The antibody most commonly associated with Holmes tremor is anti-Yo, secondary to breast or gynecological malignancies[2]. However, Holmes tremor has rarely been reported secondary to non-Hodgkin’s lymphoma.

Method: A 78 year old female presented with months of worsening tremor and unsteady gait. Exam was significant for bilateral nystagmus, high-amplitude arm tremor, dysmetria, and titubation. MRI brain was normal. CT chest/abdomen/pelvis showed enhancing retroperitoneal tissue; biopsy revealed fibrosis without overt evidence of malignancy. Given the high suspicion for a paraneoplastic syndrome, a PET scan was obtained, with increased uptake in the retroperitoneal lymph nodes, superior to the retroperitoneal fibrosis seen on CT. A repeat open biopsy revealed large B-cell lymphoma. Serum and CSF paraneoplastic panels were negative for commercially available antibodies, but CSF was reactive against neural tissue, suggesting the presence of a yet-to-be described antibody. Thus, she was diagnosed with paraneoplastic subacute cerebellar degeneration secondary to B-cell lymphoma.

Results: She underwent 6 cycles of R-CHOP therapy with repeat PET scan showing a positive treatment response. In spite of treating the underlying lymphoma, her tremor persisted. There was no improvement with primidone, clonazepam, gabapentin, levodopa, or levetiracetam. She underwent 5 days of PLEX followed by 2 rounds of IVIG treatment and 4 rounds of high dose IV methylprednisolone treatment without significant improvement.

Conclusion: This case is remarkable in that it may herald a novel paraneoplastic antibody. CSF was immunoreactive against neural tissue, though commercially available panels were negative. Aggressive pursuit of undiagnosed malignancy, to the point of repeating biopsy, led to the discovery of non-Hodgkin’s lymphoma, which is rarely associated with paraneoplastic cerebellar degeneration. Her CSF is banked for future analysis should similar cases emerge.

References: 1. Raina GB, Cersosimo MG, Folgar SS, Giugni JC, Calandra C, Paviolo JP, et al. Holmes tremor: clinical description, lesion localization, and treatment in a series of 29 cases. Neurology 2016;86(10):931-938. 2. Balint B, Vincent A, Meinck HM, Irani SR, Bhatia KP. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. Brain 2017;141(1):13-36.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/subacute-cerebellar-degeneration-and-holmes-tremor-secondary-to-paraneoplastic-non-hodgkins-lymphoma/