Clinical and imaging features of newly recognized Kelch-like protein 11 paraneoplastic syndrome

A 32-year-old man presented with hearing loss and gait difficulties. His symptoms, including double vision, dysarthria, dysphagia, neck posturing, and tremors, evolved rapidly over 9 months. Within 15 months of onset, he used a wheelchair. He experienced no improvement after trials of intravenous methylprednisolone, intravenous immunoglobulins, plasmapheresis, and rituximab. His CSF testing was unrevealing except for elevated proteins and oligoclonal bands. He underwent serial brain imaging (figure). Extensive laboratory investigations, including nutritional, metabolic, mitochondrial, infectious, autoimmune, and paraneoplastic panels, were unremarkable (video). Expanded tissue-based immunofluorescence testing revealed positive Kelch-like protein 11 immunoglobulin G in the serum, a newly recognized paraneoplastic encephalitis.^1,2

Figure. MRI brain at 12 and 20 months after the symptom onset.

(A, B) Axial T2 fluid-attenuated inversion recovery sequences with progressively worsening left hippocampal and right cerebellar dentate nuclei hyperintensities over time. (C) Rapidly progressive cerebellar atrophy over 8 months in a sagittal T1 sequence.

Video 1

The patient has an ataxic/hypokinetic dysarthria, with pronounced left arm dysmetria, and bilateral gaze-evoked nystagmus. There is an irregular, jerky tremor of bilateral upper extremities during rest, posture, and action. There is a constant jerky head tremor with the head tilting to the left and chin deviating to the right.Download Supplementary Video 1 ^{(18.3MB, mov)} via http://dx.doi.org/10.1212/009895_Video_1

Appendix. Authors

Study funding

No targeted funding reported.

Disclosure

J.K. Wong's research is supported by the NIH (1R25NS108939). J. Yu, A. Patterson, and A. Carlson report no disclosures relevant to the manuscript. A. Wagle Shukla reports grants from the NIH and has received grant support from Benign Essential Blepharospasm Research foundation, Dystonia coalition, Dystonia Medical Research foundation, National Organization for Rare Disorders, and grant support from NIH (KL2 and K23 NS092957-01A1); reports receiving honoraria from Acadia, Cavion, Elsevier, and MJFF in the past; and participates as a coinvestigator for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria. Go to Neurology.org/N for full disclosures.