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Abstract Details

KLHL11-IgG Paraneoplastic Neurologic Syndrome Across the Adult Lifespan: Clinical Spectrum and Cancer Associations
Autoimmune Neurology
P2 - Poster Session 02 (3:00 PM-4:00 PM)
1-089
To characterize the clinical spectrum, cancer associations, and outcomes of Kelch-like protein 11 (KLHL11)-IgG–associated paraneoplastic neurologic syndrome (PNS) across the adult lifespan.

KLHL11-IgG is a rare antibody associated with paraneoplastic rhombencephalitis, classically described in young males with testicular seminoma. Emerging data suggest a broader age distribution and associations with non-testicular malignancies.

We conducted a multicenter retrospective observational study of KLHL11-IgG–positive patients. Demographic, clinical, imaging, and laboratory data were analyzed. Patients with symptom onset ≥50 years were classified as late-onset. LUZP4-IgG testing was performed using ELISA where available. 
Eighty-eight patients were included (median age of onset 48 years [IQR 39–62], 89% male), of whom 41 (47%) with late-onset disease. Core clinical features reflected brainstem-cerebellar dysfunction, including ataxia (79%), diplopia (60%), vertigo (56%), nystagmus (52%), and dysarthria/dysphagia (49%). Additional manifestations included sensorineural hearing loss (37%), limbic encephalitis (20%), myelopathy (10%), and motor neuronopathy (8%).  Male predominance was lower in late-onset cases (78% vs 98%, p=0.005). Both groups had high associations with malignancy (74% in late-onset vs 66% in younger cohorts). Younger patients almost exclusively had seminoma (94% vs 45%, p=0.0089), whereas non-testicular cancers were frequent in late-onset cases (16/28, 55%, most frequent were Merkel cell carcinoma. 4/16[25%] and prostate cancer 5/16 [31%]), and absent in younger patients (p<0.0001). Clinical presentation, immunotherapy response, and survival were similar between groups, with most patients experiencing persistent disability (mRS ≥3 in 77% at last follow-up). LUZP4-IgG was detected in 14/39 (36%) cases and was associated with seminoma/regressed testicular tumors (p=0.0283), with no cases identified in non-testicular cancers.
KLHL11-IgG PNS presents with a characteristic rhombencephalitis-predominant syndrome across the adult lifespan and is associated with substantial long-term disability. While seminoma predominates in younger men, non-testicular malignancies are common in older patients. LUZP4-IgG appears specific to testicular germ cell tumor–related disease and is not associated with non-testicular cancers.
Authors/Disclosures
Marina Buciuc, MD
PRESENTER 		Dr. Buciuc has nothing to disclose.
Nimalan Harinesan, MBBS Dr. Harinesan has nothing to disclose.
Yong Guo Yong Guo has nothing to disclose.
Haidara Kherbek, MD Haidara Kherbek has nothing to disclose.
Ehab Y. Harahsheh, MBBS Dr. Harahsheh has nothing to disclose.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic) The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
Andrew McKeon, MD (Mayo Clinic) The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic) The institution of Dr. Flanagan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Merck. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received intellectual property interests from a discovery or technology relating to health care. Dr. Flanagan has received intellectual property interests from a discovery or technology relating to health care. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology that is relevant to AAN interests or activities.
Bardia Nourbakhsh, MD (Johns Hopkins University) Dr. Nourbakhsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics . Dr. Nourbakhsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alkermes. The institution of Dr. Nourbakhsh has received research support from Genentech. The institution of Dr. Nourbakhsh has received research support from National MS Society . The institution of Dr. Nourbakhsh has received research support from Department of Defense. The institution of Dr. Nourbakhsh has received research support from NIH. The institution of Dr. Nourbakhsh has received research support from Axsome Therapeutics. The institution of Dr. Nourbakhsh has received research support from TG Therapeutics .
Greer Waldrop, MD Dr. Waldrop has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Delve Bio. Dr. Waldrop has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech.
Sepideh Mokhtari, MD (Moffitt Cancer Center) Dr. Mokhtari has nothing to disclose.
Rajesh K. Gupta, MBBS (UTHealth) Dr. Gupta has nothing to disclose.
Shannon Hinson Shannon Hinson has received intellectual property interests from a discovery or technology relating to health care. Shannon Hinson has received intellectual property interests from a discovery or technology relating to health care.
Michael R. Wilson, MD, FAAN (University of California San Francisco) Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ouro Medicines. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharmaceuticals. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Indapta Therapeutics. Dr. Wilson has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Delve Bio. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cambridge Medical Experts. Dr. Wilson has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Dunham Hallmark. Dr. Wilson has stock in Delve Bio. The institution of Dr. Wilson has received research support from Genentech / Roche. The institution of Dr. Wilson has received research support from NIH. The institution of Dr. Wilson has received research support from Novartis. The institution of Dr. Wilson has received research support from National Multiple Sclerosis Society. The institution of Dr. Wilson has received research support from Fanconi Anemia Research Foundation. The institution of Dr. Wilson has received research support from Department of Defense. The institution of Dr. Wilson has received research support from Chan Zuckerberg Initiative. The institution of Dr. Wilson has received research support from Kyverna Therapeutics. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Witness with US Dept of Justice.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology) Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Divyanshu Dubey, MD, FAAN (Mayo Clinic) The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.