Dubey, Divyanshu

AbstractObjectivesTo investigate immune-mediated necrotizing myopathy (IMNM) association with cancer and its clinical implications.MethodsIMNM cases were identified 1 January 2000 to 31 December 2020 matching sex and age controls (4:1).ResultsA total of 152 patients with IMNM were identified and among serologically tested, 60% (83/140) were HMGCR-IgG+, 14% (20/140) were SRP-IgG+ and 26% (37/140) were seronegative. Cancer rates were not significantly different between serological subgroups; 18.1% (15/83) HMGCR-IgG+, 25% (5/20) SRP-IgG+ and 30% (11/37) seronegative (P = 0.34). Cancer screening was performed within 12 months from IMNM diagnosis in 88% (134/152) (whole-body CT plus FDG-PET CT in 53, CT alone in 72 and FDG-PET alone in 9). FDG-PET/CT was positive in 73% (25/34) of cancers. Increasing age was the only risk associated with cancer (P = 0.02). The odds of developing cancer at ±3 or ±5 years from IMNM diagnosis was not higher than controls (OR = 0.49; CI: 0.325–0.76). Lifetime IMNM diagnosis of cancer was less compared with controls (OR = 0.5 CI: 0.33–0.78, P = 0.002). Most patients responded to treatment (137/147, P < 0.001). Death and treatment response did not significantly differ between cancer [23% (8/34); 88% (29/33)] and non-cancer patients [19% (23/118); 92% (108/118)]. In total, 13% (20/152) of patients died during follow-up compared with 14% (41/290) of medicine and 16% (46/290) of neurology controls (P = 0.8). Seropositives had greater life expectancy than seronegatives (P = 0.01).ConclusionsGreater cancer risk is not observed in IMNM vs controls. Cancer screening in IMNM should be individualized based on age-personal and family history, including consideration of FDG-PET/CT. Immune-treatment response did not differ with cancer.

AbstractObjectiveThis study was undertaken to report clinical presentations and outcomes of CASPR2‐IgG‐associated seizures.MethodsMayo Clinic Neuroimmunology database was queried to identify CASPR2‐IgG‐seropositive (CASPR2‐IgG+) patients evaluated at our institution (2009–2019).ResultsOf the 53 CASPR2‐IgG+ patients (titer ≥ 1:10), 20 had seizures (38%). All seizure patients were male, with median onset age of 68 years. Eighteen (90%) had seizures at initial presentation. One patient was found to have malignancy (colon adenocarcinoma). Two patients had coexisting LGI1‐IgG. Twelve patients had archived sera, which on titration had CASPR2‐IgG titers ≥ 1:100. Fifteen patients (75%) met criteria for autoimmune encephalitis. Patients most commonly presented with focal onset, nonmotor seizures with impaired awareness (n = 14, 70%). Eleven patients also had focal motor and/or sensory seizures as one of the seizure semiologies. The majority of patients (n = 11, 55%) developed generalized tonic–clonic seizures during their disease course. Seizure clusters occurred in 12 patients. In addition to seizures, patients developed cognitive disturbance (n = 16, 80%), episodic emotional lability (n = 13, 65%), paroxysmal dizziness (n = 9, 45%), episodic ataxia (n = 6, 30%), and chronic ataxia (n = 9, 45%). Only three patients (15%) had coexisting peripheral nervous system involvement. Frontotemporal or temporal ictal and/or interictal electroencephalographic abnormalities were present among nine patients, and three had multifocal epileptiform abnormalities. Eight patients (40%) had medial temporal T2/fluid‐attenuated inversion recovery hyperintensity on brain magnetic resonance imaging. Elevated cerebrospinal fluid protein and/or lymphocytic pleocytosis was present in most cases (13/14, 93%). Thirteen patients reached seizure freedom following initiation of antiseizure medication (ASM; n = 4) or a combination of immunotherapy and ASM (n = 9). Median duration of follow‐up was 25 months (range = 2–136 months).SignificanceCASPR2‐IgG evaluation should be considered among older male patients with new onset focal seizures and impaired awareness often occurring in clusters with/without features of encephalitis. Coexisting neurological manifestations, including episodic emotional lability, ataxia, and paroxysmal dizziness, also aid in the diagnosis.

AbstractStudy ObjectivesRapid eye movement (REM) sleep behavior disorder (RBD) and other sleep disturbances are frequent in leucine-rich, glioma inactivated protein 1-IgG (LGI1) and contactin-associated protein 2-IgG (CASPR2) autoimmunity, yet polysomnographic analyses of these disorders remain limited. We aimed to characterize clinical presentations and analyze polysomnographic manifestations, especially quantitative REM sleep without atonia (RSWA) in LGI1/CASPR2-IgG seropositive (LGI/CASPR2+) patients.MethodsWe retrospectively analyzed clinical and polysomnographic features and quantitative RSWA between LGI1+/CASPR2+ patients and age-sex matched controls. Groups were compared with Wilcoxon rank-sum and chi-square tests. Combined submentalis and anterior tibialis (SM + AT) RSWA was the primary outcome.ResultsAmong 11 (LGI1+, n = 9; CASPR2+, n = 2) patients, Morvan syndrome sleep features were present in seven (63.6%) LGI1+/CASPR2+ patients, with simultaneous insomnia and dream enactment behavior (DEB) in three (27.3%), and the most common presenting sleep disturbances were DEB (n = 5), insomnia (n = 5), and sleep apnea (n = 8; median apnea-hypopnea index = 15/hour). Median Epworth Sleepiness Scale was nine (range 3–24; n = 10), with hypersomnia in four (36.4%). LGI1+/CASPR2+ patients had increased N1 sleep (p = .02), decreased REM sleep (p = .001), and higher levels of SM + AT any RSWA (p < .001). Eight of nine (89%) LGI1+ exceeded RBD RSWA thresholds (DEB, n = 5; isolated RSWA, n = 3). RSWA was greater in AT than SM. All 10 LGI1+/CASPR2+ patients treated with immunotherapy benefitted, and 5/10 had improved sleep disturbances.ConclusionsLGI1/CASPR2-IgG autoimmunity is associated with prominent dream enactment, insomnia, RSWA, sleep apnea, and shallower sleep. Polysomnography provides objective disease markers in LGI1+/CASPR2+ autoimmunity and immunotherapy may benefit associated sleep disturbances.