Characterization of cardiac bradyarrhythmia associated with LGI1-IgG autoimmune encephalitis.

Objective: To evaluate and characterize cardiac arrythmias associated with LGI1-IgG (Leucine-rich glioma inactivated 1-IgG) autoimmune encephalitis (AE). Patients and methods: In this retrospective descriptive study, we identified Mayo Clinic patients (May 1, 2008 - December 31, 2020) with LGI1-IgG AE who had electrocardiogram proven bradyarrhythmias during the initial presentation. Inclusion criteria were 1) LGI1-IgG positivity with a consistent clinical syndrome; 2) electrocardiographic evidence of bradyarrhythmia; and 3) sufficient clinical details. We excluded patients who were taking negative ionotropic agents at the time of their bradyarrhythmias. We collected demographic/clinical data including details of bradyarrhythmia (severity, duration, treatments), and neurologic and cardiac outcomes. Results: We found that patients with LGI1-IgG AE had bradyarrhythmia at a frequency of 8% during the initial presentation. The bradyarrhythmia was often asymptomatic (6/11, 55%); however, the episode was severe with one patient requiring a pacemaker. Outcome was also generally favorable with the majority (8/11, 73%) having full resolution without further cardiac intervention. Lastly, we found that mouse and human cardiac tissues express LGI1 (mRNA and protein). Conclusion: LGI1-IgG AE can be rarely associated with bradyarrhythmias. Although the disease course is mostly favorable, some cases may require pacemaker placement to avoid devastating outcomes.

CASPR2-IgG-associated autoimmune seizures.

OBJECTIVE: This study was undertaken to report clinical presentations and outcomes of CASPR2-IgG-associated seizures. METHODS: Mayo Clinic Neuroimmunology database was queried to identify CASPR2-IgG-seropositive (CASPR2-IgG+) patients evaluated at our institution (2009-2019). RESULTS: Of 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). SIGNIFICANCE: CASPR2-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.

Efficacy of 177Lu-Dotatate Therapy in the Treatment of Recurrent Meningioma.

A 62-year-old man presented with a history of atypical meningioma (World Health Organization grade II) and recurrent as anaplastic meningioma (World Health Organization grade III). His previous treatments included multiple surgical resections, fractionated radiation therapy, stereotactic radiosurgery, everolimus/octreotide long-acting release, bevacizumab, and hydroxyurea. Magnetic resonance imaging revealed rapid volumetric progression over the prior 9 months, with a near tripling in size from 29.9 cm3 to 80.4 cm3. Indium In 111 octreotide scanning confirmed the presence of somatostatin receptors within the tumor. Lutetium Lu 177 dotatate was administered intravenously at a dose of 200 mCi per dose every 8 weeks for 4 cycles. Treatment was tolerated very well, with no notable adverse events. Tumor volume initially increased to 98.3 cm3 after cycle 1 of treatment and subsequently decreased to 91.2 cm3 after cycle 2. Eight months after treatment onset, the tumor volume remained stable (93.4 cm3).