Samantha A. Banks

Background and ObjectivesHistiocytic neoplasms, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman-Destombes disease (RDD), have frequent nervous system...

Dipeptidyl-peptidase–like protein-6 antibody–associated encephalitis (DPPXE) is an autoimmune, multisystem disorder characterized by a triad of gastrointestinal prodrome, cognitive-psychiatric chan...

Anti-CD20 therapies for multiple sclerosis (MS) are highly effective at preventing disease activity. Recognizing infectious complications of these therapies is essential. Three MS centers shared deidentified clinical data on persons with MS (pwMS) receiving ocrelizumab who developed enterovirus encephalitis. Five pwMS (4 with relapsing-remitting MS, 1 with secondary progressive MS) on ocrelizumab were identified. At diagnosis, the median age was 34 years (range, 30-57), the median MS duration was 5 years (range, 2-13), and the median ocrelizumab exposure was 3 years (range, 2-7). Four had young children who were recently ill, including 2 with hand, foot, and mouth disease. MRI brain revealed new nonenhancing T2 hyperintensities in the thalamus (2), substantia nigra (2), cerebellum (2), and pons (1). All had CSF pleocytosis (median, 57/mcL; range, 33-175). Enterovirus was detected by reverse-transcription PCR in CSF (4) and blood (2). Hypogammaglobulinemia was present in 4 patients tested; 1 also had neutropenia. Three received IV immunoglobulin. At follow-up (median, 7 months; range, 3-15), 1 patient had fully recovered and 4 had residual symptoms (cognitive, 1; gait impairment, 3). Enterovirus encephalitis is a rare but serious complication in pwMS receiving ocrelizumab; hypogammaglobulinemia may increase risk. Clinician awareness and prompt testing may improve outcomes.

Background: Tremor in multiple sclerosis (MS) is often refractory to medications. Deep brain stimulation (DBS) may help, but possible side effects and disease exacerbation limit its use. Objectives: Evaluate outcomes of DBS for MS-associated tremor. Methods: Retrospective review of 18 patients with MS-associated tremor who underwent DBS, analyzing Expanded Disability Status Scale (EDSS) and Fahn–Tolosa–Marin (FTM) tremor scores. Results: Median age at surgery was 49.5 years (range, 28–75), with postoperative follow-up 2.5 years (range, 0–22). No relapses (0/18) or new lesions (0/8) occurred postoperatively. All had ventral intermediate nucleus leads; other targets were not used in programming. EDSS remained stable (median 6 to 6.25; p = 0.2). FTM scores improved (median 14.5 to 10, p = 0.008). Patients with EDSS 3.5–6 had variable outcomes ( p = 0.02). Conclusions: DBS is a potential treatment for severe MS tremor and did not provoke relapse. Targeting VIM alone may optimize tremor control and maintain magnetic resonance imaging (MRI) access.

Background: Falls in people with multiple sclerosis (pwMS) lead to morbidity and expense. Objective: Identify clinical metrics associated with falls. Methods: Eighty-six pwMS completed fall surveys, timed 25-foot walk (T25FW), and motion analysis with Clario Opal devices. Logistic regression models were created. Results: Median age was 54.5 years (range 21–73), 62% (53) were female. The cohort included 58% with relapsing (50) and 42% with progressive MS (36). Those who reported falling in the last year were older (median age 58 vs 52.5, p = .03) and had a higher Patient Determined Disease Step (PDDS) score (median 3 vs 1, p < .0001). Falls were associated with worse balance metrics including sway area (median 2.3 degrees ² vs 1.2, p = .01), jerk (median 3.3 m ² /s ⁵ vs 1.6, p = .005), and slower T25FW (median 11.5 s vs 8; p < .0001). A multivariable regression model based on gait aid use and T25FW time >10.8 s (c = 0.80) was derived. Having both features portended a probability of falling of 0.97, while having neither, a probability of 0.26. Conclusions: Falls in pwMS are more frequent in patients who are older, have higher PDDS, slower walking, and worse balance. Gait aid use and T25FW >10.8 s were strongly associated with falls in the past year.

To characterize the frequency and clinicoradiologic phenotype of cerebellar involvement in attacks of aquaporin-4-IgG positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) which are incompletely captured in current diagnostic criteria. Brain MRI scans from patients with AQP4+NMOSD in the Mayo Clinic database were reviewed, and those with cerebellar T2-hyperintense lesions ≤30 days from attack onset were included for clinical and radiologic characterization. From 432 patients with AQP4+NMOSD, we identified 17 (4%) with cerebellar attacks. The median age at attack onset was 47 years (range, 7-74). Cerebellar symptoms and signs were noted in 16 (94%) of 17 and the remaining patient was intubated preventing a detailed cerebellar exam. The median Expanded Disability Status Scale score at nadir was 5 (range, 2-9.5). Sixteen (94%) had other regions involved during the attack, most frequently with brainstem or area postrema involvement. Cerebellar MRI T2-lesions (8 single; 11 contiguous with the brainstem; 6/15 [35%] enhancing) were located in cerebellar peduncles, 15 (inferior, 5; middle, 10; superior, 10), and cerebellar parenchyma, 8 (dentate, 4; medial, 2; lateral, 4). T2-lesions persisted in 9 (82%) of 11 beyond 6 months. Cerebellar involvement during attacks of AQP4+NMOSD is rare but the associated neurologic deficits tend to be severe. Cerebellar peduncle or dentate nucleus T2-lesions are frequent MRI accompaniments. Clinical features and MRI lesion patterns of cerebellar involvement could be incorporated into future iterations of AQP4+NMOSD criteria.

Objective: We describe neurologic phenotype, clinical associations, and outcomes in autoimmune brainstem encephalitis.Methods: Medical records of neural‐IgG positive autoimmune brainstem encephalitis patients diagnosed at Mayo Clinic (January 1, 2006–December 31, 2022) were reviewed.Results: Ninety‐eight patients (57 male) were included. Median age of symptom onset was 51 years (range, 8 months‐85 years). Frequent presenting features were ≥1: diplopia (80%), ataxia (78%), dysarthria (68%), vestibulocochlear symptoms (67%), dysphagia (61%), nausea/vomiting (42%), and facial weakness (32%). Altered mental status (11%) was uncommon. Neural antibodies detected were as follows: KLHL‐11 (26 patients), GAD65 (high titer, 12), ANNA‐1 (anti‐Hu, 8), ANNA‐2 (anti‐Ri, 8), Ma2 (7), IgLON‐5 (6), AQP4 (6), MOG (4), glycine receptor (4), GQ1B (4), PCA‐1 (anti‐Yo, 4), DPPX (2), neurochondrin (2), neurofilament (2), NMDA‐R (2), AGNA‐1 (SOX‐1, 1), ANNA‐3 (DACH1, 1), amphiphysin (1), CRMP‐5 (1), ITPR‐1 (1), PCA‐Tr (DNER, 1), and PDE10A (1). Cancer was identified in 55 patients: germ cell (23 patients; 3 extra‐testicular), ductal breast adenocarcinoma (8), small cell carcinoma (6, lung 4), adenocarcinomas (6), neuroendocrine carcinoma (3), hematologic (2), squamous cell (2), and other (7). Median modified Ranking score (mRS) at last follow‐up was 3 (range, 0–6). Factors associated with poor outcome included abnormal brain MRI, bulbar symptoms, and elevated CSF IgG index. Kaplan–Meier analysis revealed faster progression to wheelchair in patients who were immunotherapy refractory and with elevated CSF IgG index. Diagnostic criteria for autoimmune brainstem encephalitis (definite and probable) are proposed.Interpretation: Autoimmune brainstem encephalitis is a distinct clinical subphenotype of autoimmune encephalitis. Abnormal brain MRI, bulbar symptoms, and elevated CSF‐IgG index associate with poor outcome.