MyD88-mediated signaling is critical for the generation of seizure responses and cognitive impairment in a model of anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: We previously demonstrated that interleukin-1 receptor-mediated immune activation contributes to seizure severity and memory loss in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. In the present study, we assessed the role of the myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in Toll-like receptor signaling, in the key phenotypic characteristics of anti-NMDAR encephalitis. METHODS: Monoclonal anti-NMDAR antibodies or control antibodies were infused into the lateral ventricle of MyD88 knockout mice (MyD88-/-) and control C56BL/6J mice (wild type [WT]) via osmotic minipumps for 2 weeks. Seizure responses were measured by electroencephalography. Upon completion of the infusion, the motor, anxiety, and memory functions of the mice were assessed. Astrocytic (glial fibrillary acidic protein [GFAP]) and microglial (ionized calcium-binding adaptor molecule 1 [Iba-1]) activation and transcriptional activation for the principal inflammatory mediators involved in seizures were determined using immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. RESULTS: As shown before, 80% of WT mice infused with anti-NMDAR antibodies (n = 10) developed seizures (median = 11, interquartile range [IQR] = 3-25 in 2 weeks). In contrast, only three of 14 MyD88-/- mice (21.4%) had seizures (0, IQR = 0-.25, p = .01). The WT mice treated with antibodies also developed memory loss in the novel object recognition test, whereas such memory deficits were not apparent in MyD88-/- mice treated with anti-NMDAR antibodies (p = .03) or control antibodies (p = .04). Furthermore, in contrast to the WT mice exposed to anti-NMDAR antibodies, the MyD88-/- mice had a significantly lower induction of chemokine (C-C motif) ligand 2 (CCL2) in the hippocampus (p = .0001, Sidak tests). There were no significant changes in the expression of GFAP and Iba-1 in the MyD88-/- mice treated with anti-NMDAR or control antibodies. SIGNIFICANCE: These findings suggest that MyD88-mediated signaling contributes to the seizure and memory phenotype in anti-NMDAR encephalitis and that CCL2 activation may participate in the expression of these features. The removal of MyD88 inflammation may be protective and therapeutically relevant.

A case of a patient requiring medically supervised withdrawal after ingestion of witch hazel toner as a surrogate alcohol.

Key Clinical Message: Standardized alcohol withdrawal treatments, such as the phenobarbital taper protocol, are effective in the management of alcohol withdrawal syndromes associated with surrogate alcohols including witch hazel toner. Abstract: Ingestion of alcohol not intended for consumption, also known as surrogate alcohols, is well-documented in patients with alcohol use disorder. Ingestion of surrogate alcohols may lead to higher morbidity and mortality than standard alcohol consumption alone. However, management of complications such as withdrawal syndromes in individuals consuming surrogate alcohols has received little attention in the literature. We present the case of a patient with alcohol use disorder who required medically supervised withdrawal following ingestion of witch hazel toner as a surrogate alcohol. Review of patient's history revealed routine ingestion of witch hazel toner as a substitute to traditional alcohols. Witch hazel toner is a non-FDA regulated product designed for topical use; it is commonly sold in a steam distilled formulation containing 13%-15% ethanol and small amounts of essential oil components, such as carvacrol and eugenol. During hospitalization the patient received treatment of alcohol withdrawal with a phenobarbital taper protocol and was discharged in stable condition. He also received resources for alcohol use disorder to follow-up in the outpatient setting. To our knowledge this is the first reported case of a patient requiring medically supervised withdrawal following ingestion of witch hazel toner and sheds light on the potential complications and management of patients who present following ingestion.

Spelling monosyllabic English words.

We conducted a megastudy to examine the spelling of American English monosyllables with typewritten responses. We related both sublexical and lexical/semantic factors to spelling accuracy and reaction time (RT) for the first keypress and response duration for spelling 1,856 monophonic monosyllables. We found that (a) each of 13 predictor variables was significantly related to performance for at least one measure, (b) orthographic length was unrelated to the first key RT, but did relate to accuracy and response duration, (c) sound-spelling and spelling-sound consistency was related to performance, and in particular, onset consistency related to accuracy and first key RT, but was unrelated to response duration, (d) contextual diversity was consistently related to performance across all measures, and (e) age of acquisition (AoA) was related to all measures, but was related more to the first key RT than response duration. The results indicate that people begin the spelling process once they identify the first letter, and they continue to process the spelling pattern as the response unfolds. These results are best explained by a parallel-distributed-processing framework.