Exophiala dermatitidis, a dematiaceous fungus typically found in decaying organic matter worldwide, is a rare cause of fungal infections. Cerebral phaeohyphomycosis is a sporadic but often fatal infection of the brain caused by E. dermatitidis. However, due to limited reports, little is known about its specific predisposing factors, clinical manifestation, and optimal treatment modality. Here, we report a clinical presentation and management of cerebral phaeohyphomycosis in a Chinese patient. An otherwise healthy, young male who was diagnosed with neck fungal lymphadenitis caused by E. dermatitidis 7 months prior and was treated with itraconazole, presented later with progressive intracranial hypertension and persistent coma. Culture of the neck lymphoid tissue produced growth of a black yeast-like fungus, which was identified as E. dermatitidis by sequencing of the ribosomal DNA internal transcribed spacer (ITS) domains. Accordingly, a cerebral biopsy was performed, and the pathological report showed mycelia and fungal granulomas. We also sequenced CARD9 in the patient and found him to be homozygous for loss-of-function mutation; his parents were heterozygous for the same mutation. This is a first case report of cerebral phaeohyphomycosis caused by E. dermatitidis in a CARD9-deficient Chinese patient. He eventually succumbed to brain herniation and severe lung infection with a poor response to therapy. Thus, previously healthy patients with unexplained invasive E. dermatitidis infection, at any age, should be tested for inherited CARD9 deficiency.

The Fc receptor (FcRn) inhibitors can ameliorate autoimmune conditions such as myasthenia gravis through a rapid and specific clearance of serum IgG levels, and they also have potential for future use in a wider variety of antibody-mediated autoimmune diseases. Some patients with therapy-refractory autoimmune encephalitis (AE) continue to be unresponsive to initial and secondary treatment regimens. A 32-year-old male presented with predominant psychiatric symptoms and seizures, along with imaging evidence indicating multifocal cerebral cortical involvement. Neural antibody testing revealed dual positivity for N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated 1 (LGI1) antibodies in both serum and cerebrospinal fluid (CSF). Human leukocyte antigen (HLA) genotyping revealed the presence of the DQB1*03:01 and DQB1*06:01 alleles in the patient. Treatment with efgartigimod, the FcRn inhibitor, led to significant clinical improvements accompanied by a significant decrease in both anti-NMDAR and anti-LGI1 antibody levels. Herein, we report a rare case of therapy-refractory anti-NMDAR AE coexisting with positive LGI1 antibodies. Efgartigimod demonstrates promising potential for treating antibody-mediated AE. Clinical trial number Not applicable.

Objective: Hereditary spastic paraplegias (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders. We describe the genetic and clinical features of a cohort of five HSP families from central‐southern China.Methods: Using targeted exome‐sequencing technology, we investigated the genetic and clinical features in five HSP families. We reviewed the clinical histories of these patients as well as the molecular and functional characterization of the associated gene variants. We also performed functional analysis of an intron variant of SPAST in vitro.Results: We identified a known SPAST mutation (p.Pro435Leu) in a family with autosomal dominant HSP (AD‐HSP) and four novel variants in two HSP families and a sporadic case. These identified four novel variants included a variant in SPG11 (p.Val1979Ter), two variants in B4GALNT1 (p.Ser475Phe and c.1002 + 2 T > G), and a splicing site variant in SPAST (c.1245+5G>A). Minigene analysis of the splicing variant in SPAST (c.1245+5G>A) revealed that the mutation resulted in mRNAs with a loss of exon 9. The SPG4 family carrying c.1245+5G>A variant in SPAST exhibited genetic anticipation, with a decreased age at onset and increased severity in successive generations. The proband with p.Val1979Ter variant in SPG11 showed characteristic clinical features of early‐onset, severe spasticity, and corpus callosum atrophy which were highly suggestive of the diagnosis of SPG11‐associated HSP.Conclusions: Our findings strongly support variable phenotype of B4GALNT1‐related SPG26 and also expand the clinical and mutation spectrum of HSP caused by mutations in SPAST, SPG11, and B4GALNT1. These results will help to improve the efficiency of early diagnosis in patients clinically suspected of HSP.