CNS Inflammation as the First Sign of Complement Factor I Deficiency: A Severe Myelitis Treated With Intense Immunotherapy and Eculizumab

OBJECTIVES: Complement factor I (CFI) deficiency is a rare autosomal recessive inborn error of immunity. In this report, we highlight that complete CFI deficiency may present with isolated and severe CNS inflammation without associated systemic features nor prior non-CNS episodes. This inflammation may respond to complement blockade therapy. METHODS: This is a case description of a young girl with severe longitudinal transverse myelitis treated with aggressive immunotherapy that included eculizumab. Published cases of CFI-associated CNS inflammation were reviewed and discussed. RESULTS: A primary immunodeficiency panel revealed 2 germline pathogenic variants in the CFI gene. Further complement testing of the index case and her family confirmed complete CFI deficiency. DISCUSSION: We describe a unique case of severe spinal inflammation secondary to complete CFI deficiency. Although rare, isolated CNS inflammation may be the primary manifestation of complete CFI deficiency. To halt the uncontrolled complement-mediated inflammation associated with CFI deficiency, prompt targeted blockade of the complement pathway using eculizumab may be life changing in the acute phase. Long-lasting blockade of the complement pathway is also essential to prevent relapse in this subgroup of patients.

Acute central nervous system graft-versus-host-disease after liver transplantation.

Acute Central Nervous System (CNS) Graft Versus Host Disease (GvHD) is a rare form of GvHD, only described in case reports. Knowledge about this condition is extrapolated from chronic CNS GvHD cases occurring mostly after hematopoietic stem cell transplantation. GvHD following solid organ transplantation is an unexpected complication. GvHD after liver transplantation has a poor prognosis, and the optimal management is not yet known. Here we describe the case of a 63-year-old man who underwent deceased donor liver transplantation and subsequently developed skin rash, colitis and pancytopenia followed by refractory status epilepticus. Following the identification of lymphocytes of donor origin in the cerebrospinal fluid of the patient, he was diagnosed with acute CNS GvHD. He was treated with an intensive immunosuppressive regimen, but care was withdrawn due to lack of improvement and worsening neurologic prognosis. It is the second known case of acute CNS GvHD following liver transplantation. Clinicians should be aware of this possible, although rare, complication of liver transplantation, especially when there is refractory status epilepticus of unknown origin.

Neuropsychological Impairments and Age-Related Differences in Children and Adolescents with Fetal Alcohol Spectrum Disorders.

BackgroundChildren and adolescents with Fetal Alcohol Spectrum Disorders (FASD) exhibit a range of physical, cognitive, behavioral, and/or learning deficits, as wells as poor executive functioning (EF). Children and adolescents with FASD often show greater impairments on complex neuropsychological tasks. However, little is known about age-related differences among children and adolescents with FASD.ObjectivesThe goals of this cross-sectional study were to explore the overall profile of neuropsychological impairments and extended previous reports on age-related differences among children and adolescents with FASD. MethodWe compared 117 children and adolescents diagnosed with an FASD (aged 5-17 years), clinically assessed on a broad range of tests covering 6 neurobehavioral domains. Data from a clinical database was used to generate profiles of neuropsychological impairments for clinically referred children and adolescents evaluated for FASD between 2001 and 2005. ResultsChildren and adolescents were impaired (relative to the norm) on a number of domains that include academic achievement, language, verbal memory, EF, visual-motor integration, and motor abilities. Older participants with FASD (relative to the norm) showed greater difficulty in areas involving EF or processing of complex information than younger participants. ConclusionsThese results suggest that for children and adolescents with FASD impairments in those areas important for independent functioning may become more pronounced with increasing age. However, further longitudinal research is needed to ascertain age changes over time.

Memory patterns of acquisition and retention of verbal and nonverbal information in children with fetal alcohol spectrum disorders.

BACKGROUND: Previous research indicates that children with FASD have both memory and learning deficits. However, there is no consensus about whether the deficits identified from a pattern of impairment, and whether this pattern is consistent with the current theories regarding the organization of memory. Thus, the goal of this study was to further explore memory functions and expose possible patterns that may exist in children with FASD. METHODS: The Children's Memory Scale (CMS) was used to measure visual and verbal memory, as well as learning and encoding, among 30 children with FASD (ages 9-16 years). Functioning was conceptualized through use of a model of working memory. RESULTS: A significant difference between types of verbal memory in the FASD sample was identified. Specifically, recall of word pairs was found to be more impaired than that for stories. In addition to this, recall of immediate word pairs was significantly more impaired than that for delayed word pairs, implying the presence of encoding deficits in this area. CONCLUSIONS: Children and adolescents with FASD displayed specific types of verbal memory deficits and these deficits were greater for immediate rather than delayed memory. These data are consistent with previous studies that describe deficits in immediate memory, and suggest that deficits in delayed memory are better accounted for by encoding deficits. Furthermore, their greatest difficulty arose with those items in which the phonological loop was required, which would have facilitated learning though internal recitation and adequate phonological storage. Further research into these distinctions in memory is warranted, as is exploration into educational techniques that could account for delayed encoding in children with FASD.