Our data describe the coexistence of a recent central nervous system (CNS) ZIKV infection accompanied by a severe ADEM-like syndrome outcome in a patient with clinical history of MS. A de novo immune response concomitant with ZIKV infection might be involved in the mechanism of the ADEM-like syndrome and response to immunotherapy. The present report reinforces the importance of providing the differential diagnosis of acute episodes of MS exacerbation in an environment prone to ZIKV expression.

Oligophrenin-1 (OPHN1) is one of at least seven genes located on chromosome X that take part in Rho GTPase-dependent signaling pathways involved in X-linked intellectual disability (XLID). Mutations in OPHN1 were primarily described as an exclusive cause of non-syndromic XLID, but the re-evaluation of the affected individuals using brain imaging displayed fronto-temporal atrophy and cerebellar hypoplasia as neuroanatomical marks. In this study, we describe clinical, genetic and neuroimaging data of a three generation Brazilian XLID family co-segregating a novel intragenic deletion in OPHN1. This deletion results in an in-frame loss of exon 7 at transcription level (c.781_891del; r.487_597del), which is predicted to abolish 37 amino acids from the highly conserved N-terminal BAR domain of OPHN1. cDNA expression analysis demonstrated that the mutant OPHN1 transcript is stable and no abnormal splicing was observed. Features shared by the affected males of this family include neonatal hypotonia, strabismus, prominent root of the nose, deep set eyes, hyperactivity and instability/ intolerance to frustration. Cranial MRI scans showed large lateral ventricles, vermis hypoplasia and cystic dilatation of the cisterna magna in all affected males. Interestingly, hippocampal alterations that have not been reported in patients with loss-of-function OPHN1 mutations were found in three affected individuals, suggesting an important function for the BAR domain in the hippocampus. This is the first description of an in-frame deletion within the BAR domain of OPHN1 and could provide new insights into the role of this domain in relation to brain and cognitive development or function.

Recently, we defined a minimal overlapping region for causal Xp11.22 copy number gains in males with intellectual disability (ID), and identified HECT, UBA and WWE domain-containing protein-1 (HUWE1) as the primary dosage-sensitive gene, whose overexpression leads to ID. In the present study, we used this minimal interval to search for HUWE1 copy number variations by quantitative polymerase chain reaction in a large cohort of Brazilian males with idiopathic ID. We detected two unrelated sporadic individuals with syndromic ID carrying unique overlapping duplications encompassing HUWE1. Breakpoint junction analysis showed a simple tandem duplication in the first patient, which has probably arisen by microhomology-mediated break-induced repair mechanism. In the second patient, the rearrangement is complex having an insertion of an intrachromosomal sequence at its junction. This kind of rearrangement has not been reported in Xp11.22 duplications and might have emerged by a replication- or recombination-based mechanism. Furthermore, the presence of infantile seizures in the second family suggests a potential role of increased KDM5C expression on epilepsy. Our findings highlight the importance of microduplications at Xp11.22 to ID, even in sporadic cases, and reveal new clinical and molecular insight into HUWE1 copy number gains.

We present two patients with sepsis and intracerebral microbleeds. The first case is a nine years old girl who presented visual hallucinations, tremors in the limbs, and an episode of generalized tonic-clonic seizure in the 12 th day of an otherwise successfully treatment of a pulmonary sepsis. Brain magnetic resonance imaging (MRI) showed numerous small rounded foci of decreased signal intensity on susceptibility-weighted imaging (SWI) spread throughout the brain, predominantly in the corpus callosum (Fig 1), which had high signal intensity on the phase map of SWI, suggesting blood deposits. The remaining conventional MRI sequences were normal. The patient and her mother denied any history of head trauma. During hospitalization, platelets counts, partial thromboplastin time, prothrombin time, and international normalized ratio were always normal.The second patient is a 40 years old woman treating a septic shock of urinary origin for three weeks, who presented generalized tonic-clonic seizures. SWI showed linear low signal intensity on the cortex surface, mainly in frontal lobes, and multiple foci of low signal intensity on the subcortical white matter and cerebellum, which had high signal intensity on the phase images of SWI, suggesting areas of subarachnoid hemorrhages in the frontal lobes and microbleeds into the subcortical white matter and cerebellum (Fig 2). During hospitalization, D-dimer was normal. Although she had some altered values in platelets count (100,000/mm 3 , was the lower value), prothrombin time (worst INR value was 2.3), and partial thromboplastin time, due to sepsis, she did not developed disseminated intravascular coagulation.The typical imaging features of intracerebral microbleeds are small foci of decreased signal intensity on gradient-recalled echo T2* and/or SWI on MRI, usually without correspondence on others sequences 1 . Generally, microbleeds are related with hemorrhagic transformation of an ischemic stroke, recurrence of spontaneous intracerebral bleeding, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, cerebral amyloid angiopathy and trauma 1. There are few studies correlating intracerebral microbleeds with infective endocarditis 2 , but none with other causes of sepsis. -weighted imaging (A) and phase images of susceptibility-weighted imaging (B) show multiple foci of low signal intensity on genu and splenium of the corpus callosum and subcortical white matter on susceptibility-weighted imaging, with high signal intensity on the phase images of susceptibility-weighted imaging, suggesting blood deposits. FLAIR image (C) on the same position shows no abnormalities.