Multiple Border-Zone Infarcts Triggered by Influenza A Virus Infection in a Patient With Cerebral Autosomal Dominant Arteriopathy Presenting With Subcortical Infarcts and Leukoencephalopathy.

Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can develop multiple border-zone infarcts due to hypotension, hypovolemia, or surgery. We report the case of a 41-year-old woman with CADASIL who developed multiple border-zone infarcts due to influenza A virus infection. The patient had no apparent history or episode of stroke or altered consciousness following the onset of respiratory symptoms, which were due to the influenza A infection. Diffusion-weighted magnetic resonance images of the brain showed multiple acute-phase infarcts in border-zone areas of both cerebral hemispheres and the corpus callosum; fluid-attenuated inversion-recovery magnetic resonance images showed increased signal in the subcortical areas of both temporal poles. Gene analysis identified a heterozygous mutation c.160C>T in exon 2 of the NOTCH3 gene (p.Arg54Cys). A diagnosis of CADASIL was established. Our case demonstrates that infectious conditions such as influenza A can trigger multiple border-zone infarctions in patients with CADASIL.

Inflammatory monocytes and the pathogenesis of viral encephalitis.

Monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (CNS). Ly6Chi/CCR2(hi) inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; Alzheimer's disease; stroke; and more recently in CNS infection caused by Herpes simplex virus, murine hepatitis virus, Theiler's murine encephalomyelitis virus, Japanese encephalitis virus and West Nile virus. The precise differentiation pathways and functions of inflammatory monocyte-derived populations in the inflamed CNS remains a contentious issue, especially in regard to the existence of monocyte-derived microglia. Furthermore, the contributions of monocyte-derived subsets to viral clearance and immunopathology are not well-defined. Thus, understanding the pathways through which inflammatory monocytes migrate to the brain and their functional capacity within the CNS is critical to inform future therapeutic strategies. This review discusses some of the key aspects of inflammatory monocyte trafficking to the brain and addresses the role of these cells in viral encephalitis.

GADD34 gene restores virulence in viral vector used in experimental stroke study.

GADD34 is expressed in the ischaemic brain and reverses protein synthesis shutdown. Consequently, GADD34 could have neuroprotective potential in stroke. BHK medium, a replication-deficient HSV viral vector (HSV1716) with no insert or containing full-length GADD34, the N terminal or a conserved portion of the gene, was injected into mouse brain before stroke. Infarct size was 1.0+/-0.26, 1.19+/-0.36, 1.5+/-0.36, 1.3+/-0.36, and 1.1+/-0.28 mm3, respectively. The increase in infarct size with full-length GADD34 was statistically significant (P<0.05). Immunohistochemistry confirmed viral protein expression. Tissue culture studies revealed GADD34 gene restored virulence in HSV1716, suggesting that HSV virulence, rather than increased GADD34, exacerbated ischaemic damage.

Multifocal varicella-zoster virus vasculopathy without rash.

A 51-year-old woman with CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) developed stepwise progressive focal neurological deficits without zoster rash. Multifocal ischemic infarcts were seen on magnetic resonance imaging, and cerebral angiography revealed focal stenosis of arteries affecting the intracranial circulation. A brain biopsy was nondiagnostic. Virological etiology of the disease was verified by the detection of varicella-zoster virus antibody in cerebrospinal fluid and by reduced serum-cerebrospinal fluid varicella-zoster virus IgG ratios (compared with normally high ratios of total IgG and albumin). Treatment with intravenous acyclovir stabilized but did not significantly improve her neurological deficits.