Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited autosomal dominant condition characterized by migrane, recurrent stroke, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in -33% of patients. CADASIL is commonly overlooked or misdiagnosed owing to its recent identification. The pathological hallmark of angiopathy is the presence of multiple, small, deep cerebral infarcts, leucoencephalopathy, and nonatherorosclerotic, nonamyloid angiopathy involving mainly small, deep perforating cerebral arteries. Changes also are present in vascular smooth muscle cells and consist in the presence of granular osmiophilic material (GOM). The defective gene in CADASIL is Notch 3, which encodes a large transmembrane receptor. Magnetic resonance imaging shows high intensity signal lesions, often confluent, and areas of cystic degeneration of subcortical white matter and basal ganglia. Diagnostic strategies in CADASIL are matter of discussions because the electron microscopic demonstration of GOM was reported in 100% of symptomatic patients of French authors, but only in 45% of a British study. GOMs are not present in presymptomatic patients.

An Italian case of CADASIL with mutation CGC-TCG in codon 1006, exon 19 Notch3 gene.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly overlooked or misdiagnosed owing to its recent identification. It is characterized clinically by recurrent cerebral infarcts, usually appearing between the ages of 30 and 50 years, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in approximately one-third of patients. The pathological hallmark of angiopathy is the presence of characteristic granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells. The defective gene in CADASIL is Notch3, which encodes a large transmembrane receptor, and 70% of missense mutations are in exons 3 and 4. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular N-terminal domain of the molecule. We report the case of a 53-year-old woman admitted to the hospital for transient ischemic attack and stroke-like episodes recurrent since age 43 years. The patient had pseudobulbar palsy, pyramidal signs, and cognitive impairment but not frank dementia. Cerebral MRI showed periventricular diffuse and confluent ischemic lesions. Ultrastructural study revealed an abnormal deposition of granular osmiophilic material (GOM) within the basal lamina in skin capillaries. Direct sequence analysis of the Notch3 gene was performed. Since no mutation was detected in exons 3 and 4, the remaining exons were sequenced and a missense mutation, CGC-TGC in codon 1006 of exon 19 was found. The mutation led to a gain of a cysteine residue. This is the first missense mutation in codon 1006 of exon 19 of the Notch3 gene to be described in Italy and the second reported in the literature.

Intoxicacao experimental pelo cloreto de mercurio: lipoperoxidacao hepatica e renal. / Experimental HgCl2 poisoning: renal and hepatic lipid peroxidation

Ratos Wistar machos, com 30 dias de idade, foram submetidos a intoxicacao experimental, com 100 ppm de HgCl2, por via oral.Os niveis de lipoperoxidacao hepatica e renal foram avaliados, medindo-se a quantidade total de malonildialdeido (MDA) produzido por homogenados desses orgaos. Nao se obteve nenhuma alteracao na quantidade de MDA produzida pelos homogenados. Cortes histologicos desses orgaos, nos animais tratados, nao mostraram alteracoes, quando comparados com os do grupo controle