Faculty Bibliography

BACKGROUND:Intracerebral hemorrhage (ICH) is an unusual but serious complication of bleeding disorders. ICH is believed to follow thrombocytopenia, alterations in coagulation, and vascular fragility. Information regarding its distribution is nonconclusive, and the mechanism of bleeding is not fully understood. The aim of this study was to examine the clinical and neuroimaging features of ICH in patients with bleeding disorders to predict risk factors for this condition. METHODS:All cases of ICH diagnosed from 1987 to 2004 were retrospectively identified using the centralized database of our institution. Cases were included whenever ICH was caused by a primary hematologic disorder. The clinical characteristics, neuroimages, and outcome were analyzed. RESULTS:A total of 31 patients were identified. ICH was the initial presentation of the bleeding disorder in 9 patients. Overall, 71% had systemic bleeding concurrent to the ICH. All patients had altered mental status. In 45.2% of the patients simultaneous intracranial hemorrhages were found. Eight patients had recurrent ICH. Severe thrombocytopenia (platelet count < 10,000/mm(3)) was present in 41% and very low platelets (</=1000/mm(3)) in 3%. Death occurred in 71%. CONCLUSIONS:Multiple ICH is not an unusual presentation in patients with primary bleeding disorders developing brain hemorrhage. Although low platelet counts can be blamed for the bleeding, factors different from thrombocytopenia should be considered as the principal mechanism. The best predictor of cerebral bleeding is the presence of systemic bleeding.

OBJECTIVE:To evaluate the frequency of and risk factors for epileptic seizures in patients with systemic lupus erythematosus (SLE) in a large cohort series. METHODS:One thousand two hundred patients with SLE were analyzed. The type and frequency of risk factors for seizures associated with SLE were studied and compared with two other series reported in the literature. RESULTS:One hundred and forty-two patients had seizures. Seventy-five patients were studied with a mean follow-up of 5 years from the first seizure episode. Fifty-eight (77%) patients had tonic-clonic seizures, 9 (12%) complex partial seizures (PS), 5 (7%) simple partial motor seizures and 3 (4%) secondary tonic-clonic seizures. In 41 (54%) patients, the seizures occurred within the first year of the SLE diagnosis. Recurrence occurred in 40 (53%) patients, and was associated with PS in 14 (35%; p = 0.006) and time of seizures with SLE onset in 5 (12.5%; p = 0.05). Less than one third of the patients had positive antiphospholipid antibodies. A concurrent infection was present in 16 (21%) patients. CONCLUSIONS:Epileptic seizures were more common during the first year after SLE diagnosis. Neither infection nor antiphospholipid syndrome was associated with the occurrence of seizures.

Peripheral nerve disorders are frequent complications of HIV disease. Distal symmetrical polyneuropathy (DSP) is the most common peripheral nerve disorder associated with HIV and occurs in over one third of infected patients but may occur in up to 67% if asymptomatic patients are included. Risk factors for DSP include increased age, advanced HIV disease, and history of "d-drugs" or other neurotoxic drugs. The primary manifestations of polyneuropathy are slowly progressive numbness and paresthesias, with burning sensations in the feet usually in a symmetrical pattern. The etiology of HIV-associated DSP is unknown, although neurotoxic effects of cytokines, toxicity of HIV proteins, and mitochondrial damage have been implicated. The current treatment for HIV-associated DSP is symptomatic, with pain modifying medications, including anti-inflammatory agents, opioids, antidepressants, antiepileptics, topical anesthetics, and capsaicin. Sustained virologic control may improve DSP. Novel therapies such as -acetyl-l-carnitine or neurotrophic factors are being studied for treatment of DSP.

Drosophila alcohol dehydrogenase is the most studied member of the family of short-chain alcohol dehydrogenases, although its tridimensional structure still remains unknown. We have engineered a Drosophila alcohol dehydrogenase in which tyrosine-152, an invariant residue in all members of the family, has been substituted by phenylalanine. The mutated gene has been expressed in yeast and pure mutant enzyme has been prepared by a one-step FPLC chromatographic procedure. Drosophila alcohol dehydrogenase-phenylalanine-152 shows no enzymatic activity. This result suggests not only that tyrosine-152 could constitute an essential building block of the active site but also that its hydroxyl group is directly involved in the redox reaction catalyzed by the enzyme.