Neurology
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Many missense mutations in the voltage-gated sodium channel subunit gene SCN1A were identified in patients with generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI), although GEFS+ is distinct from SMEI in terms of clinical symptoms, severity, prognosis, and responses to antiepileptic drugs. The authors analyzed the localization of missense mutations in SCN1A identified in patients with GEFS+ and SMEI to clarify the phenotype-genotype relationships. ⋯ There was a significant phenotype-genotype relationship in generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy of infancy with SCN1A missense mutations. More severe sodium channel dysfunctions including abnormal ion selectivity that are caused by mutations in the pore regions may be involved in the pathogenesis of SMEI.
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Review
Modulation of the renin-angiotensin-aldosterone system for the secondary prevention of stroke.
Recurrent stroke is a major public health concern and new treatment strategies are needed. While modulation of the renin angiotensin aldosterone system (RAAS) has proven effective in reducing recurrent cardiac events, its role in preventing recurrent cerebrovascular events remains unclear. RAAS is both a circulating and tissue based hormonal system that regulates homeostasis and tissue responses to injury in both the CNS and the periphery, via the activity of angiotensin II (Ang II). ⋯ PROGRESS, a trial of secondary stroke prevention, demonstrates that blood pressure reduction with a combination strategy including the routine use of ACE inhibitors prevents recurrent stroke. Current evidence suggests that the RAAS plays an important role in the development and progression of cerebrovascular disease. Modulation of the RAAS holds promise for the secondary prevention of stroke, however, ongoing clinical trials will better define the exact role of ACE inhibitor and angiotensin II Type 1 receptor blocker therapy in stroke survivors.
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Comparative Study Clinical Trial Controlled Clinical Trial
Initial chemotherapy in gliomatosis cerebri.
Because of the diffuse nature of gliomatosis cerebri (GC), surgery is not suitable, and large field radiotherapy carries the risk of severe toxicity. In this setting, initial chemotherapy warrants further investigation. ⋯ Initial chemotherapy is useful for some patients with gliomatosis cerebri. Temozolomide is well tolerated and appears to be a valuable alternative to procarbazine-CCNU-vincristine, especially for those with slow-growing, low-grade GC.
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The optimal therapy for gliomatosis cerebri is unclear, and the rate of response to chemotherapy is not known. Eleven radiotherapy-naive patients received a median number of 10 treatment cycles of temozolomide. An objective response was documented in 45%, and the median time to tumor progression was 13 months with a progression-free survival of 55% at 12 months. These results indicate that radiotherapy to extensive brain regions can be deferred until progressive disease is observed.
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Biography Historical Article
Americo Negrette (1924 to 2003): diagnosing Huntington disease in Venezuela.
To elucidate the role of Dr. Americo Negrette in diagnosing and reclassifying the dancing mania in Maracaibo, Venezuela as Huntington disease (HD). ⋯ The "dancing mania" of Maracaibo, because of the work of Americo Negrette, has been reclassified as Huntington disease.