Absence epilepsy in apathetic, a spontaneous mutant mouse lacking the h channel subunit, HCN2.

Analysis of naturally occurring mutations that cause seizures in rodents has advanced understanding of the molecular mechanisms underlying epilepsy. Abnormalities of I(h) and h channel expression have been found in many animal models of absence epilepsy. We characterized a novel spontaneous mutant mouse, apathetic (ap/ap), and identified the ap mutation as a 4 base pair insertion within the coding region of Hcn2, the gene encoding the h channel subunit 2 (HCN2). We demonstrated that Hcn2(ap) mRNA is reduced by 90% compared to wild type, and the predicted truncated HCN2(ap) protein is absent from the brain tissue of mice carrying the ap allele. ap/ap mice exhibited ataxia, generalized spike-wave absence seizures, and rare generalized tonic-clonic seizures. ap/+ mice had a normal gait, occasional absence seizures and an increased severity of chemoconvulsant-induced seizures. These findings help elucidate basic mechanisms of absence epilepsy and suggest HCN2 may be a target for therapeutic intervention.

Middle cerebral artery aneurysm endovascular and surgical therapies: comprehensive literature review and local experience.

The middle cerebral artery is a common location for cerebral aneurysms and is associated with a lower risk of rupture than aneurysms located in the anterior or posterior communicating arteries. No evidence supports the superiority of clipping over coiling to treat middle cerebral artery aneurysm (MCAA) or vice versa. The feasibility of treating the MCAA with endovascular therapy as the first choice of treatment in cohorts of nonselected aneurysms exceeds 90%. A randomized clinical trial comparing the 2 approaches in nonselected cases with long-term follow-up will shed light on which patients may benefit from one approach over another.

Idiopathic Intracranial Hypertension. A Systematic Analysis of Transverse Sinus Stenting.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disorder characterized by signs and symptoms of increased intracranial pressure without structural cause seen on conventional imaging. Hallmark treatment after failed medical management, has been CSF shunting or optic nerve fenestration with the goal of treatment being preservation of vision. Recently, there have been multiple case reports and case series on dural sinus stenting for this disorder. OBJECTIVE: We aim to review all published cases and case series of dural sinus stenting for IIH, with analysis of patient presenting symptoms, objective findings (CSF pressures, papilledema, pressure gradients across dural sinuses), follow-up of objective findings, and complications. METHODS: A Medline search was performed to identify studies meeting pre-specified criteria of a case report or case series of patients treated with dural sinus stent placement for IIH. The manuscripts were reviewed and data was extracted. RESULTS: A total of 22 studies were identified, of which 19 studies representing 207 patients met criteria and were included in the analysis. Only 3 major complications related to procedure were identified. Headaches resolved or improved in 81% of patients. Papilledema improved the (172/189) 90%. Sinus pressure decreased from an average of 30.3 to 15 mm Hg. Sinus pressure gradient decreased from 18.5 (n=185) to 3.2 mm Hg (n=172). Stenting had an overall symptom improvement rate of 87%. CONCLUSION: Although all published case reports and case series are nonrandomized, the low complication and high symptom improvement rate make dural sinus stenting for IIH a potential alternative surgical treatment. Standardized patient selection and randomization trials or registry are warranted.