The risk of parkinsonism with use of the antiepileptic drug (AED) valproate may not be as high as previously reported, though the risk is still five times greater than with other AEDs, according to a study in the February Journal of Neurology, Neurosurgery, and Psychiatry. In 201 patients with epilepsy, the most common movement disorder observed was postural tremor (45%), followed by parkinsonism (4.5%). However, five of the nine patients displaying parkinsonism were concurrently using other drugs or had comorbidities “that could have caused or exacerbated the parkinsonism,” noted the researchers. While none of the newer AEDs was clearly associated with the presence of movement disorders, the researchers stated that the numbers were too small to draw a formal conclusion.

The inhaled anesthetic isoflurane may induce the generation and aggregation of amyloid-β protein, starting a cycle of cell death similar to what is observed in the brains of patients with Alzheimer’s disease, according to research published in the February 7 Journal of Neuroscience. In a series of in vitro experiments, researchers reported that isoflurane increased activation of the enzyme caspase-3 in neural cells; however, cells treated with caspase inhibitor displayed markedly decreased amyloid precursor protein processing and amyloid-β generation, indicating that caspase activation is essential to the pathway leading to the formation of amyloid-β plaques. Isoflurane also increased levels of β- and g-secretase, proteases responsible for amyloid-β generation. Finally, amyloid-β aggregation can further promote cell apoptosis, resulting in a “vicious cycle … leading to cell death.”

A ketogenic diet (KD) may decrease sleep in children with therapy-resistant epilepsy; however, quality of sleep will be increased and may help improve quality of life, as reported in the January Epilepsia. Eighteen epileptic children underwent ambulatory polysomnographic recordings at baseline and after three months of KD treatment. Investigators reported significant decreases in total sleep, total night sleep, and sleep stage 2 at three months. REM sleep increased, and slow wave sleep was preserved. Eleven participants continued KD treatment and at 12 months showed a significant decrease in daytime sleep and a further increase in REM sleep. Seizure frequency, seizure severity, and quality of life were all significantly improved at both three and 12 months. Additionally, the investigators reported a significant correlation between increased REM sleep and improved quality of life.

According to a study in the January Epilepsia, agreement between EEG and magnetoencephalography (MEG) localization may be a predictor of seizure-free outcome after surgery among children with refractory epilepsy and normal or nonfocal MRI findings. Among 22 children who underwent surgery for intractable epilepsy following extraoperative intracranial EEG, 17 had a good outcome after surgery. Eight of these children were seizure-free and had an MEG cluster in the final resection area. “Restricted ictal onset zone predicted postoperative seizure freedom,” the researchers stated. “Postoperative seizure freedom was less likely to occur in children with bilateral MEG dipole clusters or only scattered dipoles, multiple seizure types and incomplete resection of the proposed epileptogenic zone.”

Investigators reported in the February Stroke that older males with early intracerebral hemorrhage who have a motor deficit and a thrombosis of the deep cerebral venous system or of the right lateral sinus may face an increased risk of dependency or mortality at six months. The investigators evaluated predictors among 245 patients with early intracerebral hemorrhage and compared these results with an analysis of 36 patients with delayed intra­cerebral hemorrhage. Among patients with early intracerebral hemorrhage, 51 (21%) had a modified Rankin score of 3 to 6 at six months; patients with delayed intracerebral hemorrhage and a modified Rankin score of 3 to 6 at six months were more likely to have had early intracerebral hemorrhage.

Anticoagulation treatment may reduce poststroke mortality in patients with ischemic stroke and atrial fibrillation, reported researchers in the February Stroke. Among 1,909 patients with both ischemic stroke and atrial fibrillation, 1,149 participants received anticoagulation treatment, while the remaining 760 did not, “despite no contraindication to such treatment,” the researchers pointed out. A total of 18.9% treated patients died during a follow-up period of four years, while among patients who did not receive treatment, 45.2% died. Participants who received treatment were younger and had less severe strokes than those who did not receive treatment. “Patients without anticoagulation treatment were at greater risk of dying compared with patients who received anticoagulation treatment,” concluded the investigators.

Transcutaneous β-amyloid immunization may be an effective and potentially safe treatment strategy for patients with Alzheimer’s disease, reported researchers in the online January 30 Proceedings of the National Academy of Sciences. The investigators targeted the skin as the route of vaccine delivery in a transgenic mouse model of Alzheimer’s disease. They found that transcutaneous immunization with β-amyloid does not appear to trigger specific toxicities associated with past immunization strategies. “Reduction in cerebral amyloidosis was not associated with deleterious side effects, including brain T cell infiltration or cerebral microhemorrhage,” the researchers pointed out. Transcutaneous β-amyloid vaccination may offer a simpler method than previous efforts to prevent or treat Alzheimer’s disease, with less risk of adverse immune reactions.

According to a study in the January American Journal of Pathology, researchers have developed a potentially promising new drug combination for the treatment of brain cancer. In an in vitro study, lovastatin was used to kill cancer cells by blocking the expression of the cell signal known as hedgehog, as well as an additional cell signal, BclII, that may increase simultaneously with hedgehog in cancer cells. Furthermore, the combination of lovastatin and cyclopamine killed 63% of medulloblastoma cells, while either agent alone killed fewer than 20% of medulloblastoma cells. “These data demonstrate that BclII is an important mediator of hedgehog activity in medulloblastoma and suggest new strategies for combined chemotherapeutic regimens,” the researchers stated.

Investigators reported further evidence in the online November 13, 2006, Neurobiology of Aging that supports the theory that herpes plays a role in the development of Alzheimer’s disease. The research team measured the activity levels of latent herpes simplex virus type 1 (HSV-1) in mice that expressed the ε2, ε3, or ε4 alleles of apolipoprotein E (APOE). The investigators found that “carriage of the different APOE alleles dramatically affects HSV-1 immediate early gene expression as well as the establishment of latency. Both of these factors are poised to impact neuronal viability, inflammation, and viral spread. Our data support the concept that HSV-1 and APOE ε4 interact to provide an environment conducive to the development and/or spread of Alzheimer’s disease.”

A multidisciplinary committee of neurologists and surgeons has released a set of screening guidelines for the detection of carotid stenosis. The guidelines were published in the January Journal of Neuroimaging. The committee strongly recommended screening selected patients undergoing coronary artery bypass grafting and all patients with symptomatic peripheral vascular disease. Screening was recommended for all patients who develop ipsilateral ischemic stroke, retinal ischemic events, or transient ischemic attacks. Screening for selected patients with at least three cardiovascular risk factors and for all patients with contralateral carotid artery stenosis of 50% or greater should be considered, the study authors stated. The committee did not recommend screening the general population, every patient who has undergone carotid endarterectomy, or all patients with renal artery stenosis.

L earning may slow the development of brain lesions associated with Alzheimer’s disease, according to researchers in the January 24 Journal of Neuroscience. The learning and memory of two groups of mice with Alzheimer’s disease were tested periodically between ages 2 and 18 months. One group was taught to swim to a platform in a water maze four times a day for one week before each testing session; control mice were tested after a single swimming session. At six and 12 months, only the trained mice displayed improved performance. Additionally, at 12 months, β-amyloid and hyperphosphorylated-tau levels were 60% less than in the mice that had not been trained; however, at 15 and 18 months, memory and neuropathology measures were similar in both groups, suggesting that the development of Alzheimer’s disease can be slowed but not prevented by spatial training.

Researchers reported in the January 23 Neurology that certain adults with epilepsy may be able to predict their own seizures. The investigators assessed patients who were 18 or older, had localization-related epilepsy, had had at least one seizure within one year, and were able to keep a diary recording their seizures. The question “Do you think you will have a seizure in the next 24 hours?” was used as the rating scale to assess seizure self-prediction. Among 15,635 diary entries from 71 participants, a positive seizure prediction was associated with a twofold increased risk of seizure. The overall specificity of a positive prediction was 83.2%, and the overall sensitivity was 31.9%. Those who predicted their own seizures were younger and had a higher seizure rate.

NR