Literature Review

New and Noteworthy Information—June 2013


 

Individuals older than 70 with nonmelanoma skin cancer may have a significantly reduced risk of developing Alzheimer’s disease, compared with individuals without nonmelanoma skin cancer, according to research published online ahead of print May 15 in Neurology. Investigators assessed 1,102 community-dwelling adults (mean age, 79) annually, and a multidisciplinary diagnostic consensus was achieved for each patient. Participants reported their cancer status and type. The researchers tested associations between nonmelanoma skin cancer and three neurocognitive disorders—only Alzheimer’s disease, any Alzheimer’s disease, and all-cause dementia. Nonmelanoma skin cancer was associated with reduced risk of only Alzheimer’s disease among subjects after adjustment for demographics, hypertension, diabetes, and coronary heart disease. No significant association was found between nonmelanoma skin cancer and subsequent development of any Alzheimer’s disease or all-cause dementia.

Consumption of fruits and vegetables that contain nicotine may reduce the risk of Parkinson’s disease, researchers reported online ahead of print May 9 in Annals of Neurology. Investigators conducted a population-based study of 490 patients with newly diagnosed Parkinson’s disease and 644 healthy controls. They examined whether Parkinson’s disease was associated with self-reported frequency of consuming fruits and vegetables from the same botanical family as tobacco, Solanaceae, including peppers, tomatoes, and potatoes. Parkinson’s disease was inversely associated with consumption of all edible Solanaceae combined, but not consumption of all other vegetables combined. Weighting edible Solanaceae by nicotine concentration strengthened the trend. Peppers specifically were inversely associated with risk of Parkinson’s disease. The potential effect of edible Solanaceae largely occurred in individuals who had never used tobacco.

The FDA has approved Nymalize, an oral solution of nimodipine, for the improvement of neurologic outcome in adults with subarachnoid hemorrhage. The drug, manufactured by Arbor Pharmaceuticals in Atlanta, is intended to reduce the incidence and severity of ischemic deficits from ruptured intracranial berry aneurysms, regardless of patients’ post-ictus neurologic condition. Before Nymalize was approved, nimodipine was available only in a gel capsule. The product is commonly administered to patients through a nasogastric tube, and health care providers sometimes extracted the product from the gel capsule with a syringe. The procedure resulted in accidental IV administrations of nimodipine instead of through the intended enteral syringe. Nymalize was designated an orphan drug, and Arbor Pharmaceuticals plans to make the product available in the coming months.

Contrary to widespread belief, African Americans may not have a lower risk of multiple sclerosis (MS) than Caucasians, researchers reported in the May 7 issue of Neurology. Investigators performed a retrospective cohort study of multiethnic, community-dwelling members of the Kaiser Permanente Southern California health plan. Overall, 496 patients were newly diagnosed with MS. The average age at diagnosis was 41.6 years, and 70.2% were women. The female preponderance was more pronounced among African American (79.3%) than in Caucasian, Hispanic, and Asian individuals with MS (67.8%, 68.1%, and 69.2%, respectively). The incidence of MS was higher in African Americans and lower in Hispanics and Asians than Caucasians. African American women had a higher risk of MS, and African American men had a similar risk of MS, compared with Caucasians.

It may be feasible to monitor patients with refractory focal seizures using an implanted seizure advisory system designed to predict seizure likelihood, according to data published online ahead of print May 2 in Lancet Neurology. Researchers implanted the advisory system in 15 patients who had between two and 12 disabling partial-onset seizures per month, a lateralized epileptogenic zone, and no history of psychogenic seizures. Within four months of implantation, 11 device-related adverse events were noted, two of which were serious. Two additional serious adverse events occurred during the first year after implantation, but they were resolved without further complication. The device met enabling criteria in 11 patients after completion of the data-collection phase, and high likelihood performance estimate sensitivities ranged from 65% to 100%.

Transplanting medial ganglionic eminence (MGE) cells into the hippocampus of adult mice with epilepsy greatly reduced the occurrence of electrographic seizures, according to a study published online ahead of print May 5 in Nature Neuroscience. The procedure also restored deficits in spatial learning, hyperactivity, and the aggressive response to handling. After transplantation, GABA progenitors migrated as far as 1,500 µm from the injection site, expressed genes and proteins characteristic of interneurons, differentiated themselves into functional inhibitory neurons, and received excitatory synaptic input. Grafts of MGE cells into the basolateral amygdala, however, restored the mice’s hyperactivity deficit, but did not affect seizure activity or other abnormal behaviors. The researchers theorized that interneurons have a crucial role in epilepsy.

The RAD6A (Ube2a) gene, which encodes for an E2 ubiquitin-conjugating enzyme, may regulate Parkin-dependent mitophagy and have a crucial role in maintaining neuronal function, according to a study published in the May 16 Molecular Cell. Researchers identified a series of patients with X-linked intellectual disability who had mutations in the RAD6A (Ube2a) gene. Drosophila deficient for dRad6 had mitochondrial failure and consequently displayed defective synaptic function. Mouse mRad6a (Ube2a) knockout and patient-derived hRad6a (Ube2a) mutant cells also had defective mitochondria. Using in vitro and in vivo ubiquitination assays, the researchers concluded that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells.

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