Role of PINK1 Gene Mutations in Parkinson’s Disease Elucidated
NEW YORK, July 4 (Reuters Health)—Research suggests that homozygous PINK1 mutations may manifest in an early-onset autosomal recessive form of Parkinson’s disease, whereas single heterozygous PINK1 mutations may play a role in the development of sporadic Parkinson’s disease and may also predispose to familial Parkinson’s disease.
Reporting their research in the June issue of the Archives of Neurology, Dr. Nobutaka Hattori, from Juntendo University School of Medicine, Tokyo, and colleagues noted that reported causative genes for autosomal recessive Parkinson’s disease are parkin (PARK2), DJ-1 (PARK7), and PINK1 (OMIM 608309).
Mutations in parkin are the major cause of autosomal recessive Parkinson’s disease, they pointed out, although “increasing numbers of patients with PINK1 mutations are being reported.” There are, however, no sufficiently large studies to define the frequency, distribution, and clinical features of Parkinson’s disease associated with PINK1 mutations.
Against this backdrop, Dr. Hattori and colleagues performed a retrospective clinical and genetic review of 414 Parkinson’s disease patients negative for parkin mutations, including 391 unrelated patients (190 patients with sporadic Parkinson’s disease and 201 probands of patients with familial Parkinson’s disease) from 13 countries.
They found 10 patients with Parkinson’s disease from nine families with PINK1 mutations and identified seven novel mutations (two homozygous and five heterozygous mutations). The frequency of homozygous mutations, Dr. Hattori and colleagues found, was 4.26% in families with autosomal recessive Parkinson’ disease and 0.53% in patients with sporadic Parkinson’s disease. The frequency of heterozygous mutations was 1.89% in families with potential autosomal dominant Parkinson’s disease and 1.05% in patients with sporadic Parkinson’s disease.
“Our results suggest that homozygous PINK1 mutations tend to be diagnosed as the early-onset autosomal recessive form of Parkinson’s disease,” they reported, noting that the mean age at onset in patients with single heterozygous mutations was higher than that in patients with homozygous mutations (53.6 vs 34.0 years).
“We can also speculate that single heterozygous mutations may be one of the risk factors in developing the sporadic or autosomal dominant form of Parkinson’s disease.”
Arch Neurol. 2008;65(6):802-808.
Reduced Creatinine Clearance and Microalbuminuria Both Predict Stroke
NEW YORK, July 23 (Reuters Health)—Impairment of the glomerular filtration rate (GFR) and the glomerular filtration barrier are independently associated with stroke, according to an analysis of data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES).
“Any screening of CKD (chronic kidney disease) in patients who have had a stroke should include assessment of impairment of both glomerular structure and function,” Dr. Bruce Ovbiagele reported in the July issue of the Archives of Neurology.
In his study, Dr. Ovbiagele, from the UCLA Medical Center in Los Angeles, included 5,624 subjects 55 or older, of whom 414 reported a history of stroke. Multivariate modeling showed that low GFR and microalbuminuria were significantly associated with stroke. The odds ratio for GFR less than 60 mL/min/1.73 m² was 1.77, and that for urinary albumin-to-creatinine ratio greater than 30 mg per 1 g of creatinine was 1.57.
Screening stroke patients will identify individuals at high risk of recurrent vascular events, as most patients with CKD tend to die of cardiovascular causes and not progression to end-stage renal disease, the investigator noted. Therefore, “averting vascular events in these patients should be a primary goal,” with such interventions as angiotensin-converting enzyme inhibitors and statins.
These findings, Dr. Ovbiagele said, confirm the value of screening patients with stroke for CKD, measuring both microalbuminuria and creatinine clearance.
Arch Neurol. 2008;65(7):934-938.
Blood-Brain Barrier Disruption Implicated in Posttraumatic Epilepsy
NEW YORK, July 24 (Reuters Health)—There is a high occurrence of prolonged and lasting breakdown of the blood-brain barrier (BBB) after mild traumatic brain injury, especially among patients who develop epilepsy, according to findings reported in the July issue of the Journal of Neurology, Neurosurgery, and Psychiatry.
“Posttraumatic epilepsy (PTE) occurs in 20% to 40% of patients after head injury and is often difficult to treat,” Dr. Alon Friedman told Reuters Health. “However, at present, there are no means to predict who will develop epilepsy and no measures for its prevention,” he explained.
Dr. Friedman, of Ben-Gurion University of the Negev, Beer-Sheva, Israel, and his colleagues have shown in recent animal experiments that “opening the BBB leads to network changes, long-lasting epileptiform activity, and eventual neurodegeneration.”
In the current study, the researchers examined the frequency and extent of increased BBB permeability in 32 head trauma patients, of whom 17 had PTE. Spectral EEG analyses showed significant slowing in patients with traumatic brain injury, but no significant differences were observed between patients with epilepsy and those without. Patients with PTE were significantly more likely to have a lesion on their MRI scans than those without epilepsy (80% vs 30.8%), but there was no significant difference in the size of the lesion between the groups.