Sleegers and colleaguesArticle provide a thorough clinical-neuropathologic-molecular analysis of the frontotemporal dementias from a group that has made several of the seminal recent molecular genetic discoveries. The discovery of the progranulin loss-of-function mutations that cause frontotemporal dementia with ubiquitin inclusions mapping to chromosome 17 marks the beginning of a new era of frontotemporal lobar degeneration (FTLD) research. An obvious question now is how a partial loss of this widely expressed protein causes such a specific disease. This insight may prove instrumental in the development of therapy. In addition, the 43-kDa transactivating responsive sequence DNA-binding protein (TDP-43) has been shown to be a major constituent of the ubiquitin-reactive neuronal inclusions in both amyotrophic lateral sclerosis (ALS) and FTLD, suggesting that ALS and FTLD share aspects of the same molecular pathogenesis. Things are speeding up and getting more interesting!
WeinerArticle reviews the battles over nosologic classification of syndromes in medicine that often reach the intensity of a religious debate. He points out that the term Parkinson disease requires new thinking in view of new genotypes, with a Parkinson phenotype now being described. He makes a good case to convince the reader that there is no one Parkinson disease, nor has there ever been.
RogawskiArticle shows that migraine and epilepsy are both comorbid episodic disorders that have some common pathophysiological mechanisms. Migraine attacks, like epileptic seizures, may be triggered by excessive neocortical cellular excitability. It is not surprising that some antiepileptic drugs are effective antimigraine agents. Rogawski offers a discussion of the shared mechanisms of disease for both epilepsy and migraine.
Schwarzschild and colleaguesArticle have studied whether serum urate, a purine metabolite and potent antioxidant, predicts progression in Parkinson disease (PD). They report that patients in the top quintile of serum urate levels reached the study end point with sufficient clinical disability to warrant dopaminergic therapy at only half the rate of patients in the bottom quintile. These findings identify serum urate as the first molecular factor directly linked to the progression of typical PD and suggest that targeting urate or its derivatives could be an effective disease-modifying therapy for PD. Editorial perspective is provided by Mya Schiess, MD, and Irene Oh, MD.Article
Kaplan-Meier estimates of the cumulative probability of reaching the end point by 24 months of follow-up according to sex-specific quintiles of baseline serum urate level. A, Men. B, Women. Log-rank tests: P = .001 in men; P = .47 in women. At 24 months, the sample size was 46 men and 21 women.
The Optic Neuritis Study GroupArticle studied 389 patients with acute optic neuritis who were enrolled between 1988 and 1991 and followed prospectively for 15 years, with final examination in 2006. The cumulative probability of developing multiple sclerosis (MS) by 15 years was 50% (95% confidence interval, 44-56) and was strongly related to the presence of lesions on a non–contrast-enhanced baseline brain magnetic resonance image (MRI). Twenty-five percent of patients with no baseline brain MRI lesions developed MS during follow-up, compared with 72% of patients with 1 or more lesions. After 10 years, the risk of developing MS was very low for patients without baseline lesions but remained substantial for those with lesions. The presence of brain MRI abnormalities at the time of an optic neuritis attack is a strong predictor of the 15-year risk of developing MS. In the absence of MRI lesions, male sex, optic disc swelling, and atypical clinical features of optic neuritis are associated with a low likelihood of developing MS. This natural history information is important when considering prophylactic treatment for MS at the time of a patient's first acute optic neuritis attack.
Ovbiagele and colleaguesArticle have studied the early risk of stroke following transient ischemic attack (TIA) in patients with intracranial arterial stenosis. They find that among individuals with intracranial atherosclerotic disease who present with TIA, a majority of subsequent strokes in the territory of a stenotic intracranial artery occur early. Thus, it is evident from these data that prompt management of TIA in patients with intracranial stenosis, particularly in those with cerebral infarction on brain imaging, is indicated.
Data presented here by Nowak and colleaguesArticle indicate that repetitive transcranial magnetic stimulation (rTMS) of the contralesional primary motor cortex may normalize neural activation within the cortical motor network after subcortical stroke. They indicate that identifying patients suitable for rTMS intervention based on the individual pattern of cortical activation may help to implement rTMS in motor rehabilitation after stroke.
Kassis et alArticle have investigated the therapeutic potential of mesenchymal stromal cells in the chronic model of experimental autoimmune encephalomyelitis. Their results in this comprehensive and elegant study indicate that stem cells derived from bone marrow may provide a feasible and practical method of neuroprotection, immunomodulation, and possible remyelination/neuroregeneration in diseases such as multiple sclerosis.
Haviv and colleaguesArticle report that simvastatin delays prion disease progression and increases survival independently of the pathogenic conversion of cellular prion protein to scrapie prion protein. This effect correlates with downregulation of cyclooxygenase 2 and induction of microglia activation in the prion-infected mouse brain. The human counterpart of this effect should be studied.
Locascio and colleaguesArticle have examined whether plasma markers of amyloid precursor protein metabolism, inflammation, and folate metabolism are associated with the rate of cognitive and functional decline in Alzheimer disease. They find that low plasma amyloid-β protein (Aβ)–40, Aβ42, and C-reactive protein levels were associated with a significantly more rapid cognitive decline than were high levels.
Andersen et alArticle show that 37 g of sucrose ingested shortly before exercise has a marked and prolonged effect on exercise tolerance in patients with McArdle disease. This treatment is more convenient for patients, and saves calories, compared with the currently recommended sucrose treatment.
Occipital predominance of microbleeds with corresponding parietooccipital leukoaraiosis are reported by Pettersen et alArticle as being frequent, often multiple, and predict greater leukoaraiosis. Their data illustrate the complexity of Alzheimer vasculopathy and the need for further studies in dementia and stroke populations.
Borroni et alArticle have measured selective white matter changes and gray matter changes in early corticobasal degeneration syndrome (CBDS), using diffusion tensor imaging (DTI). They found that DTI showed decreases in fractional anisotropy in the long frontoparietal connecting tracts, the intraparietal associative fibers, and the corpus callosum. Their findings provide new evidence of gray matter and fiber tract abnormalities in early disease that add to a clarification of the neural basis of apraxia in CBDS.
Kumazawa and colleaguesArticle find that homozygous PINK1 mutations are diagnosed as an early-onset autosomal recessive form of Parkinson disease (PD). Further, they show that single heterozygous mutations might be additional factors contributing to the susceptibilities of sporadic PD, and also could provide an additional genetic predisposition for developing familial PD.
This Month in Archives of Neurology. Arch Neurol. 2008;65(6):695-697. doi:10.1001/archneur.65.6.695