This Month in Archives of Neurology

Testai and GorelickArticle discuss in Part 2 homocystinuria, organic acidurias, and urea cycle disorders as metabolic disorders causal of stroke. Inherited metabolic disorders represent an uncommon but important etiology of stroke, primarily in neonates, children, and young adults. Recognition of these disorders is germane, as they may be a previously unrecognized, treatable or preventable cause of cryptogenic stroke.

The Dimebon in Subjects With Huntington Disease (DIMOND) InvestigatorsArticle of the Huntington Study Group evaluate the safety and tolerability of dimebon in Huntington disease and explore its effects on cognition, behavior, and motor symptoms. They report that short-term administration of dimebon is well tolerated in patients with Huntington disease and may have a beneficial effect on cognition.

Yu and colleaguesArticle delineate the range of clinical presentations associated with progranulin gene (GRN) mutations and define pathogenic candidacy of rare GRN variants. They report that pathogenic mutations were only found in frontotemporal dementia spectrum cases and not in other related neurodegenerative diseases, and haploinsufficiency of GRN is the predominant mechanism leading to frontotemporal dementia. Editorial perspective is provided by Bradley F. Boeve, MD.Article

Kelley et alArticle characterize a kindred with a familial neurodegenerative disorder associated with a mutation in progranulin (PGRN), emphasizing the unique clinical features in this kindred. They describe a large kindred in which most affected individuals had clinical presentations resembling Alzheimer disease or amnestic mild cognitive impairment in association with a mutation in PGRN and underlying frontotemporal lobar degeneration with ubiquitin-positive neuronal cytoplasmic and intranuclear inclusions neuropathology.

Spence and colleaguesArticle assessed the effect of more intensive medical therapy on the rate of transcranial Doppler microemboli and cardiovascular events in patients with asymptomatic carotid stenosis (ACS). They find that cardiovascular events and microemboli on transcranial Doppler have markedly declined with more intensive medical therapy. Less than 5% of patients with ACS now stand to benefit from revascularization; patients with ACS should receive intensive medical therapy and should only be considered for revascularization if they have microemboli on transcranial Doppler.

Oveisgharan and HachinskiArticle report that hypertension predicts progression to dementia in elderly individuals with executive, but not memory, dysfunction. Thus, control of hypertension could potentially help prevent progression to dementia in one-third of patients with cognitive impairment but without dementia.

Lee et alArticle indicate that stroke incidence increases after menopause when endogenous estrogen levels fall; yet, exogenous estrogen increases incidence of strokes in older postmenopausal women. The relationship between endogenous estrogen and stroke is unclear. They report that endogenous estradiol is an indicator of stroke risk in older postmenopausal women, especially in those with greater central adiposity.

Lehmann and colleaguesArticle state that autonomic dysfunction is a common and possibly life-threatening complication of Guillain-Barré syndrome. They find that, in Guillain-Barré syndrome, circulating antibodies directed against sympathetic neurons may contribute to autonomic dysfunction via functionally relevant changes in noradrenaline synthesis.

Lipp et alArticle have determined whether ventilatory and cardiovascular responses to hypercapnia and hypoxia during wakefulness are systematically impaired in multiple system atrophy. They report that ventilatory responses to hypercapnia and hypoxia during wakefulness may be preserved in patients with multiple system atrophy despite the presence of autonomic failure and impaired cardiovascular responses to these stimuli.

Stomrud and colleaguesArticle indicate that abnormal cerebrospinal fluid (CSF) biomarker levels predict development of Alzheimer disease (AD) with good accuracy and are thought to precede cognitive deterioration. In this group of healthy older individuals, changes in CSF biomarkers previously associated with AD correlate with decline in cognitive functions. The results implicate that CSF biomarkers might be able to detect the very early neurodegenerative processes of AD.

Groen et alArticle assessed the frequency of FUS mutations in 52 probands with familial amyotrophic lateral sclerosis and provide careful documentation of clinical characteristics. They demonstrate FUS mutations in Dutch patients with familial amyotrophic lateral sclerosis and that benign variations in the gene may occur. Therefore, caution is warranted when interpreting results in a clinical setting.

Barsdorf et alArticle studied demographics, comorbidities, expenditure, and outcomes of scoliosis surgery in pediatric neuromuscular patients based on a nationwide sample of US hospital discharges. Children with neuromuscular disease have increased lengths of stay and higher mortality associated with scoliosis surgery, highlighting the need for further study of measures that could reduce complications and improve outcomes in this population.