Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
Citations 0
This Month in Archives of Neurology
April 2008

This Month in Archives of Neurology

Author Affiliations

Copyright 2008 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2008

Arch Neurol. 2008;65(4):441-442. doi:10.1001/archneur.65.4.441
Gene-Targeted Therapies for the Central Nervous System

Miller et al (Article) point out in an elegant and pertinent review that the identification in recent years of the genes and proteins involved in many neurodegenerative diseases offers the exciting possibility of modifying those disease-linked proteins to develop novel, targeted therapies for diseases such as amyotrophic lateral sclerosis or Huntington disease. Multiple methods are currently being studied for their ability to decrease levels of unwanted proteins including immunization strategies, small molecules, RNA interference, and antisense oligonucleotides. The stage has been set for moving these new therapies from animal models to clinical trials in the near future.

Stems Cells and Therapy for Neurologic Diseases

Einstein and Ben-Hur (Article) cite new insights that indicate that stem cells have real potential for the treatment of neurologic diseases. Recent data on stem cells indicate they may attenuate deleterious inflammation, protect the central nervous system from degeneration, and enhance endogenous recovery processes.

Refining Frontotemporal Disease

Boeve and Hutton (Article) in their comprehensive and insightful review compare and contrast the demographic, clinical, radiologic, neuropathologic, genetic, and pathophysiologic features of frontotemporal disease linked to mutations in the microtubule-associated protein tau gene and mutations in the progranulin gene, highlighting the many similarities but also a few important differences. They point out that the findings provide an intriguing oddity of nature in which 2 genes can cause a similar phenotype through apparently different mechanisms yet reside so near to each other on the same chromosome.

Predicting the Risk for Parkinson Disease

Wang and colleagues (Article) estimate the risk of Parkinson disease (PD) in persons with mutations in the parkin gene. Parkin mutations were identified in 25 probands with PD, 72% of whom were heterozygotes. The cumulative incidence of PD to age 65 years in carrier relatives was estimated to be 7% compared with 1.7% in noncarrier relatives of cases and 1.1% in relatives of controls. Christine Klein, MD, and Andreas Ziegler, PhD, provide editorial perspective (Article).

Glucose Metabolism in Huntington Disease

Lalíc and colleagues (Article) report an impairment in insulin secretion capacity and decrease in insulin sensitivity with an increase in insulin resistance level in normoglycemic patients with Huntington disease compared with healthy control subjects. These data imply that progression of the insulin secretion defect in Huntington disease may lead to a failure to compensate for insulin resistance.

Image not available

Analysis of early-phase insulin secretion in patients with Huntington disease (HD) and control participants using 2 different methods: the acute insulin response (AIR) during the intravenous glucose tolerance test (A) and the insulinogenic index (Δ plasma insulin [PI]30/Δ plasma glucose [PG]30) during the oral glucose tolerance test (B). Values are given as means. Error bars represent SEM. The AIR and insulinogenic index values were significantly lower in patients with HD.

Rapid Eye Movement Sleep Disturbances in Huntington Disease

Arnulf et al (Article) found that the sleep phenotype of Huntington disease includes insomnia, advanced sleep phase, periodic leg movements, rapid eye movement sleep behavior disorders, and reduced rapid eye movement sleep but does not include narcolepsy.

Cryptogenic Epileptic Syndromes Related to SCN1A Mutations

The SCN1A gene encoding the sodium channel α 1 subunit is mutated in different forms of epilepsy. Zucca and colleagues (Article) analyzed the SCN1A gene for mutations in patients with cryptogenic epileptic syndromes. Thirteen different point mutations were identified in 12 patients. These results confirm the role of the SCN1A gene in different types of epilepsies including cryptogenic epileptic syndromes.

Nerve Conduction Features in Fragile X Permutation Carriers

Soontarapornchai et al (Article) report that male permutation carriers had significant conduction abnormalities of motor and sensory nerves that correlated with molecular measures, suggesting that the permutation FMR1 genotype is a causal factor.

Arctic Amyloid Precursor Protein Gene Mutation and Alzheimer Disease

Basun and colleagues (Article) describe features of 1 Swedish and 1 American family with an arctic amyloid precursor protein mutation. Their findings corroborate that the arctic amyloid precursor protein mutation causes a clinical and neuropathologic picture compatible with Alzheimer disease.

Progranulin Gene Mutation Causal of Frontotemporal Disease With Parietal Lobe Deficits

Rohrer et al (Article) describe the clinical, neuropsychological, and radiological features of a family with a mutation in the progranulin gene. Patients expressed deficits consisting of limb apraxia, dyscalculia, and visuoperceptual and/or visuospatial impairment. Brain imaging showed posterior extension of frontotemporal atrophy to involve the parietal lobes. Thus, parietal features may be a prominent feature of progranulin mutations and this may be due to disruption of frontoparietal functional pathways.

α-Synuclein Gene (SNCA) Duplication With Parkinsonism and Dementia

Ikeuchi and colleagues (Article) describe in great detail patients with pathologically confirmed Lewy body disease characterized by progressive parkinsonism and cognitive dysfunction caused by duplication of the SNCA gene.

Spartin Protein Deficiency and Troyer Syndrome

A family with Troyer syndrome, an autosomal recessive, complicated hereditary spastic paraplegia with associated distal amyotrophy, short stature, and dysarthria due to a 1110delA mutation in the spartin gene, is described by Bakowska et al (Article). They report that the spartin protein is undetectable in several cell lines derived from patients. They conclude that Troyer syndrome results from complete loss of spartin protein. These data advance our knowledge of the molecular-genetic basis for this unique genotypic cause of hereditary spastic paraplegia.

Muscle Excitability in Machado-Joseph Disease

Franca and colleagues (Article) describe muscle excitability abnormalities in 80% of patients with Machado-Joseph disease in their clinic and indicate it was the presenting complaint in 20% of them. They are related to altered excitability of peripheral motor axons.

Impaired Eye Movements Precede Symptoms in SCA6

Christova et al (Article) sought to identify early abnormalities of ocular motor function in subjects who had spinocerebellar ataxia (SCA) type 6 but no clinical symptoms. They describe presymptomatic subjects with normal postural sway but definite ocular motor abnormalities. The earliest functional deficits in SCA6 consist of eye movement abnormalities, including impaired saccade velocity, saccade metrics, and pursuit gain.