This Month in Archives of Neurology

In a climate of heightened concern about biological and chemical terrorism, the neurologist needs to be aware of the potential agents that may be employed. This article focuses on likely substances that may be encountered, including cyanide, cholinesterase inhibitors, botulinum toxin, and anthrax, because of their prominent neurologic manifestations. Martin and Adams have provided an important set of guidelines for the physician by reviewing specific weapons applications, clinical manifestations, and therapies that must be rapidly and accurately applied.

CYP46, the gene encoding cholesterol 24-hydroxylase, plays a key role in the hydroxylation of cholesterol synthesized by the brain and its subsequent transport from the brain. Papassotiropoulos and colleagues have studied a single-nucleotide polymorphism of CYP46 and show that it is associated with increased β-amyloid load in brain tissues as well as with increased cerebrospinal fluid levels of both β-amyloid peptides (Aβ₄₂) and phosphorylated tau protein. They find that this CYP46 polymorphism is associated with a higher risk for late-onset sporadic Alzheimer disease (AD) in 2 independent populations. Thus, rates of synthesis of 24-hydroxyl-cholesterol and its egress from the brain directly influence the biochemical events associated with the pathogenesis of AD. This newly described polymorphism and brain levels of 24-hydroxy-cholesterol are important new issues to be considered in understanding the molecular causes of AD.

Editorial comment is provided by Benjamin Wolozin, MD, PhD.

Oh and colleagues show that the initial serum level of neuron-specific enolase (NSE) was significantly higher in patients with an infarction in the anterior circulation compared with control subjects. This correlated highly with the volume of infarction on T2-weighted brain magnetic resonance imaging and with the National Institutes of Health Stroke Scale score on admission and on the seventh day after stroke. Thus, NSE may be a reliable predictor for the severity of neuronal damage and clinical neurologic deficits caused by anterior circulation infarction.

Patients with acquired multifocal sensory and motor neuropathy of otherwise unknown cause have increased levels of antiganglioside antibodies as shown by Alaedini et al. Increased levels of antiganglioside antibodies were found in 12 (48%) of the 25 patients using the agglutination immunoassay and in 7 of the 12 agglutination-positive patients by enzyme-linked immunosorbent assay. These findings are important immunologic and clinical markers of multifocal sensorimotor neuropathy and will aid in the accurate diagnosis and care of patients with this treatable form of acute neuropathy.

Schulte-Mattler and colleagues have elegantly and precisely determined whether and to what extent metabolic muscle fatigue specifically occurs in patients with mitochondrial encephalomyopathy. In general, they find that some specific mutations are causal and some are not causal for metabolic muscle fatigue. Their data are of considerable value in assessing therapies for mitochondrial and other neuromuscular disorders.

Plasma levels of homocysteine were significantly higher in patients with Parkinson disease (PD) treated with levodopa compared with patients with PD not taking levodopa. Patients whose homocysteine levels were in the higher quartile of studied patients had increased prevalence of coronary artery disease. These findings reported by Rogers and colleagues have clear implications for the treatment of PD in patients at risk for vascular disease and potentially for those at risk for dementia and depression as well.

Enzinger and colleagues measured N-acetylaspartate (NAA), a neuronal-axonal marker, in 72 patients with multiple sclerosis (MS), including those who had an apolipoprotein E (APOE) ϵ4 allele detected by proton magnetic resonance spectroscopy (¹H-MRS). Levels of NAA in patients with MS with an ϵ4 allele showed a significantly lower mean of the NAA/creatine ratio than those without this allele. Thus, APOE ϵ4 is a factor in the natural history, course, and severity of MS pathogenesis, and ¹H-MRS is an important and valuable marker to use in evaluating and caring for patients with MS. Further, it is a reliable marker of the neuronal-axonal injury that is present in specific patients.

Tumarkin falls are sudden drop attacks that occur in a subset of patients with Meniere syndrome. Ishiyama and colleagues describe the clinical features and quantitative audiovestibular results in a series of patients with Tumarkin falls, episodic vertigo, and normal hearing.

Krystkowiak and colleagues describe 10 patients who underwent bilateral subthalamic nucleus stimulation. Compared with levodopa treatment in the on-drug condition, the effect of stimulation on gait kinetic parameters included an improvement for levodopa-induced dyskinesias and Expanded Disability Status Scale scores.

Knopman and colleagues studied 479 incident cases of dementia and 479 referent subjects for the features present in vascular dementia (VaD) and survival in Rochester, Minn, from 1985 through 1989. Patients with VaD had a higher relative risk of death than patients with dementia overall or patients with Alzheimer disease. They found that dementia following stroke is common and has good validity as a diagnostic marker for VaD. This study emphasizes the importance of identifying patients with VaD for early treatment and follow-up of vascular risk factors, especially in view of the increased morbidity and mortality related to VaD compared with other types of dementia, including Alzheimer disease.

Elbaz et al compared survival in incident cases of Parkinson disease (PD) with survival in PD-free subjects. One hundred ninety-six cases and 185 referent subjects were studied for survival between 1976 and 1995 in Olmsted County, Minnesota. The median survival rate was 10.3 years in PD cases and 13.4 years in referent subjects. Patients with PD with both rest tremor and pronounced asymmetry had a better prognosis than subjects with neither clinical feature. Thus, patients with PD clearly face a higher risk of death compared with PD-free subjects in the general population. It is important to note that certain clinical characteristics and smoking modify survival.

Einum and colleagues have identified a novel spinocerebellar ataxia type 7 (SCA7) transcript and protein, which localizes to neuronal cytoplasm and not to inclusion bodies present in tissues of patients with SCA7. These data indicate that expression of multiple polyglutamine-containing proteins may play a role in generating the neurodegenerative patterns characteristic of SCA7 and other polyglutamine diseases.