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This Month in Archives of Neurology
August 2003

This Month in Archives of Neurology

Arch Neurol. 2003;60(8):1040-1041. doi:10.1001/archneur.60.8.1040

Hereditary Spastic Paraplegias: Nine Genes and Counting

John Fink reviews the great strides that have been accomplished in mapping genes for the hereditary spastic paraplegias (HSPs). Twenty HSP loci and 9 HSP genes have been discovered in recent years, and major molecular insights into the causes of HSP are beginning to emerge.

Genetic Regulation and Neurologic Disease

Aspects of neurology in which modeling gene regulation is likely to be useful include understanding and treating polygenetic neurologic disorders, using gene expression data to reconstruct the network of gene regulation in neurons and other cells, and designing vectors and transfection methods for gene therapy. Emerging aspects of molecular neurotherapeutics are elegantly provided by Smolen and Byrne in this timely review.

Treating Parkinson Disease With Nonsteroidal Agents

Chen and colleagues report that the use of nonsteroidal anti-inflammatory drugs may delay or even prevent the onset of Parkinson disease (PD). They found a 45% lower risk of PD in regular users of nonsteroidal anti-inflammatory drugs compared with nonusers. Their study provides the most compelling evidence, short of evidence from a randomized controlled clinical trial, for a clinically relevant benefit of nonsteroidal anti-inflammatory drugs in preventing PD. Editorial perspective is provided by Mya Schiess, MD.

Single-Photon Emission Computed Tomography Perfusion, Magnetic Resonance Imaging Volume, and Alzheimer Disease

El Fakhri and colleagues show that measures of structure activity concentration and volume carry independent information, and both reveal group differences in prodromal Alzheimer disease (AD). They convincingly show that both single-photon emmission computed tomography (SPECT) and magnetic resonance imaging (MRI) variables obtained at baseline are highly significant preditors of future development of AD. For the MRI variables, the most discriminating measures pertain to the medial temporal lobe. For the SPECT variables, the most discriminating measures pertain to the cingulate cortex. These findings will be important to identify and measure early events that precede clinical AD.

Remyelinated Lesions in Multiple Sclerosis

Barkhof and colleagues describe the magnetic resonance imaging appearance of remyelinated lesions in multiple sclerosis (MS). In this large sample of MS brain tissue, signs of remyelination were found in 42% of the areas that were investigated, confirming that remyelination is a frequent phenomenon in MS. Remyelinating lesions return an abnormal signal on T2-weighted images. These findings offer new and dynamic insights into the natural history of MS.

Excitatory Amino Acids and Multiple Sclerosis

Glutamate and aspartate levels were measured in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and controls to test whether the excitotoxic insult of these amino acids might contribute to the pathologic process of MS. Glutamate levels in CSF were significantly higher in patients assessed during relapse compared with those of relapsing-remitting MS patients evaluated in the stable clinical phase and of controls. Sarchielli and colleagues offer evidence that glutamate homeostasis or reduced glutamate receptor–mediated excitotoxicity may have therapeutic implications in MS.Figure 1

Glutamate levels in the cerebrospinal fluid of patients with remitting-relapsing (R-R) multiple sclerosis (MS), during relapse and during a stable clinical phase; of patients with secondary progressive (SP) MS; and of control individuals. Squares indicate the mean; rectangles, SEM; and bars, SD.

Glutamate levels in the cerebrospinal fluid of patients with remitting-relapsing (R-R) multiple sclerosis (MS), during relapse and during a stable clinical phase; of patients with secondary progressive (SP) MS; and of control individuals. Squares indicate the mean; rectangles, SEM; and bars, SD.

Pain in Multiple Sclerosis

Pain prevalence, intensity, and treatment requirement as well as impact of pain on daily life were measured in a population with definite multiple sclerosis (MS) and in a controlled population. The frequency of reported pain in patients with MS was not higher than in controls. However, pain intensity, the need for analgesic treatment, and the impact of pain in daily life were signifantly higher in patients with MS, as reported by Svendsen and colleagues.

Dentatorubral-Pallidoluysian Atrophy With Cerebellar Ataxia

Dentatorubral-pallidoluysian atrophy (DRPLA) may be expressed with significant ataxia. Le Ber and colleagues evaluated the frequency of DRPLA in European patients affected with sporadic or autosomal dominant cerebellar ataxia.

Treating Juvenile Myoclonic Epilepsy

Prasad and colleagues have studied whether lamotrigine and topiramate monotherapy or polytherapy might be effective in treating juvenile myoclonic epilepsy (JME). Lamotrigine and topiramate are effective alternative options to valproate in the treatment of JME. Lamotrigine is an effective option both as monotherapy and polytherapy. These observations extend previous knowledge concerning therapy for this common form of epilepsy.

The Meaning of White Matter Hyperintensities in the Elderly

Conventional and magnetization transfer magnetic resonance imaging (MRI) were obtained from 12 otherwise normal elderly subjects with white matter hyperintensity (WMH) and 11 age- and sex-matched control subjects. Mezzapesa and colleagues show that brain abnormalities in otherwise normal elderly subjects with nonspecific WMH extend beyond the macroscopic white matter lesions seen on conventional MRI. These findings suggest a more diffuse distribution of WMH and imply that pathologic changes in gray matter may be significant.

Cognitive Impairment With Spastin Mutations

The most frequent form of autosomal dominant hereditary spastic paraparesis (HSP), SPG4, has been associated with cognitive impairment in some patients. Tallaksen and colleagues have studied cognitive function in 10 families with HSP due to mutations in the SPG4 gene. An asymptomatic cognitive impairment that mainly affects executive functions was found in SPG4 mutation carriers.

Future Alzheimer Disease

In the year 2000, there were 4.5 million persons with Alzheimer disease in the United States. Hebert and colleagues estimate that by 2050, this will increase by almost 3-fold, to 13.2 million. Owing to the rapid growth of the oldest age groups in the United States, the number of persons older than 85 years will more than quadruple to 8.0 million, and the number of persons aged 75 to 84 years will double to 4.8 million. The number of persons aged 65 to 74 years will remain fairly constant at 0.3 to 0.5 million. To be forewarned is to be prepared, and these figures present a striking and sobering view of our future encounter with the problem of dementia.

Blood Pressure and Cognition

In an Indian population, Pandav and colleagues show that for every 10 mm Hg increase in systolic blood pressure, there was a 10% reduction in cognitive impairment, and for every 10 mm Hg increase in diastolic blood pressure, there was a 13% reduction. A similar relationship was not found in an American sample of patients. Why in the Indian population was cognitive impairment more significantly present in those with lower systolic and diastolic blood pressure? Clearly, future prospective studies from both developed and developing countries are needed to determine the basis of this relationship.

Measuring Pediatric Muscular Atrophy

Iannaccone and colleagues have provided quantitative muscle testing and outcome measures for use in clinical trials in patients with spinal muscular atrophy. Gross motor function measures, pulmonary tests, quantitative muscle testing, and quality-of-life testing, are reliable outcome measures and highly useful to monitor the progress of patients.