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Bioterrorism and the Neurologist
Neurologic issues that relate to bioterrorism are of increasing importance, and 2 major reviews on this topic are included in this issue of the ARCHIVES. The neurologic consequences of anthrax are reviewed by Meyer. Smallpox infection, complications of vaccination, and strategies for epidemic control are reviewed by Cleri and colleagues. An informed and prepared neurologic community to treat patients and large populations is of strategic value.
M-Channels: Diseases and Drugs
M-channels represent widely expressed potassium channels that mediate the effects of modulatory neurotransmitters controlling competitive neuronal discharges. Mutations in genes that code for subunits of the M-channel have been shown to cause human hereditary diseases and deafness. Cooper and Jan find that pharmacologic agents that effect M-channel activity may become useful as treatments for Alzheimer disease, epilepsy, and stroke. Cloned human M-channels can now be used for high-throughput screening of additional drug candidates. This is a dynamic and rapidly evolving field with great potential for defining the channelopathies related to common neurologic diseases and targets for future pharmacologic interventions.
Risks of Vaccination
DeStefano and colleagues evaluate the association between vaccination and onset of multiple sclerosis or optic neuritis. The good news is that vaccinations for hepatitis B, influenza, tetanus, measles, or rubella are not associated with an increased risk of multiple sclerosis or optic neuritis.
Statins and Dementia
Vega and colleagues demonstrate that statins lower plasma 24S-hydroxycholesterol levels without affecting levels of apolipoprotein, and that low-density lipoprotein lowering was more pronounced than 24S-hydroxcholesterol reductions. Statins lower 24S-hydroxycholesterol levels in plasma about 20%. A lowered 24S-hydroxycholesterol in plasma is a direct effect of statins to reduce cholesterol synthesis in the brain. As the authors point out, the effect of statins on cholesterol synthesis in the brain may protect against the development of Alzheimer disease.
Burkhard and colleagues studied cirrohtic patients who were potential candidates for liver transplantation because of the presence of extrapyramidal features. Of 51 patients screened, 11 (21.6%) exhibited moderate to severe parkinsonism sometimes associated with focal dystonia. Typical features included rapid progression over months, symmetric akinetic-rigid syndrome, postural but not resting tremor, and early postural and gait impairment. In all patients, magnetic resonance imaging scans showed striking hyperintensities on T1-weighted images involving the substantia nigra and the globus pallidus. Whole blood and cerebrospinal fluid manganese concentrations were severalfold above the normal range. Cirrhosis-related parkinsonism represents a unique, consistent, and common subset of acquired hepatocerebral degeneration. Manganese toxicity may be a factor leading to the predominantly extrapyramidal manifestations of cirrhosis in these patients.
Onset of Parkinson Disease in Middle-aged and Older Persons
The clinical comorbidities, treatment, and evolution of Parkinson disease (PD) were compared between patients with old-age onset and those with middle-age onset by Diederich and colleagues. Patients with old-age onset PD have greater motor impairment than patients with middle-age onset PD at the same disease duration. The biological basis resulting in differences in motor impairment and other comorbidities related to the age of onset of PD is a subject for thoughtful discussion.
Parkinsonism and Related Risk of Alzheimer Disease
The severity and rate of progression of Alzheimer disease (AD) and the decline in cognition related to associated parkinsonian signs remains an important issue. Wilson and colleagues studied 824 older Catholic clergy members without clinical evidence of AD or Parkinson disease) at baseline for their cognitive function and clinical degree of AD during an 8-year period. They found that the progression of parkinsonian-like signs in old age is associated with a decline in cognitive function and the development of AD. Clearly, Parkinson disease and AD are linked, and the biological linkers influence the progression of both syndromes.
Olfaction in Parkinson Disease
Patients with Parkinson Disease (PD) and controls from 5 movement disorders clinics were given the University of Pennsylvania 12-item Brief Smell Identification Test or Cross-Cultural Smell Identification Test to identify patterns and types of odors affected in Parkinson disease. Abnormal olfactory function was present in 82% of patients compared with 23% of controls. Double and colleagues found that 5 specific odors seem to be primarily affected in patients with PD. This is an interesting clinical finding, one of practical diagnostic import, and of interest in defining the extended pathologic mechanisms in in PD.
Conjugal Amyotrophic Lateral Sclerosis
Nine couples in which both spouses were affected by amyotrophic lateral sclerosis (ALS) are described by Corcia and collegues. Eight of the 9 couples had lived in southeastern France. In all cases, the spouses had been married for more than 10 years. Such a large cluster of conjugal ALS has never been reported. No precise environmental factors could be identified at the origin of these conjugal cases, but as the authors indicate, it is likely that both genetic and environmental factors are at play in the development of such a cluster.
Effects of Intraventricular Chemotherapy for Primary Central Nervous System Lymphoma
Twenty patients with histologically proven primary central nervous system lymphoma were treated with a novel chemotherapy protocol, including systemic and intraventricular administration of methotrexate and cytarabine. Fliessbach and colleagues report that 10 patients achieved durable remissions without relapse for more than 1 year after completion of chemotherapy. There was no gross cognitive decline in any of these patients during the follow-up period. Magnetic resonance imaging (MRI) showed therapy-induced white matter changes in 5 patients. It is of note that chemotherapy alone was associated with a low risk of long-term neurotoxicity in primary central nervous system lymphoma. Further white matter lesions detectable on MRI were not associated with significant cognitive impairment.
Vascular Dementia: A Population Based Study
Knopman and colleagues investigated the clinical and pathologic correlations in vascular dementia (VaD). They used the medical records in the Rochester Epidemiology Projects to identify incident cases of dementia in Rochester, Minn, from 1985 through 1989. Of 419 patients, neuropathologic examination results were available in 89 cases (21%). A pathologic diagnosis of AD was found in 45 (51%), pure VaD in 12 (13%), and combined AD and VaD in 11 (12%). Clearly, in this population-based autopsy study, pathologic vascular function and the absence of major pathologic characteristics of AD were common. Dementia temporally related to stroke was the best clinical predictor of pure VaD.
Five Years of Cognitive Impairment Without Dementia
There is limited information from large-scale studies regarding outcomes of persons specifically identified as having cognitive impairment but without dementia. Tuokko and colleagues investigated for 5 years the outcomes of persons with no cognitive impairment or cognitive impairment but without dementia. Individuals with cognitive impairment but without dementia were more likely to have a negative outcome than those with no cognitive impairment. The findings of the data from the Canadian study of Health and Aging indicate that cognitive impairment without dementia, compared with no cognitive impairment, is a risk factor for needing assisted living and for the occurrence of dementia within a 5-year period.
The occurrence of poststroke dementia was studied in patients with and without medial temporal lobe atrophy (MTLA) by Cordoliani-Mackowiak and colleagues. The risk of poststroke dementia associated with MTLA was 2.3 (95% confidence interval, 1.1-4.7). Other independent predictors of poststroke dementia were increasing age, diabetes mellitus, severity of the clinical deficit at admission, and severity of leukoaraiosis.
Oxidative Stress in Amyloidotic Polyneuropathy
Familial amyloidotic polyneuropathy (FAP1) is a dominantly inherited neuropathy due to mutations in the transthyretin gene. Fiszman and colleagues studied patients with FAP1 due to the Met-30 mutation. Six of 11 FAP1-positive patients had increased copper-zinc superoxide dismutase type 1 activity in red blood cells, and 9 of 10 patients had reduced total plasma reactive antioxidant potential levels compared with control subjects. These findings indicate that oxidative stress is a component that may be contributing to the pathologic characteristics of FAP1.
Charcot-Marie-Tooth Disease Due to a GDAP1 Gene Mutation
Birouk and colleagues report a detailed, clinical, electrophysiologic, and pathologic study of 4 siblings from a Moroccan autosomal recessive Charcot-Marie-Tooth (CMT) family with the S194X mutation in the GDAP1 gene. These patients manifested an axonal form of CMT. The GDAP1 gene is expressed in both Schwann cells and in neurons, and thus the CMT phenotype is the result of a mixed process of 2 cell types. This report provides important new information on the molecular biology of this genetic disease. Editorial comment is provided by David E. Pleasure, MD.
Size distribution of myelinated fibers in patient V:5 vs an age-matched control subject. In patient V:5, there is marked loss of large myelinated fibers, with a shift toward smaller diameters.
This Month in Archives of Neurology. Arch Neurol. 2003;60(4):478–480. doi:10.1001/archneur.60.4.478
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