Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
Citations 0
This Month in Archives of Neurology
June 2006

This Month in The Archives of Neurology

Author Affiliations

Copyright 2006 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2006

Arch Neurol. 2006;63(6):803-804. doi:10.1001/archneur.63.6.803
Finding the Causes of Inherited Neuropathies

Scherer provides a comprehensive and elegant review of the genetic causes of some inherited neuropathies. Major topics discussed are Charcot-Marie-Tooth disease, including autosomal dominant and autosomal recessive forms; congenital hypomyelinating neuropathy and Dejerine-Sottas neuropathy; hereditary sensory and autonomic neuropathies; hereditary motor neuropathies; and inherited neuropathy as part of a syndrome. As he points out, the lessons learned about the molecular pathogenesis of neuropathies may illuminate the causes of more complex neurological diseases.

Ischemic Strokes After Cardiac Catheterization: Opportune Thrombolysis Candidates?

Khatri and Kasner review issues related to stroke following cardiac catheterization procedures, which results in death and disability for thousands of patients each year. These strokes are likely amenable to thrombolysis, and issues related to this important subject are the focus of this review.

Homozygous and Heterozygous PINK1 Mutations in Parkinson Disease

Hedrich et al investigated the role of homozygous and heterozygous PINK1 mutations in a large German pedigree. The heterozygotes were all considerably younger than the affected homozygous mutation carriers. This study provides an excellent opportunity to further evaluate the role of single, heterozygous PINK1 mutations later in life, which also will have major implications on genetic counseling. Discussion of the genetic implications of this report is provided by Uwe Beffert, PhD, and Roger N. Rosenberg, MD.

Epstein-Barr Virus and Multiple Sclerosis

DeLorenze and colleagues found that serum titers of anti–Epstein-Barr virus antibodies are elevated in blood specimens collected up to 30 years prior to onset of multiple sclerosis. The elevation of anti–Epstein-Barr virus titers is probably an early event in the pathogenesis of multiple sclerosis and is likely the result of a specific immune dysregulation. These new findings are important to understanding early events in the cause of multiple sclerosis and have considerable significance in planning new therapies. The importance of this research is discussed by Amy E. Lovett-Racke, PhD, and Michael K. Racke, MD.

Multifocal Visual Evoked Potential Latency Analysis: Predicting Progression to Multiple Sclerosis

Fraser et al studied the difference in conversion rates to multiple sclerosis in patients with optic neuritis between patients with multifocal visual evoked potential latency delay and those with normal latency. Of patients with optic neuritis with latency delays, 36.4% progressed to multiple sclerosis compared with 0% of those with normal latencies. Thus, multifocal visual evoked potential latency delay may indeed be highly useful in predicting progression to multiple sclerosis.

Heterozygous Parkin Mutations and Parkinson Disease

Sun and colleagues in the GenePD Study provide important new data, which indicate that parkin mutations are not rare in affected sibships. They also show that, even though mutations in both PARK2 alleles are associated with early-onset Parkinson disease, heterozygous mutation carrier status in PARK2 significantly influences age at onset (Figure). Editorial perspective on this new genetic observation is provided by Uwe Beffert, PhD, and Roger N. Rosenberg, MD.

Image not available

Distribution of onset age in patients having 0, 1, and 2 or more mutations in the PARK2 gene for Parkinson disease, selected by alleles identical by state. Patients with 1 PARK2 mutation had a 11.7-year younger onset than patients with no mutation (P = .04); and patients with 2 or more PARK2 mutations had nearly a 13.2-year decrease in onset age compared with patients with 1 mutation (P = .04).

Neuromyelitis Optica in Patients With Myasthenia Gravis Who Underwent Thymectomy

Kister and colleagues describe 4 patients with myasthenia gravis who developed neuromyelitis optica after thymectomy. They suggest that dysregulation of B-cell autoimmunity in myasthenia, exacerbated by loss of control over autoreactive cells as a result of thymectomy, may have predisposed these patients to neuromyelitis optica.

Interleukin 23–Mediated Peripheral Nerve Demyelination

Hu and colleagues report that interleukin (IL) 23, a newly identified heterodimeric proinflammatory cytokine and a novel IL-12 family member comprising the p40 subunit of IL-12 but a different p19 subunit, is up-regulated prior to the onset of the first clinical symptoms of acute experimental autoimmune neuritis in a murine animal model of human Guillain-Barré syndrome. Its peak expression levels preceded maximum disease severity during experimental autoimmune neuritis. In patients with Guillain-Barré syndrome, IL-23p19 protein was detectable in cerebrospinal fluid samples, and endoneurial macrophages were identified as the cellular source of IL-23p19 in sural nerve biopsies. Interleukin 23 plays an important role during the early effector phase in immune-mediated demyelination of the peripheral nerve.

Cognitive Measures and Alzheimer Disease

Powell et al show that Mayo Cognitive Factor Scale scores significantly correlated with Alzheimer disease criteria. The Mayo Cognitive Factor Scale verbal comprehension and retention indices indicated a high, positive predictive value for pathologic Alzheimer disease.

Vaccination and Risk of Optic Neuritis

Payne and colleagues report that no significant associations with optic neuritis were observed in patients receiving anthrax, smallpox, hepatitis B, or influenza vaccines in the US military, whether these vaccines were administered alone or in combination. The negative findings presented here are important to the continuing discussions regarding the safety of these vaccines.

MM2 Subtype of Creutzfeldt-Jakob Disease

Krasnianski and colleagues defined the MM2 (methionine-methionine at codon 129 of the prion gene) cortical subtype of Creutzfeldt-Jakob disease. Compared with classical sporadic Creutzfeldt-Jakob disease, the MM2 subtype disease duration was prolonged but was associated with rapid-onset dementia and prominent neuropsychological signs, such as spatial disorientation, aphasia, and apraxia in all patients. The S100B (100%) and 14-3-3 (91%) protein investigations were the most sensitive diagnostic tests. They suggest that rapidly progressive dementia with early and prominent neuropsychological deficits in older patients should lead to suspicion of the MM2 cortical subtype.

Preparing for Preventive Clinical Trails: The Predict Huntington Disease Study

Paulsen and colleagues discuss potential optimal design and outcome measures for preventive clinical trials in neurodegenerative diseases, including Huntington disease. They followed up 505 at-risk participants who had previously undergone elective DNA analyses for the CAG expansion in the Huntington disease gene (predictive testing) and who currently did not have the clinical diagnosis of Huntington disease. Several variables showed progressive decline as the diagnostic ratings advanced toward manifest disease. They show that the documentation of biological and refined clinical markers suggests several clinical end points for preventive clinical trials.