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This Month in Archives of Neurology
September 2005

This Month in The Archives of Neurology

Arch Neurol. 2005;62(9):1341-1342. doi:10.1001/archneur.62.9.1341
Progression in Multiple Sclerosis

Frohman and colleaguesprovide a comprehensive and well-focused discussion of mechanisms involved in the progression of multiple sclerosis. Characterizing these mechanisms will result in a better understanding of the various forms of the disorder and how to effectively treat its clinical manifestations. This review offers both evidence-based observations and hypothesis-driven expert perspectives on what constitutes the cause for progression in multiple sclerosis. Novel research initiatives targeted at achieving a complete understanding of multiple sclerosis progression are advanced.

Science and Ethics of Sham Surgery for Parkinson Disease

Kim et al determined the perspective of Parkinson disease (PD) clinical researchers on the science and ethics of sham-surgery controls when used to test novel interventions such as gene transfer for PD. A large majority (97%) of PD clinical researchers believe sham-surgery controls are better than unblinded controls for testing the efficacy of neurosurgical interventions. Half of the researchers believe an unblinded-control efficacy trial would be unethical because it may lead to a falsely positive result. Thus, they conclude that it is unlikely that the PD clinical research community will perceive future neurosurgical interventions for PD as truly efficacious unless a sham-control condition is used to test it. Editorial perspective is provided by C. Warren Olanow, MD, FRCPC.

Oral Contraceptives and the Risk of Multiple Sclerosis

Alonso and colleaguesexamined whether oral contraceptives and pregnancy history are associated with the risk of multiple sclerosis. They report that the incidence of multiple sclerosis was 40% lower (odds ratio, 0.6) in users of oral contraceptives compared with nonusers during the last 3 years. Risk of multiple sclerosis increased in the 6 months after pregnancy (odds ratio, 2.9). These results suggest that the hormonal changes that occur during oral contraceptive use and pregnancy may be associated with a short-term reduction in the risk of multiple sclerosis.

Magnetic Resonance Imaging T2 Hypointensity Predicts Brain Atrophy in Multiple Sclerosis

Bermel et altested whether T2 hypointensity predicts brain atrophy and whether interferon impacts the relationship. They report that T2 hypointensity in gray matter correlated with baseline brain parenchymal fraction. In patients receiving placebo, baseline T2 hypointensity predicted the change in brain parenchymal fraction in the first year and over 2 years. In the interferon group, there was no relationship between baseline T2 hypointensity and change in brain parenchymal fraction.

Gambling Caused by Drugs Used to Treat Parkinson Disease

Dodd et alreport that dopamine agonist therapy was associated with pathological gambling that is potentially reversible. The medication predominantly implicated was pramipexole. It may relate to disproportionate stimulation of dopamine D3 receptors, which are primarily localized to the limbic system.

Liver Failure, Magnetic Resonance Imaging T1 Hyperintensity, and Manganese Neurotoxicity

Klos and colleaguesreport on 3 syndromes recognized in 15 patients with liver failure and basal ganglia T1 hyperintensity on magnetic resonance imaging: isolated parkinsonism; gait ataxia, plus other findings; and cognitive impairment with psychiatric features. All but 1 patient had elevated blood manganese levels. Brain manganese accumulation may be a crucial component of these syndromes.

Figure.
Sagittal T1-weighted magnetic resonance image of the brain demonstrating T1 signal change in the globus pallidus in 1 representative case of manganese toxicity secondary to chronic liver failure.

Sagittal T1-weighted magnetic resonance image of the brain demonstrating T1 signal change in the globus pallidus in 1 representative case of manganese toxicity secondary to chronic liver failure.

Cortical Atrophy in Mild Cognitive Impairment

Bell-McGinty et alcompared gray matter brain volumes in patients diagnosed with subtypes of mild cognitive impairment. Overall, the subjects with mild cognitive impairment had significantly decreased volume in the hippocampus and middle temporal gyrus, bilaterally, relative to controls. They provide convincing magnetic resonance image data of distinct brain structural abnormalities in 2 groups of mild cognitive impairment. Mild cognitive impairment may represent a more heterogeneous group, possibly reflecting 2 different etiological processes to dementia.

Magnetic Resonance Imaging in Frontotemporal Dementia

Whitwell et alstudied whether different pathological substrates of frontotemporal dementia have distinct patterns of regional atrophy on magnetic resonance images. Specific voxel-based morphometric changes on magnetic resonance images are reported that correlate with specific pathologic subtypes of frontotemporal dementia. Their findings suggest that magnetic resonance image patterns of regional gray matter atrophy constitute signatures of tissue pathology in frontotemporal dementia.

Magnetic Resonance Images in Diagnosis of Young-Onset Dementia

Likeman and colleaguesinvestigated the diagnostic accuracy of visual inspection of magnetic resonance images in subjects with a range of pathologically confirmed diseases associated with young-onset dementia and assess the sensitivity and specificity of patterns of atrophy for Alzheimer disease and frontotemporal lobar degeneration. Eighty-seven percent of dementia cases were distinguished from controls after visual inspection of magnetic resonance images, and a correct pathological diagnosis was given in 58% of cases. A bilateral symmetrical pattern of hippocampal atrophy discriminated Alzheimer disease from frontotemporal lobar degeneration cases with 47% specificity, and a posterior greater than anterior gradient of global atrophy was 92% specific for Alzheimer disease. Atrophy of the anterior, inferior, and lateral temporal lobes was suggestive of frontotemporal lobar degeneration abnormalities with greater than 90% sensitivity.

Tau H2 Haplotype and Age at Onset in Frontotemporal Dementia

Borroni et alreport that the presence of at least 1 tau H2 allele was significantly associated with an earlier age at onset in patients with frontotemporal dementia. The association between H2 and age at onset was not related to family history, clinical presentation, or apolipoprotein E (APOE) genotype. Their findings support a role of tau in modulating frontotemporal dementia phenotype.

Malignant Variant of Status Epilepticus

Holtkamp et alreport 35 episodes of status epilepticus (SE) not responding to first-line anticonvulsants in 34 patients. They refer to the term “malignant” SE (MSE) for this most severe variant of SE. They find that SE that cannot be controlled by first-line anticonvulsants results in malignant SE in 20% of cases. The patient at risk for malignant SE is young and often has encephalitis. In general, such patients should be treated aggressively early in the course of SE to prevent malignant SE.

Antiepileptic Drug Comedication on Lamotrigine Clearance

Weintraub and colleaguesreport that phenytoin increases lamotrigine clearance by about 125%, carbamazepine increases lamotrigine clearance by about 30% to 50%, and valproate decreases lamotrigine clearance by about 60%. No newer antiepileptic drug, with the possible exception of oxcarbazepine, has a major impact on lamotrigine clearance.

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