James R. Keane shows that internuclear ophthalmoplegia is a sign of exquisite localizing value, often due to either multiple sclerosis or infarction. He reviews his experience with 410 personally examined inpatients over a 33-year period. His invaluable experience points out that the differential of internuclear ophthalmoplegia should be tripartite: multiple sclerosis, stroke, and other causes (trauma, herniation, infection, tumor, hemorrhage, vasculitis, and iatrogenic).
Mega and colleagues map brain metabolism associated with the treatment response to galantamine with fludeoxyglucose F 18 positron emission tomography (FDG-PET) in patients with Alzheimer disease. In this precise and elegant clinical, metabolic, and pharmacologic study, they find that both cognitive and behavioral responders to galantamine therapy show clinically related improvements in prefrontal network metabolism along with thalamic activation.
Baracca et al report that Leber hereditary optic neuropathy mutations profoundly impair complex I–dependent synthesis of adenosine triphosphate, providing a common biochemical feature that may play a major role in Leber hereditary optic neuropathy pathogenesis. The 11778/ND4 mutation induces an uncoupling of cybrid respiration, whereas 2 other mutations impair oxygen consumption rate. Editorial perspective is provided by Michio Hirano, MD, and Salvatore DiMauro, MD.
Barragán-Campos and colleagues report on magnetic resonance imaging abnormalities in patients with mitochondrial cytopathies, a heterogeneous group of clinical entities, some of which have classic phenotypes. The most frequent abnormalities were widespread white matter hyperintensity in 19 (90.5%) of 21 patients, supratentorial cortical atrophy in 18 (85.7%) of 21 patients, and cerebellar atrophy in 13 (61.9%) of 21 patients. Further, the absence of basal ganglia hyperintensity correlated with Kearns-Sayre syndrome and the presence of supratentorial cortical atrophy with mitochondrial neurogastrointestinal encephalopathy.
Mancuso et al document new homozygous mutations in deoxyguanosine kinase in 3 children with mitochondrial DNA depletion and hepatocerebral abnormalities. These novel mutations, G352A and C269T, produce truncated proteins and affect both liver and brain, resulting in liver failure, cerebral atrophy, and nystagmus in one patient and liver cirrhosis, optic dysplasia, nystagmus, and microcephaly in another child.
Sparks and colleagues studied if treatment with atorvastatin calcium affects the cognitive or behavioral decline in patients with mild-to-moderate Alzheimer disease. Atorvastatin reduced circulating cholesterol levels and produced beneficial effects at 6 and 12 months on neuropsychological tests. Atorvastatin therapy may be of clinical benefit for patients with Alzheimer disease if the current preliminary findings are reproduced by a larger, multicenter trial.
Galvin et al studied longitudinally the clinical and cognitive features associated with the development of Alzheimer disease or other dementias using the Clinical Dementia Rating, its sum of boxes, and the neuropathologic diagnosis of dementia. The objective is to recognize the earliest signs of cognitive decline caused by Alzheimer disease and other dementing disorders. They find that increased age, depressive features, and even minimal cognitive impairment (as measured by the Clinical Dementia Rating sum of boxes and by slowed psychomotor performance) identify nondemented individuals who develop dementia.
Hampel and colleagues investigated if levels of cerebrospinal fluid (CSF) microtubule-associated tau protein abnormally phosphorylated at threonine 231 (p-tau231) correlate with rates of hippocampal atrophy as an in vivo marker of regional neuronal loss in patients with Alzheimer disease. Hippocampal volumes were measured based on serial magnetic resonance imaging examinations in 22 patients with Alzheimer disease. Levels of CSF p-tau 231 did indeed correlate with baseline hippocampal volumes (P<.001) and with rates of hippocampal atrophy (P<.02), independently of disease duration and severity. Thus, these findings support the view that CSF p-tau231 levels may be of clinical value to predict the progression of hippocampal atrophy in patients with Alzheimer disease.
Clark et al compared the age of onset of Alzheimer disease symptoms in Latino individuals and in Anglo (white non-Latino) individuals. They studied 119 Latino patients and 55 Anglo patients with Alzheimer disease, and after adjusting for study site, sex, and years of education, they noted that Latino patients had a mean age of symptom onset that was 6.8 years younger (95% confidence interval, 3.5-10.3 years) than that of Anglo patients. The basis for the younger age of symptom onset remains to be determined.
Ganguli and colleagues examined mortality rates, the duration of survival, causes of death, and the contribution of Alzheimer disease to the risk of mortality in an aging community-based cohort. They found that Alzheimer disease was responsible for 4.9% of deaths in this elderly cohort. Alzheimer disease increased the risk of mortality by 40% in the cohort as a whole and separately in women but not in men. The mean ± SD duration of survival with Alzheimer disease was 5.9 ± 3.7 years and longer with a younger age at onset.
Schwid et al studied the effect of changing from a dosage of 30 μg once a week to a dosage of 44 μg 3 times a week for patients with relapsing multiple sclerosis as an extension of the EVIDENCE study. The important finding is that patients taking interferon beta-1a improved on both clinical and magnetic resonance imaging disease measures when they changed dosages and frequency.Figure 1
Figure. Annualized relapse rate for patients continuing treatment after the transition comparing within-patient rates during the pretransition interval with those during the posttransition period. The change in relapse rate is significantly greater for patients changing their dosage regimen than for those continuing the regimen unchanged (P = .047). QW indicates 1 time per week; TIW, 3 times per week.
Prat and colleagues report their evaluation and correlation of expression of kinin B1 receptor on peripheral blood mononuclear cells from patients with multiple sclerosis with serial clinical, magnetic resonance imaging, and immunological derived measures. They find a highly significant correlation of kinin B1 receptor messenger RNA levels with dynamic clinical and imaging measures, indicating that expression of this receptor can serve as an index of disease activity in multiple sclerosis.
Gallo et al used diffusion tensor magnetic resonance imaging to study whether brain tissue abnormalities occur in patients with multiple sclerosis at the earliest clinical stage of multiple sclerosis and if their severity is predictive of short-term disease evolution. They find that normal-appearing white matter damage is present in patients with multiple sclerosis at the earliest stage using diffusion tensor magnetic resonance imaging. The severity of normal-appearing white matter damage does not predict new lesion formation in the short-term, suggesting that the diffuse component of multiple sclerosis tissue damage is in part independent of inflammation.
This Month in. Arch Neurol. 2005;62(5):709–710. doi:10.1001/archneur.62.5.709