Copyright 2006 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2006
This Month inArchives of Neurology
Muqit and colleagues review the issues related to the role of mitochondrial dysfunction in Parkinson disease (PD). The discovery of mutations in genes involved in mendelian-inherited forms of PD has expanded our understanding of PD disease mechanisms, and the report of mutations in the genes DJ-1 and PINK1 in familial PD has provided the most direct evidence in humans for a primary role of mitochondrial dysfunction in PD. These and other mitochondrial related issues are considered in this elegant and comprehensive review.
Bambauer et alext-link xlink:href="nnr50018"/ point out that tissue plasminogen activator therapy for acute stroke remains substantially underused. This article considers such issues as poor patient education, physicians' perceived risk of legal liability, and insufficient reimbursement.
Jicha et alext-link xlink:href="noc50235"/ point out that the neuropathologic outcome of amnestic mild cognitive impairment following progression to dementia is heterogeneous and includes Alzheimer disease at a high frequency. They report that complex neuropathologic findings with 2 or more distinct pathologic entities contributing to dementia may be common. Of note, they found that neither demographic variables nor cognitive measures had predictive value in determining which patients diagnosed with mild cognitive impairment will develop the neuropathologic features of Alzheimer disease. Lawrence A. Hansen, MD, indicates his views on these issues. ext-link xlink:href="ned50018"/
Khachaturian and colleaguesext-link xlink:href="noc60013"/ in the Cache County Study examined the relationship of antihypertensive medication use with incidence of Alzheimer disease. They report that use of any antihypertensive medication at baseline was associated with a lower incidence of Alzheimer disease and that the use of diuretics and specifically potassium-sparing diuretics was associated with the greatest reduction in risk for Alzheimer disease.
Apostolova et alext-link xlink:href="noc60009"/ provide data in support of the view that smaller hippocampal volumes predict conversion of mild cognitive impairment (MCI) to Alzheimer disease while larger hippocampal volumes predict cognitive stability and/or improvement. Of significance, they found that smaller hippocampi and specifically CA1 and subicular involvement are associated with increased risk for conversion from MCI to Alzheimer disease, and of note, patients with MCI who improve and no longer meet MCI criteria have larger hippocampal volumes. These elegant and convincing findings offer the means to follow patients' clinical courses more definitively.
Petersen and colleaguesext-link xlink:href="noc50236"/ weigh in on the debate regarding the specific clinical criteria, longitudinal outcome, and underlying neuropathologic features of mild cognitive impairment (Figure). There has been a paucity of pathologic material on subjects with mild cognitive impairment. In this study, they present a definitive characterization of the neuropathologic substrate of subjects with mild cognitive impairment who were followed up for as long as 18 years. Editorial perspective is provided by Harry V. Vinters, MD, FCAP, FRCPC.
Representative images of the middle frontal cortex and hippocampal sector CA1 from a healthy individual (patient 29), a patient with amnestic mild cognitive impairment (aMCI) (patient 3), and a patient with Alzheimer disease (AD) (patient 51) stained with antibodies to β-amyloid and tau (AT8), respectively (original magnification ×100).
Derry et alext-link xlink:href="noc60016"/ indicate that nocturnal frontal lobe epilepsy can be difficult to differentiate from nonepileptic parasomnias. They point out that electroencephalography monitoring is usually required to make the correct diagnosis. In this study, they developed and validated the Frontal Lobe Epilepsy and Parasomnias scale to examine the reliability of the clinical history in diagnosing nocturnal frontal lobe epilepsy. They conclude that a diagnosis of nocturnal frontal lobe epilepsy can be made reliably using the clinical features identified in the Frontal Lobe Epilepsy and Parasomnias scale. Thus, this new scale may reduce the requirement for tertiary referral and extensive inpatient monitoring.
Goetz and colleaguesext-link xlink:href="noc60008"/ point out that the phrase benign hallucinations connotes an inconsequential behavior, although studies emphasize temporal progression. They studied their data repository for subjects with Parkinson disease with 3 sets of neuropsychological testing over 3 years and Unified Parkinson's Disease Rating Scale’s thought disorder scores. They found that most patients (81%) progressed to more advanced Thought Disorder scores of 3 or 4, indicating that loss of insight or delusions had occurred. Thus, hallucinations progress to additional neurological deficits, and the concept of benign hallucination is misleading and portends serious clinical consequences.
Louis and Luchsingerext-link xlink:href="noc60003"/ examined whether mild parkinsonian signs (MPSs) are associated with a history of vascular disease and whether certain MPSs (rigidity, changes in axial function) are more strongly associated with a history of vascular disease than are other MPSs (tremor). They provide data in support of the conclusion that the presence of MPSs does indicate, in part, the accumulation of vascular pathologic abnormalities caused by preventable diseases in the basal ganglia or white matter regions.
Okun et alext-link xlink:href="noc60005"/ conducted a careful and detailed study to define the effects of testosterone replacement therapy on nonmotor and motor symptoms in men with Parkinson disease and probable testosterone deficiency. They report that testosterone replacement therapy was well tolerated, yet there were no significant differences in treated and nontreated subjects in motor and nonmotor scales at the end of 8 weeks. This is an important area for clinical trials, and these findings will be of value in considering future studies.
Oreja-Guevara et alext-link xlink:href="noc60014"/ determined whether a single-point magnetization transfer magnetic resonance imaging (MT MRI) scan can provide markers of short-term disease evolution in patients with relapsing-remitting multiple sclerosis. As shown in this study, MT is indeed a sensitive, new MRI methodology that provides a “snapshot” assessment of subtle brain tissue changes associated with short-term disability accumulation in patients with relapsing-remitting multiple sclerosis.
Chiu and colleaguesext-link xlink:href="noc60007"/ point out that the effect of oxygen therapy in acute stroke remains undetermined. They studied the use of eubaric hyperoxia therapy by Venturi mask in patients with acute ischemic stroke. They found that Venturi mask therapy may reduce mortality and comorbidities, and future randomized studies are needed.
Kaufmann and colleaguesext-link xlink:href="noc60012"/ studied 30 patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) and the A3243G mutation using neurophysiologic studies. They found that 23 patients (77%) had abnormal nerve conduction measures that were predominately axonal and sensory and mainly present in the legs.
Crippa et alext-link xlink:href="noc60001"/ studied a large series of patients with hereditary spastic paraplegia (HSP) for disease-causing mutations. They found in 60 unrelated patients with pure or complicated HSP that the overall rate of mutation in the SPG4 gene was 21%, which rose to 26% when only pure HSP forms were considered.
Lossos and colleaguesext-link xlink:href="noc50333"/ studied 7 patients with hereditary spastic paraplegia and thin corpus callosum who belong to 3 consanguineous families of Arab origin in Israel. They report that 2 families showed evidence for linkage to SPG11 and reduced the candidate region to 13.0 Mb.
This Month in Archives of Neurology. Arch Neurol. 2006;63(5):643-644. doi:10.1001/archneur.63.5.643