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This Month in Archives of Neurology
March 2007

This Month in Archives of Neurology

Arch Neurol. 2007;64(3):310-312. doi:10.1001/archneur.64.3.310
Effects of Methylphenidate on Response to Oral Levodopa

Nutt and colleagues determined whether methylphenidate, an inhibitor of the dopamine transporter, would augment the effects of oral levodopa in patients with Parkinson disease in a double-blind, randomized, placebo-controlled, crossover trial. They report that the effects of 0.4 mg/kg of methylphenidate 3 times per day on the motor response to levodopa were small and variable and judged to be clinically insignificant.

New Ideas in Epilepsy Genetics

Gurnett and Hedera review advances in the rapidly expanding field of epilepsy genetics. They indicate that the majority of genes associated with epilepsy syndromes to date are ion channel genes. There are more than 3000 genes that are expressed at the synapse as well as many other genes expressed nearby in supporting cells and glia that can likewise regulate excitability. The authors review the new novel epilepsy genes and discuss other genetic etiologies, such as chromosomal copy number alterations and gene regulation.

Frontal Lobe Involvement in Amyotrophic Lateral Sclerosis

Murphy et al summarize recent understanding of cognitive changes seen in patients with amyotrophic lateral sclerosis. They place emphasis on identifying and diagnosing subtypes of patients with amyotrophic lateral sclerosis who possess a continuum of frontotemporal impairment.

Cerebrospinal Fluid tau/β-Amyloid42 Ratio as a Prediction of Cognitive Decline in Nondemented Older Adults

Fagan and colleagues investigated the ability of cerebrospinal fluid (CSF) and plasma measures to discriminate early-stage Alzheimer disease as defined by clinical criteria and presence or absence of brain amyloid from nondemented aging and assessed whether these biomarkers can predict future dementia in cognitively normal persons. They report that individuals with very mild or mild Alzheimer disease have reduced levels of CSF β-amyloid42 and increased CSF tau and phosphorylated tau181. The level of CSF β-amyloid42 completely corresponds with the presence or absence of brain amyloid imaged with Pittsburgh Compound B (Figure). These elegant studies show that diagnosing Alzheimer disease is now more precise and accurate and can happen at an earlier point in its development.

Figure.
Cerebrospinal fluid (CSF) and plasma biomarkers as a function of clinical diagnosis and cortical amyloid. Fifty subjects were imaged with Pittsburgh Compound B (PIB) positron emission tomography. Subjects were diagnosed by blinded clinicians. There are 2 classifications of CDR 0.5 subjects with a Clinical Dementia Rating (CDR) of 0.5: the green diamonds indicate PIB− and CDR 0.5 non–Alzheimer disease (AD) dementia at follow-up. Red squares indicate PIB+ CDR 0.5 and AD dementia. Any symbol in green indicates PIB−. Any symbol in red indicates PIB+. ptau indicates phosphorylated tau; Aβ, β-amyloid.

Cerebrospinal fluid (CSF) and plasma biomarkers as a function of clinical diagnosis and cortical amyloid. Fifty subjects were imaged with Pittsburgh Compound B (PIB) positron emission tomography. Subjects were diagnosed by blinded clinicians. There are 2 classifications of CDR 0.5 subjects with a Clinical Dementia Rating (CDR) of 0.5: the green diamonds indicate PIB− and CDR 0.5 non–Alzheimer disease (AD) dementia at follow-up. Red squares indicate PIB+ CDR 0.5 and AD dementia. Any symbol in green indicates PIB−. Any symbol in red indicates PIB+. ptau indicates phosphorylated tau; Aβ, β-amyloid.

Low Plasma Aβ42/Aβ40 Ratios and Mild Cognitive Impairment and Alzheimer Disease

Graff-Radford and colleagues determined whether levels of plasma β-amyloid protein (Aβ40 and Aβ42) are useful for identifying cognitively normal elderly white subjects at increased risk of mild cognitive impairment and Alzheimer disease. They report that individuals with plasma Aβ42/Aβ40 ratios in the lower quartiles showed significantly greater risk of mild cognitive impairment and Alzheimer disease. Comparison of subjects with plasma Aβ42/Aβ40 ratios in the lowest vs the highest quartile gave a risk of 3.1 (95% confidence interval, 1.1-8.3). Thus, the plasma Aβ42/Aβ40 ratio may be a useful premorbid biomarker for identifying normal elderly white patients who are at increased risk for developing mild cognitive impairment and Alzheimer disease.

Novel Panel of Cerebrospinal Fluid Biomarkers for Alzheimer Dementia and Mild Cognitive Impairment

Simonsen and colleagues used proteomic analysis of cerebrospinal fluid to discover novel proteins and peptides to differentiate between patients with stable mild cognitive impairment and those who will progress to Alzheimer disease. They report that proteomic profiling of cerebrospinal fluid provided a novel panel of 17 potential biomarkers for prediction of mild cognitive impairment progression to Alzheimer disease. Five identified biomarkers are relevant to the pathogenesis of Alzheimer disease and could help to gain an understanding of the molecular pathways in which they function.

Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions With and Without Progranulin Gene Mutations

Whitwell and colleagues studied the patterns of atrophy in cases of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) with and without a mutation in the progranulin gene (PGRN). Voxel-based morphometry was used to assess the patterns of gray matter atrophy in the PGRN-positive and -negative groups. The authors report that PGRN mutations are associated with a specific and severe pattern of cerebral atrophy in subjects with FTLD-U. Of note, the PGRN-positive group showed a widespread and severe pattern of gray matter loss predominately affecting the frontal, temporal, and parietal lobes.

Cardiac Valve Regurgitation With Pergolide

Dewey et al determined whether cardiac valve regurgitation occurs more commonly in patients with Parkinson disease treated with pergolide mesylate than those treated with nonergot agonists at a comparable dose. They report that pergolide contributes to cardiac valve regurgitation when used chronically as a treatment for Parkinson disease. There appears to be a low risk of cardiac valve regurgitation when using non–ergot-derived dopamine agonists.

Adrenergic and Vagal Baroreflex Sensitivity in Autonomic Failure

Schrezenmaier and colleagues developed and validated an index of adrenergic baroreflex sensitivity. In a comprehensive study, they report that the 2 indices of baroreflex sensitivity separately evaluate the vagal and adrenergic components of the baroreflex. The indices when combined provide an index of composite or global baroreflex function.

Body Mass Index and Outcomes After Ischemic Stroke

Razinia et al report that elevated body mass index is associated with a lower likelihood of being discharged home and a trend toward extended hospital stay among patients hospitalized for ischemic stroke. Admission body mass index had no relation to discharge functional activity after stroke.

Adiposity and Dementia

Luchsinger and colleagues studied the associations of body mass index, waist circumference, and weight change to dementia, Alzheimer disease, and dementia with stroke. The prospective association between adiposity and dementia differs depending on the specific measurement used, and it is modified by age.

Amnesia and Antibodies to Voltage-Gated Potassium Channels

Chan et al report that encephalitis associated with voltage-gated potassium channel antibodies results in extensive retrograde amnesia that is partially reversible with immunotherapy. Magnetic resonance imaging high-signal abnormalities were primarily restricted to the hippocampi.

Normal-Appearing Brain T1 Relaxation Time as a Predictor of Disability in Early Primary Progressive Multiple Sclerosis

Manfredonia and colleagues report that T1 relaxometry is a good marker of disease progression and has prognostic potential in primary progressive multiple sclerosis.

Incidence of Dementia in Mild Cognitive Impairment

Lopez et al examined the incidence of dementia in subjects with mild cognitive impairment. They report that subjects with mild cognitive impairment are at high risk of dementia in a prospective epidemiological study conducted in the Cardiovascular Health Study Cognition Study.

Parkinson Disease, Tremor, Bell Palsy, and Parkin Mutations

Deng and colleagues report compound heterozygous parkin mutations (EX 3_6 del and EX 5 del) as the cause of early-onset Parkinson disease in a Mexican family, but the A265G variant in the HS1 binding protein 3 gene (HS1BP3), previously considered responsible for essential tremor, was probably not pathogenically related to the essential tremor in this family.

LRRK2 Exon 41 Mutations in Sporadic Parkinson Disease in Europeans

Lesage et al assessed the frequency of leucine-rich repeat kinase 2 gene (LRRK2) exon 41 mutations in a series of sporadic Parkinson disease cases to determine the clinical features of LRRK2 mutation carriers. They found that the G2019S mutation is almost as frequent in sporadic as in previously reported familial cases. They report that although the phenotype of LRRK2 mutation carriers closely resembles that of typical Parkinson disease, the age at onset was earlier than previously described.

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