This Month in Archives of Neurology

Pardridge points out in his review that small-molecule neuropharmaceuticals and virtually all large-molecule drugs do not cross the blood-brain barrier (BBB). The future development of neurotherapeutics will be accelerated by the development of BBB drug targeting technology. This will be one of the challenges for the new era of genomic neurology.

Lopez and colleagues point out the difficulties in diagnosing dementia with Lewy bodies using current clinical criteria. Caution is required in ascribing too much emphasis on present clinical indicators for dementia with Lewy bodies. New biomarkers are needed. This study defines the limits of our current knowledge in this emerging area of dementia research. Fernando Pompeu, MD, and John H. Growdon, MD, provide a critical perspective in an editorial.

Casetta and colleagues provide convincing evidence for a circadian rhythm of ischemic stroke in the morning hours. As they suggest from this provocative study, preventive pharmacological interventions aimed at the morning rise of risk factors is an important neurotherapeutic issue.

Lampl et al provide clear evidence of the clinical utility of transorbital Doppler studies to establish the presence of brain death. Specific blood flow patterns are described and discussed that can be used in support of this clinical determination.

Bakshi and colleagues report that gray matter T2 hypointensity in multiple sclerosis is associated with brain atrophy and is a stronger predictor of disability and clinical course than are conventional magnetic resonance imaging findings. They propose that iron deposition is a surrogate marker of the destructive disease process. These observations may provide an important new marker to judge the prospective clinical outcome.

Padovani and colleagues present an elegant study showing that the alteration of platelet amyloid precursor protein (APP) isoforms is an early event in Alzheimer disease (AD) and the measurement of APP isoform ratios can be very useful for the identification of preclinical AD in subjects with mild cognitive impairment. These observations confirm and extend previous observations that platelet APP metabolism parallels that of AD progression and can be a useful surrogate marker for quantifying the disease process and potential response to pharmacologic therapy.

Reuber and colleagues show the value of epilepsy surgery in patients who have additonal pseudoseizures. Additional pseudoseizures should not be an absolute contraindication to epilepsy surgery. In addition, patients should have careful preoperative psychiatric evaluations. This article provides new information about this difficult and divisive subject.

Romas et al show clearly that both early- and late-onset familial Alzheimer Disease (AD) occurs in Caribbean Hispanics. Further, late-onset familial AD among Caribbean Hispanics is strongly associated with APOE-ϵ 4. This study points out the need to search for additional susceptibility genes to take into account the effects of APOE-ϵ 4. This study is a model of how careful and stringent neuroepidemiology should be conducted and provides the means to design future molecular genetics studies.

Vorgerd et al previously reported that 60 mg/kg of creatine per day improved the work capacity of patients with McArdle disease. Now they show that 150 mg/kg of creatine per day worsened the clinical symptoms of exercise in patients with McArdle disease. Thus, their refined assessment indicates that an effective dose regimen without adverse effects may be between 60 and 150 mg/kg of creatine daily.

Apaydin and colleagues show clearly that diffuse or transitional Lewy body disease is the primary pathologic substrate for dementia developing later in the course of Parkinson disease (PD) and seems to account for end-stage, levodopa-refractory PD. It is an important finding and establishes the neuropathologic substrate for dementia encountered in about 20% of patients with long-term PD.

Hoogervorst et al compare and contrast the measurement parameters to evaluate the status of patients with multiple sclerosis as measured by the Expanded Disability Status Scale with the Multiple Sclerosis Functional Composite. They find that these 2 scales of measurement compare favorably and both have equivalent clinical utility. Time will tell which is preferred.