Copyright 2007 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2007
White-Bateman and colleagues indicate that intravenous thrombolysis with recombinant tissue plasminogen activator is the standard of care for the treatment of acute ischemic stroke within 3 hours after stroke onset. They point out that there is no standardized method to estimate capacity of patients who have had acute stroke and empirical data for this particular patient population are scarce. The authors review the elements of informed consent, the legal standards for competence that a thrombolysis candidate must meet to consent to treatment, and recommendations for assessing capacity to give direct informed consent.
Faden and Stoica review the emerging field of neuroprotection. The ability of pharmacological agents to limit secondary biochemical damage and cell death has been well established in numerous animal models of stroke, head injury, and spinal cord injury, yet the results of such neuroprotective treatment strategies in human injury have been disappointing. Both the critical problems and potential solutions are reviewed with emphasis on recent experimental and clinical work.
Di Prospero and colleagues, in an open-label, phase 1A, dose-escalation trial followed by an open-label, 1-month, phase 1B trial, determined the safety, tolerability, and pharmacokinetics of increasing doses of idebenone in subjects with Friedreich ataxia (FA). They report that higher doses of idebenone lead to a proportional increase in plasma levels up to 55 mg/kg per day and that high-dose idebenone is well tolerated by patients with FA. These findings are essential to planning efficacy trials of high-dose idebenone in FA and other degenerative diseases in which oxidative damage has been implicated.
Ribaï and colleagues evaluated the clinical and genetic features of juvenile Huntington disease. The most remarkable signs at onset were severe psychiatric and cognitive disturbances (19 of 29 cases, 65.5%). This led to misdiagnosis or diagnosis delay, especially in cases without a family history of Huntington disease. Editorial comment is provided by Kevin Biglan, MD, MPH, and Ira Shoulson, MD.
The risk factors for pedal edema among patients with Parkinson disease using pramipexole therapy were studied by Kleiner-Fisman and Fisman. Two hundred thirty-seven patients received pramipexole hydrochloride and met criteria for inclusion in the analysis. Of these, 38 (16%) developed pedal edema (Figure). A history of coronary artery disease or diabetes was a strong risk factor for the development of edema.
Outcome of pedal edema in 38 patients who developed edema while taking pramipexole hydrochloride.
Mendez et al indicate that consensus criteria for frontotemporal dementia (FTD) and neuropsychological measures were insensitive for FTD. However, they emphasize that neuroimaging, particularly functional brain scans, greatly increased the sensitivity of detecting FTD. The clinical diagnosis of FTD needs to combine neuropsychiatric features with single-photon emission computed tomography or positron emission tomography while following the changes on neuropsychological tests.
Wahner and colleagues found a greater than 2-fold increased risk of Parkinson disease among carriers of the homozygous variant genotype of interleukin-1B-511 and the homozygous variant genotype of tumor necrosis factor α and a nearly 3-fold increased risk among carriers of the homozygous variant genotype for either or both polymorphisms.
A comprehensive evaluation of clinical, magnetic resonance imaging, and genetic analysis was conducted by Battistini and colleagues in 5 Italian families affected with cerebral cavernous malformations (CCMs). Three novel and 2 previously described mutations were found in the gene KRITI. The families included 33 KRITI mutation carriers and 57.6% of them were asymptomatic. Magnetic resonance imaging examination showed CCM lesions in 82.4% of symptom-free mutation carriers. These data emphasize both the importance of magnetic resonance imaging in the diagnosis of CCMs and the potential for DNA-based diagnosis to identify subjects at risk.
An automated intensity-based measure of medial temporal atrophy in Alzheimer disease was compared with existing volumetric and visually based methods by Ridha et al. The Automated Medial Temporal Lobe Atrophy Scale (ATLAS) is a simple medial temporal atrophy measure, which has the additional advantage of being able to track Alzheimer disease progression on serial imaging.
The mechanism underlying nocturnal sudden death in patients with multiple system atrophy remains unclear. Shimohata et al studied the mechanism of sleep-disordered breathing in multiple system atrophy. They report a decrease in arterial oxygen pressure and an increase in alveolar-arterial oxygen gradient significantly correlated with disease duration. Polysomnography demonstrated Cheyne-Stokes respiration in 3 of 20 patients (15%). Vocal cord abductor paralysis was also noted. Laryngoscopy showed 11 patients (55%) had upper airway obstruction. These findings contribute to impaired respiration and sudden death in patients with multiple system atrophy.
Blacker and colleagues used detailed and comprehensive neuropsychological measures among normal persons to predict subsequent cognitive decline. They report that episodic memory performance predicts time to progression to mild impairment. Tests of both episodic memory and executive function are predictors of time to progression from mild impairment to a clinical diagnosis of Alzheimer disease.
Cardenas and colleagues compared deformation-based maps of local anatomical size between patients with frontotemporal dementia (FTD) and healthy subjects to identify regions of the brain involved in FTD. They confirm frontal and anterior temporal gray matter atrophy in FTD. They observed white matter loss, thalamic atrophy, and midbrain atrophy that are consistent with pathological findings in late-stage FTD.
This Month in Archives of Neurology. Arch Neurol. 2007;64(6):780-781. doi:10.1001/archneur.64.6.780