Mochida and Walsh describe the exciting new developments in gene identification associated with formation of the human cerebral cortex and related mutations. Recent advances in molecular genetic studies of malformations of the human cerebral cortex have led to the identification of many genes that are important regulators of cortical development. This research has provided the means to define the specific function of a gene during normal embryogenesis of the cerebral cortex and the mutational basis of cerebral malformations.
In this elegant review, Girault and Greengard define the progress that has now been accomplished in identifying the intracellular signaling pathways underlying the immediate actions of dopamine and account for its long-term effects on brain properties. They describe recent findings making it possible to pinpoint molecules that may represent interesting therapeutic targets for future therapies in neurology and psychiatry.
Newmark points out in this timely article that neurologists need to familiarize themselves with nerve toxins, the most serious and disease producing of the chemical warfare agents. Experience has conclusively demonstrated that specific therapy introduced early will save lives. The neurological community needs to be aware of this potential crisis and be prepared.
Levodopa metabolism via catechol O-methyltransferase causes increased levels of the neurotoxin homocysteine. Müller and colleagues describe altered peripheral nerve function related to elevated homocysteine levels caused by levodopa therapy. This is a new and potentially important clinical adverse effect of levodopa therapy that needs further clinical study. Editorial perspective is provided by Padraig O'Suilleabhain, MD, and Ramon Diaz-Arrastia, MD, PhD.
Arvanitakis and colleagues describe their clinical experience studying patients with diabetes mellitus and the subsequent risk of Alzheimer disease. Interestingly, they find that diabetes mellitus is associated with a significantly increased risk of developing Alzheimer disease. Vascular factors are one of several issues that may be responsible.
High plasma levels of inflammatory proteins including α1-antichymotrypsin, C-reactive protein, and interleukin 6 were associated with an increased risk of dementia as reported by Engelhart and colleagues. Plasma levels of these inflammatory proteins were increased before the clinical onset of symptoms, which emphasizes their potential diagnostic value and that these elevations occur early in the disease process.
Pregnancy registries are a new method for assessing the fetal risks from exposure to antiepileptic medication in pregnancy. Holmes and colleagues present the findings of the North American Antiepileptic Drug Pregnancy Registry for phenobarbital-exposed pregnancies. Five of 77 "pure" prospective phenobarbital monotherapy–exposed pregnancies were associated with major malformations. Thus, prenatal exposure to phenobarbital is associated with a significantly increased risk of fetal abnormalities.
Although multiple sclerosis can cause significant disability, most patients with this disease in the Olmsted County, Minnesota, prevalence cohort, described by Pittock and colleagues, continue to report a good quality of life.
Mean differences in the 8 Short Form 36 subscales and physical-component and mental-component summary scores.
Mercuri and colleagues describe patients with the same missense mutation in exon 6 of the LMNA gene, encoding the nuclear envelope proteins lamins A and C and resulting in an E358K substitution in the central rod domain. All 5 patients had muscle involvement, but the onset, severity, distribution of muscle weakness, and presence of associated features were highly variable. These observations considerably expand the clinical spectrum associated with mutations in the LMNA gene and further illustrate the overlapping phenotypes of the laminopathies.
Short-term deep brain stimulation of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson disease. Witt and colleagues examined the short-term effects of STN stimulation using several tests sensitive to executive function as well as a scale of global cognition. Of interest, they found that STN stimulation improves cognitive flexibility (giving up habitual responses) but impairs response inhibition. Thus, STN stimulation does not change global cognitive function. The cognitive effects of deep brain stimulation have not been emphasized but are of clinical importance in determining its long-term effects and practical clinical outcome.
Munhoz and colleagues describe a large family in which the inheritance of parkin Ex3Δ40 resulted in parkinsonism in a recessive pattern. Recessive and dominant phenotypes are discussed. The consequences of different parkin missense mutations on clinical and pathological outcomes are evidently complex and may depend on background genetic, environmental, and stochastic factors.
Reitz and colleagues investigated the relationship between plasma lipid levels and the risks of Alzheimer disease (AD) and vascular dementia as well as the effect of lipid-lowering agents on this association. A weak relationship was found between non–high-density lipoprotein, low-density lipoprotein, and high-density lipoprotein cholesterol levels and the risk of vascular dementia. In this study, lipid levels and the use of lipid-lowering agents were not associated with the risk of AD. The authors' data do not support the hypothesis that statin use is associated with a lower risk of AD.
Tau-related Alzheimer disease pathologic conditions and white matter lesions seen on magnetic resonance (MR) imaging represent 2 major issues in the cause of mild cognitive impairment (MCI). These factors may partly explain the variability in disease progression and type of symptoms in patients with MCI. This correlative study of cerebrospinal fluid (CSF) tau and white matter lesions on MR imaging was conducted by Maruyama and colleagues in 72 consecutive elderly patients with memory complaints to evaluate the natural history of cognitive loss. The stable MCI group had normal CSF tau levels and a high grade of white matter lesions on MR imaging. The progressive MCI/Alzheimer disease–converted MCI group had increased CSF tau levels and a low grade of white matter lesions on MR imaging. These findings are of considerable interest in predicting the clinical outcome in patients with MCI or significant memory loss for their age.
Levy and colleagues studied the relationship between pituitary tumor size and the complaint of headache in 63 patients with pituitary tumors. There was no positive correlation between clinical headache score and pituitary volume. Headache associated with a pituitary tumor, they conclude, is not simply a structural problem. Factors such as family history of headache and endocrine activity of the tumor should also be considered.
The relative prevalence of the major spinocerebellar ataxias inherited as autosomal dominant disorders in Italy was studied by Brusco and colleagues, including the SCA1-3, SCA6-8, SCA10, SCA12, and SCA17 gene CAG expansions. SCA1 and SCA2 were found in high frequency, and SCA3, SCA6, and SCA7 were rare as compared with other European countries.
Apair of monozygotic female twins discordant for Alzheimer disease (AD) were studied for serum copper and total peroxide levels as reported by Squitti and colleagues. Copper and total peroxide levels were significantly higher in the twin with greater cognitive impairment and a diagnosis of AD. These results support the hypothesis of a major involvement of copper and oxidative abnormalities in AD. Editorial perspective is provided by Ashley I. Bush, MD, PhD, and Dorothea Strozyk, MD.
This Month in Archives of Neurology. Arch Neurol. 2004;61(5):629-630. doi:10.1001/archneur.61.5.629