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This Month in Archives of Neurology
Arch Neurol. 1998;55:1281-1282.
Human Genome Project and the Brain
Evans (SEE ARTICLE) describes the objectives in the Human Genome Project and our current progress. Of the 70,000 to 80,000 genes in the human genome, he estimates that at least 50% of these genes are expressed in the brain. Only about 3% of the human genome has been sequenced, indicating that most of the genes expressed in the brain are currently undefined. A vast amount of information will be made available at the molecular level to decipher human neurologic diseases and provide genetic means to treat them. It is fair to say, as Evans points out, that "the biomedicine in the next century is likely to take on an entirely new role in society based on the beginnings inherent in the Human Genome Project."
Mitochondrial Defects
The field of mitochondrial molecular genetics is moving rapidly, and mitochondrial mutations and polymorphisms are increasing in number in rapid succession. This exciting and dynamic field is brought up to date in a well-focused review by Schapira (SEE ARTICLE) .
Human Trinucleotide Repeats
Anumber of hereditary degenerative disorders are caused by CAG trinucleotide repeats. The mechanisms by which the proteins containing the polyglutamine domain and coded by CAG repeats cause cell death remain unknown. Kish et al (SEE ARTICLE) have examined carefully the role of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase in neuronal damage.
Alzheimer Immunology
The role of the immune system in expressing the neuropathological characteristics of Alzheimer disease is gaining in interest and analysis. Bongioanni and colleagues (SEE ARTICLE) have investigated aspects of T-cell–dependent immune functions and their role in producing the neuropathological aspects of Alzheimer disease.
Hyperkinetic and Hypokinetic Movements
Litvan et al (SEE ARTICLE) have examined patients with Huntington disease (HD) and progressive supranuclear palsy (PSP) and found that patients with HD exhibited significantly more symptoms of agitation, irritability, and anxiety, whereas patients with PSP exhibited more apathy. The authors relate the hyperactive behaviors in individuals with HD to an excitatory subcortical output through the medial and orbitofrontal cortical circuits, while in PSP the hypoactive behaviors are secondary to hypostimulation of these pathways. An elegant neuroanatomical analysis is provided in support and explanation of these interesting conclusions.
Dystonia Response to Levodopa
Dewey et al (SEE ARTICLE) have studied patients with generalized dystonia who responded to treatment in the 1970s with a combination of levodopa and carbidopa. Patients were surveyed by telephone and then examined during a 3-day levodopa holiday; in addition, functional imaging with fluorodopa positron emission tomography was performed on a subset of these patients. Of note, no significant changes were seen in the dystonia scores of 3 patients with idiopathic torsion dystonia who did not receive levodopa. This carefully designed study provides objective evidence that motor fluctuations do not occur in dopa-responsive dystonia to the degree and type seen in patients with Parkinson disease treated with levodopa. This is a valuable and important clinical study.
The Outcome of Head Trauma
Counseling patients undergoing temporal lobectomy should include defining a potential history of significant head trauma. Patients with such a history are less likely to become seizure-free following anterior temporal lobectomy, as described by Schuh et al (SEE ARTICLE) . In addition, previous head trauma is a practical factor to consider in this group of patients.
Axonal Neuropathy and Alcohol
Alcohol abuse and malnutrition can cause severe acute axonal polyneuropathy. It can be differentiated from the Guillain-Barré syndrome and making this distinction is important, as described by Wöhrle and colleagues (SEE ARTICLE) .
Dopamine Receptor Polymorphisms and Behaviors in Alzheimer Disease
Sweet and colleagues (SEE ARTICLE) describe a group of patients with Alzheimer disease with selected polymorphisms in the dopamine receptor genes. Psychosis and aggression in this group of patients correlated with specific dopamine receptor polymorphism types. Polymorphisms in the DRD1 and DRD3 receptor genes influence behavior. These contributions are important to appreciate the biochemical and molecular genetics of neuroethological human behaviors.
Machado-Joseph Disease and Mortality
Lima and colleagues (SEE ARTICLE) have examined in detail the listed causes of mortality in patients with Machado-Joseph disease (MJD) from death registers. In only about 36% of patients could it be determined that MJD was a directly related cause of death from these registers. Thus, in reconstructing Azorean family pedigrees for MJD, the use of death registers should be used with caution and other independent means of verifying the presence of MJD in at-risk persons should be used. Clinical genetic epidemiology is a challenge.
Magnetic Resonance Imaging in SCA6
Murata and colleagues (SEE ARTICLE) provide magnetic resonance imaging data on molecularly defined mutations of patients with spinocerebellar ataxia 6 (SCA6). Clearly, the cerebellum and its afferent and efferent connections are effected in SCA6. The degree of detail in their analysis is impressive.
Eye Movements in Dominant Ataxias
Buttner and colleagues (SEE ARTICLE) describe oculomotor findings in patients with SCA6 with pure cerebellar involvement, in patients with SCA1 and SCA2 with pontine involvement, and in patients with Machado-Joseph disease (SCA3) with vestibular or nuclear involvement. Patients with molecularly defined mutations have rather distinct oculomotor phenotypes that can be useful for clinical diagnosis. Specific phenotypes for the spinocerebellar ataxias can be detected with quantitative eye movement testing.
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