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This Month in Archives of Neurology
September 2006

Missing Article Title

Arch Neurol. 2006;63(9):1220-1221. doi:10.1001/archneur.63.9.1220
Genetics of Parkinson Disease: A Success Story

The recent discoveries of a number of disease-causing genes, including α-synuclein, PARKIN, UCHL1, DJ-1, and LRRK2 in Parkinson disease, have generated considerable interest and debate for both physicians and patients regarding diagnostic and presymptomatic genetic testing of Parkinson disease in the clinic. Tan and Jankovicdiscuss the promises and limitations of genetic testing in Parkinson disease in this well-focused, useful, and elegant review.

Spatial Awareness: Consciousness Defined

Bartolomeoreviews current emerging concepts of the parietofrontal network for spatial awareness in the right hemisphere of patients. Patients with lesions of the right hemisphere often show signs of left unilateral neglect. When exploring a visual scene, patients with this neglect fail to pay attention to left-sided objects. The emerging concepts analyzing these phenomena indicate that impairments of spatial awareness do not result from damage of a single brain area but are the expression of the dysfunction of large hemispheric networks. Consciousness is multilayered and faceted, and this review offers interesting new ideas and views.

The LRRK2 Gene and the Clinical Heterogeneity of Parkinson Disease

Papapetropoulos and colleaguesdescribe the clinical heterogeneity present in LRRK2 kinase mutation carriers. They report on the clinical phenotype of 5 G2019S carriers. Four of these individuals presented with Parkinson disease that was both clinically and pathologically confirmed; the fifth individual was a control subject with no evidence of neurodegenerative pathology. The authors found that the underlying disease mechanisms of LRRK2 G2019S–associated parkinsonism are similar to typical Parkinson disease. The importance of LRRK2 mutations in Parkinson disease is reviewed in an insightful editorial by Anthony H. V. Schapira, MD, DSc, FRCP, FMedSci.

LRRK2 G2019S Homozygous Parkinson Disease Patients

I shihara et alpoint out that G2019S is the most common pathogenic substitution in the leucine-rich repeat kinase 2 (LRRK2) gene, which has recently been identified in familial and sporadic Parkinson disease. Of considerable importance is the finding that there are no observable differences between the homozygote and heterozygote phenotypes. This finding does not support a gene dosage effect and offers new areas for molecular genetic investigation.

PINK1 Gene Mutation and Juvenile Parkinsonism

Leutenegger et aldescribe the clinical and genetic features of the largest kindred reported to date with early-onset parkinsonism associated with PINK1 gene mutations. The disease was caused by a novel mutation located in the highly conserved adenosine triphosphate orientation site of the PINK1 kinase domain. This study extends the phenotypic and molecular spectrum of PINK1 as well as the geographical origin of patients with PINK1 gene mutations.

Subthalamic Nucleus Stimulation: Improvements in Outcome With Reprogramming

Deep brain stimulation (DBS) is currently the most effective surgical treatment for advanced Parkinson disease. Even when the electrode is well positioned in the target, the optimization of clinical results depends on careful programming of electrical parameters and changes in antiparkinsonian drugs. Moro et aldetermined whether stable outcomes from subthalamic nucleus DBS for Parkinson disease can be improved by revising stimulation parameters. They report that 54.6% of patients studied improved and that antiparkinsonian drugs were significantly reduced by 25.9% with reprogramming. They emphasize that improved patient outcomes from subthalamic nucleus DBS are obtained when postoperative care is personally managed by a neurologist expert in movement disorders and DBS.

Verbal Fluency and Motor Functions in Subthalamic Deep Brain Stimulation

Wojtecki and colleaguesexamined whether low-frequency in contrast with high-frequency subthalamic nucleus deep brain stimulation has a positive effect on frontal functions based on verbal fluency. They report that verbal fluency was significantly improved with subthalamic deep brain stimulation at 10 Hz compared with 130 Hz. Of note, this study provides evidence for a frequency-dependent modulation of cognitive circuits involving the subthalamic nucleus.

Boxing: The Neurological Consequences

Zetterberg et al, in a careful and detailed neurochemical study, found that boxing is associated with acute neuronal and astroglial injury. They emphasize that cerebrospinal fluid analyses may provide a scientific basis for medical counseling of athletes after boxing or head injury.

Figure.
Cerebrospinal fluid levels of the neuronal and astroglial markers neurofilament light protein (left) and total tau (right) after a bout are related to the number of hits to the head. Red squares represent boxers who received many (>15) or high-impact hits to the head. Blue circles represent boxers who received few hits to the head. Each boxer underwent lumbar puncture twice: the first time at 7 to 10 days after the bout and the second time after 3 months of absence from boxing.

Cerebrospinal fluid levels of the neuronal and astroglial markers neurofilament light protein (left) and total tau (right) after a bout are related to the number of hits to the head. Red squares represent boxers who received many (>15) or high-impact hits to the head. Blue circles represent boxers who received few hits to the head. Each boxer underwent lumbar puncture twice: the first time at 7 to 10 days after the bout and the second time after 3 months of absence from boxing.

Lamotrigine Effect on Cerebral Glucose Metabolism in Epilepsy

This study by Joo and colleaguesis the first to show that lamotrigine treatment reduces glucose metabolism in the thalamus, basal ganglia, and multiple regions of cerebral cortex in patients with idiopathic generalized epilepsy.

Symptomatic Stenoses and Occlusions in Patients With Acute Cerebral Ischemia

Weimar and colleaguesstudied 4157 patients who experienced acute ischemic stroke or a transient ischemic attack from 11 German departments of neurology with acute stroke units. They report that 82 patients (8.0%) with symptomatic cerebrovascular disease experienced a recurrent stroke between day 4 and 1 year, but they found no significant differences in recurrent stroke rates when comparing different locations of steno-occlusive disease.

Interferon-β–Induced Serum Antibodies in Multiple Sclerosis

A proportion of patients with multiple sclerosis receiving systemic interferon-β therapy will develop serum neutralizing antibodies (NAbs) that can reduce the activity of the drug. Using a newly developed in vitro assay, Shapiro and colleaguesreport that NAb-positive sera significantly inhibited polyinosinic-polycytidylic acid–induced chemokine CXCL10 and IL-6 production by astrocytes. Thus, high-titer NAbs to interferon-β may block endogenous interferon-β function and alter the chemokine/cytokine microenvironment within the central nervous system, thereby modulating the profile and course of the local inflammatory response.

Neocortical Atrophy, Third Ventricular Width, and Cognitive Dysfunction in Multiple Sclerosis

Benedict et alstudied whether neocortical volume would be more accurate than third ventricular width when predicting neuropsychological impairment. They found that there is an association between neocortical volume and multiple cognitive domains in multiple sclerosis and that third ventricular width accounted for the most variance.

Early-Onset Alzheimer Disease in Families With Late-Onset Alzheimer Disease

Brickell et alevaluated 136 kindreds with familial late-onset Alzheimer disease for the occurrence of early-onset Alzheimer disease and a separate group of 29 affected parent/child pairs with a 20-year or more difference in the age at onset. They found that many late-onset Alzheimer disease families (about 25%) have at least 1 early-onset individual, and in these individuals, the ratio of men to women is nearly 50%, suggesting a possible subtype of familial Alzheimer disease. As they point out, by virtue of this important study, late-onset Alzheimer disease families with early-onset cases represent an important resource for investigating these factors.

Accelerated Weight Loss and Diagnosing Alzheimer Disease

Johnson and colleaguesreport that both nondemented aging and dementia of the Alzheimer type (DAT) are associated with weight loss,which may accelerate prior to the diagnosis of DAT. Nondemented participants lost about 0.6 of a pound per year. In those with DAT, about 1 year prior to the detection of DAT, the rate of weight loss doubled (1.2 lb per year). Nondemented participants who eventually developed DAT weighed less (about 8 lb) at study entry, when nondemented, than the group of participants who remained nondemented. Specific factors contributing to the weight loss are unknown but appear to operate before the development of DAT. Thus, as they found, weight loss may be a preclinical indicator of Alzheimer disease.

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