Right hemisphere dysfunction in ADHD: visual hemispatial inattention and clinical subtype.

The relationship between right hemisphere dysfunction and attention-deficit/hyperactivity disorder (ADHD) remains controversial. We administered a random letter cancellation test to 58 carefully selected adult patients meeting DSM-IV criteria for ADHD and 29 age- and education-matched controls. Patients with ADHD had a higher mean omission rate on the left side than the controls, and a greater percentage of ADHD patients than controls made more omissions on the left than on the right (L > R errors). ADHD patients who made L > R errors had lower performance IQ scores than ADHD patients who did not make L > R errors. However, ADHD patients who made L > R errors did not differ from ADHD patients who did not make L > R errors in ADHD subtype, medication response, or neuropsychological measures of attention, executive function, verbal memory, nonverbal memory, or academic achievement. Patients without a family history of ADHD were more likely to make L > R errors than patients with a family history of ADHD. This study provides support for the concept of right hemisphere dysfunction in a subset of patients with ADHD. However, ADHD patients who make L > R errors do not appear to represent a distinct clinical subgroup in terms of medication response, ADHD subtype, or neuropsychological test performance.

Diffusion-weighted magnetic resonance imaging in Alzheimer's disease.

Diffusion-weighted imaging (DWI) is a powerful new magnetic resonance imaging technique for evaluating tissue pathophysiology in vivo. We performed DWI in three orthogonal spatial directions in 10 patients with mild to moderate Alzheimer's disease (AD) and 11 control subjects. Average apparent diffusion coefficients (ADCavg) were calculated for gray matter regions, and anisotropy indexes were calculated for white matter regions. Global measures of atrophy and white matter hyperintensities (WMH) were obtained on T2-weighted images to control for their potential confounding effects on ADCavg and anisotropy. The measures of atrophy and WMH differed between the groups and were used as covariates in the subsequent statistical analyses. Patients with AD demonstrated diminished anisotropy in the posterior white matter (p < 0.0001) and increased ADCavg in the hippocampus (p < 0.05) when compared to the control group. Diffusion measures did not correlate with the severity of dementia. DWI provides a unique, quantitative parameter that may be sensitive to the pathophysiological and/or microstructural abnormalities that occur in AD.

The neurobiology and pharmacotherapy of Alzheimer's disease.

Alzheimer's disease (AD), the most common cause of dementia, has become a major public health concern as our population ages. In recent years, AD has attracted the attention of a wide range of biological disciplines, and substantial progress has been made in understanding the mechanisms of neurodegeneration in AD. Four different genes have now been associated with AD and are providing insights into the pathogenesis of the disease. The roles of beta-amyloid, tau, hormonal changes, inflammation, and oxidative stress in the neurodegeneration of AD are also being delineated. Based on these discoveries, rational therapeutic strategies are developing rapidly. The authors review these and other recent advances in the neurobiology and pharmacotherapy of AD.

The potential application of cyclo-oxygenase type 2 inhibitors to Alzheimer's disease.

In recent years, dramatic progress has been made in the understanding of the neurogenetics and neurobiology of Alzheimer's disease (AD). A great deal of experimental evidence has accumulated to support the hypothesis that inflammatory mechanisms are involved in the pathophysiology of AD. In addition, epidemiological studies have revealed that anti-inflammatory medications reduce the risk of developing AD. However, long-term use of conventional anti-inflammatory drugs is associated with significant toxicity which limits their potential application to the treatment or prevention of AD. It is believed that the inhibition of cyclo-oxygenase type-1 (COX-1) causes much of this toxicity, while inhibition of COX type-2 (COX-2), which is induced by inflammatory stimuli, may confer the anti-inflammatory effect. COX-2 is also constitutively expressed in brain regions preferentially affected in Alzheimer's disease and may be directly involved in neuronal cell death. Therefore, selective COX-2 inhibitors represent a promising class of drugs for the treatment of AD.

Noninvasive perfusion MRI in Alzheimer's disease: a preliminary report.

We performed functional MRI using the echo-planar imaging and signal targeting with alternating radio frequency (EPISTAR) technique in 11 patients with Alzheimer's disease (AD) and 8 age-matched control subjects. Seven of the AD patients had qualitatively apparent focal areas of hypoperfusion in the posterior temporoparietal-occipital regions. At the earliest inversion time producing cortical enhancement, the ratios of parieto-occipital and temporo-occipital to whole slice signal intensity were significantly lower in the AD patients than in the controls. Parieto-occipital hypoperfusion correlated with dementia severity as measured by the Blessed Dementia Scale. EPISTAR may prove to be a rapid, noninvasive alternative to other functional neuroimaging modalities in the evaluation of patients with dementia.

Diagnostic testing and dementia.

The prevalence of dementia is expected to increase markedly as our population ages. Although only a minority of cases currently are found to have treatable causes, the personal and financial costs of misdiagnosis are great. Furthermore, progress in developing effective therapy hinges on accurate diagnosis. This article reviews the current state of diagnostic testing in the diagnosis of dementia.

Right hemisphere learning disability associated with left hemisphere dysfunction: anomalous dominance and development.

Two patients are described with the social emotional processing disorder, a developmental syndrome usually ascribed to right hemisphere dysfunction. In these two patients however, neurological examinations, EEG, and neuroimaging studies were all consistent with left hemisphere dysfunction. Both patients were left handed and had findings suggestive of anomalous dominance for language. It is proposed that early left hemisphere injury may have resulted in functional reorganisation that allowed sparing of language and motor skills but interfered with the development of functions that the right hemisphere normally subserves.

Reversed cerebral asymmetry in women with breast cancer.

Altered intrauterine hormonal environment might predispose to both atypical cerebral asymmetry and breast cancer. We therefore investigated computed tomographic scans of 79 right-handed, white patients with breast cancer and 97 controls to assess the pattern of cerebral asymmetry. Women with breast cancer had a reversed pattern of cerebral asymmetry significantly more often than did controls (p less than 0.0001 for both frontal and occipital width. Our findings suggest that an intrauterine or early life factor, probably hormonal, could predispose to breast cancer in adulthood.

Frontal lobe dysfunction following infarction of the left-sided medial thalamus.

We treated a 62-year-old woman who developed a dramatic change in personality and behavior following a discrete left-sided medial thalamic infarction involving the dorsomedial nucleus. Neuropsychological testing demonstrated severe impairment of complex executive behaviors that are usually associated with frontal lobe function. Electroencephalography and single-photon emission computed tomography strongly implicated dysfunction of the ipsilateral frontal lobe. This case further supports a functional and physiologic thalamofrontal linkage as part of a broader cerebral network modulating complex human behavior.

Spinal cord infarction. Report of 8 cases and review of the literature.

While the incidence of spinal cord ischemia is not known, it is generally considered to be rare. Diagnosis of presumed spinal cord ischemia requires the appropriate clinical picture and exclusion of other possible etiologies. Definitive diagnosis usually requires postmortem examination. During a 52-month period, 8 patients with presumed spinal cord infarction were evaluated at a 238-bed community hospital. These cases accounted for 1.2% of all admissions for stroke. Infarction of the spinal cord was confirmed on postmortem examination in 2 cases. All 6 surviving patients regained substantial motor function. Bowel and/or bladder dysfunction returned to normal in 3 patients. The literature is reviewed, and the cases are discussed in relation to the pertinent anatomic, pathogenic, and clinical aspects of spinal cord infarction.