Clinical neuroscience (New York, N.Y.)最新文献

Agrammatism is a pattern of syntactically defective speech that is frequently observed as a prominent feature in Broca's aphasia. It may range in severity from one-word utterances, completely lacking in grammatical organization, to mildly 'telegraphic' speech. First described in the early 19th century, it was originally interpreted by Pick as being due to economy of effort in finding words. Beginning with Jakobson, in 1956, there have been a succession of efforts to give an account of it in terms of linguistic theory. While the theories are still controversial, they have led to much more detailed and systematic description of the linguistic output in agrammatic speech. Cross linguistic comparisons have revealed that the features of agrammatism are not fixed, but are conditioned by the grammatical structure of the speaker's language.

To study factors associated with different mood disorders in old age, researchers need clear and meaningful definitions. "Major depression" is too broad and heterogeneous a category, and the boundaries of "dysthymia" are ill-defined, yet epidemiologic studies have focused on these disorders. Depressions in old age are commonly associated with medical conditions; prevalence rates of depression in cases of stroke, Parkinson's disease, dementia, and disabilities (all much commoner in old age) range upward from about 20%. Depressions are attributed to both psychological and biological reactions. Mania, too, can be precipitated by cerebral and other medical factors. The proportion of psychiatric inpatients who have depressions with melancholic and/or psychotic features is higher among elderly subjects, and this has been linked with white matter lesions and other brain changes that become commoner in old age. The prognostic relevance of these brain changes, and implications for treatment of mood disorders, require clarification.

Primary progressive aphasia is an important recently emphasized clinical syndrome that is a common early manifestation of Pick's disease and Pick complex pathology. It is defined clinically as slowly progressive language disturbance that remains relatively isolated from other cognitive or behavioral deficits for at least 2 years. Subsequently, it may become associated with behavioral changes similar to those in frontal lobe dementia (FLD), extrapyramidal manifestations, and apraxia similar to corticobasal degeneration (CBD) and with motor neuron disease. Both the common nonfluent or logopenic variety leading to mutism (frontal involvement) and fluent or semantic varieties (temporal involvement) are recognized. Neuroimaging with CT, MRI, and SPECT are useful adjuncts confirming the diagnosis. PPA is a manifestation of frontotemporal degeneration or Pick complex, which is probably the second most common degenerative dementia after AD.

Most intracranial aneurysms are located in the circle of Willis. They occur in 5-6% of the general population. Patients with intracranial aneurysm either present catastrophically with rupture of the aneurysm have aneurysms that are incidentally discovered. Prognosis is drastically different in each case, with a greater than 50% incidence of death if there is a rupture of the aneurysm. On the other hand, the surgical or endovascular mortality following treatment of an unruptured aneurysm is minimal, with good patient neurological outcome. In the appropriate clinical setting, it is important to find a screening study that can detect a cerebral aneurysm so that definitive cerebral angiography can be performed. The combination of magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) can detect an aneurysm in 60-85% of cases. This screening test adds a few minutes of scanning time to the average MR examination. Magnetic resonance angiography techniques continue to improve with better gradients, enhanced sequences to detect flow and reduce flow-related artifacts, shorter echo times with possible use of echo-planar (short scanning time) techniques, and improved imaging matrix, and they may, in conjunction with computed tomographic angiography (CTA), become a reliable non-invasive technique for detection of intracranial aneurysm.

Electron paramagnetic resonance (EPR) spectroscopy was used to directly measure free radical generation in ischemic/reperfused diabetic rat retina. Tissue was frozen at 77 degrees K after 90 min ischemia, and 90 min ischemia followed by 1 min, 3 min, 5 min, and 24 hours reperfusion, respectively. After 90 min of ischemia followed by 1 min, 3 min, 5 min, and 24 hours of reperfusion (n = 10 in each group), free radical signal intensity was increased from its diabetic nonischemic control value of 12 +/- 3 arbitrary units to 58 +/- 6 (P < 0.05), 62 +/- 7 (P < 0.05), 32 +/- 5 (P < 0.05), and 14 +/- 4 arbitrary units, respectively. The peak intensity of free radical production was observed after 90 min ischemia followed by 3 min of reperfusion; therefore, this time point was selected to study the retinal free radical production in superoxide dismutase (conjugated with polyethylene glycol, PEG-SOD) and EGb 761 (Ginkgo biloba extract)-treated groups. With 7,500, 15,000, and 30,000 U/liter of SOD, and 25, 50, and 100 mg/kg of EGb 761, a dose-dependent reduction in oxygen free radical production was detected, respectively, which may be responsible for the attenuation of abnormal postischemic function in ischemic and reperfused diabetic retina.

Although the detailed pathogenesis of diabetic polyneuropathy is not known, several mechanisms appear to be involved and may occur sequentially. Hence, the early and much researched activation of the polyol-pathway appears to secondarily affect nonenzymatic glycation, perturbation of vasoactive substances, the immune system and neurotrophism. These metabolic abnormalities may be differentially expressed in the neuropathy occurring in insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) diabetes. This notion is supported by differences in the structural abnormalities of the neuropathies in the two types of diabetes. Distinct and characteristic nodal changes occur in IDDM but not in NIDDM neuropathy, which also shows a milder axonal atrophy. On the other hand, nerve fiber loss which characterizes diabetic neuropathy tends to be focal in the older NIDDM patients, suggesting a more prominent vascular genesis. A further characteristic feature of diabetic neuropathy is blunted fiber regeneration, which probably is consequent to impairments of the necessary immune response and local synthesis of neurotrophic factors. Nerve biopsies from diabetic patients, although not necessary for diagnosis, provide valuable tissue for biochemical and molecular analysis of underlying mechanisms, the detailed elucidation of which will facilitate the design of targeted therapies.

Following blunt or penetrating trauma to the head and neck, a variety of traumatic vascular injuries may occur. Often the clinical presentation of a craniocervical arterial injury is delayed and neuroimaging studies are necessary to evaluate for delayed findings of intracranial infarction or hemorrhage. In this setting, magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) may allow a prompt noninvasive diagnosis of craniocervical vascular injury. MRA may be helpful in selecting those patients requiring conventional angiography and allows a noninvasive follow-up evaluation of arterial injury following institution of therapy.

Glaucoma is a leading cause of blindness worldwide and the second leading cause of irreversible blindness in the United States. The most common form of glaucoma, primary open angle glaucoma, is characterized by a chronically elevated intraocular pressure in the absence of any demonstrable structural abnormalities in the eye. The pathologic hallmark of glaucomatous optic neuropathy is the selective death of retinal ganglion cells, generally attributed to an elevated intraocular pressure. However, the histopathology of glaucomatous injury is strikingly similar to the pattern seen with the administration of toxic levels of glutamate. We have found that glaucoma is associated with elevated levels of intraocular glutamate-to a level toxic to ganglion cells. We propose that an elevation of vitreal glutamate may be responsible, at least in part, for the loss of ganglion cells seen in open angle glaucoma.

Visual sensitivity was evaluated in the central 16 degrees of the visual field in normal subjects, in patients with glaucomatous optic neuropathy, in glaucoma suspects, and in eyes of patients with multiple sclerosis without evidence of active optic neuritis. A novel method was used to assess sensitivity called contrast perimetry (CP). CP essentially samples every point in the central 16 degrees field, and the normal and deviant responses are relatable to spatial summation of contrast signals. In each visual field quadrant 1 cycles/degree sinusoidal grating stimuli limited in area by a gaussian circular aperture (called a Gabor stimulus) were presented. Contrast sensitivity was measured as a function of stimulus size. The normal curve is nearly S-shaped: For small Gabors contrast sensitivity increases slowly, then accelerates and then flattens again. Patients' results fell into two broad categories: a loss more or only evident for small Gabors and another type of loss for both small and large Gabor size. Glaucoma suspect and most glaucoma eyes showed predominant losses to small Gabors. There were more eyes and more VF quadrants identified by contrast perimetry as abnormal compared to the diagnostic yield of the Humphrey 30-2 (central) visual field even though a Humphrey VF defect was defined liberally. Apparently, contrast perimetry may yield diagnostically useful information of paracentral visual sensitivity. Furthermore, the results suggest that selective losses in POAG and some glaucoma suspects occur to spatially broad-band retinal mechanisms, presumably ganglion cells.