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

Effective management of primary (benign) headaches generally depends upon proper diagnosis and rational use of medications. Successful treatment requires adequate dosing plus choosing the optimal route for drug delivery. When oral remedies fail, transnasal, rectal, or parenteral therapy may succeed. While cure of headaches is not currently possible, control is possible for the majority of sufferers. Most patients can adequately treat their headaches without resorting to the doctor's office or emergency room. Many therapies may not only relieve head pain, but also alleviate associated symptoms.

Loss of will, decreased activity, and poverty of behavior are among the common symptoms observed in Parkinson's disease (PD). In line with these clinical observations, PD patients display prominent deficit in neuropsychological tests, requiring self-generated and effort-demanding operations. However, recent evidence suggests that this impairment is not generalized: visuo-spatial working memory and attentional set-shifting seem to be selectively impaired in the early stages of the disease. Electrophysiological studies also demonstrate the dysfunction of higher-level visual information processing. In this article, we discuss some current results to show the connection between clinical symptoms and neuropsychological deficits. We also consider dysfunction in underlying neural mechanisms, with particular emphasis on the dysregulation of fronto-striatal circuits. However, it is conceivable that visuo-cognitive impairment in PD reflects dysfunction of neural assemblies, involving basal ganglia, dorsal visual stream, and frontal-prefrontal circuits.

Several abnormalities of visual function have been demonstrated in Parkinson's disease (PD) by both electrophysiologic and psychophysical testing. Prolonged visual evoked potential latencies and abnormal electroretinographic patterns, both of which respond to levodopa therapy, have been demonstrated in Parkinson's disease patients and in primates with experimental parkinsonism suggesting that retinal dopamine deficiency is an important factor in the pathogenesis of PD visual dysfunction. Abnormalities of color perception, especially in the blue-green axis, and of visual contrast sensitivity (VCS) have also been well documented in PD patients. Although VCS impairment is likely related to retinal dopaminergic dysfunction, the fact that this visual abnormality is orientation-specific raises the possibility of visual cortex involvement as well. Visual abnormalities in PD are usually clinically occult and not likely to be uncovered during a routine neurological examination or by ordinary high contrast visual acuity testing. The clinician must be aware, however, that several forms of disability ranging from gait freezing to visual hallucinations may be linked to an underlying impairment of visual function in Parkinson's disease.

Cardiovascular dysfunction may occur in parkinsonian patients for a variety of reasons. Patients usually are more than 50 years old and on various drugs (both antiparkinsonian and for associated medical disorders), some of which may have cardiovascular effects. Autonomic failure increases with age and also is recognized in parkinsonian patients who have the disorder multiple system atrophy, in which there is substantial cardiovascular dysfunction. Thus, recognition of cardiovascular dysfunction and its causes in parkinsonian patients is of importance in diagnosis (in separating the various parkinsonian diseases), in determining prognosis, and finally in management. This article outlines the major areas of cardiovascular dysfunction, including disorders of blood pressure control, heart rate, and regional circulation, especially to vital organs. Clinical features and evaluation are described, together with abnormalities in different parkinsonian disorders and the principles of management.

This article reviews the spectrum of respiratory dysfunction in Parkinson's disease (PD). It includes the primary effects of PD on the ventilation, response to medications, and pulmonary complications of antiparkinson therapy. Primary pulmonary abnormalities include a restrictive change mainly secondary to chest wall rigidity and upper airway obstruction; both are responsive to dopaminergic modulation. Respiratory dyskinesia, a side effect of levodopa therapy, may produce both restrictive and dyskinetic ventilation. Therapy with ergot derivatives may result in pleuropulmonary fibrosis. Lastly, pulmonary infection as a consequence of disordered respiratory mechanics continues to contribute significantly to morbidity and mortality in PD.

Pain, defined as an unpleasant or distressing sensory experience, has been recognized as feature of Parkinson's disease (PD) since the first descriptions of the disorder. Pain is estimated to occur in approximately 40% of patients with PD, and in a minority of individuals becomes severe enough to overshadow the motor symptoms of the disorder. Recent studies based on patients' descriptions of pain have enabled a classification of painful sensations into 1 or more of 5 categories: musculoskeletal pain, neuritic or radicular pain, dystonia-associated pain, primary or central pain, and akathitic discomfort. The existence of a central pain syndrome, intrinsic to PD, finds support in a collection of case reports, but the precise mechanism is unknown, and a correlation with pathology has not been made. This review describes the clinical features of the pain syndromes in PD, and provides a framework for evaluating, classifying, and treating painful symptoms in PD.

The molecular mechanisms of migraine pain have not yet been clarified. Neurogenic inflammation and a subsequent plasma extravasation in the dura mater have been suggested. However, monoamine and peptide neurotransmitters involved in neurogenic inflammation do not cause significant head pain. Based on our previous studies of headache induced by i.v.infusions of glyceryl trinitrate (exogenous nitric oxide donor) and histamine (which liberates nitric oxide from vascular endothelium), we suggest that nitric oxide (NO) is a more likely candidate molecule. The present review deals with the biology of this small messenger molecule and the scientific evidence suggesting a key role for this molecule in migraine headache. We hypothesise that the release of NO from either blood vessels, perivascular nerve endings, or brain tissue is a molecule trigger mechanism of spontaneous migraine pain. These novel observations dictate new approaches to the pharmacological treatment of migraine.

Behavioral manifestations of Parkinson's disease (PD) are often more debilitating than the motor manifestations. These occur both as primary manifestations of the disease and as drug-induced complications. While dementia and abulia are common problems that are not currently treatable, depression and psychosis often respond extremely well to medication. Phenomenology, pathology, and general approaches to treatment will be discussed.

The frequency of sleep complaints in patients with Parkinson's disease (PD) is estimated to be between 60-90% and a variety of either disease-related or secondary mechanisms and the dopaminergic treatment itself contributes to the development of different sleep disturbances. These comprise slight, fragmented sleep with increased number of arousals and awakenings, and PD-specific motor phenomena such as nocturnal immobility, rest tremor, eye-blinking, dyskinesias, and other phenomena such as periodic and nonperiodic limb movements in sleep, restless legs syndrome, fragmentary myoclonus, and respiratory dysfunction in sleep. Depression and hallucinations/psychosis further complicate the picture. The incidence of REM sleep behavior disorder (RBD) with nightmares and violent behavior is increased in PD and may occur as a preclinical disease-related symptom. A careful sleep history of patients and their partners, polysomnograms when necessary, motor and psychiatric assessments should precede individual treatment strategies, which include adjusting dopaminergic daytime treatment, benzodiazepines for RBD, reduction of anticholinergic drugs, and, if necessary, clozapine for nocturnal psychosis.

The development of serotonin (5HT) agonists that have highly specific receptor profiles has fueled the study of 5HT receptor pharmacology and in particular the pharmacology of the 5HT1 sub-class of receptors. The currently accepted classification of 5HT receptors includes seven classes known as 5HT1 through 5HT7 and the class most implicated in migraine 5HT1, which consists of the A, B, D, E, and F sub-types. Currently, effective and relatively specific anti-migraine compounds, as a group, are potent 5HT1B/1D agonists. Their possible mechanisms of action include carotid territory vasoconstrictor effects and inhibitory effects on both the peripheral and central terminals of the trigeminal innervation of the pain-producing intracranial structures. Future drug development will target these individual mechanisms to dissect out which, if any, determines the clinical efficacy of the compounds.