The olfactory system is one of the nonmotor systems severely affected in Parkinson's disease (PD). Olfactory dysfunction occurs early in the disease process, is independent of disease stage, duration, and treatment. However, olfactory dysfunction appears to be dependent on disease subtype. Olfaction is mildly impaired or preserved in most of the parkinsonism-plus syndromes (PPS). This provides a means of differential diagnosis between typical PD and PPS. Olfactory function is impaired also in familial forms of parkinsonism in which the genetic defect is known. In familial parkinsonism, olfactory function is impaired in both typical PD and PPS phenotypes. Olfactory dysfunction does not appear to be a manifestation of dopamine deficiency. Olfactory dysfunction is also associated with other neurodegenerative diseases such as Alzheimer's disease (AD), Huntington's disease (HD), as well as with normal aging. The neuropathological changes observed in the olfactory system in PD and other neurodegenerative diseases appear to be disease-specific, raising the possibility that olfactory dysfunction may be the result of a central rather than a peripheral process. The cellular and molecular mechanisms underlying olfactory dysfunction in PD and other neurodegenerative diseases remain unknown.
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.
Parkinson's disease is characterized primarily as a neurodegenerative disorder that leads to disabling motor and cognitive impairment. PD is less widely appreciated as a disease causing a substantial variety of pain syndromes, although the prevalence of pain in PD is approximately 40%. In a minority of patients, pain is so severe and intractable that it overshadows the motor symptoms of the disorder. In recent years, descriptive surveys of non‐motor symptoms in PD have led to a classification of painful sensations into one or more of several categories: musculoskeletal pain, radicular or neuropathic pain, dystonia‐related pain, akathitic discomfort, and primary, central parkinsonian pain. A framework for diagnosing and treating painful PD is described in this review, together with recent insignts into the neurophysiological mechanisms and substrates of pain in PD. © 2010 Movement Disorder Society
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.
Migraine imposes substantial burdens both on individual headache sufferers and on society. Prevalence studies reveal that the condition affects about 18% of women and about 6% of men. Prevalence is highest between the ages of 25 and 55, during the peak productive years. Despite the development of new and effective treatment options, migraine remains an underdiagnosed and undertreated condition. In this article, we review the incidence, prevalence, and distribution of migraine and the conditions which are comorbid with migraine.
Urinary symptoms are very common in Parkinson's disease (PD). They are primarily irritative (frequency, urgency, urge incontinence) and correlate with the urodynamic finding of involuntary detrusor contractions at early stages of bladder filling (detrusor hyperreflexia). Obstructive symptoms (hesitancy, weak urinary stream) may be seen in a smaller number of patients by themselves or combined with irritative symptoms. They may be secondary to anticholinergics, obstructive uropathy, or point to the presence of multiple system atrophy. Dysfunction of the striated urethral sphincter and pelvic musculature can be seen in variable numbers in PD, with the main abnormality that of delayed relaxation at the time of initiation of voluntary voiding.
Parkinson's disease (PD) is a major neurologic disorder that distinctively and selectively affects movement and--by extension--the motor system. A large body of evidence has been accumulated over the years showing that movement disorders of PD are also due to sensory disturbances that affect sensorimotor integration. The aim of this review is to discuss the possible contribution of neurophysiologic techniques in evaluating the functionality of sensorimotor integration mechanisms in PD. Somatosensory evoked potentials (SEPs) are an appropriate functional approach for the evaluation of sensory processes in the human brain. SEPs from the frontal scalp sites are considered markers of the functionality of a cortico-subcortico-cortical loop that includes the basal ganglia as well as the premotor and supplementary motor areas. Over the years, it has been demonstrated that PD patients--especially in the early stages of the disease--show a severely depressed frontal responsiveness to sensory stimuli as tested via SEPs. The transient recovery of frontal SEP amplitude after apomorphine, a potent dopamine agonist drug, is a good and specific predictor of the clinical response of PD patients to L-dopa therapy.
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.
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.
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. Clinical Neuroscience 5:153-166, 1998. (C) 2000 Wiley-Liss, Inc.
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.
Sexual dysfunction is seen in a number of neurologic diseases. In this article we review normal human sexual response, some neurologic diseases in which sexual dysfunction is seen, and Parkinson's disease (PD). With PD there is often a reduction in sexual interest and function. The studies documenting these problems are detailed. In addition, we focus on the syndrome of hyper- or aberrant sexual function seen with pharmacotherapy of PD.
Neuroimaging modalities in Parkinson's Disease (PD) are primarily used for the differential diagnosis of Parkinson syndromes and to understand pathophysiological mechanisms in PD. Neuroimaging of nonmotor dysfunctions in PD mostly consist of functional studies in neuropsychologically impaired PD patients using PET or SPECT techniques. Various studies controversially discuss the probable frontal versus temporal hypometabolism in demented PD patients. Functional studies of PD patients with depression are limited to case reports showing an involvement of left frontal regions. To investigate the pathophysiology of hallucinations with functional imaging may be a promising field of future research.
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.
Headache and mood disorders co-occur at significant rates. Two psychological techniques of proven effectiveness in treating headache are biofeedback and relaxation training. For treating the mood disorders that accompany chronic headache, cognitive-behavioral and pharmacological therapies are highly effective both individually and combined. The present article discusses the importance of treating anxiety-spectrum disorders as well as pain when treating headache, and of manipulating factors known to influence the probability of a patient's developing chronic pain and disability.
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.
According to recent evoked potential studies a fundamental, probably protective, feature of cortical information processing, i.e., response habituation during stimulus repetition, is abnormal in migraine between attacks. The deficient habituation is found for different sensory modalities and experimental paradigms: pattern-reversal visual evoked potentials (same stimulus at a constant intensity), cortical auditory evoked potentials (same stimulus at increasing intensities), and auditory event-related potential obtained in a passive "oddball" paradigm (novel stimulus). The abnormal information processing is an interictal cortical dysfunction most likely due to inadequate control by the so-called "state-setting, chemically-addressed pathways" originating in the brain stem, in particular by the serotonergic pathway, leading to a low preactivation level of sensory cortices. We propose that it may play a pivotal role in migraine pathogenesis in conjunction with the reported decrease of brain mitochondrial energy reserve, by favouring a rupture of metabolic homeostasis and biochemical shifts capable of activating the trigeminovascular system and, thus, of producing a migraine attack. We postulate that both the deficient habituation in information processing and the deranged oxygen metabolism may have behavioral correlates. Which of these abnormalities are inherited, acquired, or both remains to be determined.
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.
