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To assess the prevalence, nature, and associated phenotypes of ATP13A2gene mutations among patients with juvenile parkinsonism (onset <21 years) or young onset (between 21 and 40 years) Parkinson disease (YOPD).

To assess the presence, severity, and differences in dysphagia in Parkinson disease (PD), Parkinson variant of multiple system atrophy (MSA-P), and progressive supranuclear palsy (PSP), and to study the pathophysiology of swallowing abnormalities in these disorders.

Defects of the ubiquitin-proteasome (UP) system, a multicatalytic complex degrading polyubiquitinated proteins, may intervene in the pathogenesis of neurodegenerative disorders characterized by intracellular formation of protein aggregates such as Parkinson disease (PD) and Alzheimer disease (AD) by inducing proapoptotic conditions.

To assess the prevalence, nature, and associated phenotypes of PINK1gene mutations in a large series of patients with early-onset (<50 years) parkinsonism.

Abstract: In this study, we measured the lymphocyte levels of proteins involved in apoptosis regulation, such as Bcl‐2, the peripheral benzodiazepine receptor (PBR), caspase‐3, and Cu/Zn superoxide dismutase (Cu/Zn SOD), in patients with Parkinson's disease (PD), either untreated or under therapy with dopaminergic agents (l‐Dopa alone or l‐dopa + dopamine agonists) and in healthy volunteers. All PD groups showed increased activity of caspase‐3, compared to controls, particularly those under treatment only with l‐Dopa. In this latter group, the increase in caspase‐3 activity was also paralleled by an increase in the concentration of Cu/Zn SOD. In addition, patients taking l‐Dopa + dopamine agonists showed marked decrease in Bcl‐2 levels and increased PBR expression, which seems in keeping with the hypothesis that PBR may be functionally related to Bcl‐2. In conclusion, we found clear modifications in the levels of proteins involved in the control of apoptosis in lymphocytes of PD patients. These changes were disease related but also modulated by the pharmacological treatment, which confirms the potential role of apoptosis in PD pathogenesis and the modulatory influence of dopaminergic agents.

Abstract: We studied rats with a hemi-Parkinsonian model created by lesions of mesostriatal dopaminergic neurons. Correlation between the extent of lesions and intensity of forced rotation movements (apomorphine (APO)-induced rotations, i.e., exercise) was investigated. The levels of endothelins (ET) in the circulation after rotation under normoxic and hypoxic conditions were measured. In normoxia, the rotation sessions were associated with significant decreases in circulating ET levels, from 21.32±4.06 to 9.32±1.08 pg/ml. Although hypoxia had no effect on the frequency of rotations induced by APO, it significantly attenuated a decrease in the ET levels in the circulation of rats with the most extensive lesions. We suggest that the mesostriatal dopaminergic system modulates endothelial function by an active process. This may have relevance for some clinical manifestations of disordered striatal function observed in humans.

On the long term Parkinson Disease (PD) treatment is often complicated by the occurrence of motor fluctuations. To find out whether early treatment of PD with levodopa, dopaminoagonists or 1-deprenyl is associated with any difference in motor fluctuations occurrence, the Italian Parkinson Study Groups initiated a multicenter, randomized study. Since November 1988, 475 patients cequiring effective treatment for idiopathic PD have been randomized to receive levodopa, dopoamine agonists or deprenyl. After 2 months of therapy, all patients evaluated with the Unified Parkinson Disease Rating Scale showed a significant amelioration. Daily living activities were more impaired in patients treated with deprenyl. Study design is presented and first resuts are discussed.

In this study, the 24-hour pattern of blood pressure (BP), heart rate, and urinary catecholamine (CA) excretion and the response of BP and plasma CA to the tilt test have been investigated in 13 untreated patients affected by Parkinson's disease (PD) and in 11 age-matched healthy controls. Seven of the 13 PD subjects showed a fall of supine systolic BP greater than that in controls (ie, exceeding 20 of the preprandial value). A significant relationship was found in the PD group between the degree of postprandial hypotension and the 24-hour mean value of dopamine excretion. Eight PD subjects also showed orthostatic hypotension during the tilt test (performed in the morning hours) and in the postprandial phase. Basal norepinephrine plasma levels of PD patients, as well as their percentage increases on standing, were within the range of the controls. These data suggest the existence of a subtype of PD patient, characterized by a widespread impairment of cardiovascular responsiveness and bordering on syndromes of autonomic failure such as progressive autonomic failure or multiple system atrophy, or both.

The regulation of prolactin (PRL) secretion periodicity in cluster headache (CH) and in atypical facial pain (AFP) has been studied in nine and seven patients, respectively. The physiological periodicity of the hormone secretion, with its highest levels during night sleep and its lowest during the waking hours, is upset in CH, but not in AFP. A rhythmicity occurs in CH only in the presence of severe pain, which appears to be the synchronizing event. Lithium carbonate treatment does not interfere with the mentioned changes in PRL secretion in CH.

To investigate the comorbidity of premenstrual syndrome (PMS) and menstrual migraine, the Menstrual Distress Questionnaire (MDQ) was prospectively administered for two consecutive menstrual cycles to 22 patients with menstrual migraine, 12 cases with migraine without aura and 15 patients with PMS. MDQ scores varied throughout the menstrual cycle in each patient group, the wider changes being shown by patients with PMS. Fourteen menstrual migraine patients and 4 migraine without aura patients achieved diagnostic criteria for PMS over two menstrual cycles. In these patients MDQ scores did not differ from PMS sufferers at any stage of the menstrual cycle. The premenstrual increase of each cluster of PMS symptoms was identical in menstrual migraine and PMS subjects with the exception of negative affect. We suggest that PMS symptoms should be taken into account in the IHS diagnostic criteria for menstrual migraine.

Secondary saccades bring the fovea on the target missed by primary saccades. The authors studied secondary saccades in the responses recorded from 76 healthy subjects during a normal refixation paradigm, focusing their attention on their latency (L2). L2 proved to be negatively related to target amplitude and positively to precision and latency of the corresponding primary saccade; the authors were not able to find any linear relationship with subject's age. On the basis of these relationships, they determined a three-class L2 distribution: decreased, normal and increased L2. A subject can be reliably evaluated comparing (chi-square test) his own frequency of L2 values belonging to each class with the frequencies observed in the controls; if a difference exists, the Kimball test enables the identification of the class from which this difference possibly arises.

Two groups of patients affected by Parkinson's disease (PD) were studied by electroretinography during dark adaptation (AERG) and visual evoked potentials (VEPs): nine patients had never been treated before and 31 were on therapy with L-Dopa plus Carbidopa. A significant reduction in amplitude of the 'b1' wave and 'a' wave and a significant delay of P1 wave with reduction of N1-P1 amplitude in VEPs were observed in both groups. A relationship between AERG and VEP alterations was found only in the group of patients treated with L-Dopa plus Carbidopa (p<0.02) and in the total group (p<0.05). Moreover, the degree of electrophysiological abnormalities was neither related to the severity of disease, nor to the duration of therapy and dosage. Retinal dysfunction in PD may be related to neurotransmitter abnormalities observed in this condition.

Menstrual migraine (MM) is a menstrually related disorder (MRD) characterized by several symptoms in common with premenstrual syndrome (PMS). It has been hypothesized that in both MM and PMS hormonal cyclicity could change the balance of neurotransmitters and neuromodulators like monoamine and opioid. In this article we analyze all the data collected by our group on the central opioid tonus and the adrenergic and serotonergic systems in patients affected by menstrual migraine.

Neuropeptide Y, one of the most abundant polypeptides within the nervous system, is co-stored with catecholamines, especially norepinephrine (NE), thus suggesting its possible involvement in pathologies characterized by a noradrenergic impairment. In Parkinson's disease (PD), as well as in multiple system atrophy (MSA), a central noradrenergic deficit has been demonstrated, and in the dementia of Alzheimer type (DAT) an impaired noradrenergic transmission has been postulated. In this study we determined CSF NE and MHPG levels in 29 PD, 15 MSA, 22 DAT patients and in 36 controls, while CSF NPY-immunoreactivity (NPY-ir) levels were measured in 10 PD, 7 MSA, 10 DAT patients and 20 controls. PD, MSA, and DAT patients showed a significant reduction in CSF NPY-ir and NE levels compared with controls, while CSF MHPG levels resulted in a reduction in only the MSA group.

An impairment of the monoaminergic systems has frequently been reported for Alzheimer's disease (AD) as well as an overactivity of cerebral monoamineoxidase B (MAO-B).

Chronic alcohol consumption has been shown to be associated with abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis in humans. However, conflicting data exist in the literature, with particular regard to studies performed in actively drinking or withdrawn alcoholics; in addition, the frequent presence of depressive disturbances in such patients may importantly affect the neuroendocrine findings. In this study, we investigated HPA function in 12 male alcoholics, in whom the presence of depression and other possible confounding factors was excluded, during the first and second weeks after cessation of ethanol intake. The plasma corticotropin (adrenocorticotropic hormone, ACTH) and cortisol levels in response to both a stimulation test with human corticotrophin-releasing hormone (CRH; 100 @mg IV) and an insulin (0.15 UI/kg IV)-induced hypoglycaemia (ITT) were measured; the cortisol response to a standard overnight dexamethasone (1 mg) suppression test (DST) was also tested. While the mean baseline ACTH and cortisol levels, measured in the morning (0800-0830h), were not different from those of controls, ACTH and cortisol responses to the CRH test were markedly reduced (area of secretion p < .01 and p < .05, compared to controls). Similarly, the patient group showed an almost absent ACTH and cortisol release following insulin infusion (area of secretion p < .01 compared to controls, in either case). In four patients, non-suppression of plasma cortisol levels was seen on the DST, but no significant difference from normal suppressors was noted as far as the clinical features were concerned. These findings suggest that impaired hypothalamic and pituitary responsiveness, unrelated to depressive disturbances, occurs in recently withdrawn chronic alcoholics. While the possible influence of the alcohol withdrawal syndrome shoud be taken into account, such a pattern may be due to increased activity of the HPA axis, even in the face of preserved basal adrenal secretion. Whether these findings reflect a direct effect of sustained ethanol exposure on the components of the HPA axis, or a non-specific marker of impaired adaptation in chronic alcoholics, deserves further investigation.

Introduction Headache is commonly considered a prevailing feature of the female condition. It is not a chance that headache is often regarded as one of the main factors making females occasionally unable to do something, not only in fiction but also in reality. On the other hand, besides anecdotal considerations, epidemiological data highlight hormonal changes among the major factors in headache. Hormones and brain are mutually strictly related so as to be considered a unique functional entity, namely, the neuroendocrine system. In fact, hormones are influenced by the central nervous system (CNS), while they also exert several different actions on the brain'. The key structure where most of these influences occur is the hypothalamus. Here the vegetative, emotional and temporal functions essential for living and being, both in the environment and time, are integrated and transduced into order signals that the endocrine system can execute. Most activities or diseases of the endocrine gland are not relevant to primary (idiopathic) headaches. Glands as pituitary, thyroid, adrenal or pancreas can be involved in the factors triggering headache attacks and can participate in the behavioural reactions connected with head pain. However, in most instances they are co-workers rather than protagonists.

A nocturnal polysomnographic study with infrared video-monitoring was performed in ten patients with multisystem atrophy with autonomic failure (MSA-AF) (seven males, three females; median age: 54 years), selected irrespective of the presence of sleep complaints. The MSA-AF patients showed disrupted sleep patterns. Quantitative and qualitative alterations of REM sleep were found, some of which resembled those seen in patients with REM sleep behaviour syndrome. However, only one patient reported episodes of REM behaviour. Six patients showed arterial oxyhaemoglobin (HbSaO2) drops below 90% during sleep in relation to recurrent apnoeas or hypopnoeas (HbSaO2 nadir 70%). The apnoea hypopnoea index was above the upper limit of the normal range in three of these patients in the absence of obesity or bronchopulmonary diseases. Among patients with sleep-related breathing impairment, laryngeal stridor (three cases) or snoring (one case) were observed. Patients with sleep-related breathing disorders (SBD) exhibited a higher degree of autonomic dysfunction than patients without SBD.

We studied the levels of free plasma noradrenaline (norepinephrine, NE), adrenaline (epinephrine, E), and dopamine (DA) in 143 normal subjects, either basally or, in a part of them, in response to tour tests stimulating the sympathoadrenomedullary activity: the tilt-table test (TTT), the cold-pressor test (CPT), the mental-arithmetic test (MAT), and the insulin tolerance test (ITT). In both cases we evaluated the influence of age, which is considered the main physiological variable affecting the peripheral sympathetic activity. A normal distribution of values was observed, in the basal study, only for NE, while E and particularly, DA levels were distributed in an non-homogeneous fashion; a direct correlation was observed between age of subjects and NE levels, while neither E, nor DA levels showed any correlation with the aging process; sex did not influence any of the catecholamines.In the dynamic study, CPT, ITT and, above all, TTT elicited a significant rise in NE levels, while the E release was greatly stimulated by the insulin-induced hypoglycaemia. Neither NE, nor E levels rose after the MAT stimulation. Also in this case, the elderly showed an increased noradrenergic responsiveness when compared with the young subjects, confirming the existence of an 'up-regulation' of the peripheral sympathetic tone in old people.

The authors report two cases of catechol-O-methyltransferase (COMT) inhibitor–induced asymptomatic hepatic dysfunction in women with Parkinson disease. The patients were genotyped for the UDP-glucuronosyltransferase (UGT) 1A9 gene (which encodes the main COMT inhibitor-metabolizing enzyme), and found to carry mutations leading to defective glucuronidation activity. This suggests that UGT1A9 poor metabolizer genotype(s) may be a predisposing factor for COMT inhibitor–induced hepatotoxicity.

The aim of this study is to make an evaluation of the activity of endogenous opioid tonus in patients affected by menstrual migraine. We tested the LH response to naloxone injection, an opiate receptor antagonist, in 18 migraineurs in the early and late luteal periods going towards the attacks. The lack of any response in the latter group demonstrates an opioid disregulation in this kind of pathology.Notre but a été l'études des eventuelles variation du systèm opioide chez des patientes souffrantes de maladie migraineuse en phase premenstruelle. On a mesurés la reponse de la LH a la stimulation par le Naloxone, antagoniste des recepteurs aux opiates, chez 18 femmes souffrantes de maladie migraineuse, en phase luteale moyenne et tardive. Pendants les jours immediatements precedents les règles, cette réponse a totalment fallu etant condictionnée positivement par l'augmentation du rapport Progesterone/Estradiole. Ces donnés demontrent l'existence, chez ces patientes, d'une alteration du tonus opioides.Scopo della presente ricerca è la valutazione delle modificazioni del tono oppioide centrale nel corso del ciclo mestruale di pazienti affette da cefalea catameniale. E stata valutata la risposta dei tassi plasmatici di LH alla stimolazione endovenosa con Naloxone, antagonista dei recettori per gli oppioidi, in 18 pazienti nel corso della fase luteale media e tardive del ciclo mestruale. In fase premestruale questa risposta neuroendocrina è totalmente assente e sembra essere modulata dal rapporto Progesteron/Estradiolo, sostenedo l'esistenza di una sregolazione del tono oppioide nelle cefalee catameniali.

Platelets and monoaminergic neurons share many morphological, biochemical, and pharmacological properties. In addition to its similarities to serotonergic nerve endings, the platelet has also been considered a good model for the study of the noradrenergic function, since it can selectively take up, store, and release norepinephrine (NE).