Muscarinic cholinergic mediation of the GH response to gamma-hydroxybutyric acid: neuroendocrine evidence in normal and parkinsonian subjects.

We have recently reported that parkinsonian patients show a significant GH response to gamma-hydroxybutyric acid (GHB), but not to gamma-aminobutyric acid (GABA)-ergic drug administration. In order to establish whether muscarinic cholinergic receptors mediate the GH secretion induced by GHB, normal men and parkinsonian patients were tested with GHB both in the absence and in the presence of the anticholinergic agent, pirenzepine. Both normal controls and parkinsonian patients showed a significant serum GH rise in response to GHB (25 mg/kg body weight p.o.) even though a slightly, but significantly lower response was observed in parkinsonian patients. Pretreatment with pirenzepine (100 mg p.o. 2 h before GHB) completely suppressed the GHB-induced GH release in both normal controls and parkinsonian patients. These data indicate that a cholinergic mechanism mediates the GH response to GHB in normal men. In addition the data indicate that this pathway is preserved in the parkinsonian brain.

Depression after stroke: an investigation through catamnesis.

BACKGROUND: In the early stage of stroke, depression appears to be linked to certain brain areas. The study evaluated the importance of the side of the lesion in depressed patients 3 years after their first stroke. METHOD: Patients who had suffered a stroke and been discharged after rehabilitation were identified by hospital records. We interviewed 180 patients at home. Demographic as well as socioeconomic data were collected. The North-western University Disability Scale, the Beck Depression Inventory (BDI), the Relatives' Stress Scale, and the Social Dysfunction Rating Scale were applied. The diagnosis was confirmed for each patient by a clinical assessment according to the ICD-10 criteria. Patients with previous psychiatric treatment, comprehension problems, or severe hemi-inattention were excluded. RESULTS: By using a score of 14 on the BDI as a cutoff, 62 patients (34%) proved to be affected by depressive disorders. Clinical records showed that the location of the lesion was in the right hemisphere for 37 patients and in the left hemisphere for 25 patients. Statistical analysis of the mean scores obtained in this subgroup of depressed patients showed (1) no significant relation between depression and the hemispheric location of the lesion or between depression and level of education; (2) relation between BDI score and social activities; and (3) stress on the relatives that was mainly dependent on both the disability of the patients and their loss of social activities, whereas depression played a minor role. CONCLUSION: A high percentage of patients have depressive disorders 3 years or more after the stroke, independent of the side. Such mood disorders worsen the relationship between the disabled patients and their relatives and worsen leisure independent of the affected hemisphere.

ACTH/cortisol involvement in the serotonergic disorder affecting the parkinsonian brain.

In order to establish whether the serotonergic disorder affecting the parkinsonian brain also modifies hypothalamic-pituitary function in Parkinson's disease, 10 patients (aged 57-66 years) and 10 normal controls (aged 55-69 years) were tested with the serotonergic agonist d,l-fenfluramine (60 mg p.o.), with CRH (100 micrograms i.v.) and with placebos. Plasma ACTH/cortisol levels during tests were evaluated and compared. Both groups showed similar levels of ACTH and cortisol in basal conditions and after placebo administration. A slight physiological decline in both ACTH and cortisol levels during the placebo test was observed in normal controls and parkinsonian patients. CRH induced similar ACTH/cortisol increments in all subjects. In contrast, d,l-fenfluramine significantly increased plasma ACTH/cortisol concentrations in the normal controls, but not in the parkinsonian patients. These data show a defective serotonergic control of the pituitary-adrenal axis in Parkinson's disease.

Defective 5-HT 1-receptor-mediated neurotransmission in the control of growth hormone secretion in Parkinson's disease.

In order to gain a better insight in the serotonergic disorder affecting the parkinsonian brain, the growth hormone (GH) response to the 5-HT 1 serotonergic receptor agonist sumatriptan was tested. Sumatriptan was injected subcutaneously in 10 de novo parkinsonian patients (aged 58-69 years) and in 9 age-matched normal controls. On different occasions, subjects were also tested with GH-releasing hormone (GH-RH; 1 micrograms/kg body weight in an intravenous bolus) and L-arginine (30 g in 50 ml normal saline over 30 min), which releases GH from somatostatin inhibition, to determine whether GH secretion in response to alternate secretagogues is preserved in Parkinson's disease. In addition, a control test with the administration of normal saline instead of drug treatments was performed. Plasma GH levels were recorded over 2 h in all tests. Placebo administration did not change plasma GH levels in any subject. Similar GH responses were observed in normal controls and parkinsonian patients when GH-RH or arginine were administered. A significant GH increase was observed in normal controls after sumatriptan injection; in contrast, GH secretion was not modified by sumatriptan administration in parkinsonian patients. These data show that Parkinson's disease is associated with an impairment in the 5-HT1-receptor-mediated serotonergic transmission in the control of GH secretion, suggesting that this specific defect might alter other serotonergic-mediated mechanisms in the parkinsonian brain.

beta,beta'-Iminodipropionitrile-induced persistent dyskinetic syndrome in mice is transiently modified by MPTP.

Chronic administration of iminodipropionitrile (IDPN) is known to produce a persistent dyskinetic syndrome. Recent neurochemical reports seem to point out the dopaminergic system as having an important role in mediating IDPN syndrome. In order to identify a possible role for the nigrostriatal dopaminergic pathway in determining at least some aspects of the IDPN-induced dyskinetic syndrome, we used the neurotoxin, 1-methyl, 4-phenyl,1,2,3,6-tetrahydropyridine (MPTP), as a tool for investigating which aspects of the IDPN-related syndrome could be due to enhanced dopaminergic activity in the neostriatum. In mice made permanently dyskinetic with IDPN, MPTP administration produced dramatic and biphasic effects on all behavioral patterns characteristic of the dyskinetic syndrome. Six weeks after the syndrome occurred, IDPN failed to produce any change in striatal DA levels with respect to controls. By contrast, IDPN seems to reduce striatal levels of extraneuronal metabolites of DA. These data suggest that the activity of the nigrostriatal dopaminergic pathway does not play a leading role in the maintenance of IDPN-related syndrome. The transient modification of all behavioral parameters immediately after MPTP administration could be explained by acute effects of MPTP on other dopaminergic areas which are not permanently lesioned by this neurotoxin, or by the acute effects of MPTP on the release of other neurotransmitters.

Lack of ACTH/cortisol and GH responses to intravenously-infused substance P in Parkinson's disease.

In order to test possible changes in the stimulating effect of intravenously-infused substance P (SP) on ACTH/cortisol and GH secretion in Parkinson's disease, 10 male parkinsonian patients and 10 age-matched normal controls were infused intravenously for 60 min with SP (1.0 or 1.5 pmol/kg-1/min-1 SP) or normal saline. The circulating levels of ACTH, cortisol and GH were measured during and for 20 min after SP or saline infusion. No untoward side effects or changes in blood pressure were observed during SP infusion in any subjects. In basal conditions and during saline infusion, plasma ACTH and cortisol levels were similar in normal and parkinsonian patients. During SP infusions, ACTH/cortisol concentrations in normal controls rose significantly vs baseline and saline test in a dose-dependent fashion. In contrast, at both SP infused amounts, parkinsonian patients showed ACTH/cortisol levels similar to those observed in the saline test. All subjects showed similar basal concentrations of GH. GH levels rose significantly in the normal controls when the higher dose of SP was infused, but they were not modified by the infusion of the lower dose of SP or saline. At both tested amounts of SP and during saline infusion, GH levels remained unchanged in the parkinsonian subjects. In agreement with previous observations in the literature showing SP abnormalities in the parkinsonian brain, these data fail to show significant effects of plasma SP on the ACTH/cortisol and GH secretory systems in Parkinson's disease.

Sneddon's syndrome and primary antiphospholipid syndrome: a case report.

The association between livedo reticularis and cerebrovascular accidents is known as Sneddon's syndrome. We describe a case in which Sneddon's syndrome appeared as a clinical manifestation of primary antiphospholipid syndrome.

[Cerebral cortex and HIV lesion specificity. A neuropathological study of the brain of 100 drug addicts]. / Corteccia cerebrale e specificità lesionale HIV. Studio neuropatologico sull'encefalo di 100 tossicodipendenti.

Brains of AIDS patients do often display characters of HIV specificity, in the presence or not of opportunistic lesions. Mesodermal nodules with giant cells, and a peculiar primary demyelination, the progressive diffuse leukoencephalopathy of Kleihues et al., which can be found only in brains with giant cells, have been pointed out as typical. In 100 intra venous drug user patients, younger than 32 years (mean age: 26) the HIV specificity described was observed on 49 occasions. All these patients presented with Seitelberger's glio-neuronal poliodystrophy (GP), quite similar to that encountered in several kinds of encephalopathies. Nevertheless, in 35 of the patients with HIV typical findings, there was in the cortex and some other grey matter regions, an amount of diffuse mesodermal elements uncommon in encephalopathies, and so relevant as to contradict the notion itself of this kind of cerebral lesion, where "inflammatory" events ought not to appear. This aspect of HIV encephalopathy was indicated by us as "GP plus". An optic microscopy examination of the cortex allowed us to establish how in GP plus the neuronal changes are more severe and apparently older than in the other patients considered. The fact that the astrocytes did not behave differently in the two aspects of encephalopathy lead us to conclude that GP plus sets in through processes distinct from those in encephalopathy tout-court, and to put forward that it is a further character of HIV specificity.

[Dissection of the internal carotid artery. Personal case reports and a review of the literature]. / Dissecazione dell'arteria carotide interna. Casistica personale e revisione della letteratura.

The clinical and angiographic features of 20 patients affected by internal carotid artery dissection are reported. In one patient the neurological signs were related to a traumatic event, in two cases the symptoms presented after hyperextension of the neck during athletic events, while their onset was apparently spontaneous in the remaining 17 patients. Plain CT was normal in 14 cases and positive for ischemic necrosis in 6 patients. Angiography demonstrated extensive/segmental stenosis of the internal carotid lumen in 12 cases (60%), pseudoaneurysmal dilatation in 3 cases (15%), and complete carotid occlusion in 5 patients (25%). The "double lumen" feature was seen in 3 cases at the origin of the dissection. One patient died, surgical ligature of the internal carotid artery was performed in two cases, while the other patients received medical treatment with platelet inhibitors, except for the young patient affected by post-traumatic artery dissection. Complete recovery was observed in 82% of the patients. Follow-up angiograms demonstrated normal recanalization of the internal carotid artery in 4 out of 6 patients; one of them had two false aneurysms which following angiograms demonstrated to be completely resolved. Regression of stenosis was observed in 6 of the remaining patients by Doppler US. On the whole, the recanalization of the internal carotid artery was observed in 59% of cases. Angiographic findings seemed not to play a decisive role in the prognosis of carotid dissections, which largely depends on the overall patient's condition and on the presence/absence of ischemic cerebral damages.