Cognitive [correction of cognitve] estimation: comparison of two tests in nondemented parkinsonian patients.

The Time and Weight Estimation test (STEP) and the Cognitive Estimation Task (CET) are two recently devised tests for the assessment of cognitive estimation. In the present study, we compared their performance in 30 non-demented idiopathic parkinsonian (PD) patients, also evaluated with the Frontal Assessment Battery (FAB) as an index of executive impairment, with the aim of verifying the putative frontal circuitry of cognitive estimation processes. Six patients (20%) showed a pathological performance on either or both tests. After division of the PD sample into tertiles based on the FAB score, no significant difference was detected by either estimation test. Furthermore, the two questionnaires were unrelated to each other. Thus, deficits of cognitive estimation ability appear to be mild in PD without dementia and do not correlate with executive impairment. Unexpectedly, the CET and the STEP seem to have no unique underlying construct.

Physical anhedonia in Parkinson's disease.

Anhedonia is the inability to experience physical or social pleasure. Its physical component is hypothesised to be due to dysfunction of a dopaminergic frontotemporal-subcortical circuit and has never been investigated as a possible affective complication of Parkinson's disease (PD). The aim of this study was to formally assess prevalence and correlates of physical anhedonia in PD patients compared with normal controls. Twenty five people with PD and 25 matched controls were administered a psychometric battery exploring mainly executive functions and mood. Hedonic tone was assessed using Chapman's Physical Anhedonia Scale. PD patients also underwent MRI linear measurement of frontal structures. Anhedonia levels were significantly higher in PD patients with respect to controls, although not extremely elevated; prevalence rate was 40% for parkinsonians, while no anhedonics were found among controls. Clinical, neuropsychological, and quantitative neuroradiological features did not show any significant correlation with physical anhedonia. Physical anhedonia appears to be a relatively frequent, although mild, affective disturbance of PD, independent from neurological, frontal, and depressive aspects.

Deep brain stimulation for the treatment of Parkinson's disease: the experience of the Neurosurgical Department in Monza.

deep brain stimulation is a widely accepted surgical therapy for the symptomatic treatment of advanced parkinson's disease; high frequency chronic stimulation of the subthalamic nucleus proved its efficacy to control the major motor symptoms. In the neurosurgical department of Monza we treated 72 parkinsonian patients (November 1998-January 2003). One year follow-up results are: decrease of tremor 90%, hypertonous 56%, bradykinesia 70%, voice impairment amelioration 30%, mean total daily L-dopa intake reduced 58%. Freezing and balance did not ameliorate, some voice impairment and psychic derangement have been observed. Major surgical complications were: haemorrage (1 case - transient hemiparesis), infections (2 cases), pulmonary embolisation (1 case). To optimise the surgical results, careful clinical and instrumental selection of the patients are mandatory before surgery.

Physiologic study of the subthalamic volume.

Deep brain stimulation (DBS) obtains good control of advanced PD symptoms. Chronic stimulation of Stn may alleviate rigidity, dyskinesia and tremor. Anatomical and functional intraoperative mapping are mandatory to obtain careful target localisation. Per-operative macrostimulation was carried out in 22 patients undergoing bilateral DBS in Stn; a volume 6 mm above to 4 mm below Stn was explored. Positive, collateral and adverse effects were recorded every 2 mm. Results obtained during acute stimulation were correlated to anatomical data from stereotactic atlases. Our findings suggest a volume, encompassing the zona incerta, Forel's fields and the lowermost part of anterior thalamus, functionally homogeneous to Stn. In fact, the stimulation of this volume obtains reduction of PD symptoms comparable to Stn.

Decreased platelet glutamate uptake and genetic risk factors in patients with Parkinson's disease.

Genetic risk factors seem to play a role in sporadic Parkinson's disease (PD), maybe triggering oxidative stress and excitotoxicity within substantia nigra. However, genetic factors act at systemic level: reduced activity of mitochondrial enzymes and decreased glutamate uptake have been shown in platelets from PD patients. In this study we investigated glutamate uptake in platelets from 38 sporadic PD patients, 13 patients with parkinsonian syndromes and 28 controls and assessed polymorphisms of alpha-synuclein and ApoE genes. A 48% reduction of glutamate uptake p)<0.0001) was observed in PD patients which, with respect to control groups, correlated with the disease severity (r = -0.44, p < 0.05). Genetic studies of this population did not show differences between PD and controls, nor correlations with platelet glutamate uptake.

Glutamate uptake is decreased in platelets from Alzheimer's disease patients.

Because excitotoxicity may be involved in neurodegeneration in Alzheimer's disease, we investigated possible modifications of platelet glutamate uptake in AD patients. High-affinity glutamate uptake was studied in platelets from 35 Alzheimer's disease patients, 10 multi-infarct dementia patients, and 35 age-matched normal controls; it was decreased by 40% in platelets from Alzheimer's disease patients compared with controls and with multi-infarct dementia patients. Platelet glutamate uptake could be used as peripheral marker of glutamatergic involvement and as adjunctive diagnostic tool in Alzheimer's disease patients.

Reduced platelet glutamate uptake in Parkinson's disease.

Defects in mitochondrial enzymes have been found not only in substantia nigra, but also in platelets from Parkinson's Disease (PD) patients, suggesting a systemic impairment of energy metabolism. Since platelets present an energy-dependent glutamate uptake similar to that described in central nervous system, glutamate uptake was determined in platelets from 34PD patients and 21 age-related normal controls, as Na+-dependent [3H]glutamate influx; glutamate level was also analyzed by reverse-phase HPLC. A 50% reduction of glutamate uptake (p < 0.001) was observed in idiopathic PD patients, respect to controls and secondary parkinsonian syndromes. The decrease correlated with the severity of PD, measured by the UPDRS (r = -0.54; P < 0.05). Glutamate level was increased in platelets of PD patients, but was not correlated to the uptake decrease. Both phoenomena may be explained by the modifications of mitochondrial enzymes described in platelets, which could be used as a peripheral model of glutamatergic function in PD.

Listeria rhombencephalitis: report of two cases with early diagnosis and favourable outcome.

We present 2 cases of Listeria monocytogenes rhombencephalitis (L-RE), both affecting previously healthy adult men. Each of them developed a diphasic syndrome first characterized by fever, nausea and headache, followed, in a second phase, by severe brain stem dysfunction at the level of the pons, with meningism, multiple cranial nerve palsies, ataxia, and, in one case, seizures. The early examination of the cerebrospinal fluid (CSF) demonstrated the presence of Gram-positive bacilli whose typical characteristics were compatible with those of Listeria, allowing for immediate administration of a specific therapy. Neuroimaging techniques (either CT or MRI) did not provide any evidence of brain stem involvement, and they did not positively contribute to the diagnostic process. The immediate use of a specific antibiotic therapy led to a favourable clinical outcome for both patients.

Proglumide, a cholecystokinin receptor antagonist, reduces neuroleptic action in Huntington's chorea.

In a pilot study, proglumide, a cholecystokinin receptor antagonist, was administered to 8 patients affected from Huntington's chorea under long-term haloperidol treatment. The effectiveness of haloperidol on chronic symptomatology was reduced by the concomitant administration of proglumide; the latter drug, when administered alone, did not modify the severity of chorea compared to placebo. Possible explanations of these results are discussed, stressing the modulatory role of CCK not only on the dopaminergic, but also on the GABAergic system.

Comparison of the efficacy, safety and withdrawal of alpidem and alprazolam in anxious patients.

BACKGROUND: We investigated whether a new non-benzodiazepine anti-anxiety drug, alpidem, produces weaker withdrawal symptoms than alprazolam. METHOD: Under a double-blind procedure, 122 patients suffering from general anxiety disorders were randomly allocated to either alpidem (50 mg, three times a day) or alprazolam (0.5 mg, three times a day) for six weeks, followed by a two-week placebo withdrawal phase. The diagnosis of withdrawal syndrome (WS) was made, in blind conditions, on the basis of the Withdrawal Symptom Check List (WSCL), after one or two weeks of discontinuation of active treatment. RESULTS: The WS occurred significantly less frequently in the alpidem group (n = 10, 18%) than in the alprazolam group (n = 26, 48%). Typical withdrawal symptoms on the WSCL were also significantly less severe (P = 0.044) in the alpidem group compared with the alprazolam group. CONCLUSIONS: Alpidem may be a valid alternative to current benzodiazepine anxiolytic therapy because it produces fewer and weaker withdrawal symptoms than alprazolam and is better tolerated.

Effects of alpidem in anxious elderly outpatients: a double-blind, placebo-controlled trial.

The efficacy and safety of alpidem, a new anxiolytic imidazopyridine, were compared with those of placebo in anxious elderly patients (65-80 years) by means of a randomized, double-blind, parallel group study. Following a 7-day "placebo run-in," 40 anxious patients were randomized to receive either alpidem or placebo. Daily doses ranging from 75 to 150 mg (25-50 mg t.i.d.) were administered for 3 weeks. Hamilton Rating Scale for Anxiety (HRSA), State Trait Anxiety Inventory (STAI-X1), Visual Analogue Scale (VAS), and Clinical Global Impression (CGI) were used on days 0, 3, 7, 14, and 21 for assessing efficacy. Psychomotor and mnesic performances were evaluated at the same time by means of the Digit Symbol Substitution Test (DSST), the Grünberger's test for fine motor coordination, and the Hawie's test for immediate memory. Possible adverse events were also recorded during the five visits. The anxiolytic efficacy of alpidem was significantly (p < 0.01) superior to that of placebo in all the rating scales adopted. The anxiolytic action was clearly evident from day 7. For most of the patients the active dose was 25 mg t.i.d. No relevant adverse effects were observed in both groups. No impairment of psychomotor and mnesic performances could be observed in the alpidem group. Alpidem is a new interesting anxiolytic drug for anxious elderly patients because it appears remarkably safe and, at effective doses, it does not impair psychomotor performances and cognitive functions.

Treatment of Parkinson's disease with proglumide, a CCK antagonist.

Proglumide, a cholecystokinin antagonist, did not improve Parkinson's disease in a preliminary drug treatment trial.

Effects of a MAO-B inhibitor in the treatment of Alzheimer disease.

119 patients were enrolled in a double-blind randomized parallel study versus placebo carried out to assess both the efficacy and tolerability of L-deprenyl (10 mg/day) for treatment of patients with organic mental disorders of the Alzheimer type (DAT). The treatments were given for 3 months, starting after a run-in period of 15 days to evaluate efficacy. A complete neuropsychological battery was administered monthly after the start of treatment whereas tolerability was assessed by checking, recording and classifying all the unfavorable experiences occurring. According to the results, L-deprenyl would seem to be a useful and reliable tool for the treatment of DAT patients in an attempt to improve their cognitive functions and reduce behavioral alterations, without frequent or severe side effects.

Interobserver reliability between neurologists in training of Parkinson's disease rating scales. A multicenter study.

A multicenter study has been conducted to determine the interobserver reproducibility of four of the most frequently used rating scales for Parkinson's disease: the Columbia University Rating Scale (CURS) and the Webster Rating Scale (WRS), both for assessing clinical signs; the Northwestern University Disability Scale (NUDS); and the Hoehn and Yahr staging. Four resident neurologists, inexperienced in the use of the four scales, independently examined 48 parkinsonian patients. The extent to which their assessments agreed was determined by calculating the Cohen k index after the scores had been recodified. The physicians' scores agreed substantially for the CURS and the Hoehn and Yahr scale, while those for the NUDS and the WRS agreed only moderately. Analysis of individual item scores within the scales suggests improvements that would offer greater interobserver consistency.

Decreased density of benzodiazepine receptors in lymphocytes of anxious patients: reversal after chronic diazepam treatment.

Peripheral-type benzodiazepine receptors were measured in human circulating lymphocytes using 3H-PK 11195 as specific ligand. In a group of outpatients with anxiety disorders a significant decrease of receptor density (-37%) was found compared with age-matched controls. In these patients long-term diazepam treatment restored binding density to normal levels: the effect persisted after drug withdrawal. Acute i.v. diazepam administration did not change receptor density. The observed receptor changes could reflect a down-regulation phenomenon and indicate that lymphocyte function reflect central nervous events.

Cerebrospinal fluid levels of diazepam-binding inhibitor in neurodegenerative disorders with dementia.

We investigated CSF levels of diazepam-binding inhibitor (DBI), a recently discovered neuropeptide that allosterically modulates GABAergic transmission, in various neurodegenerative disorders with dementia (28 patients with Parkinson's disease, 10 with Alzheimer's disease, 7 with Huntington's chorea). We applied a battery of neuropsychological tests to determine the degree of dementia and to exclude the presence of mood alterations. CSF DBI levels were elevated in parkinsonian subjects with dementia and in patients with Alzheimer's disease, but decreased in Huntington's chorea patients. We hypothesize that modifications of CSF DBI levels may be related to a functional or structural alteration of the GABAergic system.

Decrease in phorbol ester receptors in human brain tumors.

We have characterized the specific binding of [3H]-phorbol-12,13-dibutyrate in the white and gray matter of normal human brain and in cerebral tumors as an index of the availability of protein kinase C enzyme molecules. White matter has less than 50% phorbol-ester-binding capacity in comparison to gray matter. The binding is lower in tumors of glial origin when compared with normal white matter. Tumors of nonglial origin such as neurinoma and meningioma have a lower binding capacity than glial tumors. Metastatic tissues have the lowest binding capacity. The analysis of binding parameters in tumors and in the corresponding normal peritumoral tissues confirms the decreased binding capacity of neoplastic tissues in comparison to tissues not undergoing malignant transformation. These data suggest that brain glial tumors have a low availability of protein kinase C enzyme molecules and point to the potential involvement of this system in malignant transformation of human brain cells.

Benzodiazepine receptors and diazepam-binding inhibitor in human cerebral tumors.

Benzodiazepines can regulate neoplastic growth and immune response through specific peripheral benzodiazepine receptors. We investigated the presence of peripheral and classic central benzodiazepine receptors as well as diazepam-binding inhibitor, an endogenous ligand of both types of receptors, in different human cerebral tumors. Peripheral benzodiazepine receptors were present in all the tumor types studied, whereas central benzodiazepine receptors and diazepam-binding inhibitor were detectable in astrocytomas and glioblastomas and undetectable in meningiomas, neurinomas, and metastases. The role of diazepam-binding inhibitor and of the different benzodiazepine receptors in neoplastic cells is still to be defined.