A multicentre study with an open experimental design was carried out on 118 patients suffering from mild to moderate cognitive decline due to cerebrovascular and degenerative disorders (chronic cerebrovascular disorders, CCVD; multi-infarct dementia, MID; aging brain, AB; dementia of Alzheimer's type, DAT). All patients, after a wash-out period of 3 weeks, were treated with idebenone (45 mg twice daily by oral route) for a period of 6 months. Behavioral and cognitive measures (Sandoz Clinical Assessment of Geriatrics, SCAG; Serial Learning Test) were applied to evaluate the long term therapeutical aspects. The results, analyzed by multivariate analysis of variance and chi2 test, showed a significant improvement of the cognitive profile in all patients, more evident in CCVD and AB groups. No remarkable side-effects were found in all groups of patients, thus confirming good tolerability of idebenone.

Journal Article↗

PubMedDate not supplied

Different patterns of central and peripheral beta EP, beta LPH and ACTH throughout life.

The aim of the present study was to evaluate the relationship between central and peripheral concentrations of proopiocortin-related peptides in different periods of life. One hundred and eighty-nine plasma samples from normal subjects (18-87 years) obtained in basal conditions, and 20 cerebrospinal fluid (CSF) samples obtained by lumbar puncture from healthy volunteers (18-75 years) were studied. beta Lipotropin (beta LPH), beta endorphin (beta EP) and ACTH were measured by specific RIA after silicic acid plasma extraction and gel chromatography (beta LPH and beta EP). No sex differences were found in the patterns of the three peptides either in the plasma or in CSF. In the plasma samples, both beta LPH and beta EP concentrations showed a pattern throughout life which was expressed by a paraboloid function with the lowest values found in young and old subjects and with peaks at 51.3 and 48.2 years, respectively. On the contrary, ACTH values failed to be represented by a significant linear or curvilinear regression and presented only a slight decrease in subjects over 75 years of age. CSF levels of beta LPH were significantly lower in 45-76 year old subjects (18.8 +/- 12.6 fmol/ml, M +/- SD) than in 18-44 year old subjects (34.5 +/- 15.8; p less than 0.05), as were those of beta EP (elderly: 41.2 +/- 19.7; young: 94.2 +/- 36.7; p less than 0.05), which showed a significantly linear inverse correlation with age (r = 0.6062, p less than 0.01). These CSF samples did not show any ACTH variations connected with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Neurotensin-induced miosis: the role of dopaminergic pathways.

In this study we investigated the role that dopaminergic pathways play in the miotic effect exerted by neurotensin after intracameral administration. Neurotensin was injected into the anterior chamber (AC) at a dose of 30 micrograms to 4 groups of albino rabbits which had previously undergone the following treatment: a) desmethylimipramine IM and, after 30 min, 6-hydroxydopamine IV 7 days prior to the neurotensin administration; b) haloperidol IM for 15 days; c) haloperidol AC 10 minutes before the neurotensin administration. Our data confirm previous observations regarding the miotic activity of neurotensin and suggest that the dopaminergic system plays an important role in the miotic effect of neurotensin.

Animals↗

PubMedDate not supplied

Assessing the relative incidence of mitochondrial DNA A3243G in migraine without aura with maternal inheritance.

OBJECTIVE: To determine whether patients with migraine without aura with maternal "inheritance" are affected by a monosymptomatic form of the MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) or carry the most common mitochondrial DNA (mtDNA) mutation associated with MELAS, namely the A3243G transition in the transfer RNA (tRNA)Leu(UUR) gene. BACKGROUND: The association between migraine and abnormal mitochondrial function has been suggested on clinical, biochemical, and neuroradiological grounds. Migraine attacks with vomiting and cerebral infarctions, most often in the posterior cerebral regions, which are reminiscent of complicated migraine, are typical features of MELAS. The observation that migrainous patients have affected mothers more often than affected fathers suggests a possible role for maternally transmitted genetic factors. METHODS: We studied 25 patients with migraine with aura whose mothers were also affected. A sensitive polymerase chain reaction restriction fragment length polymorphism analysis was used to detect mutated genomes. CONCLUSIONS: We failed to detect the MELAS mutation, but migraine may still be associated with point mutations of mtDNA other than A3243G or with as-yet-unidentified nuclear DNA factors related to mitochondrial function.

Adolescent↗

PubMedDate not supplied

High-dose ropinirole in advanced Parkinson's disease with severe dyskinesias.

Levodopa (LD) is the gold standard of therapy for Parkinson's disease, but it is commonly associated with motor fluctuations and dyskinesias. Dopamine agonists are often used as adjuncts to LD in an attempt to reduce these complications. In this open-label study the authors investigated the effects of high doses of adjunctive ropinirole in 36 patients with advanced Parkinson's disease and normal cognitive status. The daily dose of ropinirole was increased from 18.4 +/- 3.5 mg to 34.7 +/- 5.5 mg, generally in four separate doses. The daily LD dose was decreased from 734.1 +/- 254.8 mg to 502.8 +/- 228.4 mg. After 12 months 25 patients were still on high doses of ropinirole whereas 11 patients had, after either the emergence of side effects or a worsening of their clinical conditions, decreased or interrupted ropinirole. At 12 months, the daily doses of LD and ropinirole were 489 +/- 243 mg and 34.6 +/- 4.6 mg respectively. There was a significant reduction in the Dyskinesia Rating Scale scores during both ON and OFF periods, indicating a reduction in dyskinesias during ON periods and a reduction in dystonias during OFF periods (p < 0.001). Both the intensity and the hours spent during OFF periods were reduced significantly (p < 0.001). Even though these results need to be confirmed through extended controlled studies, the high-dose dopamine agonist strategy is safe for patients with advanced PD in whom a marked motor response to LD (even at very low doses) is associated with severe dyskinesias, and may be used as a means of delaying surgery or as an alternative to continuous apomorphine infusion.

Aged↗

PubMedDate not supplied

Premenstrual failure of alpha-adrenergic stimulation on hypothalamus-pituitary responses in menstrual migraine.

In nine women suffering from menstrual migraine (MM), and in six healthy asymptomatic volunteers, plasma beta-endorphin (beta-EP), growth hormone (GH), norepinephrine (NE), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) concentrations were measured in response to clonidine (0.075 mg, i.v.) stimulation. In MM patients clonidine testing was performed in both the early and the late luteal phases of the menstrual cycle. Premenstrual symptoms were prospectively evaluated in the actual cycle using the Moos Menstrual Distress Questionnaire. beta-EP (after gel chromatography) and GH were measured using radioimmunoassay. NE and MHPG were evaluated by HPLC using electrochemical detection. In both phases of the menstrual cycle clonidine significantly reduced NE and MHPG levels in MM patients and controls in a similar way. In MM patients beta-EP and GH plasma levels were stimulated by clonidine only in the early luteal phase, whereas they remained unchanged when they were stimulated in the premenstrual period. In controls the response of both hormones was not affected by the menstrual cycle. The lack of hormonal response to clonidine in MM may suggest a postsynaptic alpha 2-adrenoreceptor hyposensitivity during the premenstrual period. This demonstrates a transient vulnerability of the neuroendocrine/neurovegetative systems, and could thus be a factor facilitating the precipitation of both behavioral changes and migraine attacks.

Arousal↗

PubMedDate not supplied

Active music therapy in Parkinson's disease: an integrative method for motor and emotional rehabilitation.

BACKGROUND: Modern management of Parkinson's disease (PD) aims to obtain symptom control, to reduce clinical disability, and to improve quality of life. Music acts as a specific stimulus to obtain motor and emotional responses by combining movement and stimulation of different sensory pathways. We explored the efficacy of active music therapy (MT) on motor and emotional functions in patients with PD. METHODS: This prospective, randomized, controlled, single-blinded study lasted 3 months. It consisted of weekly sessions of MT and physical therapy (PT). Thirty-two patients with PD, all stable responders to levodopa and in Hoehn and Yahr stage 2 or 3, were randomly assigned to two groups of 16 patients each. We assessed severity of PD with the Unified Parkinson's Disease Rating Scale, emotional functions with the Happiness Measure, and quality of life using the Parkinson's Disease Quality of Life Questionnaire. MT sessions consisted of choral singing, voice exercise, rhythmic and free body movements, and active music involving collective invention. PT sessions included a series of passive stretching exercises, specific motor tasks, and strategies to improve balance and gait. RESULTS: MT had a significant overall effect on bradykinesia as measured by the Unified Parkinson's Disease Rating Scale (p < .034). Post-MT session findings were consistent with motor improvement, especially in bradykinesia items (p < .0001). Over time, changes on the Happiness Measure confirmed a beneficial effect of MT on emotional functions (p < .0001). Improvements in activities of daily living and in quality of life were also documented in the MT group (p < .0001). PT improved rigidity (p < .0001). CONCLUSIONS: MT is effective on motor, affective, and behavioral functions. We propose active MT as a new method for inclusion in PD rehabilitation programs.

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