Biomedical subjects

Cristina Tassorelli

Publications and source records attributed to Cristina Tassorelli.

18 recordsLinked to original sources

PubMed2006

Unilateral lesion of the subthalamic nucleus enhances cortical fos expression associated with focally evoked seizures in the rat.

Reducing subthalamic nucleus (STN) activity has been proposed as an anti-epileptic procedure. Here we show that, on the contrary, a unilateral lesion of the STN causes slight (nonsignificant) increases in the severity of limbic seizures evoked by bicuculline infusion into the piriform cortex, associated with marked Fos expression throughout the cerebral cortex. Abolishing the STN control over the basal ganglia output may therefore play a facilitatory role on cortical activation associated with limbic seizures.

Animals↗

PubMed2006

Cardiovascular dysautonomia as a cause of falls in Parkinson's disease.

Parkinson's disease (PD) patients have a ninefold increased risk of recurring falls compared to healthy controls. The risk of falling due to cardiovascular dysautonomia (CVD) is not quantifiable. But, CVD is an integral part of the disease and at least 20% of PD patients suffer from orthostatic hypotension, an expression of CVD. One way to reduce falls due to CVD in PD patients could be to give adequate information on the relationship between falling risks and cardiovascular dysautonomia to patients and their caregivers. Moreover, drugs given for PD might contribute to OH and we propose that education and non-pharmacological strategies for its treatment might be preferable, especially because of the low efficacy of drugs available for the treatment of OH and the frailty of elderly PD patients.

Accidental Falls↗

PubMed2006

Prostaglandins, glutamate and nitric oxide synthase mediate nitroglycerin-induced hyperalgesia in the formalin test.

Increasing evidence supports a possible role for nitric oxide (NO) in the transmission of pain signals and in the development of central mechanisms of hyperalgesia. Previously, we have shown that nitroglycerin, an NO donor, is able to induce a long-lasting hyperalgesic state in rats. Nitroglycerin-induced hyperalgesia can be detected as an increase in the nociceptive behavior evoked by the formalin test. In the present study we investigated the possible mediators in the nitroglycerin-induced hyperalgesic state. Male Sprague-Dawley rats were injected with nitroglycerin and pretreated with indomethacin, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) or N(omega)-nitro-L-arginine methyl ester (L-NAME). The results obtained showed that inhibition of prostaglandins or NO synthesis prevents nitroglycerin-induced hyperalgesia in Phase II of the formalin test. A similar inhibitory effect was also observed following pretreatment with the glutamate antagonist MK801. The present findings point to the role of prostaglandins, NO synthesis and glutamate activity in the induction of nitroglycerin-induced hyperalgesia.

Animals↗

PubMed2006

Botulinum toxin and neuromotor rehabilitation: An integrated approach to idiopathic cervical dystonia.

Currently, the best treatment option for idiopathic cervical dystonia (ICD) is injection of botulinum toxin (BTX) into the affected muscles, whereas rehabilitative approaches have given disappointing results. We evaluated whether the association of an ad hoc rehabilitative program may improve the clinical efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty patients with ICD were randomly assigned to two different treatment groups: (1) BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2) BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at reinjection (284.5 vs. 325.5 units). In addition, they showed more marked reductions in their disability in activities of daily living (-9.7 vs. -4.85 points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A therapy with a specific program of physical therapy may improve ICD treatment outcome.

Activities of Daily Living↗

PubMed2006

Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease.

Mutations in the gene leucine-rich repeat kinase 2 (LRRK2) have been recently identified in families with Parkinson's disease (PD). However, the prevalence and nature of LRRK2 mutations, the polymorphism content of the gene, and the associated phenotypes remain poorly understood. We performed a comprehensive study of this gene in a large sample of families with Parkinson's disease compatible with autosomal dominant inheritance (ADPD). The full-length open reading frame and splice sites of the LRRK2 gene (51 exons) were studied by genomic sequencing in 60 probands with ADPD (83% Italian). Pathogenic mutations were identified in six probands (10%): the heterozygous p.G2019S mutation in four (6.6%), and the heterozygous p.R1441C mutation in two (3.4%) probands. A further proband carried the heterozygous p.I1371 V mutation, for which a pathogenic role could not be established with certainty. In total, 13 novel disease-unrelated variants and three intronic changes of uncertain significance were also characterized. The phenotype associated with LRRK2 pathogenic mutations is the one of typical PD, but with a broad range of onset ages (mean 55.2, range 38-68 years) and, in some cases, slow disease progression. On the basis of the comprehensive study in a large sample, we conclude that pathogenic LRRK2 mutations are frequent in ADPD, and they cluster in the C-terminal half of the encoded protein. These data have implications both for understanding the molecular mechanisms of PD, and for directing the genetic screening in clinical practice.

Adult↗

PubMed2006

Uncommon primary headaches.

PURPOSE OF REVIEW: The new International Classification of Headache Disorders was recently published by the International Headache Society. Several uncommon primary headaches, including some new clinical entities (e.g. hypnic headache), were included in the section on 'Cluster headache and other trigeminal autonomic neuralgias' and 'Other primary headaches'. The recent classification offers an interesting opportunity to evaluate the clinical role and to discuss the mechanisms of some of the more relevant uncommon primary headaches. RECENT FINDINGS: Due to the low incidence of these uncommon headache forms, their diagnostic criteria, pathogenetic mechanisms and therapy are still debated. Differential diagnosis versus secondary headaches is also a crucial issue. In this review, some of the most important uncommon primary headaches are discussed in light of the most recent contributions to the literature. SUMMARY: The review focuses on the update of the main uncommon primary headaches, intending to clarify some controversial points and to indicate some headlines for further research.

Diagnosis, Differential↗

PubMed2005

Comparative analysis of the neuronal activation and cardiovascular effects of nitroglycerin, sodium nitroprusside and L-arginine.

In this study, we compare the biological effects, Fos expression and cardiovascular responses induced in the rat, of different nitric oxide modulators (nitroglycerin, sodium nitroprusside and L-arginine). Nitroglycerin and sodium nitroprusside induced a similar pattern of neuronal activation in several areas, which include the paraventricular and supraoptic nuclei of the hypothalamus, central nucleus of the amygdala, parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius. However, only nitroglycerin activated the periaqueductal grey and nucleus trigeminalis caudalis. L-arginine-induced neuronal activation was restricted to the paraventricular and supraoptic nuclei of the hypothalamus. As regards cardiovascular effect, both nitroglycerin and sodium nitroprusside induced moderate hypotension (nitroglycerin: -23.3%, sodium nitroprusside: -24.3%) that lasted 40 min in the case of sodium nitroprusside and 80 min in the case of nitroglycerin. L-arginine did not significantly influence blood pressure. These data suggest that nitroglycerin, sodium nitroprusside and L-arginine are associated with different biological effects on both the central nervous system and the cardiovascular system. Of the NO-related drugs tested in this study, only nitroglycerin confirmed its ability to activate brainstem areas implicated in nociception.

Analysis of Variance↗

PubMed2005

Activation of the transcription factor NF-kappaB in the nucleus trigeminalis caudalis in an animal model of migraine.

The infusion of nitroglycerin (NTG) induces an inflammatory state in perivascular meningeal tissues of rat via the activation, inter alia, of nuclear factor kappa B (NF-kappaB). This phenomenon has been related to the mechanisms involved in the pathophysiology of migraine, a common neurovascular disorder. In the present study, we sought to elucidate whether NF-kappaB activation might have a role in the determinism of migraine attacks also at the neuronal level. Therefore, we investigated the transcriptional activity of NF-kappaB in the brainstem of rats systemically injected with NTG and killed 4h later. Activation of NF-kappaB in brain areas was detected by means of both the immunohistochemical technique and the Western blot analysis. A significant increase of nuclear immunostaining of p65, an indicator of NF-kappaB activation, was detected in lamina I and II of nucleus trigeminalis caudalis in rats injected with NTG when compared with the control group. Western blot analysis confirmed the activation of the NF-kappaB pathway showing an increase in the optical density of p65 in nuclear extracts of lower brainstem of rats injected with the nitric oxide (NO) donor. The present study contributes to expand on our understanding of the complex mechanisms by which NTG may trigger migraine-like headaches in migraineurs. Furthermore, these findings pave the way to new bio-molecular and pharmacological avenues for the development of innovative migraine therapies.

Animals↗

PubMed2005

Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease.

Psychotic symptoms are the main and the most disabling "nonmotor" complications of Parkinson's disease (PD), the pathophysiology of which is poorly recognized. Polysomnographic studies have shown a relationship between visual hallucinations and rapid eye movement (REM) sleep. The objective of this study is to clarify the relationship between psychotic symptoms and REM sleep behavior disorder (RBD) in PD. In a Parkinson's disease outpatient unit, 289 consecutive subjects with idiopathic PD were administered (in the period from January to December 2002) a multiple-choice questionnaire and structured interview on sleep and mental disorders. RBD was diagnosed in accordance with the minimal diagnostic criteria of the International Classification of Sleep Disorders. Hallucinations and delusional disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-IV criteria. The presence or absence of psychotic symptoms, of RBD, and of daytime sleepiness, as well as motor status, cognitive status, and mood were assessed. Approximately 32% (n = 92) of the subjects presented with psychotic disorders; 30% (n = 86) had experienced hallucinations; 2% (n = 6) had delusions without hallucinations. Sixty-two (72%) hallucinators reported nocturnal hallucinations. A total of 6.6% (n = 19) of the subjects complained of a delusional disorder. There were 26.6% (n = 77) of subjects who presented with RBD: 28 (36%) with onset before and 49 (63%) with onset after PD diagnosis. The presence of RBD was associated with an increased risk of manifesting hallucinations and delusions (odds ratio [OR], 2.73). Other independent clinical factors found to have an effect on psychotic disorders were cognitive impairment (OR, 3.92), disease duration (OR, 2.46), advanced age (OR, 2.34), and severity of motor symptoms (OR, 2.06). These results suggest that RBD is widely associated with psychosis in PD.

Aged↗

PubMed2003

Nitroglycerin induces hyperalgesia in rats--a time-course study.

Nitroglycerin is a nitric oxide (NO) donor which activates nuclei involved in nociceptive transmission following systemic administration. The effect of nitroglycerin on the nociceptive threshold was studied in rats by means of two experimental tests that explore different modalities of pain: the tail-flick test and the formalin test. Nitroglycerin induced a significant reduction in the latency of the tail flick 2 and 4 h after its administration. Similarly, formalin-induced pain-related behaviour increased significantly 2 and 4 h after nitroglycerin administration.

Animals↗

PubMed2003

Selective stimulation of striatal dopamine receptors of the D1- or D2-class causes opposite changes of fos expression in the rat cerebral cortex.

It has been suggested that activation of striatal neurons expressing D1 or D2 dopamine receptors elicits opposite changes in the net output of the basal ganglia circuitry and, consequently, in the functional interactions of the circuit with the cerebral cortex. In particular, it has been recently reported that striatal D1 receptors may regulate cortex function. To further address this issue, we mapped cerebral expression of Fos protein following intrastriatal stimulation of D1- or D2-class receptors in freely moving animals. Using permanent cannulas implanted in the right striatum, Sprague-Dawley rats received intrastriatal microinfusions of SKF 38393 (D1 agonist) or quinpirole (D2 agonist) or saline (controls), combined with systemic administration of D1 antagonist SCH 23390 or D2 antagonist eticlopride or saline. Animals treated with SKF 38393 showed dose-dependent, massive Fos increases in the motor, somatosensory, auditory, visual and limbic regions of the cerebral cortex, ipsilaterally to the injected striatum. Consistent Fos expression was also found in the injected striatum and, bilaterally, in the nucleus accumbens shell. These increases were effectively counteracted by systemic SCH 23390. Conversely, quinpirole did not induce significant cortical or striatal expression of Fos, which was instead observed after the systemic administration of eticlopride. Fos was not detected in any of the other basal ganglia nuclei, regardless of the dopamine agonists or antagonists used. Our results confirm that striatal D1 dopamine receptors play a central role in the modulation of cortical activity, thus providing additional information on the functional interaction between basal ganglia circuitry and cerebral cortex.

Analysis of Variance↗

PubMed2003

Central components of the analgesic/antihyperalgesic effect of nimesulide: studies in animal models of pain and hyperalgesia.

UNLABELLED: The analgesic action of NSAIDs has been attributed to the peripheral inhibition of prostaglandin synthesis via the blockade of the enzyme cyclo-oxygenase (COX) and prevention of bradykinin and cytokine-induced hyperalgesia via inhibition of the release of tumour necrosis factor-alpha. However, it is becoming increasingly evident that NSAIDs exert their analgesic effect through several mechanisms. Recent data suggest that significant expression of COX-2 is found in the central nervous system, where COX-2 seems to have, together with nitric oxide, an important role in spinal nociceptive transmission. Nitroglycerin is a nitric oxide donor and induces a hyperalgesic state, partially mediated by central mechanisms. Nimesulide is a preferential COX-2 inhibitor widely used to treat pain. In this study, we evaluated the analgesic effect of nimesulide in several animal models of pain, intending to provide additional information on the characteristics of the analgesic effect of nimesulide, with specific focus on a possible central component. STUDY DESIGN: Nimesulide was compared with vehicle in groups of 4-10 rats that were randomly tested with different models of pain. The experimental design also included study of the effect of nimesulide upon nitroglycerin-induced neuronal activation at central sites. Analysis of variance was used to evaluate the influence of time and treatments. Differences between groups at specific time-points were analysed by post-hoc t-test. A probability level of less than 5% was regarded as significant. METHODS: The analgesic effect of nimesulide (or vehicle) was evaluated in male Sprague-Dawley rats. The animals underwent tail-flick and formalin tests, both performed in baseline conditions and after nitroglycerin-induced hyperalgesia. Two separate groups of rats were treated with nitroglycerin alone or nimesulide followed by nitroglycerin, and their brains were processed for immunocytochemical detection of Fos protein, a marker of neuronal activation. RESULTS: Nimesulide showed a significant analgesic effect in both the tail-flick and the formalin tests in baseline conditions. In addition, the drug proved effective in counteracting nitroglycerin-induced hyperalgesia in both tests. Brain mapping of nuclei activated by the administration of nitroglycerin showed that nimesulide pretreatment significantly inhibited neuronal activation in several areas, namely the supraoptic nucleus, ventrolateral column of the periaqueductal grey, locus coeruleus, nucleus tractus solitarius and area postrema. We conclude that nimesulide possesses a strong analgesic and antihyperalgesic activity, the mechanisms of action of which are partly central.

Analgesia↗

PubMed2002

Effects of nimesulide on nitric oxide-induced hyperalgesia in humans--a neurophysiological study.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to induce analgesia mainly via the inhibition of cyclo-oxygenase. Several reports suggest that chronic pain is mediated by central sensitization, an N-methyl-D-aspartate (NMDA)-mediated phenomenon influenced by cyclo-oxygenase activity and nitric oxide (NO). In this double-blind study, we evaluated the effects of a preferential inhibitor of the inducible isoform of cyclo-oxygenase-2, nimesulide, on the spinal nociceptive flexion reflex (RIII reflex) before and after administration of an NO donor in healthy volunteers. Nimesulide caused a reduction of the RIII reflex area, which persisted after NO donor administration. Conversely, in the placebo group the RIII reflex area significantly increased following the administration of the NO donor. These data suggest a central effect for nimesulide, possibly related to a reduction of nociceptive activity at spinal level.

Adult↗

PubMed2002

Electrophysiological evidence for trigeminal neuron sensitization in patients with migraine.

The electrically elicited corneal reflex is a useful tool for exploring the trigeminal system in humans and it may provide additional evidence pointing to a dysfunction of this system in migrainous patients. Tactile perception, corneal reflex and pain thresholds were studied in 48 migraine without aura patients during pain-free periods and compared with those observed in 24 controls. Twenty-eight of the patients had strictly unilateral headache, while the other 20 had bilateral or side-shifting pain during attacks. Both migraine subgroups (bilateral and unilateral) showed significantly lower thresholds compared with controls. The lowest values were observed on the symptomatic side of unilateral migraine patients. These findings suggest that sensorimotor mechanisms and/or pain control systems at the trigeminal level are impaired in migraine. The bilateral location of these abnormalities seems to point to a centrally located dysfunction.

Adult↗

PubMedDate not supplied

Long-term evaluation of the effect of quetiapine on hallucinations, delusions and motor function in advanced Parkinson disease.

OBJECTIVES: Mental disorders (MDs) are disabling complications of Parkinson disease (PD). We set out to demonstrate the short- and long-term efficacy of quetiapine, an antipsychotic drug, in controlling hallucinations and delusions in parkinsonian patients without worsening their motor function. Since current guidelines recommend that dopaminergic drugs be decreased or even withdrawn altogether upon the appearance of MDs, we also sought to establish whether quetiapine enables a modification of this common course of action, and hence improve the management of pre-existing motor complications in affected subjects. METHOD: Thirty-five PD patients with disabling MDs were enrolled in this open-label study. Motor function, MDs and cognitive state were evaluated before starting quetiapine therapy and after 1, 3, and 12 months of treatment. RESULTS: MDs significantly improved after 1, 3, and 12 months of quetiapine treatment. At the end of the study the mean daily dose of quetiapine (185 mg) did not produce significant changes in motor or cognitive function. Isolated hallucinations responded to low doses of quetiapine (110 mg daily), while delusions needed 265 mg daily. After 12 months, global dopaminergic therapy was reduced in 3 patients, modified (purely in terms of its components) in 17 patients, and increased in 15 patients. CONCLUSIONS: Quetiapine was effective in the treatment of hallucinations and delusions in PD. It did not worsen motor functions and allowed the dopaminergic treatment in PD patients affected by MDs to be managed safely.

Aged↗

PubMedDate not supplied

Changes in nociceptive flexion reflex threshold across the menstrual cycle in healthy women.

OBJECTIVE: We assessed the influence of changes in steroid hormones across the menstrual cycle on the spinal nociceptive reflex. METHOD: We studied in 14 healthy women during the follicular and luteal phase the nociceptive flexion reflex (RIII reflex), an objective neurophysiological method that allows exploring possible abnormal functioning of the pain-control system. The basal body temperature (BBT) was used to evaluate the different phases of the ovarian cycle. The menstrual distress questionnaire (MDQ) was also applied for monitoring somatic and psychological symptoms during the cycle. RESULTS: During the luteal phase, the threshold of the RIII reflex (Tr) and the psychophysical threshold for pain (Tp) were both significantly reduced compared with the follicular phase. Moreover, the reflex threshold in the luteal phase was negatively correlated to the total MDQ score of the recording day. CONCLUSIONS: A higher sensitivity to pain stimuli was observed during the luteal phase of the menstrual cycle, which probably results from a reduction in the inhibitory descending control on spinal nociceptive flexion reflex. Complex neuromodulatory interactions of ovarian steroids with other systems of neurotransmission (especially serotonergic) may account for these observations.

Adult↗

PubMedDate not supplied

A questionnaire on sleep and mental disorders in Parkinson's disease (QSMDPD): development and application of a new screening tool.

Psychiatric, cognitive and sleep disorders are the most frequent and disabling non-motor complications of Parkinson's disease (PD). To improve the description of sleep and mental disorders in PD patients, we set out to develop a simple and reliable data collection tool (questionnaire) for the screening of large samples of PD patients. The first draft of the questionnaire was administered to a consecutive series of 120 PD patients from the outpatient department of our unit, who were instructed to fill it in with the help of their caregivers. Subsequent drafts of the questionnaire were evaluated together with the patients and their caregivers, until a final, satisfactory version was obtained. This final version was named the Questionnaire on Sleep and Mental Disorders in PD (QSMDPD). This questionnaire--we used the Italian version, named Questionario sui Disturbi del Sonno e Mentali nella Malattia di Parkinson, ODSMMP--consists of 119 questions with multiple-choice answers. The QSMDPD was mailed or handed to 400 PD patients followed at our unit's outpatient department. Three hundred and twenty (80%) were returned to us. A review of these completed questionnaires, conducted by a neurologist together with the patients, showed 90% of them (289) to be complete and to provide reliable data. This high compliance suggests that the QSMDPD is a promising tool for collecting data on sleep and mental disorders in large samples of PD patients. A short version will be administered as a follow-up tool.

Aged↗

PubMedDate not supplied

Secondary cervical dystonia in iatrogenic hypoparathyroidism associated with extensive brain calcifications.

Cervical dystonia (CD) is usually idiopathic, without a known aetiology. Hypoparathyroidism, both primary and secondary, can be associated with brain calcifications and various clinical neurological features. Anecdotal evidence suggests that patients affected by hypoparathyroidism show a rapid-onset oral dyskinesia after use of neuroleptic drugs. We report the case of a 60-year-old woman with CD, iatrogenic hypoparathyroidism and extensive brain calcifications. On the basis of the clinical features and the localization of the brain calcifications we suppose that they may have played a role in the development of this CD. This case may prove to be, after a review of literature, the first report of CD secondary to iatrogenic hypoparathyroidism in a patient with extensive brain calcifications.

Brain Diseases↗