Showing papers by "Cristina Tassorelli published in 2010"

An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment

Abstract: Objectives: Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. Methods: Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). Results: Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. Conclusions: This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

Four-week trunk-specific rehabilitation treatment improves lateral trunk flexion in Parkinson's disease.

Abstract: People with Parkinson's disease (PD) often have a posture characterized by lateral trunk flexion poorly responsive to antiparkinsonian drugs. To examine the effects of a rehabilitation programme (daily individual 90-minute-sessions, 5-days-a-week for 4-consecutive weeks) on lateral trunk flexion and mobility, 22 PD patients with mild to severe lateral trunk flexion, and 22 PD patients without trunk flexion were studied. Patients were evaluated using the Unified Parkinson's Disease Rating Scale motor subscale (UPDRS-III) score, and the kinematic behavior of the trunk was recorded by means of an optoelectronic system to determine: a) trunk flexion, inclination and rotation values in the erect standing posture; b) ranges of trunk flexion and inclination during trunk movements. After the treatment, significant decreases in trunk flexion [24 degrees (4) vs. 14 degrees (3), P < 0.001] and inclination in the static condition [23 degrees (5) vs. 12 degrees (4), P < 0.001)] were observed, both of which were maintained at the 6-month follow up. During the trunk flexion task, a significantly increased range of trunk flexion [64 degrees (15) vs. 83 degrees (15), P < 0.001] was observed; similarly, during the lateral bending task, the range of trunk inclination was found to be significantly increased, both toward the side of the trunk deviation [29 degrees (8) vs. 42 degrees (13), P < 0.01] and toward the contralateral side [14 degrees (6) vs 29 degrees (11), P < 0.01]. No further significant changes were observed at the 6-month follow-up. Trunk flexion and inclination values in the upright standing posture correlated slightly with the UPDRS-III score. Our findings show that significant improvements in axial posture and trunk mobility can be obtained through the 4-week rehabilitation programme described, with a parallel improvement in clinical status.

Alterations of the endocannabinoid system in an animal model of migraine: Evaluation in cerebral areas of rat:

Abstract: Endocannabinoids are involved in the modulation of pain and hyperalgesia. In this study we investigated the role of the endocannabinoid system in the migraine model based on nitroglycerin-induced hyperalgesia in the rat. Male rats were injected with nitroglycerin (10 mg/kg, i.p.) or vehicle and sacrificed 4 h later. The medulla, the mesencephalon and the hypothalamus were dissected out and utilized for the evaluation of activity of fatty acid amide hydrolase (that degrades the endocannabinoid anandamide), monoacylglycerol lipase (that degrades the endocannabinoid 2-arachidonoylglycerol), and binding sites specific for cannabinoid (CB) receptors. The findings obtained show that nitroglycerin-induced hyperalgesia is associated with increased activity of both hydrolases and increased density of CB binding sites in the mesencephalon. In the hypothalamus we observed an increase in the activity of fatty acid amide hydrolase associated with an increase in density of CB binding sites, while in the medulla only the activity of fatty acid amide hydrolase was increased. Anandamide also proved effective in preventing nitroglycerin-induced activation (c-Fos) of neurons in the nucleus trigeminalis caudalis. These data strongly support the involvement of the endocannabinoid system in the modulation of nitroglycerin-induced hyperalgesia, and, possibly, in the pathophysiological mechanisms of migraine.

Development and validation of the EUROLIGHT questionnaire to evaluate the burden of primary headache disorders in Europe

Abstract: We developed a 103-item self-reporting questionnaire to assess the burden of primary headache disorders on those affected by them, including headache characteristics, associated disability, co-morbidities, disease-management and quality of life. We validated the questionnaire in five languages with 426 participants (131 in UK, 60 in Italy, 107 in Spain, 83 in Germany/Austria, and 45 in France). After a linguistic and a face-content validation, we tested the questionnaire for comprehensibility, internal consistency and test-retest reliability at an interval of one month. In the different countries, response rates were between 73% and 100%. Test-retest reliability varied between -0.27 to 1.0 depending of the nature of the expected agreement. The internal consistency was between 0.69 and 0.91. The EUROLIGHT questionnaire is suitable for evaluating the burden of primary headache disorders, and can be used in English, German, French, Italian and Spanish.

Experimental models of migraine.

Abstract: In vitro studies on animal and human cephalic vessels allow the measurement of second messengers or intracellular calcium concentrations and the evaluation of the role of endogenous neuropeptides in perivascular nerve endings involved in migraine pathophysiology In addition, in vitro human models allow the assessment of receptorial cranial selectivity and the collection of reliable information regarding the behavior of these vessels in migraine headache The availability of animal models of migraine has favoured impressive advances in understanding the mechanisms and mediators underlying migraine attacks, as well as the development of new and more specific therapeutic agents The trigeminovascular system (TVS) has emerged as a critical efferent component, and the mediators of its activity have been identified and characterized, as have some of the receptors involved The similarity of the trigeminal innervation across species has made it possible to draw conclusions on the neurophysiological responses to electrical or chemical stimulation of the trigeminal fibers Studies involving substances known to induce migraine-like attacks, ie, nitric oxide (NO) donors, have provided interesting insights into the central nuclei probably involved in the initiation and repetition of migraine attacks The neuronal and vascular effects of such substances might yield an increasing body of evidence for a better understanding of the pathophysiology of migraine attacks

Focus on therapy of hypnic headache

Abstract: Hypnic headache (HH) is a primary headache disorder, which occurs exclusively during sleep and usually begins after 50 years of age. There are no controlled trials for the treatment of HH. We reviewed all the available papers, including 119 cases published in literature up to date, reporting the efficacy of the medications used to treat HH. Acute treatment is not recommended, since no drug proved to be clearly effective and also because the intensity and the duration of the attacks do not require the intake of a medication in most cases. As for prevention, a wide variety of medications were reported to be of benefit in HH. The drugs that were found to be effective in at least five cases are: lithium, indomethacin, caffeine and flunarizine. Lithium was the most extensively studied compound and demonstrated to be an efficacious treatment in 32 cases. Unfortunately, despite its efficacy, significant adverse effects and poor tolerability are not rare, mainly in elderly patients. Many patients reported a good response to indomethacin, but some could not tolerate it. Caffeine and melatonin treatments did not yield robust evidence to recommend their use as single preventive agents. Nevertheless, their association with lithium or indomethacin seems to produce an additional therapeutic efficacy. A course of lithium should be tried first, followed 3–4 months later by tapering. If headache recurs during tapering, a longer duration of therapy may be needed. If lithium treatment does not provide a significant response, indomethacin can be commenced as second-line approach. If these treatments prove to be ineffective or poorly tolerated, other agents, such as caffeine and melatonin, can be administered.

Focus on therapy of the Chapter IV headaches provoked by exertional factors: primary cough headache, primary exertional headache and primary headache associated with sexual activity.

Abstract: Primary cough headache, primary exertional headache and primary headache associated with sexual activity are distinct entities, even though they share several features: acute onset, the absence of structural brain disease and exertional factors as precipitating events. In this short review, we illustrate the possible treatment strategies on the basis of information collected from a systematic analysis of the international literature.

Focus on therapy: hemicrania continua and new daily persistent headache

Abstract: Hemicrania continua (HC) and new daily-persistent headache (NDPH) represent the only two forms of chronic daily headache in Chap. IV “Other Primary Headaches” of the second edition of the International Classification of Headache Disorders. HC and NDPH are rare and poorly defined from a pathophysiological point of view; as a consequence, their management is largely empirical. Indeed, there is a lack of prospective, controlled trials in this field, and treatment effectiveness is basically inferred from the results of sparse open-label trials, retrospective case series, clinical experience and expert opinions. In this narrative review we have summarised the information collected from an extensive analysis of the literature on the treatment of HC and NDPH in order to provide the best available and up-to-date evidence for the management of these two rare forms of primary headache. Indomethacin is the mainstay of HC management. The reported effective dose of indomethacin ranges from 50 to 300 mg/day. Gabapentin 600–3,600 mg tid, topiramate 100 mg bid, and celecoxib 200–400 mg represent the most interesting alternative choices in the patients who do not tolerate indomethacin or who have contraindications to its use. NDPH is very difficult to treat and it responds poorly only to first-line options used for migraine or tension-type headache.

Role of 2 Common Variants of 5HT2A Gene in Medication Overuse Headache

Abstract: Objective.—The aim of the present study was to evaluate a possible involvement of 2 polymorphisms of the serotonin 5HT2A receptor gene (A-1438G and C516T) as risk factors for medication overuse headache (MOH) and whether the presence of these polymorphic variants might determine differences within MOH patients in monthly drug consumption. Background.—Despite a growing scientific interest in the mechanisms underlying the pathophysiology of MOH, few studies have focused on the role of genetics in the development of the disease, as well as on the genetic determinants of the inter-individual variability in the number of drug doses taken per month. Methods.—Our study was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism on genomic DNA extracted from peripheral blood of 227 MOH patients and 312 control subjects. Genotype-specific risks were estimated as odds ratios with associated 95% confidence intervals by unconditional logistic regression and adjusted for age and gender. A stepwise multiple linear regression analysis was employed to identify significant predictors of the number of drug doses taken per month. Results.—No significant association was found between 5HT2A A and 1438G and C516T gene polymorphisms and MOH risk. In contrast, a higher consumption of monthly drug doses was observed among 516T 5HT2A carriers (median 50, range 13-120) compared to 516CC patients (median 30, range 12-128) (Mann–Whitney U-test, P = .018). In the stepwise multiple regression analysis, C516T 5HT2A polymorphism (P = .018) and class of overused drug (P = .047) emerged as significant, independent predictors of the monthly drug consumption in MOH patients. Conclusions.—Although our results do not support a major role of the A-1438G and C516T polymorphic variants of the 5HT2A gene in the susceptibility of MOH, our findings support an influence of the C516T polymorphism on the number of symptomatic drug doses taken and, possibly, on the drug-seeking behavior in these patients.

Focus on therapy of primary stabbing headache.

Abstract: Primary stabbing headache (PSH) is a short-lasting but troublesome headache disorder, which has been known for several decades. The head pain occurs as a single stab or as a series of stabs generally involving the area supplied by the first division of trigeminal nerve. Stabs last for approximately a few seconds, occurring and recurring from once to multiple times per day in an irregular pattern. For the diagnosis of PSH, it is mandatory that any other underlying disorder is ruled out. Indomethacin represents the principal option in the treatment of PSH, despite therapeutic failure in up to 35% of the cases. Recent reports showed that cyclooxygenase-2 (COX-2) inhibitors, gabapentin, nifedipine, paracetamol and melatonin may also be effective. In this report, we focus on the therapy of PSH summarizing the information collected from a systematic analysis of the international literature over the period 1980–2009.

A prospective multicentre study to evaluate the consistency of the IHS diagnostic criteria, the usefulness of brain MRI for the diagnosis, follow-up and treatment management, and the outcome after high dosage 6-methylprednisolone therapy, in subjects with Tolosa-Hunt syndrome.

Abstract: As discussed in a previous review [1], several reasons suggest the need for a revision of diagnostic criteria of the International Headache Classification (IHS) [2] for Tolosa–Hunt syndrome (THS). First of all evidence is lacking on the most appropriate steroid treatment, secondly several reports suggest that neurological signs persist beyond the time limit defined by the IHS criteria. Furthermore, specific MRI techniques are necessary for detecting the inflammatory tissue, which can extend beyond the cavernous sinus and the orbit. Since data available from the literature mostly derive from case reports which differ in terms of treatment schedules, MRI techniques, and follow-up strategies, IHS diagnostic criteria cannot be improved by adopting an evidence-based methodology. Thus, we are promoting a non-profit multicentre study aimed at revising THS diagnostic criteria, considering (1) the clinical and MRI characteristics of the disease at presentation, after a standardized steroid treatment, and during an 8-month followup from the time symptoms, signs and MRI normalize, (2) the occurrence of relapses after treatment discontinuation, and (3) the effect of the lesion site on the outcome. Any participating centre will be asked to follow a simple management protocol based on serial MRI evaluations. All data will be recorded in case report forms provided by the Coordinator Centre, and no migration of investigators or patients is needed. The study has received approval from the Ethical Committee of the Coordinator Centre IRCCS ‘‘National Neurological Institute C. Mondino’’ Foundation. All contributors will appear as co-authors of every presentation and/or scientific publication of partial or complete results of the study. The readers of The Journal of Headache and Pain who are willing to participate can download the Study Summary, a Schematic Diagram and a Time and Event Schedule (available online as supplementary material), and can ask the corresponding author for complete documentation of the study.