Nociception Coma Scale with personalized painful stimulation versus standard stimulus in non-communicative patients with disorders of consciousness.

INTRODUCTION: Persons with disorders of consciousness (DoC) may perceive pain without being able to communicate their discomfort. Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in coma survivors with DoC. OBJECTIVE: Aim of the present study was to compare, in non-communicative patients with DoC, NCS-R scores obtained with the standard pressure on fingernail bed (standard stimulus, SS) versus other personalized painful stimuli (PS), to verify possible correlations between NCS-R and Coma Recovery Scale-Revised (CRS-R). MATERIALS AND METHODS: Twenty-one patients with DoC were included in the study. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). Statistical analysis was performed with the nonparametric Wilcoxon test for comparison of both total NCS-R-SS and NCS-R-PS scores. RESULTS: NCS-R at admission showed that 9 of 21 patients (42.8%) had higher scores in response to personalized stimulus compared to standard stimulus. Significant correlation with CRS-R were found for both NCS-R-SS (R = 0.701, p = .008) and NCS-R-PS (R = 0.564, p = .045). Discussion: The preliminary results obtained in the present study suggest that NCS-R-PS may disclose pain perception in a larger number of non-communicative patients with DoC, compared to NCS-R-SS.

Effects of CGRP receptor antagonism in nitroglycerin-induced hyperalgesia.

BACKGROUND: The release of calcitonin gene-related peptide (CGRP) from trigeminal nerves plays a central role in the pathophysiology of migraine and clinical evidence shows an antimigraine effect for CGRP receptor antagonists. Systemic administration of nitroglycerin (NTG), a nitrovasodilator, consistently provokes spontaneous-like migraine attacks in migraine sufferers; in the rat, systemic NTG induces a condition of hyperalgesia, probably through the activation of cerebral/spinal structures involved in nociceptive transmission. AIM: The aim of this article is to test the analgesic effect of the CGRP receptor antagonist MK-8825 in two animal models of pain that may be relevant for migraine: the tail flick test and the formalin test performed during NTG-induced hyperalgesia. RESULTS: MK-8825 showed analgesic activity when administered alone at both the tail flick test and the formalin test. Furthermore, the CGRP antagonist proved effective in counteracting NTG-induced hyperalgesia in both tests. MK-8825 indeed reduced the nociceptive behavior when administered either simultaneously or prior to (30-60 minutes before) NTG. CONCLUSION: These data suggest that MK-8825 may represent a potential therapeutic tool for the treatment of migraine.

Experimental models of migraine.

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, i.e., 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.

Pathways to the best fit of triptans for migraine patients.

Variability in drug response is a major barrier to the successful treatment of migraine, and most treatments are only optimal in a subset of patients. Although triptans provide the best therapeutic option for the treatment of acute migraine, it has not previously been possible to predict how well patients will respond to a specific triptan or whether they will experience unpleasant adverse events. Hence, it has been difficult for physicians to match individual patients with the most suitable agent to treat their migraine pain. Intrapatient variability has been associated with polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters and drug targets. Pharmacogenetics provides the possibility of tailoring the therapeutic approach to individual patients, in order to maximize treatment efficacy while minimizing the potential for unwanted side-effects. This review demonstrates how almotriptan may overcome genetically determined responses by utilizing diverse metabolic pathways to provide therapeutic benefit to many migraineurs.

The value of the D-Dimer assay for predicting vein thrombosis in rehabilitation patients receiving prophylactic low molecular weight heparin doses.

PURPOSE: Early diagnosis and treatment of venous thrombosis biocontact="no" are essential in preventing pulmonary embolism (PE) and reducing the risk of recurrence. The objective was to assess the usefulness of the D-Dimer testing to rule out symptomatic VT in populations of patients receiving heparin in prophylactic doses. METHODS: One hundred and twenty-three rehabilitation patients with medium or high risk for VT were investigated. Patients were affected by acquired cerebral diseases (n=31), severe brain damage (n=32) or orthopaedic surgical sequelae for major joint replacement or multiple limb fractures (n=60). All patients were receiving prophylactic heparin doses. D-Dimer levels were assessed using Dimertest Latex Agglutination Assay in citrated plasma. Single blinded compression Doppler Ultrasound (DUS) examination was performed in conformity with international standards. RESULTS: In this specific setting, good sensitivity and specificity of the D-Dimer test was confirmed in patients with acquired cerebral diseases during rehabilitation, whereas false positive results were found in most patients who had undergone major joint replacement, until several weeks after surgery. CONCLUSIONS: In rehabilitation patients receiving prophylactic heparin doses, the D-Dimer test seems to confirm high sensitivity and high negative predictive value for VT and PE. Relevant clinical variables seem to reduce the usefulness of the D-Dimer test as a screening tool for VT, at least in orthopaedic patients with joint prosthesis.

The impact of prophylactic treatment on post-traumatic epilepsy after severe traumatic brain injury.

AIM: To assess the incidence of late post-traumatic epilepsy (PTE) in patients with very severe traumatic brain injury (TBI) who either received or did not receive anti-epileptic prophylactic treatment. METHODS: Two populations were studied: 55 patients retrospectively and 82 subjects prospectively. RESULTS: Ten patients (18%) in the first population showed late PTE. Although the incidence was lower in patients who did not receive prophylactic treatment, the difference between the treated and the non-treated group was not statistically significant. Sixty-nine patients in the second group (84%) had prophylactic treatment. Twenty-seven patients (39%) suffered from late PTE during the 2-year follow-up period and 17 of them (63%) showed EEG epileptic abnormalities. No patient who did not receive preventive therapy suffered from late PTE during the observation period. CONCLUSIONS: Due to the negative cognitive effects of anti-epileptic drugs, the preliminary results are of considerable interest for the rehabilitation of patients with very severe TBI.

A novel ATP1A2 mutation in a family with FHM type II.

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura with an autosomal dominant pattern of inheritance. Six FHM families underwent extensive clinical and genetic investigation. The authors identified a novel ATP1A2 mutation (E700K) in three patients from one family. In the patients, attacks were triggered by several factors including minor head trauma. In one subject a 3-day coma developed after a cerebral angiography. Overall, the phenotype of the patients closely resembles that of previously reported cases of FHM type II. The E700K variant might be regarded as the cause of the disease in this family, but this was not tested functionally.

Adult abdominal migraine: a new syndrome or sporadic feature of migraine headache? A case report.

Abdominal migraine is one of the variants of migraine headache typically occurring in children and coded as 1.3.2 in the revised edition of IHS classification within the group 'Childhood periodic syndromes that are commonly precursors of migraine'. The affected children frequently develop typical migraine later in their life. We report a case of a 23 years old woman affected by attacks of recurrent abdominal pain accompanied by migraine. Abdominal pain attacks started in the adolescence and persisted without headache until the patient was 21. At this time, she experienced migraine pain accompanied by nausea, photophobia and phonophobia and associated to acute abdominal pain. Neuroimaging investigations and laboratory testing excluded any underlying organic disease. Complete remission of abdominal attacks was obtained during 4-month treatment period with pizotifen. Attacks fulfil IHS diagnostic criteria for 'abdominal migraine', although of late onset. This case report suggests that 'abdominal migraine' is a migraineous disorder to be hypothesized in adult patients after having disclosed any organic disease. As reported in the literature, 'adult abdominal migraine' is a sporadic migraine subtype in adult patients and it is not to be considered as a new migraineous syndrome.

Familial basilar migraine associated with a new mutation in the ATP1A2 gene.

Basilar migraine (BM), familial hemiplegic migraine (FHM), and sporadic hemiplegic migraine (SHM) are phenotypically similar subtypes of migraine with aura, differentiated only by motor symptoms, which are absent in BM. Mutations in CACNA1A and ATP1A2 have been found in FHM. The authors detected a novel mutation in the ATP1A2 gene (R548H) in members of a family with BM, suggesting that BM and FHM may be allelic disorders.

Early clinical predictive factors during coma recovery.

In severe brain injury patients few studies have examined the role of early clinical factors emerging before recovery of consciousness. Patients suffering from vegetative state and minimally conscious state in fact may need variable periods of time for recovery of the ability to follow commands. In a previous study we retrospectively examined a population of very severe traumatic brain injury patients with coma duration of at least 15 days (prolonged coma), and we found, as significant predictive factors for the final outcome, the time interval from brain injury to the recovery of the following clinical variables: optical fixation, spontaneous motor activity and first safe oral feeding. Psychomotor agitation and bulimia during coma recovery were also favourable prognostic factors for the final outcome. In a further study, also as for the neuropsychological recovery, the clinical variable with the best significant predictive value was the interval from head trauma to the recovery of safe oral feeding. In the present study the presence of psychomotor agitation diagnosed by means of LCF (score 4 = confused-agitated) at the admission time in rehabilitation predicted a statistically significant better outcome at the discharge time in comparison with patients without agitation.

Time interval of oral feeding recovery as a prognostic factor in severe traumatic brain injury.

PRIMARY OBJECTIVES: To assess the outcome of severe traumatic brain injury at least 1 year after trauma, in relation to some early clinical prognostic factors occurring during coma recovery. RESEARCH DESIGN: Retrospective study conducted at the post-coma unit of a rehabilitation hospital. METHODS AND PROCEDURES: A total of 43 patients were included. All of the patients sustained severe traumatic brain injury and prolonged coma, i.e. coma lasting at least 15 days. Outcome was assessed by means of Glasgow Coma Scale, Barthel Index and Mini Mental State 1 year after trauma, in relation to some early clinical prognostic factors occurring during coma recovery. MAIN OUTCOMES AND RESULTS: At the 1 year follow-up, a statistically significant correlation was found with both the Glasgow Outcome Scale and the Barthel Index for the time interval from brain injury to recovery of the following clinical variables: optical fixation, ability to obey commands, spontaneous motor activity and first safe oral feeding. Psychomotor agitation and bulimia were also favourable prognostic factors for the final outcome. CONCLUSIONS: In the present study, first safe oral feeding during coma recovery represents the clinical feature that better predicts the final outcome of patients with severe traumatic brain injury and prolonged coma.

Peripheral and central activation of trigeminal pain pathways in migraine: data from experimental animal models.

Animal models for migraine have provided substantial advances on the mechanisms and mediators underlying migraine attacks. The neurogenic inflammation model has helped understanding the perivascular mechanisms underlying the pathophysiology of migraine attacks, the receptors involved and the effect of specific antimigraine drugs. The model based on probing the neuronal effects of nitroglycerin--an organic nitrate known to induce spontaneous-like migraine attacks in predisposed subjects--in the rat has provided interesting insights into the neuroanatomic circuits and neuropharmacological mechanisms involved in the initiation and repetition of migraine attacks [corrected].

Cavernous angiomas of the nervous system in Italy: clinical and genetic study.

We performed a clinical and genetic study of patients affected by cavernous angiomas (CA) of the nervous system. We examined initial signs and symptoms in sporadic and familial cases. We obtained clinical, neuroimaging and genetic data on 15 Italian patients with CA of the nervous system with positive, doubtful or apparently negative family history. Genetic markers surrounding three different gene regions (7q, 3q and 7p) were analysed. In one small family, genetic linkage was consistent with all chromosome loci. In another family with the unusual association of cerebral and spinal CA, linkage with chromosome 7q and, likely, 7p was excluded, while linkage with locus 3q was possible. Our results indicate that Italian families with CA may show genetic heterogeneity. Non-specific and subtle onset symptoms hide the presence of CA within families. Patients with multiple CA may have silent cerebral lesions confirming the low penetrance of clinical signs in spite of radiological ones.

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.

mtDNA A3243G MELAS mutation is not associated with multigenerational female migraine.

The authors searched for mitochondrial DNA (mtDNA) A3243G mutation in peripheral blood leukocytes from female migraine patients with pure matrilinear history of migraine along two or three generations. The current study was designed to exclude any male transmission of the disease. The mutation was absent in all patients. We conclude that mtDNA A3243G mutation does not contribute to the pathogenesis of pure matrilinear multigenerational migraine with or without aura.

New methods for evaluating acute treatments in migraine.

The crescendo of activities in the field of migraine therapy, has led to the emergence of a class of molecules, the triptans, that are similar in terms of their activity on serotonin receptors, but which actually differ from one another, as each one has its own peculiar clinical profile. A careful examination of their clinical activity and their validation with objective methods may promote the wise use of each drug, make room for new products, and allow patients to make their own choices.