Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease

Dolor posoperatorio en craneotomía

In the postoperative period, 47% to 75% of the patients report some degree of pain. This study aimed to evaluate pain in the pre and postoperative period of patients submitted to craniotomy. This prospective research was carried out at the neurosurgery unit of a large Brazilian hospital. For a quantitative evaluation of pain, the verbal numeric 0 - 10 rating scale was used. Forty patients with a mean age of 36 years were evaluated. In the preoperative period, 34 (85%) patients indicated headache as the main cause of pain. In the postoperative period, 37 (93%) patients complained of pain while three (7%) reported absence of pain. Pain peaks were observed on the 2nd postoperative day, when 12 (32%) of the patients reported severe pain and 10 (27%) moderate pain. Absence of severe pain occurred after the 8th postoperative day. It was concluded that protocols of analgesia in craniotomy are needed, such as training nurses to better evaluate and handle pain.En el periodo postoperatorio, entre el 47% y el 75% de los pacientes relatan algún grado de dolor. Los objetivos de este trabajo fueron evaluar el dolor en el pre y postoperatorio de pacientes sometidos a craneotomía. Este estudio prospectivo fue realizado en la unidad de neurocirugía del Hospital São Paulo, Brasil. Para una evaluación cuantitativa del dolor se utilizó la escala numérica verbal graduada de 0 a 10. Fueron evaluados 40 pacientes con edad mediana de 36 años. En el preoperatorio 34 (85%) pacientes, reportaran cefalea como la principal causa del dolor. En el postoperatorio, 37 (93%) pacientes se quejaron de dolor, mientras 3 (7%) pacientes indicaron ausencia de dolor. El pico de dolor fue observado en el segundo día postoperatorio, cuando 12 (32%) pacientes reportaron dolor grave y 10 (27%) moderado. La ausencia de dolor grave ocurrió después del 8º día postoperatorio. Se concluyó que son necesarios protocolos de analgesia en craneotomía, tales como el entrenamiento de enfermeros para mejor evaluar y manejar el dolor.No pós-operatório, 47 a 75% dos pacientes relatam algum grau de dor. O objetivo deste trabalho foi avaliar a dor no pré e pós-operatório de pacientes submetidos a craniotomia. Estudo prospectivo, realizado na unidade de neurocirurgia do Hospital São Paulo. Para avaliação quantitativa de dor, foi utilizada a escala numérica verbal, graduada de 0 a 10. Foram avaliados 40 pacientes, com idade mediana de 36 anos. No pré-operatório, 34 (85%) pacientes relataram cefaléia como a principal causa de dor. No pós-operatório, 37 (93%) pacientes queixaram-se de dor e 3 (7%) pacientes referiram ausência de dor. O pico da dor foi observado no 2º pós-operatório, quando 16 (40%) dos pacientes referiram dor intensa e 11 (28%) queixaram-se de dor moderada. Ausência de dor intensa ocorreu após 6º pós-operatório. Concluí-se que há necessidade de protocolos de analgesia em craniotomia, como treinamento para os enfermeiros para melhor avaliação e manejo da dor.Hospital Israelita Albert EinsteinUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Topiramate plus nortriptyline in the preventive treatment of migraine: a controlled study for nonresponders

A sizeable proportion of migraineurs in need of preventive therapy do not significantly benefit from monotherapy. The objective of the study is to conduct a randomized controlled trial testing whether combination therapy of topiramate and nortriptyline is useful in patients who had less than 50% decrease in headache frequency with the use of the single agents. Patients with episodic migraine were enrolled if they had less than 50% reduction in headache frequency after 8 weeks of using topiramate (TPM) (100 mg/day) or nortriptyline (NTP) (30 mg/day). They were randomized (blinded fashion) to have placebo added to their regimen, or to receive the second medication (combination therapy). Primary endpoint was decrease in number of headache days at 6 weeks, relative to baseline, comparing both groups. Secondary endpoint was proportion of patients with at least 50% reduction in headache frequency at 6 weeks relative to baseline. A total of 38 patients were randomized to receive combination therapy, while 30 continued on monotherapy (with placebo) (six drop outs in the combination group and three for each single drug group). For the primary endpoint, mean and standard deviation (SD) of reduction in headache frequency were 4.6 (1.9) for those in polytherapy, relative to 3.5 (2.3) for those in monotherapy. Differences were significant (p < 0.05]. Similarly, 78.3% of patients randomized to receive polytherapy had at least 50% headache reduction, as compared to 37% in monotherapy (p < 0.04). Finally we conclude that combination therapy (of TPM and NTP) is effective in patients with incomplete benefit using these agents in monotherapy

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Experience with onabotulinumtoxinA (BOTOX) in chronic refractory migraine: focus on severe attacks

The objective of this study is to analyse our experience in the treatment of refractory chronic migraine (CM) with onabotulinumtoxinA (BTA) and specifically in its effects over disabling attacks. Patients with CM and inadequate response or intolerance to oral preventatives were treated with pericranial injections of 100 U of TBA every 3 months. The dose was increased up to 200 U in case of no response. The patients kept a headache diary. In addition, we specifically asked on the effect of BTA on the frequency of disabling attacks, consumption of triptans and visits to Emergency for the treatment of severe attacks. This series comprises a total of 35 patients (3 males), aged 24–68 years. All except three met IHS criteria for analgesic overuse. The number of sessions with BTA ranged from 2 to 15 (median 4) and nine (26%) responded (reduction of >50% in headache days). However, the frequency of severe attacks was reduced to an average of 46%. Oral triptan consumption (29 patients) was reduced by 50% (from an average of 22 to 11 tablets/month). Those six patients who used subcutaneous sumatriptan reduced its consumption to a mean of 69% (from 4.5 to 1.5 injections per month). Emergency visits went from an average of 3 to 0.4 per trimester (−83%). Six patients complained of mild adverse events, transient local cervical pain being the most common. Although our data must be taken with caution as this is an open trial, in clinical practice treatment of refractory CM with BTA reduces the frequency of disabling attacks, the consumption of triptans and the need of visits to Emergency, which makes this treatment a profitable option both clinically and pharmacoeconomically

Mental turmoil, suicide risk, illness perception, and temperament, and their impact on quality of life in chronic daily headache

To evaluate the relationship among quality of life, temperament, illness perception, and mental turmoil in patients affected by chronic daily headache with concomitant medication overuse headache. Participants were 116 consecutive adult outpatients admitted to the Department of General Medicine of the Sant’Andrea Hospital in Rome, between January 2007 and December 2007 with a diagnosis of chronic daily headache (illness duration >5 years). Patients were administered the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A), the Beck Hopelessness Scale (BHS), the Hamilton Rating Scale for Depression (HAM-D), the Mini-International Neuropsychiatric Interview (MINI), the Revised Illness Perception Questionnaire (IPQ), the Suicide Score Scale (SSS), and the Quality of Life Index (QL-Index). Twenty-eight percent of the patients evidenced moderate to severe depression, and 35% evidenced severe hopelessness. Analyses also indicated that quality of life, temperament, illness perception, and psychological turmoil are associated. However, a hierarchical multivariate regression analysis with quality of life as dependent variable indicated that only a model with mental turmoil variables may fit data; further, only the MINI suicidal intent resulted associated with quality of life (standardized regression coefficient = −0.55; t = −3.06; P < 0.01). Suicide risk may play a central role in affecting the quality of life of patients with chronic headache. The investigation of the interplay of factors that precipitate suicide risk should include assessment of chronic headache and its effects on wellbeing

Neurogenic inflammation and sensitivity to environmental chemicals.

Neurogenic inflammation as a pathway distinct from antigen-driven, immune-mediated inflammation may play a pivotal role in understanding a broad class of environmental health problems resulting from chemical exposures. Recent progress in understanding the mediators, triggers, and regulation of neurogenic inflammation is reviewed. Evidence for and speculations about a role for neurogenic inflammation in established disorders such as asthma, rhinitis, contact dermatitis, migraine headache, and rheumatoid arthritis are presented. The sick building syndrome and multiple chemical sensitivity syndrome have been defined as clinical entities in which exposure to chemical inhalants gives rise to disease. Current data on the existence of chemical irritant receptors in the airway and skin are discussed; neurogenic inflammation arising from stimulation of chemical irritant receptors is a possible model to explain many of the aspects of chemical sensitivities