Secondary stabbing headache associated with intracranial tumors, aneurysms, and arteriovenous malformation: An alarming warning sign.

BACKGROUND: Stabbing headache (SH) is considered as a pure primary headache, but according to a few clinical observations it could also be secondary. Over the past decades, we have been observing the complaint of SH in patients with intracranial vascular and neoplastic lesions. OBJECTIVE: To describe a series of patients with intracranial lesions who experienced SH. METHODS: This is a cross-sectional, retrospective study of 34 patients with intracranial lesions associated with SH, admitted at Hospital das Clínicas, Federal University of Pernambuco, Brazil. RESULTS: In this series of 34 patients [29 women, 44 ± 12 years (mean ± SD)] with secondary SH, the causes were intracranial neoplasms (n = 31), cerebral aneurysms (n = 2), or arteriovenous malformation (n = 1). Pituitary tumor (n = 18), meningioma (n = 6), and vestibular schwannomas (n = 4) were the most prevalent types of intracranial neoplasms. All these lesions had intimate contact with the dura mater, including an oligodendroglioma, the only intra-axial tumor in the series. A characteristic in the secondary SH is the crescendo pattern (12/34, 35%), progressing from infrequent attacks to recurrent crises occurring several times a day. The SH lasted from 5 days to 60 months (15 ± 18 months, mean ± SD) until the correct diagnosis [16/34 (47%) of the patients ≤6 months]. The SH was triggered by the movement of the head (5/34, 15%) or Valsalva maneuver (1/34). After surgery, suppression of the SH was observed. In a few of the patients to whom dexamethasone was prescribed, the SH subsided within a few days. CONCLUSION: This study was able to identify clinical red flags associated with intracranial lesions and secondary SH, for example, recent onset of SH, exclusively unilateral (ipsilateral) at the same location, crescendo pattern, triggered by head movements, or Valsalva maneuver.

The pharmacological treatment of migraine in Brazil.

BACKGROUND/OBJECTIVES: Migraine is a chronic, disabling, and recurrent illness. Despite its burden, preventive medications are often underused, while acute strategies are frequently used injudiciously. Patients may benefit from comprehensive approaches with general informative orientation and formal medication strategies. In developing countries like Brazil, the access to comprehensive tertiary headache centers or updated specialists is somewhat limited, as are the resources available out of some private specialty care clinics. In addition, centers from the public system may not deliver effective care. The aim of this review is to perform a general description of the pharmacological treatments of migraine in tertiary headache centers of Brazil. METHODS: The data of 4 public and 6 private tertiary centers under the care of 16 neurologists involved with headache assistance in different cities of Brazil were gathered. Answers to questions directed to headache specialists, and analyzing data from previous care of patients was used to estimate a description of the general pharmacological approach used in Brazilian centers. The therapeutic options adopted by general practitioners were not considered as those from other medical specialties and holistic medicine, which also treat migraine on a common basis. RESULTS: Estimated data of nearly 4800 patients from 16 neurologists acting in headache clinics from 2005 to 2013 were collected. Headache approach by specialists in Brazil is basically divided into 2 groups. The public services, which assist nonpaying patients, deliver traditional and noncomprehensive approaches as well as prescribe mostly monotherapy. Roughly 30% of their patients do not receive preventive treatments that are generally tricyclic antidepressants or ß-blockers. Private centers, which are usually where paying people attend, as well as a few public centers of excellence, use multidisciplinary approaches and combination of drugs, despite the usual allegation of scarce evidence. Nearly 90% of the patients from these centers receive the prescription of preventive treatments, which are generally tricyclic antidepressants and/or neuromodulators and/or ß-blockers. COMMENTS: There is no consensus on whether patients turning to private tertiary centers are different from those seen in public nonpaying services. However, since it is directly related to economic status and public services may render free specific medications as well as official dispensation of work, it may be argued that patients have less headache impact, and suboptimal care is delivered in these instances. As for the studied private centers as well as for the few public excellence centers, care provided is usually varied, includes a combination of drugs, and prevention is commonly used.

Wine and headache.

BACKGROUND: The notion of migraine attacks triggered by food and beverages has been posited for centuries. Red wine in particular has been acknowledged as a migraine trigger since antiquity when Celsus (25 B.C.-50 A.D.) described head pain after drinking wine. Since then, references to the relationship between alcohol ingestion and headache attacks are numerous. The most common initiator of these attacks among alcoholic beverages is clearly wine. The aim of this review is to present and discuss the available literature on wine and headache. METHODS: A Medline search with the terms headache, migraine, and wine was performed. Data available on books and written material about wine and medicine as well as abstracts on alcohol, wine, and headache available in the proceedings of major headache meetings in the last 30 years were reviewed. In addition, available technical literature and websites about wine, grapes, and wine making were also evaluated. RESULTS: Full papers specifically on headache and wine are scarce. General literature related to medicine and wine is available, but scientific rigor is typically lacking. The few studies on wine and headache were mostly presented as abstracts despite the common knowledge and patients' complaints about wine ingestion and headache attacks. These studies suggest that red wine, but not white and sparkling wines, do trigger headache and migraine attacks independently of dosage in less than 30% of the subjects. DISCUSSION: Wine, and specifically red wine, is a migraine trigger. Non-migraineurs may have headache attacks with wine ingestion as well. The reasons for that triggering potential are uncertain, but the presence of phenolic flavonoid radicals and the potential for interfering with the central serotonin metabolism are probably the underlying mechanisms of the relationship between wine and headache. Further controlled studies are necessary to enlighten this traditional belief.

Temporomandibular disorders and chronic daily headaches in the community and in specialty care.

BACKGROUND: Chronic daily headaches (CDHs) are often associated with temporomandibular disorders (TMDs). However, large studies assessing the relationship were conducted in general, and not clinical, populations. Thus, clinical exams were not completed. Clinic-based studies with expert diagnosis are, in turn, often small and may not be representative. OBJECTIVE: To contrast the demographic and clinical symptoms of CDH and TMD in participants within the general population relative to patients seen in a headache clinic. METHODS: All inhabitants 10 years and older of a small city in Brazil were interviewed. Those with more than 15 days of headache per month were examined by a team consisting of a neurologist, a dentist, and a physical therapist. Headaches were classified as per the Second Edition of the International Classification of Headache Disorders and TMD as per the Research Diagnostic Criteria. The procedure was repeated (by the same team) with CDH sufferers consecutively seen in a headache center. RESULTS: Of 1605 inhabitants interviewed, 57 (3.6%) had CDH, and 43 completed all physical assessments. For specialty care group, of 289 patients, 92 had CDH, and 85 completed all assessments. No significant differences were seen for gender and age, but education level was significantly higher among those recruited at specialty care. Muscular TMD happened in 30.2% of CDH patients from the community vs 55.3% in the headache center (difference of -25.1%, 95% confidence interval of difference=-40.8% to -9.4%). No TMD happened in 41.9% of those recruited from the population relative to 20% of those in the headache center (21.9%, 95% confidence interval=6.7-37.1%). CONCLUSION: Individuals with CDH recruited from the general population are significantly less likely to have CDH relative to those selected from the headache center. Issues of generalizability are of concern when conducting clinic-based studies on the topic.

Adherence to migraine treatment does not depend on the number of prescribed medications.

OBJECTIVE: To compare the adherence between monotherapy and politherapy in prophylactic migraine treatment. METHOD: Five hundred consecutive patients with migraine from a tertiary center were retrospectively studied as to the number of preventive medications prescribed during the first visit. Adherence, defined as returning for the next consultation after 4 to 6 weeks and following the prescribed regimens, were also evaluated and compared between patients. RESULTS: 71.8% were women, and 6% of the patients did not receive any preventive medication, 11.4% received one drug, 22.2% two drugs, 41.4% three drugs, and 19% four drugs for the prevention of migraine. The overall adherence was 79.6%. Respectively, 73.7, 71.8, 82.6 and 86.3% of those who received the prescription of one, two, three and four drugs returned, complying with the treatment. CONCLUSION: There is no difference in adherence to monotherapy or politherapy (one to four drugs) for the prophylaxis of migraine.

Adherence to migraine treatment does not depend on the number of prescribed medications / A adesão ao tratamento da migrânea não depende do número de medicações prescritas

To compare the adherence between monotherapy and politherapy in prophylactic migraine treatment. Five hundred consecutive patients with migraine from a tertiary center were retrospectively studied as to the number of preventive medications prescribed during the first visit. Adherence, defined as returning for the next consultation after 4 to 6 weeks and following the prescribed regimens, were also evaluated and compared between patients. 71.8% were women, and 6% of the patients did not receive any preventive medication, 11.4% received one drug, 22.2% two drugs, 41.4% three drugs, and 19% four drugs for the prevention of migraine. The overall adherence was 79.6%. Respectively, 73.7, 71.8, 82.6 and 86.3% of those who received the prescription of one, two, three and four drugs returned, complying with the treatment. There is no difference in adherence to monotherapy or politherapy (one to four drugs) for the prophylaxis of migraine. .

Comparar a adesão entre monoterapia e politerapia no tratamento profilático da migrânea. Foram analisados retrospec-tivamente 500 pacientes com migrânea de um centro terciário, com vistas ao número de medicações preventivas prescritas na primeira consulta e adesão ao tratamento após 4 a 6 semanas. 71,8% da amostra era composta de mulheres. Em relação ao tratamento preventivo da migrânea, 6% não receberam medicação preventiva; 11,4% receberam uma droga; 22,2% duas drogas; 41,4% três drogas e 19% quatro drogas. A adesão média foi de 79,6%. Em relação à prescrição de uma, duas, três ou quatro drogas, essa adesão foi respectiva-mente de 73,7, 71,8, 82,6 e 86,3%. Não houve diferenças na adesão à prescrição de medicações em monoterapia ou politerapia (uma a quatro drogas) para o tratamento preventivo da migrânea. .

Utilização do diclofenaco na prática clínica: revisão das evidências terapêuticas e ações farmacológicas / Use of diclofenac in clinical practice: review of the therapeutic evidence and pharmacologic actions

JUSTIFICATIVA E OBJETIVOS: Os anti-inflamatórios não esteroides (AINES) apresentam atividade farmacológica de inibição das isoenzimas ciclo-oxigenase-1 (COX-1) e ciclo-oxigenase-2 (COX-2) em graus diversos, cujos perfis de segurança variam individualmente.A eficácia é semelhante, porém os possíveis eventos adversos são relevantes nas decisões do tratamento prescrito. O diclofenaco está disponível internacionalmente há mais de 40 anos, tendo seu perfil farmacológico e de segurança documentados em diversos estudos básicos e clínicos. O objetivo desta revisão da literatura foi de apresentar aspectos da dor e do uso de diclofenaco na prática clínica, incluindo as indicações as questões de segurança e a eficácia do medicamento. CONTEÚDO: Esta revisão da literatura apresentará a farmacologia básica do diclofenaco, bem como evidências terapêuticas com o uso deste fármaco em diversas condições dolorosas e suas implicações na prática clínica. CONCLUSÃO: O diclofenaco tem demonstrado eficácia clínica no tratamento de diversas condições dolorosas, entre estas lombalgias, artrites, dores pós-traumáticas e pós-cirúrgicas, dismenorreias,bem como cólica renal e biliar. Vale ressaltar que, na avaliação de um paciente apresentando dor e ao decidir um plano de tratamento e na prescrição de qualquer medicamento, cabe ao médico avaliar cuidadosamente o paciente para determinar o melhor curso de ação no individuo, levando-se em consideração o histórico médico do paciente, comorbidades e uso de medicamentos concomitantes, a fim de proporcionar a melhor alternativa terapêutica, com redução máxima da dor e inflamação e a restauração da funcionalidade de forma mais segura.

BACKGROUND AND OBJECTIVES: The nonsteroidal antiinflammatory-drugs (NSAIDs) exhibit pharmacological activity inhibiting the isoenzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in varying degrees, and their safety profiles vary individually. Their efficacy is similar, but the possible adverse effects are relevant in deciding treatment prescriptions. Diclofenac has been available internationally for over 40 years, and its pharmacological and safety profile has been documented in numerous preclinical and clinical studies. The objective of this literature review was to present aspects of pain and the use of diclofenac in clinical practice, including indications, safety issues, and efficacy of the drug. CONTENTS: This literature review will present the basic pharmacology of diclofenac, as well as evidence for the therapeutic use of this drug in several painful conditions and the implications for clinical practice. CONCLUSION: Diclofenac has shown clinical efficacy in the treatment of a variety of painful conditions, including lumbagos,arthritis, post-traumatic and post-surgical pain, dysmenorrhea,as well as renal and biliary colic. It is important to note that in the evaluation of a patient presenting pain and when deciding a treatment plan and the prescription of any medication, it is upto the physician to carefully assess the patient to determine the best course of action in that individual, taking into account thepatients' medical history, co-morbidities, and use of concomitant medications, in order to provide the best therapeutic alternative,with a maximum reduction of pain and inflammation and restoration of functionality in the safest possible way.

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.

Low-dose topiramate plus sodium divalproate for positive responders intolerant to full-dose monotherapy.

BACKGROUND: Neuromodulators such as topiramate (TPM) and divalproex sodium (DVS) are effective in the preventive treatment of migraine. Nonetheless, patients often discontinue their use due to side effects. OBJECTIVES: The study aims to determine whether the combination of lower doses of TPM and DVS may be useful for patients responsive to higher doses of the individual drugs but experiencing intolerable side effects. METHODS: This clinic-based study was conducted to evaluate a series of patients who experienced at least a 50% reduction in headache frequency after 6 weeks of treatment with either TPM 100 mg/day or DVS 750 mg/day, but suffered intolerable drug-related side effects. At that point, patients were switched to TPM (50 mg in the morning and 25 mg at night) plus DVS 500 mg/day (single dose) and reevaluated after 6 further weeks. RESULTS: Thirty-eight patients were evaluated. Mean age was 37 years, and 84% were female. Of the 38, 17 (77.3%) initially were using TPM only, and 10 (62.5%) initially were using DVS only. After 6 weeks on combination therapy, 27 (62.9%) reported improved tolerability without any decrease in efficacy. Five patients who initially were using TPM only and six using DVS only failed to return for follow-up or were noncompliant with treatment due to persistent or worsening side effects. CONCLUSIONS: This small, open-label study suggests that the combination of TPM and DVS in doses lower than those typically used for migraine prophylaxis may be an effective option for patients who benefited from higher doses of these same medications used as monotherapy but were unable to tolerate such treatment due to side effects.

Headaches due to external compression.

Headache is one of the most common types of recurrent pain in medical practice. Although nearly everyone has occasional headaches, there are well-defined headache disorders that vary in incidence and prevalence. Among the unusual headache syndromes, headache due to external compression is a poorly studied headache considered to arise as a result of continued stimulation of cutaneous nerves by the application of pressure over the scalp or forehead. The wearing of bands around the head, specifically goggles (such as those worn for swimming), tight hats, or even professional helmets have been described as causative factors. The pain is often constant and more severe at the location where the object is pressing the head. In predisposed patients (ie, those with migraine), external compression may lead to a more severe migrainous headache if the stimulus is prolonged. The mechanism responsible is the compression of trigeminal or occipital nerves branches. The headache resolves after pressure is relieved, or is prevented by avoiding the precipitating cause. Drugs are rarely used.

Migraine prevention trials and optimized acute therapy: translating lessons learned into clinical practice.

Different classes of drugs, discovered by serendipity, have been used successfully for migraine prevention for more than 40 years. The progressive knowledge of migraine pathophysiology, brain hyperexcitability, and the specific neurotransmitter systems involved in pain perception has driven the attempts at targeting two crucial mechanisms: the restoration of nociceptive dysmodulation and the inhibition of cortical hyperexcitability. The success of modern research trials with preventive migraine agents (mainly neuromodulators) and optimized treatment of acute attacks with drug combinations aimed at low serotonergic function, neurogenic inflammation, and central sensitization has translated into better outcomes for patients and physicians. Trials combining preventive migraine agents with nonpharmacologic behavioral headache management have yielded additional benefits over either approach alone. With the clinical application of this updated information from clinical trials, migraine impact on productivity, quality of life, and suffering will certainly be diminished. We hope that these achievements will create a stable path of management to benefit our patients, without interruption, into the foreseeable future.

Lysine clonixinate versus dipyrone (metamizole) for the acute treatment of severe migraine attacks: a single-blind, randomized study.

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Lysine clonixinate (LC) and dipyrone (metamizol) have been proven effective to treat acute migraine. The aim of this study was to evaluate the efficacy and tolerability of the intravenous formulations of LC and dipyrone in the treatment of severe migraine attacks. METHOD: Thirty patients (28 women, 2 men), aged 18 to 48 years with migraine according the International Headache Society (IHS) (2004) were studied. The patients were randomized into 2 groups when presenting to an emergency department with a severe migraine attack. The study was single-blind. Headache intensity, nausea, photophobia and side effects were evaluated at 0, 30, 60 and 90 minutes after the drug administration. Rectal indomethacin as rescue medication (RM) was available after 2 hours and its use compared between groups. RESULTS: All patients completed the study. At 30 minutes, 0% of the dipyrone group 13% of the LC group were pain free (p=0.46). At 60 and 90 minutes, 2 (13%) and 5 (33%) patients from the dipyrone group and 11 (73%) and 13 (86.7%) patients from the LC group were pain free (p<0.001). At 60 minutes, significantly more patients from the LC group were nausea-free (p<0.001). Regarding photophobia, there were no differences between groups at 60 minutes (p=0.11). The use of RM at 2 hours did not differ among groups (p=0.50). Pain in the site of the injection was reported by more patients of the LC group compared to the dipyrone group (p<0.0001). CONCLUSION: LC is significantly superior to dipyrone in treating severe migraine attacks. LC promotes significantly more burning at the site of the injection.

Lysine clonixinate versus dipyrone (metamizole) for the acute treatment of severe migraine attacks: a single-blind, randomized study / Clonixinato de lisina versus dipirona (metamizol) para o tratamento agudo de uma crise intensa de enxaqueca: estudo monocego e randomizado

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Lysine clonixinate (LC) and dipyrone (metamizol) have been proven effective to treat acute migraine. The aim of this study was to evaluate the efficacy and tolerability of the intravenous formulations of LC and dipyrone in the treatment of severe migraine attacks. METHOD: Thirty patients (28 women, 2 men), aged 18 to 48 years with migraine according the International Headache Society (IHS) (2004) were studied. The patients were randomized into 2 groups when presenting to an emergency department with a severe migraine attack. The study was single-blind. Headache intensity, nausea, photophobia and side effects were evaluated at 0, 30, 60 and 90 minutes after the drug administration. Rectal indomethacin as rescue medication (RM) was available after 2 hours and its use compared between groups. RESULTS: All patients completed the study. At 30 minutes, 0 percent of the dipyrone group 13 percent of the LC group were pain free (p=0.46). At 60 and 90 minutes, 2 (13 percent) and 5 (33 percent) patients from the dipyrone group and 11 (73 percent) and 13 (86.7 percent) patients from the LC group were pain free (p<0.001). At 60 minutes, significantly more patients from the LC group were nausea-free (p<0.001). Regarding photophobia, there were no differences between groups at 60 minutes (p=0.11). The use of RM at 2 hours did not differ among groups (p=0.50). Pain in the site of the injection was reported by more patients of the LC group compared to the dipyrone group (p<0.0001). CONCLUSION: LC is significantly superior to dipyrone in treating severe migraine attacks. LC promotes significantly more burning at the site of the injection.

CONTEXTO E OBJETIVO: Antiinflamatórios não esteroidais (AINE) são eficazes no tratamento de crises de enxaqueca. O objetivo deste estudo foi comparar a eficácia e a tolerabilidade das apresentações injetáveis do clonixinato de lisina (CL) e da dipirona no tratamento de crises intensas de enxaqueca. MÉTODO: Trinta pacientes (28 mulheres, 2 homens), com idades entre 18 e 48 anos e enxaqueca de acordo com a Classificação Internacional de Cefaléias (2004) foram estudados. Os pacientes foram randomizados em 2 grupos ao se apresentarem em uma unidade de emergência, com uma crise intensa de enxaqueca. O desenho do estudo foi monocego. A intensidade da cefaléia, a presença de náusea e fotofobia e os efeitos colaterais foram avaliados e comparados na administração das drogas e após 30, 60 e 90 minutos. Indometacina retal foi disponibilizada como droga de resgate (DR) e seu uso comparado entre os grupos. RESULTADOS: Todos os pacientes completaram o estudo. Após 30 minutos, 0 por cento do grupo da dipirona e 13 por cento do CL encontravam-se sem cefaléia (p=0,46). Após 60 e 90 minutos, 2 (13 por cento) e 5 (33 por cento) do grupo da dipirona e 11 (73 por cento) e 13 (86,7 por cento) do grupo do CL encontravam-se sem cefaléia (p<0,001). Após 60 minutos, o CL foi mais eficaz que a dipirona em eliminar a náusea (p<0,001), mas não houve diferença quanto à melhora da fotofobia entre os grupos (p=0,11). Não houve diferenças entre os grupos que utilizaram DR (p=0,50). Dor no local da injeção foi apresentada por mais pacientes que usaram CL comparados aos da dipirona (p<0,001). CONCLUSÃO: O CL é significativamente superior a dipirona no tratamento de uma crise intensa de enxaqueca, mas resulta em mais queimação no local da injeção.

Topiramato no tratamento preventivo da migrânea: variação da resposta após mudança para genérico: relato de caso / Topiramate in the preventive treatment of migraine: response variation after switching to the generic formulation: case report

O uso de genéricos se disseminou no Brasil há poucos anos devido ao menor custo do tratamento e a recomendações de balconistas de farmácia. Em pacientes com epilepsia, a troca de anticonvulsivantes originais por genéricos pode provocar crises e modificar o perfil de tolerabilidade em função de variações na bioequivalência e no nível plasmático destes medicamentos. No entanto, na prevenção da enxaqueca não há estudos disponíveis comparando o uso de anticonvulsivantes originais com genéricos na modificação dos parâmetros de eficácia e tolerabilidade. Relatamos o caso de uma paciente com enxaqueca sem aura que apresentou aumento da freqüência de crises e modificação nos efeitos colaterais com a substituição do Topamax® por topiramato genérico, tendo voltado a apresentar melhora ao retomar o uso do preparado original.

The use of generic drugs has been disseminated in Brazil due to the better costs and a pushing behavior of pharmacists. In epileptic patients, the switching from original preparations to generics may trigger seizures or change the tolerability profile promoted by the variations in plasmatic levels and bioequivalence between the different preparations. However, in migraine prevention there are no studies so far evaluating the effects of original and generic anticonvulsants regarding effectiveness and tolerability. We report the case of a patient with migraine without aura who had an increasing frequency of attacks after switching from Topamax® to a generic topiramate. In addition, the patient improved after returning to the original topiramate.

Efficacy and tolerability of a combination of uridine, cytidine, and vitamin B12 in anemia. A double-blind, comparative study versus nucleotide monotherapy

Background: Deficiency in vitamin B12 is commonly associated with pernicious anemia, presenting a number of clinical symptoms resulting from neurological alterations due to modifications in myelin formation. Treatment consists of oral or parenteral vitamin B12 supplementation. Vitamin B12 has also been shown to have analgesic action whether administered alone or in combination with other therapeutic agents. Oral or parenteral pyrimidine ribonucleotide supplementation may be advantageous in the treatment of peripheral neuropathies. Objectives: To evaluate and compare the efficacy and tolerability of an orally administered combination of vitamin B12, uridine and cytidine, versus administration of the nucleotides alone in the treatment of the signs and symptoms of anemia. Study design: Study goal was normalization of MCV and MCH and serum vitamin B12 as well as improvement in pain and paresthesia among patients presenting these symptoms at Pretreatment. The study was designed as a double-blind, randomized trial in two arms: Group A patients were treated with the vitamin + nucleotide combination Group B patients received nucleotides alone. Treatment lasted 60 days, with two interim visits at 20 and 40 days of treatment and a final evaluation after 60 days of treatment. Setting: Patients were attended in an ambulatory setting of a UNIFESO university hospital. Patients: Eligible patients were between 18-65 years of age, with clinical and laboratory presentation of anemia with or without underlying autoimmune disease, caused by vitamin B12 deficiency. Female patients were not pregnant and were required to use birth control for the duration of the treatment period. Eighty patients were randomized, with 40 patients in each treatment group. Treatment consisted of 3 daily oral doses of: 1.0 mg hydroxocobalamin acetate, 2.5 mg cytidine 5'-{sodium P'(2-(trimethylammonio)-ethyl) hydrogen diphosphate}, and 1.5 mg uridine 5'-trisodium triphosphate for Group A patients, while patients in Group B received 2.5 mg cytidine 5'-{sodium P'(2-(trimethylammonio)-ethyl) hydrogen diphosphate}, and 1.5 mg uridine 5'-trisodium triphosphate in identical capsule forms. Main outcome measure: Primary outcome measures defined in the protocol included improvements in MCV, MCH and vitamin B12 reaching laboratory reference range, 3-point improvements in Global, Pain, and Paresthesia evaluations and a 20% reduction in VAS scores. Results: Normalization of laboratory evaluations occurred only in Group A. Three-point improvement in Global evaluation by the physician was observed only in Group A, while both groups showed improvement in Global evaluation by the patient. Patient's assessment of pain improved only in Group A, although VAS score decrease was noted in both groups both groups also had improvement in paresthesia evaluations. Vital signs did not change, while weight gain was observed in both groups. Adverse events seen in both groups included nausea, diarrhea, headache and abdominal cramps. Alterations in laboratory evaluations were reported in both groups, but could be directly attributed to anemia. Conclusion: The combination of vitamin B12, uridine and cytidine was found to be safe and effective in the treatment of the signs and symptoms of anemia in the population studied. The pain reduction observed in both groups may be attributed to activity of the nucleotides.

Adherence to headache treatment and profile of previous health professional seeking among patients with chronic headache: a retrospective analysis.

BACKGROUND AND OBJECTIVES: Chronic headache is common among patients in neurology clinics. Patients may suffer important economic and social losses because of headaches, which may result in high expectations for treatment outcomes. When their treatment goals are not reached quickly, treatment may be difficult to maintain and patients may consult with numerous health professionals. This retrospective study evaluated the relationship between treatment and the profiles of previous health professionals consulted by patients in a tertiary headache center. PATIENTS AND METHODS: The records were reviewed of all patients from a headache center who were seen in initial consultation between January 2000 and June 2003. Data related to patient demographic characteristics (sex and age), headache diagnosis, and the profile (quality and quantity) of previous healthcare consultations exclusively related to headache, were collected. The headache diagnoses were confirmed according to the IHS criteria (1988) and to the Silberstein criteria (1994,1996). Although adherence includes taking the prescribed medicines, discontinuing overused symptomatic medications, and changing behavior, among other things, for this study, adherence was defined as when the patient returned at least 2 times within a 3- to 3.5-month period. Patients were separated into groups depending on the number of different healthcare professionals they had consulted, from none to more than 7. RESULTS: Data from 495 patients were analyzed; 357 were women and 138 were men (ages 6 to 90 years; mean, 41.1 +/- 15.05 years). The headache diagnoses included migraine without aura (43.2%), chronic (transformed) migraine (40%), cluster headache (6.5%), episodic tension-type headache (0.8%), and hemicrania continua (0.4%). The 24.2% of patients who sought care from no more than 1 health professional showed a 59.8% adherence rate; 29% of the total had consulted 7 or more health professionals and showed an adherence rate of 74.3% (P = .0004). COMMENTS: In Brazil, the belief is widespread that patients attending tertiary headache centers tend to be those who have consulted with numerous health professionals and are, therefore, refractory and/or have adherence problems. Despite the limitations imposed by the retrospective design and the fact that we excluded other important markers of real adherence, this study suggested the opposite. The patients who had seen the lowest number of health professionals presented the worse adherence profile. One of the possible reasons is that patients receive more comprehensive care in a specialized center. Further prospective studies to confirm these observations are warranted.

Evaluation of the safety and efficacy of an injectable B-vitamin combination in acute neuralgias

A clinical trial evaluating the safety and efficacy of the use of an intramuscular combination of vitamins B1, B6, and B12 in the treatment of the signs and symptoms of trigeminal and plantar neuralgia was performed. Patients were submitted to a 9-day, open-label treatment period with three administrations of the study medication, and underwent a series of clinical and laboratory evaluations prior to the first treatment dose and at each of the three following visits to the study center. The incidence of adverse events and the use of concomitant medications was monitored at each study visit, when efficacy evaluations were also performed, including a 100mm VAS pain assessment and global and satisfaction surveys completed by the patients and investigating physician. Additionally, at the end of the treatment period, the patients were evaluated on their willingness to continue treatment with the study medication.

Polytherapy in the preventive and acute treatment of migraine: fundamentals for changing the approach.

The pathophysiology of migraine is complex and involves multiple neurophysiological pathways. Monotherapeutic approaches for migraine are the rule but many patients discontinue their medications owing to lack of efficacy. Polytherapy may provide a rational strategy for some of these individuals. Herein, we review the basis of polytherapy treatment for migraine. We suggest that refractory patients, with previous failure to single agents, may benefit from the use of a two- or three-drug regimen combining medications that target different neurotransmitter systems. In addition, those patients with high recurrence rates or not presenting pain free at 2 h and/or sustained pain free at 24 h may also respond better to combination therapy suited to their individual profile, which must include nonsteroidal anti-inflammatory agents plus a triptan or a gastrokinetic drug. The three-drug regimen may also be considered. Finally, changing the time medicine is taken (before the development of central sensitization and allodynia cutanea) and switching the choice of formulations to non-oral potentially achieves a better response and can be determined individually. Although highly speculative, these hypotheses could stimulate further controlled studies to support changing the current paradigm of monotherapeutic migraine treatment in some patients.

The use of combination therapies in the acute management of migraine.

BACKGROUND AND OBJECTIVES: Migraine is a highly prevalent neurological disorder with multiple peripheral and central mechanisms. Targeting a single mechanism for treating individual attacks as well as for performing the prophylaxis has been shown to be only partially effective. Recently, the role of combining agents for acute migraine treatment has gained attention and the combination of a triptan plus a non-steroidal anti-inflammatory drug (NSAID) has demonstrated better efficacy. This review focuses on the fundamentals of treating migraine attacks with two or more agents, and emphasizes the characteristics of the recently approved fixed combination sumatriptan-naproxen. METHODS: A PubMed search using the terms "migraine", "treatment", "acute", "triptans", "non-steroidal anti-inflammatory drugs", "sumatriptan", "naproxen", and "combination" was used. In addition, abstracts presented in the major meetings of the American Headache and the International Headache Societies along with the American Academy of Neurology were also evaluated. RESULTS: Although most of the few studies encountered were not controlled, there is a clear trend for better efficacy in combining triptans with NSAID. Additionally, the results of two recent large and controlled studies using fixed combinations of sumatriptan (50 mg and 85 mg) with 500 mg naproxen sodium confirm the initial observations of the clear superiority of this combination over the use of each agent alone. The differences in the endpoints 24-hour pain-relief response as well as pain-free and pain-relief parameters at 2-hour time-point are the most noticeable efficacy measures. Tolerability was not different between studied drugs. CONCLUSIONS: Combining triptans with NSAID and other agents for the acute treatment of migraine suggests better outcome efficacy measures than the use of single agents. The fixed combination of sumatriptan and naproxen sodium offers improved 2-hour and 24-hour benefits over monotherapy with each one these options. Recently issued FDA approval for marketing the combination (sumatriptan 50 mg-naproxen 500 mg) emphasizes the usefulness and safety of this new treatment for migraine attacks.

Tratamento agudo da migrânea ou enxaqueca: fundamentos para uma abordagem mais eficaz / Acute treatment of migraine: fundamentals for a more efficient approach

A enxaqueca ou migrânea é uma doença altamente prevalente. A incapacidade provocada por suas crises resulta em sofrimento e em perdas econômicas e socias. O objetivo do tratamento agudo é restaurar a função normal do paciente tão rápido e consistente quanto possível. Existem várias opções de drogas para esta finalidade e a despeito dos recentes avanços na compreensão da existência de diferentes sistemas biológicos e dos mecanismos envolvidos na crise da enxaqueca, com o desenvolvimento de agonistas serotoninérgicos específicos conhecidos como triptanos, as opções atuais de drogas para o tratamento agudo das crises de migrânea ainda situam-se abaixo do ideal. Embora ainda se exerça a regra conservadora de se usar monoterapia com esses fármacos, até um terço dos pacientes suspendem seu tratamento devido a efeitos colaterais, eficácia incompleta, recorrência da cefaléia e até custo da medicação. Além disso já existem fundamentos racionais para o desenvolvimento de esquemas politerapêuticos que possa, atuar em vários sistemas biológicos envolvidos de forma simultânea. Essa revisão aborda esses fundamentos e a evidência de sua melhor eficácia.

Migraine headache is a highly prevalent neurological disorder. Its attacks promote disability whice results in suffering and considerable economic and social losses. The acute treatment of migraine aims at restoring the patient to normal function as fast and consistent as possible. Although there are numerous drugs available for this purpose and despite recent advances in the understanding of the different biological systems as well as mechanisms involved in migraine attacks, current drug options, including the selective 5-HT agonists know as triptans, still stand bellow the ideal. Despite the conservative rule of monotherapeutic approaches, up to one third of all patients discontinue their medications due to side effects, incomplete efficacy, headache recurrence and / or cost of medication. In addition, there already are rational fundamentals for the development of polytherapeutic approaches, aiming at some of the biological systems involved simultaneously. This paper reviews the fundamentals as well as the evidence for this changing approach and its better efficacy.