Prophylactic treatment of vestibular migraine / Tratamento profilático da migrânea vestibular

Abstract Introduction: Vestibular migraine (VM) is now accepted as a common cause of episodic vertigo. Treatment of VM involves two situations: the vestibular symptom attacks and the period between attacks. For the latter, some prophylaxis methods can be used. The current recommendation is to use the same prophylactic drugs used for migraines, including β-blockers, antidepressants and anticonvulsants. The recent diagnostic definition of vestibular migraine makes the number of studies on its treatment scarce. Objective: To evaluate the efficacy of prophylactic treatment used in patients from a VM outpatient clinic. Methods: Review of medical records from patients with VM according to the criteria of the Bárány Society/International Headache Society of 2012 criteria. The drugs used in the treatment and treatment response obtained through the visual analog scale (VAS) for dizziness and headache were assessed. The pre and post-treatment VAS scores were compared (the improvement was evaluated together and individually, per drug used). Associations with clinical subgroups of patients were also assessed. Results: Of the 88 assessed records, 47 were eligible. We included patients that met the diagnostic criteria for VM and excluded those whose medical records were illegible and those of patients with other disorders causing dizziness and/or headache that did not meet the 2012 criteria for VM. 80.9% of the patients showed improvement with prophylaxis (p < 0.001). Amitriptyline, Flunarizine, Propranolol and Topiramate improved vestibular symptoms (p < 0.001) and headache (p < 0.015). The four drugs were effective in a statistically significant manner. There was a positive statistical association between the time of vestibular symptoms and clinical improvement. There was no additional benefit in hypertensive patients who used antihypertensive drugs as prophylaxis or depressed patients who used antidepressants in relation to other prophylactic drugs. Drug association did not show statistically significant results in relation to the use of a single drug. Conclusions: Prophylactic medications used to treat VM improve the symptoms of this disease, but there is no statistically significant difference between the responses of prophylactic drugs. The time of vestibular symptom seems to increase the benefit with prophylactic treatment.

Resumo Introdução: A migrânea vestibular (MV) é aceita atualmente como uma causa comum de vertigem episódica. O tratamento da MV envolve duas situações: as crises de sintomas vestibulares e o período intercrise. Para esse último, pode-se usar algum método de profilaxia. A recomendação atual é que se usem os mesmos medicamentos profiláticos usados para a enxaqueca, o que inclui os β-bloqueadores, antidepressivos e anticonvulsivantes. A recente definição diagnóstica da migrânea vestibular torna escasso o número de estudos sobre seu tratamento. Objetivo: Avaliar a eficácia do tratamento profilático usado em pacientes em um ambulatório de MV. Método: Revisão de prontuários de pacientes com MV pelos critérios da Bárány Society/International Headeache Society de 2012. Foram pesquisados os medicamentos usados e resposta ao tratamento obtida através da escala visual analógica (EVA) para tontura e cefaleia. Foram comparados os escores da EVA pré e pós-tratamento (a melhoria foi avaliada em conjunto e individualmente por droga usada). Também foram pesquisadas relações com subgrupos clínicos dos pacientes. Resultados: De 88 prontuários estudados, 47 foram elegíveis. Incluíram-se os pacientes que preenchiam os critérios diagnósticos para MV, foram excluídos os prontuários ilegíveis e aqueles de pacientes com outro distúrbio causador de tontura e/ou cefaleia que não preenchiam critérios de 2012 para MV. Apresentaram melhoria com a profilaxia 80,9% dos pacientes (p < 0,001). Amitriptilina, flunarizina, propranolol e topiramato apresentaram melhoria para sintomas vestibulares (p < 0,001) e para cefaleia (p < 0,015). Os quatro medicamentos foram eficazes de forma estatisticamente significante. Houve relação estatística positiva entre tempo de sintoma vestibular e melhoria clínica. Não houve benefício adicional para hipertensos que usaram anti-hipertensivos como profilaxia ou para os deprimidos que usaram antidepressivos em relação ao uso dos outros profiláticos. A associação de medicamentos não mostrou resultados estatisticamente significantes do uso de um medicamento isolado. Conclusões: Os medicamentos profiláticos usados para MV melhoram os sintomas dessa doença, porém não há diferença estatisticamente significante entre as respostas dos medicamentos profiláticos. O tempo de sintoma vestibular parece aumentar a melhoria obtida com o tratamento profilático.

Prevalence of epilepsy and seizure disorders as causes of apparent life- threatening event (ALTE) in children admitted to a tertiary hospital / Prevalência de epilepsia e crises epilépticas como causa de eventos com aparente risco de vida (ALTE) em crianças internadas em hospital terciário

OBJECTIVE: To determine the prevalence and describe clinical characteristics of seizure disorders and epilepsy as causes of apparent life- threatening event (ALTE) in children admitted at the emergency and followed in a tertiary hospital. METHOD: Cross-sectional study with prospective data collection using specific guidelines to determine the etiology of ALTE. RESULTS: During the study, 30 (4.2 percent) children admitted to the hospital had a diagnosis of ALTE. There was a predominance of males (73 percent) and term infants (70 percent). Neonatal neurological disorders and neuropsychomotor development delay were found respectively in 13.4 percent and 10 percent of the cases. Etiological investigation revealed that 50 percent of the cases were idiopathic, and 13.4 percent were caused by epilepsy or seizure disorders. Although all patients had recurrent ALTE events, epilepsy had not been previously suspected. CONCLUSION: Epilepsy should be included in the differential diagnosis of ALTE, particularly when events are recurrent.

OBJETIVO: Determinar a prevalência e características clínicas de crises epilépticas e epilepsia como causa de eventos com aparente risco de vida (ALTE) em crianças atendidas na emergência e acompanhadas em hospital terciário. MÉTODO: Estudo transversal com coleta prospectiva de dados através de protocolo específico para identificação da etiologia de ALTE. RESULTADOS: Foram diagnosticadas 30 crianças com ALTE perfazendo 4.2 por cento das crianças internadas no período do estudo. Houve predominância no sexo masculino (73 por cento) e em neonatos a termo (70 por cento). História prévia de doenças neurológicas no período neonatal e atraso no desenvolvimento neuropsicomotor ocorreram respectivamente em 13.4 por cento e 10 por cento dos casos. A investigação etiológica identificou 13.4 por cento dos casos relacionados a epilepsia ou crise convulsivas e 50 por cento idiopáticos. Apesar destes pacientes terem apresentados episódios recorrentes em nenhum caso havia a suspeita prévia de epilepsia. CONCLUSÃO: Ao investigar pacientes com ALTE a possibilidade do diagnóstico de epilepsia deve ser fortemente considerada principalmente nos casos recorrentes.

Tratamiento del estado epiléptico refractario con topiramato oral / Treatment of refractory status epilepticus with topiramate: report of three cases

Refractory status epilepticus is a catastrophic illness of the central nervous system, with a mortality rate that reaches 50 percent. We report three patients admitted with refractory status epilepticus: a 24 year-old male that discontinued antiepileptic medications, a 46 year-old male with a focal epilepsy secondary to an encephalitis that discontinued medications due to gastrointestinal problems and a 59 year-old male with an ischemic encephalopathy AH were treated with topiramate, delivered through a nasogastric tube with a good response.

Influence of NMDA and non-NMDA antagonists on acute and inflammatory pain in the trigeminal territory: a placebo control study / Influência dos antagonistas dos receptores NMDA e não-NMDA sobre a dor aguda e inflamatória ao nível do território do trigêmeo: um estudo placebo controlado

NMDA and non-NMDA receptors are involved in spinal transmission of nociceptive information in physiological and pathological conditions. Our objective was to study the influence of NMDA and non-NMDA receptor antagonists on pain control in the trigeminal system using a formalin-induced orofacial pain model. Motor performance was also evaluated. Male Rattus norvegicus were pre-treated with topiramate (T) (n=8), memantine (M) (n=8), divalproex (D) (n=8) or isotonic saline solution (ISS) (n=10) intraperitoneally 30 minutes before the formalin test. Formalin 2.5 percent was injected into the right upper lip (V2 branch) and induced two phases: phase I (early or neurogenic) (0-3 min) and phase II (late or inflammatory) (12-30 min). For motor behavior performance we used the open-field test and measured latency to movement onset, locomotion and rearing frequencies, and immobility time. Pre-treatment of animals with M and D only attenuated nociceptive formalin behavior for phase II. T increased locomotion and rearing frequencies and reduced immobility time. Treatment with M increased immobility time and with D reduced locomotion frequency. Our results showed that the NMDA antagonist (M) is more potent than the non-NMDA antagonists (D and T) in the control of pain in the inflammatory phase. The non-NMDA topiramate improved motor performance more than did D and M, probably because T has more anxiolytic properties.

Receptores NMDA e não-NMDA estão envolvidos na transmissão das informações nociceptivas em condições fisiológicas e patológicas. Com o objetivo de estudar a influência dos antagonistas dos receptores NMDA e não-NMDA sobre o controle de dor no sistema trigeminal utilizamos modelo de dor orofacial induzida pela formalina. Testes de desempenho motor foram também avaliados. Ratos machos da espécie Rattus norvegicus foram tratados com topiramato (T) (n=8), memantina (M) (n=8), divalproato de sódio (D) (n=8) ou solução salina isotônica (SSI) (n=10), por via intraperitoneal, 30 minutos antes dos testes com a formalina. Formalina 2.5 por cento foram injetadas na região do lábio superior dos animais (segundo ramo do trigêmeo) induzindo comportamento em duas fases distintas: fase I (precoce ou neurogênica) (0-3 min ) e fase II (tardia ou inflamatória) (12-30 min). Para avaliação da atividade motora utilizou-se o teste do campo aberto mensurando-se a latência para o início dos movimentos, número de casas andadas, freqüência de levantamentos e tempo de imobilidade. Animais pré-tratados com M e D atenuaram a fase inflamatória do teste da formalina. O T aumenta o número de casas andadas, freqüência de levantamentos e reduz o tempo de imobilidade. Nossos resultados mostram que o antagonista NMDA é mais potente do que os antagonistas não-NMDA para o controle da fase inflamatória da dor. O topiramato entretanto aumenta a atividade motora provavelmente porque apresente propriedades ansiolíticas.

Craving decrease with topiramate in outpatient treatment for cocaine dependence: an open label trial / Diminuição da fissura com topiramato no tratamento ambulatorial para dependência de cocaína: um ensaio clínico aberto

OBJECTIVE: To evaluate anticraving action and tolerability of topiramate in cocaine user treatment. METHOD: Male users of inhaled cocaine which met criteria for cocaine dependence (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) were selected for outpatient 12-week, open label trial with topiramate; individual dosage ranged between 25-300 mg/day. Main clinical variables were abstinence rate, craving intensity, frequency and duration, adherence, dropouts, side effects and impulsivity measure through Barratt Impulsivity Scale. Patients received assertive strategic counseling for abstinence assistance and medication monitoring evaluation every two weeks. Comparative analysis was made with intention to treat, missing values were replaced (last observation carried forward), and significance level was 5 percent. RESULTS: Adherence to treatment was 57 percent (at least three evaluations), 32 percent dropped out (one evaluation). There were no severe side effects. Negative test average was 25.4 percent (31.2). Significant reduction in craving intensity and duration was observed in 25 percent of the sample. No statistical significant reduction in craving frequency was observed in 7.1 percent. Increase in frequency was observed in 10.7 percent and 82.1 percent did not present any variation. No significant statistical variations in Barratt Impulsivity Scale or in the total score were found in the final evaluation when compared to baseline. CONCLUSION: More randomized placebo-controlled trials with topiramate for cocaine dependants should be performed to evaluate preliminary evidence.

OBJETIVO: Avaliar a ação anticraving e tolerabilidade do topiramato em usuários de cocaína. MÉTODO: Homens usuários de cocaína inalada que preenchiam critérios para dependência de cocaína (Manual Diagnóstico e Estatístico de Desordens Mentais, quarta edição) foram selecionados para 12 semanas de tratamento ambulatorial, em ensaio clínico aberto com topiramato; dosagens escalonadas entre 25-300 mg/dia. As principais variáveis clínicas foram taxa de abstinência, intensidade, freqüência e duração do craving, aderência, perdas, efeitos colaterais e impulsividade medida por meio da Escala de Impulsividade Barratt. Os pacientes receberam estratégias assertivas de aconselhamento para manutenção da abstinência e monitoramento da medicação avaliada a cada duas semanas. Análises comparativas foram feitas com intenção de tratar, valores perdidos foram substituídos (última observação carregada ao final) e o nível de significância de 5 por cento. RESULTADOS: A aderência ao tratamento foi de 57 por cento (pelo menos três avaliações), 32 por cento de perdas (uma avaliação). Não houve efeitos colaterais graves. A média de testes negativos foi 25,4 por cento (31,2). Significante redução na intensidade e duração do craving foi observada em 25 por cento da amostra. Nenhuma redução significativa na freqüência do craving foi observada em 7,1 por cento. Aumento na freqüência foi observado em 10,7 por cento e 82,1 por cento não apresentaram nenhuma variação. Nenhuma variação estatisticamente significativa na Escala de Impulsividade Barratt ou na pontuação total foi encontrada no final da avaliação quando comparado à inicial. CONCLUSÃO: Mais ensaios clínicos placebo-controlados com o topiramato para dependentes de cocaína deveriam ser conduzidos a fim de avaliar a evidência preliminar.

Actualización del tratamiento farmacológico de la dependencia alcohólica / Pharmacological review of alcoholic dependence treatment

El objetivo de la presente actualización farmacológica es abordar la problemática de la dependencia alcohólica. Partiendo de las bases biológicas y del impacto del etanol sobre los sistemas neurobiológicos y de neurotransmisión, se hará una revisión de las principales herramientas farmacológicas para el tratamiento de la dependencia alcohólica. El disulfiram, la naltrexona y el acamprosato, todas ellas con aprobación por la FDA (Food and Drug Administration) han mostrado mecanismos de acción, perfiles de eficacia, tolerabilidad y adherencia dispares. También nos referiremos al topiramato, el que está siendo estudiado actualmente con relación a esta indicación.

The aim of the present pharmacological update is to revise the problem of alcohol dependence. Starting from the biological bases and the impact of alcohol on the neurobiological and neurotransmission systems, a revision of the main pharmacological tools for alcohol dependence treatment will be done. Disulfiram, naltrexone, acamprosate, all of them approved by the FDA (Food and Drug Administration), have shown mechanisms of action, efficacy, tolerance and adherence dissimilar. We will also refer to topiramate, which is being studied for this indication.

Abordagem terapêutica da obesidade na Síndrome de Prader-Willi / Therapeutical approach of obesity in Prader-Willi Syndrome

A Síndrome de Prader-Willi (SPW) é uma doença complexa, multissistêmica, caracterizada por hipotonia, retardo mental, características dismórficas, hiperfagia e compulsão alimentar devido à disfunção hipotalâmica. SPW ocorre pela perda de função de genes localizados no cromossomo 15q11-13, região que sofre imprinting genômico. Obesidade é a principal causa de morbidade e mortalidade entre pacientes com SPW. O objetivo desta revisão é analisar as opções terapêuticas disponíveis para o tratamento da obesidade na SPW, incluindo a terapia farmacológica e o tratamento cirúrgico.

Prader-Willi Syndrome (PWS) is a multisystemic genetic disease characterized by hypotonia, mental retardation, characteristic facial appearance, hyperphagia, and compulsive eating due to hypothalamic dysfunction. PWS is caused by loss of function of genes located in chromosome 15q11-q13, an area subject to genomic imprinting. Obesity is a major cause of increased morbidity and mortality among patients with PWS. The objective of this study was to analyze the therapeutic options available for the treatment of the obesity in PWS including pharmacological and surgical strategies.

Topiramate for the treatment of juvenile myoclonic epilepsy

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of topiramate (TPM) in juvenile myoclonic epilepsy (JME). METHOD: We assessed seizure control and adverse effects of TPM in 22 patients (18 females) aged 13 to 53 years. Target TPM dosage was up to 200 mg/day. The patients were subdivided into 3 groups: those treated with seizure control plus side effects (n=4); treated with non-controlled seizures (n=15) and with JME newly diagnosed (n=3). RESULTS: Sixteen patients completed the first year of the follow-up. Generalized tonic-clonic seizures were completely controlled in 10 (62.5%); more than 50% of reduction in 4 (25.0%) and less than 50% in 2 (12.5%). Myoclonia were controlled in 11 (68.8%) and persisted in 5 (31.2%) patients. Absence seizures were present in 5 (22.7%) of whom 2 (9.0%) showed more than 50% of seizure reduction while 3 (13.6%) presented worsening. Discontinuations were due to inadequate seizure control and adverse events (N=4), low compliance and loss of follow-up (N=2) and subject choice (N=1). CONCLUSION: TPM showed to be an effective and well-tolerated drug in the treatment of JME. Although frequently observed, TPM side effects were tolerable and the drug could be maintained in the majority of patients.

OBJETIVO: Avaliar a eficácia e tolerabilidade do topiramato (TPM) na epilepsia mioclônica juvenil (EMJ). MÉTODO: Avaliamos a resposta terapêutica e efeitos colaterais do TPM em 22 pacientes (18 mulheres) com idades entre 13 e 53 anos. A dose alvo utilizada foi até 200 mg/dia. Os pacientes foram divididos em 3 grupos no início do tratamento: aqueles com controle das crises mas que apresentavam efeitos colaterais (n=4); com crises não controladas (n=15) e com EMJ recém diagnosticada (n=3). RESULTADOS: Dezesseis pacientes completaram o primeiro ano de acompanhamento. Crises tônico-clonicas generalizadas foram completamente controladas em 10 (62,5%), tiveram redução maior de 50% em 4 (25,0%) e menor de 50% em 2 (12,5%). Mioclonias foram controladas em 11 (68,8%) e persistiram em 5 (31.2%) pacientes. As crises de ausências, presentes em 5 (22,7%) pacientes, tiveram redução maior do que 50% em 2 (9,0%) e agravamento em 3 (13,6%). A retirada do estudo foi devida principalmente ao controle inadequado das crises e efeitos colaterais indesejáveis (n=4), pouca adesão e perda do seguimento (n=2) e escolha do paciente (n=1). CONCLUSÃO: TPM foi considerada droga eficaz e bem tolerada no tratamento da EMJ. Apesar de freqüentemente observados, os efeitos colaterais do TPM foram toleráveis e a medicação pode ser mantida na maioria dos pacientes.

Urolithiasis associated with topiramate

OBJECTIVE: Topiramate is a sulfamate-substituted monosaccharide anticonvulsant used as adjunctive therapy for intractable refractory seizures. It is report a case of topiramate-induced urolithiasis. CASE REPORT: A 35-year-old man presented with acute, right-sided, colicky flank pain. He denied hematuria or dysuria. He was in use of phenytoin, risperidone, phenobarbital, and topiramate. The total daily dose of topiramate was 375 mg. A CT scan showed a 7 x 1 mm curvilinear density at the right ureterovesical junction with proximal hydrouretronephrosis. He was managed with rigid ureteroscopic stone extraction and the calculus metabolic analysis revealed the stone was composed of carbonate apatite (70 percent), calcium oxalate dihydrate (20 percent), and calcium oxalate monohydrate (10 percent). COMMENTS: The present case typifies many features of topiramate-induced urolithiasis. Those who care for patients with urinary stone disease should be aware of this association.

Topiramato: uma experiência em crianças com epilepsia parcial / Topiramate: an experience in children with partial epilepsy

Estudamos a resposta clínica ao topiramato (TPM) em crianças abaixo de 15 anos de idade. O tratamento foi iniciado com doses de 12,5 mg/kg/dia (1-7 mg/kg/dia), com aumentos semanais de 12,5 mg. Foram estudadadas 11 crianças, 9 do sexo feminino e 2 do masculino, de 3 a 14 anos de idade, com epilepsia parcial associada a etiologias diversas. Apenas um paciente teve dor abdominal intensa. Após o início do TPM, um paciente teve controle total das crises, 5 tiveram melhora maior que 75 por cento na frequência delas, 1 paciente apresentou melhora em 50 por cento e 3 näo tiveram controle. Ao final, verificamos controle adequado das crises mesmo em quadros mais graves, com doses de até 100 mg/dia do TPM e em associaçäo a carbamazepina, na maioria dos casos

A pilot study of topiramate in children with Lennox-Gastaut syndrome

We conducted an open, add-on study with topiramate (TPM) as adjunctive therapy in Lennox-Gastaut syndrome (LGS), to assess the long-term efficacy and safety and to evaluate quality of life (QL) measurements in the chronic use of TPM. We studied 19 patients (11 male; age ranging from 4 to 14 years) with uncontrolled seizures receiving 2-3 anti- epileptic drugs. Patients were followed up to 36 months of treatment. A questionnaire was used to query parents about QL. Seven patients completed the study at 36 months and seizure frequency was reduced = 75 per cent in 4, and < 50 per cent in patients. Two children became seizure free for more than 24 months. Most side effects were CNS related, with the most frequent being somnolence and anorexia. These were generally transient. One patient dropped-out due to powder in the urine. None of the patients required hospitalization. At 36 months, patients' alertness (2/7), interaction with environment (5/7), ability to perform daily activities (5/7), and verbal performance (6/7) improved on TPM. We conclude that TPM may be useful as adjunctive therapy in the treatment of LGS. The efficacy of TPM was maintained in long-term treatment in more than 40 per cent of patients, long term safety was confirmed and QL improve on TPM.

The level of metabolic control in low income Mexico City diabetics. The Mexico City diabetes study

The importance of good metabolic control in the treatment of diabetes mellitus (DM) is unquestionable. Measurements of the level control (LC) are available such as glycohemoglobin (GH) and fructosamine (FA). The aims of this study are: to estimate LC in a population based case series of type II DM patients, to assess the effect of clinical, metabolic and sociodemographic variables usually associated with the LC and to estimate the clinical impact of the LC on vascular complications of DM. A low income area of Mexico City was enumerated. All males and non-pregnant females between 35-64 years of age were considered eligible. Home interview was obtained in 2813 and a medical exam incluiding an oral glucose tolerance test was performed in 2282 (65.1 per cent). Three hundred and four subjects met the criteria (WHO) for DM. Three years later, 213 (70.1 per cent) were located for GH and FA measurements. Cases were divided according to the level of GH: Group I, good LC (GH < o = 8.6 per cent, n = 66); and group II poor LC (GH > o = 8.7 per cent, n = 147). A significant difference was observed in the mean vallue of FA between groups (Grop I 255 ñ 52.3 µmol/dl. Group II 306.4 ñ 51.1; p < 0.001). In compariso with subjects with good LC, patients with poor LC had higher values of duration of DM (p < 0.01), waist/hip ratio (p < 0.04), fasting glucose (p < 0.001) and lower values of fassting insulin (p < 0.07), LDL cholesterol (p < 0.006) and VLDL cholesterol (p < 0.09). Patinets with good LC had less diabetic retinophaty (p < 0.03). Around 48-69 per cent of type II urban Mexican diabetic population have poor LC. Variables usuallyt thougth to affect or be associated with LC do not influence th eend result. New therapeutic strategies in the management of DM are needed to reduce the long-term complications associated with DM