Acute angle closure triggered by oral benzodiazepines / Fechamento angular agudo desencadeado por uso oral de benzodiazepínicos

ABSTRACT Benzodiazepines are psychoactive drugs that are prescribed worldwide with limited information on their ocular side effects. Acute angle closure glaucoma is an adverse event with a high risk of blinding, especially in the elderly. We report two patients under 45 years old who presented with bilateral acute angle closure secondary to use of two long half-life benzodiazepines (clonazepam and alprazolam). In addition to suspending the use of these medications and administering ocular hypotensive drugs, both patients were successfully treated with bilateral peripheral laser iridotomy. To the best of our knowledge, this is the first report of bilateral acute angle closure secondary to the use of clonazepam and alprazolam.(AU)

RESUMO Os benzodiazepínicos são medicamentos psicoativos prescritos em todo o mundo, mas com poucas informações sobre seus efeitos colaterais oculares. O glaucoma por fechamento agudo do ângulo iridocorneano é um dos eventos adversos com maior risco de cegueira, sendo descrito particularmente em idosos. Relatamos aqui dois pacientes com menos de 45 anos de idade, com fechamento agudo do ângulo bilateral secundário ao uso de dois diferentes benzodiazepínicos de meia-vida longa (clonazepam e alprazolam). Além da suspensão dessas medicações e do tratamento clínico com drogas hipotensoras oculares, ambos os casos alcançaram sucesso com iridotomias periféricas bilaterais à laser. Considerando o conhecimento atual, estes são os primeiros relatos de fechamento agudo do ângulo bilateral secundária ao uso de clonazepam e alprazolam.(AU)

Transtornos do sono: atualização (parte2/2) / Sleep disorders: up to date (2/2)

Este artigo (2/2) compõe uma revisão sobre fundamentos do sono e transtornos do sono (TS), sendo aqui considerados: 1-Incapacidade de dormir na hora desejada-atraso de fase, avanço de fase, ''jet lag'', ritmo sono-vigília irregular, sono/vigília de livre curso, transtornos dos trabalhadores em turnos; 2-Movimentos ou comportamentos anormais durante o sono. Este segundo grupo é aqui subdividido em: A1-Parassonias relacionadas ao sono NREM (Non-rapid eye movement) ­ despertar confusional, sonambulismo, terror noturno, síndrome da cabeça explosiva, alucinações relacionadas ao sono, enurese noturna e parassonias causadas por doenças e medicações; A2-Parassonias relacionadas ao sono REM (rapid eye movement) - transtorno comportamental do sono REM, pesadelos, paralisias recorrentes isoladas do sono, promulgação sono ''dream enactment behavior"; B-Transtornos do movimento relacionados ao sono-bruxismo, síndrome das pernas inquietas, movimentos periódicos das pernas, câimbras do sono, movimentos rítmicos relacionados ao sono, mioclonias proprioespinhais do início do sono, movimentos relacionados à medicação, mioclonias em doenças sistêmicas e mioclonias benignas do sono em bebês.(AU)

This is the second part (2/2) of an article that intends to review major topics regarding sleep fundamentals and sleep disorders (SD), now considering: 1-Circadian rhythm disorders-delayed onset sleep phase disorder, advanced onset sleep phase disorder, jet lag, irregular sleep-wake rhythm, free-running type, shift work type; 2-Abnormal movements or behaviours during sleep. This second category is divided in two groups: A1-NREM (Non-rapid eye movement) parasomnias ­ confusional awakening, sleepwalking, night terrors, explosive head syndrome, sleep-related hallucinations, nocturnal enuresis and parasomnias related to diseases or medications; A2-REM (Rapid eye movement) parasomnias-REM sleep behaviour disorder, nightmares, recurrent isolated sleep paralysis, dream enactment behaviour; B-Sleep related movement disorders-bruxism, restless legs syndrome, periodical limb movement disorders, nocturnal leg cramps, sleep related rhythmic movement disorder, propriospinal myoclonus, movements related to medication use, myoclonus related to systemic diseases and benign myoclonus of sleep.(AU)

A Case of Aerophagia Diagnosed by Multichannel Intraluminal Impedance Monitoring / 대한소화기학회지

Aerophagia is a disorder caused by abnormal accumulation of air in the gastrointestinal tract as a result of repetitive and frequent inflow of air through the mouth. For the diagnosis of this condition, it is difficult to objectively measure the air swallowing. However, multichannel intraluminal impedance monitoring facilitates the differential diagnosis between normal air swallowing and pathologic aerophagia, and can aid in the determination of the frequency and amount of air swallowed. In this report, in addition to a literature review, we describe a case of 36-year-old man with abdominal distension who was diagnosed with aerophagia using esophageal impedance monitoring and was treated with clonazepam.

Síndrome de kinsbourne / Kinsbourne syndrome

Antecedentes: El Síndrome Kinsbourne es un desorden neurológico raro caracterizado por movimientos oculares irregulares, involuntarios y multidireccionales (opsoclonos), polimioclonias difusas y ataxia. Puede ser de etiología paraneoplásica (neuroblastoma) en el 50% de pacientes, pero existen múltiples causas dentro de ellas, las para y post infecciosas. Caso clínico: Masculino de 1 año de edad, con inestabilidad de la marcha. Como único antecedente proceso respiratorio y gastrointestinal (rinorrea hialina, tos productiva así como diarrea) una semana previa al inicio del padecimiento. A la exploración física presentaba ataxia a la bipedestación que imposibilitaba la marcha. Ante la ausencia de otra sintomatología es considerado inicialmente como una cerebelitis postinfecciosa, posteriormente se agregan al cuadro clínico polimioclonias y opsoclonos, con estos datos se hace el diagnóstico de síndrome de Kinsbourne. La Imagen de resonancia magnética cerebral, electroencefalograma, citoquímica y cultivo de líquido cefalorraquídeo no mostraron alteraciones. Se realizó tomografía axial abdominal y catecolaminas en orina en busca de neuroblastoma, ambos estudios normales. Se dio manejo con prednisolona a dosis de 2 mg/kg/día. Al mes de tratamiento el paciente estaba asintomático Conclusión: el síndrome opsoclonos mioclonos es una entidad rara que debe ser considerada como diagnóstico diferencial en los casos de ataxia aguda...

Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine

The objective of the present randomized, open-label, naturalistic 8-week study was to compare the efficacy and safety of treatment with clonazepam (N = 63) and paroxetine (N = 57) in patients with panic disorder with or without agoraphobia. Efficacy assessment included number of panic attacks and clinician ratings of the global severity of panic disorders with the clinical global impression (CGI) improvement (CGI-I) and CGI severity (CGI-S) scales. Most patients were females (69.8 and 68.4 percent in the clonazepam and paroxetine groups, respectively) and age (mean ± SD) was 35.9 ± 9.6 years for the clonazepam group and 33.7 ± 8.8 years for the paroxetine group. Treatment with clonazepam versus paroxetine resulted in fewer weekly panic attacks at week 4 (0.1 vs 0.5, respectively; P < 0.01), and greater clinical improvements at week 8 (CGI-I: 1.6 vs 2.9; P = 0.04). Anxiety severity was significantly reduced with clonazepam versus paroxetine at weeks 1 and 2, with no difference in panic disorder severity. Patients treated with clonazepam had fewer adverse events than patients treated with paroxetine (73 vs 95 percent; P = 0.001). The most common adverse events were drowsiness/fatigue (57 percent), memory/concentration difficulties (24 percent), and sexual dysfunction (11 percent) in the clonazepam group and drowsiness/fatigue (81 percent), sexual dysfunction (70 percent), and nausea/vomiting (61 percent) in the paroxetine group. This naturalistic study confirms the efficacy and tolerability of clonazepam and paroxetine in the acute treatment of patients with panic disorder.

Parasomnias: an overview.

Parasomnias are abnormal experiences or behaviours that occur during sleep and can be subdivided into disorders of arousal, disorders of rapid eye movement (REM) sleep or other parasomnias. Diagnosis rests on a thorough clinical evaluation with supporting data from a full polysomnography with time synchronized video. While the prognosis for arousal disorders is generally excellent, the diagnosis of REM behaviour disorder (RBD) is more ominous and associated with neurodegenerative disorders, and as such, requires routine neurological surveillance. The cornerstone of treatment for all parasomnias is adequate patient and bed partner education. Data supporting pharmacologic therapy are limited but clonazapam for RBD has been reported to be effective in up to 89 per cent of patients.

Síndrome de Lance-Adams: presentación de dos casos / Lance-Adams syndrome: report of two cases

Lance-Adams syndrome was described in 1963 is a rare complication due to recovered hypoxic episodes or prolonged hypotension events. Is characterized by action myoclonus and cerebellar ataxia. We report two patients studied with this syndrome. A 51 year-old men and a 72 years-old men fully recovered after a brief cardiorespiratory arrest they developed intention myoclonus, triggered by voluntary movements, posture, also by sounds, touches and emotional stimuli. It also was accompanied by cerebellar syndrome, ataxia and posture control alterations. They had a Magnetic Resonance (MR), EEG and normal metabolic parameters. Myoclonus was treated with sodium valproate and clonazepam. The neurophysiologic interpretation of this motor imbalance is an abnormal functioning of the Central Pattern Generator Netwoks (CPGN) located in the mesencephalic region. Hypoxic lesions in vermian purkinje and paravermal cerebellum neurons have an inhibitory effect in this system, producing motor control attenuation, generating an imbalance in the motoneurons of the spinal cord contraction sequence, which starts shooting in an uncoordinated way. As in almost all cerebellar lesions with time they tend to compensate and to diminish myoclonus.

El Síndrome de Lance-Adams descrito en 1963, es una rara complicación que sigue tardíamente a episodios hipóxicos o de hipotensión prolongada, ya recuperados. Se caracteriza por mioclonías de acción y ataxia cerebelosa. Se describen dos pacientes estudiados con este síndrome. Son dos hombres de 51 y 72 años que después de un paro cardiorrespiratorio breve, de recuperación completa, iniciaron mioclonías de intención, activadas por movimientos voluntarios, posturas, estímulos sonoros, táctiles y afectivos. Acompañado además de un síndrome cerebeloso, ataxia de la marcha y alteraciones del control postural. Cursaron con RM (Resonancia Magnética), EEG (Electroencefalograma) y parámetros metabólicos sin relevancia patológica. Las mioclonías fueron controladas con ácido valproico y clonazepam. La interpretación neurofisiológica de este desajuste motor es la alteración en el funcionamiento del patrón central de circuitos generadores (PCCG) ubicado en la región mesencefálica. Las lesiones hipóxicas de las neuronas de Purkinje del vermis y paravermianas del cerebelo, que tienen un efecto inhibitorio para este sistema, producen una atenuación del control motor del PCCG, generando desajuste en la secuencia de la contracción de las motoneuronas de la médula espinal, que comienzan a dispararse de manera independientemente. Como ocurre con la mayoría de las lesiones cerebelosas, con el tiempo tienden a compensarse y por consiguiente a disminuir las mioclonías.

Comparación de metoprolol versus clonazepam como tratamiento de primera intención en pacientes con síncope neurocardiogénico / Comparison of metoprolol vs clonazepam as a first treatment choice among patients with neurocardiogenic syncope

Objetivo: Comparar la eficacia de metoprolol versus clonazepam como tratamiento de primera intención en pacientes con síncope neurocardiogénico. Material y métodos: Se llevó a cabo estudio prospectivo, longitudinal y aleatorizado en el que se evaluó el efecto del metoprolol (50 mg dos veces al día) versus clonazepam (0.5 mg una vez al día) sobre la sintomatología asociada a los tres meses y la recurrencia de síncope a 12 meses. La distribución de los datos fue normal, el análisis estadístico se realizó por métodos paramétricos considerándose significancia estadística una p≤0.05. Resultados: De 54 pacientes, 32 fueron tratados con metoprolol y 22 con clonazepam. No hubo diferencias en las características basales entre ambos grupos. El número de síntomas por paciente se redujo en el grupo de metoprolol de 5.2±2.5 a 1.9±2.1 (p<0.001), y en el grupo de clonazepam de 5.5±2.5 a 1.5±2.2 (p<0.001). La recurrencia de síncope a los 12 meses fue de 10% en el primer grupo y de 5% en el grupo de clonazepam, sin diferencia estadísticamente significativa. Conclusiones: El tratamiento con metoprolol o clonazepam disminuye en forma significativa los síntomas de distonía neurovegetativa asociados y la recurrencia de síncope es similar con ambos tratamientos.

OBJECTIVE: We compared the effects of a metoprolol and clonazepam in patients with neurocardiogenic syncope. METHODS: We compared the effects of a metoprolol and clonazepam in a prospective, randomised trial in 54 patients. Patients were randomly assigned to metoprolol (starting dose 50 mg bid) or clonazepam (starting dose 0.5 mg qd). We assessed a primary combined endpoint of syncope and pre-syncope on a follow-up of 12 months. RESULTS: The primary combined endpoint of syncope and presyncope occurred in the metoprolol group in 3, 4, and 10% of patients at 3, 6, and 12 months respectively. In the clonazepam group it was no recurrence in the first 6 months, and 5% recurrence at 12 months follow-up (nonsignificant differences between groups). Clinical symptoms commonly associated with neurally mediated syncope were decreased similarly in both treatment groups, in the metoprolol group from 5.2+/-2.5 to 1.9+/-2.1 (p < 0.001) and in the clonazepam group from 5.5+/-2.5 to 1.5+/-2.2 (p<0.001). CONCLUSIONS: Pharmacological treatment of neurocardiogenic syncope with metoprolol or clonazepam resulted in similar prevention of syncope and presyncope. Both treatments decreased clinical symptoms but complete symptomatic resolution was rarely observed.

Treatment of infantile spasms with sodium valproate followed by benzodiazepines.

OBJECTIVE: To review the result of the infantile spasms' treatment with sodium valproate followed by nitrazepam or clonazepam. STUDY DESIGN: Descriptive retrospective study. SETTING: Srinagarind Hospital, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. MATERIAL AND METHOD: Twenty-four infantile spasms admitted between January 1994 and December 2003 were analyzed. The inclusion criteria were the patients with infantile spasms clinically diagnosed by the pediatric neurologist, having hypsarrhythmic pattern EEG, and receiving sodium valproate with or without nitrazepam or clonazepam. The patients who had an uncertain diagnosis, incomplete medical record, or that were incompletely followed up were excluded. Data were collected on sex, age at onset of seizure, type of infantile spasms, associated type of seizure, predisposing etiological factor, neuroimaging study, and the result of treatment including cessation of spasms, subsequent development of other seizure types, quantitative reduction of spasms, relapse rates of spasms, psychomotor development, and adverse effects of AEDs. RESULTS: The mean age at onset was 177 days. The male-to-female ratio was 1:1.2. There were 13 cryptogenic (54.2%) and 11 symptomatic (45.8%) infantile spasms. The most common predisposing etiological factors in symptomatic cases were hypoxic ischemic encephalopathy (45.5%) and microcephaly (36.4%), respectively. Ten patients received sodium valproate (41.7%), another 10 received sodium valproate with clonazepam (41.7%), and four received sodium valproate with nitrazepam (16.7%). Both, the complete cessation rate and the 50% reduction of spasms rate were 45.8%. The duration to complete cessation was 70 days. The relapse rate was 18.2%. The rate of delayed psychomotor development was 83.3%. The mean duration of follow-up was 49.6 months. CONCLUSION: The authors propose to use sodium valproate concomitantly with benzodiazepines, especially clonazepam, in situations such as unavailability, intolerability, or adverse effects of ACTH or vigabatrin, or in a patient who does not respond to ACTH or vigabatrin.

Otimizando o componente farmacológico da terapia integrada da vertigem / Optimizing the pharmacological component of integrated balance therapy

A farmacoterapia é opção importante no tratamento das vestibulopatias periféricas. OBJETIVO: Identificar a medicação que otimiza a terapia integrada da vertigem (TIV) na doença de Ménière e em outras vestibulopatias periféricas. MATERIAL E MÉTODO: Estudo de casos em que pacientes com doença de Ménière ou outras vestibulopatias periféricas receberam TIV com betaistina, cinarizina, clonazepam, flunarizina, Ginkgo biloba ou sem medicação durante 120 dias. RESULTADOS: Na doença de Ménière, TIV com qualquer um dos medicamentos foi mais eficaz do que TIV sem medicação, após 60 dias; a betaistina foi mais efetiva que todas as outras drogas, após 60 e 120 dias. Nas outras vestibulopatias periféricas, diferenças significantes foram observadas entre TIV com betaistina, cinarizina, clonazepam ou flunarizina e TIV sem medicação após 60 dias e todas as drogas foram mais efetivas que TIV sem medicação após 120 dias; betaistina, cinarizina ou clonazepam foram igualmente efetivos e betaistina foi mais efetiva que flunarizina e Ginkgo biloba. Os tratamentos foram bem tolerados. CONCLUSÕES: TIV incluindo medicação é mais efetiva que sem medicação na doença de Ménière ou em outras vestibulopatias periféricas. Betaistina foi o medicamento mais efetivo na doença de Ménière e tão eficaz quanto cinarizina ou clonazepam em outras vestibulopatias periféricas.

Drug treatment is an important option for the treatment of peripheral vestibular diseases. AIM: To identify the drug component associated with optimal integrated balance therapy (IBT) for MénièreÆs disease or other peripheral vestibular disorders. MATERIALS AND METHODS: Analysis of a series of patients with MénièreÆs disease patients or patients with other peripheral vestibular disorders that received IBT involving either no medication or betahistine, cinnarizine, clonazepam, flunarizine or Ginkgo biloba during 120 days. RESULTS: In MénièreÆs disease, significant differences were observed for all drug therapies (60 days) versus no medication; betahistine was significantly more effective than all other drugs at 60 and 120 days. For non-MénièreÆs disorders, significant differences were observed among betahistine, cinnarizine, clonazepam and flunarizine and no medication after 60 days; all drug therapies were significantly more effective than no medication after 120 days; betahistine, cinnarizine or clonazepam were equally effective and betahistine was more effective than flunarizine and EGb 761. All treatment options were well tolerated. CONCLUSIONS: Drug therapies were more effective than no medication in the IBT for patients with MénièreÆs disease or other peripheral vestibular disorders. Betahistine was the most effective medication for patients with MénièreÆs disease and was as effective as cinnarizine and clonazepam for other peripheral vestibular disorders.

Hyperekplexia in two siblings.

Hyperekplexia is a rare, hereditary, non-epileptic disorder characterized by an exaggerated startle reaction to unexpected auditory, somatosensory and visual stimuli. The authors describe a one-day-old term neonate, who presented with jitteriness and episodic tonic spasms, and his elder sister with hyperekplexia. Hyperekplexia though is a rare disorder is one of the differential diagnoses for refractory tonic spasms in infancy. The prognosis is generally good in hereditary hyperekplexia. Recent molecular studies have revealed many associated mutations in the glycine receptor alpha and beta subunit genes.

Involuntary jerking of lower half of the body (spinal myoclonus).

A 55 years old, hypertensive, diabetic lady presented with sudden onset jerky movement of lower trunk and legs. It was present both in awake and sleep and got aggravated by mental stress as well as sensory stimulation. Examination revealed rhythmic jerks affecting muscles of lower abdomen and legs. The lower limbs had normal muscle bulk and power, increased tone, exaggerated deep tendon reflexes, bilateral flexor plantar response with normal sensory autonomic and cerebellar function. Investigations including CSF study, MRI of dorsal spine and NCV were normal. A combination therapy with tizanidine, baclofen and clonazepam induced gradual improvement within 6 weeks.

Zumbido pulsátil: tratamento com clonazepan e propranolol / Pulsatile tinnitus: treatment with clonazepam and propranolol

O zumbido pulsátil sincrônico com os batimentos cardíacos é pouco freqüente, sendo de etiologia tanto vascular arterial (malformacões, fístulas artério-venosas) ou venosa (anormalidades do bulbo jugular, tumor glômico jugular ou timpânico). A identificacão precoce da etiologia é essencial para que a terapêutica adequada possa ser instituída. A angioressonância possibilita a identificacão de alteracões vasculares com maior precisão. Relatamos um caso onde, após o diagnóstico de uma alteracão vascular arterial, foi instituído o tratamento com propranolol e clonazepam, com melhora da sintomatologia.

Periodic limb movement disorder : a clinical and polysomnographic study.

Periodic limb movement disorder (PLMD) is one of the commonest neurological disorders and causes significant disability, if left untreated. However, it is rarely diagnosed in clinical practice, probably due to lack of awareness and/or lack of necessary diagnostic facilities. Restless leg syndrome (RLS), aging, pregnancy, uraemia, iron deficiency, polyneuropathy are some of the common causes of secondary PLMD. Clinical presentation, polysomnographic findings and management of six patients of PLMD have been discussed in this report.

Trastorno de pánico e hipertiroidismo: curso clínico en dos pacientes / Panic disorder and hyperthyroidism: report of 2 cases

In two females aged 27 and 32 years old, an aggravation of their panic disorder coincided with the appearance of clinical signs of hyperthyroidism. The clinical diagnosis was confirmed with the finding of raised thyroid hormone levels and undetectable TSH levels. These two cases highlight the importance of routine thyroid function assessment in patients with panic disorder, mainly in those with partial response to medications or when symptoms aggravate, despite an adequate treatment

Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats

Diabetic patients have a 20 percent higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg), moclobemide (30 mg/kg), clonazepam (0.25 mg/kg), fluoxetine (20 mg/kg) sertraline (30 mg/kg) or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50 percent glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia