Raphael Boechat-Barros

Experimental therapy of epilepsy with transcranial magnetic stimulation: lack of additional benefit with prolonged treatment

OBJECTIVE To investigate the effect of three months of low-frequency repetitive transcranial magnetic stimulation (rTMS) treatment in intractable epilepsy. METHODS Five patients (four males, one female; ages 6 to 50 years), were enrolled in the study; their epilepsy could not be controlled by medical treatment and surgery was not indicated. rTMS was performed twice a week for three months; patients kept records of seizure frequency for an equal period of time before, during, and after rTMS sessions. rTMS was delivered to the vertex with a round coil, at an intensity 5% below motor threshold. During rTMS sessions, 100 stimuli (five series of 20 stimuli, with one-minute intervals between series) were delivered at a frequency of 0.3 Hz. RESULTS Mean daily number of seizures (MDNS) decreased in three patients and increased in two during rTMS--one of these was treated for only one month; the best result was achieved in a patient with focal cortical dysplasia (reduction of 43.09% in MDNS). In the whole patient group, there was a significant (p<0.01) decrease in MDNS of 22.8%. CONCLUSION Although prolonged rTMS treatment is safe and moderately decreases MDNS in a group of patients with intractable epilepsy, individual patient responses were mostly subtle and clinical relevance of this method is probably low. Our data suggest, however, that patients with focal cortical lesions may indeed benefit from this novel treatment. Further studies should concentrate on that patient subgroup.

O uso da estimulação magnética transcraniana de baixa frequência no tratamento da depressão no Hospital Universitário de Brasília: achados preliminares

This paper reports the use of slow frequency transcranial magnetic stimulation of the right pre-frontal cortex in three patients with a diagnosis of major depressive episode according to the DSM-IV classification. There was a significant improvement in two patients, with a decrease of over 50% in the Hamilton Scale scores- 17 items. Possible indications and limitations of this therapeutic tool are discussed, as well as socio-economic aspects of this new treatment.

[Transcranial Magnetic Stimulation in depression: results of bi-weekly treatment].

OBJECTIVE Transcranial Magnetic Stimulation (TMS) has been shown to be a useful therapy for depression. This paper evaluates the results of bi-weekly low-frequency TMS of 4 weeks duration, in 10 patients with depression who do not respond or are intolerant to antidepressive medication. METHODS This is a case series study. DMS-IV criteria were used to diagnose depression. In order to disclose possible improvements in depressive symptoms, the 17 items Hamilton scale was used at three different moments: at the beginning, middle and end of the treatment period. Results were analysed using Friedmans chi2 test. RESULTS Hamiltons scale score improvement was > 50% in five patients and > 75% in 3 of these. CONCLUSIONS TMS may be efficacious, safe and easily performed as an adjunct to medical treatment of depression. We cannot differentiate a potentiation of the effect of antidepressive medication from an intrinsic effect of TMS alone, since we did not treat any subjects without the concurrent use of medication.

Transcranial magnetic stimulation and transcranial direct current stimulation appear to be safe neuromodulatory techniques useful in the treatment of anxiety disorders and other neuropsychiatric disorders

Transcranial magnetic stimulation (TMS) has recently been investigated as a possible adjuvant treatment for many neuropsychiatric disorders, and has already been approved for the treatment of drug-resistant depression in the United States and in Brazil, among other countries. Although its use in other neuropsychiatric disorders is still largely experimental, many physicians have been using it as an off-label add-on therapy for various disorders. More recently, another technique, transcranial direct current stimulation (tDCS), has also become available as a much cheaper and portable alternative to TMS, although its mechanisms of action are different from those of TMS. The use of off-label therapeutic TMS or tDCS tends to occur in the setting of diseases that are notoriously resistant to other treatment modalities. Here we discuss the case of anxiety disorders, namely panic and post-traumatic stress disorders, highlighting the uncertainties and potential problems and benefits of the clinical use of these neuromodulatory techniques at the current stage of knowledge.

Normative study of tympanic infrared thermometry: a non-invasive index of asymmetric cerebral activity

Human and primate studies have demonstrated that performance of tasks that induce asymmetrical physiological activation of the cerebral hemispheres leads to a reduction of tympanic temperature (TT) ipsilateral to the most active hemisphere. It is possible that diseases that interfere in an asymmetrical fashion with the degree of cerebral activity cause similar TT changes. There are not, however, normative studies of the acceptable interaural difference in TT in normal subjects at rest. This study was done to establish normative values for interaural TT values measured by means of infrared tympanic thermometry in resting normal subjects not engaged in any specific task. TT values were measured in 47 normal volunteers (20 men and 27 women, aged 39.38+/-12.57 years old) at rest; mean interaural differences of TT were calculated. Mean right ear TT was 36.85+/-0.50 degrees C and mean left ear TT was 36.74+/-0.57 degrees C; these values are in agreement with those already reported in the literature. Mean interaural TT difference was 0.25 degrees C (SD 0.21 degrees C). These findings indicate that maximal normal values for interaural TT differences, with confidence levels of 99% and 95%, are, respectively, 0.88 and 0.67 degrees C. The value of interaural differences of TT as a marker of asymmetrical hemispheric activity in neurological patients will have to be established by additional studies.

Estimulação magnética transcraniana de baixa freqüência no tratamento da depressão

This article describes neurophysiological and clinical aspects of repetitive transcranial magnetic stimulation (rTMS), especially low frequency rTMS. Neuroimaging techniques and hypothesis about long term actions of rTMS are discussed. Some results of low frequency rTMS on the treatment of depression are mentioned, especially one study in the University of Brasilia using low frequency rTMS twice a week, during 4 weeks in 10 patients. In this study, using the 17 item Hamilton scale, patients were scored at three different moments: T-0, T-1 and T-2, respectively, at the beginning, at the middle and at the end of the treatment. According to x2 Friedman´s test there was a significant decrease (p < 0,01) in depression scores. When the three moments were compared. Possible advantages of this technique are discussed.

Effects of Caffeine on Behavioural and Cognitive Deficits in Rats

There are many studies that have sought to find drug therapies to prevent harm arising from sepsis. Such studies have represented a progress in the support to septic patients and also in the development of new pharmacological alternatives. Our interest was to investigate the caffeine effect on sepsis behavioural and memory impairments. Male rats were anaesthetized and the surgery was made to allow exposure of the caecum, which was then squeezed to extrude a small amount of faeces from the perforation site, which was later placed back into the peritoneal cavity. This procedure, which served to generate experimental sepsis, is herein referred to as ceccum ligation and perforation (CLP). The caffeine (10 mg/kg) was administered by gavage route, once daily, during 7 or 14 consecutive days to investigate the effects of acute or subchronic caffeine treatment on long‐term behavioural and cognitive deficits induced by CLP. On the last day, 1 hr after caffeine administration, the animals were submitted to open‐field, elevated plus maze (EPM), forced swimming and step‐down inhibitory avoidance tests. The results showed that caffeine increased the percentage of open arm entries and open arm time in the EPM test, and reduced the immobility time when compared to the sham‐operated group. The caffeine also increased the latency in the inhibitory avoidance test platform. Our results demonstrated that the caffeine improved behavioural changes and improved the neurocognitive deficits of sepsis‐surviving animals. It is possible that blockage of the adenosine receptors may be responsible for the results here observed.

ASSERT trial – How to assess the safety and efficacy of a high frequency rTMS in postpartum depression ? A multicenter, double blinded, randomized, placebo-controlled clinical trial

Background Postpartum Depression affects a considerable number of women worldwide. This condition inflicts severe consequences to mother and child health. Thus far, available treatments have low response and high relapse rates. We designed this trial to evaluate a safe and more efficacious innovative therapy. Aims To report a feasible and ethical study design to assess the safety and efficacy of a high frequency repetitive Transcranial Magnetic Stimulation 10 Hz (rTMS) compared to sham rTMS in women with moderate to severe Post-Partum Depression using standard treatment (sertraline). To conduct an ancillary, exploratory, randomized, active controlled, double blind study with a hypothesis to assess the safety and efficacy of 10 Hz rTMS compared to sertraline. Methods A multicenter, parallel arm, randomized, placebo-controlled, double-blind design to assess safety and efficacy of 10 Hz rTMS compared to sham. An ancillary study will be conducted with parallel arm, randomized, active controlled and double dummy design to assess safety and efficacy of 10 Hz rTMS compared to sertraline.