Bilateral Globus Pallidus Externus Deep Brain Stimulation for the Treatment of Refractory Tourette Syndrome: An Open Clinical Trial.

OBJECTIVES: We have previously proposed that Tourette syndrome (TS) is the clinical expression of the hyperactivity of globus pallidus externus (GPe) and various cortical areas. This study was designed to test this hypothesis by verifying the efficacy and safety of bilateral GPe deep brain stimulation (DBS) for treating refractory TS. MATERIALS AND METHODS: In this open clinical trial, 13 patients were operated on. Target coordinates (center of GPe) were obtained by direct visualization. Physiological mapping was performed with macrostimulation and microrecording. Primary and secondary outcome measures were, respectively, responder and improvement rates of TS and comorbidities, according to pre- and postoperative scores on the following assessment instruments: Yale Global Tic Severity Scale, Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory/Hamilton Depression Rating Scale, Beck Anxiety Inventory/Hamilton Anxiety Rating Scale, and Concentrated Attention test. RESULTS: Intraoperative stimulation (100 Hz/5.0V) did not produce any adverse effects or impact on tics. Microrecording revealed bursting cells discharging synchronously with tics in the central part of the dorsal half of GPe. Patients were followed up for a mean of 61.46±48.50 months. Responder rates were 76.9%, 75%, 71.4%, 71.4%, and 85.7%, respectively, for TS, obsessive-compulsive disorder (OCD), depression, anxiety, and attention deficit hyperactivity disorder. Mean improvements among responders in TS, OCD, depression, and anxiety were 77.4%, 74.7%, 89%, and 84.8%, respectively. After starting stimulation, tic improvement was usually delayed, taking up to ten days to manifest. Afterward, it increased over time, usually reaching its maximum at approximately one year postoperatively. The best stimulation parameters were 2.3V to 3.0V, 90 to 120 µsec, and 100 to 150 Hz, and the most effective contacts were the two dorsal ones. Two complications were registered: reversible impairment of previous depression and transient unilateral bradykinesia. CONCLUSIONS: Bilateral GPe-DBS proved to be low risk and quite effective for treating TS and comorbidities, ratifying the pathophysiological hypothesis that led to this study. Moreover, it compared favorably with DBS of other targets currently in use.

Genetic polymorphisms of the 5HT receptors are not related with depression in temporal lobe epilepsy caused by hippocampal sclerosis.

BACKGROUND: Temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) is the most frequent form of drug-resistant epilepsy in adults. Mood disorders are the most frequent psychiatric comorbidities observed in these patients. Common pathophysiological mechanisms of epilepsy and psychiatric comorbidities include abnormalities in the serotonin pathway. The primary goal of this study was to determine the possible association between polymorphisms of genes encoding the serotonin receptors 5HT1A (rs6295), 5HT1B (rs6296), and 5HT2C (rs6318) and the presence of mood disorders in patients with TLE-HS. Our secondary goal was to evaluate the possible association between these variants and susceptibility to develop seizures in TLE-HS. METHODS: We assessed 119 patients with TLE-HS, with and without psychiatric comorbidities; 146 patients with major depressive disorder; and 113 healthy volunteers. Individuals were genotyped for the rs6295, rs6296, and rs6318 polymorphisms. RESULTS: No difference was observed between the group with TLE-HS, healthy controls, and the group with major depressive disorder without epilepsy regarding the polymorphisms that were evaluated. There was no correlation between rs6318, rs6295, rs6296, and epilepsy-related factors and history of psychiatric comorbidities. CONCLUSIONS: Our work suggests that the studied polymorphisms were not related to the presence of TLE, psychiatric comorbidities in TLE, and epilepsy-related factors.

Striatal somatotopy and motor responses evoked by acute electrical stimulation of the posterior striatum in rats.

INTRODUCTION/OBJECTIVES: Previous experiments suggest that the striatal sensorimotor territory in rats is located in its dorsolateral region, along the rostrocaudal axis, unlike what has been observed in primates. In the present study, electrical stimulation was performed to investigate the degree of participation of the posterior striatum in its motor territory, its somatotopic organization, and the motor responses evoked by stimulation. METHODS: Twenty-five rats were submitted to stereotactic stimulation of the posterior striatum under general anesthesia, receiving consecutively four different current intensities. The motor responses observed in the different body parts were registered for later comparison. We considered as threshold the smallest of these current intensities able to evoke a motor response. RESULTS: The observed motor responses were qualitatively different for each segment: forepaws: ipsilateral, adduction, and contralateral abduction; hindpaws: ipsilateral, flexion, and contralateral, extension/abduction; trunk, rotation/flexion; and tail, rotation/elevation. High-frequency, small-amplitude distal tremor occurred in the ipsilateral forepaw in 95% of the animals. Progressively larger current intensities were necessary for the induction of motor response in the forepaws, hindpaws, and trunk/tail, in that order. CONCLUSIONS: The results allowed us to infer the following posterior striatal somatotopic organization: forepaws, posterolaterally, being the contralateral medial to the ipsilateral; trunk/tail, anteromedially; and hindpaws, in an intermediate position, being the contralateral posterior to the ipsilateral. It is suggested that the tremor and the other observed motor responses derive from the excitation of striatal projection neurons and that the striatum may play an important role in the genesis of essential tremor.

Effects of unilateral stereotactic posterior striatotomy on harmaline-induced tremor in rats.

Although long known and the most prevalent movement disorder, pathophysiology of essential tremor (ET) remains controversial. The most accepted hypothesis is that it is caused by a dysfunction of the olivocerebellar system. Vilela Filho et al. [2001; Stereotact Funct Neurosurg 77:149-150], however, reported a patient with unilateral hand ET that was completely relieved after a stroke restricted to the contralateral posterior putamen and suggested that ET could be the clinical manifestation of posterior putamen hyperactivity. The present study was designed to evaluate this hypothesis in the most often used model of ET, harmaline-induced tremor in rats. Fifty-four male Wistar rats were randomly distributed into three groups: experimental (EG), surgical control (SCG), and pharmacological control (PCG) groups. EG animals underwent stereotactic unilateral posterior striatotomy. SCG rats underwent sham lesion at the same target. PCG served exclusively as controls for harmaline effects. All animals received, postoperatively, intraperitoneal harmaline, and the induced tremor was video-recorded for later evaluation by a blind observer. Thirteen animals were excluded from the study. Limb tremor was reduced ipsilaterally to the operation in 20 of 21 rats of EG and in two of nine of SCG, being asymmetric in one of 10 of PCG rats. Comparisons between EG × SCG and EG × PCG were statistically significant, but not between SCG × PCG. Limb tremor reduction was greater in anterior than in posterior paws. Lateral lesions yielded better results than medial lesions. These results suggest that the posterior striatum is involved with harmaline-induced tremor in rats and support the hypothesis presented.

Possible mechanisms involved in subthalamotomy-induced dyskinesia in patients with Parkinson's disease.

BACKGROUND/AIMS: Operation-induced dyskinesia (OID) occurs in approximately 10% of patients submitted to subthalamotomy. The goal of the authors was to determine the possible causes of this feared complication. METHODS: The 54 patients who underwent unilateral subthalamotomy were divided into two groups: the OID group (OIDG), composed of 6 patients who developed dyskinesia following the operation, and the control group (CG), consisting of 48 patients who did not present this complication. The two groups were compared regarding age; sex; presence of levodopa-induced dyskinesia (LID) and/or stimulation-induced dyskinesia (SID); side of the operation; territories of the subthalamic nucleus (STN) involved by the lesion, and degree of lesion extension towards the zona incerta (ZI). RESULTS: The lesion involved the dorsolateral territory of the STN and was almost completely restricted to this nucleus in all patients of the OIDG, while it spread to the ZI in all but 1 patient of the CG. SID was significantly (p < 0.05) more frequent in the OIDG. There was also a strong trend favoring LID (p = 0.055). CONCLUSIONS: Damage to the dorsolateral territory of the STN and sparing of the ZI seem to be essential for the development of OID. SID and, to a lesser extent, LID are apparently significant risk factors for the development of this complication.

A new strategy for treating drug-resistant focal aware seizures: thalamic specific nuclei deep brain stimulation. Illustrative case.

BACKGROUND: Focal aware seizures (FASs) are relatively common and frequently pharmaco-resistant. If the seizure onset zone (SOZ) is in eloquent cortical areas, making resective surgery risky and inadvisable, deep brain stimulation (DBS) of the anterior nucleus of the thalamus, which is efficacious in less than half of the cases, has been the main alternative. New targets should be searched to address this deficiency. The present study aims to determine if DBS of different thalamic specific nuclei can modulate the abnormal electrical activity of the SOZ located in their respective cortical projection areas. Herein, the authors present the first patient in an ongoing trial. OBSERVATIONS: A 60-year-old female patient presented with 25-year history of pharmaco-resistant focal aware visual seizures frequently evolving to focal impaired awareness seizures. The SOZ was in the right occipital lobe (positron emission tomography-computed tomography/video electroencephalography). Magnetic resonance imaging was normal. She underwent ipsilateral lateral geniculate nucleus (LGN) DBS procedure. After a 24-month follow-up, seizure frequency decreased by 97%, improving quality of life and daily functioning without complications. LESSONS: This is the first time the LGN has been targeted in humans. The results support the hypothesis that led to this study. This strategy represents a paradigm shift in the way of treating pharmaco-resistant FASs not amenable to resective surgery.

Ventral intermediate nucleus deep brain stimulation for treatment-resistant focal aware motor seizures: illustrative case.

BACKGROUND: Resection of the seizure onset zone (SOZ) is considered the gold standard for treating refractory focal aware seizures (FASs). When resective surgery is unadvisable, deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT; ANT-DBS) has been the procedure of choice. However, less than half of patients with FASs respond to ANT-DBS. The need for alternative targets to effectively treat FAS is thus evident. OBSERVATIONS: The authors report the case of a 39-year-old woman presenting with pharmaco-resistant focal aware motor seizures, with the SOZ located in the primary motor cortical area. She had previously undergone unsuccessful resection of the left temporoparietal operculum elsewhere. Considering the risk of new resective surgery, she was offered combined ventral intermediate nucleus (Vim)/ANT-DBS. Vim-DBS proved to be superior to ANT-DBS for seizure control (88% vs 32%), although the association of both provided the best results (97%). LESSONS: This is the first report on the use of the Vim as a target of DBS for the treatment of FAS. The excellent results were presumably obtained by modulation of the SOZ through Vim projections to the motor cortex. This opens a completely new avenue for treating FAS: chronic stimulation of specific thalamic nuclei.

The impact of subcaudate tractotomy on delusions and hallucinations in psychotic patients.

BACKGROUND: Delusions and hallucinations, hallmarks of the psychotic disorders, usually do not respond to surgical intervention. For many years, the surgical technique of choice for the treatment of refractory aggressiveness in psychotic patients in our Service was amygdalotomy in isolation or associated with anterior cingulotomy. No improvement of hallucinations and delusions was noticed in any of these patients. To improve the control of aggression, subcaudate tractotomy was added to the previous surgical protocol. The main goal of the present study was to investigate the impact of this modified surgical approach on delusions and hallucinations. METHODS: Retrospective analysis of the medical records of psychotic patients presenting with treatment-resistant aggressiveness, delusions, and hallucinations submitted to bilateral subcaudate tractotomy + bilateral anterior cingulotomy + bilateral amygdalotomy in our institution. RESULTS: Five patients, all males, with ages ranging from 25 to 65 years, followed up by a mean of 45.6 months (17-72 months), fulfilled the inclusion criteria. Delusions and hallucinations were abolished in four of them. CONCLUSION: These results suggest that the key element for relieving these symptoms was the subcaudate tractotomy and that the orbitofrontal and ventromedial prefrontal cortices play an important role in the genesis of hallucinatory and delusional symptoms of schizophrenia and other psychoses.

Earwax as an alternative specimen for forensic analysis.

In this work, we presented, for the first time, earwax as an alternative forensic specimen for detecting 12 neuropsychotic drugs employing liquid chromatography-tandem mass spectrometry in positive and negative ion modes after straightforward extraction with methanol. The method was validated and standard curves were established by external calibration with correlation coefficients >0.99. All precision, accuracy, matrix effects, extraction recoveries, and carryover were within acceptable limits; limits of quantification were sufficiently low to quantify almost all the samples tested. To confirm the feasibility of the study, earwax specimens were collected from actual patients treated with different combinations of the 12 drugs and analyzed by our method; the 12 drugs could be quantified from the earwax specimens of the users successfully, showing usefulness of earwax specimens, because of its noninvasive sampling and the storage of drug(s) for relatively long time together with its being relatively less contaminated by environmental impurities. This study is pioneering; many detailed studies on earwax as an alternative specimen remain to be explored.

[Central pontine and extra-pontine myelinosis in alcoholic patient with Shoshin beriberi]. / Mielinólise pontina e extra-pontina associada a Shoshin beribéri em paciente etilista.

The central pontine myelinosis is classically related with rapid correction of chronic hyponatremia. Recently, important additional factors have been described in the pathogenesis of this condition. We report the case of a 43-year-old alcoholic malnourished man, with acute renal failure with dialytic treatment, and output failure Shoshin beriberi. He had tetraplegy and coma. Confirmation of pontine and extrapontine myelinosis by magnetic resonance imaging, and abnormalities on auditive evoked potentials are described.

Vagus nerve stimulator in patients with epilepsy: indications and recommendations for use.

Epilepsy comprises a set of neurologic and systemic disorders characterized by recurrent spontaneous seizures, and is the most frequent chronic neurologic disorder. In patients with medically refractory epilepsy, therapeutic options are limited to ablative brain surgery, trials of experimental antiepileptic drugs, or palliative surgery. Vagal nerve stimulation is an available palliative procedure of which the mechanism of action is not understood, but with established efficacy for medically refractory epilepsy and low incidence of side-effects. In this paper we discuss the recommendations for VNS use as suggested by the Brazilian League of Epilepsy and the Scientific Department of Epilepsy of the Brazilian Academy of Neurology Committee of Neuromodulation.

A new method for intraoperative localization of epilepsy focus by means of a gamma probe / Um novo método para a localização intraoperatória de foco de epilepsia mediante utilização de gamaprobe

Objective To evaluate the utility of a new multimodal image-guided intervention technique to detect epileptogenic areas with a gamma probe as compared with intraoperative electrocorticography. Materials and Methods Two symptomatic patients with refractory epilepsy underwent magnetic resonance imaging, videoelectroencephalography, brain SPECT scan, neuropsychological evaluation and were submitted to gamma probe-assisted surgery. Results In patient 1, maximum radioactive count was initially observed on the temporal gyrus at about 3.5 cm posteriorly to the tip of the left temporal lobe. After corticotomy, the gamma probe indicated maximum count at the head of the hippocampus, in agreement with the findings of intraoperative electrocorticography. In patient 2, maximum count was observed in the occipital region at the transition between the temporal and parietal lobes (right hemisphere). During the surgery, the area of epileptogenic activity mapped at electrocorticography was also delimited, demarcated, and compared with the gamma probe findings. After lesionectomy, new radioactive counts were performed both in the patients and on the surgical specimens (ex-vivo). Conclusion The comparison between intraoperative electrocorticography and gamma probe-assisted surgery showed similarity of both methods. The advantages of gamma probe include: noninvasiveness, low cost and capacity to demonstrate decrease in the radioactive activity at the site of excision after lesionectomy. .

Objetivo Avaliar a utilidade de um novo método de intervenção multimodal guiado por imagem, permitindo a detecção de áreas epileptogênicas mediante utilização de gamaprobe em comparação à eletrocorticografia intraoperatória. Materiais e Métodos Dois pacientes sintomáticos com epilepsia refratária realizaram ressonância magnética, videoeletroencefalograma, SPECT cerebral, avaliação neuropsicológica e foram submetidos a neurocirurgia usando gamaprobe. Resultados No paciente 1 as contagens radioativas inicialmente estavam no máximo no giro temporal, cerca de 3,5 cm posterior à ponta do lobo temporal esquerdo. Após corticotomia, o gamaprobe apontou o ponto máximo na cabeça do hipocampo, de acordo com os achados de eletrocorticografia intraoperatória. No paciente 2 as contagens foram máximas na região occipital em sua transição com os lobos temporal e parietal (hemisfério direito). Na cirurgia, a área mapeada da atividade epileptogênica na eletrocorticografia foi também delimitada, demarcada e comparada aos dados do gamaprobe. Após a lesionectomia, procedeu-se uma nova radiocontagem no paciente e na peça cirúrgica (ex-vivo). Conclusão A comparação entre os métodos mostrou acurácia praticamente similar. As vantagens do gamaprobe foram a de não ser invasivo, ser de baixo custo e também ser relevante para mostrar a redução da atividade radioativa no local da exérese. .

Síndrome de desconexäo inter-hemisférica após calosotomia total associada a comissurotomia anterior para tratamento de epilepsia resistente: relato de um caso / Interhemispheric disconnection syndrome following total callosotomy associated with anterior commissurotomy for the treatment of intractable epilepsy: report of a case

Os autores fazem breve abordagem das indicaçöes da calosotomia para tratamento de crises resitentes e relatam um caso em que ocorreu síndrome de desconexäo inter-hemisférica clássica, após calosotomia total associada a comissurotomia anterior. A síndrome de desconexäo foi mais severa nos primeiros 5 dias de pós-operatório, com boa melhroa após o 11§ dia, ocorrendo recuperaçäo funcional quase completa e, também, reduçäo significativa da freqüência das crises

Mielinólise pontina e extra-pontina associada a Shoshin beribéri em paciente etilista / Central pontine and extra-pontine myelinosis in alcoholic patient with Shoshin beriberi

A mielinólise pontina está classicamente associada à rápida correção de hiponatremia crônica. Recentemente, fatores importantes adicionais tem sido descritos na patogênese dessa condição. Relatamos o caso de um paciente de 43 anos, etilista, desnutrido, que apresentou quadro agudo de insuficiência cardíaca por "Shoshin beribéri", insuficiência renal com tratamento por diálise. Evoluiu com tetraparesia e coma. Apresentou mielinólise pontina central e extra-pontina à ressonância magnética de crânio e anormalidades no potencial evocado auditivo.

Centros de cirurgia de epilepsia: ponto de vista (1) / Epilepsy surgery center: point of view (1)

O autor relata a história da cirurgia da epilepsia quando teve início sua prática sistemática no Instituto de Neurologia de Montreal, há cinquenta anos atrás até os dias atuais, traçando um paralelo entre as condiçöes de trabalho dos grupos de cirurgia da epilepsia nos Estados Unidos e Canadá com os do Brasil e expöe o seu ponto de vista sobre as perspectivas da cirurgia da epilepsia no Brasil

Potenciais evocados auditivos de curta latência: registro com eletrodos de foramem oval / Intracranial brainstem auditory evoked potentials with Foramen Ovale Electrodes

O registro dos Potenciais Evocados Auditivos de Tronco Cerebral, com eletrodos intracranianos crônicos, próximos ao tronco cerebral, é possível com o uso de Eletrodos de Foramem Oval. Dez pacientes com epilepsia temporal crônica, candidatos a tratamento cirúrgico, foram submetidos a implantes de Eletrodos de Foramem Oval, com múltiplos contatos, para a investigaçäo de atividade epileptiforme. Estes pacientes submeteram-se ao registro de Potenciais Evocados Auditivos, simultaneamente, com eletrodos de escalpo e através dos contatos dos Eletrodos de Foramem Oval. A localizaçä dos contatos intracranianos foi realizada através de Tomografia Computadorizada Craniana. As latência absolutas para as ondas I a V, os intervalos inter-picos, bem como as amplitudes das ondas I e V, registrados intracranialmente, mostraram-se comparóveis aos valores obtidos no escalpo. O registro de componentes subcorticais dos potenciais auditivos, através de Eletrodos de Foramem Oval, parece ser um método promissor para a monitorizaçäo trans-cirúrgica em neurologia e otologia

Secçäo microcirúrgica do corpo caloso (calosotomia) no tratamento das epilepsias generalizadas / Microsurgical section of the corpus collosum (Collosotomy) as a treatment for generalized epilepsy

15 pacientes portadores de Epilepsia Generalizada näo controlável por meditaçäo foram submetidos a secçäo parcial do Corpo Caloso, como forma auxiliar de controle terapêutico de crises generalizadas menores, principalmente constituídas por ausências e crises atômicas. Os critérios neurológicos e eletroencefalográficos de seleçäo para indicaçäo cirúrgica estäo relacionados à freqüente presença de acentuaçäo multifocal de alteraçöes difusas da excitabilidade cortical encontradas nas epilepsias generalizadas secundárias. Os aspectos epileptológicos e eletroencefalográficos dos estudos pré e pós-operatórios säo discutidos

Comparaçäo entre distribuiçäo de campo e campo máximo de potencial entre os eletrodos zigomáticos anteriores e posteriores, em epilepsia do lobo temporal / Comparison on distribution of field and maximal field potential between the anterior and posterior zygomatic elements, in temporal lobe epilepsy

10 pacientes portadores de epilepsia do lobo temporal foram submetidas a registros eletroencefalográficos nas regiöes fronto temporais com o intuito de se comparar a eficácia dos eletrodos zigomáticos anteriores e posteriores

Investigaçäo pré-operatória de epilepsias de lobo temporal com eletrodos de forame oval / Pre operative investigation of temporal lobe epilepsy with foramen ovale eletrodes (FOE)

Quinze pacientes com epilepsia do lobo temporal foram investigados com eletrodos de forame oval(EFO). A indicaçäo da implantaçäo desses eletrodos foi por incapacidade de registros de superfície/esfenoidais de permitir lateralizaçäo do início das crises ou por incongruência entre início ictal e achados de neuroimagem. Dos quinze pacientes, quatro apresentavam ressecçäo temporal prévia, um apresentava uma lesäo e os dez restantes tiveram os registros de superfície e com EFO comparados neste estudo. Nesses dez pacientes foi possível lateralizar o início de 82 (por cento) das crises com os EFO, em contraste com um índice de 33 (por cento) com eletrodos de superfície e esfenoidais (p<0,001). O lado envolvido no início das crises correlacionou com maior atrofia das estruturas mesiais, conforme a análise qualitativa do exame de ressonância magnética. Como complicaçäo grave houve um caso de meningite séptica. Dois pacientes tiveram parestesia facial transitória e um apresentou também paresia reversível do VI nervo craniano. O uso dos EFO para registro de crises em pacientes selecionados permite lateralizaçäo confiável do início das crises, com qualidade superior ao registro com eletrodos de superfície e esfenoidais e custo e complexidade inferiores à investigaçäo com eletrodos de profundidade e placas subdurais crônicas

Neuropatia motora hereditária distal tipo 1: estudo de uma familia / Inherited motor neuropathy distal type 1: study on a family

Este trabalho descreve o estudo de uma família portadora de neuropatia motora hereditária distal tipo I (harding 1.984): 5 membros acometidos em 3 geraçöes foram examinados, evidenciando herança autossômica, início anterior aos 15 anos de idade, o membro mais velho anda e tem 63 anos de idade. A concordância intrafamiliar é alta e a avaliaçäo neurofisiológica foi decisiva para o diagnóstico, evidenciando velocidades de conduçäo neural e amplitude de potenciais sensitivos normais, ao lado de sinais de desnervaçäo e motora