PI3K, mTOR and GSK3 modulate cytokines' production in peripheral leukocyte in temporal lobe epilepsy.

INTRODUCTION: Epilepsy is a common pathological condition that predisposes individuals to seizures, as well as cognitive and emotional dysfunctions. Different studies have demonstrated that inflammation contributes to the pathophysiology of epilepsy. Indeed, seizures change the peripheral inflammatory pattern, which, in turn, could contribute to seizures. However, the cause of the altered production of peripheral inflammatory mediators is not known. The PI3K/mTOR/GSK3ß pathway is important for different physiological and pharmacological phenomena. Therefore, in the present study, we tested the hypothesis that the PI3K/mTOR/GSK3ß pathway is deregulated in immune cells from patients with epilepsy and contributes to the abnormal production of inflammatory mediators. METHODS: Patients with temporal lobe epilepsy presenting hippocampal sclerosis and controls aged between 18 and 65 years-old were selected for this study. Peripheral blood was collected for the isolation of peripheral mononuclear blood cells (PBMC). Cells were pre-incubated with different PI3K, mTOR and GSK-3 inhibitors for 30 min and further stimulated with phytohaemaglutinin (PHA) or vehicle for 24 h. The supernatant was used to evaluate the production of IL-1ß, IL-6, IL-10, TNF e IL-12p70. RESULTS: Non-selective inhibition of PI3K, as well as inhibition of PI3Kγ and GSK-3, reduced the levels of TNF and IL-10 in PHA-stimulated cells from TLE individuals. This stimulus increased the production of IL-12p70 only in cells from TLE individuals, while the inhibition of PI3K and mTOR enhanced the production of this cytokine. On the other hand, inhibition of GSK3 reduced the PHA-induced production of IL-12p70. CONCLUSIONS: Herein we demonstrated that the production of cytokines by immune cells from patients with TLE differs from non-epileptic patients. This differential regulation may be associated with the altered activity and responsiveness of intracellular molecules, such as PI3K, mTOR and GSK-3, which, in turn, might contribute to the inflammatory state that exists in epilepsy and its pathogenesis.

Necrotizing Otitis Externa: A Disease Barely Known to Neurosurgeons

Necrotizing otitis externa (NOE), also known as malignant otitis externa (MOE), is a severe and rare infectious disease of the external auditory canal (EAC). Without treatment, it may progress to skull base involvement. The bacteria Pseudomonas aeruginosa is the most common causative agent (90% of the cases), and affects immunocompromised subjects, particularly diabetic patients. Severe chronic otalgia, otorrhea, and cranial nerve palsy are the most common clinical presentations. Patients with NOE are frequently referred to neurosurgery because of the neurological impairment and skull base compromise. The definitive diagnosis is frequently elusive, requiring a high index of suspicion. Several laboratorial tests, imaging modalities, and the histologic exclusion of malignancy may be required. An early diagnosis and aggressive treatment reduce morbidity and mortality. We present four NOE cases to illustrate the spectrum of clinical presentation and complementary exams. According to the literature, more effort for early diagnosis and treatment is required, and neurosurgeons play an important role in this task.

Epilepsia refratária: a experiência do Núcleo Avançado de Tratamento das Epilepsias do Hospital Felício Rocho (NATE) no período de março de 2003 a dezembro de 2006 / Refractory epilepsy: the experience of the NATE

INTRODUÇÃO: A epilepsia é um problema de saúde pública. Afeta mais de cinqüenta milhões de pessoas em todo mundo e mais de vinte milhões deles continuam apresentando crises que não controlam satisfatoriamente com o uso de medicamentos. As epilepsias refratárias correspondem a cerca de 20 por cento dos pacientes epilépticos e boa parte desses apresentam crises parciais complexas passíveis de tratamento cirúrgico. A indicação cirúrgica criteriosa tem se mostrado eficiente para o controle das crises. OBJETIVO: Apresentar dados epidemiológicos e cirúrgicos dos pacientes submetidos ao tratamento cirúrgico no NATE. METODOLOGIA: Estudo retrospectivo com análise de prontuários e classificação do controle de crises de 46 pacientes considerando a Escala de Engel. RESULTADOS: Predomina o sexo masculino, solteiros, sem história familiar para epilepsia. Pacientes procedentes do Estado de Minas Gerais e outros estados da união. Início das crises na infância para 58,8 por cento dos pacientes sendo o tipo de crise mais freqüente a crise parcial complexa. O déficit de memória foi a queixa cognitiva mais comum. CONCLUSÃO: O controle de crise foi compatível com Engel Ia (sem crise) para 67 por cento dos pacientes. O tratamento cirúrgico revelou-se eficiente para o controle das crises dos pacientes portadores de epilepsia refratária ao tratamento medicamentoso.

INTRODUCTION: Epilepsy is a health public problem. Afflicts more than 50 million people worldwide, and more than 20 million of those affected do not have satisfactory seizures control with medicine. The refractory epilepsy represents 20 percent of all epileptic patients and most of them present partial seizures which can be treated by surgical treatment. The careful surgical recommendation can be efficient to seizure control. PURPOSE: The aim of this study was to present epidemiological and surgical data about patients submitted to surgical treatment in NATE - Advanced Center of Epilepsy Treatment. METHOD: We used a retrospective assessment method and control seizure classification from Engel Scale for 46 epileptic patients submitted to surgical treatment. RESULTS: Our results showed predominant male patients, single, without family history for epilepsy. The patients were from cities of Minas Gerais State and from another States in Brazil. The first seizure occurred in the childhood for 58,8 percent of patients and the more frequent seizure type was complex partial seizure. The predominant cognitive complaint was about memory. CONCLUSION: The surgical treatment for seizure control was good for 67 percent of patients that display Engel Ia classification (without seizures) and has a high likelihood for success in medically intractable temporal lobe epilepsy.

Prefrontal cognitive dysfunction following brainstem lesion.

Prefrontal cortex (PFC) dysfunction can lead to impairment in planning and behavioral inhibition, as well as personality changes. As ascending monoaminergic brainstem systems modulate PFC functioning, it is possible that lesions in the brainstem lead to symptoms similar to prefrontal dysfunction. A 29-year-old man developed several cognitive and behavioral symptoms after neurosurgery for resection of a pilocytic astrocytoma in the pontine-mesencephalic area. A careful analysis of symptoms indicated PFC dysfunction that could be attributed to lesions in the ascending monoaminergic brainstem systems. Interestingly, the cognitive symptoms improved after treatment with methylphenidate, which is a drug that modules catecholaminergic neurotransmission, thereby supporting this hypothesis. This is a unique case of PFC dysfunction that may be related to post-operative lesion of the catecholaminergic nuclei in the brainstem.

Olanzapine for recurrent excessive irritability and psychotic symptoms after mesial temporal lobectomy in a patient with temporal lobe epilepsy.

We report the case of a patient with temporal lobe epilepsy, nonresponsive to antiepileptic drugs, who became seizure-free, but developed recurrent excessive irritability and psychotic symptoms after successful mesial temporal lobectomy. This patient was refractory to various pharmacological treatments including antipsychotics, mood stabilizers, and benzodiazepines before being successfully treated with olanzapine.

Preservation of the facial nerve in large acoustic neuromas using the combined translabyrinthine-suboccipital approach

Microsurgical technique has made possible to remove acoustic neuroma totally with preservation of the facial nerve and sometimes the cochlear nerve. A series of 66 patients with acoustic nerve tumors was reviewed and will be presented. The aim of this paper is to analyze the group with large tumors and to present the advantages in using the combined translabyrinthine-suboccipital approach.