Spontaneous periodic hypothermia and hyperhidrosis: a possibly novel cerebral neurotransmitter disorder.

Spontaneous periodic episodes of hypothermia still defy medical knowledge. In 1969, Shapiro et al. described the first two cases of spontaneous periodic hypothermia associated with agenesis of the corpus callosum. Recently, Dundar et al. reported a case of spontaneous periodic hypothermia and hyperhidrosis without corpus callosum agenesis, suggesting that the periodic episodes of hypothermia might be of epileptiform origin. Here we describe two paediatric patients with spontaneous periodic hypothermia without corpus callosum agenesis and demonstrate, to our knowledge for the first time, altered levels of neurotransmitter metabolites within the cerebrospinal fluid.

The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis.

PURPOSE: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor kappaB (NFkappaB), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control. METHOD: Immunohistochemistry, Western blot, and real-time PCR techniques were employed to analyze the expression of these receptors. RESULTS: The results showed an upregulation of AngII AT1 receptor as well as its messenger ribonucleic acid (mRNA) expression in the cortex and hippocampus of patients with MTS. In addition, an increased immunoexpression of AngII AT2 receptors was found only in the hippocampus of these patients with no changes in its mRNA levels. DISCUSSION: These data show, for the first time, changes in components of renin-angiotensin system (RAS) that could be implicated in the physiopathology of MTS.

Bone marrow cells are able to increase vessels number during repair of sciatic nerve lesion.

The aim of this study was to compare the outcomes of nerve autografts (GRF) and venous grafts containing mononuclear bone marrow cells (BMCs) in sciatic nerve-lesioned rats. Control animals underwent sham operations (SHAM), received empty venous grafts (EPV), or received venous grafts containing BMC vehicle (AGR). Outcome was evaluated through sciatic functional index (SFI), morphometric and morphologic analyses of the nerve distal to the lesion, and the number of spinal cord motor neurons positive for the retrograde tracer, Fluoro-Gold. All groups exhibited poor results in SFI when compared to SHAM animals throughout the postoperative period. All groups also had a significantly greater fiber density, decreased fiber diameter, and decreased motor neuron number than the SHAM group. No significant difference between the GRF and BMC groups was observed in any of these parameters. On the other hand, vessel density was significantly higher in BMC than all other groups. BMC-containing venous grafts are superior to nerve autografts in increasing vessel density during sciatic nerve regeneration.

Botulinum toxin A (BT-A) versus low-level laser therapy (LLLT) in chronic migraine treatment: a comparison.

OBJECTIVE: The aim of this work was to evaluate patients with chronic migraine treated with botulinum toxin A (BT-A) and compare this with low level laser therapy (LLLT), referencing: pain days, pain intensity, intake of drugs/self-medication, anxiety and sleep disorders. METHODS: Patients were randomized into two groups: BT-A group (n = 18) and LLLT group (n = 18). Each patient kept three pain diaries: one before (baseline) (30 days), one during treatment (30 days) and one after the post-treatment phase (30 days). Repeated ANOVA plus the Bonferroni post-test, Student's t test, and factorial analysis were applied, and p < 0.05 was accepted as significant. RESULTS: Our data showed that both treatments were able to reduce headache days, acute medication intake and decrease the intensity of pain. Anxiety was reduced in the BT-A group, while sleep disturbance was reduced in the LLLT group. CONCLUSION: Our data showed that both treatments can be used to treat chronic migraine, without notable differences between them.

Botulinum toxin A (BT-A) versus low-level laser therapy (LLLT) in chronic migraine treatment: a comparison / Toxina botulínica A (BT-A) versus laser terapia de baixa potência (LLLT) em enxaqueca crônica: Uma triagem comparativa

ABSTRACT The aim of this work was to evaluate patients with chronic migraine treated with botulinum toxin A (BT-A) and compare this with low level laser therapy (LLLT), referencing: pain days, pain intensity, intake of drugs/self-medication, anxiety and sleep disorders. Methods: Patients were randomized into two groups: BT-A group (n = 18) and LLLT group (n = 18). Each patient kept three pain diaries: one before (baseline) (30 days), one during treatment (30 days) and one after the post-treatment phase (30 days). Repeated ANOVA plus the Bonferroni post-test, Student's t test, and factorial analysis were applied, and p < 0.05 was accepted as significant. Results: Our data showed that both treatments were able to reduce headache days, acute medication intake and decrease the intensity of pain. Anxiety was reduced in the BT-A group, while sleep disturbance was reduced in the LLLT group. Conclusion: Our data showed that both treatments can be used to treat chronic migraine, without notable differences between them.

RESUMO O estudo comparou pacientes com cefaleia crônica (CM) tratados com toxina botulínica A (BT-A) versus terapia a laser de baixa intensidade (LLLT), relativos a: dias de dor, automedicação, nervosismo e distúrbios do sono. Métodos: Os pacientes foram randomizados em dois grupos: Grupo BT-A (n = 18) e Grupo LLLT (n = 18). Cada paciente preencheu três diários de dor, sendo um antes do início do tratamento (30 dias), durante o tratamento (30 dias) e um após tratamento (30 dias). ANOVA e pós-teste Bonferroni, teste T de Student e análise fatorial foram utilizados e valores de p < 0,05 foram considerados significativos. Resultados: Ambos os tratamentos foram capazes de reduzir os dias de dor e a ingestão aguda de medicação. Além disso, a ansiedade foi reduzida no grupo BT-A, enquanto que o distúrbio do sono foi reduzido no grupo LLLT. Conclusão: Nossos resultados mostraram que ambos os tratamentos são eficientes contra CM, sem diferença entre eles.

Consequences of pilocarpine-induced status epilepticus in immunodeficient mice.

Systemic injection of pilocarpine in rodents induces status epilepticus (SE) and reproduces the main characteristics of temporal lobe epilepsy (TLE). Different mechanisms are activated by SE contributing to cell death and immune system activation. We used BALB/c nude mice, a mutant that is severely immunocompromised, to characterize seizure pattern, neurochemical changes, cell death and c-Fos activation secondarily to pilocarpine-induced SE. The behavioral seizures were less severe in BALB/c nude than in BALB/c wild type mice. However, nude mice presented more tonic-clonic episodes and higher mortality rate during SE. The c-Fos expression was most prominent in the caudate-putamen, CA3 (p<0.05), dentate gyrus, entorhinal cortex (p<0.001), basolateral nucleus of amygdala (p<0.01) and piriform cortex (p<0.05) of BALB/c nude mice than of BALB/c. Besides, nude mice subjected to SE presented high number of Fluorojade-B (FJB) stained cells in the piriform cortex, amygdala (p<0.05) and hilus (p<0.001) in comparison with BALB/c mice. A significant increase in the level of glutamate and GABA was found in the hippocampus and cortex of BALB/c mice presenting SE in comparison to controls. However, the level of glutamate was higher in the brains of BALB nude mice than in the brains of BALB/c wild type mice, while the levels of GABA were unchanged. These results indicate that the brains of immunodeficient nude mice are more vulnerable to the deleterious effects of pilocarpine-induced SE as they present intense activation, increased glutamate levels and more cell death.

Kallikrein 1 is overexpressed by astrocytes in the hippocampus of patients with refractory temporal lobe epilepsy, associated with hippocampal sclerosis.

Kallikrein 1 (hK1) is a tissue enzyme responsible for kinin release in inflammatory cascade. This study was delineated to study the distribution and the co-localization of hK1 and kinin B1 and B2 receptors with glial and/or neuronal proteins markers, in the hippocampus of patients with refractory temporal lobe epilepsy, associated with hippocampal sclerosis (TLE-HS), comparing with control tissues. Hippocampal levels of KLK1 mRNA were also measured. hK1, kinin B1 and B2 receptors, NeuN and GFAP were analyzed using immunohistochemistry and confocal microscopy and KLK1 mRNA was quantified with real time PCR. Increased expression of hK1 by astrocytes co-localized with GFAP was found, contrasting with kinin B1 and B2 receptors, which were co-localized with NeuN in the sclerotic hippocampus. In addition, KLK1 mRNA was also up-regulated in same tissues. These data suggest an overexpression of kallikrein-kinin system and a neuron-glia interaction in the inflammatory process present in refractory TLE-HS.

Kinin B1 and B2 receptors are overexpressed in the hippocampus of humans with temporal lobe epilepsy.

Molecular biology tools have been employed to investigate the participation of peptides in human temporal lobe epilepsy (TLE). Active polypeptides and their receptors have been related to several brain processes, such as inflammation, apoptosis, brain development, K(+) and Ca(2+) channels' activation, cellular growth, and induction of neuronal differentiation. Previous works have shown a neuroprotector effect for kinin B2 receptor and a deleterious, pro-epileptogenic action for kinin B1 receptor in animal models of TLE. The present work was delineated to analyze the kinin B1 and B2 receptors expression in the hippocampus of patients presenting refractory mesial TLE. The hippocampi were removed during the patients surgery in a procedure used for seizure control and compared with tissues obtained after autopsy. Nissl staining was performed to study the tissue morphology and immunohistochemistry, and Western blot was used to compare the distribution and levels of both receptors in the hippocampus. In addition, real time PCR was employed to analyze the gene expression of these receptors. Nissl staining showed sclerotic hippocampi with hilar, granular, and pyramidal cell loss in TLE patients. Immunohistochemistry and Western blot analyses showed increased expression of kinin B1 and B2 receptors but the real-time PCR data demonstrated increased mRNA level only for kinin B2 receptors, when compared with controls. These data show for the first time a relationship between human TLE and the kallikrein-kinin system, confirming ours previous results, obtained from experimental models of epilepsy.