Primer ensayo clínico empleando la estimulación cerebral profunda en pacientes con esquizofrenia resistente / Deep brain stimulation in treatment resistant schizophrenia: A pilot randomized cross-over clinical trial

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Linfoma primario del sistema nervioso central aparentando lesión del ángulo pontocerebeloso / Primary central nervous system lymphoma mimicking cerebellopontine angle tumour

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NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.

Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.

Valor de la PET/TC cerebral con 18F-fluorocolina en la detección de recurrencias de neoplasias primarias del sistema nervioso central / The usefulness of 18F-fluorocholine PET/CT in the detection of recurrence of central nervous system primary neoplasms

Objetivo. Estudiar el impacto clínico en el manejo de los pacientes de la 18F-fluorocolina (18F-COL) en la recurrencia de neoplasias cerebrales primarias. Material y métodos. Se estudió prospectivamente a 21 pacientes con sospecha de recidiva de neoplasia cerebral primaria mediante PET/TC cerebral con 18F-COL en uso compasivo. La distribución por patología de los pacientes estudiados fue: 3 astrocitomas grado II, 3 astrocitomas grado III, un oligodendroglioma grado II, 3 oligodendrogliomas grado iii, un oligoastrocitoma grado iii, 4 glioblastomas multiformes, una gliomatosis cerebri y 5 meningiomas. Se consideraron positivos los estudios en los que había una captación visualmente significativa respecto al fondo del parénquima cerebral. Resultados. Diecisiete de los pacientes fueron positivos, comprobándose dicho resultado por histología (10 de ellos) o seguimiento clínico y por neuroimagen, sin hallarse falsos positivos o negativos. El índice target to backgroud ratio medio para los positivos fue de 8,02 y para los negativos de 0,94, lo que representa una diferencia significativa (p=0,003). Conclusión. La PET/TC con 18F-COL presenta resultados alentadores en la valoración de pacientes con sospecha de recidiva (AU)

Aim. To study the usefulness of 18F-fluorocholine (FCH) in detecting the recurrence of primary brain tumours. Material and methods. A prospective study was conducted on brain PET/CT with FCH for compassionate use in 21 patients with suspected recurrence of a primary brain tumour. The distribution by pathology was: three grade II astrocytomas, three grade III astrocytomas, one grade II oligodendroglioma, three grade III oligodendrogliomas, one grade III oligoastrocytoma, four glioblastoma multiform, one gliomatosis cerebri, and five meningiomas. Studies in which there was a visually significant uptake in the brain parenchyma were classified as positive. Results. A total of 17 patients were classified as positive, with the results being confirmed by histology (10 cases) or clinical follow-up and imaging, with no false positives or negatives. The mean SUVmax for positive patients was 8.02 and 0.94 for the negative ones, which was significantly different (P=.003) Conclusion. PET/CT with FCH shows encouraging results in the evaluation of patients with suspected recurrence of primary brain neoplasms (AU)

The usefulness of 18F-fluorocholine PET/CT in the detection of recurrence of central nervous system primary neoplasms. / Valor de la PET/TC cerebral con 18F-fluorocolina en la detección de recurrencias de neoplasias primarias del sistema nervioso central.

AIM: To study the usefulness of 18F-fluorocholine (FCH) in detecting the recurrence of primary brain tumours. MATERIAL AND METHODS: A prospective study was conducted on brain PET/CT with FCH for compassionate use in 21 patients with suspected recurrence of a primary brain tumour. The distribution by pathology was: three grade ii astrocytomas, three grade iii astrocytomas, one grade ii oligodendroglioma, three grade iii oligodendrogliomas, one grade iii oligoastrocytoma, four glioblastoma multiform, one gliomatosis cerebri, and five meningiomas. Studies in which there was a visually significant uptake in the brain parenchyma were classified as positive. RESULTS: A total of 17 patients were classified as positive, with the results being confirmed by histology (10 cases) or clinical follow-up and imaging, with no false positives or negatives. The mean SUVmax for positive patients was 8.02 and 0.94 for the negative ones, which was significantly different (P=.003) CONCLUSION: PET/CT with FCH shows encouraging results in the evaluation of patients with suspected recurrence of primary brain neoplasms.

Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression.

This corrects the article DOI: 10.1038/mp.2016.144.

Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression.

Stressful life events produce a state of vulnerability to depression in some individuals. The mechanisms that contribute to vulnerability to depression remain poorly understood. A rat model of intense stress (social defeat (SD), first hit) produced vulnerability to depression in 40% of animals. Only vulnerable animals developed a depression-like phenotype after a second stressful hit (chronic mild stress). We found that this vulnerability to depression resulted from a persistent state of oxidative stress, which was reversed by treatment with antioxidants. This persistent state of oxidative stress was due to low brain-derived neurotrophic factor (BDNF) levels, which characterized the vulnerable animals. We found that BDNF constitutively controlled the nuclear translocation of the master redox-sensitive transcription factor Nrf2, which activates antioxidant defenses. Low BDNF levels in vulnerable animals prevented Nrf2 translocation and consequently prevented the activation of detoxifying/antioxidant enzymes, ultimately resulting in the generation of sustained oxidative stress. Activating Nrf2 translocation restored redox homeostasis and reversed vulnerability to depression. This mechanism was confirmed in Nrf2-null mice. The mice displayed high levels of oxidative stress and were inherently vulnerable to depression, but this phenotype was reversed by treatment with antioxidants. Our data reveal a novel role for BDNF in controlling redox homeostasis and provide a mechanistic explanation for post-stress vulnerability to depression while suggesting ways to reverse it. Because numerous enzymatic reactions produce reactive oxygen species that must then be cleared, the finding that BDNF controls endogenous redox homeostasis opens new avenues for investigation.

Estimulación cerebral profunda (DBS) en la esquizofrenia resistente / Clinical improvement in a treatment-resistant patient with schizophrenia treated with deep brain stimulation

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Fragmentation and high entropy of neonatal experience predict adolescent emotional outcome.

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Across evolution, maternal care is a key source of environmental sensory signals to the developing brain, and a vast body of work has linked quantitative and qualitative aspects of maternal care to emotional outcome in children and animals. However, the fundamental properties of maternal signals, that promote advantageous vs pathological outcomes in the offspring, are unknown and have been a topic of intense study. We studied emotional outcomes of adolescent rats reared under routine or impoverished environments, and used mathematical approaches to analyze the nurturing behaviors of the dams. Unexpectedly, whereas the quantity and typical qualities of maternal care behaviors were indistinguishable in the two environments, their patterns and rhythms differed drastically and influenced emotional outcomes. Specifically, unpredictable, fragmented maternal care patterns translated into high-entropy rates of sensory signals to the offspring in the impoverished cages. During adolescence, these offspring had significant reductions in sucrose preference and in peer-play, two independent measures of the ability to experience pleasure. This adolescent anhedonia, often a harbinger of later depression, was not accompanied by measures of anxiety or helplessness. Dopaminergic pleasure circuits underlying anhedonia are engaged by predictable sequences of events, and predictable sensory signals during neonatal periods may be critical for their maturation. Conversely, unpredictability maternal-derived signals may disrupt these developmental processes, provoking anhedonia. In sum, high-entropy and fragmented patterns of maternal-derived sensory input to the developing brain predicts, and might promote, the development of anhedonia in rodents, with potential clinical implications.

Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress.

The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.

Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.

Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.

Implication of the chemokine CCL2 in trigeminal nociception and traumatic neuropathic orofacial pain.

BACKGROUND: Chemokine (C-C motif) ligand 2 (CCL2) participates in different mechanisms contributing to the spinal cord inflammation and pain development after sciatic nerve injury. Recent data also support its role in orofacial thermal hypersensitivity, although its implication in different phases of trigeminal pain emergence is unclear. We assessed the importance of CCL2 signalling in biochemical and behavioural alterations during the early and late stages following chronic constriction injury of infraorbital nerve (ION-CCI), a model of peripheral traumatic trigeminal pain. METHODS: After evaluating the consequences of CCL2 intracisternal injection in naïve rats, we determined the expression changes for CCL2, inflammatory and glia activation markers in the somatosensory trigeminal complex (STC) and trigeminal ganglia (TG) after ION-CCI. The role of CCL2 signalling was assessed using pre-emptive or 'curative' intracisternal treatment with specific CCL2 receptor antagonist - INCB3344. RESULTS: Exogenous CCL2 evoked spontaneous behaviour reminiscent of orofacial pain and marked mechanical hypersensitivity, associated with increased expression of proinflammatory cytokines and glial markers in STC and TG. CCL2-evoked changes were prevented by the co-administration of INCB3344. Two weeks after ION-CCI, mRNA for CCL2, glial and inflammatory markers were up-regulated, and CCL2-immunoreactivity accumulated in central and ganglionic tissues. At this time, repeated intracisternal administration of INCB3344 did not attenuate the ION-CCI-associated behavioural nor biochemical changes. By contrast, pre-emptive INCB3344 treatment delayed the emergence of trigeminal mechanical allodynia and associated biochemical alterations. CONCLUSIONS: Our data suggest that CCL2 is involved principally in the early events accompanying the ION lesion rather than in long-term alterations and the maintenance of trigeminal mechanical hypersensitivity.

[Current management of arteriovenous malformations. Retrospective study of 31 cases and literature review]. / Manejo actual de las malformaciones arteriovenosas. Estudio retrospectivo de 31 casos y revisión de la literatura.

OBJECTIVE: To establish some therapeutic criteria about the treatment of AVMs of III, IV and V grade of Spetzler and Martin and to analyse the results in the subgroup of preoperative embolization plus surgery. METHODS: We perform a retrospective analysis of a group of 31 patients with arteriovenous malformations (AVMs) treated in our center between 1999 and 2004. There were 19 women and 12 men, with a mean age of 31.6 years old (range, 1-62a). Their symptoms upon admission were intracranial hemorrhage in 77.4%, seizures in 12.9%, headache, ischemic event and incidental finding in 3.2% each group. Diagnostic angiography was performed in 29 cases and anatomopathologic diagnostic in 2 cases. The malformations were classified with Spetzler and Martin Grading Scale, in 10.3% grade I, 24.1% grade II, 37.9% grade III, 24.1% grade IV and 3.4% grade V. Patients were classified in 6 subgroups of treatment (surgery, embolization, radiosurgery, embolization plus surgery, embolization plus radiosurgery and conservative treatment). RESULTS: AVMs grade III, IV and V (19 patients) were treated with surgery (6 cases), embolization plus surgery (5 cases), but also other kind of treatments (embolization alone, radiosurgery and conservative) were used. Functional results in these groups of patients were 36.8% (7 cases) with no symptoms or slights symptoms (modified Rankin 0-1), 52.6% (10 cases) minor disability (mRankin 2), 5.3% (1 case) moderate disability and 5.3% (1 case) mortality. We observe a high rate of postembolization hemorrhage in the group of patients in which the combination of preoperative embolization plus surgery was used. In these cases, early surgery was performed with a good functional recovery. There was one case of postoperative mortality. CONCLUSION: We should consider some factors like the natural history, clinical presentation (hemorrhage), angiographic features (deep arterial supply, aneurisms), Spetzler and Martin Grading and the clinical condition of the patient before treating a cerebral AVM. In the subgroup of treatment with embolization plus surgery, we recommend to achieve a subtotal preoperative embolization > 50%, not to obliterate more than 50% in one session, to perform staged embolization waiting from 4 to 6 weeks between procedures, and from 1 to 3 weeks between the last embolization and surgery.

Manejo actual de las malformaciones arteriovenosas. Estudio retrospectivo de 31 casos y revisión de la literatura / Actual Management of arteriovenous malformations. Retrospective study of 31 cases and literature review

Objetivos. Establecer unos criterios terapéuticos en las malformaciones arterio venosas (MAVs) grados III,IV y V de Spetzler y Martin y análisis de resultados en el subgrupo de tratamiento con embolización más cirugía. Material y métodos. Estudio retrospectivo de 31pacientes con MAVs cerebrales tratados en nuestro servicio entre 1999 y 2004. Se trata de 19 mujeres y 12 hombres, con una edad media de 31,6 años (rango de 1 a 62a).La forma de presentación fue en un 77,4% hemorragiaintracraneal, en un 12,9% crisis comicial y en un 3,2%cefalea, infarto isquémico y hallazgo casual en cada uno de ellos. En 29 casos se realizó arteriografía diagnóstica y en 2 casos el diagnóstico fue anatomo-patológico. Según la clasificación de Spetzler y Martin, 10,3%fueron de Grado I, 24,1% de Grado II, 37,9% de GradoIll, 24,1% de Grado IV y 3,4% de Grado V. Se clasificaron en 6 grupos según el tratamiento realizado (cirugía, embolización, radiocirugía, embolización más cirugía, embolización más radiocirugía y tratamiento conservador).Resultados. Las MAVs grado III, IV y V (19 pacientes)fueron tratadas en su mayoría por cirugía (6 casos) y embolización más cirugía (5 casos) pero también se utilizaron otras modalidades de tratamiento (embolización, radiocirugía y conservador). Los resultados funcionales de estos 3 subgrupos muestra un 36,8% (7 casos) de asintomáticos o con mínimos síntomas (Rankin m 0-1),un 52,6% (10 casos) de discapacidad leve pero independientes(Rankin m=2), un 5,3% (1 caso) de moderada discapacidad (Rankin m=3), y un 5,3% (1 caso)de mortalidad. En el manejo combinado embolización más cirugía de malformaciones complejas, se observa un alto porcentaje de sangrado postembolización que motivó cirugía precoz con buen resultado funcional. Hubo un caso de mortalidad postquirúrgica. Conclusiones. En el tratamiento de las MAVs cerebralesse debe tener en cuenta factores como la historia natural, la forma de presentación (hemorragia), las características angioestructurales (presencia de aporte arterial profundo, aneurismas), la escala de Spetzler y Martin y el estado clínico del paciente. En el tratamiento con embolización más cirugía es recomendable obtener una embolización prequirúrgica subtotal > 50%, no ocluir más del 50% por sesión, mantener un intervalo entre sesiones de embolización entre4 y 6 semanas y un intervalo entre última embolización y cirugía entre 1 y 3 semanas

Objective. To stablish some therapeutic criteria about the treatment of AVMs of III, IV and V grade of Spetzler and Martin and to analyse the results in the subgroup of preoperative embolization plus surgery. Methods. We perform a retrospective analysis of a group of 31 patients with arteriovenous malformations(AVMs) treated in our center between 1999 and 2004.There were 19 women and 12 men, with a mean age of 31,6 years old (range, 1-62a). Their symptoms upon admission were intracranial hemorrhage in 77,4%, seizures in 12,9%, headache, ischemic event and incidental finding in 3,2% each group. Diagnostic angiography was performed in 29 cases and anatomopathologic diagnosticin 2 cases. The malformations were classified with Spetzler and Martin Grading Scale, in 10,3% grade I,24,1% grade II, 37,9% grade III, 24,1% grade IV and3,4% grade V. Patients were classified in 6 subgroups of treatment (surgery, embolization, radiosurgery, embolizationplus surgery, embolization plus radiosurgery and conservative treatment).Results. AVMs grade III, IV and V (19 patients) were treated with surgery (6 cases), embolization plus surgery(5 cases), but also other kind of treatments (embolization alone, radiosurgery and conservative) were used. Functional results in these groups of patients were36,8% (7 cases) with no symptoms or slights symptoms(modified Rankin 0-1), 52,6% (10 cases) minor disability(mRankin 2), 5,3% (1 case) moderate disability and 5,3% (1 case) mortality. We observe a high rate of postembolization hemorrhage in the group of patients in which the combination of preoperative embolization plus surgery was used. In these cases, early surgery was performed with a good functional recovery. There was one case of postoperative mortality. Conclusion. We should considerer some factors likethe natural history, clinical presentation (hemorrhage),angiographic features (deep arterial supply, aneurisms), Spetzler and Martin Grading and the clinical condition of the patient before treating a cerebral AVM. In the subgroup of treatment with embolization plus surgery, we recommend to achieve a subtotal preoperative embolization > 50%, not to obliterate more than50% in one session, to perform staged embolization waiting from 4 to 6 weeks between procedures, and from 1 to 3 weeks between the last embolization and surgery

Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.

Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3-4 years after surgery. The primary outcome measure was the change in the 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the 'off' medication UPDRS-III score at 3-4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4 years showed a significant worsening in the 'on' medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.

[Intraoperative neurophysiological monitoring of brain stem in a case of cavernoma in the pons]. / Monitorización neurofisiológica intraoperatoria del tronco del encéfalo en un caso de cavernoma en protuberancia.

Neurophysiological monitoring during surgery to avoid damaging of eloquent brain areas is a useful tool. We are performing intraoperative neurophysiological test to locate motor, sensitive and speech areas with cortical stimulation and cranial nerves during cerebellopontine cranial base surgery. Neurophysiological monitoring during brain stem surgery has been less described. Brain stem surgery implies a careful selection of patients for surgery given the high risk of morbidity and mortality. For this reason, conservative treatment is usually indicated when an asymptomatic cavernoma is incidentally found. Instead, when bleeding or neurological deficit appear, operative treatment may be indicated and then the goal of surgery is to avoid the disability linked to the natural history. We present the case of a 29 year old woman with diagnosis of multiple cavernomas. She was admitted at our hospital because she presented weakness and sensitive disturbance of left limbs and dizziness. The CT scan and MRI showed a pontine haemorrhage caused by a cavernous hemangioma. We operated her on using neurophysiological monitoring of VII, VIII, X and XII cranial nerves with electromyographic recordings. Postoperative disability could be reduced with a better knowledge of entry zone into the brain stem and early physiotherapy.

Monitorización neurofisiológica intraoperatoria del tronco del encéfalo en un caso de cavernoma en protuberancia / Intraoperative neurophysiological monitoring of brain stem in a case of cavernoma in the pons

La introducción del control neurofisiológico intraoperatorio ha conseguido minimizar el riesgo funcional quirúrgico en lesiones localizadas en áreas cerebrales funcionales. En la actualidad realizamos control neurofisiológico intraoperatorio para localizar el área motora o sensitiva y el área del lenguaje mediante estimulación cortical, así como de los pares craneales en cirugía del ángulo ponto cerebeloso. La monitorización neurofisiológica durante cirugía del tronco del encéfalo y fosa romboidea está menos instaurada. La cirugía del tronco del encéfalo implica una cuidadosa selección de los pacientes, dado el alto riesgo de morbilidad y mortalidad asociadas. Por esta razón, los cavernomas de esta región suelen ser tratados de manera conservadora cuando se trata de un hallazgo casual o no son sintomáticos. Sin embargo, la presencia de un sangrado o afectación neurológica inducen a tomar una decisión quirúrgica, dada la mala evolución natural. Presentamos el caso de una mujer de 29 años, diagnosticada de cavernomas múltiples, que ingresó por cuadro de debilidad motora y déficit sensitivo en hemicuerpo izquierdo. Se realizó TC craneal y RM que mostraba hemorragia protuberancial y se practicó una craniectomía infratentorial y resección de la lesión vascular por línea media, con control neurofisiológico intraoperatorio del VII, VIII, X y XII pares craneales con lectura electromiográfica. El control neurofisiológico ayudó a decidir el punto de acceso a la lesión que no afloraba a la superficie, minimizar las secuelas postoperatorias y pronosticar precozmente los déficits asociados con el fin de iniciar una rehabilitación precoz

Neurophysiological monitoring during surgery to avoid damaging of eloquent brain areas is a useful tool. We are performing intraoperative neurophysiological test to locate motor, sensitive and speech areas with cortical stimulation and cranial nerves during cerebellopontine cranial base surgery. Neurophysiological monitoring during brain stem surgery has been less described. Brain stem surgery implies a careful seleccion of patients for surgery given the high risk of morbidity and mortality. For this reason, conservative treatment is usually indicated when an asymptomatic cavernoma is incidentally found. Instead, when bleeding or neurological deficit appear, operative treatment may be indicated and then the goal of surgery is to avoid the disability linked to the natural history. We present the case of a 29 years old woman with diagnosis of multiple cavernomas. She was admitted at our hospital because she presented weakness and sensitive disturbance of left limbs and dizziness. The CT scan and MRI showed a pontine haemorrhage caused by a cavernous hemangioma. We operated her on using neurophysiological monitoring of VII, VIII, X and XII cranial nerves with electromyographic recordings. Postoperative disability could be reduced with a better knowledge of entry zone into the brain stem and early physiotherapy

Mania following deep brain stimulation for Parkinson's disease.

Three patients with PD developed manic behavior after bilateral implantation of electrodes for deep-brain stimulation (DBS). Common to all three patients were manic symptoms unremitting after levodopa reduction or stimulation "off," lower electrodes positioning caudal to the subthalamic nucleus area, postoperative DBS with the lower contacts (0) of the quadripolar electrodes, and resolution of the manic episodes coinciding with stimulation through higher contacts.