J. Garibi

Parkinson's disease‐like presentation of multiple system atrophy with poor response to STN stimulation: A clinicopathological case report

We report on a clinicopathological case of multiple system atrophy with good response to levodopa and subsequent development of motor complications. Because the subject complied with all the inclusion criteria (Core Assessment Program for Surgical Interventional Therapies in Parkinsons Disease), bilateral subthalamic nucleus deep brain stimulation electrodes were implanted.

Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas.

Gliomas are the most important group of malignant primary brain tumors and one of the most aggressive forms of cancer. During the last years, several studies have demonstrated that cannabinoids induce apoptosis of glioma cells and inhibit angiogenesis of gliomas in vivo. As the effects of cannabinoids rely on CB(1) and CB(2) receptors activation, the aim of the present study was to investigate both receptors protein expression in cellular membrane homogenates of human glial tumors using specific antibodies raised against these proteins. Additionally, we studied the functionality of the cannabinoid receptors in glioblastomas by using WIN 55,212-2 stimulated [(35)S]GTPgammaS binding. Western blot analysis showed that CB(1) receptor immunoreactivity was significantly lower in glioblastoma multiforme (-43%, n=10; p<0.05) than in normal post-mortem brain tissue (n=16). No significant differences were found for astrocytoma (n=6) and meningioma (n=8) samples. Conversely, CB(2) receptor immunoreactivity was significantly greater in membranes of glioblastoma multiforme (765%, n=9; p<0.05) and astrocytoma (471%, n=4; p<0.05) than in control brain tissue (n=10). Finally, the maximal stimulation of [(35)S]GTPgammaS binding by WIN 55,212-2 was significantly lower in glioblastomas (134+/-4%) than in control membranes (183+/-2%; p<0.05). The basal [(35)S]GTPgammaS binding and the EC(50) values were not significantly different between both groups. The present results demonstrate opposite changes in CB(1) and CB(2) receptor protein expression in human gliomas. These changes may be of interest for further research about the therapeutic effects of cannabinoids in glial tumors.

Surgical results and complications in a series of 71 consecutive cervical spondylotic corpectomies

BackgroundCervical corpectomy is a common procedure in spondylosis. It is normally a well-tolerated surgery and clinical improvement is widely described. However, it is associated with potential risky complications (subsidence, clinical deterioration, vertebral artery injury...); thus, a judicious surgical indication and a good technique are required.MethodsWe revised retrospectively the clinical evolution and complications of 71 spondylotic corpectomies in a series of 100 consecutive patients operated on due to different ethiological causes from January 2001 to September 2007 at our hospital.ResultsAmong the 71 cases, a single-level corpectomy was performed in 46 cases and a two level in 25. The graft we used was a titanium mesh filled with bone from the removed vertebra in 69 cases and a telescopic cage in two additional cases. We stabilized the construction with a locking plate. The presurgical clinical status of patients, according to the Nurick grading scale was as follows: 30 patients were grade 0, 12 were grade 1, eight were grade 2, 14 were grade 3, five were grade 4 and two were grade 5. After decompression, 41 patients were considered cured, three were grade 1, seven were grade 2, 11 were grade 3, seven were grade 4 and one was grade 5. One patient died in the postoperative period. Globally, 44 (62%) patients achieved good or excellent results (grades 0–1), 15 (21%) remained as previously (grade >1), six (8%) improved partially and five (7%) worsened. Forty (95%) grades 0 and 1 patients became cured, and four (50%), four (31%) and two (28%) grades 2, 3 and 4–5, respectively, experienced a postsurgical improvement. Significant complications occurred in 18 (25%) patients. The most significant were: hardware failure (n = 7), subsidence in five cases (one required intervention) and incorrect screw placement in two (one required intervention); permanent dysphagia (n = 4) and dysphonia (n = 1); postsurgical neurological worsening in three cases (two improved and one remained grade 4); vertebral artery injury in one case; and an urgent evacuation of a prevertebral hematoma. One patient died due to respiratory disturbances.ConclusionsCervical corpectomy is efficient for spinal cord decompression, especially when anterior components (disk osteophyte, OPLL...) bulge in the spinal cord. A three or more level corpectomy was not considered in this series since they may be associated to high rate morbidity. We found that this decompression led to better clinical results in patient grades 0 and 1 and to poorer results as myelopathy progressed. Among complications, subsidence was the most frequent specific one, but since it was rarely associated with symptoms, the majority of patients were successfully treated conservatively.

Electrophysiological characterization of substantia nigra dopaminergic neurons in partially lesioned rats: Effects of subthalamotomy and levodopa treatment

Progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta is the main histopathological characteristic of Parkinsons disease. We studied the electrophysiological characteristics of the spontaneous activity of substantia nigra pars compacta dopaminergic neurons in rats with a partial, unilateral, 6-hydroxydopamine lesion of the nigrostriatal pathway. In addition, the effects of subthalamotomy and prolonged levodopa treatment on the activity of dopaminergic neurons were investigated. As a result of the lesion ( approximately 50% neuronal loss), the number of spontaneously active neurons was significantly reduced. Basal firing rate, burst firing and responsiveness to intravenously administered apomorphine remained unchanged. In contrast, the variation coefficient, a measure of interspike interval regularity, was significantly increased. Ibotenic acid (10 microg) lesion of the ipsilateral subthalamic nucleus in lesioned rats did not modify the electrophysiological parameters. However, prolonged levodopa treatment (100 mg/kg/day + benserazide 25 mg/kg/day, 14 days) reversed the irregularity observed in cells from lesioned rats, while it induced an irregular firing pattern in cells from intact rats. Our results using an experimental model of moderate Parkinsons disease indicate that surviving substantia nigra pars compacta dopaminergic neurons fire irregularly. In this model, subthalamotomy does not modify the firing pattern while levodopa treatment efficiently restores normal firing of SNpc neurons and does not appear to be toxic to them.

A prospective study of a series of 356 patients with supratentorial spontaneous intracerebral haematomas treated in a Neurosurgical Department

SummaryBackground. Spontaneous supratentorial intracerebral haemorrhages (SSIH) carry high morbidity and mortality rates. At present, the proper role of surgery is not clear and data from the International STICH trial have not clarified this challenging question. On the other hand, few prospective studies have measured long term survival regardless of the treatment and clinical condition of the patient.Patients and methods. We prospectively collected data from all SSIH patients (n = 356) admitted at a tertiary reference hospital over a 40-month time period regardless of their clinical condition and treatment received. Among data investigated were preclinical neurological state, GCS on admission, history of systemic hypertension and treatment (surgical or conservative). Clinical factors influencing mortality at 1-year follow-up were analysed statistically by univariable and multivariable methods.Findings. We found that patients in the eighth decade were the most frequent. Hypertension was present in 47% of patients. Based on the prehospitalisation modified Rankin Scale, 305 (86%) patients were independent for activities of daily living (ADL). At 12-months follow-up, 91 (46% of alive patients) remained independent for ADL. The surgical rate was 22%. Although it was not a randomised study, we did not find a significantly different mortality rate according to whether the patient was treated surgically or conservatively. Overall, the mortality rate was 44% (157 patients) with a 79% of deaths taking place in the first 30 days after admission.Conclusions. This study underscores the high mortality rate of SSIH, especially so in the first month after admission. Among the subgroup of patients clinically independent before the haemorrhagic stroke, only 29.8% remained independent one year after the event. We did not find any statistically significant difference in mortality according to treatment modality received (surgical vs conservative) although treatment assignment was not randomised. Among other clinical factors, pre-ictal functional status, age, level of consciousness on admission and volume of haemorrhage strongly influence mortality as determined at the 1-year follow-up.

DNA Copy Number Variation and Gene Expression Analyses Reveal the Implication of Specific Oncogenes and Genes in GBM

To understand the pathogenesis of glioblastoma multiforme (GBM) we used high-resolution comparative genomic hybridization arrays and gene expression microarrays to identify DNA copy number alterations and gene expression changes in comparable sets of GBM samples. Gains were detected at chromosomes 1, 2, 7, 9, 12, 19, and 20 and losses at 6, 9, and 10. Gene expression analyses identified specific genes overexpressed in GBM mapping at amplified chromosomal regions. Among these genes we found genes involved in angiogenesis, extracellular matrix remodeling and several oncogenes. DNA copy number analysis along with gene expression profiles provides a powerful strategy to understand tumor progression and identification of genes involved in GBM pathogenesis.

Monoamine oxidase B activity is increased in human gliomas

Glial tumours are the most common type of brain neoplasm in humans. Tumour classification and grading represent key factors for patient management. However, current grading schemes are still limited by subjective histological criteria. In this context, gliosis has been linked to increases in monoamine oxidase B (MAO-B) activity. Thus, in the present study, MAO-B activity in membranes of glial tumours (n=20), meningiomas (n=12) and non-pathological human brains (n=15) was quantified by [14C]PEA oxidation. MAO-B activity was significantly greater in glioblastoma multiformes than in postmortem control brains (p<0.01) or meningiomas (p<0.001). There were no significant differences in MAO-B activity between glioblastoma multiformes (n=11) and low-grade astrocytomas (n=3) or anaplastic astrocytomas (n=6). In conclusion, the present results demonstrate a significant and selective increase in MAO-B activity in human gliomas when compared with meningiomas or non-tumoural tissue. These results suggest that the quantification of MAO-B activity may be a useful diagnostic tool for differentiating glial tumours from other types of brain tumours or surrounding normal brain tissue.

Outcome of bilateral deep brain subthalamic stimulation in patients carrying the R1441G mutation in the LRRK2 dardarin gene.

OBJECTIVEDeep brain subthalamic stimulation provides symptomatic relief to patients with Parkinsons disease. The present study analyzes the postoperative outcome of deep brain subthalamic stimulation in patients carrying the R1441G mutation in the leucine-rich repeat kinase-2 (LRRK2) (dardarin) gene. METHODSFive of the 48 patients treated in our unit carried a mutation in the LRRK2 (dardarin) gene. All five met the Core Assessment Program for Surgical Interventional Therapies criteria for inclusion in the surgical program. Pre- and postoperative assessment (6 mo) was made using the Unified Parkinson Disease Rating Scale II, Unified Parkinson Disease Rating Scale III, and Parkinsons Disease Questionnaire-39 scores, as well as the type and dosage of drugs used. RESULTSThe response to L-dopa after 6 months was similar to the baseline in all four patients. One suffered a stroke four months after surgery and is not eligible for evaluation. The improvements in motor response, daily life activities, and quality of life were limited (18, 22, and 33%, respectively) and were lower than those of the control group (39, 45, and 41%, respectively). DISCUSSIONCarriers of the R1441G mutation were clinically analogous to the rest of similarly operated patients with idiopathic Parkinsons disease. However, the response to deep brain subthalamic stimulation was worse among the former. The explanation for this negative result is unclear because all patients maintained an excellent response to L-dopa. Further larger studies are needed to confirm these findings.

Complicaciones intra-abdominales de la cirugía de la hernia discal lumbar

Resumen Introduccion La extirpacion de la hernia discal lumbar es actualmente el acto quirurgico mas habitual sobre el raquis en los servicios de Neurocirugia, con un numero de complicaciones muy escasas y unas estancias hospitalarias realmente cortas. Sin embargo, y a pesar de la rareza, es posible la aparicion de complicaciones intraoperatorias muy graves que son necesarias conocer puesto que un diagnostico y tratamiento precoces pueden evitar el fallecimiento del paciente. Es importante involucrar a este en el conocimiento de estas posibles complicaciones y obtener un consentimiento informado por escrito para evitar problemas medicolegales posteriores. Casos clinicos Presentamos dos casos de lumbociatica tipica secundaria a hernia discal lumbar intervenidos en el Servicio de Neurocirugia de Cruces que se complicaron con la perforacion intraoperatoria de estructuras intraabdominales. En ambos casos se realizo una flavectomia y extirpacion discal simple de forma habitual. La sintomatologia comenzo algunas horas despues de la cirugia con dolor abdominal e hipotension en uno y otro caso. El diagnostico precoz se realizo mediante TAC abdomino-pelvico. Posteriormente, y de forma urgente los Servicios de Cirugia General y Cirugia Vascular realizaron sendas laparotomias, posibilitando la reparacion de una perforacion intestinal en un paciente y de un desgarro de la arteria y vena iliacas en el otro, evitando asi fatales consecuencias. Actualmente ambos estan asintomaticos. Conclusion La cirugia de la hernia discal lumbar, en la gran mayoria de los casos muy agradecida en cuanto a la desaparicion del dolor, no esta exenta de complicaciones tan raras como graves. La perforacion intestinal y el desgarro vascular son dos ejemplos que hay que conocer y sospechar ante la aparicion de dolor abdominal o hipotension arterial sistemica en el postoperatorio, a pesar de que la extirpacion discal discurra sin incidencias. El diagnostico precoz mediante TAC abdomino-pelvico dirigira la actitud hacia un tratamiento quirurgico urgente de dichas lesiones. Es de maxima importancia que el paciente conozca la existencia de las posibles complicaciones de la cirugia de la hernia discal y obtener su consentimiento por escrito.

Compresión radicular lumbar secundaria a quistes yuxtafacetarios: revisión de 10 casos

Resumen Objetivo Se presenta una revision de la clinica, estudios radiologicos, y hallazgos operatorios e histologicos de 10 pacientes con 11 quistes yuxtafacetarios de la columna lumbar tratados en nuestro centro desde 1994 al 2000. Metodos Se han analizado las historias clinicas, imagenes radiologicas, protocolos quirurgicos e informes histopatologicos de los 10 pacientes diagnosticados de quiste yuxtafacetario lumbar (11). Resultados Seis pacientes eran mujeres y cuatro hombres. La edad media de presentacion fue de 54 anos. La clinica de mas frecuente presentacion fue la de dolor radicular, siendo poco comun el deficit motor o sensitivo. La tomografia computerizada y la resonancia magnetica son esenciales para establecer el diagnostico. Los quistes estaban localizados a nivel L4–L5 en ocho pacientes, a nivel L2–L3 en un paciente y L3–L4 en otro paciente. Ocho pacientes se trataron mediante laminec-tomia descompresiva y reseccion del quiste, y los dos restantes recibieron tratamiento conservador. Fenomenos degenerativos adyacentes a los quistes yuxtafacetarios son faciles de evidenciar. Todos los pacientes han presentado mejoria de su dolor radicular. Conclusiones Analizando nuestra casuistica, concluimos que los quistes yuxtafacetarios aparecen mas frecuentemente a nivel L4–L5, sobre todo en personas de edad avanzada, y producen habitualmente lumbalgia y radiculopatia. Aunque pueden tratarse de forma inicial-mente conservadora, ante un sindrome ciatico progresivo, es preferible optar por un tratamiento quirurgico.