Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: a pilot safety study.

The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity.

Microporous Polysaccharide Hemospheres (MPH) for cerebral hemostasis: a preliminary report.

OBJECTIVE: To report preliminary experience in using Microporous Polysaccharide Hemospheres (MPH; Medafor, Inc, Minneapolis, Minnesota, USA) for cerebral and dural sinus hemostasis. METHODS: Absorbable hemospheres for hemostasis were used in 10 patients (6 men, 4 women, mean age 56.2 years) undergoing cerebral procedures. The indication was corticosubcortical cerebral hemostasis after resection of meningiomas (n = 5) and gliomas (n = 5). In one case, absorbable hemospheres were applied for generalized oozing over the superior sagittal sinus. The surgical technique, time to bleeding control, and associated complications were recorded. RESULTS: Effective hemostasis, defined as cessation of oozing bleeding, was achieved no later than 2 minutes after topical agent application in all patients except two, in whom the hemostatic application was repeated. Mean follow-up was 12 months. No patient developed allergic reactions or systemic complications in association with hemostatic absorbable hemospheres. There was no case of cerebral hematoma, swelling, or infection after surgery. CONCLUSIONS: In this preliminary study, the direct application of absorbable hemospheres helped to control superficial cerebral bleeding, reducing the use of bipolar coagulation and shortening surgical time. Although use of absorbable hemospheres seems to be safe and effective, further investigations and prospective studies with longer follow-up are strongly recommended to arrive at final conclusions.

Case control study of periconceptional folic acid intake and nervous system tumors in children.

PURPOSE: Since 1992, the Centers for Disease Control and Prevention recommends that women of childbearing age consume 400 µg of folic acid per day to reduce the risk of neural tube defects (NTD). It has been speculated that both NTD and nervous system tumors (NST) may share common mechanisms of altered development. It examines the association between folic acid supplementation and the risk for childhood NST. METHODS: Incident cases of children with cancer in Spain registered between 2004 and 2006 were identified through the MACAPE Network Group. Tumors were classified as tumors derived from the neuroectoderm (cases) and those with a mesoderm origin (controls). In a second analysis, NST were further divided into central nervous system tumors (CNST) and sympathetic nervous system tumors (SNST). We compared folic acid supplementation between the groups. RESULTS: Overall, folic acid supplementation any time during pregnancy was similar between cases and controls (odds ratio (OR)=1.05; 95% confidence interval (CI) 0.92-1.20). However, supplementation before the 21st and 36th days of gestation resulted in significantly lower NST than in children with mesoderm tumors (OR=0.34; 95% CI 0.17-0.69 and OR=0.58; 95% CI 0.37-0.91, respectively). Preconceptional intakes of folic acid were also lower in NST although marginally nonsignificant (OR=0.44; 95% CI 0.10-1.02). When NST were divided into CNST and SNST, significant differences between tumors of mesoderm origin were only found for CNST. CONCLUSIONS: Our results support the hypothesis that folate supplementation reduces the risk of childhood NST, especially CNST. The specific mechanism and cellular role that folate may play in the development of CNST have yet to be elucidated.

[Brain abscess. The experience of 30 years]. / Abscesos cerebrales. Experiencia de 30 años.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate epidemiological and clinical aspects of brain abscess (BA) and changes in clinical patterns during the last 30 years. PATIENTS AND METHOD: Observational study of a cohort of non-pediatric patients with BA admitted at a 944-bed hospital. Data collection from clinical records was done according to a standard protocol. We analysed epidemiological, clinical and microbiological data and localization as well as changes during a 30 year period divided in 2 equal length phases: 1976-1989 (P1), and 1990-2005 (P2). RESULTS: 108 patients with BA were included (mean age: 45 years; range: 12-86; > 40 years in 42.4% P1, and 71.4% in P2, p < 0.05); 66 patients were treated in P1 and 42 in P2 (annual incidence: 4-5 cases and 2-3 cases per 10(6) population in P1 and P2, respectively). A predisposing condition was identified in 86% cases with statistically significant differences (p < 0.05) in: otitis media (18.2% vs 2.4%); dental infection (3% vs 16.7%); penetrating cranial trauma (16.7% vs 0%); post-neurosurgery (15.1% vs 21.4%), in P1 and P2, respectively; microbiologic diagnosis was made in 76% (no statistical differences P1/P2). Clinical aspects statistically different in P1/P2: severely altered mental status (10.6% vs 0%); vomiting (37.9% vs 21.4%); focal neurological deficits (37.9% vs 71.4%). No statistically significant differences were found in other epidemiological, clinical, radiological, microbiological or outcome characteristics in P1/P2. CONCLUSIONS: In spite of a lower incidence in P2 and certain epidemiological and clinical differences in P1/P2, mortality and relapses rates have not significantly changed in a 30 year period.

Abscesos cerebrales. Experiencia de 30 años / Brain abscess. The experience of 30 years

Fundamento y objetivo: Se ha realizado un estudio de las características epidemiológicas y clínicas de los pacientes con absceso cerebral (AC), y de los cambios que han tenido en los últimos 30 años. Pacientes y método: Estudio observacional de una cohorte de pacientes adultos con AC ingresados en un hospital de 944 camas. Los pacientes se evaluaron según protocolo de estudio. Analizamos las características epidemiológicas, clínicas y microbiológicas de los pacientes con AC, la localización y evolución de los AC, en un período de 30 años dividido en 2 mitades: 1976-1989 (P1) y 1990-2005 (P2). Resultados: Se valoró a 108 pacientes con AC (66 en P1 y 42 en P2), con una edad media de 45 años (extremos: 12-86). Tenían más de 40 años de edad el 42,4% de los pacientes en P1 y el 71,4% en P2 (p < 0,05). La incidencia anual fue de 4-5 y 2-3 casos por 106 habitantes/año en P1 y P2, respectivamente. El origen primario del AC se identificó en un 86% de los casos, con diferencias estadísticamente significativas entre ambos períodos en el foco (otitis media: el 18,2 frente al 2,4%; infección dental: el 3 frente al 16,7%; traumatismo craneoencefálico: el 16,7 frente al 0%; tras neurocirugía: el 15,1 frente al 21,4%, en P1 y P2, respectivamente). Hubo confirmación microbiológica en un 76% (sin diferencias significativas entre P1 y P2). En cuanto a las características clínicas, hubo diferencias significativas entre P1 y P2 en la alteración del nivel de conciencia (el 10,6 frente al 0%), vómitos (el 37,9 frente al 21,4%) y déficits neurológicos focales (el 37,9 frente al 71,4%). No hubo diferencias en otras variables epidemiológicas, clínicas, radiológicas, microbiológicas o en el pronóstico (mortalidad) de los pacientes entre P1 y P2. Conclusiones: A pesar de la menor incidencia de AC en P2 y de ciertas diferencias epidemiológicas y clínicas entre ambos períodos, la mortalidad y el porcentaje de recidivas en pacientes con AC no ha cambiado significativamente en los últimos 30 años

Background and objective: The aim of this study was to evaluate epidemiological and clinical aspects of brain abscess (BA) and changes in clinical patterns during the last 30 years. Patients and method: Observational study of a cohort of non-pediatric patients with BA admitted at a 944-bed hospital. Data collection from clinical records was done according to a standard protocol. We analysed epidemiological, clinical and microbiological data and localization as well as changes during a 30 year period divided in 2 equal length phases: 1976-1989 (P1), and 1990-2005 (P2). Results: 108 patients with BA were included (mean age: 45 years; range: 12-86; > 40 years in 42.4% P1, and 71.4% in P2, p < 0.05); 66 patients were treated in P1 and 42 in P2 (annual incidence: 4-5 cases and 2-3 cases per 106 population in P1 and P2, respectively). A predisposing condition was identified in 86% cases with statistically significant differences (p < 0.05) in: otitis media (18.2% vs 2.4%); dental infection (3% vs 16.7%); penetrating cranial trauma (16.7% vs 0%); post-neurosurgery (15.1% vs 21.4%), in P1 and P2, respectively; microbiologic diagnosis was made in 76% (no statistical differences P1/P2). Clinical aspects statistically different in P1/P2: severely altered mental status (10.6% vs 0%); vomiting (37.9% vs 21.4%); focal neurological deficits (37.9% vs 71.4%). No statistically significant differences were found in other epidemiological, clinical, radiological, microbiological or outcome characteristics in P1/P2. Conclusions: In spite of a lower incidence in P2 and certain epidemiological and clinical differences in P1/P2, mortality and relapses rates have not significantly changed in a 30 year period