Acute and chronic MRI changes in the spine and spinal cord after surgical stem cell grafting in patients with definite amyotrophic lateral sclerosis: post-infusion injuries are unrelated with clinical impairment.

OBJECTIVE: To report MRI spinal changes after surgical infusion of bone marrow stem cells (BMSc) in ALS patients and assess their correlation with clinical events and functional performance. METHODS: BMSc were surgically injected in the thoracic spinal cord of 11 ALS patients (6/5 male/female; median age 46years). We performed first-week and third, sixth, ninth and twelfth post-surgical months spinal MRIs. The spinal changes in the postsurgical week and follow-up MRIs, as well as clinical events, functional scales and respiratory and electromyography data, were longitudinally monitored. Correlations between the imaging and clinical data were evaluated with the Spearman's test. RESULTS: Transient extradural fluid collections (100%), transient spinal cord T2 hyperintensity (81.8%), and chronic spinal cord deformities (63.6%) were the dominating MRI changes. Spinal cord hemorrhages (27.3%) and cystic myelomalacia (1/11 patients) were important although unusual findings. During the follow-up, minor adverse events of mild to moderate intensity eventually improved. Initial and follow-up imaging scores showed a strongly positive correlation (r 0.879, P<0.001). The initial and delayed clinical scores did not correlate. There was no significant correlation between any of the imaging scores and clinical data. CONCLUSIONS: Infusion of BMSc produces a variety of spinal changes apparently unrelated with clinical events and disease worsening.

Wind instruments and headaches.

The authors illustrate the cases of two children with headaches, one diagnosed with Chiari type 1 malformation and the other with hydrocephalus, who played wind instruments. Both patients manifested that their headaches worsened with the efforts made during playing their musical instruments. We briefly comment on the probable role played by this activity on the patients' intracranial pressure and hypothesize that the headaches might be influenced by increases in their intracranial pressure related to Valsalva maneuvers. We had serious doubts on if we should advise our young patients about giving up playing their music instruments.

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.

Portraying disease: Sorolla's Sad Legacy.

In 1899, the Spanish painter Joaquín Sorolla represented, in a large canvas, a group of children probably with sequels of poliomyelitis bathing at Valencia's beach. The title of this painting was Sad Legacy. This work contributed to the international diffusion of Sorolla's artistic creation. We briefly report some facts regarding the painter and his work referring to those portraits of children and especially of sick children.

Hydrocephalus and arachnoid cysts.

AIM: The management of arachnoid cysts (AC) remains controversial. An additional problem derives from the management of hydrocephalus associated with an AC. In this work, we discuss existing procedures proposed in the current literature for their treatment. METHODS: We reviewed selected reports on intracranial ACs placing special interest in those about the association of hydrocephalus and ACs. We also briefly surveyed data of our patients with this association. RESULTS AND DISCUSSION: Hydrocephalus is often found in midline and posterior fossa ACs. Interhemispheric lesions may also evolve with ventriculomegaly, while middle fossa lesions rarely produce hydrocephalus. Patients' age, cyst location and size, and macrocephaly have all been related to the development of hydrocephalus. Some authors remark on the role played by hydrocephalus and hypothesize that some ACs would result from disturbed cerebrospinal fluid (CSF) dynamics. They also propose that ACs might represent a localized form of hydrocephalus. We also comment on hydrocephalus in relation to the diverse locations of ACs. Neuroendoscopic techniques have transformed previous ways of management as cystoperitoneal shunting and open fenestration. CONCLUSIONS: ACs may be pathogenetically related with hydrocephalus, and conversely, ACs may cause hydrocephalus. In some patients, aberrant CSF dynamics seems to play a major role in the development of both cyst and hydrocephalus. Hydrocephalus and ACs may be treated exclusively with neuroendoscopic procedures, although some patients will still require CSF shunting. The ideal option seems to consist of choosing the method that offers the highest success with a single procedure for treating the hydrocephalus and the AC simultaneously.

A surgical technique of spinal cord cell transplantation in amyotrophic lateral sclerosis.

We report an original method for implanting bone marrow stem cells within the spinal cord parenchyma. This method was used for the experimental treatment of patients diagnosed with amyotrophic lateral sclerosis. The methodology is reproducible and devoid of major complications even in patients showing significant spinal atrophy. Therefore, this report describes a surgical procedure that could be used in other experimental treatments involving the intraspinal delivery of stem cells.

The earliest evidence of true lambdoid craniosynostosis: the case of "Benjamina", a Homo heidelbergensis child.

BACKGROUND: The authors report the morphological and neuroimaging findings of an immature human fossil (Cranium 14) diagnosed with left lambdoid synostosis. DISCUSSION: The skull was recovered at the Sima de los Huesos site in Atapuerca (Burgos, Spain). Since the human fossil remains from this site have been dated to a minimum age of 530,000 years, this skull represents the earliest evidence of craniosynostosis occurring in a hominid. A brief historical review of craniosynostosis and cranial deformation is provided.

[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