Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial.

Amyotrophic Lateral Sclerosis (ALS) is a devastating incurable disease. Stem-cell-based therapies represent a new possible strategy for ALS clinical research. The objectives of this Phase 1 clinical study were to assess the feasibility and toxicity of mesenchymal stem cell transplantation and to test the impact of a cell therapy in ALS patients. The trial was approved and monitored by the National Institute of Health and by the Ethics Committees of all participating Institutions. Autologous MSCs were isolated from bone marrow, expanded in vitro and analyzed according to GMP conditions. Expanded MSCs were suspended in the autologous cerebrospinal fluid (CSF) and directly transplanted into the spinal cord at a high thoracic level with a surgical procedure. Ten ALS patients were enrolled and regularly monitored before and after transplantation by clinical, psychological, neuroradiological and neurophysiological assessments. There was no immediate or delayed transplant-related toxicity. Clinical, laboratory, and radiographic evaluations of the patients showed no serious transplant-related adverse events. Magnetic resonance images (MRI) showed no structural changes (including tumor formation) in either the brain or the spinal cord. However the lack of post mortem material prevents any definitive conclusion about the vitality of the MSCs after transplantation. In conclusion, this study confirms that MSC transplantation into the spinal cord of ALS patients is safe and that MSCs might have a clinical use for future ALS cell based clinical trials.

Evidence-based medicine and radiology: how to build a guideline. An attempt in minor head injury.

PURPOSE: To evaluate the use of Evidence-based Medicine (EBM) to build radiological Guidelines, with the aim to have a better compliance by users. It has been decided to work on minor head injury, where we have found, in our institution, a wide and unjustified use of conventional skull x-ray. MATERIAL AND METHODS: A Workgroup, that reunites the main figures that enter in the management of the patient with minor head injury, has been created within our Hospital. The bibliography relative to the problem has been selected, employing criteria that held account of the methodological correctness, and in particular the existing Guidelines have been carefully analysed. It is therefore proceeded drawing up a Guideline that adhered to the principles of the EBM, adapting it to the hospital environment. Subsequently it has been passed to the phase of its implementation, with reunions in small groups of the involved professional figures, the distribution of informative material and the use of poster that reassumed the diagnostic flow-chart. Moreover a survey of the relative data to the number of skull x-ray and brain TC, executed in the patients with head trauma, has been completed. RESULTS: The analysis of the data relative to the variation of the number of demands for skull Rx after introduction of the Guideline has demonstrated a great reduction (-83,8%), with little variation of the number of brain TC (+17,0%); such reduction has naturally implicated an important reduction of costs (-25,2%) and of the x-ray dose to population, measured to the crystalline (34,5%) and to thyroid (-71,0%). CONCLUSIONS: The employ of the EBM in the Guideline creation, beyond representing the more correct methodology, concurs to obtain a greater adhesion from the users involved in management of the patient; in particular this happens if the Guideline is a product of a vast contribution and if it is supported from all additional procedures that can be useful for its implementation.

De novo cavernoma case report and review of literature.

BACKGROUND: De novo cavernoma, reported with the familial form of disease, is rare in cases with a negative family history. Cranial radiation, coexistent vascular malformation, genetic and hormonal factors, previous surgery for intracranial lesions, or other apparently unrelated intracranial lesions have been reported as risk factors. METHODS: We report a case of de novo cavernoma without a family history and without previous irradiation or any other known risk factors. The genesis of this lesion is discussed. RESULTS: To our knowledge, this is the first case, based on two separate magnetic resonance imaging (MRI) studies, demonstrating evidence of de novo cavernous malformations in the absence of familial history, brain radiation therapy, or other apparently unrelated intracranial tissue lesions. Based on previous negative computed tomography scans, other cases have been presented as de novo cavernous angiomas; thus it is possible that the newly discovered cavernoma existed previously but had been missed on previous poorer quality or lower resolution imaging studies. CONCLUSIONS: Cavernoma can arise even without an associat family history; in our case, a previous head injury could have set off either a genetic cascade with attendant endothelial proliferation or a latent virus.

[Cranioplasty with polymethylmethacrylate. The clinico-statistical considerations]. / Cranioplastica con polimetilmetacrilato. Considerazioni clinico-statistiche.

BACKGROUND: The main purpose of the reconstruction of the cranium is the protection of the brain. Besides we have to consider important functional and aesthetic necessities in order to achieve satisfactory results. METHODS: Thirty-six clinical cases, operated from November 1991 to June 1996, in which the reconstruction of the cranial vault is carried out by a polymethylmethacrylate acrylic resin are analysed. The causes and locations of the most common bone defects and the main indications for reconstruction are examined. While the repair of the osseous gaps caused by neoplasms is immediate, in the traumatic occurrences, in order to reduce the probability of infectious complications, an average time of 11 months elapsed from the first operation. The surgical technique, with slightest alterations, is the same in all the presented cases, preparing the acrylic resin straight on the operating table. The resin, moulded and adapted to the defect until its complete hardening, presents, thanks to its properties, manifold advantages (and few real disadvantages). RESULTS: The results, in terms of complications, are very satisfactory, with an infectious rate of 2.7%. Besides, in one third of the patients, a considerable clinical improvement after the repair has been observed. CONCLUSIONS: According to personal experience, it is possible to affirm that polymethylmethacrylate, with its remarkable plasticity and stability in time, can always guarantee a satisfactory functional and aesthetic result.

[Postoperative neurosurgical complications in brain tumors operated in the elderly]. / Complicazioni post-operatorie neurochirurgiche in tumori cerebrali operati in età geriatrica.

200 patients of geriatric age, operated on for cerebral neoplasm, have been studied in order to estimate the most important factors influencing the post-operative course. We have considered the "Volume of the tumour", the "Pre-operative and at-discharge Karnofsky Score", the possible "Pre-existent pathologies" and the checked "Post-operative complications". As a conclusion we have considered relevant over the final outcome the following factors: a) the presence of general pre-existent pathologies, first of all diabetes and hypertension; b) the volume, more than the site and nature, of the neoplasm subject of the operation; c) the nature and the importance of local post-operative complications.

[Statistical comparison of surgical results with or without laser in neurosurgery]. / Comparaison statistique des résultats chirurgicaux avec et sans laser en neurochirurgie.

In the literature, no significant statistical studies have been published on the effectiveness of laser compared with traditional procedures in neurosurgery; we have decided to study a series of 198 gliomas and 220 meningiomas operated upon either with a laser or with conventional techniques. We considered the post-operative morbidity, the duration and the quality of survival. These data have been clearly influenced by the type of surgery. On the contrary, no significative difference was observed concerning the survival rate of gliomas whatever their grading. In the laser-group, morbidity and quality of life are improved (36 months follow-up); but the mortality rate (3 years) is equal in both groups. Concerning meningiomas, patients of both groups (with and without laser) were clinically improved during the post-operative period. A significative difference appears only for meningiomas located in functional areas and operated with a laser.