Outcome and tolerability of topiramate in brain tumor associated epilepsy.

Epilepsy in brain tumor patients is often refractory to pharmacological treatments and can complicate the therapeutic management of these patients. We conducted a prospective, observational study. The aim of this study was to investigate the efficacy and tolerability of topiramate (TPM) in brain tumor associated epilepsy. We studied 47 patients with brain tumors and epilepsy. The entire group was administered AEDs. TPM was the first therapeutic choice in 14 patients, while in the remaining 33 patients previous AEDs were modified and TPM was introduced due to side effects or inefficacy of the first drug. Follow-up ranged from 3 to 48 months (mean 16.5 months). Considering the final follow-up of each patient who assumed TPM for at least 3 months, we observed 45 patients: 25 were seizure free (55.6%), 9 had a reduction of seizure frequency (SF) higher than 50% (20%) and 11 were stable (24.4%). TPM responder rate was 75.6%. Three patients (6.4%) discontinued TPM for severe side effects (1 after 4 months and 2 after 1 month) and 4 (8.5%) had mild and reversible side effects. In the group of patients who had been in therapy with other AEDs prior to entering the study (n = 33), 19 patients had side effects (57.6%). During follow-up, the haematological parameters were in the normative ranges. Tumor-related seizures are difficult to control with AEDs; the precise reasons for this difficulty are not yet clear. Using TPM, we obtained good seizure control with a low incidence of side effects.

Early post-operative MRI: correlation with progression-free survival and overall survival time in malignant gliomas.

Forty-seven patients with Glioblastoma (42) and Anaplastic Astrocytoma (5) were studied with MR 24 hrs after surgery. In order to evaluate the role of early MR in defining the extent of surgical resection and its relation with the prognosis of malignant glioma patients, three categories of surgical resection were considered: gross total, sub-total and partial resection. The results were correlated with progression-free survival (PFS) and overall survival (ST). As demonstrated by early-MR, gross total resection was performed in 17 patients, sub-total and partial resection in 19 and 11 patients, respectively. The PFS was 6 months in gross total resection, 6 and 3 months in sub-total and in partial resection, respectively. The median survival time was 16 months in total resection patients, 13 months and 7 months in sub-total resection and partial resection patients, respectively. The study confirms that early-MR has to be considered an accurate technique for monitoring the extension of malignant glioma surgical resection and shows a good correlation between early-MR findings, PFS and ST.

[Musculoskeletal conditions of the upper and lower limbs as an occupational disease: what kind and under what conditions. Consensus document of a national working-group. ISPESL]. / Le affezioni muscolo-scheletriche degli arti superiori e inferiori come patologie professionali: quali e a quali condizioni. Documento di Consenso di un gruppo di lavoro nazionale. ISPESL.

BACKGROUND AND OBJECTIVES: In via of the progressive emergence in Italy of work-related musculoskeletal disorders, the EPM Research Unit decided to set up a national working group with the aim of producing a Consensus Document including methods and criteria as an initial attempt towards managing such diseases as true "listed" work-related diseases as is already done in the other European Union countries. The working group includes experts from INAIL, ISPESL, welfare assistance institutions, local prevention and health protection services: The group's research activity was included in ISPESL's funded research plan. CONTENTS: The Consensus Document includes a review of epidemiologic issues reported in the international literature, comments on the application of current legislation, observations on the guilt profiles of employers and occupational physicians, as well as medical-legal issues. The document proposes an analytical list of musculoskeletal disorders of upper (and lower) limbs and the operational criteria for identification of working activities involving a risk from upper limb biomechanical overload. In this case, more than on other occasions, it was realized how difficult it is to adopt consolidated task/risk/damage matrices since the same task may or may not be at risk depending both on the way the task is done and on the technical aspects (lines, work parts, procedures, tools) and organization (rate, rotas, breaks). CONCLUSIONS: For the specific aims of the present document, it is possible to identify, though not exhaustively and with some limitations, a series of jobs and working conditions where the risk may be reasonably presumed and for which it is possible to adopt a list system (at least as regards "significant exposure"). The document also includes a chapter on health surveillance recommendations for the occupational physician.

Exposure assessment of upper limb repetitive movements: a consensus document developed by the Technical Committee on Musculoskeletal Disorders of International Ergonomics Association (IEA) endorsed by International Commission on Occupational Health (ICOH).

This consensus document intends to supply a set of definitions, criteria and procedures useful to describe and, wherever possible, to assess the work conditions that can represent a physical overload for the upper limbs. The document is aimed at all the operators, i.e. occupational doctors but mainly technicians, who are, involved in risk exposure assessment and management. The document intends to provide methods and procedures easily applicable in the field, possibly not requiring sophisticated instrumentation and when possible based on observation procedures. The proposed methods shall be based as far as possible on knowledge and data from scientific literature: should they be contradictory or deficient, reference will be made to standards or pre-standards issued by national and international agencies and bodies, with the experience of researchers involved and common sense. In this regard, it is to be emphasized that the potential users increasingly demand an easily applicable method for description and assessment of work with repetitive movements. The group intends to give a response even if there are still uncertainties from a strictly scientific standpoint: however the group commits itself to perform subsequent validations especially of as yet unconsolidated issues. This document focuses specifically on identification of risk factors and describes some of the methods that have been developed for evaluating them. There is a rapidly developing body of literature on job analysis and not yet agreement on a single best way to analyze jobs. Professional judgement is required to select the appropriate methods. Analysis and design of jobs should to be integrated into an ongoing ergonomics program that includes management commitment, training, health surveillance, and medical case management. In summing up this report, space must be given to the check lists that are so often seen in the medical press, although this is not the occasion to propose a detailed analytical review.

Investigation of genetic alterations associated with development and adverse outcome in patients with astrocytic tumor.

Models describing progression in the genetic derangement of glial tumors have shown chromosomal loss and gain occurring most frequently in high-grade lesions, suggesting that identification of these aberrations may be prognostically significant. In this study, Fluorescence in situ hybridization (FISH) has been used to determine, and to confirm, loss and gain of chromosomes 1, 8, 10, 12 and 17, in formalin-fixed, paraffin-embedded brain biopsy tissue taken from 60 brain gliomas submitted to surgical resection or stereotactic biopsy. FISH analysis may be a valuable adjunct to histological grading. The results showed that this molecular cytogenetic technique is an important clinical and experimental tool that provides new insight on genetic alterations, confirming gain and loss of genetic material that occurs at the initiation and progression of human glioma. Our data suggests that potentially useful prognostic information may be obtained through this approach. Monosomy 10 was the most statistically significant negative predictor of patient survival, showing a significant correlation with the histological grading.

[Proposal and preliminary validation of a check-list for the assessment of occupational exposure to repetitive movements of the upper lims]. / Proposta e validazione preliminare di una check-list per la stima dell'esposizione lavorativa a movimenti e sforzi ripetuti degli arti superiori.

Over the last few years the Authors developed and implemented, a specific check-list for a "rapid" assessment of occupational exposure to repetitive movements and exertion of the upper limbs, after verifying the lack of such a tool which also had to be coherent with the latest data in the specialized literature. The check-list model and the relevant application procedures are presented and discussed. The check-list was applied by trained factory technicians in 46 different working tasks where the OCRA method previously proposed by the Authors was also applied by independent observers. Since 46 pairs of observation data were available (OCRA index and check-list score) it was possible to verify, via parametric and nonparametric statistical tests, the level of association between the two variables and to find the best simple regression function (exponential in this case) of the OCRA index from the check-list score. By means of this function, which was highly significant (R2 = 0.98, p < 0.0000), the values of the check-list score which better corresponded to the critical values (for exposure assessment) of the OCRA index looked for. The following correspondance values between OCRA Index and check-list were then established with a view to classifying exposure levels. The check-list "critical" scores were established considering the need for obtaining, in borderline cases, a potential effect of overestimation of the exposure level. On the basis of practical application experience and the preliminary validation results, recommendations are made and the caution needed in the use of the check-list is suggested.

Cranioplasty performed with a new osteoconductive osteoinducing hydroxyapatite-derived material.

OBJECT: Cranioplasty is required to protect underlying brain, correct major aesthetic deformities, or both. The ideal material for this purpose is autogenous bone. When this is not available, alloplastic or artificial materials may be used. These materials should be malleable, strong, lightweight, inert, noncarcinogenic, nonferromagnetic, and, if possible, inexpensive. The authors reviewed their surgical experience with a new bone substitute and discuss outcomes in patients in whom it was used. METHODS: The 11 patients presented in this series had bone defects resulting from bone-involving tumor (eight cases), trauma (two cases), or aesthetic deformity due to repeated craniotomies (one case). The defects were repaired using Osprogel, a bone substitute that consists of calcium hydroxyapatite combined with synthetic, human bone-derived gelatin, glycerol, and water. Osprogel is not only a bioinert material but also an osteoconductive and osteoinducing substrate; when it is placed in contact with healthy cancellous bone, it induces osteogenesis and angiogenesis, thus permitting the regrowth of nearly normal bone. The sheet of Osprogel was modeled onto the cranial defect intraoperatively and was kept in place either by using a titanium micronet secured to surrounding bone with microscrews (first two cases) or by using a single- or double-layer titanium mesh secured with stitches. No complications due to the procedure were observed. The results, evaluated at least 6 months after surgery by using three-dimensional (3-D) reconstructed computerized tomography scans, were excellent in seven patients, good in three, and fair in one. In the patient with a fair result, the repair was unsatisfactory because there was lack of experience in using the material. In part of the area to be repaired, the Osprogel was used as filler; here it was washed out and resorbed. The cases deemed as having a good result had good bone replacement; however, the curvature was faulty. CONCLUSIONS: In the near future, this technique may be refined to achieve good or excellent results either without the use of supporting material or with the use of individual, computer-designed 3-D prostheses.

Epilepsy and gliomas: incidence and treatment in 119 patients.

One hundred and nineteen consecutive patients affected by supratentorial gliomas were studied in order to determine the incidence of seizure at diagnosis, the occurrence of subsequent seizures and the efficacy of anticonvulsant treatment. The overall incidence of seizures as presentation symptom was 52% (62 patients). Preoperative seizures were present in 83% of patients affected by low-grade astrocytoma, in 46% of patients affected by anaplastic astrocytoma and in 36% of patients affected by glioblastoma. Postoperative epilepsy refractory to anticonvulsant treatment significantly related to low-grade histology and presence of preoperative seizures occurred in 48% of patients. Adverse effects associated with anticonvulsants were observed in 33.8% of patients treated with phenobarbital, 14.3% in the group treated with carbamazepine and 12% of patients treated with vigabatrin. We conclude that anticonvulsant treatment in patients affected by gliomas is often ineffective and prophylactic treatment should be discontinued after 6 months in patients preoperative seizures free. In patients with high risk of seizures antiepileptic drugs with good efficacy and lower incidence of adverse effects than phenobarbital are indicated.

[Musculoskeletal disorders of upper extremities caused by biomechanical overload: methods and criteria for the description of occupational exposure]. / Alterazioni muscolo-scheletriche degli arti superiori da sovraccarico biomeccanico: metodi e criteri per l'inquadramento dell'esposizione lavorativa.

This article presents and discusses a model for describing and evaluating the principal risk factors characterising occupational exposure: frequency and repetitiveness of movements, use of force, type of posture and movements, distribution of recovery periods, presence of other influential (complementary) factors. For each risk factor, the authors propose a method of practical detection in the field, as well as criteria for classifying and interpreting the results based on a critical review of the available literature on the subject. Numerous examples are supplied to better illustrate the concepts presented. The various factors considered are classified using numbers or indexes, so that they can be integrated into a concise exposure index described by the authors elsewhere in this volume.

Clinical relevance of 111In-octreotide scans in CNS tumors.

Sixty-six patients with a clinical and neuroradiological diagnosis of CNS tumors were evaluated by 111In-octreotide scintigraphy. Planar images were acquired at 2-4 and 24 hours after the injection of 111-185 MBq of 111In-octreotide (Octreoscan, Byk-Gulden). In the positive scans the tumor/non-tumor ratio was evaluated using a standard ROI method, and an uptake index (U.I.) of the lesion was determined. In vitro binding assays were performed on frozen sections from surgical specimens from 17 patients. All 32 meningiomas demonstrated a positive 111In-octreotide scan with a high U.I. Only 13 of 21 gliomas showed a positive scan, but the U.I. was significantly lower (p < 0.001 by "t"-test); one lymphoma showed a faint tracer uptake. All the other histotypes evaluated yielded negative scans. In all cases the receptorial pattern shown by the immunohistochemical staining technique was concordant with the scintigraphic results. 111In-octreotide scintigraphy allowed a differential diagnosis of meningioma versus other CNS tumors in 6 patients (4 neurinomas, 1 brain metastasis of melanoma, 1 lymphoma). In conclusion, 111In-octreotide scintigraphy is a promising tool to evaluate the SS receptorial pattern of CNS tumors and to increase the diagnostic specificity of conventional imaging providing useful information in selected cases for the therapeutic strategy.

Somatostatin receptor imaging in CNS tumours using 111In-octreotide.

This study evaluates the in vivo visualization of somatostatin (SS) receptors in central nervous system (CNS) tumours using 111In-octreotide imaging and discusses the clinical implications. Ninety-five patients with histologically confirmed diagnosis of CNS tumours were imaged 2-4 and 24 h after the intravenous injection of 111-185 MBq of 111In-octreotide. An uptake index was computed using tumour/non-tumour ratios evaluated using a standard region-of-interest method. Semi-quantitative immunohistochemical studies of SS binding sites were performed on frozen tumour sections. All meningiomas, most pituitary adenomas and many glial tumours showed a positive scan, whereas all neurinomas, craniopharingiomas and ependymomas had negative receptor scans. Radio-octreotide uptake varied among the SS receptor positive CNS tumours: very intense in meningioma, intermediate in pituitary adenoma and of a low grade in glioma. The results of immunohistochemical studies confirmed the scintigraphic findings in all cases. We believe 111In-octreotide is a suitable radiopharmaceutical for characterizing CNS tumours in vivo as SS receptor positive or negative. This new neuronuclear imaging technique may be useful for differential diagnosis in selected cases, for post-surgical follow-up and in the assessment of differentiation in glial tumours.

[Epidemics of musculotendinous pathologies of the upper limbs (cumulative trauma disorders) in a group of assembly line workers]. / Epidemia di patologie muscolo tendinee degli arti superiori (CTD) in un gruppo di addetti al montaggio di passeggini.

The study was prompted by a report concerning a group of assembly line workers in a factory producing prams who had developed various muscular and tendinous disorders of the upper limbs that can be classified under the larger category of Cumulative Trauma Disorders (CTD). The study first concentrated on the working conditions with analysis of the main factors responsible for overloading of the upper limbs during work. This analysis revealed high frequency and repetitiveness of upper limb movements together with a marked inadequacy of the length and distribution of pauses. In a significant part of the operations the workers also performed movements in positions that over loaded the wrist and hand. A parallel clinical and instrumental study carried out in collaboration with specialists in orthopedics, brain surgery and neurophysiology on all 40 workers in the shop showed that 90% of the subjects suffered from a form of CTD of the upper limbs: in particular, 40% were affected with carpal tunnel syndrome (12.5% bilateral), and there were high prevalence of tenosynovitis (32% Trigger Finger, 17% De Quervain's syndrome) and epicondylitis (20% medial or lateral). The results of the study once again emphasize the need for greater attention of occupational health practitioners in Italy for muscular and tendinous disorders of the upper limbs due to repeated strain, which Italian law defines, albeit controversially, as occupational.

[Back pain in health care workers]. / Il mal di schiena nel personale sanitario.

Back pain is a major health and economic problem for preventive medicine. It has been found to be significantly associated with nursing. The present paper reviews a number of epidemiological studies on back pain in nurses and examines the main confounding factors. The different approaches to back pain prevention are briefly discussed.

The transdural extension of gliomas.

The extraneural spreading of gliomas is an infrequent occurrence which is not necessarily related to either tumor histology or site. This paper reports two cases, a glioblastoma and an oligodendroglioma, both presenting extradural diffusion. In the first case, where there was severe intracranial hypertension, the tumor found its way out from the neurocranium, far from the site of the operation, perforating the dura and the bone of the cranial base. In the second case, the operation may have facilitated the extraneural invasion. This unusual behaviour of glial tumors is probably less rare than presumed. It may go unnoticed if the attention is concentrated on the usually severe neurological syndrome which is present in these patients.

[Degenerative changes in the coxofemoral articulation due to occupational causes. I. Radiological description of a control population]. / Alterazioni degenerative a carico dell'articolazione coxofemorale da cause professionali: I--descrizione radiologica di una popolazione di controllo.

With a view to initiating epidemiological studies aimed at demonstrating the causal or concausal role of certain working activities in degenerative diseases of the coxo-femoral articulations, the authors report data from a radiological study of a reference population and the necessary conditions for their correct use. Statistical analysis of the descriptive features leads to some interesting observations on the evolution with age of the radiological picture of the coxo-femoral joints (and on the aging of these joints). There was an increase with advancing age of some of the alterations that are characteristic of degenerative articular processes, such as sclerosis and osteophytosis. Reduction of articular "rima", however, occurs suddenly between the ages of 36 and 45 and does not seem to subsequently undergo any statistically significant evolution.

The VEP in evaluation of pituitary tumors.

12 patients with pituitary tumors were studied with VEP, to demonstrate involvement of the optic chiasma. In 3 patients VEP was recorded pre- and post-surgery to evaluate a modification in the shape and latencies of the potentials. 2 patients were studied only pre-surgery, the other 7 post-surgery. The utility of this test is discussed.

Surgical treatment of paediatric malignant neuroepithelial brain tumors.

The role of the neurosurgeon in dealing with malignant neuroepithelial brain tumors, both supra- and infratentorial, in paediatric age, is stressed; this because surgery is the main therapy, and also it is mandatory, in order to achieve the pathological diagnosis, essential for planning any kind of complementary treatment. Open surgery versus stereotactic biopsy is considered, with emphasis on brain stem tumors. The treatment of malignant tumor recurrencies is also discussed, and the indications of a second surgical look in patients harboring recurrent medulloblastoma is proposed for discussion, when long disease-free time occur and combined modality treatments are performed.

Cystic appearance of meningiomas: considerations on a series of 12 patients.

Twelve patients affected with meningiomas with a fluid component are reviewed. Six presented with intratumoral cysts and 6 with extratumoral fluid collections that in 3 cases were of clear CSF. The formation mechanism of the two types are quite different. Intratumoral cysts are caused by biological changes within the tumor, while the extratumoral ones appear to be secondary to local hydrodynamic changes and CSF reabsorption disturbances. The CT (computerized tomography) scan may be equivocal either for the diagnosis of the meningioma or, once the meningioma is suspected, for identifying the type of cyst involved. The angiography is useful for a correct preoperative diagnosis that, once suspected, can be frequently made.

Multiple sclerosis plaque simulating cerebral tumor: case report and review of the literature.

Multiple sclerosis rarely may present as a focal cerebral mass with clinical features and computed tomographic scan appearances of cerebral tumor. Distinguishing between these can be difficult or impossible. We report a case of a multiple sclerosis plaque involving the parietal lobe with mass effect; clinical and radiological features had led to a diagnosis of cerebral tumor.