Neoplastic meningitis from solid tumors: a prospective clinical study in lombardia and a literature review on therapeutic approaches.

Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging) and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC) and liposomal antitumor agents (liposomal AraC). Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

Temozolomide and thalidomide in the treatment of glioblastoma multiforme.

OBJECTIVE: The aim of this study was to assess efficacy and toxicity of temozolomide given alone or in combination with thalidomide, an anti-angiogenetic drug, in patients with newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS: 46 patients with histologically proven GBM were eligible for inclusion. Twenty-three patients (15 males and 8 females) received temozolomide on a conventional schedule; 23 patients (12 males and 11 females) received temozolomide on the same schedule and thalidomide was dose-adjusted in each individual patient based on their tolerance. RESULTS: The median survival time was 12 months for temozolomide and 13 months for temozolomide + thalidomide. CONCLUSION: The administration of temozolomide in association with thalidomide after radiotherapy (RT) does not offer an advantage over temozolomide alone in adults with newly diagnosed GBM. The two therapeutic strategies produce similar results for survival, but the latter regimen shows a moderate increase in toxicity.

Tumour-associated epilepsy: clinical impact and the role of referring centres in a cohort of glioblastoma patients. A multicentre study from the Lombardia Neurooncology Group.

Epilepsy in high-grade glioma patients is a major concern, mainly as regards indications to treatment and best choice; toxicities, and pharmocokinetic and pharmacodynamic interactions of drugs. All these generally unsolved problems complicate patients' quality of life and interfere with the evaluation of response criteria in clinical trials. A prospective, multicentre data collection on 132 adult newly diagnosed, histologically proven glioblastomas from 9 Lombardy hospitals collected in the same database during a one-year period was recently published. From this database we report epidemiological and clinical characteristics in epilepsy-symptomatic (31%) glioblastoma patients vs. the group with other presenting symptoms (69%). We analyse demographic and clinico-radiological features, timing of onset and the course of seizures, and modalities of treatment in the two groups of patients. No statistically significant differences were observed between the two groups as regards age, site of lesion(s), extent of surgery and survival in relation to anticonvulsant treatment status or pharmacokinetic properties of drugs.

A randomized phase III study: comparison between intravenous and intraarterial ACNU administration in newly diagnosed primary glioblastomas.

BACKGROUND: In this randomized phase III study, the effectiveness as well as the side-effects of intraarterial [i.a.] (17 patients) versus intravenous [i.v.] (16 patients) ACNU [Nimustine] administration in newly diagnosed glioblastoma, were compared. PATIENTS AND METHODS: All patients undenwent extensive surgical resection, and both groups were homogeneous for the other known risk factors. Thirty-three patients with glioblastoma were treated with ACNU at the dose of 80-100 mg/m2. Treatment was repeated every 5-8 weeks for a minimum of 2 and maximum of 14 cycles. Total survival time (TST) and to time to progression were chosen as outcome variables. RESULTS AND CONCLUSION: No significant differences in systemic and hematological toxicity between the i.a. and iv. ACNU administration routes were detected. In both groups, tolerance of the procedure was excellent. Analysis of the main outcome measured showed no significant differences between i.a. and i.v. ACNU administration: time to progression was 6 months for i.a. ACNU and 4 months for i.v. ACNU and total survival time was 17 months for i.a. ACNU and 20 months for i.v. ACNU. In spite of ACNU dose incrementation, obtained through i.a. route administration, and subsequent higher concentration in the tumor bed, no improvement could be achieved in effectiveness.

A multicentre prospective collection of newly diagnosed glioblastoma patients in Lombardia, Italy.

The objective was to set the basis for a prospective, multicentre data collection on newly diagnosed adult glioblastoma patients diagnosed in Lombardia by means of a common database used by neurological and neurosurgical units of various hospitals, providing epidemiological, therapy and follow-up data. All adult patients with a newly diagnosed glioblastoma in 9 Lombardia hospitals from 31 March 2003 to 31 March 2004 were followed prospectively by a form elaborated by the Lombardia Neuro-oncology Group. Demographic data were recorded, as well as symptoms at onset, entity of tumour resection, post-surgical Karnofsky Performance Score, radio- and chemotherapy, presence/absence of venous thrombosis, type of antiepileptic treatment, time to tumour progression and survival time (ST). One hundred and thirty-four newly diagnosed glioblastoma patients were enrolled during the first year of the study. Male/female ratio was 1.6:1. Median age was 61 years. The most common single sign/symptom at disease onset included seizures, followed by mood/cognition changes and headache. In 71 patients, the tumour involved 1 brain lobe at diagnosis. Twenty-five patients underwent biopsy, 51 partial removal and 51 grossly total removal. At analysis of predictive value on ST, grossly total resection and chemotherapy were significantly associated with a longer ST. Age younger than 50 showed a trend to predictive value. A very high proportion of patients were treated with antiepileptic drugs, even in the absence of seizures. Median ST was 12 months in our cohort. Data in newly diagnosed glioblastoma patients in Lombardia are in line with other case series reported in other populations.

Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis.

Randomized Controlled Trials have not let established the best pharmacological management of Acute Disseminated Encephalomyelitis (ADEM). High dose steroids are usually employed with good results, but in a few cases the clinical outcome is poor. In other patients, particularly those affected by the site restricted ADEM variants (myelitis), the disease shows a recurrent course resembling that of Multiple Sclerosis. We present here five patients, 3 of them affected by classic disseminated encephalomyelitis and 2 by a post infectious myelitis, which showed a good response to intravenous immunoglobulin (IVIg) after steroid treatment failure. In our report high dose steroids administration was substantially uneffective in all but one case, who showed a good response only during the first episode. On the contrary IVIg injection (0,4 gr/kg/day) produced a marked functional improvement in all patients starting within the first five days of drug administration and reaching a maximum within three weeks. One patient experienced a good effect nothwithstanding a steady dysability. In all cases, clinical evidence was supported by MRI controls showing improving posttreatment changes.

Dejerine's syndrome or Spiller's syndrome?

We report the difference existing between two clinical syndromes: Spiller's syndrome is caused by a complete involvement of the medial hemimedulla, while Déjérine's syndrome is determined by lesions restricted to the anterior portion of the medial hemimedulla and is characterized by hypoglossal nerve palsy and contralateral hemiparesis.

Clustering of ALS patients in central Italy due to the occurrence of the L84F SOD1 gene mutation.

OBJECTIVE: To study three new apparently unrelated Italian families with ALS and several sporadic ALS patients living in the same rural area. BACKGROUND: One Italian family with ALS carrying a superoxide dismutase 1 (SOD1) gene mutation (G41S) and no regional ALS clustering has been reported in Italy. METHODS: Genetic analysis was performed by automated and manual sequencing of the SOD1 gene in 13 family members and in 6 of 10 unrelated patients with sporadic cases of ALS living in the same area. The authors also determined SOD1 activity in erythrocytes and lymphocytes. RESULTS: The three families included a total of 28 affected members distributed over six generations. Despite a wide variability in age at onset and disease duration, the clinical pattern is uniform, with onset in the lower limbs, ascending progression, and predominant lower motor neuron involvement in all subjects. Generational anticipation is evident in the last two generations. All familial ALS patients and one of the six sporadic patients carry the same L84F missense point mutation in exon 4 of the SOD1 gene. SOD1 enzyme activity and SOD1 protein levels were not decreased significantly in the L84F patients. CONCLUSION: The ALS patients carrying the L84F mutation derive from a common ancestor. This mutation is responsible for ALS clustering in the area. The L84F mutation does not modify SOD1-specific activity.

Biotype-specific restriction and modification of DNA in Vibrio cholerae.

By using Vibrio cholerae typing phages it was possible to demonstrate that within V. cholerae of the O-1 serotype there are at least two biotype-specific DNA restriction and modification systems.