Inositols: From Established Knowledge to Novel Approaches.

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

Development and validation of the ID-EC - the ITALIAN version of the identify chronic migraine.

BACKGROUND: Case-finding tools, such as the Identify Chronic Migraine (ID-CM) questionnaire, can improve detection of CM and alleviate its significant societal burden. We aimed to develop and validate the Italian version of the ID-CM (ID-EC) in paper and as a smart app version in a headache clinic-based setting. METHODS: The study investigators translated and adapted to the Italian language the original ID-CM questionnaire (ID-EC) and further implemented it as a smart app. The ID-EC was tested in its paper and electronic version in consecutive patients referring to 9 Italian tertiary headache centers for their first in-person visit. The scoring algorithm of the ID-EC paper version was applied by the study investigators (case-finding) and by patients (self-diagnosis), while the smart app provided to patients automatically the diagnosis. Diagnostic accuracy of the ID-EC was assessed by matching the questionnaire results with the interview-based diagnoses performed by the headache specialists during the visit according to the criteria of International Classification of Headache Disorders, III edition, beta version. RESULTS: We enrolled 531 patients in the test of the paper version of ID-EC and 427 in the validation study of the smart app. According to the clinical diagnosis 209 patients had CM in the paper version study and 202 had CM in the smart app study. 79.5% of patients returned valid paper questionnaires, while 100% of patients returned valid and complete smart app questionnaires. The paper questionnaire had a 81.5% sensitivity and a 81.1% specificity for case-finding and a 30.7% sensitivity and 90.7% specificity for self-diagnosis, while the smart app had a 64.9% sensitivity and 90.2% specificity. CONCLUSIONS: Our data suggest that the ID-EC, developed and validated in tertiary headache centers, is a valid case-finding tool for CM, with sensitivity and specificity values above 80% in paper form, while the ID-EC smart app is more useful to exclude CM diagnosis in case of a negative result. Further studies are warranted to assess the diagnostic accuracy of the ID-EC in general practice and population-based settings.

TNF-α -308 G/A and -238 G/A promoter polymorphisms and sporadic Parkinson's disease in an Italian cohort.

The etiology of sporadic Parkinson's disease is (PD) still not understood but it is believed that a complex interplay between environmental and genetic factors could trigger the pathology. Pro-inflammatory TNF-α is released by activated microglia and is up-regulated in the brain and cerebrospinal fluid of PD patients; TNF-α modulates neuroinflammation and can activate the molecular mechanisms that lead to neurotoxicity and neuronal death. We analyzed two functional SNPs within the TNF-α gene promoter (rs361525 and rs1800629) in 354 Italian PD patients and 443 healthy controls (HC). In our cohort of patients, no significant associations could be observed between rs361525 and rs1800629 SNPs and either PD onset risk or PD-associated clinical parameters including age at onset of fluctuations, UPDRS-ME (Unified Parkinson Disease Rating Scale-Motor Examination), Schwab & England, Hohen & Yahr stage scale, and MMSE (Mini-Mental State Examination) score. Conflicting results on the role played by TNF-α rs1800629 SNP on PD onset risk are present in the literature. We could not find any association between TNF-α rs361525 and rs1800629 and PD.

Cognitive impairment in primary brain tumors outpatients: a prospective cross-sectional survey.

Brain tumors and anti-cancer treatments can cause a wide range of cognitive deficits that in turn, being a major cause of disability, significantly affect patients' independence and quality of life. To evaluate the neurocognitive status of a non selected population of brain tumors outpatients, investigating the correlation with clinical and demographic variables. This prospective cross-sectional survey enrolled consecutive outpatients with a histopathologically confirmed diagnosis of brain tumor. All the patients were evaluated with a battery of standardized neuropsychological tests assessing language, memory, logical-executive functions, attention, visuo-constructional abilities. An univariate regression analysis was performed to assess the impact of socio-demographical and clinical variables on the presence of cognitive impairment. 147 patients (61F/86M, mean age 52.8 ± 13.3, mean schooling 12.7 ± 4 were enrolled into the study. Out of the 147 patients evaluated, 80 (54.4 %) showed cognitive impairment: 43 (53.75 %) presented a multidomain impairment, while 37 (46.25 %) patients revealed cognitive deficits limited respectively to language (n:13, 16.25 %), memory (n:11, 13.75 %), attention (n:7, 8.75 %), logical-executive functions (n:5, 6.25 %), visuo-spatial abilities (n:1, 1.25 %). At the regression analysis the variables significantly related to the development of cognitive impairment were age (p = 0.04), lesion side (p = 0.00), chemotherapy (p = 0.03). As advances in anti-cancer treatment have prolonged life expectancy of neuro-oncological patients, standard clinical endpoints can't be limited to just survival or progression free survival, but have to consider clinical benefits on both motor and cognitive function and in general quality of life. Hence evaluation of new therapeutic strategies should routinely include longitudinal neuropsychological assessment.

Epilepsy in the end-of-life phase in patients with high-grade gliomas.

Epilepsy is common in patients with brain tumors. Patients presenting seizures as the first sign of a malignant glioma are at increased risk of recurrent seizures despite treatment with antiepileptic drugs. However, little is known about the incidence of epilepsy in the last stage of disease and in the end-of-life phase of brain tumor patients. We retrospectively analyzed the incidence of seizures in the last months of life in a series of patients affected by high-grade gliomas who were assisted at home during the whole course of the disease until death. A total of 157 patients were available for analysis. Of these patients, 58 (36.9 %) presented seizures in the last month before death. The risk of seizures in the end-of-life phase is higher in patients presenting previous history of epilepsy, particularly in patients with late-onset epilepsy. Out of the 58 patients presenting seizures in the last month of life, 86.2 % had previously had seizures and 13.8 % were seizure free. Most patients may encounter swallowing difficulties in taking anticonvulsants orally due to dysphagia and disturbances of consciousness, thus anticonvulsant treatment needs to be modified in advance. Loss of seizure control in the end-of-life phase may influence the quality of life of patients and their caregivers.

Illicit drug use in cluster headache patients and in the general population: a comparative cross-sectional survey.

BACKGROUND: The rate of illicit drug use in cluster headache (CH) patients is unknown. METHODS: Two hundred and ten CH patients (162 males and 48 females) attending two headache clinics provided information about their lifetime use (once or more in their lifetime, LTU), recent use (once or more in the past year, RU), and current use (once or more in the past 30 days, CU) of illicit drugs. General population data (IPSAD®Italia2007-2008) served as the control group. RESULTS: LTU of each illicit drug but hallucinogens, RU of cannabis, cocaine, amphetamines and ecstasy, and CU of cannabis and cocaine were significantly higher in the male CH patients than in the general population, whereas no difference was found between the CH women and the controls. In the CH group, 28.5% of patients reported having used illicit drugs for the first time after CH onset and 71.5% before CH onset. Compared with the controls, the male CH group showed a greater prevalence both of lifetime sustained intensive use of any illicit drug and of current intensive use of cannabis. CONCLUSION: The results of this study indicate that male CH patients are prone to overindulge in illicit drug use. This finding possibly reflects a common biological susceptibility that predisposes these subjects to CH and to addictive behaviour.

Quality of care and rehospitalization rate in the last stage of disease in brain tumor patients assisted at home: a cost effectiveness study.

UNLABELLED: Despite aggressive multimodality treatment the prognosis of patients with primary brain tumors (BT) remains poor. At present, there are no data about the role of palliative home-care services and their impact on quality of care. We report the results of a pilot project of palliative home care for BT patients started in 2000 in the National Cancer Institute Regina Elena of Rome. We report also the result of a cost/effectiveness analysis utilizing administrative data on re-hospitalization rate in the last two months of life. METHODS: Since October 2000 until December 2009, 572 patients have been followed by our home care staff. Among 394 patients who died, 276 (70%) were followed at home until death. A cost/effectiveness analysis was carried out evaluating the rehospitalization rate in the last 2 months of life in a subgroup of patients (group 1 assisted at home, 72 patients; group 2 not assisted at home, 71). The number of hospital readmission in the last 2 months of life, and length and cost of hospitalization were retrospectively analyzed from hospital discharge records. RESULTS: Hospitalization rate of group 1 (16.7%) was lower than group 2 (38%) (95% CI: 0.18-0.65, p = 0.001). Costs of hospitalization also differed substantially: 517 Euros (95% CI: 512-522) in group 1 vs 24, 076 Euros (95%: 24,040-24,112 Euros) in group 2. CONCLUSION: Home-care may represent an alternative to in-hospital care for the management of brain tumor patients and may improve the end-of-life quality of care.

End of life issues in brain tumor patients.

Despite aggressive antitumor treatment, the prognosis of brain tumor (BT) patients remains poor. In the last stage of disease, BT patients present severe symptoms due to the growing tumor or to treatment side-effects, which require adequate palliative management and supportive therapy. However, studies specifically addressing palliative care and end-of-life (EoL) issues in BT patients are lacking. This study explores symptoms experienced by BT patients in the last weeks of disease and EoL issues observed in a population of brain tumor patients followed at home until death by a neuro-oncological home care palliative unit set up in our Institution in 2000. From October 2000 to December 2005, 324 patients affected by brain tumor and discharged from our Institution were enrolled in a comprehensive program of neuro-oncological home care supported by the Regional Health System. Out of 324 patients enrolled in the home care program, 260 patients died of which 169 (65%) were assisted at home until the end of life and have been included in this study. Clinical symptoms, palliative treatments and EoL treatment decisions were collected from home clinical records. Among the 169 patients assisted at home until death, the most frequent symptoms observed in the last four weeks of life were: epilepsy 30%, headache 36%, drowsiness 85%, dysphagia 85%, death rattle 12%, agitation and delirium 15%. Palliative management of brain tumor patients requires a multidisciplinary approach performed by a well trained neuro-oncology team. Development of home care models of assistance may represent an alternative to in-hospital care for the management of patients dying of brain tumor and may improve the quality of end-of-life care.