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.

Lacosamide on background eeg activity in brain tumor-related epilepsy patients: A case series study.

OBJECTIVE: Therapeutic doses of antiepileptic drugs (AEDs) may alter EEG background activity, which is considered an index of the functional state of the brain. Quantitative analysis (qEEG) of EEG background activity is a valid instrument to assess the effects of many centrally active drugs on the central nervous system, including AEDs. Lacosamide (LCM) is a new AED that could be a valid therapeutic choice in patients with brain tumor-related epilepsy (BTRE). METHODS: We used qEEG to analyze the possible effect of LCM as an add-on, on background EEG activity after 4 months in patients with BTRE. RESULTS: We consecutively recruited sixteen patients with BTRE: Five dropped out for disease progression, five for scarce compliance, and six completed the study. For these reasons qEEG was performed at first visit and after 4 months only in six patients. For all frequency bands, LCM revealed no changes of mean relative power during rest with eyes closed, hyperpnoea (HP), and mental arithmetic task (MA); significant increment was found only in the theta mean relative power during opening and closing eyes (BR). After four months of therapy with LCM, one patient was seizure free, four had a seizure reduction ≥50%, and one showed a worsening in seizure frequency <50%. CONCLUSION: Despite the limitation of a small series, these findings suggest that LCM seems to have only a mild interference on EEG background activity and confirm that LCM has a good efficacy on seizure control in patients with BTRE. This is the first study that evaluates the effect of LCM on background EEG activity, using qEEG in BTRE patients. Future research in this area could include prospective studies with qEEG for a longer follow-up period to assess the impact of AEDs on brain functions in this particular fragile patient population.

Zonisamide in Brain Tumor-Related Epilepsy: An Observational Pilot Study.

OBJECTIVES: Epilepsy heavily affects the quality of life (QoL) of patients with brain tumor because in addition to taking treatments for the oncological illness, patients are required to live with the long-term taking of antiepileptic drugs (AEDs). The AEDs' adverse effects are common in these patients and can negatively influence their perceptions of their QoL.We conducted an observational pilot study in patients with brain tumor-related epilepsy to verify efficacy, tolerability, and impact on QoL and global neurocognitive performances of zonisamide (ZNS) in add-on. MATERIALS AND METHODS: We recruited 13 patients (5 females, 8 males; mean age, 49.6 years) presenting uncontrolled seizures. At first visit and at final follow-up at 6 months, patients underwent neurological examination, evaluation of adverse events, and cognitive and QoL tests. A seizure diary was given. RESULTS: Eight patients underwent chemotherapy, 3 underwent radiotherapy, and 5 had disease progression. Mean dosage of ZNS at final follow-up was 300 mg/d.Of 9 patients who reached the sixth month follow-up, the mean weekly seizure number before ZNS had been 3.2 ± 5.0, and at final follow-up, the mean weekly seizure number was 0.18 ± 0.41 (P = 0.05).Compared with baseline, we observed stability in all cognitive domains, except for verbal fluency that significantly worsened.Results on QoL tests showed that QoL remained unchanged over time, which could indicate that ZNS did not influence the patients' perceived QoL. CONCLUSIONS: Zonisamide as add-on in our patients seems to be well tolerated and efficacious in controlling seizures. Despite having limitations represented by the fact that our study is observational, with a small study population and a short follow-up period, our results confirm that when choosing an AED, in addition to efficacy, the drug's effect on patients' QoL also needs to be considered, especially for patients facing many psychosocial challenges, such as those with brain tumor-related epilepsy.

Effect of high dose cytosine arabinoside on quantitative EEG in patients with acute myeloid leukemia.

Background EEG activity is considered an index of functional state of brain. Chemotherapy (CT), used for non-central nervous system (CNS) cancer, can cross the blood brain barrier and contribute to changes in the functional state of brain that can alter background EEG activity. Quantitative EEG (qEEG) is superior to conventional EEG in the detection of subtle alterations of EEG background activity and for this reason, the use of qEEG might assist the clinician in evaluating the possible effect of CT on the CNS. The nucleoside analog cytosine arabinoside (Ara-C) is one of the milestone chemotherapeutic agents used for treatment of acute myeloid leukemia (AML). Our observational study evaluates the possible effect of Ara-C on the qEEG of patients with AML, without CNS involvement. We conducted an observational study on newly diagnosed AML patients without CNS involvement, undergoing treatment with Ara-C to analyze the possible effect of Ara-C high doses on EEG background activity using qEEG analyses. A total of nine AML patients, 5 with Ara-C i.v. high dose (≥3 g/m(2) die), 4 with standard dose (100 mg/m(2) die) underwent qEEG (at rest, during hyperpnoea, mental arithmetic task and blocking reaction). We compared the EEG background activity of the two groups at baseline and after 6 months. Statistical analysis showed no significant differences between the two groups in mean relative power for all frequency bands, at rest and during hyperpnoea, mental arithmetic task and blocking reaction. Our data indicate that high dose Ara-C i.v. did not induce significant changes on EEG background activity in our patients. Future research in this area could include prospective studies that would combine qEEG and neuropsychological testing to assess the impact of CT on brain functions.

Cognitive rehabilitation training in patients with brain tumor-related epilepsy and cognitive deficits: a pilot study.

The aim of this pilot observational study was to evaluate effect of cognitive rehabilitation training (RehabTr) on cognitive performances in patients with brain tumor-related epilepsy (BTRE) and cognitive disturbances. Medical inclusion criteria: patients (M/F) ≥ 18 years ≤ 75 with symptomatic seizures due to primary brain tumors or brain metastases in stable treatment with antiepileptic drugs; previous surgical resection or biopsy; >70 Karnofsky Performance Status; stable oncological disease. Eligible patients recruited from 100 consecutive patients with BTRE at first visit to our Center from 2011 to 2012. All recruited patients were administered battery of neuropsychological tests exploring various cognitive domains. Patients considered to have a neuropsychological deficit were those with at least one test score for a given domain indicative of impairment. Thirty patients out of 100 showed cognitive deficits, and were offered participation in RehabTr, of which 16 accepted (5 low grade glioma, 4 high grade glioma, 2 glioblastoma, 2 meningioma and 3 metastases) and 14 declined for various reasons. The RehabTr consisted of one weekly individual session of 1 h, for a total of 10 weeks, carried out by a trained psychologist. The functions trained were: memory, attention, visuo-spatial functions, language and reasoning by means of Training NeuroPsicologico (TNP(®)) software. To evaluate the effect of the RehabTr, the same battery of tests was administered directly after cognitive rehabilitation (T1), and at six-month follow-up (T2). Statistical analysis with Student T test for paired data showed that short-term verbal memory, episodic memory, fluency and long term visuo-spatial memory improved immediately after the T1 and remained stable at T2. At final follow-up all patients showed an improvement in at least one domain that had been lower than normal at baseline. Our results demonstrated a positive effect of rehabilitative training at different times, and, for these reasons, should encourage future research in this area with large, randomized clinical trials that evaluate the impact of a cognitive rehabilitation in patients with BTRE and cognitive deficits.

Weight of epilepsy in brain tumor patients.

About 20-40% of patients with brain tumor have seizures; all of whom must be treated with antiepileptic drugs (AEDs) that can cause side effects which may influence quality of life (QoL). However, little data are available regarding the weight of epilepsy on QoL in brain tumor (BT) patients, despite the fact that epilepsy is considered the most important risk factor for long-term disability in this patient population. Aim of this study is to explore the weight of epilepsy in BT patients, and to identify which factors might contribute to their epilepsy burden, as expressed by them only at their first visit in a specialized epilepsy center, in order to have a snapshot for that moment in their care cycle. We reviewed medical charts and results from a battery of tests (routinely given at our outpatient center), administered to 100 consecutive BTRE patients at their first visit, followed from 2007 to 2010. Our results reveal: (1) neurological performances and global neurocognitive status were not influenced by factors related to neoplastic disease or to epilepsy (2) side effects, cognitive deficits, and QoL concerns, as well as patients' perception of these, were significantly related to polytherapy, especially in patients who had been taking AEDs for a period longer that 6 months (3) the seizure number did not influence patients' QoL. We found that the weight of epilepsy in BTRE patients was related to AED therapy. Our study highlights the fact that epilepsy in our patients adds a significant burden, and suggests the need to give the proper attention to patients' concerns regarding the challenges that this pathology might present. Nevertheless, future studies could be designed with a follow-up period and with a patient stratification in order to better understand the weight of epilepsy for these patients.