Epilepsy in elderly patients: focus on treatment

Epilepsy is a disorder widely distributed across all age groups, although its incidence and prevalence favours elderly patients. In this population the development of epilepsy is mainlyrelated to other brain disorders that facilitate the occurrence of late seizures, mostly of focal onset. Apart from the difficulties faced in current practice with the appropriate diagnosis of the epileptic nature of the episodes, old subjects require an individualised drug treatment, tailored on their characteristics, such as comorbidity, polytherapy, age-associated biological impairment and compliance. Among the various antiepileptic drugs available for the treatment of epilepsy, rational selection and combination of drugs should drive both initiation and maintenance of the treatment. Choice of antiepileptic drugs should first focus on avoidance of adverse effects and potential drug interactions. The pharmacological control of seizures is usually favourable at this age, with a good prognosis. However, alternative therapeutic options should be considered as soon as drug-response is unsatisfactory

Impact of dealcoholization by osmotic distillation on metabolic profile, phenolic content, and antioxidant capacity of low alcoholic craft beers with different malt compositions

Beer antioxidants originate mainly from malts, classified as colored, caramel, and roasted, according to the malting process. This study aimed to characterize, in terms of phenolic antioxidants, three types of Pale Ale craft beers brewed using increasing percentage of dark malt (0, 5, and 15% Caraamber malt, called PA100, PA95, PA85, respectively) and to evaluate the impact of dealcoholization by osmotic distillation (OD) on the same antioxidants. All the alcoholic (PA, 6.2-6.8 vol %) and low alcoholic (LA-PA, 1 vol %) beers were analyzed by HPLC-ESI-MS/MS, total phenolic content (TPC), and antioxidant activity (AA): similar phenolic profiles were evidenced and 43 compounds identified or tentatively identified. Some differences were found among PA100, PA95, and PA85: PA85 was richer in free phenolic compounds (10.55 mg/L) and had a higher TPC (463.7 GAE mg/L) and AA (852.1 TE mg/L). LA-PA beers showed the same phenolic profile and similar TPC and AA compared to PA beers; however, there were some differences regarding LA-PA85 (5.91 mg/L). Dealcoholization by OD seemed to weakly affect the phenolic fraction. ESI-MS/MS infusion experiments evidenced oligosaccharides, small organic acids, and amino acids, whose presence was confirmed and quantitated by NMR: besides ethanol and other alcohols, weak to strong loss of low-molecular-weight metabolites was evidenced in LA-PA beers

Anti-alfa4beta1 integrina nella Sclerosi Multipla: risposta terapeutica a lungo termine.

Nei pazienti con Sclerosi Multipla ad elevata attività di malattia, quindi con riesacerbazioni cliniche ed incremento del carico lesionale alla Risonanza Magnetica, nonostante una terapia di prima linea con farmaci immunomodulanti, sono necessarie terapia più aggressive, tra le quali l’anticorpo monoclonale Natalizumab. Scopo di questo studio è valutare la risposta terapeutica nel breve e nel lungo termine a questo farmaco del quale conosciamo l’efficacia ma tuttavia anche il suo principale evento avverso, la leucoencefalopatia multifocale progressiva

Studio osservazionale longitudinale sull'epilessia associata a tumori cerebrali.

Le crisi epilettiche rappresentano una delle più comuni manifestazioni cliniche dei tumori cerebrali, sia prima che venga posta la diagnosi di neoplasia (crisi araldiche)che nel corso del trattamento antineoplastico e nel follow-up. La fisiopatologia dell'epilessia associata ai tumori cerebrali è poco nota, ma un ruolo fondamentale sembra riconosciuto ai cambiamenti di vario tipo (morfologia, metabolismo, pH, concentrazioni ioniche,aminoacidiche ed enzimatiche, aspetti immunologici e genetici) osservati nel tessuto peritumorale. Le caratteristiche delle crisi variano in relazione a fattori propri della neoplasia cerebrale (tipo istologico, sede, numero delle lesioni)e all'ospite (età, comorbidità,ecc.). Il nostro studio ha lo scopo di valutare, nei pazienti con diagnosi di tumore cerebrale e crisi epilettiche, gli aspetti demografici, la modalità di presentazione delle crisi prima e dopo craniotomia ed altri eventuali trattamenti antineoplastici, nonchè il ruolo della terapia/profilassi farmacologica antiepilettica. Nello studio sono stati inclusi 51 pazienti,con un follow-up della durata mediana di 21 mesi. Il tipo istologico più comune è risultato il meningioma, più frequente nel sesso femminile e con una età media di presentazione pari a 53,4 anni. Il lobo frontale,a differenza di quello occipitale, si è confermato il più epilettogeno. Indipendentemente dal tipo istologico e dalla sede del tumore, gli episodi comiziali si sono manifestati nel 59% dei pazienti prima dell'intervento chirurgico, e nel 63% nel decorso post-operatorio, ed in entrambe le fasi della malattia, le crisi di tipo parziale (semplici o complesse) sono risultate le più comuni. Tutti i pazienti sono stati dimessi con la prescrizione di farmaci anticonvulsivanti, ancorchè la terapia è stata successivamente modificata nel 90% dei pazienti, e gradualmente interrotta solo in un numero limitato di casi

Very late onset multiple sclerosis likely associated with restless legs syndrome. A case report.

Introduction: We describe the case of P.R., a 84 years-old woman suffering from Restless Legs Syndrome since 2002 and Multiple Sclerosis since 2007. Case report: MS clinical onset was characterized by walking difficulties and abnormal sensitivity in lower limbs especially in the evening. Then other symptoms added: dysesthesies on the left leg and arm and left emitrunk, visual acuity reduction, blurred vision and fatigue. She first performed an electromyographic and polysomnographic examination, with a diagnosis of Restless Legs Syndrome. At the MRI of the brain, multiple lesions in white matter were detected, unconsistent with a vascular disease but suggestive for a demielinating disease. The patient was admitted to hospital and the lumbar puncture was performed: the analysis of the cerebrospinal fluid showed 11 oligoclonal bands. VEPs, SSEPs, Trigeminus-facial reflex and a new brain MRI were performed later, and confirmed the MS. The patient regularly performed medical examinations and brain MRI to keep the condition under control. She claimed light and slow worsening of the ambulation, but her brain MRI didn’t show any increase of lesions burden nor pathological enhancement. Due to her age, she doesn’t take DM therapy for multiple sclerosis, the only drugs being represented by symptomatic agents. Discussion: The association between multiple sclerosis and restless leg syndrome has been already described especially in old patients, but the onset of MS in elderly in unusual and it’s described as LOMS (late onset multiple sclerosis), with an onset after the age of 50 with typical clinical and neuroradiological features: the presence of motor and cerebellar symptoms seem to be more frequent in this sub-group of patients, as well as low frequency of Gadolinium enhacement lesions. This could be related to a more degenerative and less inflammatory form of the disease. Moreover, in this late onset patients is essential the different diagnosis with other diseases interesting the white matter, i.e. vascular, infective, paraneoplastic, metabolic diseases or nutritional deficiencies, which could confound the true diagnosis. Conclusions: The present case report is interesting for the association between RLS and MS, but also as this comorbidity occurs I a very old patient, who could be described as a patient with a “very late onset multiple sclerosis”

May “Mitochondrial Eve” and Mitochondrial Haplogroups Play a Role in Neurodegeneration and Alzheimer's Disease?

Mitochondria, the powerhouse of the cell, play a critical role in several metabolic processes and apoptotic pathways. Multiple evidences suggest that mitochondria may be crucial in ageing-related neurodegenerative diseases. Moreover, mitochondrial haplogroups have been linked to multiple area of medicine, from normal ageing to diseases, including neurodegeneration. Polymorphisms within the mitochondrial genome might lead to impaired energy generation and to increased amount of reactive oxygen species, having either susceptibility or protective role in several diseases. Here, we highlight the role of the mitochondrial haplogroups in the pathogenetic cascade leading to diseases, with special attention to Alzheimer's disease

Hereditary spastic paraparesis in adults. A clinical and genetic perspective from Tuscany

Objective Hereditary spastic paraparesis or paraplegias (HSPs) are a group of neurogenetic conditions with prominent involvement of the pyramidal tracts. Aim of this study is the clinical and molecular characterization of a cohort of patients with HSP. Moreover, we aim to study the minimum prevalence of HSP in our area and to propose a schematic diagnostic approach to HSP patients based on the available data from the literature. Methods Retrospective/perspective study on the subjects with clinical signs and symptoms indicative of pure or complicated HSP, in whom other possible diagnosis were excluded by appropriate neuroradiological, neurophysiologic and laboratory studies, who have been evaluated by the Neurogenetic Service of our clinic in last two years (2011-2012). Results 45 patients were identified. The minimum prevalence of HSP in our area was of about 2.17-3.43/100,000. The SF-36 (quality of life) and SPRS (disease progression) scores were inversely related; the time-saving, four-stage scale of motor disability could predict the SPRS scores with a high statistical significance, and we encourage its use in HSP. Our study confirms SPG4 as the major cause of HSP. All SPG4 patients had a pure HSP phenotype, and the dominant inheritance was evident in the great majority of these subjects. SPG7 was the second genetic cause. Other genotypes were rarer (SPG10, SPG11, SPG17). Conclusion Exact molecular diagnosis will allow a more accurate patient counseling and, hopefully, will lead to specific, targeted, therapeutic options for these chronic, still incurable diseases. © 2014 Elsevier B.V

CETUXIMAB AND RADIOTHERAPY VERSUS CISPLATIN AND RADIOTHERAPY FOR LOCALLY ADVANCED HEAD AND NECK CANCER: LONG TERM SURVIVAL AND TOXICITY OUTCOMES OF A RANDOMIZED PHASE II TRIAL

Purpose: describing long-term survival and toxicity outcomes of a multicenter randomized phase II trial comparing radiotherapy (RT) plus cisplatin (CDDP) or cetuximab (CTX) as first line treatment in locally advanced head and neck cancer (LASCCHN). Materials and methods: Between January 2011 and August 2014, 70 patients were enrolled and randomized to receive RT plus weekly CDDP (40 mg/m2) or CTX (250 mg/m2 plus a loading dose of 400 mg/m2). This updated series focuses on late toxicities (graded by using CTCAE scale version 4.0) and long-term survival outcomes in terms of local control (LC), overall survival (OS), cancer-specific survival (CSS) and metastasis free survival (MFS). A supplementary analysis based on HPV status was also performed. Results: no statistically significant difference was found in terms of late effects (xerostomia, fibrosis, mucosal atrophy, weight loss). In the CDDP arm and in the CTX arm 5-year LC rates were 67% and 48%; 5-year MFS rates 83% and 97%; 5-years OS rates 61% and 52%; 5-year CSS rates 70% and 59%, respectively (none of these differences reached statistical significance). A subgroup analysis by HPV status and anatomical subsites revealed that in HPV+ oropharyngeal carcinoma (OPC) better survival were obtained in the CDDP arm (though statistical tests were not performed due to the small sample size). Conversely, no statistically significant differences were observed in HPV- OPC and other anatomical subsites, except for the confirmed better MFS rates of the CTX arm. Conclusion: long-term results are in line with current literature suggesting that RT + CTX is inferior to RT + CDDP for the definitive treatment of LASCCHN. However, if not as an alternative to CDDP, CTX might still play a role in LASCCHN, particularly in HPV- cases