Bruising following natalizumab infusion for relapsing-remitting multiple sclerosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Natalizumab is a new treatment for relapsing-remitting multiple sclerosis. Because of limited experience of this treatment, medical professionals must be alert to possible side effects.</p> <p>Case presentation</p> <p>We present a 34-year-old Caucasian woman with relapsing-remitting multiple sclerosis. She developed bruises on her legs after the first and second administrations of the new monoclonal antibody, natalizumab. Clinical and laboratory investigations revealed no hematological abnormalities. At the time of writing, she has remained on natalizumab treatment without any further side effects.</p> <p>Conclusion</p> <p>In our patient, bruises on the lower extremities may be a benign side effect of natalizumab. This is the first documented incidence of this side effect, and the patient did not require discontinuation of natalizumab treatment.</p

Telemetric Monitoring of Intracranial Pressure

Background: We present the application of a modern telemetric method that records and monitors Intracranial Pressure (ICP) over long periods in patients with possible intracranial hypertension. Methods: A telemetric devise (Raumedic, Neurovent P-tel) was surgically implanted in six (6) patients. Three (3) patients with inconclusive diagnosis of idiopathic intracranial hypertension, two (2) patients with possible diagnosis of aqueduct stenosis and one (1) patient with Normal Pressure Hydrocephalus. All patients underwent a 3-day ICP recording within the nursing unit. Two more recordings were obtained over a period of 2-6 months at outpatient base. Results: All patients had an uncomplicated post-operative course. Analysis of the data excluded the diagnosis of idiopathic intracranial hypertension in two patients. Contrary in four patients data confirmed elevated ICP values and subsequently three of them underwent shunts implantation, while one patient refused further neurosurgical treatment. Conclusions: The telemetric device could be safely implanted in selected patients. It could provide long-term ICP recordings, which are necessary to confirm diagnosis and guide to the appropriate treatment

Depression and anxiety in epilepsy: the association with demographic and seizure-related variables

<p>Abstract</p> <p>Background</p> <p>Depression and anxiety are common psychiatric symptoms in patients with epilepsy, exerting a profound negative effect on health-related quality of life. Several issues, however, pertaining to their association with psychosocial, seizure-related and medication factors, remain controversial. Accordingly, the present study was designed to investigate the association of interictal mood disorders with various demographic and seizure-related variables in patients with newly-diagnosed and chronic epilepsy.</p> <p>Methods</p> <p>We investigated 201 patients with epilepsy (51.2% males, mean age 33.2 ± 10.0 years, range 16–60) with a mean disease duration of 13.9 ± 9.5 years. Depression and anxiety were assessed in the interictal state with the Beck Depression Inventory, 21-item version (BDI-21) and the state and trait subscales of the State-Trait Anxiety Inventory (STAI-S and STAI-T), respectively. The association of mood disorders with various variables was investigated with simple and multiple linear regression analyses.</p> <p>Results</p> <p>High seizure frequency and symptomatic focal epilepsy (SFE) were independent determinants of depression, together accounting for 12.4% of the variation of the BDI-21. The STAI-S index was significantly associated with the type of epilepsy syndrome (SFE). Finally, high seizure frequency, SFE and female gender were independent determinants of trait anxiety accounting for 14.7% of the variation of the STAI-T.</p> <p>Conclusion</p> <p>Our results confirm the prevailing view that depression and anxiety are common psychological disorders in epileptics. It is additionally concluded that female gender, high seizure frequency and a symptomatic epilepsy syndrome are independent risk factors for the development of anxiety and/or depression.</p

The prognostic value of electroencephalography in epilepsy: a long-term follow-up study

Predicting the evolution of epilepsy is of obvious importance for patients and their families. Value of electroencephalography (EEG) is extensively used in the diagnosis of epilepsy yet its role as a prognostication method remains unclear. The aim of the present retrospective study is to investigate the relationship between serial EEG recordings and long-term clinical and social outcomes in a cohort of patients with epilepsy. Thirty-nine epileptic patients were monitored clinically and with repeat EEG recordings for more than 15 years. All patients who initially had epileptiform discharges ended up with poor or moderate seizure control whereas more than half of the patients with normal initial recordings had good clinical outcomes and satisfactory social adjustment. Deterioration of the recordings over time was associated with unfavourable results in a significant proportion of patients (90 %), while stable or improved EEG findings predicted a favourable outcome. It is concluded that serial EEG recordings can be used in the prognostic evaluation of epilepsy

Brand-to-generic levetiracetam switch in patients with epilepsy in a routine clinical setting

Purpose: The therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution. / Methods: A prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4 ± 16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded. / Results: Patients had epilepsy for a mean period of 14.1 ± 10.6 years and the mean daily LEV dose was 2583.3 ± 763.7 mg. The mean AUC ± SD and Cmax ± SD was 288.4 ± 86.3 (mg/L) h and 37.8 ± 10.4 mg/L respectively for brand LEV and 319.2 ± 104.7 (mg/L) h and 41.6 ± 12.3 mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded. / Conclusions: In our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV

Add-on topiramate in the treatment of refractory partial-onset epilepsy: Clinical experience of outpatient epilepsy clinics from 11 general hospitals

SummaryAn open, prospective, observational study was performed to assess efficacy and adverse-event profile of topiramate as add-on therapy in epilepsy. Outpatient neurology clinics from 11 general hospitals in Greece participated in the study. In total, 211 patients with treatment resistant partial-onset seizures who met the inclusion criteria, were studied. After baseline evaluation, topiramate was given at a target dose of 200mg/day over a 1-month titration period. In the subsequent maintenance period, the topiramate dose could be varied according to the clinical results. Patients were followed for in total 6 months, with monthly visits and regular physical, neurological and laboratory examinations. Seizure frequencies decreased to 35–40% of baseline values following 3 months of treatment and remained relatively constant thereafter. The average monthly seizure frequency over the 6-month study period was 4.61, compared to 9.21 at baseline. The number of responders (patients with at least 50% reduction in seizure frequency) followed a similar pattern, i.e., increase during the first 3 months levelling off at a final 80–85% response rate. Of those completing the study, 30% had been seizure-free for at least 3 months and 12% for 5 months. Topiramate was well tolerated, no deviations in laboratory values were found. Adverse events appeared to occur less frequently, and antiepileptic effects were more pronounced in this prospective open-label study than in earlier reports from randomised controlled trials. The nature of the patient population and the application of individualised dose optimisation are proposed as contributing factors to explain the favourable results of this study

Spastic paraplegia preceding PSEN1-related familial Alzheimer's disease.

Introduction: We investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 (PSEN1) related familial Alzheimer's disease (AD). Methods: We performed whole exome sequencing (WES) in 60 probands with hereditary spastic paraplegia (HSP) phenotype that was negative for variants in known HSP-related genes. Where PSEN1 mutation was identified, brain biopsy was performed. We investigated the link between HSP and AD with PSEN1 in silico pathway analysis and measured in vivo the stability of PSEN1 mutant γ-secretase. Results: We identified a PSEN1 variant (p.Thr291Pro) in an individual presenting with pure SP at 30 years of age. Three years later, SP was associated with severe, fast cognitive decline and amyloid deposition with diffuse cortical plaques on brain biopsy. Biochemical analysis of p.Thr291Pro PSEN1 revealed that although the mutation does not alter active γ-secretase reconstitution, it destabilizes γ-secretase-amyloid precursor protein (APP)/amyloid beta (Aβn) interactions during proteolysis, enhancing the production of longer Aβ peptides. We then extended our analysis to all 226 PSEN1 pathogenic variants reported and show that 7.5% were associated with pure SP onset followed by cognitive decline later in the disease. We found that PSEN1 cases manifesting initially as SP have a later age of onset, are associated with mutations located beyond codon 200, and showed larger diffuse, cored plaques, amyloid-ring arteries, and severe CAA. Discussion: We show that pure SP can precede dementia onset in PSEN1-related familial AD. We recommend PSEN1 genetic testing in patients presenting with SP with no variants in known HSP-related genes, particularly when associated with a family history of cognitive decline

Effect of high electric fields on the isotropic phase of a lyotropic liquid-crystalline system

The effect of high (>1000 V/mm) electric fields on solutions of a lyotropic liquid-crystalline polymer, poly( n -hexyl isocyanate) in p-xylene, is presented. The concentrations are adjusted such that the solutions are strictly within the isotropic phase domain region, thus exhibiting no spontaneous liquid crystallinity. The effects of field strength, frequency, and concentration are varied and the morphological changes are noted. The results are analyzed with birefringence measurements via comparison with the optical Kerr effect. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4116–4125, 2004Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35008/1/20219_ftp.pd