Amine-reactive crosslinking enhances type 0 collagen hydrogel properties for regenerative medicine.

Introduction: Collagen is extensively utilised in regenerative medicine due to its highly desirable properties. However, collagen is typically derived from mammalian sources, which poses several limitations, including high cost, potential risk of immunogenicity and transmission of infectious diseases, and ethical and religious constraints. Jellyfish-sourced type 0 collagen represents a safer and more environmentally sustainable alternative collagen source. Methods: Thus, we investigated the potential of jellyfish collagen-based hydrogels, obtained from Rhizostoma pulmo (R. pulmo) jellyfish, to be utilised in regenerative medicine. A variety of R. pulmo collagen hydrogels (RpCol hydrogels) were formed by adding a range of chemical crosslinking agents and their physicochemical and biological properties were characterised to assess their suitability for regenerative medicine applications. Results and Discussion: The characteristic chemical composition of RpCol was confirmed by Fourier-transform infrared spectroscopy (FTIR), and the degradation kinetics, morphological, and rheological properties of RpCol hydrogels were shown to be adaptable through the addition of specific chemical crosslinking agents. The endotoxin levels of RpCol were below the Food and Drug Administration (FDA) limit for medical devices, thus allowing the potential use of RpCol in vivo. 8-arm polyethylene glycol succinimidyl carboxyl methyl ester (PEG-SCM)-crosslinked RpCol hydrogels preserved the viability and induced a significant increase in the metabolic activity of immortalised human mesenchymal stem/stromal cells (TERT-hMSCs), therefore demonstrating their potential to be utilised in a wide range of regenerative medicine applications.

The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.

BACKGROUND: Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes. METHODS: SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. FINDINGS: For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine. INTERPRETATION: Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.

The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.

BACKGROUND: Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify. METHODS: SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm B of the study recruited 716 patients for whom valproate was considered to be standard treatment. Patients were randomly assigned to valproate, lamotrigine, or topiramate between Jan 12, 1999, and Aug 31, 2004, and follow-up data were obtained up to Jan 13, 2006. Primary outcomes were time to treatment failure, and time to 1-year remission, and analysis was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. FINDINGS: For time to treatment failure, valproate was significantly better than topiramate (hazard ratio 1.57 [95% CI 1.19-2.08]), but there was no significant difference between valproate and lamotrigine (1.25 [0.94-1.68]). For patients with an idiopathic generalised epilepsy, valproate was significantly better than both lamotrigine (1.55 [1.07-2.24] and topiramate (1.89 [1.32-2.70]). For time to 12-month remission valproate was significantly better than lamotrigine overall (0.76 [0.62-0.94]), and for the subgroup with an idiopathic generalised epilepsy 0.68 (0.53-0.89). But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy. INTERPRETATION: Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies. However, because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.

Measurement of remote memory pre- and post-temporal lobectomy: a longitudinal case study.

There is evidence that remote memory is affected by temporal lobe epilepsy (TLE) and by temporal lobectomy (TL) for the relief of epilepsy. However, remote memory is not routinely assessed when patients with epilepsy undergo neuropsychological testing either pre- or postsurgery. We present a literature review and detailed longitudinal case study of a woman (A.Z.) who had right TLE and fears about deterioration of her remote memory following right TL. Remote memory was assessed by conventional methods (remote memory questionnaire for public events) and by a novel method of seeking vividness ratings for elicited autobiographical memories with A.Z.'s partner acting as the control. A.Z.'s level of memory for remote/recent public events and her rate of forgetting were the same as her partner's, both before and after surgery. A.Z.'s vividness ratings for her own autobiographical memories were similar to her partner's ratings for his memories. Her vividness ratings for her partner's memories that involved events common to both of them were slightly lower than his. A.Z.'s rate of forgetting of her own and her partner's memories was the same as that of her partner, both before and after surgery. There are two principal conclusions. First, this assessment method of measuring remote memory is easy to use and captured the patient's clinical concerns. Second, applying the methodology in this single case suggested that right-sided unilateral TLE and TL may pose no threat to remote memory.

Clinical experience with adjunctive perampanel in adult patients with uncontrolled epilepsy: A UK and Ireland multicentre study.

PURPOSE: To derive clinically useful information about the efficacy and tolerability of adjunctive treatment with perampanel for refractory epilepsy in an outpatient setting. METHOD: We pooled retrospective casenotes data of adult patients with refractory epilepsy prescribed perampanel from 18 hospitals throughout UK and Ireland. RESULTS: Three hundred and ten patients were included (mean age 40.9 [SD=12.0], 50% women, 27.7% with learning disability). The mean duration of epilepsy was 26.7 years (range 2-67 years, SD=13.5) and 91.9% were taking two or more anti-epileptic drugs at the time of perampanel initiation. Mean retention was 6.9 months (range 1 day-22.3 months, SD=4.5). The retention was 86% at 3 months, 71% at 6 months, 47.6% at 12 months and 27% at 18 months. At final follow-up a >50% reduction in seizure frequency was reached in 57.5% of tonic-clonic seizures, 57.4% of complex partial seizures and 43.8% of simple partial seizures. Eleven patients (3.5%) became seizure free. Two hundred and nine patients (67.4%) experienced adverse effects and of these 67% withdrew treatment due to their effects. The most common were sedation, behaviour/mood disturbance, dizziness, and unsteadiness. CONCLUSION: Perampanel appears a safe and effective antiepileptic drug when used as adjunctive therapy in patients with uncontrolled partial epilepsy (including those with learning disability), although few patients achieved complete seizure control. Long-term retention was slightly lower than reported rates for other anti-epileptic drugs, potentially due to the highly refractory population. Monitoring for adverse effects on energy levels, mood and behaviour is recommended.

Clinical experience with oral lacosamide as adjunctive therapy in adult patients with uncontrolled epilepsy: a multicentre study in epilepsy clinics in the United Kingdom (UK).

INTRODUCTION: Lacosamide (LCS) is a new antiepileptic drug (AED) licensed in the European Union (EU) and United States (US) in 2008. AIMS: To evaluate the efficacy and tolerability of add-on LCS in an out-patient epilepsy clinic setting to obtain useful information for everyday practice. METHODS: We pooled data retrospectively from the case note of patients with refractory epilepsy in whom LCS had been prescribed in 19 hospitals across the United Kingdom. RESULTS: Four hundred and three patients were included (mean age 41.9 years, 50.6% women, 18.1% with learning disabilities (LD)). Mean follow-up (FU) was 11.6 months (range one day to 42 months). Most patients (86.9%) presented with symptomatic partial epilepsy (SPE) and 80% were taking two or more antiepileptic drugs (AEDs) when LCS was added (mean 2, range 0-4). Retention rates were 80% at six months, 68% at one year and 45% at two years. The efficacy of LCS was evaluated at three months and at the final FU. At three months one hundred and eight patients (31.1%) reported ≥ 50% seizure reduction and 32 (9.2%) were seizure free. At the final FU 102 (37.5%) reported ≥ 50% seizures reduction and 28 (9.8%) were seizure free. One hundred and ninety three patients (48.7%) reported adverse effects (AEs). The most frequent were sedation and dizziness, followed by nausea. Lacosamide was discontinued in 150 patients (38%), 60 due to AEs alone. CONCLUSION: LCS appears to be an effective and safe AED when used as adjunctive therapy in patients with refractory partial epilepsy.

Orgasm-induced seizures: male studied with ictal electroencephalography.

Reflex seizures can occur in response to a variety of stimuli, both sensory and emotional. Common triggers include light and music; however, in a growing number of case reports, the phenomenon of sexual activity triggering epileptic seizures is described. The majority of these case reports have been in women so far, and most have been found to localise to the right cerebral hemisphere on interictal electroencephalography (EEG). We report the case of a 34-year-old male with orgasm-induced seizures, recorded on ictal EEG. This gentleman's electrophysiology localised his seizure focus to the left cerebral hemisphere, making his case atypical in comparison with the majority of previous reports. Orgasm-induced seizures are an increasingly well-described phenomenon and we suggest that this should be taken into account when assessing patients with possible reflex seizures.

Unusually rapid and severe cognitive deterioration after mild traumatic brain injury.

A 56-year-old man (AB) presented with dramatic cognitive deterioration following a mild traumatic brain injury. There was no indication of severe brain injury or significant anoxic encephalopathy. Detailed history indicated no significant pre-morbid cognitive deficits. His pre-injury psychosocial and occupational functioning was intact. Cognition functioning was impaired immediately post-injury and remained impaired. Neuropsychological examination at 8 months post-injury showed severe cognitive deficits. The cognitive profile was consistent with Alzheimer's disease. MRI at 1-year post-injury showed minor ischaemic changes not consistent with hypoxic injury and insufficient to explain his cognitive problems. Early SPECT was consistent with a diagnosis of Alzheimer's disease and a repeat SPECT showed a significant deterioration in an Alzheimer pattern. AB was seen for detailed serial neuropsychological examination over a 3-year period, which revealed clear evidence of cognitive deterioration consistent with Alzheimer's disease. AB is presented as an unusual case of rapid progressive AD following a mild head injury.