New onset diabetes complicated by haemolysis and rhabdomyolysis: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Previously undiagnosed glucose-6-phosphate dehydrogenase (G6PD) deficiency can be unmasked by a diabetic crisis and both can be associated with rhabdomyolysis. The relationship between diabetes and G6PD deficiency is discussed and the possible triggers for haemolysis as outlined in this case report. The incidence of G6PD deficiency is 10% in African-American males and up to 35% in parts of Africa so an increased awareness of G6PD deficiency is important when treating diabetes in these populations.</p> <p>Case presentation</p> <p>A 54-year-old Kenyan man presented with a 3-day history of reduced appetite, weakness and reduced level of consciousness as a result of a hyperglycaemic diabetic crisis with both hyperosmolarity and ketoacidosis. The patient then developed haemolysis and a raised creatine kinase level. A diagnosis of G6PD deficiency and rhabdomyolysis was made.</p> <p>Conclusion</p> <p>This case highlights the importance of simple laboratory investigations in the early identification of the rarer complications of diabetic crisis such as haemolysis secondary to G6PD deficiency and rhabdomyolysis.</p

Stress and epilepsy: fact or fiction, and what can we do about it?

People with epilepsy report that stress is their most common trigger for seizures and some believe it caused their epilepsy in the first place. The extensive preclinical, epidemiological and clinical studies examining the link between stress and epilepsy have given confusing results; the clinical studies in particular are fraught with confounders. However stress is clearly bad for health, and we now have substantial preclinical evidence suggesting that chronic stress worsens epilepsy; in selected cases it may even be a causal factor for epilepsy. Healthcare professionals working with people with epilepsy should pay more attention to stress in clinical practice. This review includes some practical advice and guidance for stress screening and management

Leprosy in a patient infected with HIV.

A 60-year-old Nigerian man, who had lived in Europe for 30 years but had returned home frequently, presented with right frontalis muscle weakness and right ulnar nerve palsy, without skin lesions. Neurophysiology showed a generalised neuropathy with demyelinating features. Blood tests were positive for HIV, with a normal CD4 count. There was nerve thickening both clinically and on MRI. Nerve biopsy showed chronic endoneuritis and perineuritis (indicating leprosy) without visible mycobacteria. His neuropathy continued to deteriorate (lepra reaction) before starting treatment with WHO multidrug therapy, highly active antiretroviral therapy and corticosteroids. There are 10 new cases of leprosy diagnosed annually in the UK. Coinfection with HIV is rare but paradoxically does not usually adversely affect the outcome of leprosy or change treatment. However, permanent nerve damage in leprosy is common despite optimal therapy. Leprosy should be considered in patients from endemic areas who present with mononeuritis multiplex

Latent cluster analysis of ALS phenotypes identifies prognostically differing groups

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001). CONCLUSION The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research

Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson's disease.

The progressive nature of Parkinson's disease, its complex treatment regimens and the high rates of comorbid conditions make self-management and treatment adherence a challenge. Clinicians have limited face-to-face consultation time with Parkinson's disease patients, making it difficult to comprehensively address non-adherence. Here we share the results from a multi-centre (seven centres) randomised controlled trial conducted in England and Scotland to assess the impact of using a smartphone-based Parkinson's tracker app to promote patient self-management, enhance treatment adherence and quality of clinical consultation. Eligible Parkinson's disease patients were randomised using a 1:1 ratio according to a computer-generated random sequence, stratified by centre and using blocks of variable size, to intervention Parkinson's Tracker App or control (Treatment as Usual). Primary outcome was the self-reported score of adherence to treatment (Morisky medication adherence scale -8) at 16 weeks. Secondary outcomes were Quality of Life (Parkinson's disease questionnaire -39), quality of consultation for Parkinson's disease patients (Patient-centred questionnaire for Parkinson's disease), impact on non-motor symptoms (Non-motor symptoms questionnaire), depression and anxiety (Hospital anxiety and depression scale) and beliefs about medication (Beliefs about Medication Questionnaire) at 16 weeks. Primary and secondary endpoints were analysed using a generalised linear model with treatment as the fixed effect and baseline measurement as the covariate. 158 patients completed the study (Parkinson's tracker app = 68 and TAU = 90). At 16 weeks Parkinson's tracker app significantly improved adherence, compared to treatment as usual (mean difference: 0.39, 95%CI 0.04-0.74; p = 0.0304) with no confounding effects of gender, number of comorbidities and age. Among secondary outcomes, Parkinson's tracker app significantly improved patients' perception of quality of consultation (0.15, 95% CI 0.03 to 0.27; p = 0.0110). The change in non-motor symptoms was -0.82 (95% CI -1.75 to 0.10; p = 0.0822). 72% of participants in the Parkinson's tracker app group continued to use and engage with the application throughout the 16-week trial period. The Parkinson's tracker app can be an effective and novel way of enhancing self-reported medication adherence and quality of clinical consultation by supporting self-management in Parkinson's disease in patients owning smartphones. Further work is recommended to determine whether the benefits of the intervention are maintained beyond the 16 week study period

The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial

Background: Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. Methods: This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). Findings: 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95–1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83–1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08–1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319–1·458) compared with 1·222 (1·110–1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. Interpretation: These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. Funding: National Institute for Health Research Health Technology Assessment programme

The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial

Background: Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy. Methods: We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5–12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). Findings: 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0–94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96–1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of −0·040 (95% central range −0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years. Interpretation: Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate. Funding: National Institute for Health Research Health Technology Assessment Programme

Why neurology? The career choices of current UK neurology trainees [Conference Abstract]

Introduction It is important that we attract high-calibre medics to neurology. There are few studies of what motivated neurologists to choose their speciality, when they chose, or what else they might have become. Methods All UK neurology trainees were invited to complete an online survey. Results 160 trainees responded (53% female; 17% less-than-fulltime). 54% decided on neurology before graduating (6% before medical school), whilst 29% decided after foundation training. Common reasons to choose neurology included: academically interesting (72%); clinical exposure as a student or junior (67%); personality fit (53%); influential role-model (37%). Less common motivations included lifestyle, family friendliness, prestige, and family members with neurological conditions. Two trainees chose neurology because they personally have a neurological condition. When asked what their second choice of medical career would have been the answers were diverse and 31 different specialties were named, but only one might have been a neurosurgeon. Conclusions Careers advice should begin early in medical school and continue through medical training with direct exposure to clinical neurology. Traditional neurology values such as the intellectual challenge should be emphasised. Neurologists have a broad interest in medical and psychiatric specialties underlining the importance of core medical training to developing neurologists of the future