"iDoctor – Medical Blog"

Kornblum C, Lutterbey GG, Czermin B, Reimann J, von Kleist-Retzow J-C, Jurkat-Rott K, Wattjes MP. Whole-body high-field MRI shows no skeletal muscle degeneration in young patients with recessive myotonia congenita.Acta Neurol Scand: 2010: 121: 131[ndash]135.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Background [ndash] Muscle magnetic resonance imaging (MRI) is the most sensitive method in the detection of dystrophic and non-dystrophic abnormalities within striated muscles. We hypothesized that in severe myotonia congenita type Becker muscle stiffness, prolonged transient weakness and muscle hypertrophy might finally result in morphologic skeletal muscle alterations reflected by MRI signal changes.Aim of the study [ndash] To assess dystrophic and/or non-dystrophic alterations such as fatty or connective tissue replacement and muscle edema in patients with severe recessive myotonia congenita.Methods [ndash] We studied three seriously affected patients with myotonia congenita type Becker using multisequence whole-body high-field MRI. All patients had molecular genetic testing of the muscle chloride channel gene (CLCN1).Results [ndash] Molecular genetic analyses demonstrated recessive CLCN1 mutations in all patients. Two related patients were compound heterozygous for two novel CLCN1 mutations, Q160H and L657P. None of the patients showed skeletal muscle signal changes indicative of fatty muscle degeneration or edema. Two patients showed muscle bulk hypertrophy of thighs and calves in line with the clinical appearance.Conclusions [ndash] We conclude that (i) chloride channel dysfunction alone does not result in skeletal muscle morphologic changes even in advanced stages of myotonia congenita, and (ii) MRI skeletal muscle alterations in myotonic dystrophy must be clear consequences of the dystrophic disease process.

Nilsson S, Edvinsson L, Malmberg B, Johansson B, Linde M. A relationship between migraine and biliary tract disorders: findings in two Swedish samples of elderly twins. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01310.x. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Objectives [ndash] To investigate whether there is a relationship between the clinical occurrence of migraine and biliary tract disorders (BTD) and to study whether there is a genetic influence on such an association.Materials and Methods [ndash] The near lifetime morbidity for migraine and BTD was examined in two Swedish twin-samples: OCTO-Twin (149 MZ and 202 DZ pairs; 234 men, 468 women; 80 years of age or older at inclusion), and the GENDER study (249 unlike-sex DZ-pairs; 70[ndash]80 years of age at inclusion). The diagnosis of BTD was established by perusal of medical records from the last twenty years. The diagnosis of migraine was based on iterated questionnaires and personal interviews.Results [ndash] The odds ratio (OR) of BTD among OCTO-Twin subjects suffering from migraine was 3.5 (1.9[ndash]6.7) in monozygotic pairs and 1.7 (1.0[ndash]2.9) in dizygotic pairs The corresponding figures among the GENDER unlike-sex DZ-pairs was 2.7 (1.6[ndash]4.5). Migraine was associated with female sex and waist circumference.Conclusions [ndash] There is a relationship between the occurrence of migraine and BTD, also when controlling for the fact that both disorders are more frequent in women. The association appears to be partly attributable to genetic influences.

Wesnes K, Edgar C, Andreasen N, Annas P, Basun H, Lannfelt L, Zetterberg H, Blennow K, Minthon L. Computerized cognition assessment during acetylcholinesterase inhibitor treatment in Alzheimer’s disease. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01309.x. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Objectives [ndash] Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog) has become a standard clinical trials outcome for cognition, but has been recognized as deficient in areas including coverage of cognitive domains, sensitivity and standardization. Computerized test batteries may address some of these issues. The cognitive drug research computerized assessment (CDR) system is validated in Alzheimer’s disease (AD). This study was designed to further evaluate validity in relation to ADAS-Cog, mini mental state examination (MMSE) and cerebrospinal fluid (CSF) biomarkers and psychometric properties, in a population of Alzheimer’s patients on stable anticholinesterase treatment.Materials and methods [ndash] Patients completed cognition assessments, CSF and blood sampling at baseline and 6 months later. Data for 65 patients were evaluated.Results [ndash] The CDR system demonstrated good psychometric properties in this population. Measures of psychomotor speed showed possible sensitivity to decline over 6 months.Conclusions [ndash] There are a number of methodological problems with current cognition assessment methodology for clinical trials. Computerized measures and in particular millisecond reaction time measures, may address many of these issues.

Lingsma HF, Steyerberg EW, Scholte op Reimer WJM, van Domburg R, Dippel DWJ, the Netherlands Stroke Survey Investigators. Statin treatment after a recent TIA or stroke: is effectiveness shown in randomized clinical trials also observed in everyday clinical practice?Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01247.x.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Aim and background [ndash] The benefit of statin treatment in patients with a previous ischemic stroke or transient ischemic attack (TIA) has been demonstrated in randomized clinical trials (RCT). However, the effectiveness in everyday clinical practice may be decreased because of a different patient population and less controlled setting. We aim to describe statin use in an unselected cohort of patients, identify factors related to statin use and test whether the effect of statins on recurrent vascular events and mortality observed in RCTs is also observed in everyday clinical practice.Methods [ndash] In 10 centers in the Netherlands, patients admitted to the hospital or visiting the outpatient clinic with a recent TIA or ischemic stroke were prospectively and consecutively enrolled between October 2002 and May 2003. Statin use was determined at discharge and during follow-up. We used logistic regression models to estimate the effect of statins on the occurrence of vascular events (stroke or myocardial infarction) and mortality within 3 years. We adjusted for confounders with a propensity score that relates patient characteristics to the probability of using statins.Results [ndash] Of the 751 patients in the study, 252 (34%) experienced a vascular event within 3 years. Age, elevated cholesterol levels and other cardiovascular risk factors were associated with statin use at discharge. After 3 years, 109 of 280 (39%) of the users at discharge had stopped using statins. Propensity score adjusted analyses showed a beneficial effect of statins on the occurrence of the primary outcome (odds ratio 0.8, 95% CI: 0.6[ndash]1.2).Conclusion [ndash] In our study, we found poor treatment adherence to statins. Nevertheless, after adjustment for the differences between statin users and non-statin users, the observed beneficial effect of statins on the occurrence of vascular events within 3 years, although not statistically significant, is compatible with the effect observed in clinical trials.

Almeida L, Nunes T, Sicard E, Rocha J-F, Falcão A, Brunet J-S, Lefebvre M, Soares-da-Silva P. Pharmacokinetic interaction study between eslicarbazepine acetate and lamotrigine in healthy subjects.Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01233.x.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Objective [ndash] Anti-epileptic drugs are often used in combination. Both eslicarbazepine (main metabolite of eslicarbazepine acetate, ESL) and lamotrigine undergo conjugation with glucuronic acid, and both eslicarbazepine and its glucuronide and lamotrigine glucuronide undergo extensive renal elimination; therefore, there is a potential for interaction. This study investigated the interaction between ESL and lamotrigine in healthy subjects.Methods [ndash] Open-label study in two parallel groups of 16 healthy volunteers each. After an 8-day treatment with ESL or lamotrigine, ESL (1200 mg once-daily) and lamotrigine (150 mg once-daily) were co-administered for 19 days. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for maximum plasma concentration (Cmax) and area under the plasma concentration[ndash]time curve in the dosing interval (AUC0[ndash]24) were calculated for eslicarbazepine (ESL active metabolite) and lamotrigine.Results [ndash] The Cmax and AUC0[ndash]24 GMR (90% CI) were, respectively, 95% (87[ndash]102%) and 96% (91[ndash]102%) for eslicarbazepine, and 88% (82[ndash]94%) and 86% (81[ndash]92%) for lamotrigine. The 90% CI of the Cmax and AUC0[ndash]24 GMR fell within the prespecified acceptance interval (80[ndash]125%) both for eslicarbazepine and lamotrigine. Conclusion [ndash] There was no significant pharmacokinetic interaction between ESL and lamotrigine in healthy subjects. Therefore, no dosage adjustment appears to be usually required in either lamotrigine or ESL when the drugs are co-administered.

Jennum P, Kjellberg J. The socio-economical burden of hypersomnia.Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01227.x.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Objectives [ndash] In the absence of socio-economical consequences of hypersomnia this study addresses the factual indirect and direct costs.Methods [ndash] Two thousand two hundred and eight patients with a hypersomnia diagnosis from 1998 to 2005 were identified in the Danish national patient registry (NPR), each compared with 4 age and gender adjusted, randomly chosen citizens selected from the Civil Registration System Statistics. The health cost was decomposed in direct and indirect yearly costs, including labor supply and social transfer payments. Direct costs included frequencies and costs of discharges and outpatient use by cost weights according to diagnosis related groups and specific outpatient prices based on data from The Danish Ministry of Health. The use of and costs of drugs was based on data from the Danish Medicines Agency. The frequencies and costs from primary sectors were based on data from The National Health Security. Indirect costs were based on income data from the coherent social statistics (CSS).Results [ndash] Patients with hypersomnia presented significant higher health related contact rate, expenses and medication use. No differences were identified in employment and income. The yearly sum of direct and indirect costs were yearly [euro]3402 vs. [euro]1212 in controls (P < 0.001), corresponding to a yearly excess costs [euro]2190. The patients presented higher transfer income, total [euro]889. Conclusion [ndash] Hypersomnia patient present higher health and medication uses, and social transfer income and thus represent a significant socio-economical burden.

Lode K, Bru E, Klevan G, Myhr KM, Nyland H, Larsen JP. Coping with multiple sclerosis: a 5-year follow-up study. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01313.x. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Objectives [ndash] To examine how coping styles among patients with multiple sclerosis (MS) change over time and how patients’ coping styles after 5 years are associated with disability pension.Materials and methods [ndash] Seventy-six MS patients and 94 healthy controls were included in this study. The patients were examined at baseline and 5 years later. This included a neurological examination and information on disability pension and a questionnaire assessing coping (the COPE scale). Controls were registered at baseline only.Results [ndash] Compared to healthy controls, MS patients were more passive in coping with disease related distress. This was even more pronounced 5 years later. Disability pensioned patients employed more social support, venting of emotions and behavioural disengagement at follow-up.Conclusion [ndash] This study shows that patients with MS employ coping styles that may be inadequate and this is not improved by adaption over time. Although patients also use strategies to enhance their lives, these findings suggest that there may be a potential for improving the lives of patients with MS through interventions that may enhance adequate coping with the disease.

Dupont S, Striano S, Trinka E, Springub J, Giallonardo AT, Smith P, Ellis S, Yeates A, Baker G. Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS).Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01311.x.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Objectives [ndash] To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials.Methods [ndash] This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10[ndash]13 and 16[ndash]19).Results [ndash] At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3[ndash]41.1%; [ge]50% responder rate was 40.9[ndash]44.2%; and seizure freedom rate was 15.0[ndash]15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%).Conclusions [ndash] Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated.

Liu X, Li L, Tian W, Zhao C, Dogra V. Quantitative diffusion tensor imaging for evaluation of motor function in patients with brain infarcts. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01254.x.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Objective [ndash] To evaluate the quantitative diffusion value in ipsilateral cerebral peduncle of patients with differing motor function abilities and analyse the thresholds discriminating the poor motor function disability.Method [ndash] Twenty-nine patients who previously suffered stroke underwent diffusion tensor imaging examinations. Motor function was evaluated 8 months after the event. The ipsilateral apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of cerebral peduncle and ADC ratio and FA ratio of patients with different motor function scales were analysed.Results [ndash] The ipsilateral FA value and FA ratio were distinctly different in patients with different motor function scales, and significantly correlated with the motor function scales. There was no significant difference of ipsilateral ADC and ADC ratio, and neither had correlation with motor function scale. The patients with poor motor function scale could be discriminated by the cutoff value of ipsilateral FA of 0.453 and FA ratio of 0.623 with sensitivity of 90%, 75% and specificity of 88.9%, 88.9% respectively.Conclusions [ndash] The ipsilateral FA value and FA ratio were feasible and better imaging indices in discriminating patients with poor motor function ability.

Marousi S, Theodorou G, Karakantza M, Papathanasopoulos P, Ellul J. Serum adiponectin acutely after an ischemic stroke: implications for a long-lasting, suppressed anti-inflammatory role.Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01231.x.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.Objective [ndash] Past ischemic stroke (IS) patients display suppressed adiponectin (ADPN) levels a few months after disease onset. It is still unclear whether hypoadiponectinemia is already present by the early stages of stroke or occurs as a delayed effect of the acute ischemic reaction. In the present study we investigated ADPN levels acutely after an IS.Materials and methods [ndash] Serum ADPN was measured in 82 consecutive acute IS patients, and 30 stroke-free subjects of similar age and sex distributions.Results [ndash] Patients had significantly lower ADPN levels than controls. Higher ADPN was significantly associated with reduced odds for IS accounting for age, sex and high-density lipoproteins. This association was strengthened after further adjustments for potential confounders. ADPN levels remained suppressed even 6 months after stroke.Conclusions [ndash] ADPN is significantly suppressed already by the early phases of stroke, and remains unchanged 6 months later. We propose a stable-over-time anti-inflammatory role of ADPN in IS, unrelated to the acute ischemic reaction.