Diseases associated with multiple sclerosis and epilepsy

A defined general population of 159,200 male and female native Swedes born in the period 1911-1940 from an urban catchment area of the then only general hospital, was followed over a decade (1970-79) with regard to in-patient hospitalization for all kinds of diagnoses. As a part of this population cohort study, multiple sclerosis cases (n = 351) and epilepsy cases (n = 648) were studied for association with other diseases. Unexpectedly, a cluster of diseases encompassing tuberculosis, bronchial asthma, diabetes mellitus and myocardial infarction, among the diseases associated with multiple sclerosis, also forms a gradient; this suggests a quantitative rather than a qualitative multifactorial model of disease for the understanding of the pathogenesis of MS. In epilepsy, heterogeneity was suggested as being mainly linked to the presence or absence of co-existing alcoholism. Brain tumours in cases of epilepsy were found almost exclusively in the latter subset and prevailing among younger people independent of sex (with an almost 100-fold excess rate of that disease combination as expected by chance only).     

Drug-resistant epilepsy in children with partial onset epilepsy treated with carbamazepine

Objective: To evaluate the outcome, including drug-resistant epilepsy (DRE) in children with newly diagnosed partial onset epilepsy treated with carbamazepine (CBZ). Methods: A retrospective medical records review and telephone questionnaire were undertaken on a total of 100 subjects. Results: Long-term follow-up was obtained on 79 children with a mean duration of 7.1 years from CBZ initiation. A total of 66 (83.5%) subjects achieved 2-year seizure remission, 48 (72.7%) subjects did so with CBZ monotherapy. Seven (10.6%) had seizure recurrence after 2-year seizure remission. DRE was diagnosed in seven (8.9%) subjects and five subjects had epilepsy surgery. The mean duration from seizure onset to epilepsy surgery was 5.3 (±2.1) years. Contributing factors for the prolonged duration from seizure onset to epilepsy surgery were identified including: relapsing–remitting course of seizure, family reluctance for epilepsy surgery and uncontrolled psychological problems. Conclusions: Over 80% of children with newly diagnosed partial onset epilepsy who were initially treated with CBZ achieved 2-year seizure remission, and more than 70% of this group did so with CBZ monotherapy. The majority of these patients maintained seizure remission overtime. However, 8.9% of this population met the criteria for DRE and most of them had epilepsy surgery. The duration from seizure onset to epilepsy surgery is an important potential area for improvement in DRE patient care.     

Generalized penicillin epilepsy in the cat and the brain uptake of carbamazepine

Carbamazepine (CBZ) brain uptake was determined in cats rendered epileptic by administration of 250,000 IU penicillin/kg intramuscularly, and the results were compared with those in a control group. CBZ penetration in the brain was significantly different in the epileptic cats, the uptake of the drug in the generalized epileptic brain being decreased and delayed, although substantial binding occurred also in this case. Plasma and CSF levels behaved similarly in normal and epileptic cats. Arguably the impaired CBZ brain uptake was due to the epileptic activity itself, which per se can be responsible for marked inhibition of protein synthesis, thus modifying the proven ability of CBZ to bind to phospholipid and protein components of neuronal cells.

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Sommario L'uptake cerebrale di carbamazepina (CBZ) è stato determinato in gatti resi epilettici mediante la somministrazione di 250.000 U.I. di penicillina per Kg. intramuscolare. Confrontando i risultati con un gruppo di controllo, la penetrazione della CBZ nel cervello è stata significativamente minore nei gatti epilettici, essendo l'uptake del farmaco nel cervello affetto da epilessia generalizzata diminuito e ritardato, sebbene un binding sostanziale avvenga anche in questo caso. I livelli plasmatici e liquorali seguono un comportamento analogo nei due gruppi. Si può speculare ipoteticamente che l'alterato uptake cerebrale di CBZ sia dovuto alla stessa attività epilettica, che di per sé può essere responsabile di una marcata inibizione della sintesi proteica, così modificando la dimostrata capacità della CBZ di legarsi ai componenti fosfolipidici e proteici delle cellule nervose.

     

Topiramate,carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy

OBJECTIVES: To compare topiramate (TPM) with investigator's choice of carbamazepine (CBZ) or valproate (VPA) for initial treatment in patients with newly diagnosed epilepsy. MATERIAL AND METHODS: In patients with epilepsy diagnosed within previous 3 months, investigators selected CBZ (600 mg/day) or VPA (1250 mg/day) as preferred therapy based on the patient's clinical presentation. Based on investigators' treatment choice, patients (n=613) were assigned to the CBZ or VPA treatment branch. Within each branch, patients were randomized to double-blind treatment with the traditional antiepileptic drugs (CBZ or VPA), TPM 100 mg/day, or TPM 200 mg/day. Patients continued double-blind treatment until exiting the study or until 6 months after last patient randomized. RESULTS: No statistically significant differences between fixed doses of TPM and CBZ or VPA were observed in efficacy measures: time to exit, time to first seizure, and the proportion of patients seizure-free during the last 6 months of treatment. TPM 100 mg/day was associated with the fewest discontinuations due to adverse events. CONCLUSION: In patients with newly diagnosed epilepsy, an initial target dose of TPM 100 mg/day is at least as effective as therapeutic doses of CBZ and VPA.     

''Gender gap'' in multiple sclerosis: magnetic resonance imaging evidence

The authors evaluated the gender difference in the magnetic resonance imaging characteristics of the lesions occurring in the brain of 413 multiple sclerosis (MS) patients. Men had fewer contrast-enhancing lesions (P = 0.01), but a higher proportion of lesions evolving into 'black holes' (P = 0.001), when compared with women. Thus, our data indicate that men with MS are prone to develop less inflammatory, but more destructive lesions than women. This study results provides support for a modulation of the MS pathological changes by gender.     

Conversion from carbamazepine or oxcarbazepine to topiramate in adolescents and adults with epilepsy

Objective – To explore effectiveness, tolerability and changes in quality of life in patients with epilepsy converting to topiramate (TPM) from carbamazepine (CBZ) or oxcarbazepine (OXC) due to insufficient effectiveness and/or tolerability. Methods – A multicenter, open‐label, non‐interventional trial was used to examine patients (≥ 12 years) with epilepsy, changing to TPM monotherapy from baseline mono‐ or combination therapy with CBZ or OXC. TPM was added to the existing antiepileptic drug (AED) treatment and started at a dose of 25 mg once daily. The dose was titrated up with 25 mg/day increments, once every 1–2 weeks, until a final dose between 50 and 200 mg/day was reached. On the basis of clinical judgment, the treating physician decided whether or not the existing AED treatment with CBZ or OXC could then be withdrawn. Type and number of seizures, preferred TPM dose, quality of life (QOLIE‐10 questionnaire), subjective perception of improvement and adverse events (AE) were documented. Results – 140 patients (53.5% women, mean age 47 years) decided to switch to TPM due to insufficient effectiveness (75% of patients) and/or poor tolerability (80%) of the CBZ/OXC treatment. Average duration of follow‐up was 24 weeks with an overall discontinuation rate of 19.3%, mainly due to AEs (12.1%). At study endpoint, the intended shift to TPM monotherapy was achieved in 73% of patients at a median TPM dose of 100 mg/day. A seizure reduction of ≥ 50% was achieved in 91% of patients in the last scheduled period (weeks 12–26); 62% of patients entering that period remained seizure free. Quality of life at endpoint improved significantly when compared with baseline for all domains of QOLIE‐10 (P < 0.001). Most frequent AEs (reported by ≥ 5% of patients) were paresthesia (9.3%), weight loss (7.9%), convulsions (5.7%) and memory disorders (5.0%). Conclusion – In patients with epilepsy, previously not satisfactorily treated with CBZ or OXC, conversion to TPM may result in an improvement in seizure control as well as in quality of life.     

Pediatric multiple sclerosis

Pediatric multiple sclerosis (MS) represents a particular MS subgroup with unique diagnostic challenges and many unanswered questions. Due to the narrow window of environmental exposures and clinical disease expression, children with MS may represent a particularly important group to study to gain a better understanding of MS pathogenesis. Acute disseminated encephalomyelitis (ADEM) is more common in children than in adults, often making the differential diagnosis of MS, particularly a clinically isolated syndrome, quite difficult. Although both disorders represent acute inflammatory disorders of the central nervous system and have overlapping symptoms, ADEM is typically (not always) self-limiting. The presence of encephalopathy is much more characteristic of ADEM and may help in distinguishing between the two. Young children (under ten years old) with MS differ the most from adults. They have a lower frequency of oligoclonal bands in their cerebrospinal fluid and are less likely to have discrete lesions on MRI. Problems of cognitive dysfunction and psychosocial adjustment have particularly serious implications in both children and teenagers with MS. Increased awareness of these difficulties and interventions are needed. While clinical research on therapies to alter the disease course is limited, the available data fortunately suggests that disease-modifying therapy is well tolerated and likely to be effective. Ultimately, multinational research studies are necessary to advance our knowledge of the causes, symptoms, and treatment of pediatric MS and such collaborations are currently underway.     

多发性硬化的临床特点与预后的分析

目的分析多发性硬化(MS)的临床特点与预后。方法回顾性分析117例MS患者的临床资料,从临床、影像学等方面对视神经脊髓型(OSMS)和经典MS型(CMS)进行比较。结果117例MS患者中,OSMS型42例(35.9%),CMS型75例(64.1%)。临床表现中,OSMS患者出现肢体无力(88.1%)、感觉缺失(85.7%)、感觉异常(57.1%)、视物模糊(76.2%)、尿便障碍(73.8%)明显多于CMS患者(70.7%、56.0%、20.0%、45.3%及26.7%)(均P<0.05);出现共济失调(7.1%)、复视(0)及构音不清(0)明显少于CMS患者(42.7%、10.7%及16.0%)(P<0.05～0.01)。OSMS患者出现长节段融合性脊髓病变的比例(94.1%)显著多于CMS患者(48.2%)(P<0.01)。脑脊液检查和诱发电位检查结果OSMS组和CMS组差异无统计学意义。发病5年后扩大的残疾状态量表(EDSS)评分OSMS组(2.42±0.90)显著高于CMS组(1.50±0.88)(P<0.05)。在发病的第1年和第3年,年平均复发次数复发缓解型OSMS[(1.92±1.05)次、(1...     

Alterations in semen parameters in men with epilepsy treated with valproate or carbamazepine monotherapy

Men with epilepsy are known to have reduced fertility. Whether this is drug-induced or a result of the epilepsy itself is still under debate. Few studies have been carried out on semen from men with epilepsy. The aim of the present study was first to investigate possible drug-specific effects of long-term treatment with either valproate or carbamazepine on semen quality and testicular size, and secondly to see whether the results in epilepsy patients differed from healthy fertile males. Men with epilepsy, 20-40 years old, having used either valproate (n = 16) or carbamazepine (n = 20) for >2 years, were included. The semen data of healthy fertile men without epilepsy in the same age group (n = 90) were used as controls. The semen was examined according to WHO (1999). No significant differences in semen quality were seen between men receiving either valproate or carbamazepine. However, semen from the valproate-treated, as opposed to the carbamazepine-treated, differed from controls with regard to tail abnormalities. Absolute testicular size was not significantly different between the two treatment groups. However, after correcting for changes in body mass index (BMI), the testicular size/BMI ratio was lower in the valproate-treated patients. The valproate-treated patients gained significantly more weight than the carbamazepine-treated patients after start of current medication. No differences between the patient groups were found in terms of libido/potency or number of pregnancies fathered. When comparing all epilepsy patients with healthy fertile males, there was a significant reduction in the percentage of rapidly progressive motile sperms in the semen from epileptic patients. The semen from men with epilepsy also showed significant differences from the controls regarding neck and head abnormalities of the spermatozoa.     

Comparison of patient‐reported outcome measures in multiple sclerosis

Background

Patient‐reported outcome measurements (PROMS) have been proposed sensitive outcome parameters in multiple sclerosis (MS). In this study, we assessed a German version of the Multiple Sclerosis Impact Scale (MSIS‐29) and a revised version of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) in comparison with rater‐ and physician‐based tools.

Methods

Consecutive MS patients (n = 117) of the MS outpatient unit were included. In addition to MSIS‐29 and HAQUAMS, the following parameters were obtained: Expanded Disability Status Scale (EDSS) and modified Multiple Sclerosis Functional Composite (MSFC) [9‐hole peg test (9HPT), 25‐foot walk test and symbol digit modalities test]. We investigated validity, internal consistency and test–retest reliability as well as correlation between these measures.

Results

Internal consistency (Cronbach's α ≤ 0.96) and test–retest coefficients (ICC ≤ 0.87) of both scales were high and satisfied psychometric standards. Convergent and discriminant validity was supported by direction, magnitude and pattern of correlation with other rater‐based measures depending on the functional subdomain. Both MSIS‐29 and HAQUAMS correlated with EDSS (ρ = 0.55 vs 0.62), but stronger correlation was found between MSIS‐29 and HAQUAMS total score (ρ = 0.90). Both scales distinguished between patient groups of varied disease severity and cognitive impairment.

Conclusion

Patient‐reported outcome measurements as MSIS‐29 and HAQUAMS seem to be valid instruments to detect different impairment levels in comparison with traditional rater‐based instruments like EDSS or MSFC.     

The frequency of relapse in multiple sclerosis

Summary The authors analyze the course of 245 cased of multiple sclerosis. The mean annual frequency of attacks is 0.66 for all the patients (remittent forms and progressive forms). Although it is usually suggested that this frequency decreases with the years, this has not been found in our study. Our results also indicate that we would have to follow 590 patients over 1 year or 190 over 2 years before being able to attest the effectiveness of a treatment decreasing the frequency of attacks by 25%.Ingénieur I.N.S.E.R.M.     

Comparison of upright balance in stroke,Parkinson and multiple sclerosis

Background – Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. There is a complete lack of studies that assessed quality of life (QoL) trajectory during time in DM1 cohorts. Aim – To analyze changes of QoL in patients with DM1 during a 5‐year follow‐up period and to assess responsiveness of the SF‐36 questionnaire. Patients and Method – At the baseline, this study comprised 84 DM1 patients, of whom 62 were retested after the mean period of 64.2 ± 3.9 months. Severity of muscular weakness was assessed using the Muscular Impairment Rating Scale (MIRS). Patients completed Serbian version of the SF‐36 questionnaire as a measure of health‐related QoL. Results – After 5 years, MIRS score of our DM1 patients showed significant progression of 0.5 grade (P < 0.01). All mental subdomains, role physical, and total SF‐36 scores significantly improved after 5 years (P < 0.01). Unexpectedly, worsening of muscular weakness from mild to severe was in association with improvement of QoL. Conclusion – QoL improved in our cohort of DM1 patients during a 5‐year period despite the progression of the disease. SF‐36 should be used with caution as a patient‐reported outcome measure in DM1 clinical trials.     

Depression and neuroticism in multiple sclerosis

88 subjects (36 males and 52 females) affected by multiple sclerosis (MS), were studied with the CES-D and SRT tests for the evaluation of depressive reactions and neuroticism. Comparing the results with those of the control group, we found a significant score for depression and somatization in the MS patients, whereas the scores for anxiety and inadequacy were normal.

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Sommario Gli AA hanno eaminato 88 soggetti (36 maschi e 52 femmine) affetti da sclerosi multipla ai quali sono stati applicati i questionari del CES-D e SRT per la valutazione delle reazioni depressive e del nevroticismo. Dalla comparazione dei risultati con quelli del gruppo di controllo, emergono differenze statisticamente significative nella popolazione esaminata per quanto riguarda depressione e somatizzazione mentre i punteggi per ansia ed inadeguatezza risultano normali.

     

Increasing prevalence of multiple sclerosis in Finland

Objectives – To follow‐up the prevalence trends of MS from 1983 to 1993 in western and southern Finland. MS epidemiology has been previously followed from 1964 to 1978 in these regions. The updated prevalences were correlated with incidence trends in the same period. Methods– Age‐adjusted and age‐specific MS prevalence rates were calculated for cases classified by Poser's criteria. Results– In the western health‐care districts, Seinäjoki and Vaasa, prevalences in 1993 were 202/10⁵ and 111/10⁵. In the southern district Uusimaa the respective figure was 108/10⁵. In Seinäjoki a significant 1.7‐fold increase was found in 1993 as compared to 1983, mainly due to increased incidence. In Uusimaa a significant 1.2‐fold increase in prevalence was found in the presence of stable incidence. In Vaasa prevalence was stable, although incidence was declining. Conclusion– The prevalence of MS is increasing in Seinäjoki and Uusimaa but not in Vaasa. Both the prevalence and incidence in Seinäjoki are now among the highest reported.     

Clinical picture of multiple sclerosis with late onset

A group of 47 patients (multiple sclerosis (M.S.) diagnosed according to Schumacher's criteria) with age at onset over 40 years, was studied by statistical analysis and compared with a control group (100 M.S. patients with onset between ages 18 and 38).
The following features appear peculiar in this group:
– the most frequent initial symptoms are motor disturbances
– the onset is generally monosymptomatic
– the course is generally progressive and more severe than that of controls, as seen by Kurtzke's Disability Scale, relapse rate, interval between first and second attack
– the course is more severe when the onset is progressive and characterized by motor disturbances.     

Smoke exposure increases the risk for multiple sclerosis

Purpose and methods:  To estimate the effect of exposure to smoking on the risk for multiple sclerosis (MS), we analyzed nicotine metabolite (cotinine) levels in biobank samples from 109 MS cases and 218 matched referents.
Results:  Elevated cotinine levels, even modest elevations, were associated with an increased risk for MS (all other categories versus lowest: OR = 2.9; 95% CI: 1.3–6.3). A similar but non-significant risk increase was observed also in the small subset of individuals with samples collected before the onset of MS (all other categories versus lowest: OR = 2.4; 95% CI: 0.26–21). Elevated cotinine was associated with an increased risk for MS predominantly in women (all other categories versus lowest category: OR = 3.9; 95% CI: 1.3–12), whereas the risk increase in men was smaller and non-significant.
Discussion:  Smoke exposure is associated with a higher risk for MS than previously estimated. There seems to be a threshold effect present in the lower range of cotinine in its relation to MS. Modestly elevated cotinine levels suggestive of passive smoking are associated with an increased risk for MS. Smoke exposure may explain the higher incidence of MS in women. These preliminary findings need to be confirmed in an expanded material of prospectively collected samples.