The organisation of physiotherapy for people with multiple sclerosis across Europe: a multicentre questionnaire survey.

BACKGROUND: Understanding the organisational set-up of physiotherapy services across different countries is increasingly important as clinicians around the world use evidence to improve their practice. This also has to be taken into consideration when multi-centre international clinical trials are conducted. This survey aimed to systematically describe organisational aspects of physiotherapy services for people with multiple sclerosis (MS) across Europe. METHODS: Representatives from 72 rehabilitation facilities within 23 European countries completed an online web-based questionnaire survey between 2013 and 2014. Countries were categorised according to four European regions (defined by United Nations Statistics). Similarities and differences between regions were examined. RESULTS: Most participating centres specialized in rehabilitation (82 %) and neurology (60 %), with only 38 % specialising in MS. Of these, the Western based Specialist MS centres were predominately based on outpatient services (median MS inpatient ratio 0.14), whilst the Eastern based European services were mostly inpatient in nature (median MS inpatient ratio 0.5). In almost all participating countries, medical doctors - specialists in neurology (60 %) and in rehabilitation (64 %) - were responsible for referral to/prescription of physiotherapy. The most frequent reason for referral to/prescription of physiotherapy was the worsening of symptoms (78 % of centres). Physiotherapists were the most common members of the rehabilitation team; comprising 49 % of the team in Eastern countries compared to approximately 30 % in the rest of Europe. Teamwork was commonly adopted; 86 % of centres based in Western countries utilised the interdisciplinary model, whilst the multidisciplinary model was utilised in Eastern based countries (p = 0.046). CONCLUSION: This survey is the first to provide data about organisational aspects of physiotherapy for people with MS across Europe. Overall, care in key organisational aspects of service provision is broadly similar across regions, although some variations, for example the models of teamwork utilised, are apparent. Organisational framework specifics should be considered anytime a multi-centre study is conducted and results from such studies are applied.

Goal attainment in cognitive rehabilitation in MS patients.

The aim of the study was to investigate the predictive value of important disease-related variables on goal attainment in cognitive rehabilitation in multiple sclerosis (MS). The possible predictive value of executive functions, neurological disability, depression and general cognitive ability was assessed, employing Goal Attainment Scaling (GAS). Fifty-seven patients with MS were assessed for executive functions, neurological disability, depression and general cognitive ability, and guided through the process of formulating GAS-goals for coping with cognitive challenges in everyday life during a four week in-patient cognitive rehabilitation programme. GAS-goal attainment was scored during biweekly follow-up calls in the first three months post-discharge from the rehabilitation centre, and finally at seven months after the start of the rehabilitation. Consistent with the first study hypothesis MS patients succeeded in formulating and achieving GAS goals for coping with cognitive problems in everyday life. The patients were able to maintain a satisfactory level of goal attainment from the first measurement point after six weeks to seven months after the start of the rehabilitation. However, contrary to the second hypothesis, attainment of GAS goals was not predicted by executive functions. Neither was it predicted by neurological disability, depression or general cognitive ability. The findings suggest that GAS may be a practical and robust method in cognitive rehabilitation in MS patients, regardless of important disease-related characteristics.

NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial.

BACKGROUND: Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective, and new more effective and safe strategies are needed. Our aim was to assess the efficacy of oral methylprednisolone as an add-on therapy to subcutaneous interferon beta-1a to reduce the yearly relapse rate in patients with relapsing-remitting multiple sclerosis. METHODS: NORMIMS (NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis) was a randomised, placebo-controlled trial done in 29 neurology departments in Denmark, Norway, Sweden, and Finland. We enrolled outpatients with relapsing-remitting multiple sclerosis who had had at least one relapse within the previous 12 months despite subcutaneous interferon beta-1a treatment (44 microg three times per week). We randomly allocated patients by computer to add-on therapy of either 200 mg methylprednisolone or matching placebo, both given orally on 5 consecutive days every 4 weeks for at least 96 weeks. The primary outcome measure was mean yearly relapse rate. Primary analyses were by intention to treat. This trial is registered, number ISRCTN16202527. FINDINGS: 66 patients were assigned to interferon beta and oral methylprednisolone and 64 were assigned to interferon beta and placebo. A high proportion of patients withdrew from the study before week 96 (26% [17 of 66] on methylprednisolone vs 17% [11 of 64] on placebo). The mean yearly relapse rate was 0.22 for methylprednisolone compared with 0.59 for placebo (62% reduction, 95% CI 39-77%; p<0.0001). Sleep disturbance and neurological and psychiatric symptoms were the most frequent adverse events recorded in the methylprednisolone group. Bone mineral density had not changed after 96 weeks. INTERPRETATION: Oral methylprednisolone given in pulses every 4 weeks as an add-on therapy to subcutaneous interferon beta-1a in patients with relapsing-remitting multiple sclerosis leads to a significant reduction in relapse rate. However, because of the small number of patients and the high dropout rate, these findings need to be corroborated in larger cohorts.

[Motor symptoms in Parkinson disease]. / Motoriske symptomer ved Parkinsons sykdom.

BACKGROUND: Early Parkinson's disease is dominated by a motor syndrome called parkinsonism, but as the disease develops motor complications and non-motor problems may occur as well. This paper describes how to diagnose Parkinson's disease and the various motor complications and gives recommendations on how to treat the symptoms in these patients. MATERIAL AND METHODS: The paper builds on international evidence-based publications and the Norwegian guidelines for treatment of Parkinson's disease. RESULTS AND INTERPRETATION: Motor symptoms such as tremor at rest, akinesia, rigidity and postural instability are the cardinal signs in Parkinson's disease. After diagnosing a patient with the disease we recommend to start with selegiline as a disease-modifying treatment strategy. When symptoms lead to functional impairment, symptomatic treatment should be started in addition. Dopamine agonists are primarily recommended in younger patients and levodopa in the older ones. When the patients develop motor complications it is important to first thoroughly evaluate the problems to arrive at the best possible treatment strategy. If a sufficient response is not obtained both deep brain stimulation and treatment with continuous delivery of medication should be considered.

[Continuous treatment with levodopa of Parkinson disease]. / Kontinuerlig behandling med levodopa ved Parkinsons sykdom.

BACKGROUND: The advanced stage of Parkinson's disease is characterised by motor fluctuations which are often difficult to control on traditional, peroral levodopa medication. We present our experience and a literature search regarding a method for continuous intraduodenal administration of a levodopa/carbidopa gel (Duodopa). METHODS: In a pilot study based on the compassionate use of continuous intraduodenal levodopa, patients were tested via nasoduodenal administration of the gel and on-off registration. For patients in whom a significant improvement in time in near-normal function per day was seen, permanent administration was started through a permanent duodenal port via percutaneous endoscopic gastrostomy with an inner catheter to the duodenal-jejunal transition. RESULTS AND CONCLUSION: In the nine patients tested, a significant functional improvement over time was seen. Five patients now have a permanent system with lasting good effect. Qualitative evaluation shows maintained good effect over a follow up time of up to 2.5 years (mean 19 months). We conclude that continuous enteral levodopa administration is a good and safe alternative especially for patients not offered deep brain stimulation. Its place among other treatment methods needs further assessment.

[Optic neuritis--diagnosis, treatment and follow up]. / Optikusnevritt--diagnose, behandling og oppfølging.

A national group of neurologists and ophthalmologists have evaluated guidelines and recommendations for diagnosis, treatment and follow up of optic neuritis based on clinical experience and a review of relevant literature. Optic neuritis is a common, well characterised condition that appears as an isolated syndrome or as a manifestation of multiple sclerosis. Several other diseases must be considered for a differential diagnosis. Corticosteroid treatment of optic neuritis has been investigated in a number of trials, which show that corticosteroid treatment speeds up the recovery of vision without affecting the final visual outcome. The diagnostic procedure and the treatment options have changed over the last few years. Some aspects of investigation, treatment and follow up are still controversial.

Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis.

Objective. Patients with multiple sclerosis (MS) are often suffering from neuropathic pain. Antiepileptic drugs (AEDs) and tricyclic antidepressants (TCAs) are commonly used and are susceptible to be involved in drug interactions. The aim of this retrospective study was to investigate the prevalence of use of antiepileptic and antidepressive drugs in MS patients and to discuss the theoretical potential for interactions. Methods. Review of the medical records from all patients treated at a dedicated MS rehabilitation centre in Norway between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation stay during the study period. Of these, 342 (31%; 249 females) with mean age of 53 (±10) years and EDSS 4.8 (±1.7) used at least one AED (gabapentin 12.7%, pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6%) or amitriptyline (9.7%). Polypharmacy was widespread (mean 5.4 drugs) with 60% using additional CNS-active drugs with a propensity to be involved in interactions. Age, gender, and EDSS scores did not differ significantly between those using and not using AED/amitriptyline. Conclusion. One-third of MS patients attending a rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of polypharmacy and use of CNS-active drugs calls for awareness of especially pharmacodynamic interactions and possible excessive adverse effects.

Real life cost and quality of life associated with continuous intraduodenal levodopa infusion compared with oral treatment in Parkinson patients.

Advanced-stage Parkinson's disease (PD) strongly affects quality of life (QoL). Continuous intraduodenal administration of levodopa (IDL) is efficacious, but entails high costs. This study aims to estimate these costs in routine care. 10 patients with advanced-PD who switched from oral medication to IDL were assessed at baseline, and subsequently at 3, 6, 9 and 12 months follow-up. We used the Unified PD Rating Scale (UPDRS) for function and 15D for Quality of Life (QoL). Costs were assessed using quarterly structured patient questionnaires and hospital registries. Costs per quality adjusted life year (QALY) were estimated for conventional treatment prior to switch and for 1-year treatment with IDL. Probabilistic sensitivity analysis was based on bootstrapping. IDL significantly improved functional scores and was safe to use. One-year conventional oral treatment entailed 0.63 QALY while IDL entailed 0.68 (p > 0.05). The estimated total 1-year treatment cost was NOK419,160 on conventional treatment and NOK890,920 on IDL, representing a cost of NOK9.2 million (€1.18 mill) per additional QALY. The incremental cost per unit UPDRS improvement was NOK25,000 (€3,250). Medication was the dominant cost during IDL (45% of total costs), it represented only 6.4% of the total for conventional treatment. IDL improves function but is not cost effective using recommended thresholds for cost/QALY in Norway.

Vitamin D and disease activity in multiple sclerosis before and during interferon-ß treatment.

OBJECTIVE: Studies based on deseasonalized vitamin D levels suggest that vitamin D may influence the disease activity in multiple sclerosis (MS), and high doses are suggested as add-on treatment to interferon-ß (IFN-ß). Seasonal fluctuation of vitamin D varies between individuals, thus the relationship to disease activity should preferentially be studied by repeated and simultaneous vitamin D and MRI measurements from each patient. METHODS: This was a cohort study comprising 88 patients with relapsing-remitting MS who were followed for 6 months with 7 MRI and 4 25-hydroxyvitamin D measurements before initiation of IFN-ß, and for 18 months with 5 MRI and 5 25-hydroxyvitamin D measurements during IFN-ß treatment. RESULTS: Prior to IFN-ß treatment, each 10 nmol/L increase in 25-hydroxyvitamin D was associated with 12.7% (p = 0.037) reduced odds for new T1 gadolinium-enhancing lesions, 11.7% (p = 0.044) for new T2 lesions, and 14.1% (p = 0.024) for combined unique activity. Patients with the most pronounced fluctuation in 25-hydroxyvitamin D displayed larger proportion of MRI scans with new T1 gadolinium-enhancing lesions (51% vs 23%, p = 0.004), combined unique activity (60% vs 32%, p = 0.003), and a trend for new T2 lesions (49% vs 28%, p = 0.052) at the lowest compared to the highest 25-hydroxyvitamin D level. No association between 25-hydroxyvitamin D and disease activity was detected after initiation of IFN-ß. HLA-DRB1*15 status did not affect the results. CONCLUSION: In untreated patients with MS, increasing levels of 25-hydroxyvitamin D are inversely associated with radiologic disease activity irrespective of their HLA-DRB1*15 status.