Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis - a pilot trial.

INTRODUCTION: Patients with multiple sclerosis may have a distinct gut microbiota profile. Delayed-release dimethyl fumarate is an orally administered drug for relapsing-remitting multiple sclerosis, which has been associated with gastrointestinal side-effects in some patients. OBJECTIVES: The purpose of this study was to determine if dimethyl fumarate alters the abundance and diversity of commensal gut bacteria, and if these changes are associated with gastrointestinal side-effects. METHODS: Thirty-six patients with relapsing-remitting multiple sclerosis received either dimethyl fumarate (n = 27) or an injectable multiple sclerosis disease-modifying therapy (glatiramer acetate or interferons, n = 9) for 12 weeks. Stool samples were collected at baseline, two and 12 weeks. We included 165 healthy individuals as controls. RESULTS: At baseline, 16 microbial genera were altered in multiple sclerosis patients compared with healthy controls. In the dimethyl fumarate-treated patients (n = 21) we observed a trend of reduced Actinobacteria (p = 0.03, QFDR = 0.24) at two weeks, mainly driven by Bifidobacterium (p = 0.06, QFDR = 0.69). At 12 weeks, we observed an increased abundance of Firmicutes (p = 0.02, QFDR = 0.09), mostly driven by Faecalibacterium (p = 0.01, QFDR = 0.48). CONCLUSIONS: This pilot study did not detect a major effect of dimethyl fumarate on the gut microbiota composition, but we observed a trend towards normalization of the low abundance of butyrate-producing Faecalibacterium after 12 weeks treatment. The study was underpowered to link microbiota to gastrointestinal symptoms.

Wake-up stroke-Amendable for thrombolysis-like stroke with known onset time?

Patients suffering an acute ischemic stroke can be treated with intravenous thrombolysis in the absence of contraindications. A known onset time is a prerequisite as treatment, according to guidelines, has to be started within 4.5 hours. In patients awakening with a stroke, the last time they were seen without a neurological deficit is assumed to be the time of onset. Thus, despite of lack of contraindications on initial brain imaging, these patients are largely excluded from therapy. This review discusses the underlying pathophysiological, clinical, and radiological evidence surrounding wake-up stroke and its consequences for making treatment decisions.

Radiological imaging in acute ischaemic stroke.

Patients who suffer acute ischaemic stroke can be treated with thrombolysis if therapy is initiated early. Radiological evaluation of the intracranial tissue before such therapy can be given is mandatory. In this review current radiological diagnostic strategies are discussed for this patient group. Beyond non-enhanced computed tomography (CT), the standard imaging method for many years, more sophisticated CT stroke protocols including CT angiography and CT perfusion have been developed, and additionally an increasing number of patients are examined with magnetic resonance imaging as the first imaging method used. Advantages and challenges of the different methods are discussed.

MRI evaluation of grey matter atrophy and disease course in multiple sclerosis: an overview of current knowledge.

Multiple sclerosis (MS) is characterized by chronic inflammation of the central nervous system, and magnetic resonance imaging (MRI) is used as both a diagnostic tool and a parameter in the clinical evaluation. Multiple sclerosis was long regarded as a disease of the white matter (WM) in the brain, which can be visualized by the standard MRI used in daily practice. There is an increasing amount of evidence that grey matter (GM) pathology plays a role from the start of the MS disease and throughout the clinical course. Grey matter atrophy, both cortical and central, is present in the early course of MS and is also related above all to cognitive decline, but also to the development of physical disability as measured by EDSS. In this article, we give an overview of GM atrophy in MS evaluated by MRI and the relation to the clinical course in MS.

Health related quality of life in patients recently diagnosed with multiple sclerosis.

OBJECTIVE: To describe a representative population of patients recently diagnosed with MS in terms of both motor and non-motor disability. In particular we wanted to examine the HRQoL in this population to get a better understanding of what impact various clinical features have on the patients' experience of distress in the early phase of the disease. METHODS: Ninety three patients diagnosed with MS in Hordaland and Rogaland county in 1998-2000 and 96 healthy controls were examined through questionnaires on HRQoL (SF-36), depression (Beck's depression inventory), fatigue (fatigue severity scale) and apathy (Starkstein's apathy scale). The patients also underwent neurological examination including the expanded disability status scale and the Multiple Sclerosis Functional Composite, as well as the symbol digit memory test and the selective reminder test. RESULTS: Patients with MS reported a lower HRQoL than the controls with a mean physical health summary score of 57.3 compared to 84.5 (P < 0.001), and a mental health summary score of 66.4 vs 79.2 (P < 0.001). The controls scored significantly higher on all SF-36 sub scores except for bodily pain. The incidence of fatigue was 71% in patients compared to 27% in controls (P < 0.001), whereas 46% of patients vs 18% of controls reported depression (P < 0.001). The mean score for apathy was significantly higher among patients. CONCLUSIONS: Patients with recently diagnosed MS reported significantly lower on both physical and mental aspects of HRQoL compared with controls. Depression, fatigue and apathy were more common and more severe in MS. We found no correlation between cognitive decline and HRQoL scores.

Chronic inflammatory demyelinating polyneuropathy (CIDP).

BACKGROUND: Chronic immune-mediated demyelinating polyneuropathies can often lead to severe neurologic disability. MATERIALS AND METHODS: Literature review and personal experience with these types of neuropathies. CONCLUSIONS: It is important to recognize these immune-mediated neuropathies as they respond to treatment.

Acute ischemic stroke--from symptom recognition to thrombolysis.

OBJECTIVES: The understanding of stroke has changed in the recent years from rehabilitation to an emergency approach. We review existing data from symptom recognition to thrombolysis and identify challenges in the different phases of patient treatment. RESULTS: Implementation of treatment in dedicated stroke units with a multidisciplinary team exclusively treating stroke patients has led to significant reduction of stroke morbidity and mortality. Yet, first the introduction of treatment with intravenous rtPA (IVT) has led to the 'time is brain' concept where stroke is conceived as an emergency. As neuronal death in stroke is time dependent, all effort should be laid on immediate symptom recognition, rapid transport to the nearest hospital with a stroke treatment facility and diagnosis and treatment as soon as possible. The main cause of prehospital delay is that patients do not recognize that they suffered a stroke or out of other reasons do not call the Emergency Medical Services immediately. Educational stroke awareness campaigns may have an impact in increasing the number of patients eligible for rtPA treatment and can decrease the prehospital times if they are directed both to the public and to the medical divisions treating stroke. Stroke transport times can be shortened by the use of helicopter and a stroke mobile--an ambulance equipped with a CT scanner--may be helpful to decrease time from onset to treatment start in the future. Yet, IVT has several limitations such as a narrow time window and a weak effect in ischemic strokes caused by large vessel occlusions. In these cases, interventional procedures and the concept of bridging therapy, a combined approach of IVT and intraarterial thrombolysis or mechanical thrombectomy, might improve recanalization rates and patient outcome. CONCLUSIONS: As neuronal death in stroke patients occurs in a time-dependent fashion, all effort should be made to decrease time from symptom onset to treatment start with rtPA: major challenges are stroke recognition in the public, transport times to hospital and an efficient stroke triage in the hospital.

Ischemic stroke--novel therapeutic strategies.

OBJECTIVES: Treatment of acute, ischemic stroke has changed markedly during the last two decades. We review existing data for optimizing modern stroke care. RESULTS: Implementation of stroke units, giving systematic treatment and observation to stroke patients, has lead to a significant reduction in death and dependency. Introduction of intravenous rt-PA (IVT) within 3 h for selected stroke patients and recent extension of the time window to 4.5 h improved the outcome even further. Still, one must consider that IVT has several limitations, such as a narrow time window and several contraindications, and the effect is modest, particularly in strokes with a large vessel occlusion. Recanalization of the occluded vessel is a major predictor for good outcome and should be set as a goal. Intra-arterial rt-PA (IAT) and the concept of bridging therapy (IVT prior to IAT or thrombectomy with a mechanical device) may improve recanalization rates and outcome. Randomized controlled trials (RCT) are available for IAT, but not for thrombectomy with devices, and we mostly have retrospective non-controlled data. The Merci- and Penumbra system are the most studied devices, for which recent studies report acceptable safety and efficacy. CONCLUSIONS: Sufficiently powered RCTs to evaluate the effect of thrombectomy with mechanical devices are warranted, but as the natural course of a large vessel stroke carries a devastating prognosis, a proactive recanalization approach is justified based on today's knowledge.

Is there a need for long-term follow-up in chronic idiopathic polyneuropathy?

OBJECTIVE: To evaluate the long-term functional status and well-being in patients with chronic idiopathic polyneuropathy (CIP) in comparison to Guillain-Barré syndrome (GBS) and healthy controls. MATERIALS AND METHODS: Forty-two CIP and 42 GBS-patients were examined at median 5 and 6 years after disease onset and were compared with 50 healthy controls. The Fatigue Severity Scale (FSS), Visual Analogue Scale for pain (VAS), Disability Rating Index (DRI) and Medical Outcome Study 36-item short-form health status scale (SF-36) were used. Variables at onset and symptoms at follow-up were correlated with outcome measurements in GBS. RESULTS: Patients with CIP and GBS had more pain and disability than healthy controls. Additionally, CIP-patients were more fatigued than healthy controls. Patients with CIP were more fatigued [FSS 4.9 (SD 1.6) vs 3.8 (SD 1.8); P < 0.01] and disabled [DRI 4.1 (SD 2.3) vs 2.5 (SD 2.1); P = 0.05] than those with GBS. Physical functioning on the SF-36 was more impaired in CIP than GBS, compared with healthy controls. CONCLUSIONS: Patients with CIP and GBS seem to develop persistent impairment on long-term functional status and well-being, more clearly in CIP, reflecting the importance of long-term follow-up in further disease management.

The long-term functional status in patients with Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: The purpose of this study was to analyse the long-term impact of Guillain-Barré syndrome (GBS) on quality of life, and the relationship between clinical variables at disease onset and symptoms at follow-up to general health status. METHODS: Forty-two GBS patients were examined at median 6 years after disease onset and were compared with 50 healthy controls. The fatigue severity scale (FSS), visual analogue scale (VAS) for pain, disability rating index (DRI) and medical outcome study 36-item short-form health status scale (SF-36) were applied. Variables at onset and symptoms at follow-up were correlated with outcome measurements in GBS. RESULTS: VAS [2.9 (SD 3.3) vs. 1.5 (SD 1.9); P = 0.01] and DRI [2.5 (SD 2.1) vs. 1.0 (SD 1.5); P < 0.001] were significantly higher in patients with GBS, compared with healthy controls. Decreased physical functioning and general health were found on SF-36. Differences between GBS patients with shorter (<6 years) and longer (> or =6 years) follow-up after onset were not found. CONCLUSIONS: Relatively independent from various variables at onset, patients with GBS seem to have a reduced quality of life and functioning, and the distress seems to have become persistent after the first few years with improvement following the acute disease.

Hospital-referred polyneuropathies--causes, prevalences, clinical- and neurophysiological findings.

The aim of this study was to evaluate the causes, prevalences, clinical manifestations of hospital-referred polyneuropathies, and evaluate neurophysiological findings in idiopathic polyneuropathy. From 2000 to 2005, 226 patients with polyneuropathy were examined. Polyneuropathy was diagnosed when symptoms, clinical- and neurophysiological findings were compatible with affection of at least two peripheral nerves. They were classified in symptomatic and idiopathic polyneuropathy after investigation. Clinical manifestations were evaluated for diabetes- (DPN), inflammatory- (INPN), hereditary- (HPN) and idiopathic polyneuropathy (IDPN). Neurophysiological findings were investigated in IDPN. 72% had a symptomatic polyneuropathy. Most frequent causes were diabetes mellitus (18%), inflammation, (16%) and hereditary (14%). Most common prevalences per 100,000 were as follows: IDPN, 21; DPN, 13 and HPN, 11. Predominating clinical manifestations were: sensory and motor in INPN, HPN and IPN; sensory in DPN. Pain was more present in IDPN and DPN than in others. In IDPN axonal demyelinating affection was present in 20%. Symptomatic polyneuropathy was common and diabetes mellitus, inflammation and hereditary were frequent causes. In IDPN, DPN, HPN and INPN different clinical patterns were found. Additionally, in IDPN axonal demyelinating affection was more frequent than previously reported.

Post-polio syndrome patients treated with intravenous immunoglobulin: a double-blinded randomized controlled pilot study.

Post-polio syndrome (PPS) is characterized by new muscle weakness, atrophy, fatigue and pain developing several years after the acute polio. Some studies suggest an ongoing inflammation in the spinal cord in these patients. From this perspective, intravenous immunoglobulin (IvIg) could be a therapeutic option. We performed a double-blinded randomized controlled pilot study with 20 patients to investigate the possible clinical effects of IvIg in PPS. Twenty patients were randomized to either IvIg 2 g/kg body weight or placebo. Primary endpoints were changes in pain, fatigue and muscle strength 3 months after treatment. Surrogate endpoints were changes in cerebrospinal fluid (CSF) cytokine levels. Secondary endpoints were pain, fatigue and isometric muscle strength after 6 months. Patients receiving IvIg reported a significant improvement in pain during the first 3 months, but no change was noted for subjective fatigue and muscle strength. CSF levels of tumour necrosis factor-alpha (TNF-alpha) were increased compared with patients with non-inflammatory neurological disorders. In conclusion, in this small pilot study no effect was seen with IvIg treatment on muscle strength and fatigue, however IvIg treated PPS patients reported significantly less pain 3 months after treatment. TNF-alpha was increased in the CSF from PPS patients. The results are promising, but not conclusive because of the low number of patients studied.

EFNS guideline on diagnosis and management of post-polio syndrome. Report of an EFNS task force.

Post-polio syndrome (PPS) is characterized by new or increased muscular weakness, atrophy, muscle pain and fatigue several years after acute polio. The aim of the article is to prepare diagnostic criteria for PPS, and to evaluate the existing evidence for therapeutic interventions. The Medline, EMBASE and ISI databases were searched. Consensus in the group was reached after discussion by e-mail. We recommend Halstead's definition of PPS from 1991 as diagnostic criteria. Supervised, aerobic muscular training, both isokinetic and isometric, is a safe and effective way to prevent further decline for patients with moderate weakness (Level B). Muscular training can also improve muscular fatigue, muscle weakness and pain. Training in a warm climate and non-swimming water exercises are particularly useful (Level B). Respiratory muscle training can improve pulmonary function. Recognition of respiratory impairment and early introduction of non-invasive ventilatory aids prevent or delay further respiratory decline and the need for invasive respiratory aid (Level C). Group training, regular follow-up and patient education are useful for the patients' mental status and well-being. Weight loss, adjustment and introduction of properly fitted assistive devices should be considered (good practice points). A small number of controlled studies of potential-specific treatments for PPS have been completed, but no definitive therapeutic effect has been reported for the agents evaluated (pyridostigmine, corticosteroids, amantadine). Future randomized trials should particularly address the treatment of pain, which is commonly reported by PPS patients. There is also a need for studies evaluating the long-term effects of muscular training.

Post-polio syndrome and total health status in a prospective hospital study.

New loss of function among patients with previous polio is frequently reported and has several causes. All patients referred to the Department of Neurology, Haukeland University Hospital, Bergen, for 13 months during 2000-2001 with diagnosis late effects of polio were examined prospectively to identify their symptoms and loss of function. Eighty-five patients aged 47-91 years with mean of 61 years were included. The most common complaints were pain (44%), muscular weakness (27%), and fatigue (16%). Muscular weakness occurred in lower limbs in 75%, in respiratory muscles in only 5%. Walking in stairs was impaired in 72% and outdoor walking in 65%. Seventeen patients (19%) reported no loss of function. Post-polio syndrome was diagnosed in 26% of the patients. Polio-related loss of function including cervical and lumbosacral radiculopathies, mononeuropathies and degenerative joint disease were found in an additional 53%. Eleven patients (13%) had distinct non-polio-related disorders that caused new loss of function. The remaining 8% had a stable condition. In conclusion, the majority of polio patients who seek hospital, experience a new loss of function because of polio-related disorders. A careful neurological examination is necessary to identify the correct diagnosis and treatment.

GM1 antibodies in post-polio syndrome and previous paralytic polio.

We studied the relationship between post-polio syndrome (PPS) and GM1 antibodies, since such antibodies have been associated with PPS and motor neuron disorders. Sera from 144 patients with previous poliomyelitis (105 paralytic, 22 nonparalytic and 17 PPS), 60 with previous Guillain-Barré syndrome, 44 with amyotrophic lateral sclerosis (ALS) and 22 healthy blood donors were analyzed with ELISA for GM1 IgM, IgG and IgA antibodies. GM1 antibodies were present in 14% of the PPS patients, but the prevalence did not differ significantly from that of the other groups. Our study does not support the hypothesis that GM1 antibodies are involved in the pathogenesis of PPS.

Anaesthetic complications associated with myotonia congenita: case study and comparison with other myotonic disorders.

Myotonia congenita (MC) is caused by a defect in the skeletal muscle chloride channel function, which may cause sustained membrane depolarisation. We describe a previously healthy 32-year-old woman who developed a life-threatening muscle spasm and secondary ventilation difficulties following a preoperative injection of suxamethonium. The muscle spasms disappeared spontaneously and the surgery proceeded without further problems. When subsequently questioned, she reported minor symptoms suggesting a myotonic condition. Myotonia was found on clinical examination and EMG. The diagnosis MC was confirmed genetically. Neither the patient nor the anaesthetist were aware of the diagnosis before this potentially lethal complication occurred. We give a brief overview of ion channel disorders including malignant hyperthermia and their anaesthetic considerations.

Long term outcome after poliomyelitis in different health and social conditions.

OBJECTIVE: To examine and compare the long term outcome after polio in an east European and a west European country with different access to rehabilitation and with different medical and social conditions. DESIGN AND SETTING: The patients who were acutely hospitalised for polio 1950-54 in the University Hospital in Bergen, Norway and 1958 in the University Hospital in Tartu, Estonia received the mailed questionnaire in the period between January 1998 and December 1998. PATIENTS: Patient files concerning 334 patients hospitalised in Tartu and 243 patients hospitalised in Bergen were obtained; of these 128 Estonian and 148 Norwegian patients were re-examined. MAIN RESULTS: Despite more pronounced disability in the acute stage, significantly more Norwegian patients were working full time and part time in 1998 (p<0.0001) and also through the period 1958-1998. In both countries, 30% of patients had manual work and 18% changed profession during their career. Low income (below 50% of national average) was reported by 73% of Estonian and 35% of Norwegian patients (p<0.0001). Except for the odds ratio for muscular pain of 1.89 (95%CI =1.14 to 3.14) for Norwegian patients, new symptoms indicating late progression did not differ. Norwegian patients were more independent with significantly less need for assistance in housekeeping (p=0.02), whereas the use of orthopaedic devices did not differ. CONCLUSIONS: The long term outcome after polio is different in eastern and western Europe. Access to continuous rehabilitation seems to maintain physical independence in polio patients, improves their ability to earn their own income, and lessens the need for disability pensions.

Education, occupation, and perception of health amongst previous polio patients compared to their siblings.

Patients with previous polio represent a challenge for neurological rehabilitation. We examined 168 previous polio patients and 239 of their siblings, the patients either from the 1950-1954 epidemic cohort, or from a cohort of hospital-admitted rehabilitation patients. Ninety-four paralytic patients and 74 non-paralytic patients were included. All patients and siblings answered the same questionnaires for socioeconomic and health factors and chi-square comparisons were performed. Previous polio did not affect the level of education. Both patients and siblings rated their educational options to have been good. Significantly less patients were full-time employed at the age of 40 years compared to their siblings (P=0.015). This was the result of a lower full-time employment rate amongst the paralytic patients, only 52% of this group being employed full-time. Male patients and paralytic patients reported to have experienced reduced professional options. More patients were living alone compared to their siblings (P=0.035). The perception of general health was lower amongst patients than siblings, as was assessment of total life situation and patients reported more frequently symptoms like pain and tiredness. In conclusion, previous polio had not lowered the polio patients' educational status, but fewer patients were employed full-time at the age of 40 years.

[Acute dystonia caused by metoclopramide (Afipran) therapy]. / Akutt dystoni ved behandling med metoklopramid (Afipran).

BACKGROUND: Metoclopramide is an antiemetic drug used frequently both in general practice and hospitals. The drug has few side effects, mainly drowsiness, and can be used both in pregnancy and breastfeeding. Acute dystonia is a rare side effect mostly affecting children and young adults within 1-3 days after start of the medication. Women are more frequently affected than men. MATERIAL AND METHODS: We present a clinical description of two patients admitted to our department with acute dystonia precipitated by metoclopramide. RESULTS: Both patients received treatment with biperiden; one received additional benzodiazepine. Both recovered rapidly and were discharged symptom free the next day. INTERPRETATION: Metoclopramide-induced dystonia is frightening both for the patient and the family. Because of concomitant anxiety and psychiatric symptoms, individuals are often regarded as hysterical. The attack can be abbreviated by parenteral administration of anticholinergic drugs. It is important that all doctors prescribing metoclopramide know of this side effect, especially when their patients are young females.

Polio survivors--well educated and hard working.

243 patients were diagnosed with acute poliomyelitis (polio) in Western Norway between 1950 and 1954; 186 were paralytic and 57 non-paralytic. This study examines how polio influenced their education, employment, profession, annual income, marital status and energy for leisure activities. 149 of the patients identified were alive and 98 of the matched controls responded to a questionnaire. Education length did not differ between acute paralytic polio patients, acute non-paralytic polio patients and controls. Fifty percent of the patients with residual weakness and 77 % of the patients with normal muscle power were employed, against 73 % of the controls (P=0.014). A higher proportion of patients without motor deficits had manual work than those with weakness or controls (P=0.002). There was no significant association between severity of weakness and education, employment and profession. Physical ability had been an important factor for the choice of education and profession for all the polio patients, but not for controls (P < 0.001). Annual income did not differ significantly between patients and controls. Residual weakness increased the chance of being single (P=0.023), although as many as 79% had married. 53 % of the patients with weakness claimed that fatigue prevented hobbies, compared wich 31% of the other patients and only 16% of the controls (P < 0.001). There was no significant association between severity of weakness and fatigue. In conclusion, the polio patients are generally well educated, provide their own income and marry. However, their polio has influenced choice of education and profession, and polio patients with persisting weakness differ from controls and polio patients without motor deficits regarding employment and marital status.