Filip Eftimov

Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind, randomised, controlled trial

BACKGROUND Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in patients treated with standard oral prednisolone. METHODS In eight neuromuscular centres in the Netherlands and one in the UK, patients aged 18 years or older who had newly diagnosed definite or probable CIDP were randomly assigned to a treatment regimen of either pulsed high-dose dexamethasone or standard oral prednisolone. Randomisation was done with a random number generator. The primary outcome measure was remission at 12 months, defined as improvement of at least three points on the Rivermead mobility index and improvement of at least one point on the inflammatory neuropathy cause and treatment disability scale. Analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07779236. FINDINGS Between December, 2003, and December, 2008, 40 patients were treated: 24 received dexamethasone and 16 received prednisolone. At 12 months, 16 patients were in remission: ten in the dexamethasone group and six in the prednisolone group (odds ratio [OR] 1.2, 95% CI 0.3-4.4). Most adverse events were minor and did not differ substantially between treatment groups; however, sleeplessness and Cushings face occurred more often in the prednisolone group. INTERPRETATION Pulsed high-dose dexamethasone treatment did not induce remission more often than prednisolone treatment. A substantial proportion of patients were in remission at 12 months in both treatment groups. High-dose dexamethasone could be considered as induction therapy in CIDP, but comparison with intravenous immunoglobulin treatment is needed. FUNDING The Prinses Beatrix Fonds (MAR01-0213) and the Department of Neurology, Academic Medical Center.

Fatal human rabies due to duvenhage virus from a bat in Kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs.

11Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 2Department ofNeurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 3Department of Intensive Care, Academic Medical Center, University ofAmsterdam, Amsterdam, The Netherlands, 4Department of Clinical Virology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands,5Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands, 6Department of Radiology, Academic Medical Center, University of Amsterdam,Amsterdam, The Netherlands, 7Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 8Centre of Expertise forRabies, Canadian Food Inspection Agency, Ottawa Laboratory (Fallowfield), Ottawa, Ontario, Canada

Long-term remission of CIDP after pulsed dexamethasone or short-term prednisolone treatment

Objective: Achieving long-term remission after a limited more intense treatment period would prevent prolonged use of corticosteroids or IV immunoglobulin (IVIg) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this prospective cohort study we present long-term follow-up data on patients included in a multicenter randomized controlled trial comparing 6 monthly pulses of dexamethasone with 8 months of daily prednisolone. Methods: Treatment effect was assessed with the Inflammatory Neuropathy Cause and Treatment disability scale and the Rivermead Mobility Index and was categorized using the CIDP Disease Activity Status (CDAS) scale. Results: By March 2011, 39 out of 40 patients were included with a median follow-up of 4.5 years. Cure (>5 years off treatment) or remission according to the CDAS criteria after 1 or 2 courses of pulsed dexamethasone or daily prednisolone was achieved in 10 out of 39 patients (26%). Half of the patients who were in remission after initial treatment experienced a relapse (median treatment-free interval: 17.5 months for dexamethasone, 11 months for prednisolone). Alternative diagnosis was made in 7 out of 12 (58%) who did not respond to any therapy and in none of the treatment-responsive patients. Conclusions: Cure or long-term remission can be achieved in about one-quarter of patients with CIDP after 1 or 2 courses of pulsed dexamethasone or 8-month daily prednisolone. In treatment-nonresponsive patients, the diagnosis CIDP should be reconsidered. Classification of Evidence: This study provides Class IV evidence that pulsed dexamethasone or 8-month daily prednisolone can lead to long-term remission in CIDP.

Chronic inflammatory demyelinating polyradiculoneuropathy: update on clinical features, phenotypes and treatment options

Purpose of review In this review, we focus on less recognised signs and symptoms in typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and on the clinical presentation, course of disease and response to treatment of the atypical CIDP phenotypes. Recent findings Frequently occurring and often disabling symptoms in CIDP such as fatigue, pain and tremor have recently been emphasised, whereas autonomic dysfunction, if present, is usually mild. Sensory CIDP is probably the most frequent atypical CIDP phenotype and diagnosis can be difficult in the absence of clear demyelinating features on nerve conduction studies. The most important study comparing intravenous immunoglobulin treatment with intravenous methylprednisolone showed a lower rate of discontinuation due to inefficacy, adverse events or intolerance with intravenous immunoglobulin treatment. However, improvement after corticosteroids seems to be more long-lasting than after intravenous immunoglobulin suggesting superior long-term immunosuppressive and immunomodulating effect of corticosteroids in CIDP. Summary Symptoms other than the classical motor and sensory symptoms can lead to significant disability in CIDP patients. Based on limited evidence from largely small retrospective case series, we conclude that atypical CIDP phenotypes often have a different course of disease and sometimes response to treatment when compared with typical CIDP. Prospective multicentre cohort studies using standardised clinical description, electrophysiological parameters and outcome measures are needed to study the natural disease course of these phenotypes including response to different treatments.

Neurosarcoidosis in a Tertiary Referral Center: A Cross-Sectional Cohort Study.

AbstractThe aim of this study was to evaluate clinical characteristics, diagnostic strategy, and treatment in patients with neurosarcoidosis in a tertiary referral centre.In a cross-sectional study, we included all patients with neurosarcoidosis treated at our tertiary referral center between September 2014 and April 2015.We identified 52 patients, among them 1 patient was categorized as having definite neurosarcoidosis, 37 probable neurosarcoidosis, and 14 possible neurosarcoidosis. Neurologic symptoms were the first manifestation of sarcoidosis in 37 patients (71%). Chronic aseptic meningitis was the most common presentation (19/52 patients [37%]), followed by cranial neuropathy (16/52 patients [31%]). Serum angiotensin-converting enzyme and lysozyme levels were elevated in 18 of 41 (44%) and 12 of 26 cases (46%). Pulmonary or lymph node sarcoidosis was identified by chest X-ray in 21 of 39 cases (54%) and by computed tomography of the chest in 25 of 31 cases (81%); 18Fluorodeoxyglucose-Positron emission tomography showed signs of sarcoidosis in 15 of 19 cases (79%). Thirty-one of the 46 cases receiving treatment (67%) improved, 13 cases (28%) stabilized, and 2 cases (4%) deteriorated. First-line treatment with corticosteroids resulted in satisfactory reduction of symptoms in 21 of 43 patients (49%). Seventeen patients (33%) needed second-line cytostatic treatment, and 10 patients (19%) were treated with tumor necrosis factor-&agr; inhibitors.The majority of patients with neurosarcoidosis present with chronic meningitis without a history of systemic sarcoidosis. The diagnosis can be difficult to make because of the poor sensitivity of most diagnostic tests. Half of patients had a satisfactory reduction of symptoms on first-line therapy.

Immunotherapy of multifocal motor neuropathy.

Introduction: Multifocal motor neuropathy (MMN) is an immune-mediated disease, which usually runs a chronic course. Current treatments are aiming at modulation of the immune response to maintain functional status. Although patients can remain stable with prolonged maintenance intravenous immunoglobuin (IVIg) treatment, most patients slowly deteriorate over many years despite increasing IVIg doses. Areas covered: The paper identifies studies since 1985 for patients with MMN. Randomised and non-randomized studies examining the effects of any therapeutic agent were selected, to give a full overview of the different treatments for MMN. The review provides a treatment algorithm together with our views on current treatments, ongoing trials and possible directions for further research. Expert opinion: IVIg remains the only proven treatment for MMN, although questions around dosages and duration of treatment remain. The presence of an effective therapy for MMN should not discourage but stimulate further research into alternative treatments as ongoing axonal damage results in increasing impairment in patients with MMN.

Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyradiculoneuropathy, a time to start and a time to stop

Intravenous immunoglobulin (IVIg) is often used as preferred treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Several studies highlighted the short‐term efficacy of IVIg for CIDP yet many patients need maintenance therapy. Notwithstanding the fact IVIg has been used for over 30 years in CIDP, there is only limited evidence to guide dosage and interval during maintenance treatment. The variation in disease course, lack of biomarkers, and fear of deterioration after stopping IVIg makes long‐term treatment challenging. Recent studies suggest a proportion of patients receive unnecessary IVIg maintenance treatment. This review provides an overview of the use of IVIg for CIDP treatment, focusing on evidence for long‐term IVIg use.

Small fiber neuropathy: a disabling and underrecognized syndrome

Purpose of review To discuss cause, clinical manifestations, diagnostics, and treatment of small fiber neuropathy (SFN). The diagnosis is difficult and can be easily missed. Recent findings SFN causes high morbidity with disabling symptoms and impact on quality of life. Patients may benefit from being diagnosed with SFN, even if no underlying cause is identified and no specific treatment is yet available. Recently, genetic mutations as a possible cause of SFN were identified. Clinical diagnostic criteria have been proposed, but no gold standard exists, and each test has its limitations. The diagnosis requires a combination of typical symptoms, abnormal neurologic findings, and absence of large fiber involvement. Clinicians should be aware of overlapping symptoms of SFN and fibromyalgia. Treatment is often difficult, even when the underlying cause is identified and appropriately treated. Usually, only symptomatic relief of complaints is available. Summary Awareness of SFN and related symptoms is of great clinical relevance. Guidelines for appropriate diagnostic workup using a stepwise approach involving a combination of tests are warranted. Even if no treatment is available, patients may benefit from timely recognition of SFN.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy - An Overview of Existing Treatment Options and Prospects for the Future

a relatively rare immune-mediated polyneuropathy with an overall prevalence of one to three per 100,000 adults. The clinical diagnosis of CIDP is based on clinical, electrophysiological and cerebrospinal fluid features. A typical CIDP patient has chronically progressive, stepwise, or recurrent symmetric proximal and distal weakness and sensory dysfunction of all extremities, developing over at least two months with absent or reduced tendon reflexes in all extremities. Various other clinical phenotypes have emerged over the years, including: distal acquired demyelinating symmetric neuropathy (DADS); multifocal acquired demyelinating sensory and motor neuropathy (MADSAM or Lewis-Sumner syndrome); focal involvement of the brachial or lumbosacral plexus or of one or more peripheral nerves in one upper or lower limb; and a pure motor and pure sensory form (including chronic immune sensory polyradiculopathy). Although the majority of patients will develop the disease slowly over more than two months, approximately 5% will have an acute Guillain–Barré syndrome-type onset. Electrophysiologically, reduced nerve conduction velocities, abnormal temporal dispersion and conduction blocks are important disease features. Cerebrospinal fluid protein levels are often elevated without cellular reaction. Many sets of diagnostic criteria for CIDP have been published. Recently, the European Federation of Neurological Societies and the Peripheral Nerve Society published revised criteria, which are designed for clinical practice and are easy to use. Treatments for Chronic Inflammatory Demyelinating Polyneuropathy CIDP can cause prolonged periods of disability, with many patients becoming severely disabled (modified Rankin score of 4 or 5) at some time during their illness. More than 10% remain severely disabled despite treatment. Several open, uncontrolled studies and blinded, randomised clinical trials have shown that immunomodulatory therapy has a beneficial effect in CIDP. Corticosteroids, intravenous immunoglobulin (IVIg), plasma exchange (PE), immunosuppressive agents (such as azathioprine, methotrexate, mycophenolate mofetil, cyclophosphamide, cyclosporine A, rituximab, alemtuzumab, etanercept, tacrolimus, interferon beta and alpha) and autologous stem cell transplantation have been used in CIDP. Of these, only corticosteroids, IVIg and plasmapheresis have been shown to be effective in randomised controlled trials (RCTs). This paper reviews existing treatment options, provides a treatment algorithm and discusses prospects for the future.

Immunotherapy of chronic inflammatory demyelinating polyradiculoneuropathy

Background: chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disease. Current treatments are aimed at modulating the immune response to achieve remission and maintain functional status. However, many patients fail to make a long-term recovery with current treatments. Objectives: to review the literature on immunotherapy for CIDP. Methods: We used the Search Strategy of the Cochrane Neuromuscular Disease Review Group to search Medline and Embase. Randomised and non-randomised studies examining the effects of any therapeutic agent in patients with CIDP were selected. The references of relevant articles were scanned to identify additional reports of interest. Results/conclusion: An overview of the different treatments for CIDP is provided. Emphasis has been placed on evidence from randomised controlled trials but open non-randomised studies are discussed if appropriate. We include a treatment algorithm and provide our views on current treatments, ongoing trials and possible directions for further research.