Proposed revised electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy.

Electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were proposed by an Ad Hoc Subcommittee of the American Academy of Neurology (AAN) in 1991. Only 60% of CIDP patients fulfilled these criteria, which therefore appear poorly sensitive. We therefore sought to revise the electrophysiological criteria. We selected 40 CIDP patients and compared them with 35 patients with axonal polyneuropathy, 116 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease, and 66 patients with immunoglobulin M (IgM) monoclonal gammopathy. The proposed electrophysiological criteria identified 90% of the CIDP patients, although 3% of patients with axonal polyneuropathy were falsely identified. For the CIDP patients, sensitivity and specificity were 90% and 97%, respectively. Of the patients with IgM monoclonal gammaglobulin of undetermined significance (MGUS) and CMT1A, 100% fulfilled these new criteria, whereas 90% and 97%, respectively, fulfilled the AAN criteria. These results suggest that the AAN criteria are more appropriate for IgM MGUS and CMT1A patients than for CIDP patients. We therefore propose new electrophysiological criteria for CIDP that appear to have better sensitivity.     

Pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy

The acute lesions of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consist of endoneurial foci of chemokine and chemokine receptor expression and T cell and macrophage activation. The myelin protein antigens, P2, P0, and PMP22, each induce experimental autoimmune neuritis in rodent models and might be autoantigens in CIDP. The strongest evidence incriminates P0, to which antibodies have been found in 20% of cases. Failure of regulatory T-cell mechanism is thought to underlie persistent or recurrent disease, differentiating CIDP from the acute inflammatory demyelinating polyradiculoneuropathy form of Guillain-Barré syndrome. Corticosteroids, intravenous immunoglobulin and plasma exchange each provide short term benefit but the possible long-term benefits of immunosuppressive drugs have yet to be confirmed in randomised, controlled trials.     

Predicting response to treatment in chronic inflammatory demyelinating polyradiculoneuropathy

OBJECTIVE: To discover whether Inflammatory Neuropathy Cause and Treatment Group (INCAT) electrophysiological criteria for demyelinating neuropathy predict response to immunotherapy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: This was a retrospective case note study of patients who had attended Guy's Hospital Peripheral Nerve Clinic between January 2001 and March 2004, been diagnosed as having CIDP, and given treatment with corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange (PE). Patients' nerve conduction studies (NCS) were reviewed for evidence of demyelination and whether the abnormalities fulfilled modified INCAT electrophysiological criteria. Patients whose NCS fulfilled the criteria were assigned to the neurophysiologically definite CIDP group, while those that did not were labelled as neurophysiologically probable CIDP. Responses to any of the three immunotherapy agents were compared between the two groups. RESULTS: Out of 50 patients, 27 (54%) were classified as neurophysiologically definite and 23 (46%) as neurophysiologically probable CIDP patients. Twenty (74%) neurophysiologically definite and 17 (73.9%) neurophysiologically probable CIDP patients responded to treatment. CONCLUSIONS: INCAT electrophysiological criteria did not predict a higher rate of response to immunotherapy. Neurophysiologically probable CIDP patients should be given a trial of immunotherapy.     

Treatment of chronic inflammatory demyelinating polyradiculoneuropathy with methotrexate

We discovered many reports of other immunosuppressive drugs being used in adults with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but none of methotrexate. As weekly low dose oral methotrexate is safe, effective, and well tolerated in other diseases, we treated 10 patients with otherwise treatment resistant CIDP. Seven showed improvement in strength by at least two points on the MRC sum score and three worsened. Only two showed an improvement in disability and both were also receiving corticosteroids. We discuss the difficulty of detecting an improvement in treatment resistant CIDP and propose methotrexate as a suitable agent for testing in a randomised trial.     

Immunosuppressive treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy. A nationwide retrospective analysis

Background and purpose: There are other options open to patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are non‐responders to conventional treatment, including immunosuppressive and immunomodulatory agents (IA). The aim of this study was to assess whether the use of IA is able to increase the number of responders. Methods: Clinical and electrophysiological data of patients with refractory CIDP, followed at 10 Italian centres, were collected, and the clinical outcome (Rankin Scale) and drug side effects (SE) for the different therapies were analysed. Results: A total of 110 patients were included. These patients underwent 158 different therapeutic procedures with IA. Seventy‐seven patients were treated with azathioprine, 18 rituximab, 13 cyclophosphamide, 12 mycophenolate mofetil, 12 cyclosporine, 12 methotrexate, 11 interferon‐alpha and three interferon beta‐1a. The percentage of patients who responded to azathioprine (27%) was comparable to the percentage of responders to other therapies, after the exclusion of interferon beta‐1a that was not effective in any of the three patients treated. The percentage of SE ranges from 8% (methotrexate) to 50% (cyclosporine). Conclusions: One‐fourth of patients, refractory to conventional treatment, showed an improvement in their disability with IA. Methotrexate had the lowest SE; cyclosporine was associated with severe SE and often led to drug discontinuation.     

Cyclosporin A in resistant chronic inflammatory demyelinating polyradiculoneuropathy

The role of cyclosporin A (CsA) in the treatment of resistant chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was retrospectively reviewed in 19 patients who had failed to respond adequately to corticosteroids, plasmapheresis, intravenous immunoglobulin, and in some cases other immunosuppressive agents. Patients were subdivided into progressive or relapsing types according to the course of disease and response to therapy graded at follow-up by clinical and electrophysiological criteria. In the progressive group, the mean disability status declined from 3.8 ± 0.7 to 1.8 ± 1.1 grades on a 5-grade scale following CsA therapy (P < 0.001). In the relapsing group, the mean annual incidence of relapse declined from 1.0 ± 0.5 to 0.2 ± 0.4 after commencement of CsA (P < 0.05). Dose-dependent, reversible nephrotoxicity was the most serious complication of therapy, and necessitated cessation of CsA in 2 patients. In conclusion, CsA is an efficacious and, with appropriate monitoring, safe therapy for patients with CIDP. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:454–460, 1998.     

Response to methotrexate in a chronic inflammatory demyelinating polyradiculoneuropathy patient

We report a patient with chronic inflammatory demyelinating polyradiculoneuropathy and progressive resistance to standard treatment who showed a striking response to methotrexate, 20 mg/week. The improvement, which started 5 months after initiation of therapy, was consistent and permanent. It allowed the previously wheelchair‐dependent patient to achieve pharmacological remission. The 2‐year follow‐up of this case further illustrates the role that methotrexate may play as a treatment option for CIDP patients. Muscle Nerve 39: 386–388, 2009     

Maintenance IV immunoglobulin treatment in chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients treated with intravenous immunoglobulin (IVIg) usually start with a standard dosage of 2 g/kg bodyweight. Only a minority of patients has a sustained improvement, and most require ongoing maintenance treatment. Preferred IVIg regimens, however, vary considerably between doctors and at present it is unknown which is optimal. As there are also large differences in IVIg dosage and interval requirements between patients, optimal IVIg maintenance treatment of CIDP is even more complex. The lack of evidence‐based guidelines on how IVIg maintenance treatment should be administered may potentially lead to under‐ or overtreatment of this expensive therapy. We provide an overview of published practical IVIg maintenance treatment regimens, IVIg maintenance schedules used in randomized controlled trials and one based upon our own long‐term experience on how this treatment could be given in CIDP.     

CNS involvement in Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy

Thirteen consecutive Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were studied by MRI, evoked potentials, and EEG. We found 3 of these patients exhibited symptoms of CNS disorders. Of these 3, 2 with abnormal MRI and visual evoked potentials, and one with abnormal brainstem auditory evoked potentials were detected. Another case without clinical CNS signs showed abnormal EEG findings. The subclinical CNS abnormalities found in the Japanese patients were considered to be less frequent than in cases from Western countries reported previously.     

Employment status of patients with chronic inflammatory demyelinating polyradiculoneuropathy

It has been previously shown that patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are unemployed or retired have worse quality of life. The aim of this study was to assess predictors of early retirement in CIDP. One hundred five patients with CIDP were included. Following measures were used: questionnaire on employment status, Medical Research Council Sum Score, INCAT disability score, Beck Depression Inventory, and Krupp's Fatigue Severity Scale. At the moment of testing, 2% of patients were students, 15% were employed, 9% were unemployed due to CIDP, 9% were unemployed but not due to CIDP, 28% were retired early due to disability caused by CIDP, and finally 37% were in old‐age pension. Mean age when patients retired due to CIDP was 50 ± 8 years. Mean time from CIDP onset to retirement was 2.7 ± 2.3 years. Older age at onset, lower education, and more severe weakness at the time of diagnosis were significant predictors of early retirement due to CIDP. Retired patients were 12 times more likely to suffer from depression, compared to employed patients (OR = 12.2, 95% CI = 1.41‐100, P < 0.01), and eight times more likely to have fatigue (OR = 8.2, 95% CI = 1.89‐35.82, P < 0.01). Older patients with lower education and more severe weakness at the time of diagnosis were most likely retired due to CIDP. Early retirement was associated with depression and fatigue. Therefore, maintaining employment should be an important aim in the management of CIDP patients.     

Prospective analysis of gait characteristics in chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disorder that may lead to functional impairment, including gait abnormalities. Our aim was to analyze gait characteristics in patients with CIDP compared to healthy controls (HC). Moreover, we sought to determine changes of gait parameters after six-month follow-up period. Twenty-four patients with CIDP and 24 HCs performed basic walking task, dual-motor task, dual-mental task, and combined task using the same GAITRite system. Lower limb MRC-SS and lower limb INCAT disability score were assessed. Fourteen patients were retested after six months. Majority of gait parameters showed significant differences in all experimental conditions when compared between CIDP and HCs. The most consistent findings in CIDP were shorter stride length (SL), prolonged cycle time (CT) and double support time (DS), as well as increased variation of SL and of swing time (ST) (p < 0.05). During follow-up, INCAT improved in nine (64.3%) of 14 patients and MRC-SS improved in eight (57.1%) patients. Six-month changes of CT and its variation during combined task significantly differentiated patients with improved vs. non-improved INCAT (p < 0.05). In conclusion, patients with CIDP had slower gait with prolonged DS and with shorter SL compared to HCs. Increased variation of SL and of ST in CIDP may suggest a potential risk for instability and falls. Shorter CT duration and less CT variation during time correlated well with improvement in disability.     

Chronic inflammatory demyelinating polyradiculoneuropathy in diabetic patients

This retrospective analysis was undertaken to determine whether a subset of diabetic patients with demyelinating polyneuropathy were similar to patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Ten patients meeting the clinical criteria for idiopathic CIDP were compared to nine patients with diabetes and demyelinating polyneuropathy. The diabetic patients with demyelinating polyneuropathy displayed clinical, electrophysiologic, and histologic features that were similar to those in CIDP patients. All six patients with diabetes and demyelinating polyneuropathy who were treated with immunomodulatory therapy showed a favorable response. Our study highlights the importance of investigating diabetic patients with polyneuropathy in an attempt to identify patients with demyelinating polyneuropathy, because of the likelihood of benefit in these patients from immunomodulatory treatment.     

Acute motor response following a single IVIG treatment course in chronic inflammatory demyelinating polyneuropathy

In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the acute motor response following withdrawal and reestablishment of intravenous immunoglobulin (IVIG) therapy was studied. In a prospectively designed case series 11 CIDP patients in IVIG maintenance therapy were assessed with isokinetic dynamometry, nerve conduction studies, and functional tests. After short‐term withdrawal of IVIG, eight treatment‐responsive patients had a 14.2% (8.6–20.0) loss of isokinetic strength of 12 muscle groups. Three patients remained stable without treatment and were excluded from further study. On days 5 and 10 after reinitiation of IVIG therapy isokinetic muscle strength increased by 5.5% (1.6–9.6) and 11.9% (7.5–16.5), respectively, but there was no further increase at day 15. Improvement of walking velocity and hand function coincided. The minimal F‐wave latency shortened, whereas other electrophysiological parameters remained unchanged. In conclusion, isokinetic dynamometry is a sensitive and clinically relevant method for monitoring the acute response to IVIG treatment in CIDP. Muscle Nerve, 2009     

Chronic inflammatory demyelinating polyradiculoneuropathy with autonomic involvement

We report a case of chronic acquired neuropathy predominantly affecting sensory and autonomic nerves. Investigations showed a demyelinating polyradiculoneuropathy with axonal degeneration and depletion of postganglionic noradrenergic fibers in the rectal mucosa. Intravenous immunoglobulin and corticosteroid administration were effective in alleviating symptoms and improving electrophysiological abnormalities. This neuropathy may be a novel variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), in which autoimmunoreactivity is directed not only against myelin but also against axon- or ganglion-composing protein. Autonomic nerve involvement does not exclude a diagnosis of CIDP.     

Hyperpyrexia-triggered relapses in an unusual case of ataxic chronic inflammatory demyelinating polyradiculoneuropathy

Abstract The ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy (ataxic-CIDP) has been recently described as a subtype of chronic ataxic neuropathy, distinguished by steroid responsiveness and relative preservation of myelinated fibres at sural nerve biopsy. We report on a case of progressive, predominantly sensory, steroid-responsive neuropathy with clinical, laboratory, electrophysiological and pathological features of this uncommon form of CIDP. Moreover, the present case displays peculiar hyperpyrexia-triggered relapses leading to transitory severe tetraparesis, bilateral facial drooping, dysphonia, dysphagia and dyspnoea, which leave clinicians with some unresolved questions.     

Diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy in clinical practice: A survey among Dutch neurologists

The diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is often a challenge. The clinical presentation is diverse, accurate biomarkers are lacking, and the best strategy to initiate and maintain treatment is unclear. The aim of this study was to determine how neurologists diagnose and treat CIDP. We conducted a cross‐sectional survey on diagnostic and treatment practices among Dutch neurologists involved in the clinical care of CIDP patients. Forty‐four neurologists completed the survey (44/71; 62%). The respondents indicated to use the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 CIDP guideline for the diagnosis in 77% and for treatment in 50%. Only 57% of respondents indicated that the presence of demyelinating electrophysiological findings was mandatory to confirm the diagnosis of CIDP. Most neurologists used intravenous immunoglobulins (IVIg) as first choice treatment, but the indications to start, optimize, or withdraw IVIg, and the use of other immune‐modulatory therapies varied. University‐affiliated respondents used the EFNS/PNS 2010 diagnostic criteria, nerve imaging tools, and immunosuppressive drugs more often. Despite the existence of an international guideline, there is considerable variation among neurologists in the strategies employed to diagnose and treat CIDP. More specific recommendations regarding: (a) the minimal set of electrophysiological requirements to diagnose CIDP, (b) the possible added value of nerve imaging, especially in patients not meeting the electrodiagnostic criteria, (c) the most relevant serological examinations, and (d) the clear treatment advice, in the new EFNS/PNS guideline, would likely support its implementation in clinical practice.