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.     

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.     

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.     

Chronic inflammatory demyelinating polyradiculoneuropathy in children: II. Long-term follow-up,with comparison to adults

We previously reviewed the presentation, initial clinical course, and electrodiagnostic features of children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now report the long-term follow-up of 12 children with idiopathic CIDP, and compare these to 62 adults with idiopathic CIDP. Children often had more rapidly fluctuating courses than adults. A relapsing course was significantly more common in children than in adults. The recovery of children from each episode of deterioration was usually excellent, and better, on average, than in adults. Ventilatory support was never required for children with slowly evolving illness; only 2 children with a precipitous onset clinically resembling Guillain-Barré syndrome required ventilatory support. Prednisone, plasma exchange, and intravenous immunoglobulin (IVIg) usually were effective in children. Multiple courses of IVIg could be given with continued efficacy. Treatment often could be discontinued in children with relapsing courses. The prognosis for children was excellent. Adults demonstrated a good, but more variable, outcome. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1569–1575, 1997     

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.     

Chronic inflammatory demyelinating polyradiculoneuropathy in patients with liver transplantation

We report two patients with orthotopic liver transplantation (OLT) who developed a syndrome that fulfilled criteria for definite chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One patient had OLT because of alcoholic cirrhosis and one following hepatitis C-induced hepatic failure. Both had immunosuppressive therapy, with cyclosporine and prednisolone in one case and tacrolimus in the other case. Treatment with intravenous immune globulin (IVIG) significantly improved the neuropathy in both patients. In patients with OLT developing disabling sensorimotor neuropathies, CIDP should be considered as should the use of potentially beneficial immunosuppressive treatment.     

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.     

Chronic inflammatory demyelinating polyradiculoneuropathy with tumefactive central demyelination

A 46-year-old man with a 1-year history of distal paresthesias and mild distal weakness subacutely developed paralysis of the left hand. Electrodiagnostic evaluation revealed a demyelinating peripheral neuropathy that met criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Magnetic resonance imaging of the brain revealed a mass that enhanced with contrast, but revealed focal myelin loss with intense macrophage activity and axonal preservation on biopsy. The mass and hand weakness improved following steroid therapy. The combination of CIDP and central demyelination with mass effect broadens the spectrum of demyelinating disease in association with CIDP.     

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.     

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     

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.     

Chronic inflammatory demyelinating polyradiculoneuropathy in children: I. Presentation,electrodiagnostic studies,and initial clinical course,with comparison to adults

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is rare in children. We reviewed features of 15 children with idiopathic CIDP, and compared these to 69 adults with idiopathic CIDP. Children demonstrated many similarities to adults: (1) Antecedent events were uncommon. (2) There was a high frequency of weakness and reflex loss, a relatively high frequency of sensory loss, and a low frequency of pain and cranial neuropathies. (3) Cerebrospinal fluid protein levels were usually elevated. (4) On electrodiagnostic testing, not all nerve segments were abnormal, and not all children satisfied electrodiagnostic criteria for CIDP. Children differed from adults with CIDP in several ways: (1) The onset of symptoms was usually more precipitous. (2) Gait abnormalities were a more frequent presenting symptom. (3) Children always presented with significant neurological dysfunction, and not with the minor symptoms initially seen in some adults. The initial response of children with CIDP to immunomodulating therapy was excellent. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1008–1015, 1997     

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.     

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     

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.     

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.     

Clinical factors,diagnostic delay,and residual deficits in chronic inflammatory demyelinating polyradiculoneuropathy

Management of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is complicated by the challenging diagnosis, monitoring of disease activity, and treatment response. Real world data about the current practice of care in CIDP are rare, but important to improve clinical guidelines. In this study, we determined the current practice of diagnosis and treatment in relation to the clinical outcome of patients with CIDP in a cross‐sectional study in The Netherlands. All patients registered at the Dutch neuromuscular patient organization and patients at the Erasmus Medical Center were approached. CIDP diagnosis was confirmed by using patient files and expert consensus. The response rate was 137/197 (70%) and the diagnosis CIDP was confirmed in 112 patients. The time from onset of symptoms until CIDP diagnosis was median 5 months and > 12 months in 26% of the patients. Patients with a late diagnosis (>5 months) compared to patients with an early diagnosis (≤5 months) more frequently had another initial diagnosis (P < .001), multifocal abnormalities (P = .011), final diagnosis made in university hospitals (P = .001), and more (residual) complaints, also illustrated via two patient reported, validated clinical outcome measures. Although 97% of patients received treatment, 88% reported (residual) neurological symptoms and deficits. CIDP diagnosis is often delayed, especially in patients with atypical CIDP variants. Diagnostic delay may result in delayed initiation of treatment. A more rapid and accurate diagnosis of CIDP may prevent or at least reduce residual neurological deficits and accompanying disability in CIDP.