Refractory Chronic Inflammatory Demyelinating Polyneuropathy Research Articles

BCMA-CD19 bispecific CAR-T therapy in refractory chronic inflammatory demyelinating polyneuropathy

BCMA-CD19 bispecific CAR-T therapy in refractory chronic inflammatory demyelinating polyneuropathy

Insights into refractory chronic inflammatory demyelinating polyneuropathy: a comprehensive real-world study.

Refractory chronic inflammatory demyelinating polyneuropathy (CIDP) is a challenging subset of CIDP. It does not respond well to immune therapy and causes substantial disability. A comprehensive understanding of its clinical profile, electrophysiological characteristics and potential risk factors associated with refractoriness remains to be further elucidated. Data in this cross-sectional study was collected and reviewed from the Huashan Peripheral Neuropathy Database (HSPN). Included patients were categorized into refractory CIDP and non-refractory CIDP groups based on treatment response. The clinical and electrophysiological characteristics were compared between refractory and non-refractory CIDP groups. Potential risk factors associated with refractory CIDP were explored with a multivariate logistic regression model. Fifty-eight patients with CIDP were included. Four disease course patterns of refractory CIDP are described: a relapsing-remitting form, a stable form, a secondary progressive form and a primary progressive form. Compared to non-refractory CIDP patients, refractory CIDP exhibited a longer disease duration (48.96 ± 33.72 vs. 28.33 ± 13.72 months, p = 0.038) and worse functional impairment (MRC sum score, 46.08 ± 12.69 vs. 52.81 ± 7.34, p = 0.018; mRS, 2.76 ± 0.93 vs. 2.33 ± 0.99, p = 0.082; INCAT, 3.68 ± 1.76 vs. 3.03 ± 2.28, p = 0.056, respectively). Electrophysiological studies further revealed greater axonal impairment (4.15 ± 2.0 vs. 5.94 ± 2.77 mv, p = 0.011, ulnar CMAP) and more severe demyelination (5.56 ± 2.86 vs. 4.18 ± 3.71 ms, p = 0.008, ulnar distal latency, 7.94 ± 5.62 vs. 6.52 ± 6.64 ms, p = 0.035, median distal latency; 30.21 ± 12.59 vs. 37.48 ± 12.44 m/s, p = 0.035, median conduction velocity; 58.66 ± 25.73 vs. 42.30 ± 13.77 ms, p = 0.033, median F-wave latency), compared to non-refractory CIDP. Disease duration was shown to be an independent risk factor for refractory CIDP (p < 0.05, 95%CI [0.007, 0.076]). This study provided a comprehensive description of refractory CIDP, addressing its clinical features, classification of clinical course, electrophysiological characteristics, and prognostic factors, effectively elucidating its various aspects. These findings contribute to a better understanding of this challenging subset of CIDP and might be informative for management and treatment strategies.

Efficacy of hematopoietic stem cell transplantation treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis.

Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive drugs. However, a substantial proportion of patients with CIDP remain refractory to treatment and develop severe functional disability. A systematic review and a meta-analysis of the efficacy of hematopoietic stem cell transplantation (HSCT) treatment in refractory CIDP patients was performed. The study is based on queries in the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science and clinicaltrials.gov databases on 4 December 2022. Articles that met our eligibility criteria were included after screening. Patients' characteristics, treatment regime and outcome measures were extracted. Eighty-nine patients in 11 studies were included. The pooled estimate of responsiveness amongst the four included studies was 87.04% (95% confidence interval 66.7%-99.5%) and the pooled estimate of freedom of all immune modulating or suppressive drugs was 80.75% (95% confidence interval 71.2%-90.2%). This meta-analysis and systematic review suggested that HSCT can be effective in the treatment of refractory CIDP. Whilst there are risks involved, HSCT may be a beneficial and viable therapy for refractory CIDP when carefully evaluated.

S3505 A Case of Invasive Gastrointestinal Mold Infection

IntroductionL: Invasive mold infections can be devastating and are mostly seen in patients with hematologic malignancies, profound neutropenia, solid organ or hematopoietic cell transplantation, and poorly controlled diabetes mellitus. Mucormycosis is caused by a group of ubiquitous molds called Mucormycetes and characterized by tissue infarction and necrosis that results from invasion of the vasculature by hyphae. We present a rare case of a patient with invasive gastrointestinal mold infection. Case Description/Methods: A 40-year-old male with chronic inflammatory demyelinating polyneuropathy (CIDP) was admitted for autologous stem cell transplantation (ASCT). Initial hospitalization was complicated by neutropenic fever and C. difficile enteritis treated with Fidaxomicin. He was admitted one month later for nausea, vomiting and push enteroscopy revealed two circumferential deep small bowel ulcerations and a jejunal stricture too distal to be reached. Ulcer biopsies showed granulation tissue and was positive for Cytomegalovirus. He was treated with Valganciclovir and initiated on TPN. One week later, he had a third admission for intractable nausea and vomiting due to a small bowel obstruction. He failed conservative management and underwent diagnostic laparoscopy that revealed five strictures in the distal small bowel which were all resected with two small bowel resections and re-anastomosed. Histopathology of resected jejunum showed necrotizing granulomatous inflammation with aseptated fungal hyphae concerning for Mucormycosis, which was not identified on fungal PCR. He was treated with liposomal Amphotericin B then transitioned to oral Isavuconazole before making a full recovery. (Figure) Discussion: The most common presentation of Mucormycosis is a rhino-orbital-cerebral infection. Gastrointestinal infection is rare in living patients and has been estimated to occur in around 7% of all Mucormycosis cases and carries mortality as high as 85%. Our patient had a history of refractory CIDP and underwent chemotherapy for ASCT that was complicated by development of C. difficile and CMV gastrointestinal infections and small bowel obstruction necessitating endoscopic intervention which led to exploratory laparoscopy for surgical resection and the diagnosis of invasive Mucormycosis. Although invasive GI Mucormycosis is rare, in severely immunocompromised patients with unexplained gastrointestinal symptoms and multiple risk factors as presented in our patient, this infectious organism can be considered in the differential.Figure 1.: (A, B) Circumferential ulcerations seen in the small bowel on push enteroscopy. (C) Mucosal ulceration with underlying necrotizing granulomatous inflammation in the deep muscularis propria/pericolonic adipose tissue with non-septated fungal hyphae present.

P-PN003. Refractory chronic inflammatory demyelinating polyneuropathy treated with subcutaneous bortezumib

Introduction. A 73-year-old man with underlying diabetes presented in May 2017 with progressive bilateral upper and lower limb weakness and numbness for 3 months. Examination revealed power of 2-3 on lower limbs and 3 on upper limbs. Reflexes were absent with gloves and stocking sensory loss. NCS showed diffused sensorimotor demyelinating polyneuropathy. Monoclonal IgG kappa was detected. Urine free light chain showed raised kappa. However, BMAT showed no evidence of myeloma. Abdominal fat pad biopsy showed no evidence of amyloidosis. Anti-ganglioside and paraneoplastic antibodies were not detected. Sural nerve biopsy showed axonal loss. CT NTAP was unremarkable. He responded initially with IVIG therapy but In July 2017, he had a relapse with worsening lower limb weakness. He was given IVIG 1 g/kg maintenance together with dexamethasone 4 weekly pulse therapy with some improvement. In Oct 2017, he presented again with worsening weakness. Besides, there was dysphagia and dysphonia. He developed type 2 respiratory failure requiring NIV and ICU admission, requiring 2 weekly plasmapheresis to rescue him from recurrent respiratory failure. IV Rituximab was tried but with little success even after 1 month of completion. Subcutaneous Bortezumib was given for 2 courses; Feb 2018 and Aug 2018. Results. After first course of Bortezumib, he improved significantly; with no more dysphagia and respiratory failure. He was subsequently discharged in Apr 2018, since then on monthly maintenance plasmapharesis and later 3 monthly. Upon latest review in Nov 2019, he was able to ambulate independently; muscle power improved with upper limbs proximal 5, distal 3; lower limbs proximal 5, distal 4. NCS showed improvement of motor CMAP especially in upper limbs. Conclusion. Bortezumib can be considered in refractory CIDP despite limited experience in the literature. However it should be reserved after conventional therapies have failed due to its neurotoxic side effects.

Refractory CIDP with chronic lymphocytic leukaemia responding to chemoimmunotherapy

Chronic inflammatory demyelinating polyneuropathy (CIDP) has a variable clinical course with 15% remaining refractory to treatment. We report a woman with severe refractory CIDP and coexisting chronic lymphocytic leukaemia (CLL)...

Progress in Hematopoietic Stem Cell Transplantation for CIDP

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a kind of autoimmune-mediated inflammation and demyelinating disease. The etiology is mainly related to autoimmune dysfunction. The conventional treatments of CIDP have relied on immunomodulation and inhibition therapies such as adrenal cortex hormone, intravenous immunoglobulin (IVIg) and plasma exchange. Hematopoietic stem cell transplantation (HSCT) is known as a novel therapy for autoimmune disorders, which provides the chance to cure CIDP. More than 70 patients with refractory CIDP have received HSCT. The clinical symptoms and electrophysiological examination results of most patients have been improved. However, the treatment still has risks. This review describes the pathogenesis of CIDP and the current conventional treatments, and highlights the application of HSCT in CIDP, including its efficacy and safety.

Severe Chronic Inflammatory Demyelinating Polyneuropathy Ameliorated following High-dose (3 g/kg) Intravenous Immunoglobulin Therapy

We report the case of a 53-year-old woman with severe chronic inflammatory demyelinating polyneuropathy (CIDP) who developed progressive tetraplegia with respiratory failure despite receiving a standard dose of intravenous immunoglobulin therapy (IVIg), steroid pulse therapy, plasma exchange, and cyclosporine. We administered high-dose IVIg (3 g/kg; 0.6 g/kg/day for 5 consecutive days at monthly intervals). The patient's muscle weakness gradually improved after IVIg. She recovered completely 2 years after the onset of symptoms. The effects of IVIg treatment in individuals with CIDP may vary in each patient. In patients with refractory CIDP receiving standard-dose IVIg, repeated high-dose IVIg treatment can be considered.

Short-term and long-term effects of immunoadsorption in refractory chronic inflammatory demyelinating polyneuropathy: a prospective study in 17 patients.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, autoimmune-inflammatory disease of the peripheral nervous system. Recently, various immunoglobulin G4 (IgG4) type auto-antibodies have been described in patients with CIDP which can effectively be removed by immunoadsorption (IA). Therefore, we prospectively evaluated the therapeutic effect of IA in 17 patients with progressive CIDP not responding to other treatment. We prospectively evaluated the course of disease of 17 patients with CIDP who had insufficiently responded to steroids and/or IVIg previously and who received at least one cycle of IA. As clinical outcome parameter, we used a combined CIDP score of three validated scales comprising disability, motor score, and sensitivity. Seven patients received repeated treatments in regular intervals over a prolonged period up to 46 months. We observed a small, but significant improvement of the overall score after 2 weeks that mainly reflected an improvement of muscle strength. The median value of the combined CIDP score was 308.0 (266.0-374.5) points before IA and 330.0 (290.0-393.5) points 2 weeks after IA (p = 0.019). More importantly, all but one of seven progressive patients who received long-term immunoadsorption in regular intervals stabilized almost completely. Before IA, these patients lost 6.7 (3.0-13.1) points of combined CIDP score per month. During IA, they lost - 0.1 (0.0-0.8) points per month (p < 0.0001). Our results suggest that IA might constitute a promising and well-tolerated therapeutic alternative in CIDP for short-term and long-term treatment. We showed that long-term treatment with IA in regular intervals can stabilize the course of disease at least in a subgroup of patients.

Teaching Neuro Images : Cranial nerve hypertrophy in IgG4 anti-neurofascin 155 antibody–positive polyneuropathy

A 45-year-old man presented with an 11-year history of severe refractory chronic inflammatory demyelinating polyneuropathy (CIDP). Clinical examination revealed distal weakness of all 4 limbs, ataxia, facial diplegia, dysphonia, and facial sensory disturbance. Several therapeutics were tried: IV immunoglobulins (IVIg), corticosteroids, plasma exchange, cyclophosphamide, and mycophenolate mofetil. Anti-NF155 immunoglobulin G4 (IgG4) antibodies were detected by ELISA (1:2,000). Brain MRI revealed diffuse hypertrophy of multiple cranial nerves (figure).

Evaluation of patients with refractory chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a common treatable neuropathy, however, nearly 20% of patients remain refractory to standard therapy for unclear reasons. We did a retrospective review of 37 patients referred for CIDP refractory to intravenous immunoglobulin (IVIg), plasmapheresis, and/or corticosteroids. Clinical findings, electrophysiological studies, and response to further therapeutic interventions were assessed. Forty-six percent of patients had CIDP, while 54% had alternate diagnoses. Of patients with confirmed CIDP, 87% showed improvement with escalation of therapy. Distal leg weakness, vibratory sensory loss, and widespread areflexia were significantly more common in patients with confirmed CIDP. Reasons for therapeutic failure in CIDP are inadequate immunotherapy and alternative diagnoses. Certain clinical and electrophysiological features help to distinguish true CIDP from mimics. Once CIDP is confirmed, optimization of IVIg dosing, addition of corticosteroids, plasmapheresis, or chemotherapy results in consistent improvement. Caution is advised when using response to therapy to diagnose CIDP. Muscle Nerve 55: 476-482, 2017.

Rituximab in a childhood-onset idiopathic refractory chronic inflammatory demyelinating polyneuropathy

Childhood-onset chronic inflammatory demyelinating polyneuropathy (CIDP) are generally responsive to conventional immunosuppressant treatments. However about 20% of patients may be refractory to several treatments and the disease has poor outcome. Rituximab is becoming a promising treatment in selected adult cases of severe CIDPs. We report the effectiveness of Rituximab in a refractory childhood-onset CIDP and we suggest this treatment as an effective choice in unresponsive childhood CIDP.

NONMYELOABLATIVE AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR REFRACTORY CIDP

Most patients with chronic inflammatory demyelinating polyneuropathy (CIDP) initially respond to corticosteroids, immunosuppressive drugs, IV immune globulin (IVIg), and plasma exchange (PE). However, more than half relapse, with some developing a recurrent or persistent clinical course resulting in severe disability and even death.1,2 Nonmyeloablative autologous hematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases has demonstrated promising results, with reports of durable remissions and lower toxicity compared to myeloablative HSCT.3 Herein, we report the first patient treated in a phase I trial of autologous HSCT utilizing a nonmyeloablative regimen for refractory CIDP. ### Methods. Eligibility criteria include age 65 years or less; definite or probable CIDP according to the criteria of the Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force; failure of standard therapy, i.e., incomplete response or relapse after corticosteroids, IVIg, or PE; and failure to respond to at least one second-line immunosuppressive drug (methotrexate, azathioprine, cyclosporine, tacrolimus, or mycophenolate mofetil [MMF]). CD34-enriched peripheral blood stem cells …

Treatment of refractory chronic inflammatory demyelinating polyneuropathy with interferon β1B

Sirs: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy [13] characterized by symmetrical sensory and/or motor symptoms persisting for more than 8 weeks. The disease course may be progressive or relapsing [13]. On the basis of randomized trials, high dose intravenous immunoglobulin (IVIg), corticosteroids and plasma exchange have been established as effective treatments for CIDP. The main limitations of these approaches are lack of long term efficacy, difficulties in their use and high costs; thus, alternative immunosuppressive treatments have been proposed (azathioprine, cyclosporine and cyclophosphamide) [2, 9, 11]. The immune-mechanisms responsible for CIDP resemble those implicated in multiple sclerosis (MS) [13], thus making CIDP the peripheral counterpart of MS. In addition, similar to MS, neuropathological studies support heterogeneity of CIDP pathogenesis, with concomitant demyelination and axonal damage [13]. Some studies have recently been performed to evaluate the usefulness of Interferon (IFN) β1a in CIDP patients unresponsive to conventional therapies [1, 7, 14]. We present the case of a 43year-old woman, who in July 1997 complained of progressive weakness in both lower limbs, as well as sensory symptoms. Clinical symptoms persisted until December 1997 and a diagnosis of CIDP was made according to INCAT criteria [3]. Neurological examination revealed generalized areflexia, while an electrophysiological study showed partial conduction block for stimulation at the fibular head of peroneal nerves (–50 % amplitude on the right and –49 % on the left) and absent F wave on the left median nerve and right peroneal nerve. Cerebrospinal fluid analysis produced evidence of albuminocytological dissociation (total protein 82 mg/dL without cells) and isoelectrofocusing was within normal limit. After a first treatment schedule of IVIg with a good response, she became refractory to this treatment. She presented nine relapses throughout 27 months (treated with plasma exchange with transient and partial response) despite the specific drugs used (Figure). In July 2001 she started IFNβ-1b (Betaferon) 8MUI with subcutaneous injections every other day. No other relapses occurred. At present, she has been relapsefree for 40 months and shows marked improvement in clinical conditions (Table 1). Nerve conduction studies also showed marked improvement in motor and sensory velocities (Figure). In April 2002, serological examination showed the presence of anti-thyreoglobulin and anti-thyroid peroxidase antibodies, with an increase in free triiodothyronine and free thyroxin. Autoimmune thyreopathy was diagnosed, and the patient started treatment with an antithyroid drug. IFN beta has been proven efficient in treating MS [4, 5, 12] reducing the number of relapses. Due to clinical similarities between MS and CIDP, there is emerging interest in the use of IFN in CIDP. As far as we know, this is the first report in which IFNβ-1b has been used to treat a CIDP patient. Our patient showed good clinical and neurophysiological response to long-term IFNβ1b treatment (40 months). The stabilization observed was judged by the absence of relapses. IFN beta acts as an immunomodulatory agent, exerting its action at different levels in the inflammatory process. Two recombinant forms of IFN beta are used in clinical practice: IFNβ-1a and INFβ-1b. The use of IFNβ-1a in the treatment of CIDP is controversial, and contradictory results have been reported in different studies [1, 6, 12]. It should be noted that LETTER TO THE EDITORS

High‐dose cyclophosphamide results in long‐term disease remission with restoration of a normal quality of life in patients with severe refractory chronic inflammatory demyelinating polyneuropathy

We previously reported the improvement of clinical parameters in severe, refractory chronic inflammatory demyelinating polyneuropathy (CIDP) following high-dose cyclophosphamide therapy. Here, we examine effects of this therapy on quality of life, report long-term clinical follow-up, and include new data on a fifth patient. Patients completed The Medical Outcomes Short Form 36 to assess quality of life impact. Pretherapy and post-therapy scores were compared with the Wilcoxon Signed Ranks Test. Patient's post-therapy scores were compared with the normal United States population. Functional status was assessed with the Modified Rankin score. Strength was assessed using a summated MRC strength. Nerve conduction studies were conducted using standard techniques with supramaximal stimulation. The median follow-up for the five patients is 2.9 (range: 1.6-4.8) years. The first four patients remain off all immunomodulatory medications. In six of the eight quality of life scales measured, patients enjoyed clinically significant improvement. Their overall strength increased by a median change of 10 (range: -1 to 20); their overall Modified Rankin score increased by a median of 3 (range: 0-4), and their summated compound motor action potential amplitudes increased by a mean of 3.69 mV (range: 0.156-7.83). Patient 5 has had stabilization of motor strength. High-dose cyclophosphamide can markedly improve functionality and quality of life for patients with severe refractory CIDP.

High-Dose Immunosuppression for Refractory CIDP?

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy for which treatment with plasma exchange, intravenous

High-dose cyclophosphamide without stem-cell rescue for refractory CIDP.

Four patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who were refractory to conventional treatment were treated with high-dose cyclophosphamide (200 mg/kg over 4 days). All improved in functional status and muscle strength. Nerve conduction studies improved in three of four. Other immunomodulatory medications have been discontinued. High-dose cyclophosphamide can be given safely to patients with CIDP and patients with disease persistence after standard therapy may have a response that lasts for over 3 years and results in long-term disease remission.

Prognosis in long-term immunosuppressive treatment of refractory chronic inflammatory demyelinating polyradiculoneuropathy

Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) frequently includes use of immunosuppressive agents. Controlled treatment trials demonstrating efficacy are available only for prednisone and therapeutic plasma exchange (TPE). When these fail to achieve lasting clinical improvement after reduction or cessation of therapy, subsequent regimens are empiric, often leading to prolonged immunosuppression. It is not possible to predict who will respond to which agent and when. Administered individually, immunosuppressive agents may pose an acceptable risk, but cumulative effects of multiple agents in refractory patients may suppress the immune system and contribute to increased morbidity and mortality. Treatment difficulties with refractory CIDP patients have not been emphasized, and long-term effects of immunosuppression have focused on the risk of malignancy. In reviewing our clinical experience treating over 100 CIDP patients we identified approximately 20 patients who could be considered refractory to multiple immunosuppressive therapies and dependent upon long-term intermittent TPE. Two of these patients exemplify the morbidity associated with CIDP and its associated treatment. Our review of the clinical course of these patients raised issues about the use of multiple immunosuppressive agents, long-term goals, and long-term prognosis in CIDP.