Multifocal Motor Neuropathy With Conduction Block Research Articles

Predicting long-term trends in inflammatory neuropathy outcome measures using latent class modelling.

Immunoglobulin (Ig) is used to treat chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). Regular infusions may be used for symptom control. Disease activity is monitored with clinical outcome measurements. We examined outcome measure variation during clinically stable periods in Ig-treated CIDP and MMNCB patients. We explored utility of serial outcome measurement in long-term outcome prediction. Retrospective longitudinal analysis of a single neuroscience centre's Ig-treated CIDP and MMNCB patients, 2009-2020, was performed. Mean and percentage change for grip strength, Rasch-built overall disability scales (RODS) and MRC sum scores (MRC-SS) during periods of clinical stability were compared to score-specific minimal clinically important differences (MCID). Latent class mixed modelling (LCMM) was used to identify longitudinal trends and factors influencing long-term outcome. We identified 85 CIDP and 23 MMNCB patients (1423 datapoints; 5635 treatment-months). Group-averaged outcome measures varied little over time. Intra-individual variation exceeded MCID for RODS in 44.2% CIDP and 16.7% MMNCB datapoints, grip strength in 10.6% (CIDP) and 8.8%/27.2% (MMNCB right/left hand) and MRC-SS in 43.5% (CIDP) and 20% (MMNCB). Multivariate LCMM identified subclinical trends towards improvement (32 patients) and deterioration (73 patients) in both cohorts. At baseline, CIDP 'deteriorators' were older than 'improvers' (66.2 vs 57 years, P= .025). No other individual factors predicted categorisation. The best model for 'deteriorator' identification was contiguous sub-MCID decline in more than one outcome measure (CIDP: sensitivity 74%, specificity 59%; MMNCB: sensitivity 73%, specificity 88%). Outcome measure interpretation determines therapeutic decision-making in Ig-dependent neuropathy patients, but intra-individual variation is common, often exceeding MCID. Here we show sub-MCID contiguous changes in more than one outcome measurement are a better predictor of long-term outcome.

Treatment Approaches for Atypical CIDP.

The variants of chronic inflammatory demyelinating polyneuropathy (CIDP) differ not just in their clinical, pathological and electrophysiological characteristics, but often in their indifferent response to conventional immunosuppressive agents which are effective in typical CIDP. High quality evidence is lacking as far as the management of these atypical variants is concerned. In this review, we summarize the treatment approaches to each of these CIDP variants based on existing data. Distal acquired demyelinating symmetric polyneuropathy (DADS) has the phenotype of a symmetric, demyelinating sensory, length-dependent polyneuropathy and is frequently associated with paraproteinemia and anti myelin associated glycoprotein (MAG) antibodies. While the management of idiopathic DADS (DADS-I) is the same as CIDP, DADS-M responds suboptimally and has a favorable response to rituximab. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) manifests as a chronic progressive demyelinating mononeuropathy multiplex which can evolve to a confluent pattern indistinguishable from CIDP. Evidence favors treating MADSAM with conventional immunomodulatory therapy (IMT), but this disorder responds less favorably than CIDP. Some patients present with purely sensory symptoms, known as pure sensory CIDP or chronic inflammatory sensory polyradiculoneuropathy (CISP), the latter localizing to a pre-ganglionic pathology. Both respond well to first line IMT, particularly to intravenous immunoglobulin (IVIG), but patients relapse without maintenance therapy. Pure motor CIDP resembles multifocal motor neuropathy with conduction block (MMNCB), but the previously reported worsening status after steroid treatment was not reproduced in recent studies, and IVIG remains the first-line therapy. Some focal forms of CIDP defy exact classification, but respond well to first-line IMT including IVIG. Overall, atypical CIDP responds to treatment with first-line IMT, but has a suboptimal response compared to CIDP. There is evidence for effectiveness with agents such as rituximab, especially in DADS-M, and this medication can also be used in cases refractory to conventional IMTs. Rituximab is also effective in CIDP with IgG4 antibodies which has distinct clinical features and is mostly refractory to first-line IMT.

Dramatic clinical response to ultra-high dose IVIg in otherwise treatment resistant inflammatory neuropathies

Background Intravenous immunoglobulin (IVIg) has short and long-term efficacy in both chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). There is potential for under and over-treatment if trial regimens are strictly adhered to in clinical practice where titrating dose to clinical response is recommended. Methods We report the response to high-dose IVIg (>2 g/kg/6 weeks) in a subgroup of patients with definite CIDP or MMNCB who were unresponsive to ‘usual’ dosing. IVIg frequency and dosing was determined for each individual by subjective and objective outcome measures for impairment, grip strength, and activity and participation. Results Six patients (three with chronic inflammatory demyelinating polyneuropathy (CIDP), three with MMN) were included. Two patients (one CIDP and one MMNCB) returned to full-time work on fractionated IVIg doses of 5 g/kg/month and 9 g/kg/month. Patient three (CIDP) failed numerous other immunosuppressants but responded to short-term fractionated 4 g/kg/month of IVIg. Patient four has severe, refractory, childhood-onset CIDP, remains stable but dependent currently on 6.9 g/kg/month of IVIg. Patients five and six, both with MMNCB, required short term 4.5–5 g/kg/month to recover significant bilateral hand strength. No IVIg-related adverse events occurred in any individual. Conclusions These six cases demonstrate the safety and effectiveness of a treatment approach that includes individualised but evidence-based clinical assessment and, when necessary, high-doses of IVIg to restore patients’ strength and ability to participate in activities of daily activities. Careful patient selection is important.

Multifocal Motor Neuropathy Associated With Infliximab

Multifocal motor neuropathy with conduction block (MMN-CB) is purely a motor neuropathy with progressive weakness that is characteristically caused by conduction blocks. Association with antiganglioside antibodies and a good response to immunomodulating therapies suggest an autoimmune etiology. In rare cases, MMN-CB has been reported as an adverse effect of infliximab, a tumor necrosis factor-α blocker. We present a case of MMN-CB due to infliximab in a 45-year-old man with psoriatic arthritis who was exposed to the drug for 2 years because of a delayed diagnosis. We emphasize the possibility of this adverse effect and the importance of detailed electrophysiological examinations, which is supported by a review of the literature.

Neutropenia Following Intravenous Immunoglobulin Administration in a Patient with Multifocal Motor Neuropathy with Conduction Block

Intravenous immunoglobulin (IVIG) is the treatment of choice in patients with multifocal motor neuropathy with conduction block (MMNCB). Although IVIG is considered generally safe, neutropenia following IVIG infusion has been recognized as a rare hematologic side effect. Herein we report a patient with MMNCB who developed severe neutropenia following IVIG administration. A 41 year old woman presented with progressive weakness of her left lower extremity with frequent muscle cramps. Nerve conduction study revealed marked conduction blocks on right ulnar and right tibial nerves. Serum IgM anti-GM1 antibody was detected. Neutrophil count decreased from day 2 and recovered after 2 weeks following IVIG infusion. To our knowledge, neutropenia following IVIG infusion in MMNCB has never been discussed apart, although it can be an important clinical issue especially for patients with MMNCB.

Multifocal Motor Neuropathy with Conduction Block Following Treatment with Infliximab

To the Editor: Anti-tumor necrosis factor-α (anti-TNF) therapy is a frequent therapeutic modality in patients with autoimmune disease. There is increased recognition that these agents may cause various inflammatory demyelinating neuropathies. We describe a 36-year-old man with Crohn’s disease who developed multifocal motor neuropathy with conduction block (MMNCB) after treatment with infliximab. He was diagnosed in 1997 with severe fistulizing Crohn’s disease. He was started on infliximab in hospital in February 2000 as he had not responded to treatment with azathioprine, metronidazole, and ciprofloxacin. He had 2 further infusions of infliximab in April and May 2000. On May 30, 2000, he underwent ileocolic resection. Preoperatively he reported mild hand numbness; postoperatively he developed progressive bilateral weakness of his wrists, finger extensors, and interossei as well as marked weakness in the extensors of his toes and moderate weakness of his ankle dorsiflexors. Sensation was preserved. Nerve conduction studies revealed mildly delayed ulnar F-wave latency at 32.7 ms. The remainder of the study was normal. Conduction block was not found. Electromyography revealed reduced recruitment in muscles of the upper and lower extremity, with fibrillation potentials and positive sharp waves identified in tibialis anterior, medial gastrocnemius, extensor digitorum, and first dorsal interosseus. The electrophysiological diagnosis was a motor neuropathy … Address correspondence to Dr. Barber. E-mail: claire.barber{at}utoronto.ca

Sensory loss in multifocal motor neuropathy: A clinical and electrophysiological study

Some patients fulfilling the criteria for the diagnosis of multifocal motor neuropathy with conduction block (MMN-CB) at the onset of disease may subsequently develop a sensory loss associated with electrophysiological sensory abnormalities. The latter could represent an overlap between MMN-CB and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. The objective was to specify the features of MMN-CB with sensory loss (MMN-CB-Se). Five patients in a series of 11 consecutive patients who fulfilled the criteria of the American Association of Neuromuscular and Electrodiagnostic Medicine for MMN-CB at the first examination and were treated periodically with intravenous immunoglobulin (IVIg) developed sensory loss in the course of the disease. In these five patients we compared the clinical, laboratory, and electrophysiological features found after the development of sensory loss with those at the first examination. The mean time to appearance of objective sensory signs was 7.2 years. In three of the five patients the sensory loss was preceded by intermittent paresthesias in the same nerve territories as the motor involvement. The most frequent electrophysiological abnormality was amplitude reduction of sensory nerve action potentials. There were no bilateral or symmetrical clinical and electrophysiological sensory abnormalities. Anti-GM1 IgM antibodies were positive in four patients. MMN-CB-Se could be an overlap between MMN-CB and MADSAM. It shares the distribution of the sensory disorders encountered in MADSAM, but it is closer to MMN-CB on clinical and therapeutic levels. Study of more patients would be useful to classify this subgroup more accurately.

Triple‐stimulation technique in multifocal neuropathy with conduction block

In patients with multifocal neuropathy with conduction block (CB), CBs located between the root and Erb's point are not detected in nerve conduction studies. We therefore examined whether the triple-stimulation technique (TST) might provide a useful means of detecting CB proximal to Erb's point. Clinical assessments, extensive nerve conduction studies (NCS), conventional transcranial magnetic stimulation, and TST were performed on 10 patients with multifocal motor neuropathy with CB (MMNCB) and 6 patients with Lewis-Sumner syndrome. Conduction blocks located proximal to Erb's point were detected in 9 patients. Of the CBs, 58% were associated with muscle weakness. The use of TST to detect proximal CB improved the sensitivity of the American Association of Neuromuscular and Electrodiagnostic Medicine criteria for definite or probable MMNCB from 60% to 90%. Thus, the TST is a useful means for detection of proximal CB and gives NCS considerable additional diagnostic power.

Infliximab-associated neuropathy in RA patients—the importance of considering the diagnosis of mononeuritis multiplex

Accurate recognition of demyelinating syndromes affecting the peripheral and central nervous system is increasingly important in rheumatoid arthritis (RA) patients, given the association of TNF-alpha inhibitors with multiple sclerosis and demyelinating neuropathies. Tektonidou et al. report on two patients with RA developing neuropathy during treatment with Infliximab, including a patient with electrodiagnostic features reportedly consistent with a diagnosis of multifocal motor neuropathy with conduction block (MMNCB) [1]. However, there are several clinical and electrodiagnostic features of this patient’s neuropathy, which are potentially more consistent with an axonal mononeuritis multiplex. First, MMNCB is a diagnostic entity characterized by the insidious progression of asymmetric motor neuropathy developing over months to years, with reports of symptoms persisting for decades before diagnosis [2]. The chronicity of lower motor signs, such as wasting and fasciculation, can be confused with ALS. Therefore, the relative acuity of asymmetric motor neuropathy with rapid deterioration after an Infiximab infusion is highly atypical of MMNCB. In a case report referenced by the authors, Singer et al. describe a multifocal neuropathy with conduction blocks developing over 3 weeks in a RA patient treated with Infliximab. In this report, Singer et al. carefully note that the acuity of neuropathic symptoms, coupled with overlapping axonal electrodiagnostic features, necessitated a diagnosis other than MMNCB [3]. In another case report putatively describing MMNCB in a RA patient treated with Infliximab, the presence of cryoglobulins imply that the salient neuropathic mechanism might be a cryoglobulinemic vasculitis [4]. It is important to appreciate that “conduction block” is an electrodiagnostic term, which is not synonymous with demyelinating neuropathies, but can also be found in the axonal neuropathy of mononeuritis multiplex [5, 6]. The conduction block of mononeuritis multiplex is usually transient, occurring at focal regions of axonal ischemia. Over time, the conduction block disappears, and is replaced by electrodiagnostic features of an axonal neuropathy— leading to its designation as a “pseudo-conduction block” [5, 6]. Therefore, in the current patient, the multifocal regions of distal weakness, which presumably correspond electrodiagnostically to multiple conduction blocks, could also have a vasculitic as well as a demyelinative etiology. Sequential EMGs are useful to determine whether a conduction block is due to a demyelinating or an axonal neuropathy. In the authors’ case, if followup EMGs showed evolution of axonal changes, —i.e., decrease in amplitude of distal compound motor action potentials (CMAP) on nerve conduction studies, or evolution of fibrillations in denervated muscles—then this would be more suggestive of an axonal mononeuritis multiplex with a “pseudo-conduction block”. Although, neither specific nor necessary for diagnosis of MMNCB, the anti-GM1 antibody is associated with MMNCB in approximately 50% of cases [2], and would further have been useful in distinguishing between a demyelinating Clin Rheumatol (2007) 26:281–282 DOI 10.1007/s10067-006-0436-6

P29.5 Multifocal motor neuropathy with conduction block (MMNCB) masquerading as recurrent strokes – an unusual presentation and a clinical lesson

P29.5 Multifocal motor neuropathy with conduction block (MMNCB) masquerading as recurrent strokes – an unusual presentation and a clinical lesson

Multifocal motor neuropathy with conduction block associated with metastatic lymphoma of the nervous system

Peripheral neuropathies occur in 5% of patients with Non-Hodgkin Lymphoma and represent the effects of therapy, direct compression or nerve infiltration by tumor, or paraneoplastic effects. Multifocal motor neuropathy with conduction block (MMNCB) is a rare demyelinating disorder of unknown etiology characterized by progressive, distal, asymmetric weakness mostly of the upper limbs with minimal or no sensory loss. We report a patient, who developed MMNCB at the time of isolated CNS relapse from a diffuse large B-cell lymphoma. Marked neurological improvement was achieved using intravenous immunoglobulin treatment. To our knowledge, MMNCB has thus far not been described as part of the spectrum of lymphoma-related peripheral neuropathies.

Treatment of immune-mediated inflammatory neuropathies.

Experimental models have suggested potential new treatments for human inflammatory neuropathy, but current practice is largely based on empirical trials. Evidence from randomized trials supports the use of intravenous immunoglobulin in Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). In Guillain-Barré syndrome and CIDP intravenous immunoglobulin is equivalent to but more convenient than plasma exchange. In MMNCB adequate comparative studies of intravenous immunoglobulin and plasma exchange have not been performed. Corticosteroid treatment is beneficial in CIDP, but not in Guillain-Barré syndrome and may worsen MMNCB. More randomized trials and systematic reviews are needed to improve the evidence base for clinical practice.