Do A‐waves help predict intravenous immunoglobulin response in multifocal motor neuropathy without block?

Introduction: Are there electrophysiological findings that predict response to intravenous immunoglobulin (IVIg) in patients with lower motor neuron (LMN) syndromes without multifocal conduction block (MCB)? Methods: We enrolled 9 patients with LMN syndromes without MCB to receive 18 weeks of IVIg therapy. Response was measured at weeks 2 and 18 using the Appel Amyotrophic Lateral Sclerosis (AALS) score (includes grip and pincer strength measures), ALS Functional Rating Scale (ALSFRS), and electrophysiological measures, including motor unit estimates (MUNEs). Results: No change occurred in AALS or ALSFRS scores posttreatment. Grip/pincer strength increased in 7 patients (P = 0.028) after initial treatment (responders); 2 showed no improvement (non‐responders). No electrophysiological measure changed after treatment in either group but MUNEs trended higher (P = 0.055). “Abnormal A‐waves” (complex, repetitive biphasic, or present in multiple nerves) occurred in pretreatment studies more often in responders (P = 0.028).Discussion:“Abnormal A‐waves” may signal IVIg‐responsive LMN syndromes even if conduction block is absent. Muscle Nerve, 2011     

Prediction of response to IVIg treatment in patients with lower motor neurone disorders

The distinction between multifocal motor neuropathy, treatable by intravenous immunoglobulins (IVIg), and degenerative motor neurone disorders is often difficult. To find predictive factors for the response to IVIg treatment, 40 consecutive patients with pure lower motor neurone disorders (LMND) were prospectively examined. They all received at least two times IVIg (2 g/kg bodyweight). Prior to the first and before all the following treatments a standardized evaluation was performed including clinical examination, neurophysiological and laboratory evaluation. According to changes in the neurological examination and the Neuromuscular Symptom Score, the patients were divided into responders and non-responders after the second course of treatment. In our study, no single clinical, neurophysiological, or laboratory parameter was sensitive enough to predict response. The only single parameter that highly correlated with a positive response to treatment was an elevated GM1 antibody titre. Lack of response to IVIg treatment is likely in patients with generalization of electromyographic signs of denervation beyond the clinically involved site, proximal localization of the weakness, and an elevated level of the creatinekinase. Conduction blocks do not distinguish between both groups. We propose a scoring system combining clinical, serological and neurophysiological data in order to decide which patients with LMND may receive IVIg.     

Multifocal motor neuropathy improved by IVIg: randomized, double-blind, placebo-controlled study

OBJECTIVE: To determine the effect of IV immunoglobulin (IVIg) on neurologic function and electrophysiologic studies in multifocal motor neuropathy with conduction block (MMN). BACKGROUND: MMN is characterized by progressive, asymmetric, lower motor neuron weakness and is probably immune-mediated. IVIg treatment has been shown to have beneficial effects in several open-label studies and in one small controlled trial. However, larger randomized controlled studies are lacking. METHODS: The authors recruited 16 patients with MMN. All subjects were given each of two treatments (IVIg [0.4 g/kg/d for 5 consecutive days] or placebo [dextrose or saline]) that were assigned according to a randomized, crossover design under double-blind conditions. Patients were evaluated before and about 28 days after trial treatment for subjective functional improvement, neurologic disability score, grip strength, distal and proximal compound muscle action potential amplitude, and conduction block. RESULTS: Subjective functional improvement with IVIg treatment was rated as dramatic or very good in nine patients, moderate in one, mild in one, and absent in five patients. This improvement was absent after placebo. The neurologic disability score improved by 6.7+/-3.3 points with IVIg treatment, whereas it decreased by 2.1+/-3.0 with placebo (p = 0.038). Grip strength on the weaker side was increased by 6.4+/-1.9 kg with IVIg treatment; it decreased by 1.0+/-0.8 kg with placebo (p = 0.0021). Conduction block worsened by 12.98+/-6.52 % with placebo, but improved by 12.68+/-5.62 % with IVIg treatment (p = 0.037). Conduction block was reversed in five patients with IVIg but not placebo. CONCLUSION: IVIg improved conduction block as well as subjective and objective clinical measures of function in patients with MMN.     

Acute-onset multifocal motor neuropathy (AMMN): how we meet the diagnosis

Multifocal motor neuropathy (MMN) usually progresses insidiously with lower motor neuron-type weakness, minimal or no sensory symptoms. Diagnostic criteria include motor conduction block (CB) at sites not exposed to compression or entrapment. CBs may persist or reverse irrespective of clinical outcome. Acute onset with generalized weakness is uncommon. We report four patients who presented acutely areflexia, pure motor deficits without sensory disturbances, multifocal CBs persisting at the same motor nerves on serial electrophysiological studies. Three patients had preceding infections; two showed IgM reactivity against the ganglioside GM1. Intravenous immuneglobulin (IVIg) improved or stabilized symptoms. Patients 2,3,4 receive maintenance therapy with IVIg for years. Acute-onset MMN (AMMN) should be differentiated from other immune-mediated neuropathies such as acute inflammatory polyneuropathy either demyelinating (AIDP) or axonal (AMAN), acute motor conduction block neuropathy (AMCBN), acute-onset chronic inflammatory demyelinating polyneuropathy (CIDP). The correct diagnosis deserves implications for patient long-term treatment and prognosis. Moreover, the authors address the problem of defining the spectrum of MMN particularly in the acute setting.     

Multifocal motor neuropathy with conduction block: a study of 24 patients.

Twenty four patients with pure motor neuropathy are reported. The chronic motor involvement associated with fasciculations and cramps, mainly in the arms, led, in most patients, to an initial diagnosis of motor neuron disease. In some patients (nine of 24), there was no appreciable muscle atrophy. Tendon reflexes were often absent or weak. The finding of persistent multifocal conduction block confined to motor nerve fibres raises questions about the nature and the importance of this syndrome. Segmental reduction of motor conduction velocity occurred at the site of the block, but significant slowing of motor nerve conduction was not found outside this site. The response to intravenous IVIg treatment seems to be correlated with the absence of amyotrophy. Patients with little or no amyotrophy had an initial and sustained response to IVIg, and did not develop amyotrophy during the follow up study. They could be considered to have a variant of chronic inflammatory demyelinating polyneuropathy. Patients with pronounced amyotrophy independent of the disease duration did not respond as well to IVIg treatment, suggesting the existence of a distinct entity. Among the patients treated about two thirds who had an initial good response to IVIg had high or significant antiganglioside GM1 (anti-GM1) antibody titres, but there was no correlation between the high titres before treatment and long lasting response to IVIg treatment.     

多灶性运动神经病的临床表现及肌电图特征

目的 探讨多灶性运动神经病(multifocal motor neuropathy,MMN)的临床表现及肌电图(electromyography,EMG)特征.方法 选择2016 年6 月至2019 年12 月南京医科大学附属南京医院(南京市第一医院)收治的7 例MMN 患者,对其临床资料及神经电生理检查结果进行回顾性...     

Disease severity in multifocal motor neuropathy and its association with the response to immunoglobulin treatment

Disease progression in multifocal motor neuropathy (MMN) was studied by comparing severity and duration of disease. We assessed disease severity by determining muscle weakness, disability, conduction block (CB), and distal and proximal compound muscle action potential (CMAP)- amplitude in 38 patients with MMN in whom disease duration ranged from 6 months to 34 years. As indicator for an ongoing immune-mediated process, the response to one course of IVIg treatment was measured in 34 patients and associated with disease severity. With increasing disease duration, weakness and disability became significantly more severe, and the distal and proximal CMAP-amplitude decreased significantly. The number of CBs was significantly higher in patients with a disease duration longer than 10 years than in those affected less than 10 years. Thirty of the 34 patients responded to IVIg treatment. Non-responsiveness to IVIg was not associated with any of the disease variables. Severe and widespread weakness was significantly associated with a response ≥ 2 on the MRC-sumscore. Our results provide evidence for a slowly progressive disease course of MMN. The good response to IVIg treatment in patients with severe and prolonged disease indicates that progression may be the result of an ongoing immune-mediated process. These findings imply that early treatment may prevent future progression of weakness and disability in patients with MMN. Received: 26 April 2001, Received in revised form: 25 July 2001, Accepted: 2 August 2001     

BEDSIDE SCORING PROCEDURE FOR THE DIAGNOSIS OF DIABETIC PERIPHERAL NEUROPATHY IN YOUNG PATIENTS WITH TYPE 1 DIABETES MELLITUS

Disease progression in multifocal motor neuropathy (MMN) was studied by comparing severity and duration of disease. We assessed disease severity by determining muscle weakness, disability, conduction block (CB), and distal and proximal compound muscle action potential (CMAP) amplitude in 38 patients with MMN in whom disease duration ranged from 6 months to 34 years. As indicator for an ongoing immune-mediated process, the response to one course of IVIg treatment was measured in 34 patients and associated with disease severity. With increasing disease duration, weakness and disability became significantly more severe, and the distal and proximal CMAP-amplitude decreased significantly. The number of CBs was significantly higher in patients with a disease duration longer than 10 years than in those affected less than 10 years. Thirty of the 34 patients responded to IVIg treatment. Non-responsiveness to IVIg was not associated with any of the disease variables. Severe and widespread weakness was significantly associated with a response greater than or equal to 2 on the MRC-sum-score. Our results provide evidence for a slowly progressive disease course of MMN. The good response to IVIg treatment in patients with severe and prolonged disease indicates that progression may be the result of an ongoing immune-mediated process. These findings imply that early treatment may prevent future progression of weakness and disability in patients with MMN.     

Multifocal acquired demyelinating neuropathy masquerading as motor neuron disease

We report five patients with pure motor neuropathy characterized by multifocal weakness, muscle atrophy that was sometimes profound, cramps, and fasciculations with relatively preserved reflexes. The clinical picture led to an initial diagnosis of motor neuron disease in all cases, but nerve conduction studies revealed multifocal conduction block confined to motor axons and predominantly involving proximal nerve segments. Routine sensory nerve conduction studies, ascending compound nerve action potentials, and somatosensory evoked potentials were all normal even through nerve segments in which motor conduction was severely blocked. Onset of symptoms was insidious, and progression was indolent. In two cases, after many years of neuropathy, sensory abnormalities developed but remained clinically trivial. These unusual cases probably have the same pathogenesis as previously described patients with persistent multifocal conduction block. Distinction from motor neuron disease is critical, since chronic demyelinating neuropathy may respond to treatment.     

Multifocal motor neuropathy with conduction block: slow but not benign

OBJECTIVE: To describe a patient with multifocal motor neuropathy with conduction block who had annual clinical and physiological examinations for 18 years but declined treatment for personal reasons. DESIGN: Case report. SETTING: Collaboration between 2 academic tertiary care hospitals. Patient One patient with multifocal motor neuropathy with conduction block. RESULTS: At age 44 years, there was weakness and wasting of the left biceps with conduction block in the left musculocutaneous and right ulnar nerves. The left median nerve was inexcitable. The right median, ulnar, and left peroneal nerves developed axonal change (loss of distal compound muscle action potential amplitude) at years 5, 12, and 13. By 2005, new weakness had appeared in 20 muscles (16 in the arms); he could not use a keyboard, button buttons, or write his name. Nerves that initially showed conduction block became inexcitable over the course of the illness. CONCLUSIONS: Multifocal motor neuropathy with conduction block is a disease that may be "only" slowly progressive but is not always benign. Nerves showing conduction block may develop axonal change. Better markers for this disease are needed.     

Multifocal motor neuropathy: clinical and immunological features and response to IVIg in relation to the presence and degree of motor conduction block

OBJECTIVE: To determine whether patients with clinically typical multifocal motor neuropathy (MMN) with or without definite or probable conduction block (CB) differ in terms of clinical presentation, immunological findings, or response to treatment with intravenous immunoglobulin (IVIg). METHODS: 23 consecutive patients were studied with the typical clinical features of MMN, consisting of a progressive multineuropathic motor impairment with minimal or no sensory loss. In 14 patients, electrophysiological studies disclosed the presence of a definite or probable CB according to the criteria proposed by the American Association of Electrodiagnostic Medicine (AAEM) in at least one motor nerve. Six patients had possible CB, defined as a degree of CB 10% less than that required by the AAEM for probable CB, while no CB was detected in three patients. RESULTS: Patients with possible CB did not differ from those with a definite or probable CB in terms of age at disease onset (mean 38.8 v 38.2 years, respectively), distribution and severity of limb weakness, clinical impairment (mean Rankin score 2.2 in both), and frequency of antiganglioside antibodies (33% v 29%). Patients with possible CB had a longer mean disease duration (9 v 5.9 years, p < 0.05) and a less frequent consistent response to IVIg (67% v 86%) than those with a definite or probable CB. Patients without a detectable CB had a similar frequency of antiganglioside antibodies (33%) but had a longer disease duration (20.3 years), greater impairment (Rankin score 2.7), and more frequent signs of axonal degeneration (41% of examined motor nerves) than patients with CB (13-15%, p < 0.005). Only one patient without detectable CB (33%) consistently improved with IVIg. CONCLUSIONS: Patients with possible CB were clinically and immunologically indistinguishable from those with definite or probable CB, albeit with a slightly less frequent response to IVIg. This finding suggests that failure to fulfil AAEM criteria for CB in patients with otherwise clinically typical MMN should not preclude this diagnosis and consequently a treatment trial with IVIg. Whether the longer duration and greater severity of the disease and more frequent axonal impairment in patients without detectable CB than in those with CB explain their lower response to IVIg remains to be established.     

Long term follow up of multifocal motor neuropathy with conduction block under treatment.

Eighteen patients (15 men, three women; age range 30 to 71 years, mean 45.8 years) with multifocal motor neuropathy treated with high dose intravenous immunoglobulin (IVIg) were evaluated for nine to 48 months (mean follow up 25.3 months). The median time between onset of multifocal motor neuropathy and treatment was 5.8 years. The dose of IVIg was 0.4 g/day for three to five days. The interval between each treatment was determined for each patient by the evaluation of the effect of the first course. Muscle strength was evaluated by a computerised analyser. Clinical improvement was seen in 12 patients treated with IVIg (67%). Isometric strength increased from 32% to 97% (mean 54.5%) of the initial value. Functional scales corroborated these findings. No clear predictive factors of response to IVIg was found except the presence of high titres of IgM anti-GM1 antibodies. Often, patients needed repeated courses of IVIg to maintain the improvement. In two patients, IVIg infusions were stopped without signs of relapse after one year. Four patients were initially treated with prednisone (1 mg/kg/day), without any clear improvement. Five patients with no response to IVIg or who were IVIg dependent were treated with cyclophosphamide, but only one showed improvement. These results show the long term benefits and safety of IVIg in multifocal motor neuropathy but also the transient effect of this expensive treatment in most patients.     

Long-term follow-up of multifocal motor neuropathy with conduction block under intravenous immunoglobulin

INTRODUCTION: Multifocal motor neuropathy with conduction block is an immune-mediated motor neuropathy, which usually responds to intravenous immunoglobulin. However, efficacy of long-term intravenous immunoglobulin is controversial. Our aim was to establish the long-term effects of intravenous immunoglobulin therapy on clinical and neurophysiological outcome measures and to determine the criteria predicting a good response to long-term intravenous immunoglobulin treatment. METHODS: We retrospectively included all multifocal motor neuropathy with conduction blocks patients followed for at least 4 years who received intravenous immunoglobulin therapy. We compared clinical data, MRC sumscores and electrophysiological data between the first and the last examination in the department. RESULTS: Seventeen patients were followed for an average of 8 years (range 4 to 18 years). At last examination, weakness remained asymmetric, predominant in the upper limbs, with a peripheral nerve distribution. At last examination, 3 patterns of evolution was seen: 6/17 patients had muscle strength improvement and need no more intravenous immunoglobulin therapy, 6/17 had initial improvement but became intravenous immunoglobulin dependent and 5/17 did not respond to intravenous immunoglobulin. MRC sumscores, number of conduction blocks and distal compound muscle action potential amplitudes were comparable between the first and the last examination (p>0.05). Improvement of MRC sumscores was not correlated with the clinical, biological and electrophysiological data that we analysed: age, gender, duration of disease, time from onset to intravenous immunoglobulin therapy, number of involved nerves, number of affected limbs, presence of muscle atrophy, MRC sumscores at diagnosis, number of conduction blocks, mean amplitude of the motor evoked potentials, presence of anti-GM1 antibodies, titers and IgM or IgG type of anti-GM1 antibodies. CONCLUSIONS: In this study, one third of multifocal motor neuropathy with conduction blocks patients have clinical improvement at last examination and need no more treatment, one third are intravenous immunoglobulin dependent and one third have never responded to intravenous immunoglobulin. Electrophysiological data are comparable between the first and the last examination. No predictive factor has been disclosed for long-term response to intravenous immunoglobulin.     

Multifocal motor neuropathy with conduction block with sensory fibre involvement in a diabetic patient. Case report

Multifocal motor neuropathy with conduction block (MMNcb) is a relatively rare disease characterized clinically by asymmetric limb weakness with spared sensation and electrophysiologically by persistent focal motor conduction block. We present the case of a 40-year-old male patient with six-year history of progressive, asymmetric weakness of upper and lower extremities without sensory symptoms. Electroneurography revealed definite or probable motor conduction block in several nerves. However, features of axonal lesion of sensory fibres were also found. Laboratory studies were unremarkable apart from an abnormal glucose tolerance test, and type 2 diabetes was diagnosed. In the presented case the differential diagnosis should take into consideration MMNcb with coexisting diabetic sensory polyneuropathy and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM).     

Acute-onset painful upper limb multifocal demyelinating motor neuropathy

We report three patients who presented with acute onset of shoulder and upper arm pain followed within a few days by predominantly distal upper limb weakness. Nerve conduction studies showed severe and unequivocal focal motor conduction block in the forearm and/or upper arm along with slowing of motor conduction and prolonged F wave responses. Only very mild changes in sensory nerve conduction were found. One patient made partial clinical improvement after 17 months, and there was a significant improvement in the degree of motor conduction block and the motor conduction velocities. A second patient remained unchanged after 5 months. Idiopathic brachial neuritis (IBN) typically presents acutely with brachialgia and acute or subacute non-progressive weakness. Multifocal motor conduction block in nerves in the arm or forearm has not been described in patients with IBN. Multifocal motor conduction block restricted to the upper limbs has been described in focal chronic inflammatory demyelinating polyneuropathy (CIDP) and in multifocal motor neuropathy with multifocal motor conduction block (MMNCB). However, both these conditions have hitherto usually been described as largely painless chronic progressive disorders with a subacute onset. Our patients, with features overlapping MMNCB/CIDP and IBN, represent an as yet unreported clinical variant. Received: 9 February 2000 / Received in revised form: 18 May 2000 / Accepted: 28 June 2000     

Differential weakness of finger extensor muscles: A clinical pattern of multifocal motor neuropathy

Introduction: Several studies have suggested that differential weakness in muscles supplied by the same motor nerve supports the diagnosis of multifocal motor neuropathy (MMN). Methods: We describe the clinical, electrophysiological, neuroimaging, and laboratory findings of patients with a lower motor syndrome whose clinical presentation included differential finger extension weakness that we have seen in our neuromuscular clinic. Results: We identified 3 patients with hand weakness and 1 patient with asymmetric weakness of the upper extremity. Conduction blocks (CBs) were identified in 1 patient. Anti‐GM1 immunoglobulin M antibodies were detected in 2 of the 3 patients tested. Only 1 patient responded to intravenous immunoglobulin (IVIg). Rituximab was administered in another patient, but we did not detect a response. Conclusions: We suggest that differential finger extension weakness is a feature that may be seen in MMN, even in the absence of CB or response to IVIg. Muscle Nerve 55 : 433–437, 2017     

Diagnosis and treatment of multifocal motor neuropathy (Lewis-Sumner)]

We made a retrospective long-term follow-up study of 25 patients with multifocal motor neuropathy (Lewis-Sumner). The diagnosis was based upon criteria modified from those of AAEM (Sumner 1997). The electrophysiological findings indicating conduction block or focal demyelinative lesions were more diagnostic than anti-GM 1 antibody titers, which were elevated in only 40% of these patients. Demonstration of definite conduction block was not always possible in those patients who responded favorably to intravenous immunoglobulins (IVIg), whereas indirect pieces of evidence such as F-wave abnormalities or focal conduction delay or dispersion were equally helpful. IVIg had superior outcome to cyclophosphamide, which sometimes caused serious adverse effects. Three patients with severe axonal involvement showed elevated monospecific antibodies to GalNAc-GD1a.     

Consensus criteria for the diagnosis of multifocal motor neuropathy

At this time, there are no widely accepted criteria for the diagnosis of multifocal motor neuropathy. Furthermore, there is insufficient empirical data to define clinical and laboratory features that may reliably separate certain lower motor neuron syndromes with overlapping features as distinct. The AAEM therefore developed five criteria through a formal consensus process that are described in this document to act as a guide for diagnosing multifocal motor neuropathy with a high level of confidence (definite multifocal motor neuropathy) or with a moderate level of confidence (probable motor neuropathy). In brief, the diagnosis requires clinical weakness without objective sensory loss or upper motor neuron signs in the distribution of two or more named nerves that is due to conduction block in two or more motor nerves outside of common entrapment sites. Furthermore, normal results are required for sensory nerve conduction studies.     

Multifocal acquired demyelinating sensory and motor neuropathy: report of a case and review of the literature

Multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy is characterized by an asymmetric multifocal pattern of motor and sensory loss, and conduction block and other features of demyelination in nerve conduction studies. MADSAM neuropathy needs to be differentiated from chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). In classic CIDP, there are symmetric proximal and distal weakness, sensory deficit in both upper and lower extremities and reduced deep tendon reflex. In MMN, limb weakness without sensory loss is asymmetric in the distribution of individual peripheral nerves and the weakness typically begins in the distal upper extremities. We report one patient with chronic progression of asymmetric numbness and weakness in four extremities. MADSAM neuropathy was diagnosed after extensive clinical and laboratory evaluations. It is very important to distinguish between CIDP, MADSAM neuropathy, and MMN by clinical, laboratory, and histological features because of different effective therapeutic strategies.     

Slow resolution of multifocal weakness and fasciculation: a reversible motor neuron syndrome

A 25-year-old man with multifocal weakness and fasciculation was thought to have motor neuron disease. Signs progressed for 1 year, plateaued, and 3 years later resolved almost completely. There was no evidence of paraproteinemia, lymphoproliferative disorder, or vasculitis, and myelography was normal. Electrodiagnostic study disclosed multifocal, acute and chronic denervation that evolved into a picture consistent with residuals of old multifocal radiculopathy without active denervation. Prolongation of F response, absence of H-reflex, and conduction block in a proximal nerve segment suggested multifocal demyelination. A proximal motor neuropathy, perhaps demyelinating, may cause some of the benign motor neuron syndromes that simulate motor neuron disease.