Multifocal motor sensory demyelinating neuropathy: inflammatory demyelinating polyradiculoneuropathy

The authors present two cases that provide the first autopsy findings in multifocal acquired demyelinating sensory and motor neuropathy (MADSAMN). Both cases documented multifocal but asymmetric demyelinating neuropathy with rare axonal degeneration. One case clearly documented an inflammatory polyradiculoplexoneuropathy, confirming the inflammatory nature of this neuropathy. This study showed that MADSAMN is an inflammatory demyelinating polyradiculoneuropathy that shares histologic features observed in chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy (MMN), suggesting a similar immunopathogenesis for these entities.     

Multifocal acquired demyelinating sensory and motor neuropathy presenting as a peripheral nerve tumor

A man with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), or Lewis-Sumner syndrome, presented with a progressive left lumbosacral plexus lesion resembling a neurofibroma. After 7 years he developed a left ulnar nerve lesion with conduction block in its upper segment. Treatment with intravenous immunoglobulin improved the symptoms and signs of both lesions. We conclude that inflammatory neuropathy must be considered in the differential diagnosis of peripheral nerve tumors, and that unifocal lesions may precede multifocal involvement in MADSAM by several years. In addition, we discuss the clinical features in 9 patients attending a specialist peripheral nerve clinic and review the literature.     

Childhood multifocal acquired demyelinating sensory and motor neuropathy

We report the first pediatric cases of multifocal acquired demyelinating sensory and motor neuropathy with electrophysiologic evidence of proximal conduction abnormalities but no definite conduction block. Intravenous immunoglobulin caused clinical improvement followed by long-term remission without maintenance therapy; one patient has exhibited a monophasic course and the other has had a single relapse during the last 5 years. These cases suggest that there may be a long-term sustained beneficial effect of intravenous immunoglobulin therapy for children with this neuropathy.     

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.     

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.     

Lewis-Sumner syndrome and multifocal motor neuropathy

We compared the clinical, electrophysiological, laboratory, and pathological features of 13 patients with Lewis-Sumner syndrome (LSS) with those of 20 patients with multifocal motor neuropathy (MMN). LSS and MMN patients have several common clinical features: age at onset, weakness in the distribution of individual peripheral nerves, mild wasting, cramps and fasciculations, partial areflexia, and frequent stepwise disease course. Cerebrospinal fluid protein level was normal or slightly elevated, but always less than 100 mg/dl. Conduction blocks are the electrophysiological hallmarks of these two neuropathies, and no differences in distribution and number of blocks were found. Contrary to MMN, lower-limb involvement at onset was frequent in LSS but extension to the upper limbs was a frequent later feature of the disease. Cranial nerve involvement was noted in 4 LSS patients during relapses and absent in all MMN patients. The major distinguishing features were the clinical and electrophysiological sensory involvement in LSS, and the lack of anti-GM1 antibodies in LSS, whereas IgM anti-GM1 were found in 40% of MMN patients. Some LSS patients responded to steroid therapy, whereas this was ineffective in MMN. From these features, LSS can be considered an entity distinct from MMN, with its own clinical, laboratory, and electrophysiological characteristics, and as an intermediate link between chronic inflammatory demyelinating polyneuropathy and MMN.     

Chronic acquired demyelinating motor neuropathy

A patient with chronic, acquired, demyelinating, pure or predominantly motor asymmetric neuropathy is described. Electrophysiological tests showed multifocal conduction block in motor nerves. The sensory system was intact and the first signs of slight trival involvement appeared after 4 years of disease duration. The antiganglioside antibodies were present in serum and the patient responded to immunosuppressive therapy (azathioprine). Distinction of such cases from motor neuron disease is critical since motor demyelinating neuropathy is treatable in most cases.     

Multifocal sensory demyelinating neuropathy: Report of a case

Introduction: Multifocal sensory demyelinating neuropathy has not been adequately reported in the literature. Methods: A 42‐year‐old man with numbness of the left hand for 3 years and of the right hand for 6 months had a pure multifocal sensory neuropathy involving both hands, most prominently affecting 2‐point discrimination, number writing, and object recognition of the left hand. Near‐nerve needle sensory and mixed nerve conduction studies were performed on the left ulnar nerve. Results: Studies of the left ulnar nerve documented a demyelinating neuropathy characterized by temporal dispersion and marked decrease in the amplitudes of the sensory and mixed compound nerve potentials in the above‐elbow‐axilla segment. With intravenous immunoglobulin treatment, there was improvement in his neuropathic condition. Conclusion: In this study I describe a case of multifocal sensory demyelinating neuropathy as a counterpart of multifocal motor neuropathy. Muscle Nerve 56 : 825–828, 2017     

Multifocal demyelinating polyneuropathy with persistent conduction block (Lewis-Sumner syndrome)

Multifocal demyelinating neuropathy with persistent conduction block (Lewis-Sumner syndrome) is a variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which often clinically simulates a motor neuron disease (MND). We report here three patients initially suspected to have MND, who later were diagnosed as a Lewis-Sumner syndrome. One of them showed a remarkable clinical improvement after immunoglobulin therapy. The definitive diagnosis of this syndrome rests upon nerve conduction studies, uncovering multiple sites of persistent conduction block. Technically, it is important to exclude insufficient stimulus which may lead to an erroneous impression of conduction block. Magnetic stimulation, as compared to electric current, elicited larger responses possibly because of deeper current penetration. We found this mode of stimulation useful especially in testing focal demyelination requiring full activation of a diseased nerve at a most proximal segment.     

Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome

Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.     

Multifocal motor neuropathy.

We believe that our present understanding of these syndromes is insufficient to separate CIDP from MMN clearly and consider MMN to be a remarkably multifocal, predominantly motor variant of CIDP with the very unusual electrophysiologic feature of conduction block confined to motor axons. Further studies are clearly needed to clarify fully the relationship between CIDP and MMN and the relationship of MMN and other motor syndromes to various ganglioside antibodies.     

Multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterised by slowly progressive, asymmetrical weakness of limbs without sensory loss. The clinical presentation of MMN mimics that of lower-motor-neuron disease, but in nerve-conduction studies of patients with MMN motor-conduction block has been found. By contrast with chronic inflammatory demyelinating polyneuropathy, treatment with prednisolone and plasma exchange is generally ineffective in MMN and even associated with clinical worsening in some patients. Of the immunosuppressants, cyclophosphamide has been reported as effective but only anecdotally. Various open trials and four placebo-controlled trials have shown that treatment with high-dose intravenous immunoglobulin leads to improvement of muscle strength in patients with MMN. Although clinical, pathological, imaging, immunological, and electrophysiological studies have improved our understanding of MMN over the past 15 years, further research is needed to elucidate pathogenetic disease mechanisms in the disorder.     

Multifocal motor neuropathy

PURPOSE OF THIS REVIEW: To conduct a critical review of recent studies on the clinical and therapeutic aspects of multifocal motor neuropathy, and to analyse their implications for patient management. RECENT FINDINGS: Recent studies have contributed to defining the specific position of multifocal motor neuropathy within the spectrum of chronic immune-mediated polyneuropathies. One study compared features of this condition with multifocal acquired demyelinating sensory and motor neuropathy, while others have focused on pathological alterations at the site of conduction blocks. A further study described six new cases of multifocal acquired motor neuropathy, which should be considered as a variant of multifocal motor neuropathy. Several Cochrane reviews and review articles have shown evidence of the efficacy of intravenous immunoglobulins in the treatment of multifocal motor neuropathy. The issue of long-term intravenous immunoglobulins in multifocal motor neuropathy, however, has yielded controversial results. Two studies have shown progressive motor deterioration in most patients, correlated with electrophysiological signs indicative of axonal degeneration, while a third study found signs of sustained clinical and electrophysiological improvement after a mean follow up of 7.25 years. SUMMARY: Multifocal motor neuropathy is a distinct clinical entity that differs from chronic inflammatory demyelinating polyradiculoneuropathy and multifocal acquired demyelinating sensory and motor neuropathy, although they share some electrophysiological characteristics. Although the aetiology remains unsolved, frequent association with high-titer antibodies against ganglioside GM1, together with an often positive response to intravenous immunoglobulins further support an autoimmune mechanism. New therapeutic strategies are required, however, that focus on the effects and the costs of treatment over long-term follow up.     

Multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is a recently identified peripheral nerve disorder characterized by progressive, predominantly distal, asymmetric limb weakness mostly affecting upper limbs, minimal or no sensory impairment, and by the presence on nerve conduction studies of multifocal persistent partial conduction blocks on motor but not sensory nerves. The etiopathogenesis of MMN is not known, but there is some evidence, based mostly on the clinical improvement after immunological therapies, that the disease has an immunological basis. Antibodies, mostly IgM, to the gangliosides GM1, and though less frequently, GM2 and GD1a, are frequently detected in patients' sera, helping in the diagnosis of this disease. Even if there is some experimental evidence that these antibodies may be pathogenic in vitro, their role in the neuropathy remains to be established. Patients with MMN do not usually respond to steroids or plasma exchange, which may occasionally worsen the symptoms, while the efficacy of cyclophosphamide is limited by its relevant side effects. More than 80% of MMN patients rapidly improve with high dose intravenous immunoglobulin therapy (IVIg). The effect of this therapy is, however, transient and improvement has to be maintained with periodic infusions. A positive response to interferon-beta has been recently reported in a minority of patients, some of whom were resistant to IVIg. Even if many progresses have been made on the diagnosis and therapy of MMN, there are still several issues on the nosological position, etiopathogenesis and long-term treatment of this neuropathy that need to be clarified.