Multifocal Acquired Demyelinating Sensory And Motor Research Articles

Clinical and long-term characteristics of the subtypes of chronic inflammatory demyelinating polyneuropathy

To clarify the clinical and long-term characteristic of each subtype of chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated data from 30 consecutive CIDP patients who met the criteria proposed by the European Federation of Neurological Societies and the Peripheral Nerve Society. Patients were classified as having typical CIDP (t-‍CIDP) (10/30, 33%), multifocal acquired demyelinating sensory and motor (MADSAM) (12/30, 40%), DADS (4/30, 13%), sensory CIDP (3/30, 10%) or motor CIDP (1/30, 3%). Nerve conduction studies showed more prolonged distal motor latencies/F-wave latencies and slower motor nerve conduction in the typical CIDP group than in the MADSAM group. Intravenous immunoglobulin (IVIg) was effective in 80% (8/10) of t-‍CIDP, 100% (12/12) of MADSAM, 100% (4/4) of DADS, and 100% (3/3) of sensory CIDP cases. Maintenance therapy with immunoglobulin was administered in patients with t-‍CIDP (5/10, 50%), MADSAM (9/12, 75%), DADS (1/4, 25%), and sensory CIDP (2/3, 67%). There were no patients with CIDP, in whom CIDP subtype was transformed from the initial diagnosis during five years of follow-up. Percentage of MADSAM was the most common phenotype in our cohort of CIDP patients, and IVIg/immunoglobulin maintenance was effective for MADSAM as well as t-‍CIDP in contrast to findings from the previous reports.

Intravenous immunoglobulin-induced eczematous eruption in autoimmune neuromuscular diseases

Intravenous immunoglobulin (IVIg) have been administrated for the long time in patients with several autoimmune neuromuscular diseases. Eczematous eruption has been described as IVIg-induced adverse effect. The purpose of this study is to clarify the incidence and characteristic of IVIg-induced eczematous eruption in autoimmune neuromuscular disease. We retrospectively collected the data from 92 patients with autoimmune neuromuscular diseases, including 35 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 8 patients with multifocal motor neuropathy (MMN), 25 patients with myositis, 15 patients with Guillain-Barré syndrome (GBS), and 9 patients with myasthenia gravis (MG), who have administrated IVIg in Yamaguchi University Hospital. There are 10 patients (6 CIDP/4 MMN), who had an eczematous skin reaction after IVIg infusion. The frequencies of IVIg-induced eczematous eruption were significantly higher in patients with multifocal acquired demyelinating sensory and motor (MADSAM) and MMN than in patients with GBS, myositis, and MG. In addition, corticosteroids or immunosuppressive drugs had been administrated before IVIg treatment more frequently in patients with myositis and MG than in those with MADSAM and MMN. MADSAM or MMN patients had more frequently IVIg-induced eczematous eruption than other autoimmune neuromuscular diseases. Pathophysiology of MADAM and MMN is considered to be cell-mediated immunity against the peripheral nerve and the accumulation of IgG in both epidermis and dermis of the hand after IVIg may induce the infiltration of inflammatory cells around the vessels in the skin, causing eczematous eruption in MADSAM and MMN.

Spotlight on the October 5 Issue

#### Notable in Neurology This Week This issue features an article that examines the perspectives of patients with myasthenia gravis on the severity of their symptoms; another investigates predictors of early neurologic deterioration in patients with lacunar stroke. A featured Special Article presents the American Academy of Neurology's position on high drug costs and distributive justice. ### Pure Motor Onset and IgM-Gammopathy Occurrence in Multifocal Acquired Demyelinating Sensory and Motor Neuropathy ![Graphic][1]</img> This retrospective review of 76 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy revealed the … [1]: /embed/inline-graphic-1.gif

Pathophysiology of Chronic Inflammatory Demyelinating Polyneuropathy: Insights into Classification and Therapeutic Strategy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is classically defined as polyneuropathy with symmetric involvement of the proximal and distal portions of the limbs. In addition to this “typical CIDP”, the currently prevailing diagnostic criteria proposed by the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) define “atypical CIDP” as encompassing the multifocal acquired demyelinating sensory and motor (MADSAM), distal acquired demyelinating symmetric (DADS), pure sensory, pure motor, and focal subtypes. Although macrophage-induced demyelination is considered pivotal to the pathogenesis of CIDP, recent studies have indicated the presence of distinctive mechanisms initiated by autoantibodies against paranodal junction proteins, such as neurofascin 155 and contactin 1. These findings led to the emergence of the concept of nodopathy or paranodopathy. Patients with these antibodies tend to show clinical features compatible with typical CIDP or DADS, particularly the latter. In contrast, classical macrophage-induced demyelination is commonly found in some patients in each major subtype, including the typical CIDP, DADS, MADSAM, and pure sensory subtypes. Differences in the distribution of lesions and the repair processes underlying demyelination by Schwann cells may determine the differences among subtypes. In particular, the preferential involvement of proximal and distal nerve segments has been suggested to occur in typical CIDP, whereas the involvement of the middle nerve segments is conspicuous in MADSAM. These findings suggest that humoral rather than cellular immunity predominates in the former because nerve roots and neuromuscular junctions lack blood–nerve barriers. Treatment for CIDP consists of intravenous immunoglobulin (IVIg) therapy, steroids, and plasma exchange, either alone or in combination. However, patients with anti-neurofascin 155 and contactin 1 antibodies are refractory to IVIg. It has been suggested that rituximab, a monoclonal antibody to CD20, could have efficacy in these patients. Further studies are needed to validate the CIDP subtypes defined by the EFNS/PNS from the viewpoint of pathogenesis and establish therapeutic strategies based on the pathophysiologies specific to each subtype.

Clinicopathological characteristics of subtypes of chronic inflammatory demyelinating polyradiculoneuropathy

ObjectiveTo evaluate the clinical and pathological correlations characterising each clinical subtype of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).MethodsWe assessed 106 consecutive patients who had CIDP fulfilling the European Federation of Neurological...

S37. A surprising diagnosis of a longstanding leg weakness

Multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy is an asymmetric variant of chronic inflammatory demyelinating polyradiculoneuropathy. It presents with multifocal motor and sensory deficits, typically affecting the arms initially and the legs subsequently. Tinel’s sign is frequently elicited at the sites of disease. Nerve conduction studies (NCS) are characterized by evidence of focal demyelination. Spinal fluid often reveals mild to moderate increase of protein. Anti-GM1 antibodies can be present but never in a high titer. Sural nerve biopsy may reveal demyelinating changes. MADSAM responds to intravenous immunoglobulin and in 40% of cases to steroids. Chart review. 52-year-old woman presented with a 10-year history of progressive right leg weakness. She had frequent muscle cramps in the right leg and numbness up to the knee. She denied low back pain, left leg weakness, urinary or bowel symptoms. The neurological examination revealed muscle atrophy of the left forearm and hand, as well as the right posterior thigh and calf. She had no fasciculations. Muscle strength testing of the left hand revealed the following: wrist flexors 4+/5, wrist extensors 4/5, distal finger flexors 4+/5, finger abductors 4−/5, thumb flexor 3/5 and thumb abductor 4/5; and that of the right leg showed: right hip extensor 3/5, knee flexor 4−/5, ankle plantar flexion 2/5, dorsiflexion 5/5, inversion 4−/5, eversion 5/5 and toes extension 5/5. The right arm and left leg examination was unremarkable. Deep tendon reflexes were preserved except for the right ankle jerk which was absent. Sensory examination disclosed only a right-sided pinprick gradient from the toes to the mid-foot. Serum protein electrophoresis with immunofixation was normal and anti-GM1 antibodies were absent. Lumbar spine MRI was unremarkable. MRI of the right leg showed atrophy of the posterior compartment of the thigh and proximal calf. Nerve conduction studies revealed partial conduction block and temporal dispersion of left ulnar and bilateral median motor responses in the forearm, mild median motor conduction slowing through the forearms, an absent right tibial motor response, and absent sural sensory responses. The abnormal sensory responses argue against multifocal motor neuropathy. These findings were interpreted as being consistent with MADSAM with secondary axonal loss particularly in the leg where motor and sensory responses were unevocable. MADSAM typically presents with upper limbs weakness. The striking feature in this patient was the longstanding right leg weakness which overshadowed the left hand weakness. The importance of more extensive clinical and electrodiagnostic evaluation in patients presenting with focal neurological complaints is born out in this patient in whom diagnostic demyelinative findings were evident only in the less affected upper limbs.

Composite ganglioside autoantibodies and immune treatment response in MMN and MADSAM.

Multifocal motor neuropathy (MMN) is a motor only, asymmetric onset neuropathy that is relatively treatment-refractory compared with classic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. We reviewed 35 patients seropositive for GM1 (monosialo-asialo [immunoglobulin M, IgM; immunoglobulin G, IgG]) and/or GD1b (disialo [IgG, IgM]) autoantibodies having MMN, classic CIDP, or MADSAM. Immune-treatment responsiveness and clinical course was compared with antibody negative disease controls. Seventy-nine percent of seropositives with an initial diagnosis of MMN were immunotherapy responsive compared with 46% of seronegatives (P = 0.045). Eight ganglioside antibody positive MMN patients of 19 (42%) developed sensory findings consistent with MADSAM compared with 3 of 41 (7%) seronegative MMN patients (P = 0.003). MMN and MADSAM patients with ganglioside antibody positivity had more sustained treatment responses (P = 0.03). Patients initially diagnosed with MMN seropositive for diverse GM1 autoantibodies appear more likely to have sustained treatment response and evolution to MADSAM. Muscle Nerve 57: 1000-1005, 2018.

Poster 114 Multifocal Acquired Demyelinating Sensory and Motor (MADSAM) Neuropathy Secondary to Infliximab Infusion: A Case Report

Disclosures: A. Sinha, No Disclosures. Case Description: A 69-year-old man with a history of ulcerative colitis, status post C4-C7 fusion (secondary to myelopathy over 10 years ago), presented with a 1-year history of right upper extremity pain and paresthesia. Recent MRI of the cervical spine showed evidence of a well-healed fusion from C4-C7 with findings of degenerative changes at C3-4 and C7-T1. The patient did have an MRI of the brachial plexus, which was unremarkable. The patient denied any lower extremity symptoms; however, he did have some paresthesias in the sole of his feet. The patient noted that most of his symptoms began after infliximab infusion therapy for ulcerative colitis. His last infliximab infusion was 8 weeks prior to this appointment. He denied any bowel or bladder dysfunction. On physical examination, the patient was neurologically intact, except for except for 4/5 strength in the right hand intrinsics. There were no upper motor neuron signs. Setting: Outpatient spine practice. Results or Clinical Course: Electrodiagnostic studies of the upper and lower extremities showed prolonged latencies, diminished amplitudes and conduction velocities, in multiple nerves in a non-focal distribution. Diminished recruitment and polyphasic potentials were found in the majority of muscles in the upper and lower extremities. The patient was diagnosed with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. He was referred to neurology where he was advised to begin intravenous immunoglobulin (IVIg) therapy. Discussion: Multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy is defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and features of demyelination. Also known as Lewis-Sumner syndrome, this neuropathy is a rarely reported complication in patients undergoing treatment with the antitumor necrosis factor (TNF) monoclonal antibody infliximab. Symptoms may resolve after cessation of the antibody treatment; however IV Ig infusion therapy is the treatment of choice if symptoms persist. Conclusions: We present a rarely reported case of MADSAM, or Lewis-Sumner syndrome, following infliximab treatment. Clinicians should be aware that electrodiagnostic studies are essential in the diagnosis of this complex neuropathy.

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.

Neuropathie motrice multifocale : existe-t-il une altération de la conduction sensitive au long cours ? Une étude rétrospective chez 21 patients

Introduction Multifocal motor neuropathy is a well described condition characterized by slowly progressive, predominantly distal, asymmetric limb weakness and wasting, predominantly in the arms within an anatomical distribution of individual motor nerves, with minimal or no sensory involvement. Method The aim of this retrospective study was to look for a significant reduction of the amplitude of sensory potentials in a cohort of 21 patients with defined multifocal motor neuropathy according to the Workshop Report criteria [Workshop Report, 2001. 79th ENMC International Workshop. Multifocal motor neuropathy 14–15 April 2000, Hilversum. The Netherlands. Muscle Nerve 11, 309–314], within a follow-up of at least 3 years. Result Thirteen patients (62%) (Group 1) had a reduction of the amplitude of at least one sensory potential, of whom four patients had abnormalities of two or more sensory potentials, while eight patients (Group 2) had no abnormality. No significant differences were found for gender, age at onset, number of involved motor nerves, CSF protein count, presence/absence of anti-GM1 serum antibodies and response to IgIV between the two groups. Conclusion This study underlines the difficulty in defining criteria for multifocal motor neuropathies capable of distinguishing them from other chronic acquired demyelinating polyneuropathies, and mainly from multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, also called Lewis–Sumner's syndrome.

Research criteria for defining patients with CIDP.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is one of several chronic acquired demyelinating neuropathies that are considered to be autoimmune diseases. The prevalence of these illnesses may be underestimated because of limitations in clinical, serologic, and electrophysiologic diagnostic criteria. An Ad Hoc Subcommittee of the American Academy of Neurology (AAN) proposed a set of diagnostic criteria for CIDP to be used for research purposes, and several other criteria followed. Of these, the AAN electrophysiologic criteria are the most restrictive and fit only a subset of patients with CIDP. Other criteria, including the Inflammatory Neuropathy Cause and Treatment (INCAT) clinical and electrophysiologic criteria and the Nicolas or Thaisetthawatkul electrophysiologic criteria, are more sensitive and can therefore identify a broader range of patients with CIDP for clinical trials. Regardless of which criteria are chosen for use in clinical trials, patients who fall outside of these criteria may also have CIDP and may benefit from treatment. Unfortunately, because of the lack of clarity with regard to diagnostic criteria for CIDP, many patients remain untreated. In addition, certain CIDP variants may also respond to treatment. These include sensory CIDP, multifocal motor neuropathy (MMN) with or without conduction block, multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, distal acquired demyelinating sensory (DADS) neuropathy, and multifocal acquired sensory and motor (MASAM) neuropathy. Therefore, although patients may not meet the diagnostic criteria for inclusion in clinical trials of CIDP, they may still benefit from current and future treatments used in CIDP.

Therapy of CIDP and related immune-mediated neuropathies.

This study assesses the data supporting the current use of immunotherapy for management of neuropathies with a presumed autoimmune basis. Immune or inflammatory mechanisms are implicated in an increasing number of disorders that involve damage to peripheral nerves and sensory ganglia. The most prevalent of these is chronic inflammatory demyelinating polyradiculoneuritis (CIDP). CIDP is clinically distinguishable from a series of other immune- or inflammation-mediated neuropathies. These include the following: multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy associated with conduction block; brachial or lumbar plexitis; multifocal motor neuropathy, a distal demyelinating neuropathy associated with antibodies to the myelin-associated glycoprotein (MAG); and sensory neuronopathy. We reviewed the literature of the National Library of Medicine using the above terms and their variations. The results from short-term, randomized, controlled trials support the efficacy of intravenous immunoglobulin (IVIg), plasma exchange, and corticosteroids in the treatment of CIDP, and the efficacy of IVIg in the treatment of MMN. Only anecdotal experience is available for assessing the treatment of MADSAM neuropathy, lumbar and brachial plexitis, MAG neuropathy, and sensory neuronopathy. Cytotoxic and immunosuppressive drugs are frequently used to treat patients with many of these disorders when they are refractory to standard treatments, but no controlled trials have been done to support their use. This review discusses the complications and criteria for use of these therapies. Selecting the best immunotherapy for an individual patient should be based on the proven efficacy of a given regimen in modulating the pathophysiology underlying the neuropathy, the anticipated duration of disease, and the patient's age, reproductive status, and coexisting metabolic derangement.

Acquired Inflammatory Demyelinating Neuropathies

The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

Clinical spectrum of chronic acquired demyelinating polyneuropathies

A number of presentations of chronic demyelinating polyneuropathy have been identified, each distinguished by its phenotypic pattern. In addition to classic chronic inflammatory demyelinating polyneuropathy (CIDP), which is characterized clinically by symmetric proximal and distal weakness and sensory loss, several regional variants can be recognized: multifocal motor neuropathy (MMN: asymmetric and pure motor), multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy (asymmetric, sensory, and motor), and distal acquired demyelinating symmetric (DADS) neuropathy (symmetric, distal, sensory, and motor). There are also temporal, pathological, and disease-associated variants. This review describes a clinical scheme for approaching the chronic acquired demyelinating polyneuropathies that leads to a rational use of supportive laboratory studies and treatment options. In addition, we propose new diagnostic criteria for CIDP that more accurately reflect current clinical practice. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 311–324, 2001

Clinical spectrum of chronic acquired demyelinating polyneuropathies.

A number of presentations of chronic demyelinating polyneuropathy have been identified, each distinguished by its phenotypic pattern. In addition to classic chronic inflammatory demyelinating polyneuropathy (CIDP), which is characterized clinically by symmetric proximal and distal weakness and sensory loss, several regional variants can be recognized: multifocal motor neuropathy (MMN: asymmetric and pure motor), multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy (asymmetric, sensory, and motor), and distal acquired demyelinating symmetric (DADS) neuropathy (symmetric, distal, sensory, and motor). There are also temporal, pathological, and disease-associated variants. This review describes a clinical scheme for approaching the chronic acquired demyelinating polyneuropathies that leads to a rational use of supportive laboratory studies and treatment options. In addition, we propose new diagnostic criteria for CIDP that more accurately reflect current clinical practice.

Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.

We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.