Partial Motor Conduction Block Research Articles

14. Multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is a rare inflammatory neuropathy with supposed prevalence of 1/100,000 individuals characterized by slowly progressive, asymmetric distal limb weakness without sensory loss. MMN can mimic amyotrophic lateral sclerosis or other variants of motor neuron disease, and asymmetric form of chronic inflammatory demyelinating neuropathy (Lewis–Sumner syndrome). The underlying pathological mechanisms of MMN are not completely understood, but IgM autoantibodies against the ganglioside GM1 may be the cause of changes in nodal and perinodal structures that compromise nerve conduction. The electrophysiological finding of conduction block in the absence of abnormalities in sensory nerves is the hallmark of MMN, but can be difficult to detect. Intravenous humane immunoglobulin (IVIG) is currently the only standard therapy of MMN. IVIG efficacious in most patients, but long-term maintenance therapy does not prevent slowly progressive axonal degeneration. Aim of the presentation will be a summary of current diagnostic criteria and current therapeutic strategy in MMN with stress laid on pitfalls in electrodiagnostic detection of partial motor conduction block. Difficulties in diagnostics and therapy of this orphan disease together with high cost of immunoglobulin therapy justify implementation of a national MMN registry.

Treatment of Multifocal Motor Neuropathy

Multifocal motor neuropathy (MMN) is a treatable immune disorder of the peripheral nerves that is characterized clinically by slowly progressive or stepwise asymmetric distal > proximal, upper > lower limb weakness in multiple motor nerve distributions; electrophysiologically by multifocal motor demyelination, specifically partial motor conduction block; laboratory evidence of high serum anti-GM1 IgM antibodies; and remarkable treatment response to intravenous immunoglobulin (IVIG). IVIG has become the treatment of choice, and the U.S. Food and Drug Administration (FDA) has approved Gammagard Liquid 10% [immune globulin infusion (human)] as a treatment for multifocal motor neuropathy (MMN). Response to IVIG in MMN is dose- and frequency-dependent, most patients needing high (2g/kg) and frequent (every 4-8weeks) doses for several years. Over time, response to IVIG may decrease despite higher and more frequent dosing of IVIG treatment. Subcutaneous immunoglobulin (dose equivalent to IVIG) given in weekly fashion has recently been used with equal efficacy and fewer side effects. There are some case reports and non-randomized trials suggesting variable results from therapeutic or adjunctive use of other immunosuppressive or immunomodulatory agents such as cyclophosphamide, cyclosporine, methotrexate, azathioprine, interferon beta-1a, and rituximab. Of these, cyclophosphamide and rituximab are the only immune treatments that have shown some benefits in case reports. One randomized controlled trial of mycophenolate mofetil used as adjunctive agent did not prove efficacious in altering the disease course. Although MMN, like chronic inflammatory demyelinating polyneuropathy (CIDP), is a chronic immune-mediated demyelinating neuropathy, the use of corticosteroids and plasma exchange - two other therapies used in CIDP - is not beneficial for MMN. Further investigations are warranted to evaluate the immunopathogenesis of MMN and to explore options for dose, frequency, and duration of IVIG treatment as well as the use of alternative immunomodulatory agents either as primary therapeutic or adjunctive agents.

Cervical root stimulation in anti‐myelin associated glycoprotein) neuropathy

AbstractWe report a heretofore undescribed use of cervical root stimulation (CRS) in the evaluation of a patient with anti‐myelin‐associated glycoprotein (MAG) neuropathy. A 62‐year‐old man developed progressive difficulty walking. His neurological examination was significant for an unsteady gait and mild weakness. Laboratory tests showed elevated anti‐MAG antibody. CRS showed proximal partial motor conduction block (CB) of the right radial nerve and bilateral ulnar nerves. CRS may be useful in the diagnosis of anti‐MAG neuropathy when the demyelinating process predominantly affects the proximal nerve segments of the upper extremities.

Fulminant Multifocal Motor Neuropathy: A Report of Two Cases

ABSTRACTMultifocal motor neuropathy (MMN) shows stepwise progression over decades. The multifocal weakness usually remains asymmetric, confined to distal limb muscles, while sparing cranial, phrenic, and sensory nerves. One electrophysiological hallmark is partial motor conduction block (CB) at sites not exposed to compression; whether CB is an essential feature remains debatable. High titer of anti-GM1 antibodies is found with figures usually between 40% and 50% of patients. Intravenous immuneglobulin (IVIg) is effective in almost 80%, but plasmapheresis and steroids are not. The condition is reported as lethal exceptionally, mimicking motor neuron diseases (MND). We have studied two patients who failed to respond to treatment and who died with respiratory failure; one of the two had high titer of IgM antibody to the ganglioside GM1. Our cases confirm that great attention should be paid in order to define the borderland between MMN and MND and the entity of their clinical and electrophysiological overlaps.

Asymmetric Phenotype Associated With Rare Myelin Protein Zero Mutation

Myelin protein zero (MPZ) mutations cause demyelinating neuropathies that range from severe neonatal to milder adult forms. We report a 36-year-old man who developed weakness of his left little finger adduction 3 years earlier. The weakness progressed to his other limbs. Examination revealed mildly high-arched feet with asymmetric weakness of ulnar-innervated muscles (left > right) and asymmetric weakness of peroneal-innervated muscles (right > left). Motor nerve conduction velocities ranged from 18.4 to 24.4 m/s in the upper extremities and from 14.8 to 22.7 in the lower extremities. Left median partial motor conduction block was noted at the forearm segment. Genetic testing demonstrated MPZ mutation with ARG98HIS amino acid change. The patient's father is a 68-year-old man who was asymptomatic and who was noticed to have high-arched feet and asymmetric leg muscle atrophy and weakness (right > left). The patient's 2-year-old son is "clumsy" with history of neonatal laryngomalacia. He has flat feet, areflexia, and difficulty standing on individual right versus left leg. The patient's paternal grandfather had high-arched feet and hearing loss. We conclude that ARG98HIS MPZ mutation may cause hereditary and relatively mild and asymmetric demyelinating sensorimotor polyneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with inflammatory bowel diseases: questioning the autoimmunity hypothesis

Dear Editor: Inflammatory bowel diseases (IBD) are chronic disorders encompassing Crohn’s disease (CD) and ulcerative colitis (UC) characterized by abnormal mucosal immune response. Early pathology coincides with intestinal, mesenteric T-cell infiltration, cytokine production, bowel inflammation, and vasculitis. There is evidence that CD4 and CD8 T-cells can trigger autoimmunity when peripherally activated by antigens in a proinflammatory setting. Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) are caused by immune responses mounted against uncharacterized epitopes. Polyneuropathies associated with IBD exhibit different phenotypes. We studied two patients with CIDP associated with IBD supporting the view of common causality. A 63-year-old woman experienced rectal hemorrhage, acral numbness, and unsteady gait during acute hepatitis. Intestinal biopsy diagnosed CD. Neurologic examination showed absent jerks and distal loss of all sensory modalities. Muscle strength was minimally affected. Normal laboratory results included B12, E vitamin serum level, tumor markers, microbial, and immunological screenings. Sural-evoked responses were either absent or diminished in amplitude with slowed velocity. There were prolonged F wave and distal latencies of median, tibial, and peroneal muscle action potentials. Sural biopsy showed fiber loss and demyelination in 30% of fibers teased. Onion bulbs and mononuclear inflammatory cells were absent. Patient was treated with long-term steroids. On clinical follow-up, her neurological disability progressed in the absence of CD recurrence. Sixteen years after onset, distal strength was graded 3/5, whereas ataxia was marked and distal sensation was severely impaired. Electrophysiology confirmed demyelination. The second patient when aged 33 was diagnosed having UC. Twelve months later, he developed acral paresthesias and extremity weakness graded 3/5 on examination. Deep jerks were unevokable; Romberg sign was positive, and touch and deep sensation was distally impaired. In nerve conduction, there were partial motor conduction block, abnormal temporal dispersion, and diminished velocity along median, ulnar, peroneal, and tibial nerves. Patient refused spinal tap. Treatment with metronidazole was not given. Repeated courses of intravenous immuneglobulins had benefit. Our patients presented common features of moderate distal rather than proximal weakness and ataxia due to proprioceptive sensory loss. Electrophysiology suggested in both ongoing multifocal demyelination, which was histologically proven in case 1. Neurological illness began acutely in patient 1 at CD onset, raising the question of a sensory variant of acute inflammatory demyelinating polyradiculoneuropathy or of CIDP with acute onset. UC of case 2 predated by 12 months his neuropathy, which improved with immunemodulating therapy and ultimately relapsed. Gondim et al. reported seven CIDP cases associated in three with CD and in four with UC: The three CD had more proximal than distal Int J Colorectal Dis (2009) 24:603–604 DOI 10.1007/s00384-009-0646-x

Nine‐year case history of monofocal motor neuropathy

A 36-year-old man had a 6-year history of progressive left hand and finger extension weakness. Extensive electrophysiological studies showed only a partial motor conduction block along the left radial nerve at the mid-arm. Several intravenous immunoglobulin treatments were clinically successful. A 3-year follow-up did not show any clinical or electrophysiological involvement of other nerves. A monofocal motor neuropathy, as a variant of multifocal motor neuropathy, was diagnosed.

Selten untersuchte Nerven und Innervationsanomalien

The repertoire of nerve conduction studies in most neurophysiological laboratories comprises the major motor and sensory distal nerves of the upper and lower extremities. However, several additional nerves are amenable to nerve conduction studies with well reproducible results, and their examination may be useful to investigate specific clinical problems. Other uncommon nerve conduction studies do not produce consistent results, restricting their clinical usefulness. In clinical practice, nerve conduction studies of the axillary nerve, the phrenic nerve, the lateral femoral cutaneous nerve, the femoral nerve, the saphenous nerve and the plantar nerves are of some clinical utility. This review describes the techniques and the clinical use of nerve conduction studies of these nerves. Another topic of this review is variations of the normal motor nerve anatomy of the extremities. In subjects with a Martin-Gruber anastomosis, motor nerve fibres of the ulnar nerve follow the median nerve at the level of the elbow and cross to the ulnar nerve at the forearm. The Martin-Gruber anastomosis is of particular clinical importance since its existence may mimic a partial motor conduction block of the ulnar nerve at the level of the forearm. It may also lead to the erroneous localisation of proximal lesions of the median and ulnar nerve. Other anatomic variants are also discussed.

Multifocal motor neuropathy with abrupt onset and spontaneous recovery

Sirs: Multifocal motor neuropathy (MMN) is characterized by asymmetric weakness without sensory disturbances, with muscle wasting and fasciculations. It has a slowly, stepwise progressive course. Electrophysiological studies show partial or persistent motor conduction blocks [1]. Although unilateral wrist drop or grip weakness can be a presenting symptom in MMN, an acute onset and almost full recovery within a few days has not yet been described. A 34 year old man presented with abrupt, painless onset of weakness of his right hand. On examination he only had distal weakness of the right arm: strength in finger and wrist extensors 3/5, abductor pollicis brevis and opponens pollicis 4/5, and intrinsic muscle function 4/5 (MRC). Sensory examination was normal. The deep tendon reflexes were brisk and symmetric, the plantar reflex normal on both sides. Ancillary investigations including MRI imaging of the brain were unremarkable. Nerve conduction studies of the right arm were normal. There was an almost full recovery within 5 days, except for a slight impairment of right-sided rapid finger movements. During three years of follow-up his minor signs remained stable. Then he noticed a gradually progressive weakness of the right arm and left leg. He complained of cramps in the abdominal muscles and all four limbs. Examination revealed fasciculations in the both abductor pollicis brevis and distal weakness of his right arm comparable with the examination three years previously. Additionally there was weakness of the left foot flexors and extensors(4/5). Sensory testing was normal. Deep tendon reflexes had become hypoactive at the right arm and absent at both ankles. Extensive nerve conduction studies showed a bilateral partial motor conduction block of the median nerve in the lower arm, and a complete motor conduction block in the left peroneal nerve. Motor and sensory nerve conduction velocities, distal latencies, and F-waves were within normal values. IgM anti-GM1 antibodies were present (1 : 100). CSF analysis showed 3 white cells and total protein was 0.49 g/L. The diagnosis of MMN was made and the patient was treated with 2 g/kg intravenous immunoglobulin (IVIg) in two days. He showed a clear improvement after IVIg starting within four days after onset of the infusion . Within two weeks there was an almost complete recovery with only slight weakness of finger extension at the right and normal strength of left foot. There was a relapse after three weeks, which again responded to IVIg. He presently still needs 80 g of IVIg every 4 weeks to avoid full relapses between treatments. MMN is a chronic demyelinating neuropathy. It is characterized by slowly progressive asymmetrical weakness of the limbs without sensory involvement [2]. The diagnosis of MMN is based on clinical, laboratory and electrophysiological characteristics [2]. The distinguishing electrophysiological characteristics are the presence of multifocal motor conduction blocks outside the usual sites of nerve compression [3–4]. These results of electrophysiological testing and the normal CSF protein are not compatible with the diagnosis chronic inflammatory demyelinating polyneuropahty (CIPD). This patient’s history illustrates that MMN can present with abrupt onset of weakness of one limb and rapid, spontaneous and almost complete recovery. Although the asymmetry is often remarkable in MMN, both limbs are usually involved. The patient had multifocal motor weakness, however, without a clear distribution of a multiple mononeuropathy, the more frequent distribution pattern in MMN. Slow spontaneous remissions in MMN have been reported [5], but a spontaneous recovery within a few days has not yet been described.

Multifocal motor neuropathy

Recognition of new clinical phenotypes requires knowledge and clinical experience together with a new insight, often provided by an unexpected test result. Sometimes, as in multifocal motor neuropathy (MMN), the abnormal test result becomes the gold standard for diagnosis, superceding the clinical phenotype that initially defined the syndrome. MMN has a prevalence of 1 to 2 per 100,000. Despite its rarity, it is important because it is treatable, although not curable. It was initially recognized as a disorder that could be confused with ALS1 but is now well known as a distinct motor neuropathy. Clinically, MMN is characterized by slowly progressive asymmetric distal weakness, generally affecting the upper limbs. Initially, muscle bulk is relatively well preserved, and weakness is in the distribution of one or more peripheral nerves. Sensation is intact, although in 20% there may be patchy distal loss. Tendon reflexes are usually asymmetrically reduced. There are often local fasciculations and cramps, suggesting ALS as a possible diagnosis, but electrodiagnostic testing in MMN, and not in ALS, reveals partial motor conduction block (CB), defined as reduction in proximally stimulated muscle evoked response compared with the distally stimulated response, in one or more nerves at sites away from potential points of nerve compression. Patients with MMN improve …

129th ENMC International Workshop: Clinical Trials for Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy, 27th October 2004, Schiphol airport, The Netherlands

There is uncertainty about the best immunosuppressive treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) and consequently a wide variation in practice. CIDP affects between 2 and 8 per 100,000 and MMN has a prevalence about 10 times lower. Both conditions are economically important because intravenous immunoglobulin (IVIg) is often used in their treatment and is very expensive especially because of the need for repeated courses. Multicentre trials are necessary to provide sufficient participants for adequately powered trials and need to be conducted at a multinational level. The evidence for treatment has been systematically reviewed in Cochrane reviews [1,2] and a previous ENMC workshop had already considered MMN [3]. In CIDP steroids, IVIg or plasma exchange (PE) and in MMN IVIg provide short-term benefit but the value of immunosuppressant treatment has not been adequately evaluated. Encouragingly there are four ongoing trials in CIDP and one in MMN. A Bayer trial compares IVIg with placebo over a longer period than has been tested before (M MaasEnriquez, personal communication). A Biogen-Idec trial tests whether interferon-beta 1a will reduce the requirement for IVIg [4]. A Dutch trial aims to find out whether pulsed high dose dexamethasone induces remissions more often and more rapidly and is more effective than standard prednisolone treatment (I van Schaik personal communication). An Italian trial aims to compare IVIg and high dose

ACUTE MOTOR NEUROPATHY WITH CONDUCTION BLOCKS: ANOTHER GUILLAIN‐BARRÉ SYNDROME (GBS) VARIANT?

Up to now four patients with acute, purely motor, demyelinating neuropathy and conduction blocks have been described. Three cases had Campylobacter Jejuni (CJ) enteritis. In two ab anti‐GM1 were detected, along with ab anti‐GalNAc‐GD1a in one. Two men (41 and 20 years old) developed weakness respectively ten days after enteritis and rubella. Examination showed in both proximal and distal weakness in all limbs with no sensory loss. Tendon reflexes were normal in the first patient, and brisk in the second. CSF proteins were increased. Serological tests did not support a recent CJ infection. High titres of IgG anti‐GD1a and IgM anti‐GM1 were found in the first patient. Electrophysiological examination showed, since the first days after onset, partial motor conduction block in ulnar nerves of the first patient and in eight motor nerves of the second patient. Sensory conductions were normal even across the sites of conduction block. Four plasmaphereses were performed. In the first patient conduction blocks gradually improved to disappear in 3 weeks without excessive temporal dispersion of proximal motor responses. In the second patient conduction blocks disappeared in 8–16 weeks with development of excessive temporal dispersion in 4 / 8 nerves.We deem that acute motor neuropathy with conduction block is a GBS variant in which only motor fibers are involved with early conduction block in intermediate nerve segments. Our electrophysiological findings indicate that conduction block may be of the “anaesthetic type” followed by fast recovery or may progress to de‐remyelination with a slower course.

Long term effect of intravenous immunoglobulins and oral cyclophosphamide in multifocal motor neuropathy

Objectives—To report the long term effect of the combined treatment with high dose intravenous immunoglobulins (IVIg) and oral cyclophosphamide (CTX) in patients with multifocal motor neuropathy, and to determine whether...

Multifocal motor neuropathy: Electrodiagnostic features

Diagnosis of multifocal motor neuropathy (MMN), a syndrome characterized by progressive asymmetric weakness with intact sensation, is important because the disorder often responds to treatment. Multifocal partial motor conduction block (PMCB) has been emphasized as a cardinal feature in the diagnosis of this syndrome, but detailed nerve conduction studies are not available. Nine patients, ages 28-58, had chronic, progressive, asymmetric, predominantly distal limb weakness for 5-18 years. Sensation was normal and reflexes were reduced asymmetrically. Although all 9 demonstrated PMCB localized to short nerve segments, additional features of multifocal motor demyelination were present, including temporal dispersion (5 patients), segmentally reduced motor nerve conduction velocity (7 patients), prolonged distal motor latency (4 patients), and prolonged F-wave latency (9 patients). The strength of all patients improved after treatment with human immune globulin. A reduction in the degree of PMCB or an increase in the distal motor amplitude or both accompanied the clinical improvement. These studies suggest that patients with MMN demonstrate widespread evidence of motor demyelination in addition to the well-described PMCB, and that reduction of PMCB accounts for the increase in strength following therapy.

Multifocal motor neuropathy: response to human immune globulin.

Multifocal motor neuropathy (MMN) is a progressive disorder producing asymmetrical weakness and muscle wasting. Case reports suggest that patients with MMN improve after cyclophosphamide therapy, but not after prednisone or plasmapheresis. Because MMN is likely to be immune mediated, we investigated the therapeutic response to human immune globulin (HIG) in an open, uncontrolled trial. Nine patients, ages 28 to 58 years, had chronic, progressive, asymmetrical, predominantly distal, limb weakness for 5 to 18 years. Sensation was normal, and reflexes were reduced asymmetrically. All had physiological evidence of multifocal motor demyelination with partial motor conduction block, and 7 had elevated serum titers of anti-GM1 IgM antibody. All patients were treated with HIG, 1.6 to 2.4 gm/kg, given intravenously over 3 to 5 days. Strength improved in all patients 3 to 10 days after treatment, with improvement peaking at 2 weeks and lasting for an average of 2 months. The range of functional improvement varied from dramatic to mild. The degree of partial motor conduction block was reduced, at least partially, in 7 of 8 patients. The serum anti-GM1 antibody titers did not change. Repeated courses of HIG resulted in similar improvements. We conclude that HIG may be an effective therapy for patients with MMN.