Criteria For Multifocal Motor Neuropathy Research Articles

Assessment of diagnostic criteria for multifocal motor neuropathy in patients included in the Italian database.

This study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real-life data in multifocal motor neuropathy (MMN) patients. Clinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty-six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis. Analyses were conducted on 73 patients with a confirmed MMN diagnosis and 11 patients who did not meet the diagnostic criteria. The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria were variably applied. When applying the American Association of Electrodiagnostic Medicine criteria, an additional 17% of patients fulfilled the criteria for probable/definite diagnosis whilst a further 9.5% missed the diagnosis. In 17% of the patients only compound muscle action potential amplitude, but not area, was measured and subsequently recorded in the database by the treating physician. Additional investigations, including anti-GM1 immunoglobulin M antibodies, cerebrospinal fluid analysis, nerve ultrasound and magnetic resonance imaging, supported the diagnosis in 46%-83% of the patients. Anti-GM1 immunoglobulin M antibodies and nerve ultrasound demonstrated the highest sensitivity. Additional tests were frequently performed outside the EFNS/PNS guideline recommendations. This study provides insights into the real-world diagnostic and management strategies for MMN, highlighting the challenges in applying diagnostic criteria.

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy*

Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus guidelines on the definition, investigation and treatment of multifocal motor neuropathy. Disease experts and a patient representative considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed good practice points to define clinical and electrophysiological diagnostic criteria for multifocal motor neuropathy and investigations to be considered. The principal recommendations and good practice points were: (i) IVIg (2 g/kg given over 2-5 days) should be considered as the first line treatment (level A recommendation) when disability is sufficiently severe to warrant treatment. (ii) Corticosteroids are not recommended (good practice point). (iii) If initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2-4 weeks or 2 g/kg every 4-8 weeks (good practice point). (iv) If IVIg is not or not sufficiently effective then immunosuppressive treatment may be considered. Cyclophosphamide, ciclosporin, azathioprine, interferon beta1a, or rituximab are possible agents (good practice point). (v) Toxicity makes cyclophosphamide a less desirable option (good practice point).

European Federation of Neurological Societies/Peripheral Nerve Society Guideline* on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

Several diagnostic criteria for multifocal motor neuropathy (MMN) have been proposed in recent years, and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The aim of this guideline was to prepare consensus guidelines on the definition, investigation, and treatment of MMN. Disease experts and a representative of patients considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements that were agreed in an iterative fashion. The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for MMN and investigations to be considered. The principal recommendations and good practice points were as follows: (1) IVIg (2 g/kg given over 2-5 days) should be considered as the first line of treatment (level A recommendation) when disability is sufficiently severe to warrant treatment; (2) corticosteroids are not recommended (good practice point); (3) if initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2-4 weeks or 2 g/kg every 4-8 weeks (good practice point); (4) if IVIg is not (or not sufficiently) effective, then immunosuppressive treatment may be considered. Cyclophosphamide, cyclosporine, azathioprine, interferon-beta1a, or rituximab are possible agents (good practice point); and (5) toxicity makes cyclophosphamide a less desirable option (good practice point).

A misdiagnosis of multifocal motor neuropathy

A 60-year-old man had progressive asymmetric weakness in his arms and legs for 11 years. The weakness first appeared in the distal muscles and progressed to involve the proximal muscles in the left leg. 5 years into the illness the patient developed distal weakness in his left hand, which spread to involve his left forearm, arm, and shoulder girdle muscles. 8 years after the onset of motor symptoms he developed weakness in his right hand, which gradually affected his right arm, shoulder, and leg muscles over 3 years. He also noticed progressive wasting of muscles, especially in his left arm and both legs. He also complained of frequent fasciculation over all the affected muscles. There were no cranial nerve, sensory, or autonomic symptoms. He was diagnosed with atypical motor-neuron disease in 1993. The diagnosis was confirmed by doctors at another institution in 1994. We first saw the patient in Jan, 2001. His higher mental functions and cranial nerves were intact. We detected hypotonia in the left arm and legs, and winging of the left scapula. Fasciculation was observed in both arms and the left thigh. All deep tendon jerks were hypoactive. There were neither sensory deficits nor incoordination of the limbs. Muscle strength—as assessed by use of the Medical Research Council (MRC) rating scale in ten of the most affected arm and leg muscles (total 20 muscles, maximal score=100)—was 23/100. The baseline modified Rankin disability scale was grade 4. The functional impairment scale for arms and legs was grade 4. The clinical differential diagnosis was progressive spinal muscular atrophy and multifocal motor neuropathy with conduction block. We did nerve conduction studies using a Nicolet Viking IV-D (Madison, WI, USA) and a Cadwell Excel EMG/EP system (Kennewick, WA, USA). The skin temperature was maintained at 34 C. Bilateral median, ulnar, radial, peroneal, and tibial motor nerves were studied. The stimulation sites were at the wrist, elbow, proximal part of the upper arm, and Erb’s point in the upper limb. The peroneal nerve was stimulated at the ankle, and above and below the fibular head in the popliteal fossa. Ankle and popliteal fossa were the stimulation sites for the tibial nerve. The intensity and the duration of the current were raised to the highest levels to ensure supramaximal stimulation. Negative-peak amplitude, area, and duration were measured for the compound muscle action potential obtained from each stimulation site. Distal motor latency, conduction velocity, and F-wave latency were recorded. Antidromic sensory conduction was investigated in the median, ulnar, radial, and sural nerves. Conduction block was detected by use of electrodiagnostic criteria for multifocal motor neuropathy with conduction block. We did the tests with both the electromyography machines, as well as on a healthy volunteer in order to exclude technical artefacts. Conduction block was seen in axilla-to-Erb’s segment in the left median and right radial nerves. In the elbow-to-axilla segment, definite conduction block was observed in the right ulnar and median nerves. In the right median nerve there was definite conduction block in the long segment of wristto-elbow (figure). The F-wave latency was 130% of the normal upper limit in the right tibial nerve. The motor conduction velocity was reduced in the right median nerve. Electromyography showed neurogenic changes in the muscles sampled. CSF examination did not reveal any cells; the protein was 0·6mmol/L (0·15–0·40 mmol/L) with normal sugar. The IgM anti-GM1 ganglioside antibody titre was less than 1 in 600 (Ranbaxy Laboratories, Mumbai, India). MRI of brachial and lumbosacral plexus was normal. Haemogram, blood sugar, renal, and liver function tests were normal. Serum and urine protein electrophoresis were normal. HIV and CSF venereal disease research laboratory serology were non-reactive. A chest x-ray and abdomen ultrasonogram were normal. We started the patient on intravenous immunoglobulins (IVIg) 400 mg/kg/day for 5 days, which were followed by oral cyclophosphamide 1–2 mg/kg. The patient had improved remarkably by the first follow-up examination at 1 month. The total MRC score had increased from 23/100 to 56/100. The modified Rankin disability score increased from grade 4 to grade 2. The functional impairment scale was grade 2. The patient was given IVIg for 2 days (400 mg/kg/day) every 3 months, for 1 year. Recently, IVIg therapy has been spaced to 6 months and his neurological findings are stable without any further worsening of symptoms. We did a repeat electrodiagnostic study after 18 months of IVIg therapy; there was probable conduction block in the right ulnar nerve and both median nerves in the elbow-toaxilla segment. There was pronounced improvement in the distal compound muscle action potential amplitudes compared with the previous study. The patient fulfilled the clinical, laboratory, and electrodiagnostic criteria for definite multifocal motor neuropathy with conduction block. Our patient was initially diagnosed with atypical motor-neuron disease (progressive spinal muscular atrophy) at another hospital.

Intravenous immunoglobulin therapy in multifocal motor neuropathy: A double-blind, placebo-controlled study

We conducted a double-blind, placebo-controlled, study of 19 patients fulfilling eligibility criteria for multifocal motor neuropathy with persistent conduction block. They were enrolled and divided into two groups: those who had never been treated previously with intravenous immunoglobulins (IVIg) (Group 1: 10 patients) and those who presented recurrent symptoms after previously successful treatment with IVIg (Group 2: nine patients). They were randomized prospectively to receive either IVIg or placebo at a dose of 500 mg/kg/day for 5 consecutive days, once a month for 3 months. At month 4, patients found to be responders remained on the same treatment for the 3 following months, while non-responders were switched to the alternative study drug for the 3 following months. Clinical assessment was conducted with the MRC score in 28 muscles and a self-evaluation scale (five daily motor activities scored from 0 to 5). In Group 1, nine patients completed the study, of whom initially four received IVIg and five placebo; four patients responded to IVIg (two at months 4 and 7, and a further two at month 7 after switching treatment at month 4), two patients responded to placebo at months 4 and 7, and three patients did not respond to either treatment. In Group 2, nine patients completed the study. Five patients first received IVIg and all responded at months 4 and 7. Four patients first received placebo and none responded at month 4; all were then switched to IVIg and three responded at month 7. When the 18 patients were considered together, seven out of the nine patients who received IVIg first were responders at month 4, compared with two of the nine patients who received placebo first, a difference that was statistically significant (P = 0.03). On the other hand, there was no significant difference in MRC score but a significant difference in the self-evaluation score, at month 4, between IVIg patients and placebo patients. Electrophysiological studies did not show significant differences at month 4 in motor parameters between IVIg patients and placebo patients. IgM anti-GM1 titres did not change significantly in patients treated with IVIg compared with those who received placebo, between baseline, month 4 and month 7. However, of five patients who had significantly high anti-GM1 titres (>3200) at baseline, four responded to IVIg. This trial confirms that IVIg is a promising therapeutic option for multifocal motor neuropathy.