Multifocal motor neuropathy with conduction block that was shown by the flexor digitorum profundus muscle innervated from the ulnar nerve

Abstract

To the Editor, Multifocal motor neuropathy (MMN) is a rare immune-mediated neuropathy characterized by progressive asymmetric limb weakness with the expression of anti-GM1 immunoglobulin M (IgM) antibodies. Conduction block (CB) shown by nerve conduction studies (NCS) is the most important feature for its diagnosis. A 28-year-old Japanese woman presented with a week-long history of progressive right hand muscle weakness without any sensory dysfunction. Her grip strength was 12/25 kg (right/left), the muscle strength of both the abductor pollicis brevis and abductor digiti minimi was 5/5. That of both the wrist extensor and wrist flexor was 5/5 according to the Medical Research Council grade. Her tendon reflexes were normal in the upper and lower limbs. The Babinski sign was bilaterally negative. Routine NCS recorded from the abductor pollicis brevis (Figure 1a) and abductor digiti minimi (Figure 1b) was in the normal range (skin temperature was maintained at 32 C). A cerebrospinal fluid examination detected no cells and showed a normal protein concentration (22.3 mg/ dL). Serum immunoglobulin G (1603 mg/dL) and IgM (166 mg/dL) were within the normal range, and serum anti-nuclear antibodies were negative. Serological testing for anti-ganglioside antibodies were positive for anti-GM1 IgM (+) and anti-GalNAc-GD1a IgM (++) antibodies. We initially suspected MMN without CB. The patient was given a 5-day course of high-dose intravenous immunoglobulin (IVIG) therapy (0.4 g/kg/day). Her right grip strength improved to 25 kg (left 25 kg). Both the anti-GM1 IgM (+) and antiGalNAc-GD1a IgM (++) antibodies were still positive 8 weeks after the first IVIG therapy. After another 6 months, her right grip strength declined to 12 kg. The muscle strength of the flexor digitorum profundus (FDP) was 4/5 (right/left), although that of the abductor pollicis brevis, abductor digiti minimi, extensor carpi radialis longus, extensor carpi ulnaris, flexor carpi radialis, extensor digitorum communis, abductor pollicis longus, extensor pollicis brevis, extensor pollicis longus, flexor pollicis longus, wrist extensor and wrist flexor was 5/5 (right/left; Medical Research Council grade). We carried out NCS of the FDP muscle innervated from the ulnar nerve (Figure 1c), CB was shown by a 19.6% reduction in compound muscle action potentials (CMAP; 5.1 to 4.1 mV) and 33.5% reduction in the CMAP area (33.1 to 22.0 mVms) between 42 and 18 mm from the medial epicondyle with normal motor conduction velocities (Figure 1d,e; 42 to 18 mm from the medial epicondyle = 68.6 m/s). These electrophysiological findings fulfilled the European Federation of Neurological Societies' electrophysiological criteria for possible motor CB in MMN; we finally diagnosed her with MMN. IVIG therapy was effective and her right grip strength improved to 28 kg. One month after the second IVIG treatment, the CB improved to 6.5% (4.6 to 4.3 mV) for the CMAP and 9.9% for CMAP area (26.3 to 23.6 mVms) at the same distance as the previous examination in NCS recorded by FDP (Figure 1f,g). The titer of anti-GM1 IgM antibodies did not change (+), although the titer of anti-GalNAcGD1a IgM antibodies decreased to (+). After >3 years of maintenance IVIG treatment, we gradually extended the treatment interval of IVIG, then eventually discontinued. She had no recurrence for >8 years after her relapse. We described a Japanese woman with MMN who showed CB based on tests of the FDP muscle, and anti-GM1 IgM and anti-GalNAc-GD1a IgM antibody positivity. Initially, we could not prove CB with routine NCS. Although there are several reports about MMN without CB, it is undeniable that CB might not be fully proven in such cases. Muscle weakness is not always uniform for each muscle innervated by the same nerve in MMN. When MMN is suspected, it is important to identify the muscles that are selected in NCS. It is useful to examine the anti-ganglioside antibody assays in diagnosing MMN in which CB cannot be identified, because IVIG would be effective for such cases.