Multifocal Motor Neuropathy Patients Research Articles

Prevention of axonal loss after immediate dosage titration of immunoglobulin in multifocal motor neuropathy.

To evaluate whether ongoing axonal loss can be prevented in multifocal motor neuropathy (MMN) treated with immunoglobulin G (IgG), a group of patients with a median disease duration of 15.7 years (range: 8.3-37.8), treated with titrated dosages of immunoglobulins, was studied electrophysiologically at time of diagnosis and at follow-up. At follow-up, the Z-score of the compound motor action potential amplitude of the median, fibular, and tibial nerves and the neurological performances were determined. In seven patients with a treatment-free period of 0.3 years (0.2-0.4), there was no progression of axonal loss (p = 0.2), whereas a trend toward further axonal loss by 1.3 Z-scores (0.9-17.0, p = 0.06) was observed in five patients with a treatment-free period of 4.0 years (0.9-9.0). The axonal loss in the group with a short treatment delay was significantly smaller than in the group with a longer treatment delay (p = 0.02). Also, there was an association between treatment delay and ongoing axonal loss (p = 0.004). The electrophysiological findings at follow-up were associated with the isokinetic strength performance, the neurological impairment score, and the disability, supporting the clinical relevance of the electrophysiological estimate of axonal loss. Swift initiation of an immediately titrated IgG dosage can prevent further axonal loss and disability in continuously treated MMN patients.

IgM anti-GM2 antibodies in patients with multifocal motor neuropathy target Schwann cells and are associated with early onset.

Multifocal motor neuropathy (MMN) is a rare, chronic immune-mediated polyneuropathy characterized by asymmetric distal limb weakness. An important feature of MMN is the presence of IgM antibodies against gangliosides, in particular GM1 and less often GM2. Antibodies against GM1 bind to motor neurons (MNs) and cause damage through complement activation. The involvement of Schwann cells (SCs), expressing GM1 and GM2, in the pathogenesis of MMN is unknown. Combining the data of our 2007 and 2015 combined cross-sectional and follow-up studies in Dutch patients with MMN, we evaluated the presence of IgM antibodies against GM1 and GM2 in serum from 124 patients with MMN and investigated their binding to SCs and complement-activating properties. We also assessed the relation of IgM binding and complement deposition with clinical characteristics. Thirteen out of 124 patients (10%) had a positive ELISA titer for IgM anti-GM2. Age at onset of symptoms was significantly lower in MMN patients with anti-GM2 IgM. IgM binding to SCs correlated with IgM anti-GM2 titers. We found no correlation between IgM anti-GM2 titers and MN binding or with IgM anti-GM1 titers. IgM binding to SCs decreased upon pre-incubation of serum with soluble GM2, but not with soluble GM1. IgM anti-GM2 binding to SCs correlated with complement activation, as reflected by increased C3 fixation on SCs and C5a formation in the supernatant. Circulating IgM anti-GM2 antibodies define a subgroup of patients with MMN that has an earlier onset of disease. These antibodies probably target SCs specifically and activate complement, similarly as IgM anti-GM1 on MNs. Our data indicate that complement activation by IgM antibodies bound to SCs and MNs underlies MMN pathology.

Cytokines and chemokines in patients with chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: A systematic review.

Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty-five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3-71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)-6, IL-17, CXCL10, and tumor necrosis factor alpha (TNF-α), were elevated in CIDP compared to controls in most of the studies. IL-6 and TNF-α levels are also correlated with disability. In MMN patients, IL-1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL-6, IL-17, CXCL10, and TNF-α might play a role in CIDP pathogenesis. Larger studies are needed in MMN.

Comparative multimodal sensory testing in multifocal motor neuropathy and multifocal variant of chronic inflammatory demyelinating polyradiculoneuropathy

Comparative multimodal sensory testing in multifocal motor neuropathy and multifocal variant of chronic inflammatory demyelinating polyradiculoneuropathy

Multifocal motor neuropathy as a mimic of amyotrophic lateral sclerosis: Serum neurofilament light chain as a reliable diagnostic biomarker.

The clinical presentation of multifocal motor neuropathy (MMN) may mimic early amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron (LMN) involvement, posing a diagnostic challenge. Both diseases have specific treatments and prognoses, highlighting the importance of early diagnosis. The aim of this study was to assess the diagnostic value of serum neurofilament light chain (NfL) in differentiating MMN from LMN dominant ALS. NfL was measured in serum in n = 37 patients with MMN and n = 37 age- and sex-matched patients with LMN dominant ALS, to determine the diagnostic accuracy. Clinical and demographic data were obtained at the time of NfL sampling. Serum NfL concentration was significantly lower in MMN patients compared to ALS patients (mean 20.7 pg/mL vs. 59.4 pg/mL, p < .01). NfL demonstrated good diagnostic value in discriminating the two groups (AUC 0.985 [95% CI 0.963-1.000], sensitivity 94.6%, specificity 100%, cut-off 44.00 pg/mL). NfL could be a helpful tool in differentiating MMN from LMN dominant ALS in those patients in whom electrophysiological and clinical examinations remain inconclusive early in the diagnostic process.

Epidemiology and Clinical Course of Chronic Autoimmune Neuropathies During the SARS-CoV-2 Pandemic in Latvia

Background: Chronic autoimmune neuropathies are a group of rare neurological disorders caused by the immune response to autoantigens in the peripheral nervous system. Objective: This study aimed to report epidemiological data in Latvia on the most common chronic autoimmune neuropathies and evaluate SARS-CoV-2 infections or vaccinations’ impact on our patient’s clinical course of the disease. Methods: A single-center observational study was performed, which included all patients diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) in Latvia since 2015. Prevalence and incidence were calculated by using population data from the corresponding time of the Central Statistics Bureau of Latvia. Detailed clinical evaluation and re-assessment of diagnostic criteria were performed in the whole study group. All patients underwent telephone interviews regarding their SARS-CoV-2 vaccination or infection status. Results: This study included 23 CIDP and 8 MMN patients. The point prevalence and incidence of CIDP were 1.21 per 100 000 people and 1.16 per 100 000 people, respectively. The point prevalence and incidence of MMN were 0.42 per 100 000 individuals and 0.40 per 100 000 individuals, respectively. Most of the patients involved in this study (90%, n=28) with CIDP or MMN were vaccinated against SARS-CoV-2 infection, and none of the patients experienced fluctuations or relapse regarding autoimmune polyneuropathy. Conclusion: The incidence and prevalence of CIDP and MMN in Latvia are similar to previously reported European studies. In our study group, vaccination against SARS-CoV-2 was safe and did not negatively affect the clinical course of CIDP and MMN patients.

Chronic inflammatory neuropathies and their impact on activities and participation.

Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are inflammatory neuropathies that can lead to considerable limitations in daily activities and in social participation. However, systematic evaluation of these self-reported limitations is lacking in the currently available studies. Understanding the impact of these diagnoses on patients' life is important to optimize management strategies. To systematically assess the self-reported limitations in activities and participation and determine associated factors. A survey study was conducted in 2021 in a cohort of patients with CIDP (n = 257) and MMN (n = 148) from a university hospital. The survey included the Rasch-built Overall Disability Scale and the Utrecht Scale for Evaluation of Rehabilitation-Participation, questions addressing personal and disease-related factors and treatment. Multivariate linear regression analysis was used to determine associations with disease-related and personal factors. A total of 147 CIDP and 103 MMN patients responded. Limitations in activities were reported by 70.7% CIDP and 52.2% MMN patients with moderate to severe limitations in 22.4% and 5.9% patients, respectively. Participation restrictions were reported by 50% of CIDP and 40% of MMN patients, nevertheless satisfaction with participation was high. Fatigue, pain and resilience were independently associated with limitations in activities and satisfaction with participation in CIDP patients. Activity limitations and restrictions in participation are common in CIDP patients and to a lesser extent in MMN patients. Fatigue, pain and resilience independently contributed to perceived limitations in CIDP patients. Referral to a rehabilitation physician is warranted to address these limitations appropriately.

Risk of disease relapse, safety and tolerability of SARS-CoV-2 vaccination in patients with chronic inflammatory neuropathies.

The aim was to evaluate the risk of relapse after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, and its safety and tolerability, in patients with chronic inflammatory neuropathies. In this multicenter, cohort and case-crossover study, the risk of relapse associated with SARS-CoV-2 vaccination was assessed by comparing the frequency of relapse in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) patients who underwent or did not undergo vaccination. Frequency of relapse in the 3 months prior to and after vaccination, and safety and tolerability of SARS-CoV-2 vaccination, were also assessed. In all, 336 patients were included (278 CIDP, 58 MMN). Three hundred and seven (91%) patients underwent SARS-CoV-2 vaccination. Twenty-nine patients (9%) did not undergo vaccination. Mild and transient relapses were observed in 16 (5%) patients (13 CIDP, 3 MMN) after SARS-CoV-2 vaccination and in none of the patients who did not undergo vaccination (relative risk [RR] 3.21, 95% confidence interval [CI] 0.19-52.25). There was no increase in the specific risk of relapse associated with type of vaccine or diagnosis. Comparison with the 3-month control period preceding vaccination revealed an increased risk of relapse after vaccination (RR 4.00, 95% CI 1.35-11.82), which was restricted to CIDP patients (RR 3.25, 95% CI 1.07-9.84). The safety profile of SARS-CoV-2 vaccination was characterized by short-term, mild-to-moderate local and systemic adverse events. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in CIDP and MMN patients does not seem to be associated with an increased risk of relapse at the primary end-point, although a slightly increased risk in CIDP patients was found compared to the 3 months before vaccination.

Clinical features of 8 patients with multifocal motor neuropathy in the long-term follow-up

To clarify the clinical and long-term characteristics of multifocal motor neuropathy (MMN). We retrospectively evaluated data from 8 consecutive MMN patients in Yamaguchi University Hospital from 2005 to 2020. Clinical information including dominant hand, occupations, hobbies, nerve conduction data, protein level in cerebrospinal fluid (CSF), responsiveness to intravenous immunoglobulin (IVIg) therapy as initial therapy as well as maintenance therapy were collected. Unilateral upper limb was initially affected in all patients and a dominant upper extremity was affected in six of them. Seven patients had occupations or hobbies which were associated with overuse of their dominant upper extremity. CSF protein level was normal or slightly elevated. Nerve conduction studies showed conduction blocks in 4 cases. Effectiveness of IVIg treatment as initial therapy was observed in all patients. Maintenance therapy was not needed in 2 patients because of mild symptoms with stable clinical course. Long-term maintenance therapy with immunoglobulin was effective in 5 patients during the follow-up period. Dominant upper extremity was frequently affected and most patients had job or habit associated with its overuse, suggesting that physical overload induces inflammation or demyelination in MMN. IVIg was commonly effective as both introduction and long-term maintenance therapies. Complete remission was achieved after several IVIg treatments in some patients.

Peripheral nerve ultrasound in ALS patients

Introduction. Peripheral nerve ultrasound helps in the differential diagnosis of amyotrophic lateral sclerosis (ALS) and treatable diseases with a similar clinic. The cross–sectional area (CSA) values of the nerves of the hands and spinal nerves in ALS is normal or even reduced in comparison with control. The CSA of the nerves in a clinically similar condition – multifocal motor neuropathy (MMN) increases and has a characteristic ultrasound pattern of changes in the form of an increase in CSA in the proximal parts of the nerves of the hands and spinal nerves of the brachial plexuses.Materials and methods. Cervical root and peripheral nerve CSA on both sides was performed in 31 patients with ALS and 25 patients with MMN, using a 8–15 MHz linear array probe (ultrasound scanner «Sonoscape S20» (China). The control group included 92 healthy people without diseases of the nervous system, as well as conditions potentially causing damage to the peripheral nervous system.Results. The average values of the CSA of cervical roots and peripheral nerves in the upper limb in ALS patients were normal. However, there was an increase in the CSA of the median nerve at the shoulder level on the left by 23 %, the radial nerve on the right by 24 %, and the ulnar nerve on the left at the wrist level by 33 % in the ALS group compared with the control group. The CSA of nerves in MMN patients was significantly higher than in ALS and compared with the control group. In MMN nerve trunks increase was observed in the proximal parts of the nerves in the upper limb and cervical roots on both sides.Conclusions. Peripheral nerve ultrasound is a reliable tool for differential diagnosis ALS and ALS mimics. It can be widely used in routine clinical practice.

Prevalence of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy in two regions of Australia.

Immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) produce significant disability and often require maintenance treatment. There is a paucity of epidemiological data on these conditions in Australia. We undertook a prevalence study of CIDP and MMN in North Queensland and Tasmania, coinciding with a national census. Diagnoses were classified against the diagnostic criteria of the European Federation of Neurological Societies/Peripheral Nerve Society. Case ascertainment was undertaken via multiple methods, including survey of local neurologists across public and private clinics, search of neurophysiology, neurology and hospital databases, search of admitted hospital database collections using ICD codes and through immunoglobulin therapy prescription lists. The crude prevalence of CIDP was 5.00 per 100,000 (95% confidence interval [CI] 3.79-6.62) and the crude prevalence of MMN was 1.33 per 100,000 (95% CI 0.78-2.27). Prevalence was also investigated using National Blood Authority numbers of cases prescribed immunoglobulin therapy, indicating a CIDP prevalence of 5.72 per 100,000 (95% CI 4.41-7.43) and MMN prevalence of 1.94 per 100,000 (95% CI 1.24-3.03). There was no significant difference between these numbers and those calculated through access of patient records locally. There was no significant difference in prevalence between Tasmania and North Queensland for any category. This study updates the prevalence of CIDP and MMN in Australia. Understanding the distribution of CIDP and MMN patients and their need for treatment is essential for future resource planning and to enable monitoring and coordination of therapies such as immunoglobulin.

HP51 : Motor unit integrity in multifocal motor neuropathy: A systematic evaluation with CMAP scans

To systematically study the yield of CMAP scan recordings in a large sample of MMN patients. Introduction: We identified motor unit (MU) integrity in a large cohort of patients with multifocal motor neuropathy (MMN). Methods: We performed compound muscle action potential (CMAP) scans in 40 MMN patients and 24 age-matched healthy controls. We derived the maximum CMAP amplitude (CMAPmax), a MU number estimate (MUNE) and the largest MU amplitude using MScanFit, stimulus current required to elicit 5% (S5), 50% (S50) and 95% (S95) of CMAPmax and relative ranges ([S95-S5]x100/S50). These MU characteristics were compared with clinical, laboratory and nerve conduction study (NCS) results. Results: CMAPmax and MUNE were reduced in MMN patients (both p<0.001). Largest MU amplitude as a percentage of CMAPmax was increased in MMN patients (p<0.001). Neither treatment duration nor presence of anti-GM1 antibodies were associated with MUNE. Relative range was larger in patients with confirmed presence of anti-GM1 antibodies than those without anti-GM1 antibodies (p=0.016) and controls (p<0.001). Largest MU amplitudes were larger in patients without anti-GM1 antibodies than patients with presence of anti-GM1 antibodies (p=0.037) and controls (p=0.044). Conclusion: We found that MU loss is common in MMN and accompanied by enlarged MUs. The presence of anti-GM1 antibodies is associated with an increase in relative range of MU thresholds and a reduction of largest MU amplitude, but not to MU loss. Our findings indicate that CMAP scan complements routine NCS, and may have potential for practical monitoring of treatment efficacy and disease progression.

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.

Investigation of oxidative stress in patients with multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a rare, immune-mediated illness attacking ex-clusively motor nerves. It is known that oxidative stress is present in peripheral neuropathies, but it has not been investigated MMN. We measured in our prospective study the L-arginine, symmetric and asymmetric dimethylarginine (SDMA, ADMA) serum concentrations of 10 patients and 10 controls before and after intravenous immunoglobulin treatment (IVIG), as markers of the L-arginine/NO pathway involved in chronic inflammation and oxidative stress. The functions of motor nerves were tested in all patients and the serum antiganglioside antibody levels were de-tec-ted, as well. MMN patients showed significantly higher ADMA (p = 0.0048; 0.98 and 0.63, respectively) and SDMA le-vels (p = 0.001; 0.88 and 0.51, respectively) than healthy controls, while L-arginine was not different. Controlling for the covariant age, ADMA (B = -0.474; p = 0.041) or SDMA (B = -0.896; p < 0.0005) serum levels proved to be the significant predictors of the presence of MMN. IVIG therapy decreased significantly ADMA concentrations (p = 0.025; 0.98 and 0.84, respectively) and showed a trend to reduce SDMA levels (p = 0.1; 0.88 and 0.74, respectively). The dimethylamine levels did not correlate with the number of affected nerves, disease duration, or the presence of ganglioside antibodies. The conduction block-related peripheral motor dysfunction improved right after the IVIG treatment. Dimethylamine levels are elevated in the serum and are responsive to IVIG therapy in MMN. These findings support the presence of oxidative stress in MMN.

Motor unit integrity in multifocal motor neuropathy: A systematic evaluation with CMAP scans.

Introduction/AimsProgressive axonal loss in multifocal motor neuropathy (MMN) is often assessed with nerve conduction studies (NCS), by recording maximum compound muscle action potentials (CMAPs). However, reinnervation maintains the CMAP amplitude until a significant portion of the motor unit (MU) pool is lost. Therefore, we performed more informative CMAP scans to study MU characteristics in a large cohort of patients with MMN.MethodsWe derived the maximum CMAP amplitude (CMAPmax), an MU number estimate (MUNE), and the largest MU amplitude stimulus current required to elicit 5%, 50%, and 95% of CMAPmax (S5, S50, S95) and relative ranges ([S95 − S5] × 100 / S50) from the scans. These metrics were compared with clinical, laboratory, and NCS results.ResultsForty MMN patients and 24 healthy controls were included in the study. CMAPmax and MUNE were reduced in MMN patients (both P < .001). Largest MU amplitude as a percentage of CMAPmax was increased in MMN patients (P < .001). Disease duration and treatment duration were not associated with MUNE. Relative range was larger in patients with anti‐GM1 antibodies than in those without anti‐GM1 antibodies (P = .016) and controls (P < .001). The largest MU amplitudes were larger in patients without anti‐GM1 antibodies than in patients with anti‐GM1 antibodies (P = .037) and controls (P = .044).DiscussionWe found that MU loss is common in MMN and accompanied by enlarged MUs. Presence of anti‐GM1 antibodies was associated with increased relative range of MU thresholds and reduction in largest MU amplitude. Our findings indicate that CMAP scans complement routine NCS, and may have potential for practical monitoring of treatment efficacy and disease progression.

Multifocal motor neuropathy: Long-term treatment with subcutaneous immunoglobulin

Multifocal motor neuropathy (MMN) is a rare disease with a prevalence of less than 1 per 100,000 people. Intravenous immunoglobulin therapy (IVIG), performed for a long-term period, has been demonstrated able to improve the clinical picture of MMN patients, ameliorating motor symptoms and/or preventing disease progression. Treatment with subcutaneous immunoglobulin (SCIg) has been shown to be as effective as IVIG. However, previously published data showed that follow-up of MMN patients in treatment with SCIg lasted no more than 56 months.

P-NU004. Nerve ultrasound in multifocal motor neuropathy: Correlation with electrophysiology and functional disability

Introduction . Increased nerve cross-sectional area (CSA) on ultrasound is associated with conduction block in multifocal motor neuropathy (MMN). We investigated the ultrasound features of peripheral nerves in MMN and their correlation with electrophysiology and functional disability. Methods . MMN patients fulfilling the EFNS/PNS criteria were recruited from University Malaya Medical Centre, Kuala Lumpur, Malaysia. All patients underwent neurological assessment with MRC sumscore, grip strength, INCAT disability score, and had nerve conduction studies. Each patient also underwent nerve ultrasound study using a standardized protocol. Age- and gender-matched healthy controls were recruited for comparison. Results . Three MMN patients (2 men) aged 46.3±10.6 years and three normal controls were included. Mean disease duration was 4.3±2.5 years (ranged 1.5-6.0). CSF protein ranged 0.25-0.50 g/L with a mean 0.40±0.13 g/L. One patient was positive for anti-GM1 IgM. Mean MRC was 55.0±5.3 (range 49-59), handgrip (right: 13.2±8.1 kg; left: 21.7±11.9 kg) and INCAT 3.7±1.1 (range 3-5). Nerve CSAs were significantly larger in MMN patients than normal controls in median (forearm: p=0.043), ulnar (forearm: p=0.047), tibial (knee: p=0.002), radial (p=0.002) and sural (p<0.001) nerves. The side-to-side difference ratio of intranerve CSA variability (ICSAV) for ulnar nerve (p=0.046) was significantly larger in MMN patients. The nerve CSAs were significantly correlated with MRC [median midarm/forearm ratio (p=0.004); ulnar ICSAV (p=0.037)] and INCAT [median: elbow (p=0.029), midarm (p=0.030) and midarm/forearm ratio (p=0.007); ulnar ICSAV (p=0.029)]. Correlation analysis with electrophysiology found increased nerve CSAs significantly correlated with distal motor latency [median: wrist (p=0.042), ICSAV (p=0.005)]; and inversely correlated with motor conduction velocity [median ICSAV (p=0.042)] and proximal/distal CMAP ratio [tibial knee (p=0.005)]. Conclusion . In MMN, nerve enlargement was focal, at non-entrapment sites, asymmetrical and can involve the sensory nerve. Nerve ultrasound significantly correlates with functional disability and electrophysiological parameters suggesting that it may be useful as an additional diagnostic biomarker in MMN.

Long-term treatment with subcutaneous immunoglobulin in multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is a rare disease with a prevalence of less than 1 per 100,000 people. Intravenous immunoglobulin (IVIG) therapy, performed for a long-term period, has been demonstrated able to improve the clinical picture of MMN patients, ameliorating motor symptoms and/or preventing disease progression. Treatment with subcutaneous immunoglobulin (SCIg) has been shown to be as effective as IVIG. However, previously published data showed that follow-up of MMN patients in treatment with SCIg lasted no more than 56 months. We report herein the results of a long-term SCIg treatment follow up (up to 96 months) in a group of 8 MMN patients (6 M; 2F), previously stabilized with IVIG therapy. Clinical follow-up included the administration of Medical Research Council (MRC) sum-score, the Overall Neuropathy Limitation Scale (ONLS) and the Life Quality Index questionnaire (LQI) at baseline and then every 6 months. Once converted to SCIg, patients’ responsiveness was quite good. Strength and motor functions remained stable or even improved during this long-term follow-up with benefits on walking capability, resistance to physical efforts and ability in hand fine movements.

High-resolution mapping identifies HLA class II associations with multifocal motor neuropathy

ObjectiveTo gain further insight in the immunopathology underlying multifocal motor neuropathy (MMN) by exploring the association between MMN and the human leukocyte antigen (HLA) class II DRB1, DQB1, and DQA loci in depth and by correlating associated haplotypes to detailed clinical and anti-ganglioside antibody data. MethodsWe performed high-resolution HLA-class II typing for the DRB1, DQB1, and DQA1 loci in 126 well-characterized MMN patients and assessed disease associations with haplotypes. We used a cohort of 1305 random individuals as a reference for haplotype distribution in the Dutch population. ResultsThe DRB1*15:01-DQB1*06:02 haplotype (OR 1.6 [95% CI 1.1–2.2], p < 0.05) and the DRB1*12:01-DQB1*03:01 haplotype (OR 2.7 [95% CI 1.2–5.5], p < 0.05) were more frequent in patients with MMN than in controls. These haplotypes were not associated with disease course, response to treatment or anti-ganglioside antibodies. ConclusionsMMN is associated with the DRB1*15:01-DQB1*06:02 and DRB1*12:01-DQB1*03:01 haplotypes. These HLA molecules or gene variants in their immediate vicinity may promote the specific inflammatory processes underlying MMN.

Difference in distribution of fasciculations between multifocal motor neuropathy and amyotrophic lateral sclerosis

ObjectiveTo examine differences in fasciculation distribution between patients with multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS) based on muscle ultrasound. MethodsForty-one muscles (tongue muscle and 40 muscles of the trunk and limbs on both sides) in 5 MMN patients and 21 muscles (tongue muscle and 20 muscles on the onset side) in 21 ALS patients were subjected to muscle ultrasound individually for 60 seconds to detect the presence of fasciculations. ResultsFasciculation detection rates on the onset side were significantly higher in ALS (42.4 ± 18.3%, mean ± SD) than in MMN (21.9 ± 8.8%) patients (p < 0.05). In MMN patients, no fasciculation was detected in the tongue or truncal muscles. There was no difference in the fasciculation detection rate between the onset and non-onset sides or between upper and lower limbs in MMN patients. ConclusionsIn MMN patients, fasciculations were detected extensively in the limbs. However, the detection rate in patients with MMN was lower than in those with ALS. SignificanceDemonstration of the absence of fasciculations in the tongue and truncal muscles in MMN patients by extensive muscle ultrasound examination may help distinguish MMN from ALS.