Clinical outcomes in multifocal motor neuropathy: A combined cross-sectional and follow-up study.

OBJECTIVE: To assess the clinical course of multifocal motor neuropathy (MMN) in a large cohort of patients and to identify predictive factors of a progressive disease course. METHODS: Between May 2015 and February 2016, we collected clinical data from 100 patients with MMN, of whom 60 had participated in a nationwide cross-sectional cohort study in 2007. We documented clinical characteristics using standardized questionnaires and performed a standardized neurologic examination. We used multiple linear regression analysis to identify factors that correlated with worse outcome. RESULTS: We found that age at diagnosis (45.2 vs 48.6 years, p < 0.02) was significantly increased between 2007 and 2015-2016, whereas diagnostic delay decreased by 15 months. Seven out of 10 outcome measures deteriorated over time (all p < 0.01). Patients who had a lower Medical Research Council (MRC) sumscore and absence of 1 or more reflexes at the baseline visit showed a greater functional loss at follow-up (p = 0.007 and p = 0.016). CONCLUSIONS: Our study shows that MMN is a progressive disease. Although 87% of patients received maintenance treatment, muscle strength, reflexes, vibration sense, and the Self-Evaluation Scale score significantly deteriorated over time. Lower MRC sumscore and absence of reflexes predicted a more progressive disease course. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that lower MRC sumscore and the absence of reflexes predict a more progressive disease course in patients with MMN.

Nerve ultrasound can identify treatment-responsive chronic neuropathies without electrodiagnostic features of demyelination.

INTRODUCTION: We present a case series of six treatment-naive patients with clinical phenotypes compatible with chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy without electrodiagnostic features of demyelination but with abnormal peripheral ultrasound findings who responded to treatment. METHODS: All six patients underwent a complete set of ancillary investigations, including extensive nerve conduction studies. We also performed standardized nerve ultrasound of median nerves and brachial plexus as part of a larger effort to evaluate diagnostic value of sonography. RESULTS: Nerve conduction studies did not show conduction block or other signs of demyelination in any of the six patients. Sonographic nerve enlargement was present in all patients and was most prominent in proximal segments of the median nerve and brachial plexus. Treatment with intravenous immunoglobulin resulted in objective clinical improvement. DISCUSSION: Our study provides evidence that nerve ultrasound represents a useful complementary diagnostic tool for the identification of treatment-responsive inflammatory neuropathies.

Neuropathy associated with immunoglobulin M monoclonal gammopathy: A combined sonographic and nerve conduction study.

INTRODUCTION: We assessed the specific sonographic pattern of structural nerve abnormalities in immunoglobulin M (IgM) neuropathy and disease controls. METHODS: We enrolled 106 incident patients-32 patients with IgM neuropathy, 42 treatment-naive patients with chronic inflammatory demyelinating polyneuropathy, and 32 patients with axonal neuropathies. All patients underwent standardized ancillary testing in addition to standardized sonography of the brachial plexus and the large arm and leg nerves bilaterally. RESULTS: We found widespread nerve enlargement in IgM neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP), with specific enlargement of brachial plexus and proximal segments of median nerve but not in axonal disease controls (P < .001). Sonographic nerve hypertrophy in IgM neuropathy was not associated with nerve conduction, clinical, or laboratory characteristics. DISCUSSION: Immunoglobulin M neuropathy is characterized by widespread nerve enlargement indistinguishable from CIDP. Our data provide evidence to confirm that the disease process is not confined to the more distal parts of nerves in either classical demyelinating or axonal variants of neuropathy with associated IgM.

Nerve ultrasound: A reproducible diagnostic tool in peripheral neuropathy.

OBJECTIVE: To determine interobserver variability of nerve ultrasound in peripheral neuropathy in a prospective, systematic, multicenter study. METHODS: We enrolled 20 patients with an acquired chronic demyelinating or axonal polyneuropathy and 10 healthy controls in 3 different centers. All participants underwent an extensive nerve ultrasound protocol, including cross-sectional area measurements of median, ulnar, fibular, tibial, and sural nerves, and brachial plexus. Real-time image acquisition was performed blind by a local and a visiting investigator (reference). Five patients were investigated using different types of sonographic devices. Intraclass correlation coefficients were calculated, and a random-effects model was fitted to identify factors with significant effect on interobserver variability. RESULTS: Systematic differences between measurements made by different investigators were small (mean difference 0.11 mm2 [95% confidence interval 0.00-0.23 mm2]). Intraclass correlation coefficients were generally higher in arm nerves (0.48-0.96) than leg nerves (0.46-0.61). The hospital site and sonographic device did not contribute significantly to interobserver variability in the random-effects model. CONCLUSIONS: Interobserver variability of nerve ultrasound in peripheral neuropathy is generally limited, especially in arm nerves. Different devices and a multicenter setting have no effect on interobserver variability. Therefore, nerve ultrasound is a reproducible tool for diagnostics in routine clinical practice and (multicenter) research.

High-resolution ultrasound in patients with Wartenberg's migrant sensory neuritis, a case-control study.

OBJECTIVE: Wartenberg's migrant sensory neuritis (WMSN) is a rare, patchy, pure sensory neuropathy of unknown etiology. High-resolution ultrasonography (HRUS) is an emerging diagnostic technique for neuropathies, but it has not been applied in WMSN. In this study we aimed to determine HRUS abnormalities in WMSN. METHODS: We performed a case-control study of 8 newly diagnosed patients with WMSN and 22 treatment-naive disease controls (16 patients with pure sensory axonal neuropathy and 6 with pure sensory chronic inflammatory demyelinating polyneuropathy (CIDP) or Lewis-Sumner syndrome (LSS)). All patients underwent routine diagnostic evaluations and a predefined HRUS protocol. RESULTS: We found multifocal nerve enlargement in all 8 WMSN patients. The median nerve in the upper arm and the sural nerve were significantly larger in WMSN than in axonal controls (p = 0.01 and p = 0.04). In CIDP/LSS, sonographic enlargement was more extensive. Furthermore we found brachial plexus involvement in 3 of 8 (38%) WMSN patients. CONCLUSION: HRUS showed enlargement of multiple nerves in all WMSN patients even if clinical testing and NCS were normal. SIGNIFICANCE: The feature of multifocal nerve enlargement may be of additional value in establishing the diagnosis of WMSN and may support the suggestion of an auto-immune etiology.

Diagnostic value of sonography in treatment-naive chronic inflammatory neuropathies.

OBJECTIVE: To determine the diagnostic value of high-resolution ultrasound (HRUS) for detection of chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis-Sumner syndrome (LSS), and multifocal motor neuropathy (MMN). METHODS: Between January 2013 and January 2015, we enrolled 75 consecutive treatment-naive patients with chronic inflammatory neuropathies and 70 disease controls. We performed extensive nerve conduction and standardized HRUS studies bilaterally of large arm and leg nerves and brachial plexus. We determined optimal sonographic cutoff values of nerve size and used receiver operating characteristic analysis and logistic regression models to identify nerve combinations with optimal diagnostic performance. RESULTS: Enlargement of median nerve at forearm >10 mm2, upper arm >13 mm2, and any trunk of brachial plexus >8 mm2 was 99% specific for chronic inflammatory neuropathies. A shortened HRUS protocol for detecting this abnormal nerve enlargement showed high sensitivity (83%-95%), positive predictive value (100%), and negative predictive value (98%) in discriminating CIDP, LSS, and MMN from clinical mimics. CONCLUSIONS: Sonographic enlargement of proximal median nerve segments in the arms and brachial plexus is a key feature of chronic inflammatory neuropathies, which helps to reliably distinguish them from axonal neuropathies and amyotrophic lateral sclerosis. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, in absence of clinical features that suggest a hereditary demyelinating neuropathy, sonographic enlargement of proximal median nerve segments and brachial plexus accurately identifies patients with chronic inflammatory neuropathies.

Nerve sonography to detect peripheral nerve involvement in vasculitis syndromes.

BACKGROUND: We sought to determine the usefulness of sonography in the detection of nerve involvement in patients with vasculitic neuropathy. METHODS: We enrolled 16 consecutive patients with vasculitic neuropathy (11 systemic vasculitis and 5 single organ peripheral nerve vasculitis), who met the diagnostic criteria of the Peripheral Nerve Society, and 16 disease controls with noninflammatory axonal polyneuropathy (10 cryptogenic, 4 metabolic, 2 hereditary). Patients underwent standardized nerve conduction studies and assessment of muscle strength (Medical Research Council scale), in addition to sonography of large arm and leg nerves, and brachial plexus. Nerves were evaluated bilaterally at predetermined sites for nerve size (cross-sectional area) and presence of hypervascularization. RESULTS: We found enlarged nerves at common sites of nerve compression in all vasculitic and control patients. Multifocal enlargement in arm nerves, proximal to common sites of nerve compression, was sensitive (94%) and specific (88%) for vasculitic neuropathy. Sonography showed nerve enlargement in 51% of clinically or electrodiagnostically unaffected nerves. Sonography of the brachial plexus was normal. We found hypervascularization in 3 patients with systemic vasculitis. CONCLUSIONS: Sonographic enlargement of arm nerves proximal to sites of nerve compression with sparing of the brachial plexus may indicate a pattern characteristic of patients with vasculitic neuropathy. Sonography may represent a sensitive and specific technique for the detection of inflammatory neuropathy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that sonographic enlargement of arm nerves proximal to sites of nerve compression accurately identifies patients with vasculitic neuropathy.

Cold paresis in multifocal motor neuropathy.

Increased weakness during cold (cold paresis) was reported in single cases of multifocal motor neuropathy (MMN). This was unexpected because demyelination is a feature of MMN and symptoms of demyelination improve, rather than worsen, in cold. It was hypothesized that cold paresis in MMN does not reflect demyelination only, but may indicate the existence of inflammatory nerve lesions with permanently depolarized axons that only just conduct at normal temperature, but fail at lower temperatures. We investigated symptoms of cold paresis in 50 MMN patients, 48 chronic inflammatory demyelinating polyneuropathy (CIDP) patients, 35 progressive spinal muscular atrophy (PSMA) patients, and 25 chronic idiopathic axonal polyneuropathy patients. We also investigated symptoms of increased weakness during warmth (heat paresis). Cold paresis was reported more often than heat paresis. Cold paresis was most frequently reported in MMN. Multivariate analysis indicated that MMN patients had a 4- to 6-fold higher risk of reporting cold paresis than CIDP or PSMA patients. Because cold paresis is not consistent with demyelination, the lesions in MMN may involve other mechanisms than demyelination only. In conclusion, symptoms of cold paresis are common in peripheral nervous system disorders, particularly in MMN. This supports the above-described hypothesis.

Multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterised by slowly progressive, asymmetrical weakness of limbs without sensory loss. The clinical presentation of MMN mimics that of lower-motor-neuron disease, but in nerve-conduction studies of patients with MMN motor-conduction block has been found. By contrast with chronic inflammatory demyelinating polyneuropathy, treatment with prednisolone and plasma exchange is generally ineffective in MMN and even associated with clinical worsening in some patients. Of the immunosuppressants, cyclophosphamide has been reported as effective but only anecdotally. Various open trials and four placebo-controlled trials have shown that treatment with high-dose intravenous immunoglobulin leads to improvement of muscle strength in patients with MMN. Although clinical, pathological, imaging, immunological, and electrophysiological studies have improved our understanding of MMN over the past 15 years, further research is needed to elucidate pathogenetic disease mechanisms in the disorder.

Role of magnesium in the reduction of ischemic depolarization and lesion volume after experimental subarachnoid hemorrhage.

OBJECT: Ischemia-induced tissue depolarizations probably play an important role in the pathophysiology of cerebral ischemia caused by parent vessel occlusion. Their role in ischemia caused by subarachnoid hemorrhage (SAH) remains to be investigated. The authors determined whether ischemic depolarizations (IDs) or cortical spreading depressions (CSDs) occur after SAH, and how these relate to the extent of tissue injury measured on magnetic resonance (MR) images. In addition, they assessed whether administration of MgSO4 reduces depolarization time and lesion volume. METHODS: By means of the endovascular suture model, experimental SAH was induced in 52 rats, of which 37 were appropriate for analysis, including four animals that underwent sham operations. Before induction of SAH, serum Mg++ levels were measured and 90 mg/kg intravascular MgSO4 or saline was given. Extracellular direct current potentials were continuously recorded from six Ag/AgCl electrodes, before and up to 90 minutes following SAH, after which serum Mg++ levels were again measured. Next, animals were transferred to the MR imaging magnet for diffusion-weighted (DW) MR imaging. Depolarization times per electrode were averaged to determine a mean depolarization time per animal. No depolarizations occurred in sham-operated animals. Ischemic depolarizations occurred at all electrodes in all animals after SAH. Only two animals displayed a single spreading depression-like depolarization. The mean duration of the ID time was 41 +/- 25 minutes in the saline-treated controls and 31 +/- 30 minutes in the Mg++-treated animals (difference 10 minutes: p = 0.31). Apparent diffusion coefficient (ADC) maps of tissue H2O, obtained using DW images approximately 2.5 hours after SAH induction, demonstrated hypointensities in both hemispheres, but predominantly in the ipsilateral cortex. No ADC abnormalities were found in sham-operated animals. The mean lesion volume, as defined on the basis of a significant ADC reduction, was 0.32 +/- 0.42 ml in saline-treated controls and 0.11 +/- 0.06 ml in Mg++-treated animals (difference 0.21 ml; p = 0.045). Serum Mg++ levels were significantly elevated in the Mg++-treated group. CONCLUSIONS: On the basis of their data, the authors suggest that CSDs play a minor role, if any, in the acute pathophysiology of SAH. Administration of Mg++ reduces the cerebral lesion volume that is present during the acute period after SAH. The neuroprotective value of Mg++ after SAH may, in part, be explained by a reduction in the duration of the ID of brain cells.