Jan-Thies H. van Asseldonk

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.

Inhibition of vascular NADH/NADPH oxidase activity by thiol reagents: lack of correlation with cellular glutathione redox status.

Vascular NAD(P)H oxidase activity contributes to oxidative stress. Thiol oxidants inhibit leukocyte NADPH oxidase. To assess the role of reactive thiols on vascular oxidase, rabbit iliac/carotid artery homogenates were incubated with distinct thiol reagents. NAD(P)H-driven enzyme activity, assessed by lucigenin (5 or 250 microM) luminescence, was nearly completely (> 97%) inhibited by the oxidant diamide (1mM) or the alkylator p-chloromercuryphenylsulfonate (pCMPS, 0.5mM). Analogous inhibition was also shown with EPR spectroscopy using DMPO as a spin trap. The oxidant dithionitrobenzoic acid (0.5mM) inhibited NADPH-driven signals by 92% but had no effect on NADH-driven signals. In contrast, the vicinal dithiol ligand phenylarsine oxide (PAO, 1 microM) induced minor nonsignificant inhibition of NADPH-driven activity, but significant stimulation of NADH-triggered signals. The alkylator N-ethyl maleimide (NEM, 0.5mM) or glutathione disulfide (GSSG, 3mM) had no effect with each substrate. Coincubation of N-acetylcysteine (NAC, 3mM) with diamide or pCMPS reversed their inhibitory effects by 30-60%, whereas NAC alone inhibited the oxidase by 52%. Incubation of intact arterial rings with the above reagents disclosed similar results, except that PAO became inhibitor and NAC stimulator of NADH-driven signals. Notably, the cell-impermeant reagent pCMPS was also inhibitory in whole rings, suggesting that reactive thiol(s) affecting oxidase activity are highly accessible. Since lack of oxidase inhibition by NEM or GSSG occurred despite significant cellular glutathione depletion, change in intracellular redox status is not sufficient to account for oxidase inhibition. Moreover, the observed differences between NADPH and NADH-driven oxidase activity point to complex or multiple enzyme forms.

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.

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.

Chapter 12 Multifocal and other motor neuropathies.

Publisher Summary This chapter discusses the extensive literature on multifocal motor neuropathy (MMN) reported in recent times, much of which is also applicable to the pure motor form of chronic inflammatory demyelinating polyneuropathy (CIDP). Acquired motor neuropathies that mimic motor neuron diseases are MMN and, to a lesser extent, the pure motor form of CIDP. MMN is characterized by slowly progressive, asymmetric weakness initially without muscle atrophy of limbs that develops gradually or in a stepwise manner over several years. Men are more frequently affected than women. Conduction block on motor conduction studies is the electrophysiological hallmark of MMN. The hypothesis that MMN is an immune-mediated neuropathy has led to the trial of several immunological treatments. Several noncontrolled studies have shown a beneficial effect of intravenous immunoglobulin (IVIg) treatment. The effect of IVIg in MMN was confirmed in four double-blind placebo-controlled trials.

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

OBJECTIVE Wartenbergs 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.

P12-19 Cold paresis in multifocal motor neuropathy

Somatosensory evoked potentials that change during the evolution of the disease. Conclusions: Like in other types of Guillain Barré syndrome, we need to perform almost two neurophysiological examinations to define the distribution and degree of neurological impairment that in our Miller Fisher Syndrome patients is defined as a sensory demyelinating neuropathy or polyradiculoneuropathy with good recovery.