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 cell

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

Nerve ultrasound improves detection of treatment-responsive chronic inflammatory neuropathies

OBJECTIVE: To examine the diagnostic accuracy of nerve ultrasound in a prospective cohort of consecutive patients with a clinical suspicion of chronic inflammatory neuropathies, including chronic inflammatory demyelinating polyneuropathy, Lewis Sumner syndrome, and multifocal motor neuropathy, and to determine the added value in the detection of treatment-responsive patients. METHODS: Between February 2015 and July 2018, we included 100 consecutive incident patients with a clinical suspicion of chronic inflammatory neuropathy. All patients underwent nerve ultrasound, extensive standardized nerve conduction studies (NCS), and other relevant diagnostic investigations. We evaluated treatment response using predefined criteria. A diagnosis of chronic inflammatory neuropathy was established when NCS were abnormal (fulfilling criteria of demyelination of the European Federation of Neurological Societies/Peripheral Nerve Society) or when the degree of nerve enlargement detected by sonography was compatible with chronic inflammatory neuropathy and there was response to treatment. RESULTS: A diagnosis of chronic inflammatory neuropathy was established in 38 patients. Sensitivity and specificity of nerve ultrasound and NCS were 97.4% and 69.4% and 78.9% and 93.5%, respectively. The added value of nerve ultrasound in detection of treatment-responsive chronic inflammatory neuropathy was 21.1% compared to NCS alone. CONCLUSIONS: Nerve ultrasound and NCS are complementary techniques with superior sensitivity in the former and specificity in the latter. Addition of nerve ultrasound significantly improves the detection of chronic inflammatory neuropathies. Therefore, it deserves a prominent place in the diagnostic workup of chronic inflammatory neuropathies. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that nerve ultrasound is an accurate diagnostic tool to detect chronic inflammatory neuropathies

Nerve ultrasound: A reproducible diagnostic tool in peripheral neuropathy

ObjectiveTo determine interobserver variability of nerve ultrasound in peripheral neuropathy in a prospective, systematic, multicenter study.MethodsWe 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.ResultsSystematic differences between measurements made by different investigators were small (mean difference 0.11 mm 2 [95% confidence interval 0.00-0.23 mm 2 ]). 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.ConclusionsInterobserver 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

Nerve ultrasound for diagnosing chronic inflammatory neuropathy: A multicenter validation study

OBJECTIVE: To validate the diagnostic accuracy of a previously described short sonographic protocol to identify chronic inflammatory neuropathy (CIN), including chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis Sumner syndrome, and multifocal motor neuropathy (MMN), and to determine the added value of nerve ultrasound to detect treatment-responsive patients compared to nerve conduction studies (NCS) in a prospective multicenter study. METHODS: We included 100 consecutive patients clinically suspected of CIN in 3 centers. The study protocol consisted of neurologic examination, laboratory tests, NCS, and nerve ultrasound. We validated a short sonographic protocol (median nerve at forearm, upper arm, and C5 nerve root) and determined its diagnostic accuracy using the European Federation of Neurological Societies/Peripheral Nerve Society criteria of CIDP/MMN (reference standard). In addition, to determine the added value of nerve ultrasound in detecting treatment-responsive patients, we used previously published diagnostic criteria based on clinical, NCS, and sonographic findings and treatment response (alternative reference standard). RESULTS: Sensitivity and specificity of the sonographic protocol for CIN according to the reference standard were 87.4% and 67.3%, respectively. Sensitivity and specificity of this protocol according to the alternative reference standard were 84.6% and 72.8%, respectively, and of NCS 76.1% and 93.4%. With addition of nerve ultrasound, 44 diagnoses of CIN were established compared to 33 diagnoses with NCS alone. CONCLUSIONS: A short sonographic protocol shows high diagnostic accuracy for detecting CIN. Nerve ultrasound is able to detect up to 25% more patients who respond to treatment. CLASSIFICATION OF EVIDENCE: This multicenter study provides Class IV evidence that nerve ultrasound improves diagnosis of CIN

Prognostic value of nerve ultrasonography: A prospective multicenter study on the natural history of chronic inflammatory neuropathies

Background and objective: Nerve ultrasound is a promising new tool in chronic inflammatory neuropathies. The aim of this study was to determine its prognostic value in a prospective multicenter cohort study including incident and prevalent patients with CIDP and MMN. Methods: We enrolled 126 patients with CIDP, and 72 with MMN; 71 were treatment-naive. Patients with chronic idiopathic axonal polyneuropathy (CIAP; n = 35) were considered as disease controls. Standardized neurological examination, questionnaires, and nerve ultrasonography were obtained at time of inclusion and 1-year follow-up. Nerve size development over time and correlation between nerve size and clinical outcome measures were determined using linear mixed effects models. Results: Nerve size development over time was heterogeneous. Only in MMN was there a correlation between C5 nerve root size and deterioration of grip strength (−1.3 kPa/mm2 (95% confidence interval [CI] −2.3 to −0.2). No other significant correlations between nerve size and clinical outcome measures were found. In MMN, presence of nerve enlargement at inclusion predicted deterioration of grip strength, and MMN patients with enlargement confined to the brachial plexus seemed to have more favorable outcomes. No other predictive effects of sonographic nerve size were found. Conclusions: The present study indicates that the natural course of nerve size development in CIDP and MMN is heterogeneous, and that the prognostic value of sonographic nerve enlargement is limited. It had some predictive effect in patients with MMN. Further research in specific subgroups of chronic inflammatory neuropathy is necessary to determine the usefulness of nerve ultrasonography after the diagnostic phase