Facing the diagnostic challenge: Nerve ultrasound in diabetic patients with neuropathic symptoms.

INTRODUCTION: We describe the nerve ultrasound findings in patients with type II diabetes mellitus who have neuropathic symptoms and signs. METHODS: Fifty-five healthy controls and 44 diabetic patients underwent clinical, sonographic, and electrophysiological evaluation. Patients were studied at a mean of 14.3 years after disease onset. RESULTS: Nerve ultrasound revealed increased cross-sectional area (CSA) in peripheral nerves at compression sites (although no clinical symptoms were present) and noncompression sites. No correlation was detected between sonographic and electrophysiological findings. A CSA increase of the tibial nerve in the popliteal fossa was detected in 5 patients with neuropathic symptoms, although electrophysiology was normal. CONCLUSIONS: Nerve ultrasound revealed crucial morphological alterations in diabetic patients. CSA enlargement at compression sites indicates subclinical nerve affection and may indicate susceptibility to entrapment syndromes. CSA increase at noncompression sites despite normal electrophysiology suggests early morphological abnormalities. Further longitudinal studies are required to confirm our results. Muscle Nerve, 2015 Muscle Nerve 54: 18-24, 2016 Muscle Nerve 54: 18-24, 2016.

Bochum ultrasound score versus clinical and electrophysiological parameters in distinguishing acute-onset chronic from acute inflammatory demyelinating polyneuropathy.

INTRODUCTION: The aim of this study was to evaluate whether a nerve ultrasound score (Bochum ultrasound score, BUS), clinical, and electrophysiological parameters could distinguish subacute chronic (CIDP) from acute inflammatory demyelinating polyneuropathy (AIDP). METHODS: Phase 1: The charts of 35 patients with polyradiculoneuropathy were evaluated retrospectively regarding BUS, clinical, and electrophysiological parameters (A-waves, sural nerve sparing pattern, sensory ratio>1). Phase 2: All parameters were evaluated prospectively in 10 patients with subacute polyradiculoneuropathy. RESULTS: Phase 1: A sum score of ≥2 points in BUS and the presence of sensory symptoms were significantly more frequent in the subacute CIDP group than in the AIDP group (P<0.001).The electrophysiological parameters showed no significant changes between the 2 groups. Phase 2: BUS (83.3%; 100%;), sensory symptoms (100%; 75%), absence of autonomic nervous system dysfunction (83.3%; 75%), or bulbar palsy (83.3%; 50%) showed the best sensitivity and specificity in distinguishing subacute CIDP from AIDP. CONCLUSIONS: BUS is a useful diagnostic tool for distinguishing subacute CIDP from AIDP.

Multifocal motor neuropathy: correlation of nerve ultrasound, electrophysiological, and clinical findings.

We present nerve ultrasound findings in multifocal motor neuropathy (MMN) and examine their correlation with electrophysiology and functional disability. Eighty healthy controls and 12 MMN patients underwent clinical, sonographic, and electrophysiological evaluation a mean of 3.5 years (standard deviation [SD] ± 2.1) after disease onset. Nerve ultrasound revealed significantly higher cross-sectional area (CSA) values of the median (forearm, p < 0.001), ulnar (p < 0.001), and tibial nerve (ankle, p < 0.001) when compared with controls. Electroneurography documented signs of significantly lower values of the motor conduction velocity and compound muscle action potentials (cMAPs) in the upper arm nerves (median, ulnar, radial, p < 0.001). A significant correlation between sonographic and electrophysiological findings in the MMN group was found only between cMAP and CSA of the median nerve at the upper arm (r = 0.851, p < 0.001). Neither nerve sonography nor electrophysiology correlated with functional disability. MMN seems to show inhomogeneous CSA enlargement in various peripheral nerves, with weak correlation to electrophysiological findings. Neither nerve sonography nor electrophysiology correlated with functional disability. Multicentre, prospective studies are required to prove the applicability and diagnostic values of these findings.

Correlation of nerve ultrasound, electrophysiological, and clinical findings in post Guillain-Barré syndrome.

We aimed to correlate functional disability, electrophysiology, and nerve ultrasound in patients after Guillain-Barré syndrome (GBS). Seventy-five healthy controls and 41 post-GBS patients (mean 3.4 years, SD ± 2.91 years after onset) underwent clinical, sonographic, and electrophysiological evaluation. Compared to healthy controls, the post-GBS patients showed: (1) a mean Rasch-built Overall Disability Scale score of 31.8 (SD ± 11.6), modified Rasch-built fatigue severity scale score of 15.6 (SD ± 3.2), Medical Research Council sum score of 22 (SD ± 5.6); (2) electrophysiological signs of permanent axonal loss in the majority of the peripheral nerves; (3) sonographical evidence of higher cross-sectional area values (CSA) of the ulnar (elbow, p < 0.001), radial (spiral groove, p < 0.001), tibial nerve (popliteal fossa, p < 0.001) and brachial plexus (supraclavicular space, p < 0.001). No correlation between sonographic and electrophysiological findings was found. Neither nerve ultrasound nor electrophysiology correlated with muscle strength, overall disability, and fatigue scale. Compared to healthy controls, post-GBS patients had significant functional disability. Despite significant abnormalities in both electrophysiology and ultrasound compared to healthy controls, neither electrophysiology nor nerve ultrasound correlated with functional disability of these patients.

General principles and escalation options of immunotherapy in autoantibody-associated disorders of the CNS.

Autoimmune diseases associated with antineuronal and antiglial autoantibodies (Abs) is one of the most rapidly expanding research fields in clinical neuroimmunology, with more than 30 autoantibodies described so far. Being associated with a wide range of clinical presentations these syndromes can be diagnostically challenging. Surface or intracellular antigen localizations are crucial for the treatment response and outcome. In the latter Abs are mostly of paraneoplastic cause and tumor management should be performed as soon as possible in order to stop peripheral antigen stimulation. Immunotherapy should be started early in both groups, before irreversible neuronal loss occurs. Despite serious prognosis, aggressive therapeutic approaches can be effective in many cases. In this article we review main pathogenic mechanisms leading to Abs-related syndromes and describe standard as well as emerging strategies of immunotherapy, including tocilizumab and bortezomib. Several special therapeutic approaches will be illustrated by clinical cases recently treated in our department.

Dagibatran Etexilate: Is There Any Need for Coagulation Monitoring After Initiation?

INTRODUCTION: Activated prothrombin time (aPTT) and thrombin time (TT) can serve as indicators for anticoagulation effect of dabigatran etexilate (Pradaxa), the new oral reversible, competitive inhibitor of thrombin. Further, a significant elevation of these coagulation parameters might demonstrate an increased risk of bleeding probably due to an accumulation of dabigatran. CASE REPORTS: We present 2 cases of patients with atrial fibrillation as well as mild and moderate renal impairment, which were treated with dabigatran. The patient with the mild renal impairment [creatinine clearance in 24-hour urine collection (CrCl) 50.2 mL/min] had a comorbid slightly disturbed liver synthesis and prolongation of aPTT. Increased risk of bleeding could be identified by significant elevated coagulation parameters (TT and aPTT) during dabigatran treatment. Further speculative in this case increased risk of bleeding might be due to an accumulation of dabigatran possibly caused by comorbid kidney and liver impairment and an effective gain of dabigatran caused by reduced hepatic synthesis of coagulation factors. CONCLUSIONS: Especially in multimorbid elderly patients with comorbid liver and kidney dysfunction, a measurement of coagulation parameters not only before but also soon after initiation of treatment might provide additional information about the risk of bleeding.

Increased cerebrospinal fluid protein and motor conduction studies as prognostic markers of outcome and nerve ultrasound changes in Guillain-Barré syndrome.

OBJECTIVE: Our study examined the prognostic role of increased cerebrospinal fluid protein and motor conduction studies on outcome and nerve ultrasound changes in Guillain-Barré syndrome (GBS). METHODS: Fifty post-GBS patients underwent clinical and nerve ultrasound examination, with a mean of 3.4 years (SD=2.8) after disease onset. Outcome was measured using the Medical Research Council Sum Score (MRC), the Rasch-built Overall Disability Scale (R-ODS) and the Rasch-built fatigue severity scale (R-FSS). Ιn addition, the results of the motor conduction studies and cerebrospinal fluid (CSF) examination at disease onset were retrospectively evaluated. RESULTS: No significant changes in outcome were noted between patients with (p-CSF) and without increased CSF protein (n-CSF). The p-CSF group showed significant lower cross-sectional area (CSA) values of the radial nerve in spiral groove (p<0.001) and higher values of the internerve-CSA variability (p<0.001) compared to n-CSF patients. GBS patients with axonal affection in motor studies (GBS-a) showed significantly lower values of the R-ODS and MRC sum scores (p>0.001), but not of the R-FSS Score (p=0.018). Sonographically the GBS-a patients showed significant lower values of the median and ulnar nerve in the upper arm (p<0.001). DISCUSSION: Axonal affection in motor studies, but not increased CSF protein at disease onset, seems to be an infavourable prognostic factor for outcome in GBS. Both axonal affection and increased CSF protein have a minor prognostic role in the development of nerve ultrasound changes.

Cross sectional area reference values for sonography of peripheral nerves and brachial plexus.

OBJECTIVE: Ultrasound measurements of the cross sectional area (CSA) variability have been recently introduced to quantify pathological changes in peripheral nerves (PN). METHODS: Reference values from 75 healthy subjects and their correlation to age, height, weight and sex are reported. RESULTS: The mean values in PN were: (1) intranerve CSA-variability: median 1.05 (SD ± 0.13), ulnar 1.53 (SD ± 0.51), fibular 1.33 (SD ± 0.37), tibial 1.39 (SD ± 0.39), (2) internerve CSA-variability 1.76 (SD ± 0.37), (3) intraplexus CSA-variability 1.52 (SD ± 0.37), (4) side-to-side difference ratio of the CSA-variability: median 1.21 (SD ± 0.04), ulnar 1.2 (SD ± 0.25), fibular 1.19 (SD ± 0.23), tibial 1.28 (SD ± 0.24) and brachial plexus 1.19 (SD ± 0.23). CSA did not correlate with height in PN, but correlated with weight in the ulnar nerve [Guyon's canal, r = 0.411, p = 0.0237, elbow r = 0.409, p = 0.0248]. Significant changes between sex were found only in the ulnar (Guyon's canal, p = 0.0265), fibular (popliteal fossa, p = 0.0336) and sural nerve (p = 0.048). CSA decreased with age in the median (axilla, p = 0.0236), and radial nerve (spiral groove, p = 0.0037) and increased in the tibial nerve (ankle, p < 0.0001). CONCLUSIONS: The CSA reference values reported seem to correlate at certain sites with age, weight and sex but not with height. SIGNIFICANCE: The new CSA variability measures may be helpful in investigating pathologies of the PN.

The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium.

PURPOSE: The c-Jun N-terminal kinases (JNK) are involved in the activation of T cells and the synthesis of proinflammatory cytokines. Several studies have established the relevance of the JNK pathway in inflammatory bowel diseases. The present study analyzed the therapeutic effect of D-JNKI-1, a specific JNK-inhibiting peptide, in a low-dose dextran sulfate sodium (DSS) model of chronic colitis. METHODS: DSS colitis was induced in female C57/BL6 mice by cyclic administration using different concentrations of DSS (1.0% and 1.5%). Mice in the intervention groups received subcutaneous administration of 1 µg/kg D-JNKI-1 on days 2, 12, and 22. They were monitored daily to assess the severity of colitis, body weight, stool consistency, and the occurrence of occult blood or gross rectal bleeding using evaluation of the disease activity index. The animals were sacrificed after 30 days, and the inflamed intestine was histologically evaluated using a crypt damage score. Immunohistochemical quantification of CD4(+) and CD8(+) cells was also carried out. RESULTS: Administration of 1 µg/kg D-JNKI-1 resulted in a significant decrease in the disease activity index (P = 0.013 for 1.0% DSS; P = 0.007 for 1.5% DSS). As a mild form of colitis was induced, histological examination did not show any distinct damage to the mucosa and crypts. However, expression of CD4(+) and CD8(+) cells was reduced in mice treated with D-JNKI-1 (not significant). CONCLUSION: Administration of D-JNKI-1 resulted in a clinical attenuation of chronic DSS colitis, and a therapeutic effect of D-JNKI-1 must therefore be assumed. The decrease in CD4(+) and CD8(+) cells may reflect the influence of D-JNKI-1 on T-cell activation, differentiation, and migration.