Sensory nerve conduction studies in probable painful neuropathy: comparing surface and near-nerve nerve conduction techniques

INTRODUCTION: We compared sensory nerve conduction studies (NCS) using surface and near-nerve recording electrodes in 53 patients with clinical probable painful neuropathy. Our aim was to validate the use of both recording techniques in that limited patient group. METHODS: Patients had sensory NCS using two established recording methods and quantitative sensory tests (QST). We compared normalised amplitudes of sensory sural nerve action potentials (SNAP) and sensory thresholds and used receiver operated curve (ROC) analysis of absolute SNAP amplitudes to find discriminatory levels predicting abnormal sensory thresholds. RESULTS: Mean sural SNAP z-scores differed depending on recording techniques (surface −1.0: SD 1.9; near-nerve −2.5: SD 1.7) with a numeric mean difference of −1.49 (Bland-Altman test: CI −1.872 to −1.12) with surface technique giving the z-value closest to zero. We documented a significant bias between the methods. Fifteen patients (28.3%) and 30 (56.6%) patients had abnormal results, respectively (χ2 test: p<0.001). Sural SNAP amplitudes correlated significantly with vibration thresholds using the near-nerve (p<0.02) but not using the surface technique (p=0.11). ROC analysis gave an optimal discriminative value of SNAP amplitudes for each QST measure, which were similar to our lower limit of normal values from investigating normal controls using near-nerve but not surface recording. CONCLUSION: In patients with probable painful neuropathy, choosing sensory NCS technique introduces a bias in the diagnostic outcome. Differences in test performance suggest that using a normal sural NCS alone to delineate small fibre neuropathy from mixed neuropathy could result in poorly defined diagnostic groups

Tyrosine Kinase Inhibition Reduces Inflammation in the Acute Stage of Experimental Pneumococcal Meningitis

Bacterial meningitis is an acute inflammatory disease of the central nervous system with a mortality rate of up to 30%. Excessive stimulation of the host immune system by bacterial surface components contributes to this devastating outcome. In vitro studies have shown that protein tyrosine kinase inhibitors are highly effective in preventing the release of proinflammatory cytokines induced by pneumococcal cell walls in microglia. In a well-established rat model, intracisternal injection of purified pneumococcal cell walls induced meningitis characterized by increases in the regional cerebral blood flow and intracranial pressure, an influx of leukocytes, and high concentrations of tumor necrosis factor alpha (TNF-α) in the cerebrospinal fluid. Compared with the values at the beginning of the experiment, intraperitoneal injection of tyrphostin AG 126 reduced the increases in regional cerebral blood flow (at 6 h, 127% ± 14% versus 222% ± 51% of the baseline value; P < 0.05) and intracranial pressure (at 6 h, 0.8 ± 2.4 versus 5.4 ± 2.0 mm of Hg; P < 0.05), the influx of leukocytes (at 6 h, 1,336 ± 737 versus 4,350 ± 2,182 leukocytes/μl; P < 0.05), and the TNF-α concentration (at 6 h, 261 ± 188 versus 873 ± 135 pg/μl; P < 0.05). These results demonstrate that inhibition of AG 126-sensitive tyrosine kinase pathways may provide new approaches for preventing excessive inflammation and reducing the increases in blood flow and intracranial pressure in the acute phase of bacterial meningitis

Illustration of the affected individuals of the Danish Fabry cohort at diagnosis and/or baseline assessment from 2001 onwards and at the end of the study period.

Index patients and their family members were described in terms of age at diagnosis, sex, dead/alive at end of study, age at end of the study or age at death, no contact and first organ manifestation of the index patients.</p

The 26 families, their 115 Fabry disease patients and their corresponding <i>GLA</i>-gene variants of the Danish Fabry disease register.

Type of the GLA gene pathogenic variants, protein nomenclature, colloquial nomenclature, coding sequence (according to http://varnomen.hgvs.org), site of mutation and genotype classification (according to International Fabry Disease Genotype-Phenotype Database (dbFGP) http://dbfgp.org/dbFgp/fabry/ and the http://fabry-database.org) are presented. Sex, age (in years) and the primary clinical manifestation at Fabry disease diagnosis of the index-cases are presented.</p

Residual α-galactosidase A activity in Fabry males and females.

Activity is expressed, as nmol/h/mg protein. Grey area represents the normal α-galactosidase A activity range (20–65 nmol/h/mg protein). Available measurements in n = 35/39 males and females n = 61/76 females. ****: p-value <0.001.</p

S1 Data -

(SAV)</p

Flow chart of the principle of the procedure of the cascade screening.

Cascade screening begins once an index-case has been identified. Three generations surrounding the index-case are genetically screened. Each time a family member with a pathogenic GLA variant is identified, the procedure is repeated. When the index-case/family member with a pathogenic GLA variant was male, his mother, his daughter and all his siblings were offered testing. When the index-case/family member with a pathogenic GLA variant was female, both her parents, and all her children were offered testing and depending on the parents’ result, either only her female siblings in case of a father with pathogenic GLA variant or all her siblings in case of a mother with pathogenic GLA variant were tested (♂ = male, ♀ = female).</p

Structure of human <i>GLA</i> and positions of the amino acid substitutions resulting from the missense pathogenic variants identified in the Danish Fabry patients.

The backbone is displayed as a ribbon model, and the ligand and sugars as a stick model. The amino acids involved in the substitutions and the catalytic residues (D170 and D231) are indicated as a space-filling calotte (Corey-Pauling-Koltun CPK) model. Front view (top) and back view (bottom).</p