Correction: Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience.

[This corrects the article DOI: 10.1371/journal.pone.0277767.].

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.

Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience.

The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of the Danish Fabry cohort and report 20 years' (2001-2020) experience in cascade genetic screening at the Danish National Fabry Disease Center. The Danish Fabry cohort consisted of 26 families, 18 index patients (9 males and 9 females, no available data for 8 index-patients) and 97 family members with a pathogenic GLA variant identified by cascade genetic testing (30 males and 67 females). Fourteen patients (5 males and 9 females; mean age of death 47.0 and 64.8 years respectively) died during follow-up. The completeness of the Fabry patient identification in the country has resulted in a cohort of balanced genotypes according to gender (twice number of females compared to males), indicating that the cohort was not biased by referral, and further resulted in earlier diagnosis of the disease by a lower age at diagnosis in family members compared to index-patients (mean age at diagnosis: index-patients 42.2 vs. family members 26.0 years). Six previously unreported disease-causing variants in the GLA gene were discovered. The nationwide screening and registration of Fabry disease families provide a unique possibility to establish a complete cohort of Fabry patients and to advance current knowledge of this inherited rare lysosomal storage disorder.

Anti-myelin oligodendrocyte glycoprotein antibodies in a girl with good recovery after five episodes of prior idiopathic optic neuritis.

PURPOSE: To describe the clinical, radiological, immunological and electrophysiological features of a myelin oligodendrocyte glycoprotein (MOG)-IgG positive girl with five prior episodes of idiopathic bilateral optic neuritis (ON). OBSERVATIONS: We report a Danish girl who has been followed by pediatricians and pediatric neurologists since the age of 10 with recurrent episodes of idiopathic bilateral ON. Since the age of 15 there has been no recurrence of ON, and the patient has been thoroughly investigated for Multiple Sclerosis (MS) several times, but with negative findings. At the age of 19 the patient was referred to the Clinic of Optic Neuritis where she was tested seropositive for antibodies against MOG (MOG- IgG) on a conventionally cell-based assay. Despite 5 previous episodes of ON, the latency and amplitude signals of pattern-reversal visual evoked potentials (pVEP) including multifocal VEP were detected within the normal range. CONCLUSION: The clinical implications of MOG- IgG are not yet clear, but in cases where the diagnosis of MS is less likely and where ON is the main symptom, testing for both IgG antibodies against AQP4 and MOG while having atypical optic neuropathies in mind is important. MOG-IgG positive patients may have a good prognosis with regards to visual function.

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-alpha) 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/microl; P < 0.05), and the TNF-alpha concentration (at 6 h, 261 +/- 188 versus 873 +/- 135 pg/microl; 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.