Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome

Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

     

The Helsinki approach to face transplantation

Aim

We herein describe the establishment of the Helsinki Vascularized Composite Allotransplantation (VCA) program and its execution in the first two face transplant cases.

Empirical treatment of lower urinary tract infections in the face of spreading multidrug resistance: in vitro study on the effectiveness of nitroxoline

The spread of antimicrobial resistance challenges the empirical treatment of urinary tract infections (UTIs). Among others, nitrofurantoin is recommended for first-line treatment, but acceptance among clinicians is limited due to chronic nitrofurantoin-induced lung toxicity and insufficient coverage of Enterobacteriaceae other than Escherichia coli. Nitroxoline appears to be an alternative to nitrofurantoin owing to its favourable safety profile, however data on its current in vitro susceptibility are sparse. In this study, susceptibility to nitroxoline was tested against 3012 urinary clinical isolates (including multidrug-resistant bacteria and Candida spp.) by disk diffusion test and/or broth microdilution. At least 91% of all Gram-negatives (n?=?2000), Gram-positives (n?=?403) and yeasts (n?=?132) had inhibition zone diameters for nitroxoline ≥18?mm. Except for Pseudomonas aeruginosa, nitroxoline MIC₉₀ values were ≤16?mg/L and were 2- to >16-fold lower compared with nitrofurantoin. In extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA), MIC₉₀ values of nitroxoline were two-fold higher compared with non-ESBL-producing enterobacteria and methicillin-susceptible S. aureus (MSSA). The in vitro efficacies of nitroxoline and nitrofurantoin against ATCC strains of E. coli, Enterococcus faecalis and Proteus mirabilis were compared by time–kill curves in Mueller–Hinton broth and artificial urine. Nitroxoline was non-inferior against E. coli, P. mirabilis and E. faecalis in artificial urine. In conclusion, nitroxoline showed a broad antimicrobial spectrum, with inhibition zone diameters and MICs of nitroxoline well below the EUCAST breakpoint for E. coli for most organisms, and thus may also be a target for therapy of uncomplicated UTIs.     

Risk factors of nerve injury during mandibular sagittal split osteotomy

There is little objective data about whether surgical technique or mandibular anatomy are a risk for inferior alveolar nerve (IAN) injury during bilateral sagittal split osteotomy (BSSO). Orthodromic sensory nerve action potentials (SNAPs) of the IAN were continuously recorded on both sides in 20 patients with mandibular retrognathia during BSSO operation. Changes in latency, amplitude, and sensory nerve conduction velocity (SNCV) at baseline and at different stages of the operation were analyzed. The SNAP latencies prolonged, the amplitudes diminished, and the SNCVs slowed down during BSSO (P = 0.0000 for all parameters). The most obvious changes occurred during surgical procedures on the medial side of the mandibular ramus. There was a clear tendency towards more disturbed IAN conduction with longer duration of these procedures (right side R = -0.529. P = 0.02; left side R = -0.605, P = 0.006). Exposure or manipulation of the IAN usually had no effect on nerve function, but the IAN conduction tended to be more disturbed in cases with nerve laceration. Low corpus height (R = 0.802, P = 0.001) and the location of the mandibular canal near the inferior border of the mandible (R = 0.52, P = 0.02) may increase the risk of IAN injury. There was no correlation between the age of the patients and the electrophysiological grade of nerve damage.     

Combined mechanical and antibiotic periodontal therapy in a case of Papillon-Lefèvre syndrome

BACKGROUND: Papillon Lefèvre syndrome (PLS) is a rare entity and, as such, it is almost impossible to evaluate an effective therapy in a randomized controlled study. The amount of success reported after therapy for prepubertal periodontitis (PP) in PLS is highly variable from case to case. The goal of this case report is to evaluate the effects of a combined mechanical and antibiotic periodontal therapy regimen in the management of PLS. METHODS: A male patient was diagnosed as suffering from PP associated with PLS at the age of 7 years. He showed hyperkeratosis of the palms and soles, as well as advanced periodontal disease already affecting permanent teeth with maximal probing depth and vertical attachment loss of 12 mm and 11 mm, respectively. Subgingival debridement was performed with simultaneous administration of oral 250 mg amoxicillin 3 times daily and 250 mg metronidazole twice daily for one week. Clinical parameters were assessed and subgingival plaque was collected from all teeth prior to therapy and 7 and 26 months after treatment. Selective cultures for A. actinomycetemcomitans were incubated for each individual tooth and DNA probe analysis was performed for various periodontal pathogens. RESULTS: Prior to combined mechanical and antibiotic treatment, all teeth but one harbored Actinobacillus actinomycetemcomitans subgingivally. However, at 7 and 26 months after therapy A. actinomycetemcomitans could be detected neither by culture nor by DNA probes. Clinical parameters improved markedly and teeth erupting after therapy did not exhibit attachment loss of more than 1.5 mm during the observation period. CONCLUSIONS: Eradication (suppression beneath detection levels) of A. actinomycetemcomitans seems to play a significant role in the successful treatment of localized prepubertal periodontitis in PLS.     

Accuracy of the Third Molar Eruption Predictor in predicting eruption

OBJECTIVE: To evaluate the possibility of applying the Third Molar Eruption Predictor to all panoramic radiographs. STUDY DESIGN: Panoramic radiographs were retrospectively analyzed from a 4-year follow-up study of third molars carried out at the University of Copenhagen, Denmark. The radiographs, taken at a mean age of 20.6 years, included 45 unerupted or partially erupted mandibular third molars in 28 subjects. Because the device was calibrated both with simple proportions and by use of the methods of Bayes' Decision Theory, the separation point of the device was therefore adjusted at 12 mm from the distal surface of the second molar. RESULTS: The predictions of future eruption or impaction made with the calibrated device and the actual clinical outcome 4 years later were in conformity for 80% of the mandibular third molars. CONCLUSION: The Third Molar Eruption Predictor may be applied to all panoramic radiographs, but it seems to require calibration before use.