Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome.

BACKGROUND AND OBJECTIVE: The spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking. The objective of the study is to assess the clinical and laboratory prognostic parameters for a risk of relapse and the temporal dynamics of MOG-IgG titers in children with MOGAD in correlation with clinical presentation and disease course. METHODS: In this prospective multicenter hospital-based study, children with a first demyelinating attack and complete data set comprising clinical and radiologic findings, MOG-IgG titer at onset, and clinical and serologic follow-up data were included. Serum samples were analyzed by live cell-based assay, and a titer level of ≥1:160 was classified as MOG-IgG-positive. RESULTS: One hundred sixteen children (f:m = 57:59) with MOGAD were included and initially diagnosed with ADEM (n = 59), unilateral ON (n = 12), bilateral ON (n = 16), myelitis (n = 6), neuromyelitis optica spectrum disorder (n = 8) or encephalitis (n = 6). The median follow-up time was 3 years in monophasic and 5 years in relapsing patients. There was no significant association between disease course and MOG-IgG titers at onset, sex, age at presentation, or clinical phenotype. Seroconversion to MOG-IgG-negative within 2 years of the initial event showed a significant risk reduction for a relapsing disease course. Forty-two/one hundred sixteen patients (monophasic n = 26, relapsing n = 16) had serial MOG-IgG testing in years 1 and 2 after the initial event. In contrast to relapsing patients, monophasic patients showed a significant decrease of MOG-IgG titers during the first and second years, often with seroconversion to negative titers. During the follow-up, MOG-IgG titers were persistently higher in relapsing than in monophasic patients. Decrease in MOG-IgG of ≥3 dilution steps after the first and second years was shown to be associated with a decreased risk of relapses. In our cohort, no patient experienced a relapse after seroconversion to MOG-IgG-negative. DISCUSSION: In this study, patients with declining MOG-IgG titers, particularly those with seroconversion to MOG-IgG-negative, are shown to have a significantly reduced relapse risk.

Intrathecal baclofen therapy for treatment of spasticity in infants and small children under 6 years of age.

PURPOSE: The aim of this study is to prove the efficacy and safety of intrathecal baclofen therapy in infants and children below 6 years of age by retrospective analysis of our pediatric cohort of 135 primary pump implantations. METHODS: Between 2007 and 2018, 17 patients with pump implantations were below 6 years of age. Data were acquired retrospectively with a follow-up of 12 months to 11 years regarding complications. RESULTS: The youngest infant was 11 months at implantation with a bodyweight of 6, 4 kg, and 63 cm length. Surgical complications were comparable to published literature and mainly involved the catheter (2 catheter dislocations and 1 catheter transection) and one pump infection resulting in 4 revision surgeries in 3 patients. One baclofen-related apnea during titration and an overdose after refill were treated conservatively. Using a subfascial implantation technique, we observed neither skin ulceration nor pump infection since 2007. In a growing child, catheter slides are common and related to growth, scoliosis, spine surgery, and surgical failure. CONCLUSION: Intrathecal baclofen therapy in infants and small children is as safe and effective as published for older pediatric patients; therefore, intrathecal baclofen can be considered in all infants as long as an 8-cm incision fits into the triangle of the anterior superior iliac spine, costal margin of the 10th rib, and navel. We suggest the utilization of subfascial surgical technique for implantation pump and catheter. Titration of intrathecal baclofen should be performed slowly to avoid bradycardia in infants. This is a retrospective study (level of evidence 4).

The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester on neuropeptide-induced vasodilation and protein extravasation in human skin.

Endogenous neuropeptides released from nociceptors can induce vasodilation and enhanced protein extravasation (neurogenic inflammation). The role of nitric oxide (NO) in the induction of neurogenic inflammation is controversial. In this study, dermal microdialysis was used in awake humans (n = 39) to deliver substance P (SP; 10(-7) and 10(-6)M) or calcitonin gene-related peptide (CGRP; 5 x 10(-7)M and 2 x 10(-6)M). Neuropeptide-induced local and axon reflex erythema was assessed by laser Doppler imaging. Total protein concentration in the dialysate was measured to quantify local protein extravasation. The responses were assessed in the absence and the presence of the nitric oxide synthase inhibitor, N-nitro-L-arginine-methyl ester (L-NAME) added to the perfusate at concentrations of 5, 10 or 20 mM. L-NAME (5 mM) applied via the dialysis catheters reduced local blood flow by approximately 30%. In addition, L-NAME inhibited SP-induced vasodilation by about 40% for 10(-7)M SP and 30% for 10(-6)M SP (n = 11, p < 0.01). In contrast, CGRP-induced vasodilation was only marginally inhibited by L-NAME. SP, but not CGRP, provoked a dose-dependent increase in protein extravasation. L-NAME (5 mM) inhibited this increase by up to 40% for both SP concentrations used (n = 11, p < 0.01). Higher concentrations of L-NAME did not further reduce SP- or CGRP-induced vasodilation or SP-induced protein extravasation. Exogenously applied SP induces vasodilation and protein extravasation, which is partly NO mediated, whereas CGRP-induced vasodilation appears to be NO independent.

Prostaglandin E2 induces vasodilation and pruritus, but no protein extravasation in atopic dermatitis and controls.

BACKGROUND: Prostaglandin E(2) (PGE(2)) has well-established vasodilatory effects, whereas its effects on protein extravasation and its sensory effects are less clear. OBJECTIVE: Vasoactive effects of PGE(2) were correlated to its ability to evoke pain or itch in healthy volunteers and patients with atopic dermatitis (AD). METHODS: Intradermal microdialysis was used to apply PGE(2) (10(-8)-10(-4) M) via microdialysis capillaries in 8 patients and 8 controls. Large pore size membranes (3000 kd) enabled simultaneous analysis of protein extravasation. Itch and pain sensations were measured psychophysically, and superficial blood flow was measured by laser Doppler imaging. RESULTS: PGE(2) dose dependently provoked intense local vasodilation, weak pruritus, and pain, but no protein extravasation. No differences were found between patients with AD and controls for any parameter. CONCLUSION: We conclude that PGE(2) is a potent vasodilator and a weak pruritic agent in normal skin and in patients with AD, but does not provoke increased protein extravasation.