Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology.

BACKGROUND: Kabuki Syndrome is a rare and genetically heterogenous condition with both ophthalmic and systemic complications and typical facial features. We detail the macular phenotype in two unrelated patients with Kabuki syndrome due to de novo nonsense variants in KMT2D, one novel. A follow-up of 10 years is reported. Pathogenicity of both de novo nonsense variants is analyzed. METHODS: Four eyes of two young patients were studied by full clinical examination, kinetic perimetry, short wavelength autofluorescence, full field (ff) ERGs, and spectral-domain optical coherence tomography (SD-OCT). One patient had adaptive optic (AO) imaging. Whole exome sequencing was performed in both patients. RESULTS: Both patients had de novo nonsense variants in KMTD2. One patient had c.14843C>G; p. (Ser4948ter) novel variant and the second c.11119C>T; p. (Arg3707ter). Both had a stable Snellen visual acuity of 0.2-0.3. The retinal multimodal imaging demonstrated abnormalities at the fovea in both eyes: hyperreflectivity to blue light and a well-delimited gap-disruption of ellipsoid and interdigitation layer on OCT. The dark area on AO imaging is presumed to be absent for, or with structural change to photoreceptors. The ff ERGs and kinetic visual fields were normal. The foveal findings remained stable over several years. CONCLUSION: Kabuki syndrome-related maculopathy is a distinct loss of photoreceptors at the fovea as shown by multimodal imaging including, for the first time, AO imaging. This report adds to the literature of only one case with maculopathy with two additional macular dystrophies in patients with Kabuki syndrome. Although underestimated, these cases further raise awareness of the potential impact of retinal manifestations of Kabuki syndrome not only among ophthalmologists but also other healthcare professionals involved in the care of patients with this multisystem disorder.

Dexamethasone Is Superior to Dexmedetomidine as a Perineural Adjunct for Supraclavicular Brachial Plexus Block: Systematic Review and Indirect Meta-analysis.

BACKGROUND: Both dexamethasone and dexmedetomidine are effective peripheral nerve block (PNB) perineural adjuncts that prolong block duration. However, each is associated with side effects. With paucity of head-to-head comparisons of these adjuncts, the question of the best adjunct to mix with local anesthetics (LA) for PNB is unanswered. This meta-analysis aims to inform current practice and future research by identifying the superior adjunct by comparing dexamethasone and dexmedetomidine. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, trials comparing the combination of perineural dexamethasone or dexmedetomidine with LA to LA alone for PNB were sought. The Cochrane Risk of Bias Tool was used to assess the methodological quality of trials, and indirect or network meta-analyses using random-effects modeling were planned. We designated duration of analgesia as a primary outcome. Secondary outcomes included sensory and motor block durations, sensory and motor block onset times, and the risks of hypotension, sedation, and neurological symptoms. RESULTS: Fifty trials were identified, including only 1 direct comparison, precluding a network meta-analysis. Indirect meta-analysis of 49 trials (3019 patients) was performed. Compared to dexmedetomidine, dexamethasone prolonged the duration of analgesia by a mean difference (95% confidence interval [CI]) of 148 minutes (37-259 minutes) (P = .003), without prolonging sensory/motor blockade. Dexmedetomidine increased rates of hypotension (risk ratio [95% CI], 6.3 [1.5-27.5]; P = .01) and sedation (risk ratio [95% CI], 15.8 [3.9-64.6]; P = .0001). Overall risk of bias was moderate, and publication bias was noted, resulting in downgrading evidence strength. CONCLUSIONS: There is low-quality evidence that both adjuncts similarly prolong sensory/motor blockade. However, dexamethasone may be a superior adjunct; it improves the duration of analgesia by a statistically significant increase, albeit clinically modest, equivalent to 2.5 hours more than dexmedetomidine, without the risks of hypotension or sedation. Future direct comparisons are encouraged.

Optimal Dose of Perineural Dexamethasone to Prolong Analgesia After Brachial Plexus Blockade: A Systematic Review and Meta-analysis.

BACKGROUND: Perineural dexamethasone has gained popularity in regional anesthesia to prolong analgesia duration. However, uncertainty remains regarding the optimal perineural dose. Clarification of this characteristic is of significant importance as the administration of dexamethasone may lead to dose-dependent complications. The objective of this meta-analysis was to define the optimal perineural dexamethasone dose to prolong analgesia after brachial plexus blockade for adult patients undergoing upper limb surgery. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines and searched databases including MEDLINE, PubMed, and EMBASE until January 2017, without language restriction. Only trials comparing perineural dexamethasone and local anesthetics with local anesthetics alone for brachial plexus blocks were included in the present meta-analysis. The Cochrane Collaboration's Risk of Bias Tool was used to assess the methodological quality of each trial and meta-analyses were performed following a random effects model. The primary outcome was duration of analgesia for each type of local anesthetic (short-/intermediate-acting and long-acting local anesthetics). A meta-regression followed by a subgroup analysis were performed to assess the impact of different perineural dexamethasone doses on duration of analgesia; for the latter analysis, trials were grouped in low (1-4 mg) and moderate (5-10 mg) dexamethasone doses. Secondary outcomes included the rate of neurologic complication and resting pain scores and morphine consumption within the first 24 hours. RESULTS: Thirty-three controlled trials, including 2138 patients, were identified. The meta-regression revealed a ceiling effect with a perineural dexamethasone dose of 4 mg when combined with short-/intermediate-acting (8 trials; 366 participants) or long-acting local anesthetics (23 trials; 1869 participants). This finding was confirmed by subgroup analyses comparing low and moderate dexamethasone doses. With short-/intermediate-acting local anesthetics, the mean difference (95% confidence interval) of analgesia duration with low and moderate doses was 277 (234-322) minutes and 229 (161-297) minutes, respectively. With long-acting local anesthetics, the mean differences with low and moderate doses were 505 (342-669) minutes and 509 (443-575) minutes. Perineural dexamethasone did not increase the rate of neurologic complications (risk ratio [95% confidence interval], 1.40 [0.54-3.63]). The Grades of Recommendation, Assessment, Development, and Evaluation quality of evidence for the primary and secondary outcomes were very low, due mainly to limitations, inconsistency, indirectness, and publication bias. CONCLUSIONS: There is currently very low quality evidence that 4 mg of perineural dexamethasone represents a ceiling dose that prolongs analgesia duration by a mean period of 6 and 8 hours when combined with short-/intermediate- or long-acting local anesthetics, respectively. Additional data are needed to explore the threshold for this effect, particularly with doses below 4 mg. The risk of neurologic complications is probably not increased (very low evidence).

Extending Levelt's Propositions to perceptual multistability involving interocular grouping.

Levelt's Propositions are central to understanding a wide range of multistable perceptual phenomena, but it is unclear whether they extend to perceptual multistability involving interocular grouping. We presented split-grating stimuli with complementary halves of the same color (either red or green) to human subjects. The subjects reported four percepts in alternation: the two stimuli presented to each eye (half red and half green), as well as the two single color (all red or all green), interocularly grouped percepts. Increasing color saturation lead to increased reports of the single color percept in most subjects, indicating increased predominance of grouped percepts (Levelt's Proposition I). This increase in predominance was due to a decrease in the average dominance duration of single-eye percepts, with grouped percept dominance largely unaffected. This agrees with a generalization of Levelt's Proposition II, as the average dominance duration of the stronger (in this case single-eye) percept was primarily affected by changes in stimulus strength. Moreover, in agreement with Levelt's Proposition III the alternation rate between percepts increased as the difference in the strength of the percepts decreased.