Genotypic and Phenotypic Spectrum of Foveal Hypoplasia: A Multicenter Study.

PURPOSE: To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). DESIGN: Multicenter, observational study. PARTICIPANTS: A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384). METHODS: Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans. MAIN OUTCOME MEASURES: Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA). RESULTS: The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH. CONCLUSIONS: We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value.

Anastomotic Ulcers: A Tertiary Centre Experience of Endoscopic Management Techniques.

ABSTRACT: Improvements in neonatal care and surgical advances, has led to an increased prevalence of children with small and large bowel anastomoses. Ulceration at the site of anastomosis is a rare, but well-recognised phenomenon, with no clearly understood pathogenesis. Paediatric case series have been reported but there remains no clear effective treatment strategy and there is limited experience with endoscopic techniques in their management. We report our tertiary centre experience of managing nine anastomotic ulcer patients, including endoscopic treatment with argon plasma coagulation and clips.Two patients with inflammatory bowel disease (IBD) responded to optimisation of medical therapy. In our non-IBD patients, those requiring a blood transfusion (n = 2) ultimately required surgery and those who did not require a blood transfusion responded to aminosalicylate treatment (n = 1) or endoscopic therapeutic techniques (n = 3).We conclude that endoscopic interventions can be an effective management strategy for anastomotic ulcers when a blood transfusion isn't required.

Tibial motor and sural electrophysiological relationship in subjects without and patients with mild axonal peripheral neuropathy.

The distal motor fibers of the tibial and sural nerves are predominantly derived from the S1 root. We aimed to describe the electrophysiological relationship of these two nerves. Clinical, radiological and neurophysiological data of patients with mild, length-dependent, peripheral neuropathy (PN) and subjects without PN were retrospectively collected and analyzed. Eighty-eight individuals without PN and 24 patients with mild axonal PN who had no evidence of lumbosacral radiculopathy were included for analysis. Significant positive correlations were observed for the tibial CMAP and the sural SNAP for both controls and patients. Multivariate linear regression analyses showed that the predicted tibial CMAP can be calculated using the following equations: for male subjects without PN, tibial CMAP = 20.7 - 0.21 × age; for female subjects without PN, tibial CMAP = 23.3 - 0.21 × age and for patients with mild PN, tibial CMAP = 2.7 + sural SNAP. This study demonstrates the high correlation between the tibial CMAP and the sural SNAP in subjects without PN and patients with mild axonal peripheral neuropathy, and provides mathematical equations for the calculation of the predicted tibial CMAP for such individuals.

Repetitive Magnetic Stimulation for the Management of Peripheral Neuropathic Pain: A Systematic Review.

INTRODUCTION: Repetitive magnetic stimulation (rMS) is a safe and well-tolerated intervention. Transcranial magnetic stimulation (TMS) is used for the treatment of depression and for the treatment and prevention of migraine. Over the last few years, several reports and randomised controlled studies of the use of rMS for the treatment of pain have been published. The aim of this systematic review was to identify the available literature regarding the use of rMS in the treatment of peripheral neuropathic pain. METHODS: After a systematic Medline search we identified 12 papers eligible to be included in this review. RESULTS: The majority of the studies were on patients with phantom limb pain, followed by radiculopathy, plexopathy, post-traumatic pain and peripheral neuropathy. The treatment protocols vary significantly from study to study and, therefore, pooling the results together is currently difficult. However, rMS has a definite immediate effect in pain relief which, in the majority of studies, is maintained for a few weeks. CONCLUSION: rMS seems to be a promising intervention in the treatment of peripheral neuropathic pain. Further research is in the field is needed. Use of neuronavigation might increase the precision of stimulation and subsequently its effectiveness.

Quality of life in idiopathic dystonia: a systematic review.

OBJECTIVE: Dystonia is characterised by sustained muscular contractions frequently producing repetitive, twisting and patterned movements. The primary aim of this systematic review was to establish how quality of life (QoL) is affected in idiopathic focal, multifocal and segmental dystonia. This review aimed to evaluate variations in QoL between different subtypes of dystonia, identify the determinants of QoL and assess the effects of different treatments on QoL. METHODOLOGY: A systematic computer-based literature search was conducted using the PubMed database to search for papers on QoL in idiopathic focal, segmental, multifocal and generalized dystonia. We identified 75 studies meeting our inclusion criteria. Information was extracted regarding prevalence, demographics and response to treatment where indicated. RESULTS: This review revealed QoL to be a significant yet often overlooked issue in idiopathic dystonia. Data consistently showed that dystonia has a negative effect on QoL in patients compared to healthy controls, when measured using disease-specific and generic QoL measures. The majority of studies (n = 25) involved patients with cervical dystonia, followed by benign-essential blepharospasm (n = 10). Along with the beneficial effect to the dystonia symptoms, treatment using Botulinum Toxin and Deep Brain Stimulation is also effective in improving overall QoL across the majority of subtypes. CONCLUSION: The findings demonstrate that patients' QoL should routinely be assessed and monitored, as this may affect subsequent management. Further research will allow for more robust management of factors contributing to impaired QoL, aside from the physical defects found in dystonia.

Quality of Life in Painful Peripheral Neuropathies: A Systematic Review.

Objective: Neuropathic pain is a common presenting complaint of patients with peripheral neuropathy (PN) and is considered one of the most disabling neuropathic symptoms, with detrimental effects on patients' quality of life (QoL). The aim of this review was to overview the current literature that focuses on QoL in painful PN of various aetiologies. We sought to clarify the direct effect of pain and its treatment on patients' QoL. Methodology: A systematic computer-based literature search was conducted using the PubMed database to search for papers on QoL in painful PN. Information was extracted regarding prevalence, demographics, and response to treatment where relevant. Results: We identified 66 articles eligible for inclusion. The vast majority of studies (n=47) focused on patients with diabetic PN. Other aetiologies of painful PN where QoL has been studied to date include gluten, immune-mediated, HIV, chemotherapy-induced, and chronic idiopathic axonal polyneuropathy. Pharmacological treatment is the mainstay in managing pain and has a direct positive and independent effect on the overall QoL. Other nonpharmacological approaches can also be of benefit, either alone or as adjuvant treatments, and are discussed. Conclusion: The findings demonstrate that QoL is impaired in painful PN and should not be neglected in clinical practice. Patients' pain management and subsequent impact on QoL should routinely be assessed and monitored.