Clinical phenotyping and genetic diagnosis of a large cohort of Sudanese families with hereditary spinocerebellar degenerations.

Hereditary spinocerebellar degenerations (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include hereditary spastic paraplegia (HSP), cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment and overlap with many neurological conditions, including neurodevelopmental disorders. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates. We used next-generation sequencing, genotyping, bioinformatics analysis, and candidate gene approaches to study 90 affected patients from 38 unrelated Sudanese families segregating multiple forms of SCDs. The age-at-onset in our cohort ranged from birth to 35 years; however, most patients manifested childhood-onset diseases (the mean and median ages at onset were 7.5 and 3 years, respectively). We reached the genetic diagnosis in 63% and possibly up to 73% of the studied families when considering variants of unknown significance. Combining the present data with our previous analysis of 25 Sudanese HSP families, the success rate reached 52-59% (31-35/59 families). In this article we report candidate variants in genes previously known to be associated with SCDs or other phenotypically related monogenic disorders. We also highlight the genetic and clinical heterogeneity of SCDs in Sudan, as we did not identify a major causative gene in our cohort, and the potential for discovering novel SCD genes in this population.

Ketamine versus midazolam as an adjuvant to peribulbar block using a single inferonasal injection in patients undergoing vitreoretinal surgery: A randomized controlled trial.

INTRODUCTION AND OBJECTIVES: This study aimed to assess the safety and efficacy of midazolam and ketamine as adjuvants to the peribulbar block in vitreoretinal surgeries. PATIENTS AND METHODS: This randomized controlled trial included 93 adult patients undergoing vitreoretinal surgeries performed with peribulbar anaesthesia. Patients were randomly allocated to 3 groups (31 participants each): control (standard anaesthetic mixture), midazolam (standard mixture + midazolam), and ketamine (standard mixture + ketamine). The primary outcomes were onset of globe akinesia and duration of analgesia. Secondary outcomes were duration of motor blockade, onset of corneal anaesthesia and lid akinesia, and changes in vital data (blood pressure, oxygen saturation, and pulse rate). RESULTS: The ketamine group vs. the control and midazolam groups showed the most rapid onset of lid and globe akinesia (p < 0.001) and corneal anaesthesia (0.7 ± 0.2 vs. 1.5 ± 0.5 and 1.2 ± 0.4, respectively; p < 0.001) and the longest duration of both analgesia (3.7 ± 0.6 vs. 2.3 ± 0.4 and 3.1 ± 0.6, respectively; p < 0.001) and akinesia (3.8 ± 0.5 vs. 3.0 ± 0.4, and 3.7 ± 0.5, respectively; p < 0.001). The midazolam group showed better outcomes than controls, but the drug was less effective than ketamine. There were no significant differences in vital data among groups (p > 0.05). CONCLUSIONS: Ketamine is an effective adjuvant for peribulbar blockade. It enhances both motor and sensory blockade by hastening onset and prolonging duration. These effects are desirable in lengthier ophthalmic procedures such as vitreoretinal surgeries. The effects of ketamine were superior to those of midazolam.

A customized regimen of intravitreal aflibercept for the treatment of choroidal neovascularization secondary to different chorioretinal diseases.

BACKGROUND: To assess the response of CNV secondary to chorioretinal diseases to IVA and to explore the adequate dosing regimen and the long-term results. METHODS: A retrospective study including patients with treatment-naïve active CNV secondary to chorioretinal diseases. All patients received an initial IVA injection followed by a PRN regimen. The main outcome measures were improvement of BCVA, improvement of anatomical morphology and vascularity of the CNV on SS-OCT, and SS-OCTA, respectively, and ocular or systemic complications attributed to IVA. RESULTS: The study included 17 eyes of 15 patients. Nine patients (60%) were females. The median age was 20 years. The main primary chorioretinal disease was vitelliform macular dystrophy (29%). The mean baseline BCVA was 0.16. The mean follow-up period was 15 months. Final BCVA improved by a mean of 6 lines. The CNV regressed or became inactive in all eyes. The median number of IVA injections was 2. There were no ocular or systemic complications attributed to IVA. CONCLUSION: The customized IVA regimen is effective in inducing long-term regression of secondary CNV and in improving BCVA. Multimodal imaging is fundamental in establishing the diagnosis of CNV, and in monitoring its response to IVA.

Seasonal Variations in the Digestive Tract of the Little Owl, Athene noctua: Anatomical, Histological, and Scanning Electron Microscopical Studies.

The digestive tract of the little owl, Athene noctua (Strigiformes: Strigidae), is described in two different seasons. The digestive tract of this bird follows the basic model for that of a predatory bird. The cervical esophagus is not expanded to form a crop. The internal surface of the esophagus forms numerous longitudinal folds provided with numerous mucous glands. These longitudinal folds increase in number and vary in depth posteriorly. The folds of the proventriculus are composed of simple branched tubular glands. The ventriculus is lined by a thin layer of koilin. The number of goblet cells gradually increases from the duodenum to the rectum, and the lymphatic tissue diffuses within the lamina propria. The esophageal glands secrete acid mucopolysaccharides, while the gastric glands of the stomach, the goblet cells, and crypts of Lieberkühn secrete acid mucopolysaccharides. Proteins were observed in the different histological structures of the digestive tract. Morphometric and histometric studies showed differences between summer and winter in the esophagus and glandular stomach (especially in winter), but no seasonal differences were seen in the muscular stomach, or small and large intestines.

An identical-by-descent novel splice-donor variant in PRUNE1 causes a neurodevelopmental syndrome with prominent dystonia in two consanguineous Sudanese families.

PRUNE1 is linked to a wide range of neurodevelopmental and neurodegenerative phenotypes. Multiple pathogenic missense and stop-gain PRUNE1 variants were identified in its DHH and DHHA2 phosphodiesterase domains. Conversely, a single splice alteration was previously reported. We investigated five patients from two unrelated consanguineous Sudanese families with an inherited severe neurodevelopmental disorder using whole-exome sequencing coupled with homozygosity mapping, segregation, and haplotype analysis. We identified a founder haplotype transmitting a homozygous canonical splice-donor variant (NM_021222.3:c.132+2T > C) in intron 2 of PRUNE1 segregated with the phenotype in all the patients. This splice variant possibly results in an in-frame deletion in the DHH domain or premature truncation of the protein. The phenotypes of the affected individuals showed phenotypic similarities characterized by remarkable pyramidal dysfunction and prominent extrapyramidal features (severe dystonia and bradykinesia). In conclusion, we identified a novel founder variant in PRUNE1 and corroborated abnormal splicing events as a disease mechanism in PRUNE1-related disorders. Given the phenotypes' consistency coupled with the founder effect, canonical and cryptic PRUNE1 splice-site variants should be carefully evaluated in patients presenting with prominent dystonia and pyramidal dysfunction.