Central Nervous System Abnormalities Research Articles

Application of Whole-Exome Sequencing in the Prenatal Diagnosis of Foetuses With Central Nervous System Abnormalities.

To investigate the clinical value of whole-exome sequencing (WES) in the diagnosis of foetuses with central nervous system (CNS) abnormalities but having a normal karyotyping and chromosomal microarray result. During the period of 2016-2022, there were a total of 149 foetuses with CNS abnormalities but having negative karyotyping and chromosomal microarray analysis results; WES was performed on these foetuses and their parents. Variants were classified according to ACMG guidelines, and the association of pathogenic variants with specific types of CNS abnormalities was explored. Among these 149 foetuses, three categories of abnormalities, namely, single CNS abnormality, multiple CNS abnormalities, CNS abnormalities along with other organ system abnormalities were identified, for which the detection rate of P/LP variants is 17.4% (12/69), 28.6% (14/49) and 54.8% (17/31), respectively. WES brought about an increase of 28.9% in diagnostic yield in the prenatal evaluation of foetuses with CNS abnormalities but having negative karyotyping and chromosome array results. WES may also be of benefit for the diagnosis of foetuses with isolated CNS abnormalities, as well as for making more informed interpretations of imaging findings and for providing better genetic counselling.

Heteroduplex oligonucleotide technology boosts oligonucleotide splice switching activity of morpholino oligomers in a Duchenne muscular dystrophy mouse model

The approval of splice-switching oligonucleotides with phosphorodiamidate morpholino oligomers (PMOs) for treating Duchenne muscular dystrophy (DMD) has advanced the field of oligonucleotide therapy. Despite this progress, PMOs encounter challenges such as poor tissue uptake, particularly in the heart, diaphragm, and central nervous system (CNS), thereby affecting patient’s prognosis and quality of life. To address these limitations, we have developed a PMOs-based heteroduplex oligonucleotide (HDO) technology. This innovation involves a lipid-ligand-conjugated complementary strand hybridized with PMOs, significantly enhancing delivery to key tissues in mdx mice, normalizing motor functions, muscle pathology, and serum creatine kinase by restoring internal deleted dystrophin expression. Additionally, PMOs-based HDOs normalized cardiac and CNS abnormalities without adverse effects. Our technology increases serum albumin binding to PMOs and improves blood retention and cellular uptake. Here we show that PMOs-based HDOs address the limitations in oligonucleotide therapy for DMD and offer a promising approach for diseases amenable to exon-skipping therapy.

Clinical and prognostic significance of neurosonography of lateral ventricles for infants treated with therapeutic hypothermia during the early neonatal period

Background. Currently, therapeutic hypothermia (TH) is the only approved method for treating hypoxic-ischemic encephalopathy (HIE) that helps improve outcomes. However, it also has significant drawbacks, including the necessity for expensive equipment and treatment technologies, poorly understood pathophysiological mechanisms, and, most importantly, not always well-understood long-term results. Numerous scientific studies report the potential benefits of TH, but the actual risk/benefit ratio is still unknown. The results of long-term follow-up of children who underwent TH and did not have serious neuromotor or intellectual disorders are variable. It is believed that the correlation between neonatal neuroimaging and the degree of nervous system impairment remains poorly defined. Chronic brain injuries diagnosed after the neonatal period, such as parenchymal volume loss, appear to be more prognostically significant, which may be reflected by moderate enlargement of the ventricular system of the brain. The method for determining the size of the ventricular system using ultrasound can be accessible for infants of the first year of life who had HIE but do not have direct indications for magne­tic resonance imaging. Therefore, this study aimed to explore the characteristics of the cerebral ventricular system in infants of the first year of life who suffered severe asphyxia at birth, depen­ding on the method of post-resuscitation care (with or without TH). Materials and ­methods. The study examined the results of neurosonographic examinations of 309 infants during their first year of life. Inclusion criteria were gestational age at birth ≥ 36 weeks and birth weight ≥ 2000 g, manifestations of HIE in the early neonatal period without adverse short-term outcomes (at the time of discharge from the neonatal hospital, the children showed no signs of destructive hypoxic-ischemic lesions of the central nervous system (CNS), seizures, or pathological muscle tone, and had full oral feeding). Exclusion criteria were diagnosed congenital CNS abnormalities, neuroinfections, psychomotor development delay of more than 3 months during the first years of life, progressive obstructive ventriculomegaly or ventriculomegaly associated with non-atrophic subarachnomegaly. The children were divided into three groups: hypothermia group — 19 infants who underwent TH after birth; normothermia group — 14 children who conditio­nally had indications for TH but did not undergo it; comparison group — 276 children in their first year of life who did not require TH (Apgar score > 5 at 10 minutes of life, manifestations of mild or moderate HIE (according to the Sarnat scale) during the first days of life). Neurosonographic examinations were conducted at the age of 2–7 months (mean of 2.12 ± 0.07 months). The sizes of the lateral ventricles were assessed in comparison with the results from the control group of infants of the same age (34 healthy children with no recorded factors of complicated perinatal period, no signs of neurological dysfunction during the neonatal period, and the seven-month observation). Enlargement of the lateral ventricles was recorded when the size of the anterior horn or body of the ventricle in the parasagittal projection exceeded the 95th percentile of the corresponding measurements from the control group. Results. Enlargement of the lateral ventricles during the neurosonographic examination was detected in 36.8 % of children in the hypothermia group, 14.3 % in the normothermia group, and 8.0 % of children in the comparison group. Significant differences were registered only when comparing the results of the hypothermia group with the comparison group (p < 0.05, Fisher’s exact test). Significant correlations (p < 0.05) were found between the size of the lateral ventricles and clinical signs such as sleep disturbances, decreased muscle tone in the arms, increased tendon reflexes, delayed motor development, increased muscle tone in a pyramidal pattern, and diffuse muscle hypotonia. Conclusions. Thus, infants who had severe asphyxia at birth and underwent TH significantly more often had enlargement of the cerebral ventri­cular system (versus the comparison group). Therefore, although therapeutic hypothermia improves outcomes for the development of the nervous system in children who have moderate and severe hypoxic-ischemic encephalopathy, brain morphology (particularly the state of the ventricular system) may still be altered in infants during the first year of life. And the presence of significant correlations between the size of the lateral ventricles and clinical signs of neurological dysfunction argues for further clinical monitoring of children after therapeutic hypothermia throughout the first years of life and in the absence of short-term adverse outcomes of HIE or significant delays in psychomotor development during the first year of life.

Preoperative neurologic comorbidity and unanticipated early postoperative reintubation: a multicentre cohort study

BackgroundThe risk of respiratory complications is highest in the first 72 h post-surgery. Postoperative respiratory events can exacerbate pre-existing respiratory compromise and lead to reintubation of the trachea, particularly in patients with neurologic disorders. This study examined the association between neurologic comorbidities and unanticipated early postoperative reintubation in children. MethodsThis multicentre, 1:1 propensity score-matched study included 420 096 children who underwent inpatient, elective, noncardiac surgery at National Surgical Quality Improvement Program reporting hospitals in 2012–22. The primary outcome was unanticipated early postoperative reintubation within 72 h after surgery. The secondary outcome was prolonged postoperative mechanical ventilation, defined as ventilator use >72 h. We also evaluated 30-day mortality in patients requiring reintubation. ResultsCerebral palsy was associated with the highest risk of early reintubation (adjusted relative risk [RRadj]: 1.97, 95% confidence interval [CI]: 1.44–2.69; P<0.01), followed by seizure disorders (RRadj: 1.87, 95% CI: 1.50–2.34; P<0.01), neuromuscular disorders (RRadj: 1.76, 95% CI: 1.41–2.19; P<0.01), and structural central nervous system abnormalities (RRadj: 1.35, 95% CI: 1.13–1.61; P<0.01). Unanticipated early postoperative reintubation was associated with an eight-times increased risk of 30-day mortality (adjusted hazard ratio: 8.1, 95% CI: 6.0–11.1; P<0.01). Risk of prolonged postoperative mechanical ventilation was also increased with neurologic comorbidities, particularly seizure disorders (RRadj: 1.73, 95% CI: 1.55–1.93; P<0.01). ConclusionsChildren with neurologic comorbidities have an increased risk of unanticipated early postoperative reintubation and prolonged mechanical ventilation. Given the high mortality risk associated with these outcomes, children with neurologic comorbidities require heightened monitoring and risk assessment.

Central neurodegeneration in Kennedy’s disease accompanies peripheral motor dysfunction

Spinal and bulbar muscular atrophy (SBMA), or Kennedy’s disease (KD), is a rare hereditary neuromuscular disorder demonstrating commonalities with amyotrophic lateral sclerosis (ALS). The current study aimed to define functional and central nervous system abnormalities associated with SBMA pathology, their interaction, and to identify novel clinical markers for quantifying disease activity. 27 study participants (12 SBMA; 8 ALS; 7 Control) were recruited. SBMA patients underwent comprehensive motor and sensory functional assessments, and neurophysiological testing. All participants underwent whole-brain structural and diffusion MRI. SBMA patients demonstrated marked peripheral motor and sensory abnormalities across clinical assessments. Increased abnormalities on neurological examination were significantly associated with increased disease duration in SBMA patients (R2 = 0.85, p < 0.01). Widespread juxtacortical axonal degeneration of corticospinal white matter tracts were detected in SBMA patients (premotor; motor; somatosensory; p < 0.05), relative to controls. Increased axial diffusivity was significantly correlated with total neuropathy score in SBMA patients across left premotor (R2 = 0.59, p < 0.01), motor (R2 = 0.63, p < 0.01), and somatosensory (R2 = 0.61, p < 0.01) tracts. The present series has identified involvement of motor and sensory brain regions in SBMA, associated with disease duration and increasing severity of peripheral neuropathy. Quantification of annualized brain MRI together with Total Neuropathy Score may represent a novel approach for clinical monitoring.

Fetal autopsy: Clinicopathologic correlation in consecutive cases

Background: Fetal and neonatal mortality serves as the most sensitive index of maternal and neonatal care. Congenital malformations remain a common cause of perinatal deaths and account for 10–15% in developing countries. Antenatal anomaly scan has become a standard element of obstetric care and their time for a fetal malformation is about 18 weeks. Fetal autopsy serves as a methodology to confirm the sonogram findings with regard to fetal anomalies. Aims and Objectives: The aim of our present study is to review and evaluate fetal autopsy of stillbirth/fetal losses and to confirm the malformations that were diagnosed by ultrasound. Materials and Methods: A cross-sectional study of a total of 10 cases received during the period of September 2023–October 2023 at the Institute of Obstetrics and Gynaecology. All the cases were spontaneous fetal losses. A standard protocol of autopsy procedure was followed which included external, internal, and histopathological examination. In fetuses with prenatally diagnosed malformations, ultrasound findings were compared with autopsy findings. Results: We analyzed a total of 10 fetuses, which included one chromosomal abnormality, four cardiac anomalies, one multiple anomaly, three central nervous system (CNS) anomalies, and one lethal skeletal dysplasia. The fetal autopsy confirmed the prenatal ultrasound findings in eight cases. Fetuses with CNS abnormality were not appreciated grossly due to early autolysis of the brain in the post-mortem. Conclusion: Prenatal imaging and screening are considered milestone development which detects fetal anomalies. However, the time-tested clinical autopsy which used to be conducted for all hospital deaths to find the cause of death was the norm of yesteryears which threw light on many unidentified causes and many syndromic associations not detected antemortem. Likewise, this case highlights the importance of autopsy correlation with prenatal imaging to highlight the same findings and to detect findings not picked up during imaging.

Virtual reality as a treatment for chronic musculoskeletal pain syndromes

Chronic musculoskeletal pain syndromes, including fibromyalgia, are often resistant to conventional medications and invasive therapies. Central hypersensitization, neurotransmitter dysregulation, and autonomic nervous system abnormalities are key pathomechanisms, frequently resulting in widespread pain and a variety of psychosomatic symptoms. Virtual Reality (VR) applications have demonstrated effectiveness in reducing pain, both during and after interventions, and in chronic conditions such as fibromyalgia and back pain. The proposed mechanisms behind VR's effectiveness include distraction and immersion, coupled with cognitive behavioral therapy, which promote neuroplasticity and alter pain perceptions. Functional MRI studies have shown the impact of VR interventions on specific brain regions. Advances in hardware and software, potentially combined with treatments like biofeedback, could enhance VR's role in managing chronic pain. Currently, VR for musculoskeletal pain syndromes is primarily used within multimodal programs, but it is also available for home use as a standalone health application. Future research should focus on the ‘drug-like’ effects of VR, requiring controlled trials with comparable study populations and appropriate sham interventions.

Factors Associated With Unplanned Readmissions and Prolonged Length of Stay in Patients Undergoing Primary Fusion for Congenital Scoliosis.

Approximately 50% of patients with congenital scoliosis will require surgical treatment to prevent further progression. Outcomes following congenital scoliosis are sparse in the literature. The purpose of this study was to identify independent risk factors associated with unplanned readmission and prolonged length of stay (LOS) in patients undergoing primary surgical treatment for congenital scoliosis. The National Surgical Quality Improvement Database-Pediatric was queried for database years 2016-2018 to identify patients with congenital scoliosis who underwent primary posterior fusion of the spine. Patient demographics, comorbidities, and operative variables, such as the number of levels fused and the American Society of Anesthesiologists (ASA) classificaiton, were collected. Univariate and multivariate analyses of patient factors were performed to test for association with readmission within 30 days and prolonged LOS (>4 days). Eight hundred sixteen patients were identified. The average age was 11.3 ± 4.02 years, and the mean postoperative LOS was 4.64 ± 3.71 days. Forty-three patients (5.40%) were readmitted, and 73 patients (8.96%) had prolonged LOS. Independent risk factors associated with prolonged LOS included chronic lung disease (P < 0.001), presence of a tracheostomy (P < 0.001), structural central nervous system abnormality (P = 0.039), oxygen support (P < 0.001), and number of levels fused (P = 0.008). The factors independently associated with unplanned readmission were fusion to the pelvis (P = 0.004) and LOS >4 days (P = 0.008). Prolonged LOS and readmission are widely being used as quality and performance metrics for hospitals. Congenital scoliosis, which often progresses rapidly resulting in significant deformity, frequently requires surgery at an earlier age than idiopathic and neuromuscular deformity. Nevertheless, 30-day outcomes for surgical intervention have not been thoroughly studied. The present study identifies risk factors for prolonged LOS and readmission, which can facilitate preoperative planning, patient/family counseling, and postoperative care. Congenital scoliosis management poses certain challenges that may be mitigated by understanding the risk factors for adverse outcomes following primary fusion surgery.

Fatal SARS-CoV-2 Infection among Children, Japan, January-September 20221.

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases.

Propagation of distinct CWD prion strains during peripheral and intracerebral challenges of gene-targeted mice

Since prion diseases result from infection and neurodegeneration of the central nervous system (CNS), experimental characterizations of prion strain properties customarily rely on the outcomes of intracerebral challenges. However, natural transmission of certain prions, including those causing chronic wasting disease (CWD) in elk and deer, depends on propagation in peripheral host compartments prior to CNS infection. Using gene-targeted GtE and GtQ mice, which accurately control cellular elk or deer PrP expression, we assessed the impact that peripheral or intracerebral exposures play on CWD prion strain propagation and resulting CNS abnormalities. Whereas oral and intraperitoneal transmissions produced identical neuropathological outcomes in GtE and GtQ mice and preserved the naturally convergent conformations of elk and deer CWD prions, intracerebral transmissions generated CNS prion strains with divergent biochemical properties in GtE and GtQ mice that were changed compared to their native counterparts. While CWD replication kinetics remained constant during iterative peripheral transmissions and brain titers reflected those found in native hosts, serial intracerebral transmissions produced 10-fold higher prion titers and accelerated incubation times. Our demonstration that peripherally and intracerebrally challenged Gt mice develop dissimilar CNS diseases which result from the propagation of distinct CWD prion strains points to the involvement of tissue-specific cofactors during strain selection in different host compartments. Since peripheral transmissions preserved the natural features of elk and deer prions, whereas intracerebral propagation produced divergent strains, our findings illustrate the importance of experimental characterizations using hosts that not only abrogate species barriers but also accurately recapitulate natural transmission routes of native strains.

Early Cranioplasty in an Apert's Syndrome Infant With Occipital Encephalocele.

Apert's syndrome (AS) is a rare congenital malformation characterized by distinctive clinical manifestations such as syndactyly of the extremities and midface retrusion, which set it apart from other syndromes. This condition often presents with craniosynostosis and, less commonly, central nervous system abnormalities like encephalocele. In this report, we present a typical case of Apert syndrome with an occipital encephalocele. The infant had plagio-brachycephaly due to craniosynostosis and required urgent repair of the occipital encephalocele. At 1 month of age, we performed both the encephalocele repair and early cranioplasty for autologous bone grafting. This case underscores the importance of early diagnosis and surgical interventions in Apert's syndrome cases with encephalocele.

Perinatal management for fetal oral epignathus with duplication of the pituitary gland (DPG)-plus syndrome: A case report and literature review.

The prenatal diagnosis of epignathus presents a unique challenge for physicians. Differential diagnosis is usually based on the anatomic location of the tumor. Typical prenatal ultrasound characteristics of epignathus include a mixed solid and cystic lesion with vascularity in the solid component, originating from the hard or soft palate, and it is often associated with other anomalies such as craniofacial clefts or trans-sphenoidal intracranial extension. Herein, we present a case of prenatal diagnosis of epignathus with rare ultrasonographic findings, prenatal management requiring collaborative efforts of a multidisciplinary team, and a well-planned innovative ex utero intrapartum treatment procedure. In addition, this report highlights the evolving postnatal diagnosis of the rare developmental anomaly, duplication of the pituitary gland-plus syndrome, which includes various midline craniofacial, central nervous system, spinal, and endocrine abnormalities.

Regional anesthesia in a patient with primary ciliary dyskinesia: A case report

BACKGROUND Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases, otolaryngological diseases, central nervous system abnormalities, reproductive system abnormalities, and cardiac function abnormalities. General anesthesia in these patients is associated with a higher incidence of respiratory complications than in patients without the disease. CASE SUMMARY A 16-year-old male patient was referred to the emergency room complaining of right ankle pain due to distal tibiofibular fracture. Three years prior, he had been diagnosed with PCD. At that time, he had experienced several episodes of pneumonia, sinusitis, and chronic middle ear infections, for which he underwent surgical interventions. At the current admission, he presented with cough and sputum but no other respiratory symptoms. A chest computed tomography scan revealed centrilobular ground-glass opacities in both lower lobes and a calcified nodule in the left lower lobe. For the surgical procedure and postoperative pain management, combined spinal-epidural anesthesia was employed. The patient’s postoperative pain score was measured by the numerical rating scale (NRS). On the day of surgery, his NRS was 5 points. By the second postoperative day, the NRS score had decreased to 2–3 points. The epidural catheter was removed on the fourth day following the operation. The patient was subsequently discharged no respiratory complications. CONCLUSION We performed combined spinal-epidural anesthesia in a patient with PCD. The patient experienced no additional respiratory complications and was discharged with a low NRS score for pain.

Protective effect of cholecalciferol against cobalt-induced neurotoxicity in rats: ZO-1/iFABP, ChAT/AchE and antioxidant pathways as potential therapeutic targets.

Cobalt (Co) toxicity has been reported to produce central nervous system and gastrointestinal abnormalities. This study assessed the therapeutic effect of cholecalciferol (Cho) supplementation against damages caused by sub-acute (14-day) cobalt chloride (CoCl2) exposure in the brain and intestines. Thirty-five male Wistar rats were divided equally into five groups: Group I (control) received no treatment; Group II received oral CoCl2 (100 mg/kg) only; Groups III, IV, and V received 1000, 3000 and 6000 IU/kg of cholecalciferol, respectively by oral gavage, and concurrently with CoCl2. Cobalt-treated rats showed neuronal vacuolation and presence of pyknotic nuclei in the cerebral cortex and hippocampus, depletion of Purkinje cells in the cerebellum, as well as inflammation and congestion in the intestinal mucosa. Cobalt also increased brain and intestinal hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations, while simultaneously reducing glutathione (GSH) content, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities. Further, CoCl2 induced increases in brain acetylcholinesterase (AchE) activity and serum zonulin (ZO-1) levels. Conversely, Cho administration suppressed CoCl2-induced damages in the brain and intestines by reducing lipid peroxidation and increasing the activities of antioxidant enzymes. Remarkably, Cho produced stimulation of brain choline acetyltransferase (ChAT) and suppression of AchE activity, along with dose-dependent reduction in serum levels of ZO-1, intestinal fatty acid-binding protein (iFABP) and nitric oxide. In conclusion, the protective role of cholecalciferol against cobalt-induced toxicity occurred via modulation of cholinergic, intestinal permeability and antioxidant pathways. The results may prove significant in the context of the role of gut-brain connections in neuroprotection.

E031 Retinal vasculitis with Libman-Sacks endocarditis as presenting features of a systemic lupus erythematosus with antiphospholipid antibody syndrome patient

Abstract Background/Aims Ocular manifestations of systemic lupus erythematosus (SLE) are rarely reported at the time of disease onset. Retinal vasculitis is usually associated with the active generalised disease. We report a case of a 22-year-old lady who was diagnosed with SLE with antiphospholipid antibody syndrome (APS) as the initial presentation of retinal vasculitis and Libman-Sacs endocarditis. Methods A 22-year-old lady with a background history of benign hypermobility spectrum disorder, presented to the eye casualty with a 4-week history of right-sided visual disturbances and was diagnosed with retinal vasculitis associated with uveitis, central retinal vein occlusion with multiple emboli in the retinal artery of the right eye and a single embolus in the left eye. In terms of family history, both father and brother were diagnosed with spondyloarthropathy, and the maternal uncle had Sjogren’s syndrome. She was then referred to the medical team for proper evaluation. On query, she mentioned photosensitive rash on her face getting worse in sunlight, a history of Raynaud’s phenomenon, significant hair loss, and one miscarriage before the 10 weeks of gestation. On examination, mild alopecia and a faint butterfly rash on the face were noted. Cardiac auscultation revealed pansystolic murmur. The rest of the systemic examinations were unremarkable. Results The blood test showed thrombocytopenia (130 u/L), positive antinuclear antibody (1:80, speckled pattern) with anti-double stranded DNA (26 IU/L), low complement (C3-0.74, C4- 0.12), markedly raised anticardiolipin antibody IgG (2016 u/ml), anti beta 2 glycoprotein 1 IgG ( &amp;gt;6100 u/ml) including presence of lupus anticoagulant. Her urinary protein creatinine ratio was 66mg/mmol. 3 sets of blood cultures came back negative. Transthoracic echo showed vegetation on the posterior mitral valve leaflet (0.95x 1.2cm) with moderate mitral regurgitation while transesophageal echo additionally found the possibility of perforation at the junction of leaflets of the mitral valve which was later confirmed by cardiac magnetic resonance imaging (MRI). The head MRI scan did not show any central nervous system abnormality. She was initially treated with 500mg intravenous methylprednisolone for 3 days followed by 20mg oral prednisolone daily with gradual tapering. Hydroxychloroquine and mycophenolate mofetil were added. Her case was discussed in the cardiology multidisciplinary team meeting and an opinion from the cardiothoracic surgery was taken to consider valve replacement in the future. Due to aspirin allergy, only warfarin was considered for APS. She had 2 sessions of pan-retinal photocoagulation as well. In subsequent follow-up, it was noted significant improvements in terms of her symptoms. Conclusion Vaso-occlusive retinopathy is a rare, potentially vision-threatening initial manifestation of SLE, which can be an indicator of active disease. Early identification of patients is necessary for timely intervention and multidisciplinary team involvement is required for comprehensive treatment plans. Disclosure M. Islam: None. S. Quddus: None. M. Hughes: None. R. Kumar: None.

Fetal and neonatal outcomes of posterior fossa anomalies: a retrospective cohort study

The primary aim of this study was to estimate the incidence of posterior fossa anomalies (PFA) and assess the associated outcomes in King Abdulaziz Medical City (KAMC), Riyadh. All fetuses diagnosed by prenatal ultrasound with PFA from 2017 to 2021 in KAMC were analyzed retrospectively. PFA included Dandy–Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC), and isolated vermian hypoplasia (VH). The 65 cases of PFA were 41.5% DWM, 46.2% MCM, 10.8% VH, and 1.5% BPC. The annual incidence rates were 2.48, 2.64, 4.41, 8.75, and 1.71 per 1000 anatomy scans for 2017, 2018, 2019, 2020, and 2021, respectively. Infants with DWM appeared to have a higher proportion of associated central nervous system (CNS) abnormalities (70.4% vs. 39.5%; p-value = 0.014) and seizures than others (45% vs. 17.9%; p-value = 0.041). Ten patients with abnormal genetic testing showed a single gene mutation causing CNS abnormalities, including a pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1, and a variant of uncertain significance in the PNPLA8 gene. Our result showed that the most common PFA is DWM and MCM. The autosomal recessive pathogenic mutation is the major cause of genetic disease in Saudi patients diagnosed with PFA.

Клинические случаи ранней офтальмологической диагностики септо-оптической дисплазии

Identification of a genetic variant of a hereditary disease of the visual organ is necessary not only to determine the features of clinical manifestations and course of the disease, but also to carry out preventive measures to prevent the birth of a sick child. Therefore, the identification of ophthalmopathology requires a mandatory assessment of the condition of the patient's body as a whole. The article presents two clinical cases of ophthalmological diagnosis of septo-optic dysplasia. It is a clinically heterogeneous condition representing a combination of hypoplasia of the optic nerves, pituitary hypoplasia and abnormal formation of structures along the midline of the brain. The diagnosis is established in the presence of two or more signs of the classical triad. Hypoplasia of the optic nerves leads to decreased vision, amblyopia. Violation of the hypothalamic-pituitary system requires hormone replacement therapy. The prognosis of mental development depends on central nervous system abnormalities, if any, mental retardation occurs. The first clinical case: a boy R., 11 months old, was directed by a neurologist due to the presence of a pendulum-like nystagmus, hypoplasia of the optic nerves of both eyes, uneven caliber and convoluted course of retinal vessels were also revealed upon examination. The lag in physical and neuropsychic development drew attention to itself. To clarify the diagnosis, the child was recommended to perform an MRI of the head, which revealed aplasia of the septum pellucidum. Septo-optic dysplasia was diagnosed on the basis of the revealed disorders. The second patient, a girl, 2 days old, was referred to an ophthalmologist by a neurologist, the absence of a septum pellucidum was revealed on the neurosonogram, hypoplasia of the optic nerves and tortuosity of the retinal vessels were found on examination of the fundus. Septo-optic dysplasia was diagnosed. Thanks to the early detection of this severe hereditary pathology, timely maintenance and replacement therapy by a neurologist and endocrinologist, and observation by a geneticist, it is possible not only to prevent complications of the disease itself, but also to prevent the re-birth of a sick child in the family. Keyword: septo-optic dysplasia; hypoplasia of the optic nerves; aplasia of the septum pellucidum

Epidemiological Profile and Management of Central Nervous System (CNS) Malformations in Dera Ghazi Khan

Introduction: Malformation of the central nervous system (CNS) typically leaves the family in chaos and medical team helpless. The strict use of preventative measures has significantly decreased the frequency of congenital abnormalities in industrialized nations. Materials &amp; Methods: At Dera Ghazi Khan Medical College conducted this Cross-sectional analytical study was conducted from January 2023 to December 2023 to evaluate the epidemiological profile and management CNS malformations. All cases of CNS malformations treated in the neurosurgery department were included in the study. The data were analyzed using SPSS version 25.0. Results: Total 61 cases were included in the study. The patient’s age ranged from 1 d to 70 years old. Six (9.8%) patients with CNS abnormalities had prenatal diagnoses. There were 34.8% CT scans, 1.7% MRIs (7 after CT), and 23.7% ultrasound scans, among other tests. In 49 instances (80.32%), there was a surgical rationale: 20 cases (40.81%) could be treated, whereas 29 cases (59.18%) did not. In 11 cases (18%), the surgical rationale was not maintained. Conclusion: CNS abnormalities were frequent in our study. They cause numerous neurological aftereffects and permanent impairments, and are not usually amenable to surgical treatment. Therefore, it is imperative that the DG Khan region concentrates on enhancing preventative measures.

Evaluation of Congenital Cytomegalovirus Infection in Pregnant Women Admitted to a University Hospital in Istanbul.

Cytomegalovirus (CMV) can cause serious complications in immunocompromised individuals and fetuses with congenital infections. These can include neurodevelopmental impairments and congenital abnormalities in newborns. This paper emphasizes the importance of concurrently evaluating ultrasonography findings and laboratory parameters in diagnosing congenital CMV infection. To examine the prenatal characteristics of CMV DNA-positive patients, we assessed serum and amniotic fluid from 141 pregnant women aged 19-45 years, each with fetal anomalies. ELISA and PCR tests, conducted in response to these amniocentesis findings, were performed at an average gestational age of 25 weeks. Serological tests revealed that all 141 women were CMV IgG-positive, and 2 (1.41%) had low-avidity CMV IgG, suggesting a recent infection. CMV DNA was detected in 17 (12.05%) amniotic fluid samples using quantitative PCR. Of these, 82% exhibited central nervous system abnormalities. Given that most infections in pregnant women are undetectable and indicators non-specific, diagnosing primary CMV in pregnant women using clinical findings alone is challenging. We contend that serological tests should not be the sole means of diagnosing congenital CMV infection during pregnancy.

Risk factors associated with congenital central nervous system abnormalities in the National Hospital of Zinder, Niger

IntroductionCongenital malformations of the central nervous system (CNS) are morphological abnormalities of the brain and spinal cord that occur during fetal development. They constitute the second most common congenital disability, after congenital cardiac defects. Many risk factors have been identified; however, these studies included various types of congenital abnormality. Furthermore, there is a lack of information on risk factors for congenital CNS malformation, and notably in the Zinder region of Niger. ObjectiveThis study aimed to identify the risk factors associated with congenital CNS malformations in the Zinder region. MethodsIn a case-control design, patients with congenital CNS malformation were enrolled between June 2022 and April 2023 in the Department of Neurosurgery of the National Hospital of Zinder. ResultsFamily history of malformation (aOR:3.31, 95% CI:1.25−8.78) and consanguine marriage (aOR:2.28, 95% CI:1.23−4.20) were significantly associated with congenital CNS malformation. In contrast, folic acid supplementation (aOR:0.34, 95% CI:0.13, 0.89), multiparity (aOR:0.34, 95% CI:0.13, 0.89), and grand multiparity (aOR, 0.47; 95% CI:0.23, 0.97) had a protective effect. ConclusionRisk factors such as family malformation history and consanguine marriage increased the risk of developing congenital malformations of the central nervous system. In contrast, folic acid supplementation in the index period and multiparity had a significant protective effect.