Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases.

Developmental and/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early-onset, therapy-resistant seizures and developmental delay. Here we report on 22 individuals from 15 families presenting with a severe form of intractable epilepsy, severe developmental delay, progressive microcephaly, visual disturbance and similar minor dysmorphisms. Whole exome sequencing identified a recurrent, homozygous variant (chr2:64083454A > G) in the essential UDP-glucose pyrophosphorylase (UGP2) gene in all probands. This rare variant results in a tolerable Met12Val missense change of the longer UGP2 protein isoform but causes a disruption of the start codon of the shorter isoform, which is predominant in brain. We show that the absence of the shorter isoform leads to a reduction of functional UGP2 enzyme in neural stem cells, leading to altered glycogen metabolism, upregulated unfolded protein response and premature neuronal differentiation, as modeled during pluripotent stem cell differentiation in vitro. In contrast, the complete lack of all UGP2 isoforms leads to differentiation defects in multiple lineages in human cells. Reduced expression of Ugp2a/Ugp2b in vivo in zebrafish mimics visual disturbance and mutant animals show a behavioral phenotype. Our study identifies a recurrent start codon mutation in UGP2 as a cause of a novel autosomal recessive DEE syndrome. Importantly, it also shows that isoform-specific start-loss mutations causing expression loss of a tissue-relevant isoform of an essential protein can cause a genetic disease, even when an organism-wide protein absence is incompatible with life. We provide additional examples where a similar disease mechanism applies.

A mutation of EPT1 (SELENOI) underlies a new disorder of Kennedy pathway phospholipid biosynthesis.

Mutations in genes involved in lipid metabolism have increasingly been associated with various subtypes of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative motor neuron disorders characterized by spastic paraparesis. Here, we report an unusual autosomal recessive neurodegenerative condition, best classified as a complicated form of hereditary spastic paraplegia, associated with mutation in the ethanolaminephosphotransferase 1 (EPT1) gene (now known as SELENOI), responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine. Phosphatidylethanolamine is a glycerophospholipid that, together with phosphatidylcholine, constitutes more than half of the total phospholipids in eukaryotic cell membranes. We determined that the mutation defined dramatically reduces the enzymatic activity of EPT1, thereby hindering the final step in phosphatidylethanolamine synthesis. Additionally, due to central nervous system inaccessibility we undertook quantification of phosphatidylethanolamine levels and species in patient and control blood samples as an indication of liver phosphatidylethanolamine biosynthesis. Although this revealed alteration to levels of specific phosphatidylethanolamine fatty acyl species in patients, overall phosphatidylethanolamine levels were broadly unaffected indicating that in blood EPT1 inactivity may be compensated for, in part, via alternate biochemical pathways. These studies define the first human disorder arising due to defective CDP-ethanolamine biosynthesis and provide new insight into the role of Kennedy pathway components in human neurological function.

Longitudinal extensive transverse myelitis (LETM) in children: A twenty-year study from Oman.

OBJECTIVE: The data on children with diagnosis of idiopathic transverse myelitis (ITM) was searched to find the pattern of myelitis in Oman. METHODS: A retrospective study was carried out from January1995 to December 2014. Electronic medical records and patient medical files were seen to get the complete data of the children with ITM. This work was carried out at Sultan Qaboos University hospital, Muscat, Oman. The ethical committee of the hospital had approved the study. The diagnosis was based on the established criteria. Other causes of myelopathy were excluded. RESULTS: 19 children with idiopathic transverse myelitis were found. There were 18 out of 19 (94.6%) children with longitudinal extensive transverse myelitis (LETM). CONCLUSION: Longitudinal transverse extensive myelitis is the most common form of ITM in Oman.

A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory and neurodegenerative processes leading to irreversible neurological impairment. Brain atrophy occurs early in the course of the disease at a rate greater than the general population. Brain volume loss (BVL) is associated with disability progression and cognitive impairment in patients with MS; hence its value as a potential target in monitoring and treating MS is discussed. METHODS: A group of MS neurologists and neuro-radiologists reviewed the current literature on brain atrophy and discussed the challenges in assessing and implementing brain atrophy measurements in clinical practice. The panel used a voting system to reach a consensus and the votes were counted for the proposed set of questions for cognitive and brain atrophy assessments. RESULTS: The panel of experts was able to identify recent studies, which demonstrated the correlation between BVL and future worsening of disability and cognition. The current evidence revealed that reduction of BVL could be achieved with different disease-modifying therapies (DMTs). BVL provided a better treatment and monitoring strategy when it is combined to the composite measures of "no evidence of disease activity" (NEDA). The panel recommended a set of cognitive assessment tools and MRI methods and software applications that may help in capturing and measuring the underlying MS pathology with high degree of specificity. CONCLUSION: BVL was considered to be a useful measurement to longitudinally assess disease progression and cognitive function in patients with MS. Brain atrophy measurement was recommended to be incorporated into the concept of NEDA. Consequently, a consensus recommendation was reached in anticipation for implementation of the use of cognitive assessment and brain atrophy measurements on a regional level.

Evolution of epileptic encephalopathy in an infant with non-accidental head injury.

A 5-month-old child, previously healthy, was hospitalized with frequent episodes of tonic seizures. The seizures were controlled with antiepileptic medication. However, the parents did not continue medications after discharge from the hospital. The child was admitted several times with breakthrough seizures. Over time the seizures became refractory to treatment. Neurometabolic work up and imaging studies for uncontrolled seizures revealed non-accidental head injury (shaken baby syndrome) as the underlying cause. His first EEG was normal and changed from normal to an epileptic encephalopathy pattern during his several admissions for uncontrolled seizures. From a normal child at the first admission, the child was severely regressed at the last admission. The present paper highlights the evolution of EEG changes in a child with non-accidental head injuries. This report also highlights considering non-accidental head injury as the underlying cause in younger children presenting with unexplained epileptic encephalopathy.

Identification of Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections Among Healthcare Workers at Sultan Qaboos University Hospital, Oman.

Objectives: This study aimed to describe the incidence and features of asymptomatic COVID-19 infections among healthcare workers (HCWs) at a tertiary hospital in Oman. Methods: This cross-sectional study was conducted between August 2020 and February 2021 among HCWs with no history of COVID-19 infection. An online questionnaire collected sociodemographic and clinical data. COVID-19 infection was diagnosed using nasopharyngeal/throat swabs, which were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Analyses were performed using the Chi-squared test, Fisher's exact test or univariate ordinary least squares regression, as appropriate. Results: A total of 583 HCWs participated in the study, most of whom were female (56.6%), and the mean age was 35 ± 8 years. Only 9.6% (95% confidence interval [CI]: 7.3-12.3%) of the HCWs were at high exposure risk as they were directly involved in the care of COVID-19-infected patients. Overall, 4.1% (95% CI: 2.7-6.1%) of the HCWs screened positive for SARS-CoV-2, of which 20.8% developed symptoms within two weeks. The frequency of SARS-CoV-2 positivity among HCWs working in high-, intermediate-, low- and miscellaneous-risk areas was 1.8% (95% CI: <0.1-9.6%), 2.6% (95% CI: <0.1-6.5%), 5.3% (95% CI: 0.3-9.3%) and 4.8% (95% CI: <0.1-69.3%), respectively. Working in high-risk areas was associated with increased compliance with various infection control strategies (P <0.001). Conclusion: There was a greater frequency of SARS-CoV-2 positivity among HCWs working in low-risk areas, whereas HCWs who worked in high-risk areas were significantly more likely to report increased compliance with infection control strategies.

Spontaneous Near Fatal Hemorrhage into Neurofibromatosis Type 1 Lesion in the Scalp.

Neurofibromatosis type 1 (NF1) (von Recklinghausen's disease) is an autosomal dominant disorder characterized by café-au-lait spots, pigmented hamartomas of the iris, and multiple neurofibromas. Patients can present with hemorrhage secondary to trauma or rarely with spontaneous hemorrhage, both of which can be lethal and life-threatening. We report a 14-year-old girl with a rapidly expanding hematoma in a rare presentation of spontaneous bleed into the NF1 lesion in her scalp. Soon after presentation, she went into hemorrhagic shock. Emergency coiling of the left maxillary artery and branches successfully arrested the bleeding, while resuscitation reversed the hemorrhagic shock.

Necrotizing vacuolar myopathy presenting with recurrent myoglobinuria.

Myoglobinuria occurs in a variety of systemic and neurological disorders and can pose diagnostic challenges. We report on a 23-year-old man in whom recurrent myoglobinuria was observed due to necrotizing vacuolar myopathy confirmed on muscle biopsy. Histopathologically the intramuscular vacuoles lacked the typical findings reported in vacuolar myopathy due to disorders of glycogen and lipid metabolism. We discuss the management approach to recurrent myoglobinuria. Recurrent myoglobinuria in the absence of toxin or drug exposure and seizure is more often due to primary muscle disease. Recognizing the presence of myoglobinuria and the proximate cause is essential in preventing the development of renal dysfunction and the future recurrence of symptoms.

"Virtual Interdisciplinary COVID-19 Team": A Hospital Pandemic Preparedness Approach.

The COVID-19 pandemic continues to move at record speed. Health systems and hospitals worldwide face unprecedented challenges to effectively prepare and respond to this extraordinary health crisis and anticipated surge. Hospitals should confront these unparalleled challenges with a comprehensive, multidisciplinary, coordinated, and organized strategy. We report our experience with the systematic application of the "4S" principle to guide our institutional preparedness plan for COVID-19. We used an innovative "virtual interdisciplinary COVID-19 team" approach to consolidate our hospital readiness.

Dissecting Aneurysm of the Internal Carotid Artery as a Complication of Facial Bone Trauma.

The involvement of the internal carotid artery in dissecting aneurysm is rarely reported in the literature and may occur as a complication of trauma, surgery, and other medical conditions. We report a case of a 22-year-old male who was involved in a motor vehicle accident with associated multiple orthopedic and maxillofacial fractures. During surgical management, the patient was incidentally diagnosed with a dissecting aneurysm involving the right internal carotid artery.

Maxillary Artery Pseudoaneurysm as a Complication of Maxillofacial Injuries: Report of three cases and literature review.

Traumatic maxillary artery pseudoaneurysm is an uncommonly reported complication in the field of oral and maxillofacial surgery. It is usually discovered incidentally, either early after trauma or weeks-to-months later. Quick recognition and prompt management are essential to avoid devastating consequences. In this paper, we report three uncommon cases of maxillary artery pseudoaneurysm recognised during the surgical management of maxillofacial injuries in Muscat, Oman. All cases presented as sudden brisk bleeding during the intraoperative surgical repair and were subsequently diagnosed and successfully managed by endovascular embolisation with platinum coils. This case report highlights the clinical presentation, diagnosis and management of maxillary artery pseudoaneurysm, in addition to a brief review of the literature.

State-of-the-art imaging of acute stroke.

Stroke is a leading cause of mortality and morbidity in the developed world. The goals of an imaging evaluation for acute stroke are to establish a diagnosis as early as possible and to obtain accurate information about the intracranial vasculature and brain perfusion for guidance in selecting the appropriate therapy. A comprehensive evaluation may be performed with a combination of computed tomography (CT) or magnetic resonance (MR) imaging techniques. Unenhanced CT can be performed quickly, can help identify early signs of stroke, and can help rule out hemorrhage. CT angiography and CT perfusion imaging, respectively, can depict intravascular thrombi and salvageable tissue indicated by a penumbra. These examinations are easy to perform on most helical CT scanners and are increasingly used in stroke imaging protocols to decide whether intervention is necessary. While acute infarcts may be seen early on conventional MR images, diffusion-weighted MR imaging is more sensitive for detection of hyperacute ischemia. Gradient-echo MR sequences can be helpful for detecting a hemorrhage. The status of neck and intracranial vessels can be evaluated with MR angiography, and a mismatch between findings on diffusion and perfusion MR images may be used to predict the presence of a penumbra. The information obtained by combining various imaging techniques may help differentiate patients who do not need intravenous or intraarterial therapy from those who do, and may alter clinical outcomes.

Relapse of Multiple Myeloma Presenting as Lower Lip Numbness.

Multiple myeloma (MM) is an uncommon malignancy characterised by the proliferation of clonal plasma cells. There are few published reports describing the extramedullary presentation of MM manifesting primarily in the head and neck region. In addition, the occurrence of an isolated relapse of MM in these sites is exceedingly rare. We report a 56-year-old female who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2010 with sudden-onset numbness of the lower lip. She had a history of MM in remission following chemotherapy and a bone marrow transplant. Clinical and radiographic examinations were indicative of a possible relapse of MM, which was subsequently confirmed by bone marrow aspiration and histopathological evaluation. This unique case highlights the unusual site of relapse of a haematolymphoid malignancy.

Spontaneous Arachnoid Cyst Rupture with Subdural Hygroma in a Child.

Arachnoid cyst of the brain is common in children but its association with spontaneous subdural hygroma is rare. A case of a nine-year-old boy, without any preceding history of trauma, is presented here who came to the emergency department of a tertiary care hospital with complaints of headache, nausea, and vomiting for the last two weeks but more for the last two days. Examination showed a young, fully conscious oriented boy with positive Cushing's reflex and papilledema of left eye. MRI (magnetic resonance imaging) of the brain showed left temporal extra-axial cystic lesion of 5.40 × 4.10 cm in size, representing arachnoid cyst, with bilateral frontoparietal subdural hygromas. Cyst was partially drained through left temporal craniectomy and subdural hygromas were drained through bilateral frontal burr holes. Postoperatively the child recovered uneventfully and was discharged on the seventh postoperative day. Histopathology proves it to be arachnoid cyst of the brain with subdural CSF (cerebrospinal fluid) collection or hygroma.

Cognitive profiles in patients with multi-infarct dementia: an omani study.

BACKGROUND: Studies on neurocognitive impairment among patients presenting with multi-infarct dementia (MID) have received little attention from non-Western societies, and the Arab world is no exception. To our knowledge, this is the first study to characterize neurocognitive, affective and vegetative functioning in patients with MID in Oman. METHODS: In this study, we recruited 20 Omani patients presenting with MID and age- and gender-matched controls at the outpatient clinic of the Department of Behavioral Medicine, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman. In addition to the collection of clinical and demographic information, various cognitive batteries were administered to the consenting participants, including those indexing nonverbal reasoning abilities, working memory (attention, concentration and recall) and executive functioning. Questionnaires that elicit the affective range and the quality of sleep were also administered. RESULTS: Compared with the matched healthy subjects, the patients diagnosed with MID significantly differed in the presently operationalized indices of visuospatial function, semantic memory and affective and vegetative functioning. In contrast, episodic memory and some attentional capacities were not significantly different compared with the control subjects. CONCLUSIONS: The present study was explorative and clinically designed to describe neurocognitive functioning in patients with MID seeking consultation at a tertiary care center in Oman. Our data are necessary for planning and setting up community services and health care programs for demented patients in a society where dementia is a growing silent epidemic.

Varicella zoster virus pneumonitis and brainstem encephalitis without skin rash in an immunocompetent adult.

Varicella zoster virus (VZV) pneumonitis and brainstem encephalitis developed in an immunocompetent adult without rash. Chest computed tomography exhibited nodularity; lung biopsy revealed multinucleated giant cells, Cowdry A inclusions, VZV antigen, and DNA. Varicella zoster virus central nervous system disease was verified by cerebrospinal fluid (CSF) anti-VZV IgG antibody with reduced serum/CSF ratios.

Bilateral Ocular Ischaemic Syndrome-Rare Complication of Rhinocerebral Mucormycosis in an Omani Patient: Case report and literature review.

Ocular ischaemic syndrome (OIS) is a relatively uncommon condition. Simultaneous bilateral involvement is even less common and has been reported in only 22% of all cases of OIS. It has variable clinical presentations, of which visual loss and ocular pain are the most common. It is believed to occur when there is a 90% or greater carotid artery obstruction. This syndrome is often associated with a number of systemic diseases including diabetes mellitus, hypertension, coronary artery disease, and cerebrovascular disease. Only occasionally has it been described as a complication of rhinocerebral mucormycosis. We report an unusual case of bilateral OIS secondary to bilateral internal carotid artery thrombosis as a complication of invasive rhinocerebral mucormycosis. In addition, a review of clinical presentation, diagnostic work-up and treatment options for OIS is provided.

Clinical Spectrum of Hereditary Spastic Paraplegia in Children: A study of 74 cases.

OBJECTIVES: The aim of the study was to explore the spectrum of hereditary spastic paraplegia (HSP) in children in Oman. METHODS: This retrospective study was carried out between January 1994 and August 2011 on children with delayed development, gait disorders and motor handicaps, with signs of symmetrical pyramidal tract involvement. A detailed perinatal and family history, including the age of onset of symptoms, was recorded. The children were labelled as having either the pure or complicated form of HSP based on the established diagnostic criteria. In families with more than one affected child, parents and all other siblings were also examined. RESULTS: Within the study, 74 children from 31 families were diagnosed with HSP. Parental consanguinity was seen in 91% of cases, with 44 children (59.4%) experiencing onset of the disease under one year of age. Complicated HSP was the most common type, seen in 81.1%. Speech involvement, mental retardation, and epilepsy were the most common associated abnormalities. Nonspecific white matter changes and corpus callosum abnormalities were noted in 24.3% of cases on magnetic resonance imaging. CONCLUSION: The study described clinical features of 74 children with HSP. Autosomal recessive complicated HSP was seen in 81.1% of cases.

Septo-optic dysplasia complex: Clinical and radiological manifestations in Omani children.

BACKGROUND: Septo-optic dysplasia (SOD), also known as de-Morsier's syndrome, is a rare disorder characterized by any combination of optic nerve hypoplasia (ONH), pituitary gland hypoplasia, and midline abnormalities of the brain including absence of septum pellucidum and corpus callosum dysgenesis. It is typically diagnosed in infancy and has a variable presentation that includes visual, neurologic, and/or hypothalamic-pituitary endocrine deficits. PURPOSE: To demonstrate the ophthalmic, endocrine, and neurologic spectrum of SOD in five Omani children and address the crucial role of high-resolution neuroimaging for its early and accurate diagnosis. MATERIALS AND METHODS: A retrospective chart review was performed in 2010 of all children in the pediatric ophthalmology database of Sultan Qaboos University Hospital (SQUH) who were diagnosed to have ONH. All relevantdemographic, ophthalmic, neurologic, endocrine, and neuro-radiological manifestations were recorded in a data collection form. All previous neuroimaging results were reviewed by a neuro-radiologist. RESULTS: Five patients (four males, one female) with the diagnosis of ONH were included in the study. They presented during the period 1998-2008. All patients were born at term, with normal birth weights to healthy mothers with insignificant antenatal history. Age at presentation ranged from three months to one year. Manifestations at presentation included severe visual impairment (5/5), neonatal hypoglycemia (3/5), seizure disorder (2/5), and failure to thrive (4/5). ONH was bilateral in 3/5 patients and unilateral in (2/5). Brain and orbit imaging revealed varying anomalies in all patients. These included absent septum pellucidum (3/5), severe corpus callosum agenesis (1/5), ectopic pituitary (5/5), falx cerebri deficiency (1/5), optic nerve hypoplasia (5/5), optic chiasmal hypoplasia (5/5), and olfactory tract hypoplasia (1/5). Endocrine deficits were detected in 4/5 patients (3 with panhypopituitarism, and 1 with growth hormone deficiency) and necessitated replacement therapy. CONCLUSION: SOD is a clinically heterogeneous disorder with a wide spectrum of ophthalmic, endocrine, and neurologic manifestations. All features might not be present in a single patient. A high consanguinity rate and lack of history of alcohol and drug use were observed in our cohort. Most affected children present first to the pediatrician with failure to thrive. Radiological confirmation of ONH necessitates high-resolution imaging and interpretation by an experienced neuro-radiologist. In our cohort, all patients with ONH had associated optic chiasmal hypoplasia. Early detection and treatment reduces disease-related morbidity, and can be life saving.