Meningoencephalitis in a novel mutation in MNGIE (mitochondrial neurogastrointestinal encephalomyopathy) ending a familial diagnostic odyssey: A case series report.

MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) is an ultra-rare autosomal recessive disorder that leads to mutations in the nuclear genes encoding thymidine phosphorylase. Symptoms include gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia, sensorimotor neuropathy and asymptomatic leukoencephalopathy. We describe the first case of MNGIE with meningoencephalitis that ultimately led to a familial diagnosis ending a diagnostic odyssey. We retrospectively reviewed the electronic medical records and sent whole exome sequencing for the index case and his family members. We report the variant c.877T>C p.(Cys293Arg) found in TYMP gene in all affected siblings showed typical clinical manifestations related to MNGIE. To the best of our knowledge, this is not described in the literature nor in the population databases dbSNP (Single Nucleotide Polymorphism Database) and gnomAD (Genome Aggregation Database). Additionally, it is located in a highly conserved residue and the bioinformatic analysis suggests it is most probably deleterious. Moreover, we estimated 550 number of cases of MNGIE (including 5 cases in this study) after performing an extensive search in the literature across 3 databases from 1983-2023. In addition, we identified 44 patients with MNGIE-like phenotype in genes other than TYMP. MNGIE-like phenotype affects POLG1, RRM2B, LIG3, RRM1, MTTV1, and MT-RNR1 genes.

A rare neurological presentation unravels a family's medical mystery after years of no diagnosis: MNGIE is a rare disease caused by changes in a gene that cause deficiency in an enzyme called thymidine phosphorylase. Patients complain of significant weight loss, tingling and numbness in their extremities, muscle weakness, digestive issues and drooping eyelids. We encountered a patient with symptoms and signs of inflammation of the brain and it's protective lining. However, laboratory tests were inconclusive whilst his condition kept deteriorating. A genetic analysis revealed a new mutation not described in the literature before. This has also helped to diagnose the entire family after years of not receiving an answer regarding their symptoms. We also found 550 cases of MNGIE published in the scientific literature from 1983 to 2023. This case highlights the importance of taking a family's entire family history and genetic testing to solve complex medical cases.

Things are not what they seem neurologically and radiologically: An apt descriptor for spinal dural arteriovenous fistula (SDAVF).

Spinal dural arteriovenous fistulas (SDAVF) are the most common vascular malformations affecting the spinal cord. It is infrequently encountered in clinical practice and is believed to be acquired, predominantly affecting middle-aged and elderly men with unknown etiology. It is usually misdiagnosed despite presenting with conventional clinical findings and radiological features. Insidious onset of myelopathic findings is seen in addition to pathognomonic findings of cord edema and intrathecal flow voids on MRI. We present a case of SDAVF that was missed by the treating orthopedic surgeon and underwent spinal decompression with subsequent persistence of myelopathic symptoms. Angiography is required to confirm the diagnosis location of the fistula. Treatment is with embolization using liquid embolic agents or surgical through ligation of the draining vein. Endovascular techniques are minimally invasive, safe, and effective. Knowledge of the characteristics and advantages/disadvantages of each agent helps in planning and appropriate selection of agents for the patient. We report successful embolization with improved clinical outcomes for the patient using precipitating hydrophobic injectable liquid (PHIL) embolic agent. The outcome and prognosis of SDAVF depend on the duration of symptoms, severity of neurological symptoms, and successful occlusion of the fistulous draining vein. Awareness of this rare condition amongst clinicians and radiologists, would enable an earlier diagnosis and avoid morbid outcomes of this treatable condition.

Predictors of Vascular Cognitive Impairment Poststroke in a Middle Eastern (Bahrain) Cohort: A Proposed Case-Control Comparison.

BACKGROUND: Poststroke dementia and cognitive impairment are associated with poor long-term outcomes after stroke. The contribution of genetic factors such as the presence of apolipoprotein (ApoE) ɛ4 allele and its association with cognitive impairment poststroke remains inconclusive, particularly in Middle Eastern regions. OBJECTIVE: The aim of this study is to examine all correlates and potential predictors of cognitive impairment including self-awareness and regulation deficits in stroke patients and compare these functions with healthy older adults from a Middle Eastern population. METHODS: A prospective stroke sample of 200 patients (case group) and 100 healthy aging individuals (control group) will be recruited from the largest medical complex in Bahrain. A neuropsychological battery of cognitive assessments (global, executive, and metacognition) will be conducted on all participants. Participants will be categorized into 4 subgroups (nonvascular cognitive impairment, vascular cognitive impairment with no dementia, vascular dementia, and mixed dementia) using standardized cognitive assessment scores and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, dementia criteria. Biomarkers will include ApoE genotype, soluble form of receptor for advanced glycation end products, neprilysin, beta-secretase 1, biochemistry, and hematology measurements. RESULTS: The primary study outcome is to determine early risk factors for cognitive impairment after stroke in a Bahraini cohort. The study has received full ethical approval from the Bahrain Ministry of Health and from the affiliated university. CONCLUSIONS: With increasing stroke incidence rates in the Middle East, this research study will provide useful biological and epidemiological data for future development and planning of health policies and guidelines for stroke care within the Gulf region.

Metacognitive function poststroke: a review of definition and assessment.

Metacognition is the conscious knowledge individuals have about their own cognitive capacities and the regulation of these activities through self-monitoring. The aim of this review was to identify the definitions and assessment tools used to examine metacognition in relation to stroke studies. A computer database search was conducted using MEDLINE, CINAHL, PsycINFO, Cochrane Reviews, Scopus and Web of Science. A total of 1412 publications were retrieved from the initial database search. Following the removal of unrelated articles, 34 articles remained eligible. 5 studies examined metacognition in relation to cognitive and/or emotional functioning, 4 examined the concept in relation to memory, while others investigated its relationship to driving, employment or restrictions in daily living. 12 studies examined metacognitive function exclusively in stroke. Only 1 study examined metacognition in the acute phase of stroke. 7 studies adhered to the standard definition of metacognition in line with the neuropsychological literature. The main assessment tools utilised included the Self-Regulation and Skills Interview (SRSI), the Self-Awareness of Deficits Interview (SADI), the Awareness Questionnaire (AQ) and the Patient Competency Rating Scale (PCRS). Assessment of metacognition has tended to focus on traumatic and other acquired brain injury in comparison to stroke. The majority of the studies that examined metacognition in stroke did not assess patients in the acute phase. The heterogeneity of assessment tools was in keeping with the variation in the definition of metacognition. The emergence of a standard metacognitive assessment tool may have important implications for future rehabilitative programmes.

Impact of VEGFA -583C > T polymorphism on serum VEGF levels and the susceptibility to acute chest syndrome in pediatric patients with sickle cell disease.

We investigated the association of VEGFA -583C > T on VEGF serum levels and acute chest syndrome (ACS) in 351 pediatric patients with sickle cell disease (SCD), of whom 90 had ACS, and 261 were ACS-free controls. Significant differences in -583C > T minor allele and genotype frequencies were seen between ACS cases and controls, evidenced by enrichment of -583T/T genotypes in patients with ACS, which were linked with reduction in VEGF serum levels. VEGFA -583C > T and reduced VEGF serum levels may influence ACS risk in patients with SCD, which will aid in identifying patients with SCD who are at high risk of ACS.