Compressive Myelopathy Secondary to TRPV4 Skeletal Dysplasia: Spondylometaphyseal Dysplasia, Kozlowski Type.

Transient receptor potential vanilloid 4 channel ( TRPV4 ) gene mutations have been described in skeletal system and peripheral nervous system pathology. The case described here is a 9-year-old male child patient, born to a nonconsanguineous marriage with normal birth history who had difficulty in walking and stiffness of joints for the last 7 years, and progressive weakness of all four limbs and urine incontinence for 1 year following falls. Physical examination showed below-average weight and height and short trunk. Musculoskeletal examination revealed bony prominence bilaterally in the knee joints and contractures in knee and elbow joints with brachydactyly; muscle tone was increased, with brisk deep tendon reflexes. Skeletal survey showed platyspondyly with anterior beaking with metaphyseal dysplasia. Magnetic resonance imaging of the spine revealed atlantoaxial instability with hyperintense signal changes at a cervicomedullary junction and upper cervical cord with thinning and spinal canal stenosis suggestive of compressive myelopathy with platyspondyly and anterior beaking of the spine at cervical, thoracic and lumbar vertebrae. Exome sequencing revealed a heterozygous de novo variant c.2389G > A in exon 15 of TRPV4 , which results in the amino acid substitution p.Glu797Lys in the encoded protein. The characteristics observed indicated spondylometaphyseal dysplasia, Kozlowski type (SMD-K). The child underwent surgical intervention for compressive myelopathy by reduction of atlantoaxial dislocation with C1 lateral mass and C2 pars fusion using rib graft and fixation using screws and rods. To conclude, for any child presenting with progressive kyphoscoliosis, short stature, platyspondyly, and metaphyseal changes, a diagnosis of SMD-K should be considered and the patient and family should be advised to avoid spinal injuries.

The unintended consequences of artificial intelligence in paediatric radiology.

Over the past decade, there has been a dramatic rise in the interest relating to the application of artificial intelligence (AI) in radiology. Originally only 'narrow' AI tasks were possible; however, with increasing availability of data, teamed with ease of access to powerful computer processing capabilities, we are becoming more able to generate complex and nuanced prediction models and elaborate solutions for healthcare. Nevertheless, these AI models are not without their failings, and sometimes the intended use for these solutions may not lead to predictable impacts for patients, society or those working within the healthcare profession. In this article, we provide an overview of the latest opinions regarding AI ethics, bias, limitations, challenges and considerations that we should all contemplate in this exciting and expanding field, with a special attention to how this applies to the unique aspects of a paediatric population. By embracing AI technology and fostering a multidisciplinary approach, it is hoped that we can harness the power AI brings whilst minimising harm and ensuring a beneficial impact on radiology practice.

Biotinidase Deficiency in the Second Decade with Atypical Neuroimaging Findings.

Biotinidase deficiency is a rare autosomal recessive neurometabolic disorder resulting in biotin deficiency. Our patient presented with seizures and developmental delay since infancy and was started on megavitamin supplements. At 14 years, she presented with motor regression with encephalopathy after discontinuation of vitamins. There were no skin and hair changes. Magnetic resonance imaging (MRI) of the brain showed bilateral symmetrical posterior putamen signal changes. Tandem mass spectroscopy showed increased methyl malonyl carnitine and 3-OH isovaleryl carnitine. There was a low biotinidase level, and a pathogenic variant in the BTD gene in the next-generation sequencing was identified. Special importance is placed on the unusual symmetric posterior putamen involvement seen in MRI of the brain.

Mitochondrial Complex I Deficiency Masquerading as Stroke-Like Episode Clinically and as Alexander Disease Radiologically Following Chicken Pox.

Mitochondrial disorders are a group of metabolic disorders with variable presentation and usually affect organs with high energy requirements like the brain, eye, and heart. Seventeen-month-old girl child presented with right hemiparesis and regression of milestones following chicken pox. Investigations showed elevated lactate, white matter signal changes in both periventricular and subcortical white matter with frontal predominance in the MRI of the brain, cardiomyopathy in the echocardiography, with complex I deficiency in respiratory enzyme assay in the muscle biopsy. A homozygous missense variant c.304C>T (p. Arg102Cys) in exon 5 of NDUFS8 gene (chr11:67800682C>T; NM_002496.4) was detected on whole exome sequencing with positive parental Sanger for the same gene. The child was started on a mitochondrial cocktail, ramipril, and frusemide. Mitochondrial complex deficiency should be considered in cases with stroke-like episodes, and predominant white matter involvement on imaging mimicking classical genetic leukodystrophy like Alexander disease.

Recurrent Bilateral Lower Motor Neuron Type of Facial Palsy with Hearing Impairment: Hyperphosphatemic Familial Tumoral Calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg 2 /mL 2 ) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in FGF23 gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.

A Comparative Study on Accuracy of SRK-T And Haigis Formulas in IOL Power Calculation in Axial Myopes Undergoing Cataract Surgery.

Background and Objective: It has been a significant challenge since the advent of intraocular lens to give the best postoperative visual acuity and prevent refractive surprises due to biometry error. Among myopic eyes, it has been a debate among the various formulas introduced and their efficacy to prevent postoperative refractive surprises. Hence, the need for an accurate formula in high myopic eyes is obligatory. Objectives of the Study: To compare the accuracy of SRK-T and Haigis formulas in IOL power calculation in axial myopic eyes undergoing cataract surgery. Methods: A total of 50 cases with axial length >24 mm were taken up for the study and were examined in detail and error between both formulas were assessed. Results: The mean age of the subjects in the study was 53.50 ± 16.12 years; 27 were males, and 23 were females. The majority of patients had PSC + NS II. Seven out of 50 cases had posterior staphyloma. Most of the patients had average K value in the 44-46-D range. AL of most of the patients (66%) was between 24 and 26 mm. The majority of patients had IOL power >15 D, and 82% (41 eyes) were found to have no post-op complications. Four eyes had severe iritis, and five eyes had striate keratopathy. At the follow-up at 6th week postoperatively, 82% were found to have 6/6-6/9 vision on Snellen's chart. Four eyes had 6/12-6/24 post-op vision, mainly attributed to primary PCO. Five eyes (10%) had <6/24 post op vision at the end of 1 week due to the presence of posterior staphyloma. A higher percentage of eyes in the SRK/T group had a mean error >0.5 D. Upon comparing the mean error between the two groups, P was 0.005; hence, the results are statistically very significant, showing that Haigis formula is better than SRK/T formula in achieving target refraction (-1) in myopic eyes undergoing phacoemulsification. Interpretation and Conclusion: Our study shows that Haigis formula was better than SRK/T formula for achieving the target postoperative refraction in high axial myopes.

A Treatable Cause of Myelopathy: Biotinidase Deficiency Presenting as Acute Flaccid Paralysis.

Biotinidase deficiency (BD) is a rare treatable cause of neurometabolic disorders. It is an autosomal recessive disorder that manifests with cutaneous and neurological manifestations. Spinal cord involvement is uncommon with only a few cases reported in the literature. A 6-year-old female child presented with progressive difficulty in walking since 2 months. At 6 months of age, the child was elsewhere evaluated for global developmental delay and suspected as metabolic disorders and started on megavitamins, following which the child was improved. For the past 2 years, she has stopped medicines. On examination, irritable, alopecia, eczema, hypotonia, and power of two-fifths in all four limbs, and exaggerated deep tendon reflexes. The magnetic resonance imaging (MRI) brain and spine showed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities in periaqueductal gray matter, dorsal midbrain, pons, medulla, and cervical cord. She was suspected to have BD and confirmed by low enzyme levels and pathogenic variant in BTD . She was started on biotin supplements that resulted clinically dramatic improvement and MRI became normal within 4 weeks. Any child presenting with acute flaccid paralysis with brainstem and spinal cord noncompressive lesions on MRI, rare treatable conditions like BD should be considered in developing countries, like India, where still no universal newborn screening facilities are available.

Neurological Manifestations of Congenital Cytomegalovirus Infection at a Tertiary Care Centre from Southern India.

Background Cytomegalovirus (CMV) is a ubiquitous herpes virus. It is the most common congenital viral infection. Data on congenital CMV in India are lacking and hence the present study was undertaken. Objectives The aim of the study is to evaluate the clinical and radiological profile of neurological manifestations of congenital CMV infections in tertiary care hospital. Methods This is a retrospective chart review of the clinical and laboratory profile of congenital CMV infections presenting from January 2018 to February 2020 to a tertiary care hospital in Southern India. Details of clinical profile, serological and neuroimaging data were obtained and analyzed. Results A total of 42 cases with female preponderance (57%) were reported during the study period. The mean age of presentation was 2.9 years. Clinical features were developmental delay (81%), microcephaly (93%), seizures (33%), intrauterine growth restriction (19%), neonatal encephalopathy (10%), anemia (9%), jaundice (10%), hepato-splenomegaly (7%), and eye abnormalities (14%). Antenatal maternal fever was reported by 12%. Sensorineural hearing loss was present in 57%. Neuroimaging showed periventricular calcification (79%), cerebral atrophy (69%), ventricular dilatation (55%), malformations (26%), dysmyelination (12%), and temporal lobe cysts (5%). CMV-immunoglobulin-M positivity was seen in 14 cases (33%), urinary polymerase chain reaction for CMV was positive in 21 cases (50%), and clinical diagnosis was done in seven cases (16%). Conclusion Common findings in congenital CMV are microcephaly, developmental delay, seizures, anemia, and sensorineural hearing loss. Common neuroimaging findings are periventricular calcification, cerebral atrophy, malformation, white matter signal changes, and cysts. CMV can mimic like cerebral palsy, malformations of the brain, demyelinating disorders, and calcified leukoencephalopathies like Aicardi-Goutières syndrome.

Evolution and Utility of Preimplantation Genetic Testing for Monogenic Disorders in Assisted Reproduction - A Narrative Review.

Preimplantation genetic testing (PGT) for monogenic disorders and assisted reproductive technology have evolved and progressed in tandem. PGT started with single-cell polymerase chain reaction (PCR) followed by fluorescent in situ hybridisation for a limited number of chromosomes, later called 'preimplantation genetic diagnosis (PGD) version 1'. This review highlights the various molecular genetic techniques that have evolved to detect specific inherited monogenic disorders in the preimplantation embryo. Literature review in English was performed in PubMed from 1990 to 2021, using the term 'preimplantation genetic diagnosis'. With whole-genome amplification, multiple copies of embryonic DNA were created. This helped in avoiding misdiagnosis caused by allele dropout. Multiplex fluorescent PCR analysed informative short tandem repeats (STR) and detected mutations simultaneously on automated capillary electrophoresis sequencers by mini-sequencing. Comparative genomic hybridisation (CGH) and array CGH were used for 24 chromosome aneuploidy screening. Subsequently, aneuploidies were detected by next-generation sequencing using single-nucleotide polymorphism arrays, while STR markers were used for haplotyping. 'PGD version 2' included accurate marker-based diagnosis of most monogenic disorders and detection of aneuploidy of all chromosomes. Human leukocyte antigen matching of embryos has important implications in diagnosis and cure of haemoglobinopathies and immunodeficiencies in children by means of matched related haematopoietic stem cell transplantation from an unaffected 'saviour sibling' obtained by PGT.

In vivo morphometry of menisci of the knee in South Indians: a preliminary study.

BACKGROUND: Since the in vivo morphometric data on the menisci of the knee joint of Indian subjects are scarce, we hereby studied the width and thickness of the menisci using Magnetic Resonance Imaging (MRI) to establish standard dimensions of the normal medial and lateral meniscus as an aid to orthopaedic surgery. METHODS: Eighty menisci from 40 knee joints were analysed in each of three regions, the anterior horn, the mid body and the posterior horn. The thickness and width of the menisci were measured in sagittal and coronal T1-weighted and T2-weighted MRI images and analysed statistically. RESULTS: The mean thickness of medial meniscus at the anterior horn, mid body, and posterior horn were 6.3 ± 1.1 mm, 5.2 ± 1.3 mm, and 6.9 ± 1.1 mm, respectively. The respective values for the lateral meniscus were 4.8 ± 0.7 mm, 6.4 ± 1.1 mm, and 7.0 ± 0.9 mm. The mean width of medial meniscus at the anterior horn, mid body, and posterior horn were 10.5 ± 1.2 mm, 7.8 ± 1 mm and 13.9 ± 0.9 mm, respectively. The widths of lateral meniscus at the same regions were 11.8 ± 1.4 mm, 8.6 ± 1.2 mm, and 12.0 ± 0.9 mm, respectively. The lateral meniscus was significantly wider than medial at the anterior horn and mid body (p = 0.00). In contrast, the posterior horn of medial meniscus was significantly wider than lateral meniscus. Both menisci were significantly wider at their posterior horn, followed by the anterior horn and were significantly narrower at their mid body. CONCLUSION: The present study provides new information on the meniscal thickness and width in South Indians that can be used in planning of orthopaedic and arthroscopic surgeries of the knee joint. However, the study needs to be analyzed with a large sample size for the better interpretation.

Plant latex: a promising antifungal agent for post harvest disease control.

Bioactive compounds from plant latex are potential source of antifungic against post harvest pathogens. Latex from a total of seven plant species was investigated for its phytochemical and antifungal properties. Six fungi namely Aspergillus fumigatus, A. niger, A. terreus, F. solani, P. digitatum and R. arrhizus were isolated from infected fruits and vegetables and tested against various solvent extracts of latex. Analysis of latex extracts with phytochemical tests showed the presence of alkaloids, flavonoids, glycosides, phenols, saponins, steroids, tannins and terpenoids. Antifungal assay revealed the potential inhibitory activity of petroleum ether extracts against the postharvest fungal isolates. Various degree of sensitivity was observed irrespective of plant species studied with A. terreus and P. digitatum as the most susceptible ones. F. solani and A. fumigatus were moderately sensitive to the latex extracts tested. Among the plants, latex of Thevetia peruviana (75.2%) and Artocarpus heterophyllus (64.8%) were having potential antifungal activity against the isolates followed by Manilkara zapota (51.1%). In conclusion, use of plant latex makes interest to control postharvest fungal diseases and is fitting well with the concept of safety for human health and environment.

Radiology and morphology of spotted bone: a case report with review of literature.

Spotted bone disease (osteopoikilosis) is a rare type of osteosclerotic dysplasia usually noticed as an incidental finding during routine radiological investigations. Here we report a case of a male patient who had chronic history of right wrist pain and low backache. His radiographs showed unique morphological features of the bones. The upper end of femora, pelvic bones showed multiple small discrete, round and oval, radiodense lesions which were symmetrical in distribution. The lesions were more obvious at the epiphysis and metaphysis. The case was finally diagnosed to have spotted bone disease. In this report we emphasize on the radiological anatomy of this condition with clinical highlights. The importance of its differential diagnosis is stressed with relevant review of the literature. We believe that this report is enlightening not only for orthopedicians and radiologists, but also for the clinical anatomists and researchers in the field of medicine.

Median frontal sutures - incidence, morphology and their surgical, radiological importance.

AIM: To determine the incidence of metopic suture in Indian human adult skulls and to study their morphology. MATERIAL AND METHODS: The study included 81 human adult dry skulls which were obtained from the neuroanatomy laboratory of our institution. The skulls were macroscopically inspected at the norma frontalis for the presence of the metopic suture and the sutures were morphologically analyzed. The sutures were classified as complete and incomplete types. The incomplete ones included linear type, 'V' shape and double type. RESULTS: From our observations, the metopic suture was present in 52 (64.1%) cases. The complete metopic suture was seen in only 1 skull (1.2%). The majority of the metopics were of incomplete type, 51 (62.9%). Among the incomplete ones, 18 (22.2%) were linear, 17 (21%) were 'V' shaped and 16 were double metopics (19.7%). No metopic sutures were associated with the Wormian bones. CONCLUSION: The morphological knowledge of the metopic suture is important for the radiologists and neurosurgeons in day to day practice. While reading the X-ray / CT and MRI films, the possibility of the metopic suture should be kept in mind. This will prevent confusion and a wrong diagnosis in emergency situations.

Accessory transverse foramina in the cervical spine: incidence, embryological basis, morphology and surgical importance.

AIM: To study the incidence of accessory foramina transversaria in cervical spine and to analyze them morphologically with emphasize on their embryological and surgical importance. MATERIAL AND METHODS: The study included 363 human cervical vertebrae which were procured from the bone collections of the Department of Anatomy. The foramen transversarium was observed macroscopically on both sides of all the vertebras, the accessory foramina were noted. RESULTS: Out of 363 specimens, only 6 (1.6%) vertebrae showed the accessory foramina. Among them 5 (1.4%) vertebra had double foramina and only 1 (0.3%) vertebra showed three foramina. Only 1 (0.3%) vertebrae showed the foramen on both sides and the remaining 5 (1.4%) had unilateral foramina. Among the unilateral, 4 were present on the right side and only 1 was on the left side. No vertebrae showed the absence of foramen transversarium. CONCLUSION: The present study observed the accessory foramina transversarium in 1.6% of cases. The unilateral presence was more common than the bilateral. The surgical anatomy of these variations is important for the neurosurgeons and radiologists for interpreting the computed tomogram and magnetic resonance image scans. Their morphological knowledge is clinically important since the course of the vertebral artery may be distorted in such situations.

Neurovascular foramina of the human clavicle and their clinical significance.

PURPOSE: To study the topographic anatomy and morphology of neurovascular foramina of the human adult clavicles. METHODS: The study comprised 52 clavicles, which were obtained from the anatomy laboratory. The clavicles were macroscopically observed for the number, location and direction of the nutrient foramina. The foramen index was calculated for each clavicle by applying the Hughes formula. RESULTS: The neurovascular foramen was observed in 50 (96.1%) clavicles. The foramen was single in 20 (38.5%) clavicles, double in 23 cases (44.2%), and there were more than 2 foramina in 7 clavicles (13.4%). The foramen was present at the middle 1/3 region in 92.3% clavicles, at the medial 1/3 region in 9.6% and at the lateral 1/3 part in 1.9% clavicles. It was on the inferior surface in 55.8% clavicles, on the posterior surface in 69.2% and at the superior surface in only 1.9% of clavicles. The average distance of the foramen from the sternal end was 64.4 mm and the mean foraminal index was 44.72. CONCLUSIONS: The present study observed that the foramina were more common on the posterior surface and were often multiple, directed toward the acromial end. Knowledge of the localization of nutrient foramina can be useful in certain surgical procedures to preserve circulation. We believe that the data obtained from the present study would be of interest to clinicians who are involved in procedures such as bone grafting, surgical approach for internal fixation and coracoclavicular ligament repair.

Inhibition of tumor necrosis factor alpha-mediated NFkappaB activation and leukocyte adhesion, with enhanced endothelial apoptosis, by G protein-linked receptor (TP) ligands.

Tumor necrosis factor (TNF) alpha is a critical mediator of inflammation; however, TNFalpha is rarely released alone and the "cross-talk" between different classes of inflammatory mediators is largely unexplored. Thromboxane A(2) (TXA(2)) is released during I/R injury and exerts its effects via a G protein-linked receptor (TP). In this study, we found that TXA(2) mimetics stimulate leukocyte adhesion molecule (LAM) expression on endothelium via TPbeta. The potential interaction between TXA(2) and TNFalpha in altering endothelial survival and LAM expression was examined. IBOP, a TXA(2) mimetic, attenuated TNFalpha-induced LAM expression in vitro, in a concentration-dependent manner, by preventing TNFalpha-enhanced gene expression, and also reduced TNFalpha-induced leukocyte adhesion to endothelium both in vitro and in vivo. IBOP abrogated TNFalpha-induced NFkappaB activation in endothelial cells, as determined by reduced IkappaB phosphorylation and NFkappaB nuclear translocation, by inhibiting the assembly of signaling intermediates with the intracellular domain of TNF receptors 1 and 2 in response to TNFalpha. This inhibition resulted from the Galpha(q)-mediated enhancement of STAT1 activation and was reversed by anti-STAT1 antisense oligonucleotides. TNFalpha-mediated TNFR1-FADD association and caspase 8 activation were not inhibited by IBOP co-stimulation, however, resulting in a 2.6-fold increase in endothelial cell apoptosis. By stimulating the vessel wall and inducing endothelial cell apoptosis, TXA(2), in combination with TNFalpha, may hamper the angiogenic response during inflammation or ischemia, thus reducing revascularization and tissue viability.