Identification & characterization of leucine-rich repeat kinase 2 & parkin RBR E3 ubiquitin protein ligase variants in patients with Parkinson's disease.

BACKGROUND & OBJECTIVES: Parkinson's disease (PD) is a motor disorder that affects movement. More than 24 loci and 28 associated genes have been identified to be associated with this disease. The present study accounts for the contribution of two candidates, leucine-rich repeat kinase 2 ( LRRK2) and parkin RBR E3 ubiquitin protein ligase ( PRKN) in the PD patients, and their characterization in silico and in vitro. METHODS: A total of 145 sporadic PD cases and 120 ethnically matched healthy controls were enrolled with their informed consent. Mutation screening was performed by direct DNA sequencing of the targeted exons of LRRK2 and all exons flanking introns of PRKN. The effect of the pathogenic PRKN variants on a drug (MG-132) induced loss of mitochondrial membrane potential (△ΨM) was measured by a fluorescent dye tetramethylrhodamine methyl ester (TMRM). RESULTS: Twelve and 20 genetic variants were identified in LRRK2 and PRKN, respectively. Interestingly, five out of seven exonic LRRK2 variants were synonymous. Further assessment in controls confirmed the rarity of two such p.Y1527 and p.V1615. Among the pathogenic missense variations (as predicted in silico) in PRKN, two were selected (p.R42H and p.A82E) for their functional study in vitro, which revealed the reduced fluorescence intensity of TMRM as compared to wild type, in case of p.R42H but not the other. INTERPRETATION & CONCLUSIONS: About 6.2 per cent of the cases (9/145) in the studied patient cohort were found to carry pathogenic (as predicted in silico) missense variations in PRKN in heterozygous condition but not in case of LRRK2 which was rare. The presence of two rare synonymous variants of LRRK2 (p.Y1527 and p.V1615) may support the phenomenon of codon bias. Functional characterization of selected PRKN variations revealed p.R42H to cause disruption of mitochondrial membrane potential (△ΨM) rendering cells more susceptible to cellular stress.

Homocysteine and vitamin B12: Other causes of neural tube defects in Eastern Uttar Pradesh and Western Bihar population.

BACKGROUND: Neural tube defects (NTDs) are congenital malformations with an incidence of 1-10/1000 live births. Homocysteine and vitamin B12 metabolism have been shown to be associated with NTDs. AIM: To investigate the status of maternal and neonate's folic acid, homocysteine, and vitamin B12 levels and their association with the risk of development of NTDs in the population of Eastern Uttar Pradeshand Western Bihar, India. MATERIALS AND METHODS: This study is a cross-sectional, retrospective study where 96 mothers who either had a first NTD child or had a history of NTD child in the family and 126 neonates with spina bifida were recruited during the period 2012-2015. Eighty-four control mothers whose previous and current pregnancies were normal, and 87 control neonates who had no defects and were within the same age range as the NTD affected neonates, recruited from the department of pediatric surgery, were enrolled in the study. Plasma concentrations of folic acid, vitamin B12, and homocysteine were compared between cases and controls. RESULTS: The folic acid level in the mothers and neonates was within the normal limit. A significant increase in the level of homocysteine in mothers with affected pregnancy and in neonate cases in comparison to control mothers was obseved. Further, a significant decrease in the level of vitamin B12 in mothers with NTD neonates and in the affected neonates was noted. A negative correlation was found between homocysteine and vitamin B12 levels in case and control mothers. CONCLUSION: A correlation of an increase in serum homocysteine with a decrease in vitamin B12 was seen in mothers of neonates with NTD. A similar observation as made in the neonates with NTDs. It may be suggested that maternal decrease in vitamin B12, in mothers who have normal folic acid may be associated with NTD in their children.

A prospective pilot study on serum cleaved tau protein as a neurological marker in severe traumatic brain injury.

OBJECTIVE: Neurotrauma has been labelled as a "silent epidemic" affecting both the developed and the developing nations. To date, no single brain-specific biomarker has been unanimously accepted for routine clinical use in TBI. Our study aims to determine the correlation of "cleaved-tau protein" in severe traumatic brain injury (TBI) with Glasgow Coma Scale (GCS) at the time of admission, mode of injury, CT findings and outcome at discharge. METHODS: The study has been approved by the institutional ethical committee. 40 cases with severe TBI and 40 randomly selected healthy controls were included in this prospective study. Venous blood samples were collected and serum cleaved tau protein levels were measured and correlated with gender, mode of injury, CT findings GCS score and GOS score at discharge. RESULTS: In the severe TBI group, the mean serum cleaved tau protein levels in males were 91.65 ± 41.34 pg/ml (mean ± S.D.), and females were 104.43 ± 53.08 pg/ml (mean ± S.D.), (p = 0.27). Mean serum C-tau level in study group was 95.48 ± 44.87 pg/ml (range 36.44-192.34), 95% C.I. (81.13-109.83) and in controls was 33.82 ± 13.65 pg/ml (range 2.48-66.54), 95% C.I. (29.46-38.19) (p < 0.001). The distribution of serum C-tau was in severe TBI group varied in all categories of GCS at 0th day (p < 0.001). Serum cleaved tau protein levels in the good outcome group were 74.26 ± 25.43 pg/ml (mean ± S.D.), range 36.44-144.54, 95% C.I. (63.52-85.00) and the poor-outcome group were 127.32 ± 49.40 pg/ml, range 66.65-192.34, 95% C.I. (100.99-153.64) (p = 0.001). CONCLUSION: In severe TBI, serum cleaved tau protein levels were significantly higher as compared to the controls in this prospective study. However, results of this study are preliminary in nature and there is a need to undertake larger prospective studies to reach a definitive conclusion.

Bilateral Mirror Image Cervical Neurofibroma in an Adult with Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterised by various phenotypic features like hyperpigmented spots, neurofibromas, Lisch nodules, skeletal abnormalities and tendency to develop neoplasms. Only few cases of Non-Familial Spinal Neurofibromatosis-1 (Non-FSNF1) have been described in literature with tumors involving the spinal roots at every level being even rarer. We reported an interesting case of bilateral symmetrical cervical neurofibroma with multiple spinal neurofibromas appearing as mirror image on CT, associated with non familial NF-1 as a rare presentation in a 25-year-old adult male.

Ethyl Pyruvate as a Potential Defense Intervention against Cytokine Storm in COVID-19?

COVID-19 is a deadly pandemic and has resulted in a huge loss of money and life in the past few months. It is well known that the SARS-CoV-2 gene mutates relatively slowly as compared to other viruses but still may create hurdles in developing vaccines. Therefore, there is a need to develop alternative routes for its management and treatment of COVID-19. Based on the severity of viral infection in COVID-19 patients, critically ill patients (∼5%, with old age, and comorbidities) are at high risk of morbidities. The reason for this severity in such patients is attributed to "misleading cytokine storm", which produces ARDS and results in the deaths of critically ill patients. In this connection, ethyl pyruvate (EP) controls these cytokines/chemokines, is an anti-inflammatory agent, and possesses a protective effect on the lungs, brain, heart, and mitochondria against various injuries. Considering these facts, we propose that the site-selective EP formulations (especially aerosols) could be the ultimate adjuvant therapy for the regulation of misleading cytokine storm in severely affected COVID-19 patients and could reduce the mortalities.

Epidemiological and Clinico-radiological Evaluation of Head Injury in Pediatric Population.

BACKGROUND: Head injury in infancy and childhood has been documented as the single most common cause of death. In India, children aged <15 years constitute 35% of the total population and contribute to 20-30% of all head injuries. In this study, we attempted to analyze the epidemiological factors, management, and outcome of traumatic brain injury (TBI). The objective of this study were to find the causes of head injury in children and its pattern of distribution in this population and to analyze the efforts required to prevent the injury and management focusing on limiting the progression of primary brain injury and minimizing secondary brain insult. RESULTS: A total of 2714 patients with head injury were admitted at our hospital during the study period and, out of them, 508 (18.17%) were pediatric patients with age less than 18 years. Of the 508 patients, only 497 patients were included in this study. In the present study, 357 (71.83%) were males and 140 (28.16%) were females. In total, 351 cases were managed conservatively whereas surgical intervention was conducted in 146 cases (P < 0.001). In this study, the most common mode of injury was a road traffic accident (RTA) (46.88%; n=233), followed by fall from height (34.8%; n=173) (P < 0.001). It was also seen that epidural hematoma and fracture hematoma were the most common computed tomography findings in pediatric patients with head injury followed by parenchymal contusion or contusion with or without fracture followed by diffuse axonal injury. A total of 344 cases out of 497 cases were discharged with Glasgow outcome score (GOS)-5 whereas nine cases remained in a persistent vegetative state (GOS-2). CONCLUSION: Early intervention aimed at the primary lesion in TBI in children generally carries a good outcome, and limits as much as possible the ongoing biomechanical, physiological, and pathological sequelae post-TBI. In teenagers, the importance of proper self-care along with adequate safety gears while doing any TBI-prone activity should be emphasized.

Bilateral Traumatic Intracranial Hematomas and its Outcome: a Retrospective Study.

The objective of this study was to evaluate the age distribution, mode of injury, type of hematomas, and their surgical outcome in patients with bilateral traumatic head injuries. The present study included 669 cases of traumatic head injury who presented at the neurosurgery emergency out of which 94 cases had bilateral head injuries from the period of August 2009 to April 2014. The data from the hospital computerized database were retrospectively analysed. Cases of bilateral traumatic head injury included 94 patients out of which 88.29 % (n = 83) were males and 11.70 % (n = 11) were females. Commonest mode of injury was road traffic accident in 56.38 % (n = 53) followed by fall from height in 29.78 % (n = 28). In our study, 25.53 % patients had epidural hematoma (EDH) with intracerebral hematoma (ICH) or contusion (n = 24), followed by EDH with subarachnoid hemorrhage (SAH) in 18.08 % (n = 17). At the time of discharge, all those patients managed conservatively had good Glasgow outcome scale (GOS) while with surgical intervention 58 % patients had good GOS, 19 % had moderate disability, and 9 % remained with severe disability. In cases of bilateral hematomas, EDH is most common and should be managed in neurosurgical emergency. Other combinations of bilateral intracranial hematomas should be managed according to the surgical indication and serial CT imaging.

Dorsal spinal epidural psammomatous meningioma in an adult male.

Meningiomas are benign in nature and arise from the arachnoid cells. They are mostly situated in the intracranial compartment, whereas spinal meningiomas are rare. Approximately, in 10% of cases, an extradural component is seen but an exclusively extradural meningioma is quite uncommon. However, WHO Grade II (atypical) and Grade III (anaplastic) tumors can behave aggressively. We reported a case of purely extradural psammomatous meningioma in an adult male affecting the dorsal spine although uncommon meningiomas should be included in the differential diagnosis of extradural intraspinal masses.

Uncommon presentation of choroid plexus papilloma in an infant.

Choroid plexus tumors are relatively rare primary brain tumors that arise from the epithelial differentiated tissue, majority being well-differentiated papillomas. In adults, fourth ventricle and in children, lateral ventricles are the most common site of these tumors. We reported a case of choroid plexus papilloma in the temporal horn of lateral ventricle in a female child who presented with the uncommon symptoms of sudden intraventricular hemorrhage and multiple episodes of seizure without symptoms of raised intracranial tension.

Supratentorial haemangioblastoma without von Hippel-Lindau syndrome in an adult: A rare tumor with review of literature.

Supratentorial hemangioblastomas (HBLs) are rare, benign vascular tumors of the central nervous system neoplasms. Very scarce literature is available regarding supratentorial HBL without von Hippel-Lindau (VHL) syndrome in an adult. We reviewed the literature and PubMed advanced search showed only a few results of supratentorial HBL without VHL syndrome. We reported a rare case of cystic supratentorial HBL in 39-year-old male affecting the parietal lobe without VHL syndrome. Supratentorial HBL is a rare tumor and supratentorial HBL without VHL syndrome are even rarer. Being a rare entity, not much clinical data is currently available regarding supratentorial HBLs, thus necessitating the need for further reporting and review of such cases.

Acquired dorsal intraspinal epidermoid cyst in an adult female.

BACKGROUND: Epidermoid and dermoid cyst comprise <1% of spinal tumors and may be congenital (hamartoma) or acquired (iatrogenic) in origin. Epidermoid cysts within the neuraxis are rare benign neoplasms that are most commonly located in the intracranial region. CASE DESCRIPTION: Here, we report the a case of an acquired intradural extramedullary epidermoid cyst involving the thoracic region in an adult female who had no associated history of an accompanying congenital spinal deformity. CONCLUSION: Early diagnosis and immediate surgical intervention reduce patient morbidity. Near complete or subtotal excision of the cyst wall is warranted to prevent inadvertent injury to the spinal cord thus minimizing neurological morbidity.

High incidence of neural tube defects in Northern part of India.

BACKGROUND: In the absence of primary care and prevailing associated social stigma, many patients of neural tube defects (NTDs) from remote areas die without getting any treatment. The high number of such untreated cases and unregistered deaths in these areas made us ponders to the fact that tertiary care center-based studies do not represent the true incidence of NTDs. MATERIALS AND METHODS: We did a population-based survey for NTDs births of rural areas from Jaunpur to Ghazipur district in Eastern Uttar Pradesh. These districts are among the least developed areas of Northern India in Uttar Pradesh among other 17. RESULTS: The data show an incidence of 7.48 per 1000 live births. CONCLUSION: Besides of unawareness regarding periconceptional folate supplementation, intensive effort is required to design adequately powered studies to search other key factors responsible for high prevalence of NTDs.

Bilateral occipital extradural hematoma in a child.

Extradural hematoma (EDH) occurs in approximately 2% of all patients with head injuries. Bilateral EDHs account for 2-10% of all acute EDHs in adults but are exceedingly rare in children. Posterior fossa EDHs occurs in 5% of all cases of EDHs. EDHs in children are more frequently venous (from tears of a dural sinus or diploic veins) and consequently have a better prognosis than EDHs in adults. Once the diagnosis of BEH is confirmed, urgent surgical treatment should be considered. We are reporting such rare form of injury as bilateral occipital EDH with supratentorial extension in 12 years child following road traffic accident.

Spinal intradural extramedullary mature cystic teratoma in an adult: A rare tumor with review of literature.

BACKGROUND: Spinal intradural extramedullary teratoma is a rare condition, more common in children than in adults often with a history of spinal dysraphism. METHOD: We reviewed the literature and Pubmed advanced search showed nine results of intradural extramedullary teratoma in adults which included five independent case reports and three cases in a case series. We reported a rare case of intradural extramedullary teratoma in an adult located opposite L4 vertebra with neither spinal dysraphism nor any history of the prior spinal procedure. RESULTS: The occurrence of teratomas in the spine is extremely rare. Further, spinal intradural extramedullary teratoma is more common in children but a rare entity in adults. CONCLUSION: Although uncommon, spinal cord neoplasm should be considered in the differential diagnosis of backache or radicular pain associated with neurological deficits even in absence of spinal dysraphism or any spinal procedure.

Cerebral intraventricular echinococcosis in an adult.

BACKGROUND: Echinococcosis in humans occurs as a result of infection by the larval stages of taeniid cestodes of the genus echinococcus. Intracranial hydatid cysts usually develop at an intraparenchymal site. Hydatid cyst within the cerebral ventricle is quite unusual. METHODS: We reviewed the literature on adult intraventricular hydatid cyst and found case reports mainly in children with an only handful of cases in adults. We reported a rare case of cerebral intraventricular (left lateral ventricle) hydatid cyst in a 21-year-old adult female. RESULTS: Although cerebral hydatid cysts are most commonly seen in children and young adults cerebral intraventricular hydatid cyst are comparatively rarer in adults. CONCLUSION: The possibility of infection with Echinococcus granulosus should be included in the differential diagnosis of raised intracranial hypertension in patients from endemic areas.

Validation of data on the use of twin mix in minor oral surgery: comparative evaluation of efficacy of twin mix versus 2 % lignocaine with 1:200000 epinephrine based on power analysis and an UV spectrometry study for chemical stability of the mixture.

INTRODUCTION: There is convincing evidence supporting the addition of dexamethasone to lignocaine and its administration as an intra-space injection to achieve benefit of a single dose steroid after third molar surgery. This study was undertaken to validate the existing data on the use of twin mix in minor oral surgery based on power analysis, statistical sample size estimation and an ultraviolet (UV) spectrometry study for chemical stability of the mixture. MATERIAL AND METHODS: A prospective, randomized, double-blind trial was designed to validate the pilot study on the efficacy of twin mix and 2 % lignocaine with 1:200,000 epinephrine in the surgical removal of impacted mandibular third molars. Clinical parameters of anaesthetic latency, anaesthetic duration, efficacy of twin mix as an anaesthetic and post-operative patient discomfort were assessed. The stability of active ingredients in the solution was assessed using a double beam UV-visible spectrophotometery. RESULTS: The results of the study showed better post-operative outcome with administration of dexamethasone and lignocaine as an intra-space injection in decreasing the post-operative patient discomfort. The anaesthetic efficacy of the twin-mix admixture was found statistically similar to the control solution of 2 % lignocaine with 1:200,000 epinephrine. The λmax recorded for dexamethasone and local anaesthetic individually was obtained with the twin-mix solution, which indicated no change in the active pharmacological compounds. DISCUSSION: Clinical anaesthetic efficacy of twin mix is comparable to 2 % lignocaine with 1:200,000 epinephrine when administered in the pterygomandibular space with the additional advantage of a single prick co-administration of dexamethasone with local anaesthetic, lesser sting of the local anaesthetic injection, shorter anaesthetic latency, prolonged duration of the soft tissue anaesthesia and decrease in post-operative discomfort after the oral surgical procedure.

A Prospective Randomized Study Comparing Non-absorbable Polypropylene (Prolene®) and Delayed Absorbable Polyglactin 910 (Vicryl®) Suture Material in Mass Closure of Vertical Laparotomy Wounds.

Wound dehiscence is a postoperative complication encountered following abdominal surgery. A prospective randomized study was conducted to compare the incidence of wound dehiscence with a delayed absorbable and a nonabsorbable suture material in the mass closure of vertical laparotomy wounds. In one group, 100 patients were analyzed after closure with Prolene®, and in another group, 100 patients were analyzed after closure with Vicryl®. The incision was closed by continuous far and near suture technique using polypropylene (Prolene) suture in one group and a synthetic delayed absorbable polyglactin 910 (Vicryl) suture in the other group. There was significant difference in the incidence of wound dehiscence between the two groups: 6 % with Prolene and 17 % with Vicryl, (χ (2) = 5.944, 1 DF, P value = 0.0148). The overall incidence of wound dehiscence was 11.5 % in this study. The incidence of wound dehiscence in both the study groups was higher than expected as compared to previous literature. There was a significant difference between the two suture materials. In our study, Prolene is a better suture material for closure of vertical laparotomy wounds.