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Objectives:Recent literature documents a trend of gradual decline in temporal lobe (resective) epilepsy surgery over the past decade. Amongst these, a large scale, comprehensive survey done in selected European, Australian and American centres documents trends of resective temporal epilepsy surgery across two decades. Montreal Neurological Institute has been the leading epilepsy surgery centre for more than 50 years now. It has been at the forefront of investigating and managing epilepsy in Canada. We have looked into the trends of epilepsy surgery in our institute in the past 44 years.Methods:The records of all adult epilepsy surgery procedures (excluding reoperations) performed by the senior authors were analysed from 1971 to 2015. Data retrieved for analysis included type of surgery (intracranial recording, resective, and neuromodulatory) and the specific surgical target for resection. Procedures were grouped into temporal resective, extratemporal (ET) resective and placement of intracranial electrodes (stereotactic electroencephalogram (SEEG)).Results:A total of 2,078 new procedures were performed from 1971 to 2015 at the Montreal Neurological Institute. Temporal procedures constituted the bulk of the proportion of all procedures each year and the entire study period. SEEG group shows linear increase in the number of cases over the years catching up with the total number of temporal procedures.Conclusions:Our study involving a homogenous dataset spanning nearly 50 years shows a decline in temporal lobe surgeries and an increase in intracranial investigations despite the class I evidence of its effectiveness. This corroborates the trends in epilepsy surgery practice profiles in tertiary centres of developed countries.

Insulin resistance is thought to be a common link between obesity and Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD has now reached epidemic status worldwide and identification of molecules or pathways as newer therapeutic strategies either to prevent or overcome insulin resistance seems critical. Dysregulated hepatic lipogenesis (DNL) is a hallmark of NAFLD in humans and rodents. Therefore, reducing DNL accretion may be critical in the development of therapeutics of NAFLD. In our in vivo model (high-fat-diet fed [HFD] obese mice) we found Zinc oxide nanoparticles (ZnO NPs) significantly decreased HFD-induced hepatic steatosis and peripheral insulin resistance. This protective mechanism of ZnO NPs was signaled through hepatic SIRT1-LKB1-AMPK which restricted SREBP-1c within the cytosol limiting its transcriptional ability and thereby ameliorating HFD mediated DNL. These observations indicate that ZnO NP can serve as a therapeutic strategy to improve the physiological homeostasis during obesity and its associated metabolic abnormalities.

Circular RNAs (circRNAs) are a class of noncoding RNA molecules formed by the back splicing process. Compared to linear mRNA molecules they are more stable. CircRNA acts as miRNA sponges, regulates translation, epigenetic alterations, etc. However, the most significant aspect of circRNAs has been its role in regulating the hallmark of cancer and diabetes mellitus. Several circRNAs are extensively expressed in individuals with cancer and diabetics. Dysregulated expression of various circRNAs plays a crucial part in the development of type 2 diabetes mellitus. In the present review, we present the current understanding of cricRNAs biogenesis, regulatory mechanisms, reviews of recent findings and circRNA as potential biomarker.

Remarkable discoveries over the last two decades have elucidated the autoimmune basis of several, previously poorly understood, neurological disorders. Autoimmune disorders of the nervous system may affect any part of the nervous system, including the brain and spinal cord (central nervous system, CNS) and also the peripheral nerves, neuromuscular junction and skeletal muscle (peripheral nervous system, PNS). This comprehensive overview of this rapidly evolving field presents the factors which may trigger breakdown of self-tolerance and development of autoimmune disease in some individuals. Then the pathophysiological basis and clinical features of autoimmune diseases of the nervous system are outlined, with an emphasis on the features which are important to recognize for accurate clinical diagnosis. Finally the latest therapies for autoimmune CNS and PNS disorders and their mechanisms of action and the most promising research avenues for targeted immunotherapy are discussed.

Increasing evidence suggests selenium nanoparticles (Se NPs) as potential cancer therapeutic agents and emerging drug delivery carriers, yet, the molecular mechanism of their anticancer activity still remains unclear. Recent studies indicate thioredoxin reductase (TrxR), a selenoenzyme, as a promising target for anticancer therapy. The present study explored the TrxR inhibition efficacy of Se NPs as a plausible factor impeding tumor growth. Hyaluronic acid (HA)-functionalized selenopolymeric nanocarriers (Se@CMHA NPs) were designed wielding chemotherapeutic potential for target specific Doxorubicin (DOX) delivery. Se@CMHA nanocarriers are thoroughly characterized asserting their chemical and physical integrity and possess prolonged stability. DOX-loaded selenopolymeric nanocarriers (Se@CMHA-DOX NPs) exhibited enhanced cytotoxic potential toward human cancer cells compared to free DOX in an equivalent concentration eliciting its selectivity. In first-of-its-kind findings, selenium as Se NPs in these polymeric carriers progressively inhibit TrxR activity, further augmenting the anticancer efficacy of DOX through a synergistic interplay between DOX and Se NPs. Detailed molecular studies on MCF7 cells also established that upon exposure to Se@CMHA-DOX NPs, MCF7 cells endure G2/M cell cycle arrest and p53-mediated caspase-independent apoptosis. To gauge the relevance of the developed nanosystem in in vivo settings, three-dimensional tumor sphere model mimicking the overall tumor environment was also performed, and the results clearly depict the effectiveness of our nanocarriers in reducing tumor activity. These findings are reminiscent of the fact that our Se@CMHA-DOX NPs could be a viable modality for effective cancer chemotherapy.

The anticancer properties of selenium (Se) and curcumin nanoparticles in solo formulations as well as in combination with other therapeutic agents have been proved time and again. Exploiting this facet of the two, we clubbed their tumoricidal characteristics and designed curcumin loaded Se nanoparticles (Se-CurNPs) to achieve an enhanced therapeutic effect. We evaluated their therapeutic effects on different cancer cell lines and Ehrlich's ascites carcinoma mouse model. In vitro results showed that Se-CurNPs were most effective on colorectal carcinoma cells (HCT116) compared to the other cancer cell lines used and possessed pleiotropic anticancer effects. The therapeutic effect on HCT116 was primarily attributed to an elevated level of autophagy and apoptosis as evident from significant up-regulation of autophagy associated (LC3B-II) and pro-apoptotic (Bax) proteins, down-regulation of anti-apoptotic (Bcl-2) protein and Cytochrome c (cyt c) release from mitochondria along with reduced NFκB signaling and EMT based machineries marked by downregulation of inflammation (NFκB, phospho-NFκB) and epithelial-mesenchymal transition (CD44, N-cadherin) associated proteins. In vivo studies on Ehrlich's ascites carcinoma (EAC) mice model indicated that Se-CurNPs significantly reduced the tumor load and enhanced the mean survival time (days) of tumor-bearing EAC mice.

It is a known fact that depression is the one of the leading causes of years lived with disability and the fourth leading cause of disability-adjusted life-years worldwide. Depression is often under-recognized among patients of epilepsy due to lack of awareness of depressive symptoms. Due to improper management of depression in epileptic patients, it can interfere with treatment outcomes and hence can impair the quality of life. Undermanaged depression in epilepsy is generally associated with work absenteeism and direct medical costs. Electronic JR_liographic databases like PubMed and Google Scholar were searched using the format “(depression, epilepsy and symptoms)”. Cross-linked searches were made taking the lead from key articles. Recent articles and those exploring the etiological factors & symptomatic presentation of depression were focused upon. The main purpose of this review was to study the causative association between epilepsy and depression and to discuss the varied symptomatic presentation.

Background: Opioid substitution therapy (OST) is an evidence-based intervention for opiate-dependent persons that replaces illicit drug use with medically prescribed, orally administered opiates such as buprenorphine and methadone. OST reduces HIV risk behaviors and harms associated with injecting opioid. Most of the evidence for OST effectiveness has been generated in middle- and high-income countries where programs are mostly located in dedicated health-care settings; evidence regarding the outcomes of OST programs in low-income countries where OST is often provided in grassroots settings such as drop-in centers is limited. Aims and Objectives: To study the sociodemographic variables, HIV ELISA status, HIV risk behavior, comorbid substance use pattern, and required dose of buprenorphine used for treatment of injection drug users (IDUs) attending oral substitution therapy (OST) center at a tertiary health care center. Methodology: A total of IDUs aged 18–60 years who attended the OST center during 1-year period at a government medical college are included in the study. Results: Majority of the IDUs are male with mean age of 32.8 years. The mean dose of buprenorphine used for the substitution was 4.6 mg/day at the start of therapy. Most of the IDUs are of lower educational status and educated up to primary or middle school. 32.50% of the participants who are unemployed are totally dependent on the family. Most common substance abuse among IDU users were tobacco (74.17%), followed by heroine (57.5%). High-risk behavior found among OST clients was unprotected sexual intercourse (19.17%), sharing needle (11.67%), and sexual intercourse with multiple partners (6.67%). HIV ELISA testing showed positive among 2 (1.67%). Conclusion: These findings have relevance to other parts of India and Asia, where injecting drug use is common and is a first step toward filling the gap in knowledge regarding the effectiveness of community-based OST programs delivered in resource-constrained settings.

Metastasis of colorectal carcinoma to the kidney is a rare phenomenon and least-investigated mechanistically. Both exosomal and non-exosomal vesicles (NEVs) from tumor tissues have been proven to be important metastatic mediators. In this light, the current work focuses on the investigation of the role of NEVs obtained from colorectal cancer cell line HCT116 in developing metastatic traits in normal human embryonic kidney cell line HEK293. ECVs were isolated via filtration method from spent media of HCT116 culture. Dynamic light scattering (DLS) analysis showed ECVs which are obtained as a retentate of 220 nm filters had an average size of 147 nm and hence may be classified as non-exosomal vesicles. NEVs obtained from HCT116 spent media were poured onto compact culture plates of HEK293 cell lines. A systematic image analysis of crystal violet-stained plates was done using the snake model for segmentation by MATLAB and analysis by ImageJ. It is evident from the image analysis data that the number of disseminated cells/colony of cells was more in NEVs treated wells than that of the untreated ones. The average distance of centrifugal cell migration (analogous to invasion) was also found to be higher in case of nECV-treated HEK293 compact cultures. Although early, but in conclusion, it can be said that NEVs from colon carcinoma could be a metastatic mediator for human kidney cells. Secondly, it is indicated that 2D compact culture in combination with inexpensive image analytics can be a potential tool in anti-metaplastic drug discovery applications.

Intracranial Langerhans cell histiocytosis commonly presents as skull lesions in children. An intratumoral cyst with fluid level and epidural hematoma occurring with eosinophilic granuloma is very rare. We report a 15-year-old boy who presented with a spontaneous epidural hematoma which was the result of a temporal eosinophilic granuloma. Multiple explanations for epidural hematoma in such cases have been discussed. Intratumoral hemorrhage followed by cyst formation and rupture may explain the pathophysiology of epidural hemorrhage formation.

Osteoid osteoma (OO) affects proximal femur in 20%–25% of cases.[1 2][1] When they are intra-articular, they can mimic inflammatory synovitis and be difficult to diagnose.[3 4][2] CT scan is the imaging modality of choice.[5][3] Various treatment modalities have been described in literature but

Background Neurologic complications are increasingly being reported in dengue epidemics. Intraspinal hematomas are rare, and those associated with dengue fever are still rarer with only 1 being reported in the literature. Case Description We report a case of dengue fever presenting with acute-onset quadriparesis (upper limbs Medical Research Council [MRC] 4/5 and lower limbs 0/5) and urinary incontinence. The patient was radiologically diagnosed with cervicodorsal acute to subacute anterior epidural hematoma. On the basis of clinical and radiologic evaluations, the patient underwent an anterior cervical approach via a split-manubriotomy, C6-D4 right anterolateral partial oblique corpectomies for evacuation of the hematoma. Intraoperatively, however, there was no evidence of anterior epidural collection and the dura revealed a bluish hue. A durotomy revealed a subdural hematoma. After evacuation of the hematoma, the patient remained paraplegic and her upper limb power worsened by MRC 1 grade. Postoperative magnetic resonance imaging revealed good evacuation and no new bleed; however, the intramedullary T2-weighted signal hyperintensities extending up to C2 persisted. She was on ventilatory support for almost 5 months. For diaphragmatic incapacity she underwent bilateral cervical phrenic nerve stimulation (diaphragmatic pacing). Despite initial improvement, she succumbed to multiple underlying comorbidities. Conclusions Acute spontaneous spinal subdural hematoma (SSDH) is extremely rare but should be kept in mind in patients with dengue hemorrhagic fever. The radiologic findings could be deceptive and plain computed tomography and magnetic resonance imaging should be used as complementary studies to establish the diagnosis of acute spontaneous SSDH. The outcomes of SSDH are guarded, and elaborate patient counseling should be done preoperatively, keeping these in perspective.

Tardive dyskinesia is one of the most significant side effects of antipsychotic medications. Antipsychotic treated schizophrenia patients with diabetes mellitus are more likely to develop tardive dyskinesia than those without diabetes. Clozapine is probably best supported for management of tardive dyskinesia. But clozapine has been strongly linked to hyperglycaemia and impaired glucose tolerance, so it is not preferred in patients with diabetes mellitus. We present a case of 35-year-old male with a diagnosis of schizophrenia and type 2 diabetes mellitus with tardive dyskinesia, who was successfully treated with quetiapine and clonazepam.

Lesch-Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase-1. Few reports on behavioral aspects especially self-injurious behavior in LNS patients are available. We report a case of LNS in an 8-year-old male child, who presented with characteristic self-injurious behavior.

Objective: To objectively document autonomic dysfunction in the affected arm with traumatic brachial plexus injury (TBPI) using quantitative sudomotor axon reflex test (QSART). Materials and Methods: Patients with TBPI presenting to the neurosurgical outpatient department from August 2013 to November 2014 were included in the study. The QSART was administered to each patient with prior informed consent detailing the procedure. A total of 20 patients with TBPI were included in the study. The age, sex, mode of injury, date of injury, side of injury, and type of injury (pan brachial plexus vs preserved distal function) were recorded. The presence of any pain was also recorded. The injuries were also grouped as preganglionic and postganglionic injuries based on clinical, electroneuromyography (ENMG) and magnetic resonance imaging (MRI) findings. The results of the test for the affected and normal limb were recorded and analyzed with appropriate statistical tests to determine any significant differences. Results: The study included 20 patients, with their age ranging from 15 to 50 years. Out of the 20 patients, one was female and the rest 19 were males. Seven (35%) of the injuries were complete (pan brachial plexus) and 13 (65%) were incomplete (preserved distal function). All patients had preganglionic TBPI. There was no evidence of any statistically significant difference between the affected and normal arm for total sweat volume (P = 0.20) and latency period (P = 0.42). However, the average mean values for the same were lower in the affected arm as compared to the normal. The baseline sweat output (P = 0.010), however, was significantly lower in the affected arm as compared to the normal arm. Conclusion: QSART has demonstrated reduced baseline sweat output in the affected arm in patients with TBPI. This indicates the presence of autonomic dysfunction in the injured arm.

Background and objectives Anxiety disorders are the most common group of psychiatric disorders in children and adolescents. But few studies on specific anxiety disorders in children and adolescents are available in India. Therefore, this study was planned to identify anxiety disorders in children and adolescents in an Indian psychiatry outpatient setting and elicit its phenomenology and co-morbidities. Methods 1465 persons were screened using screen for child anxiety related emotional disorders (SCARED) scale. The screen positive patients were assessed and diagnosis of anxiety disorders was established according to DSM-IV-TR. Detailed assessment of the phenomenology of anxiety disorders was done by K-SADS-PL. Results 42 (2.86%) patients had different anxiety disorders. Out of which 16 (38.1%) patients had obsessive compulsive disorder, 10 (23.81%) patients with specific phobias, 6 (14.29%) patients with generalized anxiety disorder, 4 (9.52%) patients with social anxiety disorder and 3 (7.14%) patients each with separation anxiety disorder and panic disorder. Co-morbidities were found in 54% of patients with anxiety disorders. Dissociative disorder, specific phobias and social anxiety disorder were the common co-morbidities. Interpretation and conclusion Anxiety disorders are less commonly found in clinic settings (2.86%). No case of posttraumatic stress disorder or acute stress reaction was found in this study.

Context: The pathology of classic Burkitt lymphoma (BL) remains a challenge despite being a well-defined entity, in view of the significant overlap with atypical BL and B-cell lymphoma intermediate between DLBL (diffuse large B cell lymphoma) and BL. They are difficult to be segregated in resource-limited setups which lack molecular testing facilities. This is further affected by interobserver variability and experience of the reporting pathologist. Aims: The aim of our study was to quantitate variability among a group of pathologists with an interest in lymphomas (albeit with variable levels of experience) and quantitate the benefit of joint discussions as a tool to increase accuracy and reduce interobserver variability of pathologists, in the diagnosis of BL in a resource-limited setup. Materials and Methods: A set of 25 non-Hodgkin lymphoma cases in which a diagnosis of BL was entertained were circulated to 14 participating pathologist within the Mumbai lymphoma study group. A proforma recorded the morphologic and immunohistochemical features perceived during the initial independent diagnosis followed by a consensus meeting for discussion on morphology and additional information pertinent to the case. Statistical analysis and Results: The concordance was poor for independent diagnosis among all the pathologists with kappa statistics (±SE) of 0.168 (±0.018). Expert lymphoma pathologists had the highest (albeit only fair) concordance (kappa = 0.373 ± 0.071) and general pathologists the lowest concordance (kappa = 0.138 ± 0.035). Concordance for morphological diagnosis was highest among expert lymphoma pathologists (kappa = 0.356 ± 0.127). Revision of diagnoses after consensus meeting was highest for B-cell lymphoma intermediate between DLB and BL. To conclude, interobserver variation is a significant problem in BL in the post WHO 2008 classification era. Experience with a larger number of cases and joint discussion exercises such as the one we conducted are needed as they represent a simple and effective way of improving diagnostic accuracy of pathologists working in a resource-limited setup.

Background: Nonunion of patella is an uncommon entity prevalent more commonly in developing countries. Many of them have a functional knee joint and only those with a wide gap and failed extensor mechanism need surgery. We report an analysis of nonunion of fracture patella treated by 3 surgical method. Materials and Methods : 35 patients of nonunion/delayed union of patella with significant gap and failure of quadriceps mechanism, underwent three different methods surgically: 1) V-Y plasty and tension band wiring (n=10); 2) patellar traction followed by tension band wiring without V-Y plasty (n=15); and 3) patellar traction followed by partial or total patellectomy (n=10). We compared the results of the treatment in terms of Knee Society Score (KSS), Melbourne patella score, time of union, pain, range of movement, quadriceps power, and ability to do daily activities and complications encountered. Results: The 15 cases of patellar traction followed by tension band wiring showed the best results in terms of time to return to normal activities and complications encountered. Cases with patellectomy showed the next best results but they had a longer period of rehabilitation with ultimately lesser patient satisfaction. V-Y plasty gave the worst results both in complication rate and function return. Conclusion : Preoperative patellar traction followed by tension band wiring is a good procedure giving better results than either patellectomy or V-Y plasty.

Disulfiram is the commonly prescribed drug for the treatment of alcohol dependence. It’s major metabolite (diethyldithiocarbamate) is an inhibitor of dopamine-betahydroxylase, an enzyme that catalyzes the metabolism of dopamine to norepinephrine resulting in psychosis. We recommend that disulfiram should be used at the lowest effective dose, possibly 250 mg daily and caution should be taken while prescribing disulfiram for patients with personal and familial antecedents of psychosis.

Objective To share our experience of DREZOTOMY in the management of post brachial plexus injury neuropathic pain. Method Records of patients with severe neuropathic pain following brachial plexus injury who underwent microsurgical C4-T1 DREZOTOMY were analyzed. Pain relief in the immediate postoperative period, 6 weeks and 6 months was analyzed. Results Total of 7 patients from July 2010 to May 2013 were included in the study. Mean age was 41.1 (26–63). There were 6 male and 1 female patients. Five patients had right-sided pain and 2 had left sided dysesthetic pain. All patients had intractable pain not relieved by medications and was affecting their activities of daily living (ADL's). After psychological counseling and detailed analysis cervical laminectomy and DREZOTOMY was performed. Findings were that the posterior rootlets were absent from the DREZ, arachnoid over the area was dull and multiple microcysts were present. Pain relief was assessed in the immediate postoperative period and later. Control of pain was graded as absence or minimal pain, requiring minimal or no analgesics in 3 patients (VAS 0 OR 1), moderate pain as requiring atypical analgesics in 4 patients (VAS 3–4). Pain control at 6 weeks follow up was good for 2 and moderate for 2 patients. At 6 months showed good pain relief in 2 patients and moderate for 2. Conclusion Patients whose ADL'S are affected by such pain, microsurgical DREZOTOMY can provide good relief thereby helping them to get back to a better quality of life post trauma.

The use of stem cells to repair and replace damaged skeletal muscle cells in chronic, debilitating muscle diseases such as the muscular dystrophies holds great promise. Different stem cell populations, both of embryonic and adult origin display the potential to generate skeletal muscle cells and have been studied in animal models of muscular dystrophy. These include muscle derived satellite cells; bone marrow derived mesenchymal stem cells, muscle or bone marrow side population cells, circulating CD133+ cells and cells derived from blood vessel walls such as mesoangioblasts or pericytes. The design of effective stem cell based therapies requires a detailed understanding of the molecules and signaling pathways which determine myogenic lineage commitment and differentiation. We discuss the great strides that have been made in delineating these pathways and how a better understanding of muscle stem cell biology has the potential to lead to more effective stem cell based therapies for skeletal muscle regeneration for devastating muscle diseases.

Embryonic stem (ES) cells have great therapeutic potential because of their capacity to proliferate extensively and to form any fully differentiated cell of the body, including skeletal muscle cells. Successful generation of skeletal muscle in vivo, however, requires selective induction of the skeletal muscle lineage in cultures of ES cells and following transplantation, integration of appropriately differentiated skeletal muscle cells with recipient muscle. Duchenne muscular dystrophy (DMD), a severe progressive muscle wasting disease due to a mutation in the dystrophin gene and the mdx mouse, an animal model for DMD, are characterized by the absence of the muscle membrane associated protein, dystrophin. Here, we show that co-culturing mouse ES cells with a preparation from mouse muscle enriched for myogenic stem and precursor cells, followed by injection into mdx mice, results occasionally in the formation of normal, vascularized skeletal muscle derived from the transplanted ES cells. Study of this phenomenon should provide valuable insights into skeletal muscle development in vivo from transplanted ES cells.

Fahr's disease (FD) is a rare idiopathic degenerative neurological disorder, which can be present in different heterogeneous manifestations and characterized by bilateral symmetrical cerebral calcification. We present a case of a 55-year-old male who presented with the psychotic feature, bilateral tremors of hand and bilateral symmetrical calcification of basal ganglia. Hence our case suggests that psychiatrists should evaluate the cases of psychosis thoroughly when the age of presentation is atypical, and they should consider the diagnosis of FD when psychosis presents with motor abnormalities.

Peripheral neuropathy secondary to lithium is under-recognized. Most cases of polyneuropathy were reported with lithium intoxication. However, very few cases were reported without lithium toxicity. We present a case of motor neuropathy due to the use of lithium in a 26-year-old male with a therapeutic lithium level.

Childhood disintegrative disorder (CDD) is characterized by late onset (>3 years of age) of developmental delays in language, social function and motor skills. Commonly there is no antecedent physical disorder leading to childhood disintegrative disorder. The present case report describes a child who developed childhood disintegrative disorder at the age of 6 years after an episode of chicken pox.

[Author Affiliation]Satyakam Mohapatra. Mental Health Institute, SBC Medical College, Cuttack, Orissa, India.Alok Jyoti Sahoo. Mental Health Institute, SBC Medical College, Cuttack, Orissa, India.Address correspondence to: Satyakam Mohapatra, MD, Mental Health Institute, SBC Medical College, Cuttack, Orissa 753007, India, E-mail: satyakgmu@gmail.comTo the Editor:Ivermectin and albendazole are antihelminthics used alone and in combination for a wide variety of parasitic infections. The combination regime of albendazole and ivermectin is found to be a useful tool in the integrated or combined control of both lymphatic filariasis and trichuriasis, and has a more favorable tolerability profile in terms of side-effects (Belizario et al. 2003). Psychotic symptoms have not been commonly reported with ivermectin or albendazole use. To best of our knowledge, only a single case of psychosis following the use of albendazole-ivermectin combination therapy was reported in an adult until now (Sinha et al. 2012). We report the first case of psychosis following use of albendazole-ivermectin combination therapy in a 10-year-old boy.Case ReportA 10-year-old boy with an uneventful birth and developmental history without past or family history of neurological and psychiatric illness, presented to the outpatient department with complaints of fearfulness, suspiciousness, irritability, and decreased sleep for the previous 5 days. There was no history of any substance use. No ongoing stressor could be elicited. On evaluation it was found that 24 hours before the onset of symptoms, the child had taken a single dose of albendazole 400 mg and ivermectin 6 mg combination therapy for suspected gastrointestinal worm infestation, prescribed by a general physician.A detailed medical evaluation, including a neurological examination, revealed no significant findings. Hematological and biochemical indices were within normal limits. The patient was hospitalized and the possibility of psychosis induced by combination therapy with of albendazole and ivermectin was entertained. The patient was started on tablet lorazepam 1 mg twice daily. After 3 days, the patient's suspiciousness and fearfulness improved significantly. Over the next 7 days, his psychotic symptoms resolved completely. After 2 weeks, lorazepam was tapered and stopped gradually. The patient was discharged from the hospital, and 8 weeks after discharge was completely asymptomatic.DiscussionIn our patient, the strength of association between with albendazole-ivermectin combination therapy use and the emergence of psychotic symptoms is strengthened by factors such as the absence of a past history, family history, or substance use, the fast remission of psychotic symptoms with the stoppage of the medication even without the use of antipsychotic medication. …

Sir, Balami et al. (2013) state that intravenous tissue plasminogen activator thrombolysis is beneficial for the treatment of acute ischaemic stroke and that strokes are now a treatable medical emergency. A critical analysis of the data, however, raises doubts about the expansive claims of efficacy made by them and others (Wardlaw et al. , 2012). The aim of tissue plasminogen activator treatment is lysis of the thrombus and recanalization of occluded cerebral arteries, to promptly restore blood flow. To prove therapeutic efficacy of the administered thrombolytic agent, angiographic demonstration of arterial recanalization is critically important as it is the only way, in patients, to conclusively demonstrate that clot lysis has occurred. Arterial recanalization has been assessed using different methods: transcranial Doppler studies, magnetic resonance angiography, CT angiography or conventional catheter angiography. However, these tests have widely variable accuracy and reliability. Conventional catheter angiography is the reference standard because of its superb accuracy for imaging evaluation of arteries. Although transcranial Doppler studies have been frequently used to determine recanalization frequency (Alexandrov et al. , 2001, 2004; Demchuk et al. , 2001; Molina et al. , 2001; Ribo et al. , 2006; Saqqur et al. , 2007) their accuracy in assessing steno-occlusive disease is suboptimal and less than either CT angiography or magnetic resonance angiography studies (Feldmann et al. , 2007; Jauch, 2013). Time of flight magnetic resonance angiography (Neumann-Haefelin et al. , 2004; Davis et al. , 2008; Marks et al. , 2008; Kimura et al. , 2009) is limited by loss of flow signal intensity in stenotic regions (Bash et al. , 2005) and does not provide the same degree of spatial resolution as CT angiography or conventional angiography (Bash et al. , 2005; Cloft, 2005; Jauch, 2013). Overall, …

Molecular evaluation of KRAS, BRAF, and PIK3CA mutation has become an important part in colorectal carcinoma evaluation, and their alterations may determine the therapeutic response to anti-EGFR therapy. The current study demonstrates the evaluation of KRAS, BRAF, and PIK3CA mutation using direct sequencing in 204 samples. The frequency of KRAS, BRAF, and PIK3CA mutations was 23.5, 9.8, and 5.9 %, respectively. Five different substitution mutations at KRAS codon 12 (G12S, G12D, G12A, G12V, and G12C) and one substitution type at codon 13 (G13D) were observed. KRAS mutations were significantly higher in patients who were >50 years, and were associated with moderate/poorly differentiated tumors and adenocarcinomas. All mutations in BRAF gene were of V600E type, which were frequent in patients who were ≤ 50 years. Unlike KRAS mutations, BRAF mutations were more frequent in well-differentiated tumors and right-sided tumors. PIK3CA-E545K was the most recurrent mutation while other mutations detected were T544I, Q546R, H1047R, G1049S, and D1056N. No significant association of PIK3CA mutation with age, tumor differentiation, location, and other parameters was noted. No concomitant mutation of KRAS and BRAF mutations was observed, while, interestingly, five cases showed concurrent mutation of KRAS and PIK3CA mutations. In conclusion, to our knowledge, this is the first study to evaluate the PIK3CA mutation in Indian CRC patients. The frequency of KRAS, BRAF, and PIK3CA was similar to worldwide reports. Furthermore, identification of molecular markers has unique strengths, and can provide insights into the pathogenic process and help optimize personalized prevention and therapy.

To the Editor: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is common, with 25% to 60% of patients having neurological symptoms, and a higher percentage displaying CNS pathology in imaging studies or on post mortem examination1,2. The most common clinical manifestations are cognitive decline, psychosis, seizures, and strokes. Abnormalities on magnetic resonance imaging (MRI) scans are usually nonspecific, such as cortical atrophy or scattered focal high-intensity white-matter signals3. Occasionally, larger infarcts or hemorrhages may be seen. We describe a young girl with CNS lupus who presented with the very uncommon MRI findings of hyperintense lesions in the…

Hypertensive encephalopathy typically presents with headache and confusion and bilateral parietooccipital vasogenic edema. Brain stem and cerebellar edema in hypertensive encephalopathy usually occurs in association with these typical supratentorial changes and is usually asymptomatic. We report here an uncommon hypertensive patient with isolated, severe, and symptomatic brain stem and cerebellar edema with fourth ventricular obstruction and mild hydrocephalus. Rapid treatment of hypertension resulted in clinical and radiological improvement. Prompt recognition of the cause and aggressive treatment of hypertension in such patients are crucial to relieve edema and prevent life-threatening progression.

Acute muscarinic and nicotinic side effects of organophosphate (OP) poisoning are well known and easily recognized, but neuropsychiatric changes are rarely reported. We are reporting a case of a 22-year-old male who developed psychotic features and motor neuropathy following acute OP poisoning.

The HER-2/neu proto-oncogene is amplified in 15%-25% of breast cancers. In the current study, we evaluated HER-2/neu status of 396 cases of breast cancer by fluorescence in situ hybridization (FISH), and the results were correlated with immunohistochemistry (IHC) for HER-2/neu protein expression.Overall, HER-2/neu amplification was observed in 38.4% of cases. Concordance between IHC and FISH was 90.4% considering only IHC score 0, 1 (negative), and 3 (positive). However, only 37.3% of the IHC score 2 (equivocal) cases showed HER-2/neu gene amplification. A majority of the discordant cases within the IHC negative (score 0 and 1) and IHC positive (score 3) were high-grade tumors. Polysomy 17 and monosomy 17 was seen in 7.3% of the total cases of each. Furthermore, a majority of FISH positive cases were noted in Intraductal Carcinoma grade III and cases with regional lymph nodal metastasis. Polysomy 17 was seen in 7.9% of the FISH positive cases and in 6.3% of the FISH negative cases. Monosomy 17, however was more preponderant in FISH negative cases.We believe that the FISH test should be considered as the gold standard in the estimation of the HER-2/neu status due to its increased sensitivity and better appreciation of aneusomy 17.

Organophosphate poisoning is the most common poisoning in developing countries. Although the acute muscarinic and nicotinic side-effects of organophosphate poisoning are well known and easily recognized, but neuropsychiatric changes are rarely reported. We are reporting a case of a 33-year-old female who developed manic episode following acute organophosphate poisoning.

Cerebral toxoplasmosis is a frequent complication in immunosuppressed patients such as AIDS (acquired immunodeficiency syndrome). Frequently, lesions are located deep in the brain which are inaccessible for biopsy making rapid diagnosis dependent on accurate interpretation of neuroimaging findings. The commonest cranial CT findings reported in toxoplasmosis are ring enhancing hypodense lesions in basal ganglia or cortical gray matter. Hemorrhage has only rarely been described and is usually seen following antitoxoplasma treatment. We reviewed the records of 11 AIDS patients with cerebral toxoplasmosis and found multiple hemorrhagic cerebral, cerebellar, or brain stem lesions in 7 of 11 patients. Six patients had hemorrhage at the time of initial clinical presentation and one developed hemorrhage following 2 weeks of antitoxoplasma treatment. We conclude that hemorrhagic lesions are frequently found on cranial MRI scans in cerebral toxoplasmosis. AIDS patients presenting with hemorrhagic cerebral lesions should be considered for a trial of presumptive antitoxoplasma treatment.

Primary malignant phyllodes tumor of the breast accounts for 0.3-1% of all the tumors of breast and only a couple of cases of pleomorphic liposarcoma (PL) arising in a malignant phyllodes (MP) tumor have been reported. A thorough sampling is most essential in phyllodes tumor, not only to detect high grade component of the neoplasm but also to diagnose heterologous elements in the same lesion elsewhere, as it may affect the prognosis adversely and may have a greater metastatic potential.

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