Role of vitreous cytology in the diagnosis of primary central nervous system lymphoma: A report of an unusual presentation.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma confined to the brain, spinal cord, meninges, intraocular compartment, and cranial nerves. Intraocular lymphoma (IOL) is a rare subtype of PCNSL. Intravitreal involvement by a PCNSL is an infrequent but potentially fatal event. The role of vitreous cytology in diagnosing IOLs is vital but has been sporadically described in the literature due to its variable sensitivity. Herein, we present a case of PCNSL, who primarily presented with ocular symptoms and could be accurately diagnosed based on vitreous cytology and subsequently confirmed on stereotactic brain biopsy.

PERK inhibitor, GSK2606414, ameliorates neuropathological damage, memory and motor functional impairments in cerebral ischemia via PERK/p-eIF2ɑ/ATF4/CHOP signaling.

The protein kinase R-like endoplasmic reticulum kinase/eukaryotic initiation factor 2ɑ (PERK/eIF2α), the branch of unfolded protein response (UPR), is responsible for transient arrest in translation to counter the enhanced levels of misfolded or unfolded proteins in the endoplasmic reticulum (ER) following any acute condition. In neurological disorders, overactivation of PERK-P/eIF2-P signaling, leads to a prolonged decline in global protein synthesis resulting in synaptic failure and neuronal death. Our study has shown, PERK/ATF4/CHOP pathway gets activated following cerebral ischemia in rats. We have further demonstrated, PERK inhibitor, GSK2606414 ameliorates ischemia induced neuronal damage by preventing additional neuronal loss, minimizing brain infarct, reducing brain edema, and preventing neurological symptoms from appearing. GSK2606414 was found to improve the neurobehavioral deficits and reduce the pyknotic neurons in ischemic rats. Also, it decreased glial activation and apoptotic protein mRNA expression while enhanced the synaptic protein mRNA expression in rat brain following cerebral ischemia. In conclusion, our findings suggest that PERK/ATF4/CHOP activation play a vital role in cerebral ischemia. Thus, PERK inhibitor, GSK2606414 might be a potential neuroprotective agent in cerebral ischemia.

Expressional Study of Permeability Glycoprotein and Multidrug Resistance Protein 1 in Drug-resistant Mesial Temporal Lobe Epilepsy.

Introduction: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue. Methods: We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15). Results: Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy. Conclusion: Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.

The outcome of TSHoma from a tertiary care institute in India.

BACKGROUND: Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is the rarest functioning pituitary adenoma. METHODS: A retrospective analysis of eight patients of TSHomas to highlight the presentations, diagnostic challenges, and treatment outcomes. RESULTS: Median age at diagnosis was 42 years, median latency to diagnosis was 2.5 years, and thyrotoxic and compressive symptoms were the most common presenting symptoms. At presentation, three cases were plurihormonal, six cases were on medical treatment including thyroxine, and two cases were incidentally discovered. Imaging revealed macroadenoma in all cases. Seven cases underwent pituitary surgery, after which three achieved remission. Another case entered remission after adjunctive radiotherapy. Thyrotropin (TSH) immunostaining was demonstrated in six out of seven adenomas. CONCLUSION: TSHoma is a rare functioning pituitary tumor with both silent and symptomatic presentations. Diagnosis can be established with biochemical and imaging features, even without dynamic tests.

Palmoplantar Involvement in Leprosy: A Clinicopathological Study.

Palmoplantar involvement has been infrequently reported in leprosy and is an easily misdiagnosed entity. The institutional database of leprosy clinic from 2015 to 2018 was accessed. Details pertaining to demography, clinical presentation, comorbidities (if any), treatment received, and outcome were analyzed in leprosy patients with palmoplantar involvement. Among the 520 patients studied, the involvement of palms and/or soles was reported in 49 (9.4%) patients. Isolated palm involvement was the most frequent (26/49, 53.1%), followed by both palm and sole involvement (12/49, 24.5%) and sole involvement alone (11/49, 22.4%). A higher incidence of lepra reactions and disabilities was noted in patients with palmoplantar involvement than in those without (P < 0.0001). Palmoplantar involvement in leprosy, although uncommon, is associated with a higher risk of reactions and disabilities. A knowledge of this aspect of leprosy can help in maintaining a high index of suspicion and reduce misdiagnosis.

Cervico Medullary Junction "Intramedullary Schwannoma" Masquerading As Glioma: A Surprise During Surgery.

BACKGROUND: Intramedullary schwannomas (IS) at cervicomedullary junction (CMJ) are exceedingly uncommon. There is hardly any clinicoradiological marker for preoperative diagnosis and prognostication. CASE: We report a case of a 17-year-old boy with progressive spastic quadriparesis of six months duration. On radiology, there was a contrast-enhancing lesion expanding the cord extending from the medulla to C5 level. During surgery, the cord was expanded and the tumor was eccentric. Histopathology and immunohistochemistry were suggestive of schwannoma. In view of the ill-defined plane of separation from the normal neural tissue, only subtotal resection could be achieved. CONCLUSION: Schwannoma should be considered as a remote differential of intramedullary lesions. The extent of resection should be tailored according to the plane of dissection and intraoperative neuromonitoring guidance. Though a masquerader, schwannoma carries better prognosis than rest of the pathologies.

Dermoscopy of Follicular Dowling-Degos Disease.

Dowling-Degos disease (DDD) is a late-onset genodermatosis characterized by hyperpigmented macules on the flexures along with scattered comedo-like lesions and pitted acneiform scars. Follicular Dowling-Degos is a rare type of DDD, with only two reports so far. It presents with follicular papules and comedo-like lesions predominantly on the face and trunk. Dermoscopy of follicular DDD shows irregular star-shaped/Chinese letter pattern pigmentation along with comedo-like lesions. Herein, we describe diagnostic clues including dermoscopy in three patients of follicular DDD which can help in differentiating it from other disorders presenting with comedo-like lesions.

Nevoid hyperkeratosis of male breast: Successful treatment with minocycline.

Nevoid hyperkeratosis of the nipple and/or areola (NHNA) is an uncommon disease with no definite etiology. NHNA of the male breast is rare in clinical practice. Despite being a benign disease, it is distressing for patients and therapeutically challenging for clinicians. We report a male patient with NHNA who responded favorably to minocycline treatment.

Proteomic Analysis of the Human Anterior Pituitary Gland.

The pituitary function is regulated by a complex system involving the hypothalamus and biological networks within the pituitary. Although the hormones secreted from the pituitary have been well studied, comprehensive analyses of the pituitary proteome are limited. Pituitary proteomics is a field of postgenomic research that is crucial to understand human health and pituitary diseases. In this context, we report here a systematic proteomic profiling of human anterior pituitary gland (adenohypophysis) using high-resolution Fourier transform mass spectrometry. A total of 2164 proteins were identified in this study, of which 105 proteins were identified for the first time compared with high-throughput proteomic-based studies from human pituitary glands. In addition, we identified 480 proteins with secretory potential and 187 N-terminally acetylated proteins. These are the first region-specific data that could serve as a vital resource for further investigations on the physiological role of the human anterior pituitary glands and the proteins secreted by them. We anticipate that the identification of previously unknown proteins in the present study will accelerate biomedical research to decipher their role in functioning of the human anterior pituitary gland and associated human diseases.

Imatinib Inhibits GH Secretion From Somatotropinomas.

Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in children with chronic myeloid leukemia probably by targeting the growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib targets expression in pituitary adenomas and study the effect of imatinib on GH secretion in somatotropinoma cells and GH3 cell line. Materials and Methods: The expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-α/ß) was studied using immunohistochemistry and immunoblotting 157 giant (≥4 cm) pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas, and four prolactinomas) and compared to normal pituitary (n = 4) obtained at autopsy. The effect imatinib on GH secretion, cell viability, immunohistochemistry, electron microscopy, and apoptosis was studied in primary culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell-line. A receptor tyrosine kinase array was applied to human samples to identify altered pathways. Results: Somatotropinomas showed significantly higher immunopositivity for c-kit and platelet-derived growth factor receptor-ß (PDGFR-ß; P < 0.009 and P < 0.001, respectively), while staining for platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor (VEGF) revealed a weaker expression (P < 0.001) compared to normal pituitary. Imatinib inhibited GH secretion from both primary culture (P < 0.01) and GH3 cells (P < 0.001), while it did not affect cell viability and apoptosis. The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via PDGFR-ß pathway. Conclusion: Imatinib inhibits GH secretion in somatotropinoma cells without affecting cell viability and may be used as an adjunct therapy for treating GH secreting pituitary adenomas.

Clinical, demographic and immunopathological spectrum of subepidermal autoimmune bullous diseases at a tertiary center: A 1-year audit.

BACKGROUND: The subepidermal autoimmune bullous diseases are a subset of immunobullous diseases encountered less frequently in the Indian population. There is a paucity of data on the prevalence, demographic and clinicopathological spectrum of various subepidermal autoimmune bullous diseases from India. AIM: To determine the demographic and clinicopathological profile of subepidermal autoimmune bullous diseases in Indian patients, presenting to the Immunobullous Disease Clinic of Postgraduate Institute of Medical Education and Research, Chandigarh. METHODS: Patients seen from November 2013 to November 2014 who fulfilled the preset diagnostic criteria of subepidermal autoimmune bullous diseases were identified from case records. Data regarding demographic characteristics, clinical profile, immunopathological findings and treatment were collected from the predesigned proforma. RESULTS: Of 268 cases of autoimmune bullous diseases registered, 50 (18.7%) were subepidermal autoimmune bullous diseases. Bullous pemphigoid was most frequently seen in 20 (40%) cases, followed by dermatitis herpetiformis in 14 (28%), mucous membrane pemphigoid in 6 (12%), chronic bullous dermatosis of childhood / linear immunoglobulin A bullous dermatosis in 5 (10%), lichen planus pemphigoides in 3 (6%), pemphigoid gestationis and epidermolysis bullosa acquisita in 1 (2%) case each. None of the patients had bullous systemic lupus erythematosus. LIMITATIONS: We could not perform direct and indirect immunofluorescence using salt-split skin as a substrate and immunoblotting due to non-availability of these facilities. Therefore, misclassification of subepidermal autoimmune bullous diseases in some cases cannot be confidently excluded. CONCLUSION: Subepidermal autoimmune bullous diseases are not uncommon in Indian patients. Bullous pemphigoid contributes maximally to the burden of subepidermal autoimmune bullous diseases in India, similar to that in the West, although the proportion is lower and disease onset is earlier. Dermatitis herpetiformis was observed to have a higher prevalence in our population, compared to that in the West and the Far East countries. The prevalence of other subepidermal autoimmune bullous diseases is relatively low. Detailed immunofluorescence and immunoblotting studies on larger patient numbers would help better characterize the pattern of subepidermal autoimmune bullous diseases and their features in Indian patients.

Which Classification of Cavernous Sinus Syndrome is Better - Ishikawa or Jefferson? A Prospective Study of 73 Patients.

INTRODUCTION: Ishikawa and Jefferson are the two most commonly used systems used for the classification of cavernous sinus syndrome (CSS). However, relative utilities of these two classification systems have not been evaluated in detail in developing countries. In this study, we compared relative utilities of these two classification schemes in the evaluation of CSS. OBJECTIVE: To compare the utility of Jefferson and Ishikawa classifications in the evaluation of CSS. PATIENTS AND METHODS: A total of 73 consecutive patients of CSS were prospectively classified using either Ishikawa or Jefferson classification and relative utility of these two classification schemes in determining etiology of CSS was compared. RESULTS: While only 46.6% of patients could be classified using Jefferson classification, 95.5% of patients could be classified using Ishikawa scheme. CSS was classified as anterior, middle, and posterior in 17.8%, 21.9%, and 8.2% of patients, respectively, as per the Jefferson classification. As per the Ishikawa classification, 37% of patients each showed anterior and posterior CSS, 16.4% showed middle CSS, whereas 4.1% had whole CSS. Middle CSS was significantly associated with the presence of fungal infections (P = 0.045) as per Jefferson classifications, and anterior CSS was significantly associated with a vascular etiology (P = 0.005) as per Ishikawa classification. Overall, inflammatory causes were the most common cause for anterior CSS, while tumors accounted for maximum cases of posterior CSS. CONCLUSION: Although more number of patients could be classified using Ishikawa classification, there was no advantage of Ishikawa classification over Jefferson with regard to determination of etiology of CSS.

Clinical profile and outcome of patients with acromegaly according to the 2014 consensus guidelines: Impact of a multi-disciplinary team.

AIM: The diagnosis and treatment of acromegaly, a rare and possibly curable disease, has undergone a paradigm shift in the past few decades. Our aim was to study the changing trends in clinical presentation, management and outcome of the disease in the last fifteen years. METHODOLOGY: 271 consecutive patients with acromegaly treated at the Departments of Endocrinology and Neurosurgery, PGIMER, Chandigarh, between 2000 and 2014, were included in the study. Clinical and hormonal profiles, comorbidities, treatment modalities, outcome and mortality data were evaluated. The cure rate was assessed according to the present consensus criteria. RESULTS: The gender distribution was equal with the mean age (±SD) of 37.1 ± 12.3 years at diagnosis. The average lag period to diagnosis was 4.7 ± 4.2 years. The most common presenting manifestations were acral enlargement and headache followed by visual deficits. The overall mortality rate was 5%, with the perioperative mortality being 1.5%. The most prevalent comorbidities in our series were hypertension (17.7%), diabetes mellitus (16.2%), arthropathy (11.8%) and obstructive sleep apnea (10.3%). Overall, 2 patients in our series suffered from extra-pituitary neoplasms and 12 patients had apoplexy as the presenting manifestation. As per the present consensus criteria, cure rate in our series was 28.5%. The cure rate was only 7.9% when many surgeons were operating. It increased to 25.5% when surgeries were being performed by one surgeon exclusively; and, when a sub-specialty clinic exclusively for pituitary diseases was set up, the cure rates improved upto 56%. CONCLUSION: Acromegaly has wide-ranging manifestations from acral enlargement to altered sensorium; incidental diagnosis was not prevalent in our series. Majority of the cases were due to the presence of a pituitary macroadenoma. Better cure rate can be achieved only when a dedicated group of multi-disciplinary team is involved.

True mycotic aneurysm in a patient with gonadotropinoma after trans-sphenoidal surgery.

BACKGROUND: Immunosuppressive therapy, prolonged antibiotic use, and intrathecal injections are known risk factors for the development of invasive aspergillosis. Central nervous system (CNS) aspergillosis can manifest in many forms, including mycotic aneurysm formation. The majority of the mycotic aneurysms presents with subarachnoid hemorrhage after rupture and are associated with high mortality. Only 3 cases of true mycotic aneurysms have been reported following trans-sphenoidal surgery. CASE DESCRIPTION: A 38-year-old man was admitted with nonfunctioning pituitary adenoma for which he underwent trans-sphenoidal surgery. Three weeks later, he presented with cerebrospinal fluid (CSF) rhinorrhea and meningitis. He was treated with intrathecal and intravenous antibiotics, stress dose of glucocorticoids, and lumbar drain. The defect in the sphenoid bone was closed endoscopically. After 3 weeks of therapy, he suddenly became unresponsive, and computed tomography of the head showed subarachnoid hemorrhage. He succumbed to illness on the next day, and a limited autopsy of the brain was performed. The autopsy revealed extensive subarachnoid hemorrhage and aneurysmal dilatation, thrombosis of the basilar artery (BA), multiple hemorrhagic infarcts in the midbrain, and pons. Histopathology of the BA revealed the loss of internal elastic lamina and septate hyphae with an acute angle branching on Grocott's methenamine silver stain, conforming to the morphology of Aspergillus. CONCLUSION: The possibility of intracranial fungal infection should be strongly considered in any patient receiving intrathecal antibiotics who fails to improve in 1-2 weeks, and frequent CSF culture for fungi should be performed to confirm the diagnosis. Since CSF culture has poor sensitivity in the diagnosis of fungal infections of CNS; empirical institution of antifungal therapy may be considered in this scenario.