Cryptococcal infection causing longitudinal extensive transverse myelitis in an immunocompetent individual: Case report and literature review.

Cryptococcal CNS infections in immunocompetent individuals are occasionally reported in literature. The spinal manifestations of cryptococcal CNS infections are epidural abscess, chronic arachnoiditis, intramedullary granuloma, myelitis and vasculitis. We report a rare case of CNS cryptococcal infection presenting as a longitudinal extensive transverse myelitis (LETM) in an immunocompetent male. This report highlights cryptococcus as an important etiology among infectious causes in acute LETM patients in-spite of the immunocompetent status of the patient and the utility of CRAG (cryptococcal antigen) for diagnosis in such patients. We also present a literature review of all reported cases of cryptococcal myelitis.

Autoimmune Encephalitis versus Creutzfeldt-Jakob disease in a patient with typical Facio-brachial dystonic seizures: A case report with Diagnostic challenges.

BACKGROUND: Diagnosis of rapidly progressive dementia (RPD) is very challenging. There are many conditions that fall into category of RPD ranging from autoimmune causes to neurodegenerative causes. Autoimmune encephalitis should be readily diagnosed and treated because of its response to immunomodulators. However there is no treatment available for conditions like Creutzfeldt-Jakob disease (CJD). CASE PRESENTATION: Here we present a case of anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis who presented with only typical facio-brachial dystonic seizures at presentation. On follow up, patient had a rapid cognitive decline with development of myoclonic jerks, akinetic mute state and ultimately death. Neuroimaging showed presence of hyperintensities in two cortical regions namely parietal and occipital on fluid-attenuated inversion recovery (FLAIR) sequence. Electroencephalogram showed diffuse slowing with occasional periodic sharp wave complexes. Thus a diagnosis of probable CJD was made. CONCLUSION: Autoimmune encephalitis mimicking CJD or vice versa is not a very commonly encountered phenomenon. This case discusses the clinical overlap of these two conditions and its diagnostic dilemmas. This case presented with typical LGI1 encephalitis and in spite of therapy with immunomodulators had a rapid decline and ultimately turned out to be CJD. This has been rarely described in literature.

Evidence-Based Discriminant Analysis: A New Insight into Iron Profile for the Diagnosis of Parkinson's Disease.

INTRODUCTION: Parkinson's disease is the second most common neurodegenerative disorder. Neurochemical studies have implicated metals in pathogenesis of PD. OBJECTIVES: To examine the association of serum iron, transferrin, ferritin, transferrin saturation and UIBC in PD patients and to derive the Discrimination Function with scores of these variables to correctly classify PD cases and healthy controls. METHODS: In the present study, identification of biomarker pool in case-control study involving 79 PD cases and 80 healthy controls were performed. RESULTS: The results of independent t-test analysis showed that PD cases presented significantly higher (P < 0.01) level of transferrin, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and urea than controls. As only one-third of transferrin is saturated with iron, so the transferrin present in serum has the extra binding capacity (67%), this is called UIBC. Discriminant analysis was performed to determine the factors that best discriminate between the categories of an outcome variables (Disease status = PD and Control) and total of five biochemical independent variables (UIBC, transferrin, iron, transferrin saturation, and copper) were taken into consideration. UIBC has emerged out to be highest discriminating, powerful and independent variable among considered independent variables, which indicates iron deficiency. After development of Discriminant Function (Z) and calculation of discriminant function cut points, a cross-validation analysis of PD cases and controls were conducted. The sensitivity of the developed model was 98.73% and specificity 83.75%. Receiver operating characteristics (ROC) was plotted, and the findings of ROC curve corroborated with the results obtained from discriminant function analysis. CONCLUSION: Prospective validation of Discriminant model in large cohort is warranted in future studies.

Viral Induced Oxidative and Inflammatory Response in Alzheimer's Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach.

Alzheimer's disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets. These genes were individually used to create protein-protein interaction network using STRING database (score≥0.7). The interactions of candidate genes with known viruses were mapped using virhostnet v2.0 database. Drug molecules targeting candidate genes were retrieved using the Drug- Gene Interaction Database (DGIdb). Data mining resulted in 2095 APP, 116 MAPT, 214 oxidative stress, 1269 inflammatory genes. After STRING PPIN analysis, 404 APP, 109 MAPT, 204 oxidative stress and 1014 inflammation related high confidence proteins were identified. The overlap among all datasets yielded eight common markers (AKT1, GSK3B, APP, APOE, EGFR, PIN1, CASP8 and SNCA). These genes showed association with hepatitis C virus (HCV), Epstein- Barr virus (EBV), human herpes virus 8 and Human papillomavirus (HPV). Further, screening of drugs targeting candidate genes, and possessing anti-inflammatory property, antiviral activity along with a suggested role in AD pathophysiology yielded 12 potential drug candidates. Our study demonstrated the role of viral etiology in AD pathogenesis by elucidating interaction of oxidative stress and inflammation causing candidate genes with common viruses along with the identification of potential AD drug candidates.

Endoscopic Treatment of Hydrocephalus with Minimal Resources: Resource Utilization and Indigenous Innovation in Developing Countries like India.

CONTEXT: Neuroendoscopic surgeries need specialized equipments, unavailable in neurosurgical departments of majority of public healthcare institutions of India. Aims: Neuroendoscopic treatment of hydrocephalus in the setting of minimal resources using utilization of available resources, inter-departmental co-ordination and indigenous innovations. METHODS: Study was carried out at a public sector institute of India with scarce resources. Senior author (DKJ) used indigenously designed stainless steel working sheath along with equipments of 'awake endoscopic intubation system' of department of neuroanesthesia and 18 cm, 4 mm, 0° rigid telescope for neuroendoscopic surgeries for various intraventricular pathologies. RESULTS: Thirty-four neuroendoscopic surgeries in 32 patients were done over last 3 years. There were 18 males and 14 females with average age of 23 years. It included hydrocephalus due to tubercular meningitis (n = 19), neurocysticercosis (NCC) (n = 4), intra-ventricular (n = 2) and para-ventricular (n = 2) space occupying lesions, aqueduct stenosis with (n = 2) or without (n = 1) shunt malfunction and one case each of pyogenic meningitis and right cerebellar infarction. Endoscopic third ventriculostomy (ETV) (n = 28), septostomy (n = 6), removals of cystic lesions (n = 3) and biopsies of intraventricular lesions (n = 2) were done in a total of 34 neuroendoscopic surgeries. Overall there were four failures of ETVs, which were managed by ventriculo-peritoneal shunts. Two mortalities in the study group were unrelated to the surgical procedures. CONCLUSION: Indigenous innovations and interdisciplinary co-ordination are the way ahead to tackle resource scarcity in public sector healthcare institutions of India in the scenario of plenty of neuroendoscopic trainings opportunities for young neurosurgeons and paucity of equipments required.

Peripheral neuropathy and the role of nerve biopsy: A revisit.

BACKGROUND: Nerve biopsy has been widely used to investigate patients with peripheral neuropathy and in many centers, it is still a part of the diagnostic armamentarium. In this study, the histopathological spectrum of the nerve biopsies received is being revisited to analyze the various clinical and pathologic features and also to assess their relevance. MATERIALS AND METHODS: Retrospective analysis of the data retrieved was done for 74 cases of nerve biopsies. RESULTS: On the basis of the data and histopathological features, broad diagnoses were obtained in 52 cases and further categorized into biopsies being supportive for patient management (including acute and chronic axonopathies and demyelinating neuropathies) and biopsies considered essential for patient management (including vasculitic neuropathies, leprous neuropathies, hereditary neuropathies, and chronic inflammatory demyelinating neuropathies). Nine nerve biopsies did not show any abnormal histopathological features, while 13 nerve biopsies were found to be inadequate for diagnosis, both these groups were categorized as noncontributory. CONCLUSION: With advanced nerve conduction studies available, nerve biopsy is losing its relevance. However, in our experience, nerve biopsy did complement the clinical findings and nerve conduction studies, with which a close correlation is required to make the histopathology of nerve biopsy more relevant in terms of guiding further specific workup and management.

Hyper Acute Demyelinating Encephalomyelitis of Childhood: A Rare Entity.

A young child with catastrophic neurological illness diagnosed as a rare variant of acute demyelinating encephalomyelitis (ADEM). She succumbed to her illness despite of aggressive and appropriate management. Malignant demyelinating encephalomyelitis should be considered in children who are refractory to the treatment of ADEM.

Role of Iron and Copper in the Pathogenesis of Parkinson's Disease.

Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization of α-synuclein protein and formation of intercellular inclusions known as "Lewy bodies" in substantia nigra and caudate nuclei in brain which is progressive in nature. It is second most prevalent neurodegenerative disorder characterized by tremor at rest, muscle rigidity, slowness of movement (bradykinesia, akinesia), and changes in posture (instability). Both excess and deficiency in levels of transition metals (especially iron, copper) can be detrimental to the central nervous system. Abnormalities in iron (Fe) and copper (Cu) metabolism have been reported to produce oxidative stress which is one of the major cause in pathogenesis of PD. In the present study 35 PD patients and 33 controls of Northern Indian population were included and serum levels of Fe, Cu and ceruloplasmin (Cp) were measured. Serum Fe (p < 0.01) and Cu (p < 0.01) levels were found to be significantly decreased in PD, whereas there was no significant change in Cp levels in PD patients as compared to controls. These results suggest the existence of a defect in iron which over the time, may hasten the entry of iron into the brain and decrease iron in the extracellular compartment in PD patients.

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population.

BACKGROUND: Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. METHODS: We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk. RESULTS: The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0.0001, OR = 2.66, 95% CI 1.58-4.46) in AD as compared to controls, whereas ε2 (p = 0.0430, OR = 0.29, CI 0.07-1.10) was overrepresented in controls. In biochemical assays, significant differences in levels of total copper, free copper, zinc, copper/zinc ratio, iron, epidermal growth factor receptor (EGFR), leptin, and albumin were also observed. The AD risk score (ADRS) as a linear combination of 6 candidate markers involving age, education status, APOE ε4 allele, levels of iron, Cu/Zn ratio, and EGFR was created using stepwise linear discriminant analysis. The area under the ROC curve of the ADRS panel for predicting AD risk was significantly high (AUC = 0.84, p < 0.0001, 95% CI 0.78-0.89, sensitivity = 70.0%, specificity = 83.8%) compared to individual parameters. CONCLUSION: These findings support the multifactorial etiology of AD and demonstrate the ability of a panel involving 6 biomarkers to discriminate AD cases from non-demented healthy controls.

Skull Base Surgery with Minimal Resources.

BACKGROUND: Skull base surgery needs advanced equipment and is performed at few public sector hospitals in India. For financial and infrastructure reasons, the facilities available are insufficient for the large number of poor patients who need this surgery. METHODS: Neurologically deteriorating poor patients who failed to receive skull base surgery at overloaded public sector hospitals underwent surgery with basic neurosurgical instruments, using the available resources and indigenously designed instruments adhering to the basic principles of skull base surgery. Various lesions operated on in the study were analyzed based on their location and surgical approach. RESULTS: Ninety-one skull base surgeries in 84 patients were performed during 2013-2015. There were 46 males and 38 females, with an average age of 35 years. Surgical treatment included surgery of the craniovertebral junction (n = 43) and lesions of the anterior skull base (n = 7), middle skull base (n = 10), and posterior skull base (n = 31). Lesions were operated on through anterior (n = 10), lateral (n = 14), and posterior and posterolateral (n = 67) skull base approaches. CONCLUSIONS: The facilities available in low-income countries such as India are insufficient to take care of poor patients who need skull base surgery. Indigenous innovations, use of the available resources, and interdisciplinary coordination help overcome the challenges of resource scarcity to a reasonable extent in many ill-equipped public sector hospitals for the safe and efficient management of many patients who need skull base surgery.

Intrinsic Vertebral Markers for Spinal Level Localization in Anterior Cervical Spine Surgery: A Preliminary Report.

STUDY DESIGN: Prospective clinical study. PURPOSE: To observe the usefulness of anterior cervical osteophytes as intrinsic markers for spinal level localization (SLL) during sub-axial cervical spinal surgery via the anterior approach. OVERVIEW OF LITERATURE: Various landmarks, such as the mandibular angle, hyoid bone, thyroid cartilage, first cricoid ring, and C6 carotid tubercle, are used for gross cervical SLL; however, none are used during cervical spinal surgery via the anterior approach. We present our preliminary assessment of SLL over anterior vertebral surfaces (i.e., intrinsic markers) in 48 consecutive cases of anterior cervical spinal surgeries for the disc-osteophyte complex (DOC) in degenerative diseases and granulation or tumor tissue associated with infectious or neoplastic diseases, respectively, at an ill-equipped center. METHODS: This prospective study on patients undergoing anterior cervical surgery for various sub-axial cervical spinal pathologies aimed to evaluate the feasibility and accuracy of SLL via intraoperative palpation of disease-related morphological changes on anterior vertebral surfaces visible on preoperative midline sagittal T1/2-weighted magnetic resonance images. RESULTS: During a 3-year period, 48 patients (38 males,10 females; average age, 43.58 years) who underwent surgery via the anterior approach for various sub-axial cervical spinal pathologies, including degenerative disease (n= 42), tubercular infection (Pott's disease; n=3), traumatic prolapsed disc (n=2), and a metastatic lesion from thyroid carcinoma (n=1), comprised the study group. Intrinsic marker palpation yielded accurate SLL in 79% of patients (n=38). Among those with degenerative diseases (n=42), intrinsic marker palpation yielded accurate SLL in 76% of patients (n=32). CONCLUSIONS: Intrinsic marker palpation is an attractive potential adjunct for SLL during cervical spinal surgeries via the anterior approach in well-selected patients at ill-equipped centers (e.g., those found in developing countries). This technique may prove helpful when radiographic visualization is occasionally inadequate.

Muscle histopathology in today's era of molecular genetics: Role and limitations.

INTRODUCTION: Past few decades have seen an increasing application of techniques like electron microscopy, western blotting, and molecular genetics in the evaluation of muscle diseases. However, due to their limited availability, histopathological interpretation of muscle biopsies still remains an important component of diagnostic approach to muscle diseases. A systematic methodology is required in the evaluation and interpretation of muscle biopsies. This study was undertaken to analyze the histopathological spectrum of 164 muscle biopsies and to assess the diagnostic yield of basic histopathological procedures in the work up of muscle biopsy. MATERIALS AND METHODS: Retrospective analysis was done for 164 cases of muscle biopsies. Step-wise approach was adopted to assess the efficacy of routine stains, enzyme histochemistry, and immunohistochemistry. Based on hematoxylin and rosin (H and E) appearance, biopsies were broadly categorized into destructive, nondestructive but myopathic, and inflammatory morphology. Role of special stains, enzyme, and immunohistochemical stains in each category was then evaluated. RESULTS: On the basis of histopathological features, 164 muscle biopsies were broadly categorized into biopsies with abnormal histopathological features (115) and biopsies with normal histopathology (49). Abnormal muscle biopsies were further categorized into destructive morphology (56.5%), nondestructive but myopathic morphology (30.5%), and inflammatory pathology (13%). A near definitive diagnosis could be made in 115 cases out of 164 muscle biopsies on the basis of routine histopathology, enzyme histochemistry, and immunohistochemistry. CONCLUSION: Though advanced techniques like electron microscopy, western blotting, and molecular genetics are essential for confirmatory diagnosis, a substantive diagnostic yield can be offered with the basic armamentarium of routine (frozen) stains, enzyme histochemistry, and immunohistochemistry.

Intravascular lymphoma: an unusual cause of rapid cognitive decline and the role of brain biopsy.

Intravascular lymphoma (IVL) is a rare extra nodal variant of non Hodgkin's lymphoma characterised by neoplastic lymphoid cells growing inside the lumina of medium and small vessels. IVL limited to the central nervous system (CNS) is an extremely rare condition as IVL is usually found with systemic lesions. Most cases of IVL are not diagnosed until post mortem because of variable clinical presentation and non-specific laboratory findings. Even if diagnosed early the disease is clinically aggressive and usually fatal, even with early detection and treatment. We present a case of a 37-year-old woman with a short history of behavioural abnormality, rapidly progressive cognitive decline and seizures. There were no cutaneous manifestations. Diagnosis was established only after the brain biopsy. The case is presented for the rarity of its presentation and role of brain biopsy in diagnosis.

Prevalence of HIV-associated cryptococcal meningitis and utility of microbiological determinants for its diagnosis in a tertiary care center.

CONTEXT: Human immunodeficiency virus (HIV) infection continues to be the most important risk factor for the development of central nervous system (CNS) cryptococcosis, which in turn is an important contributor to morbidity and mortality in HIV-infected patients. Early diagnosis of such patients is the key to their therapeutic success. AIMS: This study was undertaken to find out the prevalence of CNS cryptococcosis and to assess the role of microbiological parameters for its specific diagnosis in HIV-reactive hospitalized patients admitted with meningeal signs in a tertiary care setting. MATERIALS AND METHODS: A total of 104 patients suspected to be suffering from meningitis/meningoencephalitis were subjected to cerebrospinal fluid (CSF) analysis (including India ink preparation, culture by conventional methods and Bactec MGIT 960 system, antigen detection) and tests for HIV antibodies by standard laboratory operating procedures. RESULTS: The prevalence of HIV infection in our study group was 12.5% (13/104), while the prevalence of cryptococcal CNS infection in HIV-reactive cohort was 46% (6/13). Additionally, 15.3% (2/13) of the patients from this cohort were positive for Mycobacterium tuberculosis. CONCLUSIONS: High prevalence of cryptococcal CNS infections in HIV-infected patients underscores the importance of precise and early microbiological diagnosis for better management of such patients.