Background: Evidence from various consortia on vascular contributions has been inconsistent in determining the etiology of sporadic Alzheimer's disease (AD). Objective: To investigate vascular risk factors and cerebrovascular pathologies associated in manifestation of AD-related neuropathological c hanges of an elderly population. Methods: Postmortem brain samples from 76 elderly subjects (≥50 years) were used to study genetic polymorphisms, intracranial atherosclerosis of the circle of Willis (IASCW), and microscopic infarcts in deep white matters. From this cohort, 50 brains (≥60 years) were subjected to neuropathological diagnosis using immunohistopathological techniques. Results: Besides the association with age, the apolipoprotein E ɛ4 allele was significantly and strongly associated with Thal amyloid-β phases ≥1 [odds ratio (OR) = 6.76, 95% confidence interval (CI) 1.37–33.45] and inversely with Braak neurofibrillary tangle (NFT) stages ≥III (0.02, 0.0–0.47). Illiterates showed a significant positive association for Braak NFT stages ≥IV (14.62, 1.21–176.73) and a significant negative association for microscopic infarcts (0.15, 0.03–0.71) in deep white matters. With respect to cerebrovascular pathologies, cerebral small vessel lesions (white matter hyperintensities and cerebral amyloid angiopathy) showed a higher degree of associations among them and with AD-related neuropathological changes (p < 0.05) compared to large vessel pathology (IASCW), which showed a significant association only with Braak NFT stages ≥I (p = 0.050). Conclusion: These findings suggest that besides age, education, and genetic factors, other vascular risk factors were not associated with AD-related neuropathological changes and urge prompt actions be taken against cerebral small vessel diseases since evidence for effective prevention is still lacking.
Cavitron Ultrasonic Surgical Aspirator (CUSA) is a technique used for the surgical treatment of tumors that aids the surgeon in highly selective tumor sampling with minimal injury to surrounding tissues. The utility of the tissue obtained from CUSA for histopathological diagnosis of central nervous system tumors is not as well-known as its surgical benefits. Even though a few studies have evaluated the diagnostic accuracy of CUSA specimen, these have dealt with very few cases.In this study, we nil analysed 73 cases of CNS tumors (glial and non-glial) where CUSA specimen was available for histopathological examination and compared with findings on conventional samples as gold standard.Most frequent types of artefacts induced by CUSA included tissue breakdown resembling necrosis, empty spaces in tissues, and crush artefacts particularly in cellular tumors, that interfered with interpretation. CUSA samples were found optimal for diagnosis of non-glial tumors (45/73), (mainly mesenchymal), wherein the diagnostic utility was comparable to the conventional samples. Difficulties were encountered in glial neoplasms, medulloblastomas and meningiomas. In glial neoplasms (28/73), accurate grading was not possible (9/28, 32%) utilising CUSA samples alone as necrosis and mitosis were not represented. Similarly in meningiomas, mitosis and brain invasion, essential for grading, was not recognizable in CUSA samples. In medulloblastomas, extensive crush artefacts interfered with diagnosis and histological subtyping making it mandatory to examine conventional tissue samples and CUSA. Immunohistochemistry results were optimal with CUSA tissue, wherever performed.The greatest benefits of CUSA, is its ability to sample multiple areas enhancing the yield in heterogenous tumors like gliosarcomas and its utility in tumors at surgically inaccessible sites. As a policy, we recommend that it is beneficial that all surgically excised tissues including those from the CUSA bottle and suction be sent for histopathological analysis for optimising diagnostic accuracy.
Chemotherapeutic drugs like Cisplatin, Taxols used in cancer are associated with the development of peripheral neuropathy (PN). Severe neuropathy can occur in 3% to 7% of treated cases with single agents but the severity can increase to 38% with combined regimens. The treatment options for PN currently include anti-depressants, anti-convulsants and opioid analgesics. These agents are modestly effective for symptomatic relief, but they neither affect the underlying pathology nor do they slow progression of the disease. Therefore, effective treatment for chemotherapy induced neuropathy would be a major advantage for cancer patients. Benfotiamine (BT) a lipid soluble form of thiamine plays important role in various biological pathways reported beneficial effect in diabetic retinopathy. Erythropoietin (EPO) has recently been considered as a tissue protective cytokine.EPO is reported to protect neurons from ischemia reperfusion-induced injury, metabolic stress, HIV-induced damage or even mechanical injury such as nerve compression or trauma . Thereforethe present study was undertaken to evaluate the individual and combination effects of BT and EPO in cisplatin induced peripheral neuropathy in rats . PN was induced by Cisplatin - 2mg/kg,i.p. twice weekly for 8 weeks. The degree of protection was determined by measuring electrophysiological properties of sciatic nerve like nerve conduction velocity, behavioralparameters like motor in-coordination, thermal & cold hyperalgesia, grip strength, biochemal parameters like measurement of endogenous antioxidants and histopathological studies.PN was evidenced in Cisplatin control rats and ameliorated with administration of BT (100 mg/kg p.o daily)and EPO (500U/kg i.p. thrice weekly) for 8 weeks by augmenting all the above parameters.T4 exhibited neuroprotective activity, which would be attributed to its activity as neurotrophic effect.
We report an unusual case of unilateral limb pseudo hypertrophy in a 21-year-old lady who developed progressive enlargement of the right calf followed by thigh in association with chronic leg pain. Magnetic resonance imaging (MRI) of the affected limb confirmed enlargement of various muscles. Electromyography revealed neurogenic features consistent with S1 radiculopathy. MRI of the lumbosacral spine showed tethered cord with a lipoma infiltrating multiple sacral roots. Our case illustrates that muscular pseudo hypertrophy may follow chronic denervation as a consequence of spinal neural compressive disease. The various mechanisms postulated for this distinct condition are outlined.
The WHO 2016 classification of diffuse gliomas combines histological and molecular parameters for diagnosis. However, in view of cost constraints for molecular testing, an economical working formula is essential to reach a meaningful diagnosis in a resource-limited setting. The aim of this study was to establish a practical algorithmic approach using histology and immunohistochemistry (IHC) in the classification of diffuse gliomas in such a set-up.Diffuse gliomas of WHO grade II and III diagnosed in our institute in the year 2016 were analysed for histological and IHC features, using the markers isocitrate dehydrogenase 1 (IDH1R132H) and α thalassemia/mental retardation syndrome X-linked gene (ATRX). Fluorescence in situ hybridisation (FISH) for 1p/19q co-deletion was performed when requested.449 diffuse gliomas (grades II/III) were included in the study. Integrating histology and IHC features, as per the WHO 2016 guidelines, we derived the following groups: Astrocytoma, IDH-mutant (A,IDH-mt, 37.2%); astrocytoma, not otherwise specified (A,NOS, 12.7%); oligoastrocytoma, NOS (OA,NOS, 4.5%); and oligodendroglioma, NOS (ODG,NOS, 45.6%). FISH was performed in a subset of ODG,NOS, OA,NOS and A,NOS gliomas. This revealed 1p/19q co-deletion in all cases of ODG,NOS, 15.8% of OA,NOS and 37.5% of A,NOS. Sequencing for rare IDH 1/2 mutations was not carried out in this study.In a resource-limited set-up, histology with IHC (IDH1(R132H) and ATRX) form the baseline to reasonably derive four histomolecular subgroups of diffuse glioma. Of these, we recommend, OA,NOS and IDH1(R132H)-non-mt ODG,NOS to be our priority for performing 1p/19q co-deletion studies in comparison to IDH-mt ODG,NOS, and it would not be mandatory for astrocytoma. Sequencing for rare IDH mutations is advised for A,NOS and OA,NOS groups, but not for the IDH1(R132H)-non-mutant diffuse gliomas with 1p/19q co-deletion.
Choroid plexus neoplasms are rare intracranial neoplasms. Significant differences exist in their presentation and management in paediatric and adult populations. The present study aims to study the differences among the paediatric and adult population, various factors affecting the outcome, and the clinical and histological correlation. This is a retrospective study of 47 patients with choroid plexus neoplasms managed at NIMHANS from 1984 to 2004. The case records and images were retrieved and reviewed. The various histopathological features were outlined and histopathology reviewed accordingly. For follow-up, patients were contacted by letter or telephone and the necessary information obtained. Follow-up was available in 41 out of 47 patients. Sixty per cent patients were in the paediatric age group and 40% were adults. Forty-three per cent of children with tumours were less than 1 year of age. The lateral ventricle was the most common site of involvement in the paediatric group compared with the fourth ventricle in adults. Calcification is seen on CT scan more often in papillomas and in adult tumours. Invasion of surrounding parenchyma may be seen in both papillomas and carcinomas. However, in papillomas it is by nests of tumour cells compared with carcinomas wherein invasion is by individual tumour cells. Hydrocephalus is present irrespective of location and size of the tumour. Gross total excision is more feasible in adults. Large tumour size, excessive blood loss, higher incidence of carcinomas result in partial excision of these tumours in the paediatric group. Subdural collections and tumour bed haematomas are more common complications in the paediatric group after resection of tumour. These tumours have significant differences among paediatric and adult groups. Carcinomas are predominantly seen in younger children. Invasion of brain parenchyma by nests of cells does not carry a poor prognosis. The outcomes are better in adults.
Background: Neurological affection in Sjogren's syndrome (SS) can occur in the central and peripheral nervous system. Literature describing the neurological involvement in SS among Indian patients is lacking. Materials and Methods: Six patients of SS fulfilling the histological or serological criteria of the American European Consensus Group for SS were studied prospectively. The patients underwent clinical examination and laboratory investigations. Their clinical and investigation features are described. Results: The age of the patients ranged from 26 to 48 years, with a male to female ratio of 2:4. In our series, peripheral sensori-motor neuropathy and sensory ataxic neuropathy was seen in 3/6, mononeuritis multiplex in 2/6, cranial neuropathy in 2/6, autonomic neuropathy in 1/6, myelopathy in 4/6, optic neuropathy in 2/6, with presence of classical sicca features in 5/6 patients. Positive lip biopsy was seen in three, altitudinal field defect in one and positive Schirmer's test in five patients. Nerve conduction study abnormalities were seen in three and evidence of vasculitis was seen in nerve biopsy of one patient and chronic nonuniform axonopathy was seen in another. Antibody to Ro (SSA) or La (SSB) was positive in five patients. Conclusions: SS involves different parts of the nervous system with varied presentations. Clinical suspicion and adequate laboratory testing helps to diagnose and manage this disorder that is relatively rare in Indian patients.
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