Glutathione Depletion and Concomitant Elevation of Susceptibility in Patients with Parkinson's Disease: State-of-the-Art MR Spectroscopy and Neuropsychological Study.

Parkinson's disease (PD) is characterized by extrapyramidal motor disturbances and nonmotor cognitive impairments which impact activities of daily living. Although the etiology of PD is still obscure, autopsy reports suggest that oxidative stress (OS) is one of the important factors in the pathophysiology of PD. In the current study, we have investigated the impact of OS in PD by measuring the antioxidant glutathione (GSH) levels from the substantia nigra (SN), left hippocampus (LH) and neurotransmitter γ-amino butyric acid (GABA) levels from SN region. Concomitant quantitative susceptibility mapping (QSM) from SN and LH was also acquired from thirty-eight PD patients and 30 age-matched healthy controls (HC). Glutathione levels in the SN region decreased significantly and susceptibility increased significantly in PD compared to HC. Nonsignificant depletion of GABA was observed in the SN region. GSH levels in the LH region were depleted significantly, but LH susceptibility did not alter in the PD cohort compared to HC. Neuropsychological and physical assessment demonstrated significant impairment of cognitive functioning in PD patients compared to HC. GSH depletion was negatively correlated to motor function performance. Multivariate receiver operating characteristic (ROC) curve analysis on the combined effect of GSH, GABA, and susceptibility in the SN region yielded an improved diagnostic accuracy of 86.1% compared to individual diagnostic accuracy based on GSH (65.8%), GABA (57.5%), and susceptibility (69.6%). This is the first comprehensive report in PD demonstrating significant GSH depletion as well as concomitant iron enhancement in the SN region.

Skull Vault Plasmacytoma Mimicking Parasagittal Meningioma: "Mini-Brain Appearance".

Plasmacytomas occur as lesions in soft tissue or bone. Skull vault plasmacytomas are rare lesions comprising 0.7% of all plasmacytomas. Workup for myeloma must be done in such cases to rule out multiple myeloma. Here, we report a case of a 63-year-old female who presented to us with a large skull vault swelling which appeared to mimic a parasagittal meningioma on imaging. Histopathological imaging revealed it to be a plasmacytoma. A retrospective review of the radiology revealed the characteristic "mini-brain appearance" in our case. Literature on the subject is also reviewed.

Glioma Simultaneously Present with Adjacent Meningioma: Case Report and Literature Review.

A 51-year-old male patient presented to us with an episode of generalized tonic-clonic seizure. Magnetic resonance imaging revealed a dural-based contrast-enhancing lesion in the right temporal lobe and another heterogeneously contrast-enhancing intra-axial lesion in the right insula adjacent to it. Histopathology confirmed it as a meningioma adjacent to an anaplastic oligodendroglioma. This is only the second such case reported in literature. Literature on "adjacent site" gliomas and meningioma was also reviewed.

Five Hundred Patients with Memory Loss in One Clinic in India: Does the Prevalence Vary Between Communities?

This observational study reports on the cause of memory loss in 500 consecutive patients. It confirms the previously reported finding in a smaller sample of 100 patients. There have been several publications suggesting that the prevalence of dementia is lower in certain communities but the reason is not known. This study was conducted to see if it could explain the variation between communities. Also, the observation that dementia with Lewy bodies (24.4%) outnumbers cases of Alzheimer's disease (5.8%) has not been reported by any other investigators and needs to be verified. This finding could open a new topic of research and also help in the management of patients.

Basal Ganglia Infarct following Trivial Trauma in a Child: Case Report and Review of Literature.

A 2-year-old boy was presented to us with right-side hemiparesis after trivial fall. Diffusion-weighted magnetic resonance imaging showed an infarct in left basal ganglia and thalamic region. Secondary causes of stroke were ruled out. The child was managed conservatively. Basal ganglia infarct secondary to minor trauma is a rare event. Possible mechanisms leading to such an event and its management are discussed.

Distribution of Types of Dementia in the First 100 Patients Seen at a Dementia Clinic in India.

The aim of our study was to determine if the distribution of types of dementia could explain the reported lower prevalence of dementia in India. The study is an observational study of the first 100 cases of dementia. All patients were evaluated clinically and with blood tests and MRI of the brain. The causes of dementia were: Lewy body dementia (22%), depression (20%), Alzheimer's disease (13%), and mild cognitive impairment (18%). Other dementias were less common. The distribution of dementia types in this series is different from that reported globally. The observation of Lewy body dementia being the most common cause of dementia needs to be verified.

Giant pediatric intraventricular meningioma: Case report and review of literature.

Intraventricular meningiomas are rare in the pediatric population. These tumors are often large in size and aggressive in behavior when they occur in children. The management of these tumors is a surgical challenge.

TGF-ß-induced hCG-ß regulates redox homeostasis in glioma cells.

Transforming growth factor (TGF-ß) is associated with the progression of glioblastoma multiforme (GBM)-the most malignant of brain tumors. Since there is a structural homology between TGF-ß and human chorionic gonadotropin (hCG) and as both TGF-ß and hCG-ß are known regulators of oxidative stress and survival responses in a variety of tumors, the role of TGF-ß in the regulation of hCG-ß and its consequences on redox modulation of glioblastoma cells was investigated. A heightened hCG-ß level was observed in GBM tumors. TGF-ß treatment increased hCG-ß expression in glioma cell lines, and this heightened hCG-ß was found to regulate redox homeostasis in TGF-ß-treated glioma cells, as siRNA-mediated knockdown of hCG-ß (i) elevated reactive oxygen species (ROS) generation, (ii) decreased thioredoxin Trx1 expression and thioredoxin reductase (TrxR) activity, and (iii) abrogated expression of TP53-induced glycolysis and apoptosis regulator (TIGAR). Silencing of hCG-ß abrogated Smad2/3 levels, suggesting the existence of TGF-ß-hCG-ß cross-talk in glioma cells. siRNA-mediated inhibition of elevated TIGAR levels in TGF-ß-treated glioma cells was accompanied by an increase in ROS levels. As a farnesyltransferase inhibitor, Manumycin is known to induce glioma cell apoptosis in a ROS-dependent manner, and we investigated whether Manumycin could induce apoptosis in TGF-ß-treated cells with elevated hCG-ß exhibiting ROS-scavenging property. Manumycin-induced apoptosis in TGF-ß-treated cells was accompanied by elevated ROS levels and decreased expression of hCG-ß, Trx1, Smad2/3, and TIGAR. These findings indicate the existence of a previously unknown TGF-ß-hCG-ß link that regulates redox homeostasis in glioma cells.

48-year-old woman with a cerebellopontine angle mass.

Intracranial chondromas are rare benign neoplasms with an estimated incidence rate of 0.2­0.3%. They usually occur at the skull base, or arise from the dura and leptomeninges. Rarely, they have been reported at the cerebellopontine (CP) angle. Here we describe an interesting case of CP angle chondroma which was clinically and radiologically diagnosed as schwannoma and meningioma.

Balantidium coli: an unrecognized cause of vertebral osteomyelitis and myelopathy.

Balantidium coli is a ciliated protozoan parasite that primarily infects primates and pigs. It is the largest protozoan to infect humans and is a well-known cause of diarrhea and dysentery. Extraintestinal disease is uncommon, and extraintestinal spread to the peritoneal cavity, appendix, genitourinary tract, and lung has rarely been reported. The authors describe a case of vertebral osteomyelitis with secondary cervical cord compression caused by B. coli. The patient was a 60-year-old immunocompetent man presenting with quadriplegia of short duration. Magnetic resonance imaging of the cervical spine showed extradural and prevertebral abscess at the C3-4 level. Drainage of the abscess, C3-4 discectomy, and iliac bone grafting were performed. Histologically B. coli was confirmed in an abscess sample. To the best of the authors' knowledge, involvement of bone by B. coli has never been reported, and this case is the first documented instance of cervical cord compression due to B. coli osteomyelitis of the spine in the literature.

26-year-old man with a cerebellar mass.

Medulloblastoma accounts for only 1% of all adult CNS tumors. Recently, we have encountered a case of medulloblastoma in a 26 year old man with divergent differentiation including myoblastic, glial, osteoblastic and chondroblastic differentiation. Here we present the results of immunohistochemical staining using several specific antibodies with a discussion and a review of literature.

ß-defensin-3 negatively regulates TLR4-HMGB1 axis mediated HLA-G expression in IL-1ß treated glioma cells.

The non-classical HLA class I antigen HLA-G contributes to immune escape mechanisms in glioblastoma multiforme (GBM). We have previously shown that IL-1ß-HIF-1α axis connects inflammatory and oncogenic pathways in GBM. In this study, we investigated the role of IL-1ß induced inflammation in regulating HLA-G expression. IL-1ß increased HLA-G and Toll like receptor 4 (TLR4) expression in a HIF-1α dependent manner. Inhibition of TLR4 signaling abrogated IL-1ß induced HLA-G. IL-1ß increased HMGB1 expression and its interaction with TLR4. Inhibition of HMGB1 inhibited TLR4 and vice versa suggesting the existence of HMGB1-TLR4 axis in glioma cells. Interestingly, HMGB1 inhibition prevented IL-1ß induced HLA-G expression. Elevated levels of HMGB1 and ß-defensin 3 were observed in GBM tumors. Importantly, ß-defensin-3 prevented IL-1ß induced HLA-G, TLR4, HMGB1 expression and release of pro-inflammatory mediators. Our studies indicate that ß-defensin-3 abrogates IL-1ß induced HLA-G expression by negatively affecting key molecules associated with its regulation.

TNFα regulates the localization of CD40 in lipid rafts of glioma cells.

Resistance of glioblastoma multiforme (GBM) to TNFα induced apoptosis is attributed to NFκB activation. As TNF-receptor family member CD40 regulates NFκB activation, we investigated the role of CD40 in NFκB activation in GBM. We observed elevated CD40 levels in human glioma samples as compared to the surrounding normal tissue. Treatment with TNFα elevated CD40 levels in glioma cells and inhibition of CD40 signaling failed to abrogate TNFα induced NFκΒ activity. While TNFα increased the interaction between TRAF2/6, IκBα, IKKα/ß in the CD40 signalosome, the level of CD40 in the signalosome remained unaffected upon TNFα treatment. Interestingly, TNFα decreased the spatial localization of CD40 and increased TRAF2/6 co-localization with lipid raft marker Caveolin. As localization of CD40 signalosome in lipid raft is crucial for NFκB activation, TNFα mediated decreased clustering of CD40 in lipid rafts could have possibly contributed to its non-involvement in NFκB activation.

Picture-naming in patients with left frontal lobe tumor - a functional neuroimaging study.

The objective of this study was to investigate behavioral performance as well as cortical activation patterns while picture-naming, in patients with left frontal lobe tumor prior to surgery. Functional magnetic resonance imaging was used to compare behavior and brain activations while 10 patients with a tumor in the left frontal lobe and 9 controls, named aloud simple pictures presented in a block design inside a 3 T Philips Achieva scanner. Evaluations of task performance included naming accuracy and articulation time. Behaviorally, patients took significantly longer to articulate picture names but naming accuracy was preserved. Analysis of brain activations showed differences only in the frontal regions of the cortical network. In particular, while the frontal activations in the control population were focused and localized in the left inferior orbito-frontal gyrus, in patients the frontal network was distributed and included a significantly greater number of clusters that were distributed in homologous or near homologous areas of the (orbito-frontal gyrus) left and/or right hemisphere of the frontal lobe. Our results suggest that in patients with a left frontal lobe tumor the process of naming simple pictures is preserved but the cortical network of activation in the frontal region is altered and is distributed in the frontal regions of both hemispheres.

Programmable valve shunts: are they really better?

Programmable valve shunts allows selection of opening pressure of shunt valve. In the presented article, a unique complication pertaining to programmable shunts has been discussed. A 5-year-old boy who had tectal plate low grade glioma with obstructive hydrocephalus was managed with Codman programmable ventriculoperitoneal shunt. There was a spontaneous change in the opening pressure of the shunt valve leading to shunt malfunction. Routinely used household appliances produce a magnetic field strong enough to cause change in the setting of shunt valve pressure and may lead to valve malfunction. Other causes of programmable valve malfunction also discussed.