Incidental Findings from 16,400 Brain MRI Examinations of Research Volunteers.

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.

Beyond Diffusion Tensor MRI Methods for Improved Characterization of the Brain after Ischemic Stroke: A Review.

Ischemic stroke is a worldwide problem, with 15 million people experiencing a stroke annually. MR imaging is a valuable tool for understanding and assessing brain changes after stroke and predicting recovery. Of particular interest is the use of diffusion MR imaging in the nonacute stage 1-30 days poststroke. Thousands of articles have been published on the use of diffusion MR imaging in stroke, including several recent articles reviewing the use of DTI for stroke. The goal of this work was to survey and put into context the recent use of diffusion MR imaging methods beyond DTI, including diffusional kurtosis, generalized fractional anisotropy, spherical harmonics methods, and neurite orientation and dispersion models, in patients poststroke. Early studies report that these types of beyond-DTI methods outperform DTI metrics either in being more sensitive to poststroke changes or by better predicting outcome motor scores. More and larger studies are needed to confirm the improved prediction of stroke recovery with the beyond-DTI methods.

Recovery of slow-5 oscillations in a longitudinal study of ischemic stroke patients.

Functional networks in resting-state fMRI are identified by characteristics of their intrinsic low-frequency oscillations, more specifically in terms of their synchronicity. With advanced aging and in clinical populations, this synchronicity among functionally linked regions is known to decrease and become disrupted, which may be associated with observed cognitive and behavioral changes. Previous work from our group has revealed that oscillations within the slow-5 frequency range (0.01-0.027 Hz) are particularly susceptible to disruptions in aging and following a stroke. In this study, we characterized longitudinally the changes in the slow-5 oscillations in stroke patients across two different time-points. We followed a group of ischemic stroke patients (n = 20) and another group of healthy older adults (n = 14) over two visits separated by a minimum of three months (average of 9 months). For the stroke patients, one visit occurred in their subacute window (10 days to 6 months after stroke onset), the other took place in their chronic window (> 6 months after stroke). Using a mid-order group ICA method on 10-minutes eyes-closed resting-state fMRI data, we assessed the frequency distributions of a component's representative time-courses for differences in regards to slow-5 spectral power. First, our stroke patients, in their subacute stage, exhibited lower amplitude slow-5 oscillations in comparison to their healthy counterparts. Second, over time in their chronic stage, those same patients showed a recovery of those oscillations, reaching near equivalence to the healthy older adult group. Our results indicate the possibility of an eventual recovery of those initially disrupted network oscillations to a near-normal level, providing potentially a biomarker for stroke recovery of the cortical system. This finding opens new avenues in infra-slow oscillation research and could serve as a useful biomarker in future treatments aimed at recovery.

Low functional robustness in mesial temporal lobe epilepsy.

OBJECTIVES: Brain functional topology was investigated in patients with mesial temporal lobe epilepsy (mTLE) by means of graph theory measures in two differentially defined graphs. Measures of segregation, integration, and centrality were compared between subjects with mTLE and healthy controls (HC). METHODS: Eleven subjects with mTLE (age 36.5±10.9years) and 15 age-matched HC (age 36.8±14.0years) participated in this study. Both anatomically and functionally defined adjacency matrices were used to investigate the measures. Binary undirected graphs were constructed to study network segregation by calculating global clustering and modularity, and network integration by calculating local and global efficiency. Node degree and participation coefficient were also computed in order to investigate network hubs and their classification into provincial or connector hubs. Measures were investigated in a range of low to medium graph density. RESULTS: The group of patients presented lower global segregation than HC while showing higher global but lower local integration. They also failed to engage regions that comprise the default-mode network (DMN) as hubs such as bilateral medial frontal regions, PCC/precuneus complex, and right inferior parietal lobule, which were present in controls. Furthermore, the cerebellum in subjects with mTLE seemed to be playing a major role in the integration of their functional networks, which was evident through the engagement of cerebellar regions as connector hubs. CONCLUSIONS: Functional networks in subjects with mTLE presented both global and local abnormalities compared to healthy subjects. Specifically, there was significant separation between groups, with lower global segregation and slightly higher global integration observed in patients. This could be indicative of a network that is working as a whole instead of in segregated or specialized communities, which could translate into a less robust network and more prone to disruption in the group with epilepsy. Furthermore, functional irregularities were also observed in the group of patients in terms of the engagement of cerebellar regions as hubs while failing to engage DMN-related areas as major hubs in the network. The use of two differentially defined graphs synergistically contributed to findings.

Hepatoprotective activity of aqueous extract of Portulaca oleracea in combination with lycopene in rats.

OBJECTIVE: To investigate the hepatoprotective activity of the aqueous extract of the aerial parts of Portulaca oleracea (P. oleracea) in combination with lycopene against carbon tetrachloride induced hepatotoxicity in rats. MATERIALS AND METHODS: Hepatotoxicity was induced in male Wistar rats by intraperitoneal injection of carbon tetrachloride (0.1 ml/kg b.w for 14 days). The aqueous extract of P. oleracea in combination with lycopene (50 mg/kg b.w) was administered to the experimental animals at two selected doses for 14 days. The hepatoprotective activity of the combination was evaluated by the liver function marker enzymes in the serum [aspartate transaminases (AST), alanine transaminases (ALT), alkaline phosphatase (Alk.P), total bilirubin (TB), total protein (TP) and total cholesterol (TC)], pentobarbitone induced sleeping time (PST) and histopathological studies of liver. RESULTS: Both the treatment groups showed hepatoprotective effect against carbon tetrachloride induced hepatotoxicity by significantly restoring the levels of serum enzymes to normal which was comparable to that of silymarin group. Besides, the results obtained from PST and histopathological results also support the study. CONCLUSIONS: The oral administration of P. oleracea in combination with lycopene significantly ameliorates CCl(4) hepatotoxicity in rats.

Impact of brain tumor location on morbidity and mortality: a retrospective functional MR imaging study.

BACKGROUND AND PURPOSE: fMRI is increasingly used in neurosurgery to preoperatively identify areas of eloquent cortex. Our study evaluated the efficacy of clinical fMRI by analyzing the relationship between the distance from the tumor border to the area of functional activation (LAD) and patient pre- and postoperative morbidity and mortality. MATERIALS AND METHODS: The study included patients with diagnosis of primary or metastatic brain tumor who underwent preoperative fMRI-based motor mapping (n=74) and/or language mapping (n=77). The impact of LAD and other variables collected from patient records was analyzed with respect to functional deficits in terms of morbidity (paresis and aphasia) and mortality. RESULTS: Significant relationships were found between motor and language LAD and the existence of either pre- or postoperative motor (P < .001) and language deficits (P=.009). Increasing age was associated with motor and language deficits (P=.02 and P=.04 respectively). Right-handedness was related to language deficits (P=.05). Survival analysis revealed that pre- and postoperative deficits, grade, tumor location, and LAD predicted mortality. Motor deficits increased linearly as the distance from the tumor to the primary sensorimotor cortex decreased. Language deficits increased exponentially as the distance from the tumor to the language areas decreased below 1 cm. Postoperative mortality analysis showed an interaction effect between motor or language LAD and mortality predictors (grade and tumor location, respectively). CONCLUSIONS: These findings indicate that tumors may affect language and motor function differently depending on tumor LAD. Overall, the data support the use of fMRI as a tool to evaluate patient prognosis and are directly applicable to neurosurgical planning.

Relative seroprevalence of cysticercus antigens and antibodies and antibodies to Taenia ova in a population sample in south India suggests immunity against neurocysticercosis.

We evaluated the exposure of a community in Vellore district of south India to Taenia solium infection and its relationship to the prevalence of neurocysticercosis (NCC) causing active epilepsy. Seroprevalence of Taenia cysticercus antigens and antibodies were determined in 1064 randomly chosen asymptomatic individuals, antibodies to T. solium ova in 197 selected sera, and prevalence of taeniasis by a coproantigen test in 729 stool samples. The prevalence of NCC causing active epilepsy in Vellore district was determined in a population of 50 617. Coproantigens were detected in 0.8% (6 samples), Taenia cysticercus antigens in 4.5% (48 sera) and cysticercus IgG antibodies in 15.9% (169 sera) of the population. Cysticercus antibodies were directed against relatively low molecular weight cyst glycoprotein antigens in 14.9% (158 sera) of the population. IgG antibodies to Taenia ova were found in 81 (41.1%) of the selected samples. Prevalence of NCC causing active epilepsy was 1.3 per 1000 population. These results show high exposure of the population to the parasite and a relatively high prevalence of active infections (4.5% antigen positives) but a low prevalence of NCC causing active epilepsy (0.13%). These findings may indicate that the population is protected against developing neurocysticercosis. IgG antibodies directed against Taenia ova and low molecular weight cyst antigens may contribute to protection.

Long-term clinical evaluation of asymptomatic subjects positive for circulating Taenia solium antigens.

Although presence of cysticercal antigens in serum is presumed to indicate active cysticercosis not all positive persons are symptomatic. The significance of a positive antigen test in asymptomatic individuals, in predicting development of symptomatic cysticercosis on long-term follow up, is unknown. Forty two of 48 persons from Vellore district, India who were positive for circulating serum cysticercal antigens were followed up for four to five years. None of them developed clinical evidence of neurocysticercosis or subcutaneous cysts. We conclude that asymptomatic individuals with circulating cysticercal antigens have a low risk of developing symptomatic cysticercosis within four to five years.

Detecting spatial clusters of Taenia solium infections in a rural block in South India.

Neurocysticercosis (NCC) is a major cause of seizures/epilepsy in countries endemic for the disease. The objectives of this study were to spatially map the burden of active epilepsy (AE), NCC, taeniasis, seroprevalence for cysticercal antibodies and positivity to circulating cysticercal antigens in Kaniyambadi block (approximately 100 villages comprising 100 000 population) of Vellore district and to detect spatial clusters of AE, NCC, taeniasis and seroprevalence. Using geographic information system (GIS) techniques, all 21 study villages with over 8000 houses (population of 38 105) were mapped. Clustering of different indices of Taenia solium infection was determined using a spatial scan statistic (SaTScan). There was a primary spatial cluster of AE with a log likelihood ratio (LLR) of 10.8 and relative risk (RR) of 22.4; however, no significant clustering for NCC was detected. Five significant spatial clusters of seropositivity for cysticercal antibodies, two clusters of seropositivity for cysticercal antigens and one for taeniasis were detected (LLR of 8.35 and RR of 36.67). Our study has demonstrated the use of GIS methods in mapping and identifying 'hot spots' of various indices of T. solium infection in humans. This spatial analysis has identified pockets with high transmission rates so that preventive measures could be focused on an intensive scale.

Ocular adnexal diffuse large B-cell lymphoma: local disease correlates with better outcomes.

PURPOSE: To describe the clinical, immunohistochemical and prognostic features, as well as outcomes of a large series of patients with orbital and periorbital diffuse large B-cell lymphoma (DLBCL). DESIGN: This study is a multicentre, retrospective non-comparative consecutive case series. METHODS: The setting for this study was institutional. A total of 37 consecutive patients identified from the institutions' databases with periorbital and orbital DLBCL were enrolled in the study. A retrospective chart review was used for observation. The main outcome measures were patient demographics, clinical features, imaging, immunohistochemical and histopathological data, treatments administered, and survival. RESULTS: A total of 20 out of 37 cases (54.1%) represented localised periorbital disease (group L), 11 of 37 (29.7%) had systemic disease at presentation with periorbital disease (group S1), and 6 of 37 (16.2%) had previous history of systemic lymphoma (group S2). In all, 28 out of 30 (93.3%) patients were CD20+, 5 of 25 (20%) were CD3+, and 11 of 11 (100%) were CD79a+ (varying denominators reflect the different numbers of patients tested). A total of 25 out of 32 patients (78.1%) received chemotherapy, 14 (43.8%) received rituxmab plus chemotherapy, and 19 (59.3%) received radiotherapy. Nine deaths occurred, one in group L (not lymphoma related), six in group S1, and two in group S2. Five-year Kaplan-Meier survival estimates were 55.9% for all cases, 90.9% for group L, 36.0% for group S1, and 0% for group S2. One-year progression-free survival estimates in groups S1 and S2 combined were 58.3% for patients treated with rituximab and 28.6% for those who were not. CONCLUSIONS: To our knowledge, this report represents the largest series of patients with periorbital and orbital DLBCL in the literature. The difference in survival between groups L, S1 and S2 was striking, reflecting the grave prognosis of systemic DLBCL, but conversely the relatively optimistic outlook for patients with localised disease. Rituximab plus chemotherapy may be associated with increased survival.

Pleomorphic adenoma of the lacrimal gland: is there a role for biopsy?

AIM: To review the literature on biopsy of lacrimal gland pleomorphic adenoma (LGPA) and to examine the validity of the prohibition against biopsy in LGPA. METHOD: Literature review. RESULTS: LGPA is usually diagnosed preoperatively based on clinical and radiological characteristics, as current teaching advises complete excision without prior incisional biopsy. The caveat against biopsy is based on older studies that reported increased recurrence rates with increased risk of malignant transformation after incomplete excision or biopsy. On the basis of a detailed examination of the literature on biopsy of both LGPA and pleomorphic adenoma of the salivary glands, it appears that there is no clear evidence to support the claim that biopsy increases the risk of recurrence or of malignant transformation of LGPA. CONCLUSION: Lacrimal gland tumours are uncommon lesions and optimal management depends to a great extent on a definite preoperative diagnosis. Preoperative biopsy should therefore be considered in all lacrimal gland mass lesions and management should be tailored to the biopsy findings. If surgical resection is then required, it may be prudent to excise the biopsy tract to ensure complete removal of the tumour.

Metastatic renal cell carcinoma presenting as a circumscribed orbital mass.

PURPOSE: To report a case of renal cell carcinoma presenting as a well-circumscribed orbital tumor. METHODS: Retrospective interventional case report. RESULTS: A 60-year-old woman presented with proptosis of the left eye. Imaging showed a well circumscribed tumor in the region of the medial rectus muscle. Excision biopsy revealed a diagnosis of metastatic renal cell carcinoma that was confirmed on abdominal imaging. CONCLUSIONS: Renal cell carcinoma can rarely present as a well-circumscribed orbital mass and should be included in the differential diagnosis of such lesions.

Seroprevalence of Taenia solium antibodies in Vellore district, south India.

Although Taenia solium neurocysticercosis is the cause of almost one-third of epilepsy in Vellore district, south India, the level of exposure to T. solium in the district is not known. This study determined the seroprevalence of cysticercus antibodies in seizure-free, study subjects aged 2-60 years from urban and rural areas of Vellore district. Cysticercus antibodies, as determined by immunoblots, were noted in 15.9% of 1063 people and were significantly higher in the rural population (17.7%) compared with the urban population (6.0%). Twenty-four percent of the rural population and 12% of the urban population ate pork. One-third of all households in the district had one or more members seropositive for cysticercus antibodies. The high index of exposure to T. solium in south India calls for improved animal husbandry and sanitation.

Neural substrates of word generation during stroke recovery: the influence of cortical hypoperfusion.

Several studies have demonstrated reorganization of cognitive and motor function caused by stroke. This study examined the influence of hypoperfused brain regions, in addition to the area of the infarct itself, on reorganization of the cognitive processes underlying word generation in stroke patients. In addition, we also sought to determine the influence of hypoperfusion on the blood oxygen level dependent/(BOLD) effect. Subjects with left and right subacute or chronic subcortical strokes, along with normal controls, were imaged while performing a verbal fluency task (word generation). The study population included six normal subject and six stroke patients with subcortical infarcts and cortical hypoperfusion in the middle cerebral artery territory who had recovered or improved markedly in word fluency. While normal subjects displayed a left-lateralized fronto-temporo-parietal and bilateral cingulo-striatal-thalamic-cerebellar network, the activation pattern of stroke patients was determined both by the hypoperfused regions and infarcted areas of the brain. Specifically, patients showed diminished BOLD effect in the cortical regions that were hypoperfused, even though their infarcts were subcortical, and showed increased BOLD effect in the homologous regions of the normal hemisphere. This finding raises the possibility that cortical hypoperfusion in the absence of infarct can cause shift of language functions to the opposite, intact hemisphere. However, reduced BOLD effect in the task relative to rest was found in hypoperfused regions in two patients, raising the possibility that regional function persisted, even though vascular reactivity was impaired. Results illustrate the complexities of functional imaging studies of recovery in patients with vascular lesions.

Active epilepsy as an index of burden of neurocysticercosis in Vellore district, India.

OBJECTIVE: To determine the contribution of neurocysticercosis (NCC) to the causation of active epilepsy (AE) in a south Indian community. METHODS: We conducted a door-to-door survey of 50,617 people between the ages of 2 and 60 years in a rural (38,105 people) and urban setting (12,512 people) in the Vellore district of the south Indian state of Tamil Nadu to identify patients with AE. Patients with AE were investigated with a contrast-enhanced CT scan and serologic study using enzyme-linked immunotransfer blot (EITB) for cysticercal antibodies. RESULTS: We identified 194 patients with AE. The prevalence of AE was 3.83 per 1,000 people, with the prevalence in the urban clusters more than twice that in the rural clusters (6.23 vs 3.04 per 1,000) (p < 0.0001). A diagnosis of NCC was made in 46 (28.4%) of the 162 patients undergoing a CT scan, and EITB was positive in 21 (13%) patients. Overall, 55 (34%) patients were diagnosed with NCC (11 definitive NCC and 44 probable NCC). There was no significant difference in the prevalence of NCC causing AE in the urban (1.28 per 1,000) and rural (1.02 per 1,000) communities. CONCLUSIONS: NCC is the cause of nearly one-third of all cases of AE in both the urban and rural regions. Extrapolating our results to the country as a whole leads to an estimated disease burden of 1 million patients in India with AE attributable to NCC.

Taenia solium metacestode glycoproteins as diagnostic antigens for solitary cysticercus granuloma in Indian patients.

Taenia solium metacestode glycoproteins specific for lentil lectin were evaluated as diagnostic antigens for solitary cysticercus granulomas in Indian patients, using both an ELISA and immunoblotting. In 250 patients suspected to have neurocysticercosis and subjected to a computerized tomography scan or magnetic resonance imaging, the proteins were diagnostic by the ELISA in 86 patients (80%) and by immunoblots in 67 (62%) of 107 patients with solitary cysticerus granuloma. Among 100 non-cysticercosis patients, the ELISA and immunoblot were negative in 94% and 97% respectively. No cross-reactions were observed with sera from patients with central nervous system tuberculosis. Proteins of

Rostrolateral prefrontal cortex involvement in relational integration during reasoning.

Patient and neuroimaging studies indicate that complex reasoning tasks are associated with the prefrontal cortex (PFC). In this study, we tested the hypothesis that the process of relational integration, or considering multiple relations simultaneously, is a component process of complex reasoning that selectively recruits PFC. We used fMRI to examine brain activation during 0-relational, 1-relational, and 2-relational problems adapted from the Raven's Progressive Matrices and hypothesized that PFC would be preferentially recruited by the 2-relational problem type. Event-related responses were modeled by convolving a canonical hemodynamic response function with the response time (RT) associated with each trial. The results across different analyses revealed the same pattern: PFC activation was specific to the comparison between 2- and 1-relational problems and was not observed in the comparison between 1- and 0-relational problems. Furthermore, the process of relational integration was specifically associated with bilateral rostrolateral PFC (RLPFC; lateral area 10) and right dorsolateral PFC (areas 9 and 46). Left RLPFC showed the greatest specificity by remaining preferentially recruited during 2-relational problems even after comparisons were restricted to trials matched for RT and accuracy. The link between RLPFC and the process of relational integration may be due to the associated process of manipulating self-generated information, a process that may characterize RLPFC function.