Neuroimaging in manganism

Neuroimaging such as magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) have been used in the last decade for investigating the neurotoxicolgy of manganese (Mn). Increased signal intensities on a T1-weighted image may reflect increased Mn deposits (e.g., due to exposure to Mn) but not necessarily manganism. In a biologically based dose-response model, our recent results strongly suggest that signal intensities in T1-weighted MRI reflect a target site dose. However, the threshold of signal intensity associated with clinical symptoms of manganism remains to be solved. Functional neuroimaging such as PET or SPECT examines the integrity of the nigrostriatal dopaminergic system, and thus is very important for the differential diagnosis of manganism. However, neuroimaging research should also aim at developing specific and sensitive parameters for manganism in Mn-exposed individuals.     

Brain magnetic resonance imaging and manganese concentrations in red blood cells of smelting workers: search for biomarkers of manganese exposure

The MRI technique has been used in diagnosis of manganism in humans and non-human primates. This cross-sectional study was designed to explore whether the pallidal signal intensity in T1-weighted MRI correlated with Mn levels in the blood compartment among Mn-exposed workers and to understand to what extent the MRI signal could reflect Mn exposure. A group of 18 randomly selected male Mn-exposed workers of which 13 were smelting workers with high exposure (mean of airborne Mn in work place: 1.26 mg/m3; range: 0.31-2.93 mg/m3), and 5 power distribution control workers with low exposure (0.66 mg/m3 and 0.23-0.77 mg/m3) from a ferroalloy factory, and another group of 9 male subjects as controls from a non-smelting factory who were office or cafeteria workers (0.01 mg/m3 and 0-0.03 mg/m3) were recruited for neurological tests, MRI examination, and analysis of Mn in whole blood (MnB), plasma (MnP) or red blood cells (MnRBC). No clinical symptoms and signs of manganism were observed among these workers. MRI data showed average increases of 7.4% (p<0.05) and 16.1% (p<0.01) in pallidal index (PI) among low- and high-exposed workers, respectively, as compared to controls. Fourteen out of 18 Mn-exposed workers (78%) had intensified PI values, while this proportion was even higher (85%) among the high Mn-exposed workers. Among exposed workers, the PI values were significantly associated with MnRBC (r=0.55, p=0.02). Our data suggest that the workers exposed to airborne Mn, but without clinical symptoms, display an exposure-related, intensified MRI signal. The MRI, as well as MnRBC, may be useful in early diagnosis of Mn exposure.     

Idiopathic parkinsonism with superimposed manganese exposure: utility of positron emission tomography.

It is difficult to distinguish manganism from idiopathic parkinsonism by clinical signs only. Case history and examination: A 48-year-old welder for over 10 years complained of masked face, right side (arm and leg) resting tremor, and bradykinesia for over one year. Magnetic resonance imaging (MRI) findings showed symmetrical high signal intensities in the globus pallidus on T1 weighted image. These intensities disappeared almost completely six months after cessation of exposure. 18F-6-fluorodopa (18F-dopa) positron emission tomography (PET) findings showed reduced 18F-dopa uptake in the left putamen, findings which appear in idiopathic parkinsonism. A PET study is necessary to distinguish manganism from idiopathic parkinsonism, especially in a working environment with elevated Mn concentrations, such as welding.     

Ex vivo magnetic resonance imaging in South African manganese mine workers

BackgroundManganese (Mn) exposure is associated with increased T1-weighted magnetic resonance imaging (MRI) signal in the basal ganglia. T1 signal intensity has been correlated with occupational Mn exposure but not with clinical symptomatology or neuropathology.ObjectivesThis study investigated predictors of ex vivo T1 MRI basal ganglia signal intensity in neuropathologic tissue obtained from deceased South African mine workers.MethodsA 3.0 T MRI was performed on ex vivo brain tissue obtained from 19 Mn mine workers and 10 race- and sex-matched mine workers of other commodities. Basal ganglia regions of interest were identified for each subject with T1-weighted intensity indices generated for each region. In a pathology subset, regional T1 indices were compared to neuronal and glial cell density and tissue metal concentrations.ResultsIntensity indices were higher in Mn mine workers than non-Mn mine workers for the globus pallidus, caudate, anterior putamen, and posterior putamen with the highest values in subjects with the longest cumulative Mn exposure. Intensity indices were inversely correlated with the neuronal cell density in the caudate (p = 0.040) and putamen (p = 0.050). Tissue Mn concentrations were similar in Mn and non-Mn mine workers. Tissue iron (Fe) concentration trended lower across all regions in Mn mine workers.ConclusionsMn mine workers demonstrated elevated basal ganglia T1 indices when compared to non-Mn mine workers. Predictors of ex vivo T1 MRI signal intensity in Mn mine workers include duration of Mn exposure and neuronal density.     

High signal intensity on magnetic resonance imaging as a predictor of neurobehavioral performance of workers exposed to manganese

INTRODUCTION: Using previously obtained cross-sectional data from a nationwide survey on workers exposed to manganese (Mn), we assessed the relation of high signal intensity with neurobehavioral effects, and reevaluated the preexisting cross-sectional data to get additional findings on the relation of high signals with other Mn-exposure indices. SUBJECTS AND METHODS: Subjects were the same as those in the previous study. The exposure status was reassessed based on similar exposure groups. The signal intensity of the globus pallidus (GP) relative to frontal white matter was subjectively evaluated as either with or without increased signals, and the increased signals were further graded into three categories. For quantitative evaluation of signal intensities of the GP we also calculated the pallidal index (PI). Neurobehavioral function was assessed using the World Health Organization Neurobehavioral Core Test Battery. In addition, computerized finger tapping speed was included to assess motor speed. RESULTS: The mean blood Mn for those with grade III was significantly greater than those without increased signals and those with grade I. Airborne Mn and PI also showed similar findings. PI paralleled subjective MRI gradings. The proportion of workers with increased signals increased with all the Mn-exposure variables, airborne and blood Mn, the duration of work, and cumulative exposure. The PI was significantly associated with a correct score of pursuit aiming II tests and finger tapping of the dominant hand after control of age and educational level among neurobehavioral performances. DISCUSSION: The present findings showed that signal index on T1-weighted MRI showed a dose-response relationship with all the Mn-exposure variables. The two neurobehavioral tests reflecting fine motor function were significantly decreased above 107.1 of PI, the cutoff point between those with and without increased signals. Hence, signal intensity on MRI is an effective predictor of the neurobehavioral performance of Mn exposed workers.     

Parkinsonism due to manganism in a welder: neurological and neuropsychological sequelae

A 33-year-old welder with 3 years of exposure to manganese (Mn) bearing welding fumes was seen by neurologists for cognitive and motor complaints. He exhibited signs and symptoms of Parkinson's disease, including tremor, bradykinesia, gait disturbance and cogwheel rigidity. However, he was young and had significant inattention and forgetfulness, had found levodopa unhelpful and moved with a cock-walk gait, all of which suggested manganism. His serum and urine levels of Mn were, in fact, elevated, and his brain MRI had increased T1-weighted signal intensities in the basal ganglia bilaterally (globus pallidus) consistent with Mn deposition. Two years later, he underwent comprehensive neuropsychological testing. Clinical history indicated a mild tremor and emotional dysfunction with irritability, anxiety, and depression with psychotic features. He showed deficits in cognitive flexibility, information processing and speed, and greatly reduced motor speed, which are consistent with a fronto-subcortical process. These findings support a diagnosis of early onset parkinsonism from welding.     

Calcification mimicking manganese-induced increased signal intensities in T1-weighted MR images in a patient taking herbal medicine: case report

Characteristic high signal intensities confined to the globus pallidus on T1-weighted magnetic resonance image (MRI) can be observed in manganese (Mn)-exposed workers, however, these high signals should be differentiated from those due to other causes such as fat, hemoglobin breakdown products, melanoma, neurofibromatosis, and calcification. A 39-year-old woman was admitted with mutism and involuntary movements which had developed the day before. She had ingested two packs of liquid herbal medicine containing 0.53 mg of Mn daily for 4 months prior to visiting our hospital. Her MRI showed high signals, confined mainly to the globus pallidus on T1-weighted images. Follow-up brain MRI at an interval of 11 months showed no interval change. Brain computed tomography (CT) at the time of the second MRI showed symmetric calcification on both globus pallidus. Blood levels of liver function tests, calcium, phosphorus, and parathyroid hormone were within normal ranges. The increased signals, which were first presumed to be induced by Mn, were concluded to be due to calcification based on the following reasons. First, follow-up brain MRI at an interval of 11 months did not show any interval change. Second, the ingested amount of 1.06 mg Mn daily for 4 months is even less than that added to mineral supplements for adults. Third, Mn-induced high signals in T1-weighted MRI do not show any abnormal findings in brain CT. The present case report suggests that brain CT should be performed to rule out symmetric calcification on basal ganglia in patients showing increased signals in T1-weighted MRI, but who do not have a significant exposure history to Mn. The present report also showed that the amount of 1.06 mg Mn daily ingested for 4 months did not cause the high signal in brain MRI.     

Blood manganese concentration is elevated in iron deficiency anemia patients, whereas globus pallidus signal intensity is minimally affected

OBJECTIVES: To determine whether blood manganese (Mn) concentration is elevated in patients with iron deficiency anemia (IDA), and whether this affects signal intensities in the globus pallidus. METHODS: Twenty-seven patients with IDA and 10 control subjects were tested for blood Mn, and brain magnetic resonance images (MRI) were also examined. Seventeen of the 27 patients were followed-up after iron therapy. RESULTS: IDA patients had a mean blood Mn concentration of 2.05 +/- 0.44 microg/dl, which was higher than controls. The mean pallidal index (PI) of anemic patients was not different from that of controls. There was a correlation between log blood Mn and PI (rho = 0.384, P = 0.048; n = 27) in IDA patients. None of the patients showed increased signals in the globus pallidus in T1-weighted MRI. Blood Mn levels decreased and hemoglobin levels increased after iron therapy (P < 0.05). CONCLUSION: Although blood Mn is elevated in IDA patients, there is no increase in globus pallidus MRI signal intensity. These findings stand in contrast to those of our other studies showing patients with chronic liver disease or occupational Mn exposure have elevated signal intensities remarkably.     

Clinical,neuroimaging and neurophysiological features in addicts with manganese‐ephedrone exposure

Sikk K, Taba P, Haldre S, Bergquist J, Nyholm D, Askmark H, Danfors T, Sörensen J, Thurfjell L, Raininko R, Eriksson R, Flink R, Färnstrand C, Aquilonius S‐M. Clinical, neuroimaging and neurophysiological features in addicts with manganese‐ephedrone exposure.
Acta Neurol Scand: 2010: 121: 237–243.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To identify biomarkers supporting the clinical diagnosis of manganism in patients several years after exposure to manganese (Mn). Methods – Neurophysiological examinations, magnetic resonance imaging (MRI), single‐photon emission computed tomography and fluorodeoxyglycose (FDG) positron emission tomography were performed in four former ephedrone addicts with extrapyramidal symptoms. Results – Peripheral nervous system was not affected. No patients had reduced uptake of ¹²³I Ioflupane in the striatum. MRI signal intensities were slightly changed in the basal ganglia. All patients showed a widespread, but not uniform, pathological pattern of FDG uptake with changes mainly located to the central part of the brain including the basal ganglia and the surrounding white matter. Conclusions – Presynaptic neurons in the nigrostriatal pathway are intact in Mn‐induced parkinsonism after prolonged abstinence from ephedrone. The diagnosis is principally based on clinical signs and the history of drug abuse.     

Evaluation of MR signal index for the assessment of occupational manganese exposure of welders by measurement of local proton T1 relaxation time

Magnetic resonance (MR) imaging has become a useful tool for the estimation of occupational exposure to manganese (Mn). However, validity of signal indices on T1-weighted imaging, a proxy measurement of T1 relaxation time shortening due to Mn deposition, needs to be evaluated in an occupationally exposed population. We performed MR imaging on 20 male welders and 10 age- and gender-matched, non-office workers in a shipyard. We measured the relative signal intensity ratio of the globus pallidus (GP) to the frontal white matter on T1-weighted MR images (pallidal index, PI). We also assessed the visual scale for the relative signal intensity of the GP, which was graded as 0-2 by a radiologist. We evaluated both signal index and visual scale in relation to the T1 relaxation time measured at the GP. Both PI and T1 relaxation time were significantly increased in the welders compared to the non-welders. T1 relaxation time began to decrease from visual scale 2, while PI began to increase from visual scale 1. Environmental Mn exposure indices correlated well with both T1 relaxation time and PI. However, blood Mn level correlated only with T1 relaxation time, and not with PI. T1 relaxation time correlated with PI only at the higher level of PI. These results indicate the possible inaccuracy of visual scoring and the discrepancy between T1 relaxation time and PI, especially at the lower level of signal intensity. Although both T1 and PI are good biomarkers for the environmental Mn exposure, non-linearity of the relationship between T1 and PI must be considered in the assessment of Mn exposure using MRI.     

Whole blood manganese correlates with high signal intensities on T1-weighted MRI in patients with liver cirrhosis

We examined whole blood (MnB), plasma (MnP) and urinary Mn (MnU) concentrations in 33 cirrhotics and 11 healthy controls to clarify: (1) whether, in chronic liver diseases, MnB or MnP reflects pallidal signal intensities in magnetic resonance imaging (MRI); and (2) which factors in chronic liver diseases correlate with pallidal signal intensities in T1-weighted MRI. Increased signal intensity in the pallidum was observed in 27 (81.8%) of 33 patients with liver cirrhosis in T1-weighted MRI. There was a significant correlation between MnB and pallidal index (PI) (gamma = 0.559, P < 0.01) in the patients. However, no significant correlation was observed between MnP and PI (gamma = 0.353, P > 0.05). According to a multiple linear regression, MnB reflected the signal intensities of T1-weighted MRI better than MnP or MnU. Child/Pugh score and total bilirubin level also correlated with PI. However, the hemoglobin level did not correlate with PI significantly.     

Research capacity development in South African manganese mines to bridge exposure and neuropathologic outcomes

Manganese (Mn) is a common occupational exposure worldwide. Recent studies indicate clinical and imaging evidence of neurotoxicity in chronically exposed workers. The pathologic significance of these findings is unclear. South Africa produces over 80% of the world's Mn from mines from a desert region in the Northern Cape Province. An autopsy program at the National Institute for Occupational Health (NIOH) in South Africa has provided compensation to families for mining-related lung diseases for almost 100 years. Building on this, we implemented a brain autopsy program to investigate the feasibility of obtaining brains from South African Mn miners and non-exposed reference miners to investigate neuropathologic consequences of chronic Mn exposure. Employing an experienced occupational health nurse, we identified deceased miners within 100 square km of the Mn mines. The nurse was notified of any Mn (case) or other (reference) miner or ex-miner death by local medical practitioners, occupational health and mine physicians, and community members, and families were approached for consent to remove the brains in addition to the cardio-respiratory organs. Families of deceased miners who had an autopsy at the NIOH in Johannesburg were also approached. To confirm exposure in Mn miners, mean pallidal indices were compared between Mn miners and non-exposed reference miners. Sixty-eight potential brain donors were identified; we obtained consent from the families to remove 51 (75%). The mean autopsy interval was seven days. With optimized fixation methods, the tissue quality of the brains for gross and regular microscopic examination was excellent. Ex vivo MRI demonstrated increased pallidal index in Mn miners compared to reference miners. We conclude that obtaining brain tissue from deceased miners in South Africa is highly successful with only a modest investment in local infrastructure. Tissue quality was excellent and should be ideal to investigate the neuropathologic consequences of chronic occupational Mn exposure.     

MRI pallidal signal in children exposed to manganese in drinking water

BackgroundManganese (Mn) can have neurotoxic effects upon overexposure. We previously reported poorer cognitive and motor development in children exposed to Mn through drinking water, suggesting possible neurotoxic effects from Mn in water. Hyperintensity in the globus pallidus (GP) on T1-weighted magnetic resonance imaging (MRI) indicates excessive brain Mn accumulation. Previous studies have reported GP hyperintensity related to Mn exposure in occupationally exposed individuals. However, no study has used MRI in children exposed to Mn in drinking water and who show no sign of overt intoxication.ObjectiveTo examine MRI signal intensity in the GP in children exposed to contrasted levels of Mn in drinking water.MethodsWe enrolled 13 children exposed to low Mn concentration in water and 10 children (ages 9–15 years) with high concentration (median of 1 and 145 μg/L, respectively). We calculated three MRI T1 indexes: (i) standard pallidal index (PI) using frontal white matter as reference; (ii) PI using pericranial muscles as reference; and (iii) T1 relaxation time. Each MRI index was compared between exposure groups, and with respect to the estimated Mn intake from water consumption.ResultsThe standard PI did not differ between Mn-exposure groups. However, children in the group with high water-Mn concentration had significantly lower pericranial muscles PI than those with lower exposure and, accordingly, higher T1 relaxation time. Mn intake from water consumption was not correlated with the standard PI, but was significantly related to the pericranial muscles PI and T1 relaxation time. Motor performance was significantly lower in the high-exposure group.ConclusionWe observed lower signal intensity in the GP of children with higher exposure to Mn from drinking water. This result stands in contrast to previous MRI reports showing GP hyperintensity with greater Mn exposure. Differences in exposure pathways are discussed as a potential explanation for this discrepancy.     

Neuropsychiatric symptoms and past manganese exposure in a ferro-alloy plant

INTRODUCTION: Psychiatric manifestations have been reported in cases of manganism, and mood disorders are often observed in manganese (Mn) exposed workers. We examined neuropsychiatric symptoms among formerly Mn-exposed workers 14 years after cessation of exposure. MATERIALS AND METHODS: A study was conducted in 1990 among workers from a ferro- and silico-Mn plant and unexposed working men referents from the same region in South-West Quebec. At follow-up in 2004, 77 former Mn-workers and 81 referents agreed to participate and responded to a neuropsychiatric symptom checklist, the Brief Symptom Inventory (BSI); scores were transformed into T-scores based on a normative population. Cumulated exposure indices (CEI) were computed for each former Mn-worker. Linear and logistic regression analyses were used. RESULTS: Mean T-scores were significantly higher among former Mn-workers than referents on scales of Depression and Anxiety. Mean T-scores of psychological distress increased with the CEI tertiles, with significant associations for the scales Somatization, Depression, Anxiety and Hostility. Former Mn-workers in the two highest tertiles of CEI showed a higher risk for T-scores >or=63 for Hostility (OR, 7.5; 95% CI, 1.5-38.9), Depression (OR, 2.6; 95% CI, 1.1-8.4) and Anxiety (OR, 3.0; 95% CI, 1.1-8.4). CONCLUSION: These results suggest that past exposure to Mn may have lasting consequences on neuropsychiatric symptoms.     

Diffusion-weighted MRI and 99mTc-HMPAO SPECT in delayed relapsing type of carbon monoxide poisoning: evidence of delayed cytotoxic edema

BACKGROUND: Carbon monoxide (CO) is a common cause of poisoning, and its sequelae include a progressive (25%) and a delayed relapsing form (75%). We report the diffusion-weighted MRI (DWI) findings in the delayed relapsing form of CO poisoning and characterize the types of edema. METHODS: From November 1, 2000 to June 1, 2003, 5 consecutive patients (2 men, 3 women, range of age: 54-67 years), who had the delayed relapsing type of CO poisoning, underwent DWI, conventional MRI, MR angiography and SPECT. CO poisoning was diagnosed by the presence of a typical clinical history, an abnormally increased level of serum carboxyhemoglobin and MRI findings. Apparent diffusion coefficient (ADC) values were measured in all of the abnormal lesions with visual inspection of DWI and T(2)-weighted echo-planar imaging. RESULTS: DWI showed high signal intensities in bilateral periventricular white matter, in the splenium of the corpus callosum, in internal capsules, and brainstem showing moderately decreased ADC values. In the globus pallidus, the ADC values were rather increased with low signal intensities on DWI. Brain SPECT showed decreased perfusion in bilateral white matter and some parts of the cerebral cortex, which correlated well with the DWI findings. CONCLUSIONS: We suggest that prominent, symmetric restricted diffusion can occur in periventricular white matter, brainstem, and corpus callosum after the delayed relapsing type of CO poisoning. Delayed cytotoxic edema can occur in this setting, which provides a new guidance for the pathogenesis of CO poisoning and the differential diagnosis of white matter diseases.     

Chronic acquired hepatocerebral degeneration,pallidal T1 MRI hyperintensity and manganese in a series of cirrhotic patients

Chronic acquired hepatocerebral degeneration (CAHD) is a rare neurological disorder of cirrhotic patients, characterized by parkinsonism and cognitive impairment. A T1 hyperintensity on the globus pallidum due to an accumulation of manganese (Mn) is found in these patients. The aim of the study was to investigate CAHD, Mn and the MRI pallidal signal in a series of cirrhotic patients. The association between pallidal T1 hyperintensity, CAHD, and blood levels of Mn, the effect of orthotopic liver transplantation (OLT) on the MRI signal and neurological findings, and the role of the pallidal signal as a predictor of CAHD were evaluated. Twenty-six out of 90 patients with cirrhosis had pallidal T1 hyperintensity. Seven patients had CAHD. OLT was followed by the disappearance of CAHD and MRI signal in 2/2 patients. The MRI signal disappeared after OLT in 8/13 patients after a median follow-up time of 24 months. In the patients who did not undergo OLT, CAHD did not present after a median follow-up time of 18 months. The cause of cirrhosis, episodes of acute hepatic encephalopathy and signal intensity were not correlated with CAHD. The blood levels of Mn did not reflect either the MRI signal or CAHD. In conclusion, the pallidal T1 hyperintensity is a prerequisite for the clinical manifestations of CAHD but is not sufficient. The blood levels of Mn as routinely monitored are not a useful marker of Mn burden. The MRI pallidal signal is not a predictor of CAHD.     

Dopamine transporter binding study in differentiating carbon disulfide induced parkinsonism from idiopathic parkinsonism

Long-term exposure to carbon disulfide (CS(2)) may induce parkinsonian features. There may be confusion in distinguishing between CS(2) parkinsonism and idiopathic parkinsonism, especially for workers who developed parkinsonian features in viscose rayon plants. We performed clinical examinations, and laboratory studies including magnetic resonance imaging (MRI) and dopamine transporter (DAT) studies with (99m)Tc-TRODAT-1 brain single photon emission computed tomography (SPECT) in three workers who had long-term exposure to CS(2). Patient 1 had polyneuropathy, and encephalopathy with tremor; patient 2 had polyneuropathy, and encephalopathy with parkinsonian features; and patient 3 had pure parkinsonian features without polyneuropathy or cerebellar signs. The treatment with l-dopa was effective in patient 3, but non-effective in patient 2. Brain MRI revealed multiple high signal intensities over the subcortical white matter, basal ganglia, and/or even the brainstem in patients 1 and 2, but normal in patient 3. In DAT studies, the bindings were normal in patients 1 and 2 and was decreased in patient 3. We conclude that CS(2) exposure may induce polyneuropathy, and cerebellar dysfunction in addition to parkinsonian features and that brain MRI may show multiple lesions in the cerebral white matter and basal ganglia. In addition, DAT with (99m)Tc-TRODAT-1 brain SPECT may provide a useful information in differential diagnosis between CS(2) parkinsonism and idiopathic parkinsonism.     

Subacute toxicity of exogenous manganese on rat hippocampal neurons Examination by MRI and optical microscopy

BACKGROUND: Manganism may cause learning and memory impairment by influencing the normal function of the hippocampus, however, this effect requires further examination.OBJECTIVE: To investigate the effects of manganism on the rat hippocampus using immunohistochemistry and MRI examination.DESIGN, TIME AND SETTING: A randomized controlled study, performed in the School of Medicine and Life Science, Jianghan University and the State Key Laboratory of Atomic & Molecular Physics and Spectroscopy, Chinese Academy of Science, from July to September 2005.MATERIALS: Fourteen healthy SD rats aged two months were selected for this study. MnCl2 4H2O (BIID, UK) (batch number: 9791325); glial fibrillary acidic protein (GFAP) staining kit (Beijing Zhongshan Biotechnology); Biospec 4.7T/30 animal MRI formatter (Bruker, Germany).METHODS: Fourteen rats were randomly divided into a control group (n=7) and a manganism group (n=7). Rats in the manganism group Received intraperitoneal injection of MnCl2·4H2O (50mg/kg), once a day, for four successive days. Rats in the control group were injected according to the manganism regimen, but using saline instead of manganese solution.MAIN OUTCOME MEASURES: Twenty-four hours after the last injection, rats were examined using MRI. Immunohistochemically stained GFAP and hematoxylin-eosin stained hippocampal sections were observed under optical microscopy.RESULTS: Fourteen rats were included in the final analysis. After manganese treatment, T1 weighted image and inversion recovery MRI demonstrated that the signal intensity was significantly enhanced in hippocampus, compared to controls. Neuronal necrosis was not observed in the hippocampus after HE staining. As compared to the control group, GFAP expression was markedly enhanced in the hippocampus of the manganism group.CONCLUSION: Within the rat brain, manganese preferentially localizes to the hippocampus and can induce astroctye activation.     

Clinical equipoise and treatment decisions in cervical spondylotic myelopathy

OBJECTIVE: The primary objective of this study is to evaluate clinician attitudes towards the treatment of cervical spondylotic myelopathy (CSM) in order to determine whether clinical equipoise exists for a segment of this patient population. The secondary objective is to examine the factors that influence treatment decisions. METHODS: Cross-sectional internet-based survey of neurologists, neurosurgeons and orthopedic surgeons. RESULTS: Between 40-60% of respondents recommended surgery for (1) patients with minimal or no symptoms, but incidentally discovered increased T2 signal within the cervical cord on MRI, (2) patients with mild symptoms and indentation of the cervical cord but without increased T2 signal and (3) those with at least moderately severe clinical findings accompanied by MRI showing effacement of the thecal sac but without indentation of the cord or increased T2 signal. The severity of the radiological abnormalities most strongly influence treatment decisions. CONCLUSIONS: We conclude that clinical equipoise does exist for certain groups of patients with CSM, suggesting that a randomized controlled trial could be performed in this population.