Association between symptom severity and internal capsule volume in obsessive-compulsive disorder

Neurobiological models support an involvement of white matter tracts in the pathophysiology of obsessive-compulsive disorder (OCD), but there has been little systematic evaluation of white matter volumes in OCD using magnetic resonance imaging (MRI). We investigated potential differences in the volume of the cingulum bundle (CB) and anterior limb of internal capsule (ALIC) in OCD patients (n = 19) relative to asymptomatic control subjects (n = 15). White matter volumes were assessed using a 1.5T MRI scanner. Between-group comparisons were carried out after spatial normalization and image segmentation using optimized voxel-based morphometry. Correlations between regional white matter volumes in OCD subjects and symptom severity ratings were also investigated. We found significant global white matter reductions in OCD patients compared to control subjects. The voxel-based search for regional abnormalities (with covariance for total white matter volumes) showed no specific white matter volume deficits in brain portions predicted a priori to be affected in OCD (CB and ALIC). However, large clusters of significant positive correlation with OCD severity scores were found bilaterally on the ALIC. These findings provide evidence of OCD-related ALIC abnormalities and suggest a connectivity dysfunction within frontal-striatal-thalamic-cortical circuits. Further studies are warranted to better define the role of such white matter alterations in the pathophysiology of OCD, and may provide clues for a more effectively targeting of neurosurgical treatments for OCD. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Acute Damage to the Posterior Limb of the Internal Capsule on Diffusion Tensor Tractography as an Early Imaging Predictor of Motor Outcome after Stroke

Background and Purpose Early prediction of motor outcome is of interest in stroke management. We aimed to determine whether lesion location at DTT is predictive of motor outcome after acute stroke and whether this information improves the predictive accuracy of the clinical scores. Methods We evaluated 60 consecutive patients within 12 hours of MCA stroke onset. We used DTT to evaluate CST involvement in the MC and PMC, CS, CR, and PLIC and in combinations of these regions at admission, at day 3, and at day 30. Severity of limb weakness was assessed using the m-NIHSS (5a, 5b, 6a, 6b). We calculated volumes of infarct and FA values in the CST of the pons. Results Acute damage to the PLIC was the best predictor associated with poor motor outcome, axonal damage, and clinical severity at admission (P&.001). There was no significant correlation between acute infarct volume and motor outcome at day 90 (P=.176, r=0.485). The sensitivity, specificity, and positive and negative predictive values of acute CST involvement at the level of the PLIC for 4 motor outcome at day 90 were 73.7%, 100%, 100%, and 89.1%, respectively. In the acute stage, DTT predicted motor outcome at day 90 better than the clinical scores (R2=75.50, F=80.09, P&.001). Conclusions In the acute setting, DTT is promising for stroke mapping to predict motor outcome. Acute CST damage at the level of the PLIC is a significant predictor of unfavorable motor outcome.

Cromomicose cerebral: registro de um caso

A case of brain abscess and meningitis due to pigmented fungi is reported. The patient was a 59-year-old white male, who had enjoyed excellent health until October 1977, when he developed headache, later accompanied by paresthesias and weakness in the left-sided extremities. These symptoms worsened progressively and in November of that year he had to quit his job. From February 1978 on he became inactive and anorexic. Intense continuous headache was associated with frequent episodes of vomiting. He gradually became tor-porous, and according to his relatives, suffered from visual and possibly auditory deficiency. On examination, he was malnourished and dehydrated, with decubitus ulcers. Temperature was 38,5°C. A left-sided spastic hemiplegia and prominent meningorradicular signs were noted. The CSF was examined six times between May 17th and June 1st and showed variable hypercytosis (143 to 4,437 leucocytes/ cu mm) with predominance of neutrophils (up tp 95%), low glucose and high protein concentrations. No microorganisms were identified. Electroencephalographic study disclosed a low background activity especially in left temporal areas. Despite supportive care and antibiotic therapy he lapsed into coma. Carotid angiography was normal on June 1st. He remained in deep coma until his death on June 6th, 1978. Necropsy was limited to the brain, which weighed 1,550 g after fixation and showed diffuse intense edema and hyperemia. On coronal sectioning an encapsulated abscess was found in the right basal ganglia, which also involved the internal capsule, and measured 1.5 cm in diameter. Microscopical examination disclosed large numbers of brownish fungi, appearing both as oval yeasts and as septate hyphae in the thick fibrous capsule and in the necrotic content of the abscess. The same organisms were demonstrated in moderate numbers in the leptomeninges of the medulla oblongata and , less frequently, of the hippo-campal region and cerebellum.

Excitatory synaptic inputs to pyramidal neurons of the lateral amygdala

Whole-cell patch clamp recordings were made from pyramidal neurons in the rat lateral amygdala (LA). Synaptic currents were evoked by stimulating in either the external capsule (ec), internal capsule (ic) or basolateral nucleus (BLA). Stimulation of either the ic, ec or BLA evoked a glutamatergic excitatory synaptic current (EPSC) which was mediated by both non-NMDA and NMDA (N-methyl-D-aspartic acid) receptors, The ratio of the amplitude of the NMDA receptor-mediated component measured at +40 mV to the amplitude of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component measured at -60 mV was similar regardless of whether EPSCs were evoked in the ec, ic or BLA. At resting membrane potentials, excitatory synaptic potentials evoked from either the ec or putative thalamic inputs were unaffected by application of the NMDA receptor antagonist APV. Spontaneous glutamatergic currents had two components to their decay phase. The slow component was selectively blocked by the NMDA receptor antagonist D-APV, indicating that AMPA and NMDA receptors are colocalized in spiny neurons. We conclude that pyramidal cells of the LA receive convergent inputs from the cortex, thalamus and basal nuclei. At all inputs, both AMPA/kainate and NMDA-type receptors are active and colocalized in the postsynaptic density.

Development and reorganization of corticospinal projections in EphA4 deficient mice

The Eph family of receptor tyrosine kinases and their ligands, the ephrins, are important regulators of axon guidance and cell migration in the developing nervous system. Inactivation of the EphA4 gene results in axon guidance defects of the corticospinal tract, a major descending motor pathway that originates in the cortex and terminates at all levels of the spinal cord. In this investigation, we report that although the initial development of the corticospinal projection is normal through the cortex, internal capsule, cerebral peduncle, and medulla in the brain of EphA4 deficient animals, corticospinal axons exhibit gross abnormalities when they enter the gray matter of the spinal cord. Notably, many corticospinal axons fail to remain confined to one side of the spinal cord during development and instead, aberrantly project across the midline, terminating ipsilateral to their cells of origin. Given the possible repulsive interactions between EphA4 and one of its ligands, ephrinB3, this defect could be consistent with a loss of responsiveness by corticospinal axons to ephrinB3 that is expressed at the spinal cord midline. Furthermore, we show that EphA4 deficient animals exhibit ventral displacement of the mature corticospinal termination pattern, suggesting that developing corticospinal axons, which may also express ephrinB3, fail to be repelled from areas of high EphA4 expression in the intermediate zone of the normal spinal cord. Taken together, these results suggest that the dual expression of EphA4 on corticospinal axons and also within the surrounding gray matter is very important for the correct development and termination of the corticospinal projection within the spinal cord. J. Comp. Neurol. 436: 248-262, 2001. (C) 2001 Wiley-Liss, Inc.

Effects of intravenous injection of Clostridium perfringens type D epsilon toxin in calves

In cattle, a neurological lesion similar to that produced in sheep and goats by Clostridium perfringens type D enterotoxaemia has been reported. However, no causal relationship has been established between this disease and the lesion in cattle. The effects of single and multiple intravenous injections of epsilon toxin in three calves aged 6 months were studied. A further calf was inoculated intravenously with saline solution and used as a control. Epsilon toxin invariably produced neurological signs within 2-60 min of the end of the injection process. Clinical signs consisted of loss of consciousness, recumbency, convulsions, paddling, opisthotonus, hyperaesthesia and dyspnoea. Gross changes consisted of severe acute pulmonary oedema, which was particularly marked in the interlobular septa. The histological lesions consisted of intra-alveolar and interstitial oedema of the lung and variable degrees of perivascular proteinaceous oedema in the internal capsule, thalamus and cerebellar white matter. No clinical or post-mortem changes were observed in the control calf. These results show that calves are susceptible to the intravenous injection of epsilon toxin, and that they can show at least some of the histological lesions produced in sheep and goats by this toxin. (C) 2002 Harcourt Publishers Ltd.

Caracterização de regiões encefálicas no cérebro normal por tensor de difusão e aplicação à epilepsia pós-traumática

Mestrado em Radiações Aplicadas às Tecnologias da Saúde.

Pure monoparesis: a particular stroke subgroup?

BACKGROUND: Acute stroke presenting as monoparesis is rare, with a pure motor deficit in the arm or leg extending to an isolated facial paresis. OBJECTIVE: To raise the question if acute stroke presenting as monoparesis is a different entity from stroke with a more extensive motor deficit. PATIENTS: In the Lausanne Stroke Registry (1979-2000), 195 (4.1%) of 4802 patients met the clinical criteria for pure monoparesis involving the face (22%), arm (63%), or leg (15%). RESULTS: In the vast majority of cases (> 95%), monoparesis corresponded to ischemic stroke with a favorable outcome, with initial computed tomography scans or magnetic resonance images showing no signs of hemorrhage. The lesion for a facial deficit was most frequently located subcortically (internal capsule); for an arm deficit, in the superficial middle cerebral artery; and for a leg deficit, in the anterior cerebral artery territory. In pure monoparesis, only 17% of the patients had more than 1 risk factor as compared with 26% of those with bimodal and trimodal hemiparesis and with 46% of all patients with stroke other than those with pure motor stroke. The only frequent risk factor was hypertension (53%); however, this frequency was no different from that in other patients with stroke. No major stroke etiology could be identified in any of the 3 subgroups of monoparesis. CONCLUSION: Our finding of a wide range of stroke localization and etiology in monoparesis without any particular subgroup suggests that no specific plan of investigation can be recommended for these patients.

Thalamic connectivity in patients with essential tremor treated with MR imaging-guided focused ultrasound: in vivo fiber tracking by using diffusion-tensor MR imaging.

PURPOSE: To use diffusion-tensor (DT) magnetic resonance (MR) imaging in patients with essential tremor who were treated with transcranial MR imaging-guided focused ultrasound lesion inducement to identify the structural connectivity of the ventralis intermedius nucleus of the thalamus and determine how DT imaging changes correlated with tremor changes after lesion inducement. MATERIALS AND METHODS: With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a HIPAA-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand. Fourteen patients were ultimately included. DT MR imaging studies at 3.0 T were performed preoperatively and 24 hours, 1 week, 1 month, and 3 months after the procedure. Fractional anisotropy (FA) maps were calculated from the DT imaging data sets for all time points in all patients. Voxels where FA consistently decreased over time were identified, and FA change in these voxels was correlated with clinical changes in tremor over the same period by using Pearson correlation. RESULTS: Ipsilateral brain structures that showed prespecified negative correlation values of FA over time of -0.5 or less included the pre- and postcentral subcortical white matter in the hand knob area; the region of the corticospinal tract in the centrum semiovale, in the posterior limb of the internal capsule, and in the cerebral peduncle; the thalamus; the region of the red nucleus; the location of the central tegmental tract; and the region of the inferior olive. The contralateral middle cerebellar peduncle and bilateral portions of the superior vermis also showed persistent decrease in FA over time. There was strong correlation between decrease in FA and clinical improvement in hand tremor 3 months after lesion inducement (P < .001). CONCLUSION: DT MR imaging after MR imaging-guided focused ultrasound thalamotomy depicts changes in specific brain structures. The magnitude of the DT imaging changes after thalamic lesion inducement correlates with the degree of clinical improvement in essential tremor.

Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

Prognostic value of cortically induced motor evoked activity by TMS in chronic stroke: caveats from a very revealing single clinical case

Background: We report the case of a chronic stroke patient (62 months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand. Case presentation: Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations. Conclusions: The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients.

Focal symmetrical encephalomalacia in sheep

Focal symmetrical encephalomalacia (FSE) is the most prominent lesion seen in the chronic form of enterotoxemia by Clostridium perfringens type D. This paper reports FSE in sheep in Brazil. Six deaths occurred within a seven days period in a flock of 70, four to 30-month-old Santa Inês sheep in the state of Paraíba in the Brazilian semiarid. The flock was grazing a paddock of irrigated sprouting Cynodon dactylon (Tifton grass), and supplemented, ad libitum, with a concentrate of soybean, corn and wheat. Nervous signs included blindness and recumbence. A 19 month-old sheep was examined clinically and necropsied after a clinical course of three days. Gross lesions were herniation of the cerebellar vermis and multifocal, bilateral, symmetric brownish areas in the internal capsule, thalamus and cerebellar peduncles. Histologic lesions were multifocal, bilateral malacia with some neutrophils, swelling of blood vessels endothelium, perivascular edema, and hemorrhages. The flock was vaccinated, before the outbreak, with only one dose of Clostridium perfringens type D vaccine. Two factors are suggested to be important for the occurrence of the disease: insufficient immunity due to the incorrect vaccination; and high nutritional levels by the supplementation with highly fermentable carbohydrates.

Fetal and maternal lesions of cyanide dosing to pregnant goats

The present work evaluated the pathological effects in both dams and their fetuses of cyanide ingestion during pregnancy using goat as animal model. From the Day 24 of pregnancy, three pregnant goats were dosed by gavage with 3.0 mg KCN/kg bw/day, and two others received only tap water. All dams were euthanized and necropsied at Day 120 of pregnancy. The fetuses were examined carefully for gross abnormalities. Determinations of cyanide and thiocyanate were performed in maternal and fetal blood and in amniotic fluid. Samples of several organs were collected for histopathologic evaluation. No clinical changes were seen in any animal throughout the pregnancy. No malformations or dead fetuses were observed: however, placenta from one treated goat presented increased cotyledon surface area occupied by vascular lumina. Histological lesions in KCN-treated dams consisted of vacuolation of hepatocytes and thyroid follicular cells, increased number of vacuoles on thyroid follicular colloid. and spongiosis of cerebral, internal capsule, and cerebellar peduncles tracts. Fetuses from these mothers showed vacuolation of hepatocytes and thyroid follicular cells, and spheroids in the cerebellar white matter. Levels of cyanide and thiocyanate were higher in maternal than fetal blood, which suggests that these substances were largely but not freely transferred from mothers to fetuses. (C) 2009 Elsevier B.V. All rights reserved.