Texture analysis of high resolution MRI allows discrimination between febrile and afebrile initial precipitating injury in mesial temporal sclerosis

A computational pipeline combining texture analysis and pattern classification algorithms was developed for investigating associations between high-resolution MRI features and histological data. This methodology was tested in the study of dentate gyrus images of sclerotic hippocampi resected from refractory epilepsy patients. Images were acquired using a simple surface coil in a 3.0T MRI scanner. All specimens were subsequently submitted to histological semiquantitative evaluation. The computational pipeline was applied for classifying pixels according to: a) dentate gyrus histological parameters and b) patients' febrile or afebrile initial precipitating insult history. The pipeline results for febrile and afebrile patients achieved 70% classification accuracy, with 78% sensitivity and 80% specificity [area under the reader observer characteristics (ROC) curve: 0.89]. The analysis of the histological data alone was not sufficient to achieve significant power to separate febrile and afebrile groups. Interesting enough, the results from our approach did not show significant correlation with histological parameters (which per se were not enough to classify patient groups). These results showed the potential of adding computational texture analysis together with classification methods for detecting subtle MRI signal differences, a method sufficient to provide good clinical classification. A wide range of applications of this pipeline can also be used in other areas of medical imaging. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.

Mesial temporal lobe epilepsy: Clinical and neuropathologic findings of familial and sporadic forms

Purpose: To evaluate the clinical and hippocampal histological features of patients with mesial temporal lobe epilepsy (MTLE) in both familial (FMTLE) and sporadic (SMTLE) forms. Methods: Patients with FMTLE (n = 20) and SMTLE (n = 39) who underwent surgical treatment for refractory seizures were studied at the University of Sao Paulo School of Medicine at Ribeirao Preto. FMTLE was defined when at least two individuals in a family had clinical diagnosis of MTLE. Hippocampi from all patients were processed for Nissl/HE and Timm`s stainings. Both groups were compared for clinical variables, hippocampal cell densities, and intensity of supragranular mossy fiber staining. Results: There were no significant differences between FMTLE and SMTLE groups in the following: age at the surgery, age of first usual epileptic seizure, history of initial precipitating injury (IPI), age of IPI, latent period, ictal and interictal video-EEG patterns, presence of hippocampal atrophy and signal changes at MRI, and postoperative outcome. In addition, no differences were found in cell densities in hippocampal cornu ammonis subfields (CA1, CA2, CA3, CA4), fascia dentata, polymorphic region, subiculum, prosubiculum, and presubiculum. However, patients with SMTLE had greater intensity of mossy fiber Timm`s staining in the fascia dentata-inner molecular layer (p < 0.05). Discussion: Patients with intractable FMTLE present a clinical profile and most histological findings comparable to patients with SMTLE. Interestingly, mossy fiber sprouting was less pronounced in patients with FMTLE, suggesting that, when compared to SMTLE, patients with FMTLE respond differently to plastic changes plausibly induced by cell loss, neuronal deafferentation, or epileptic seizures.

On the relationship between neurocysticercosis and mesial temporal lobe epilepsy associated with hippocampal sclerosis: coincidence or a pathogenic relationship?

Neurocysticercosis (NCC) and mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) are two common worldwide forms of focal epilepsy. In regions where NCC is endemic, both diseases can be observed in the same patient. There is recent and growing evidence suggesting that NCC might contribute to or even cause MTLE-HS. In this article, we review the literature regarding NCC and temporal lobe epilepsy, specifically addressing the relationship between NCC and MTLE-HS. In addition, we review some scenarios where NCC seems to emerge as a causative agent or contributor to the development of MTLE-HS in some patients. This association is important because it may have an impact on the evaluation and treatment of a sizable proportion of patients with epilepsy. Insights from these clinical observations might also contribute to the understanding of the neurobiology of both NCC and MTLE-HS. We hope that our review might shed some light on this interesting interplay between two of the most common worldwide conditions associated with human focal epilepsy.

Interictal hyperemia correlates with epileptogenicity in polymicrogyric cortex

Objective: To investigate pathophysiological factors underlying the presence of interictal hyper-perfusion within the limits of the polymicrogyric (PMG) cortex in epileptic patients. Methods: Retrospective observational study on interictal perfusion by Single Photon Emission Computed Tomography (SPECT) in 16 patients with PMG and its correlations with a number of clinical and neurophysiological variables. Patients underwent video-EEG monitoring, neurological and psychiatric assessments, invasive EEG, and the interictal SPECT coregistered to Magnetic Resonance Imaging (MRI). Results: Patients with interictal hyperperfusion within the PMG cortex had a significantly higher spike rate on interictal EEG than patients with normal perfusion. Interictal hyperperfusion was not correlated to sex, age at epilepsy onset, age at evaluation, number of seizures per month, presence of initial precipitating insult (IPI), abnormal neurological examination, EEG findings, ictal serniology, and seizure outcome. The high interictal spike rate did not correlate to a high frequency of seizures per month. Conclusions: Our work provides further evidences for an intrinsic epileptogenesis of the PMG cortex during the interictal state, which accounts for the major rote of PMG tissue in seizure generation. These results might help to increase our understanding about epileptogenesis related to the PMG cortex, providing new toots for more tailored epilepsy surgery in PMG patients. (c) 2008 Elsevier B.V. All rights reserved.

Injuries and envenoming by aquatic animals in fishermen of Coxim and Corumbá municipalities, state of Mato Grosso do Sul, Brazil: identification of the causative agents, clinical aspects and first aid measures

INTRODUCTION: The fishes of continental Brazil have socioeconomic importance due to their potential for sport fishing and commercial and subsistence uses, as seen in the Upper Paraguay River Basin, particularly in the municipalities of the Pantanal region, where it is the second largest economic activity. Injuries caused in professional fishermen are common and poorly studied, as in other regions of the country. METHODS: Data were obtained from questionnaires and interviews with 100 professional fishermen, 50 in each municipality, between December 2008 and October 2009. RESULTS: All the fishermen reported some kind of injury caused by fish stings (78% of injuries) and fish, alligator and snake bites (22%) on the hands (46% of cases) and feet (35% of cases). Most of the patients had mild symptoms. The most severe cases were associated with secondary bacterial infections and required specific treatment and prolonged recovery associated with social and economic losses. CONCLUSIONS: The results of this study indicate that the stressful work conditions, inattention to basic preventive measures and carelessness were factors that contributed to accidents and that the toxicity and ability to inflict mechanical trauma of some aquatic species, plus the ineffective use of first aid and hospital treatment, contributed to the high morbidity and complications in many cases. Data from this study are relevant to the fishing communities of the Pantanal region, since they reveal high rates of accidents, lack of knowledge concerning first aid, initial treatment, injury prevention and lack of medical follow-up of the population.

Injuries and envenoming by aquatic animals in fishermen of Coxim and Corumbá municipalities, state of Mato Grosso do Sul, Brazil: identification of the causative agents, clinical aspects and first aid measures

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Dystrophic cardiomyopathy: amplification of cellular damage by Ca2+ signalling and reactive oxygen species-generating pathways

AIMS: Cardiac myopathies are the second leading cause of death in patients with Duchenne and Becker muscular dystrophy, the two most common and severe forms of a disabling striated muscle disease. Although the genetic defect has been identified as mutations of the dystrophin gene, very little is known about the molecular and cellular events leading to progressive cardiac muscle damage. Dystrophin is a protein linking the cytoskeleton to a complex of transmembrane proteins that interact with the extracellular matrix. The fragility of the cell membrane resulting from the lack of dystrophin is thought to cause an excessive susceptibility to mechanical stress. Here, we examined cellular mechanisms linking the initial membrane damage to the dysfunction of dystrophic heart. METHODS AND RESULTS: Cardiac ventricular myocytes were enzymatically isolated from 5- to 9-month-old dystrophic mdx and wild-type (WT) mice. Cells were exposed to mechanical stress, applied as osmotic shock. Stress-induced cytosolic and mitochondrial Ca(2+) signals, production of reactive oxygen species (ROS), and mitochondrial membrane potential were monitored with confocal microscopy and fluorescent indicators. Pharmacological tools were used to scavenge ROS and to identify their possible sources. Osmotic shock triggered excessive cytosolic Ca(2+) signals, often lasting for several minutes, in 82% of mdx cells. In contrast, only 47% of the WT cardiomyocytes responded with transient and moderate intracellular Ca(2+) signals. On average, the reaction was 6-fold larger in mdx cells. Removal of extracellular Ca(2+) abolished these responses, implicating Ca(2+) influx as a trigger for abnormal Ca(2+) signalling. Our further experiments revealed that osmotic stress in mdx cells produced an increase in ROS production and mitochondrial Ca(2+) overload. The latter was followed by collapse of the mitochondrial membrane potential, an early sign of cell death. CONCLUSION: Overall, our findings reveal that excessive intracellular Ca(2+) signals and ROS generation link the initial sarcolemmal injury to mitochondrial dysfunctions. The latter possibly contribute to the loss of functional cardiac myocytes and heart failure in dystrophy. Understanding the sequence of events of dystrophic cell damage and the deleterious amplification systems involved, including several positive feed-back loops, may allow for a rational development of novel therapeutic strategies.

Anti-glomerular basement membrane glomerulonephritis: Characterization of an epitope, antibody response, and the potential role of IL-4Ralpha in disease progression

Anti-Glomerular Basement Membrane Glomerulonephritis (anti-GBM GM) is one of the earliest described autoimmune disorders. Patients present with proteinuria, anti-GBM antibodies, and renal failure. Studies have implicated a T Helper 1 (TH1) response in disease induction and a T Helper 2 (TH2) response for disease progression. A 13 amino acid long peptide sequence spanning residues 28 through 40 [pCol(28–40)] of the Collagen IV α3 non-collagen domain (Col IV α3 NCD) is immunogenic and induces anti-GBM GN. In order to fully understand disease initiation, this peptide was further characterized. Peptides were created containing one amino acid substitution for the entire length of pCol(28–40) and induction of anti-GBM GN was monitored. When residues 31, 33, or 34 contained the substitution, anti-GBM GN was unable to be induced. Thus, residues 31, 33, and 34 of pCol(28–40) are required for induction of anti-GBM. Glomerular injury is observed as early as 14 days post anti-GBM GN induction. However, the presence of anti-GBM antibodies is not observed until 20 days post immunization. An enlarged lymph node adjacent to the diseased kidney exhibits B cell activation after renal injury and produces antibodies toward GBM. Thus, anti-GBM antibodies are a consequence of the initial renal injury. Differences between disease susceptible and disease resistant rat strains exist in the expression of IL-4Rα, a major player in the TH2 response. IL-4Rα signaling is regulated by soluble IL-4Rα (sIL-4Rα). Low expression levels of sIL-4Rα result in the stabilization of IL-4 binding, while elevated expression sequesters IL-4. Quantitative PCR experiments noted low siL-4Rα expression levels in disease susceptible rats. Induction of an immune response toward sIL-4Rα in this strain was responsible for delayed disease progression in 15 out of the 17 experimental animals. Antibody transfer and in vivo biological activity experiments confirmed that delayed disease development was due to anti-sIL-4Rα antibodies. Together these experiments indicate that a T-cell epitope is required for activation of a TH1 autoimmune response and anti-GBM antibodies are a consequence of renal injury. More importantly, a role for IL-4Rα signaling is implicated in the progression of anti-GBM GN. ^

Instabilidade crónica da tíbio-társica

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Are initial radiographic and clinical scales associated with subsequent intracranial pressure and brain oxygen levels after severe traumatic brain injury?

BACKGROUND: Prediction of clinical course and outcome after severe traumatic brain injury (TBI) is important. OBJECTIVE: To examine whether clinical scales (Glasgow Coma Scale [GCS], Injury Severity Score [ISS], and Acute Physiology and Chronic Health Evaluation II [APACHE II]) or radiographic scales based on admission computed tomography (Marshall and Rotterdam) were associated with intensive care unit (ICU) physiology (intracranial pressure [ICP], brain tissue oxygen tension [PbtO2]), and clinical outcome after severe TBI. METHODS: One hundred one patients (median age, 41.0 years; interquartile range [26-55]) with severe TBI who had ICP and PbtO2 monitoring were identified. The relationship between admission GCS, ISS, APACHE II, Marshall and Rotterdam scores and ICP, PbtO2, and outcome was examined by using mixed-effects models and logistic regression. RESULTS: Median (25%-75% interquartile range) admission GCS and APACHE II without GCS scores were 3.0 (3-7) and 11.0 (8-13), respectively. Marshall and Rotterdam scores were 3.0 (3-5) and 4.0 (4-5). Mean ICP and PbtO2 during the patients' ICU course were 15.5 ± 10.7 mm Hg and 29.9 ± 10.8 mm Hg, respectively. Three-month mortality was 37.6%. Admission GCS was not associated with mortality. APACHE II (P = .003), APACHE-non-GCS (P = .004), Marshall (P < .001), and Rotterdam scores (P < .001) were associated with mortality. No relationship between GCS, ISS, Marshall, or Rotterdam scores and subsequent ICP or PbtO2 was observed. The APACHE II score was inversely associated with median PbtO2 (P = .03) and minimum PbtO2 (P = .008) and had a stronger correlation with amount of time of reduced PbtO2. CONCLUSION: Following severe TBI, factors associated with outcome may not always predict a patient's ICU course and, in particular, intracranial physiology.

Altered left ventricular diastolic function in subjects with spinal cord injury

Study design: This is cross-sectional study. Objectives: The aim of this study is to investigate the cardiac structure and function of subjects with spinal cord injury (SCI) and the impact of metabolic, hemodynamic and inflammatory factors on these parameters. Setting: Sao Paulo, Brazil. Methods: Sixty-five nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI and 31 healthy subjects) were evaluated by medical history, anthropometry, laboratory tests, analysis of hemodynamic and inflammatory parameters and echocardiography. Results: Subjects with SCI had lower systolic blood pressure and higher levels of C-reactive protein and tumor necrosis factor receptors than the healthy ones. Echocardiography data showed that the SCI group presented similar left ventricular (LV) structural and systolic parameters, but lower initial diastolic velocity (Em) (9.2 +/- 0.5 vs 12.3 +/- 0.5 cm s(-1); P<0.001) and higher peak early inflow velocity (E)/Em ratio (7.7 +/- 0.5 vs 6.1 +/- 0.3; P = 0.009) compared with the able-bodied group, even after adjustment for systolic blood pressure and C-reactive protein levels. Furthermore, injured subjects with E/Em >8 had lower peak spectral longitudinal contraction (Sm) (9.0 +/- 0.7 vs 11.6 +/- 0.4cm s(-1); P<0.001) and cardiac output (4.2 +/- 0.2 vs 5.0 +/- 0.21 min(-1); P = 0.029), as well as higher relative wall thickness (0.38 +/- 0.01 vs 0.35 +/- 0.01; P = 0.005), than individuals with SCI with E/Em<8, but similar age, body mass index, blood pressure, injury level, metabolic parameters and inflammatory marker levels. Conclusion: Subjects with SCI presented impaired LV diastolic function in comparison with able-bodied ones. Moreover, worse LV diastolic function was associated with a pattern of LV concentric remodeling and subclinical decreases in systolic function among injured subjects. Overall, these findings might contribute to explain the increased cardiovascular risk reported for individuals with SCI. Spinal Cord (2011) 49, 65-69; doi: 10.1038/sc.2010.88; published online 27 July 2010

Increased EMG response following electromyographic biofeedback treatment of rectus femoris muscle after spinal cord injury

Objective To study increases in electromyographic (EMG) response from the right and left rectus femoris muscles of individuals with long-term cervical spinal cord injuries after EMG biofeedback treatment. Design Repeated measure trials compared EMG responses before and after biofeedback treatment in patients with spinal cord injuries. Main outcome measures The Neuroeducator was used to analyse and provide feedback of the EMG signal and to measure EMG response. Setting Department of Traumatic Orthopaedics, School of Medicine, University of Sao Paulo, Brazil. Participants Twenty subjects (three men and 17 women), between 21 and 49 years of age, with incomplete spinal cord injury at level C6 or higher (range C2 to C6). Of these subjects, 10 received their spinal cord injuries from motor vehicle accidents, one from a gunshot, five from diving, three from falls and one from spinal disc herniation. Results Significant differences were found in the EMG response of the right rectus femoris muscle between pre-initial (T1), post-initial (T2) and additional (T3) biofeedback treatment with the subjects in a sitting position [mean (standard deviation) T1: 26 mu V (29); T2: 67 mu V (50); T3: 77 mu V (62)]. The mean differences and 95% confidence intervals for these comparisons were as follows: T1 to T2, -40.7 (-53.1 to -29.4); T2 to T3, -9.6 (-26.1 to 2.3). Similar differences were found for the left leg in a sitting position and for both legs in the sit-to-stand condition. Conclusions The EMG responses obtained in this study showed that treatment involving EMG biofeedback significantly increased voluntary EMG responses from right and left rectus femoris muscles in individuals with spinal cord injuries. (C) 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury

Herein, we describe a confirmed case of Loxosceles spider bite that illustrates the critical complications seen in loxoscelism, including skin necrosis, rhabdomyolysis, hemolysis, coagulopathy, acute kidney failure, and electrolyte disorders. Upon initial assessment, laboratory studies revealed the following: the white blood cell count was 29 400 WBCs/mm(3), hemoglobin was 9.2g/dL, and the platelet count was 218000cells/mm(3). Coagulation studies revealed the following: international normalized ratio, 1.83; activated partial-thromboplastin time, 62s; D-dimer, 600 ng/mL (normal range < 500 ng/mL); free protein S, 37% (normal range = 64-114%); protein C, negative; and antithrombin III, negative. Various serum levels were abnormal: urea, 110mg/dL; creatinine, 3.1 mg/dL; indirect bilirubin, 3.8 mg/dL; creatine kinase, 1631 U/L, lactate dehydrogenase, 6591 U/L; potassium 6.2mmol/L. Urine tests were positive for hemoglobin and bilirubin. In addition, concentrations of interleukin-6 and tumor necrosis factor-alpha were notably elevated in the serum. In conclusion, physicians must be alert to the possibility of loxoscelism when a patient presents with the clinical and laboratory findings described above, especially if the patient resides in an endemic area. Advances in our understanding of multiple pathways and mediators that orchestrate the response to Loxosceles venom might reveal new possibilities for the management of loxoscelism. (C) 2007 Elsevier Ltd. All rights reserved.

EVALUATION OF FUNCTIONAL GAIN OF THE ELBOW FOLLOWING STEINDLER SURGERY FOR BRACHIAL PLEXUS INJURY

Objective: To evaluate the gain in strength and range of motion after modified Steindler surgery of the elbow in patients with lesions of the upper trunk of the brachial plexus. Method: From 1998 to 2007, eleven patients with traumatic closed upper trunk lesion of the brachial plexus were studied. All the patients had development of at least 1 year of injury and degree of strength of elbow flexion ranging from M1 to M3. The patients underwent Steindler surgery with at least 6 months of follow-up. Pre- and post-operative assessments were carried out to determine gain in muscle strength, range of motion of the elbow, and DASH scale score. Results: Of the eleven patients studied, nine (82%) achieved a level of strength equal to or greater than M3 (MRC) with good functional recovery. Two (18%) reached strength level M2 (MRC). We observed that the patients had an average postoperative gain in range of motion of the elbow of 43.45 degrees. The average elbow flexion after surgery was 88 degrees. There was an improvement in elbow function, as demonstrated in the DASH Scale, in 81% of the patients studied. Conclusion: Modified Steindler surgery was effective in the treatment of patients with injuries of the upper trunk of the brachial plexus, with statistically significant gains in range of motion. In all the cases studied, there was some degree of gain in strength and range of elbow flexion, the gain being correlated with the initial muscle strength. Level of Evidence: Level II, prospective clinical trial.

Dynamic assessment of tongue function in children with dysarthria associated with acquired brain injury using electromagnetic articulography

The study to be presented is the first to use a new physiological device, the electromagnetic articulograph, to assess articulatory dysfunction in children with acquired brain injury. Two children with dysarthria subsequent to acquired brain injury participated in the study. One child, a female aged 12 years 9 months exhibited a mild-moderate ataxic dysarthria following traumatic head injury while the other, a male aged 13 years 10 months, demonstrated a moderate-severe flaccid-ataxic dysarthria also following traumatic head injury. The speed and accuracy of their tongue movements was assessed using the Carstens AG100 electromagnetic articulograph. Movement trajectories together with a range of quantitative kinematic parameters were estimated during performance of ten repetitions of the lingual consonants /t, s, k/ and consonant cluster /kl/ in the word initial position of single syllable words. A group of ten non-neurologically impaired children served as controls. Examination of the kinematic parameters, including movement trajectories, velocity, acceleration, deceleration, distance travelled and duration of movement, revealed differences in the speed and accuracy of the tongue movements in both children with acquired brain injury compared to those produced by the non-neurologically impaired controls. The results are discussed in relation to contemporary theories of the effects of acquired brain injury on neuromuscular function. The implications of the findings for the treatment of articulatory dysfunction in children with motor speech disorders associated with acquired brain injury are highlighted.