Differential cytokine profiles produced by anti-epileptic drug re-exposure of peripheral blood mononuclear cells derived from severe anti-epileptic drug patients and non-allergic controls.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) are the most common severe cutaneous adverse drug reactions (SCARs). Anti-epileptic drugs are one of the most common drugs causing SCARs. Cytokine profiles of SCARs during culprit drug exposure have never been characterized. This study aimed to identify cytokine patterns between SCARs and non-SCARs in epilepsy patients and the patterns of DRESS and SJS/TEN. Epilepsy patients that showed allergic responses to anti-epileptic drugs that manifested as SJS/TEN or DRESS were recruited. Epilepsy patients with no drug allergy symptoms and healthy people were also recruited as control groups. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with assigned anti-epileptic drugs according to the lymphocyte transformation test (LTT). LTT and measurement of cytokine levels in supernatants were performed on day six of cell cultivation. This study identified different cytokine expression patterns between SCAR and non-SCAR in epilepsy patients. Significant levels of IL-10, IL-12, IL-17, and GM-CSF were detected in non-SCAR epilepsy. However, the levels of IL-2, IL-5, IL-13, and IFN-gamma were significantly higher in supernatants of PBMCs of DRESS cultivated with AEDs relative to those of SJS/TEN. These cytokine levels were positively correlated with the cell proliferation index. Production of IL-5 and IL-13 was a unique characteristic of DRESS PBMCs. This study was the first to demonstrate distinct differences in cytokine levels between SCAR and non-SCAR PBMCs in epilepsy, which could help explain the immune-pathomechanism of drug hypersensitivity in SCARs. Different patterns of cytokine production and cell proliferation between DRESS and SJS/TEN in AED hypersensitivity were also demonstrated. Production of IL-5 and IL-13 might be a promising marker to define drug hypersensitivity in DRESS.

Connectivity in ictal single photon emission computed tomography perfusion: a cortico-cortical evoked potential study.

Subtraction ictal and interictal single photon emission computed tomography can demonstrate complex ictal perfusion patterns. Regions with ictal hyperperfusion are suggested to reflect seizure onset and propagation pathways. The significance of ictal hypoperfusion is not well understood. The aim of this study was to verify whether ictal perfusion changes, both hyper- and hypoperfusion, correspond to electrically connected brain networks. A total of 36 subtraction ictal and interictal perfusion studies were analysed in 31 consecutive medically refractory focal epilepsy patients, evaluated by stereo-electroencephalography that demonstrated a single focal onset. Cortico-cortical evoked potential studies were performed after repetitive electrical stimulation of the ictal onset zone. Evoked responses at electrode contacts outside the stimulation site were used as a measure of connectivity. The evoked responses at these electrodes were compared to ictal perfusion values noted at these locations. In 67% of studies, evoked responses were significantly larger in hyperperfused compared to baseline-perfused areas. The majority of hyperperfused contacts also had significantly increased evoked responses relative to pre-stimulus electroencephalogram. In contrast, baseline-perfused and hypoperfused contacts mainly demonstrated non-significant evoked responses. Finally, positive significant correlations (P < 0.05) were found between perfusion scores and evoked responses in 61% of studies. When the stimulated ictal onset area was hyperperfused, 82% of studies demonstrated positive significant correlations. Following stimulation of hyperperfused areas outside seizure onset, positive significant correlations between perfusion changes and evoked responses could be seen, suggesting bidirectional connectivity. We conclude that strong connectivity was demonstrated between the ictal onset zone and hyperperfused regions, while connectivity was weaker in the direction of baseline-perfused or hypoperfused areas. In trying to understand a patient's epilepsy, one should consider the contribution of all hyperperfused regions, as these are likely not random, but represent an electrically connected epileptic network.

Stroke awareness and factors influencing hospital arrival time: a prospective observational study.

BACKGROUND: Data concerning stroke awareness and factors associated with time of hospital arrival for acute stroke patients in Thailand are still lacking. OBJECTIVE: To assess stroke awareness and to identify factors influencing hospital arrival time after an acute stroke. MATERIAL AND METHOD: This is aprospective study comprising consecutive acute stroke patients admitted in Siriraj Hospital, Bangkok, Thailand between August 2010 and December 2011. Demographic data, stroke severity using the NIHSS, diagnosis and stroke awareness questionnaire were collected. RESULTS: Of 217 acute stroke patients, mean age was 66 ± 13.7 years. Mean stroke severity was 10 ± 7.6. Patients arrived at the Emergency Department within 4.5 hours (early hospital arrival: EHA) in 38.2% of the cases, 16.6% by ambulance. Only 34.6% of patients recognized that they were having stroke. Factors associated with EHA were 1) stroke awareness (OR 1.96, 95% CI 1.07-3.60, p = 0.030), 2) arrival by ambulance (OR 2.23, 95% CI 1.03-4.81, p = 0.042), and 3) NIHSS >15 (OR 2.26, 95% CI 1.17-4.35, p = 0.015). CONCLUSION: Only one-third of patients were aware of stroke symptoms. Only one in six patients used emergency transportation. Public educational campaign is needed to increase the community awareness of stroke warning symptoms and the urgent emergency medical services.

Extensive bilateral ischemic stroke after platelet transfusion in thrombotic thrombocytopenic purpura (TTP): a case report.

A 36-year-old woman presented with abdominal pain followed by fever, confusion, right sided weakness and nuchal rigidity. The investigation showed severe anemia, thrombocytopenia and left middle cerebral artery (MCA) territory infarction. The platelet was given before the lumbar puncture. After that, the patient's clinical was deteriorating to quadriplegia and stuporous. Then the patient was referred to Siriraj Hospital. The patient was diagnosed thrombotic thrombocytopenic purpura (TTP) following pentad of clinical features: microangiopathic hemolytic anemia, thrombocytopenia, fever neurologic, and renal abnormalities. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of brain showed extensive bilateral MCA and mid basilar artery stenosis. That was uncommon findings in TTP. The authors believed that platelet transfusion made the clinical deterioration and develop extensive intracranial vessels stenosis. Even the plasma exchange was performed but the neurological symptoms did not improved. Finally, the patient succumbed from ventilator associated pneumonia at 2 months after diagnosis.

Concurrent myasthenia gravis-related cervical thymoma in a patient with diffuse large B-cell lymphoma: a case report.

BACKGROUND: Cervical thymoma is a rare thymic epithelial neoplasm. Evidence supports an increased risk of second primary malignancies in patients with thymoma. We report a rare case of a patient with synchronous cervical thymoma and diffuse large B-cell lymphoma. CASE PRESENTATION: An 81-year-old Thai woman was referred for further treatment of diffuse large B-cell lymphoma at Siriraj Hospital, Bangkok, Thailand. While waiting for a review of the original pathological examination of a mass in the left neck and a mass in the left arm, the attending physician noticed ptosis of the upper eyelids, which was proven to be caused by myasthenia gravis. The final pathology review confirmed that the arm mass was diffuse large B-cell lymphoma, but the neck mass was cervical thymoma, type B1, not diffuse large B-cell lymphoma. Interestingly, the patient reported that the arm mass had been present for 2 years, while the neck mass had grown rapidly in the past month. A diagnostic challenge had arisen when the initial morphological evaluation was not performed with care, causing the first pathologist to misinterpret that the neoplastic cells in both masses were the same. CONCLUSION: Concurrent cervical thymoma and diffuse large B-cell lymphoma were proven after a careful pathology review, leading to better clinical management.

Subcortical SISCOM hyperperfusion: Should we pay more attention to it?

PURPOSE: Demonstrating cerebral blood flow changes during seizures, ictal-interictal single photon emission computed tomography (SPECT) with co-registration to MRI (SISCOM) reflects brain activation and its pathways of spread. To investigate subcortical ictal hyperperfusion patterns during focal seizures, we retrospectively reviewed SISCOM analysis of patients who became seizure-free after cortical resection. Our aim was to evaluate the relationship between epileptogenic zones and subcortical hyperperfusion. METHOD: 67 patients were identified as having SISCOM evaluation and having remained seizure-free for at least one year after surgical resection. SISCOM analysis was blindly reviewed for localization of basal ganglia (BG), thalamic (TN) and cerebellar (CH) hyperperfusion based on three different thresholds. Subcortical activation and epilepsy characteristics were then compared between patients. For a given region of interest and threshold, the sensitivity, specificity and positive and negative predictive value for correct lateralization of the epilepsy side was calculated. RESULTS: Depending on the threshold used, BG hyperperfusion was found in 37.3-73.9% of patients, TN hyperperfusion in 31.3-68.1% and CH hyperperfusion in 13.5-29%. For a threshold of 1.5, the best predictive positive value for correct lateralization of the epilepsy side was obtained with BG/CH coactivation (89%). For a threshold of 2.0 and 2.5, it was obtained with BG/TN coactivation (88%) and BG activation (82%), respectively. CONCLUSION: Subcortical SISCOM hyperperfusion could offer additional clues in terms of lateralization.