The Propagation Display Method Improves the Reproducibility of Pancreatic Shear Wave Elastography.

Evaluation of the pancreatic elastic modulus (PEM) using shear wave elastography (SWE) requires at least 5 measurements to ensure reproducibility. The aim of this study was to evaluate improvement in reproducibility of SWE, using the propagation display method in normal pancreas ([NP] phase 1) and to examine the differences in PEM between NP and chronic pancreatitis (CP), intraductal papillary mucinous neoplasm (IPMN) and autoimmune pancreatitis ([AIP] phase 2). In phase 1, the measurement success rate, median PEM in repeated measurements and appropriate number of SWE measurements were determined in 109 cases with NP. In phase 2, PEM was measured in CP (n = 10), IPMN (n = 31) and AIP (n = 5), using the required number of SWE measurements determined in phase 1. In phase 1, the measurement success rate was 93.9% (92/109 cases). The median PEM for NP was 14.6 kPa and the appropriate number of SWE measurements was at least 3. In phase 2, the median PEMs in CP, IPMN and AIP were 19.6, 18.1 and 17.2 kPa, respectively, with significant differences between NP and CP (p = 0.0133) and between NP and IPMN (p = 0.0436). Use of the propagation display method in SWE improves the reproducibility of measurement of PEM.

Multiphase evaluation of contrast-enhanced endoscopic ultrasonography in the diagnosis of pancreatic solid lesions.

BACKGROUND/OBJECTIVES: Time-intensity curve (TIC) under contrast-enhanced EUS (CE-EUS) allows continuous and quantitative evaluation of targeted area in the pancreas. However, TIC is not always available and the procedure is complicated. We aimed to propose a simplified method by evaluating multiple phases of CE-EUS in the diagnosis of pancreatic solid lesions. METHODS: We retrospectively reviewed 210 patients with pancreatic solid lesions including 142 with pancreatic ductal cancer (PDAC), 31 with pancreatic neuroendocrine neoplasm, 13 with solid pseudopapillary neoplasm and 24 with mass-forming pancreatitis who underwent CE-EUS and achieved final diagnoses. The CE-EUS images were continuously recorded for 60 s, and each image at 20, 40 and 60 s was used for the evaluation. The images were classified into three patterns as hypoechoic, hyperechoic and isoechoic vascular patterns compared with the surrounding pancreas, and the relevance between the multiphase evaluation of CE-EUS and each disease group was investigated. RESULTS: In PDAC group, majority of the lesions showed hypovascular pattern at 20 or 40 s after injection of contrast medium following early enhancement. The sensitivity, specificity and accuracy of PDAC pattern in the differentiation of PDAC from other lesions was 83.1%, 86.8% and 84.3%, respectively. On histopathological analysis, significant differences were seen in histologic types, infiltration (INF), and neural invasion (ne) between those who showed PDAC pattern and those who didn't. CONCLUSIONS: Multiphase evaluation of CE-EUS is convenient and useful method for the differentiation of pancreatic solid lesions which can be alternatively used for TIC.

Quantitative diagnosis of chronic pancreatitis using EUS elastography.

BACKGROUND: It is difficult to diagnose chronic pancreatitis (CP) objectively because of a lack of standard diagnostic criteria. Endoscopic ultrasonography (EUS) has been used to assess the severity of CP, but the diagnosis of CP using EUS depends on an endosnonographer. The aim of this study was to establish an objective diagnostic method for CP using EUS elastography (EUS-EG). METHODS: A retrospective study was designed and 96 patients underwent EUS-EG for follow-up of known CP, or who were clinically suspected as having CP. CP patients were categorized CP patients as 4 stages using the Rosemont classification (RC). EUS-EG was performed and the "Mean value", which was negatively correlated with pancreatic fibrosis, was calculated using histogram analysis. RESULTS: The "Mean value" of each RC stage (normal, indeterminate for CP, suggestive of CP, and consistent with CP) was 90.1 ± 19.3, 73.2 ± 10.6, 63.7 ± 14.2, and 56.1 ± 13.6, respectively, and showed significant differences for each stage (p < 0.001). There was a significant negative correlation between the "Mean value" and the number of EUS features (r s = -0.59, p < 0.001). Multiple linear regression analysis was used to assess the diagnostic finding of the "Mean value" and showed that hyperechoic foci with shadowing and lobularity with honeycombing maintained their independent diagnostic findings. CONCLUSIONS: EUS-EG was an objective diagnostic apparatus for CP and provided objective information to support EUS features.

[A case of successful treatment of granulocyte colony-stimulating factor producing hepatocellular carcinoma accompanying type B hepatitis with tegafur-uracil].

A 37-year-old man underwent lobectomy of the right liver for granulocyte colony-stimulating factor (G-CSF) producing hepatocellular carcinoma accompanying type B hepatitis. Within two months after the surgery, lung metastases were revealed and administration of sorafenib was begun, however, the lung metastases continued to enlarge. Changing the patient's medication to tegafur-uracil provided remarkable reduction of the lung metastases. The patient is alive two years after diagnosis and receives outpatient chemotherapy. We concluded that this case is valuable with regard to the extreme rarity of G-CSF producing hepatocellular carcinoma and its successful treatment in this case.

Epileptic focus stimulation and seizure control in the rat model of kainic acid-induced limbic seizures.

The inhibitory effects of deep brain stimulation (DBS) were investigated in a rat model of kainic acid (KA)-induced limbic status epilepticus. Wistar rats were injected with 1.0 microg KA into the left amygdala after stereotactic implantation of a guide cannula and electrodes. Bipolar rectangular pulses of 0.1 msec duration and 0.1-0.3 mA amplitude were applied intermittently to the left amygdala (10 Hz or 130 Hz), left ventral hippocampus (10 Hz), and left dorsomedial thalamus (130 Hz). Seizure frequency was evaluated by video electroencephalography monitoring and compared to control animals that did not receive DBS. All rats developed limbic status epilepticus 60-90 minutes after KA injection. Seizure frequency was significantly reduced by 10 Hz stimulation of the amygdala and by 130 Hz stimulation of the dorsomedial thalamus. No significant effects were observed with other types of stimulation. Seizure behaviors or duration of seizure were not changed significantly by DBS treatment. DBS of an epileptic focus may attenuate KA-induced limbic seizures, depending on the stimulation sites and parameters.

Experimental petit mal-like seizure induced by microinjection of kainic acid into the unilateral mediodorsal nucleus of the thalamus.

The mediodorsal nucleus (MD) of the thalamus has reciprocal projections with the frontal cortex and limbic system, and may be involved in absence seizures. Kainic acid was injected into the left MD of Wistar rats, and behavior and electroencephalography were monitored for 24 hours, then continued intermittently for 8 weeks. The rat brains were then examined histologically. Brain metabolic changes were also investigated by intravenous injection of 100 microCi/kg of [(14)C]2-deoxyglucose to measure local cerebral glucose metabolism. Bilateral synchronous spike and wave complexes appeared almost 2 hours after kainic acid injection, and the waveforms continued for about 5-7 hours in the bilateral MDs, ipsilateral sensorimotor cortex, and basolateral nucleus of the amygdala. The associated behavioral changes were mainly those of behavioral arrest and staring, associated with occasional limbic seizures. Clear metabolic increases were found in the ipsilateral frontal cortex, hippocampus, and amygdala. The present results suggest that the MD was involved in both the mechanism of spike and wave complexes in the bilateral frontal cortices, and in seizure propagation to the limbic system. Consequently, kainic acid-induced MD seizure is associated with significant cognitive impairment and may explain the mechanism of petit mal seizure.

Anti-convulsant effect of electrical stimulation and lesioning of the anterior thalamic nucleus on kainic acid-induced focal limbic seizure in rats.

PURPOSE: We examined the effect of electrical stimulation and lesioning of the anterior nucleus of the thalamus (ANT) on focal limbic seizures induced by intraamygdaloid kainic acid (KA) injection in a rat model. To address the mechanism underlying these anti-convulsant actions, cerebral glucose metabolism following ANT electrical stimulation and lesioning was also assessed. METHODS: Wistar rats were divided into five major groups: control, unilateral and bilateral ANT electrical stimulation, and unilateral and bilateral ANT lesioning. After KA injection, average clinical-seizure frequencies in each group were measured. Local cerebral glucose utilization (LCGU) was also measured using [(14)C] 2-deoxyglucose autoradiography in three groups: control, ANT electrical stimulation and ANT lesioning. RESULTS: Animals subjected to ANT electrical stimulation and lesioning exhibited significantly decreased mean seizure frequency and secondary generalized seizure frequency, compared with control-animals. In control-group, LCGU was markedly increased at both the limbic and corticothalamic circuits sites. While in ANT stimulation or lesioning-group, there was significant reduction in LCGU at the corticothalamic circuit sites, but not so considerable decrease at the limbic structures. CONCLUSION: ANT electrical stimulation and lesioning in the focal limbic seizure model were effective on convulsive seizures and secondary generalization, specifically with respect to the severity of these seizures.

The effect of electrical stimulation and lesioning of the anterior thalamic nucleus on kainic acid-induced focal cortical seizure status in rats.

PURPOSE: The present study aimed to clarify the effect of electrical stimulation and lesioning of the anterior nucleus of the thalamus (ANT) on kainic acid (KA)-induced focal cortical seizures in a rat model. To address the mechanism underlying these anticonvulsant actions, cerebral glucose metabolism after ANT electrical stimulation and lesioning was also examined. METHODS: Wistar rats were divided into five major groups: control (n = 9), unilateral (n = 9), and bilateral (n = 9) ANT electrical stimulation, and unilateral (n = 9) and bilateral (n = 9) ANT lesioning. After KA injection, average clinical-seizure frequencies in each group were measured. Electrical stimulation of ANT was introduced after induction of seizure status epilepticus. Stimulation was on for 30 min and off for 30 min per 60-min cycle. Local cerebral glucose utilization (LCGU) was also measured by using [(14)C] 2-deoxyglucose autoradiography in three groups of rats: control (n = 7), bilateral ANT stimulation (n = 7), and bilateral ANT lesioning (n = 7). RESULTS: Unilateral ANT electrical stimulation and lesioning significantly reduced clinical seizure frequency, compared with control animals. Strikingly, no animals treated with bilateral ANT procedures demonstrated any clinical seizure. LCGU was markedly increased in the sensorimotor cortex, striatum, thalamus, mammillary body, and midbrain tegmentum of control group rats after KA injection, but no increase in LCGU was noted in rats treated with bilateral ANT lesioning or stimulation. CONCLUSIONS: The electrical stimulation and lesioning of ANT suppressed focal cortical clinical seizures induced by KA injection. Additionally, an analysis of cerebral metabolic changes indicated that these procedures might suppress the function as amplifier and synchronizer of seizure activity.

Focal cortical dysplasia: pathophysiological approach.

OVERVIEW: Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out. MATERIALS AND METHODS: For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted in five rats. Their behavior and electroencephalogram (EEG) were recorded using a digital-video-EEG monitoring system. After observation periods of 1, 2, and 6 months, rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than 1 month after the injection. RESULTS AND DISCUSSIONS: EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in GABA-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were subjected to the clinical study. Neuro-imaging studies including high-resolution magnetic resonance imaging and single-photon emission computed tomography were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed to localize epileptic foci under neuroleptoanalgesia. Thirteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and the characteristics of the FCD in relation to EEG findings were analyzed. Patients in whom total lesionectomy with complete focus resection was performed had favorable postoperative courses. Nine patients (64.3%) have been seizure-free with reduced medication, and significant improvement was achieved in two patients (14.3%). Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. The immunohistochemical studies showed a decrease in GABA-A receptors and an increase in GABA-B receptors in both the lesions and perilesional areas, but N-methyl-D: -aspartate receptors were almost negative in both areas. Glutamate R1 was decreased in both areas, but glutamate R2 was increased in both areas. These findings support the results of a electrophysiological study. CONCLUSIONS: In conclusion, not only the epileptic property of experimental focal cortical dysplasia but also perilesional epileptogenesis was demonstrated. These findings supported the results of surgery for patients with focal cortical dysplasia. In cases of FCD, total removal of the lesion and resection of the perilesional epileptic focus are needed for a good outcome.

[A case of coexistence with cavernous angioma and focal cortical dysplasia].

There have recently been a number of new pathological findings of specimens from epileptic foci that have become widespread of surgical treatment. We reported a case with seizures resulting from brain lesions which pathologically demonstrated a coexistence with a cavernous angioma and a focal cortical dysplasia. A 24-year-old man was admitted to our hospital because of generalized convulsion from 1 year ago. Brain MRI revealed an enhanced mass lesion, in diameter 1.5 cm, with hemosiderin rim in the left temporal tip. Ictal EEG showed the initiation of the spike from the lateral side of the left temporal lobe. Because the epileptogenic focus was thought to be the lateral side in the left temporal lobe, anterolateral temporal resection was performed and subsequently total removal of the tumor was performed. He had no seizure after surgery. A light microscopic examination was performed on specimens stained with hematoxilin and eosin. We verified to be pathologically coexistent with a cavernous angioma and a focal cortical dysplasia. We also found unusual neurons that were accompanied by perineuronal glial satellitosis in the subcortical white matter, those were occasionally observed in epileptic foci and were thought to be a form of neuronal migration disorders.

Clinical application of experimental cortical dysplasia in rats.

This report details clinical and experimental studies of focal cortical dysplasia. The first part deals with 14 surgical cases of children with intractable epilepsy. At surgery, intraoperative electrocorticography was performed to localize the epileptic foci under neuroleptanalgesia. Thirteen patients showed epileptiform discharges on this preresection electrocorticography. All foci in noneloquent areas were resected. Patients who had undergone total lesionectomy with complete focus resection showed the most favorable postoperative results. However, the positive correlation between the intraoperative electrocorticographic findings and the pathologic classification of cortical dysplasia was not found in the present study. Nine patients have been seizure free with reduced medication and two patients have achieved worthwhile improvement. We conclude that intraoperative electrocorticography can improve the surgical outcome for intractable epilepsy by localizing epileptic foci for resection. The second part describes a kainic acid-induced experimental model of focal cortical dysplasia, which demonstrated not only the epileptic properties of the dysplasia but also the perilesional epileptogenicity. The findings supported the surgical results for the patients with focal cortical dysplasia.

Correct localization of epileptogenic focus with I-123 iomazenil cerebral benzodiazepine receptor imaging: a case report of temporal lobe epilepsy with discordant ictal cerebral blood flow SPECT.

A 26-year-old female with intractable epileptic seizures was studied with I-123 iomazenil cerebral benzodiazepine receptor, I-123 IMP inter-ictal and Tc-99m ECD ictal cerebral blood flow SPECT. The ictal cerebral blood flow SPECT indicated the location of the seizures to be in the left temporal lobe, where increased regional cerebral blood flow was noted in marked contrast to the inter-ictal SPECT. Ictal electroencephalograms (EEGs) recorded with scalp and sphenoidal electrodes also suggested the left temporal lobe as the location of the seizures. On I-123 iomazenil SPECT, however, decreased benzodiazepine receptor density was demonstrated in the right temporal lobe. MRI showed mild atrophy and abnormal signal intensity in the right temporal lobe. Ictal EEGs recorded with intracranial electrodes revealed that abnormal electrical activity of the brain always emerged from the right temporal lobe and then propagated to the contralateral side. Based on the findings of intracranial EEGs, partial resection of the right anterior temporal lobe including hippocampus was performed. After the surgery, no seizure occurred. Pathological examination of the surgical specimens revealed hippocampal sclerosis. This case suggested that cerebral benzodiazepine receptor imaging with I-123 iomazenil can be helpful for correct localization of epileptogenic foci.

Clinical and experimental studies of epilepsy associated with focal cortical dysplasia.

The results of clinical and experimental studies on epilepsy associated with focal cortical dysplasia (FCD) are presented. We have been interested in the findings of abnormal increases in the numbers of small vessels in specimens of FCD resected from epilepsy patients. In the clinical study of 13 patients with epilepsy, specimens of FCD or dysembryoplastic neuroepithelial tumor (DNT) were examined using immunohistochemistry. The number of vessels in both lesions were greater than those in cortical specimens of autopsy cases without epilepsy. Because the vessels showed negative staining of VEGF, it was thought that the phenomenon of increase in the number of vessels was simply a hypervascularity, not a neovascularity. The local hypervascularity was expected to show local hyperperfusion in CBF-SPECT study, but interictal SPECT demonstrated local hypoperfusion and ictal SPECT showed hyperperfusion. This may have been caused by a functional change in those vessels. In the experimental study, we tried to make a new animal model of FCD to study epileptogenicity of FCD. When kainic acid had been infused into the neocortex in the neonatal rats, FCD was induced in adult Wistar rats. Histopathological examination revealed cortical dyslamination and abnormal neurons. On EEG, local spike bursts were elicited from the lesions, however, clinical seizures were not detected. Although the data are preliminary and observation over a longer period is required to determine whether spontaneous seizures will occur in this model, it is expected that this new model will be useful for studying epilepsy associated with FCD.

[Three-dimensional neuroimaging in diagnosis and surgical treatment for epilepsy].

Development of functional neuroimaging is contributed to diagnosis and treatment in epilepsy patients. The dipole analysis of interictal spikes on EEG or MEG provides 3D-localization of the irritable zone. Interictal and ictal CBF-SPECT reveals the local change in CBF associated to epileptic focus. Three-dimensional stereotactic surface projection (3D-SSP) of SPECT is useful to recognize the seizure generation area. Furthermore, Subtraction ictal SPECT coregistration of MRI (SISCOM), that is fusion image of anatomical and functional brain images, is beneficial to understand the localization of seizure-induced hyperperfusion area. During epilepsy surgery, image-guided system makes less-invasive and accurate surgery possible. Functional image-guided surgery for epilepsy will be available in near future.

Diffusion-weighted imaging in kainic acid-induced complex partial status epilepticus in dogs.

OBJECTIVE: To investigate diffusion-weighted imaging (DWI) in status epilepticus, a canine model of kainic acid (KA)-induced complex partial status epilepticus (CPSE) was produced. In order to validate its usefulness, MR imaging was carried out at various times following onset of CPSE followed by histopathology. MATERIAL AND METHODS: Six normal dogs were used in this study. In each dog, a cannula was stereotactically inserted into the left amygdala. One week after surgery, all dogs were imaged at MRI. Pre-injection imaging consisted of T2 weighted (T2W) imaging, fluid attenuated inversion recovery (FLAIR), and DWI. Two weeks after surgery, five dogs received intraamygdaloid KA microinjections. One dog was used as a control. MRI was carried out at 3, 6, 12, 24 and 48 h after onset of CPSE. Animals were euthanized immediately after MRI for histopathological evaluation. The average of each apparent diffusion coefficient (ADC) in the regions of interest was calculated from each DWI. RESULTS: At 3 and 6 h, DWI hyperintensity and low ADC were found in the injected amygdala, without any T2W and FLAIR imaging changes. At 12 and 24 h, all imaging showed hyperintensity with higher ADC in the amygdala and the hippocampus. At 48 h, all imaging techniques showed continued hyperintensity, but ADC showed a trend towards normalization. This increasing hyperintensity in DWIs were in agreement with the degree of histopathology during CPSE. SUMMARY: This study suggests that DWI is a useful imaging method for finding the epileptic focus or for examining potential epileptic brain damage in status epilepticus.

Complex partial status epilepticus induced by a microinjection of kainic acid into unilateral amygdala in dogs and its brain damage.

OBJECTIVE: In order to investigate kainic acid (KA)-induced amygdaloid seizure and seizure-induced brain damage in dogs, and to compare these findings with that in other species, a KA-induced seizure model in dogs was produced. MATERIAL AND METHODS: Normal beagle dogs were used. A Teflon cannula for KA injection was inserted into the left amygdala, and cortical or depth electrodes were positioned. One week after surgery, 1.5 microg of KA was microinjected into the left amygdala. EEGs and the behavior of the animals were monitored for 2 months after KA injection. In addition, neuron-specific enolase levels in the cerebrospinal fluid (CSF-NSE) were measured intermittently. At 2 months after the injection, histopathological studies were performed. RESULTS: KA-treated dogs showed limbic seizures that started from the left amygdala within 30 min after injection. The seizures developed into complex partial status epilepticus (CPSE), and started independently from the bilateral amygdala during the CPSE. The CPSE lasted for 1-3 days, and the animals showed no spontaneous seizures during the 2-month observation period. A significant increase in CSF-NSE was observed immediately after CPSE. Histopathologically, extensive necrosis, which formed large cavity lesions, was observed around the bilateral amygdala. SUMMARY: A microinjection of KA into unilateral amygdala in dogs induced CPSE. The seizures elicited independently from bilateral amygdala, and bilateral limbic structures suffered extensive injury. In addition, CSF-NSE was demonstrated as a useful marker of acute neuronal damage.

Electrophysiological, behavioral and metabolical features of globus pallidus seizures induced by a microinjection of kainic acid in rats.

There has been few studies of the globus pallidus in relation to epilepsy. In this study, kainic acid (KA)-induced globus pallidus seizure was electrophysiologically, electroencephalographically, histopathologically and metabolically investigated in rats. Sixteen Wistar rats weighing 250-350 g were used. Under intraperitoneal pentobarbital anesthesia, a stainless-steel cannula was inserted stereotaxically into the left globus pallidus pars externa (GPe) for KA injection. For recording EEG, a depth electrode was inserted into the left GPe, just posterior to the tip of the injection guide cannula. Electrodes were also inserted into the right globus pallidus and bilateral sensorimotor cortex (SMC). EEG changes after KA injection were classified as follows: Continuous low-voltage spikes were observed in the left GPe on EEG at stage 1. Intermittent multiple spikes and wave complexes began to propagate to the left SMC at stage 2. Continuous spikes and wave complexes began to propagate to the bilateral SMC at stage 3. Secondary generalized seizures were observed at stage 4. Globus pallidus seizures recurred every 7-9 min and lasted for 4-6 h. However, the seizures gradually subsided and became normal within 18 h. No spontaneous seizure was detected for the next 30 days. Histopathological study revealed a small gliotic lesion with neuronal cell loss around the cannula tip. Neither degeneration nor neuronal cell loss in the ipsilateral hippocampus were observed. The autoradiogram using [14C]2-deoxyglucose during seizure status demonstrated a remarkable increase of local cerebral glucose utilization not only in the GPe but also in the GPi. An increase glucose metabolism was also found in the follows: the medial and lateral septal nucleus, substantia nigra, hippocampus, frontal cortex, parietal cortex, piriform cortex, entorhinal cortex, accumbens nucleus, ventral and lateral nucleus of the thalamus, amygdala, and ventral nucleus of hypothalamus. KA injection into the unilateral GPe evoked not only epileptic excitation of the cortex but also transient enhancement of the globus pallidus-substantia nigra circuit.