Akitaka Yamamoto

Bim regulation may determine hippocampal vulnerability after injurious seizures and in temporal lobe epilepsy

Programmed cell death pathways have been implicated in the mechanism by which neurons die following brief and prolonged seizures, but the significance of proapoptotic Bcl-2 family proteins in the process remains poorly defined. Expression of the death agonist Bcl-2-interacting mediator of cell death (Bim) is under the control of the forkhead in rhabdomyosarcoma (FKHR) transcription factors. This prompted us to examine the response of this pathway to experimental seizures and in hippocampi from patients with intractable temporal lobe epilepsy. A short period of status epilepticus in rats that damaged the hippocampus activated FKHR/FKHRL-1 and induced a significant increase in expression of Bim. Blocking of FKHR/FKHRL-1 dephosphorylation after seizures improved hippocampal neuronal survival in vivo, and Bim antisense oligonucleotides were neuroprotective against seizures in vitro. Inhibition of Akt increased the FKHR/Bim response and DNA fragmentation within the normally resistant cortex. Analysis of hippocampi from patients with intractable epilepsy revealed that Bim levels were significantly lower than in controls and FKHR was inhibited; we were able to reproduce these results experimentally in rats by evoking multiple brief, noninjurious electroshock seizures. We conclude that Bim expression may be a critical determinant of whether seizures damage the brain, and that its control may be neuroprotective in status epilepticus and epilepsy.

Endoplasmic reticulum stress and apoptosis signaling in human temporal lobe epilepsy.

Apoptosis signaling pathways are implicated in the pathogenesis of temporal lobe epilepsy (TLE), but the role of endoplasmic reticulum (ER) stress and ER-localized apoptosis signaling components remains largely unexplored. Presently, we investigated ER stress and ER localization of proapoptotic Bcl-2 family members and initiator and effector caspases in resected hippocampus from patients with intractable TLE and compared findings with autopsy controls. Hippocampal immunoreactivity for KDEL (Lys-Asp-Glu-Leu), a motif in ER stress chaperones glucose-regulated proteins 78 and 94, and calnexin, was significantly higher in TLE hippocampus compared with controls. The ER-containing microsomal fraction in control brain contained Bid, Bim, and caspase 3, whereas Bad and caspases 6, 7, and 9 were very low or absent. In contrast, caspases 6, 7, and 9 were present within the microsomal fraction of TLE brain. Furthermore, cleaved caspases 7 and 9 were detected in TLE samples but not controls, and KDEL-expressing neurons coexpressed cleaved caspase 9. Potentially adaptive changes were also detected, including lowered Bim levels in this fraction, and binding of caspase 7 to the X-linked inhibitor of apoptosis protein. These data suggest seizures may induce ER stress and trigger proapoptotic signaling pathways in the ER that are counteracted by antiapoptotic signals in chronic human TLE.

Evidence of tumor necrosis factor receptor 1 signaling in human temporal lobe epilepsy

Seizures, particularly when prolonged, may cause neuronal loss within vulnerable brain structures such as the hippocampus, in part by activating programmed (apoptotic) cell death pathways. Experimental modeling suggests that seizures activate tumor necrosis factor receptor 1 (TNFR1) and engage downstream pro- and anti-apoptotic signaling cascades. Whether such TNFR1-mediated signaling occurs in human temporal lobe epilepsy (TLE) is unknown. Presently, we examined this pathway in hippocampus surgically obtained from refractory TLE patients and contrasted findings to matched autopsy controls. Western blotting established that total protein levels of the TNFR1 proximal signaling adaptor TNFR-associated protein with death domain (TRADD), cleaved initiator caspase-8 and apoptosis signal-regulating kinase 1 (ASK1) were higher in TLE samples than controls. Intracellular distribution analyses revealed raised cytoplasmic levels of TNFR1, TRADD and the caspase-8 recruitment adaptor Fas-associated protein with death domain (FADD), and higher levels of TRADD and cleaved caspase-8 in the microsomal fraction, in TLE samples. Immunoprecipitation studies detected TRADD-FADD binding, and fluorescence microscopy revealed TRADD co-localization with FADD in TLE hippocampus. These data suggest that TNFR1 signaling is engaged in the hippocampus of patients with refractory temporal lobe epilepsy.

Endovascular management of vertebral artery dissecting aneurysms: review of 25 patients.

AIM Management of Vertebral Artery (VA) dissections remains controversial. The clinical and angiographic variables of VA dissections were evaluated to demonstrate the safety and efficacy of endovascular intervention in treatment of VA dissecting aneurysms. MATERIAL AND METHODS 25 patients with 27 VAdissecting aneurysms were treated with endovascular intervention during the last 10 years.17 patients were admitted with subarachnoid hemorrhage. 23 aneurysms treated using destructive endovascular trapping, while reconstructive techniques were used in 3 aneurysms treated with stent-assisted coiling and one aneurysm treated with false lumen embolization. RESULTS The right VA was involved in 14 patients, the left VA in 9 patients, while 2 patients had bilateral VA dissection. The pearl and string sign was the commonest angiographic sign in 12 aneurysms. Perioperative complications included; rebleeding in one patient, symptomatic brain stem infarction in two patients and silent cerebellar ischemic lesion in one patient. Afavorable outcome was evident more in patients with unruptured VA dissection (100%) versus (76.5%) in patients presented with SAH. CONCLUSION The endovascular technique should be individualized according to the clinical status of the patient, angiographic variables, condition of the posterior circulation and the available supplies.

Food poisoning associated with Kudoa septempunctata.

BACKGROUND Kudoa septempunctata is a recently identified cause of food poisoning. We report three cases of food poisoning due to ingestion of this parasite. CASE REPORTS Among the 358 people exposed during the same catered meal, 94 (including our 3 patients) developed vomiting and diarrhea within 1-9 h after ingestion of raw muscle from contaminated aquacultured olive flounders (Paralichthys olivaceus). These symptoms occurred frequently but were temporary; only 1 patient was hospitalized for dehydration and was discharged 2 days later. CONCLUSION In Japan, cases of food poisoning due to eating olive flounder have increased during recent years. This increase should prompt heightened awareness among clinicians diagnosing food poisoning.

Detection of 14-3-3ζ in cerebrospinal fluid following experimentally evoked seizures

Abstract Surrogate and peripheral (bio)markers of neuronal injury may be of value in assessing effects of seizures on the brain or epilepsy development following trauma. The presence of 14-3-3 isoforms in cerebrospinal fluid (CSF) is a diagnostic indicator of Creutzfeldt–Jakob disease but these proteins may also be present following acute neurological insults. Here, we examined neuronal and 14-3-3 proteins in CSF from rats after seizures. Seizures induced by intra-amygdala microinjection of 0.1 µg kainic acid (KA) caused damage which was mainly restricted to the ipsilateral CA3 subfield of the hippocampus. 14-3-3ζ was detected at significant levels in CSF sampled 4 h after seizures compared with near absence in control CSF. Neuron-specific nuclear protein (NeuN) was also elevated in CSF in seizure rats. CSF 14-3-3ζ levels were significantly lower in rats treated with 0.01 µg KA. These data suggest the presence of 14-3-3ζ within CSF may be a biomarker of acute seizure damage.

A case of Strongyloides hyperinfection associated with tuberculosis.

Strongyloidiasis is a parasitic infection that occurs in tropical regions. Hyperinfection, which is an accelerated autoinfection, is often associated with an immunosuppressive state, such as HTLV-1 infection or steroid use. Immunosuppression can also lead to reactivation of tuberculosis infection. These infections may have interacted as a result of impaired cellular immunity. A 28-year-old Nepali male was referred to our hospital for slight abdominal pain and high fever. An abdominal CT scan showed ascites and intestinal swelling. He was admitted with suspected gastroenteritis. Results of stool microscopy on the third day of hospitalization revealed abundant strongylid larvae. We diagnosed a Strongyloides hyperinfection and prescribed ivermectin. Although the numbers of strongylid organisms in the patient’s stool soon diminished, his temperature remained high. After receiving a second dose of ivermectin on day 17, he was transferred to a nearby hospital for observation, where he was noted to have massive pleural effusion. He returned to our hospital where his pleural effusion was found to be positive for adenosine deaminase (ADA), and he was diagnosed with a tuberculosis infection. Strongyloides hyperinfection can occur in a non-endemic region. It can be associated with tuberculosis infection possibly due to impaired cellular immunity. It is important to consider other possible infections when treating a patient with an infection associated with impaired cellular immunity.

Management of inadvertent vertebral artery injury due to central venous catheterization in a coagulopathic patient

A 72‐year‐old man was admitted to the intensive care unit for severe pancreatitis with coagulopathy. He underwent hemodialysis catheter insertion into the internal jugular vein that subsequently leaked arterial blood; vertebral artery cannulation was suspected following a computed tomography scan.

Arbekacin treatment of a patient infected with a Pseudomonas putida producing a metallo-beta-lactamase

Treatment of infections caused by multidrug-resistant Pseudomonas species is difficult because few antibiotics active against such organisms are available. Arbekacin, a relatively new aminoglycoside, is effective against Pseudomonas spp. in vitro. However, no clinical report on arbekacin treatment of a human infection with a multidrug-resistant Pseudomonas has appeared to date. We encountered a case of pneumonia caused by a Pseudomonas strain producing a metallo-beta-lactamase; the patient was successfully treated with arbekacin. A 69-year-old male presented to our hospital experiencing cardiac arrest after rescue from water. Spontaneous circulation had earlier resumed after brief application of cardiopulmonary resuscitation. The patient was subjected to induced hypothermia. He experienced severe acute respiratory distress syndrome. The patient regained consciousness on day 8 post-admission. Episodes of ventilator-associated pneumonia were recorded on days 5 and 12. The causative organism was a strain of Pseudomonas putida that produced a metallo-beta-lactamase. Combination therapy with arbekacin and levofloxacin successfully resolved the pneumonia. The patient was transferred to another hospital on day 37 to undergo further rehabilitation. Strains of P. putida producing metallo-beta-lactamases have become more widespread in recent years. Colistin is traditionally the drug of last resort to treat infections with multidrug-resistant Pseudomonas. However, colistin use is associated with a very high frequency of adverse effects, and the costs of such therapy are not covered by the Japanese health insurance system. Our results indicate that arbekacin is an efficient alternative to multidrug-resistant Pseudomonas.

Cortical blindness induced by hepatic encephalopathy: case report and review of published case reports

Cortical blindness induced by hepatic encephalopathy is an extremely rare complication and its epidemiology has not been studied in great detail. We report a 63‐year‐old man with liver cirrhosis who developed sudden bilateral visual impairment.