Acute inhibition of AMPA receptors by perampanel reduces amyloid ß-protein levels by suppressing ß-cleavage of APP in Alzheimer's disease models.

Hippocampal hyperexcitability is a promising therapeutic target to prevent Aß deposition in AD since enhanced neuronal activity promotes presynaptic Aß production and release. This article highlights the potential application of perampanel (PER), an AMPA receptor (AMPAR) antagonist approved for partial seizures, as a therapeutic agent for AD. Using transgenic AD mice combined with in vivo brain microdialysis and primary neurons under oligomeric Aß-evoked neuronal hyperexcitability, the acute effects of PER on Aß metabolism were investigated. A single oral administration of PER rapidly decreased ISF Aß40 and Aß42 levels in the hippocampus of J20, APP transgenic mice, without affecting the Aß40 /Aß42 ratio; 5 mg/kg PER resulted in declines of 20% and 31%, respectively. Moreover, PER-treated J20 manifested a marked decrease in hippocampal APP ßCTF levels with increased FL-APP levels. Consistently, acute treatment of PER reduced sAPPß levels, a direct byproduct of ß-cleavage of APP, released to the medium in primary neuronal cultures under oligomeric Aß-induced neuronal hyperexcitability. To further evaluate the effect of PER on ISF Aß clearance, a γ-secretase inhibitor was administered to J20 1 h after PER treatment. PER did not influence the elimination of ISF Aß, indicating that the acute effect of PER is predominantly on Aß production. In conclusion, acute treatment of PER reduces Aß production by suppressing ß-cleavage of amyloid-ß precursor protein effectively, indicating a potential effect of PER against Aß pathology in AD.

Japanese spotted fever with post-infectious encephalitis.

Japanese spotted fever (JSF) is a rickettsial disease caused by Rickettsia japonica. To the best of our knowledge, there have only been five reported cases of JSF involving the central nervous system. A 74-year-old man was admitted after 1 week of fever and maculopapular rash. JSF was definitively diagnosed by PCR; however, the patient showed mental disturbance and abnormal behavior. After intravenous immunoglobulin, his mental state and behavior improved. The findings of cerebrospinal fluid analysis, electroencephalography, and 99 mTcHM-PAO single photon computed emission tomography suggested post-infectious encephalitis. JSF causes post-infectious encephalitis and early treatment is recommended.

Serial assessment of multimodality imaging in anti-leucine-rich glioma-inactivated 1 antibody encephalitis: A case report.

In autoimmune encephalitis, abnormalities of diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), arterial spin labeling (ASL) in magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) have been reported. However, there are few studies of long-term follow-up of imaging. We report a case of anti-leucine-rich glioma-inactivated 1 antibody encephalitis whose MRI (DWI, FLAIR and ASL), 99mTcHM-PAO SPECT (PAO-SPECT) and 18F-FDG-PET were evaluated through the clinical course. ASL, PAO-SPECT and 18F-FDG-PET consistently showed abnormalities in almost the same area. Serial assessment of these imaging modalities is useful in evaluating disease activity and efficacy of treatment.

Punctate Enhancement of Bilateral Basal Ganglia in a Case of Epstein-Barr Virus Encephalitis.

Epstein-Barr virus (EBV) encephalitis is caused by initial infection or reactivation of EBV. In adults, the risk factors of EBV encephalitis include human immunodeficiency virus infection, immunosuppressant drugs, congenital immune deficiencies, post-stem cell transplantation, and post-solid organ transplantation. However, a few cases of adult-onset EBV encephalitis without these risk factors were also reported. The efficacy of steroid or intravenous immunoglobulin remains unclear in the treatment of EBV encephalitis. Herein, we report a case of an 82-year-old man with fever and disturbance of consciousness who was diagnosed as having EBV encephalitis. Gadolinium-enhanced magnetic resonance imaging showed punctate enhancement in the bilateral basal ganglia, which resembled chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Symptoms and enhanced lesions improved after immunotherapy. Immunotherapy may be effective in the treatment of EBV encephalitis with CLIPPERS-like lesions.

An autopsy case of adult-onset neuronal intranuclear inclusion disease with perivascular preservation in cerebral white matter.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by appearance of eosinophilic hyaline intranuclear inclusions. While the main symptoms of adult-onset NIID are dementia or limb weakness, some patients present with encephalitic episodes and transient neurological symptoms. The pathophysiology of these acute, transient symptoms, however, remains unknown. Here, we describe an autopsy case of adult-onset NIID with progressive dementia and transient hemiparesis. The patient was a 70-year-old man without a relevant family history, and initially presented with progressive dementia. He then exhibited transient left hemiparesis at 75 years of age and died of ureteral cancer at 77 years of age. Neuropathological examination revealed the presence of multiple areas of focal spongiosis in the subcortical white matter and patchy myelin pallor of the white matter, as in previous reports. However, perivascular areas were preserved even in the damaged white matter. In addition, dense glial fibrillary acidic protein (GFAP)-immunoreactive astrocytic processes were observed in these areas. [Correction added on 23 January 2022, after first online publication: the preceding sentence has been corrected to improve readability.] GFAP immunohistochemistry revealed decreased density and morphological abnormalities of astrocytes in the affected white matter. These pathological findings might reflect blood-brain barrier impairment and dysregulation of blood flow, which may be related to the pathophysiology of the acute, transient symptoms observed in NIID.

[Primary angiitis of the central nervous system with cerebral infarction and spinal hemorrhage].

A 61-year-old woman presented with acute intense lower back pain and weakness in her left leg. She also presented with throbbing headache on the same day. On admission, muscle weakness in her left leg, lower left quadrantanopia and left lower extremity deep sensory disturbance were observed. Laboratory data showed no coagulopathy and autoimmune antibody was negative. Cerebrospinal fluid examination showed bloody and inflammatory findings. Brain MRI revealed cerebral infarction with multiple intracranial arterial stenosis and convexal subarachnoid hemorrhage. Spinal MRI revealed spinal hemorrhage in the cervical, thoracic, and part of the lumbar spine. Because these lesions occurred simultaneously, we made a diagnosis of vasculitis. After high dose corticosteroids therapy was undertaken, the multiple arterial stenosis improved. Primary angiitis of the central nervous system is sometimes difficult to distinguish from reversible cerebral vasoconstriction syndrome in its initial stage; although symptoms, examination findings and treatment differ in both.

Traumatic left ventricular free-wall laceration by a gunshot: report of a case.

This report describes the case of a 47-year-old man who shot himself in the left side of the chest in an attempted suicide, and was transferred to the hospital. Two gunshot wounds were found in the left side of the chest and the back. CT scans revealed left hemopneumothorax, the accumulation of pericardial blood, and lacerations of the heart and the spleen. Emergency thoracotomy and laparotomy were performed. There was a contusion of the left lung and lacerations of the left ventricular free wall, the diaphragm, and the spleen. The laceration of the heart was repaired by 3 pairs of mattress sutures with felt strips, and covered with fibrin glue and a TachoComb(®) tissue sealing sheet without the use of cardiopulmonary bypass. The patient was discharged on foot on the 18th postoperative day. Such patients can only be saved with an efficient emergency medical-care system including quick transportation, and close cooperation of the hospital staff.

A new method to detect cerebral blood flow waveform in synchrony with chest compression by near-infrared spectroscopy during CPR.

OBJECTIVE: The objective of the study is to demonstrate the utility of near-infrared spectroscopy (NIRS) in evaluating chest compression (CC) quality in cardiac arrest (CA) patients as well as determine its prognosis predictive value. METHODS: We present a nonconsecutive case series of adult patients with CA whose cardiopulmonary resuscitation (CPR) was monitored with NIRS and collected the total hemoglobin concentration change (ΔcHb), the tissue oxygen index (TOI), and the ΔTOI to assess CC quality in a noninvasive fashion. RESULTS: During CPR, ΔcHb displayed waveforms monitor, which we regarded as a surrogate for CC quality. Total hemoglobin concentration change waveforms responded accurately to variations or cessations of CCs. In addition, a TOI greater than 40% measured upon admission appears to be significant in predicting patient's outcome. Of 15 patients, 6 had a TOI greater than 40% measured upon admission, and 67% of the latter were in return of spontaneous circulation after CPR and were found to be significantly different between return of spontaneous circulation and death (P = .047; P < .05). CONCLUSION: Near-infrared spectroscopy reliably assesses the quality of CCs in patients with CA demonstrated by synchronous waveforms during CPR and possible prognostic predictive value, although further investigation is warranted.

Microdialysis detection of lactate in subcutaneous tissue as a reliable indicator of tissue metabolic disorders in an animal sepsis model.

PURPOSE: Tissue dysoxia is thought to be a fundamental cause of the organ failure that occurs as a result of shock. Plasma lactate has been frequently measured as an indicator of the state of systemic tissue metabolism. On the other hand, tissue lactate levels can directly indicate a disorder in the state of cytological tissue metabolism. The continuous monitoring of lactate levels in subcutaneous tissue will reflect the state of tissue dysoxia more precisely than levels of lactate in the plasma lactate. We have investigated the differences in the levels of plasma and tissue lactate using a microdialysis (MD) technique in an animal septic shock model. METHOD: Male 8-week-old Wistar/ST rats were used. We prepared an animal model by injection of lipopolysaccharide (LPS) into the abdominal cavity. LPS was given to 9 animals in the experimental group while physiological saline was given to 6 animals in the control group. A MD probe was used to quantify the lactate levels in the subcutaneous tissue. The mean arterial pressure, blood gas content and lactate levels were measured every 50 min up to 400 min after injection and compared between both groups. RESULT: The MAP of both groups showed similar changes after injection. Plasma lactate levels in the LPS group showed a significant increase after 100 min and reached a plateau from 150 min to 250 min. Subcutaneous lactate in the LPS group showed a significant increase after 150 min. Subcutaneous pyruvate in the LPS group showed a significant increase after 100 min. The lactate/pyruvate (L/P) ratio in the subcutaneous tissue showed a sustained increase from 300 min in the LPS group. CONCLUSION: Monitoring plasma lactate levels is useful for the early assessment of anaerobic metabolism before hypotension. Plasma lactate levels did not increase during some periods. This phenomenon was due to the balance between production and utilization. However, tissue lactate showed a chronological increase. These results suggest that the measurement of tissue lactate levels is reliable for assessing local energy metabolic disturbances. Under conditions of septic shock, an increase in lactate levels was found to be a sensitive marker of tissue metabolism disorder.

Utility of microdialysis to detect the lactate/pyruvate ratio in subcutaneous tissue for the reliable monitoring of hemorrhagic shock.

The present experiments were carried out to investigate the usefulness of measuring peripheral tissue metabolism for the clinical assessment of shock. Male Wistar/ST rats (8 weeks-old) were used. All rats were placed in a supine position while anesthetized. A tube for measuring arterial pressure and collecting blood samples was cannulated into the femoral artery. For microdialysis, the introducer was inserted into the subcutaneous tissue in the abdominal wall. Blood was exsanguinated to maintain the mean arterial pressure at 40 +/- 5 mmHg. Mean arterial pressure, arterial blood gas and serum lactate levels were measured. Microdialysis was performed to quantify the levels of lactate and pyruvate in the subcutaneous tissue. Six rats died due to hemorrhagic shock by 350 min (Group D) while six rats had survived for the 350 min period after exsanguination (Group A). These data was obtained at intervals of 50 min after exsanguination up to a period of 250 min and compared between Groups A and D. In Group A, serum lactate levels did not increase throughout the entire period of observation. Serum lactate levels in Group D transiently increased, but did not show a dramatic increase during the blood pressure maintenance period. In particular, serum lactate levels increased again after a period of more than 150 min following exsanguination. Lactate levels in the subcutaneous tissue gradually increased and were significantly higher in Group D than that in Group A after 150 min. The L/P ratio in Group A remained fairly constant during the period of observation. In contrast, the L/P ratio in Group D increased gradually, and was significantly higher than that in Group A after 100 min. It was concluded that the continuous increase in the L/P ratio in the subcutaneous tissue in Group D was indicative of tissue circulatory failure and of an abnormality in tissue oxygen metabolism prior to the detection of the collapse of compensatory mechanisms appearing in the vital signs. These findings suggest that measuring the L/P ratio is useful for the clinical assessment and monitoring of shock.