Alzheimer's disease: Report of two autopsy cases with a clinical diagnosis of corticobasal degeneration

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Corticobasal degeneration (CBD) is a rare neurodegenerative disease affecting adults, being characterized clinically by a combination of extrapyramidal signs and focal cortical syndromes. In both diseases, tau deposits are a characteristic neuropathological feature. We report two new patients with autopsy‐proven AD, in whom clinical diagnoses of CBD were made during life. The ages of the patients at onset were 52 and 67 years, and the disease durations were 9 and 15 years, respectively. At autopsy, both cases exhibited marked cortical atrophy with evident neuronal loss in the convex areas of the frontal and parietal lobes. Immunohistochemically, AT8‐positive neurofibrillary tangles (NFTs) and Aβ‐positive senile plaques (SPs) were widespread and abundant in the cerebral cortex (Alzheimer pathology stage VI/C of Braak and Braak), leading us to the final pathological diagnosis of AD. No tau lesions suggestive of CBD were observed, and the deep gray matter areas, including the substantia nigra, were unremarkable (exceptionally, only mild neuronal loss was noted in the putamen in case 2). These findings further strengthen the idea that in AD, neurodegeneration with tau and Aβ deposits may begin in the fronto‐parietal neocortical areas, which are often preferentially affected in CBD, earlier than, or as early as the medial temporal lobe, and that extrapyramidal signs, such as rigidity and tremor, can occur in the absence of neuronal loss in the basal ganglia and substantia nigra.     

Morel's laminar sclerosis showing apraxia of speech: Distribution of cortical lesions in an autopsy case

A 57‐year old man with chronic alcoholism presented with apraxia of speech and disturbance of consciousness. He had a history of gastrectomy and had been drinking alcohol. The symptoms improved with administration of thiamine, but he later developed diarrhea and delirium, and died approximately 40 days after the onset. Autopsy findings were consistent with Wernicke's encephalopathy and pellagra encephalopathy. Furthermore, laminar cortical necrosis with vacuoles and astrocytosis was found in the second and third layers of the bilateral frontal cortices, suggesting Morel's laminar sclerosis. The lesions were mainly located in the bilateral primary motor cortices. Involvement of the lower part of the left primary motor cortex may be associated with apraxia of speech in our case.     

Voxel-based analyses of gray/white matter volume and diffusion tensor data in major depression

The purpose of this study is to use voxel-based analysis to simultaneously elucidate regional changes in gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) in patients with unipolar major depressive disorder. We studied 21 right-handed patients and 42 age- and gender-matched right-handed normal subjects. Local areas showing significant gray matter volume reduction in depressive patients compared with controls were observed in the right parahippocampal gyrus, hippocampus, bilateral middle frontal gyri, bilateral anterior cingulate cortices, left parietal and occipital lobes, and right superior temporal gyrus. Local areas showing an increase of MD in depressive patients were observed in the bilateral parahippocampal gyri, hippocampus, pons, cerebellum, left frontal and temporal lobes, and right frontal lobe. There was no significant difference between the two groups for FA and white matter volume in the entire brain. Although there was no local area where brain volume and MD were significantly correlated with disease severity, FA tended to correlate negatively with total days depressed in the right anterior cingulate and the left frontal white matter. These results suggest that the frontolimbic neural circuit might play an important role in the neuropathology of patients with major depressive disorder.     

Efficacy of the American Heart Association/American Stroke Association guidelines for ultra-early,intentional antihypertensive therapy in intracerebral hemorrhage

Whether the intentional antihypertensive therapy recommended by the American Heart Association/American Stroke Association (AHA/ASA) guidelines has clinical benefit for patients who have acute spontaneous intracerebral hemorrhage (ICH) has yet to be proven. We retrospectively reviewed the clinical charts of 175 patients with putaminal or thalamic ICH with acute hypertension to examine the correlation between the efficacy of antihypertensive therapy within 3 hours of onset, hematoma expansion (HE) after hospitalization and clinical outcome. The aim of the antihypertensive therapy was to achieve and maintain a systolic blood pressure of 120 mm Hg to 160 mm Hg until the second CT scan. The mean arterial pressure (MAP) after admission was the average MAP values measured every hour for the first 3 hours of hospitalization or until the second CT scan, if this was performed within the same timeframe. Thirty-two (18.3%) patients were found to have HE. Prior to the second CT scan, antihypertensive medications were administered to all patients without any major complications. A multiple logistic regression analysis revealed that a MAP of >110 mm Hg after admission was the only variable independently associated with HE (odds ratio [OR] = 3.455; 95% confidence interval [CI] = 1.510–8.412; p = 0.004). Modified Rankin Scale scores of ?3 on day 30 were significantly more common in those patients without HE (p = 0.002).Our findings suggest that there are clinical benefits, by the prevention of subsequent HE, in maintaining a MAP level lower than that recommended by the AHA/ASA (110 mm Hg) after hospitalization for patients who have ICH.     

Effects of epalrestat,an aldose reductase inhibitor,on diabetic peripheral neuropathy in patients with type 2 diabetes,in relation to suppression of Nɛ-carboxymethyl lysine

ObjectiveWe investigated the efficacy of epalrestat, an aldose reductase inhibitor, for diabetic peripheral neuropathy in Japanese patients with type 2 diabetes.MethodsA total of 38 type 2 diabetic patients (22 men and 16 women; mean±S.E.M. age 63.3±1.0 years; duration of diabetes 9.6±0.8 years) with diabetic neuropathy were newly administered 150 mg/day epalrestat (EP group). Motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV), and minimum F-wave latency were evaluated before administration of epalrestat and after 1 and 2 years. Serum N^?-carboxymethyl lysine (CML) as a parameter of advanced glycation end products (AGEs), lipid peroxide, and soluble vascular cell adhesion molecule (sVCAM)-1 as a parameter of angiopathy were measured before administration and after 1 year. We compared the results with those of 36 duration of diabetes-matched type 2 diabetic patients (mean±S.E.M. duration of diabetes 8.2±0.7 years) as control (C group).ResultsThe EP group showed significant suppression of deterioration of MCV (P<.01) and minimum F-wave latency (P<.01) in the tibial nerve and SCV (P<.05) in the sural nerve compared to those in the C group after 2 years. There was a significant difference in change in CML level between groups (?0.18±0.13 mU/ml in the EP group vs. +0.22±0.09 mU/ml in the C group, P<.05) after 1 year.ConclusionsEpalrestat suppressed the deterioration of diabetic peripheral neuropathy, especially in the lower extremity. Its effects might be mediated by improvement of the polyol pathway and suppression of production of AGEs.     

Evaluation of performance of two high-frequency oscillatory ventilators using a model lung with a position sensor

Purpose

High-frequency oscillatory ventilation (HFOV) is thought to protect the lungs of acute respiratory distress syndrome (ARDS) patients. The performance and mechanical characteristics of high-frequency oscillatory ventilators, especially with regard to delivering appropriate tidal volume (V _T) to compromised lungs, might affect the outcome of patients. We evaluated the performance of two such ventilators using a model lung with a position sensor.

Methods

We tested the Metran R100 and SensorMedics 3100B. V _T was measured using the model lung with the compliance set at 20 or 50 ml/cmH₂O and the resistance at 0 or 20 cmH₂O/l/s. Oscillator frequency was set at 5, 7, and 9 Hz, and amplitude was set at 25%, 50%, 75%, and 100% (100% being maximum amplitude available at each setting configuration).

Results

At each model lung setting, R100 delivered greater V _T at 5 Hz. V _T differences between the ventilators decreased as frequency increased and were negligible at 9 Hz. At each model lung setting and frequency, as amplitude increased from 25% to 100%, V _T increased proportionally more with R100. With an I:E ratio of 1:1, 3100B delivered greater V _T than with 1:2.

Conclusion

Because it is able to deliver comparably greater V _T, R100 may be a better choice for HFOV in critical ARDS patients. Better proportionality may be a result of more effective amplitude titration for adjusting PaCO₂ during oscillation.     

Upper extremity deep vein thrombosis treated by a filter in the superior vena cava placed intraoperatively to allow safe esophageal surgery: Report of a case

Upper extremity deep vein thrombosis (UEDVT) is an infrequent but dangerous vascular event, especially for patients undergoing thoracic surgery. However, there is no standard perioperative management to reduce the risk of pulmonary thromboembolism in such patients. We describe how we performed successful esophagectomy in a patient with UEDVT treated by placing a filter in the superior vena cava during surgery.     

Prediction of the external work of the native heart from the dynamic H-Q curves of the rotary blood pumps during left heart bypass

The ventricular performance is dependent on the drainage effect of rotary blood pumps (RBPs) and the performance of RBPs is affected by the ventricular pulsation. In this study, the interaction between the ventricle and RBPs was examined using the pressure-volume (P-V) diagram of the ventricle and dynamic head pressure-bypass flow (H-Q) curves (H, head pressure: arterial pressure minus ventricular pressure vs. Q, bypass flow) of the RBPs. We first investigated the relationships in a mock loop with a passive fill ventricle, followed by validation in ex vivo animal experiments. An apical drainage cannula with a micro-pressure sensor was especially fabricated to obtain ventricular pressure, while three pairs of ultrasonic crystals placed on the heart wall were used to derive ventricular volume. The mock loop-configured ventricular apical-descending aorta bypass revealed that the external work of the ventricle expressed by the area inside the P-V diagrams (EW(Heart) ) correlated strongly with the area inside dynamic H-Q curves (EW(VAD)), with the coefficients of correlation being R2 = 0.869 ～ 0.961. The results in the mock loop were verified in the ex vivo studies using three Shiba goats (10-25 kg in body weight), showing the correlation coefficients of R2 = 0.802 ～ 0.817. The linear regression analysis indicated that the increase in the bypass flow reduced pulsatility in the ventricle expressed in EW(Heart) as well as in EW(VAD) . Experimental results, both mock loop and animal studies, showed that the interaction between cardiac external work and H-Q performance of RBPs can be expressed by the relationships "EW(Heart) versus EW(VAD) ." The pulsatile nature of the native heart can be expressed in the area underneath the H-Q curves of RBPs EW(VAD) during left heart bypass indicating the status of the level of assistance by RBPs and the native heart function.