Conservative Treatment of Chronic Subdural Hematoma with Gorei-san.

Most asymptomatic patients with chronic subdural hematoma (CSDH) are followed conservatively but can require surgical treatment if the hematoma expands. We conducted a retrospective evaluation of the effect of Gorei-san on CSDH. This study included patients treated between April 2013 and March 2015. In total, 289 patients were diagnosed with CSDH and 110 patients received conservative management. Finally, 39 patients who met the requirements were registered. We retrospectively examined the age, gender, medical history, hematoma thickness, clarity of sulci below hematomas, and midline shift of the patients. The primary outcome was the median surgery-free interval, and the secondary results were the rate of CSDH shrinkage and surgery avoidance. A comparison of patient characteristics between the Gorei-san (G) and non-Gorei-san (NG) groups found no significant differences in the percentage of men, average ages, past history, thickness of CSDH (15.0 ± 3.1 mm vs. 15.3 ± 2.6 mm, p = 0.801), or midline shift (2.0 ± 2.7 mm vs. 4.0 ± 5.0 mm, p = 0.230). The median surgery-free interval was significantly different between the G and NG groups [n. r. vs. 41 days (95% CI: 5-79), log-rank p = 0.047]. The CSDH avoidance rate was not significantly different between the two groups (70.0% vs. 34.4%, p = 0.071). Additionally, the CSDH shrinkage rate was significantly different between the two groups (60.0% vs. 10.3%, p = 0.004). This retrospective study demonstrated that CSDH treatment with Gorei-san reduces hematoma significantly more than treatment that does not include Gorei-san.

Stroke Mimics and Accuracy of Referrals Made by Emergency Department Doctors in Japan for Patients with Suspected Stroke.

BACKGROUND: Stroke mimics (SMs)are medical conditions that are at first considered to be of cerebrovascular etiology but turn out to be a condition other than stroke. While many reports on SMs have been published, there have been none from Japan. Thus, we sought to assess the current state of SMs in a Japanese population. METHODS: We collected data of patients referred with suspicion of stroke to neurosurgeons by emergency department (ED) doctors, and we retrospectively evaluated the diagnosis concordance rate between the ED doctors and the neurosurgeons. We also assessed the plausible causes leading to misdiagnosis of stroke. RESULTS: Of the 226 consecutive referrals with suspicion of stroke, only 71.7% were accurate. Furthermore, 75% of the SMs were disorders unrelated to neurosurgery, such as psychiatric disorders, peripheral dizziness/vertigo, and cardiovascular events. In other words, referring those patients to neurosurgeons was inappropriate. We found that perceived notion or premature assumption of stroke accounted for 43.8% of the stroke mimic patients and was the most important reason for the misdiagnosis. CONCLUSIONS: This is the first report on SMs in a Japanese population. About one-third of all referrals with suspicion of stroke made by ED doctors were inappropriate. Including more information on stroke diagnosis in the educational program for young doctors in Japan would be beneficial for improving the quality of the initial medical examination of patients with suspected stroke.

Effects of Gait Treatment With a Single-Leg Hybrid Assistive Limb System After Acute Stroke: A Non-randomized Clinical Trial.

We hypothesized that a single-leg version of the Hybrid Assistive Limb (HAL) system could improve the gait and physical function of patients with hemiparesis following a stroke. In this pilot study, we therefore compared the efficacy of HAL-based gait training with that of conventional gait training (CGT) in patients with acute stroke. Patients admitted to the participating university hospital were assigned to the HAL group, whereas those admitted to outside teaching hospitals under the same rehabilitation program who did not use the HAL were assigned to the control group. Over 3 weeks, all participants completed nine 20 min sessions of gait training, using either HAL (i.e., the single-leg version of HAL on the paretic side) or conventional methods (i.e., walking aids and gait orthoses). Outcome measures were evaluated before and after the nine training sessions. The Functional Ambulation Category (FAC) was the primary outcome measure, but the following secondary outcome measures were also assessed: National Institutes of Health Stroke Scale, Fugl-Meyer Assessment (Lower Extremity), comfortable walking speed, step length, cadence, 6-min walk distance, Barthel Index, and Functional Independence Measure. In total, 22 post-stroke participants completed the clinical trial: 12 in the HAL group and 10 in the CGT group. No serious adverse events occurred in either group. The HAL group showed significant improvement in FAC after nine sessions when compared with the CGT group (P = 0.014). However, secondary outcomes did not differ significantly between the groups. Our results demonstrate that HAL-based gait therapy may improve independent walking in patients with acute stroke hemiplegia who are dependent on ambulatory assistance. A larger-scale randomized controlled trial is needed to clarify the effectiveness of single-leg HAL therapy. Clinical Trial Registration: UMIN Clinical Trials Registry, identifier UMIN000022410.

Regular medications prescribed to elderly neurosurgical inpatients and the impact of hospitalization on potentially inappropriate medications.

Objective: This study aimed to evaluate the regular medications prescribed to elderly neurosurgical inpatients in community hospitals in Japan. Materials and Methods: Elderly patients (aged ≥ 65 years) who had been admitted to neurosurgery departments from April 2015 to March 2017 were enrolled in this study. We collected data on regular medications at the time of admission and discharge. Furthermore, we retrospectively analyzed factors associated with potentially inappropriate medications (PIMs). PIMs were defined as polypharmacy (≥ 6 medications used concurrently) or taking any of the unfavorable medications on the "list of drugs to be prescribed with special caution" in the "Guidelines for Medical Treatment and Its Safety in the Elderly 2015". Results: We gathered data on over 1900 medications (mean number, 5.04) prescribed to 197 patients (mean age, 76.9 years). PIMs were observed in 51.3% of patients on admission. The most common prescriptions resulting in PIMs were benzodiazepine agents, followed by loop diuretics and H2 receptor antagonists. The multivariate analysis revealed that age (odds ratio, 1.08; p < 0.01) and the number of prescribers (odds ratio, 6.16; p < 0.01) were significantly related to PIMs on admission. PIM exposure at the time of discharge accounted for 39.1%, a 12.2% decrease. Conclusion: More than half of the elderly patients were prescribed PIMs on admission; however, this exposure decreased by 12.2% at the time of discharge. Hospitalization is an optimal opportunity for reconsidering the necessity of medications and for changing the prescriptions according to patients' conditions.

Paraplegia caused by cerebral contusions in the bilateral precentral gyri.

BACKGROUND: Paraplegia is mainly caused by spinal cord disease and rarely occurs due to head trauma. In this report, we describe a case of paraplegia caused by cerebral contusions in the bilateral precentral gyri. CASE DESCRIPTION: A 72-year-old man was admitted to our hospital with mildly impaired consciousness and severe pure motor paralysis in both legs. He was healthy until the morning of the day, but his wife found him injured in front of his house upon returning home. He had a subcutaneous hematoma in his occipital region, and seemed to have slipped by accident. Computed tomography of the brain and magnetic resonance imaging (MRI) of his spinal cord revealed no apparent cause of the paraplegia, although an MRI of his brain clearly revealed cerebral contusions in the bilateral precentral gyri. The cerebral contusion was diagnosed as the cause of pure motor paralysis of lower extremities. He received rehabilitation, and manual muscle testing of his legs revealed improvements. In the subacute phase, the precentral gyrus lesion disappeared on MRI. CONCLUSION: We must emphasize that cerebral contusion can be a differential diagnosis for paraplegia. In the acute phase, fluid-attenuated inversion recovery (FLAIR) MRI coronal and sagittal images are useful for identifying precentral gyri contusions. Paraplegia caused by a cerebral contusion may be misdiagnosed as a spinal concussion due to the disappearance of the precentral gyrus lesion on FLAIR MRI in the subacute phase.

Model-Based Estimation of Aortic and Mitral Valves Opening and Closing Timings in Developing Human Fetuses.

Electromechanical coupling of the fetal heart can be evaluated noninvasively using doppler ultrasound (DUS) signal and fetal electrocardiography (fECG). In this study, an efficient model is proposed using K-means clustering and hybrid Support Vector Machine-Hidden Markov Model (SVM-HMM) modeling techniques. Opening and closing of the cardiac valves were detected from peaks in the high frequency component of the DUS signal decomposed by wavelet analysis. It was previously proposed to automatically identify the valve motion by hybrid SVM-HMM based on the amplitude and timing of the peaks. However, in the present study, six patterns were identified for the DUS components which were actually variable on a beat-to-beat basis and found to be different for the early gestation (16-32 weeks), compared to the late gestation fetuses (36-41 weeks). The amplitude of the peaks linked to the valve motion was different across the six patterns and this affected the precision of valve motion identification by the previous hybrid SVM-HMM method. Therefore in the present study, clustering of the DUS components based on K-means was proposed and the hybrid SVM-HMM was trained for each cluster separately. The valve motion events were consequently identified more efficiently by beat-to-beat attribution of the DUS component peaks. Applying this method, more than 98.6% of valve motion events were beat-to-beat identified with average precision and recall of 83.4% and 84.2% respectively. It was an improvement compared to the hybrid method without clustering with average precision and recall of 79.0% and 79.8%. Therefore, this model would be useful for reliable screening of fetal wellbeing.

Vaginal LPS changed gene transcriptional regulation response to ischemic reperfusion and increased vulnerability of fetal brain hemorrhage.

During pregnancy, both ischemic reperfusion and bacterial agent LPS are known risk factors for fetal brain damage. However, there is a lack of evidence to explain whether vaginal LPS affects the fetus response to ischemic reperfusion. Here we reported that there was more than 2 folds higher vulnerability of fetal brain hemorrhage response to ischemic reperfusion when mother mouse was treated with vaginal LPS. As our previously reported, ischemic reperfusion induces P53-dependent fetal brain damage was based on a molecular mechanism: the transcriptional pattern was changed from HIF-1alpha-dependent to P53-dependent immediately. In the present work, only with vaginal LPS precondition, phosphorylation of activated transcriptional factor (ATF) 2 at Thr71 appeared in response to ischemic reperfusion. Moreover, this phosphorylation was completely blocked by pre-treatment with a P53 inhibitor, pifithrin-α. We concluded that vaginal LPS precondition trigged the p53-dependent phosphorylation of ATF2 in response to ischemic reperfusion, which played an important role of increasing vulnerability to hemorrhage in fetus.

Intrauterine ischemic reperfusion switches the fetal transcriptional pattern from HIF-1α- to P53-dependent regulation in the murine brain.

Ischemic reperfusion (IR) during the perinatal period is a known causative factor of fetal brain damage. So far, both morphologic and histologic evidence has shown that fetal brain damage can be observed only several hours to days after an IR insult has occurred. Therefore, to prevent fetal brain damage under these circumstances, a more detailed understanding of the underlying molecular mechanisms involved during an acute response to IR is necessary. In the present work, pregnant mice were exposed to IR on day 18 of gestation by clipping one side of the maternal uterine horn. Simultaneous fetal electrocardiography was performed during the procedure to verify that conditions resulting in fetal brain damage were met. Fetal brain sampling within 30 minutes after IR insult revealed molecular evidence that a fetal response was indeed triggered in the form of inhibition of the Akt-mTOR-S6 synthesis pathway. Interestingly, significant changes in mRNA levels for both HIF-1α and p53 were apparent and gene regulation patterns were observed to switch from a HIF-1α-dependent to a p53-dependent process. Moreover, pre-treatment with pifithrin-α, a p53 inhibitor, inhibited protein synthesis almost completely, revealing the possibility of preventing fetal brain damage by prophylactic pifithrin-α treatment.

Evaluation of cardiac performance by abdominal fetal ECG in twin-to-twin transfusion syndrome.

OBJECTIVE: To investigate fetal cardiac performance by abdominal fetal electrocardiography (ECG) in monochorionic diamniotic pregnancies with twin-to-twin transfusion syndrome (TTTS-MCDA). METHODS: Abdominal fetal ECG was attempted in 16 singleton, 21 non-TTTS-MCDA, and 14 TTTS-MCDA pregnancies at 16-27 weeks' gestation. Standard ECG parameters were compared across study groups and evaluated for their correlation with Doppler ultrasound indices. RESULTS: Clear P-QRST complexes were recognized in all cases. In the TTTS-MCDA pregnancies, the QT interval and QTc were significantly longer than in both singletons and the non-TTTS-MCDA pregnancies (p = 0.002 and p = 0.0002, respectively), whereas in the recipient fetus, both the PR interval and PR/RR were significantly longer when compared with all other study groups (p = 0.019 and p = 0.012, respectively). Further comparison with Doppler ultrasound indices yielded significant reciprocal correlations between ductus venosus pulsatility index and the QT interval (r = 0.552, p = 0.041) and between umbilical artery pulsatility index and PR/RR (r = 0.654, p = 0.011) both demonstrated in recipient fetuses alone. CONCLUSIONS: Abdominal fetal ECG is feasible in second-trimester twin pregnancies. In TTTS, there is evidence of a higher risk of cardiac dysfunction in the recipient twin.

Maternal undernutrition induces the expression of hypoxia-related genes in the fetal brain.

Maternal undernutrition during pregnancy is a risk factor for cerebrovascular and cardiovascular diseases in adulthood. Hypoxia-inducible factor 1 alpha (HIF1α) plays an essential role in cellular hypoxic responses, and its increased expression is associated with cerebrovascular and cardiovascular diseases. However, it is not known whether maternal undernutrition influences HIF1α expression in the fetal brain. We therefore analyzed the expression levels of HIF1α and its downstream genes in the fetal brain (day 17.5 of gestation, 1-2 days before birth). Maternal undernutrition did not noticeably affect the fetal body and brain weights. Both HIF1α mRNA and protein levels were increased in the brain under maternal undernutrition, despite the absence of hypoxia, as judged by the staining profile with hypoxyprobe-1 that identifies hypoxic cells. Importantly, maternal undernutrition caused the accumulation of HIF1α protein in oligodendrocyte precursor cells at the subventricular zone, a site of neurogenesis in the fetal brain. Maternal undernutrition also increased the mRNA level of mammalian target of rapamycin (mTOR), which could increase the level of HIF1α protein under normoxia. Furthermore, microarray analysis revealed that expression levels of mRNAs for 10 HIF1α downstream targets, including enolase 1 and hexokinase 1, were increased in the fetal brain under maternal undernutrition. Thus, the biochemical consequence of maternal undernutrition is similar to that of mild hypoxia. In conclusion, maternal undernutrition induces the expression of HIF1α in oligodendrocyte precursor cells at the subventricular zone, and it also induces the expression of hypoxia-related genes in the fetal brain probably via activation of the mTOR pathway.

Pilot study of the safety of starting administration of low-dose aspirin and cilostazol in acute ischemic stroke.

Progressive stroke is a serious problem due to the associated morbidity and mortality. Aspirin is recommended for acute ischemic stroke, but does not reduce the frequency of stroke progression. No standard treatment has been approved for the prevention of stroke progression. Cilostazol, which reduces platelet aggregation about 3 hours after single administration, does not increase the frequency of bleeding events when compared with aspirin or a placebo. Moreover, the combination of 100 mg aspirin and 200 mg cilostazol does not increase the frequency of bleeding events compared with only 100 mg aspirin, and thus is expected to prevent stroke progression with a high degree of safety. The present study investigated the safety of this combination of two drugs administered at the above concentrations in 54 patients with acute ischemic stroke within 48 hours of stroke onset. Modified National Institutes of Health Stroke Scale (NIHSS) measurements were performed at baseline and again on day 4 to 7. Progressive stroke was defined as an increase greater than or equal to 1 point on NIHSS. Patient scores on the modified Rankin Scale (mRS) were evaluated at baseline and 3 months after enrollment. Stroke progression occurred in 11.1% of the patients. The percentages of patients with mRS score from 0 to 2 were 42.6% and 75% at baseline and 3 months, respectively. No symptomatic intracranial hemorrhage or major extracranial hemorrhage occurred. These results suggest that administration of aspirin and cilostazol is safe for acute ischemic stroke.

Successful detection of the fetal electrocardiogram waveform changes during various states of singletons.

Accurate assessment of fetal well-being is one of the most important tasks for obstetricians. It is still difficult to measure fetal electrocardiogram (ECG) during fetal movements. Recently, a new method, blind source separation with reference signals, was proposed for stable measurements. This method distinguishes weak signals from noisy mixed signals with little information about the sources. The aim of this study is to estimate the ability of this method for fetal ECG monitoring and to establish standard fetal ECG electrocardiogram values of normal singletons including during fetal movement. The subjects enrolled were 167 pregnant women with normal single pregnancy from 18- to 41-week gestation, who regularly visited Tohoku University Hospital, and 12 pregnant women with fetal abnormality. Fetal signals were successfully separated in 163 of 179 subjects at 91.1% success rate regardless of fetal movements. Time intervals of ECG (P, PR and QRS intervals and QTc) were measured. The standard curves of each interval through the gestational period were obtained. The data in active phase were compared to that in rest phase and the data obtained from normal and abnormal fetuses were investigated. PR intervals in the rest phase were prolonged compared to those in the active phase. Fetal ECG showed anomalous values such as PR interval or QTc prolongation in the abnormal fetuses. The fetal ECG was measured by the new method with or without fetal movements, and the standard fetal ECG values have been established. This study provides a foundation for further detailed clinical studies.

Understanding congenital heart defects through abdominal fetal electrocardiography: case reports and clinical implications.

AIMS: Congenital heart defects are the most common fetal structural anomalies of which a significant number remain unrecognized during postnatal life. Fetal electrocardiography (FECG) is an ideal clinical tool to complement ultrasonography for the screening and management of these cases where early and accurate diagnoses would allow definite rather than palliative treatment. The objective of this report was to correlate the particular FECG results found with the different types of congenital heart defects involved and to further demonstrate the usefulness of FECG in clinical settings. MATERIAL & METHODS: This is a report of four cases of prenatally diagnosed congenital heart defects seen at a university hospital in Sendai, Japan. Their complete and thorough evaluation included, among other tests, abdominal FECG analysis. RESULTS: The presence of premature ventricular contractions, a prolonged pre-ejection period (PEP > 75 msec), and prolonged QTc intervals (QTc > 440 msec) served as markers of hemodynamic alteration but were unlikely determinants of disease severity precluding further investigation. CONCLUSIONS: In practice, similar findings found on FECG should raise the index of suspicion for the presence of congenital heart disease and prompt a targeted ultrasound scan.

Antepartum non-invasive evaluation of opening and closing timings of the cardiac valves in fetal cardiac cycle.

In this study, we propose a non-invasive algorithm to recognize the timings of fetal cardiac events on the basis of analysis of fetal ECG (FECG) and Doppler ultrasound signals. Multiresolution wavelet analysis enabled the frequency contents of the Doppler signals to be linked to the opening (o) and closing (c) of the heart's valves (Aortic (A) and Mitral (M)). M-mode, B-mode and pulsed Doppler ultrasound were used to verify the timings of opening and closure of these valves. In normal fetuses, the time intervals from Q-wave of QRS complex of FECG to opening and closing of aortic valve, i.e., Q-Ao and Q-Ac were found to be 79.3 +/- 17.4 and 224.7 +/- 13.3 ms, respectively. For the mitral valve, Q-Mc and Q-Mo were found to be 27.7 +/- 9.4 and 294.6 +/- 21.3 ms, respectively. Correlations among the timings in opening and closing of cardiac valves were found to be higher in abnormal fetuses than that in normal ones.

Osteolytic lumbar discal cyst: case report.

A 25-year-old man presented with left lumboischialgia refractory to medical treatment. Neurological examination revealed L5 and S1 radiculopathy which rapidly worsened over a short period. Magnetic resonance imaging demonstrated disk bulging with a discal cyst at the L4-5 intervertebral space and disk herniation at the L5-S1 intervertebral space. Computed tomography showed osteolytic change of the L5 vertebral body adjacent to the cyst. Resection of the cyst and removal of the herniated disk were performed following fenestration of the L4-5 and L5-S1 interlaminar spaces. Bloody serous fluid followed by clear serous fluid was recognized during the aspiration and partial resection of the cyst at the L4-5 level. Histological examination demonstrated a cyst wall consisting of fibrous connective tissue without a single-layer lining of cells, and fibrin deposits. The patient's symptoms disappeared immediately after the operation. This osteolytic lumbar discal cyst possibly occurred subsequent to hemorrhage from the epidural venous plexus following intervertebral disk injury, hematoma encapsulation by connective fibrous tissue, and cyst wall formation in reaction to the disk injury and hemorrhage. The cyst may have enlarged due to the inflow of the serous fluid from the water-containing degenerated disk.

In vitro effect of cyclosporin A, mitomycin C and prednisolone on cell kinetics in cultured human umbilical vein endothelial cells.

INTRODUCTION: Vascular endothelial cell damage plays an important role in microvascular thrombogenesis. In vivo administration of cyclosporin A or mitomycin C sometimes results in thrombotic microangiopathy in patients. MATERIALS AND METHODS: The effects of cyclosporin A, mitomycin C and/or prednisolone on the cell cycle in cultured human umbilical vein endothelial cells were investigated to evaluate drug-induced endothelial cell damage and the protective effect of prednisolone on endothelial cells against the damage by cyclosporin A or mitomycin C in vitro. RESULTS: The addition of cyclosporin A to cultures caused proliferation arrest in the G1-phase in a dose-dependent manner, while mitomycin C inhibited DNA synthesis, which resulted in cell cycle arrest and inhibition of BrdUrd incorporation in the S-phase. The administration of prednisolone also caused cell cycle arrest in the G1 by itself, and protected the cells from the damage caused by mitomycin C. The inhibitory effects of cyclosporin A and prednisolone on the cell cycle were reversible, while mitomycin C was not. The highly phosphorylated retinoblastoma protein expressed in human umbilical vein endothelial cells decreased in the presence of mitomycin C. Soluble thrombomodulin levels in the culture supernatant were elevated by the addition of cyclosporin A. CONCLUSION: These effects of the drugs may cause the cell cycle arrest and the prolonged repair of damaged endothelial cells in patients.

Acute promyelocytic leukemia developing in untreated essential thrombocythemia.

We describe a patient with untreated essential thrombocythemia (ET) who developed microgranular variant of acute promyelocytic leukemia, 9 years after the initial diagnosis of ET. He achieved complete remission (CR) but relapsed 11 months later. After achieving the second CR, he received peripheral stem cell transplantation from his HLA complete-matched sibling. Five months after the transplantation, he relapsed again with meningeal infiltration of leukemic cells. In this paper, we review cases of promyelocytic transformation of myeloproliferative diseases (MPD) other than chronic myeloid leukemia (CML). To our knowledge, this is the first case of promyelocytic transformation of Philadelphia chromosome negative untreated ET, in whom both t(15;17) and PML-RAR alpha fusion were proven.