Tsukasa Kawase

Hypersomnia, asterixis and cataplexy in association with orexin A-reduced hypothalamic tumor

Sirs: There is an absence or low level of orexin in the cerebrospinal fluid (CSF) in a majority of patients with narcolepsy-cataplexy, a chronic sleep disorder characterized by excessive daytime sleepiness (EDS) and cataplexy [6]. Orexin deficiency has been reported in several symptomatic cases of narcolepsy or hypersomnia associated with neurodegenerative, surgical, ischemic and postinfectious insults to hypothalamus [1, 5, 7]. Here we report a patient with a hypothalamic tumor and low CSF orexin A level whose symptoms improved with non-surgical therapy. We discuss the clinical presentation of orexin-reduced hypersomnia in comparison with idiopathic narcolepsy-cataplexy. A 66-year-old woman without remarkable family history was admitted to our hospital reporting symptoms typical of EDS for 1 month including falling asleep when riding in a car and during eating.Also, her family had noted that she sustained abrupt falls without loss of consciousness.Visual hallucinations also were noted but it was not of the sleep-onset type, and there was no history suggestive of sleep paralysis.Although alert, able to follow commands, and answer questions her time orientation was disturbed and she scored 21/30 on minimental state examination (MMSE). The cranial nerves, muscle tone, motor strength, and sensory were normal.When the arms were outstretched with wrists and fingers extended, abrupt downward movements of the hands occurred bilaterally consistent with asterixis. In the ward the patient suffered from facial injury from falls at night several times and she said it had been caused by an abrupt tone reduction of legs without loss of consciousness. Routine blood chemistry analysis was normal and endocrinological studies were consistent with mild anterior hypopituitarism. CSF examination revealed a protein concentration of 57 mg/dl, mild mononuclear pleocytosis, and an orexin A concentration of 62 pg/ml measured by radioimmunoassay using methodology reported previously [6]. Magnetic resonance T2 weighted images of the brain exhibited high signal intensities in the hypothalamus, thalamus, and midbrain bilaterally, with gadolinium enhancement on T1 images (Fig. 1A, B) consistent with tumor.A daytime polysomnogram demonstrated REM sleep latency of eleven minutes with five minute sleep latency. She underwent radiation therapy (total of 46 Gy), and nimustine hydrochloride and interferon β administered. The patient improved cognitively (MMSE 28/30) and behaviorally. EDS, disturbed sleep-wake cycle, falls, arm asterixis and night confusion subsided. MR images taken 4 months after completion of her therapy demonstrated reduction of tumor size and edema (Fig. 1C, D). Features of symptomatic narcolepsy or hypersommnia can vary widely according to histopathology, lesion size and location. Memory disturbance in our patient may have been due to dysfunction of amygdalofugal pathways to the ventromedial nuclei [2]. Her arms showed typical asterixis and although she had no walking difficulty in daytime she fell at night without disturbance of consciousness so we estimated that she had cataplexy-like drop attacks independent of emotional stimulus as well as upper asterixis. Similar atypical cataplexy has been reported in hypothalamic tumor cases with hypersomnia [5]. Patients with focal lesions of the basal ganglia or midbrain can show asterixis [3], but there has been no reported case having both upper asterixis and drop attack. Bril et al. have discussed the similarities between asterixis and drop attack or cataplexy and suggested upper asterixis is a segmental form of drop attack [3]. Our case also suggests that there might be common pathophysiology or anatomical site, within the hypothalamus or brainstem, for abrupt hypotonus, thus linking asterixis with cataplexy. Most cases of symptomatic narcolepsy involve lesions of the hypothalamus and rostral brainstem, and only one previously reported case fulfills the narcoleptic tetrad [7]. The reduction of orexin level supports the hypothesis that hypersomnia is caused by decreased orexin. Typically, primary narcolepsy patients show extremely low, and even undetectable levels of orexin A in the CSF [4, 6]. Narcolepsy without cataplexy or idiopathic hypersomnia cases shows only relatively low orexin levels [4]. In our patient CSF orexin A (62 pg/ml) showed relative reduction compared with controls (280 ± 33pg/ml) [6]. LETTER TO THE EDITORS

Analyses of proliferative potential in schwannomas

We report studies of schwannomas with a high percentage of MIB-1 positive cells. Thirty-eight specimens from 36 cases of schwannoma in the intracranial and spinal regions comprise the substance of this study. The MIB-1 positive cells were measured using immunohistochemical staining. In nine cases with a positivity index (PI) of 5% or more, immunohistochemical staining using DNA topoisomerase IIα (topo-II) and CD68 was performed. In some cases, we also searched for apoptosis with the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Three of nine cases with 5% or more positive MIB-1 cells had a very high cellularity with mitotic figures and were considered cellular Schwannomas. Their MIB-1 PI values were 8.21%, 10.00%, and 21.37%. However, the remaining six cases showed little evidence of malignancy. Their PIs were comparatively low, ranging from 5.19% to 8.41%, and the positive findings were localized in many cases. In these cases, we examined the sites where MIB-1 was measured and found that they corresponded to the borderline site between Antoni type A and B patterns and tended to be associated with an infiltration of CD68-positive macrophage. Furthermore, apoptotic cells appeared in the sites. With topo-II staining, the PIs in the same sites of these six cases were low, ranging from 0.78% to 1.93%. This implies that the high MIB-1 PI that was seen in these six cases was caused by reaction of MIB-1 to tumor cells that brought about an abnormality in the cell cycle by degeneration, such as apoptosis. In the site of formation of Antoni type B, MIB-1 may be a false positive in tumors with degenerative findings such as schwannomas. Topo-II was useful in these cases.

Dual-Image Videoangiography During Intracranial Microvascular Surgery

OBJECTIVE Indocyanine green videoangiography (ICG-VA) is a valuable tool to assess vessel and aneurysm patency during neurovascular surgical procedures. However, ICG-VA highlights vascular structures, which appear white over a black background. Anatomic relationships are sometimes difficult to understand at first glance. Dual-image videoangiography (DIVA) enables simultaneous visualization of light and near-infrared fluorescence images of ICG-VA. METHODS The DIVA system was mounted on an OPMI Pentero Flow 800 intraoperative microscope. DIVA was used during microsurgical procedures on 5 patients who were operated for aneurysm clipping and superficial temporal artery-middle cerebral artery bypass. RESULTS DIVA provides real-time simultaneous visualization of aneurysm and vessels and surrounding structures including brain, nerves, and surgical clips. Although visual contrast between vessels and background is higher with standard black-and-white imaging, DIVA makes it easier to understand anatomic relationships between intracranial structures. DIVA also provides better vision of the depth of field. CONCLUSIONS DIVA has the potential to become a widely used intraoperative tool to check patency of intracranial vessels. It should be considered as an adjunct to standard ICG-VA for better understanding of vascular anatomy in relation to surrounding structures and can have an impact on decision making during surgery.

Radiological features of supratentorial gliomas are associated with their genetic aberrations

Gliomas are the most common primary neoplasms of the central nervous system [1]. Histopathological examination of surgically resected tissue is essential for the diagnosis of gliomas, and it forms the basis on which decisions regarding the use of adjuvant therapies are taken. This methodology has several potential difficulties, however. These include the fact that even pathologically identical tumors may have a different prognosis, that occasionally different areas of the same tumor tissue can have different histological characteristics [2], and that there is no entirely objective way of interpreting cellularity, anaplasia, or even cell type. To address these problems, many studies have tried to distinguish tumors on the basis of genetic and protein markers with the aim of standardizing decisions regarding therapeutic strategy based on the tumor subtypes they defined [3, 4]. Of particular note are the allelic losses of chromosomes 1p and 19q (−1p/19q), which have been reported as being positive predictors of chemotherapeutic response for anaplastic oligodendroglial tumors [5, 6]. Moreover, after Parsons et al. demonstrated that some gliomas carry a mutation in the IDH1 gene, genetic investigations have become increasingly important in the study of glioma biology [7]. However, although genetic analysis does provide important information, it requires an invasive surgical procedure. In addition to information provided by genetic analysis, some recent studies have suggested an association between radiological features and tumor type. To better understand the association between the radiological and genetic features of gliomas and to establish prognostic radiological criteria, we designed a study to test whether certain radiological features could be used to predict genetic aberrations in World Health Organization (WHO) grade II–III astrocytic and oligodendroglial tumors.

Stimulation-Dependent Intraspinal Microtubules and Synaptic Failure in Alzheimer's Disease: A Review

There are many microtubules in axons and dendritic shafts, but it has been thought that there were fewer microtubules in spines. Recently, there have been four reports that observed the intraspinal microtubules. Because microtubules originate from the centrosome, these four reports strongly suggest a stimulation-dependent connection between the nucleus and the stimulated postsynaptic membrane by microtubules. In contrast, several pieces of evidence suggest that spine elongation may be caused by the polymerization of intraspinal microtubules. This structural mechanism for spine elongation suggests, conversely, that the synapse loss or spine loss observed in Alzheimers disease may be caused by the depolymerization of intraspinal microtubules. Based on this evidence, it is suggested that the impairment of intraspinal microtubules may cause spinal structural change and block the translocation of plasticity-related molecules between the stimulated postsynaptic membranes and the nucleus, resulting in the cognitive deficits of Alzheimers disease.

Comparison of computational fluid dynamics findings with intraoperative microscopy findings in unruptured intracranial aneurysms- An initial analysis.

Context: The increase in the detection of unruptured cerebral aneurysms has led to management dilemma. Prediction of risk based on the size of the aneurysm is not always accurate. There is no objective way of predicting rupture of aneurysm so far. Computational fluid dynamics (CFDs) was proposed as a tool to identify the rupture risk. Aims: To know the correlation of CFD findings with intraoperative microscopic findings and to know the relevance of CFD in the prediction of rupture risk and in the management of unruptured intracranial aneurysms. Settings and Design: A prospective study involving nine cases over a period of 6 months as an initial analysis. Subjects and Methods: Both males and females were included in the study. Preoperative analysis was performed using computed tomography angiogram, magnetic resonance imaging in all cases and digital substraction angiogram in some cases. Intraoperatively microscopic examination of the aneurysm wall was carried out and images recorded. The correlation was done between microscopic and CFD images. Results: Seven cases were found intraoperatively to have a higher risk of rupture based on the thinning of the wall. Two cases had an atherosclerotic wall. All cases had low wall shear stress (WSS).Only two cases with atherosclerotic wall had a correlation with low WSS. Conclusions: While the pressure measured with CFD technique is a good predictor of rupture risk, the WSS component is controversial. Multicentric trials involving a larger subset of population are needed before drawing any definite conclusions. On-going development in the CFD analysis may help to predict the rupture chances accurately in future.

Flow Arrest for Complex Intracranial Aneurysm Surgery by Using Adenosine

The term complex intracranial aneurysms (CIAs) refers to aneurysm at a narrow and difficult location, difficult shape, and also giant size (aneurysm that is bigger than 25 mm in diameter) [1]. Giant aneurysms are more likely to bleed and present as subarachnoid hemorrhage, or sometimes they become partly thrombosed with ischemic brain causing mass effect with progressive symptoms or even death. Microsurgery and clip ligation can be challenging in CIAs because it is very difficult to have a panoramic view of the aneurysm, where sometimes the parent vessel is laid beneath the aneurysm, difficult to identify all branches and perforators, and also the surgical corridor could be very deep and narrow and surrounded by important neurovascular structures. During the clipping, it is important to make sure the aneurysm is well clipped to prevent injury from any perforator (Figs. 27.1, 27.2, and 27.3). Flow arrest can be induced by using adenosine; it will briefly reduce cerebral perfusion pressure and the tension on aneurysm, thereby facilitating the clip ligation. The length of time for the flow arrest will provide the surgeon to work at the aneurysm and the parts surrounding it or even reduce the bleed if it was ruptured during dissection. It will provide the time interval for the surgeon to be able to secure the neck of the aneurysm. The adenosine is working by inducing the transient asystole for a few minutes.

Transparent Sheath for Neuroendoscopic Intracerebral Hematoma Surgery

Neuroendoscopic procedures for spontaneous cerebral hemorrhage have recently increased. This is a result of the reports published by Nishihara et al. in 2000 [1], describing how to use the neuroendoscopic to evacuate the intracerebral hematoma by using a transparent sheath. Following this, 300 surgical cases of spontaneous intracerebral hemorrhage have been performed with an endoscope in our institution, and in related facilities, between 2000 and 2015. This procedure is commonly performed with only one or two burr holes under local anesthesia. If the transparent sheaths are introduced into hematoma safely, endoscopic procedures will be successful in any location of spontaneous hematomas.

Moyamoya Disease, Basic Concepts of Diagnostics, and Treatment

Moyamoya disease (MMD) is a rare condition where the supraclinoid part of internal carotid artery is slowly and progressively becoming stenotic, and also it often involves both middle cerebral arteries and anterior cerebral arteries (Fig. 26.1) [1]. The term moyamoya means a puff of smoke in Japanese, and it was first reported by Takeuchi and Shimizu in 1957 with Japanese language [2].

Real-time patency verification during clipping aneurysm and STA-MCA by-pass with dual-image videoangiography

Abstract The dual-image videoangiography (DIVA) is a new tool which helps identify vessels and surrounding structure. This method is based on use of indocyanine green video angiography (ICG-VA) technology on real time microscopic operative image. In this two case, we report of using DIVA in STA-MCA bypass surgery of 46 years old, female patient of stenosis of right MCA. And using DIVA during clipping ICA paraclinod aneurysm of 35 years old, female. During surgery, it helped in identifying temporal and frontal branches of the STA and there careful selection. After anastomosis, DIVA was used to refine vessel patency and functioning of the anastomosis. DIVA has the potential to replace ICG-VA as a tool for checking the patency of graft during bypass procedures and obliteration of aneurysm along with surgical procedures for AVM and d-AVF. DIVA allows visualization of vessels against a background of normal brain and has better visualization at greater depth and high magnification. This is particularly important during bypass surgery, which very often is performed in deep surgical fields and high magnification.