We reported double-dissociation between the visual processing of the edges and the surfaces of objects. Patients with lateral occipital damage showed selective impairment in the perception of edges whereas those with medial ventral occipital damage showed selective impairment in the perception of the 3D structure of the surface. Patients with medial ventral occipital damage also exhibited impaired perception of color, which is also a surface property. Those results were consistent with those from neuroimaging studies. Taken together, those studies suggest that objects may be processed in two separate pathways in the ventral occipital cortex: the edges of objects are processed in the lateral pathway and the surface of objects are processed in the medial pathway. Both edges and surfaces play important roles in object recognition, and both types of perception should be evaluated in patients with visual agnosia.
We report an unusual case of subarachnoid hemorrhage (SAH) due to ruptured aneurysm originating at the caudal loop of posterior inferior cerebellar artery (PICA). The patient was a 77-year-old female presented with a sudden onset of headache and vomiting. Initial CT scan demonstrated a SAH with thick hematoma mainly in the cisterna magna. Vertebral angiogram revealed a saccular aneurysm arising from the tonsillomedullary segment of the left PICA, and communicating artery with supplying a territory of contralateral vermis as an anastmotic vessel. At surgery, no vessel branches were confirmed in the vicinity of the aneurysm, and this aneurysm was successfully clipped. In the fetus, numerous basilar and vertebral arteries are organized in plexiform formations around the brain stem. It has been suggested that the pathogenesis of such aneurysm or communicating artery could be related with a remnant of a primitive vertebrobasilar anastomosis. Based on these considerations, congenital vessel-wall weakness and hemodynamic stress associated with communicating artery may contribute to the development of distal PICA aneurysms.
Ten newer antiepileptic drugs have been developed since 1990s. These drugs have wider therapeutic spectra, fewer side-effects, and lesser drug-to-drug interactions compared with the older typical antiepileptic drugs. Among them, zonisamide was developed in Japan and has been used from 1989. Gabapentin was at length approved in 2006. The other newer antiepileptic drugs are not approved yet in Japan. Felbamate can not be used in Europe because it may induce lethal hepatic toxicity and aplastic anemia. Vigabatrin is not approved in USA because it may induce permanent visual field deficit. The USA guideline for epilepsy treatment recommends that patients with newly diagnosed epilepsy can be treated with gabapentin, lamotrigine, topiramate, and oxcarbazepine. In contrast, based on epilepsy treatment guideline in England, newer antiepileptic drugs are considered only when patients with newly diagnosed epilepsy are unable to use the older antiepileptic drugs for some reasons. All newer antiepileptic drugs are used for intractable partial epilepsies, and lamotrigine and topiramate can also be used for idiopathic generalized epilepsies. The response rate (seizure reduction rate with 50% or more) and drop-out rate are overlapping among all newer antiepileptic drugs. Gabapentin, levetiracetam, and pregabalin are eliminated from kidney, and they had no drug-to-drug interactions and can be titrated rapidly. The serum concentration of lamotrigine is decreased with co-administration of hepatic enzyme inducing drugs and is increased with co-administration of valproic acid. Hypersensitivity reactions are rare with gavapentin, levetiracetam, topiramate, and tiagabin. Psychoses are reported to be induced with zonisamide, however, they can be induced with the other newer drugs (topiramate, levetiracetam, etc.). Drug-induced psychiatric symptoms, especially depression, may be often underdiagnosed. Many of these newer drugs (gabapentine, lamotrigine, levetiracetam, oxycarbazepine, etc.) have effects on chronic neuropathic pain. Some newer drugs show mood stabilizing effects (lamotrigine, oxycarbazepine, etc.), or antianxiety effect (gabapentin, topiramate, levetiracetam, pregavalin, etc.). Wide range of action to central nervous system of these newer antiepileptic drugs may serve not only for clinical seizure suppression, but also for neuroprotection.
Adult-onset citrullinemia (CTLN2) is a rare hereditary metabolic disorder characterized by highly increased concentration of citrulline and ammonia in the plasma, which is ascribed to a deficiency of argininosuccinate synthetase (ASS), one of the urea cycle enzymes mainly located in the liver. Neurological manifestation in CTLN2 patients closely resemble those of hepatic encephalopathy and in the past, most patients usually followed rapidly deteriorating clinical courses and died of severe brain edema within a few years after onset. However, in 1995 the first CTLN2 patient who was successfully treated by living-related liver transplantation was reported and since then more than 30 patients had underwent this operation in our country, showing good outcomes. No primary defect had not been found within ASS gene locus, but the causative gene of this disorder is now identified as the "citrin gene", which might act as a aspartate/glutamate transporter in mitochondria. Different phenotypes are seen in the individuals with a citrin deficiency: neonatal intrahepatic cholestasis, juvenile-onset chronic pancreatitis and hepatocellular carcinoma without cirrhosis can precede the appearance of CTLN2. The precise pathogenesis of this disease that includes the relationship between the mutations of citrin gene and a deficiency of hepatic ASS activity remains unclear.
Progressive multifocal leukoencephalopathy (PML) is caused by opportunistic infection of JC virus which belongs to Papovavirus, and presents with progressive demyelinating lesion in the central nervous system. PML was originally reported as a rare complication of hematologic disorders, but later greatly increased in number in association with acquired immunodeficeincy syndrome (AIDS). Original neuropathological features of PML consist of demyelination lacking inflammatory reaction or necrosis, accompanying oligodendroglial nuclear inclusions in the periphery of demyelination. The lesion is preferentially localized to gray-white junction of the cerebral hemisphere and manifests as characteristic demyelinating lesion, called scallopping. Detection of JC virus is essential for the final diagnosis of PML and is achieved via immunohistochemical detection of JC virus with antibodies raised against their components, ultrastructural demonstration of virions characteristic of JC virus, or detection with in-situ hybridization of the genome of JC virus. JC virus can replicate only in oligodendroglial cells, but astrocytes are frequently infected by the virus. The resume of immunological function through therapeutic intervention develops new pathology in PML, exhibiting severe inflammatory reaction with edema and necrosis. This new pathological feature is called immune reconstruction syndrome and clinically presents with severe progression in symptoms of the central nervous system. Nevertheless, treatment of PML is directed for the elimination of the viruses by host immune system. The modification of the above immune reconstruction syndrome is essential for successful outcome of such therapeutic trial.
For five years, a 56-year-old woman had undergone "Shiatsu" (a technique that uses fingers and the palm of the hand to apply pressure to particular sections of the body's surface to correct neck stiffness and body imbalances in order to maintain and promote health). She suddenly developed neck pain, dizziness, dysphagia, and speech and gait disturbances during treatment. A neurological examination detected bradylalia and truncal and mild bilateral limb ataxia of the cerebellar type. Diffusion-weighted brain MRI showed multiple hyperintense signal lesions at the bilateral cerebellar hemisphere in the posterior inferior cerebellar artery territory. Three-dimensional computed tomographic angiography (3D-CTA) revealed irregular stenosis of the intracranial right vertebral artery (string sign). Dissection of the intracranial portion of the vertebral artery owing to trauma is rare. Physicians need to be aware of patients who have acute dissecting infarction after long periods of repeated trivial pressure such as "Shiatsu". 3D-CTA is a very useful diagnostic procedure for arterial dissection.
"Placebo" is Latin for "I shall please". The placebo effect has been widely documented by randomized placebo-controlled drug studies. One of the best examples of placebo effectiveness is that have been shown in clinical trials of anti-parkinsonian drugs. The placebo effect is observable not only in drug trials but also with deep brain stimulation. Recent advances in research on the placebo effect in Parkinson's disease (PD) have suggested that motor symptoms of PD can be essentially improved by placebo. A recent study using positron emission tomography (PET) with raclopride demonstrated that release of endogeneous dopamine in the dorsal striatum occurs in placebo-responsive patients with PD. This suggests that placebo-induced expectation of clinical improvement may activate endogenous dopamine in the striatum, and that placebo effectiveness is thus achieved by endogenous dopamine supplementation. Indeed, decreased neuronal activities in the subthalamic nucleus (STN), that were recorded during surgery to implant deep brain stimulation electrodes, correlated well with placebo-induced clinical improvement in patients with PD. Although the detailed pathophysiological mechanism underlying the placebo effects remains uncertain, theoretically, the placebo effect has generally been explained by two different mechanisms: one is conditioning theory (pavlovian conditioning), and the other is cognitive theory (expectation of clinical improvement). Although both mechanisms may contribute to placebo effects, the placebo effect in PD may be attributed more to cognitive mechanisms such as expectation of improvement, because the placebo effect can be obtained in de novo PD patients. There have been accumulating findings that suggest a functional relationship between dopamine and the expectation of clinical improvement (reward). Further basic studies are required to clarify the complex link between dopamine and the reward system, but such findings will contribute to a better understanding of the pathophysiological mechanism underlying the placebo effect in PD.
The authors herein report a case of a ruptured dissection of the superior cerebellar artery (SCA). A 68-year-old man presented with symptons of sudden headache and nausea. The CT scan revealed the presence of both a subarachnoid hemorrhage (SAH) and acute hydrocephalus. The left vertebral angiogram showed an fusiform dilatation in the cerebellomesencephalic segment of the left SCA. Endovascular embolization of the aneurysm and SCA was successfully performed using Guglielmi detachable coils (GDCs). No delayed ischemic deficits were observed after the treatment. A dissection of the distal segment of the SCA is a very rare occurrence. We believe endovascular embolization using GDCs to be an effective and less invasive therapy for the treatment of an SCA dissection with SAH.
Visual experience depends critically on visual attention, which selects a particular aspect of a visual display. Recent clinical, neuroimaging, and animal studies revealed that visual attention was divided into active and passive or top-down and bottom-up attention. Although these dichotomies are clear-cut in definition, visual attention could be modulated by many factors. Detailed observation of brain-injured patients provides with evidence for dynamic and fine control of visual attention. We observed patients with dorsal simultanagnosia and that with callosal disconnection syndrome. Patients with dorsal simultanagnosia demonstrated that extent of visual attention was dynamically changed depending on the level of visual processing. Despite the ability to read a kanji character and to describe its components correctly, a patient could not notice a component that he had just written and could not assemble individual components to make up a correct kanji character. He could point to an overlapping area of two figures. But once he started to color the overlapping area, he missed the margin of the area and colored much larger area. Another patient with dorsal simultanagnosia missed borderlines between columns of a newspaper and read letters continuously across columns. In contrast, he could point to lines between figures or meaningless patterns easily. These findings indicated that visual attention was directed automatically to meaningful characters. A patients with callosal disconnection syndrome demonstrated left unilateral spatial neglect only when he used his right hand to draw figures. Right hand movement, controlled by the left hemisphere, elicited visual attention to the right hemispace, resulting in the left unilateral spatial neglect. Thus visual attention is not simply top-down or bottom up, but is implicitly affected by the visual recognition as well as motor component of the task.
In recent years, population of elder people has increased in Japan, following augmentation of the number of people with dementia in Japan. Then it is important to detect cognitive impairment in early stage for adequate treatment, care and prevention. We studied 135 subjects, 49 patients with Alzheimer's disease (AD) and 86 healthy controls using Telephone Interview for Cognitive Status (TICS), and developing Japanese version of the TICS (TICS-J). The sensitivity and the specificity of the TICS-J to differentiate AD patients from healthy controls was 98.0% and 90.7%, respectively. Pearson's correlation coefficiency between the TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p < 0.001). On the receiver operating curves, the area under the curve for the TICS-J was 98.7% (95% CI: 97.5%-100%). These results indicate that TICS-J is sensitive and specific instrument for differentiating AD patients from healthy controls.
JC virus (JCV) is a causative agent of progressive multifocal leukoencephalopathy and belongs to Polvomavirus. In this article we describe our recent research relating to this virus. First, JCV's major capsid protein VP1 possesses a nuclear localization signal (NLS) and has the ability to construct a virus-like particle (VLP). We have investigated the mechanism of nuclear entry of JCV using VLP, and clarified the role of NLS. In vitro transport assay revealed that wild type VLP (wtVLP), but not ANLSVLP, entered the nuclei of cells. The nuclear transport of wtVLP was dependent on the addition of importins alpha and beta and was prevented by antibodies to nuclear pore complex (NPC). These results suggested that JCV VLP binds to cellular importins via the NLS of VP1 and is transported into the nucleus through the NPC. Second, a yeast two-hybrid screen of a human brain cDNA library demonstrated that the fasciculation and elongation protein zeta 1 (FEZ1) and the heterochromatin protein 1alpha (HP1alpha) are proteins that interacted with JCV agnoprotein (Agno). In vitro binding assay showed that Agno interacts directly with FEZ1 and HP1alpha. We have also shown that Agno induces the dissociation of FEZ1 from microtubules and dissociates the interaction between HP1alpha and lamin B receptor. We have demonstrated that interaction between Agno and these host proteins inhibited nuclear egress of JCV. Third, in order to inhibit JCV infection in infected cells, we synthesized siRNA which is specific for JCV Agno. Immunoblotting and immunocytochemical analysis demonstrated that expression levels of agnoprotein and VP1 were significantly inhibited by specific siRNA. In addition, levels of viral mRNAs and viral production were decreased in the cells transfected with Agno siRNA. Furthermore, viral production of cell treated with Agno siRNA was significantly inhibited. These results indicate that post-infection treatment with siRNAs, that targets JCV Agno suppresses virus production in JCV infected cells. Thus, siRNA directed against JCV encoding genes may provide a useful tool for suppression of JCV infection.
The patients with cardioembolic stroke sometimes suffer from severe neurological deficit and from recurrent strokes. Since atrial fibrillation, especially non-valvular atrial fibrillation (NVAF) is associated with over half of the cardioembolic strokes, the prevention of cardioembolic stroke in patients with NVAF is important. There have been some reports about how to prevent stroke. They have indicated that the best medication for preventing from stroke was anticoagulation by warfarin. Therefore, the guidelines recommended the patients with NVAF to take warfarin. In case with the older patients under 70 years, prothrombin international normalized ratio (PT-INR) should be kept from 2.0 to 3.0. On the other hand, if the patients with NVAF are over 70 years, PT-INR has to be controlled from 1.6 to 2.6. Before extraction of a tooth, anticoagulation should not be call off.
Several neuropsychological studies have reported dissociation between motion vision and object vision. One patient with motion blindness had a bilateral MT/V5 lesion and could see objects, but could not see the motion of the objects (Zihl et al, 1983). By contrast, some blindsight patients with primary visual cortex lesions cannot see objects but can see their movement (e.g. Riddoch, 1917). These results imply that movement vision and form vision rely on independent mechanisms. However one patient with motion blindness had controversial symptoms concerning motion vision. She could not perceive the movement of objects, although she could walk without colliding with obstacles and could catch incoming objects. It has also been reported that patients with a bilateral parietal lesion had well-preserved primary motion vision, but had problems walking and catching a ball (Vaina, 1998). Therefore, motion for vision and motion for action might have independent mechanisms. Such dissociation has also been noted in patients with Bálint syndrome. Some patients behave like a blind person but can walk and catch a ball, while other patients bump into obstacles while walking. These results indicate that the neural bases of motion vision are distinct from those of form vision and that there are subdivisions of motion vision.
We review recent researches in neural mechanisms of facial recognition in the light of three aspects: facial discrimination and identification, recognition of facial expressions, and face perception in itself. First, it has been demonstrated that the fusiform gyrus has a main role of facial discrimination and identification. However, whether the FFA (fusiform face area) is really a special area for facial processing or not is controversial; some researchers insist that the FFA is related to 'becoming an expert' for some kinds of visual objects, including faces. Neural mechanisms of prosopagnosia would be deeply concerned to this issue. Second, the amygdala seems to be very concerned to recognition of facial expressions, especially fear. The amygdala, connected with the superior temporal sulcus and the orbitofrontal cortex, appears to operate the cortical function. The amygdala and the superior temporal sulcus are related to gaze recognition, which explains why a patient with bilateral amygdala damage could not recognize only a fear expression; the information from eyes is necessary for fear recognition. Finally, even a newborn infant can recognize a face as a face, which is congruent with the innate hypothesis of facial recognition. Some researchers speculate that the neural basis of such face perception is the subcortical network, comprised of the amygdala, the superior colliculus, and the pulvinar. This network would relate to covert recognition that prosopagnosic patients have.
It was previously reported that Mato cells (Mato's fluorescent granular perithelial cells) were frequently localized in the bifurcating areas of cerebral arterioles and occasionally, collagen fibers appeared close to Mato cells of aged rats. It has also been established that Mato cells were scavenger cells in the cerebral tissue and provided with MHC-class II antigen. The present paper deals with the relationship between the distribution of collagen fibers and Mato cells in the bifurcating area of cerebral arterioles. 6 Wistar rats (3 rats aged 4 months and 3 rats aged 16 months) were employed for this electron microscopical study. They were perfused with the mixture of paraform-glutaraldehyde solution, and cerebral cortices were excised and fixed with 1% osmic solution and embedded in Epon 812. In order to observe the bifurcating area of cerebral arterioles, serial semithin sections cutting with the diamond knife were stained with toluidine blue, and checked under the light microscope. After obtaining available regions, serial thin sections were stained with uranyl acetate and lead nitrate, and observed with Hitach H7600 electron microscope. In order to survey the distribution of collagen fibers, 2 groups of the specimens of 4 months old (2 rats) and 5 groups of specimens of 16 months old rats (2 rats) were prepared. Each group consisted of serial 10 thin sections. Other rats of young and aged were used for complementary use. From the observation, it is confirmed that in the cerebral arteriole, collagen fibers are localized only in the interstices around Mato cells, and the fibers appear in a small quantity in the rats aged 4 months, while a certain amounts of the fibers are arranged sporadically in the rats aged 16 months. However, no collagen fibers can be detected in the subendothelial space and in the interstices among smooth muscle cells of cerebral arteriole. If Mato cells lack in some regions of cerebral arterioles, collagen fibers cannot be recognized. The following is also to be stressed that no fibroblastoid cells do appear in any serial sections of cerebral arterioles. From these findings, it seems possible that Mato cells play a principal role in the formation of collagen fibers in the cerebral arterioles, and associate with the sclerosis of cerebral arterioles.
We reported double-dissociation between the visual processing of the edges and the surfaces of objects. Patients with lateral occipital damage showed selective impairment in the perception of edges whereas those with medial ventral occipital damage showed selective impairment in the perception of the 3D structure of the surface. Patients with medial ventral occipital damage also exhibited impaired perception of color, which is also a surface property. Those results were consistent with those from neuroimaging studies. Taken together, those studies suggest that objects may be processed in two separate pathways in the ventral occipital cortex: the edges of objects are processed in the lateral pathway and the surface of objects are processed in the medial pathway. Both edges and surfaces play important roles in object recognition, and both types of perception should be evaluated in patients with visual agnosia.
