Impulse response function based on multivariate AR model can differentiate focal hemisphere in temporal lobe epilepsy

The purpose of this study is to propose and investigate a new approach for discriminating between focal and non-focal hemispheres in intractable temporal lobe epilepsy, based on applying multivariate time series analysis to the discharge-free background brain activity observed in nocturnal electrocorticogram (ECoG) time series. Five unilateral focal patients and one bilateral focal patient were studied. In order to detect the location of epileptic foci, linear multivariate autoregressive (MAR) models were fitted to the ECoG data; as a new approach for the purpose of summarizing these models in a single relevant parameter, the behavior of the corresponding impulse response functions was studied and described by an attenuation coefficient. In the majority of unilateral focal patients, the averaged attenuation coefficient was found to be almost always significantly larger in the focal hemisphere, as compared to the non-focal hemisphere. Also the amplitude of the fluctuations of the attenuation coefficient was significantly larger in the focal hemisphere. Moreover, in one patient showing a typical regular sleep cycle, the attenuation coefficient in the focal hemisphere tended to be larger during REM sleep and smaller during Non-REM sleep. In the bilateral focal patient, no statistically significant distinction between the hemispheres was found. This study provides encouraging results for new investigations of brain dynamics by multivariate parametric modeling. It opens up the possibility of relating diseases like epilepsy to the properties of inconspicuous background brain dynamics, without the need to record and analyze epileptic seizures or other evidently pathological waveforms.     

Tissue plasminogen activator in primary afferents induces dorsal horn excitability and pain response after peripheral nerve injury

The extracellular protease cascade of plasminogen activators and plasminogen are known to regulate neuronal plasticity and extracellular matrix modification, and to be important factors involved in producing long-term potentiation in the CNS. The purpose of this study is to examine the expression of plasminogen activators in primary afferents and its role in nociceptive pathways after peripheral nerve injury. We found the induction of mRNAs for tissue type plasminogen activator (tPA) and urokinase plasminogen activator (uPA) in the rat dorsal root ganglia following sciatic nerve transection. Immunoreactivity for tPA was increased in laminae I and II of the dorsal horn and, importantly, the increase in proteolytic activity mediated by tPA was observed in the same area. As neither immunoreactivity for uPA nor uPA-mediated proteolysis was observed, we further examined the effects of tPA on dorsal horn excitability and neuropathic pain behaviour. Intrathecal injection of a specific inhibitor of tPA decreased electrical stimulation-induced Fos expression in dorsal horn neurons following axotomy, and also prevented the development of thermal hyperalgesia following partial sciatic nerve ligation. These findings suggest that the increased tPA in the dorsal horn due to mRNA expression in the dorsal root ganglia increases the dorsal horn excitability and has an important role in pain behaviour after peripheral nerve injury. The tPA-mediated hypersensitivity in dorsal horn neurons may be a novel molecular mechanism of neuropathic pain.     

Link between linear hyperintensity objects in cerebral white matter and hypertensive intracerebral hemorrhage

BACKGROUND: We retrospectively studied the relationship between linear hyperintensity objects (LHOs) on T(2)-weighted magnetic resonance images (MRI) in the cerebral white matter and the occurrence of hypertensive intracerebral hemorrhage (HIH). METHODS: Forty-nine hypertensive patients with a fixed imaging condition MRI were classified into three groups: HIH (n = 17), ischemic stroke due to hypertensive vasculopathy (n = 19), and hypertension only (n = 13). After assessing clinical and radiological background information among these groups and the reliability of LHO measurements, polynomial logistic regression analysis was used to identify the factors relating to HIH. RESULTS: HIH had a significantly higher LHO number (p = 0.002) and larger diameter (p = 0.007). The LHO number showed an excellent interrater (kappa = 0.91, 95% CI = 0.87-0.94, SEM = 6.2%) and intrarater reliability (kappa = 0.95, 95% CI= 0.92-0.97, SEM = 4.8%), and was the most significant independent indicator of HIH (OR = 1.29, 95% CI = 1.05-1.60, p = 0.017). The number of microbleeds was an additional indicator (OR = 3.73, 95% CI = 1.10-12.65, p = 0.034). CONCLUSIONS: LHOs are closely linked to HIH. A prospective, longitudinal study is needed to clarify whether LHOs can predict HIH.     

Do olfactory reference syndrome and jiko-shu-kyofu (a subtype of taijin-kyofu) share a common entity?

OBJECTIVE: Olfactory reference syndrome (ORS) in the Western literature is characterized as preoccupation with the idea that the body emits a foul odor. Japanese patients with a feature similar to ORS have long been recognized as jiko-shu-kyofu, which is believed to be a culture-bound syndrome and specific to Japan. The aim of the study was to clarify the relationship between the two separate syndromes that had independently been recognized in culturally different settings. METHOD: The phenomenology and treatment of seven patients with jiko-shu-kyofu were described. A feature of jiko-shu-kyofu was then compared with that of ORS. RESULTS: In our cases, clinical characteristics of jiko-shu-kyofu such as symptomatology, insight, and pharmacotherapy response were found identical to those of ORS except for the onset at relatively younger ages. CONCLUSION: Jiko-shu-kyofu and ORS may share a common clinical entity, hence the former is not a culturally distinctive disorder.     

Deactivation by benzodiazepine of the basal forebrain and amygdala in normal humans during sleep: a placebo-controlled [15O]H2O PET study

OBJECTIVE: The authors' goal was to identify differences in regional brain activity between physiological and benzodiazepine-induced sleep to clarify the brain structures involved in the drug's hypnotic effect. METHOD: Using positron emission tomography, they compared regional cerebral blood flow during non-REM sleep in nine volunteers treated with placebo or triazolam, a short-acting benzodiazepine, in a double-blind, crossover design. RESULTS: Blood flow in the basal forebrain and amygdaloid complexes was lower during non-REM sleep when subjects were given triazolam than when they were given placebo. CONCLUSIONS: The hypnotic effect of the benzodiazepines may be mediated mainly by deactivation of the forebrain control system for wakefulness and also by the anxiolytic effect induced by deactivation of the emotional center.     

Cognitive impairments in Machado-Joseph disease

BACKGROUND: Cognitive function of Machado-Joseph disease (MJD) patients has not been clarified. OBJECTIVES: To determine the characteristics of cognitive dysfunction in MJD patients and to assess the relationship of dysfunction to age at onset, age at examination, disease duration, education, ataxia, depression, anxiety, and CAG repeat length. DESIGN: Case-control study. SETTING: Research-oriented hospitals. PARTICIPANTS: Sixteen genetically confirmed MJD patients able to complete neuropsychological tests and 20 control subjects matched to patients by age and education. MAIN OUTCOME MEASURES: Neuropsychological tests, including general cognition, verbal and visual memory, working memory, visuospatial and constructional ability, language, executive function, depression, and anxiety. RESULTS: Machado-Joseph disease patients scored significantly lower than controls in verbal and visual memory, in visuospatial and constructional tasks, and in phonemic and semantic fluency tasks. None of these impairments correlated with CAG repeat length, age at onset, age at examination, disease duration, or education. Verbal fluency (words named in a category) correlated with the International Cooperative Ataxia Rating Scale score. CONCLUSION: Machado-Joseph disease patients have verbal and visual memory deficits, visuospatial and constructional dysfunction, and verbal fluency deficits, all unrelated to CAG repeat length.     

"Points to consider" regarding safety assessment of biotechnology-derived pharmaceuticals in non-clinical studies (English translation)

Regulatory and industrial scientists collaborated to publish a "points to consider" document regarding the safety assessment of biotechnology-derived pharmaceuticals in non-clinical studies in 2002 (Pharmaceutical Non-clinical Investigation Group, 2002). The collaboration team intended to clarify the interpretation of ICH-S6 guideline and furthermore share recent Japanese practices on this matter. However, the document was written in Japanese. Thus, we share here an English translation of the document so that non-native Japanese correctly understand the contents.     

Dai-kenchu-to raises levels of calcitonin gene-related peptide and substance P in human plasma

Sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptides [calcitonin gene-related peptide (CGRP), substance P, etc.], which play various physiologic roles and are gastroprotective. To determine whether the pharmacologic effects of Dai-kenchu-to (DKCT) on the gastrointestine are due to changes in gastrointestinal mucosa regulatory peptide levels, we examined the effects of the DKCT on the levels of CGRP-like immunoreactive substances (IS) and substance P-IS in plasma taken from five healthy subjects. A single oral administration of DKCT 7.5 g caused significant increases in plasma CGRP-IS at 40 min, and in substance P-IS levels at 20 and 60 min, compared with a placebo group. The present study may indicate that the pharmacologic action of DKCT is closely related to changes in CGRP- and substance P-IS levels.     

3D flash lag illusion

Objective of this research is to study the presence of 3D flash lag illusion created by a moving object that has a motion-in-depth and a flash object. An object consisting of two thin sticks was simulated to approach the subject who observed it with a stereoscope. In the process of approaching, another stick was briefly presented in the middle of the moving sticks. Five human subjects took part in our experiments and all perceived 3D flash lag illusion. The perceived depth created by 3D flash lag illusion was measured by two different psychophysical experiments, by use of a vernier caliper and by a method of nulling with another depth cue. We studied relation between the perceived depth and the presentation distance. The experimental results indicate that the perceived gap by 3D flash lag illusion is independent from the presentation distance.