Role of PIN1 on in vivo periodontal tissue and in vitro cells.

BACKGROUND: Although expression of peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) was reported in bone tissue, the precise role of PIN1 in periodontal tissue and cells remain unclear. MATERIAL & METHODS: To elucidate the roles of PIN1 in periodontal tissue, its expression in periodontal tissue and cells, and effects on in vitro 4 osteoblast differentiation and the underlying signaling mechanisms were evaluated. RESULTS: PIN1 was expressed in mouse periodontal tissues including periodontal ligament cells (PDLCs), cementoblasts and osteoblasts at the developing root formation stage (postnatal, PN14) and functional stage of tooth (PN28). Treatment of PIN1 inhibitor juglone, and gene silencing by RNA interference promoted osteoblast differentiation in PDLCs and cementoblasts, whereas the overexpression of PIN1 inhibited. Moreover, osteogenic medium-induced activation of AMPK, mTOR, Akt, ERK, p38 and NF-jB pathways were enhanced by PIN1 siRNA, but attenuated by PIN1 overexpression. Runx2 expressions were induced by PIN1 siRNA, but downregulated by PIN1 overexpression. CONCLUSION: In summary, this study is the first to demonstrate that PIN1 is expressed in developing periodontal tissue, and in vitro PDLCs and cementoblasts. PIN1 inhibition stimulates osteoblast differentiation, and thus may play an important role in periodontal regeneration.

Role of resistin in the inflammatory response induced by nicotine plus lipopolysaccharide in human periodontal ligament cells in vitro.

BACKGROUND AND OBJECTIVE: Resistin was recently reported to play a role in inflammation-related diseases such as arthritis. However, the precise role of resistin in chronic inflammatory diseases, such as periodontal disease, remains unclear. The aim of this study was to investigate the combined effects of nicotine and lipopolysaccharide (LPS) on the expression of resistin and to assess whether resistin expression influences the levels of inflammatory cytokines, extracellular matrix (ECM) molecules and MMPs in human periodontal ligament cells (PDLCs) stimulated with both nicotine and LPS. MATERIAL AND METHODS: PDLCs were pretreated with isoproterenol or resistin-specific small interfering RNA (siRNA), stimulated with LPS plus nicotine for 24 h, and then monitored for the production of inflammatory mediators. The concentrations of prostaglandin E2 (PGE2) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method, respectively. RT-PCR and western blot analysis were used to measure the levels of mRNA and protein, respectively. Western blot analysis was also used to assess the activation of various signal-transduction pathways. RESULTS: Treatment with nicotine plus LPS up-regulated the expression of resistin mRNA and the production of resistin protein in PDLCs in a time- and concentration-dependent manner. Isoproterenol-mediated interference with the function of resistin, or siRNA-mediated knockdown of resistin expression, markedly attenuated the LPS plus nicotine-mediated stimulation of PGE2 and NO production, the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase proteins and the expression of proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and IL-12] and MMPs (MMP-1, MMP-2 and MMP-9); however, these treatments restored the expression of ECM molecules. Furthermore, pretreatment with isoproterenol or resistin-specific siRNA blocked nicotine plus LPS-induced activation of phosphoinositide-3-kinase, glycogen synthase kinase-3 beta, ß-catenin, p38, ERK, JNK and nuclear factor-κB. CONCLUSION: This is the first study to show that the inhibition of resistin, by either a pharmacological or a genetic silencing approach, has anti-inflammatory effects. These effects include decreased levels of inflammatory cytokines and the prevention of ECM breakdown in a nicotine plus LPS-stimulated PDLC model.

The role of external defects in chemical sensing of graphene field-effect transistors.

A fundamental understanding of chemical sensing mechanisms in graphene-based chemical field-effect transistors (chemFETs) is essential for the development of next generation chemical sensors. Here we explore the hidden sensing modalities responsible for tailoring the gas detection ability of pristine graphene sensors by exposing graphene chemFETs to electron donor and acceptor trace gas vapors. We uncover that the sensitivity (in terms of modulation in electrical conductivity) of pristine graphene chemFETs is not necessarily intrinsic to graphene, but rather it is facilitated by external defects in the insulating substrate, which can modulate the electronic properties of graphene. We disclose a mixing effect caused by partial overlap of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of adsorbed gas molecules to explain graphene's ability to detect adsorbed molecules. Our results open a new design space, suggesting that control of external defects in supporting substrates can lead to tunable graphene chemical sensors, which could be developed without compromising the intrinsic electrical and structural properties of graphene.

Two-step forecast of geomagnetic storm using coronal mass ejection and solar wind condition.

To forecast geomagnetic storms, we had examined initially observed parameters of coronal mass ejections (CMEs) and introduced an empirical storm forecast model in a previous study. Now we suggest a two-step forecast considering not only CME parameters observed in the solar vicinity but also solar wind conditions near Earth to improve the forecast capability. We consider the empirical solar wind criteria derived in this study (Bz ≤ -5 nT or Ey ≥ 3 mV/m for t≥ 2 h for moderate storms with minimum Dst less than -50 nT) and a Dst model developed by Temerin and Li (2002, 2006) (TL model). Using 55 CME-Dst pairs during 1997 to 2003, our solar wind criteria produce slightly better forecasts for 31 storm events (90%) than the forecasts based on the TL model (87%). However, the latter produces better forecasts for 24 nonstorm events (88%), while the former correctly forecasts only 71% of them. We then performed the two-step forecast. The results are as follows: (i) for 15 events that are incorrectly forecasted using CME parameters, 12 cases (80%) can be properly predicted based on solar wind conditions; (ii) if we forecast a storm when both CME and solar wind conditions are satisfied (∩), the critical success index becomes higher than that from the forecast using CME parameters alone, however, only 25 storm events (81%) are correctly forecasted; and (iii) if we forecast a storm when either set of these conditions is satisfied (∪), all geomagnetic storms are correctly forecasted.

Where has the tumor gone? The characteristics of cases of negative pathologic diagnosis after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Discrepancies can occur between the histopathological findings from forceps biopsy and endoscopic mucosal resection (EMR), and occasionally in embarrassing cases tumorous tissue is not found at EMR. The aim of the present study was to evaluate the clinical, endoscopic, and histological features of gastric tumors in patients with pathololgically negative findings at EMR. PATIENTS AND METHODS: We retrospectively reviewed data from all patients with gastric tumor treated with EMR or endoscopic submucosal dissection (ESD) between August 1999 and April 2007 at our institution, and enrolled into the study patients with no tumor tissue found at mucosal resection. Their biopsy and EMR specimen slides were reviewed by a single pathologist. Patient characteristics, including demographic and clinical features, and the endoscopic appearance of mucosal lesions were evaluated. RESULTS: Out of 633 patients treated with EMR or ESD, 20 patients (3.2 %) were included. The mean +/- SD maximal dimension of the mucosal lesions was 6.40 +/- 2.19 mm (range 3 - 10). Mean number of forceps biopsy fragments was 3.80 +/- 1.96 and mean sampling ratio was 2.08 +/- 1.07 mm/fragment. Before resection, histological findings from forceps biopsy were: 13 low grade dysplasias (65.0 %), 2 high grade dysplasias (10.0 %), and 5 intramucosal carcinomas (25.0 %). CONCLUSIONS: In the case of pathologically negative findings at EMR, tumors might have been small enough to have been removed by the previous forceps biopsy. However, the possibility of sampling error or of a different location should be considered. Furthermore, appropriate communication between endoscopists and pathologists is essential.

The effect of Zn(2+) on human brain creatine kinase: unfolding and aggregation studies.

We studied the effects of Zn(2+) on human brain creatine kinase (HBCK). Zn(2+) inactivated the activity of HBCK in a dose dependent manner (IC50 = 0.06 mM). The time-interval kinetic studies showed that the inactivation followed first-order reaction kinetics with a biphasic process. The spectroflurorimetry results showed that Zn(2+) conspicuously induced the tertiary structural change of HBCK with exposure of its hydrophobic surfaces. On the contrary, the secondary structure was slightly changed by Zn(2+). We also found that HBCK aggregation was induced by Zn(2+). This aggregation was dependent on the temperature and the enzyme and Zn(2+) concentrations. Some added osmolytes such as glycine and proline were able to successfully block CK aggregation and fully recover the conformation and activity of HBCK. Our study provides important insight into the unfavorable effect of Zn(2+) on HBCK and it increases the understanding of the Zn(2+) ligand-binding mechanism to the metabolic brain enzyme.

Factors related to lymph node metastasis and the feasibility of endoscopic mucosal resection for treating poorly differentiated adenocarcinoma of the stomach.

BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) is currently not accepted as an alternative treatment to surgery in early gastric cancer (EGC) of the undifferentiated histologic type. The present retrospective analysis examined the correlation of various histologic factors with the presence of lymph node metastasis (LNM). PATIENTS AND METHODS: A retrospective analysis on 234 patients with poorly differentiated EGC who underwent radical gastrectomy with D2 lymph node dissection was undertaken. Several clinicopathologic factors were investigated to identify predictive factors for LNM: age, sex, type of operation, tumor location, tumor size, gross type, ulceration, lymphatic invasion, and depth of invasion. RESULTS: Of the 234 lesions with poorly differentiated EGC, half (n = 116) already showed submucosal invasion in the resection specimen; 25.9 % of those (30/116) were limited to the upper third (SM1). Of the lesions confined to the mucosa, LNM was found in 3.4 % (4/118). With minor submucosal infiltration (SM1), the LNM rate was lower (0/30) in our patient population. Only with SM2/3 infiltration did the LNM rate sharply rise to around 30 %. The cut-off for submucosal infiltration depth was 500 microm (0/32 LNM), above which LNM rates were substantial (31.2 %; 24/77). There was limited correlation between the SM1-3 classification and actual measurement of submucosal infiltration depth. In a multivariate analysis, tumor size ( P = 0.033), depth of invasion ( P = 0.004), and lymphatic invasion ( P < 0.001) were associated with LNM. CONCLUSION: Poorly differentiated EGC confined to the mucosa or with minimal submucosal infiltration (

Effects of complex decongestive physiotherapy on the oedema and the quality of life of lower unilateral lymphoedema following treatment for gynecological cancer.

There is increasing interest in the health-related quality of life (QOL) of patients with chronic lymphoedema. The purpose of the present study was to ascertain whether or not complex decongestive physiotherapy (CDP) for 57 gynecological cancer patients with unilateral lymphedema results in a measurable change in the oedema and QOL, and % excess volume correlated with change in QOL. % excess volume was significantly (P<0.05) decreased after CDP. The QOL scores were significantly (P<0.05) higher than the scores at baseline, indicating an improvement in the QOL. The change in % excess volume was associated with a change in physical functioning, social functioning, role-physical, bodily pain and general health at baseline and 1 month (P<0.05). This study suggests that significant improvements are made in the QOL of gynecological cancer patients with unilateral lymphoedema after CDP, which is necessarily correlated with limb reduction.

Prophylactic fresh frozen plasma may prevent development of hepatic VOD after stem cell transplantation via ADAMTS13-mediated restoration of von Willebrand factor plasma levels.

We initially conducted a multicenter, randomized trial (n=43), and subsequently a questionnaire study (n=209) of participating hospitals, to evaluate whether infused fresh frozen plasma (FFP) could prevent the occurrence of hepatic veno-occlusive disease (VOD) after stem cell transplantation (SCT). Forty-three patients were divided into two groups: 23 receiving FFP infusions and 20 not receiving it. VOD developed in three patients not receiving FFP. Plasma von Willebrand factor (VWF) antigen levels were lower at days 0, 7 and 28 after SCT in patients receiving FFP than in those not receiving it, whereas plasma ADAMTS13 activity (ADAMTS13:AC) did not differ between them. Plasma VWF multimer (VWFM) was demonstrated to be defective in the high approximately intermediate VWFM during the early post-SCT phase, but there was a significant increase in high VWFM just before VOD onset. This suggests that a relative enzyme-to-substrate (ADAMTS13/high-VWFM) imbalance is involved in the pathogenesis of VOD. To strengthen this hypothesis, the incidence of VOD was apparently lower in patients receiving FFP infusions than in those not receiving it (0/23 vs 3/20) in the randomized trial. Further, the results combined with the subsequent questionnaire study (0/36 vs 11/173) clearly showed the incidence to be statistically significant (0/59 vs 14/193, P=0.033).

Post-annealing effect on the electronic structure of Mn atoms in Ga(1-x)Mn(x)As probed by resonant inelastic x-ray scattering.

The electronic structure of as-grown and post-annealed Ga(1-x)Mn(x)As epilayers (x≈0.055) has been investigated using resonant inelastic x-ray scattering. Mn L2,3 x-ray emission spectra show that the integral intensity ratio of Mn L2 to L3 emission lines increases with annealing temperature and comes close to that of manganese oxide. The oxygen K-emission/absorption spectra of post-annealed Ga0.945Mn0.055As show 1.5-3.0 times higher degree of oxidation on the film surface than that of the as-grown sample. These experimental findings are attributed to the diffusion of Mn impurity atoms from interstitial positions in the GaAs host lattice to the surface where they are passivated by oxygen.

Unfolding and inactivation of fatty acid synthase from chicken liver during urea denaturation.

The inactivation and conformational changes of the multifunctional fatty acid synthase (acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing and thioester-hydrolyzing), EC 2.3.1.85) from chicken liver have been studied in urea solution. The results show that complete inactivation of the fatty acid synthase occurs before obvious conformational changes with regard to the overall, beta-ketoacyl reduction and acetoacetyl-CoA reduction reactions. Significant conformational changes indicated by the changes of the intrinsic fluorescence emission and the circular dichroism spectra occurred at higher urea concentrations. The kinetic rate constants for the two phase inactivation and unfolding reactions were measured and semilogarithmic plots of the activity versus time gave curves which could be resolved into two straight lines, indicating that both the inactivation and unfolding processes consisted of fast and slow phases as a first-order reaction. The results from Lineweaver-Burk plots indicated that urea is a competitive inhibitor for acetyl-CoA and malonyl-CoA, with K(m) increasing with increasing urea concentrations. However, urea is a noncompetitive inhibitor for NADPH, the substrate of the overall reaction and beta-ketoacyl reduction reaction, and acetylacetate, the substrate of the beta-ketoacyl reduction reaction. Activation by low concentrations of urea was observed although this activation was only temporarily induced in an early stage of inactivation. The aggregation phenomenon of the fatty acid synthase in a certain concentration range of urea (3-4 M) was also observed during unfolding. This result shows that this multifunctional enzyme unfolds with competition with misfolding in the folding pathway. Comparison of inactivation and conformational changes of the enzyme as well as aggregation imply that unfolding intermediates may exist during urea denaturation. The possible unfolding pathway of fatty acid synthase is also discussed in this paper.

Reactivation and refolding of rabbit muscle creatine kinase denatured in 2,2,2-trifluoroethanol solutions.

The unfolding and refolding of creatine kinase (ATP:creatine N-phosphotransferase (CK), EC 2.7.3.2) during denaturation and reactivation by trifluoroethanol (TFE) have been studied. Significant aggregation was observed when CK was denatured at TFE concentrations between 10% and 40% (v/v). 50% TFE (v/v) was used to study the denaturation and unfolding of CK. The activity loss of CK was a very quick process, as was the marked conformational changes during denaturation followed by fluorescence emission spectra and far-ultraviolet CD spectra. DTNB modification and size exclusion chromatography were used to find that CK dissociated and was in its monomer state after denaturation with 50% TFE. Reactivation and refolding were observed after 80-fold dilution of the denatured CK into 0.05 M Tris-HCl buffer, pH 8.0. The denatured CK recovered about 38% activity following a two phase course (k(1)=4.82+/-0.41x10(-3) s(-1), k(2)=0.60+/-0.01x10(-3) s(-1)). Intrinsic fluorescence maximum intensity changes showed that the refolding process also followed biphasic kinetics (k(1)=4.34+/-0.27x10(-3) s(-1), k(2)=0.76+/-0.02x10(-3) s(-1)) after dilution into the proper solutions. The far-ultraviolet CD spectra ellipticity changes at 222 nm during the refolding process also showed a two phase course (k(1)=4.50+/-0.07x10(-3) s(-1), k(2)=1.13+/-0.05x10(-3) s(-1)). Our results suggest that TFE can be used as a reversible denaturant like urea and GuHCl. The 50% TFE induced CK denaturation state, which was referred to as the 'TFE state', and the partially refolded CK are compared with the molten globule state. The aggregation caused by TFE during denaturation is also discussed in this paper.

Smoke-like echo in the left atrial cavity in mitral valve disease: its features and significance.

In some patients with mitral stenosis, a smoke-like echo is observed in the left atrial cavity. The present study in 116 consecutive patients with rheumatic mitral valve disease investigated the echocardiographic features and clinical significance of this echo. The smoke-like echo is characterized by the following echocardiographic features: 1) it is composed of numerous microechoes; 2) it curls up slowly in the enlarged left atrial cavity; and 3) it vanishes as soon as it pours into the ventricular cavity. Hemostasis in the left atrial cavity was considered to be an important underlying condition for development of the echo. Hemorheologic conditions indicated that the shear rate of blood flow in the left atrial cavity was calculated to be low enough for the development of red blood cell aggregation. These conditions suggest that the source of the smoke-like echo might be aggregated cells due to hemostasis in the left atrial cavity. Left atrial thrombi were detected in many patients who had this echo in the left atrial cavity. Although it has not been conclusively determined that the presence of the smoke-like echo is a necessary condition for thrombus formation, this echo appears to be closely related to thrombus formation in the left atrial cavity. It is concluded that the presence of this echo indicates severe left atrial hemostasis and is a warning for thrombus formation.

Diagnosis of mitral valve perforation by real-time two-dimensional Doppler flow imaging technique.

It has been difficult to diagnose mitral regurgitation due to valve perforation using either noninvasive or invasive methods, differentiating it from that resulting from incomplete coaptation of the mitral valve. This report describes three patients with infective endocarditis and mitral valve perforation, which was definitively diagnosed by the real-time two-dimensional Doppler flow imaging technique. In these three patients, B-mode echocardiography demonstrated an echo interruption on the anterior mitral leaflet. However, it was not certain whether this interruption was simply an echo dropout or indicated an interruption of the valve tissue. Doppler flow imaging then demonstrated unusual flow in the vicinity of the echo interruption, which appeared to flow from the left ventricular cavity into the left atrial cavity across the midportion of the anterior mitral valve leaflet during systole and in the opposite direction during diastole. This was interpreted as mitral valve perforation. In general, Doppler flow imaging may play a complementary role with B-mode echocardiography in cardiac diagnosis.

Doppler echocardiographic features of ventricular septal rupture in myocardial infarction.

Doppler echocardiography was used to evaluate the features of interventricular septal rupture in six patients with acute myocardial infarction and to substantiate the hemodynamic data and morphologic findings at surgery or autopsy. Although echocardiographic visualization of the septal rupture was obtained in only two of the six patients, unusual Doppler flow signals were detected in the apical portion of the right ventricle in all six patients. Five patients had unusual flow signals during both systole and diastole; one had such signals only during systole. The location of these unusual flow signals coincided with the site of septal rupture confirmed at surgery or autopsy. The pattern of the flow signals in one cardiac cycle was very similar to that of the pressure difference between the left and right ventricular cavities. These findings indicate that the unusual flow signals represent the left to right shunt flows resulting from septal rupture. In conclusion, Doppler echocardiography may be a very useful tool for diagnosing interventricular septal rupture easily and noninvasively in patients with acute myocardial infarction.

Unrelated donor bone marrow transplantation for 100 pediatric patients: a single institute's experience.

In all, 100 unrelated donor bone marrow transplantations (UD-BMT) were performed in our institute between October 1993 and January 2003. Of 93 evaluable patients, 73 patients had hematological malignancy, 13 had nonmalignancy and seven had lymphoproliferative disease. The estimated 9-year event-free survival (EFS) rate was 57.1+/-5.5% in all patients. In the following analyses of the patients with hematological malignancy, the standard group had significantly better EFS than the high-risk group (61.5+/-7.0 vs 35.6+/-9.7%, P=0.02), and the EFS rate of the tacrolimus (FK-506)+methotrexate (MTX)+/-methylprednisolone prophylactic group for graft-versus-host disease was superior to that of the FK-506 without MTX group (75.7+/-8.0 vs 55.8+/-7.6%, P=0.02). When we compared the EFS rates of the FK506+MTX+/-methylprednisolone (mPSL) group and the HLA-matched related donor BMT group in our institute, these were almost similar (75.7+/-8.1 vs 68.4+/-9.3%). Therefore, UD-BMT using FK-506+MTX+/-mPSL is a safe and useful method for children with hematological malignancy who require allogeneic BMT.

Chaperone-like activity of peptidyl-prolyl cis-trans isomerase during creatine kinase refolding.

Porcine kidney 18 kD peptidyl-prolyl cis-trans isomerase (PPIase) belongs to the cyclophilin family that is inhibited by the immunosuppressive drug cyclosporin A. The chaperone activity of PPIase was studied using inactive, active, and alkylated PPIase during rabbit muscle creatine kinase (CK) refolding. The results showed that low concentration inactive or active PPIase was able to improve the refolding yields, while high concentration PPIase decreased the CK reactivation yields. Aggregation was inhibited by inactive or active PPIase, and completely suppressed at 32 or 80 times the CK concentration (2.7 microM). However, alkylated PPIase was not able to prevent CK aggregation. In addition, the ability of inactive PPIase to affect CK reactivation and prevent CK aggregation was weaker than that of active PPIase. These results indicate that PPIase interacted with the early folding intermediates of CK, thus preventing their aggregation in a concentration-dependent manner. PPIase exhibited chaperone-like activity during CK refolding. The results also suggest that the isomerase activity of PPIase was independent of the chaperone activity, and that the proper molar ratio was important for the chaperone activity of PPIase. The cysteine residues of PPIase may be a peptide binding site, and may be an essential group for the chaperone function.

Aggregation of creatine kinase during refolding and chaperonin-mediated folding of creatine kinase.

The course of refolding and reactivation of urea-denatured creatine kinase (ATP; creatine N-phosphotransferase, EC 2.7.3.2) has been studied in the absence and presence of molecular chaperonin GroEL. The enzyme was denatured in Tris--HCl buffer containing 6 M urea for 1 h. In the refolding studies, the denatured enzyme was diluted 60-fold into the same buffer containing GroEL or not for activity, turbidity, fluorescence measurements and polyacrylamide gel electrophoresis. The results show that the reactivation process is dependent of creatine kinase concentration in the concentration range 2.5--4 microM. The levels of activity recovery decrease with increasing enzyme concentration because of the formation of wrong aggregates. The molecular chaperonin GroEL can bind the refolding intermediate of creatine kinase and thus prevent the formation of wrong aggregates. This intermediate is an inactive dimeric form that is in a conformation resembling the 'molten globule' state.

Ictal cognitive assessment of partial seizures and pseudoseizures.

BACKGROUND: Previous studies suggest that responsiveness is impaired during complex partial seizures (CPS) and pseudoseizures (PS); however, to our knowledge, there has been no systematic comparison using both response and memory testing. OBJECTIVE: To compare CPS with PS using ictal cognitive assessment (ICA) of responsiveness and memory. PATIENTS AND METHODS: We used a nonautomated method of ICA by bedside observers, consisting of family members and staff, during video electroencephalographic monitoring to test responsiveness and memory during the ictal phase in 245 events. We assessed the adequacy of testing and compared the testing results in 31 patients during CPS and 13 patients during PS. RESULTS: The ictal presentation of a command was successful in 58% of the events. The ictal presentation of at least 2 memory items with testing for recall after orientation was adequate in 57% of events. Impaired responsiveness was shown during both CPS and PS. However, some response was detected during 48% of PS compared with 18% of CPS (P<.01). Memory items were recalled during 63% of PS but during only 4% of CPS (P<.001). The International Classification of Epileptic Seizures remained useful, but in 11 events (8%), distinguishing complex from simple partial seizures was difficult. Recall of various types of stimuli (aural-verbal vs visual-pictorial) during ICA did not correlate with the side or location of the seizure focus, but this may have been confounded by the rarity of any memory recall during CPS. CONCLUSIONS: Ictal cognitive assessment by bedside observers is practical and provides the interaction necessary for properly classifying seizures; ICA, especially memory, may help to distinguish CPS from PS.

Pathophysiology of altered consciousness during seizures: Subtraction SPECT study.

BACKGROUND: The mechanisms underlying altered consciousness during seizures are poorly understood. Previous clinicopathologic studies suggest a role for the thalamus and upper brainstem in consciousness mechanisms. OBJECTIVE: To examine blood flow changes associated with altered consciousness during seizures. METHODS: Seventy-one patients with epilepsy who underwent video-EEG monitoring and ictal/interictal SPECT were studied. Patients were divided into three groups depending on their conscious state during seizures: 1) complete impairment of consciousness (CI), 2) no impairment of consciousness (NI), or 3) uncertain impairment of consciousness (UI). The distribution of blood flow changes during these seizures was assessed by subtraction (ictal - interictal) SPECT co-registered to MRI. Conscious state was assessed in relation to secondary ictal hyperperfusion in subcortical regions (i.e., thalamus and upper brainstem). RESULTS: Impairment of consciousness showed a strong association with secondary hyperperfusion in the thalamic/upper brainstem region (p = 0.01), occurring in 92% (45/49) of CI, 69% (9/13) of UI, and 11% (1/9) of NI. CONCLUSIONS: These findings are consistent with a role for the thalamus and upper brainstem in consciousness mechanisms. The authors suggest that the spread of epileptic discharges or a trans-synaptic activation (diaschisis) of these structures is an important mechanism in the alteration of consciousness during seizures. Variance in the results may be due to differences in timing of radioisotope injection, sensitivity of the subtraction SPECT technique, and the ability to clinically assess the conscious state.