US and Digital Breast Tomosynthesis in Women with Focal Breast Complaints: Results of the Breast US Trial (BUST).

Background Digital breast tomosynthesis (DBT) followed by targeted US is commonly performed to evaluate women with localized breast complaints. However, the added value of DBT in addition to targeted US is unknown. Omitting DBT may be cost-effective and improve patient comfort but may miss potential breast cancer. Purpose To assess whether an imaging protocol consisting of targeted US alone may be feasible for the diagnostic work-up of women with localized symptoms and to assess the supplemental value of DBT in this reversed setting. Materials and Methods This prospective study enrolled consecutive women aged 30 years or older with focal breast complaints in three hospitals in the Netherlands between September 2017 and June 2019. In all participants, first, targeted US was evaluated, and if needed, biopsy was performed, followed by DBT. The primary outcome was the frequency of breast cancer detected with DBT when US was negative. Secondary outcomes were frequency of cancer detected with DBT elsewhere in the breast and combined overall sensitivity of US plus DBT. The reference standard was 1 year follow-up or histopathologic examination. Results There were 1961 women (mean age ± SD, 47 years ± 12) enrolled. Based on initial US alone, 1587 participants (81%) had normal or benign findings and 1759 (90%) had a definitive accurate diagnosis. In total, 204 breast cancers were detected during initial work-up. The frequency of malignancy was 10% (192 of 1961 participants) with US (US sensitivity, 98.5% [95% CI: 96, 100]; US specificity, 90.8% [95% CI: 89, 92]). DBT depicted three unobserved malignant lesions at the complaint site and 0.41% (eight of 1961 participants) of incidental malignant findings in participants without symptomatic cancer. Conclusion Compared with combined US and DBT, US was accurate as a stand-alone breast imaging modality in the assessment of focal breast complaints. The rate of cancer detection of cancers elsewhere in the breast with DBT is comparable to cancer detection rate of screening mammography. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Newell in this issue.

The value of mammography in women with focal breast complaints in addition to initial targeted ultrasound.

PURPOSE: To determine the added value of mammography in women with focal breast complaints and the utility of initial targeted ultrasound in this setting. METHODS: Women with symptomatic breast disease who were evaluated by breast imaging (mammography/digital breast tomosynthesis and ultrasound) between January 2016 and December 2016 in the Radboud University Medical Centre were included. We retrospectively collected the following data: date of birth, indication of imaging, visibility on mammography/ultrasound, whether biopsy was taken, additional findings, BI-RADS-classification, pathology and follow-up results. RESULTS: A total of 494 women were included (mean age 46.5, range 30 to 93). In 49 women (9.9%), symptomatic breast cancer was diagnosed, all visible during targeted ultrasound. The negative predictive value of targeted ultrasound was very high (99.8%). Additional findings on mammography were significantly more often malignant when the symptomatic lesion was also malignant (3.8% vs 70%, P < 0.05). In only one patient with symptoms caused by a benign finding, an incidental malignancy was detected on mammography outside the area of complaint (detection rate 2.2/1000 examinations). CONCLUSIONS: The contribution of mammography for cancer detection in women with focal breast complaints is very low when targeted ultrasound is performed. Additional findings are most common in patients with symptomatic breast cancer. Our results suggest that initial targeted ultrasound is a more appropriate initial tool for the evaluation of focal breast complaints. Mammography could be performed on indication only.

Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: The fetal brain is vulnerable to severe and sustained hypoxia during and after birth, which can lead to hypoxic-ischemic encephalopathy (HIE). HIE is characterized by clinical and laboratory evidence of acute or subacute brain injury. The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates are not fully understood. In this study, we investigated cytokine profile related to cerebral palsy (CP) with neonatal hypoxic ischemic encephalopathy (HIE) and HIE severity. METHODS: Eligible subjects were HIE newborns with a gestational age between 36 and 42 weeks. We included newborns who was born at our NICU and did not admit to NICU as healthy controls. The study comprised 52 newborns, including 13 with mild to severe HIE and 39 healthy control. Serum cytokine profiles were performed using a LUMINEX cytokine kit (R&D Systems). RESULTS: VEGF, MCP-1, IL-15, IL-12p70, IL-12p40, IL-1Ra, IL-2, IL-6, IL-7, IL-8, IL-10, IFN-γ, G-CSF and eotaxin in the HIE patients were significantly increased compared with the healthy neonates. In the subgroup analysis, IL-6 and G-CSF were significantly increased in CP infants (n = 5) compared with non-CP infants (n = 8). Five and eight HIE patients were classified into the mild HIE and moderate-severe HIE groups, respectively. IL-6, 10, 1Ra, and G-CSF in the moderate-severe HIE group were significantly higher than those in the mild HIE group. CONCLUSION: We demonstrated that higher serum IL-6 and G-CSF at birth in HIE patients were associated with CP and moderate-severe HIE.

Modification of The Paris System for urinary tract washing specimens using diagnostic cytological features.

OBJECTIVE: The Paris System (TPS), which was recently introduced, emphasised the key features of malignant urine cytology: a high nuclear to cytoplasmic ratio, nuclear hyperchromasia, irregular nuclear membranes and coarse chromatin. Although other diagnostic features have been described, the diagnostic significance of such features and their application to TPS have not been fully defined for urinary tract washing specimens. METHODS: A total of 142 cases of urinary tract washing specimens with corresponding surgical pathology samples were examined for the key features of TPS and 13 previously described features. The diagnostic performance of TPS and our proposed modification of TPS was compared with that of the current system. RESULTS: In addition to the key features of TPS, in the present study, high-grade urothelial carcinoma (HGUC) frequently exhibited tumour diathesis, a ragged edge of urothelial cell groups, anisonucleosis, India ink nuclei, apoptotic bodies and pleomorphism. As anisonucleosis and India ink nuclei remained independent predictors of HGUC for the multivariate analysis, they were used to modify TPS. The reporting rate of the atypical urothelial cell (AUC) category decreased from 25.3% in the current system to 14.8% in TPS and 11.3% in our proposed modification of TPS. The sensitivity increased from 59.4% in the current system to 70.8% in TPS and 90.0% in this study. The diagnostic accuracy increased from 0.786 in the current system and 0.754 in TPS to 0.859 in this study. CONCLUSIONS: TPS is a useful diagnostic system for urinary tract washing specimens by decreasing the number of AUC cases and increasing sensitivity. In this study, anisonucleosis and India ink nuclei improved the diagnostic accuracy of HGUC.

Is ultrasound-guided fine-needle aspiration cytology of adequate value in detecting breast cancer patients with three or more positive axillary lymph nodes?

This study evaluated the accuracy of ultrasound-guided fine-needle aspiration cytology of the sonographically most suspicious axillary lymph node (US/FNAC) to select early breast cancer patients with three or more tumour-positive axillary lymph nodes. Between 2004 and 2014, a total of 2130 patients with histologically proven early breast cancer were evaluated and treated in the Noordwest Clinics Alkmaar. US/FNAC was performed preoperatively in all these patients. We analysed the results of US/FNAC retrospectively. Pathological axillary node status (sentinel node biopsy and/or axillary lymph node dissection) was used as reference standard. A total of 634 (29.8 %) of 2130 patients had axillary lymph node metastases on final histology. 248 node positive patients (11.6 %) had three or more positive lymph nodes. The accuracy of US/FNAC to detect three or more positive lymph nodes was 89.8 %, sensitivity was 44.8 %, specificity was 95.7 %, PPV was 58.1 %, and NPV was 92.9 %. This study shows a more than adequate accuracy of preoperative US/FNAC to detect three or more positive lymph nodes (89.8 %). However, when US/FNAC was chosen as the only axillary staging method, 6.4 % of all patients (false negative group) would have been undertreated and 3.8 % of all patients (false positive group) would have been overtreated according to the ACOSOG Z0011 criteria.

Ultrasound and fine needle aspiration cytology of axillary lymph nodes in breast cancer. To do or not to do?

AIM: The purpose of our study was to evaluate the accuracy of axillary ultrasound and ultrasound-guided fine needle aspiration cytology (FNAC) in the preoperative diagnosis of axillary metastases. METHODS: Between 2004 and 2009, 1132 female patients were evaluated and treated in our clinic for histologically proven breast carcinoma. Preoperative axillary ultrasound with subsequent FNAC in case of suspicious lymph nodes was performed in 1150 axillae (18 bilateral breast carcinomas). We analyzed the results of axillary ultrasound and FNAC retrospectively. Pathological node status was used as the reference standard (based on axillary dissection or sentinel node biopsy). RESULTS: Axillary ultrasound showed suspicious lymph nodes in 327 axillae (28.4%). FNAC showed axillary metastases in 107 of these 327 axillae. Final histological analysis confirmed 106 metastases (one false positive). Histological analysis showed metastatic disease in 429 of 1150 axillae (37.3%). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of axillary ultrasound alone were 43.8% (188/429), 80.7% (582/721), 57.5% (188/327) and 70.7% (582/823), respectively. When combining axillary ultrasound with FNAC of suspicious lymph nodes, sensitivity was 24.7% (106/429), specificity was 99.9% (720/721), PPV was 99.1% (106/107) and NPV was 69.0% (720/1043). CONCLUSIONS: 106/429 (24.7%) Node-positive axillae were identified by ultrasound-guided FNAC and spared unnecessary sentinel node biopsy. Unfortunately, the percentage of false negative results of ultrasound-guided FNAC (28.1%, 323/1150) was very high.

Tankyrase-1 function at telomeres and during mitosis is regulated by Polo-like kinase-1-mediated phosphorylation.

Telomere length is critical for chromosome stability that affects cell proliferation and survival. Telomere elongation by telomerase is inhibited by the telomeric protein, TRF1. Tankyrase-1 (TNKS1) poly(ADP-ribosyl)ates TRF1 and releases TRF1 from telomeres, thereby allowing access of telomerase to the telomeres. TNKS1-mediated poly(ADP-ribosyl)ation also appears to be crucial for regulating the mitotic cell cycle. In searching for proteins that interact with polo-like kinase-1 (Plk1) by using complex proteomics, we identified TNKS1 as a novel Plk1-binding protein. Here, we report that Plk1 forms a complex with TNKS1 in vitro and in vivo, and phosphorylates TNKS1. Phosphorylation of TNKS1 by Plk1 appears to increase TNKS1 stability and telomeric poly(ADP-ribose) polymerase (PARP) activity. By contrast, targeted inhibition of Plk1 or mutation of phosphorylation sites decreased the stability and PARP activity of TNKS1, leading to distort mitotic spindle-pole assembly and telomeric ends. Taken together, our results provide evidence of a novel molecular mechanism in which phosphorylation of TNKS1 by Plk1 may help regulate mitotic spindle assembly and promote telomeric chromatin maintenance.

CT appearance of primary peritoneal serous borderline tumour: a rare epithelial tumour of the peritoneum.

Primary peritoneal serous borderline tumour (PPSBT) is a rare epithelial neoplasm which is histologically identical to serous borderline tumour of the ovary. PPSBT is distinguishable from primary peritoneal serous carcinoma because the tumour cells do not invade the underlying tissue and affected patients have a good prognosis. We report the CT findings of surgically proven PPSBT in which multiple peritoneal cysts were seen. Although rare, PPSBT should be considered in the differential diagnosis of primary peritoneal tumours. Since the prognosis of the disease is good, conservation of the uterus and ovaries should be a consideration in young female patients during surgery.

Green tea consumption, abdominal obesity as related factors of lacunar infarction in Korean women.

OBJECTIVES: Our purpose was to evaluate interaction of green tea consumption and abdominal obesity as related factors for lacunar infarction in Korean women. DESIGN: A hospital-based, incident case-control study. SETTINGS: The Prevention and Managements of Stroke in Women study. PARTICIPANTS: Cases (n=233) of first incident lacunar infarction were enrolled and matched by age to stroke-free hospital controls (n=204). MEASUREMENTS: The data were collected through face-to-face interviews by well trained research assistants to assess demographic, medical, lifestyle, marital status, religions status, green tea consumptions, family history of stroke, smoking status, alcohol consumption, meat and vegetable intake frequency, and past history of hypertension. Biochemical analysis, fasting blood specimens for lipid, glucose, and cholesterol level were acquired. RESULTS: Compared with the non green tea consumer and obese women group, only the green tea consumption and non obese women group had a protective effect of lacunar infarction when adjusted for age, and age plus diet factors (OR, 0.23; 95% CI, 0.09, 0.59; OR, 0.21; 95% CI, 0.08, 0.56 respectively), but lost their significance after adjustment for age, diet factors, vascular risk factors and full model included atherogenic index factors (OR, 0.32; 95% CI, 0.09 to 1.01; OR, 0.49; 95% CI, 0.12, 1.89 respectively). CONCLUSIONS: The interaction of green tea consumption and non obesity have reduced risk of lacunar infarction, but not after adjustment for age, diet factors, vascular risk factors and atherogenic index. Also individually green tea consumption and abdominal obesity have failed to find an independent relationship with lacunar infarction after adjustment by all risk factors. Green tea consumption and green tea consumption with non obese group seemed to have a protective effect for lacunar infarction. In the results of our study, these results still remain controversial, and then we need further and larger study to get at the root of real causal effect of both relationships.

Effect of proanthocyanidin-rich extract from Pinus radiata bark on immune response of specific-pathogen-free White Leghorn chickens.

Proanthocyanidins are naturally occurring compounds that are widely found in fruits, vegetables, nuts, seeds, flowers, and bark. We evaluated the immunomodulatory effects of proanthocyanidin-rich extract (PAE) from Pinus radiata bark in specific-pathogen-free White Leghorn chickens. Proliferation of peripheral blood mononuclear cells was significantly enhanced in chickens treated for 2 wk with 20 mg/kg of PAE. Proliferation of splenocytes and bursal cells was significantly enhanced in chickens treated for 5 wk with 5, 10, and 20 mg/kg of PAE. Thymocyte proliferation was significantly enhanced in chickens treated for 5 wk with 5 and 10 mg/kg of PAE. These effects were markedly enhanced by the presence of lipopolysaccharide, which acted on B cells responsible for humoral immunity, and concanavalin A, which acted directly on T cells involved in cell-mediated immunity. The PAE significantly promoted the expression of T helper 1 cytokine (interferon-γ) and decreased the expression of T helper 2 cytokine (IL-6). Thus, P. radiata PAE has immunomodulatory effects in specific-pathogen-free White Leghorn chickens.

Two patients with focal segmental glomerulosclerosis complicated by cyclosporine-induced reversible posterior leukoencephalopathy syndrome.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a distinctive clinicoradiological entity observed in a variety of clinical settings. Cyclosporine (CyA)-RPLS has been reported in a few patients with focal segmental glomerulosclerosis (FSGS); however, there had been no reports on developed RPLS after the re-administration of CyA treatment. We report two patients with FSGS who developed CyA-induced RPLS and summarize the results of a literature review for similar patients. The two patients with FSGS presented here were a 4-year-old boy and a 9-year-old boy, who presented with steroid-resistant nephrotic syndrome (NS) and were treated with CyA. The first patient developed CyA-induced RPLS at the 7th day after the start of CyA treatment, and the second patient at the 16th day after the re-start of CyA treatment. The two patients complained of a visual disorder and exhibited signs of a disturbance in consciousness and hypertension. Electroencephalography (EEG) examinations revealed a generalized slow wave pattern, and magnetic resonance imaging (MRI) disclosed an area of high signal intensity in the white matter. Subsequently, CyA was discontinued and neurological symptoms improved and recrudescence of RPLS did not occur. Our findings suggest that patients with FSGS and NS who are treated with CyA should be closely monitored for the possible onset of RPLS, presenting as a disturbance in consciousness, visual disturbances and/or convulsions.

An extremely low body weight infant born to a mother with measles.

The incidence of measles epidemics has decreased recently owing to the development and widespread use of measles vaccine in the United States of America and Europe. However, repeated measles epidemics have been reported in Japan. Here, the authors report a case of an extremely low body weight infant (ELBWI) whose mother had a measles virus infection. Real-time PCR was performed on the infant's blood and urine samples and skin, nasal secretion, and anal swabs, as well as on the mother's breast milk, blood samples and throat swabs. The infant was found to be positive for measles virus by PCR, but not immunoglobulin M positive. An earlier report showed that there were no such cases in which the patient was found to be positive for measles virus by real-time PCR but was not infected by the measles virus.

Quantification by HPLC-MS/MS of atropine in human serum and clinical presentation of six mild-to-moderate intoxicated atropine-adulterated-cocaine users.

An unexpectedly high number of initially suspected cocaine-intoxicated patients was presented to a general hospital in Lelystad, The Netherlands. Based on the unusual toxidram rate of not fitting cocaine intoxication, the suspicion of co-presence of an anticholinergic agent was raised. A newly developed HPLC-MS/MS analytical method revealed the presence of 10% atropine in a cocaine sample retrieved and subsequently in the sera of 6 intoxicated patients.

Sentinel lymph node biopsy in thin melanoma patients.

BACKGROUND: We sought to determine the incidence of positive sentinel lymph nodes in thin melanoma (or= III and thicker lesions (mean 0.77 mm vs. 0.47 mm), but were not different in regards to age, sex, or lesion location. Eight percent and 58% of sentinel nodes were positive by routine histology and RT-PCR, respectively. Among mapped patients, younger age was the only significant prognostic factor for node positivity. With a median follow-up of 18 months among all patients, one regional recurrence (at 2 years) has been identified. CONCLUSIONS: Given the low morbidity of sentinel lymph node biopsy, this procedure should be discussed with selected thin melanoma patients to detect microscopic disease, however PCR positivity by our methods is too commonly seen to be clinically significant in thin melanoma patients and requires additional study.

The use of a percutaneous closure device for closure of an accidental puncture of the aortic arch; a simple solution for a difficult problem.

Percutaneous closure devices are now often used for closure of the femoral puncture site after percutaneous vascular interventions. We describe a case were an accidental puncture in the aortic arch during placement of a central venous catheter is successfully closed with a closure device.

Structure-activity relationship of neuropeptide gamma derived from mammalian and fish.

This study of relationship between structure and biologic activity was performed using five neuropeptide gammas [NPgamma; mammalian-NPgamma (M-NPgamma), trout-NPgamma (T-NPgamma), goldfish-NPgamma (G-NPgamma), bowfin-NPgamma (B-NPgamma), and shark-NPgamma (S-NPgamma)]. Circular dichroism (CD) spectra showed that all peptides took random structure in buffer solution. In neutral and acidic liposomes, M-NPgamma, T-NPgamma, B-NPgamma, and S-NPgamma still adopted random structure, while G-NPgamma had an alpha-helical structure. The biologic activity of NPgammas has been estimated by their effects on the intestinal motility and arterial relaxation. The intestinal motility was investigated with rat duodenum (RD), carp intestine (CI), and guinea-pig ileum (GPI). The arterial relaxing effect was tested with guinea-pig aorta (GPA) and rat mesenteric artery (RMA). In RD, the order of potency compared with the EC50 value was M-NPgamma >> S-NPgamma >> B-NPgamma >> G-NPgamma >> T-NPgamma. G-NPgamma was the most contractile agent in CI. S-NPgamma was the most contractile agent in GPI. Using an arterial relaxing test, the order of potency was G-NPgamma >> T-NPgamma >> B-NPgamma >> S-NPgamma >> M-NPgamma in GPA, and all NPgammas remarkably reduced relaxing activity in RMA. Despite their structural similarities to NPgammas, G-NPgamma has high affinity to tachykinin receptor-binding sites in GPA and CI, indicating an alpha-helical structure may have a critical role for receptor binding. However, an alpha-helical structure does not play a critical role in recognizing receptor-binding sites in RD and GPI.

A comparative study to validate the use of ultrasonography and computed tomography in patients with post-operative intra-abdominal sepsis.

PURPOSE: To validate abdominal ultrasonography and helical computed tomography in detecting causes for sepsis in patients after abdominal surgery and to determine improved criteria for its use. MATERIALS AND METHODS: Eighty-five consecutive surgical patients primarily operated for non-infectious disease were included in this prospective study. Forty-one patients were admitted to the intensive care unit. All patients were suspected of an intra-abdominal sepsis after abdominal surgery. Both ultrasonography (US) and helical abdominal computed tomography (CT) were performed to investigate the origin of an intra-abdominal sepsis. The images of both US and CT were interpreted on a four-point scale by different radiologists or residents in radiology, the investigators were blinded of each other's test. Interpretations of US and CT were compared with a reference standard which was defined by the result of diagnostic aspiration of suspected fluid collections, (re)laparotomy, clinical course or the opinion of an independent panel. Likelihood ratios and post-test probabilities were calculated and interobserver agreement was determined using kappa statistics. RESULTS: The overall prevalence of an abdominal infection was 0.49. The likelihood ratio (LR) of a positive test-result for US was 1.33 (95% CI: 0.8-2.5) and for CT scan 2.53 (95% CI: 1.4-5.0); corresponding post-test probabilities for US 0.57 (95% CI: 0.42-0.70) and for CT 0.71 (95% CI: 0.57-0.83). The LR of a negative test-result was, respectively, 0.60 (95% CI: 0.3-1.3) and 0.18 (95% CI: 0.06-0.5); corresponding post-test probabilities for US 0.37 (95% CI: 0.20-0.57) and for CT 0.15 (95% CI: 0.06-0.32) were calculated. CONCLUSION: Computed tomography can be used as the imaging modality of choice in patients suspected of intra-abdominal sepsis after abdominal surgery. Because of the low discriminatory power ultrasonography should not be performed as initial diagnostic test.

Pattern analysis of sleep-deprived human EEG.

Progress during the past decade in non-linear dynamics and instability theory has provided useful tools for understanding spatio-temporal pattern formation. Procedures which apply principle component analysis (using the Karhunen-Loeve decomposition technique) to the multichannel electroencephalograph (EEG) time series have been developed. This technique shows localized changes of cortical functioning; it identifies increases and decreases of the activity of localized cortical regions over time while the subject performs a simple task or test. It can be used to demonstrate the change in cortical dynamics in response to a continuous challenge. Using 16 EEG electrodes, the technique provides spatio-temporal information not obtained with power spectrum analysis, and includes the weighted information given with omega complexity. As an application, we performed a pattern analysis of sleep-deprived human EEG data in 20 healthy young men. Electroencephalograph recordings were performed on subjects for <2 min, with eyes closed after normal sleep and after 24 h of experimentally-induced sleep deprivation. The significant changes in the eigenvector components indicated the relative changes of local activity in the brain with progressive sleep deprivation. A sleep deprivation effect was observed, which was hemispherically correlated but with opposite directional dynamics. These changes were seen in the temporo-parietal regions bilaterally. The application of the technique showed that the simple test task was performed with a limited unilateral hemispheric involvement at baseline, but needed a much larger cortical participation with decreased frontal activity and increased coherence and bilateral hemispheric involvement. The calculations performed demonstrated that the same weighted changes as those obtained with omega complexity were shown, but the technique had the added advantage of showing the localized directional changes of the principle eigenvector at each studied electrode, pointing out the cortical localized region affected by the sleep deprivation and toward which direction the environmental challenge induced the spatial change. This methodology may allow the evaluation of changes in local dynamics in brain activity in normal and pathological conditions.

The effect of total sleep deprivation on cognitive functions in normal adult male subjects.

This study was conducted to evaluate the effect of acute sleep deprivation on cognitive functions. A total of 18 healthy right handed males were deprived of sleep for 24 hours. Luria-Nebraska Neuropsychological Battery and calculation & digit-span subtest of K-WAIS were administered before and after sleep deprivation in order to examine the changes of cognitive functions. There were no differences in freedom from distractibility, tacile function, visual function, reading, writing, arithmetic and intellectual process function. However, the cognitive functions such as motor, rhythm, receptive & expressive speech, memory and complex verbal arithmetic function were decreased after sleep deprivation. All of these functions are known to be related to the right anterior hemisphere. For localization scales, the scores of right frontal and right temporal dysfunction scale were increased after sleep deprivation. These results indicate that sleep deprivation has a negative effect on cognitive functions, especially those associated with right anterior hemisphere or subcortical areas.

Synergetic analysis of spatio-temporal EEG patterns: Alzheimer's disease.

A spatio-temporal analysis has been employed on EEG signals recorded in groups of patients with Alzheimer's disease (AD). The so-called Karhunen-Loeve analysis method was applied to four groups of subjects: 12 patients who were diagnosed as having severe AD, 8 mild AD patients, 10 vascular dementia patients, and 10 normal aged controls, to obtain the spatio-temporal eigenpatterns. The local difference of the global EEG pattern in mild AD patients from that of normal controls was expanded to the frontal regions in the case of severe AD. The analysis showed significant bilateral temporal functioning differences and inter-hemispheric connection difficulty, along with remarkable intra-hemispheric correlation in severe AD patients. Compared to the normal controls, severe AD patients' brains exhibit only weak local connections and correlations, resulting into limited harmonious inter-hemispheric information processing. The results from the spatio-temporal EEG study of AD patients can be considered to be due to a change in the relative activity of the brain corresponding to the pathologic variation in AD, and the results are in accordance with reported clinical studies.