Computed diffusion-weighted imaging in patients with transient neurovascular symptoms with and without ischemic infarction.

PURPOSE: Detection of ischemic lesions in patients with transient neurovascular symptoms is relevant for the estimation of the risk of a subsequent stroke and etiological classification. To improve detection rates, different technical approaches have been used, such as diffusion-weighted imaging (DWI) with high b-values or higher magnetic field strength. Here, we sought to investigate the value of computed DWI (cDWI) with high b-values in these patients. METHODS: From an MRI report database we identified patients with transient neurovascular symptoms who underwent repeated MRI including DWI. cDWI was calculated with a monoexponential model with high b-values (2000, 3000, and 4000 s/mm2) and compared to the routinely used standard DWI with regard to presence of ischemic lesions and lesion detectability. RESULT: Overall 33 patients with transient neurovascular symptoms (71 [IQR 57-83.5] years; 21 [63.6%] male) were included. On DWI, acute ischemic lesions were observed in 22 (78.6%). Acute ischemic lesions were observed in 17 (51.5%) patients on initial DWI, and in 26 (78.8%) patients on follow-up DWI. Lesion detectability was rated significantly better on cDWI at 2000s/mm2 compared to standard DWI. In 2 (9.1%) patients, cDWI at 2000s/mm2 revealed an acute ischemic lesion proven on follow-up standard DWI which was not detected with certainty on the initial standard DWI. CONCLUSION: cDWI might be a valuable addition to routinely acquired standard DWI in patients with transient neurovascular symptoms since its use might result in improved ischemic lesion detection. A b-value of 2000s/mm2 seems most promising for clinical practice.

GLOS and HARM in patients with transient neurovascular symptoms with and without ischemic infarction.

BACKGROUND AND PURPOSE: Gadolinium leakage in ocular structures (GLOS) on fluid attenuated inversion recovery images (FLAIR) is a novel imaging marker in acute ischemic stroke and other neurological disorders. METHODS: In patients with transient neurovascular symptoms who underwent repeated MRI with intravenous contrast agent administration, the presence of acute ischemic lesions on diffusion-weighted images (DWI) as well as the frequency and pattern of blood-brain barrier and blood-retina barrier impairment as demonstrated by the hyperintense acute reperfusion marker (HARM) and GLOS respectively on postcontrast FLAIR were evaluated. RESULTS: Overall 28 patients with transient neurovascular symptoms (median age 70.5 years; 18 (64.3%) male) were included. Follow-up MRI was performed within 35 (IQR 21-47) hours after the initial MRI. On DWI, acute ischemic lesions were observed in 22 (78.6%). On contrast-enhanced FLAIR, GLOS was observed in 12 (42.9%) patients: in 1 (3.6%) only in the anterior chamber, and in 11 (39.3%) in the anterior chamber and vitreous body. HARM was observed in 3 (10.7%) patients. In one patient without ischemic lesion on DWI or HARM on FLAIR, GLOS was observed in the anterior chamber and vitreous body. Presence of GLOS was associated with higher age (p = 0.04) and detection of HARM (p = 0.03). CONCLUSIONS: In patients with transient neurovascular symptoms, GLOS is a frequent finding and associated with HARM on contrast-enhanced FLAIR. As GLOS was observed in one patient without an ischemic lesion or HARM, it might be useful as an additional imaging marker.

A conceptual framework for an oral cancer awareness campaign in Northern Germany - Challenges in campaign development and assessment.

Initial impetus for action: Oral cancer is still an underestimated disease in terms of incidence as well as mortality rates; it requires urgent prevention and early detection. At present, there is no best-practice systematic approach to raising awareness and informing the public about about this type of cancer in Germany. This article describes a framework that covers the significant stages of conceptual development and campaign design to promote oral cancer awareness in Germany. Solution: The challenges of the development, as well as evaluation of an oral cancer awareness campaign are shared in this article. Four key stages of the campaign are defined: (1) mass media, (2) target groups, (3) health care professionals, and (4) epidemiology. For each section, the following levels of assessment are proposed: (a) campaign development (formative assessment), (b) controlling and optimising campaign implementation (process assessment) and (c) measuring outcomes (summative assessment). Outcome: A process-oriented assessment concept for each of the four campaign sections was developed and merged to form a matrix, which includes each of the above sections regarding the prevention and early detection of oral cancer, as well as the three stages of campaign assessment. Future implications and learning points: The conceptual framework demonstrated that systematic planning and evaluation of different components helped to describe and evaluate an oral cancer campaign: For future campaigns, the use of a matrix covering different campaign targets as well as the entire campaign process, is recommended as a basis for campaign design and evaluation.

Hippocampal infarction: Identification of three new types.

BACKGROUND AND PURPOSE: Hippocampal infarction (HI) is common but yet still not comprehensively studied. In the present study, we aimed to identify novel HI patterns and to describe additional ischemic lesions outside the hippocampus to draw conclusions regarding the underlying vessel occlusion. METHODS: In 222 patients (mean age 69.9 (±13.6) years; 129 (58.1%) male, 93 (41.9%) female) with HI, diffusion-weighted images were analyzed with emphasis on HI patterns and associated ischemic lesions outside the hippocampus. HI were classified as type 1 (complete), 2 (lateral), 3 (dorsal), and 4 (circumscribed). Further possible HI patterns were defined and classified as type 5 (ventral), 6 (ventrolateral), and 7 (dorsolateral). RESULTS: Unilateral HI was found in 218 (98.2%) patients. In these, type 5 and 6 were identified in 5 (2.3%) patients, and type 7 in 8 (3.7%) patients respectively. Type 1 was found in 62 (28.4%), 2 in 53 (24.3%), 3 in 57 (26.1%), and 4 in 28 (12.8%) patients. Further ischemic lesions were found in the territory of the anterior cerebral artery (3.6%), middle cerebral artery (14.9%), anterior choroidal artery (AChA) (7.2%), posterior cerebral artery (89.6%), and in the brainstem (6.3%) and cerebellum (20.3%). Type 5 and 6 were significantly associated with acute ischemic lesions in the AChA territory (6/10 (60%) vs. 11/200 (5.5%), P<0.001). CONCLUSIONS: We identified three novel HI types. Probably, type 5 and 6 can be attributed to occlusion of the AChA. Overall, these HI types are rare, possibly due to a better collateralization in the case of AChA occlusion.

Patient characteristics support unfavorable psychiatric outcome after treatment of unruptured intracranial aneurysms.

INTRODUCTION: Previous studies demonstrated an unfavorable psychological outcome after treatment of unruptured intracranial aneurysms despite an objectively favorable clinical and radiological outcome. The current study was therefore designed to analyze the psychiatric vulnerability of this specific patient collective. MATERIALS AND METHODS: Patients treated for a WHO grade I meningioma and incidental intracranial aneurysms in two German neurosurgical centers between 2007 and 2013 were screened for exclusion criteria including malignant/chronic diseases, recurrence of the tumor/aneurysm after more than 12 months and focal neurological deficits, among others. Seventy-five meningioma patients (M) and 56 incidental aneurysm patients (iA) met the inclusion criteria. The past medical psychiatric history, post-morbid personality characters and coping strategies were determined by questionnaires mailed to the patients in a printed version (Brief COPE, Big Five Personality Test). RESULTS: Fifty-eight M and 45 iA patients returned the questionnaires. Patients with iA demonstrated significantly higher pre-interventional rates of depressive episodes (p = 0.002) and psychological supervision (p = 0.038). These findings were especially aggravated in iA patients who received their cranial imaging for unspecific symptoms such as dizziness, headaches or tinnitus (n = 33, history of depressions: 39.4%; previous psychological supervision: 33.3%). Furthermore, the analysis of the Big Five personality traits revealed remarkably elevated neuroticism scores in the iA collective. CONCLUSION: The current study demonstrates an increased rate of positive pre-interventional psychiatric histories in the iA collective. Although those patients represent only a small subgroup, they still may play an important role concerning the overall outcome after iA treatment. Early detection and psychological support in this subgroup might help to improve the overall outcome. Further studies are needed to evaluate the influence of this new aspect on the multifactorial etiology of unfavorable psychiatric outcome after treatment of iA.

Using an audience response system to improve learning success in practical skills training courses in dental studies - a randomised, controlled cross-over study.

INTRODUCTION: The aim of this study was to examine whether the use of an audience response system (ARS) in a high-quality study design, in a course in pre-clinical dentistry leads to an improvement in cognitive and psycho-motor performance. MATERIALS AND METHODS: As part of the Phantom Course I, a randomised, controlled study in cross-over design with 63 students was conducted over 4 weeks. The intervention was carried out by means of an ARS (TurningPoint(®) ), while a verbal question-and-answer session was conducted within the control group. Differences in learning success were determined via a formative multiple-choice (MC) test (cognitive) and a summative practical test (psycho-motor). RESULTS: Both groups achieved significantly better results in the MC tests with the use of the intervention, when compared with the control group (group A 11.6 vs. 9.5 and group B 13.7 vs. 12.1, maximum 16 points). A further analysis of the results showed that the overall effect was induced primarily by a marked improvement in below-average students. The practical tests showed no clear effect. Despite the careful selection and set-up of the conditions for the study in the regular course of the semester, a cohort effect emerged. This was due to varying degrees of performance between the two groups, because no adequate performance parameters were available, which could have been taken into account for the stratified randomisation. CONCLUSIONS: The results indicate that the use of the ARS leads to better results in cognitive performance, especially where independent learning is required and should be encouraged. Weaker students in particular seem to benefit.

Value of diffusion-weighted imaging in central pontine and extrapontine myelinolysis.

INTRODUCTION: Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are rare neurological disorders characterized by demyelination in and/or outside the pons. Whether diffusion-weighted imaging (DWI) might facilitate an earlier diagnosis has not yet been studied systematically. METHODS: We describe demographics, clinical presentation, and early magnetic resonance imaging (MRI) findings with special emphasis on the relevance for diagnosis of CPM and/or EPM in eight patients. RESULTS: Of the analysed eight patients (aged 37-70 years; two men, six women), CPM was diagnosed in three, EPM in one, and a combination of CPM and EPM in four patients. Aetiology was rapid correction of sodium in two patients; a combination of hyponatremia, alcoholism and alcohol withdrawal in five patients and unclear in one patient. Seven patients suffered from chronic alcoholism and four from malnutrition. Demyelinating lesions were found in the pons, thalamus, caudate nucleus, putamen and midbrain. While the lesions could be clearly delineated on T2- and T1-weighted images, DWI demonstrated a strong signal in only six patients. Furthermore, DWI demonstrated lesions only to some extent in two patients and was completely negative in two patients on initial MRI. In none of the patients did the demonstration of hyperintense lesions on DWI precede detection on conventional MRI sequences. Apparent diffusion coefficient (ADC) values were heterogenous with a decrease in two cases and an increase in the remainder. CONCLUSIONS: We conclude that early DWI changes are a common finding in CPM/EPM but do not regularly precede tissue changes detectable on conventional MRI sequences. Heterogenous ADC values possibly represent different stages of disease.

Recent trends in incidence and mortality of oral and pharyngeal cancer in Schleswig-Holstein in Northern Germany.

OBJECTIVE: Oral and pharyngeal cancer is still a serious public health problem with more than 10,000 new cases every year in Germany, more than 4,000 patients die of this tumour each year. Aim of the project was a detailed analysis on incidence and mortality rates by age, gender and tumour sites in Northern Germany. METHODS: The data on incidence and mortality rates from the population-based Cancer Registry of Schleswig-Holstein in Northern Germany were evaluated by age, gender and tumour sites from 2000 to 2006. RESULTS: Some 3,127 new cases of oral and pharyngeal cancer (72% men, 28% women) were registered. About half of all cases were aged 60-79 years. The incidence trends for 40-59 years described a slight decrease. Trends for pharyngeal cancer showed the highest incidence rates for both genders in those aged 60-79. This detailed analysis with subgroups showed interesting differences and revealed considerable variations, especially compared to the increasing trends in several European countries. CONCLUSIONS: These population-based data of Schleswig-Holstein showed interesting differences in the trends for incidence and mortality rates for age groups and tumour sites within the state and compared to the national German data and revealed noticeable different trends compared to several European countries. This population-based information informs effective cancer control.

[Diagnostic value of transthoracic ultrasound compared to chest radiography in the detection of a post-interventional pneumothorax]. / Diagnostische Wertigkeit der transthorakalen Sonografie vergleichend zur Thoraxübersicht beim Nachweis eines postinterventionellen Pneumothorax.

PURPOSE: Chest radiography is standard for the diagnosis of a pneumothorax. However, also ultrasound of the chest has considerable value in the detection of a pneumothorax. A typical sonographic feature is the lack of the lung gliding sign. Aim of our trial was to evaluate the significance of ultrasound of the chest in the diagnosis of a pneumothorax supplemented by using power colour Doppler imaging. PATIENTS AND METHODS: Following transbronchial biopsy, patients received transthoracic ultrasound of the chest for evaluation of a pneumothorax. Immediately afterwards, a chest radiograph was performed and results were compared. RESULTS: 1023 patients (321 female, 702 male, median age 47 years) were examined. In 30 patients (2.9%) chest radiograph revealed a pneumothorax, while in ultrasound of the chest a pneumothorax was diagnosed in 36 of the cases. Defining chest radiography as gold standard, ultrasound of the chest had a sensitivity of 100%, a specificity of 83% and an accuracy of 99%. CONCLUSION: Transthoracic ultrasound of the chest is a highly sensitive and specific diagnostic tool in the diagnosis of a pneumothorax. In comparison to chest radiography, it is better available and prevents administration of ionizing radiation. However, a disadvantage of ultrasound is the lack of quantification of a pneumothorax and the assessment of the indication for chest tube drainage.

Asymmetrical Gadolinium Leakage in Ocular Structures in Stroke Due to Internal Carotid Artery Stenosis or Occlusion.

PURPOSE: Gadolinium leakage in ocular structures (GLOS) on fluid-attenuated inversion recovery images (FLAIR) is a novel imaging marker in acute ischemic stroke. The present study sought to investigate the frequency and pattern of blood-retina barrier impairment in acute ischemic stroke due to internal carotid artery (ICA) stenosis or occlusion as demonstrated by GLOS. METHODS: From a magnetic resonance imaging (MRI) report database patients were identified with acute ischemic stroke due to ICA stenosis/occlusion who underwent repeated MRI with intravenous contrast agent administration and FLAIR and MR angiography (MRA). On FLAIR the presence of GLOS was noted in the vitreous body. RESULTS: Overall 51 patients with a median age of 70 years (interquartile range, IQR 63-77 years) were included. Of these, 22 (43.1%) patients had an ICA stenosis and 29 (56.9%) an ICA occlusion. On contrast-enhanced FLAIR, GLOS was observed in 29 (56.9%) patients: in 7 (13.7%) unilateral, in 15 (68.2%) bilateral asymmetrical and in 7 (31.8%) bilateral symmetrical. In unilateral asymmetrical GLOS, more pronounced enhancement was always found ipsilateral to ICA stenosis/occlusion. In 4 (5.9%) patients with asymmetrical GLOS a pre-existing signal increase in the vitreous body was found on native FLAIR. The presence of GLOS was associated with an impaired collateralization through the circle of Willis (p < 0.001) and external carotid artery branches (p = 0.03). CONCLUSION: In patients with ischemic stroke due to ICA stenosis/occlusion, GLOS is frequent, commonly unilateral or bilateral asymmetrical, and in some patients associated with pre-existing ocular signal abnormalities. An insufficient collateralization may contribute to the development of unilateral/asymmetrical GLOS.

Gadolinium leakage in ocular structures: A novel MRI finding in transient global amnesia.

BACKGROUND AND PURPOSE: We investigated the frequency and pattern of blood-brain barrier as well as blood-retina barrier impairment in transient global amnesia (TGA) as demonstrated by hyperintense acute reperfusion marker (HARM) and gadolinium leakage in ocular structures (GLOS) respectively on fluid attenuated inversion recovery images (FLAIR). METHODS: Patients with TGA who underwent repeated MRI after intravenous contrast agent administration were identified and the presence of GLOS in the anterior chamber and vitreous body and HARM noted on FLAIR. RESULTS: Overall 10 patients (IQR 64.25-71.75 years; 4 (40%) patients were male) were included. On contrast-enhanced FLAIR, GLOS was observed in 3 (30%) patients; in all of these in the anterior chamber and vitreous body as well as bilateral and symmetrical. HARM was observed in none of the patients. Frequency of hippocampal DWI lesions, as well as extent of age related white matter lesions did not differ significantly between patients with and without GLOS. CONCLUSIONS: In contrast to HARM, GLOS is a relatively common finding in TGA patients. As GLOS is thought to share its pathophysiology at least to some extent with HARM and is associated with HARM in ischemic stroke, it might be used as surrogate marker for blood-brain barrier impairment in TGA.

Isolated punctuate hippocampal infarction and transient global amnesia are indistinguishable by means of MRI.

Background Small punctuate lesions in the hippocampus on diffusion-weighted images are a typical finding in transient global amnesia. Consequently, it has been suggested that diffusion-weighted images findings might corroborate the diagnosis of transient global amnesia. However, isolated punctuate hippocampal infarction might be a differential diagnosis of transient global amnesia. Aim Evaluation of isolated punctuate hippocampal infarction frequency and comparison of its clinical presentation and MRI findings to transient global amnesia. Methods From an MRI database, we identified 10 patients with isolated punctuate hippocampal infarction and compared these to 12 patients with transient global amnesia with diffusion-weighted images lesion with regard to clinical symptoms and MRI findings. Results Disorientation and memory deficits were more common in transient global amnesia patients, whereas dysphasia/aphasia and vertigo were more common in hippocampal infarction patients. MRI findings in isolated punctuate hippocampal infarction and transient global amnesia did not differ significantly, neither regarding the affected hemisphere, lesion distribution, size, nor relative ADC values. Conclusions Differentiation of isolated punctuate hippocampal infarction and transient global amnesia based on neuroimaging findings is not possible. Thus, in the case of isolated punctuate hippocampal diffusion-weighted images lesions the final diagnosis of hippocampal infarction or transient global amnesia should be based on the clinical presentation.

[Hyponatremia-induced life-threatening cerebral edema after ecstasy use]. / Hyponatriämieinduziertes lebensbedrohliches Hirnödem nach Ecstasykonsum.

Ecstasy, a psychoactive amphetamine derivative, is a popular party drug. We report the cases of 2 young adults who developed cerebral edema due to hyponatremia. One patient was released from the hospital without any sequelae, whereas the second patient died due to cerebral edema. Severe cases of symptomatic hyponatremia after ecstasy consumption are described in the literature with partially fatal clinical outcomes. Thus, physicians should be aware of early and consequent control of the sodium and choose an interdisciplinary treatment decision.

The SNPlex genotyping system: a flexible and scalable platform for SNP genotyping.

We developed the SNPlex Genotyping System to address the need for accurate genotyping data, high sample throughput, study design flexibility, and cost efficiency. The system uses oligonucleotide ligation/polymerase chain reaction and capillary electrophoresis to analyze bi-allelic single nucleotide polymorphism genotypes. It is well suited for single nucleotide polymorphism genotyping efforts in which throughput and cost efficiency are essential. The SNPlex Genotyping System offers a high degree of flexibility and scalability, allowing the selection of custom-defined sets of SNPs for medium- to high-throughput genotyping projects. It is therefore suitable for a broad range of study designs. In this article we describe the principle and applications of the SNPlex Genotyping System, as well as a set of single nucleotide polymorphism selection tools and validated assay resources that accelerate the assay design process. We developed the control pool, an oligonucleotide ligation probe set for training and quality-control purposes, which interrogates 48 SNPs simultaneously. We present performance data from this control pool obtained by testing genomic DNA samples from 44 individuals. in addition, we present data from a study that analyzed 521 SNPs in 92 individuals. Combined, both studies show the SNPlex Genotyping system to have a 99.32% overall call rate, 99.95% precision, and 99.84% concordance with genotypes analyzed by TaqMan probe-based assays. The SNPlex Genotyping System is an efficient and reliable tool for a broad range of genotyping applications, supported by applications for study design, data analysis, and data management.

The pre-interventional psychiatric history - an underestimated confounder in benign intracranial lesions studies.

OBJECTIVES: The current study was designed to analyze the influence of a positive pre-interventional psychiatric history on the quality of life (QOL) after successful treatment of benign intracranial extra-cerebral lesions. METHODS: Patients treated due to meningioma WHO I or unruptured intracranial aneurysms in two German neurosurgical centers between 2007 and 2013 were screened for exclusion criteria including malignant/chronic diseases, recurrence of the tumor/aneurysm and neurological deficits among others. 131 patients who met the criteria of an objectively unaffected health status were included. The pre-interventional psychiatric histories and the rates of post-interventional headaches, sleeping disorders, symptoms of chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD) and QOL were determined by questionnaires which were mailed to the patients. RESULTS: 103 patients returned the questionnaires. Despite the objectively unaffected health status, the patients with a positive pre-interventional psychiatric history demonstrated a post-interventionally significantly lower QOL (p=0.002), a significantly higher Pittsburgh Sleep Quality Index sum score (p=0.009), as well as significantly higher rates of symptoms of a chronic fatigue syndrome (p=0.003) and PTSD (p=0.024), compared to the patient collective with a negative pre-interventional psychiatric status. CONCLUSION: The results of the current study demonstrate the importance of taking the pre-interventional psychiatric history as a significant and independent confounder into consideration when evaluating the outcome after treatment of benign intracranial extra-cerebral lesions. A pre-interventional psychiatric screening and an early psychological intervention might help to improve the overall outcome after successful treatment of such lesions.

De novo aneurysm of the anterior communicating artery presenting with subarachnoid hemorrhage 7 years after initial cryptogenic subarachnoid hemorrhage: a case report and review of the literature.

Spontaneous subarachnoid hemorrhage (SAH) is usually caused by a ruptured cerebral aneurysm. Despite the use of initial four-vessel cerebral digital subtraction angiography (DSA), 15 % of all cases remain idiopathic. According to the initial computed tomographic scan, the spontaneous SAH can be divided into a perimesencephalic group associated with a benign nature and a nonperimesencephalic group with a similar clinical course as aneurysmal SAH. We present a case of a 49-year-old man with a de novo aneurysm formation of the anterior communicating artery with SAH 7 years after initial cryptogenic nonperimesencephalic SAH. This observation suggests that in some cases, long-term angiographic studies might be justified.

Identification of known p53 point mutations by capillary electrophoresis using unique mobility profiles in a blinded study.

This study is part of an ongoing project at the National Institute of Standards and Technology (NIST) that generates a panel of DNA clones containing the most common mutations found in the human p53 tumor suppressor gene. This panel will be made available as a reference source for evaluation and testing for p53 mutations. Single strand conformation polymorphism (SSCP) analysis has found widespread acceptance as a tool for simply and rapidly screening for mutations, albeit with a detection rate that can be below 100%. We have begun to analyze mutations found in exon 7 of the p53 gene by SSCP using laser induced fluorescence capillary electrophoresis (LIF-CE). PCR fragments, containing single point mutations, were amplified from genomic DNA isolated from cell lines using primers labeled with two different fluorophores. This dual labeling approach allowed better traceability of mobility shifts as a function of the experimental conditions. While analyzing the clones H596, Colo320, Namalwa and wild type (reference samples) at different temperatures, ranging from 25 to 45 degrees C, it was observed that each mutation responded in a unique way to changes in temperature both in magnitude and direction of shifts relative to the wild type sample. In a blinded study, ten p53 exon 7 samples were matched automatically, using ABI PRISM Genotyper software, against the four reference samples. From these 10 samples, six were correctly identified as containing one of the reference mutations, two corresponded to wild type, and two were correctly identified as non-reference mutations. This approach should prove helpful in the rapid screening of target sequences that are known to bear a limited number of mutations.

Applications of focused ion beam systems in gunshot residue investigation.

Scanning ion microscopy technology has opened a new door to forensic scientists, allowing the GSR investigator to see inside a particle's core. Using a focused ion beam, particles can be cross-sectioned, revealing interior morphology and character that can be utilized for identification of the ammunition manufacturer.

ENFSI proficiency test program on identification of GSR by SEM/EDX.

Within the framework of the ENFSI Expert Working Group "Firearms," a proficiency test on the detection and identification of GSR by SEM/EDX was organized and performed. The test material was designed by the Bundeskriminalamt and manufactured to order by an external company for SEM accessories. The participating laboratories were requested to determine the total number of PbSbBa-containing particles on the test samples following their own laboratory specific methods of automated GSR particle search and detection by SEM/EDX. Two similar samples with synthetic GSR particles were dispatched to all participants in order to gain additional information on systematic errors within the obtained results (split-level study), whereas one sample was supplied only with PbSbBa particles, and the second one was additionally contaminated with some environmental particles. This report summarizes the results of the study as well as a statistical evaluation and comparison with previous studies.

Robust detection of sleep apnea from Holter ECGs. Joint assessment of modulations in QRS amplitude and respiratory myogram interference.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems". OBJECTIVES: Detect presence of sleep-related breathing disorders (SRBD) in epochs of 1 min by signal analysis of Holter ECG recordings. METHODS: In 121 patients, 140 synchronized polysomnograms (PSGs) and 8-channel Holter ECGs were recorded. The only excluded condition was persistent arrhythmias. Respiratory events as scored from the PSGs were mapped to a 1 min grid and served as reference for ECG-based detection. Moreover, 69/70 recordings of the Physionet Sleep Apnea ECG Database (PADB) were included. We performed receiver operating characteristics analysis of a single, novel time-domain feature, the joint local similarity index (jLSI). Based on cross-correlation, the jLSI quantifies the time-locked occurrence of characteristic low-frequency (LF) modulations in ECG respiratory myogram interference (RMI), QRS amplitude (QRSA) and heart rate. RESULTS: Joint oscillations in QRSA, RMI and the envelope of RMI identified positive epochs with a sensitivity of 0.855 (PADB: 0.873) and a specificity of 0.86 (PADB: 0.88). Inclusion of heart rate did not improve detection accuracy. CONCLUSIONS: Joint occurrence of LF-modulations in QRSA and RMI is a characteristic feature of SRBD that is robustly quantified by the jLSI and permits reliable and reproducible detection of sleep apnea in very heterogeneous settings.