Impaired heart rate variability in cervical dystonia is associated to depression.

Causes of cardiovascular autonomic dysfunction in cervical dystonia (CD) are poorly understood. Studies examining effects of botulinum neurotoxin (BoNT) therapy on heart rate variability (HRV) yielded contradictory results. There is compelling evidence that depression shifts autonomic balance towards sympathetic predominance. As depression is the most frequent non-motor symptom in CD, we sought to determine if it is associated to dysfunction of cardiovascular autonomic regulation. Standardized interviews, clinical examinations, self-rating forms, autonomic symptom questionnaire, and automated autonomic testing in outpatients with idiopathic CD were used. Cardiovascular autonomic screening encompassed five different analyses of HRV, and testing of orthostasis. 85 CD patients participated in the study. 21% of them had HRV impairment, 14% orthostatic hypotension. 30% of CD patients had symptoms of depression. In those, decreased HRV was more frequent than in CD patients without mood disturbance (40 vs. 13%; p = 0.008). CD patients with and without depression had no other significant differences, including demographics, dystonia severity, comorbidity, medication, or BoNT therapy. Cardiovascular autonomic imbalance with sympathetic predominance is a non-motor manifestation of CD, associated to depression. Impaired HRV is a cardiovascular risk factor, moreover, emphasizing the need to identify and treat depression in dystonia.

Medium term (> 12 months) outcomes after laparoscopic hiatal hernia repair without conventional fundoplication using PH4B-mesh implant (Phasix™) in 176 reflux patients: experience and technique.

BACKGROUND: Hiatal mesh repair remains a controversial topic among anti-reflux surgeons. Biosynthetic mesh cruroplasty may prevent early recurrence while avoiding late esophageal erosion and strictures associated with non-resorbable materials. So far, medium-term results on hiatal PH4B (Poly-4-Hydroxybutyrate) mesh repair from high-volume centers are lacking. METHODS: We analyzed the medium-term efficacy and safety of PH4B mesh cruroplasty in 176 consecutive patients (≥ 18 years) with symptomatic hiatal hernias. Treatment failure was defined as the clinical recurrence of reflux symptoms. Patients could choose between mesh augmented hiatal repair (combined with a modified anterior hemifundoplication and fundophrenicopexy), Nissen fundoplication, and magnetic sphincter augmentation at their discretion. We also describe the surgical approach to mesh augmented hiatal repair used at our center. RESULTS: On average, patients were 55 (± 14) years old and followed up for 22 (± 7; sum: 3931) months. Treatment failed in 6/176 (3%, 95% CI: 2-7%) patients. The 24-month Kaplan-Meier failure estimate was 2.8% (95% CI: 0.4-5%). Each centimeter in hernia size increased the risk of failure by 52% (p = 0.02). Heavier patients (BMI > 27) had an 11% higher probability of clinical symptom recurrence (p = 0.03). The dysphagia and bloating/gas rate were 13/176 (7%), each. 8 (5%) patients required endoscopy due to dysphagia but without intervention. No serious complications, including mesh infection and erosion, or fatalities, occurred. CONCLUSION: Augmented PH4B mesh cruroplasty without conventional fundoplication shows excellent intermediate-term results in patients with reflux disease due to hiatal hernia. Around one in thirty patients experience treatment failure within 2 years of surgery. Hernia size and overweight are key determinants of treatment failure.

Association of CETP polymorphisms with the risk of vascular dementia and white matter lesions.

Cholesteryl ester transfer protein (CETP), a component of the high density lipoprotein (HDL), plays a central role in reverse cholesterol transport. We investigated the association of two putative functional CETP polymorphisms (C-629A and I405V) with the risk of vascular dementia (VD) and tested if this association is influenced by the presence of APOE4 allele. Our study included 163 VD patients (mean age: 74.25 +/- 7.9 years) and 452 cognitively healthy probands (mean age: 70.81 +/- 7.9 years). As a biological correlate, the association of CETP gene variants with white matter lesion (WML) load was investigated. Neither the C-629A (P = 0.169) nor the I405V (P = 0.840) polymorphism was associated with VD risk in the whole sample. However, in non-carriers of the APOE4 allele, homozygote carriers of the CETP C-629A A allele presented with an increased risk of VD (P = 0.01). Whereas in APOE4 carriers, no association of CETP polymorphisms with VD risk was detected. In addition, carriers of the CETP C-629A AA genotype presented with decreased WML load in the frontal brain (P = 0.009). Our results suggest that CETP gene polymorphisms might influence WML load and the risk of VD, the latter in non-carriers of the APOE4 allele.

Brain imaging and neuropsychology in late-onset dementia due to a novel mutation (R93C) of valosin-containing protein.

Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD, MIM 167320) is a recently identified autosomal dominant disorder due to mutations in the valosin-containing protein (VCP) that affects muscle, bone and brain. Brain involvement and neuropsychological findings of IBMPFD have not been described in detail. A patient carried a novel heterozygous base pair change, 47832C>T, in the VCP gene that resulted in substitution of an arginine residue by cysteine at position 93 (R93C). He presented first with myopathy while bone involvement remained subclinical. The patient developed behavioral abnormalities in his 60s and showed frank personality change with fluent empty speech at the age of 74 years. This syndrome was best classified as semantic dementia. Magnetic resonance imaging disclosed slight but progressive cerebral atrophy with prominent callosal and frontal white matter loss. Positron emission tomography demonstrated glucose hypometabolism of the frontal and temporal lobes disproportionate to their structural involvement. This first comprehensive clinical and neuroimaging study in IBMPFD may raise the awareness among clinicians as well as basic scientists for this exemplary genetic model of dementia.

ACE I/D polymorphism is a risk factor of Alzheimer's disease but not of vascular dementia.

Different studies have investigated the effect of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism on the risk of Alzheimer dementia (AD). However, results on the association of the ACE-I allele with AD have been inconclusive. A recent meta-analysis reported an association of the I-allele with the risk of AD. A few small studies also investigated the effect of ACE polymorphism on the risk of vascular dementia (VD). We have investigated the effect of ACE I/D polymorphism in 351 AD and 155 VD patients and 348 healthy controls. We found the I/I genotype to be associated with an increased risk of AD, but not with the risk of VD. Cell-specific effects of ACE polymorphism are suggested, additional studies on neuronal cells might help to understand the role of this polymorphism in AD.

[Quantification of microangiopathic lesions in brain parenchyma and age-adjusted mean scores for the diagnostic separation of normal from pathological values in senile dementia]. / Quantifizierung mikroangiopathischer Hirnparenchymläsionen zur Abgrenzung altersnormaler gegenüber pathologischer Ausprägung bei Altersdemenzen.

PURPOSE: To quantify microangiopathic lesions in the cerebral white matter and to develop age-corrected cut-off values for separating normal from dementia-related pathological lesions. MATERIALS AND METHODS: In a memory clinic, 338 patients were investigated neuropsychiatrically by a psychological test battery and by MRI. Using a FLAIR sequence and a newly developed rating scale, white matter lesions (WMLs) were quantified with respect to localization, number and intensity, and these ratings were condensed into a score. The WML scores were correlated with the mini-mental state examination (MMSE) and clinical dementia rating (CDR) score in dementia patients. A non-linear smoothing procedure was used to calculate age-related mean values and confidence intervals, separate for cognitively intact subjects and dementia patients. RESULTS: The WML scores correlated highly significantly with age in cognitively intact subjects and with psychometric scores in dementia patients. Age-adjusted WML scores of cognitively intact subjects were significantly different from those of dementia patients with respect to the whole brain as well as to the frontal lobe. Mean value and confidence intervals adjusted for age significantly separated dementia patients from cognitively intact subjects over an age range of 54 through 84 years. CONCLUSION: A rating scale for the quantification of WML was validated and age-adjusted mean values with their confidence intervals for a diagnostically relevant age range were developed. This allows an easy to handle, fast and reliable diagnosis of the vascular component in senile dementia.

[Reliability of quantifying vascular white matter brain lesions -- a contribution to reproducible quantitative diagnosis]. / Reliabilität der Quantifizierung von vaskulären Läsionen der weissen Hirnsubstanz -- ein Beitrag zur replizierbaren quantitativen Diagnostik.

PURPOSE: Microangiopathic lesions of the brain tissue correlate with the clinical diagnosis of vascular subcortical dementia. The "experience-based" evaluation is insufficient. Rating scales may contribute to reproducible quantification. MATERIALS AND METHODS: In MRI studies of 10 patients, 9 neuroradiologists quantified vascular white matter lesions (WMLs) at two different points in time for 12 anatomically defined regions with respect to number, size and localization (score). For 9 observers and 10 studies, 90 intra-observer differences were obtained for each of the 12 WML scores. To calculate the inter-observer reliability, rating pairs were formed. Furthermore, 360 differences were computed for each score and rating for 12 anatomically defined WML scores, and the intraclass correlation (ICC) was calculated as a measure of agreement (reliability). RESULTS: As to the intra-observer reliability, the median of the differences was 1.5 for the entire brain as opposed to 0 for defined brain regions. The corresponding values for the inter-observer reliability were 3 and 1, respectively. The mean intra-class correlation coefficient for the 10 studies was 0.88, whereas the mean interclass correlation concerning the inter-observer reliability was 0.70, with the first and second rating being averaged. The rating of each study took about 6 minutes. CONCLUSION: The rating scale with high intra- and inter-observer reliability can dependably quantify WMLs and correlates with the clinical diagnosis of vascular dementia. Using a reliable rating scale, the diagnostic distinction of age-associated physiological vs. pathological size of the WML can make a contribution to the reproducible quantifiable diagnostic evaluation of vascular brain tissue lesions within the framework of dementia diagnostics.

Cell detachment during sinusoidal reperfusion after liver preservation: an in vitro model.

BACKGROUND: Sinusoidal endothelial cells (SEC) are significantly more vulnerable to cold storage and reperfusion than hepatocytes. Swelling and disruption of the sinusoidal lining induce the microcirculatory disturbances seen after reperfusion. In this article, the investigation of a method to assess the adhesion and morphology of SEC in vitro during reperfusion after preservation is described. METHODS: Time-lapse video microscopy analysis was performed and cell detachment rates and cell lengths were determined. Preservation intervals between 6 and 24 hr and flow rates ranging from 3 L/min to 9 L/min (resulting in shear stresses between 5.1 and 15.3 dynes/cm2 on the monolayer surface) during reperfusion period were compared. SEC that were stored for 6 hr in University of Wisconsin solution and nonpreserved control cultures were compared. RESULTS: Varying the preservation intervals from 6 hr to 24 hr during reperfusion at a flow rate of 3 L/min led to increased cell erosion rates (6 hr, 35.5+/-15.2%; 12 hr, 38.0+/-7.6%; 18 hr, 54.3+/-5.7%; 24 hr, 76.7+/-6.7%; nonpreserved cells, 3.4+/-3.4%). Storage periods from 12 hr to 24 hr led to significantly higher cell detachment rates than occurred in nonpreserved cells. CONCLUSIONS: This method allows the investigation of the adhesion capability and morphology of individual cells in vitro. Indications of the kind of preservation/reperfusion injury that occurs after treatment with several preservation solutions and the resultant repair behavior can be obtained.

Quantitative EEG in frontal lobe dementia.

A study on quantitative EEG in 14 patients with frontal lobe dementia (FLD), 14 patients with Alzheimer's disease (AD), and 14 healthy controls was conducted using a complete set of EEG parameters: band power, coherence and fractal dimension. Contrary to earlier studies, we observed higher theta power and sagittal interactions in higher frequency bands in the FLD than in the control group. Lateral interactions of coherence and two indices of fractal dimension were lower in FLD than in controls. There was greater electrophysiological resemblance between the control group and FLD than between any of these groups and AD. This was documented by the results of a discriminant analysis which led to a correct overall classification of 66% of the subjects with misclassifications occurring primarily between control and FLD group.

Proton magnetic resonance spectroscopy in acute, juvenile anorexia nervosa.

Anorexia nervosa is usually associated with a shrinkage of the brain that is at least partially reversible with weight gain. The pathogenesis of this brain abnormality is unclear. The purpose of this study was to investigate potential alterations in localized proton magnetic resonance (1H MR) spectra of anorectic patients immediately after an interval of excessive weight loss. Twelve patients and seventeen control subjects were examined. Water suppressed 1H MR spectra were recorded from two voxels placed in the thalamus and in the parieto-occipital white matter. The spectra of ten patients could be evaluated. Comparing patients and control subjects, significantly higher signal intensity ratios of choline containing compounds (Cho) relative to total creatine (Cr) as well as significantly lower ratios of N-acetyl-aspartate (NAA) relative to Cho were found in the white matter region. We hypothesize that these results indicate an abnormal starvation, associated membrane turnover, which predominantly takes place in the white matter. No evidence for neuronal degeneration was found in the thalamus or in the white matter region.

[Further possibilities for the application of the digital subtraction technique in neuroradiologic diagnosis]. / Weitere Anwendungsmöglichkeiten der digitalen Subtraktionstechnik (DST) in der neuroradiologischen Diagnostik.

The article presents, as methods that can be used in addition to digital subtraction angiography, ventriculography, myelography, discography as well as control examinations of shunts and port systems to widen the scope of digital subtraction techniques (DST) in neuroradiological diagnostics. Besides the reduction of amount and concentration of contrast media, more comprehensive and better diagnostic results were achieved for all examination methods with regard to the functional and dynamic aspects, the spatial resolution being of comparable quality.

[Does magnetization transfer ratio (MTR) contribute to the diagnosis and differential diagnosis of the dementias?]. / Leistet die Magnetization-Transfer-Ratio (MTR) einen Beitrag zur Diagnostik und Differenzialdiagnostik der Demenzen?

PURPOSE: The magnetization transfer ratio (MTR) is a MR-based neuroimaging procedure aiming at the quantification of the structural integrity of brain tissue. Its contribution to the differential diagnosis of dementias was examined and discussed in relation to the pathogenesis of age-related dementias. MATERIALS AND METHODS: Sixty-one patients from a memory clinic were diagnosed by general physical and neuropsychiatric examination, and underwent neuropsychologic testing and neuroimaging using MRI. Their clinical diagnoses were based on standard operational research criteria. Additionally, the MTR in 10 defined regions of interest (ROI) was determined. This investigation was performed using a T1-weighted SE sequence. Average MTR values were determined in the individual ROI and their combinations and correlated with the age, gender, cognitive impairment and clinical diagnosis. Sensitivity, specificity, positive and negative predictive value were determined, as well as the rate of correct classifications. RESULTS: For cognitive healthy subjects, the MRT values correlate only mildly, though significantly, with age in the hippocampus and with gender in the dorsal corpus callosum. In contrast, the MTR in the frontal white matter correlates strongly and highly significantly with cognitive impairment in patients with dementia. The differential diagnostic assignment of Alzheimer's disease versus vascular dementia by MTR provides a correct classification of approximately 50 % to 70 %. PPV for no dementia vs. vascular dementia or the NPV for vascular vs. Alzheimer's disease are considerably higher exceeding 80 %. For no dementia vs. Alzheimer's disease, the NPV was over 90 %. CONCLUSION: MTR values indicate functional changes in the brain tissue between cognitive healthy and demented patients, and correlate with the cognitive loss, but not with age and gender. In principle, the MTR is suitable for the diagnosis of age-related dementias, but does not contribute substantially to the differential diagnosis of vascular dementia vs. Alzheimer's disease. The present results support the assumption of a synergy between vascular and degenerative components of age-related dementias.

[Estimation of radiation exposure in interventional neuroradiology of the head in children compared to exposure of adult patients]. / Abschätzung der Strahlenbelastung bei interventionellen neuroradiologischen Eingriffen am Kopf von Kindern im Vergleich zur Exposition erwachsener Patienten.

PURPOSE: We reviewed different dosimetric results in three children investigated for haemangioma, arteriovenous malformation, and angioma of the head in comparison to global results in 11 adults. METHOD: The detailed patient dosimetry was performed using thermoluminescence dosimetry (TLD), area-dose exposure meter (ADE), and Alderson phantom. RESULTS: The patient doses of relevant organs ranged in the milli-Grays (mGy) level. The irradiation-induced risk is on a per mil level in respect of ICRP-60. The risk of cerebral angiographic procedures, radiotherapy, or surgical interventions is on a per cent level. The organ doses for staff are on a micro-Gray (microGy) scale and are higher in examination of children than of adults. A statistical limit of examinations depends on yearly or life-time dose limits with regard to the "Röntgenverordnung" (Germany).

[Evaluation of the contribution of the importance of neuroimaging for the diagnostics of dementias--comparison to the psychological diagnostics]. / Evaluation des Beitrages der radiologischen bildgebenden Diagnostik bei demenziellen Erkrankungen--ein Vergleich mit der psychologischen Diagnostik.

OBJECTIVE: While psychology is accepted as a necessary component of the dementia diagnostics, the extended clinical diagnostics with neuroimaging is differently estimated. The goal of the study is the quantification of the individual contribution of the two different methods. METHODS: Of 100 patients the diagnosis of entrance, the neurological, the psychological, and the final clinical diagnosis were documented. For both imaging and psychology the sensitivity, specificity, and the positive predictive value were computed. The diagnostic of each method was determined from the change of the final in relation to the initial clinical diagnosis. The neuroradiological investigation took place with MRI, the psychological examination used both usual power and special speed tests. RESULTS: The extended clinical diagnostics led for 26 % of the patients to the change of the clinical diagnosis. Imaging and psychology supplied different own but supplementing contributions. In the case of annihilation imaging contributed with 73.3 %, psychology with 54.1 % to the diagnosis of a neurodegenerative dementia, whereas the contributions to the diagnosis of a vascular dementia were 83.3 % and 70.8 %, respectively. However psychology diagnosed and quantified the dementia. The contribution of neuroimaging consisted in the differential diagnosis of the dementias. Organic causes of symptomatic dementias and vascular encephalopathy without dementia but with consequences for a secondary prophylaxis were additional information also. CONCLUSION: Psychology improves the diagnostic accuracy of dementias. Neuroimaging improves the differential diagnosis of dementias and supplies additional clinically relevant findings. In the qualified diagnostics and differential diagnostics of the dementias both methods are indispensable.

[1H-MR spectroscopy in anorexia nervosa: reversible cerebral metabolic changes]. / 1H-MR-Spektroskopie bei Anorexia nervosa: reversible zerebrale Metabolitenänderungen.

PURPOSE: By using localized 1H-MR spectroscopy in the brain of patients with anorexia nervosa we wanted to verify our preliminary results and to look for a reversibility of the metabolic changes under therapy. METHODS: In 22 patients and 17 healthy volunteers (11 follow-up examinations) single voxel 1H-MR spectroscopy (TE = 50 ms, TM = 30 ms, TR = 1500 ms, voxel (2 cm)3, acq.: 256) was used in two different localizations (thalamus and parieto-occipital region). The first examination of the patients was performed before therapy, the follow-up examination at the end of therapy. RESULTS: In both regions of the brain we found a statistically significant elevation of the Cho/Cr-ratio in comparison to normal controls. The follow-up examinations revealed reversibility of the metabolic changes under successful therapy. CONCLUSIONS: 1H-MR spectroscopy reveals metabolic changes in the brain of patients with anorexia nervosa, which are reversible under successful therapy. These metabolic changes can be conclusively explained using a biochemical model.

[The fractal dimension as an imaging parameter in CT scans of patients with anorexia nervosa before and after therapy]. / Die fraktale Dimension als Bildbearbeitungsparameter im CT bei Anorexia nervosa vor und nach Therapie.

Brain development is a self-organizing process and hence the brain structures correspond to a highly recursive system consisting of a multitude of parts. Quantitative analysis of recursive, self-similar structures is possible in CT scans as what is termed synergistic diagnostic using the fractal dimension. In 10 patients with anorexia nervosa (ICD-10, F50.0) we determined the fractal dimension of the cerebral cortex contour in a CT image using the "boxcounting method" after filtering of the data and separation with a defined cut-off. There was a significant difference between the results from CTs obtained before and after therapy. There was a high correlation between the fractal dimension and body weight, brain volume and sulcal cerebrospinal fluid volume, but only a low correlation with ventricular volume. The findings suggest that the qualification of the fractal dimension may be useful as one of postprocessing methods on CT scans. Further studies will be necessary to assess its importance for diagnosis.