[Agenesis of the corpus callosum]. / Balkenfehlbildungen.

CLINICAL ISSUE: Agenesis of the corpus callosum is reported to have an incidence of about 1:4000 live births. In 30-45% of cases, genetic etiologies can be identified, e. g., 10% chromosomal anomalies and 20-35% genetic syndromes. Environmental factors like fetal alcohol syndrome are also known to be prone to callosal agenesis. Callosal agenesis can be complete or partial and can be isolated or associated with other central nervous system (CNS) anomalies (e. g., cortical developmental disorders, callosal lipoma, intracranial cysts) or extra-CNS anomalies (e. g., eyes, face, cardiovascular). STANDARD RADIOLOGICAL METHODS AND METHODICAL INNOVATIONS: Diagnosis is made using ultrasound, computed tomography (CT) or best with magnetic resonance imaging (MRI). Typical imaging findings in callosal agenesis are colpocephaly, high riding enlarged third ventricle, Texas Longhorn configuration of frontal horns and so-called Probst bundles parasagittal. Diffusion tensor imaging and fiber-tracking, based on diffusion-weighted techniques, can also visualize fiber/tract anomalies in the patients' brains. ASSESSMENT: Clinical correlations of callosal agenesis is difficult in general because of the common association of other CNS malformations. Differential diagnosis of primary complete or partial callosal agenesis are secondary callosal changes, e. g. vascular, inflammatory or posttreatment in origin.

[Autoimmune reactions and paraneoplastic syndromes]. / Autoimmunreaktionen und Paraneoplasien.

CLINICAL ISSUE: Autoimmune disorders of the central nervous system (CNS) are common but are also a heterogeneous group of diseases. The most common form is multiple sclerosis (MS), others are clinically isolated syndrome (CIS), acute demyelinating encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD). Paraneoplastic syndromes are rare and tumor-associated, they are not induced by direct invasion of tumor tissue but by tumor-associated autoantibodies mostly against specific CNS proteins, e. g. limbic encephalitis and paraneoplastic cerebellar ataxia or degeneration. DIAGNOSTICS, STANDARD RADIOLOGICAL METHODS, PERFORMANCE AND ACHIEVEMENTS: The correct diagnosis of autoimmune and paraneoplastic syndromes can still be challenging. In addition to the patient history, clinical examination and blood as well as cerebrospinal fluid (CSF) tests, magnetic resonance imaging (MRI) is gaining importance in the diagnostics. It is important not only in primary diagnostics but also in follow-up and therapy monitoring, especially in MS with specific therapies to detect therapy complications, such as progressive multifocal leukoencephalopathy as early as possible. In paraneoplastic syndromes MRI can also be an important component in the diagnostics but can also initially be negative and typical signal changes become visible only in follow-up scans. PRACTICAL RECOMMENDATIONS: In paraneoplastic syndromes the correct diagnosis is based on laboratory tests for specific autoantibodies in serum and CSF. TREATMENT: The treatment of autoimmune and paraneoplastic disorders of the CNS ranges from steroids and immunosuppressive agents to plasmapheresis, depending on the specific disorder.

[Tumors of the sellar region]. / Tumoren der Sellaregion.

METHODICAL ISSUE: The anatomy of the sellar region is complex and tumors of the sellar region are very variable because they arise from the many different tissue types in the sellar region, ranging from benign to life-threatening. Despite this variety, approximately 80% of sellar region tumors are due to the 5 most common lesions: adenomas, meningiomas, aneurysms, astrocytomas and craniopharyngiomas. STANDARD RADIOLOGICAL METHODS: In addition to clinical and laboratory results, the magnetic resonance imaging (MRI) and computed tomography (CT) results including the exact anatomical position and the proliferation pattern of the lesion are decisive for the diagnosis. The gold standard for diagnostic imaging is multiplanar, thin section, contrast-enhanced MRI with soft tissue contrast. Vessel imaging and CT are complementary modalities in selected cases and often for preoperative planning. METHODICAL INNOVATIONS: Whereas most sellar region tumors can be well visualized with multiplanar, contrast-enhanced MRI, for very small intrapituitary microadenomas dynamic contrast-enhanced T1-weighted sequences can be necessary. Microadenomas can often only be clearly demarcated from the rest of the pituitary tissue due to the different perfusion pattern. Optimized diffusion-weighted images can also be useful for narrowing down the differential diagnoses of sellar region tumors. PERFORMANCE AND ACHIEVEMENTS: Tumors of the sellar region can be subdivided in intrahypophysial and extrahypophysial lesions as well as intrinsic skull base lesions. The most common sellar tumors are adenomas of the pituitary gland, which can be subdivided into microadenoma and macroadenoma and into secretory and non-secretory. PRACTICAL RECOMMENDATIONS: If there is suspicion of a sellar region lesion due to clinical or laboratory results, multiplanar contrast enhanced thin section MRI of the sellar region should be used as the primary imaging modality. The keys to the diagnosis are the precise anatomical location of the lesion and the proliferation pattern. The most common lesions in the sellar region are pituitary gland adenomas, which can be small and often secretory or larger and often non-secretory.

[Normal pressure hydrocephalus]. / Normaldruckhydrozephalus.

CLINICAL ISSUE: Normal pressure hydrocephalus (NPH) is a disorder found mainly in the elderly (> 60 years) with an increasing prevalence with age and is one of the few treatable causes of dementia. If untreated NPH often leads to severe motor, psychomotor and irreversible cognitive deficits. The pathogenesis is not yet fully understood. Clinical symptoms consist of the (not always complete) classical triad of equilibrium and gait disturbances followed later by incontinence and dementia. Symptoms often show a gradual progression to irreversibility in non-treated patients; therefore, early diagnosis and treatment are mandatory. Important differential diagnoses are Parkinson's disease (similar gait), Alzheimer's disease and vascular dementia, not least due to the high comorbidity of these conditions with NPH. STANDARD RADIOLOGICAL METHODS: The standard radiological method for evaluation of NPH is conventional cross-sectional imaging that typically shows ventriculomegaly (Evans' index > 0.3 and cella media index < 4) often combined with the so-called disproportionately enlarged subarachnoid space hydrocephalus (DESH) pattern (tight convexity sulci and enlarged sylvian fissure). These findings should be differentiated from ventriculomegaly in atrophy combined with enlarged convexity sulci. METHODICAL INNOVATIONS: Special magnetic resonance imaging (MRI) techniques can be used to evaluate cerebrospinal fluid (CSF) flow but are not yet part of the diagnostic guidelines. ACHIEVEMENTS/PRACTICAL RECOMMENDATIONS: Combined with cross-sectional imaging, well-established clinical and invasive diagnostic tests, such as repeated spinal tap or lumbar drainage with re-evaluation of clinical symptoms lead to a diagnosis and help with preoperative patient selection for CSF diversion. Ventriculoperitoneal CSF shunting has proven to be safe and is the only known successful therapy for NPH.

[Postoperative spine]. / Postoperative Wirbelsäule.

Approximately 15-30 % of surgical procedures involving the lumbar spine are associated with complications that require further diagnostic work-up. The choice of imaging modality for postoperative complications depends on the extent, pattern and temporal evolution of the postoperative neurological signs and symptoms as well as on the preoperative clinical status, the surgical procedure itself and the underlying pathology. The interpretation of imaging findings, in particular the distinction between postoperative complications and normally expected nonspecific postoperative imaging alterations can be challenging and requires the integration of clinical neurological information and the results of laboratory tests. The combination of different imaging techniques might help in cases of equivocal imaging results.

[Orbital inflammatory diseases]. / Entzündliche Erkrankungen der Orbita.

CLINICAL/METHODICAL ISSUE: Inflammatory orbital processes on imaging are often misinterpreted as tumors. STANDARD RADIOLOGICAL METHODS: Imaging comprises computed tomography (CT) and magnetic resonance imaging (MRI). ACHIEVEMENTS: Clinical and laboratory data play a crucial role in diagnosing many inflammatory orbital diseases. Radiological imaging provides a supporting but relevant role. PRACTICAL RECOMMENDATIONS: Clinical examination, including specialized ophthalmological examinations, laboratory diagnostics, and MRI are important in the diagnosis of inflammatory orbital diseases.

[Osler's disease]. / Morbus Osler.

Osler's disease, also known as hereditary hemorrhagic telangiectasia (HHT) and Osler-Weber-Rendu syndrome, is an autosomal dominant disorder leading to abnormal blood vessel formation in the skin, mucous membranes and often in organs, such as the lungs, liver and brain (arteriovenous malformations AVM). Various types are known. Patients may present with epistaxis. Teleangiectasia can be identified by visual inspection during physical examination of the skin or oral cavity or by endoscopy. Diagnosis is made after clinical examination and genetic testing based on the Curacao criteria. Modern imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI) have become more important as they can depict the AVMs. Pulmonary AVMs can be depicted in CT imaging even without the use of a contrast agent while other locations including the central nervous system (CNS) usually require administration of contrast agents. Knowledge of possible clinical manifestations in various organs, possible complications and typical radiological presentation is mandatory to enable adequate therapy of these patients. Interventional procedures are becoming increasingly more important in the treatment of HHT patients.

Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association.

We determined the distribution of repressor-activator protein 1 (Rap1) and the accessory silencing proteins Sir2, Sir3 and Sir4 in vivo on the entire yeast genome, at a resolution of 2 kb. Rap1 is central to the cellular economy during rapid growth, targeting 294 loci, about 5% of yeast genes, and participating in the activation of 37% of all RNA polymerase II initiation events in exponentially growing cells. Although the DNA sequence recognized by Rap1 is found in both coding and intergenic sequences, the binding of Rap1 to the genome was highly specific to intergenic regions with the potential to act as promoters. This global phenomenon, which may be a general characteristic of sequence-specific transcriptional factors, indicates the existence of a genome-wide molecular mechanism for marking promoter regions.

[Pediatric posterior fossa tumors]. / Infratentorielle Hirntumoren bei Kindern.

CLINICAL ISSUE: Tumors of the posterior fossa account for about 50-55% of brain tumors in childhood. DIAGNOSTIC WORKUP: The most frequent tumor entities are medulloblastomas, pilocytic astrocytomas, ependymomas, diffuse midline gliomas and atypical teratoid-rhabdoid tumors. Neuroradiological differential diagnosis with magnetic resonance imaging (MRI) is of considerable importance for preoperative planning as well as planning of follow-up therapy. PERFORMANCE: Most important findings for differential diagnosis of pediatric posterior fossa tumors are tumor location, patient age and the intratumoral apparent diffusion assessed by diffusion-weighted imaging. ACHIEVEMENTS: Advanced MR techniques like MRI perfusion and MR spectroscopy can be helpful both in the initial differential diagnosis and in tumor surveillance, but exceptional characteristics of certain tumor entities should be kept in mind. PRACTICAL RECOMMENDATIONS: Standard clinical MRI sequences including diffusion-weighted imaging are the main diagnostic tool in evaluating posterior fossa tumors in children. Advanced imaging methods can be helpful, but should never be interpreted separately from conventional MRI sequences.

Rapid point-of-care detection of SARS-CoV-2 infection in exhaled breath using ion mobility spectrometry: a pilot study.

BACKGROUND: An effective testing strategy is essential for pandemic control of the novel Coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Breath gas analysis can expand the available toolbox for diagnostic tests by using a rapid, cost-beneficial, high-throughput point-of-care test. We conducted a bi-center clinical pilot study in Germany to evaluate breath gas analysis using multi-capillary column ion mobility spectrometry (MCC-IMS) to detect SARS-CoV-2 infection. METHODS: Between September 23, 2020, and June 11, 2021, breath gas measurements were performed on 380 patients (SARS-CoV-2 real-time polymerase chain reaction (PCR) positive: 186; PCR negative: 194) presenting to the emergency department (ED) with respiratory symptoms. RESULTS: Breath gas analysis using MCC-IMS identified 110 peaks; 54 showed statistically significant differences in peak intensity between the SARS-CoV-2 PCR-negative and PCR-positive groups. A decision tree analysis classification resulted in a sensitivity of 83% and specificity of 86%, but limited robustness to dataset changes. Modest values for the sensitivity (74%) and specificity (52%) were obtained using linear discriminant analysis. A systematic search for peaks led to a sensitivity of 77% and specificity of 67%; however, validation by transferability to other data is questionable. CONCLUSIONS: Despite identifying several peaks by MCC-IMS with significant differences in peak intensity between PCR-negative and PCR-positive samples, finding a classification system that allows reliable differentiation between the two groups proved to be difficult. However, with some modifications to the setup, breath gas analysis using MCC-IMS may be a useful diagnostic toolbox for SARS-CoV-2 infection. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on September 21, 2020 (NCT04556318; Study-ID: HC-N-H-2004).

[Inflammatory diseases of the spinal column and the myelon]. / Entzündliche Erkrankungen der Wirbelsäule und des Myelons.

Inflammatory diseases of the spine and the spinal cord (myelon) can be caused by a wide range of pathological conditions. Except for degenerative inflammatory diseases of the spine, infectious and autoimmune disorders are relatively rare. The latter can also be a significant source of pain and disability, especially if these hard to diagnose conditions go untreated. In cases of advanced disease some entities, such as spondylodiscitis or rheumatoid arthritis can cause severe neurological impairment especially by progressive intraspinal spread. Inflammation of the myelon cannot be depicted with conventional radiographs in general and by computed tomography only occasionally. In these cases magnetic resonance imaging is the method of choice to detect early abnormalities of the myelon and to provide detailed information for the differential diagnosis.

[Postoperative findings in the spinal column]. / Postoperative Befunde an der Wirbelsäule.

Postoperative imaging after spinal surgery is usually performed to document the correct positioning of implants or to rule out complications if patients still suffer from pain after surgery. Depending on the question various imaging modalities can be used all of which have benefits and limitations. Conventional X-ray is used for the documentation of the correct positioning of spinal implants, stability (olisthesis) and during follow-up to rule out fractures or instability of the implants, whereas soft tissue changes cannot be completely assessed. Besides these indications, imaging is usually performed because of ongoing symptoms (pain for the most part) of the patients. Soft tissue changes including persistent or recurrent herniated disc tissue, hematoma or infection can best be depicted using magnetic resonance imaging (MRI) which should be performed within the immediate postoperative period to be able to distinguish physiological development of scar tissue from inflammatory changes in the area of the surgical approach. Often imaging alone cannot differentiate between these and imaging can therefore only be considered as an adjunct. Computed tomography is the modality of choice for the evaluation of bony structures and an adjunct of new therapies such as image-guided application of cement for kyphoplasty or vertebroplasty.

In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins.

BACKGROUND: Reflectance confocal microscopy (RCM) images skin at cellular resolution and has shown utility for the diagnosis of nonmelanoma skin cancer in vivo. Topical application of aluminium chloride (AlCl(3)) enhances contrast in RCM images by brightening nuclei. OBJECTIVES: To investigate feasibility of RCM imaging of shave biopsy wounds using AlCl(3) as a contrast agent. METHODS: AlCl(3) staining was optimized, in terms of concentration vs. immersion time, on excised tissue ex vivo. RCM imaging protocol was tested in patients undergoing shave biopsies. The RCM images were retrospectively analysed and compared with the corresponding histopathology. RESULTS: For 35% AlCl(3) , routinely used for haemostasis in clinic, minimum immersion time was determined to be 1 min. We identified three consistent patterns of margins on RCM mosaic images by varying depth: epidermal margins, peripheral dermal margins, and deep dermal margins. Tumour islands of basal cell carcinoma were identified at peripheral or deep dermal margins, correlating on histopathology with aggregates of neoplastic basaloid cells. Atypical cobblestone or honeycomb patterns were identified at the epidermal margins in squamous cell carcinomas, correlating with a proliferation of atypical keratinocytes extending to biopsy margins. CONCLUSIONS: RCM imaging of shave biopsy wounds is feasible and demonstrates the future possibility of intraoperative mapping in surgical wounds.

Dermoscopic patterns and subclinical melanocytic nests in normal-appearing skin.

BACKGROUND: Dermoscopic patterns of normal-appearing skin have received little scrutiny. We have recently completed an analysis of dermoscopic patterns of naevi in children. OBJECTIVES: To describe dermoscopic patterns in the normal-appearing skin surrounding naevi and to explore histological features of patterned background skin. METHODS: Dermoscopic images of back naevi were obtained from a population-based sample of fifth grade students. The dermoscopic pattern of the background skin around the naevi was analysed. We examined histopathological features of background skin patterns in a convenience sample of seven specimens from six adult patients. RESULTS: We observed a dermoscopic pattern in the background of normal-appearing skin in 41% of 1192 dermoscopic images from the backs of the 443 children. The background skin pattern was less frequent in individuals with a fair skin (P < 0.001). A globular pattern was observed in 201 images (17%) and a reticular pattern was seen in 287 images (24%), of which 112 images also showed globules. Inter-rater reliability between the two observers for a random sample of 100 images was excellent (kappa = 0.77). In four specimens with a globular background pattern, microscopic melanocytic nests were observed in the normal-appearing skin. No subclinical naevus nests were observed in three reticular pattern specimens. CONCLUSIONS: Dermoscopically recognized patterns are commonly present in clinically normal skin of children. Microscopic melanocytic nests may be observed in normal-appearing skin with a globular skin pattern.

Sex-specific assembly of a dosage compensation complex on the nematode X chromosome.

In nematodes, flies, and mammals, dosage compensation equalizes X-chromosome gene expression between the sexes through chromosome-wide regulatory mechanisms that function in one sex to adjust the levels of X-linked transcripts. Here, a dosage compensation complex was identified in the nematode Caenorhabditis elegans that reduces transcript levels from the two X chromosomes in hermaphrodites. This complex contains at least four proteins, including products of the dosage compensation genes dpy-26 and dpy-27. Specific localization of the complex to the hermaphrodite X chromosomes is conferred by XX-specific regulatory genes that coordinately control both sex determination and dosage compensation.

DPY-26, a link between dosage compensation and meiotic chromosome segregation in the nematode.

The DPY-26 protein is required in the nematode Caenorhabditis elegans for X-chromosome dosage compensation as well as for proper meiotic chromosome segregation. DPY-26 was shown to mediate both processes through its association with chromosomes. In somatic cells, DPY-26 associates specifically with hermaphrodite X chromosomes to reduce their transcript levels. In germ cells, DPY-26 associates with all meiotic chromosomes to mediate its role in chromosome segregation. The X-specific localization of DPY-26 requires two dosage compensation proteins (DPY-27 and DPY-30) and two proteins that coordinately control both sex determination and dosage compensation (SDC-2 and SDC-3).

Systematic Radiation Dose Reduction in Cervical Spine CT of Human Cadaveric Specimens: How Low Can We Go?

BACKGROUND AND PURPOSE: While the use of cervical spine CT in trauma settings has increased, the balance between image quality and dose reduction remains a concern. The purpose of our study was to compare the image quality of CT of the cervical spine of cadaveric specimens at different radiation dose levels. MATERIALS AND METHODS: The cervical spine of 4 human cadavers (mean body mass index; 30.5 ± 5.2 kg/m2; range, 24-36 kg/m2) was examined using different reference tube current-time products (45, 75, 105, 135, 150, 165, 195, 275, 355 mAs) and a tube voltage of 120 kV(peak). Data were reconstructed with filtered back-projection and iterative reconstruction. Qualitative image noise and morphologic characteristics of bony structures were quantified on a Likert scale. Quantitative image noise was measured. Statistics included analysis of variance and the Tukey test. RESULTS: Compared with filtered back-projection, iterative reconstruction provided significantly lower qualitative (mean noise score: iterative reconstruction = 2.10/filtered back-projection = 2.18; P = .003) and quantitative (mean SD of Hounsfield units in air: iterative reconstruction = 30.2/filtered back-projection = 51.8; P < .001) image noise. Image noise increased as the radiation dose decreased. Qualitative image noise at levels C1-4 was rated as either "no noise" or as "acceptable noise." Any shoulder position was at level C5 and caused more artifacts at lower levels. When we analyzed all spinal levels, scores for morphologic characteristics revealed no significant differences between 105 and 355 mAs (P = .555), but they were worse in scans at 75 mAs (P = .025). CONCLUSIONS: Clinically acceptable image quality of cervical spine CTs for evaluation of bony structures of cadaveric specimens with different body habitus can be achieved with a reference mAs of 105 at 120 kVp with iterative reconstruction. Pull-down of shoulders during acquisition could improve image quality but may not be feasible in trauma patients with unknown injuries.

The paradoxical advantages and disadvantages of natural selection: the case history of Charles Darwin.

The biology of natural selection is an enduring mystery, as is the nature of Charles Darwin's chronic illness. Of the theories advanced to explain the latter, Oedipal conflicts and Chagas' disease are preeminent. Hypomania, however, propelled Darwin to the pinnacle of scientific achievement and good health, the depression that followed condemning him to intellectual stagnation, lethargy, impaired memory and concentration, and incapacitating gastrointestinal disorders. Examples of natural selection in humans are much sought after when, ironically, one need look no further than Darwin himself.

The Caenorhabditis elegans dosage compensation machinery is recruited to X chromosome DNA attached to an autosome.

The dosage compensation machinery of Caenorhabditis elegans is targeted specifically to the X chromosomes of hermaphrodites (XX) to reduce gene expression by half. Many of the trans-acting factors that direct the dosage compensation machinery to X have been identified, but none of the proposed cis-acting X chromosome-recognition elements needed to recruit dosage compensation components have been found. To study X chromosome recognition, we explored whether portions of an X chromosome attached to an autosome are competent to bind the C. elegans dosage compensation complex (DCC). To do so, we devised a three-dimensional in situ approach that allowed us to compare the volume, position, and number of chromosomal and subchromosomal bodies bound by the dosage compensation machinery in wild-type XX nuclei and XX nuclei carrying an X duplication. The dosage compensation complex was found to associate with a duplication of the right 30% of X, but the complex did not spread onto adjacent autosomal sequences. This result indicates that all the information required to specify X chromosome identity resides on the duplication and that the dosage compensation machinery can localize to a site distinct from the full-length hermaphrodite X chromosome. In contrast, smaller duplications of other regions of X appeared to not support localization of the DCC. In a separate effort to identify cis-acting X recognition elements, we used a computational approach to analyze genomic DNA sequences for the presence of short motifs that were abundant and overrepresented on X relative to autosomes. Fourteen families of X-enriched motifs were discovered and mapped onto the X chromosome.