[Presacral lesion at the rima ani]. / Präsakrale Raumforderung an der Rima ani.

A 26-year-old woman presented with a painful bulge at the rima ani. The tumor was located in the presacral region. Histological examination revealed a well-circumscribed biphenotypical tumor with papillary configured myxoid areas and strongly sclerosing regions. This case of a myxopapillary ependymoma is a rare example of a myxoid neoplastic lesion in the sacral region.

Final results from the Betaseron (interferon ß-1b) Pregnancy Registry: a prospective observational study of birth defects and pregnancy-related adverse events.

OBJECTIVE: Women with multiple sclerosis are often diagnosed and treated during their reproductive years. Limited data are available on the safety of treatment during pregnancy. The Betaseron Pregnancy Registry prospectively monitored women exposed to interferon ß-1b (IFNß-1b) during pregnancy to estimate the rates of birth defects, spontaneous abortions (SABs) and other negative outcomes in this population. DESIGN: From 2006 to 2011, this observational registry enrolled women exposed prior to conception or during pregnancy (but prior to or without abnormalities on prenatal screening). Follow-up continued from enrolment through the 4-month paediatric visit. SETTING: Patients in the USA who met these criteria were enrolled in the registry. RESULTS: The registry enrolled 99 pregnant women; 3 were lost to follow-up. The earliest exposure to IFNß-1b occurred during the first trimester for 95 pregnancies and in the third trimester for 1 pregnancy. There were 99 birth outcomes (3 twins), including 86 (86.9%) live births, 11 (11.1%) SABs and 2 (2%) stillbirths. Birth defects were reported in five (5.1%) cases. Rates of birth defects and SAB were not significantly different from population comparators. No developmental concerns were identified at the 4-month paediatric visit. CONCLUSIONS: The small sample size limits the ability to draw definitive conclusions; however, there was no pattern to suggest increased negative outcomes with IFNß-1b. CLINICAL TRIALS REGISTRATION NUMBER: NCT00317564.

[The histological confirmation of diffuse axonal injury in severe brain injury survivors]. / Der histologische Nachweis des diffusen axonalen Hirnschadens bei Überlebenden schwerer Schädel-Hirntraumen.

Diffuse axonal injury (DAI) plays a major role after traumatic brain injury (TBI). Its imaging is based on computed tomography (CT) or magnetic resonance imaging (MRI). However, DAI is a histological diagnosis. Histopathological findings on survival after TBI are very rare. Hence, it is unclear whether the neuroradiological findings are of clinical relevance. Cerebral specimens were taken in 24 patients with TBI requiring surgery. The presence of histopathological evidence for DAI was evaluated. Specimens were taken from an extracranial brain prolapse (n = 2) and from peripheral parts of a brain contusion (n = 22). Histological findings were correlated to the clinical course and the neurological status. A clinical follow-up was carried out 6 months after the surgery using the Glasgow Outcome Score (GOS). The study was approved by the local ethics committee. Specimens taken were temporal (n = 11), frontal (n = 8), parietal (n = 4) and cerebellar (n = 1). The incidence of DAI within these specimens was 30% (7 with DAI, 17 without DAI). DAI was verifiable up to 3 days after trauma. There was no correlation between DAI and Marshall classification in CT. The period of coma was longer in subjects with DAI. There was no difference in GOS in the case of a verified DAI. These results enforce the prognostic and neuroradiologic relevance of DAI. However, it is debatable whether the pathomorphologic findings in CT or MRI represent the histological findings of DAI. We suggest a multicentre study for further clarification.

[Severe bilateral keratomalacia]. / Schwere bilaterale Keratomalazie.

In contrast to developing countries, xerophthalmia is rather rare in developed countries. Malnutrition (e.g. in mentally deficient or psychiatric patients), chronic liver diseases (e.g. due to alcoholism), or bowel surgery can be reasons for vitamin A deficiency in developed countries. The prodromal stage of hypovitaminosis A is characterized by nyctalopia, which often manifests subclinically. Longer lasting and severe cases of vitamin A deficiency may be complicated by the occurrence of keratinizing metaplasia in the cornea and conjunctiva, xerosis, keratomalacia or blindness.

Aldehyde dehydrogenase and HSP90 co-localize in human glioblastoma biopsy cells.

The concept of a stem cell subpopulation as understood from normal epithelial tissue or bone marrow function has been extended to our understanding of cancer tissue and is now the target of treatment efforts specifically directed to this subpopulation. In glioblastoma, as well as in other cancers, increased expression of aldehyde dehydrogenase (ALDH) has been found localized within a minority sub-population of tumor cells which demonstrate stem cell properties. A separate body of research associated increased expression of heat-shock protein-90 (HSP90) with stem cell attributes. We present here results from our initial immunohistochemistry study of human glioblastoma biopsy tissue where both ALDH and HSP90 tended to be co-expressed in high amounts in the same minority of cells. Since 12% of all cells in the six biopsies studied were ALDH positive and 17% were HSP90 positive, by chance alone 2% would have been expected to be positive for both. In fact 7% of all cells simultaneously expressed both markers-a significant difference (p = 0.037). That two previously identified proteins associated with stem cell attributes tend to be co-expressed in the same individual glioblastoma cells might have clinical utility. Disulfiram, used to treat alcoholism for half-a century now, is a potent ALDH inhibitor and the old anti-viral drug ritonavir inhibits HSP90. These should be explored for the potential to retard aspects of glioblastoma stem cells' function subserved by ALDH and HSP90.

[Functional diagnostic options for advanced and end stage glaucoma]. / Funktionsdiagnostische Möglichkeiten bei fortgeschrittenem oder präterminalem Glaukom.

The visual functional diagnostics for patients with advanced glaucomatous optic neuropathy are subject to challenge. Reduced visual acuity, instable fixation and extensive scotomata frequently lead to incorrect results within the central 30° or 24° field. Static automatic perimetry (SAP) in particular is often hampered by extended examination time and fatigue especially in older patients. Focusing of the examination towards the central 10° field using a dense test grid (2° distance between stimulus locations) allows a more exact assessment of the small remaining central island. Tailoring the examination area towards the central 10° field may be useful even in cases with a mean deviation (MD) of 15 dB. In cases of advanced visual field loss kinetic perimetry is superior to static perimetry for various reasons: sharply demarcated visual field defects can be comparatively easily delineated (edge detection); the results are more reliable because fixation can be easily controlled and fatigue is much less pronounced in this interactive examination procedure. However, manual kinetic visual field testing within the central 5° using the conventional Goldmann perimeter is almost impossible due to technical reasons. Semi-automated kinetic perimetry, presenting moving stimuli along interactively defined vectors is a useful tool under these circumstances. The standardized presentation of kinetic stimuli is also feasible within the pericentral region and has particular advantages also with regard to follow-up examinations. On the other hand, detection and delineation of small visual field remnants are comparatively difficult to handle with this kind of vector-based kinetic perimetry.

[Fundus perimetry in functional diagnostics of glaucoma. Applicable in the practice?]. / Fundusperimetrie in der Glaukomdiagnostik. Schon praktisch anwendbar?

Examination of the visual field using static automated perimetry (SAP) is the method of choice for the detection of functional damage secondary to glaucoma. However, with SAP early visual field defects might be missed even if there is already visible damage of the retinal nerve fibre. The microperimetry or beter fundus perimetry provides a detailed examination of the differential luminance threshold within defined retinal areas. However, in contrast to lesions of the retinal receptors, in cases of glaucomatous damage the retinal fibre course has to be considered resulting in a displacement between the structural lesion and the location of the related functional defect. The functional damage may be detected at earlier stages and with enhanced spatial resolution compared to conventional SAP. The extra costs and time associated with the application of fundus perimetry have prevented its widespread use. Current developments are leading to new options.

Prenatal diagnosis and cesarean section in a large, population-based birth defects registry.

OBJECTIVE: To describe the patterns of cesarean section (CS) and vaginal delivery by type of birth defect and determine whether prenatal diagnosis predicts a higher or lower likelihood of CS for selected defect categories. METHODS: Data from a large population-based registry were analyzed to determine percentages of vaginal versus CS delivery for each of 49 categories of birth defects. Odds ratios and statistical significance were computed to determine if a record of prenatal diagnosis (PND) predicted delivery mode. Cases were liveborn children with any of these defects born in Texas between 1997 and 2005. RESULTS: Forty-three percent of infants in the study were delivered by CS, with a range of 25.3% (aniridia) to 62.4% (spina bifida). A record of prenatal diagnosis of the primary assigned birth defect was found in 43.0% of all records but varied substantially by defect category. PND significantly predicted higher CS percentages for spina bifida without anencephaly, encephalocele, hydrocephaly, transposition of the great vessels, ventricular septal defect, pulmonary valve atresia/stenosis, craniosynostosis, diaphragmatic hernia, gastroschisis, and trisomy 21. Vaginal delivery was predicted by PND of anencephaly, agenesis, aplasia, or hypoplasia of the lung, renal agenesis or dysgenesis, and trisomy 18. CONCLUSION: Texas children with birth defects are more likely to have been delivered by CS than the population in general. For several types of defects, prenatal diagnosis is predictive of higher odds of CS; for others, especially fatal defects, PND predicts lower CS likelihood.

[Headaches from an ophthalmological perspective]. / Kopfschmerzen aus ophthalmologischer Sicht.

Headaches are a common and widespread complaint. Differential diagnostics are crucial for successful therapy and often require an interdisciplinary approach. General practitioners tend to refer patients with extraordinary types of headaches to physicians specialized in neurology, ophthalmology and otolaryngology. This article offers an overview about the range of headache disorders particularly associated with the ophthalmologic anatomy and function.

[Measurement of the central corneal thickness using optical reflectometry and ultrasound]. / Messung der zentralen Hornhautdicke mittels optischer Reflektometrie im Vergleich zur Ultraschall-Pachymetrie.

AIM: The aim of this study was to evaluate measurements of the central corneal thickness using OLCR and ultrasound pachymetry (IOPac). MATERIALS AND METHODS: In a retrospective observational study, fifty patients were assessed. Central corneal thickness was measured using OLCR and ultrasound. RESULTS: The IOPac system shows results for the central corneal thickness between 419 µm and 613 µm. The OLCR values ranged between 421 and 598 µm. The coefficient of variation was 1.12 % in the case of the IOPac and 0.97 % in the case of the OLCR. The paired Student's t-test showed no significant differences between the two methods. The agreement between the two methods was high with r = 0.929. CONCLUSIONS: The agreement between the results for the central corneal thickness using OLCR and ultrasound is high. The OLCR is a non-touch technology that does not require local anaesthesia, thus further reducing the risk of infection or mechanical trauma. Especially in surgical applications or glaucoma assessments, movement artefacts need to be ruled out, which potentially could cause wrong values and thus lead to wrong decisions.

Mutations in FAM20C also identified in non-lethal osteosclerotic bone dysplasia.

Raine syndrome is an osteosclerotic bone dysplasia, which has proved to be lethal within the first few weeks of life in all the reported cases to date. We recently identified a chromosomal rearrangement and telomeric microdeletion in a patient with Raine syndrome and subsequently identified mutations in the FAM20C gene, located within the deleted region, in six additional Raine syndrome cases. The phenotype of Raine syndrome in the cases examined was remarkably consistent with generalized osteosclerosis of all bones, periosteal bone formation, characteristic facial phenotype and lethal within the first few weeks of life. In the current study, we have identified two unrelated individuals who presented at birth with a sclerosing bone dysplasia with features very similar to those in Raine syndrome but who survived infancy and are now aged 8 and 11 years, respectively. Mutations in FAM20C, consistent with autosomal recessive inheritance, were identified in both cases. In the first case, a homozygous non-synonymous mutation in exon 7 (1309G>A D437N) was identified, and in the second case, compound heterozygosity for non-synonymous mutations in exon 2 (731T>A I244N) and in exon 3 (796G>A G266R) was revealed. Raine syndrome has been previously considered to be a neonatal lethal condition. However, the identification of mutations in these two patients confirms a broader phenotypic spectrum and that mutation of FAM20C does not always lead to the infantile lethality previously seen as a prerequisite for Raine syndrome diagnosis.

[Endophthalmitis after repeated bevacizumab injections]. / Endophthalmitis nach mehrfachen Bevacizumab-Injektionen. Diagnose: Immunreaktion mit Pseudohypopyon nach mehrfachen Bevacizumab-Injektionen.

Symptoms resembling endophthalmitis developed 1 day after the seventh injection of bevacizumab in a 76-year-old woman with extrafoveal occult choroidal neovascularization in conjunction with age-related macular degeneration. The diagnosis reached was an immune reaction with pseudohypopyon after repeated bevacizumab injections. The condition resolved completely within 5 days under sole administration of corticosteroids. Treatment was then continued with pegaptanib and no further intraocular irritation occurred.

Genomic duplication resulting in increased copy number of genes encoding the sister chromatid cohesion complex conveys clinical consequences distinct from Cornelia de Lange.

BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder. Heterozygous point mutations in three genes (NIPBL, SMC3 and SMC1A), encoding components of the sister chromatid cohesion apparatus, are responsible for approximately 50-60% of CdLS cases. Recent studies have revealed a high degree of genomic rearrangements (for example, deletions and duplications) in the human genome, which result in gene copy number variations (CNVs). CNVs have been associated with a wide range of both Mendelian and complex traits including disease phenotypes such as Charcot-Marie-Tooth type 1A, Pelizaeus-Merzbacher, Parkinson, Alzheimer, autism and schizophrenia. Increased versus decreased copy number of the same gene can potentially cause either similar or different clinical features. METHODS AND RESULTS: This study identified duplications on chromosomes 5 or X using genome wide array comparative genomic hybridisation (aCGH). The duplicated regions contain either the NIPBL or the SMC1A genes. Junction sequences analyses revealed the involvement of three genomic rearrangement mechanisms. The patients share some common features including mental retardation, developmental delay, sleep abnormalities, and craniofacial and limb defects. The systems affected are the same as in CdLS, but clinical manifestations are distinct from CdLS; particularly the absence of the CdLS facial gestalt. CONCLUSIONS: The results confirm the notion that duplication CNV of genes can be a common mechanism for human genetic diseases. Defining the clinical consequences for a specific gene dosage alteration represents a new "reverse genomics" trend in medical genetics that is reciprocal to the traditional approach of delineation of the common clinical phenotype preceding the discovery of the genetic aetiology.

[OCT-based re-injections for anti-VEGF-treatment for neovascular ARMD]. / OCT-Befund als Reinjektionskriterium bei der Anti-VEGF-Therapie für neovaskuläre AMD.

BACKGROUND: We present an optical coherence tomography (OCT)-based individual reinjection procedure for bevacizumab treatment in neovascular age-related macular degeneration (ARMD). METHODS: Thirty-two patients with active subfoveal occult choroidal neovascularisation in ARMD received a single intravitreal injection of 1.25 mg bevacizumab and were reinjected based on new or persisting subretinal or intraretinal fluid on OCT. Patient visits were every 6-8 weeks. RESULTS: After a single injection, 74% of patients demonstrated complete retinal fluid absorption, with 44% of patients showing no relapse during a follow-up of 30+/-13 weeks. Fifty-six percent of patients required a second injection after a mean of 19+/-8 weeks, with 82% of patients showing absorption of macular fluid thereafter with regain of their previous achieved best-corrected visual acuity. Thirty-two percent did not require any further injection (follow-up 32+/-12 weeks). Of those patients not showing retinal fluid absorption after the first injection (26%), 44% demonstrated retinal fluid absorption after the second injection. All patients achieved stabilisation of visual acuity during follow-up, with 30% of patients showing a significant gain of >or=3 lines. CONCLUSIONS: OCT-based reinjections of bevacizumab in neovascular ARMD reduce the number of injections and lead to anatomic and functional retinal stabilisation.

Intraneural perineuriomas; a rare entity. Clinical, surgical and neuropathological details in the management of these lesions.

OBJECTIVE: Perineuriomas are rare benign peripheral nerve sheath tumors, which have only been included in the WHO classification system since 2000. They are divided into intraneural perineuriomas and soft tissue tumors. Intraneural perineuriomas were previously known as localized hypertrophic neuropathies. Because of their rarity there are only case reports in the literature. METHODS: Between 1992 and 2006 surgery was performed on four patients suffering from intraneural perineuriomas in our hospital. All patients were males, aged five, ten, twenty and twenty-nine years old. One of the tumors occurred in the ulnar nerve, one in the common peroneal part of the sciatic nerve and two of them in the radial nerve. In a retrospective study the clinical, electrophysiological and imaging data of the patients was analyzed. Two of these patients had previously been treated with decompression and neurolysis of the nerve for the suspicion of a nerve compression syndrome. Revisions were necessary following progressive neurological deterioration postoperatively. Explorations of the nerves showed nerve tumors. The tumors were resected and nerve grafting was performed. CONCLUSIONS: These tumors tend to affect the nerves of the upper extremities in children or young adults. The predominant symptom is a slow-progressive paralysis. Two of the four patients showed a partial improvement of their motor and sensorial nerve deficits in the long-term follow-up following complete tumor resection and interpositional autologous nerve grafts. No relapse could be observed. In cases of slow-progressive neurological deficits of a peripheral nerve in young patients the differential diagnosis should include the intraneural perineuriomas.

[OCT-guided reinjection of 2.5 mg bevacizumab for treating macular edema due to retinal vein occlusion]. / OCT-Befund als Reinjektionskriterium für die 2,5-mg-Bevacizumab-Therapie bei venösen retinalen Verschlüssen.

BACKGROUND: Macular edema (ME) due to retinal vein occlusion can be successfully treated with intravitreal bevacizumab therapy. There is no common recommendation concerning time intervals and criteria for reinjection. METHOD: Sixty-three patients (follow-up 30+/-18 weeks) received intravitreal injections of 2.5 mg bevacizumab. Reinjection was performed only if optical coherence tomography (OCT) showed persistent or recurrent ME. Check-ups were performed every 6-8 weeks. RESULTS: There was complete resolution of macular edema in 31 patients after the first injection (improvement in visual acuity 3.7+/-3.7 lines); 65.2% of these patients developed recurrence of ME within 13.3+/-4.4 weeks, which completely resolved again after a second injection. Visual acuity gained the same level as after the first injection. Another relapse of ME in this group occurred in 69% of patients after another 13.4+/-5.4 weeks. Patients with persistent ME after the first injection (n=32) received a second injection, initially leading to resolution of ME in 33.3%, but all of these patients had a relapse within 13.9+/-4.1 weeks. CONCLUSION: OCT-guided reinjection leads to anatomic and functional stabilization or improvement even if transient recurrence of ME occurs.

[Results of the ocular hypertension treatment study and the confocal scanning laser ophthalmoscopy ancillary study and evaluation of the heidelberg retina tomograph]. / Konsequenzen der "Ocular Hypertension Treatment Study" und der "Confocal Scanning Laser Ophthalmoscopy Ancillary Study" auf die Befundauswertung des Heidelberg Retina Tomographen.

The Ocular Hypertension Treatment Study (OHTS) has shown that analyzing changes of the optic disc configuration is superior to evaluating visual field findings for the early detection of primary open angle glaucoma. The Confocal Scanning Laser Ophthalmoscopy Ancillary Study (CSLO) is the first study to reveal that certain topographic baseline measurements of the optic disc are significantly associated with the development of primary open angle glaucoma in patients with ocular hypertension. An abnormally increased "mean height contour" value proved to be the individual parameter connected with the highest risk. The reliability of the Moorfields Regression Analysis of certain individual sectors during early detection of a primary angle glaucoma is higher than that of the global measurement. The temporal superior and inferior as well as the nasal inferior sectors have the highest positive predictive values and the largest risks in both univariate and multivariate analysis.