[Diagnostics and surgical treatment of painful neuromas]. / Diagnostik und chirurgische Therapie schmerzhafter Neurome.

BACKGROUND: Painful neuromas that often develop after peripheral nerve injury require adequate diagnosis and treatment because of the suffering they cause. The scientific basis for the development of painful neuromas has not yet been sufficiently investigated. In addition to conservative procedures, a larger number of surgical techniques are available for treatment of painful neuromas. OBJECTIVE: A review of the basic principles, diagnostic and treatment options for painful neuromas. MATERIAL AND METHODS: Presentation of the scientific basis regarding the development of painful neuromas. Illustration and discussion of the most common diagnostic and treatment procedures. RESULTS: The scientific basis regarding the development of painful neuromas after peripheral nerve injury has not yet been adequately developed. In order to be able to make a correct diagnosis, the use of standardized diagnostic criteria and adequate imaging techniques are recommended. In the sense of a paradigm shift, the use of the formerly neuroma-bearing nerve for reinnervation of target organs is to be preferred over mere burying in adjacent tissue. CONCLUSION: In addition to standardized diagnostics the management of painful neuromas often requires a surgical intervention after all conservative therapeutic measures have been exhausted. As an alternative to restoring the continuity of the injured nerve, targeted reinnervation of electively denervated target organs by the formerly neuroma-bearing nerve is preferable over other techniques.

MR Imaging and Clinical Characteristics of Diffuse Glioneuronal Tumor with Oligodendroglioma-like Features and Nuclear Clusters.

BACKGROUND AND PURPOSE: Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a new, molecularly defined glioneuronal CNS tumor type. The objective of the present study was to describe MR imaging and clinical characteristics of patients with DGONC. MATERIALS AND METHODS: Preoperative MR images of 9 patients with DGONC (median age at diagnosis, 9.9 years; range, 4.2-21.8 years) were reviewed. RESULTS: All tumors were located superficially in the frontal/temporal lobes and sharply delineated, displaying little mass effect. Near the circle of Willis, the tumors encompassed the arteries. All except one demonstrated characteristics of low-to-intermediate aggressiveness with high-to-intermediate T2WI and ADC signals and bone remodeling. Most tumors (n = 7) showed a homogeneous ground-glass aspect on T2-weighted and FLAIR images. On the basis of the original histopathologic diagnosis, 6 patients received postsurgical chemo-/radiotherapy, 2 were irradiated after surgery, and 1 patient underwent tumor resection only. At a median follow-up of 61 months (range, 10-154 months), 6 patients were alive in a first complete remission and 2 with stable disease 10 and 21 months after diagnosis. The only patient with progressive disease was lost to follow-up. Five-year overall and event-free survival was 100% and 86±13%, respectively. CONCLUSIONS: This case series presents radiomorphologic characteristics highly predictive of DGONC that contrast with the typical aspects of the original histopathologic diagnoses. This presentation underlines the definition of DGONC as a separate entity, from a clinical perspective. Complete resection may be favorable for long-term disease control in patients with DGONC. The efficacy of nonsurgical treatment modalities should be evaluated in larger series.

TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

The role of ICP overnight monitoring (ONM) in children with suspected craniostenosis.

PURPOSE: Secondary craniostenosis is a relevant problem pediatric neurosurgeons are confronted with and poses challenges regarding reliable diagnosis of raised ICP, especially in case of absent or questionable papilledema. How to identify children with elevated ICP is still controversial and diagnostics vary. We report on our experience with computerized ICP ONM in relation to imaging derived parameters. METHODS: Thirty-four children with primary or secondary craniostenosis and clinical suspicion of raised ICP were investigated. We compared clinical signs, history, and radiographic assessment with the results of computerized ICP ONM. Differences were significant at a p < 0.05. RESULTS: Baseline ICP was significantly higher in patients with combined suture synostosis, who also had a higher rate of questionable papilledema. Children with narrowed external CSF spaces in MRI had significantly higher ICP levels during REM sleep. Mean RAP was significantly elevated in patients with multi-suture synostosis, indicating poor intracranial compensatory reserve. Syndromal craniostenosis was associated with elevated ICP, RAP was significantly lower, and skull X-rays showed more impressions (copper beaten skull). RAP increased with more severe impressions only to decline in most severe abnormalities, indicating exhaustion of cerebrovascular reserve at an upper ICP breakpoint of 23.9 mmHg. Headaches correlated to lower ICP and were not associated with more severe X-ray abnormalities. CONCLUSION: Narrowed external CSF spaces in MRI seem to be associated to elevated ICP. Skull X-rays can help to identify patients at risk for chronically elevated ICP. Severe X-ray changes correlate with exhausted cerebrovascular reserve as indicated by RAP decline. Only ICP monitoring clearly identifies raised ICP and low brain compliance. Thus, in cases with ambiguous imaging, ONM constitutes an effective tool to acquire objective data for identification of surgical candidates.

Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) - a molecularly defined glioneuronal CNS tumour class displaying recurrent monosomy 14.

AIMS: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. PATIENTS AND METHODS: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. RESULTS: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. CONCLUSIONS: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters.

Age-adjusted CSF ß2-microglobulin and lactate are increased and ACE is decreased in patients with multiple sclerosis, but only lactate correlates with clinical disease duration and severity.

We compared cerebrospinal fluid levels of lactate, ß2-microglobulin and angiotensin-converting enzyme (ACE) between 438 untreated patients with multiple sclerosis and 276 patients with non-inflammatory neurological disorders. Age-adjusted ß2-microglobulin and lactate were significantly higher and ACE was significantly lower in MS patients than in controls. ß2-microglobulin and ACE positively correlated with high significance both in MS patients and controls. While disease duration negatively correlated and progression index, defined as EDSS score divided by disease duration in years, positively correlated with age-adjusted lactate levels, both did neither correlate with ß2-microglobulin nor with ACE. Both CSF ß2-microglobulin and ACE deserve further investigation as biomarkers of multiple sclerosis pathophysiology.

Treatment responses in multidrug-resistant tuberculosis in Germany.

BACKGROUND: Excellent treatment outcomes have recently been reported for patients with multi/extensively drug-resistant tuberculosis (M/XDR-TB) in settings where optimal resources for individualised therapy are available. OBJECTIVE: To ascertain whether differences remain in treatment responses between patients with M/XDR-TB and those with non-M/XDR-TB. METHOD: Patients with TB were prospectively enrolled between March 2013 and March 2016 at five hospitals in Germany. Treatment was conducted following current guidelines and individualised on the basis of drug susceptibility testing. Two-month and 6-month sputum smear and sputum culture conversion rates were assessed. A clinical and radiological score were used to assess response to anti-tuberculosis treatment. RESULTS: Non-M/XDR-TB (n = 29) and M/XDR-TB (n = 46) patients showed similar rates of microbiological conversion: 2-month smear conversion rate, 90% vs. 78%; culture conversion rate, 67% vs. 61%; time to smear conversion, 19 days (IQR 10-32) vs. 31 days (IQR 14-56) (P = 0.066); time to culture conversion, 39 days (IQR 17-67) vs. 39 days (IQR 6-85) (P = 0.191). Both clinical and radiological scores decreased after the introduction of anti-tuberculosis treatment. CONCLUSION: There were no significant differences in scores between the two groups until 6 months of treatment. Under optimal clinical conditions, with the availability of novel diagnostics and a wide range of therapeutic options for individualised treatment, patients with M/XDR-TB achieved 6-month culture conversion rates that were compatible with those in patients with non-M/XDR-TB.

The minimal important difference for target lobe volume reduction after endoscopic valve therapy.

Objective: Endoscopic valve therapy aims at target lobe volume reduction (TLVR) that is associated with improved lung function, exercise tolerance and quality of life in emphysema patients. So far, a TLVR of >350 mL was considered to be indicative of a positive response to treatment. However, it is not really known what amount of TLVR is crucial following valve implantation. Patients and methods: TLVR, forced expiratory volume in 1 second (FEV1), residual volume (RV) and 6-minute walk distance (6-MWD) were assessed before and 3 months after valve implantation in 119 patients. TLVR was calculated based on computed tomography (CT) scan analysis using imaging software (Apollo; VIDA Diagnostics). Minimal important difference estimates were calculated by anchor-based and distribution-based methods. Results: Patients treated with valves experienced a mean change of 0.11 L in FEV1, -0.51 L in RV, 44 m in 6-MWD and a TLVR of 945 mL. Using a linear regression and receiver operating characteristic analysis based on two of three anchors (ΔFEV1, ΔRV), the estimated minimal important difference for TLVR was between 890 and 1,070 mL (ie, 49%-54% of the baseline TLV). Conclusion: In future, a TLVR between 49% and 54% of the baseline TLV, should be used when interpreting the clinical relevance.

Paradigm-shift: radiological changes in the asymptomatic iNPH-patient to be: an observational study.

BACKGROUND: Many radiological signs are known for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH). However, there is little information about these signs in the pre-symptomatic phase. For pathophysiological investigative purposes we conducted a descriptive image analysis study on pre-symptomatic patients. METHODS: Patients that had contact with either the neurological or neurosurgical department of the university hospital Tuebingen from 2010 through 2016 with magnetic resonance images > 3 years before onset of symptoms, were included. The date of onset and severity of symptoms, date of first imaging and birth date were recorded. Evan's index (EI), width of the third ventricle (3VW), tight high convexity (THC), Sylvian fissure, extent of white matter hyperintensities and aqueductal flow were assessed in images before and around symptom onset. RESULTS: Ten patients were included. In all ten patients the first symptom was gait disturbance. Nine of ten pre-symptomatic images showed classic signs for iNPH. EI showed a significant increase between the pre-symptomatic and symptomatic phase. 3VW showed a trend for increase without significance. THC changed back and forth over time within some patients. CONCLUSIONS: In accordance with the scarce literature available, radiological changes are present at least 3 years before onset of iNPH-symptoms. EI seems to be a robust measure for pre-symptomatic radiological changes. Extrapolating the data, the development of iNPH typical changes might be an insidious process and the development of THC might be a variable and non-linear process. Further studies with larger sample sizes are necessary to put these findings into the pathophysiological perspective for the development of iNPH.

Next generation of ventricular catheters for hydrocephalus based on parametric designs.

BACKGROUND: The flow pattern of the cerebrospinal fluid is probably the most important factor related to obstruction of ventricular catheters during the normal treatment of hydrocephalus. To better comprehend the flow pattern, we have carried out a parametric study via numerical models of ventricular catheters. In previous studies, the flow was studied under steady and, recently, in pulsatile boundary conditions by means of computational fluid dynamics (CFD) in three-dimensional catheter models. OBJECTIVE: This study aimed to bring in prototype models of catheter CFD flow solutions as well to introduce the theory behind parametric development of ventricular catheters. METHODS: A preceding study allowed deriving basic principles which lead to designs with improved flow patterns of ventricular catheters. The parameters chosen were the number of drainage segments, the distances between them, the number and diameter of the holes on each segment, as well as their relative angular position. RESULTS: CFD results of previously unreleased models of ventricular catheter flow solutions are presented in this study. Parametric development guided new designs with better flow distribution while lowering the shear stress of the catheters holes. High-resolution 3D printed catheter solutions of three models and basic benchmark testing are introduced as well. CONCLUSIONS: The next generation of catheter with homogeneous flow patterns based on parametric designs may represent a step forward for the treatment of hydrocephalus, by possibly broadening their lifespan.

Pulsatile flow in ventricular catheters for hydrocephalus.

The obstruction of ventricular catheters (VCs) is a major problem in the standard treatment of hydrocephalus, the flow pattern of the cerebrospinal fluid (CSF) being one important factor thereof. As a first approach to this problem, some of the authors studied previously the CSF flow through VCs under time-independent boundary conditions by means of computational fluid dynamics in three-dimensional models. This allowed us to derive a few basic principles which led to designs with improved flow patterns regarding the obstruction problem. However, the flow of the CSF has actually a pulsatile nature because of the heart beating and blood flow. To address this fact, here we extend our previous computational study to models with oscillatory boundary conditions. The new results will be compared with the results for constant flows and discussed. It turns out that the corrections due to the pulsatility of the CSF are quantitatively small, which reinforces our previous findings and conclusions.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.

[Recommendation on temperature management after cardiopulmonary arrest and severe traumatic brain injury in childhood beyond the neonatal period : Statement of the German Society for Neonatology and Pediatric Intensive Care Medicine (GNPI) and the scientific Working Group for Paediatric Anaesthesia (WAKKA) of the German Society of Anaesthesiology and Intensive Care (DGAI)]. / Empfehlung zum Temperaturmanagement nach Atem-Kreislauf-Stillstand und schwerem Schädel-Hirn-Trauma im Kindesalter jenseits der Neonatalperiode : Stellungnahme der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI) und der AG Kinderintensivmedizin des Wissenschaftlichen Arbeitskreises Kinderanästhesie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (WAKKA).

The available data on the effectiveness of therapeutic hypothermia in different patient groups are heterogeneous. Although the benefits have been proven for some collectives, recommendations for the use of hypothermia treatment in other groups are based on less robust data and conclusions by analogy. This article gives a review of the current evidence of temperature management in all age groups and based on this state of knowledge, recommends active temperature management with the primary aim of strict normothermia (36-36.5 °C) for 72 hours after cardiopulmonary arrest or severe traumatic brain injury for children beyond the neonatal period.

Parental perception of treatment and medical care in children with craniosynostosis.

Surgery for craniosynostosis implies a relevant strain on the child and the parents. The development of the child's self-perception and self-confidence is mainly influenced by parental attitudes. The outcomes of 46 patients were analysed, taking into consideration parental perceptions. Parents were asked to indicate their satisfaction with the medical care and treatment provided using a questionnaire. Aesthetics were evaluated by the parents and doctors using a score (1=perfect, 5=deficient). Major surgical complications (2.2%) were reported only in the case of complex synostosis. Reoperation was necessary in 2.9% of isolated cases and 45.5% of complex cases. In general, parents were satisfied with the medical (1.3) and nursing (1.6) inpatient care. Aesthetic assessments differed between parents and surgeons, although not significantly (P=0.27). The surgeons perceived the results to be better than the parents, especially for complex synostosis (1.3 vs. 2.7). Alopecia and persistent asymmetry led to a worse perception of aesthetics. Persistent bone defects did not influence parental satisfaction. All participating parents would opt for surgery again. Surgery led to satisfactory results with a low risk of severe complications. Nevertheless, the outcomes and limits of the surgical procedure must be communicated effectively to parents, especially in complex cases, to avoid a mismatch in expectations. It would be desirable to implement structured interviews with parents during regular treatment management.

Bevacizumab treatment for symptomatic spinal ependymomas in neurofibromatosis type 2.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome associated with vestibular schwannomas, meningiomas, and spinal ependymomas. There have been anecdotal reports of radiographic response of spinal ependymomas in NF2 patients being treated for progressive vestibular schwannomas with bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF). AIMS: The aim of this study was to review the clinical effects of bevacizumab treatment for symptomatic, NF2-associated ependymomas METHODS: We conducted a retrospective review of all patients with NF2 treated with bevacizumab for symptomatic ependymoma at three NF2 specialty centers. Tumor size was evaluated by linear measurements; radiographic response was defined as >20% reduction in tumor size. We also performed immunohistochemical evaluation of NF2-associated symptomatic ependymomas from five patients, including two from this clinical series. RESULTS: Eight patients with NF2 and symptomatic ependymoma were treated with bevacizumab. All patients had subjective clinical improvement with bevacizumab, although only five of eight patients evaluated had radiographic response. All tumors expressed VEGF-R2. Four of five evaluated ependymomas expressed VEGF-R1; one without VEGF-R1 expression was from a patient who showed clinical but not radiographic response. CONCLUSIONS: Treatment using bevacizumab improved symptoms related to NF2-associated ependymomas, often without concurrent radiographic response. This treatment effect may be related to VEGF-R1 expression in NF2-associated ependymoma.

Accumulation of non-compressive fascicular lesions underlies NF2 polyneuropathy.

A distinct polyneuropathy (PNP) syndrome affects up to 66 % of patients with neurofibromatosis II (NF2). Whether this is primarily a diffuse PNP or due to single, surgically amenable mass lesions has not yet been conclusively demonstrated. We aimed to solve this question by investigating the pathomorphological MR imaging correlate of this rare disorder. Eight patients with NF2-PNP were characterized by clinical examination, electrophysiological studies, and genetic analysis. All patients additionally underwent extended peripheral nerve imaging by a novel protocol of large-coverage high-resolution MRI. Quantitative analyses were performed by separately evaluating cross-sectional images, and by categorizing lesions into non-compressive fascicular microlesions (<2 mm), intermediate lesions (2-5 mm), and compressive macrolesions (>5 mm). The predominant imaging findings were non-compressive fascicular microlesions and intermediate lesions. Proximal-to-distal cumulative lesion burden of these lesions correlated strongly with the severity of clinical symptoms of NF2-PNP. In contrast, compressive macrolesions were not found at all in several symptomatic extremities. We conclude that proximal-to-distal accumulation of non-compressive fascicular lesions instead of compressive mass lesions predominantly underlies the clinical manifestation and severity of NF2-associated PNP. Diagnostic management may now be assisted by large-coverage high-resolution imaging of plexus and peripheral nerves. Additionally, the results underscore the feasibility of this new method, which may open up new diagnostic and investigative possibilities for other disseminated disorders of the peripheral nervous system.

Value of high-resolution ultrasound in the differential diagnosis of scaphocephaly and occipital plagiocephaly.

Secondary to the increase in deformational plagiocephaly a growing number of infants with cranial deformity present to craniofacial teams. Computed tomography (CT) is diagnostic, but uses ionizing radiation. The purpose of this study was to evaluate ultrasound as a screening test for the patency of cranial sutures in scaphocephaly and occipital plagiocephaly. The cranial sutures of 54 infants with this cranial deformity were assessed by ultrasound. Sutures were read as patent or fused if a hypoechoic gap could or could not be demonstrated between the hyperechoic clavarial bones, respectively. Seven children suffered from true craniosynostosis of either the sagittal or the lambdoid suture. In five cases the ultrasound findings were diagnostic for a fused suture, in two cases the results were inconclusive. Forty-seven infants presented with deformational plagiocephaly. Ultrasound examination demonstrated patent sutures in 45 cases and was inconclusive in two cases. Sonography of the cranial sutures is a good screening tool to distinguish fused from patent cranial sutures in scaphocephaly and occipital plagiocephaly and avoids the radiation exposure associated with CT examinations.

Effect of leukotriene inhibitors on evolution of experimental brain contusions.

AIMS: Leukotriene levels increase in cerebrospinal fluid (CSF) following controlled cortical impact (CCI) injury in rats. We investigated the impact of two different leukotriene inhibitors in the CCI model on CSF leukotriene levels, brain water content (BWC), brain swelling (BS) contusion size and cellular response. METHODS: 134 male Sprague Dawley rats were investigated at 4, 24 and 72 h after CCI for CSF leukotriene levels and BWC/BS, lesion size in T2-weighted magnetic resonance imaging and immunohistochemistry. Animals received vehicle, MK-886, an inhibitor of 5-lipoxygenase activating protein, or Boscari(®) , a mixture of boswellic acids, acting as competitive nonredox 5-lipoxygenase inhibitors before trauma and then every 8 h until sacrifice. RESULTS: The intracranial pressure (ICP) was unaffected by treatment. Boscari treatment reduced CSF leukotriene C4 increase by -45% at 4 h (P < 0.03) and increase of BWC and BS by 49% (P < 0.05) and -58% at 24 h. Treatment with both substances showed a reduction of lesion volume at 72 h by -21% (P < 0.01) in T(2) -weighted magnetic resonance imaging, which was reflected in a smaller lesion area determined from a NeuN labelled section (-17% to -20%, P < 0.05). Triple immunofluorescence and Fluoro-Jade B staining showed rarefaction of neurones, glia and vasculature in the contusion core, whereas in the pericontusional zone astro- and microglia were upregulated in the presence of dying neurones. Treatment resulted in an improved survival of NeuN labelled neurones in the pericontusional cortex (+15% to +20%, P < 0.05). CONCLUSIONS: Leukotriene inhibition should be further investigated as therapeutic option to counteract secondary growth of traumatic brain contusions and to possibly improve pericontusional neuronal survival.

Endobronchial ultrasound-guided lymph node biopsy with transbronchial needle forceps: a pilot study.

One limitation of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the size of the available needles, frequently yielding only cells for cytological examination. The aim of this pilot study was to evaluate the efficacy and safety of newly developed needle forceps to obtain tissue for the histological diagnosis of enlarged mediastinal lymph nodes. Patients with enlarged, positron emission tomography (PET)-positive lymph nodes were included. The transbronchial needle forceps (TBNF), a sampling instrument combining the characteristics of a needle (bevelled tip for penetrating through the bronchial wall) with forceps (two serrated jaws for grasping tissue) was used through the working channel of the EBUS-TBNA scope. Efficacy and safety was assessed. 50 patients (36 males and 14 females; mean age 51 yrs) with enlarged or PET-positive lymph nodes were included in this pilot study. In 48 (96%) patients penetration of the bronchial wall was possible and in 45 patients tissue for histological diagnosis was obtained. In three patients TBNF provided inadequate material. For patients in whom the material was adequate for a histological examination, a specific diagnosis was established in 43 (86%) out of 50 patients (nonsmall cell lung cancer: n=24; small cell lung cancer: n=7; sarcoidosis: n=4; Hodgkin's lymphoma: n=4; tuberculosis: n=2; and non-Hodgkin's lymphoma: n=2).No clinically significant procedure-related complications were encountered. This study demonstrated that EBUS-TBNF is a safe procedure and provides diagnostic histological specimens of mediastinal lymph nodes.

Prenatal evaluation of the position of the fetal conus medullaris.

OBJECTIVES: To determine the position of the fetal conus medullaris during pregnancy in relation to the last vertebral body and to examine its use in detecting skin-covered spinal dysraphism. METHODS: This was a retrospective study involving 300 consecutive ultrasound examinations between 15 weeks of gestation and term. Two operators independently assessed images of the spine to determine whether the conus medullaris and the last vertebral body could be visualized in a single image in a midsagittal plane. The distance between these two landmarks (the conus distance) was measured twice by both operators who were not aware of any previous measurements. Intra- and interobserver variability was assessed by 95% limits of agreement. Linear regression analysis was used to determine the relevant contributors to the conus distance and a normal range was computed based on the best-fit model. The normal results were compared with five cases of prenatally detected skin-covered spinal dysraphism. RESULTS: In 84.7% of the 300 cases, both operators were able to visualize the conus medullaris and the last vertebral body. Ninety-five percent limits of agreement for the intraobserver variability in measurement of conus distance were ± 1.9 mm. For the interobserver variability, they were - 3.7 and 2.5 mm. We found a linear relationship between conus distance and gestational age, biparietal diameter and abdominal circumference. The strongest relationship was observed for femur length (conus distance = - 8.2 + femur length (mm)). In the five abnormal cases, conus distance was well below the 5(th) percentile. CONCLUSIONS: Determination of conus distance allows for an objective and feasible assessment of the conus medullaris position. This parameter promises to be useful in the prenatal detection of skin-covered spinal dysraphism.