A rare cause of peripheral arthralgia in inflammatory bowel disease: multifocal osteonecrosis.

Osteonecrosis (ON) is characterized by an infarction of osseous tissue in the subchondral regions of the bone. We report the case of a young male patient with ulcerative colitis (UC) developing severe and multifocal, large joint ON resulting in severe disability. Since typical symptoms of ON, like joint pain, might be misinterpreted as common extraintestinal manifestations, ON might easily be overlooked in patients with inflammatory bowel disease (IBD). Plain radiographs detect only advanced cases, MRI is the diagnostic method of choice with a specificity and sensitivity of > 90 %. We discuss the incidence of ON specifically in IBD and provide an update on risk factors like treatment with corticosteroids (CS), although ON has been reported in IBD patients without previous CS treatment. Apart from that, underlying inflammation, thromboembolic events and genetic risk factors might be involved in ON development supporting the hypothesis of a complex cascade. Causative therapies for ON are not available, and surgical interventions like trepanning, core decompression and prosthetic replacement are often necessary. Our intention is to direct attention to this severe complication in the differential work-up of joint pain in IBD patients.

T Cell Response After SARS-CoV-2 Vaccination in Immunocompromised Patients with Inflammatory Bowel Disease.

BACKGROUND: Vaccination is a promising strategy to protect vulnerable groups like immunocompromised inflammatory bowel disease [IBD] patients from an infection with SARS-CoV-2. These patients may have lower immune responses. Little is known about the cellular and humoral immune response after a SARS-CoV-2 vaccination in IBD patients. METHODS: Totals of 28 patients with IBD and 27 age- and sex-matched healthy controls were recruited at Jena University Hospital. Blood samples were taken before, after the first, and in a subgroup of 11 patients after second dose of a SARS-CoV-2 vaccination. Cellular immune response, including IFN-γ and TNF-α response and antibody titres, were analysed. RESULTS: Overall, 71.4% of the IBD patients and 85.2% of the controls showed levels of anti-SARS-CoV-2 antibodies above the cutoff of 33.8 BAU/ml [p = 0.329] after the first dose. Even in the absence of SARS-CoV-2 antibodies, IBD patients showed significant T cell responses after first SARS-CoV-2 vaccination compared with healthy controls, which was not influenced by different immunosuppressive regimens. Associated with the vaccination, we could also detect a slight increase of the TNF production among SARS-CoV-2-reactive TH cells in healthy donorsn [HD] and IBD patients. After the second dose of vaccination, in IBD patients a further increase of humoral immune response in all but one patient was observed. CONCLUSIONS: Already after the first dose of a SARS-CoV-2 vaccination, cellular immune response in IBD patients is comparable to controls, indicating a similar efficacy. However, close monitoring of long-term immunity in these patients should be considered.

Inflammatory Bowel Disease in the COVID-19 Pandemic: the Patients' Perspective.

BACKGROUND: The coronavirus disease 2019 [COVID-19] pandemic is affecting lives worldwide. The influence of inflammatory bowel disease [IBD] medication and IBD itself on COVID-19 is controversial. Additionally, IBD-focused guidance is scarce. OBJECTIVE: Our aims were to determine COVID-19 prevalence/exposure, perception and information sources, medication compliance, patient behaviour and physician contact among patients with IBD compared with non-IBD controls. METHODS: A cross-sectional anonymous survey of patients with IBD [N = 415] at one university IBD clinic and one gastroenterology practice, matched 4:1 with control participants [N = 116], was performed. RESULTS: Patients with IBD had a high fear of infection. This was more pronounced in patients taking immunosuppressants and it extended to hospitals, private practices and public places, such as supermarkets. IBD patients reported leaving their homes less frequently than their peers without IBD. A total of 90% of patients with IBD reported washing their hands more frequently. Patients taking immunosuppressants were concerned about interactions between medication and COVID-19, whereas patients taking 5-aminosalicylates were not. Nonetheless, 96.4% of patients adhered to continuing their medication. Patients sought guidance primarily from television and internet news sites. Video consultations were found to be a suitable solution for a subset of patients who are young, have a high level of fear and leave their home less frequently than their peers, whereas overall acceptance of video consultations was limited. CONCLUSION: Patients with IBD are significantly more affected by the COVID-19 pandemic than their non-IBD peers, but they continue to adhere to their medication regimens. IBD-focused COVID-19 information should be actively conveyed.

Vascular Decompression of Trigeminal and Facial Nerves in the Posterior Fossa under Endoscope-Assisted Keyhole Conditions.

OBJECTIVE: The aim of this study was to determine the use and safety of the endoscope as an adjunct during trigeminal and facial nerve decompression procedures performed under keyhole conditions in the posterior fossa. METHOD: We performed 67 surgeries in 65 patients with symptomatic trigeminal and facial nerve compression syndromes. The diagnosis was made mainly on the basis of clinical history, examination, and magnetic resonance imaging scans. Surgery was performed in all cases under endoscope-assisted keyhole conditions. The follow-up was 1 week postoperatively, 6 months, and then yearly up to 7 years. All 34 patients with trigeminal neuralgia received preoperative medication treatment and experienced failure with it. Eighteen patients out of 30 with hemifacial spasm had been previously treated with botulinum toxin injections. One patient suffered from both trigeminal neuralgia and facial spasm, because of a megadolichobasilar and vertebral artery with compression of both cranial nerves. RESULTS: Sixty-four of the 65 patients became symptom free after surgical treatment; one revision surgery was necessary because of disappearance of the decompression muscle piece. No mortalities or minor morbidities were observed in this series. CONCLUSION: A precise planned keyhole craniotomy and the simultaneous use of the microscope and the endoscope render the procedure of the decompression less traumatic.

A new device for interstitial 125Iodine seed implantation.

A new device for interstitial implantation of I125 seeds is presented. The technical details and function of the system are described and compared with well-known commercial systems. Its unique design allows for simple, fast, and safe treatment of most tumor sites including stereotactic implantation of brain. Radiation measurements indicate low exposure to both patients and personnel during implantation.

Species specific immunoassays to measure blood platelet and coagulation activation in the rat.

The purpose of this study was to develop specific and sensitive immunoassays to detect early indices of hypercoagulability in the rat. Rat platelet factor 4 (rPF4) and rat fibrinopeptide A (rFPA) assays, tools for the detection of activation of platelets and coagulation respectively, were designed using antibodies raised against purified rPF4 and against synthetic rFPA. The relevance of these new assays and of the commercially available ELISA kit for thrombin-antithrombin III (TAT) complexes was demonstrated in a rat model of a prethrombotic state induced by intravenous infusion of varying doses of thrombo-plastin (90 to 2400 microliters/kg/h). In this model, the immunoassays allowed simultaneous detection of low levels of rFPA and rPF4 which were correlated with fibrinogen and platelet consumption and TAT generation and further proved to be of higher sensitivity than the classical methods of platelet count or measurement of fibrinogen levels. Plasma concentrations of rFPA, rPF4 and TAT were dependent on infusion time and thromboplastin dose, while hirudin (1 mg/kg) prevented their appearance. Thus the new specific immunoassays for rPF4 and rFPA and the commercial human TAT assay represent useful tools for pathophysiological studies or the screening of antithrombotic drugs in rats.

Endoscopic third ventriculostomy: outcome analysis of 100 consecutive procedures.

OBJECTIVE: Endoscopic third ventriculostomy (ETV) has been shown to be a sufficient alternative in the surgical treatment of occlusive hydrocephalus. To elucidate the ongoing discussion of timing, indication, and surgical technique, a retrospective analysis of 100 consecutive ETVs was conducted. METHODS: One hundred ETVs were performed in 95 patients (43 female and 52 male patients). Their age ranged from 3 weeks to 77 years (mean age, 36 yr). Hydrocephalus was caused by aqueductal stenosis in 40 patients, space-occupying lesions in 42, and intraventricular or subarachnoid hemorrhage in 8. One patient had postinflammatory hydrocephalus, and four patients had occlusive hydrocephalus of unknown origin. In 33 cases, surgery was performed using stereotactic guidance. RESULTS: ETV was accomplished in 98 of 100 cases. The overall success rate was 76%. Patients with benign space-occupying lesions and nontumorous aqueductal stenosis had the highest success rates, which were 95 and 83%, respectively. Complications were arterial bleeding in one case, venous bleeding in three cases, intracerebral bleeding in one case, and infection in one case. There were no permanent morbidities or mortalities. CONCLUSION: ETV is most effective in treating uncomplicated occlusive hydrocephalus caused by aqueductal stenosis and space-occupying lesions. ETV is still effective in two-thirds of the patients with previous infections or intraventricular bleeding. Patients who have previously undergone shunting and who have occlusive hydrocephalus should undergo ETV at the time of shunt failure, with immediate ligation or removal of the shunt device. In selected cases of distorted anatomy or impaired visual conditions, stereotactic guidance is helpful.

The need for adjunctive focused radiation therapy in pituitary adenomas.

In pituitary adenomas radiation therapy regardless of the technique should be limited to surgical failures. The delayed onset of beneficial effects and the high rate of pituitary insufficiency have to be weighed against the good surgical and/or medical results in the treatment of these tumours. Unfortunately surgical outcome is almost invariably correlated with invasive growth. Invasiveness is statistically significantly correlated with tumour size, as well as with high proliferation rates, which can be measured by immunohistological methods such as mAB KI-67. Owing to the good results of medical treatment, radiation therapy is usually unnecessary in prolactinomas. Patients with persistent hypersecretion of growth hormone after unsuccessful surgery may represent the ideal candidates for radiation therapy, whereas patients with persistent Cushing's disease need cure for hypercortisolism without delay. In patients with residual tumour due to non functioning adenomas, radiation therapy should only be given if the proliferation rate is high.

[Stereotaxic biopsy of brain tumors]. / Stereotaktische Biopsie von Hirntumoren.

The management of patients with a brain tumour is essentially dependent on the knowledge of the histology. Because of its high accuracy and low complication rate stereotactic tumour biopsy has proven to be an important diagnostic procedure, especially in deep-seated lesions. Stereotactic tumour biopsy was carried out in 18 patients with target calculation either from computerized tomography (CT) or magnetic resonance imaging (MR).

[Stereotaxic biopsy of intracranial processes: validity of histologic diagnosis]. / Stereotaktische Biopsie intrakranieller Prozesse: Validität der histologischen Diagnostik.

The diagnostic validity of stereotactic intracranial biopsies was investigated in 70 patients retrospectively. In 56 cases (80%) the presence of a neoplastic lesion as well as its grade of malignancy was proved by cytological, histological and immunohistochemical techniques. An inflammatory or vascular lesion was found in 8 patients (11.4%). In 6 patients (8.6%) the nature of the lesion remained unclear because of nonspecific histological findings. In 27 cases a correlation was found between the biopsy specimens and corresponding material obtained during open surgery or autopsy. 24 concordant results were found (88.9%). In one case a malignant tumour was classified only according to the findings obtained at operation. In two cases subsequently diagnosed as glioblastoma biopsy reported a higher differentiated astrocytoma and a non-neoplastic lesion, respectively. These results confirm stereotactic biopsy of intracranial lesions as a method with low complication rate and high diagnostic validity.

Basic principles and clinical applications of neuronavigation and intraoperative computed tomography.

Computed tomography (CT) images in combination with a navigation device enable three-dimensional (3-D) localization of intracranial lesions. Furthermore, CT scanning can be adapted for intraoperative application to actualize the image data and to check the anatomical situation during the operation. Frameless navigation was used in 100 patients. The procedure was performed in 46 cases with an optical navigation system, in 38 cases with a sensory arm, and in 16 cases with a navigated microscope. Six skin markers were used for registration. Mean fiducial registration error was 2.18 mm with a standard deviation of 1.03 mm. The indication for navigation was tumor localization and planning of the craniotomy in 81 cases, stereotactic biopsy in eight cases, and endoscopic procedures in 11 cases. Technical problems with the navigation system were observed in nine cases. In two additional cases the tumor was not found by navigation. All eight biopsy cases were successful, and histologically relevant specimens were obtained without complications. Navigation was helpful in 11 endoscopic cases for choosing an optimal trajectory through the foramen of Monro or for connecting multiple intraventricular cysts. For intraoperative CT imaging, the mobile Philips Tomoscan M was adapted to the needs of the operating environment. The mobile CT was used in 78 cases in the operating room: 16 patients who underwent a stereotactic procedure had only preoperative CT scans, 36 patients had an intraoperative CT during tumor surgery, and 26 patients during the test period of the device had only a postoperative CT investigation. In 10 cases (28%) of the intraoperative group the remaining tumor tissue could be demonstrated on the CT scans. The tumor remnants that were not visible in the microscopical surgical field were subsequently removed. According to our results, intraoperative navigation seems superior for the localization of intracranial lesions and intraoperative CT is more useful when considering the radicality of tumor removal.

Establishment of a novel in vitro test setup for electric and magnetic stimulation of human osteoblasts.

When large defects occur, bone regeneration can be supported by bone grafting and biophysical stimuli like electric and magnetic stimulation (EMS). Clinically established EMS modes are external coils and surgical implants like an electroinductive screw system, which combines a magnetic and electric field, e.g., for the treatment of avascular bone necrosis or pseudarthrosis. For optimization of this implant system, an in vitro test setup was designed to investigate effects of EMS on human osteoblasts on different 3D scaffolds (based on calcium phosphate and collagen). Prior to the cell experiments, numerical simulations of the setup, as well as experimental validation, via measurements of the electric parameters induced by EMS were conducted. Human osteoblasts (3 × 10(5) cells) were seeded onto the scaffolds and cultivated. After 24 h, screw implants (Stryker ASNIS III s-series) were centered in the scaffolds, and EMS was applied (3 × 45 min per day at 20 Hz) for 3 days. Cell viability and collagen type 1 (Col1) synthesis were determined subsequently. Numerical simulation and validation showed an adequate distribution of the electric field within the scaffolds. Experimental measurements of the electric potential revealed only minimal deviation from the simulation. Cell response to stimulation varied with scaffold material and mode of stimulation. EMS-stimulated cells exhibited a significant decrease of metabolic activity in particular on collagen scaffolds. In contrast, the Col1/metabolic activity ratio was significantly increased on collagen and non-sintered calcium phosphate scaffolds after 3 days. Exclusive magnetic stimulation showed similar but nonsignificant tendencies in metabolic activity and Col1 synthesis. The cell tests demonstrate that the new test setup is a valuable tool for in vitro testing and parameter optimization of the clinically used electroinductive screw system. It combines magnetic and electric stimulation, allowing in vitro investigations of its influence on human osteoblasts.

From the idea to its realization: the evolution of minimally invasive techniques in neurosurgery.

Minimally invasive techniques in neurosurgery evolved in two steps. Many minimally invasive concepts like neuronavigation, endoscopy, or frame based stereotaxy were developed by the pioneers of neurosurgery, but it took decades till further technical developments made the realization and broad clinical application of these early ideas safe and possible. This thesis will be demonstrated by giving examples of the evolution of four minimally invasive techiques: neuronavigation, transsphenoidal pituitary surgery, neuroendoscopy and stereotaxy. The reasons for their early failure and also the crucial steps for the rediscovery of these minimally invasive techniques will be analysed. In the 80th of the 20th century endoscopy became increasingly applied in different surgical fields. The abdominal surgeons coined as first for their endoscopic procedures the term minimally invasive surgery in contrast to open surgery. In neurrosurgery the term minimally invasive surgery stood not in opposiotion to open procedures but was understood as a general concept and philosophy using the modern technology such as neuronavigation, endoscopy and planing computer workstations with the aim to make the procedures less traumatic.

Concept and treatment of hydrocephalus in the Greco-Roman and early Arabic medicine.

In the ancient medical literature hydrocephalus was not often described although its existence and symptomatology were well known. Most detailed descriptions of hydrocephalus including the surgical treatment are extant in the encyclopaedic works on medicine of the physicians Oreibasios and Aetios from Amida from the 4th and 6th centuries AD, respectively. Because of their broad scientific interests, this type of physicians, typical for the late Roman empire, were known as philosophy-physicians (iota alpha tau rho o sigma o phi iota sigma tau alpha iota). They defined hydrocephalus in contrast to our present understanding as a fluid collection excluding abscesses visible as a bulging tumour localised either outside or inside the skull of an infant. They classified the hydrocephalus similar as stated first by Galen in the 2nd century AD in four types corresponding to the assumed anatomic localisation of the fluid collection: 1st Type between the skin and the pericranium corresponding to the subgaleal haematoma or caput succedaneum of the newborn in our terminology, 2nd Type between the pericranium and the skull corresponding to the cephal haematoma after delivery, 3rd Type between skull and the meninges with increased head circumference, bone sutures being increasingly driven apart corresponding most likely to the hydrocephalus in our understanding, and 4th Type between the menings and the brain characterised by severe neurological deficit with lethal prognosis corresponding probably to all pathologies which were accompanied by an excessive increase of the intracranial pressure with a bulging fontanel. Due to the lack of autopsies in ancient times, the hydrocephalus was never linked to the pathology of the ventricles. All forms of hydrocephalus were believed to be caused by improper handling of the head by the midwife during delivery. Only the extracranial fluid collections, but not hydrocephalus in our sense, were considered to be suitable for surgical treatment. The surgery consisted in one or more incisions and evacuation of the fluid. The wound was not closed but let open for three days. Thereafter plasters or sutures closed the incisions. The surgical technique goes back probably to Antyllos a surgeon from the 3rd century AD whose considerations were cited in the work of Oreibasios. The early Arabic physicians took over the surgical indications, the operative technique and modified the Greek concept of hydrocephalus. Avicenna separated the traumatic haematomas outside the skull from the term hydrocephalus. However Avicenna, as all previous authors, had not linked hydrocephalus with the ventricular system. The autopsy of a child with an exorbitant hydrocephalus performed by the anatomist Vesalius in the 16th century revealed as a single pathology an extremely dilative ventricular system filled with water-like fluid which made it necessary to change completely the ancient concept of hydrocephalus.

Accuracy of stereotactic coordinate transformation using a localisation frame and computed tomographic imaging. Part II. Analysis of matrix-based coordinate transformation.

The accuracy of coordinate transformation from a CT image to a stereotactic frame was investigated for stereotactic systems using a localisation frame and matrix-based coordinate transformation. The main source of error influencing calculation was input data, due to inaccurate calculation of the centres of the rods of the localisation frame in the CT image, and the propagation of this input error during subsequent matrix calculation. Systemic errors during matrix calculation do not exist, and rounding off errors were of subordinate importance compared to the input data error. The influence of input data error on coordinate transformation was studied by geometric methods, computer simulation, and numerical analysis. In the geometric model, input data errors affected the calculation of the centres of the three oblique rods in the frame space and shifted them three points upwards or downwards on the axis of each rod. The three centres of the oblique rods defined the "CT plane" in the 3D space of the stereotactic frame. Displacements of these three centres caused a characteristic tilting of the CT plane. The positions of the correct and tilted CT planes defined the spatial error properties for all target points on the CT plane. The computer simulation investigated the effects on matrix-based transformation of all possible displacement combinations on the three oblique rods by 1 pixel (1. 16 mm) in the x and y directions. A characteristic, space-dependent distribution of the frame-related coordinates was obtained for each target point. In the centre of the frame, we found a maximal deviation of 1.0 mm in the xy direction and 2 mm in the z direction. This corresponded to an error amplification of 0.73 in the xy direction and 1.22 in the z direction relative to the error at the centres of the rods. The maximum deviation (found in the periphery) for all combinations on the three oblique rods was 1.7 mm in the xy direction and 3.3 mm in the z direction. This resulted in an amplification of 1.03 in the xy direction and 2.01 in the z direction. This results had to be multiplied by 2 to obtain a maximal error estimate for displacements including all nine rods of the localisation frame. Numerical analysis showed stable solutions with low error amplification for hexagonal frame arrangements.

[Cerebral seizure following lumbar myelography with iopamidol]. / Zerebraler Anfall nach einer lumbalen Myelographie mit Jopamidol.

This is a report of a case of a serious side effect following lumbar radiculography with the water soluble contrast medium Iopamidol. The complication consisted of a generalized seizure after an episode of myoclonic jerking of the legs. This was the first complication in a series of 1070 lumbar and cervical myelograms with this medium.

Target point calculation in the computerized tomography. Comparison of different stereotactic methods.

The adaptation of computerized tomography for stereotactic operations requires the transformation of the coordinates of the target point from the CT image space into the stereotactic frame space. Two basic solutions for this transformation are realized in the most of the contemporary stereotactical systems. The indirect geometric method adjusts the frame coordinate system mechanically and identifies its origin in the CT image. There are 6 degrees of freedom: 3 of rotation and 3 of translation which have to be taken into consideration. The second method is a based on direct algebraic coordinate transformation and is independent of the explicite knowledge of the relationship between the image and the frame space. A localization frame serves to determine a transformation matrix which, applied to any point in the image, transforms the coordinates directly into the frame coordinate system. Only the algebraic method is independent of the position of the patient in the gantry. All other methods require high mechanical precision of the alignment and stability for the CT table.

[Long-term results of thoracic chordotomies in the treatment of intractable pain in tumors of the pelvis]. / Langzeitergebnisse thorakaler Chordotomien in der Behandlung unstillbarer Schmerzen bei Malignomen des kleinen Beckens.

In 38 patients a high thoracal cordotomy has been performed. All patients suffered from intractable pain due to malignant tumor in the basin. In all patients the follow-up extended till their death. Based on these results the indication for a cordotomy is discussed.

[Results of cervical chordotomy with and without rhizotomy in therapy-resistant pain in the shoulder and arm]. / Ergebnisse der zervikalen Chordotomie mit und ohne Rhizotomie bei konservativ therapieresistenten Schmerzen im Schulter-Arm-Bereich.

Herein we report on 39 patients, who were treated with the upper cervical cordotomy (C1/C2), because of intractable pain of the shoulder and arm region. 30 patients suffered from malignant tumors, 9 had a benign lesion. A simultaneous cordotomy and rhizotomy was performed in 9 tumor patients and in 2 patients with a benign lesion. The upper cervical cordotomy proofed successful in the treatment of pain of cancer bearing patients. However, our results demonstrated that the combination of cordotomy and rhizotomy did not provide further advantage than the cordotomy alone.