Embryoscopy and karyotype findings of repeated miscarriages in recurrent pregnancy loss and spontaneous pregnancy loss.

PURPOSE: The aim of the study was to assess cytogenetic and embryoscopic characteristics in subsequent miscarriages of spontaneous pregnancy losses (SPL) and recurrent pregnancy losses (RPL). METHODS: A retrospective cohort of 75 women was affected by repeated pregnancy loss. Of those, 34 had SPL, 24 primary RPL, and 17 secondary RPL. Ploidy status and morphology was analyzed by transcervical embryoscopic examination of the embryo and cytogenetic analysis of the chorionic villi in subsequent miscarriages. RESULTS: Similar rates of recurrent ploidy status were observed between first and second miscarriage in SPL and RPL (82.4% recurrent ploidy status in SPL, p > 0.999; 73% recurrent ploidy status in RPL, p = 0.227). No difference was found regarding recurrent abnormal morphology between SPL and RPL (p = 0.092). However, secondary RPL resulted significantly more often in recurrent abnormal morphology compared to primary RPL (p = 0.004). CONCLUSIONS: High rates of recurrent normal/abnormal karyotypes were observed in all groups with a majority of embryos presenting with recurrent abnormal morphology. Secondary RPL presented significantly more often with recurrent abnormal morphology compared to primary RPL. These findings offer prognostic information for the affected patient and might impact treatment choice.

Neurogenic differentiation of amniotic fluid stem cells.

In 2003, human amniotic fluid has been shown to contain stem cells expressing Oct-4, a marker for pluripotency. This finding initiated a rapidly growing and very promising new stem cell research field. Since then, amniotic fluid stem (AFS) cells have been demonstrated to harbour the potential to differentiate into any of the three germ layers and to form three-dimensional aggregates, so-called embryoid bodies, known as the principal step in the differentiation of pluripotent stem cells. Marker selection and minimal dilution approaches allow the establishment of monoclonal AFS cell lineages with high proliferation potential. AFS cells have a lower risk for tumour development and do not raise the ethical issues of embryonic stem cells. Compared to induced pluripotent stem cells, AFS cells do not need exogenic treatment to induce pluripotency, are chromosomal stable and do not harbour the epigenetic memory and accumulated somatic mutations of specific differentiated source cells. Compared to adult stem cells, AFS can be grown in larger quantities and show higher differentiation potential. Accordingly, in the recent past, AFS became increasingly accepted as an optimal tool for basic research and probably also for specific cell-based therapies. Here, we review the current knowledge on the neurogenic differentiation potential of AFS cells.

Combining midfacial degloving, LeFort-I osteotomy and inferiorly extended lateral orbitotomy (Krönlein) for removal of an orbital cavernous haemangioma: a new approach.

Orbital tumours, located in the medial extraconal and intraconal compartment of the orbit, represent a challenge, with regard to surgical exposure. In the present paper removal of a cavernous haemangioma, located in the medial intraconal compartment was accomplished by combining lateral orbitotomy, midfacial degloving and LeFort-I osteotomy. Resection of the tumour could be performed under direct vision. Surgical exposure and removal of the lesion were obtained, without causing damage to surrounding tissues. Aesthetical results and postoperative eye function proved to be highly satisfactorily. With regard to limitations, concerning the combination of these methods, extended surgery duration and invasiveness have to be named. According to the technical feasibility and postoperative results, this new surgical approach represents a reliable and fully viable alternative method for the removal of medial orbital tumours.

In-depth comparison of N-glycosylation of human plasma-derived factor VIII and different recombinant products: from structure to clinical implications.

Essentials Glycosylation heterogeneity of recombinant proteins affects pharmacokinetics and immunogenicity. N-glycomics/glycoproteomics of plasma-derived Factor VIII and 6 recombinant FVIIIs were compared. Depending on cell line, significant differences to plasma-derived FVIII were observed. Recombinant FVIIIs expressed distinct and immunologically relevant epitopes. SUMMARY: Background/Objective Human factor VIII (FVIII) is a plasma glycoprotein, defects of which result in hemophilia A. Current substitution therapy uses FVIII products purified from human plasma or from various cell lines (recombinant FVIII) with different levels of B-domain deletion. Glycosylation is a post-translational protein modification in FVIII that has a substantial influence on its physical, functional and antigenic properties. Variation in glycosylation is likely to be the reason that FVIII products differ in their pharmacokinetics, pharmacodynamics and immunogenicity. However, the literature on FVIII glycosylation is inconsistent, preventing assembly into a coherent model. Seeking to better understand the glycosylation mechanisms underlying FVIII biology, we studied the N-glycosylation of human plasma-derived (pd)FVIII and six rFVIII products expressed in CHO, BHK or HEK cell lines. Methods FVIII samples were subjected to head-to-head detailed glycomic and glycoproteomic characterization using a combination of MALDI-MS and MS/MS, GC-MS and UPLC-UV-MSE technologies. Results/Conclusion The results of our study detail the N-glycan repertoire of pdFVIII to an unprecedented level, and for the first time, provide evidence of N-glycolylneuraminic acid (NeuGc) found on pdFVIII. Although site-specific glycosylation of rFVIII proved consistent with pdFVIII regardless of the expression system, the entire N-glycan content of each sample appeared significantly different. Although the proportion of biologically important epitopes common to all samples (i.e. sialylation and high-mannose) varied between samples, some recombinant products expressed distinct and immunologically relevant epitopes, such as LacdiNAc (LDN), fucosylated LacdiNAc (FucLDN), NeuGc, LewisX/Y and Galα1,3 Gal epitopes. rFVIII expressed in HEK cells showed the greatest glycomic differences to human pdFVIII.

Removal of a pellet from the left orbital cavity by image-guided endoscopic navigation.

In the cranio-maxillofacial field, computer-aided surgery based on computed tomography data is becoming increasingly important. Complex surgical procedures can be performed utilizing preoperative imaging to provide real-time localization of surgical instruments in the surgical field. Image-data-based navigation plays an ever-increasing role in cases of minimal invasive surgery. The case is presented here of a 58-year-old male patient referred after a hunting accident with a pellet in the left orbit. After transferring the preoperatively acquired computed tomography data to a commercially available navigation system, the bullet was removed through the original wound canal using an intraoperatively calibrated high-resolution endoscope.

Cardiac metastasis after squamous cell carcinoma of the oral cavity: case report.

A 58-year-old woman presented with respiratory problems 6 months after she had had a squamous cell carcinoma in the oral cavity resected. We found on computed tomography a large lesion in the cardiac muscle. There were no abnormalities in the electrocardiogram. The patient died 7 days later and necropsy confirmed a solitary metastasis in the myocardium that originated from a squamous cell carcinoma of the mouth.

Comparison of clonidine to sleep deprivation in the potential to induce spike or sharp-wave activity.

OBJECTIVE: This study aimed to investigate previously observed side effects, i.e. increased epileptic activity during clonidine medication. The safety and effectiveness of clonidine as spike inducing agent compared to sleep deprivation were tested. METHODS: Patients suffering from drug-resistant localization related epilepsy took part in 3 magnetoencephalography (MEG) sessions. One session was recorded without any activating measures. The other two sessions were either performed after sleep deprivation or after medication with clonidine. Target parameter was the number of spikes or sharp-waves during a 30 min recording period. RESULTS: About 67% of the patients showed increased spike activity after clonidine, whereas sleep deprivation increased the number of spikes in 33%, and 29% of the patients did not show any activation at all. Clonidine was most effective in temporal lobe epilepsy, when the focus was located in the right hemisphere, and when clonidine serum concentrations were ranging between 0.6 and 1.0 ng/ml. CONCLUSIONS: This study showed for the first time that clonidine can be considered an effective spike or sharp-wave inducing drug that is superior to the potency of sleep deprivation. SIGNIFICANCE: The administration of clonidine increases the probability of recording ictal and interictal epileptic activity during limited acquisition time.

Ictal dystonic posturing in mesial versus neocortical temporal lobe seizures.

PURPOSE: Ictal contralateral dystonic posturing is a frequently observed clinical feature in temporal lobe seizures. It is generally interpreted as the result of spread of the ictal discharge into basal ganglia structure. In previous reports, analysing ictal behavior, a precise definition and description of the upper limb ictal dystonia is often lacking or contradictory. In our study we aimed to determine whether different subtypes of dystonia and their latency from the clinical onset of seizure might be of value for the differentiation between mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE). METHODS: Eighty seizures (51 MTLE and 29 NTLE) and 30 patients (20 MTLE and 10 NTLE) were analyzed with regard to dystonic posturing of the upper limb. Ictal dystonia was subdivided into different subtypes according to distinct clinical features. Their frequency and latency from the clinical onset of seizure were assessed. RESULTS: Frequencies of all subtypes were similar in MTLE and NTLE. Concerning the latencies contralateral dystonic posturing characterized by sustained muscle contractions with flexion of the wrist and fist closure, a frequently appearing feature, occurred significantly earlier in NTLE than in MTLE seizures. CONCLUSIONS: This difference between the two groups may provide a differentiation between an epileptic focus of mesial from neocortical temporal lobe origin.

Ictal fear in temporal lobe epilepsy: surgical outcome and focal hippocampal changes revealed by proton magnetic resonance spectroscopy imaging.

BACKGROUND: Ictal fear (IF) is most frequently associated with epileptic discharges from mesial temporal areas. OBJECTIVES: To determine whether patients with IF were more likely to become seizure free after anteromesial temporal lobe resection compared with those without IF and whether they show more anteriorly pronounced metabolic changes assessed by means of multivoxel magnetic resonance spectroscopy (MRS) along the hippocampal axis. METHODS: Surgical outcome was assessed in 33 consecutive patients with temporal lobe epilepsy after a mean follow-up of 25 months (range, 12-38 months). Proton multivoxel MRS of the hippocampal formation was applied to detect regional differences along the axis of the hippocampus in patients with and without IF. Magnetic resonance tomography showed typical features of hippocampal sclerosis in all patients. RESULTS: Twelve (36%) of the 33 patients reported fear at the beginning of their habitual seizures. Eleven of these patients were seizure free postoperatively. In contrast, only 11 of 21 patients without IF had a favorable outcome. Results of MRS revealed significantly higher pathologic N-acetylaspartate-choline ratios in the anterior portion of the hippocampal formation in patients with than in those without IF, indicating focal metabolic and/or morphologic changes in the head of the hippocampus. CONCLUSIONS: These results indicate the importance of diagnosing auras with IF to provide a more detailed prognosis of the surgical outcome. In addition, our data emphasize that multivoxel MRS is a valuable tool in the presurgical evaluation, as it may reveal different topographical patterns of hippocampal sclerosis.

Gamma-Knife radiosurgery of mesiotemporal tumour epilepsy observations and long-term results.

PURPOSE: The efficacy of radiosurgery in cases of mesiotemporal tumours associated with long standing epilepsy has not clearly been documented up to now. The authors present a retrospective analysis of 19 cases treated by Gamma-Knife radiosurgery (GKRS) for mesiotemporal tumour epilepsy. METHODS: Between 1992 and 1997 19 patients (12 male and 7 female) with a mean age of 31 years (5-72) and mesiotemporal tumour-induced epilepsy of a mean duration of 8.6 years (0.9-28) were treated by GKRS. All tumours were within the mesiotemporal structures and the pathohistology proven by biopsy or resective procedure revealed 15 (79%) low grade astrocytomas, 3 (16%) gangliogliomas and 1 (5%) cavernoma. Beside tumour control, the main aim of GKRS was alleviation of epilepsy by irradiating the presumed epileptic foci outside the tumour volume. The 50% isodose volumes surrounding the tumours measured a mean of 6.2 ccm (1.1-18 ccm). Doses given at marginal isodoses ranged from 12 to 30 Gy (mean 17.3 Gy). The outcome with respect to epileptic seizures was evaluated by the Engel classification. RESULTS: After a follow-up (FU) of 1.7 to 9.7 years (mean 6.5 years) 11 patients (57.9%) were significantly ameliorated (Engel I and Engel II), 7 patients (36.8%) worthwhile improved (Engel III) and 1 patient (5.3%) unchanged. In 11 patients (58%) radiosurgically induced image changes were seen on MRI. INTERPRETATION: Although microsurgical approach guided by electrocorticography (EcoG) is the state of art for treatment of mesiotemporal tumour epilepsy, GKRS can be used as a non-invasive, safe and effective alternative to resective surgery for selected cases.

Stereotactic radiosurgery for hypothalamic hamartomas.

Hypothalamic hamartomas are nonneoplastic lesions often characterized by central precocious puberty and gelastic epilepsy. Due to the delicate location surgery is often unsuccessful and associated with considerable risks. In the presented series, Gamma Knife radiosurgery was applied. Four cases (aged between 5-13 years) who presented with medically intractable gelastic epilepsy and increasing secondary generalization, abnormal behaviour and precocious puberty (3 cases) are reported. Hypothalamic hamartomas sized 11-17 mm had been diagnosed by MR imaging. Radiosurgical treatment was performed in general anaesthesia with margin doses of 12-14 Gy to the 50-90% isodoses covering volumes of 600-2300 mm3. After follow-up periods of 12 to 68 months, a continuing decrease both in seizure frequency and intensity was noted (outcome according to Engel: II a (3 cases) and III a (1 case)). All patients are socially reintegrated. MR imaging did not reveal significant changes concerning the size of the lesions. Gamma Knife radiosurgery can be an effective and safe alternative treatment modality for HH capable of achieving good seizure control and improving behavioural disorders in selected cases.

Future aspects of the presurgical evaluation in epilepsy.

Epilepsy surgery is a successful therapeutic approach in patients with medically intractable epilepsy. The presurgical evaluation aims to detect the epileptogenic brain area by use of different diagnostic techniques. In this review article the current diagnostic procedures applied for this purpose are described. The diagnostic armamentarium can be divided conceptually into three different groups: assessment of function/dysfunction, structural/morphologic imaging methods and functional neuroimaging techniques. Properties, diagnostic power and limits of all diagnostic tools used in the diagnostic evaluation are discussed. In addition, future perspectives and the diagnostic value of new technologies are mentioned. Some are increasingly gaining acceptance in the routine preoperative diagnostic procedure like MR volumetry or MR spectroscopy of the hippocampus in patients with temporal lobe epilepsy. Some, on the other hand, like MEG and 11C-flumazenil PET, still remain experimental diagnostic tools as they are technically demanding and cost intensive. Besides the refinement of established techniques, co-registration of different modalities like spike-triggered functional MRI will play an important role in the non-invasive detection of the epileptic seizure focus and may change the regimen of the preoperative diagnostic work up of epilepsy patients in the future.

Is IgM of diagnostic value in case of delayed intrathecal production of IgG antibodies?

The neurological manifestations of Lyme borreliosis comprise a wide range of clinical signs. However, these symptoms might have other aetiologies. Therefore detection of intrathecal production of specific antibodies is necessary to confirm the clinical assumption of neuroborreliosis (NB). In case of delayed intrathecal production of specific IgG antibodies, detection of IgM could play a role in the early diagnosis of NB. To clarify whether IgM is of diagnostic value in such cases, paired CSF serum samples from 176 patients with suspected NB admitted to the department of Neurology, Karl Franzens University, Graz, Austria, were tested. Testing was performed with the IDEA Neuroborreliosis Kit (Dako, Denmark) and Enzygnost Borreliosis (Behring, Germany) and results of both methods were compared. According to well defined criteria 63 of the 176 patients had defined NB and 113 were regarded as possible NB. Twelve out of 63 patients with defined NB had delayed intrathecal IgG production. Only one patient with delayed IgG production had an intrathecal IgM production prior to IgG. In all patients with possible NB no intrathecal production of IgM was detected. At the time of the first lumbar puncture IgG intrathecal production could be detected with the IDEA seven times more often than with the Enzygnost Borreliosis. The determination of intrathecal production of IgM does not appear to be of diagnostic value in patients with delayed IgG antibody production. Therefore a consecutive lumbar puncture is more likely to confirm clinical assumption if there is strong clinical evidence of NB.

Surgical treatment of synovial chondromatosis of the temporomandibular joint with erosion of the skull base: a case report and review of the literature.

Synovial chondromatosis (SC) is a rare metaplastic disease of the larger joints. It is rarely observed in smaller joints, especially in the temporomandibular joint (TMJ). This disease is considered to be metaplastic and shows no malignant tendencies, but can become locally aggressive, erode the cranial base, and even spread intracranially. To date, nine cases of spread into the intracranial space have been reported in the literature; however, the disease remained extradural in all cases. The authors present a review of the literature and report the case of a 70-year-old man with SC of the right TMJ that had eroded the cranial base, reaching the dura mater; a large intracranial mass was not present. The disease was considered to be stage 3 according to Milgram's classification. The patient was treated surgically, the tumour mass was removed, reconstruction of the cranial base was performed using titanium mesh, and the joint was reconstructed with a temporal muscle interposition flap. Diagnostic images and intraoperative photographs are also presented.

Surgical treatment of macroglossia caused by systemic primary amyloidosis.

Amyloidosis is a heterogeneous group of disorders caused by the extracellular deposition of a fibrillar protein called amyloid. Amyloid involvement of the tongue is almost universally secondary to systemic disease. The clinical manifestations result from the progressive extracellular deposition of amyloid within the suprahyoid muscles. In the late stages, the progressive enlargement of the tongue causes hypo- and oropharyngeal blockage, with obstruction of the upper airways. Conservative excision is a satisfactory treatment for local amyloid masses; the role of surgery in systemic forms is controversial. The authors present a case of systemic primary amyloidosis of the tongue treated surgically by a partial glossectomy via a pull-through approach and discuss the indications and rationale for surgical intervention.

Surgically assisted rapid maxillary expansion: feasibility of not releasing the nasal septum.

Surgically assisted rapid maxillary expansion (SARME) is commonly used to correct maxillary transverse deficiency. The aim of this study was to analyse the need for intraoperative liberation of the nasal septum during the procedure. SARME was performed in 25 patients by combining a lateral osteotomy with an inter-radicular maxillary osteotomy. The deviation of the nasal septum after SARME was evaluated by comparing measurements between radiologically defined landmarks on pre- and postoperative computed tomographic images. Two defined angles (angle I, between crista galli-symphysis mandibulae and crista galli-septum nasi; angle II, between maxillary plane and septum nasi) were measured based on four representative planes and septal movement was analysed. The mean changes in angles I (0.03° ± 0.78°) and II (0.25° ± 1.04°) did not differ significantly from zero (p=0.87 and p=0.24, respectively). Observed variations and displacements were considered to be acceptable because they were insignificant in every respect. Intranasal airway function was also examined pre- and postoperatively to evaluate any loss of ventilation. The described surgical technique is a successful method of maxillary segment distraction. The authors found no compelling reason to release the nasal septum in the context of SARME.

Trans-tragal incision for improved exposure of diacapitular and condylar neck fractures.

The authors present a modification of the preauricular approach that improves the exposure of the condyle whilst reducing diacapitular and condylar neck fractures. The incision is a combination of the hockey-stick and endaural incisions. Its inferior part runs within the ear on the posterior face of the tragus; the tragal cartilage is transected together with the retrotragal skin and included in the anterior skin flap. Between May 2009 and December 2010, 16 patients with diacapitular or condylar neck fractures were treated with this approach. All patients showed good occlusion postoperatively and satisfactory aesthetic results. No infection or cartilage necrosis was observed in this series. This approach improves the exposure of the condylar head during the reduction of diacapitular and condylar neck fractures, ensuring easier internal fixation and good cosmetic results.

Extraosseous schwannoma of the mental nerve clinically simulating intraosseous.

We report a case of a benign neurilemmoma arising from the right mental nerve. Schwannomas are rare neurogenic tumours that originate from Schwann cells of the peripheral nervous system. Frequent locations are the head and neck region. Most of the tumours occur in the soft tissue whereas intraosseous schwannomas are rare. This case report deals with a young patient who was referred to our hospital with an unidentified fast-growing tumour located mainly in the premolar region of the right mandible. The tumour presented as an expansive, unilocular, well defined, radiolucent lesion on orthopantomography. No expansion of the mandibular canal could be seen. Computerized tomography scans of the mandible helped to identify the solid nature of the tumour. A biopsy was necessary to make the final diagnosis and the tumour was then excised surgically. Postoperative magnetic resonance imaging scans and a histological examination of the surgical specimen showed no signs of neurofibromatosis type 2.