What to report in sellar tumor MRI? A nationwide survey among German pituitary surgeons, radiation oncologists, and endocrinologists.

PURPOSE: While MRI has become the imaging modality of choice in the diagnosis of sellar tumors, no systematic attempt has yet been made to align radiological reporting of findings with the information needed by the various medical disciplines dealing with these patients. Therefore, we aimed to determine the prevailing preferences in this regard through a nationwide expert survey. METHODS: First, an interdisciplinary literature-based catalog of potential reporting elements for sellar tumor MRI examinations was created. Subsequently, a web-based survey regarding the clinical relevance of these items was conducted among board certified members of the German Society of Neurosurgery, German Society of Radiation Oncology, and the Pituitary Working Group of the German Society of Endocrinology. RESULTS: A total of 95 experts (40 neurosurgeons, 28 radiation oncologists, and 27 endocrinologists) completed the survey. The description of the exact tumor location, size, and involvement of the anatomic structures adjacent to the sella turcica (optic chiasm, cavernous sinus, and skull base), occlusive hydrocephalus, relationship to the pituitary gland and infundibulum, and certain structural characteristics of the mass (cyst formation, hemorrhage, and necrosis) was rated most important (> 75% agreement). In contrast, the characterization of anatomic features of the nasal cavity and sphenoid sinus as well as the findings of advanced MRI techniques (e.g., perfusion and diffusion imaging) was considered relevant by less than 50% of respondents. CONCLUSION: To optimally address the information needs of the interdisciplinary treatment team, MRI reports of sellar masses should primarily focus on the accurate description of tumor location, size, internal structure, and involvement of adjacent anatomic compartments.

Prevalence of perioperative asymptomatic venous thromboses of the lower extremity in 30 consecutive patients undergoing transsphenoidal surgery for Cushing's disease.

Cushing´s disease is a rare endocrinological disorder which is caused by an adrenocorticotropic hormone secreting pituitary adenoma. The condition is associated with an increased risk for venous thromboembolism. While there exist reports on symptomatic venous thromboses complicating Cushing's disease, the prevalence of incidental leg vein thromboses accompanying pituitary surgery for Cushing's disease is yet unknown. 30 consecutive patients (9 male; age 25-77 years) with histologically confirmed Cushing's disease underwent transsphenoidal adenomectomy between October 2018 and September 2019. All patients received perioperative pharmacological thromboprophylaxis. Whole leg compression ultrasound was performed within one week after surgery (median 2 days) to exclude leg vein thromboses (primary endpoint). Preoperative laboratory values including plasma cortisol and various coagulation parameters were evaluated as secondary outcome measures. A comparison was made between patients with and without thrombotic events (p value ≤ 0.05). A total of 2 out of 30 patients (6.7%; CI 0.8-24.1%) presented with asymptomatic perioperative deep vein thromboses of the lower legs. Thrombosis patients differed not significantly from their counterparts with respect to age, sex, and comorbidities, but preoperative morning plasma cortisol was significantly higher in patients with venous thromboses (421.0 ± 49.5 µg/l vs. 188.1 ± 78.2 µg/l; p = 0.01). Moreover, von Willebrand factor activity was markedly increased in one case (409.0%) compared to the mean value obtained from 28 patients without phlebothromboses (146.9 ± 60.7%; p < 0.01). Perioperative asymptomatic leg vein thrombosis can be found with the aid of compression ultrasound in a considerable proportion of patients undergoing transsphenoidal adenomectomy for Cushing's disease despite the administration of pharmacological thromboprophylaxis.

Cystic versus non-cystic silent corticotrophic adenomas: clinical and histological analysis of 62 cases after microscopic transsphenoidal surgery-a retrospective, single-center study.

Silent corticotrophic adenomas (SCAs) represent a rare group of non-functioning adenomas with a potentially aggressive clinical course. Cystic component is a very common finding among SCAs, but its clinical relevance has not yet been investigated. The aim of this study was to analyze clinical features of cystic and non-cystic SCAs, perioperative complications after microscopic transsphenoidal surgery, clinical outcome after first and repeat surgery along with risk factors for recurrence. We conducted a retrospective analysis of 62 silent corticotrophic adenomas treated at our university medical center via microscopic transsphenoidal surgery between January 2008 and July 2019. Parameters investigated included histology, invasiveness, intratumoral haemorrhage or cystic component on MRI, perioperative alteration of visual field, tumor size, pre- and postoperative ACTH, FSH, GH, LH, TSH, prolactin, cortisol, free T4, free T3, IGF-1, estrogen and testosterone levels, perioperative complications, neoadjuvant and adjuvant therapy along with clinical outcomes. A total of 62 patients were analyzed. The mean follow up was 28.3 months. Tumors with a cystic component occur statistically significant more often among male than non-cystic (80.6% vs. 44.4%, p = 0.02) and display lower rates of cavernous sinus invasion and sphenoid sinus invasion were significantly lower for cystic lesions comparing to non-cystic tumors (42.3% vs. 69.4%, p = 0.04 and 3.8% vs. 47.2%, p < 0.001). GTR after MTS was not statistically significant higher by cystic SCAs (80% vs. 57.1%, p = 0.09). Cystic lesions were also associated with higher risk of hyperprolactinemia (19.4% vs. 2.8%, p = 0.02) and only densely granulated cystic SCAs presented with preoperative intratumoral hemorrhage (19.2% vs. 0%, p = 0.01). Mean duration of first surgery was significantly shorter for cystic SCAs (71.6(± 18.7) vs. 94.8(± 31.1) minutes, p = 0.01). Preoperative pituitary insufficiency (25% vs. 16.7%, p = 0.49), intraoperative CSF space opening (21.1% vs. 37.5%, p = 0.32), along with postoperative new pituitary insufficiency (15% vs. 10%, p = 0.67) or diabetes insipidus/SIADH (10% vs. 13.3%, p > 0.99) with histological markers such as Ki67 (21.1% vs. 13.8%, p = 0.70) and p53 expression (6.3% vs. 0%, p = 0.39) as well as mitotic rate (5.3% vs. 10.3%, p > 0.99) were comparable between both groups. The presence of cystic component did not affect the tumor recurrence (10% vs. 16%, p = 0.68). Mean duration of surgery was first surgeries was not statistically shorter than repeat surgeries (85.4 ± 29.1 vs. 93.8 ± 28 min, p = 0.15). Patients undergoing first surgery had a higher probability of gross total resection (74.4% vs. 30%, p = 0.01) and lower probability of intraoperative CSF space opening (26% vs. 58.3%, p = 0.04) as well as a lower rate of preoperative anterior pituitary insufficiency (20% vs. 58.3%, p = 0.01). The incidence of new postoperative anterior pituitary insufficiency (10% vs. 0%, p = 0.57) and transient diabetes insipidus/SIADH (12% vs. 8.3%, p > 0.99) between those groups were comparable. No statistical difference was observed between patients with remission and with recurrent tumor regarding cortisol and ACTH levels, incidence of different histological subgroups, invasively growing tumors and lesions with cystic components as well as the percentage of cases with increased Ki67 proliferation index, p53 expression and mitotic indices. Our study presents one of the largest available cohorts of SCAs after microscopic transsphenoidal surgery and first clinical analysis of cystic versus non-cystic SCAs so far. We also performed the first comparison of index and repeat surgeries for this tumor entity. Cystic tumors presented with characteristic clinical aspects like male predominance, higher risk of hyperprolactinemia as well as lower rates of cavernous sinus and sphenoid sinus invasion comparing to non-cystic lesions. Mean duration of first surgery was significantly shorter for cystic SCAs. Moreover preoperative intratumoral hemorrhage had 100% specificity and 60% sensitivity for densely granulated cystic SCAs. All these clinical hallmarks may suggest a novel subgroup of SCAs with distinct clinical and biological features, however further clinical and molecular investigations are required. Second surgeries are associated with a higher incidence of preoperative pituitary insufficiency, and a higher risk of subtotal resection, and a higher probability of CSF space opening intraoperatively compared to first surgeries. On the other hand, the risk of new postoperative pituitary insufficiency was higher after first surgeries. In our cohort of patients, no prognostic factor for recurrence among histological diagnosis, Ki67-proliferation index, p53 expression, number of mitoses, invasive growth or cystic lesions for SCAs could be detected.

Exoscopic vs. microscopic transsphenoidal surgery for Cushing's disease: a retrospective single-center study on 388 patients.

Microscopic and endoscopic transsphenoidal surgeries represent the standard treatment for Cushing's disease (CD). At our institution a new exoscopic approach was implemented. After proof of the general use for transsphenoidal pituitary surgery, the aim of this study was to compare the exoscopic 4K3D video microscope with the microscopic transsphenoidal surgery for patients with CD. We conducted a retrospective analysis on 388 patients with CD treated in our medical center via microscopic transsphenoidal surgery (MTS) between January 2008 and July 2019 or via exoscopic transsphenoidal surgery (ExTS) between May 2019 and May 2021. Parameters investigated included histology, pre- and postoperative MRI with tumor size, pre- and postoperative ACTH and cortisol levels, duration of surgery, perioperative and postoperative complications as well as clinical outcome. Patients who underwent ExTS in CD experienced a lower incidence of SIADH/diabetes insipidus (p = 0.0164), a higher rate of remission (p = 0.0422), and a shorter duration of surgery (p < 0.0001), compared to MTS. However, there was no significant difference regarding new postoperative pituitary insufficiency and intraoperative CSF space opening. We found that ExTS had multiple benefits compared to MTS for tumor resection in case of CD. These results are in line with our previous publication on the general applicability of an exoscope in pituitary surgery. To our knowledge, this is the first clinical study proving the superiority of ExTS in CD. These results are promising, nevertheless further studies comparing exoscopic with the endoscopic approach are necessary to finally evaluate the utility of the new technique.

[MRI reporting of gliomas : What neuro-oncology clinicians expect from radiologists]. / MRT-Befundung hirneigener Tumoren : Was neuroonkologisch tätige Kliniker vom Radiologen erwarten.

BACKGROUND AND OBJECTIVE: Structured reporting of MRI examinations using consensus-based content categories has the potential to improve interdisciplinary communication in neuro-oncology. Therefore, the aim of this study was to determine the essential reporting categories in the imaging of gliomas from a clinical perspective within the setting of a nationwide survey of members of medical societies working in neuro-oncology. MATERIALS AND METHODS: An online questionnaire was created based on an interdisciplinary developed catalog of possible MRI reporting elements. Subsequently, specialist members of the German Societies of Neurosurgery, Radiation Oncology, Hematology and Medical Oncology, Neurology, and Neuropathology were invited to evaluate the items with regard to their clinical relevance. RESULTS: A total of 171 specialists from Germany participated in the survey (81 neurosurgeons, 66 radiation therapists, and 24 other neuro-oncology experts). Number and anatomic extent of tumors in the contrast-enhanced T1 and 2D T2 sequences (98.8% vs. 97.1%) as well as newly diagnosed lesions at follow-up (T1 + contrast 98.2%; T2 94.7%) were overall most frequently considered crucial. In addition, the experts particularly rated the description of ependymal and/or leptomeningeal tumor dissemination (93.6%) and signs of mass effect including occlusive hydrocephalus and parenchymal mass shifts (> 75.0% each) as essential. Standard mention of intratumoral calcifications, hemorrhages, tumor vascular architecture, or advanced imaging modalities such as MR perfusion, diffusion, tractography, and proton spectroscopy were considered fundamental to their everyday practice by only a minority of neuro-oncology colleagues. CONCLUSION: A referring physician-oriented minimum content standard for MRI examinations in primary brain tumor patients should include as clinically relevant core elements the exact anatomic spread of the lesion(s), including ependymal and meningeal involvement, and the pertinent signs of mass effect.

Determining the applicability of the RSNA radiology lexicon (RadLex) in high-grade glioma MRI reporting-a preliminary study on 20 consecutive cases with newly diagnosed glioblastoma.

BACKGROUND: The implementation of a collective terminology in radiological reporting such as the RSNA radiological lexicon (RadLex) yields many benefits including unambiguous communication of findings, improved education, and fostering data mining for research purposes. While some fields in general radiology have already been evaluated so far, this is the first exploratory approach to assess the applicability of the RadLex terminology to glioblastoma (GBM) MRI reporting. METHODS: Preoperative brain MRI reports of 20 consecutive patients with newly diagnosed GBM (mean age 68.4 ± 10.8 years; 12 males) between January and October 2010 were retrospectively identified. All terms related to the tumor as well as their frequencies of mention were extracted from the MRI reports by two independent neuroradiologists. Every item was subsequently analyzed with respect to an equivalent RadLex representation and classified into one of four groups as follows: 1. verbatim RadLex entity, 2. synonymous/multiple equivalent(s), 3. combination of RadLex concepts, or 4. no RadLex equivalent. Additionally, verbatim entities were categorized using the hierarchical RadLex Tree Browser. RESULTS: A total of 160 radiological terms were gathered. 123/160 (76.9%) items showed literal RadLex equivalents, 9/160 (5.6%) items had synonymous (non-verbatim) or multiple counterparts, 21/160 (13.1%) items were represented by means of a combination of concepts, and 7/160 (4.4%) entities could not eventually be transferred adequately into the RadLex ontology. CONCLUSIONS: Our results suggest a sufficient term coverage of the RadLex terminology for GBM MRI reporting. If applied extensively, it may improve communication of radiological findings and facilitate data mining for large-scale research purposes.

The Impact of Surgery-Related Muscle Injury on Prevalence and Characteristics of Acute Postcraniotomy Headache - A Prospective Consecutive Case Series.

BACKGROUND: The latest third edition of the International Classification of Headache Disorders delineates diagnostic criteria for acute headache attributed to craniotomy (AHAC), but data on possible predisposing factors are sparse. This prospective observational study aims to evaluate the impact of surgery-related muscle incision on the prevalence, severity, and characteristics of AHAC. PATIENTS AND METHODS: Sixty-four consecutive adults (mean age: 54.2 ± 15.2 years; 26 males and 38 females) undergoing cranial neurosurgery for various reasons without preoperative headache were included. After regaining consciousness, all patients reported their average daily headache on a numeric pain rating scale (NRS; range: 0-10), headache characteristics, as well as analgesic consumption from day 1 to 3 after surgery. Three distinct patient cohorts were built with respect to the surgical approach (craniotomy ± muscle incision; burr hole surgery) and group comparisons were performed. Additionally, patients with AHAC ≥ 3 NRS were reevaluated at 7.2 ± 2.3 months following treatment by means of standardized questionnaires to determine the prevalence of persistent headache attributed to craniotomy as well as headache-related disability and quality of life. RESULTS: Thirty of 64 (46.9%) patients developed moderate to severe AHAC (NRS ≥ 3) after cranial neurosurgery. There were no significant group differences with regard to age, gender, or general health condition (American Society of Anesthesiologists Physical Status Classification). Craniotomy patients with muscle incision suffered from significantly higher early postoperative mean NRS scores compared with their counterparts without procedure-related muscle injury (3.4 ± 2.3 vs. 2.3 ± 1.9) as well as patients undergoing burr hole surgery (1.2 ± 1.4; p = 0.02). Moreover, the consumption of nonopioid analgesics was almost doubled following muscle-transecting surgery as compared with muscle-preserving procedures (p = 0.03). Young patient age (odds ratio/95% confidence interval for each additional year: 0.93/0.88-0.97) and surgery-related muscle injury (5.23/1.62-19.41) were identified as major risk factors for the development of AHAC ≥ 3 NRS. There was a nonsignificant trend toward higher pain chronification rate as well as headache-related disability after craniotomy with muscle injury. CONCLUSION: Surgery-related muscle damage may be an important predisposing factor for AHAC. Therefore, if a transmuscular approach is unavoidable, the neurosurgeon should be aware of the need for adequately adjusted intra- and postoperative analgesia in these cases.

Prevalence of Signs and Symptoms of Pseudotumor Cerebri Syndrome Before and After Transsphenoidal Surgery for Cushing's Disease - A Prospective Consecutive Case Series.

INTRODUCTION: Pseudotumor cerebri syndrome (PTCS) has anecdotally been described after successful treatment of Cushing's disease (CD), but the prevalence following transsphenoidal surgery has not been determined so far in a prospective study. PATIENTS AND METHODS: 41 consecutive adult CD patients were prospectively screened for signs and symptoms of PTCS, headache-related impairment, and ophthalmological features associated with intracranial pressure elevation before surgery and at follow-up (mean 4 months). RESULTS: Biochemical remission was achieved in 36 of 41 (87.8%) patients after surgery. The most frequent preoperative complaints were visual acuity impairment (19 cases; 46.3%), headache (13 cases; 31.7%), and ear noise (9 cases; 22.0%). A significant reduction of visual disturbances was seen at follow-up. Overall, CD patients presented with fairly low headache-related emotional and functional restrictions before and after surgery. One of 34 (2.9%) patients with sufficient ophthalmological follow-up showed new-onset papilledema combined with temporary worsening of visual acuity and scotoma. CONCLUSION: Our results suggest a very low frequency of signs and symptoms of PTCS after surgical treatment for CD in adults. This estimate is in line with previous outcomes from retrospective pediatric CD series. Further large-scale studies are needed to determine the actual prevalence of this condition following biochemical remission of CD.

Damage to the eye and optic nerve in seriously traumatized patients with concomitant head injury: analysis of 84,627 cases from the TraumaRegister DGU® between 2002 and 2015.

BACKGROUND: To determine the prevalence and characteristics of prechiasmatic visual system injuries (VSI) among seriously injured patients with concomitant head trauma in Europe by means of a multinational trauma registry. METHODS: The TraumaRegister DGU® was searched for patients suffering from serious trauma with a Maximum Abbreviated Injury Scale (AIS) ≥ 3 between 2002 and 2015 in Europe. After excluding cases without significant head injury defined by an AIS ≥ 2, groups were built regarding the existence of a concomitant damage to the prechiasmatic optic system comprising globe and optic nerve. Group comparisons were performed with respect to demographic, etiological, clinical and outcome characteristics. RESULTS: 2.2% (1901/84,627) of seriously injured patients with concomitant head trauma presented with additional VSI. These subjects tended to be younger (mean age 44.7 versus 50.9 years) and were more likely of male gender (74.8% versus 70.0%) compared to their counterparts without VSI. The most frequent trauma etiologies were car accidents in VSI patients (28.5%) and falls in the control group (43.2%). VSI cases were prone to additional soft tissue trauma of the head, skull and orbit fractures as well as pneumocephalus. Primary treatment duration was significantly longer in the VSI cohort (mean 23.3 versus 20.5 days) along with higher treatment costs and a larger proportion of patients with moderate or severe impairment at hospital discharge despite there being a similar average injury severity at admission in both groups. CONCLUSIONS: A substantial proportion of patients with head injury suffers from additional VSI. The correlation between VSI and prolonged hospitalization, increased direct treatment expenditures, and having a higher probability of posttraumatic impairment demonstrates the substantial socioeconomic relevance of these types of injuries.

The burden of headache following aneurysmal subarachnoid hemorrhage: a prospective single-center cross-sectional analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) as a serious type of stroke is frequently accompanied by a so-called initial thunderclap headache. However, the occurrence of burdensome long-term headache following SAH has never been studied in detail so far. The aim of this study was to determine the prevalence and characteristics of long-term burdensome headache in good-grade SAH patients as well as its relation to health-related quality of life (HR-QOL). METHODS: All SAH cases treated between January 2014 and December 2016 with preserved consciousness at hospital discharge were prospectively interviewed regarding burdensome headache in 2018. Study participants were subsequently scrutinized by means of a standardized postal survey comprising validated pain and HR-QOL questionnaires. A retrospective chart review provided data on the initial treatment. RESULTS: A total of 93 out of 145 eligible SAH patients participated in the study (62 females). A total of 41% (38/93) of subjects indicated burdensome headache at follow-up (mean 32.6 ± 9.3 months). Comparison between patients with (HA+) and without long-term headache (HA-) revealed significantly younger mean age (47.9 ± 11.8 vs. 55.6 ± 10.3 years; p < .01) as well as more favorable neurological conditions (WFNS I/II: 95% vs. 75%; p = .03) in HA+ cases. The mean average headache of the HA+ group was 3.7 ± 2.3 (10-point numeric rating scale), and the mean maximum headache intensity was 5.7 ± 2.9. Pain and HR-QOL scores demonstrated profound alterations in HA+ compared to HA- patients. CONCLUSIONS: Our results suggest that a considerable proportion of SAH patients suffers from burdensome headache even years after the hemorrhage. Moreover, long-term headache is associated with reduced HR-QOL in these cases.

Quantitative Sensory Changes Following Gasserian Ganglion Radiofrequency Thermocoagulation in Patients with Medical Refractory Trigeminal Neuralgia: A Prospective Consecutive Case Series.

BACKGROUND AND OBJECTIVE: Microsurgical vascular nerve decompression and percutaneous ablative interventions aiming at the Gasserian ganglion are promising treatment modalities for patients with medical refractory trigeminal neuralgia (TN). Apart from clinical reports on a variable manifestation of facial hypoesthesia, the long-term impact of trigeminal ganglion radiofrequency thermocoagulation (RFT) on sensory characteristics has not yet been determined using quantitative methods. MATERIAL AND METHODS: We performed standardized quantitative sensory testing according to the established protocol of the German Research Network on Neuropathic Pain in a cohort of patients with classical (n = 5) and secondary (n = 11) TN before and after percutaneous Gasserian ganglion RFT (mean follow-up: 6 months). The test battery included thermal detection and thermal pain thresholds as well as mechanical detection and mechanical pain sensitivity measures. Clinical improvement was also assessed by means of renowned pain intensity and impairment questionnaires (Short-Form McGill Pain Questionnaire, Pain Disability Index, and Pain Catastrophizing Scale), pain numeric rating scale, and anti-neuropathic medication reduction at follow-up. RESULTS: All clinical parameters developed favorably following percutaneous thermocoagulation. Only mechanical and vibration detection thresholds of the affected side of the face were located below the reference frame of the norm population before and after the procedure. Statistically significant persistent changes in quantitative sensory variables caused by the intervention could not be detected in our patient sample. CONCLUSION: Our data suggest that TN patients improving considerably after RFT do not undergo substantial long-term alterations regarding quantitative sensory perception.

Nerve injury in severe trauma with upper extremity involvement: evaluation of 49,382 patients from the TraumaRegister DGU® between 2002 and 2015.

BACKGROUND: Peripheral nerve injury (PNI) as an adjunct lesion in patients with upper extremity trauma has not been investigated in a Central European setting so far, despite of its devastating long-term consequences. This study evaluates a large multinational trauma registry for prevalence, mechanisms, injury severity and outcome characteristics of upper limb nerve lesions. METHODS: After formal approval the TraumaRegister DGU® (TR-DGU) was searched for severely injured cases with upper extremity involvement between 2002 and 2015. Patients were separated into two cohorts with regard to presence of an accompanying nerve injury. For all cases demographic data, trauma mechanism, concomitant lesions, severity of injury and outcome characteristics were obtained and group comparisons performed. RESULTS: About 3,3% of all trauma patients with upper limb affection (n = 49,382) revealed additional nerve injuries. PNI cases were more likely of male gender (78,6% vs.73,2%) and tended to be significantly younger than their counterparts without nerve lesions (mean age 40,6 y vs. 47,2 y). Motorcycle accidents were the most frequently encountered single cause of injury in PNI patients (32,5%), whereas control cases primarily sustained their trauma from high or low falls (32,2%). Typical lesions recognized in PNI patients were fractures of the humerus (37,2%) or ulna (20,3%), vascular lacerations (arterial 10,9%; venous 2,4%) and extensive soft tissue damage (21,3%). Despite of similar average trauma severity in both groups patients with nerve affection had a longer primary hospital stay (30,6 d vs. 24,2 d) and required more subsequent inpatient rehabilitation (36,0% vs. 29,2%). CONCLUSION: PNI complicating upper extremity trauma might be more commonly encountered in Central Europe than suggested by previous foreign studies. PNI typically affect males of young age who show significantly increased length of hospitalization and subsequent need for inpatient rehabilitation. Hence these lesions induce extraordinary high financial expenses besides their impact on health related quality of life for the individual patient. Further research is necessary to develop specific prevention strategies for this kind of trauma.

Towards unambiguous reporting of complications related to deep brain stimulation surgery: A retrospective single-center analysis and systematic review of the literature.

BACKGROUND AND OBJECTIVE: To determine rates of adverse events (AEs) related to deep brain stimulation (DBS) surgery or implanted devices from a large series from a single institution. Sound comparisons with the literature require the definition of unambiguous categories, since there is no consensus on the reporting of such AEs. PATIENTS AND METHODS: 123 consecutive patients (median age 63 yrs; female 45.5%) treated with DBS in the subthalamic nucleus (78 patients), ventrolateral thalamus (24), internal pallidum (20), and centre médian-parafascicular nucleus (1) were analyzed retrospectively. Both mean and median follow-up time was 4.7 years (578 patient-years). AEs were assessed according to three unambiguous categories: (i) hemorrhages including other intracranial complications because these might lead to neurological deficits or death, (ii) infections and similar AEs necessitating the explantation of hardware components as this results in the interruption of DBS therapy, and (iii) lead revisions for various reasons since this involves an additional intracranial procedure. For a systematic review of the literature AE rates were calculated based on primary data presented in 103 publications. Heterogeneity between studies was assessed with the I2 statistic and analyzed further by a random effects meta-regression. Publication bias was analyzed with funnel plots. RESULTS: Surgery- or hardware-related AEs (23) affected 18 of 123 patients (14.6%) and resolved without permanent sequelae in all instances. In 2 patients (1.6%), small hemorrhages in the striatum were associated with transient neurological deficits. In 4 patients (3.3%; 0.7% per patient-year) impulse generators were removed due to infection. In 2 patients electrodes were revised (1.6%; 0.3% per patient-year). There was no lead migration or surgical revision because of lead misplacement. Age was not statistically significant different (p>0.05) between patients affected by AEs or not. AE rates did not decline over time and similar incidences were found among all patients (423) implanted with DBS systems at our institution until December 2016. A systematic literature review revealed that exact AE rates could not be determined from many studies, which could not be attributed to study designs. Average rates for intracranial complications were 3.8% among studies (per-study analysis) and 3.4% for pooled analysis of patients from different studies (per-patient analysis). Annual hardware removal rates were 3.6 and 2.4% for per-study and per-patient analysis, respectively, and lead revision rates were 4.1 and 2.6%, respectively. There was significant heterogeneity between studies (I2 ranged between 77% and 91% for the three categories; p< 0.0001). For hardware removal heterogeneity (I2 = 87.4%) was reduced by taking study size (p< 0.0001) and publication year (p< 0.01) into account, although a significant degree of heterogeneity remained (I2 = 80.0%; p< 0.0001). Based on comparisons with health care-related databases there appears to be publication bias with lower rates for hardware-related AEs in published patient cohorts. CONCLUSIONS: The proposed categories are suited for an unequivocal assessment of AEs even in a retrospective manner and useful for benchmarking. AE rates in the present cohorts from our institution compare favorable with the literature.

Nerve trauma of the lower extremity: evaluation of 60,422 leg injured patients from the TraumaRegister DGU® between 2002 and 2015.

BACKGROUND: Nerve lesions are well known reasons for reduced functional capacity and diminished quality of life. By now only a few epidemiological studies focus on lower extremity trauma related nerve injuries. This study reveals frequency and characteristics of nerve damages in patients with leg trauma in the European context. METHODS: Sixty thousand four hundred twenty-two significant limb trauma cases were derived from the TraumaRegister DGU® between 2002 and 2015. The TR-DGU is a multi- centre database of severely injured patients. We compared patients with additional nerve injury to those with intact neural structures for demographic data, trauma mechanisms, concomitant injuries, treatment and outcome parameters. RESULTS: Approximately 1,8% of patients with injured lower extremities suffer from additional nerve trauma. These patients were younger (mean age 38,1 y) and more likely of male sex (80%) compared to the patients without nerve injury (mean age 46,7 y; 68,4% male). This study suggests the peroneal nerve to be the most frequently involved neural structure (50,9%). Patients with concomitant nerve lesions generally required a longer hospital stay and exhibited a higher rate for subsequent rehabilitation. Peripheral nerve damage was mainly a consequence of motorbike (31,2%) and car accidents (30,7%), whereas leg trauma without nerve lesion most frequently resulted from car collisions (29,6%) and falls (29,8%). CONCLUSION: Despite of its low frequency nerve injury remains a main cause for reduced functional capacity and induces high socioeconomic expenditures due to prolonged rehabilitation and absenteeism of the mostly young trauma victims. Further research is necessary to get insight into management and long term outcome of peripheral nerve injuries.

Adverse events in deep brain stimulation: A retrospective long-term analysis of neurological, psychiatric and other occurrences.

BACKGROUND AND OBJECTIVE: The extent to which deep brain stimulation (DBS) can improve quality of life may be perceived as a permanent trade-off between neurological improvements and complications of therapy, comorbidities, and disease progression. PATIENTS AND METHODS: We retrospectively investigated 123 consecutive and non-preselected patients. Indications for DBS surgery were Parkinson's disease (82), dystonia (18), tremor of different etiology (21), Huntington's disease (1) and Gilles de la Tourette syndrome (1). AEs were defined as any untoward clinical occurrence, sign or patient complaint or unintended disease if related or unrelated to the surgical procedures, implanted devices or ongoing DBS therapy. RESULTS: Over a mean/median follow-up period of 4.7 years (578 patient-years) 433 AEs were recorded in 106 of 123 patients (86.2%). There was no mortality or persistent morbidity from the surgical procedure. All serious adverse events (SAEs) that occurred within 4 weeks of surgery were reversible. Neurological AEs (193 in 85 patients) and psychiatric AEs (78 in 48 patients) were documented most frequently. AEs in 4 patients (suicide under GPI stimulation, weight gain >20 kg, impairment of gait and speech, cognitive decline >2 years following surgery) were severe or worse, at least possibly related to DBS and non reversible. In PD 23.1% of the STN-stimulated patients experienced non-reversible (or unknown reversibility) AEs that were at least possibly related to DBS in the form of impaired speech or gait, depression, weight gain, cognitive disturbances or urinary incontinence (severity was mild or moderate in 15 of 18 patients). Age and Hoehn&Yahr stage of STN-simulated PD patients, but not preoperative motor impairment or response to levodopa, showed a weak correlation (r = 0.24 and 0.22, respectively) with the number of AEs. CONCLUSIONS: DBS-related AEs that were severe or worse and non-reversible were only observed in PD (4 of 82 patients; 4.9%), but not in other diseases. PD patients exhibited a significant risk for non-severe AEs most of which also represented preexisting and progressive axial and non-motor symptoms of PD. Mild gait and/or speech disturbances were rather frequent complaints under VIM stimulation. GPI stimulation for dystonia could be applied with negligible DBS-related side effects.

Why Does Threshold Level Change in Transcranial Motor-evoked Potentials During Surgery for Supratentorial Lesions?

BACKGROUND: Rising threshold level during monitoring of motor-evoked potentials (MEP) using transcranial electrical stimulation (TES) has been described without damage to the motor pathway in the cranial surgery, suggesting the need for monitoring of affected and unaffected hemisphere. We aimed to determine the factors that lead to a change in threshold level and to establish reliable criteria for adjusting stimulation intensity during surgery for supratentorial lesions. MATERIALS AND METHODS: Between October 2014 and October 2015, TES-MEP were performed in 143 patients during surgery for unilateral supratentorial lesions in motor-eloquent brain areas. All procedures were performed under general anesthesia using a strict protocol to maintain stable blood pressure. MEP were evaluated bilaterally to assess the percentage increase in threshold level, which was considered significant if it exceeded 20% on the contralateral side beyond the percentage increase on the ipsilateral side. Patients who developed a postoperative motor deficit were excluded. Volume of subdural air was measured on postoperative magnetic resonance imaging. Logistic regression was performed to identify factors associated with the intraoperative recorded changes in threshold level. RESULTS: A total of 123 patients were included in the study. On the affected side, 82 patients (66.7%) showed an increase in threshold level, which ranged from 2% to 48% and 41 patients (33.3%) did not show any change. The difference to the unaffected side was under 20% in all patients. The recorded range of changes in the systolic and mean pressure did not exceed 20 mm Hg in any of the patients. Pneumocephalus was detected on postoperative magnetic resonance imaging scans in 87 patients (70.7%) and 81 of them (93.1%) had an intraoperative increase in threshold level on either sides. Pneumocephalus was the only factor associated with an increase in threshold level on the affected side (P<0.001), while each of pneumocephalus and length of the procedure correlated with a change in threshold level on the unaffected side (P<0.001 and 0.032, respectively). CONCLUSIONS: Pneumocephalus was the only factor associated with increase in threshold level during MEP monitoring without damaging motor pathway. Threshold level on the affected side can rise up to 48% without being predictive of postoperative paresis, as long as the difference between the increased threshold of the affected and unaffected side is within 20%. Changes in systolic or mean blood pressure within a range of 20 mm Hg do not seem to influence intraoperative MEP.

BCL6-translocations affect the phenotype of follicular lymphomas only in the absence of t(14;18)IgH/BCL2.

BACKGROUND: The translocation t(14;18)IgH/BCL2 is the molecular hallmark of follicular lymphomas (FL). A subset of cases harbours translocations involving the BCL6-gene locus. This study aimed to determine the frequency of BCL2- and BCL6-translocations in FL and to identify morphological and immuno-histochemical features with respect to the presence of BCL2- and BCL6-translocations. MATERIALS AND METHODS: Fluorescence-in-situ-hybridisation (FISH) was used to determine the BCL2- and BCL6-translocation status of 102 FL and these were compared to morphological and immunohistochemical parameters. RESULTS: Lymphomas with BCL6- and BCL2-translocations were very similar to t(14;18)-positive lymphomas without BCL6-translocations. In contrast, t(14;18)-negative lymphomas with BCL6-translocations were amongst others of higher grade, less often CD10-positive, involved the bone marrow less frequently and did not infiltrate the lymph node capsule. CONCLUSION: BCL2- and BCL6-translocations correlate with particular phenotypes of follicular lymphomas. BCL6-translocations seem to affect the phenotype only when they are not accompanied by BCL2-translocations.