Klinik und Poliklinik für Neurochirurgie
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Objective: The main objective of the present prospective, randomized, single-blinded controlled study was to measure heat during bony decompression of lumbar spinal stenosis with high-speed drills and an ultrasonic bone-cutting knife.
Methods: Ninety patients diagnosed with lumbar spinal stenosis were included in this study and randomized for lumbar spinal canal decompression using either a high-speed drill with automatic irrigation, high-speed drill with manual irrigation, or an ultrasonic bone-cutting knife with automatic irrigation (USBCD). For evaluation of group homogeneity, a visual analog scale pain score and neurologic findings were measured preoperatively and postoperatively. Temperatures during bony decompression were measured using a forward-looking infrared camera system.
Results: Clinical results among the 3 groups did not differ in pain reduction, improvement of neurologic findings, or the rate of complications. However, significantly lower values were found for absolute and mean maximal temperatures during bony decompression in the USBCD group compared with the groups of patients who received the high-speed drill with automatic irrigation and the high-speed drill with manual irrigation, indicating this technique to be less aggressive in terms of thermal induction of bone necrosis. USBCD allows more precise bone removal compared with high-speed drills, and despite increased device time, no significant difference in the overall decompression time was observed.
Conclusions: All methods examined produced short temperature peaks with possible, at least temporary, damage to bone and neural tissue. Automatic irrigation was associated with lower heat development compared with manual irrigation. Despite evidence of critical temperatures, no clinical correlation (e.g., neurologic deficits) was encountered in this study. Clinically, all 3 methods presented equally good results.
Prospective Multicenter Trial of Cervical Arthroplasty with the ROTAIO® Cervical Disc Prosthesis
(2022)
Study design
Clinical observational study.
Objective
The ROTAIO® cervical disc prosthesis is a novel unconstrained implant with a variable center of rotation aiming at physiological motion. The objective of this multicenter prospective trial was to evaluate clinical outcome and complications within 2 years.
Material and Methods
120 patients (72 females and 48 males with median age of 43.0 years [23-60 yrs] underwent ACDA (ROTAIO®, SIGNUS Medical, Alzenau, Germany) and were prospectively followed for 24 months. Preoperative complaints were mainly associated with radiculopathy (n = 104) or myelopathy (n=16). There were 108 monosegmental and 12 bisegmental procedures including 6 hybrid constructs. Clinical outcome was evaluated at 3, 12 and 24 months in 100%, 96% and 77% of the cohort by VAS, NDI, WL-26, Patient`s Satisfaction Index (PSI), SF-36, Nurick Score, mJOA, Composite Success Rate, complications, patient`s overall satisfaction and analgesics use.
Results
Highly significant clinical improvements were observed according to NDI and VAS (P < .0001 (arm); P < .001 (neck); P = .002 (head)) at all time points. Analgetic use could be reduced in 87.1 to 95.2%. Doctor`s visits have been reduced in 93.8% after 24 months. Patient`s overall satisfaction was high with 78.4 to 83.5% of patients. The composite success rate was 77.5% after 12 months and 76.9% after 24 months. There were no major complications in this series. Slight subsidence of the prosthesis was observed in 2 patients and 3 patients demonstrated fusion after 24 months. 2 patients developed symptomatic foraminal stenosis, so that implant removal and fusion was performed resulting in a revision rate of 1.7% in 2 years.
Conclusion
The ROTAIO® cervical disc prosthesis is a safe and efficient treatment option for symptomatic degenerative disc disease demonstrating highly significant clinical improvement and high patient`s overall satisfaction with very low revision rates at 2 years.
Das Glioblastom ist ein hochmaligner und aggressiver Hirntumor, der von der WHO als Grad IV eingestuft wird. Die Betroffenen haben eine mittlere Überlebenszeit von 12 bis 15 Monaten, was auf dem invasiven Wachstum und der Chemo- und Radioresistenz des Tumors beruht. Dadurch existiert keine kurative Behandlung und es kommt in nahezu allen Fällen zu Rezidiven. Zunehmend wird deutlich, dass das Glioblastom einen stark veränderten Energiestoffwechsel aufweist, wobei das sogenannte lipidomic remodelling (Koundouros und Poulogiannis, 2020), welches für maßgebliche Alterationen im Fettsäuremetabolismus sorgt, besonders interessant erscheint. Die Fettsäureoxidation sowie damit assoziierte Prozesse und Proteine sind als eine bedeutende Energiequelle in den Fokus der Forschung getreten. So auch der hoch-affine Carnitintransporter OCTN2 (SLC22A5), welcher essentiell für den Carnitinhaushalt und damit die β-Oxidation der Zelle ist. In der vorgelegten Arbeit wurde daher das komplexe OCTN2/L-Carnitin System in seiner Funktion als potenzielle pharmakologische Zielstruktur zur therapeutischen Intervention beim Glioblastom tiefergehend untersucht und vorhandenes Wissen weiter ausgebaut. Hierzu diente eine Vielzahl experimenteller Bedingungen und Methoden, um Teilcharakteristiken des Glioblastoms darzustellen und die Bedeutung des OCTN2/L-Carnitin System zu überprüfen.
Da in vorausgegangenen Studien eine erhöhte Expression von OCTN2 mit einem signifikant schlechteren Überleben von Patienten mit Glioblastom nachgewiesen werden konnte, wurden als weitere potentiell interessante Zielstrukturen der niedrig-affine Carnitintransporter OCTN1 (SLC22A4) sowie Komponenten der β-Oxidation (CPT1C, CRAT) in die Patientenanalysen eingeschlossen. Zwar konnte für OCTN1 eine signifikant erhöhte mRNA-Expression in den humanen Glioblastomproben festgestellt werden, diese war jedoch nicht mit dem Überleben der Patienten assoziiert. Auch CPT1C und CRAT zeigten sich nicht als relevante Zielstrukturen beim Glioblastom.
In den durchgeführten Zellkulturexperimenten mit humanen LN-18 und murinen GL261 Glioblastomzellen zeigten sich partiell signifikante Effekte auf die wachstumsfördernden Kinasen AKT1 und ERK1/2, deren Phosphorylierungsgrad durch L-Carnitin moduliert wurde und die damit möglicherweise an carnitinvermittelten Wirkungen beteiligt sein könnten. Auf die Zellviabilität und Zellvitalität ließen sich hemmende Wirkungen des OCTN2-Inhibitors Meldonium sowie des CPT1-Hemmstoffes Etomoxir nachweisen, welche teilweise durch die zusätzliche Gabe von L-Carnitin revertiert wurden. Hinsichtlich der durch Zytostatika (Doxorubicin, Carmustin, Vincristin und Temozolomid) induzierten Apoptose konnte L-Carnitin nur die durch Carmustin in niedriger Dosierung ausgelöste Caspase-3 Aktivierung verhindern. Ein durch L-Carnitin ausgelöster Effekt auf die Migration der Glioblastomzellen konnte nicht nachgewiesen werden, jedoch wurde die migratorische Aktivität durch die Zytostatika Temozolomid und Carmustin, sowie interessanterweise auch durch den CPT1-Inhibitor Etomoxir, beeinträchtigt.
Um die Möglichkeit einer zielgerichteten Therapie gegen das OCTN2/L-Carnitin System präklinisch zu evaluieren, wurden tierexperimentelle Studien durchgeführt. Unter Verwendung eines orthotopen Glioblastommodelles der Maus konnte gezeigt werden, dass Etomoxir und Meldonium einen hemmenden Einfluss auf das in vivo Tumorwachstum besitzen, wobei dieser Effekt nur für den OCTN2-Inhibitor Meldonium signifikant ausfiel. In den OCTN2-defizienten jvs(-/-)-Mäusen konnte keine ausreichende Anzahl von Versuchstieren erreicht werden, um zuverlässige und finale Aussagen zu tätigen. In den heterozygoten jvs(+/-)-Mäusen, die zwar phänotypisch unauffällig sind, aber durch die geringere OCTN2 Ausstattung verminderte Carnitin-Gewebespiegel aufweisen, zeigte sich eine leichte, nicht signifikante Reduktion des intrazerebralen Tumorwachstums im Vergleich zu den C57BL/6-Wildtyp Mäusen.
Zusammenfassend wurde in der vorliegenden Arbeit das OCTN2/L-Carnitin System und seine Bedeutung für das Glioblastom umfassend dargelegt und experimentell überprüft. Als Endresultat dieser Studie können Etomoxir und Meldonium als Substanzen zur zielgerichteten Beeinflussung des Glioblastomwachstums angesehen werden und sollten in weiteren Versuchsreihen detailliert auf ihre Eignung für die Entwicklung neuer Therapieformen überprüft werden.
Purpose
Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunting are well-established treatments of obstructive hydrocephalus (HCP) in adult and pediatric patients. However, there is a lack of data with regard to the quality of life (QoL) of these patients during long-term follow-up
Methods
Inclusion criteria were pediatric patients with endoscopic treatment of hydrocephalus at the University Medicine Greifswald between 1993 and 2016. Patients older than 14 years at present were assessed with the Short Form-12 (SF-12) questionnaire. Patients younger than 14 years of age were assessed with the KINDL-R questionnaire that was completed by their parents. Patients’ values were compared with the scores of a corresponding age-matched group of the healthy population and with patients who received later shunt treatment. Information about comorbidities, current symptoms, and educational level were gained by an additional part. Comparative analysis between patients with ETV success and failure (defined as shunt implantation after ETV) was performed.
Results
A total of 107 patients (53 m, 54f) were included. Fifty-seven/107 patients (53.3%) were considered as ETV success. Mean age at ETV was 6.9 ± 5.9 years. Fifty-four statements of 89 patients that are still alive were gained (response rate 63%). Of these, 49 questionnaires were complete and evaluable (23 m, 26f; mean age 19.8 ± 10.0 years with an average follow-up period of 13.7 ± 7.2 years). Twenty-six/49 patients (53.1%) are considered ETV success. No statistically significant differences could be obtained between patients with ETV success and ETV failure. Patients older 14 years show QoL within normal range, patients younger than 14 years show significantly lower result regarding their environment of peers and social contacts. Patients younger than 6 months at the time of ETV and patients with posthemorrhagic HCP show significantly lower physical QoL. Gait disturbance, fatigue, and seizures are associated with a lower QoL, and educational level is lower than in the normal population.
Conclusions
Patients who underwent ETV in childhood do not have a lower health-related QoL in general. Subsequent insertions of ventriculoperitoneal (vp) shunts do not lower QoL. Certain subgroups of the patients show lower results compared to the healthy population.
Indications for surgery of pineal cysts without ventriculomegaly are still under debate. In view of the limited data for pineal cyst resection in the absence of hydrocephalus, and the potential risk of this approach, we have analyzed our patient cohort focusing on strategies to avoid complications according to our experience in a series of 73 pineal cyst patients. From 2003 to 2015, we reviewed our database retrospectively for all patients operated on a pineal cyst. Furthermore, we prospectively collected patients from 2016 to 2020. In summary, 73 patients with a pineal cyst were treated surgically between 2003 and 2020. All patients were operated on via a microscopic supracerebellar-infratentorial (SCIT) approach. The mean follow-up period was 26.6 months (range: 6–139 months). Seventy-three patients underwent surgery for a pineal cyst. An absence of enlarged ventricles was documented in 62 patients (51 female, 11 male, mean age 28.1 (range 4–59) years). Main presenting symptoms included headache, visual disturbances, dizziness/vertigo, nausea/emesis, and sleep disturbances. Complete cyst resection was achieved in 59/62 patients. Fifty-five of 62 (89%) patients improved after surgery with good or even excellent results according to the Chicago Chiari Outcome Scale, with complete or partial resolution of the leading symptoms. Pineal cysts resection might be an indication in certain patients for surgery even in the absence of ventriculomegaly. The high percentage of postoperative resolution of quality-of-life impairing symptoms in our series seems to justify surgery. Preoperatively, other causes of the leading symptoms have to be excluded.
Purpose
Despite being rarely reported, ischemic insults resulting from compromising small brainstem perforators following microvascular decompression (MVD) remain a potential devastating complication. To avoid this complication, we have been using indocyanine green (ICG) angiography intraoperatively to check the flow within the small brainstem perforators. We aim to evaluate the safety and usefulness of ICG videoangiography in MVD.
Methods
We extracted retrospective data of patients who received ICG videoangiography from our prospectively maintained database for microvascular decompression. We noted relevant data including demographics, offending vessels, operative technique, outcome, and complications.
Results
Out of the 438 patients, 15 patients with a mean age (SD) of 53 ± 10.5 years underwent intraoperative ICG angiography. Male:female was 1:1.14. The mean disease duration prior to surgery was 7.7 ± 5.3 years. The mean follow-up (SD) was 50.7 ± 42.0 months. In 14 patients, the offending vessel was an artery, and in one patient, a vein. Intraoperative readjustment of the Teflon pledget or sling was required in 20% (3/15) of the cases. No patient had any sort of brainstem ischemia. Eighty percent of the patients (12/15) experienced complete resolution of the spasms. 86.7% (13/15) of the patients reported a satisfactory outcome with marked improvement of the spasms. Three patients experienced slight hearing affection after surgery, which improved in two patients later. There was no facial or lower cranial nerve affection.
Conclusion
Intraoperative ICG is a safe tool for evaluating the flow within the brain stem perforators and avoiding brainstem ischemia in MVD for hemifacial spasm.
Purpose
Controversies regarding venous compression and trigeminal neuralgia (TN) still exist. The study demonstrates our experience for microvascular decompression (MVD) in TN caused by purely venous compression. The goal was to identify prognostic anatomical or surgical factors that may influence the outcome.
Methods
Between 2004 and 2020, 49 patients were operated with purely venous compression. Average age was 58.4 years. Mean history of TN was 7.8 years. Microsurgical procedures included transposition or separation of the vein, coagulation, and division. Several features have been analyzed with respect to BNI scores.
Results
Evaluation on discharge revealed a complete pain relief in 39 (80%), partial improvement in 7 (14%), and no benefit in 3 (6%) patients. Facial hypesthesia was reported by 14 (28.6%) patients. Mean follow-up (FU) was 42.1 months. BNI pain intensity score on FU revealed 71.4% excellent to very good scores (score 1: 32 (65.3%); 2: 3 (6.1%)). BNI facial numbness score 2 could be detected in 13 patients (26.5%) during FU. There was no statistical relationship between immediate pain improvement or BNI pain intensity score on FU with respect to surgical procedure, size of trigeminal cistern, type of venous compression, venous caliber, trigeminal nerve indentation, or neurovascular adherence. BNI facial numbness score was dependent on type of venous compression (p < 0.05).
Conclusion
We did not find typical anatomical features that could either predict or influence the outcome regarding pain improvement or resolution in any form. Neither classic microvascular decompression (interposition/transposition) nor sacrificing the offending vein made any difference in outcome.
Background
Microvascular decompression (MVD) success rates exceed 90% in hemifacial spasm (HFS). However, postoperative recovery patterns and durations are variable.
Objective
We aim to study factors that might influence the postoperative patterns and duration needed until final recovery.
Method
Only patients following de-novo MVD with a minimum follow-up of 6 months were included. Overall trend of recovery was modeled. Patients were grouped according to recognizable clinical recovery patterns. Uni- and multivariable analyses were used to identify the factors affecting allocation to the identified patterns and time needed to final recovery.
Results
A total of 323 (92.6%) patients had > 90% symptom improvement, and 269 (77.1%) patients had complete resolution at the last follow-up. The overall trend of recovery showed steep remission within the first 6 months, followed by relapse peaking around 8 months with a second remission ~ 16 months. Five main recovery patterns were identified.
Pattern analysis showed that evident proximal indentation of the facial nerve at root exit zone (REZ), males and facial palsy are associated with earlier recovery at multivariable and univariable levels. anterior inferior cerebellar artery (AICA), AICA/vertebral artery compressions and shorter disease durations are related to immediate resolution of the symptoms only on the univariable level. Time analysis showed that proximal indentation (vs. distal indentation), males and facial palsy witnessed significantly earlier recoveries.
Conclusion
Our main finding is that in contrast to peripheral indentation, proximal indentation of the facial nerve at REZ is associated with earlier recovery. Postoperative facial palsy and AICA compressions are associated with earlier recoveries. We recommend a minimum of 1 year before evaluating the final outcome of MVD for HFS.
BACKGROUND
Eosinophilic granuloma (EG) belongs to the family of Langerhans cell histiocytosis (LCH) and is considered to be a benign disease typically found in children younger than 15 years of age. Here, the authors describe an EG of unusual localization and clinical presentation.
OBSERVATIONS
The authors report a 9-year-old girl with an EG presenting as an osteolytic lesion of the clivus. After transsphenoidal resection and histological confirmation, adjuvant chemotherapy was initiated. Presenting signs and symptoms were weight loss, episodic grimacing, and moderate ballism-like movements. After a follow-up-period of 32 months, the patient presented with a total resolution of initial symptoms and no further tumor growth.
LESSONS
Although these lesions are rare, one should consider EG as a differential diagnosis when confronted with osteolytic lesions of the clivus.
Das Glioblastom (WHO Grad IV) ist der häufigste und aggressivste hirneigene Tumor des erwachsenen Menschen. Trotz Standardtherapie, bestehend aus neurochirurgischer Resektion aller im MRT kontrastmittelaufnehmenden Tumoranteile, Radiotherapie und Chemotherapie mit Temozolomid, liegt das mittlere Überleben der Patienten bei nur knapp über einem Jahr.
In früheren Arbeiten unserer Gruppe wurde die PSGL-1-Expression auf Tumor-assoziierten Makrophagen (TAM) mittels FACS und Immunhistochemie (IHC) untersucht. Die FACS- und IHC-Ergebnisse korrelierten nicht miteinander, da die Proben für beide Methoden aus unterschiedlichen Regionen im Tumor stammten. Die vorliegende Studie zielte darauf ab, die intratumorale Heterogenität sowie Phänotypen von TAM und Zytokinen beim GBM mit besonderem Fokus auf der PSGL-1-Expression zu untersuchen. Tumorproben von elf GBM-Patienten wurden zum Zeitpunkt der Erstdiagnose unter neuronavigatorischer Anleitung aus bis zu sechs verschiedenen definierten Regionen pro Tumor des kontrastverstärkten Tumorrandes gewonnen. Anschließend wurden die Proben sofort eingefroren. Insgesamt 12 Antigene wurden mittels Immunfluoreszenzfärbung (IF) als Komplett-Aufnahmen von Gewebeschnitten mikroskopiert und digital zusammengefügt. Die IF-Analyse erfolgte ausschließlich Algorithmus-basiert. Die Flüssigkeitsüberstände der 24-stündig inkubierten Tumorproben wurden durchflusszytometrisch gemessen. Die Gesamtexpressionsintensitäten sowie die Heterogenität der Expressionen zwischen verschiedenen Regionen eines Tumors wurde formelbasiert quantifiziert. Erwartungsgemäß zeigte sich GFAP als Tumorzellmarker mit dem höchsten Expressionsniveau über alle Patienten und Probenorte hinweg. Ein mittleres Expressionsniveau zeigte sich für CCR7, CD204, Arg1, iNOS, CD163 und CSF1R. MHC-II, CD206, CD16 und CD68 gehörten zu den niedrig exprimierten Antigenen. Interessanterweise zeigten diese niedrig exprimierten Antigene den höchsten Score bei der Bewertung der intratumoralen Heterogenität. Die geringste intratumorale Heterogenität wurde bei der GFAP-Expression gesehen (Score 5,5).
Die vorliegende Studie zeigt eine ausgeprägte intratumorale Heterogenität der gemeinsamen Oberflächenexpressionsmarker von TAM sowie der Zytokine im GBM. Insbesondere niedrig exprimierte Antigene, wie PSGL-1, weisen eine hohe intratumorale Heterogenität auf. Dennoch haben die TAM einen überwiegend antiinflammatorischen Phänotyp. Dies zeigt, dass immunologische Studien mit einer Probe pro Tumor in ihrer Aussagekraft eher begrenzt sind.