Cavernous malformations of the central nervous system: An international consensus statement.

Introduction: Cavernous malformations (CM) of the central nervous system constitute rare vascular lesions. They are usually asymptomatic, which has allowed their management to become quite debatable. Even when they become symptomatic their optimal mode and timing of treatment remains controversial. Research question: A consensus may navigate neurosurgeons through the decision-making process of selecting the optimal treatment for asymptomatic and symptomatic CMs. Material and methods: A 17-item questionnaire was developed to address controversial issues in relation to aspects of the treatment, surgical planning, optimal surgical strategy for specific age groups, the role of stereotactic radiosurgery, as well as a follow-up pattern. Consequently, a three-stage Delphi process was ran through 19 invited experts with the goal of reaching a consensus. The agreement rate for reaching a consensus was set at 70%. Results: A consensus for surgical intervention was reached on the importance of the patient's age, symptomatology, and hemorrhagic recurrence; and the CM's location and size. The employment of advanced MRI techniques is considered of value for surgical planning. Observation for asymptomatic eloquent or deep-seated CMs represents the commonest practice among our panel. Surgical resection is considered when a deep-seated CM becomes symptomatic or after a second bleeding episode. Asymptomatic, image-proven hemorrhages constituted no indication for surgical resection for our panelists. Consensus was also reached on not resecting any developmental venous anomalies, and on resecting the associated hemosiderin rim only in epilepsy cases. Discussion and conclusion: Our Delphi consensus provides an expert common practice for specific controversial issues of CM patient management.

Bringing pathology to nanomedicine: a comparison of in vivo toxicity of polymeric nanoparticle carriers with and without chitosan coating.

Over the last years, there has been an increasing number of proposals for the use of nanomaterials in medicine. The safety of novel technologies must be verified, prior to their clinical application. Pathology has much to contribute towards this end. In this study, we compared the in vivo toxicity effects of poly- (lactic-co-glycolic acid) nanoparticles with and without chitosan shell. Both nanoparticle types were loaded with curcumin. The nanoparticles were assessed in vitro for potential cytotoxicity with cell viability studies. For the in vivo test, 36 adult Wistar rats were used, four of which were the control group. The remaining 32 were divided into 2 groups, each of which was administered differentially coated drug carriers: (A) nanoparticles without chitosan coating and (B) nanoparticles with chitosan coating. For both groups, the subcutaneous route was used for administration. Each group was further divided into 2 sub-groups of 8 animals each. The animals of the first sub-groups were sacrificed 24 h after the injection and those of the second on the 7th day. The control group was also divided into 2 subgroups of 2 animals each. At the appointed post-administrative date, the rats were sacrificed, and specimens from the brain, liver, kidneys, heart, stomach, lungs, and from the skin at the injection site were collected and studied histopathologically. The evaluation of both in vitro and in vivo testing shows that nanoparticles with chitosan have significantly less, if any, toxic effects compared to those without chitosan.

Comparison of the prognostic value of coma scales among health-care professionals: a prospective observational study.

OBJECTIVE: To assess the predictive value of the Full Outline of Unresponsiveness (FOUR) Score and the Glasgow Coma Scale (GCS), investigating whether they are comparable in predicting short- and long-term functional outcome and if their predictive ability remains unaffected by the raters' background and experience. METHODS: Patients treated in the Neurosurgery Department and the Intensive Care Unit in need for consciousness monitoring were assessed between October 1st, 2018, and December 31st, 2020, by four raters (two consultants, a resident and a nurse) using the two scales on admission and at discharge. Outcome was recorded at discharge and at 6 months. Areas under the receiver operating characteristic curve (AUCs) were calculated for the prediction of mortality and poor outcome, and the identification of coma. RESULTS: Eighty-six patients were included. AUCs values were > 0.860 for all outcomes and raters. No significant differences were noted between the two scales. Raters' experience did not affect the scales' predictive value. Both scales showed excellent accuracy in identifying comatose patients (AUCs > 0.950). The difference between admission and discharge values was not a reliable predictor. CONCLUSION: Both the FOUR Score and GCS are reliable predictors of short- and long-term outcome, with no clear superiority among them. The application of the FOUR Score by inexperienced raters is equally reliable, without influencing negatively the predictive value.

Remote Supratentorial Recurrent Medulloblastoma: Case Study and Literature Review.

Medulloblastomas comprise 10% of pediatric brain tumors. Subfrontal recurrence is uncommon and has been associated with prone positioning, inadequate irradiation of the cribriform plate area, and hydrocephalus management. We discuss the case report of an 8-year-old boy with subfrontal medulloblastoma recurrence. The literature was reviewed using terms such as "medulloblastoma," "subfrontal recurrence," and "child." Forty-eight cases of subfrontal medulloblastoma recurrence were identified. The mean age at presentation was 12.3 years. Gross total resection was achieved in 44%, most patients received adjuvant radiation therapy, and approximately 25% received chemotherapy. The mean recurrence interval was 2.6 years. The mean number of recurrences per patient was 1.2 and the mean survival period was 3.3 years. Even in the case of meticulous resection and sufficient irradiation, recurrences may still occur. Our case indicates that resection of the recurrent lesion and repeat irradiation may benefit patients with satisfactory short-term results.

Clinimetric study and review of the Reaction Level Scale.

OBJECTIVES: Although the Reaction Level Scale (RLS) is still used for the assessment of the level of consciousness in distinct centers, its clinical characteristics and significance have been incompletely researched. In the current study, the clinimetric properties, the prognostic value, and the impact of the raters' background on the application of the RLS, in comparison with the Glasgow Coma Scale (GCS), are investigated. MATERIALS AND METHODS: A systematic review on the available clinical evidence for the RLS was first carried out. Next, the RLS was translated into Greek, and patients with neurosurgical pathologies in need of consciousness monitoring were independently assessed with both RLS and GCS, by four raters (two consultants, one resident, and one nurse) within one hour. Interrater reliability, construct validity, and predictive value (mortality and poor outcome, at discharge and at 6 months) were evaluated. RESULTS: Literature review retrieved 9 clinimetric studies related to the RLS, most of low quality, indicating that the scale has not been thoroughly studied. Both versions of the RLS (original and modified) showed high interrater reliability (κw >0.80 for all pairs of raters), construct validity (Spearman's p > .90 for all raters), and prognostic value (areas under the curve >0.85 for all raters and outcomes). However, except for broader patients' coverage, it failed to show any advantage over the GCS. CONCLUSIONS: The RLS has not succeeded in showing any advantage over the GCS in terms of reliability and validity. Available evidence cannot justify its use in clinical practice as a substitute to the widely applied GCS.

Cross-Cultural Adaptation and Validation of the Greek Version of the "Full Outline of Unresponsiveness Score": A Prospective Observational Clinimetric Study in Neurosurgical Patients.

BACKGROUND: The Full Outline of Unresponsiveness (FOUR) score is a clinical instrument for the assessment of consciousness which is gradually gaining ground in clinical practice, as it incorporates more complete neurological information than the Glasgow Coma Scale (GCS). The main objectives of the current study were the following: (1) translate and cross-culturally adapt the FOUR score into Greek; (2) evaluate its clinimetric properties, including interrater reliability, internal consistency, and construct validity; and (3) evaluate the reliability of assessments among health care professionals with different levels of experience and training. METHODS: The FOUR score was initially translated into Greek. Next, patients with neurosurgical pathologies in need of consciousness monitoring were independently assessed with the GCS and FOUR score within one hour by four raters who had different levels of experience and training (two board-certified neurosurgeons, a neurosurgery resident, and a registered nurse). Interrater reliability, internal consistency, and construct validity were evaluated for the scales using weighted Cohen's κ (κw) and intraclass correlation coefficients (ICC), Cronbach's α and Spearman's ρ values, respectively. RESULTS: A total of 408 assessments were performed for 99 patients. The interrater reliability was excellent for both the FOUR score (ICC = 0.941) and GCS (ICC = 0.936). The values of κw exceeded 0.90 for all pairs, suggesting that the FOUR score can be reliably applied by raters with varying experience. Among the scales' components, FOUR score's brainstem and respiratory items showed the lowest, yet high enough (κw > 0.60), level of agreement. The interrater reliability remained excellent (κw > 0.85, ICC > 0.90) for all diagnosis and age groups, with a trend toward higher FOUR score values in the most severe cases (ICC = 0.813 vs. 0.723). Both the FOUR score and GCS showed high internal consistency (Cronbach's α > 0.70 for all occasions). The FOUR score correlated strongly with GCS (Spearman's ρ > 0.90 for all raters), suggesting high construct validity. CONCLUSIONS: The Greek version of the FOUR score is a valid and reliable tool for the clinical assessment of patients with disorders of consciousness. It can be applied successfully by nurses, residents, and specialized physicians. Therefore, its use by medical practitioners with different levels of experience and training is strongly encouraged.

Intrathecal Administration of Nusinersen Using the Ommaya Reservoir in an Adult with 5q-Related Spinal Muscular Atrophy Type 1 and Severe Spinal Deformity.

Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder, typically caused by survival motor neuron 1 (SMN1) gene deletion in chromosome 5q resulting in loss of SMN protein. SMA type 1 progresses rapidly leading to increased mortality usually before the age of 2 years. Nusinersen, the first approved disease-modifying treatment for all 5q-SMA types and ages, is an antisense oligonucleotide administered intrathecally via repeated lumbar punctures. However, adult SMA patients typically present with severe scoliosis and spinal deformity. We present a 28-year-old patient with SMA type 1 and severe spinal deformity, who received nusinersen via a subcutaneously implanted Ommaya reservoir connected with an intrathecal catheter at the thoracic level. The repetitive administrations were completed uneventfully, obviating the need for repeated laborious lumbar punctures and eliminating radiation exposure. In adult SMA patients, performing recurrent lumbar punctures can be technically challenging raising the need for an alternative route of administration. The use of Ommaya reservoirs is a viable, practical for repeated infusions, and safe option for the intrathecal delivery of nusinersen for select cases such as an adult SMA type 1 survivor with severe spinal deformity.

Acute-onset diplopia from intracranial hypertension due to torcular herophili obstruction by an hemorrhagic intradiploic epidermoid cyst.

BACKGROUND: Epidermoid cysts are benign slow-growing congenital lesions, constituting approximately 1% of all cranial tumors. Most of these lesions are located intradurally, while about 10-25% of them are located within the diploic spaces. Intradiploic epidermoid cysts are usually discovered incidentally and may remain asymptomatic for many years, but in rare instances, they may grow intracranially and produce brain compression. Sometimes, intradiploic epidermoid cysts may occlude the main cranial venous sinuses causing intracranial hypertension. CASE DESCRIPTION: We present the case of a 24-year-old male harboring a paramedian right occipital intradiploic cyst with erosion of both outer and inner bony tables, which occluded the torcular herophili producing a worsening symptomatology with acute-onset diplopia from right sixth cranial nerve palsy; the patient also presented bilateral papilledema, but only reported mild headache and dizziness. Neuroradiological studies evidentiated a lesion compatible with intradiploic epidermoid cyst with intralesional hemorrhagic component, overlying and almost completely occluding the torcular herophili. Considering the fast worsening of symptomatology and the evidence of intracranial hypertension, the patient was operated on immediately after completion of clinical and radiological assessment. The lesion was radically removed with almost immediate reversal of signs and symptoms. Histopathology confirmed the diagnosis of epidermoid cyst with intralesional hemorrhagic components. CONCLUSION: Intradiploic epidermoid cysts may cause intracranial hypertension by occlusion of main cranial venous sinuses; intralesional hemorrhage may act as precipitating factor in occlusion of the torcular herophili, producing rapidly worsening intracranial hypertension, which requires prompt surgical treatment to reverse symptomatology. Radical surgical resection is necessary to avoid recurrence.

Adaptive Physics-Based Non-Rigid Registration for Immersive Image-Guided Neuronavigation Systems.

Objective: In image-guided neurosurgery, co-registered preoperative anatomical, functional, and diffusion tensor imaging can be used to facilitate a safe resection of brain tumors in eloquent areas of the brain. However, the brain deforms during surgery, particularly in the presence of tumor resection. Non-Rigid Registration (NRR) of the preoperative image data can be used to create a registered image that captures the deformation in the intraoperative image while maintaining the quality of the preoperative image. Using clinical data, this paper reports the results of a comparison of the accuracy and performance among several non-rigid registration methods for handling brain deformation. A new adaptive method that automatically removes mesh elements in the area of the resected tumor, thereby handling deformation in the presence of resection is presented. To improve the user experience, we also present a new way of using mixed reality with ultrasound, MRI, and CT. Materials and methods: This study focuses on 30 glioma surgeries performed at two different hospitals, many of which involved the resection of significant tumor volumes. An Adaptive Physics-Based Non-Rigid Registration method (A-PBNRR) registers preoperative and intraoperative MRI for each patient. The results are compared with three other readily available registration methods: a rigid registration implemented in 3D Slicer v4.4.0; a B-Spline non-rigid registration implemented in 3D Slicer v4.4.0; and PBNRR implemented in ITKv4.7.0, upon which A-PBNRR was based. Three measures were employed to facilitate a comprehensive evaluation of the registration accuracy: (i) visual assessment, (ii) a Hausdorff Distance-based metric, and (iii) a landmark-based approach using anatomical points identified by a neurosurgeon. Results: The A-PBNRR using multi-tissue mesh adaptation improved the accuracy of deformable registration by more than five times compared to rigid and traditional physics based non-rigid registration, and four times compared to B-Spline interpolation methods which are part of ITK and 3D Slicer. Performance analysis showed that A-PBNRR could be applied, on average, in <2 min, achieving desirable speed for use in a clinical setting. Conclusions: The A-PBNRR method performed significantly better than other readily available registration methods at modeling deformation in the presence of resection. Both the registration accuracy and performance proved sufficient to be of clinical value in the operating room. A-PBNRR, coupled with the mixed reality system, presents a powerful and affordable solution compared to current neuronavigation systems.

The current significance of the FOUR score: A systematic review and critical analysis of the literature.

BACKGROUND: The Full Outline of Un-Responsiveness Score (FOURs) is a scale for clinical assessment of consciousness that was introduced to overcome disadvantages of the widely accepted Glasgow Coma Scale (GCS). OBJECTIVE: To carry out a systematic review and critical analysis of the available literature on the clinical application of FOURs and perform a comparison to GCS, in terms of reliability and predictive value. METHODS: Initial search retrieved a total of 147 papers. After applying strict inclusion criteria and further article selection to overcome data heterogeneity, a statistical comparison of inter-rater reliability, in-hospital mortality and long-term outcome prediction between the two scales in the adult and pediatric population was done. RESULTS: Even though FOURs is more complicated than GCS, its application remains quite simple. Its reliability, validity and predictive value have been supported by an increasing number of studies, especially in critical care. A statistically significant difference (p = .034) in predicting in-hospital mortality in adults, in favor of FOURs when compared to GCS, was found. However, whether it poses a clinically significant advantage in detecting patients' deterioration and outcome prediction, compared to other scaling systems, remains unclear. CONCLUSIONS: Further studies are needed to discern the FOURs' clinical usefulness, especially in patients in non-critical condition, with milder disorders of consciousness.

Crocus sativus L. Causes a Non Apoptotic Calpain Dependent Death in C6 Rat Glioma Cells, Exhibiting a Synergistic Effect with Temozolomide.

Crocus sativus L., a dietary herb, has been used for various diseases including cancer. This is an in vitro study investigating the antineoplastic effect of the extract of the plant against C6 glioma rat cell line. The mechanism of cellular death and the synergistic effect of the extract with the alkylating agent temozolomide (TMZ) were investigated. Cellular viability was examined in various concentrations of the extract alone or in combination with TMZ. Apoptosis was determined with flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and autophagy by western blotting of the light chain 3 (LC3)-II. Cellular viability was reduced after exposure to the extract with half maximal inhibition concentration at 3 mg/ml. Flow cytometry and TUNEL assay suggested that the extract does not induce apoptosis. Moreover, their combination increased the ratio dead/apoptotic cells 10-fold (P < 0.001). LC3-II protein levels reduced after Crocus extract while this effect was reversed when the calpain inhibitor MDL28170 was added, suggesting a calpain-dependent death possibly through autophagy. We concluded that the extract of Crocus increases dead cell number after 48 h of exposure. Our results suggest that the cell undergoes calpain-dependent programmed cell death while co-exposure to Crocus extract and TMZ enhances the antineoplastic effect of the latter.

Does proximity to the subventricular zone and expression of CXCR-4 and nestin affect prognosis in high-grade glioma?

BACKGROUND: It is suspected that infiltration of stem cell areas with high-grade glioma (HGG) generates a population that compromises treatment results and survival. In this prospective study we set to assess the prognostic value of the proximity of the contrast-enhancing lesion (CEL) on MRI to the subventricular zone (SVZ) and the expression of CXCR4 and nestin as potential factors in the stem cell migration pathway. METHOD: All patients diagnosed with high-grade glioma over a three-year period from a single institution were enrolled in this prospective study. Based on MRI preoperative findings, the patients were classified into 4 Groups (I-IV) according to the proximity of the CEL on MRI to the SVZ. Histological samples were assessed with immunohistochemistry for nestin and CXCR4. Classification into groups and the presence of nestin and CXCR4 were evaluated as predictive factors for overall (OS) and progression free survival (PFS). RESULTS: Fourty patients were included in the study. In multivariate analysis, Groups II, III and IV predicted longer OS in comparison to group I (p = 0.01; p < 0.01; p < 0.01 respectively) and group III and IV predicted longer OS in comparison to group II (p < 0.01; p = 0.04 respectively). Group III predicted longer PFS than group I and II (p = 0.01; p < 0.01 respectively). The expression rates of CXCR-4 and nestin could not predict OS or PFS. CONCLUSIONS: In our study the classification according to the proximity of the contrast enhancing part of the lesion and the SVZ proved to be prognostically significant for both OS and PFS. Presence of CXCR4 or nestin was not predictive for OS or PFS.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Somatostatin Analogue Treatment of a TSH-Secreting Adenoma Presenting With Accelerated Bone Metabolism and a Pericardial Effusion: A Case Report.

Increased bone turnover and other less frequent comorbidities of hyperthyroidism, such as heart failure, have only rarely been reported in association with central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma (TSHoma). Treatment is highly empirical and relies on eliminating the tumor and the hyperthyroid state.We report here an unusual case of a 39-year-old man who was initially admitted for management of pleuritic chest pain and fever of unknown origin. Diagnostic work up confirmed pericarditis and pleural effusion both refractory to treatment. The patient had a previous history of persistently elevated levels of alkaline phosphatase (ALP), indicative of increased bone turnover. He had also initially been treated with thyroxine supplementation due to elevated TSH levels. During the diagnostic process a TSHoma was revealed. Thyroxine was discontinued, and resection of the pituitary tumor followed by treatment with a somatostatin analog led to complete recession of the effusions, normalization of ALP, and shrinkage of pituitary tumor.Accelerated bone metabolism and pericardial and pleural effusions attributed to a TSHoma may resolve after successful treatment of the tumor. The unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with these rare pituitary adenomas.

Expression pattern of the Hedgehog signaling pathway in pituitary adenomas.

Several studies have demonstrated the role of Wnt and Notch signaling in the pathogenesis of pituitary adenomas, but data are scarce regarding the role of Hedgehog signaling. In this study we investigated the differential expression of gene targets of the Hedgehog signaling pathway. Formalin-fixed, paraffin-embedded specimens from adult patients who underwent transphenoidal resection and normal human pituitary tissues that were obtained from autopsies were used. Clinical information and data from pre-operative MRI scan (extracellular tumor extension, tumor size, displacement of the optic chiasm) were retrieved from the Hospital's database. We used a customized RT(2) Profiler PCR Array, to investigate the expression of genes related to Notch and Hedgehog signaling pathways (PTCH1, PTCH2, GLI1, GLI3, NOTCH3, JAG1, HES1, and HIP). A total of 52 pituitary adenomas (32 non-functioning adenomas, 15 somatotropinomas and 5 prolactinomas) were used in the final analysis. In non-functioning pituitary adenomas there was a significant decrease (approximately 75%) in expression of all Hedgehog related genes that were tested, while Notch3 and Jagged-1 expression was found significantly increased, compared with normal pituitary tissue controls. In contrast, somatotropinomas demonstrated a significant increase in expression of all Hedgehog related genes and a decrease in the expression of Notch3 and Jagged-1. There was no significant difference in the expression of Hedgehog and Notch related genes between prolactinomas and healthy pituitary tissues. Hedgehog signalling appears to be activated in somatotropinomas but not in non-functioning pituitary adenomas in contrast to the expression pattern of Notch signalling pathway.

Lumbar puncture complicated by spinal epidural hematoma in a child with leukemia.

We report a case of spinal epidural hematoma (SEH) preceded by diagnostic lumbar puncture (LP) in a 5-year-old boy with acute lymphoblastic leukemia. MRI confirmed the presence of SEH between T7 and L5 levels, but the patient showed fast recovery during the next hours and conservative management was elected.

Tones and numbers: a combined EEG-MEG study on the effects of musical expertise in magnitude comparisons of audiovisual stimuli.

This study investigated the cortical responses underlying magnitude comparisons of multisensory stimuli and examined the effect that musical expertise has in this process. The comparative judgments were based on a newly learned rule binding the auditory and visual stimuli within the context of magnitude comparisons: "the higher the pitch of the tone, the larger the number presented." The cortical responses were measured by simultaneous MEG\EEG recordings and a combined source analysis with individualized realistic head models was performed. Musical expertise effects were investigated by comparing musicians to non-musicians. Congruent audiovisual stimuli, corresponding to the newly learned rule, elicited activity in frontotemporal and occipital areas. In contrast, incongruent stimuli activated temporal and parietal regions. Musicians when compared with nonmusicians showed increased differences between congruent and incongruent stimuli in a prefrontal region, thereby indicating that music expertise may affect multisensory comparative judgments within a generalized representation of analog magnitude.

Pilomyxoid astrocytoma of the cervical spinal cord in a child with rapid progression into glioblastoma: case report and literature review.

INTRODUCTION: Pilomyxoid astrocytoma (PMA) is a recently described glial tumor with similarities to pilocytic astrocytomas, yet with distinct histopathological characteristics and a more aggressive behavior. It occurs predominantly in the hypothalamic/chiasmatic region. Only four patients with spinal cord PMA have been reported in the pediatric population. The 2007 WHO Working Group recognized PMA as a new variant and recommended an assignment to WHO grade II. OBJECTIVE: The purpose of this paper was to report a rare location, address the aggressive behavior and rapid progression, and based on the specific patient, to review the literature and discuss current treatment strategies. CASE PRESENTATION: A 12-year-old girl presented with motor and sensory deficits of the left side as well as gait disturbance. Imaging revealed an intramedullary tumor extending from C2 to C7. The patient improved impressively after surgical resection. Histopathological findings were consistent with PMA. Three months later, the patient presented with rapid neurological deterioration. Histopathology after the second operation was consistent with glioblastoma. The outcome was fatal 12 months after initial diagnosis, despite adjuvant therapy. CONCLUSIONS: This is the fifth pediatric spinal cord PMA in literature. Furthermore, it is the only documented patient with rapid recurrence and progression within 3 months into a glioblastoma. The question of a sampling error affecting initial pathology is raised. Based on contemporary literature data, we discuss the further treatment options, as there are no guidelines yet. Efforts towards registries should be encouraged, as the documentation of PMA might lead to more evidence based treatment strategies.