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Prognostic risk factors for postoperative hemorrhage in stereotactic biopsies of lesions in the basal ganglia
Clinical Neurology and Neurosurgery 174 (2018) 180–184
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Prognostic risk factors for postoperative hemorrhage in stereotactic biopsies of lesions in the basal ganglia
T
Dana Farahmanda,b,c, Fee Keilb, Marie Göhringc, Nazife Dinca, Volker Seiferta, ⁎ Gerhard Marquardta, Sae-Yeon Wona,1, Johanna Quick-Wellera, ,1 a
Department of Neurosurgery, Goethe University, Frankfurt, Germany Institute for Neuroradiology, University Hospital, Goethe University, Frankfurt am Main, Germany c Department for Anesthesiology, Goethe University, Frankfurt, Germany b
A R T I C LE I N FO
A B S T R A C T
Keywords: Stereotactic biopsy Hemorrhage Basal ganglia Frame guided
Objective: The risk of hemorrhages after stereotactic biopsy is known to be low. Nevertheless hemorrhages in eloquent areas result in neurological deficit for the patients. Since the basal ganglia resemble a particularily high vascularized and eloquent location, which is often the source of hypertensive hemorrhages, we aimed to analyse possible risk factors for hemorrhage after stereotactic biopsy in this region. Patients and methods: We performed a retrospective analysis including patients who underwent stereotactic biopsies of lesions in the basal ganglia between January 2012 and January 2017. 63 patients were included in this study. We accessed age, gender, histopathological diagnosis, hypertension, blood pressure intraoperative, anticoagulative medication and postoperative hemorrhage. Results: Fishers exact test revealed no significant p-values concerning anticoagulative therapy, gender, smoking and hypertension concerning postoperative hemorrhage. Wilcoxon-Mann-Whitney-Test showed no significant correlation for systolic blood pressure intraoperative, number of tissue samples and age with hemorrhage. A trend for lymphoma in correlation with postoperative hemorrhage was in patients with Lymphoma (Wilcoxon-Mann-Whitney Test). Conclusion: Stereotactic biopsies even in eloquent areas as the basal ganglia are a safe procedure even if patients suffer under hypertension or are smoker. None of the here examined risk factors showed a significant correlation with postoperative hemorrhage. Accessing tumor tissue for histopathological diagnosis is mandatory for adequate therapy.
1. Introduction Nowadays, stereotactic biopsies are performed on an every day routine in many neurosurgical departments. Since exact tumor grading combines histopathological and molecular analysis, the assessment of tumor tissue is inevitable. While imaging techniques have tremendously improved over the last years, final diagnosis can still only be established after tumor tissue has been examined. In 90% of cases the pathologist can establish an accurate diagnosis by performing histopathologic, molecular, and immunologic analysis [1]. The further treatments of the patient, such as radiotherapy, chemotherapy or resection are based on these results. The procedure itself can be performed frame-based or frame-less and patients can undergo the procedure under local or general
anesthesia [2–4]. It remains unclear whether local or general anesthesia is less stressful for the patient and whether frame-guided or frame-less procedures offer more safe. Even if the stereotactic biopsy is performed frame-less the procedure can be conducted under local anesthesia in combination with conscious sedation [5]. Although the procedure itself goes in hand with a very low complication risk, every surgeon is afraid of causing postoperative hemorrhage especially in eloquent and highly vascularized regions such as the basal ganglia. Furthermore, many tumors are highly vascularized. Studies have shown so far that even eloquent regions like the brainstem and cerebellar can be reached stereotactically with maximum safety and even children can undergo the procedure [6–8]. Not only the brainstem but also the basal ganglia represent a deep seated and eloquent region. It resembles a predestination for
⁎
Corresponding author at: Department of Neurosurgery, University Hospital, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany. E-mail address: [email protected] (J. Quick-Weller). 1 Both authors contributed equally. https://doi.org/10.1016/j.clineuro.2018.09.008 Received 25 July 2018; Received in revised form 26 August 2018; Accepted 3 September 2018 Available online 18 September 2018 0303-8467/ © 2018 Elsevier B.V. All rights reserved.
Clinical Neurology and Neurosurgery 174 (2018) 180–184
D. Farahmand et al.
hypertensive hemorrhages and irresectable tumors are often seated in the basal ganglia [9,11]. To access tumor tissue they can only be reached by stereotactic biopsy. We evaluated whether lesions in this location have a higher risk of postoperative hemorrhage and whether this risk goes in hand with a history of hypertension, smoking, gender, age or elevated intraoperative blood pressure. Since patient population grows older diseases of the elderly are common also in patients who undergo stereotactic biopsy. Quick-Weller et al. showed that also elderly patients aged 80 years and older want to be treated even if a malignoma is histologically proven [10]. Therefore it is important for the surgeon to know whether his patient shows a higher risk of postoperative hemorrhage and might require postoperative CT scan and monitoring.
Table 1 Overview of patient characteristics. Variable
Gender female male
All STX (n = 63)
No bleeding (n = 46)
ICH < 1 cm (n = 11)
ICH > 1 cm (n = 6)
28 (44.4) 35 (55.6)
19 (41.3) 27 (58.7)
6 (54.5) 5 (45.5)
3 (50) 3 (50)
33 (71.7) 9 (19.6) 2 (4.3)
10 (90.9) 1 (9.1) 0
5 (83.3) 1 (16.7) 0
Anticoagulative therapy no anticoagulation 48 (76.2) Aspirin 11 (17.5) Phenprocumon 2 (3.2) Plavix 0 Rivaroxaban 1 (1.6) Kombi 1 (1.6)
2. Patients and methods We performed a retrospective analysis of our database and included patients who underwent stereotactic biopsy of lesions in the basal ganglia between January 2012 and January 2017. 514 patients underwent stereotactic biopsy at our department during this five years period, among these were 63 who underwent biopsy of lesions in the basal ganglia. We only included patients who underwent the procedure for diagnostic reasons. Patients who underwent cyst puncture or puncture of hemorrhages were excluded from this study. We evaluated age, gender, hypertension, blood pressure levels intraoperative, history of smoking, anticoagulation and histopathological diagnosis in correlation to postoperative bleeding as possible prognostic factors. In the patients with preoperative anticoagulative therapy, medication was paused 7–10 days before surgery. Every stereotactic procedure was performed frame-based (Leksell Frame). Trajectory planning was performed using BrainLab iPlan software 2.0 (BrainLab, Munich, Germany). 3. Description of the procedure All patients underwent thin slice MRI with contrast media in advance. On the day of the surgery all patients underwent CT with the frame attached to their heads. Leksell frame was attached with two pins frontal and two pins occipital. CT and MRI imaging were then fused and a trajectory was calculated by using BrainLab iplan software 2.0 (Brainlab, Munich, Germany). The trajectory was planned from right or left frontal, if possible in order to avoid eloquent structures. All parameters were then applied to the frame. Skin incision was about 2.5 cm long and the burrhole was about 1 cm in diameter. After the dura mater has been coagulated the dura was incised. Tissue samples were taken with a biopsy forceps, which generates samples of 1 mm. During every procedure a neuropathologist was present. He confirmed, that tumor tissue has been taken therefore the surgeon was sure to have reached the lesion of pathological tissue. After confirmation, the biopsy forceps is drawn back and the skin was closed. The frame was detached from the head and the anesthesia ended. After the procedure the patient was brought to the recovery room and finally to the normal ward (Table 1).
1 (2.2) 1 (2.2)
Smoking yes no unsure
12 (19) 22 (34.9) 29 (46)
7 (15.2) 17 (37) 22 (47.8)
3 (27.3) 3 (27.3) 5 (45.5)
2 (33.3) 2 (33.3) 2 (33.3)
Hypertension yes no
27 (42.9) 36 (57.1)
16 (34.8) 30 (65.2)
7 (63.6) 4 (36.4)
4 (66.7) 2 (33.3)
Histopathological diagnosis GBM 31 (49.2) Lymphoma 14 (22.2) Astrocytoma I 3 (4.8) Astrocytoma II 5 (7.9) Astrocytoma III 3 (4.8) Metastasis 3 (4.8) Others 4 (6.3)
23 (50) 7 (15.2) 3 (6.5) 5 (10.9) 3 (6.5) 2 (4.3) 3 (6.5)
5 (45.5) 5 (45.5)
3 (50) 2 (33.3)
Age < 57 =57 > 57
31 (49.2) 2 (3.2) 30 (47.6)
24 (52.2) 1 (2.2) 21 (45.7)
3 (27.3) 1 (9.1) 7 (63.6)
4 (66.7)
Number of tissue samples < 15 29 (46) = 15 6 (9.5) > 15 28 (44.4)
21 (45.7) 4 (8.7) 21 (45.7)
4 (36.4) 2 (18.2) 5 (45.5)
4 (66.7)
1 (9.1) 1 (16.7)
2 (33.3)
2 (33.3)
each. Postoperative hemorrhage was found in 17 patients. 6 of these hemorrhages had a mass effect, which was definined as > 1 cm [3]. Fisher’s exact test was used to correlate gender, anticoagulative therapy, smoking and hypertension. P-values of 0.05 and below were considered statistically significant. Analysis of the above mentioned parameters revealed no significant p-values (gender p = 0.6, anticoagulative therapy p = 0.5, smoking p = 0.6, histopathological diagnosis p = 0.6, Glioblastoma versus other histopathological diagnosis p = 1,0 and for Lymphoma versus other histopathological diagnosis p = 0.06). For age, number of tissue samples and systolic intraoperative blood pressure Wilcoxon-Mann-Whitney Test for non- parametric values was used. P-value for age was 0.4, for numbers of tissue samples taken p values was 0.5 and for intraoperative systolic blood pressure p was also 0.5. An overview of the statistical evaluation can be found in Table 2. 13 Patients (20.6%) showed clinical worsening postoperative
4. Results
Table 2 Overview of the statistical analysis for possible risk factors.
Median age of the included patients was 57. 28 (44.4%) patients were female and 35 (55.6%) patients male. In all patients a definitive diagnosis was be established. Median number of tissue samples taken was 15. Histopathological analysis revealed glioblastoma in 31 patients (49.2%), lymphoma was diagnosed in 14 patients (22.2%), astrocytoma WHO I in 3 (4.8%), astrocytoma WHO II in 5 (7.9%) and astrocytoma WHO III in 3 patients (4.8%). In also 3 patients (4.8%) metastases was diagnosed. Toxoplasmosis, encephalopathia, gliosis and gliosarkoma were diagnosed in one patient 181
Riskfactors
P-Values
Gender Anticoagulative Therapy Smoking Hypertension Histopathological Diagnosis Age Number of tissue samples
n.s. n.s. n.s. n.s. n.s. n.s. n.s.
(0.6) (0.5) (0.6) (0.5) (0,1) (0.6/1.0) (0.4) (0.5)
Clinical Neurology and Neurosurgery 174 (2018) 180–184
D. Farahmand et al.
Table 3 Overview of pre- and postoperative Symptoms and hemorrhages. Initial Symptome
New Symptoms postoperative
Hemorrhage intraoperative
Hemorrhage in postoperative CT
Hemorrhage in CT > 1cm
Parästhesia Fatigue Hemparesis right Paresis left leg Worsening of general condition Vision impairment left Worsening of Vigilance Hemparesis left Headache/ difficulties in word making Difficulties in word making Worsening of general condition Forgetfulness Worsening of general condition Aphasia, Facial palsy Desorientation Hydrocephalus, Desorientation Forgetfulness Gait disturbance Gait disturbance, Hemparesis Hemiparesis right Worsening of general condition, Fall Worsening of general condition Gait disturbance Aphasia Personality change Desorientation Hemiparesis left, Desorientation Disturbance of Coordination Desorientation Desorientation, Vomiting Gait disturbance Change of Personality Hemiparesis right Hemparesis right Forgetfulness Hemparesis right Worsening of general condition Hemparesis right Hemparesis left Fatigue, Vomiting Hemorrhage Hemparesis left Hydrocephalus Change of Personality Facial palsy Gait disturbance Fatigue Dizziness Gait disturbance Seizures Change of Personality Hypaesthesia Gait disturbance Difficulties in word finding Hemiparesis left, Hydrocephalus Hypaesthesia Dizziness Seizures Forgetfulness Aphasia Change of Personality Hemparesis right Hemparesis right
no no no no no no no Reduction of vigilance no no no no no Prolonged awakening no Reduction of vigilance Headache, Vomiting no Reduction of vigilance no Reduction of vigilance Reduction of vigilance Desorientation no no Desorientation no no no no no Reduction of vigilance no no no no no no no no Difficulties in word finding no no no no no no no no no no Seizures no no no no no no no no Seizures no no
no no no no no no no no yes no no no no yes no no no no no no no no no no yes no yes no no no no yes no no no no no no no yes yes no no no no yes yes no no no no no no no no no no no no no no no no
no no no no no no yes yes yes yes no yes no yes no yes no no no no no yes no no yes no yes no no no no yes no no no no no no no yes yes no no no no yes yes no no no yes no no no no no no no no yes no no no
no no no no no no yes no no no no no no no no yes no no no no no yes no no no no yes no no no no yes no no no no no no no yes no no no no no no no no no no no no no no no no no no no no no no no
5. Illustrative case
(Table 3). 11 of these patients (85%) showed bleeding complication, 4 with intraoperative bleeding and 7 with hemorrhage in CT. Of these 6 Patients (86%) showed hemorrhage with more than 1 cm in CT scan. Overall 17 (27%) patients showed hemorrhage in the postoperative CT, only 6 (35%) showed hemorrhage of > 1 cm. Taking the whole patient number into account, hemorrhage rate with > 1 cm is 9.5%.
A 75-year-old woman presented with left sided hemiparesis and disorientation for 10 days. The MRI showed a contrast-enhancing lesion reaching into the right basal ganglia, surrounded by perifocal edema (Fig. 1). We suggested stereotactic biopsy for histopathological analysis of the tissue. The patient had chosen to undergo the procedure under local anesthesia. During the procedure blood dripping out of the 182
Clinical Neurology and Neurosurgery 174 (2018) 180–184
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6. Discussion Hithero literature concerning tumors of the basal ganglia is rare. They are estimated to be 1–12% of cerebral tumors depending on the literature source [12–14]. Malikova et al. have even shown that patients with central nervous system lymphoma show an infiltration of the basal ganglia in 38% [15]. The basal ganglia form a high eloquent area of the brain. They are embedded deep in the cerebrum adjacent to the ventricles and the capsula interna and include striatum and globus pallidus. Functionally, the basal ganglia ensure a precise coordination of all movement impulses. They are responsible for direction and extend of movement, muscle strength and movement velocity [9,11]. Movement disorders such as dystonia, tremor or chorea are often related to lesions of the basal ganglia [13]. An involvement of the capsula interna can display clinical signs of paralysis on contralateral side. So a postoperative hemorrhage of the basal ganglia has a significant impact on the clinical outcome of the patient. There are numerous studies that have evaluated the incidence of postoperative complications such as hemorrhage associated with stereotactic brain biopsies. The reported hemorrhage rate varies between 4.7–59% [12,16–18]. Yet there is no standard to postoperative imaging and the definition of bleeding is not clearly described. Kulkarni et al. reported intracranial hemorrhage in 59% if a postoperative CT scan is obtained routinely. 90% of these postoperative hemorrhages did not lead to any neurological symptoms [18]. Most of these hemorrhages remain clinically silent and do not experience neurological deficit. One should consider carefully if a routinely CT scan should be performed to exclude hemorrhage and discharge patients on the day of stereotactic biopsy or if it is better to observe the patient over night after operation. Eibach et al. concluded in his study that postoperative CT examinations should be restricted to patients with intraoperative bleeding, clinical symptoms or if there was another high suspicion of hemorrhage [19]. Our own data show that stereotactic biopsies can be associated with a risk as high as 10% for intracranial bleeding. Most of them present no neurological worsening. In this study 20.6% of the patients (N = 13) showed neurological worsening postoperatively. Of these 6 (46%) showed hemorrhage of > 1 cm in postoperative CT. Postoperative CT might not only be useful in order to exclude hemorrhage, but also to verify that the correct targetpoint had been reached. In our study a neuropathologist was present in the OR to confirm the tumortissue has been biopsied, but a postoperative CT and fusion with preoperative planning (like it is also used in other stereotactical procedures e.g. deep brain stimulation) adds useful information. Nevertheless, our clinical experience also showed that the location of the stereotactic biopsy is important. We were able to provide evidence that for example stereotactic biopsy of pineal lesions show a higher risk of bleeding and consecutive hydrocephalus [20]. Grossmann et al. have shown that also lesions located in the brainstem showed a significantly higher occurrence of hemorrhagic complications [12]. As mentioned above a hemorrhage of the basal ganglia has a significant impact on the clinical outcome of the patient. If a biopsy in this region should be performed and there is a higher risk for bleeding, the patient should be informed. This is important to consider when counseling patients about the risks of stereotactic brain surgery. However, it should be evaluated if the biopsy is necessary and if the patient will have a benefit from the surgical procedure. Only a histopathological, immunologic and molecular analysis of tumor tissue samples can lead to the adequate treatment of the patient. In case of a malignant tumor this could be chemotherapy, radiology or a combination of both. On this account a precise diagnosis is in the majority of cases indispensable. As MRI techniques have tremendously improved over the last years studies have shown that the number of incorrect diagnosis based on MRI only is extremely high. Rachinger et al. found that in 60% of
Fig. 1. Preoperative MRI, T1 with contrast enhancement, showing a contrast enhancing lesion involving the right basal ganglia.
Fig. 2. Postoperative CT showing the blood collection along the trajectory.
stereotactic mandrin was observed. Therefore a CT scan was performed postoperativelym (Fig. 2). The scan revealed a small hemorrhage along the biopsy canal and a smaller blood collection deepseated were the tissue samples had been taken. No further surgical therapy concerning the hemorrhage was required. The patient left our department after three days without new neurological deficits. Histopathological analysis revealed a glioblastoma multiforme. Further therapy was radiochemotherapy according the suggestion of our interdisciplinary tumorboard.
183
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radiological diagnosed malignant gliomas this diagnosis was different to the histopathological results [21]. This underlines that tissue diagnosis is mandatory for the appropriate further treatment and should be pursued in these patients. Also the number of tissue samples is important. A recent published study of our department underlined that two taken tissue samples are not enough to confirm a diagnosis. In a group of patients with suspected glioblastoma just 73% were correctly diagnosed by analyzing only two tissue samples in comparison with a median number of 12 taken tissue samples [22]. A very important finding of this study is also that there is no higher bleeding risk by taking more tissue samples. As mentioned above there are two different procedures of stereotactic brain biopsy that are equally precise. The frame-based stereotactic brain biopsy is a fast cost-efficient procedure that may be performed in local anesthesia. This enables intraoperative patient feedback, which can be important when operating in eloquent regions of the brain. The frameless image-guided surgical navigation systems have higher costs, a longer operating room time, usually necessitate general anesthesia and is used for lesions larger than 15 mm. Bjartmarz et al. showed that accuracy and precision for hitting a planned stereotactic target in the brain are better with the conventional framebased procedure. Thus, frame-based stereotactic biopsy should remain a first-line approach [23,24]. In the last few years, a new procedure of stereotactic brain biopsy is trying to establish. Just a few neurosurgical centers routinely perform robot-assisted biopsies. Lefranc et al. published one of the first major studies by a series of 100 successive cases about this new technique. In their opinion robotic stereotactic biopsy combines the advantages of frameless and frame-based techniques. The accuracy is equivalent to both other procedures. A precise histopathological diagnosis can be achieved also for lesions smaller than 15 mm and even eloquent regions like the brainstem or pineal region operated robotized in 10 cases in total [25]. On the other hand this procedure is associated with general anesthesia of the patient, higher costs and an operating time on average of 2 h. It remains to be seen how this procedure will prevail. The evaluated prognostic factors of our present paper showed no statistical correlation between risk factor and increased post biopsy hemorrhage. Therefor we advise patients with lesions of the basal ganglia to be operated stereotactic to access tumor tissue for histopathological analysis regardless of their age, gender, smoking, intraoperative blood pressure or history of hypertension. But this decision should be based on the recommendation of the interdisciplinary tumor board and the individual attitude of the patient.
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9] [10]
[11]
[12]
[13]
[14] [15]
[16]
[17]
[18]
[19]
[20]
7. Conclusion [21]
Stereotactic biopsies are safe procedures with proven high diagnostic yield. Even in patients with lesions in eloquent areas such as the basal ganglia frame guided stereotactic biopsies resemble a safe procedure. None of the here analyzed possible prognostic factors predicted a higher risk for postoperative hemorrhage. Neither hypertension, nor smoking, number of tissue samples assessed, nor histological diagnosis showed a significant correlation to postoperative hemorrhage.
[22]
[23]
[24]
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[25]
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Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Prognostic risk factors for postoperative hemorrhage in stereotactic biopsies of lesions in the basal ganglia
T
Dana Farahmanda,b,c, Fee Keilb, Marie Göhringc, Nazife Dinca, Volker Seiferta, ⁎ Gerhard Marquardta, Sae-Yeon Wona,1, Johanna Quick-Wellera, ,1 a
Department of Neurosurgery, Goethe University, Frankfurt, Germany Institute for Neuroradiology, University Hospital, Goethe University, Frankfurt am Main, Germany c Department for Anesthesiology, Goethe University, Frankfurt, Germany b
A R T I C LE I N FO
A B S T R A C T
Keywords: Stereotactic biopsy Hemorrhage Basal ganglia Frame guided
Objective: The risk of hemorrhages after stereotactic biopsy is known to be low. Nevertheless hemorrhages in eloquent areas result in neurological deficit for the patients. Since the basal ganglia resemble a particularily high vascularized and eloquent location, which is often the source of hypertensive hemorrhages, we aimed to analyse possible risk factors for hemorrhage after stereotactic biopsy in this region. Patients and methods: We performed a retrospective analysis including patients who underwent stereotactic biopsies of lesions in the basal ganglia between January 2012 and January 2017. 63 patients were included in this study. We accessed age, gender, histopathological diagnosis, hypertension, blood pressure intraoperative, anticoagulative medication and postoperative hemorrhage. Results: Fishers exact test revealed no significant p-values concerning anticoagulative therapy, gender, smoking and hypertension concerning postoperative hemorrhage. Wilcoxon-Mann-Whitney-Test showed no significant correlation for systolic blood pressure intraoperative, number of tissue samples and age with hemorrhage. A trend for lymphoma in correlation with postoperative hemorrhage was in patients with Lymphoma (Wilcoxon-Mann-Whitney Test). Conclusion: Stereotactic biopsies even in eloquent areas as the basal ganglia are a safe procedure even if patients suffer under hypertension or are smoker. None of the here examined risk factors showed a significant correlation with postoperative hemorrhage. Accessing tumor tissue for histopathological diagnosis is mandatory for adequate therapy.
1. Introduction Nowadays, stereotactic biopsies are performed on an every day routine in many neurosurgical departments. Since exact tumor grading combines histopathological and molecular analysis, the assessment of tumor tissue is inevitable. While imaging techniques have tremendously improved over the last years, final diagnosis can still only be established after tumor tissue has been examined. In 90% of cases the pathologist can establish an accurate diagnosis by performing histopathologic, molecular, and immunologic analysis [1]. The further treatments of the patient, such as radiotherapy, chemotherapy or resection are based on these results. The procedure itself can be performed frame-based or frame-less and patients can undergo the procedure under local or general
anesthesia [2–4]. It remains unclear whether local or general anesthesia is less stressful for the patient and whether frame-guided or frame-less procedures offer more safe. Even if the stereotactic biopsy is performed frame-less the procedure can be conducted under local anesthesia in combination with conscious sedation [5]. Although the procedure itself goes in hand with a very low complication risk, every surgeon is afraid of causing postoperative hemorrhage especially in eloquent and highly vascularized regions such as the basal ganglia. Furthermore, many tumors are highly vascularized. Studies have shown so far that even eloquent regions like the brainstem and cerebellar can be reached stereotactically with maximum safety and even children can undergo the procedure [6–8]. Not only the brainstem but also the basal ganglia represent a deep seated and eloquent region. It resembles a predestination for
⁎
Corresponding author at: Department of Neurosurgery, University Hospital, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany. E-mail address: [email protected] (J. Quick-Weller). 1 Both authors contributed equally. https://doi.org/10.1016/j.clineuro.2018.09.008 Received 25 July 2018; Received in revised form 26 August 2018; Accepted 3 September 2018 Available online 18 September 2018 0303-8467/ © 2018 Elsevier B.V. All rights reserved.
Clinical Neurology and Neurosurgery 174 (2018) 180–184
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hypertensive hemorrhages and irresectable tumors are often seated in the basal ganglia [9,11]. To access tumor tissue they can only be reached by stereotactic biopsy. We evaluated whether lesions in this location have a higher risk of postoperative hemorrhage and whether this risk goes in hand with a history of hypertension, smoking, gender, age or elevated intraoperative blood pressure. Since patient population grows older diseases of the elderly are common also in patients who undergo stereotactic biopsy. Quick-Weller et al. showed that also elderly patients aged 80 years and older want to be treated even if a malignoma is histologically proven [10]. Therefore it is important for the surgeon to know whether his patient shows a higher risk of postoperative hemorrhage and might require postoperative CT scan and monitoring.
Table 1 Overview of patient characteristics. Variable
Gender female male
All STX (n = 63)
No bleeding (n = 46)
ICH < 1 cm (n = 11)
ICH > 1 cm (n = 6)
28 (44.4) 35 (55.6)
19 (41.3) 27 (58.7)
6 (54.5) 5 (45.5)
3 (50) 3 (50)
33 (71.7) 9 (19.6) 2 (4.3)
10 (90.9) 1 (9.1) 0
5 (83.3) 1 (16.7) 0
Anticoagulative therapy no anticoagulation 48 (76.2) Aspirin 11 (17.5) Phenprocumon 2 (3.2) Plavix 0 Rivaroxaban 1 (1.6) Kombi 1 (1.6)
2. Patients and methods We performed a retrospective analysis of our database and included patients who underwent stereotactic biopsy of lesions in the basal ganglia between January 2012 and January 2017. 514 patients underwent stereotactic biopsy at our department during this five years period, among these were 63 who underwent biopsy of lesions in the basal ganglia. We only included patients who underwent the procedure for diagnostic reasons. Patients who underwent cyst puncture or puncture of hemorrhages were excluded from this study. We evaluated age, gender, hypertension, blood pressure levels intraoperative, history of smoking, anticoagulation and histopathological diagnosis in correlation to postoperative bleeding as possible prognostic factors. In the patients with preoperative anticoagulative therapy, medication was paused 7–10 days before surgery. Every stereotactic procedure was performed frame-based (Leksell Frame). Trajectory planning was performed using BrainLab iPlan software 2.0 (BrainLab, Munich, Germany). 3. Description of the procedure All patients underwent thin slice MRI with contrast media in advance. On the day of the surgery all patients underwent CT with the frame attached to their heads. Leksell frame was attached with two pins frontal and two pins occipital. CT and MRI imaging were then fused and a trajectory was calculated by using BrainLab iplan software 2.0 (Brainlab, Munich, Germany). The trajectory was planned from right or left frontal, if possible in order to avoid eloquent structures. All parameters were then applied to the frame. Skin incision was about 2.5 cm long and the burrhole was about 1 cm in diameter. After the dura mater has been coagulated the dura was incised. Tissue samples were taken with a biopsy forceps, which generates samples of 1 mm. During every procedure a neuropathologist was present. He confirmed, that tumor tissue has been taken therefore the surgeon was sure to have reached the lesion of pathological tissue. After confirmation, the biopsy forceps is drawn back and the skin was closed. The frame was detached from the head and the anesthesia ended. After the procedure the patient was brought to the recovery room and finally to the normal ward (Table 1).
1 (2.2) 1 (2.2)
Smoking yes no unsure
12 (19) 22 (34.9) 29 (46)
7 (15.2) 17 (37) 22 (47.8)
3 (27.3) 3 (27.3) 5 (45.5)
2 (33.3) 2 (33.3) 2 (33.3)
Hypertension yes no
27 (42.9) 36 (57.1)
16 (34.8) 30 (65.2)
7 (63.6) 4 (36.4)
4 (66.7) 2 (33.3)
Histopathological diagnosis GBM 31 (49.2) Lymphoma 14 (22.2) Astrocytoma I 3 (4.8) Astrocytoma II 5 (7.9) Astrocytoma III 3 (4.8) Metastasis 3 (4.8) Others 4 (6.3)
23 (50) 7 (15.2) 3 (6.5) 5 (10.9) 3 (6.5) 2 (4.3) 3 (6.5)
5 (45.5) 5 (45.5)
3 (50) 2 (33.3)
Age < 57 =57 > 57
31 (49.2) 2 (3.2) 30 (47.6)
24 (52.2) 1 (2.2) 21 (45.7)
3 (27.3) 1 (9.1) 7 (63.6)
4 (66.7)
Number of tissue samples < 15 29 (46) = 15 6 (9.5) > 15 28 (44.4)
21 (45.7) 4 (8.7) 21 (45.7)
4 (36.4) 2 (18.2) 5 (45.5)
4 (66.7)
1 (9.1) 1 (16.7)
2 (33.3)
2 (33.3)
each. Postoperative hemorrhage was found in 17 patients. 6 of these hemorrhages had a mass effect, which was definined as > 1 cm [3]. Fisher’s exact test was used to correlate gender, anticoagulative therapy, smoking and hypertension. P-values of 0.05 and below were considered statistically significant. Analysis of the above mentioned parameters revealed no significant p-values (gender p = 0.6, anticoagulative therapy p = 0.5, smoking p = 0.6, histopathological diagnosis p = 0.6, Glioblastoma versus other histopathological diagnosis p = 1,0 and for Lymphoma versus other histopathological diagnosis p = 0.06). For age, number of tissue samples and systolic intraoperative blood pressure Wilcoxon-Mann-Whitney Test for non- parametric values was used. P-value for age was 0.4, for numbers of tissue samples taken p values was 0.5 and for intraoperative systolic blood pressure p was also 0.5. An overview of the statistical evaluation can be found in Table 2. 13 Patients (20.6%) showed clinical worsening postoperative
4. Results
Table 2 Overview of the statistical analysis for possible risk factors.
Median age of the included patients was 57. 28 (44.4%) patients were female and 35 (55.6%) patients male. In all patients a definitive diagnosis was be established. Median number of tissue samples taken was 15. Histopathological analysis revealed glioblastoma in 31 patients (49.2%), lymphoma was diagnosed in 14 patients (22.2%), astrocytoma WHO I in 3 (4.8%), astrocytoma WHO II in 5 (7.9%) and astrocytoma WHO III in 3 patients (4.8%). In also 3 patients (4.8%) metastases was diagnosed. Toxoplasmosis, encephalopathia, gliosis and gliosarkoma were diagnosed in one patient 181
Riskfactors
P-Values
Gender Anticoagulative Therapy Smoking Hypertension Histopathological Diagnosis Age Number of tissue samples
n.s. n.s. n.s. n.s. n.s. n.s. n.s.
(0.6) (0.5) (0.6) (0.5) (0,1) (0.6/1.0) (0.4) (0.5)
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Table 3 Overview of pre- and postoperative Symptoms and hemorrhages. Initial Symptome
New Symptoms postoperative
Hemorrhage intraoperative
Hemorrhage in postoperative CT
Hemorrhage in CT > 1cm
Parästhesia Fatigue Hemparesis right Paresis left leg Worsening of general condition Vision impairment left Worsening of Vigilance Hemparesis left Headache/ difficulties in word making Difficulties in word making Worsening of general condition Forgetfulness Worsening of general condition Aphasia, Facial palsy Desorientation Hydrocephalus, Desorientation Forgetfulness Gait disturbance Gait disturbance, Hemparesis Hemiparesis right Worsening of general condition, Fall Worsening of general condition Gait disturbance Aphasia Personality change Desorientation Hemiparesis left, Desorientation Disturbance of Coordination Desorientation Desorientation, Vomiting Gait disturbance Change of Personality Hemiparesis right Hemparesis right Forgetfulness Hemparesis right Worsening of general condition Hemparesis right Hemparesis left Fatigue, Vomiting Hemorrhage Hemparesis left Hydrocephalus Change of Personality Facial palsy Gait disturbance Fatigue Dizziness Gait disturbance Seizures Change of Personality Hypaesthesia Gait disturbance Difficulties in word finding Hemiparesis left, Hydrocephalus Hypaesthesia Dizziness Seizures Forgetfulness Aphasia Change of Personality Hemparesis right Hemparesis right
no no no no no no no Reduction of vigilance no no no no no Prolonged awakening no Reduction of vigilance Headache, Vomiting no Reduction of vigilance no Reduction of vigilance Reduction of vigilance Desorientation no no Desorientation no no no no no Reduction of vigilance no no no no no no no no Difficulties in word finding no no no no no no no no no no Seizures no no no no no no no no Seizures no no
no no no no no no no no yes no no no no yes no no no no no no no no no no yes no yes no no no no yes no no no no no no no yes yes no no no no yes yes no no no no no no no no no no no no no no no no
no no no no no no yes yes yes yes no yes no yes no yes no no no no no yes no no yes no yes no no no no yes no no no no no no no yes yes no no no no yes yes no no no yes no no no no no no no no yes no no no
no no no no no no yes no no no no no no no no yes no no no no no yes no no no no yes no no no no yes no no no no no no no yes no no no no no no no no no no no no no no no no no no no no no no no
5. Illustrative case
(Table 3). 11 of these patients (85%) showed bleeding complication, 4 with intraoperative bleeding and 7 with hemorrhage in CT. Of these 6 Patients (86%) showed hemorrhage with more than 1 cm in CT scan. Overall 17 (27%) patients showed hemorrhage in the postoperative CT, only 6 (35%) showed hemorrhage of > 1 cm. Taking the whole patient number into account, hemorrhage rate with > 1 cm is 9.5%.
A 75-year-old woman presented with left sided hemiparesis and disorientation for 10 days. The MRI showed a contrast-enhancing lesion reaching into the right basal ganglia, surrounded by perifocal edema (Fig. 1). We suggested stereotactic biopsy for histopathological analysis of the tissue. The patient had chosen to undergo the procedure under local anesthesia. During the procedure blood dripping out of the 182
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6. Discussion Hithero literature concerning tumors of the basal ganglia is rare. They are estimated to be 1–12% of cerebral tumors depending on the literature source [12–14]. Malikova et al. have even shown that patients with central nervous system lymphoma show an infiltration of the basal ganglia in 38% [15]. The basal ganglia form a high eloquent area of the brain. They are embedded deep in the cerebrum adjacent to the ventricles and the capsula interna and include striatum and globus pallidus. Functionally, the basal ganglia ensure a precise coordination of all movement impulses. They are responsible for direction and extend of movement, muscle strength and movement velocity [9,11]. Movement disorders such as dystonia, tremor or chorea are often related to lesions of the basal ganglia [13]. An involvement of the capsula interna can display clinical signs of paralysis on contralateral side. So a postoperative hemorrhage of the basal ganglia has a significant impact on the clinical outcome of the patient. There are numerous studies that have evaluated the incidence of postoperative complications such as hemorrhage associated with stereotactic brain biopsies. The reported hemorrhage rate varies between 4.7–59% [12,16–18]. Yet there is no standard to postoperative imaging and the definition of bleeding is not clearly described. Kulkarni et al. reported intracranial hemorrhage in 59% if a postoperative CT scan is obtained routinely. 90% of these postoperative hemorrhages did not lead to any neurological symptoms [18]. Most of these hemorrhages remain clinically silent and do not experience neurological deficit. One should consider carefully if a routinely CT scan should be performed to exclude hemorrhage and discharge patients on the day of stereotactic biopsy or if it is better to observe the patient over night after operation. Eibach et al. concluded in his study that postoperative CT examinations should be restricted to patients with intraoperative bleeding, clinical symptoms or if there was another high suspicion of hemorrhage [19]. Our own data show that stereotactic biopsies can be associated with a risk as high as 10% for intracranial bleeding. Most of them present no neurological worsening. In this study 20.6% of the patients (N = 13) showed neurological worsening postoperatively. Of these 6 (46%) showed hemorrhage of > 1 cm in postoperative CT. Postoperative CT might not only be useful in order to exclude hemorrhage, but also to verify that the correct targetpoint had been reached. In our study a neuropathologist was present in the OR to confirm the tumortissue has been biopsied, but a postoperative CT and fusion with preoperative planning (like it is also used in other stereotactical procedures e.g. deep brain stimulation) adds useful information. Nevertheless, our clinical experience also showed that the location of the stereotactic biopsy is important. We were able to provide evidence that for example stereotactic biopsy of pineal lesions show a higher risk of bleeding and consecutive hydrocephalus [20]. Grossmann et al. have shown that also lesions located in the brainstem showed a significantly higher occurrence of hemorrhagic complications [12]. As mentioned above a hemorrhage of the basal ganglia has a significant impact on the clinical outcome of the patient. If a biopsy in this region should be performed and there is a higher risk for bleeding, the patient should be informed. This is important to consider when counseling patients about the risks of stereotactic brain surgery. However, it should be evaluated if the biopsy is necessary and if the patient will have a benefit from the surgical procedure. Only a histopathological, immunologic and molecular analysis of tumor tissue samples can lead to the adequate treatment of the patient. In case of a malignant tumor this could be chemotherapy, radiology or a combination of both. On this account a precise diagnosis is in the majority of cases indispensable. As MRI techniques have tremendously improved over the last years studies have shown that the number of incorrect diagnosis based on MRI only is extremely high. Rachinger et al. found that in 60% of
Fig. 1. Preoperative MRI, T1 with contrast enhancement, showing a contrast enhancing lesion involving the right basal ganglia.
Fig. 2. Postoperative CT showing the blood collection along the trajectory.
stereotactic mandrin was observed. Therefore a CT scan was performed postoperativelym (Fig. 2). The scan revealed a small hemorrhage along the biopsy canal and a smaller blood collection deepseated were the tissue samples had been taken. No further surgical therapy concerning the hemorrhage was required. The patient left our department after three days without new neurological deficits. Histopathological analysis revealed a glioblastoma multiforme. Further therapy was radiochemotherapy according the suggestion of our interdisciplinary tumorboard.
183
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radiological diagnosed malignant gliomas this diagnosis was different to the histopathological results [21]. This underlines that tissue diagnosis is mandatory for the appropriate further treatment and should be pursued in these patients. Also the number of tissue samples is important. A recent published study of our department underlined that two taken tissue samples are not enough to confirm a diagnosis. In a group of patients with suspected glioblastoma just 73% were correctly diagnosed by analyzing only two tissue samples in comparison with a median number of 12 taken tissue samples [22]. A very important finding of this study is also that there is no higher bleeding risk by taking more tissue samples. As mentioned above there are two different procedures of stereotactic brain biopsy that are equally precise. The frame-based stereotactic brain biopsy is a fast cost-efficient procedure that may be performed in local anesthesia. This enables intraoperative patient feedback, which can be important when operating in eloquent regions of the brain. The frameless image-guided surgical navigation systems have higher costs, a longer operating room time, usually necessitate general anesthesia and is used for lesions larger than 15 mm. Bjartmarz et al. showed that accuracy and precision for hitting a planned stereotactic target in the brain are better with the conventional framebased procedure. Thus, frame-based stereotactic biopsy should remain a first-line approach [23,24]. In the last few years, a new procedure of stereotactic brain biopsy is trying to establish. Just a few neurosurgical centers routinely perform robot-assisted biopsies. Lefranc et al. published one of the first major studies by a series of 100 successive cases about this new technique. In their opinion robotic stereotactic biopsy combines the advantages of frameless and frame-based techniques. The accuracy is equivalent to both other procedures. A precise histopathological diagnosis can be achieved also for lesions smaller than 15 mm and even eloquent regions like the brainstem or pineal region operated robotized in 10 cases in total [25]. On the other hand this procedure is associated with general anesthesia of the patient, higher costs and an operating time on average of 2 h. It remains to be seen how this procedure will prevail. The evaluated prognostic factors of our present paper showed no statistical correlation between risk factor and increased post biopsy hemorrhage. Therefor we advise patients with lesions of the basal ganglia to be operated stereotactic to access tumor tissue for histopathological analysis regardless of their age, gender, smoking, intraoperative blood pressure or history of hypertension. But this decision should be based on the recommendation of the interdisciplinary tumor board and the individual attitude of the patient.
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9] [10]
[11]
[12]
[13]
[14] [15]
[16]
[17]
[18]
[19]
[20]
7. Conclusion [21]
Stereotactic biopsies are safe procedures with proven high diagnostic yield. Even in patients with lesions in eloquent areas such as the basal ganglia frame guided stereotactic biopsies resemble a safe procedure. None of the here analyzed possible prognostic factors predicted a higher risk for postoperative hemorrhage. Neither hypertension, nor smoking, number of tissue samples assessed, nor histological diagnosis showed a significant correlation to postoperative hemorrhage.
[22]
[23]
[24]
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[25]
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