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4. BRAIN TUMORS Chikezie Eseonu, Jordina Rincon- T orroella, and Alfredo Quiñones- Hinojosa rain tumor cases make up a significant part of the neurosurgery oral board examination. Having a good understanding of the management of com mon cases is essential for the examination. A  multitude of brain tumors exist, and they can be intraaxial or extra axial. When considering the differential diagnosis of a brain lesion, infection, hematomas, infarctions, thrombosed aneurysms, inflammation, and demyelinating disease must be considered in addition to tumors. Common adult brain tumors include gliomas, meningiomas, metastases, and pituitary tumors. Management of brain tumors includes understand ing preoperative care, indications for surgery, surgical approaches, preoperative and postoperative imaging, intraoperative and postoperative complications, and adjuvant therapy. Reviewing these essential points for the most common brain tumor cases and mastering the current treatment recommendations for common tumors will also be helpful for the boards. T echnology and management approaches for brain tumor treatment continue to evolve. With intraoperative stereotactic image guidance, direct cortical electrical stim ulation in awake craniotomies, and numerous less invasive surgical approaches, management of brain tumor patients requires an understanding of the disease process as well as knowledge of safe and efficient methods of treatment. Current technologies and approaches to brain tumors will continue to make up a large part of the oral examination. CASE 1 HISTORY AND PHYSICAL EXAMINA TION A 35- year- old man presents with a new onset of clonic sei zures in his left upper and lower extremity with postictal weakness. He is found to have 4+/ 5 left lower extremity strength and 3+ left patellar and ankle reflexes. Seizures are controlled with levetiracetam (Keppra), but now the patient reports numbness and tingling on his left side. IMAGING STUDIES The imaging studies demonstrate a right frontoparietal parasagittal region lesion without demonstrable contrast enhancement (Figure 4.1). ANALYSIS OF CASE AND SURGICAL PLAN This patient has a frontoparietal parasagittal lesion near the right motor strip area. With a lesion in an eloquent region of the brain, the examiner would want to determine your assessment on whether to operate, what surgical approach you would propose, and your evaluation of safety concerns. The differential diagnosis in this case would include lowgrade glioma, lymphoma, demyelinating lesion, infectious pathology, and arachnoid cyst. It is also important to know that the data show that a small percentage of these lesions, even if they are non– contrast enhancing, can be high- grade gliomas.1,2 Additional imaging for initial assessment and planning can include functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to help identify motor cortex and subcortical motor pathways. This imaging helps with the surgical resection of the lesion while sparing the eloquent cortex. Rationale for Surgery Management of low- grade gliomas is still a subject of controversy, although recent data support a more com plete resection when safe to do. With low- grade gliomas, 50% to 75% of patients die as a result of either recur rence or degeneration to a malignant glioma. 3 Some sur geons still recommend serial follow- up with imaging,

of low- grade gliomas is still a subject of controversy, although recent data support a more com plete resection when safe to do. With low- grade gliomas, 50% to 75% of patients die as a result of either recur rence or degeneration to a malignant glioma. 3 Some sur geons still recommend serial follow- up with imaging, 12 • G OODMAN ’S N EUROSURGERY O RAL B OARD R E v IEW but the National Comprehensive Cancer Network (NCCN) practice guidelines in oncology support max imal safe resection of a low- grade glioma as a first- line therapy. Class 1 data supporting this guideline include a population- based parallel cohort study that evaluated 153 patients in two hospitals; in this study, the expected 7- year survival rate was increased by more than 50% in patients who underwent surgical resection compared with those who received only biopsy and watchful waiting. 4– 7 Observation with follow- up magnetic resonance imag ing (MRI) should be reserved for cases in which the lesion is stable, the patient is asymptomatic and with out seizures, and there are no concerns of malignant progression (e.g., new or increased contrast enhance ment). In some cases, surgery or biopsy may be followed by chemotherapy or radiotherapy (RT), or both. W e discuss the indications for this treatment in subsequent paragraphs. In this particular case, given the worsening of symptoms for this patient, the need to prevent further invasion into eloquent regions, and the need to stop possible progres sion to a malignant tumor, surgical intervention would be recommended. A thorough removal of the tumor would allow for sei zure control, diagnosis, possible improvement of neurological deficits, reduced mass effect, and improved survival. 8 However, the benefits of a gross total resection in this case must be weighed against the risks of operating on the sur rounding structures (i.e., premotor and motor strip). Risks for permanent iatrogenic neurological deficits could also result and must be discussed with the patient.9 Approach Selection The surgical options for this tumor would require some combination of stereotactic intraoperative cranial navi gation, functional imaging, and direct cortical electrical stimulation for motor mapping. Intraoperative image guidance can be used for resection of the tumor while preserving functionally important areas based on preoperative fMRI. When preparing for intraoperative motor cortical and subcortical mapping, it is important to identify the borders of the tumor because often the difference between normal brain and the tumor is not evident to the surgeon and knowing the borders will allow for a supramarginal resection if indicated. Other intraoperative imaging techniques that are not influenced by brain shift, such as ultrasound, can also be used for tumor localization. An awake craniotomy can be used to localize the eloquent region intraoperatively, thus preserving brain function and relevant anatomy. Languageprocessing areas and Broca’s area can also be mapped out in a similar fashion. Given this tumor’s location in the perirolandic region, an awake craniotomy with motor mapping is preferred to solely intraoperative navigation and functional imaging.10,11 This patient went to surgery and underwent a right frontoparietal awake craniotomy for tumor resection. Direct electrical stimulation (DES) was used for corti cal and subcortical motor mapping. A  bipolar handheld stimulator, either the Ojemann Cortical Stimulator (Integra) or Osiris Cortical Stimulator (Inomed), delivers biphasic square wave pulses, with current ranging from 2 to 6 mA. 12 Figure 4.1 A: Preoperative axial T1- weighted magnetic resonance imaging (MRI) with contrast shows a hypointense non– contrast- enhanced right frontoparietal lesion located just posterior to the right motor strip.

ortical Stimulator (Inomed), delivers biphasic square wave pulses, with current ranging from 2 to 6 mA. 12 Figure 4.1 A: Preoperative axial T1- weighted magnetic resonance imaging (MRI) with contrast shows a hypointense non– contrast- enhanced right frontoparietal lesion located just posterior to the right motor strip. B: The lesion is hyperintense in the preoperative axial T2- weighted MRI.

ortical Stimulator (Inomed), delivers biphasic square wave pulses, with current ranging from 2 to 6 mA. 12 Figure 4.1 A: Preoperative axial T1- weighted magnetic resonance imaging (MRI) with contrast shows a hypointense non– contrast- enhanced right frontoparietal lesion located just posterior to the right motor strip. B: The lesion is hyperintense in the preoperative axial T2- weighted MRI. B RAIN  TUMORS • 13 Postoperatively, the patient is observed with follow- up clinic appointments and consecutive MRI scans indefinitely. The follow- up interval varies between neurosurgeons. W e recommend a baseline immediate postoperative MRI with contrast at 3 months, 6 months, and then yearly if the dis ease is stable. W e do not generally recommend stopping the follow- up because low- grade lesions may eventually recur or progress to a higher grade in some cases. After surgery, additional therapy (RT, chemotherapy, or both) is ultimately required, but the timing for adju vant therapy is uncertain. Four phase 3 randomized trials have been performed to study the role of RT in treat ing low- grade gliomas. The results of these trials showed that early postoperative RT improves progression- free but not overall survival (class I). Low doses of radiation were also shown to be as effective as high doses but were better tolerated (class  I). 13- 16 Factors to consider when selecting patients for immediate postoperative therapy include risks for worse outcomes, such as being older than 40  years or having a large preoperative tumor ( ≥5  cm), incomplete resection, elevated MIB- 1 labeling index of greater than 3%, astrocytic histology, absence of an iso citrate dehydrogenase ( IDH) mutation, or absence of a 1p19q codeletion. For patients younger than 40  years who undergo complete resection with favorable molecu lar features, initial observation after surgery is suggested. For older patients with residual disease and one or more molecular features that are unfavorable, immediate post operative therapy is recommended. For patients who do not fall into either category, the more risk factors that are present, the more likely immediate postoperative therapy will be implemented. 17,18 After postoperative therapy is chosen for a patient, RT or chemotherapy, or both, can be used. According to the guidelines from the NCCN, in patients older than 45 years, external- beam RT with or without chemotherapy is recommended for patients with tumors with 1p/ 19q codeletion.19 RT immediately after surgery can prolong progression- free survival, but does not improve overall survival. T wo recent clinical trials, the Radiation Therapy and Oncology Group (RTOG) 9402 study and the European Organization for Research and T reatment of Cancer (EORTC) 26961 study, have resulted in reconsideration of the most ade quate therapeutic approaches to these tumors. Both stud ies evaluated the role of PCV chemotherapy (procarbazine, lomustine [CCNU], and vincristine regimen) in combination with RT compared with RT alone. Both trials have demonstrated that tumors presenting a 1p/ 19q codeletion (oligodendroglial lineage marker) strongly benefit from the addition of PCV chemotherapy to RT.17,18 COMPLICA TIONS Intraoperative Complications One potential complication is intraoperative seizure fol lowing direct cortical stimulation. If seizure activity starts during stimulation of the patient’s cortex, cold irrigation can be used to suppress the seizure. Intravenous levetirace tam (500– 1500mg/ kg), phenytoin (15– 18 mg/ kg loading bolus given at 50 mg/ min), or midazolam (0.1– 0.3 mg/ kg) can be given for seizures unresponsive to cold irrigation. Postoperative Complications Another possible complication is severe left leg weak ness developing about 30 minutes after the resection is completed.

m (500– 1500mg/ kg), phenytoin (15– 18 mg/ kg loading bolus given at 50 mg/ min), or midazolam (0.1– 0.3 mg/ kg) can be given for seizures unresponsive to cold irrigation. Postoperative Complications Another possible complication is severe left leg weak ness developing about 30 minutes after the resection is completed. On examination, the patient is found to have good tone and is able to move spontaneously when not paying attention to the affected limb. Postoperative imaging shows a total resection with no signs of hemor rhage or new ischemic events (Figure 4.2). In this case, the patient presents with postoperative supplementary motor area (SMA) syndrome, which is characterized by complete akinesia and often mutism if the lesion is near the left dominant SMA. This syndrome usually spontane ously resolves in about 10  days but can last longer. The patient will need to be observed during this time and may require rehabilitation for 1 to 3 months to achieve com plete recovery. 20 Long- term Complications Other complications that can occur with this case include wound dehiscence after RT. Depending on the severity of the infection, antibiotics, with or without surgical debridement, will be required. PEARLS • DTI and fMRI can be used to identify eloquent cortex around a brain tumor. fMRI is highly dependent on the tested paradigms and the experience of the team. • Stereotactic intraoperative cranial surgical navigation, ultrasound, and direct cortical electrical stimulation are potential aides for tumor resection.

PEARLS • DTI and fMRI can be used to identify eloquent cortex around a brain tumor. fMRI is highly dependent on the tested paradigms and the experience of the team. • Stereotactic intraoperative cranial surgical navigation, ultrasound, and direct cortical electrical stimulation are potential aides for tumor resection. 14 • G OODMAN ’S N EUROSURGERY O RAL B OARD R E v IEW • An awake craniotomy with motor mapping can localize eloquent brain regions intraoperatively, preserving brain function and relevant anatomy. • Intraoperative seizures during DES in awake craniotomies can be treated with cold irrigation on the cortex or methohexital. • Factors to consider when determining timing of postoperative therapy include risks factors for worse outcomes, such as being older than 40 years or having a large preoperative tumor (≥5 cm), incomplete resection, elevated MIB- 1 labeling index of greater than 3%, astrocytic histology, absence of an isocitrate dehydrogenase (IDH) mutation, or absence of a 1p19q codeletion. • For low- grade gliomas with a 1p/ 19q codeletion (oligodendrogliomas), adjuvant external- beam RT with or without chemotherapy is recommended. • Resection of lesions in the SMA may result in postoperative SMA syndrome (transient akinesia and mutism). CASE 2 HISTORY AND PHYSICAL EXAMINA TION A 26- year- old man presents with new seizure onset, severe left facial droop, and left- sided upper extremity weakness. On neurological examination, he demonstrates left- sided facial drooping, and in the left upper extremity, he has 4/ 5 strength in the deltoids, biceps, and triceps, 3/ 5 in wrist flexion and extension, and 1/ 5 in the finger intrinsics. IMAGING STUDIES Imaging shows an intraaxial rim- enhancing brain lesion in the right premotor rolandic area with some surrounding edema (Figure 4.3). ANALYSIS OF CASE AND SURGICAL PLAN This patient has a symptomatic rim- enhancing lesion in the right frontal subcortical region. The differential diagnosis would include malignant astrocytoma, metastasis, abscess, lymphoma, resolving hematoma, cysticercosis cyst, and infarction. T reatment options are resection, open biopsy, stereotactic biopsy, or observation. Complete resection of this lesion could be difficult given its location in the premotor region, surrounding vascular structures, and subcortical location. This patient underwent an awake right frontal craniotomy for tumor resection, with direct cortical stimulation for motor mapping (Figure 4.4). Intraoperative stereotactic cranial navigation imaging and fMRI were used to guide resection of this tumor, and the postoperative MRI showed a successful resection (see Figure 4.4). Pathology showed pseudopalisading pleomor phic tumor cells, necrosis, nuclear atypia, and mitotic activity consistent with glioblastoma multiforme (GBM). Figure 4.2 Postoperative axial magnetic resonance imaging (MRI). T1- weighted MRI with contrast (A) and T2- weighted MRI (B) show a complete resection of the lesion with normal postoperative changes. Pathology showed a W orld Health Organization grade II diffuse astrocytoma. The patient recovered well. He had a transient left foot drop that recovered several months after surgery with physical therapy.

th contrast (A) and T2- weighted MRI (B) show a complete resection of the lesion with normal postoperative changes. Pathology showed a W orld Health Organization grade II diffuse astrocytoma. The patient recovered well. He had a transient left foot drop that recovered several months after surgery with physical therapy. B RAIN  TUMORS • 15 A better prognosis for GBM is seen in patients who are younger than 40 years old and those who have a Karnofsky Performance Status (KPS) score greater than 70, cystic components, more than 70% resection, no preexisting medical conditions, or adjuvant therapy (surgery + chemotherapy + RT ).21– 27 Postoperatively, the patient is treated with temo zolomide, a methylating agent, and RT simultaneously. The RT regimen includes 60 Gy given over 6 weeks. The temo zolomide dosage is 75 mg/ m2 daily, taken 7 days a week for the duration of the RT. Four weeks after RT, six cycles of 150 to 200 mg/ m2 of temozolomide is administered for 5 days every 28 days. 28 The patient’s prognosis with chemotherapy and RT is 14.6 months, with a 26% 2- year survival rate. In patients who receive RT alone, the median survival is 12.1 months, with a 10% 2- year survival rate.29,30 Progression of the Disease The patient has recurrence of symptoms after 11  months. MRI demonstrates an enhancing lesion at the resection site (Figure 4.5). The differential diagnosis includes recurrence of tumor, radiation necrosis, abscess, or inflammation. AB C Figure 4.3 Preoperative T1- weighted magnetic resonance imaging with contrast. The axial (A), coronal (B), and sagittal (C) images show a ringenhancing lesion at the right frontal lobe with central T1 hypointensity compatible with necrosis and prominent surrounding edema and mass effect with narrowing of the lateral ventricle and midline shift. Figure 4.4 Postoperative T1- weighted magnetic resonance imaging with contrast. The axial (A) and coronal (B) images show resection of the tumor after a right frontoparietal craniotomy.

ty compatible with necrosis and prominent surrounding edema and mass effect with narrowing of the lateral ventricle and midline shift. Figure 4.4 Postoperative T1- weighted magnetic resonance imaging with contrast. The axial (A) and coronal (B) images show resection of the tumor after a right frontoparietal craniotomy. 16 • G OODMAN ’S N EUROSURGERY O RAL B OARD R E v IEW Evaluation of this finding would include a basic laboratory panel and MRI spectroscopy, which can help differenti ate tumor versus radiation necrosis (T able 4.1).31 Cerebral blood volume (CBV) of more than 2.6 mL blood per gram of tissue indicates tumor; a value of less than 0.6 is consis tent with radiation necrosis. Positron emission tomography (PET) can also show increased metabolic activity in tumors and decreased metabolic activity in radiation necrosis.32 Reoperation is reserved for patients with tumor in accessible locations, KPS score greater than 70, lengthy disease- free survival, and generally good medical condition. This patient, however, had poor overall health and a right frontoparietal cortex tumor recurrence. COMPLICA TIONS Postoperative Complications Complications that can occur in this scenario include postoperative abscess formation at or around the resection site. It can be difficult to differentiate between the necrotic center of a GBM and an abscess on conventional MRI. Using DTI, such as diffusion- weighted imaging and apparent diffusion coefficient, an abscess can be differentiated from a GBM.33 Surgical debridement followed by antibiotic ther apy would be the treatment in this scenario. Long- term Complications Following radiation and chemotherapy, a patient can be subject to wound dehiscence of the incision. Depending on the severity of the infection, antibiotics, with or without surgical debridement, would be needed. Another potential long- term complication relates to the use of steroids for high- grade glioma. Dexamethasone is recommended for symptom relief in adult patients with high- grade glioma with cerebral edema. Often patients are maintained on steroids for an extended amount of time, and longer duration of steroid therapy increases the frequency of side effects. T reatment for longer than 3 weeks has been associated with toxicity.34 Side effects such as hyperglycemia, myopathy, osteoporosis, avascular necrosis, peptic ulceration, psychosis, mania, and suppression of the hypothalamicpituitary- adrenocortical axis can occur. A patient should be carefully monitored for potential side effects, and a rapid taper should be considered whenever appropriate.35 PEARLS • Postoperative adjuvant therapy with temozolomide and RT is the accepted practice. Bevacizumab (Avastin) is usually reserved as a second- line treatment. Figure 4.5 A: Follow- up magnetic resonance image 11 months after the first surgery shows a new contrast- enhancing lesion at the posteromedial margin of the resection cavity. B: Axial view of the positron emission tomography scan. T able 4.1 DI ff ERENTIA TION BETWEEN RECURRENCE AND RADIA TION NECROSIS DEPENDING ON THE METABOLIC ACTI v ITY DEMONSTRA TED BY MAGNETIC RESONANCE SPECTROSCOPY GLIOMA RADIA TION NECROSIS N- acetyl aspartate ↓ ↓ Creatine ↓ ↔ Choline ↑ ↓

gin of the resection cavity. B: Axial view of the positron emission tomography scan. T able 4.1 DI ff ERENTIA TION BETWEEN RECURRENCE AND RADIA TION NECROSIS DEPENDING ON THE METABOLIC ACTI v ITY DEMONSTRA TED BY MAGNETIC RESONANCE SPECTROSCOPY GLIOMA RADIA TION NECROSIS N- acetyl aspartate ↓ ↓ Creatine ↓ ↔ Choline ↑ ↓ B RAIN  TUMORS • 17 Reoperation is usually challenging after treatment with bevacizumab because of an increased risk for intraoperative bleeding. • MRI spectroscopy, cerebral blood volume, and PET scan can help differentiate GBM from radiation necrosis. • First- choice medications for seizure management in tumor patients include levetiracetam (Keppra), phenytoin, and valproic acid. Secondchoice medications can include topiramate and oxacarbazepine.36– 39 CASE 3 HISTORY AND PHYSICAL EXAMINA TION A 74- year- old woman presents with increased worsening of vision during the past 6  months and reports that she is no longer able to see out of her left eye. On examina tion she is found to have bitemporal hemianopsia, which has progressed to cause decreased vision in her left eye (Figure 4.6). The remainder of her neurological examina tion is normal. IMAGING STUDIES MRI is ordered and demonstrates coronal and sagittal views of a large sellar and suprasellar mass that homogenously enhances with contrast. This large tumor is displacing the optic chiasm superiorly and invades the left cavernous sinus (Figure 4.7). ANALYSIS OF CASE AND SURGICAL PLAN A patient who presents with a sellar mass needs to be evaluated for endocrine signs and symptoms because the mass can cause compression to the pituitary stalk or secrete a specific pituitary hormone. The patient needs to be asked about symptoms related to various pituitary adenomas (T able 4.2). Questions should also be asked about symptoms from tumor mass effect on surrounding structures (i.e., the optic chiasm and cavernous sinus), such as visual field cuts, decreased visual acuity, ptosis, facial pain, diplopia, proptosis, and chemosis. Endocrine laboratory tests should include prolactin (for prolactinoma), follicle- stimulating hormone, luteinizing hormone, thyroid- stimulating hormone, free thyroxine (for gonadotroph or thyrotroph adenoma), insulin- like growth hormone (for somatotroph adenoma), 24- hour urinary free cortisol, and a morning cortisol (for corticotroph adenoma). The differential diagnosis of a sellar mass includes pituitary adenoma, meningioma, sarcoma, teratoma, cra niopharygioma, carcinoma, metastases, hamartoma, optic glioma, and aneurysm. Indications for surgery include documented growth on serial imaging, symptomatic mass causing either visual or endocrinologic effects, or compression of the optic chiasm. Prolactinomas and growth hormone– secreting tumors can be treated with dopamine agonists (e.g., cabergoline, bro mocriptine) and somatostatin, respectively. Medical treat ment is usually the first- line option for prolactinoma cases, and surgery is reserved for nonresponsive growing tumors or unbearable side effects.40 The surgical approaches to a sellar mass is either an open craniotomy or transsphenoidal surgery. An open cra niotomy can entail a pterional, orbitozygomatic, bifrontal, Figure 4.6 Preoperative visual test field showing the patient has bitemporal hemianopsia.

r nonresponsive growing tumors or unbearable side effects.40 The surgical approaches to a sellar mass is either an open craniotomy or transsphenoidal surgery. An open cra niotomy can entail a pterional, orbitozygomatic, bifrontal, Figure 4.6 Preoperative visual test field showing the patient has bitemporal hemianopsia. 18 • G OODMAN ’S N EUROSURGERY O RAL B OARD R E v IEW or supraorbital approach, depending on the features and extension of the tumor. 41,42 For this case, the transsphe noidal approach is used to gain access to the tumor, given the easy accessibility of the suprasellar component through a transsphenoidal approach. If the suprasellar component does not descend during the initial approach, then a staged procedure can be planned. An endoscopic or microscopic transsphenoidal approach can be used based on surgeon preference. For this patient, a lumbar drain is placed preopera tively to help push down the suprasellar component of the tumor. Intraoperative stereotactic cranial navigation is used to identify the anatomy of the sella and surrounding structures. An endonasal transsphenoidal approach is used to resect the tumor, and frozen pathology demonstrates a pituitary adenoma. After the tumor is resected, a fat graft is taken from the abdomen and used to pack the sella with fibrin glue to prevent downward herniation of the optic chiasm and cerebrospinal fluid (CSF) leak. Postoperatively, the lumbar drain is maintained at 10 to 15 mL/ hr for about 3  days to reduce chances of CSF leak, particularly if there was a high CSF flow leak at the end of the tumor resection. The head of the bed is set at 30 degrees at all times, and the patient is cautioned to not blow her nose. COMPLICA TIONS Intraoperative Complications Possible intraoperative issues include injury to the carotid artery or cavernous sinus injury. These injuries would need to be immediately addressed by attempting to find the source of bleeding and packing it off using a fat or fascia graft. The operation should be halted, and an intraoperative or postoperative angiogram should be ordered. If a pseu doaneurysm is identified, it must be addressed with either an endovascular technique or surgical clipping and trapping to prevent lethal rupture. Injury to the optic nerve or the nerves within the cavernous sinus can also occur. Figure 4.7 Preoperative T1- weigthed contrast- enhancing coronal (A) and sagittal (B) magnetic resonance images show a large contrast- enhancing sellar and suprasellar mass that represents a macroadenoma. The mass is abutting the undersurface of the optic chiasm with extension into the right cavernous sinus. T able 4.2 CLINICAL PRESENTA TION Of  PA TIENTS WITH v ARIOUS PITUITARY ADENOMAS TYPE OF PITUITARY ADENOMA PRESENTA TION Oversecretion Prolactinoma Amenorrhea, galactorrhea, impotence GH Acromegaly, gigantism ACTH Cushing’s disease, Nelson syndrome TSH Hyperthyroidism Undersecretion GH deficiency Growth delay, metabolic syndrome f SH/ LH deficiency Hypogonadism, amenorrhea, loss of libido, infertility TSH deficiency Hypothyroidism ACTH deficiency Orthostatic hypotension, easy fatigability ACTH, adrenocorticotropic hormone; FSH, follicle- stimulating hormone; GH, growth hormone; TSH, thyroid- stimulating hormone (thyrotropin).

etabolic syndrome f SH/ LH deficiency Hypogonadism, amenorrhea, loss of libido, infertility TSH deficiency Hypothyroidism ACTH deficiency Orthostatic hypotension, easy fatigability ACTH, adrenocorticotropic hormone; FSH, follicle- stimulating hormone; GH, growth hormone; TSH, thyroid- stimulating hormone (thyrotropin). B RAIN  TUMORS • 19 Intraoperative CSF leak can occur during surgery, especially during resection of the suprasellar component of a macroadenoma, increasing the risk for postoperative CSF leak. In these situations, a lumbar drain can be placed intraoperatively or a nasoseptal flap can be elevated to prevent postoperative CSF leak.43,44 Postoperative Complications In this case, the patient’s serum sodium level increased to 150 mEq/ L postoperatively over 4  days with high urine output. She was suspected to have diabetes insipidus (DI) and was given vasopressin as needed to normalize her sodium. Within 3 days of starting vasopressin, the patient’s sodium level dropped from the150s to the mid- 120s. Her mental status remained unchanged, and the vasopressin was discontinued. Over the next few days while under inpatient observation, her sodium levels normalized. This patient presented with a triphasic response. The first stage presents as DI, in which the pituitary gland is injured during surgery and produces a reduced amount of antidi uretic hormone (ADH) for 4 to 5  days. DI is diagnosed when the serum sodium level is more than 145 mEq/ L, urine output is more than 250 mL/ hr (or >3 mL/ kg/ hr in children), and the patient has a low specific gravity (<1.003; ranges, 1.001 to 1.005) with normal or high serum osmolality. This is followed by the second stage, in which there is pituitary cell death and ADH is released over an additional 4 to 5  days, causing a transient normalization or even syndrome of inappropriate ADH. At this point, vasopressin or desmopressin acetate should be stopped to prevent significant hemodilution. The third stage involves a reduced or depleted amount of ADH that causes a tran sient or prolonged stage of DI requiring vasopressin replacement.45 In patients receiving long- term steroid replacement, a stress dose of steroids can be administered before the surgery to prevent intraoperative or postoperative adrenal insufficiency. T wo weeks after surgery, the patient develops a partial oculomotor palsy in her right eye. Postoperative MRI is unremarkable, with no residual tumor (Figure 4.8). Serum laboratory tests show an elevated white blood cell (WBC) count of 20,000. A  lumbar puncture is performed that shows no white blood cells and no organisms. A  possible cause of this delayed third cranial nerve palsy is inflamma tion if the right cavernous sinus was entered during surgery. Infection is less likely, given the LP results. Local trauma from excessive fat packing of the sella and fracture to the surrounding orbital bone are less likely owing to the delayed presentation. The patient is started on a high- dose steroid taper for a suspected inflammatory response and sent to her ophthalmologist to monitor the progress of her deficit. Over the next 3 days, her palsy resolves. Another possible postoperative complication is CSF leak. Postoperative CSF leak can present as nasal dripping when the patient leans forward, or as postnasal dripping with cough and headache. CSF leak may be differentiated from normal rhinorrhea or dripping of dissolving fat pad, based on color, with the latter usually appearing yellow. A ß2- transferrin level can be obtained to test for the presence of CSF .

as nasal dripping when the patient leans forward, or as postnasal dripping with cough and headache. CSF leak may be differentiated from normal rhinorrhea or dripping of dissolving fat pad, based on color, with the latter usually appearing yellow. A ß2- transferrin level can be obtained to test for the presence of CSF . If conservative measures, such as rest, fail, then a lumbar drain can be placed, or surgery for skull base reconstruction may be required.46,47 Figure 4.8 Postoperative T1- weigthed coronal (A) and sagittal (B) magnetic resonance images after resection of a pituitary macroadenomas with fat graft and no residual tumor at the surgical cavity.

es, such as rest, fail, then a lumbar drain can be placed, or surgery for skull base reconstruction may be required.46,47 Figure 4.8 Postoperative T1- weigthed coronal (A) and sagittal (B) magnetic resonance images after resection of a pituitary macroadenomas with fat graft and no residual tumor at the surgical cavity. 20 • G OODMAN ’S N EUROSURGERY O RAL B OARD R E v IEW Postoperative epistaxis can also occur and can be treated with bedside nasal packing followed by operative reexploration if conservative measures are unsuccessful.48 Other postoperative complications may include visual impairment that results from secondary empty sella syn drome, in which the chiasm retracts into the evacuated sella. This complication can be avoided by using a fat graft to fill the sella after tumor resection. A patient can also develop hydrocephalus and coma after surgery. Hydrocephalus can result in pituitary adeno mas with suprasellar components from traction on the third ventricle during resection or cerebral edema. In these cases, ventriculostomy placement should be considered. Long- term Complications A long- term complication associated with transsphenoi dal hypophysectomies is the development of sphenoid sinusitis, whereby the patient presents with headaches and nasal discharge that can persist for up to 3 years. 49 In these situations, antibiotic medical management is the first line of treatment, followed by endoscopic sphenoidotomy for intractable disease. In cases in which a large resection of nasal structures (i.e., turbinates, nasal septum) is performed for an expanded endonasal approach, empty nose syndrome, although rare, may occur. A patient with this syndrome may present with chronic nasal dryness, paradoxical obstruction, or neuro pathic pain. Nasal saline sprays or surgical narrowing of the nasal cavity is used to treat this condition.50 It is important to remember that long- term endocri nologic abnormalities may occur after manipulation of the pituitary gland or as a result of tumor invasion and may require chronic hormonal replacement. PEARLS • Patients with sellar masses should undergo an endocrine hormonal workup with a preoperative ophthalmologic evaluation. • Indications for surgery for a sellar lesion include documented growth on serial imaging, symptomatic mass identified either visually or endocrinologically, and compression of the optic chiasm. • Some secreting tumors can be treated medically (e.g., prolactinomas, growth hormone– secreting tumors). • The surgical approach is either an open craniotomy or transsphenoidal surgery. • Intraoperative complications consist of injury to the carotid artery, optic nerve, cavernous sinus, or nerves within the cavernous sinus. • Postoperative medical complications, such as DI and triphasic response, and surgical complications, such as secondary empty sella syndrome and hydrocephalus, can occur. • Delayed third cranial nerve palsy can result postoperatively from inflammation, infections, orbital fractures, or overpacking of the sella with a fat graft. • The long- term complication of sphenoid sinusitis has been seen after transsphenoidal surgery. CASE 4 HISTORY AND PHYSICAL EXAMINA TION A 59- year- old woman presents to the emergency depart ment after having a tonic- clonic seizure that lasted 5 min utes and self- resolved. She reports having had a stiff neck and mild headache for the past 2  days. On examination, she is confused and agitated but otherwise neurologically intact. Her family reports a long- standing and progressive history of personality change, disinhibition, and problems concentrating. IMAGING STUDIES The imaging studies demonstrate a large extraaxial enhancing mass arising from the planum sphenoidale.

mination, she is confused and agitated but otherwise neurologically intact. Her family reports a long- standing and progressive history of personality change, disinhibition, and problems concentrating. IMAGING STUDIES The imaging studies demonstrate a large extraaxial enhancing mass arising from the planum sphenoidale. There are significant mass effect and vasogenic edema in the bifrontal lobes (Figure 4.9). ANALYSIS OF CASE AND SURGICAL PLAN The patient is transferred to the intensive care unit for monitoring. The differential diagnosis of this extraaxial lesion includes meningioma, hemangiopericytoma, pituitary adenoma, dural based metastasis, and craniopharyngioma. Initial management includes obtaining a basic metabolic panel, complete blood cell count, coagulation studies, and a preoperative medical evaluation for surgery. The patient receives 10 mg of intravenous dexamethasone followed by 4 mg given intravenously every 6 hours and was started on levetiracetam, 1000 mg every 12 hours. This patient should also be assessed for symptoms of Foster- Kennedy syndrome, which include anosmia, con tralateral papilledema, and unilateral optic atrophy. An

ient receives 10 mg of intravenous dexamethasone followed by 4 mg given intravenously every 6 hours and was started on levetiracetam, 1000 mg every 12 hours. This patient should also be assessed for symptoms of Foster- Kennedy syndrome, which include anosmia, con tralateral papilledema, and unilateral optic atrophy. An B RAIN  TUMORS • 21 magnetic resonance angiogram or conventional angiogra phy can be used to assess the arterial feeders of the lesion. Olfactory groove meningiomas differ from tubercu lum sellae meningiomas based on the location of the optic chiasm. In the olfactory groove meningioma, the chiasm is inferolateral to the tumor, whereas in a tuberculum sellae meningioma, the chiasm is superolateral to the tumor. Given the symptomatic nature of the lesion, surgery is the chosen treatment option. Three surgical approaches can be used to resect this lesion. A subfrontal approach with or without orbital osteotomies allows for early access to vascular feeds along the skull base. A bicoronal incision provides a vascularized pericranial flap that can be used to prevent CSF leak during skull base reconstruction. Orbital osteotomies can also be performed to help reduce the amount of brain retraction that is needed. 51 Potential complications for this approach include opening the frontal sinus, which creates a risk for CSF leak or a mucocele. A  preoperative computed tomography scan allows for evaluation of the extension of the frontal sinus in these patients. Also, the anterior section of the superior sagittal sinus must be sacrificed with this approach. The pterional approach provides early exposure of the optic nerve and carotid artery and involves a shorter dis tance to the tumor. The access to the basal cisterns can help early drainage of CSF for brain relaxation. The disadvan tages of the pterional approach include a narrow working space that may not provide adequate access to the supe rior portion of the tumor. Also, accessing skull base arter ies or repairing skull base defects can be difficult with this approach.51 An interhemispheric approach preserves the superior sagittal sinus and frontal sinus, but the operative route to the tumor is longer, and often frontal contusions develop.51 This approach also makes it difficult to access the skull base vascular supply. For this patient, a bicoronal subfrontal approach with bilateral orbital osteotomies is used. T o perform the orbital osteotomies, the facial nerve in the temporal fat pad must be protected while elevating the skin flaps. The subfrontal approach provides wide access to the anterior skull base without the need for frontal lobe retraction and allows for early devascularization of the anterior and posterior ethmoidal arteries, which are usually the vascular supply for these meningiomas. Early disconnection of the tumor arterial feeders will decrease the bleeding from the tumor, preventing obscuration of the surgical field and limiting the blood loss. The tumor can be centrally debulked using an ultrasonic aspirator. Caution must be taken along the pos terior aspect of the tumor to separate it from the anterior cerebral arteries (ACAs), optic nerves, and chiasm. Frozen pathology shows a meningioma. Aggressive resection of the tumor and dural attach ments is required to reduce the chances of recurrence. This includes drilling any hyperostotic bone and removing tumor- invaded dura. Late recurrence has been shown to happen in 30% of patients with these tumors at 5 years and in 41% at 10 years. 52 The Simpson classification system predicts meningioma tumor recurrence after surgical resection.

e the chances of recurrence. This includes drilling any hyperostotic bone and removing tumor- invaded dura. Late recurrence has been shown to happen in 30% of patients with these tumors at 5 years and in 41% at 10 years. 52 The Simpson classification system predicts meningioma tumor recurrence after surgical resection. The extent of surgical resection and recurrence rate in this system include five grades: grade 1— macroscopically complete tumor removal with dura and bone, 10% recurrence; Figure 4.9 Preoperative T1- weigthed axial (A) and sagittal (B) magnetic resonance images with contrast showing a contrast- enhancing lesion emerging from the planum sphenoidale, which is most consistent with a meningioma.

five grades: grade 1— macroscopically complete tumor removal with dura and bone, 10% recurrence; Figure 4.9 Preoperative T1- weigthed axial (A) and sagittal (B) magnetic resonance images with contrast showing a contrast- enhancing lesion emerging from the planum sphenoidale, which is most consistent with a meningioma. 22 • G OODMAN ’S N EUROSURGERY O RAL B OARD R E v IEW grade 2— macroscopically complete tumor removal with dural coagulation, 15% recurrence; grade 3— complete tumor resection without dural attachments, 30% recur rence; grade 4— incomplete resection, up to 85% recur rence; and grade 5— biopsy, 100% recurrence. Postoperatively, radiation can be used for recurrent tumors or meningiomas with malignant pathologies. Radiosurgery has been shown to reduce or stop tumor growth rates in 84% to 100% of cases. Complications of radiosurgery often result from worsening edema and can result in permanent morbidity in 5.7% of cases. These morbidities can present as seizure, cranial nerve deficits, hemi paresis, mental status changes, and headaches.53 COMPLICA TIONS Intraoperative Complications One potential complication that can occur intraoperatively is that after making the bicoronal incision and flipping the skin flap over the eyes to expose the orbital bar, the patient becomes severely bradycardic. In these cases, the anesthe siologist reports giving no new medication or inhalational anesthetic. The patient is likely experiencing an oculocardiac reflex, in which a decrease in pulse rate is associated with the traction applied to extraocular muscles or compression of the eye. The reflex is mediated by the trigeminal cranial nerve through the ciliary ganglion and the vagus nerve of the parasympathetic system.54 Relieving the pressure of the skin flap on the orbits should reverse the bradycardia. Another potential complication is injury to the carotid or ACA. In this situation, the bleed should be isolated and controlled, and an intraoperative or postoperative angio gram is required to assess the vascular anatomy. Preoperative computed tomography angiography, magnetic resonance angiography, or conventional angiography can be used to determine the location of the ACA relative to the tumor. When the patient is slow to wake up from anesthesia, an immediate computed tomography scan should be done to evaluate the possibility for hematoma, edema, hydrocephalus, pneumocephalus, or ACA infarction. The patient could be experiencing frontal lobe syndrome as a result of cerebral edema or ischemia. Postoperative steroids can be used after surgery for at least 2 weeks to treat the cerebral edema.55 Postoperative Complications T wo days after surgery, the patient experiences a severe headache and a tonic- clonic seizure that resolves with intravenous lorazepam (Ativan). MRI shows extensive bifrontal edema with no residual tumor (Figure 4.10). The patient is started on dual antiepileptic treatment, levetiracetam and phenytoin, and put on a high- dose dexamethasone taper. The headache dissipates over the next few days, and seizures remain well controlled. Other postoperative complications include vision loss that can occur after a large meningioma is removed owing to excessive traction on the optic apparatus during resection. Care must be taken intraoperatively during the resection of the posterior component of the tumor, which can often Figure 4.10 Postoperative axial T1- weigthed contrast- enhanced (A) and T2- weighted fluid- attenuated inversion recovery (FLAIR) (B) magnetic resonance imaging (MRI) shows complete resection of the meningioma with blood products at the resection site and residual extensive frontal lobes edema, as seen in the T2- weighted FLAIR MRI.

stoperative axial T1- weigthed contrast- enhanced (A) and T2- weighted fluid- attenuated inversion recovery (FLAIR) (B) magnetic resonance imaging (MRI) shows complete resection of the meningioma with blood products at the resection site and residual extensive frontal lobes edema, as seen in the T2- weighted FLAIR MRI. B RAIN  TUMORS • 23 adhere to the optic nerve, ACA, or internal carotid artery. Steroid use may help to reduce the swelling of the nerve. Postoperative venous congestion and venous stroke are also potential postoperative complications of this surgery. The anterior third of the superior sagittal sinus is relatively safe to sacrifice in attempting a total resection. Care must be taken to prevent ligation or thrombosis of the posterior two thirds of the superior sagittal sinus during tumor and frontal lobe manipulation because this may cause a venous stroke. Preoperative venography can be used to study the anatomic relation between the tumor and the sinus, sinus patency, and collateral veins. CSF leak can present as rhinorrhea postoperatively in this type of case. The use of a pericranial flap to aid in reconstruction of the skull base helps to prevent this leak from occurring. Long- term Complications During bifrontal or extended bifrontal craniotomies, if the frontal sinus is exposed during the craniotomy, simple packing of the frontal sinus with bone wax or muscle can increase the chance of mucocele formation. The posterior wall of the frontal sinus must be removed, and the sinus must then be exenterated. It is important to remove the sinus mucosa from the sinus wall down to the nasofrontal duct. 56 A dia mond bur can then be used to remove the tiny remnants of mucosa found on the surface of bone, which can also lead to a mucocele. Abdominal fat, a piece of temporalis muscle, hemostatic agents, or optimally, a piece of pericranial vascularized flap can then be used to fill the corners of the cavity if small remnants remain.57 PEARLS • Olfactory groove meningiomas can present with Foster- Kennedy syndrome (anosmia, contralateral papilledema, and unilateral optic atrophy). • Olfactory groove meningiomas differ from tuberculum sellae meningiomas based on the location of the optic chiasm (inferolateral in olfactory groove meningiomas and superolateral in tuberculum sellae meningiomas). • Subfrontal, pterional, and interhemispheric approaches can all be used to approach olfactory groove meningiomas. • The Simpson classification system predicts meningioma tumor recurrence based on the extent of surgical resection. • Radiosurgery can be used for recurrent meningiomas or meningiomas with malignant pathologies. • Complications of arterial injury, nerve injury, stroke, seizures, frontal lobe syndrome, vision loss, CSF leak, and mucoceles can occur after the resection of olfactory groove meningiomas. REf ERENCES 1. Chaichana KL, Kosztowski T, Niranjan A, et  al. Prognostic sig nificance of contrast- enhancing anaplastic astrocytomas in adults. J Neurosurg. 2010;113(2):286– 292. 2. Chaichana KL, McGirt MJ, Niranjan A, Olivi A, Burger PC, Quiñones- Hinojosa A. Prognostic significance of contrastenhancing low- grade gliomas in adults and a review of the literature. Neurol Res. 2009;31(9):931– 939. 3. Keles GE, Lamborn KR, Berger MS. Low- grade hemispheric glio mas in adults: A critical review of extent of resection as a factor influencing outcome. J Neurosurg. 2001;95(5):735– 745. 4. Markert JM. The role of early resection vs biopsy in the management of low- grade gliomas. JAMA. 2012;308(18):1918– 1919. 5. Jakola AS, Myrmel KS, Kloster R, et al. Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low- grade gliomas. JAMA. 2012;308(18):1881– 1888. 6. Smith JS, Chang EF, Lamborn KR, et al.

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