Benign Tumors

Meningioma

These are the most common primary intracranial tumor, comprising 14.3-19% of primary intracranial neoplasms. They are defined as slow-growing, well-circumscribed, benign lesions with pathologically distinct “psamomma bodies,” or calcifications. Meningiomas arise from arachnoid cap cells and thus can arise from any structure in the CNS that is covered by arachnoid mater, a meningeal layer surrounding the brain and spinal cord beneath the skull and vertebrae. The peak incidence occurs at 45 years of age and is more common in females, with a male: female ratio of 1:1.8. Women are even more likely than men to have spinal meningiomas, with reported incidence 3.37 times more likely in women¹. Only 1.5% of meningiomas occur in childhood and adolescence. Of those lesions, 19-24% are associated with neurofibromatosis type 1 (NF1). Meningiomas are most commonly located in the parasagittal space (20.8%), followed by convexity (over the surface of the brain – 15.2%), within the tuberculum sellae (12.8%), and the sphenoidal ridge (11.9%).

Histopathology is used to guide WHO grading, which has 3 levels. Meningothelial, psammomatous, and microcystic meningiomas – amongst others – are the lowest grade, WHO I. These have low risk of recurrence following gross total resection and aggressive growth. Chordoid, clear cell, and atypical meningiomas are WHO grade II. Papillary, rhabdoid, and anaplastic lesions are malignant, WHO grade III. These have the highest risk of recurrence and aggressive growth. Brain invasion by meningiomas independently should not be used to associate with malignancy, but there is higher risk of recurrence. Metastases overall are extremely rare.

Symptoms are associated with tumor location, but many meningiomas remain asymptomatic for years, even throughout a patient’s entire life. A common presenting symptom is seizure due to irritation of the cerebral cortex with supratentorial meningiomas.

Asymptomatic meningiomas found incidentally on imaging are recommended to be followed up with imaging in 3 months to rule out aggressive growth and on a 6-month follow-up and if still stable, on a 1-year follow up and if still stable, then with annual imaging every 2-3 years.

The first-line treatment for symptomatic meningiomas is surgical resection. If patients are not surgical candidates or the tumor is inaccessible, malignant, or recurrent, radiation therapy may be considered. Radiation therapy may also be used as an adjunct for partially resected lesions. Note that there are reports converting a grade I benign meningioma to a higher grade more aggressive tumor. Therefore, it is our opinion that if an asymptomatic meningioma continues to grow and is surgically resectable, or if it causes symptoms, it should be resected as the first-line therapy.

As these tumors tend to be bloody, preoperative embolization and autologous blood donation are essential for uncomplicated surgical removal.

The Simpson grading system is used to evaluate the extent of resection, with grade I being macroscopically gross total resection with removal of dural attachment and abnormal bone, and grade V being simple decompression with or without biopsy, without tumor removal. Degree of tumor resection is the most significant factor associated with recurrence. Recurrence after total removal occurs in 11-15% of cases but 29% with partial removal². Convexity meningiomas may recur more rapidly than skull base meningiomas, and thus Simpson grade I resection is recommended³.

Convexity Meningioma

One of the most common locations of meningiomas (12.8%). Recurrence depends on grade, with 1.5% five-year recurrence for benign lesions and 44% for malignant/atypical meningiomas¹.

Olfactory Groove Meningioma

Account for 9.8% of meningiomas. Remain asymptomatic until lesion has grown significantly in size. May cause Foster Kennedy Syndrome, which has a triad of symptoms: anosmia, ipsilateral optic atrophy (due to compromise of the nerve), and contralateral papilledema (due to compromise of the venous flow). Can also be associated with mental status changes and urinary incontinence due to frontal lobe mass effect. Lesions located posteriorly within the olfactory groove may cause visual impairment due to compression of the optic chiasm and/or optic nerves. Very large lesions may cause seizures or short-term memory loss due to compression of the fornix. Lesions > 3 cm in size are difficult to resect completely and have higher morbidity and mortality. Surgical resection entails gross total resection. For smaller tumors than 4 cm, it can be done through frontotemporal craniotomy but for tumors larger than 4 cm, it needs extrnsive skull base approach through a bicoronal craniotomy and naso-orbital osteotomy through the frontal sinus, in order to access the olfactory groove and resect the origin of the tumor in order to avoid recurrence¹.

References

1. Kshettry VR, Hsieh JK, Ostrom QT, Kruchko C, Benzel EC, Barnholtz-Sloan JS. (2015). Descriptive epidemiology of spinal meningiomas in the United States. Spine. 40(15): E886-E889.
2. Yamashita J, Handa H, Iwaki K, et al. (1980). Recurrence of intracranial meningiomas, with special reference to radiotherapy. Surg Neurol. 14: 33-40.
3. Hasseleid BF, Meling TR, Ronning P, Scheie D, Helseth E. (2012). Surgery for convexity meningioma: Simpson Grade I resection as the goal. Journal of Neurosurgery. 117(6): 999-1006.
4. Morokoff AP, Zauberman J, Black PM. (2008). Surgery for convexity meningiomas. Neurosurgery. 63(3): 427-434.
5. Mortazavi MM, Mantovani A, Da Silva HB, and Sekhar LN F (2015). Olfactory groove and planum sphenoidale, and tuberculum sellae meningiomas In Sekhar LN, Fessler RG (second edition), Atlas of Neurosurgical Techniques. Brain. (pp. 227-237) New York, NY: Thieme Publishers.

Malignant Tumors

Glioma/Astrocytoma

Glioma is a general name for any primary CNS tumor of glial origin. Gliomas may be classified by cell type, grade and location. Gliomas of different cell types include astrocytoma, ependymoma, oligodendroglioma, oligoastrocytomas, ganglogliomas and optic nerve glioma. Location may be supratentorial or infratentorial, meaning above or below the tentorium, a meningeal layer that separates the cerebrum from the cerebellum and brainstem. Supratentorial locations are more common in adults and infratentorial locations are more common in children. Grading is based on tumor pathology and involvement. WHO grades I-II are generally benign while III-IV are malignant. WHO grade I has low proliferation rate and may be cured with surgical resection alone¹. These typically occur in younger individuals, for instance, juvenile pilocytic astrocytoma. WHO grade II is more infiltrative but still has pathologic features of benign tumors including well-differentiated cells. With recurrence, these tumors may progress to malignancy¹. WHO grade III tumors have malignant features, including high mitotic activity and nuclear atypia¹. These should be treated with adjuvant radiation and/or chemotherapy in addition to surgical resection. Astrocytomas broadly can be WHO grade I-III. WHO grade IV lesions are cytologically malignant, mitotically active, necrosis-prone neoplasms with poor prognoses¹. These include glioblastoma multiforme and embryonal tumors.

Glioblastoma

Glioblastoma multiforme (GBM) is the most severe presentation of astrocytoma, classified as WHO Grade IV. Distinguishing criteria include microvascular proliferation and necrosis.

There are 3 known genetic pathways that may be dysregulated: receptor tyrosine kinase (RTK), phosphatidylinositol-3-OH kinase (PI3K)/AKT/mTOR, and the p53 and retinoblastoma (Rb) tumor suppressor pathways.

Primary GBMs comprise the majority of GBMs, most commonly occurring in older patients (mean age 55 years) with a rapid clinical course.

Figure : Glioblastoma multiforme (GBM) A: Axial T1-weighted MRI with contrast. B. Sagittal T1-weighted MRI. C. Coronal T1-weighted MRI.

Secondary GBMs arise from malignant degeneration of WHO grade II or III astrocytomas in younger patients (mean age 40 years) and progress more slowly than primary GBMs.

The endpoints of surgery for GBMs are cytoreduction, relieving mass effect, and obtaining tissue for histological and molecular analysis. Standard therapy for GBM combines surgery, radiation, and temozolomide (temodar) chemotherapy. Temodar is member of the oral alkylating agent class of chemotherapeutic agents. It is metabolized to an active agent at physiological pH, which has a cytotoxic effect on tumor cells due to addition of alkyl groups to DNA. This typically causes irreparable damage to tumor DNA in addition to side effects due to damage of host DNA, typically in fast growing cells (i.e. hair and gastrointestinal mucosa). Surgical resection should aim for gross total resection with preservation of eloquent and critical structures. Awake craniotomy is performed for lesions in eloquent brain regions. Studies have shown that excision of 97% or more of a GBM is associated with increased survival time and likely also improves time to tumor progression.

See Video: https://www.youtube.com/watch?v=4CAwuhEfdyg

5-aminolevulinic-acid (5-ALA) may be used to visually identify the tumor intraoperatively. It is metabolized into fluorescent porphyrins that are taken up by malignant glioma cells.

Partial GBM resection carries risk of postoperative hemorrhage and/or edema, known as wounded glioma syndrome, with risk of herniation. Therefore, patients with extensive, multicentric, or bilateral cortical involvement are not candidates for surgical debulking.

Patients who are not surgical candidates due to tumor location in eloquent or inaccessible areas of the brain or inability to undergo general anesthesia may undergo stereotactic biopsy instead. However, stereotactic biopsy may underestimate GBM in up to 25% of cases due to sampling error.

Recurrent GBM may be treated with the chemotherapeutic agent Bevacizumab, known as Avastin. It is a recombinant human monoclonal antibody that prevents the proliferation of blood vessels by blocking vascular endothelial growth factor A (VEGF-A). Cancers such as GBM upregulate VEGF concentrations to promote angiogenesis for supporting growth of the tumor cells. Avastin has increased tendency to bleed as a side effect and is reserved for recurrent glioblastomas. Other chemotherapeutic agents include Nivolumab (Opdivo). Nivolumab is a human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor Programmed death-1 (PD-1). Nivolumab binds and blocks the activation of PD-1. Activated PD-1 inhibits T-cell activation and effector function through the suppression of P13k/Akt pathway activation.

Brainstem Glioma

Brainstem gliomas are a heterogenous group of low and high grade tumors that typically present with cranial nerve palsies and white matter tract findings. They are more likely to occur during childhood and adolescence, with 77% of those affected less than 20 years of age. They are also more likely to be malignant and invasive. Common symptoms include gait disturbance, headache, nausea and vomiting, diplopia, facial asymmetry, distal motor weakness, papilledema, and hydrocephalus depending on the tumor location in the brainstem. Patients less than 2 years of age may present with failure to thrive.

Lower grade tumors have a predilection for the upper brainstem, while high grade tumors (such as glioblastoma) are more likely to arise in the lower brainstem. The four growth patterns of brainstem gliomas are diffuse, cervicomedullary, focal, and dorsally exophytic. All diffuse tumors are malignant, most being anaplastic astrocytomas and glioblastomas. In contrast, most cervicomedullary and focal neoplasms are low-grade astrocytomas. Dorsally exophytic tumors may be an extension of the focal growth pattern, with many being low grade gliomas including pilocytic astrocytomas and gangliogliomas. Surgery is only recommended for removal of dorsally exophytic tumors with radical subtotal resection. Complications include exacerbation of pre-operative symptoms such as ataxia and cranial nerve palsies, although these usually resolve over time. Long-term survival tends to be favorable with low incidence of disease progression at follow-up. Radiation therapy is the next in line for treatment when surgery is not possible. Most children with malignant brainstem gliomas die within 6-12 months of diagnosis.

Tectal Glioma

This is a subgroup of brainstem gliomas mainly comprised of low-grade astrocytomas. The average age of presentation is 6-14 years of age. The most common complication is obstructive hydrocephalus, with associated symptoms of headache, nausea, and vomiting. Focal neurologic deficits are rare, and may include gaze disturbances. Long-term management with Endoscopic Third Ventriculostomy (ETV) or Ventriculoperitoneal shunt (VPS) for hydrocephalus is recommended, due to low risk of progression and morbidity of surgery. Tumor progression is described in 15-25% of cases and may be treated with stereotactic radiosurgery. (See figure)

Figure : Axial T1-weighted MRI with contrast showing tectal glioma with obstructive hydrocephalus.

Pontine Glioma

Pontine gliomas are another subtype of brainstem gliomas, also known as diffuse intrinsic pontine glioma. These are generally malignant, aggressive, infiltrative tumors with a poor 5-year survival rate of <1%. Children are mainly affected. Symptoms are due to cranial nerve palsies, including problems with eye and facial movements, speech, chewing, and swallowing. Other symptoms include extremity weakness and ataxia. Due to the infiltrative nature of these neoplasms in a sensitive brain region, surgical resection is not recommended. Radiation therapy is first-line for palliative therapy with symptomatic improvement. However, rapid progression still occurs within a year of treatment. Chemotherapy is experimental at this time.

Chordoma

Chordomas are rare tumors with an incidence of 0.51 cases/million arising from the remnant of the primitive notochord, which typically develops into the nucleus pulposus of the intervertebral disks. Although they may arise anywhere along the neuroaxis, they tend to arise at the two ends of the primitive notochord. 35% occur at the cranial end in the spheno-occipital region at the clivus and 53% occur in the spine at the sacrococcygeal region.

Cranial chordomas occur most frequently in patients 50-60 years of age with an approximately equal male:female incidence. The most common presentation is of cranial nerve palsy typically involving the oculomotor or abducens nerve. In contrast, spinal chordomas occur more commonly in males and in older patients. As they most commonly occur in the sacrum, presenting symptoms include pain, sphincter disturbance, or nerve root symptoms from local nerve root compression.

These tumors are generally slow growing, locally aggressive, and osseodestructive. They are difficult to excise completely, have a high recurrence rate, and can metastasize in late stages, most commonly to the lung, liver, and bone. Pathologically they are distinguished by physaliphorous cells, a type of vacuolated cells likely representing cytoplasmic mucus vacuoles. Radiographically chordomas appear lytic with calcifications, and they enhance on CT with contrast. Bony destruction is commonly seen on CT and MRI with spinal chordomas.

Gold-standard treatment is wide en-bloc surgical excision with postoperative radiation, including high-dose radiation such as proton beam therapy. There is a high risk of surgically induced metastasis, which is reduced by piecemeal tumor removal. Decompression should be avoided for this reason. Resection of sacral chordomas is complicated by injury to nerve roots responsible for bowel and bladder function risking incontinence. If the nerve roots extending up to S1 are spared, there is a 50% chance of retaining normal bowel and bladder control. If the S1 level is not spared, the patient will likely have impairment of bowel and bladder continence. (See figure)

Figure : Cranial chordoma. A. Axial T1-weighted MRI with contrast B. Coronal T1- weighted MRI with contrast. C. Sagittal T1-weighted MRI with contrast.

CNS-Lymphoma

CNS lymphomas may be classified as primary or secondary. Primary CNS lymphoma is a rare, malignant neoplasm that originates with the CNS and comprises 0.85-2% of all brain tumors. Men are more commonly affected, with a male: female ratio of 1.5:1. The median age at diagnosis is 52 years. These may occasionally metastasize outside the CNS. Immunocompromised patients such as AIDS and transplant patients are more likely to be affected than the general population. They also have a younger overall median age of diagnosis at 34 years. Primary CNS lymphoma may occur supra- or infratentorially. Supratentorial locations include the frontal lobes and basal ganglia as well as periventricular regions. The most common infratentorial location is the cerebellum.

Secondary CNS lymphoma is due to metastatic spread of systemic lymphoma, usually non-Hodgkin’s lymphoma, generally occurring in 1-7% of all lymphoma patients.

Primary and secondary CNS lymphoma present in similar ways. The most common symptoms arise from epidural spinal cord compression and carcinomatous meningitis, with multiple cranial nerve deficits. Seizures also commonly occur. Other non-focal, non-specific symptoms include mental status changes and symptoms indicating increased intracranial pressure, including headache and nausea and vomiting. Focal symptoms such as hemimotor or hemisensory deficits, aphasia, and visual field deficits may also be present.

First-line treatment following biopsy is radiation therapy with choice of adjuvant chemotherapy. For large tumors causing mass effect, severe perifocal brain edema and/or seizure, total resection is preferred. Chemotherapy has been shown to prolong survival in non-immunocompromised patients. Choice agents are methotrexate and rituximab. Generally, surgery is only for biopsy and confirmation of diagnosis but for larger lesions causing mass effect or severe edema or intractable seizure, total resection during open biopsy is recommended. These tumors are also highly responsive to steroids. Unfortunately, recurrence rate is high at 78% at 15 months following treatment. Median survival after radiation is 10 months, with 5-year survival 3-4%. One-year survival after gross total resection is estimated to be 56.6% and 31.8% following partial resection¹. Intraventricular methotrexate has been shown to prolong median time to recurrence to 41 months. Prognosis is worse in immunocompromised individuals such as AIDS patients, with median survival only 3-5 months. This is generally due to opportunistic infection and not CNS complications.

Chondrosarcoma

A chondrosarcoma is a malignant cartilaginous tumor. They are lobulated tumors with calcifications. Despite the name, it is clinically a less aggressive tumor than chordomas. However, it is resistant to chemotherapy and radiation. Symptoms include back or thigh pain, sciatica, bladder problems, and unilateral edema. Surgical resection is the mainstay of therapy.

Esthesioneuroblastoma

Esthesioneuroblastoma, also known as olfactory neuroblastoma, is a malignant tumor arising from the neural crest cells of the upper nasal tract that commonly extends intracranially. It is extremely rare, with an annual incidence of 0.4 per 1,000,000 people. It affects a wide age group ranging from 3 to 90 years, with one peak between the second and third decade of life and a second peak between the sixth and seventh decades. The most common symptoms are epistaxis (76%), nasal obstruction (71%), tearing (14%), pain (11%), diplopia, proptosis, anosmia, and endocrinopathy. MRI can be used for imaging. Treatment is most commonly with surgical resection followed by radiation therapy. Chemotherapy may be added on as well, of which platinum-based chemotherapy is the standard. Diagnostic biopsy is typically done by otolaryngology in office prior to surgery. The Kadish system is most commonly used to clinically classify extent of disease and correlates with survival:

• A: Confined to nasal cavity
• B: Extension to paranasal sinus
• C: Local extension (orbit or cribiform plate)
• D: Distant metastasis

Pathologic grading may be undergone using the Hyams grading system, which is used to classify all upper respiratory tract carcinomas for nuclear pleomorphism, mitotic activity, presence of rosettes, necrosis, and summates. Grade 1 and 2 lesions have been shown to have a benign disease course while grades 3-4 confer a poor prognosis.

Surgical treatment involves endoscopic tumor resection. Should the tumor extend to the inferior lateral orbit or maxilla, lateral rhinotomy may be utilized to access and excise the lesion. Many institutions use a purely endoscopic approach so long as negative margins are obtained. If not, conversion to an open approach is necessary. Some institutions may opt for stereotactic radiosurgery instead.

The mean overall survival is 7.2 ± 0.7 years. Mean progression free survival is 4.8 ± 0.7 years. Five-year survival is 63%, and 10-year survival is 40%. The most significant prognostic factors are Kadish staging, lymph node involvement, and age at diagnosis.

Choroid Plexus Carcinoma

Choroid plexus carcinoma is a malignant variant of the benign choroid plexus papilloma, a rare neuroepithelial tumor arising from the choroid plexus in the interventricular space. The choroid plexus is responsible for producing the cerebrospinal fluid (CSF) that is within the ventricles and surrounds the brain and spine¹. These tumors are most commonly located in the lateral or fourth ventricles or the cerebellopontine angle from extension of the choroid plexus through the foramen of Luschka. Infratentorial locations are more common in adults, while in pediatric patients, supratenotrial locations are more common. Symptoms arise from increased intracranial pressure related to hydrocephalus such as headache, nausea, vomiting and craniomegaly. Other possible symptoms include seizure, subarachnoid hemorrhage and focal neurologic deficit such as hemiparesis, sensory deficits, cerebellar signs or cranial nerve palsy of the oculomotor (CN III), trochlear (CN IV) or abducens (CN VI) nerve. Hydrocephalus may be caused by overproduction of CSF, obstruction of CSF outflow by tumor or communicating hydrocephalus from blockage of CSF reabsorption by CSF-borne particulates.

Surgical resection is the choice of therapy for both benign and malignant lesions. Surgery can be complicated by tumor fragility and bleeding of the choroidal arteries. If gross total resection is not possible during the first procedure, a second and even third are recommended until complete resection is achieved, as five-year survival is 84%. In one study, recurrence rate following gross total resection was 9.6% and required repeat surgery².

Malignant Meningioma

Malignant meningiomas are WHO grade III lesions characterized by anaplastic, papillary, or sarcomatous pathology. They have a greater recurrence risk than classic, benign meningiomas and typically more aggressive growth. They are characterized by cortical invasion and rapid recurrence following surgical resection. Frequent mitotic figures (≥4 mitoses per high-power field) or papillary features are strong pathological predictors of malignancy. Younger patients are more commonly affected. Surgical resection should be attempted and is first-line regardless of recurrence. Radiation therapy may be attempted if the patient is not a surgical candidate or declines surgical intervention after recurrence. These tumors may be bloody and steps including preoperative embolization of the arterial feeders should be taken to minimize blood loss in surgery, including early interruption of tumor blood supply during surgery prior to central debulking, dissection of the tumor capsule from the brain by dissecting and coagulating vascular and arachnoid attachments, and removal of attached bone and dura when possible. The Simpson grade establishes the extent of meningioma resection during surgery and correlates this with risk of symptomatic recurrence. Grade I entails complete removal with resection of underlying bone and associated dura. There is a 9% symptomatic recurrence at 10 years after resection. Grade II describes complete removal of the tumor and coagulation of the dural attachment. There is a 19% symptomatic recurrence at 10 years after resection. Grade III is complete removal without resection or coagulation of the dura, with 29% of patients experiencing symptomatic recurrence at 10 years after resection. Grade IV is subtotal resection, and 44% of patients have symptomatic recurrence at 10 years after resection. Finally, grade V is simple decompression with or without biopsy, and there is a 100% symptomatic recurrence at 10 years after surgery. Recently, the Simpson grading scheme has been called into question for different histological meningioma types. As convexity meningiomas tend to recur more rapidly than skull base meningiomas, Simpson grade I resection should be the goal²², meaning the goal is complete resection of the meningioma including its origin, attached dura and involved boned, in order to minimize future recurrence.

Ependymoma

An ependymoma is a neoplasm originating from the ependymal cells lining the ventricular system of the CNS. In children, these tumors most commonly occur in the posterior fossa, usually originating from the part of the roof of the 4^th ventricle called the inferior medullary velum whereas in adults, they are more common in the spine. Sixty-nine percent of intracranial ependymomas occur in pediatric patients with a mean age of 17.5 years across all patients. There are about 200 cases of pediatric intracranial ependymoma per year. Prognosis is worse with younger age. Ninety-six percent of intraspinal ependymomas occur in adults with a mean age of 40 years in all patients. Ependymomas can spread throughout the CNS via seeding through the CSF. Higher grade lesions are more likely to do this. WHO Grade I subtypes include myxopapillary ependymoma and subependymoma. WHO Grade II variants include cellular, papillary, clear cell and tanycytic (rare). WHO Grade III class ependymomas are anaplastic. Due to high propensity of seeding local metastasis, the entire spine needs to undergo diagnostic MRI to rule out drop-metastasis.

Intracranial ependymomas tend to be benign and most often occur in the floor of the 4^th ventricle. As such, symptoms secondary to increased intracranial pressure due to hydrocephalus are most common, such as headache (80%), nausea and vomiting (75%), ataxia and vertigo (60%), seizures and cranial nerve palsies of the abducens (VI) and facial (VII) nerves. MRI is used for neuroimaging.

First-line treatment is neurosurgical intervention and gross total resection¹. Lumbar puncture should be undergone 2 weeks following surgery to exclude seeding. Ependymomas are sensitive to radiation therapy, which can be administered postoperatively. Radiation therapy as an adjuvant to surgical resection increases 5-year survival from 20-40% to 40-80%. Adults fare better than children, with an 80% five-year survival compared with a 20-30% five-year survival in pediatric patients. Recurrence can occur at initial site of treatment following gross total resection. Seeding via CSF is another cause of treatment failure, occurring in 9-25% of patients.

Medulloblastoma

Medulloblastomas are the most common pediatric brain malignancy, peaking in the first decade of life with a median age of diagnosis of 5-7 years. Girls have significantly better outcomes than boys. These tumors are embryonal in origin arising from neuroectodermal cells within the cerebellum. As they tend to arise in the cerebellar vermis and grow into the roof of the 4^th ventricle, associated symptoms are generally related to hydrocephalus – headache, nausea, vomiting and ataxia. All medulloblastomas are classified as high grade or WHO grade IV, pathologically. Seeding throughout the neuroaxis is a problem, with 10-35% of patients presenting with seeding at diagnosis. Poor prognostic indicators include younger age (especially < 3 years), metastatic or disseminated disease, inability to perform gross-total resection (particularly with residual > 1.5 cm²) and histological differentiation along glial, ependymal or neuronal lines.

The treatment of choice for medulloblastoma is surgical debulking of the tumor to the greatest extent possible, followed by radiation therapy. Radiation to the whole craniospinal axis is necessary as the tumor has a high propensity to recur and spread via seeding. As the tumor is usually in a high risk location – the floor of the 4^th ventricle, immediately adjacent to the facial colliculus in the pons – leaving residual is preferred to total resection to avoid neurologic deficit. Adjuvant chemotherapy may be used in patients with recurrent lesions or poorer overall outcomes. Commonly used agents are lomustine, cisplatin and vincristine. Up to 40% of patients with posterior fossa tumors may require permanent ventriculoperitoneal shunt following surgery.

Atypical Teratoid Rhabdoid Tumor (AT/RT)

This is an aggressive embryonal malignancy unique to the CNS. Infants and children are predominantly affected, with more than 90% of patients < 5 years of age, and most < 2 years. A minority of AT/RT are associated with primary renal rhabdoid tumor. There is a genetic relationship with deletion or monosomy of chromosome 22. Half of AT/RTs are located in the posterior fossa, particularly within the cerebellopontine angle. Thirty-three percent of patients have CSF seeding on presentation. Most die within 1 year of diagnosis.

Malignant Nerve Sheath Tumor

Malignant peripheral nerve sheath tumors – also known as malignant schwannomas, neurofibrosarcoma, and neurosarcoma – are a rare disease of the connective tissue surrounding nerves. There is a strong association with neurofibromatosis, especially type 1. Lifetime risk in patients with NF1 is estimated to be 8-13%. Symptoms of a malignant nerve sheath tumor include painless swelling of the extremities, difficulty moving an affected extremity, soreness, neurologic deficit, pain or sensory abnormality, dizziness, and balance problems.

Diagnosis is made using biopsy. First-line treatment is surgical excision with wide margins. Radiation therapy is usually undergone following surgery. Invasive tumors may require limb amputation. Chemotherapy is a possible adjuvant treatment. Thirty-nine percent of patients experience tumor metastasis, especially to the lung. Poor prognostic factors are large primary tumor (> 5 cm), high grade, neurofibromatosis, presence of metastasis, and young age.

Metastatic Brain Tumor

Metastases to the brain are the most common brain tumor. Imaging studies show that they comprise approximately 30% of cases. Unfortunately, 70% of these patients will have multiple lesions on imaging at the time of symptom onset. If only a solitary lesion is noted and the patient has a history of cancer, biopsy should be undergone as primary CNS tumor is more likely. The median survival with optimal treatment is 26-32 weeks, thus the aim of management is largely palliative¹. Patients with neurologic symptoms have a median survival of 1 month without treatment. Other indications for resection are if the tumor is giving neurological compromise and/or if no primary tumor is present and the tumor needs to be resected for obtaining diagnosis. In our opinion, if the tumor is resectable, it is better to resect it than only obtaining a surgical biopsy, if surgical risks are reasonable.

The incidence of new cases of metastatic tumor in the U.S. has reached 170,000 annually. Most tumors spread hematogenously, but direct extension can occur. Cerebral metastases are in part due to lack of efficacy of most chemotherapeutic agents beyond the blood-brain barrier (BBB). Others can even weaken the BBB temporarily and promote CNS seeding.

The most common cancers with spread to the brain are lung cancer (44%), breast (10%), kidney – renal cell carcinoma (7%), GI tract cancers, especially colorectal cancers (6%), melanoma (3%), and undetermined source (10%).

Small-cell lung cancer is specifically most likely to metastasize to the CNS, with an 80% metastasis rate in patients with survival of 2 or more years after diagnosis. These tumors are highly radiosensitive and may be treated with radiation therapy with possible adjuvant chemotherapy.

Melanoma metastasis usually involves the pia and arachnoid meningeal layers. Surgical resection is first-line treatment, as these tumors are radioresistant. If gross total resection is not possible (i.e. > 4 metastases or inaccessible location), stereotactic radiosurgery and chemotherapy may be considered. Melanoma metastases are especially prone to bleed.

The most common tumors that metastasize to the brain in children are neuroblastoma, rhabdomyosarcoma, and Wilm’s tumor.

Signs and symptoms of metastatic disease are dependent on tumor location. Mass effect with large tumors or blockage of CSF drainage causing hydrocephalus results in symptoms due to increased intracranial pressure, including headache – present in 50%, the most common presenting symptom – and nausea and vomiting. Focal neurologic deficits due to compression of brain parenchyma or edema are also common. Seizures occur in 15% of patients. Mental status changes such as depression, lethargy, apathy, and confusion are also possible.

The typical workup of a patient with suspected metastasis to the brain is:

1. CT of chest, abdomen, and pelvis with contrast to locate primary tumor
2. Radionuclide bone scan (particularly in prostate, breast, kidney, thyroid, and lung cancers)
3. Mammogram in women
4. Prostate specific antigen (PSA) in men
5. PET scan

References

1. Taillibert S, Delattre JY. (2005). Palliative care in patients with brain metastases.Current Opinions in Oncology. 17(6): 588-592
2. Vanuytsel LJ, Bessell EM, Ashley SE, Bloom HJ, Brada M. (1992). Intracranial ependymoma: long-term results of a policy of surgery and radiotherapy. International Journal of Radiation Oncology, Biology, and Physics. 23(2): 313-319.
3. Mortazavi MM, Griessenauer CJ, Adeeb N, Deep A, Bavarsad Shahripour R, Loukas M, Tubbs RI, Tubbs RS. (2014). The choroid plexus: a comprehensive review of its history, anatomy, function, histology, embryology, and surgical considerations.Child’s Nervous System. 30(2): 205-214.
4. Jeibmann A, Wrede B, Peters O, Wolff J, Paulus W, Hasselblatt M. (2007). Malignant progression in choroid plexus papillomas.Journal of Neurosurgery. 107: 199-202.
5. Bierman PJ. (2014). Surgery for primary central nervous system lymphoma: Is it time for reevaluation? 28(7): 632-637.
6. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. (2007). The 2007 WHO classification of tumours of the central nervous system.Acta Neuropathol. 114(2): 97-109.

Skull Base Tumors

Planum Sphenoidale Meningioma

Meningiomas in this location arise from the flat segment of the sphenoid bone anterior to the chiasmatic sulcus within the anterior cranial fossa.

References

1. Mortazavi MM, Mantovani A, Da Silva HB, and Sekhar LN F (2015). Olfactory groove and planum sphenoidale, and tuberculum sellae meningiomas In Sekhar LN, Fessler RG (second edition), Atlas of Neurosurgical Techniques: Brain. (pp. 227-237) New York, NY: Thieme Publishers.

Tuberculum Sellae Meningiomas

The tuberculum sellae is the bony elevation between the chiasmatic sulcus and the sella tursica. It is 2 cm posterior to the olfactory groove and lies within the middle cranial fossa. These meningiomas are most commonly associated with visual loss due to compression of the optic chiasm, causing bitemporal hemianopsia. Differentials on imaging may include pituitary macroadenoma. These tumors usually involve the optic canals and encase internal carotid and/or anterior cerebral arteries. They can encase the superior hypophyseal artery. They can breach into the sphenoid sinus. Surgical resection requires especial techniques including extradural resection of the anterior clinoid process on the side with most vascular encasement. After entering the dura, the falciform ligament of the ipsilateral optic nerve needs to be sectioned in order to let the optic nerve be mobilized and avoid optic nerve injury. The origin of the tumor at the tuberculum sellae needs to be drilled even if it would risk to open towards the phenoid sinus. Before resecting the tumor, the contralateral falciform ligament needs also to be sectioned in order to mobilize both optic nerves. Also, a majority of the tumors have extension into the optic canal and this technique gives access to resecting those extensions. Avoiding doing this, would not only risk putting tension on the optic nerves during resection of the tumor, but also risk leaving tumor residuals in the optic canals and risk of recurrence of the tumor. Once this important step is done, tumor needs to be dissected off potentially encased internal carotid artery and or anterior cerebral artery. Not unusually, we see the superior hypophyseal artery in the midst of the tumor. It needs to be dissected and saved. Central debulking is key here as the space surrounding the tumor is small and surrounded by both optic nerves, cerebral arteries and pituitary stalk. Once central debulking has shrunken the tumor, the entire tumor can be resected. If sphenoid sinus is opened, it can be filled with abdominal fat graft and covered with autologeous pericranium. Classification for surgical resection is proposed by Sekhar-Mortazavi¹.

References

1. Mortazavi MM, Mantovani A, Da Silva HB, and Sekhar LN F (2015). Olfactory groove and planum sphenoidale, and tuberculum sellae meningiomas In Sekhar LN, Fessler RG (second edition), Atlas of Neurosurgical Techniques: Brain. (pp. 227-237) New York, NY: Thieme Publishers.

Petroclival Meningioma

Petroclival meningiomas may arise off the petrous or clival bones and are in close proximity to the sphenoid bone and cavernous sinus. Surgery can be challenging due to proximity and adhesion to cranial nerves, major blood vessels, and the brainstem¹. Cranial nerve morbidity and motor deficits are the common postoperative neurological complications after resection of petroclival meningiomas¹. These tumors are among the most challenging tumors in skull base surgery. They often involve both the middle and posterior cranial fossae, being both supra-, and infratemtorial. This means that they need extensive combined approaches for gross total resection. Tailored skull base approach for this type of tumor is a combined petrosal approach which includes a temporal craniotomy and a retosigmoid craniectomy, in order to access the pre-sigmoid area where the posterior petrous bone is at the junction of the middle and posterior cranial fossae. The posterior petrous bone just posterior to the posterior semi-circular canal is drilled. The space if then offers, will be enough to remove the tumor. Many cranial nerves are usually attached to the tumor and many times the abducens (6^th cranial nerve) and cochlear (part of the 8^th cranial nerve) although not injured, can become dysfunctional after surgery if not already. Many patients come with facial weakness and hemi-body weakness as the infratentorial part of the tumor compresses the brain stem. Many tumors encase the basilar artery and its branches partially and careful dissection needs to be done. The trochlear (4^th cranial nerve) nerve is especially prone to injury as it is closely adjacent to the edge of the tentorium and access to the intradural compartment requires sectioning of the tentorium and closing of the adjacent superior petrosal sinus. Closure of the superior petrosal sinus does not cause patient harm as its venous return usually re-routs through the inferior petrosal sinus and other veins. Sometimes, these tumors extend anteriorly to the cavernous sinus as well, requiring a tailored skull base approach with a modified frototemporal craniotomy with zygomatic osteotomy in access to the approaches described above for full access and resection of the tumor. Sometimes the tumor extends inferiorly down to beyond foramen magnum, necessitating adding a far-lateral or extreme lateral craniectomy to the above skull base approaches. (See figure)

Figure : Petroclival Meningioma. A. Axial T1-weighted MRI with contrast B. Axial T2- weighted MRI. C. Coronal T1-weighted MRI with contrast. D. Sagittal T1- weighted MRI.

References

1. DiLuna ML and Bulsara KR. (2010). Surgery for petroclival meningiomas: A comprehensive review of outcomes in the skull base surgery era. Skull Base. 20(5): 337-342.

Pineal region tumors

There are many different tumors that may arise in the pineal region. They may be neoplastic or non-neoplastic in origin. These include tumors of pineal glandular tissue – pineocytomas and pineoblastomas; glial cells – astrocytomas, oligodendrogliomas, and glial cysts; arachnoid cells – meningiomas and arachnoid cysts; ependymal lining – ependymomas; sympathetic nerves – chemodectomas; germ cells – choriocarcinoma, germinoma, embryonal carcinoma, endodermal sinus tumor, and teratoma; and remnants of the ectoderm – epidermoid or dermoid cysts. Germ cell tumors are the most common mass type. Despite the diversity of tumor classifications, symptomatic presentation is similar. Obstruction of cerebrospinal fluid outflow through the aqueduct may cause obstructive hydrocephalus, with associated symptoms of headache and nausea and vomiting. Compression of the brainstem and cerebellum are possible. Due to vicinity of the tectum and the quadrigeminal plate, symptoms may include abnormal eye movements, such as the inability to look upward and diplopia, ataxia, and disequilibrium are among other symptoms. Endocrine dysfunction is a rare complication arising from disruption of pineal gland function and potential compression of the nearby hypothalamus. Symptoms may include diabetes insipidus, the inability to regulate water homeostasis, and slowing of growth in children and adolescents. Surgical resection of pineal tumors is preferred for management. Guidelines for treatments and outcome of pineal tumors were recently published¹.

References

1. Abecassis IJ, et al. A single Institute Experience with Pineal Region Tumors: 50 tumors Over 1 Decade. Operative Neurosurgery. (A head of published)

Dermoid

Dermoid cysts are rare, benign brain lesions, accounting for 0.3% of all brain tumors. They are developmental tumors arising from early ectodermal tissue, and can contain keratin, cellular debris, hair, and sebum. They are most commonly located in the midline within the posterior fossa in adults and the lower spine in children and adolescents. They are associated with other congenital anomalies in up to 50% of cases. Dermoid cysts within the spinal tract typically have a dermal sinus tract draining to the skin and thus have high rates of recurrent bacterial meningitis. Complete surgical resection is the treatment of choice.

Epidermoid

Epidermoid cysts are also rare neoplasms, comprising 0.5-1.5% of brain tumors and peak at 40 years of age. Like dermoids, they too arise from early ectodermal tissue, but unlike dermoid cysts, contents are generally limited to stratified squamous epithelium, keratin, cellular debris, and cholesterol, with occasional hair. They are most commonly located in the cerebellopontine angle, fourth ventricle, suprasellar region, and spinal cord and are usually lateral. These are isolated lesions and may even occur iatrogenically following lumbar puncture in the lower spine. Very rarely do these lesions behave malignantly so as to destroy bone or degenerate to squamous cell carcinoma. Complications including aseptic meningitis and hydrocephalus may arise from cyst rupture. A rare variant of aspetic meningitis called Mollaret’s meningitis is associated with epidermoid cysts specifically. Complete surgical excision is first-line treatment, with care not to spill cyst contents. In comparison with Dermoids, Epidermoids are usually located laterally and Dermoids are more located medially.

Pituitary Adenoma

Pituitary adenomas are extremely common skull base lesions, constituting 10-15% of all intracranial neoplasms⁷. Whereas non-secretory pituitary adenomas are often clinically silent, secretory adenomas can cause various clinical symptoms related to the hormone produced⁷. Prolactin and growth hormone secretion are most frequently experienced, comprising 35% and 20% of all pituitary adenomas, respectively, but adrenocorticotropic hormone and thyroid-stimulating hormone production occur in some^1,2. Medical management is possible, for instance dopamine agonists such as cabergoline and bromocriptine can be used to suppress prolactin secretion. Cabergoline is more effective than bromocriptine hormonally but is known to be associated with valvular heart disease and lung fibrosis. Should any sellar mass enlarge to a great extent, compression of the pituitary gland can produce hypopituitarism, while compression of the optic chiasm commonly results in visual disturbance. Compressive or hormone-related symptoms typically prompt surgical resection. Transsphenoidal surgery is the treatment of choice, with cure rates of approximately 85% for microadenomas, defined as being ≤ 1 cm in diameter, but lower for macroadenomas. Injury to the carotid artery is a serious intraoperative complication. Therefore, pituitary tumors with significant extension to the cavernous sinus and lateral to the internal carotid artery, or those with significant extension above the optic chiasm are proposed to undergo craniotomy alone or craniotomy in combination with endoscopic traanssphenoidal approach to minimize risk of injury to internal carotid artery and optic chiasm. Perioperative complications include hormonal disruption due to injury to the pituitary, especially diabetes insipidus secondary to alterations in antidiuretic hormone (ADH) secretion from the posterior pituitary³. This is typically transient. Recurrence of pituitary adenomas is about 12% within 4-8 years following surgery.

References

1. Alvero R: Pituitary Adenoma, in F.F. Ferri, Editor (2017). Ferri’s Clinical Advisor 2017, Philidelphia: Elsevier, Inc.
2. Mortazavi MM, Suriya SS, Quadri SA, Khan MA, Hassanzadeh T, Adeeb N, Fard SA, Rezaee O, Tubbs RS. Current Concepts for Surgical Resection of Pituitary Adenoma: A Systematic Review with Meta-analysis. 85th AANS Annual Scientific Meeting, 22-26 April 2017.
3. Sekhar L, Mantovani A, Mortazavi M, Schwartz TH, Couldwell WT. (2014). Open vs endoscopic: when to use which. Neurosurgery. 61(Suppl 1): 84-92.

Craniopharyngioma

These are tumors that develop from residuals of Rathke’s pouch in the sella tursica. Rathke’s pouch is an embryological derivative of the oropharynx that develops into the anterior pituitary gland, or adenohypophysis. Craniopharyngiomas make up 2.5-4% of all brain neoplasms. Approximately 50% occur in early childhood, most commonly between ages 5-10 years. They are commonly located in the anterior superior margin of the pituitary, although some may arise within the third ventricle. These lesions generally have both solid and cystic components, including cholesterol crystals and calcifications. Large tumors can cause hormonal dysfunction due to compression of the pituitary gland. First-line treatment is surgical removal. Recurrence most often occurs if excision is not complete, typically arising less than 1 year following surgery. Mortality can occur from hypothalamic injury and hormonal dysregulation, but 5-year survival is about 55-85%. Radiation therapy for craniopharyngiomas is controversial with side effects of endocrine dysfuntion, optic neuritis, and dementia and should be avoided in pediatric patients. Most important aspect of surgical removal of these tumors lies in being very careful not injuring its posterior margin that not unusually is attached to the hypothalamus. Hypothalamus injury risks to affects patients water regulation and eating habits throughout their life. It is recommended to leave some tumor residual attached to the hypothalamus and bears a good neurological outcome rather than perform a gross total resection but have a patient with disturbed satiety center function who will be in a state of constant uncontrollable eating.

Hypothalamic Hamartoma

A hamartoma is a malformation of cells found within the local region that resembles a tumor, but is not a true neoplasm. Hypothalamic hamartomas therefore rare, non-neoplastic congenital malformations originating from the inferior hypothalamus or tuber cinereum. The tuber cinereum is gray matter situated between the mammillary bodies and optic chiasm and a part of the hypothalamus. Hypothalamic hamartomas may occur in association with Pallister-Hall syndrome, which is caused by a defect in the GL13 gene. Seizures are the most common symptomatic presentation, especially gelastic seizures, which involve brief fits of unprovoked laughter. These seizures may degenerate into epileptic encephalopathy including complex partial seizures, drop attacks, and tonic-clonic seizures. Precocious puberty is another presentation due to release of gonadotropin-releasing hormone (GnRH) from hamartoma cells. These are the most common CNS lesion to cause precocious puberty. Developmental delay and behavioral disturbances are also possible.

The pathology of hypothalamic hamartomas may be pedunculated (parahypothalamic) or sessile (intrathalamic). Pedunculated hamartomas have a more narrow base attached to the floor of the hypothalamus without distortion of the third ventricle. Sessile hamartomas have a broad attachment to the hypothalamus and arise from within the hypothalamus, distorting the third ventricle. Therefore, precocious puberty is more commonly associated with pedunculated hamartomas and seizures with sessile hamartomas.

Precocious puberty can be managed medically with GnRH analogs, which suppress GnRH release. Anti-epileptics may be used to manage seizures. Indications for surgery are inadequate medical management or neurological deficit due to mass effect of the lesion. Risks of surgery include cranial neuropathy and stroke for pedunculated hamartoma resection and memory impairment, endocrine disruption, and weight gain for sessile hamartoma removal. Same principles of surgery as for craniopharyngiomas apply to this. Please see above. During surgical resection, it is important, not to injure the hypothalamus.

Choroid Plexus Papilloma

Choroid plexus papillomas are benign, WHO grade I, tumors of the choroid plexus, which produces the cerebrospinal fluid (CSF) that surrounds the CNS. These are the most common type of choroid plexus tumor. Transformation to malignancy is rare. Choroid plexus tumors comprise 0.4-1% of all intracranial neoplasms. Seventy percent of those affected are less than 2 years of age. They are typically found supratentorially in children and infratentorially in adults (unlike most other tumors). The most common presenting symptoms are related to increased intracranial pressure from hydrocephalus including headache, nausea/vomiting, and craniomegaly (head enlargement). Hydrocephalus may arise either from overproduction of CSF or blockage of CSF outflow.

Surgical resection is the best treatment option. Bleeding from choroidal arteries is the most common complication and may necessitate shunt placement. Recurrence is relatively rare. (See figure)

Figure : Choroid Plexus Papiloma. A. Sagittal T1-weighted MRI with contrast B. Axial T1- weighted MRI with contrast. C. Sagittal T2-FLAIR D.Axial T2- FLAIR MRI.

Vestibular Schwannoma (Acoustic Neuroma)

Vestibular schwannomas, also previously known as acoustic neuromas, are common, histologically benign tumors of the vestibulocochlear nerve (cranial nerve VIII) found in the cerebellopontine angle (CPA). Their name comes from their more common location arising from the inferior division of the vestibular nerve of cranial nerve VIII. They comprise 8-10% of all intracranial tumors with an annual incidence around 1.5 cases per 100,000 population. Symptoms arise generally after 30 years of age. Early symptoms include hearing loss (usually high frequency), tinnitus (high-pitched), and dysequilibrium. Hearing loss is insidious and progressive. Only 10% of patients experience sudden hearing loss. Larger tumors may cause facial numbness or weakness, headache, and focal brainstem signs including weakness. Workup for all patients involves brain MRI with and without contrast and audiometrics. Most vestibular schwannomas are unilateral. Bilateral vestibular schwannomas are characteristic of neurofibromatosis type 2 (NF2, discussed under neurosurgical syndromes).

Management options include expectant management for small non-progressive asymptomatic tumors, radiation therapy, surgery, and chemotherapy. About 83% of vestibular schwannomas show little or no growth and may be conservatively managed in the absence of symptoms and small in size. Large tumors (> 25 mm diameter) should be treated with microsurgical resection in order to minimize mass effect and decompress the brainstem. Patients with contraindications to surgery such as the elderly or those with co-morbidities may undergo stereotactic radiosurgery (SRS) instead. Treatment approach for symptomatic, small (

Radiosurgery and SRS better preserve hearing than microsurgery, especially for larger-sized tumors and in patients with greater preoperative hearing loss. However, direct cochlear nerve monitoring intraoperatively has improved preservation of hearing following microsurgery. In contrast, trigeminal neuropathy has a greater incidence with SRS, particularly for large tumors with high doses of radiation. This is not a common complication of microsurgery. Although the goal of surgery is total tumor resection, this may not be possible due to the proximity of the facial nerve. However, near total or subtotal resection both have excellent long-term tumor control with only observation or postoperative radiation. Facial nerve’s course, from its emergence form the brainstem, through its course within the temporal bone of the skull base and over the face has been classified by multiple authors. Surgery can be achieved through a Retrosigmoid craniectomy for all the tumors that do not have extension beyond the fundus segment of the facial nerve’s course within the temporal bone of the skull base^1,2. If the tumor extension is lateral to the fundus, a middle fossa approach can be utilized.

Postoperative complications include facial nerve damage, with inability to close the eyes; vestibular nerve damage, a common complication with nausea, vomiting, and potential long-term ataxia; lower cranial nerve deficits, with problems swallowing and risk of aspiration; and brainstem dysfunction, with ataxia and contralateral paresthesia. CSF fistula, rhinorrhea, meningitis, and stroke are also possible complications. CSF rhinorrhea is the most common surgical complication, occurring in 4-27% of cases. This may resolve on its own (25-35%) or require surgical re-exploration and shunt placement. Hearing loss has been found to be worse with retrosigmoid than middle fossa craniotomy, even when controlling for tumor size³. Preservation of functional hearing after gamma knife radiosurgery is high with 49% of patients in one clinical trial retaining functional hearing at 10-year follow-up⁴.

References

1. Mortazavi MM, Adeeb N, Latif B, Watanabe K, Deep A, Griessenauer CJ, Tubbs RS, Fukushima T. Gabriele Fallopio (1523-1562) and his contributions to the development of medicine and anatomy. Childs Nerv Syst. 2013 Jun;29(6):877-80. doi: 10.1007/s00381-012-1921-7. PMID: 22965774
2. Tubbs RS, Fries FN, Kulwin C, Mortazavi MM, Loukas M, Cohen-Gadol AA. (2016). Modified skin incision for avoiding the lesser occipital nerve and occipital artery during retrosigmoid craniotomy: potential applications for enhancing operative working distance and angles while minimizing the risk of postoperative neuralgias and intraoperative hemorrhage. Journal of Clinical Neurosurgery. 32:83-87.
3. Wilkinson EP, Roberts DS, Cassis A, Sochwartz MS. (2016). Hearing outcomes after middle fossa or retrosigmoid craniotomy for vestibular schwannoma tumors. J Neurol Surg B Skull Base. 77(4): 333-340.
4. Boari N, Bailo M, Gagliardi F, Franzin A, Gemma A, del Vecchio A, Bolognesi A, Picozzi P, Motini P. (2014). Gamma Knife radiosurgery for vestibular schwannoma: clinical results at long-term follow-up in a series of 379 patients. Journal of Neurosurgery. 121 Suppl: 123-142.

Trigeminal Schwannoma

These are uncommon, benign tumors also comprised of schwann cells, like vestibular schwannomas. However, they surround the trigeminal nerve (cranial nerve V). They make up 0.2% of all intracranial neoplasms. Peak incidence is between the 3^rd and 4^th decades of life. Symptoms are related to trigeminal nerve dysfunction, including facial pain, numbness, or weakness. Surgical resection is usually curative with preservation of trigeminal nerve function and thus first-line treatment¹. (See figure)

Figure : Trigeminal Schwannoma. A. Axial T1-weighted MRI. B. Axial T1-wieghted with contrast. C. Sagittal T1-wieghted MRI with contrast.

References

1. Ramina R, Mattei TA, Soria MG, da Silva EB, Leal AG, Neto MC, Fernandes YB. (2008). Surgical management of trigeminal schwannomas. Neurosurgical Focus. 25(6): E6.

Glomus Tumor

Glomus tumors, also known as paragangliomas, are rare neuroendocrine neoplasms arising from paraganglion cells of the neural crest. Ninety-seven percent are histologically benign with most showing slow growth. Most are located in the abdomen (97%), with only 3% located intracranially. Some may secrete catecholamines, which can cause life-threatening hypertension and/or cardiac arrhythmias. Up to 50% are inherited, with the rest being sporadic. Most of them are sensitive to radiation as the main treatment or in order to shrink the tumor for resection of a smaller residual. Some glomus tumors can be observed or managed medically with alpha- and beta-blockers as needed for hormone secretion. For those that require resection, surgery has usually been first-line but the advent of radiosurgery has provided an alternative. Studies have shown good tumor control with low risk of cranial nerve injuries following gamma knife radiosurgery^1-3.

References

1. Chen PG, Nguyen JH, Payne SC, Sheehan JP, Hashisaki GT. (2010). Treatment of glomus jugulare tumors with gamma knife radio surgery. Laryngoscope. 120: 1856-1862.
2. Jacob JT, Pollock BE, Carlson ML, Driscoll CL, Link MJ. (2015). Stereotactic radiosurgery in the management of vestibular schwannoma and glomus jugulare: indications, techniques, and results. Otolaryngol Clin North Am. 48(3): 515-526.
3. Sanna M, Piazza P, Ho Shin S, Flanagan S, Mancini F.(2013) Microsurgery of Skull Base Paragngliomas. New York, NY: Thieme Publishers.

Neurosurgical Syndromes

Neurofibromatosis, type 1 & 2

Neurofibromatosis is the most common neurocutaneous disorder. The two most common types are neurofibromatosis 1 (NF1, also known as Von Recklinghausen’s Disease) and neurofibromatosis 2 (NF2). The incidence of NF1 is 1/3000 births versus 1 in 40,000 for NF2, making NF1 much more common. NF1 is associated with an abnormality of chromosome 17, while NF2 is associated with a defect of chromosome 22. Up to 50% of cases of NF1 and NF2 may be inherited in an autosomal dominant fashion.

Diagnostic criteria for NF1 are two or more of the following: ≥6 café au lait spots, ≥2 neurofibromas of any type or 1 plexiform neurofibroma, optic glioma, ≥2 Lisch nodules (pigmented iris hamartomas), distinctive osseous abnormality such as sphenoid dysplasia or thinning of long bone cortex, and a first degree relative with NF1 by this criteria. Schwannomas are associated with NF1, but bilateral vestibular schwannomas are only seen in NF2. Pheochromocytomas and intellectual impairment may also be seen in NF1. Management of optic gliomas in NF1 is usually conservative, as most rarely involve the nerve and are non-progressive. Intracranial tumors should be managed using the same criteria as in the general population.

Definitive diagnostic criteria for NF2 are as follows: bilateral vestibular schwannomas on imaging or a first degree relative with NF2 and either a unilateral vestibular schwannoma at age nd to 3^rd decades of life with rapid hearing loss and multiple associated tumors. The second form is milder, presenting later in life with slower loss of hearing and fewer associated tumors. Bilateral vestibular schwannomas are best excised surgically when small in order to maximize hearing preservation. If removal of 1 tumor restores hearing, the second tumor may be observed or removed surgically as well. A subtotal resection may be undergone to avoid total deafness. Stereotactic radiosurgery is another option. Most patients will become eventually become deaf.

Hereditary Hemorrhagic Teliangiectasia (HHT, aka Osler Weber Randu)

Hereditary hemorrhagic telangiectasia (HHT, also known as Osler-Weber-Rendu syndrome) is a genetic vascular disease inherited in an autosomal dominant fashion. Capillaries become slightly enlarged with low flow. About 1 in 5,000 people are affected. Cerebrovascular malformations include telangiectasias, arteriovenous malformations (AVM, discussed separately), and venous angiomas and aneurysms. A common presenting symptom is recurrent epistaxis. Surgery is only necessary for evacuation of a hematoma or diagnosis. It also may be considered for recurrent hemorrhages or medically intractable seizures.

Foster Kennedy syndrome

This is a syndrome typically produced by olfactory groove or medial third sphenoid wing tumors, such as meningiomas. The classic triad of symptoms is ipsilateral anosmia, ipsilateral central scotoma, and contralateral papilledema. Central scotoma occurs due to optic atrophy from tumor compression of the optic nerve. Papilledema results from increased intracranial venous pressure.

Tuberous sclerosis

Tuberous sclerosis has a prevalence of 1 in 6,000-10,000 live births. The clinical triad of symptomatic presentation is seizures, mental retardation, and sebaceous adenomas. Subependymal nodules (“tubers”), a type of hamartoma, are a common intracranial finding. Hamartomas occur throughout the entire body. Subependymal giant cell astrocytomas are also seen. There are two tumor suppressor genes that are commonly mutated, TSC1 on chromosome 9 (encoding hamartin), and TSC2 on chromosome 16 (encoding tuberlin).

Von Hippel-Lindau Disease (VHL)

This is a familial disorder presenting with hemangioblastomas of the cerebellum, retina, brainstem, and spinal cord. Pheochromocytomas and renal cysts and tumors are also commonly seen. The main genetic mutation is inactivation of a tumor suppressor gene on chromosome 3, and it is inherited in an autosomal dominant fashion. It occurs in 1 in 31,000-36,000 live births. Thirty percent of patients with cerebellar hemangioblastomas have VHL. The age of presentation is variable.

Wyburn-Mason syndrome:

Wyburn-Mason syndrome is considered one of the nonhereditary congenital neurocutaneous disorder and is characterized by arteriovenous malformations (AVMs) of eyes and brain, typically involving the retina, visual pathways, midbrain, and facial structures. In contrast to other neurocutaneous disorders, Wyburn-Mason syndrome does not commonly cause cutaneous manifestations. Common presenting symptoms includes seizure, mental changes, hemiparesis, and papilledema, which are frequently a source of hemorrhage, unlike the hemangioma of SWS.