Spinal Cord Tumors - Management of Intradural Intramedullary Neoplasms

Background

Intradural or primary spinal cord tumors (neoplasms) are uncommon lesions and fortunately affect only a minority of the population. However, when lesions grow, they result in compression of the spinal cord, which can cause limb dysfunction, motor and sensation loss, and, possibly, lead to death. Spinal tumors are classified based on their anatomic location as related to the dura mater (lining around the spinal cord) and spinal cord (medullary) as epidural, intradural extramedullary, or intradural intramedullary. Primary spinal tumors are typically intradural in location, where extradural spinal tumors are typically due to metastatic disease.
This article focuses on the evaluation and management of intradural intramedullary spinal cord tumors. The typical histopathological types that account for 95% of these intramedullary neoplasms include astrocytomas, ependymomas, and hemangioblastomas. Spinal cord astrocytomas and ependymomas can be further classified as glial cell neoplasms. See the image below.

This T1-weighted sagittal MRI is from a 19-year-old man with 4-month history of progressive motor loss and an inability to ambulate. He underwent spinal biopsy that confirmed an intramedullary glioblastoma.

History of the Procedure

In 1887, Sir Victor Horsley performed the first successful resection of an intradural neoplasm diagnosed by William Gower. This lesion was an intradural extramedullary tumor that compressed the spinal cord. However, the patient did not survive the intervention. Due to limited operative techniques, the first successful removal of an intradural intramedullary tumor, performed by Eiselsberg-Renzi, did not occur until 1907.

In 1925, Charles Elsberg published the first large series of patients who underwent resections of primary spinal cord neoplasms. Unfortunately, again because of the limited operative techniques of this period, these patients endured significant surgical morbidity and mortality. However, subsequent advances in imaging, sterile operative techniques, microsurgical dissection, operating microscopy, and neurophysiologic monitoring have facilitated removal of these lesions with substantially improved clinical results.

Problem

Spinal cord parenchyma consists of both gray (neurons and supporting glial cells) and white matter (axonal) and tracts that transmit impulses between the brain and body. These tracts, or circuits, control posture, movement, sensation, and autonomic system function, including bowel, bladder, and sexual function.

Neurologic dysfunction develops as the spinal cord tumors enlarge and compress adjacent healthy neural tissue, disrupting these pathways. Upon further compression, patients can lose complete motor function and sensation below the lesion. In addition to weakness and sensory loss, patients may experience pain, particularly at night. This pain is believed to be related to disturbances in venous outflow by the tumor, causing engorgement and swelling of the spinal cord.

Epidemiology

Frequency

Intramedullary spinal cord tumors account for approximately 2% of adult and 10% of pediatric central nervous system neoplasms. In adults, 85-90% of intramedullary tumors are the glial subtypes, astrocytoma or ependymoma. Ependymomas account for approximately 60-70% of all spinal cord tumors found in adults, while, in children, 55-65% of intramedullary spinal cord tumors are astrocytomas. Hemangioblastomas account for 5% of tumors, whereas paragangliomas, oligodendrogliomas, and gangliogliomas account for the remaining lesions.

Etiology

The pathogenesis of spinal neoplasms is unknown, but most arise from normal cell types in the region of the spinal cord in which they develop. A genetic predisposition is likely, given the higher incidence in certain familial or syndromic groups (neurofibromatosis). Astrocytomas and ependymomas are more common in patients with neurofibromatosis type 2, which is associated with an abnormality on chromosome 22. In addition, spinal hemangioblastomas can develop in 30% of patients with von Hippel-Lindau syndrome, which is associated with an abnormality on chromosome 3.

Pathophysiology

The spinal cord consists of numerous nerve bundles that descend from and ascend to the brain. Electrical impulses are carried and transmitted to facilitate movement and sensation. With intramedullary spinal cord tumors, compression and stretching of these fiber tracts results in loss of the motor and sensory function. As the tumors grow, the patient's neurologic function further deteriorates.

Presentation

Patients with intramedullary glial spinal cord tumors (ie, ependymomas, astrocytomas) typically present with back pain referred from the level of the lesion, sensory changes, or worsening function. The symptoms can be of a long duration, since these lesions tend to grow slowly and typically have a benign histopathology. Patients with low-grade astrocytomas tend to experience symptoms over a mean duration of 41 months. This is in contrast to patients with malignant astrocytomas, whose symptoms persist for a mean duration of only 4-7 months before diagnosis.

Tumor-specific characteristics

Ependymomas are associated with the following:

• Mean age at presentation of 43 years
• Slight female predominance
• Pain localized to the spine (65%)
• Pain worse at night or upon awakening
• Dysesthetic pain (burning pain)
• Long history of symptoms
• Myxopapillary variant (mean age of presentation of 21 y; slight male predominance)

Astrocytomas are associated with the following:

• Equal male and female prevalence
• Pain localized to spine
• Pain worse at night or upon awakening
• Paresthesias (abnormal sensation)

Hemangioblastomas are associated with the following:

• Onset of symptoms by the fourth decade of life, 80% symptomatic by age 40 years
• Familial disorder (ie, von Hippel-Lindau syndrome) present in a third of patients
• Decreased posterior column sensation
• Back pain localized over lesion

Physical examination findings

Sensory findings include the following:

• Decreased touch, pain, and/or temperature sensation
• Hyperesthesias
• Decreased proprioception (inability to localize limbs in space)
• Abnormal sensation below the level of lesion
• Abnormal sensation only at level of lesion (suspended level)

Hyperreflexia findings include the following:

• Hoffman sign for cervical lesions
• Clonus
• Extensor plantar response (Babinski sign)

Other findings include the following:

• Motor weakness (late finding)
• Spasticity
• Increased tone
• Muscle atrophy (late finding)

Indications

Intramedullary spinal cord neoplasms or tumors are typically histopathologically "benign" or slow growing. However, patients can have more aggressive neoplasms as well as morbidity due to the location of the lesion. Consequently, compared with similar intracranial neoplasms, patients may have a prolonged survival after diagnosis.

Optimal treatment options depend on the patient's clinical symptoms and neurologic finding. When and whether to treat these lesions as well as perform radiosurgery or surgical excision of lesions remains controversial. However, cures have been reported only after complete surgical resection. Therefore, patients with neurologic symptoms and confirmatory findings from imaging studies may benefit most from surgical excision, with the surgical goal of total gross resection of the lesion.

Relevant Anatomy

Arterial

Understanding the normal spinal cord vascular supply is essential to treating intramedullary spinal cord lesions; specifically because these vessels may have a variable and inconsistent distribution.

The great vessels (aorta, carotids) contribute arterial supply to the spinal cord via segmental arteries, which further branch into medullary and radicular arteries. The radicular artery provides extramedullary blood supply to the nerve root and dura; the medullary artery bifurcates into anterior and posterior divisions to form the spinal arteries. One anterior and 2 posterior spinal arteries then transverse the longitudinal axis of the spinal cord and provide the blood supply to the spinal cord. Neoplasms acquire their blood supply by leaching blood from these vessels.

Venous

The venous plexus of the spinal column, termed the Batson plexus, is unlike other venous systems in the body because the veins do not contain valves. Therefore, blood can have pathologic retrograde flow. This retrograde flow blood can back up and cause venous congestion. This can manifest as venous hypertension. Because oxygenated blood cannot pass through the spinal cord because of the congestion of outflow, patients present with progressive neurologic dysfunction.

Spinal cord

The spinal cord parenchyma consists of a central canal surrounded by an H-shaped gray matter region that contains neurons. Outer myelinated nerve tracts, termed white matter, surround the central gray matter. The central canal represents an embryologic remnant from neurulation of the neural plate and is lined with ependymal cells. Ependymomas arise from these cells and, therefore, are typically located centrally in the spinal cord parenchyma. In contrast, astrocytes support gray matter neurons and white matter axons. Neoplastic transformation of these supporting cells results in the development of astrocytomas and may occur almost anywhere within the cord.

Contraindications

Observation with serial imaging studies over a variable period is a treatment option for patients who pose a high surgical risk, who are elderly, and/or who only have minimal neurologic signs. Patients in whom pathology tissue shows a malignant neoplasm may be best treated with radiotherapy because they are expected to have an accelerated deterioration and complete surgical resection is not possible.

Spinal Cord Tumors - Management of Intradural Intramedullary Neoplasms Workup

Laboratory Studies

Not diagnostic of tumor pathology and reserved as part of preoperative planning

• CBC count
• Sequential Multiple Analysis-7
• Prothrombin time/activated partial thromboplastin time
• Sequential Multiple Analysis-12 (optional)

Imaging Studies

Plain radiography

See the list below:

• Not accurate for diagnosis
• Abnormalities identified in 20% of patients
• Scalloping of the vertebral bodies on lateral radiographs
• Widening of interpedicular distance on anteroposterior radiographs
• Scoliosis in children that results from neuromuscular impairment

Myelography

See the list below:

• Not optimal because it is invasive and can alter spinal fluid dynamics, causing neurologic worsening
• Nonspecific spinal canal and spinal cord widening
• Multisegmental involvement
• Block of contrast dye
• Conus region lesions, possible meniscus around the tumor

CT scan

See the list below:

• Nonspecific spinal canal and spinal cord widening
• Scalloping of vertebral bodies
• Possible intraparenchymal syringomyelia

MRI of spine with and without gadolinium

This is the criterion standard. See the images below.

This T1-weighted sagittal MRI is from a 19-year-old man with 4-month history of progressive motor loss and an inability to ambulate. He underwent spinal biopsy that confirmed an intramedullary glioblastoma.

This T2-weighted MRI is from a 19-year-old man with 4-month history of progressive motor loss and an inability to ambulate. He underwent spinal biopsy that confirmed an intramedullary glioblastoma.

See the list below:

• Most accurate and noninvasive technique
• Gadolinium (contrast) requires evaluation of kidney function because cases of malignant fibrosis reported
• Enlargement of the spinal cord
• Syringomyelia or cystic cavity associated within the lesion

Ependymoma findings are as follows:

• T1-weighted images - Isointense signal with spinal cord
• T2-weighted images - Hyperintense signal
• Strong homogeneous enhancement with contrast

Astrocytoma findings are as follows:

• T1-weighted images - Isointense or hypointense signal with spinal cord
• T2-weighted images - Hyperintense signal
• Cyst formation
• Heterogeneous enhancement with contrast

Hemangioblastoma findings are as follows:

• T1-weighted images - Isointense signal to spinal cord
• T2-weighted images - Hyperintense signal
• Cystic with tumor nodule (50-70%)
• Enhances strongly with contrast
• Extramedullary extension in 15%

Spinal arteriography

This is beneficial only if a hemangioblastoma is suggested as a differential diagnosis. Hemangioblastoma arteriography findings include a vascular blush with a prominent draining vein.

Other Tests

Baseline urodynamics

Findings may assist in diagnosing abnormal bladder function.

Neurophysiologic testing (EMG/NCS/SSEP)

Findings may quantify degree of neurologic injury from tumor.

Diagnostic Procedures

Lumbar puncture is not indicated unless the patient is being evaluated for drop metastasis or leptomeningeal spread of intracranial disease (as in cranial ependymomas). In addition, lumbar puncture may be useful to differentiate if due to infectious or inflammatory myelitis (multiple sclerosis). However, clinical presentation and imaging studies can typically exclude these etiologies.

Neurological deterioration can be precipitated after lumbar puncture if a complete myelographic block is present from changes in the compliance of the lesion and position of the neoplasm.

Spinal Cord Tumors - Management of Intradural Intramedullary Neoplasms Treatment & Management

Medical Therapy

Pharmacological treatment of intramedullary spinal cord tumors is of limited benefit. High-dose intravenous corticosteroid therapy may improve neurologic function transiently but is not appropriate for long-term treatment. Although steroids decrease vasogenic edema, they do not treat the underlying pathologic condition. Prolonged use of steroids can be associated with gastric ulceration, hyperglycemia, and immunosuppression with cushingoid features.

Chemotherapeutic regimens have limited success in the treatment of spinal cord neoplasms. This may be partly due to the inability of the chemotactic agents to cross the blood-brain barrier.

Standard fractionated radiation is used for astrocytomas of residual and recurrent neoplasm.

Stereotactic spinal radiosurgery may be helpful for treating these lesions. Although similar symptomatic control may be achieved over the short term when compared with surgical resection, recurrence and malignant tumor transformation have been observed after radiotherapy. This treatment may be most effective in dealing with malignant lesions only. In the future, stereotactic or intensity-modulated radiosurgery may play larger role in treatment options available for patients. Because of the precision with which the radiation is delivered, radiosurgery helps to minimize spinal cord radiation toxicity and/or necrosis. Recent research has confirmed that the spinal cord is generally tolerant to the doses of radiation normally used in these procedures. 

Surgical Therapy

Patients presenting with neurologic deficits and mass lesions in the spinal cord require histopathology in order to define the neoplasm such that treatment options can be maximized. The surgical approach to these lesions typically consists of preparing for gross total resection. The neoplasm is identified and then biopsy is performed. Surgery then proceeds based on the histology from the frozen specimen as well as the ability to define a surgical plane to resect the lesion. If the lesion is an astrocytoma, then the goal is debulking the tumor while not injuring the normal neural tracts. Ependymomas are attempted to be resected completely as long as a viable plane can be established and normal neural tracts are not disturbed. 

Preoperative Details

Any patient suspected of having an intrinsic spinal cord neoplasm should undergo a detailed history and physical examination. The preoperative evaluation should consist of a detailed neurologic examination and appropriate imaging studies to confirm the diagnosis. Detailed imaging studies should consist of MRI with and without gadolinium. If MRI is not available, myelography with CT scanning should be used. If appropriate, obtain a preoperative medical evaluation.

Intraoperative Details

Surgical resection is performed with the patient under general anesthesia, typically in a prone position. Intraoperative neurophysiological monitoring provides real-time feedback regarding possible ischemia or retraction injury to the spinal cord during the resection and is used by some surgeons.

A laminectomy (laminoplasty in children) is performed after radiographic confirmation of the appropriate spinal level. The laminectomy defect should be of sufficient size to allow visualization of healthy spinal cord above and below the suspected neoplasm.

Some patients have a kyphosis (curve) or straightening of the spine and removing the laminae can cause further progression of this curve. Therefore, some surgeons opt to fuse (arthrodesis) the spine over the area the laminectomy is performed to prevent it from bending forward further.

The dura mater is exposed at the correct levels. An intraoperative ultrasound study can be used to confirm adequate bony decompression and the lesion is center prior to the dural opening. Intraoperative ultrasound can also reveal the extent of the lesion and the degree of resection. Some surgeons are now using more advanced techniques to determine the margins of the tumor, such as inserting an intravenous dye that localizes to the tumor margins and can be visualized on a video camera.  The dura mater is incised or opened in the midline and then secured laterally to maintain the exposure.

Using the intraoperative microscope or magnification, the spinal cord is inspected and the pia mater is opened directly over the tumor exposing the spinal cord. The spinal cord is incised sharply typically through the midline raphe. Once the tumor is exposed, a plane is established at the periphery.

A biopsy specimen is obtained from the center of the lesion and sent for histopathological analysis. If pathologic evaluation confirms a low-grade neoplasm, the median exposure is opened until the full extent of the intraparenchymal lesion can be visualized. The dissection plane is further developed between the tumor and the normal spinal cord parenchyma. Often, cystic cavities help define the caudal and rostral margins of the tumor. Ependymomas tend to be encapsulated, brownish-red, sausage-shaped masses, whereas astrocytomas are ill-defined, whitish enlargements with associated cysts.

The goal for benign or low-grade neoplasms is gross total resection. Once the tumor-spinal cord interface is defined, the tumor can be debulked internally with gentle dissection or an ultrasonic cavitation to reduce spinal cord manipulation. Complete resection of benign neoplasms cannot always be achieved without neurological injury, particularly if the tumor–spinal cord interface is indistinct.

Patients with biopsy-proven high-grade lesions typically have a rapid progression in neurological dysfunction, even after aggressive resections. Consequently, only biopsy and a dural patch graft (to enlarge the space for the spinal cord) may be an alternate approach to attempted resection. When surgical resection is completed, the dura and muscles are closed in layers.

Postoperative Details

Patients are closely monitored in an ICU setting to monitor their neurologic examination and acutely detect and neurologic deterioration. Incisional pain should be minimal and should be relieved with intravenous analgesics. Patients typically have some degree of posterior column dysfunction due to traction and manipulation during surgery. This usually is in the form of "numbness" below the region of resection as well as proprioception difficulty. The proprioception difficulties can be disabling for the patients because they impair ambulation and fine motor control. These deficits tend to progressively improve with time. In Brotchi's series of 239 patients with low-grade spinal tumors, 5% of patients worsened, 50% of patients stabilized, and 40% of patients improved after surgical intervention.  Overall, patients typically maintained their preoperative level of function postoperatively.

Depending on the needs of patients, they are either discharged home or transferred to a rehabilitation facility.

Follow-up

Follow-up care should include serial neurologic examinations and MRI to monitor for recurrence or progressive growth of residual tumor. If patients experience any neurologic worsening, perform contrast-enhanced MRI. The recurrence rate for low-grade tumors is less than 5%; approximately 10% of patients have progression of residual tumor.

Consider radiotherapy or stereotactic radiosurgery for the treatment of malignant neoplasms. Its role in benign neoplasms is unclear, but, typically, serial observation is recommended.

Complications

See the list below:

• Bladder and bowel dysfunction
• Bleeding or hematoma
• Cerebrospinal fluid leak
• Chronic pain
• Injury to central nervous system tissue
• Meningitis
• Paralysis
• Sensory loss
• Sexual dysfunction
• Skin infection or cellulitis
• Spine instability
• Ventilator dependence and death
• Wound dehiscence

Outcome and Prognosis

The 5-year survival rate for patients with benign or low-grade spinal cord neoplasms is greater than 90%. In Brotchi's series of 239 patients with low-grade spinal tumors and operative intervention, 5% worsened, 50% stabilized, and 40% improved.  In the series by Karikari et al, the patients with ependymomas, the more common and less aggressive tumor, had a tumor recurrence rate of 7%. Patients with astrocytoma, the more aggressive and less common tumor type, had a recurrence rate of 48%. A patient's neurologic function after surgical intervention directly depended on his or her preoperative neurological status. Therefore, the goal of surgical treatment is to prevent further neurologic dysfunction from compression by the neoplasm, to obtain a diagnosis, and to potentially cure the neoplastic condition with a complete resection.

A patient's overall prognosis depends on the neoplasm's histopathology. This is the most important predictor of patient outcome because it predicts if the tumor will be resectable and if it will recur.

Future and Controversies

Intraoperative microscopy, neurophysiologic monitoring, and improved neuroimaging have improved the success of surgical intervention. Further advances in technology for tumor resection and neuroimaging may lead to further improvements in surgical outcomes. Better understanding of the genetics of these neoplasms may provide for earlier medical intervention with improved care and treatment of these disorders.

Radiosurgical techniques, specifically the use of stereotactic radiosurgery or IMRT, are improving such that these options will have an increased role in the treatment of benign disease and more aggressive neoplasms. The difficulty with this modality is that a histologic diagnosis should be obtained prior to deciding on treatment. Also, because this is a new technique, further research into the safety and efficacy of the procedure is needed before it becomes a standard of care. The promise of this technique is in its noninvasiveness compared with open surgery.

Other minimally invasive surgical techniques are currently being developed. One involves a "mini-open" procedure that uses a smaller surgical incision, and another uses a minimally invasive retractor system to limit spinal cord manipulation during surgery. The aim of these techniques is to reduce hospitalization time and complications such as infection.

A Neurosurgeon & a Neurologist .. What's the diffrence ?

Neurosurgeons treat conditions caused by accident or injury, as well as illness.

Diseases, injuries and disorders of the brain and nervous system are some of the most wide-ranging and difficult to treat in all of medicine. Neurological conditions can impair learning or mental function, affect balance and mobility, alter a patient's personality or cause debilitating, long-term pain. These conditions are treated by physicians in two closely related specialties, neurology and neurosurgery.

Neurologists

Neurologists specialize in the diagnosis and treatment of diseases or conditions occurring in the brain and nervous system, as well as their supporting systems and tissues. Some focus on neurophysiology, using diagnostic tests such as electroencephalograms and electromyography to detect neurological conditions. Others specialize in the treatment of neurodevelopmental disorders, attempting to manage cerebral palsy, learning disabilities and similar chronic conditions. Neurologists might also specialize in pain management, treating patients with debilitating chronic pain or acute short-term pain. Vascular neurologists study and treat conditions of the circulatory system that affect the function of the brain or nerves.

Neurosurgeons

Neurosurgeons use a variety of therapies, from endoscopic microsurgery to radiation to traditional open surgery, to treat neurological conditions. These include traumas of the brain and spine, tumors, strokes and aneurysms, and many other conditions of the spine, brain and skull base areas. These are complex areas of practice, and neurosurgeons' work often overlaps with that of neurologists, orthopedic surgeons, and plastic or reconstructive surgeons. Often, several of these practitioners will work collaboratively with a single patient to ensure a successful outcome in complex procedures.

Similarities and Differences

Neurosurgery is closely aligned with neurology, and both require an in-depth understanding of the nervous system and its functions. Conditions that require management, or can be improved by medications or other therapies, are generally treated by neurologists. Neurologists are also more likely to act as diagnosticians, isolating and defining neurological conditions for neurosurgeons to rectify. When diagnosis reveals a physical cause for neurological conditions, neurosurgeons can usually perform a surgical procedure to remove or correct that condition, often bringing about a dramatic improvement in the patient's condition. Both neurologists and neurosurgeons can use minimally invasive endoscopic or catheter-based procedures, using miniature instruments to repair or reinforce blood vessels in the brain.

Income

One key difference between neurology and neurological surgery is income. Neurosurgeons out-earn their neurologist peers by a substantial margin, beginning in their first year of practice. Medical recruiting firm Profiles, which specializes in new physicians, reports a median first-year income of $190,000 for neurologists, while neurosurgeons starting practice earned a median income of $395,000 a year. Across all career stages, the American Medical Group Association reported a median income of $236,500 for neurologists and $592,811 per year for neurosurgeons. Staffing firm Jackson and Coker found an even broader disparity, reporting an average salary of $209,394 for neurologists but $671,086 per year for neurological surgeons.

Craniopharyngiomas Surgery

Background

Craniopharyngiomas are benign epithelial tumors of the sellar region but can have significant neurological and endocrinological consequences and may require treatment that will cause further morbidity. The first description of a craniopharyngioma is credited to Zenker, who made this observation in 1857. Following this, Mott and Barrett, in 1899, documented the occurrence of these tumors and postulated that they arose from the hypophyseal duct or Rathke pouch. This was subsequently partially confirmed in 1904, when Erdheim described the tumors histologically and suggested that they arose from remnants of the Rathke duct. Finally, in 1932, Cushing introduced the term “craniopharyngioma,” which has been widely used thereafter.

Coronal MRI shows a craniopharyngioma in the suprasellar space that causes compression of the optic nerves and chiasm. 

a Critical Images slideshow, to review cases including meningiomas, glioblastomas and craniopharyngiomas, and to determine the best treatment options based on the case history and images.

History of the Procedure

Evolution of surgical treatment for craniopharyngiomas is closely related to development of the surgical techniques of sella turcica. The first surgical techniques for craniopharyngioma originated in 1891 with the first trepanation done by Selke, then the first successful transcranial approach performed by Horsley in 1907.
The progress of the surgical techniques continued with the first successful resection of craniopharyngioma through a transsphenoidal approach by Eiselsberg in 1910, which was improved by Halstead as a sublabial transsphenoidal resection in the same year. Harvey Cushing created the foundations of craniopharyngioma patient treatment with hormone replacement therapy, but also, in 1919, he developed and performed the first successful resection through the trans-lamina terminalis approach of a retrochiasmatic craniopharyngioma. Later, in 1924, he performed a transcallosal resection of a craniopharyngioma.As technology in diagnostic imaging has improved so has the surgical treatment of craniopharyngioma.

Problem

Craniopharyngiomas are benign, extra-axial, slow-growing tumors that arise from the anterior margin of the sella turcica and predominantly involve the sella and suprasellar space.They rarely metastasize but are locally invasive (typically the hypothalamus), and treatment, particularly surgical attempts at total resection, can result in significant morbidity. As craniopharyngiomas grow, they can cause significant neurological complications, including visual loss, pituitary insufficiency, and hypothalamic damage, and recurrence, both local and meningeal, is often seen and adds to patient morbidity. Malignant transformation of craniopharyngiomas is rare but has been reported after multiple recurrences and after radiation.

Epidemiology

Frequency

The incidence of newly diagnosed craniopharyngiomas is 0.13-2 persons per 100,000 population per year. Even though in some regions such as Japan and parts of Africa, craniopharyngiomas appear with a higher incidence In the United States, approximately 350 new cases of craniopharyngioma are diagnosed every year. Distribution by age is bimodal, with the peak incidence in children at aged 5-14 years and in adults at age 50-75 years. Craniopharyngiomas account for 1-3%of all brain tumors, and half of these tumors occur in childhood. Craniopharyngiomas account for 5-10% of brain tumors in children.^, No sex predilection exists, and they equally occur in males and females. No genetic relationship is currently known; however, a few familial cases have been reported in the literature.

Etiology

Although the histologic description of craniopharyngiomas was first described over a century ago, considerable debate still exists. Currently, 3 theories are widely accepted, and from these, 3 histologic variants have been derived. They are as follows:

• The embryogenetic theory suggests that the adamantinomatous type ("adamantinoma") arises from epithelial remnants of the Rathke pouch or the craniopharyngeal duct (the embryonal structure along which the eventual adenohypophysis and infundibulum migrate). Tumors can occur anywhere along the course of this duct, from the pharynx to the sella turcica and third ventricle, which partially explains the location of the tumor.
• The metaplastic theory suggests that the squamous papillary type results because of metaplasia of squamous epithelial cell rests that arise from squamous cell nests normally found at the junction of the pituitary stalk and pars distalis.
• Another theory postulates that this tumor is a midline congenital tumor not fundamentally different from an epidermoid cyst.

Pathophysiology

In the World Health Organization (WHO) classification, craniopharyngiomas are divided into 2 groups, adamantinomatous and papillary. There does not appear to be a difference in terms of prognosis, surgical resection, radiosensitivity, and life-expectancy between these groups.

Presentation

The onset of symptoms is generally insidious, with a delay of approximately 1-2 years between initial symptoms and diagnosis. The clinical presentation can include a wide range of symptoms, which depend on the location of the tumor and involvement of adjacent structures. Headache is the most common presenting symptom, followed by endocrine deficiencies and visual disturbances. Headache is usually due to either the tumor’s mass effect or hydrocephalus (from obstruction of the foramen of Monro, third ventricle, or aqueduct of Sylvius), which occurs in 15-30% of patients. This obstructive hydrocephalus may, on rare occasion, require emergent neurosurgical management.
Endocrine disturbances are related to direct compression from the tumor. Endocrine deficiency is most commonly in growth hormone (75%), followed by gonadotropin deficiency (40%), thyroid-stimulating hormone (25%), and corticotropin (25%).Growth failure can be seen in up to 93% of children with craniopharyngioma and is related to either growth hormone deficiency, hypothyroidism, or both. Adults have more varied presentation and may develop sexual or menstrual dysfunction. Eighty-eight percent of men experience decreased sex drive, while 82% of women have amenorrhea. Other endocrine dysfunction may lead to precocious puberty and obesity.
Large tumors in adults can cause psychiatric symptoms, memory loss, apathy, incontinence, depression, and hypersomnia. Long-standing cognitive deficits and profound memory loss have been reported and suggest a worse prognosis. Visual deficits are caused by compression of the optic chiasm from suprasellar tumor growth. Classically, the tumor presents as a bitemporal hemianopsia, but it may also manifest as homonymous hemianopsia, scotoma, or optic atrophy with papilledema.
Other presenting symptoms can include chemical meningitis from rupture of cyst contents into the subarachnoid space and resulting in headaches, stiff neck, and seizures.

Indications

Surgical treatment is indicated in most cases of craniopharyngioma, but surgeons have often approached this tumor with either an aggressive attempt at gross total resection of the tumor or a more conservative approach with a planned subtotal removal of the tumor followed by radiation therapy. Contemporary radiation techniques deliver radiation more accurately, thus preserving the important anatomic structures around or near the tumor.
The decision for either approach should take into consideration the anatomic localization of the tumor, size, invasion of the nearby structures, and the nature of the tumor. The most common indication for surgery is neurologic compromise from tumor mass effect. In children, hypothalamic and endocrine dysfunction may develop before visual defects are noticed. Obesity and lethargy are common in children with craniopharyngiomas. In general, any mass lesion in the pituitary sella and suprasellar area should undergo a biopsy or resection, if feasible. Radiotherapy is indicated in recurrence or in the treatment of residual tumor.

Relevant Anatomy

Craniopharyngiomas have been surgically divided into 3 groups: sellar, prechiasmatic, and retrochiasmatic. Sellar-located tumors may be suprasellar (75%), infrasellar (21%), or intrasellar (4%). These tumors occasionally grow into the third ventricle, causing hydrocephalus. The arterial supply is usually from the anterior cerebral and anterior communicating arteries or from the internal carotid and posterior communicating arteries.
Craniopharyngiomas are usually avascular on angiography but may encase or displace vessels that form the circle of Willis. Usually, the internal carotid artery (ICA) is displaced laterally, the anterior cerebral artery (ACA) is displaced anteriorly, and the basilar artery is displaced posteriorly.
A craniopharyngioma does not receive blood supply from the posterior circulation, unless it is parasitized from the floor of the third ventricle. As these tumors enlarge, they may elevate and infiltrate the optic chiasm as well as the hypothalamic region. Occasionally, they extend into the pituitary fossa or posteriorly to the ventral pons, and rarely, they invade the basal ganglia or the brain parenchyma.
When predominantly in the sella, these tumors erode the bony floor and enlarge the sella.

Contraindications

Surgery is contraindicated in patients with cardiac or respiratory abnormalities that make the risk of general anesthesia unacceptably high. Moreover, patients who take chronic anticoagulation medication must cease medication and demonstrate normal coagulation studies prior to surgery. Asymptomatic patients or those with a small tumor may be monitored with serial MRI scans. A small tumor in the pituitary region without mass effect or endocrine dysfunction may also be monitored with serial MRIs.

Laboratory Studies

Endocrine assessment

A full pituitary endocrine workup is usually mandatory. This includes evaluating the following:

• Adrenocorticotropic hormone (ACTH or corticotropin)
• Growth hormone (GH) and insulin growth factor (IGF-1)
• Cortisol
• Prolactin
• Luteinizing hormone (LH)
• Follicle-stimulating hormone (FSH)
• Thyrotropin (ie, thyroid-stimulating hormone [TSH])
• Triiodothyronine (T ₃)
• Thyroxine (T ₄).

Any abnormalities should be corrected preoperatively but, at the very least, low cortisol levels and diabetes insipidus should be treated prior to any surgical procedure.

Imaging Studies

CT and MRI are the complementary examinations of choice. Today, the best imaging tool is MRI without and with contrast enhancement.

CT scan

Craniopharyngiomas can vary greatly in size, from a few millimeters to greater than 5 cm. On CT scan, 90% are at least partially cystic, 90% have calcifications, and 90% have nodular or rim enhancement. These tumors are heterogeneous, with the cystic component being hypodense on CT scan and the solid component being isodense or slightly hyperdense with variable enhancement with contrast.

MRI

An MRI with and without contrast is the preferred sequence of choice. On T1-weighted images, the cystic component is often hyperintense and the solid component is isointense, with enhancement of the rim or tumor nodule. On T2-weighted images, the cystic component is hyperintense, as is the solid component.
In the immediate postoperative period (within the first 48 hr), a contrast-enhanced MRI is usually performed to determine whether residual tumor is present, as well as to establish a baseline for future follow-up.

Other Tests

Ophthalmology assessment

Visual acuity and visual field assessment is required to delineate any deficit, including papilledema.

Histologic Findings

Craniopharyngiomas are usually composed of both solid and cystic components. Cyst walls may vary from thin membranes to thick, tough structures that may be hard and rigid because of calcifications. The interior is lined with stratified squamous epithelium with pearly keratin formations. The outside layer is columnar epithelium on a collagenous basement membrane. Calcifications are common; 90% of tumors in children have calcifications, as do 40% of these tumors in adults. Inside the tumor, fibrous tissue, necrotic debris, cholesterol clefts, and keratin pearls are commonly found.
The following 3 histologic phenotypes are seen in craniopharyngioma:

• Adamantinomatous tumors (seen predominantly in children) resemble enamel-forming oropharyngeal neoplasms. The classic appearance is that of a cystic tumor, usually with a solid component. The cyst may contain fluid that can vary in color, but it usually has a tan appearance that is classically described as resembling “motor oil.” Extensive fibrosis and inflammation have also been observed, which result in dense adhesions between the mass and vasculature, a phenomenon that further contributes to the difficulty in resecting craniopharyngiomas.
• Squamous papillary tumors (seen predominantly in adults) generally involve only a solid component, which is typically seen without calcifications. It is frequently located in the third ventricle and is usually more encapsulated than the other types and, thus, more easily resectable.
• Mixed tumors are a combination of the adamantinomatous and papillary forms.

Craniopharyngiomas are known to not undergo malignant degeneration and are usually well defined.However, at the tumor margins, the epithelial fronds tend to penetrate deep into the brain tissue. This may cause a glial reaction in the surrounding brain, making complete resection difficult and possibly predisposing this tissue to traction injuries, particularly in the hypothalamus. The characteristic location of these tumors in the sellar and parasellar region, together with the different histologic subtypes, allows for the above theories that may explain the origin of these tumors.

Medical Therapy

No primary medical therapy exists for this tumor. Hormonal replacements are administered as needed if endocrine abnormalities exist.

Surgical Therapy

The initial surgical decision concerns the approach. If the predominant portion of the tumor is intrasellar, the approach is usually transsphenoidal. Often, the suprasellar component can be delivered into the sella and evacuated. Further, the transsphenoidal approach is well tolerated by patients and is preferable to a craniotomy, when feasible.
If the pituitary sella is not enlarged, the transsphenoidal approach is generally not preferred. A craniotomy is usually necessary when the predominant component is suprasellar, although certain suprasellar masses may be located through an extended transsphenoidal approach. New technology in optics and instrumentation has now permitted many transsphenoidal procedures to be done exclusively through the endoscope. Specialized training is needed in these techniques, but in some instances, even large tumors in the suprasellar space can be safely removed or debulked.
The pterional craniotomy is the standard craniotomy approach to suprasellar lesions because it allows good visualization of the optic nerves, chiasm, and surrounding structures. Variations of the pterional craniotomy have been proposed to include resection of the orbital rim and zygoma so as to provide a more defined view of the skull base and thereby allow better access to the superior aspects of this tumor. These approaches lend themselves to less frontal lobe retraction in order to visualize the operative site.
A subfrontal approach is appropriate for lesions that lie anterior to the optic chiasm, but this may be difficult to determine preoperatively. Under rare circumstances, a transcallosal approach is necessary when the tumor is entirely within the third ventricle. The drawback to this approach is the inability to identify the optic chiasm and pituitary stalk early in the dissection.
Cystic tumors are amenable to either a transsphenoidal approach or a pterional craniotomy. The solid components often adhere to the optic chiasm or hypothalamus and, therefore, may be difficult to remove in their entirety.
Cyst aspiration combined with intracavitary phosphorus-32 (³² P) instillation is an alternative to traditional surgical resection (see video below). Good long-term control of tumor growth has been demonstrated; however, a tumor with significant solid components is not likely to respond to(³²P) .Intracystic chemotherapy with bleomycin has also been tried, with some success in short-term reduction of cyst size.Intracavitary therapy requires that an Ommaya reservoir be placed into the cyst. Care needs to be taken that the catheter tip openings are in the cyst itself and that there is no spillage of cyst contents or injected material outside the cyst wall.

Dissection of craniopharyngioma cyst with aspiration.

Grading

In an attempt to balance the advantages of an aggressive surgical resection against the risk of significant morbidity, a preoperative grading system (for children) has been proposed. This system considers the extent of invasion of the hypothalamus by the tumor and is as follows:

• Type 0: The tumor represents no hypothalamic involvement.
• Type 1: The tumor distorts or elevates the hypothalamus, but the latter is still visible.
• Type 2: The hypothalamus is no longer visible.

Consequently, some proposed that a gross total resection be attempted in type 0 and type 1 tumors and that a subtotal resection be attempted in a type 2 tumor, leaving only the hypothalamic component. Although this grading system was developed in a pediatric population, applying it to an adult population is certainly feasible. Some evidence exists, however, that the craniopharyngiomas that arise in adults are less likely to invade the hypothalamus.
A newer classification system proposed by Kassam et al uses a scheme that divides tumors according to their suprasellar extension, based upon the endoscopic expanded endonasal approach (EEA), and is as follows:

• Type I - Preinfundibular
• Type II - Transinfundibular (extending into the stalk)
• Type III - Retroinfundibular, extending behind the gland and stalk, and has 2 subdivisions (IIIa, extending into the third ventricle; and IIIb, extending into the interpeduncular cistern)
• Type IV - Isolated to the third ventricle and/or optic recess and is not accessible via an endonasal approach

Radiation therapy

Radiation is indicated in patients who had a subtotal resection of craniopharyngioma or with recurrence of the disease. Types of radiation therapy include stereotactic radiosurgery (SRS) and fractionated external beam radiation therapy.

Stereotactic techniques (SRS) are based on localization of the target through stereotactic frame coordinates (attached to the head as in Gamma Knife) or non–frame-based techniques (CyberKnife). Small tumors can be treated with a single fraction of radiation that delivers a high dose of radiation with rapid falloff to minimize the dose to surrounding structures. A larger target volume or proximity to the optic nerve and chiasm may require use of fractionated SRS techniques designed to minimize damage to healthy structures. The dose delivered is usually limited by the optic chiasm, which ideally should receive less than 10 Gy.
External beam radiation therapy uses 3-dimensional planning to deliver radiation with a margin around the tumor. Up to 30 fractions may be used to deliver an effective total dose while keeping daily doses low. Recurrence of tumor is higher when total dose is less than 54 Gy, while complications increase with doses greater than 62 Gy.
Recent data support the concept of subtotal resection followed by radiation therapy as an effective therapy equal in outcome to gross total resection but with fewer complications.

Sagittal MRI shows a cystic craniopharyngioma in the suprasellar space with extension into the third ventricle.

Preoperative Details

Preoperative workup includes an endocrinologic evaluation, particularly to exclude hypoadrenalism and hypothyroidism, both of which increase surgical mortality rates. Dexamethasone may be started prior to surgery to decrease edema.

Intraoperative Details

Successful transsphenoidal resection of a craniopharyngioma requires a generous removal of the contents of the sella turcica. Adequate suprasellar decompression occurs when the arachnoid membrane that surrounds the tumor descends into the operative field. Cerebrospinal fluid (CSF) leakage occurs if the arachnoid is disrupted.
The goal of a craniotomy is gross total removal of the tumor with preservation of the optic apparatus and pituitary stalk. Understanding the anatomy in this region is key to accomplishing this goal. The optic chiasm is nearly always elevated, and the pituitary stalk is usually displaced posteriorly. The stalk may be identified by the striate pattern of portal vessels along its surface. The lamina terminalis may need to be opened for access into the third ventricle. The goal of tumor removal must not outweigh the need for preservation of neural structures; therefore, leaving undisturbed a tumor that is densely adherent to the optic apparatus, anterior cerebral artery, or hypothalamus is advisable.
In general, because long-term tumor control is excellent with radiation therapy following subtotal tumor removal, a conservative approach to tumor resection is usually advised.In some patients, however, a good cleavage plane exists between tumor and brain, and a true complete resection can be accomplished. Surgical judgment is crucial in the assessment of this possibility.

Follow-up

Performing a full postoperative endocrine evaluation as well as repeated imaging studies is advisable. MRI scans are typically obtained immediately postoperatively (within 48 h), at approximately 3 months, and annually thereafter. Long-term follow-up also includes visual-field and pituitary hormone testing.

Complications

The most common complications are related to injury of the adjacent neural structures. Vision may worsen because of unavoidable optic apparatus manipulation.
Postoperatively, many patients demonstrate hypopituitarism. In order to offset this, they are usually given physiologic doses of hydrocortisone as well as a dexamethasone taper to decrease the edema associated with the surgical approach.
Diabetes insipidus may develop and may require treatment with fluid replacement and, occasionally, vasopressin or its synthetic analogue, desmopressin. Some patients have diabetes insipidus as well as disruption of their thirst sensation. These patients pose a difficult management problem and are at high risk for developing hypernatremia. Injuries to the hypothalamus can cause other behavioral changes, including caloric balance disturbance, memory disturbance, and changes in affective behavior.
In rare cases, development of radiation-induced gliomas may occur. This long-term complication has a latency period of greater than 10 years, frequently involves the temporal lobe, and has been predominantly reported in patients who underwent conventional fractionated radiotherapy in their childhood.

Axial MRI shows a craniopharyngioma cyst that contains proteinaceous fluid in the third ventricle. The cyst fluid appears hyperintense.

Outcome and Prognosis

Total resection is the best chance for cure, although some series have reported good results with subtotal resection and fractionated radiation therapy. Small residual tumor, confirmed on postoperative MRI, is generally treated with external beam radiotherapy; however, stereotactic radiosurgery has been used. The use of proton beam radiotherapy for residual disease is currently being investigated. Although the amount of radiation is limited by the proximity to the optic chiasm, good long-term results are now being reported after radiosurgery.
Adverse effects of radiation therapy include endocrine dysfunction, optic neuritis, dementia, and radiation necrosis. In addition, radiation can induce tumors such as meningiomas, sarcomas, and gliomas. In pediatric cases, radiation is postponed to minimize its effects on intelligence quotient and growth. Survival rates for patients with surgery and radiation are better than with surgery alone because radiation helps deter regrowth when residual tumor is present.
Brachytherapy has also been used to treat cystic craniopharyngiomas. Radioisotopes are placed into the cystic portions of the craniopharyngioma. Phosphorus-32 (³² P), colloidal gold-198, colloidal yttrium-91, and bleomycin have all been used. Bleomycin causes shrinkage of the cyst but is highly toxic to neural structures.
In a review of brachytherapy for craniopharyngiomas, Van den Berge followed 31 patients for an average of 41 months.Twenty-nine percent showed improvement of visual acuity, while 13% had stable visual acuity, and 58% deteriorated. Similarly, 28% showed improvement of their visual fields, with 20% showing no change, and 52% deteriorating.

Mortality and morbidity

Overall, the surgical mortality rate is less than 5%, mostly from hypothalamic injury. Bilateral hypothalamic injuries lead to hyperthermia and somnolence. The 10-year survival rate, excluding non–tumor-related deaths, is 90%.
The recurrence of craniopharyngiomas is reported to be up to 24% with approximately a 7-year follow-up. The main risk factor for recurrence is the presence of the residual tumor. Tumor recurrence is higher in the first 3 years after surgery.
In patients with gross total removal of a craniopharyngioma, the 5-year recurrence-free rate is 84.9%, compared to 48.3% in patients with subtotal removal.Morbidity and mortality rates are higher with recurrence and mainly present as visual deficits, endocrine abnormalities, hypothalamic injury, and neurocognitive and neurobehavioral deficits.The visual impairment can be caused by direct damage during surgery or from a daily dose of radiation greater than 2 Gy. The cumulative probability for visual deficits after surgery/radiation is reported to be 36-48% with a 10-year follow-up.
Endocrine abnormalities are commonly seen in postoperative patients with craniopharyngioma. It presents as hypopituitarism and is reported with deficiencies of at least 3 pituitary hormones in 54-100%.Preoperative endocrine deficits do not improve after the surgery, although patients with diabetes insipidus may improve.Hypothalamic dysfunction after the surgery may present as obesity because of hyperphagia, water balance impairment, loss of temperature control, sleep disorders, and neurocognitive disorders. Hypothalamic damage may result from tumor invasion, direct surgical damage from the resection of adherent tumor, tumor recurrence, and radiation.
Hoffman followed 50 children with craniopharyngiomas.In his 1992 report, 90% had total excision, and tumor recurred in 34%. Of all 50 children, 56% were leading normal or nearly normal lives, often requiring endocrine replacement. Twenty-four percent were able to function reasonably well and to attend school despite intellectual, visual, or weight problems; 8% were significantly handicapped; and 6% died. Effenterre et al reported that failure to achieve an independent living function with poor integration and performance at work or school is seen in 16% of adults and 26% of children.The data from literature show the importance of preoperative planning with a reasonable decision in terms of maximal safe tumor resection and the avoidance of complications.

Future and Controversies

The largest divide in the treatment of craniopharyngiomas regards whether to perform a gross total excision or perform a subtotal resection followed by radiation therapy. Retrospective series support both philosophies. Surgical judgment must temper the enthusiasm for gross total removal at all costs. The use of 3-dimensional conformal radiation treatment (3D CRT), stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT), and intensity-modulated radiation therapy (IMRT) will further allow treatment of small tumor residua with little risk of neurologic deficit. The development of endoscopic techniques has placed greater emphasis on minimally invasive approaches, but this should not detract from surgical techniques that the surgeon feels most comfortable using.