abc Figure 2. Differential diagnosis A differential diagnosis is mandatory because various diseases can mimick a primary spinal tumor. a T2W sagittal image shows a tumorous lesion at the conus level. Frozen section biopsy revealed a sarcoidosis and further surgery was stopped subsequent to the biopsy. b Preoperative T2W image and c postoperative MRI of another case with a conus lesion being a metastasis of a malignant melanoma. non-Hodgkin’s lymphoma hypertrophic neuropathies, e.g., Dejerine-Sottas disease, Charcot-Marie- Tooth disease [31] Intradural-Intramedullary Tumors Ependymomas Myxopapillary ependymo- mas exclusively occur in the conus and filum terminale Spinal ependymomas are usually well circumscribed (Case Introduction), arising from ependymal cells lining the central canal or its remnants and from the cells of the ventriculus terminalis in the filum terminale. Myxopapillar y ependymo- mas occur exclusively in the conus medullaris and filum terminale. Hemorrhage and cystic degeneration are common. Ependymomas account for 60% of glial spinal cord tumors and comprise 90% of primary tumors in the filum terminale and cauda equina [30, 31]. Mean age is 43 years withaslightfemalepredomi- nance. For myxopapillary ependymomas of the cauda equina region the mean age is 28 years with a slight male predominance. Intramedullary tumors are mainly benign tumors found in children or young adults. Complaints of back pain or neck pain are found in 65% of patients with intramedullary ependymo- mas. Previous history is usually often long, because these tumors are slow grow- ing and there are often mild objective neurological deficits. The average reported Symptoms precede diagnosis by years duration between the onset of such symptomatology and diagnosis has been reported to be around 3.5 years [2, 3, 14, 27, 31]. 1002 Section Tumors and Inflammation Ependymomas (in adults) and astrocytomas (in children) are the two most frequent intramedullary tumors Low back pain or sacral pain, leg weakness and sphincter dysfunction are the complaints and signs found in patients with myxopapillary ependymomas of the cauda equina region. Some sacral and presacral lesions can behave aggressively and can metastasize to the lymph nodes, the lung and the bone [34]. Astrocytoma Most spinal cord astrocytomas are low-grade tumors. Malignant gliomas are rare: 15% are anaplastic astrocytoma and 1% are glioblastoma multiforme. Intramedullary astrocytomas diffusely expand the spinal cord, cyst formation is common and there is often an associated syrinx. Tumor cysts are often eccentri- cally positioned within the cord, whereas the syrinx and benign cysts are rostral or caudal to the tumor and cause symmetric cord expansion. Astrocytoma is the most common intramedullary tumor in children. Median age is 21 years.The predominant location is the cervical spine ( Fig. 3), followed by the thoracic spine [6, 13, 14, 20, 26, 32]. Pain is the early presenting symptom. Symptoms or signs of neurological dysfunction are often lacking early in the course of disease. Hemangioblastoma About one-third of patients with hemangioblastomas suffer from von Hippel- Lindau disease Hemangioblastomas comprise 3–8% of intramedullary tumors. About one- third of patients with hemangioblastomas have von Hippel-Lindau disease. Ret- inal or cerebellar involvement often precedes spinal cord symptoms. A highly vascular nodule with an extensive cyst is found in around half of cases ( Case Study 2 ), usually emerging at the dorsal portion of the spinal cord. Half of hemangioblastomas are found at the thoracic level followed by the cervical level. There are usually prominent leptomeningeal vessels near the lesion. More than 80% of patients are symptomatic before the age of 40 years. Eighty percent of spinal cord hemangioblastomas are solitary lesions [31]. Figure 3. Astrocytoma A case of cervical astrocytoma with cyst formation at the caudal tumor pole and within the tumor. Intraoperatively, no clear cleavage plane could be found, so the surgery ended up with partial removal and remnant tumor left to the anterior part. The postoperative follow-up revealed only slight sensory disturbance and no other neurological abnormalities. Intradural Tumors Chapter 35 1003 a b c d e f g Case Study 2 A case of hemangioblastoma of 5 years history beginning with sen- sory disturbance on the left hand progressing more recently to tetra- paresis with gait disturbance. This was embolized twice without subse- quent surgical removal 1.5 years and 6 months ago respectively. T1W image with CE ( a, b) revealing an intramedul- lary hemangioblastoma at C2– C4 with hydromyelia formation extending cranially to the medulla and caudally to C6. Conventional vertebral angiography ( c) in the lateral view displaying the tumor staining supplied by radicular arteries and the anterior spinal artery. MR angiography AP view ( d) displaying the tumor with a vascular supply from the anterior spinal artery and the radicular arteries. The patient underwent microsurgical complete removal of the tumor. Postopera- tive T1W sagittal ( e)andT2Waxial(f) images revealed complete removal of the tumor with disappearing hydromyelia. MR angiography ( g) revealing opacification neither of the tumor nor of the feeding arteries. At 3 years follow-up the patient presented with good recovery of neurological findings and no signs of recurrence depicted on neuroimagings. 1004 Section Tumors and Inflammation Other Intramedullary Tumors Although intramedullary metastases are very rare, they must be considered as an important differential diagnosis Oligodendroglioma, ganglioglioma and intramedullary neurinoma can occur but are rare. Intramedullary metastases are very rare. Intramedullary metastasis occurs as a result of primary malignancies such as: breast cancer lung cancer lymphomas leukemia malignant melanoma ( Fig. 2b, c) [31] Cavernous angiomas are briefly mentioned here as these should be differentiated from other intramedullary tumors and are encountered rather occasionally as is showninourseries( Table 4). They are similar to intracranial cavernous angio- mas of typical blackberry appearance associated with localized hemorrhage in different ages. They become symptomatic between the 3rd and 6th decades and have a female predominance of 2:1. They are found most frequently at the tho- racic level followed by the cervical level [31]. Clinical Presentation History The symptoms of a slowly growing tumor are insidious The key feature of slowly growing tumors is the long history of signs and symp- toms due to the substantial plasticity of the spinal cord. The time course of symp- toms and signs is very insidious and longstanding but can be of abrupt onset due to hemorrhage in cases of ependymomas and cavernous angiomas. Acute onset with a subarachnoid hemorrhage can also be a rare presentation of spinal cord tumors such as neurinomas, cavernous angiomas and ependymomas. The signs and symptoms differ depending on: level location size of tumor speed of growth In general, intramedullary tumors produce segmental deficits while extramedul- lary tumors produce radicular and segmental deficits. Both tumors reveal long tract symptoms and signs in their advanced stage. Lateralization or asymmetry of early signs and symptoms reflects the lateral location of a tumor. Hemicord syndrome or Brown-S´equard’s syndrome is observed commonly at the advanced stage. Mainly in the German literature some stagings of spinal compression have been advocated: early stage – neuralgic stage second stage –Brown-S´equard’s syndrome or incomplete transsectional lesion third stage – complete transsectional stage [30] The cardinal symptoms are: The cardinal symptoms are pain and neurologic deficits progressive local pain (stiff neck or back pain) pain during recumbency (nocturnal pain) radicular or myelopathic pain non-painful sensory disturbances motor weakness (gait disturbance) Intradural Tumors Chapter 35 1005 clumsiness and ataxia sphincter disturbances (usually urogenital, less commonly anal) Nocturnal pain is the most common form of pain The pain might be of the radicular type, with radiation often increasing with Val- salva’s maneuver and/or spine movement. Segmental or medullary pain (non- radicular, diffuse non-describable pattern) might be present continuously, radi- ating into the whole leg or one-half of the body without affection of movement. Suboccipital pain and distal arm weakness with atrophy and clumsiness of the intrinsic hand muscles reported to be peculiar to upper cervical and foramen magnum tumors have been attributed to probable venous return insufficiency [26]. Physical Findings A thorough neurological exam is compulsory A thorough neurological examination is key to the assessment of spinal tumors. Findings on clinical examination include: sensory deficits (without sacral sparing) motor weakness gait disturbance ataxia bowel and bladder dysfunction Horner’s syndrome headache (due to increased intracranial pressure) torticollis spinal deformity (scoliosis and kyphosis) Motor weakness including gait disturbance usually occurs late Sensory disturbance of intramedullary tumors is often characterized by dissoci- ated sensory disturbance in which pain and temperature sensation are impaired already in the early stage and touch and position sense are intact. The motor weakness which often follows the sensory symptoms results in a gait disturbance. If sacral sparing is present, an intramedullary tumor should be suspected Long tract symptoms are presented with clumsiness and ataxia. Sphincter dis- turbancesareusuallyurogenital(lesscommonlyanal)withdifficultyinevacua- tion, retention, incontinence, and impotence. They are usually of late manifesta- tion except for tumors at the conus and cauda equina. Findings of sacral sparing, however, are frequently observed in patients with intramedullary tumors, since a distal portion of the impaired level tends to be spared as the sacral fibers locate peripherally in the lateral spinothalamic tract. Increased intracranial pressure often associated with papilledema might occur at any level of extramedullary tumor (preferably at the upper cervical lev- els) presumably due to elevated protein in the cerebrospinal fluid (CSF); hence its flow impairment and absorption. Horner’s syndrome (enophthalmos, proptosis, myosis and loss of sweating) appears at the time of impairment of the lateral horn between C8 and T3 or of sympathetic pathways in the C8 and T1 anterior roots. Scoliosis, loss of lordosis or torticollis can take place within the scope of root irri- tation and muscle weakness or atrophy and has been reported to be present in one-third of cases with intramedullary tumors. Diagnostic Work-up Magnetic resonance imaging should be performed as the first diagnostic modal- ity when symptoms and signs indicate a spinal tumor should be suspected. The other imaging modalities are second in line. 1006 Section Tumors and Inflammation Imaging Studies Standard Radiography Standard radiography sometimes exhibits clues to intradural tumors Plain films are still routinely obtained but have a limited diagnostic value. Abnor- mal findings of intradural tumors can be: bonydestructioninmetastasisoranaplastictumors widening of the spinal canal represented by widening of the intrapedicular distance thinning of the pedicle “scalloping” of the posterior vertebral surface (in cases with slow-growing tumors) widening of the intervertebral foramen (especially in patients with neurino- mas) disappearance of the normal spinal curvature progressive scoliosis tumor calcification Myelography Myelography has been superseded by MRI for the diagnostic work-up of intradu- ral spinal tumors. Myelon distension in intramedullary tumors is outlined by contrast dye remaining at its periphery. Distension of the myelon is more diffuse andsmoothinastrocytomasthaninependymomas.Extramedullarytumors show an extramedullary block with cord displacement and “shoulder of contrast material.” CT and Myelo-CT These are the methods of choice in patients in whom MRI cannot be performed because of contraindications (e.g., pacemaker) ( Case Study 1 ). Typical findings are: bony deformation such as destruction, scalloping, widening of the spinal canal and/or the intervertebral foramen calcification contrast enhancement spinal cord compression expanding medullary mass Magnetic Resonnance Imaging MRI is the first choice in the diagnosis of spinal cord tumors MRI is the diagnostic imaging procedure of choice. T1W- and T2W-weighted (= W) images as well as gadolinium-enhanced T1W images should be systemati- cally obtained. The entire spinal cord must be studied. At least two different imaging planes must be used in order to locate the tumor properly and to differentiate intramedullary tumors from extramedullary tumors. Coronal sections (anteroposterior view) can demonstrate a tumor in relation to the bony structures in the same view as in the operating room, which can be helpful in planning the extent of the laminectomy. General findings in intradural spinal tumors are: Extramedullary tumors and many intramedullary tumors such as ependy- momas or hemangioblastomas have clear demarcations, but infiltrating tumors or aggressive tumors of the latter have ill-defined borders. Contrast enhancement (CE) can be seen quite often, but an enhancing medullary Intradural Tumors Chapter 35 1007 mass does not necessarily mean a neoplasm. Both edema and hydromyelia associated with intramedullary tumors can be very extensive but usually dis- appear after total tumor removal. Solid nodules can be distinguished from cystic elements (the signal behav- ior of these cysts is usually different from CSF, due to the high protein con- tent of the fluid). Most tumors are isointense but enhance with contrast medium Hemorrhage may complicate spinal cord tumors and can be recognized on T1W images as hyperintense areas, when the hemorrhage is 1 week to approximately 4 weeks old. Hemosiderin deposits can later be identified as low-signal areas on T2W images, preferably obtained by gradient-echo sequences. Specific findings for intradural spinal tumors are: Nerve sheath tumors are usually isointense on T1W images and hyperin- tense on T2W images; almost 100% CE positive; foraminal widening; calcifi- cation rare. Meningiomas present as isointense with cord on both T1W images and T2W images; moderate CE with or without association of dural tail; no bone destruction; calcification occasional. Ependymomas are isointense with cord on T1W images and hyperintense on T2W images; CE strong somewhat inhomogeneous due to cyst formation or hemorrhage; foci of points or trails of signal void due to strong vasculari- zation; vertebral body scalloping in conus tumors. Astrocytoma are iso- to hypointense on T1W images and hyperintense on T2W images with no sharp delineation; almost 100% CE positive but rather spotty; cyst formation common. Hemangioblastoma are isointense to cord on T1W images, hyperintense on T2W images; foci of signal void spots and trails due to high vascularization; CE strongly positive; cyst formation common. Cavernous angioma present with mixed signals “popcorn-like or cat’s eye” lesion; blooms on T2W images and gradient echo; multiple lesions in more than half of cases. Angiography Spinal angiography has a place in the definitive diagnosis of hemangioblastoma (showing dense vascular stain and prominent draining veins) and vascular mal- formations and/or their endovascular treatment ( Case Study 2). Lumbar Puncture Lumbar puncture as an invasive method has a limited diagnostic value. Quecken- stedt’s sign (a rapid rise in the intracranial pressure measured by spinal puncture at the time of jugular vein compression) is only of classic significance. Further- more, spinal puncture is considered to be a contraindication in cases of sus- pected complete block of the subarachnoid space because of the risk of sudden neurological deterioration. Laboratory CSF findings obtained from the puncture have now practically only supportive significance: Elevated protein (500–100 mg/dl) in the CSF below the blocked level of the subarachnoid space due to spinal cord tumors is found especially in cases with extramedullary intradural tumor rather than intramedullary tumors. Froin’s syndrome of coagulation of CSF due to high protein contents has been well described in the book so far. 1008 Section Tumors and Inflammation Laboratory findings of CSF aresupportiveratherthan diagnostic in value Cytology can be obtained to find neoplastic cells. There is no pleocytosis and no change in glucose and chlorine contents in intradural tumors. Xanthochromia might indicate tumor bleeding so that ependymomas, cav- ernous angiomas or other vascular malformations are brought into question. Treatment Non-surgical Treatment Recent developments in chemotherapy and radiotherapy have made it possible to apply these modalities, especially the former for intramedullary gliomas of children and the latter for high-grade gliomas [28]. In the case of hemangiobla- stomas, endovascular embolization in trained hands can be a good preparation forsurgicalremovaloritcanevensufficeasatreatment.Furtherdiscussionon this topic is, however, beyond the scope of this chapter. Surgical Treatment General Principles The goal is tumor debulking and preserving function The goal of surgery for any benign intradural neoplasms is gross total resection. The goal for a malignant glioma is debulking with preservation of the function. Recent technological developments such as MRI, ultrasonography, the Cavitron Ultrasound Aspirator (CUSA), and microsurgical technique with intraoperative neurophysiological monitoring have brought about a remarkable improvement in surgical results [12, 19]. Perioperative administration of steroids according to the regime for intracra- nial tumors is now a routine procedure. Administration of a high dosis of Solu- medrol (methylprednisolone 30 mg/kg, followed by 5.4 mg/kg/h for 23 h) instead of dexamethasone especially for intramedullary tumors is preferred to prevent spinal shock due to surgical manipulation by some authors and in our depart- ment [5, 22]. The sitting po sit i on is used for tumor removal when tumors are located above the level of T5, and for tumors below this level the prone position is the usual position in our department [40]. The target level should be marked under the fluoroscope prior to surgery. For tumors associated with hemorrhage-hematoma such as cavernous angio- mas and ependymomas, the optimal timing of surgery might be the subacute stage in which the acute stage of edema is declining and hematoma begins to be absorbed, as delineation and dissection of tumors is rather easy without damag- ing the surrounding neural structures [22]. Noticeable space-occupying hemato- mas should be removed, however, at the acute stage. Extension of laminectomies should be one more lamina above and below tumor extension. This enables surgical manipulation to be easy and safe and is also appropriate for decompression. If benign extramedullary tumors or intra- medullary ependymomas are found, osteoplastic laminotomy might also be con- sidered to prevent traction damage or kyphosis. Care should be taken at least to maintain the integrity of the facets to preserve spinal stability. The surgery outcome has been improved with the advent of microsurgical techniques, CUSA and neuromonitoring Intraoperative neurophysiological monitoring with somatosensory evoked potentials (SSEPs) is recommended. A noticeable change in SSEP findings at the time of myelotomy or at the time of suturing the spread myelotomy margins of the pia to the dura and their recovery at the time of closure of the spread myelon is observed. But there is no convincing reliable and useful monitoring system which includesmotorevokedpotentialsatthemoment[1,4,5,8,10,14,19,26,27]. Intradural Tumors Chapter 35 1009 Knowledge of standard peri- and intraoperative management such as: edema prevention respiratory management in cervical tumors critical interpretation of neurophysiological monitoring Complete total resection is a realistic goal for intradural tumors is key to successful surgery. Respiratory disturbances encountered at the time of removal of high cervical intramedullary tumors should be checked carefully postoperatively and the cor- responding timely use of a respirator should be kept in mind. Ondine’s curse or sleep apnea are also well known such respiratory complications [14, 22, 26]. Possible surgical complications (amongst other complications) include: bladder and bowel dysfunction bleeding or hematoma CSF leak infection chronic pain neurological deterioration sexual dysfunction spinal instability ventilator dependence wound dehiscence Troublesome chronic dysesthetic pain is the most persistent noticeable com- plaint after a successful removal of intramedullary tumors as shown in our case presentation. Postoperative neurological complications are less than 15% in extramedullary tumors In terms of outcome ( Table 1 ), postoperative neurological morbidity in the surgeryofextramedullarytumorsisusuallylessthan15%.Surgicalresultsare usually curative in nerve sheath tumors, while a total recurrence rate of meningio- mas is 7–15%. The neurological deterioration in filum terminale ependymomas is more frequent, also the recurrence rate. Postoperativeradiotherapy and chemo- therapy are often applied in such situations. In Brotchi’s series of 239 patients with low-grade intramedullary tumors, 5% of them worsened, 50% stabilized and 40% improved. These figures are in close correspondence with our series as shown in Table 1 . Neurological function of a patient after surgical intervention mostly depends on his or her preoperative neurological condition. The 5-year survival rate for patients with spinal cord neoplasm is greater than 90 %.Prognosis depends on the histopathology of the neoplasm [13, 14, 26, 31, 36]. Surgical Techniques Surgical Approach for Intradural Extramedullary Tumors Localization of intradural extramedullary tumors can be classified as: posterior posterolateral lateral anterolateral anterior Laminectomy is the standard approach for removal of intradural spinal cord tumors Although most tumors can be managed by standard laminectomy, the approach can be varied accordingly such as by using: hemilaminectomy and complete laminectomy costotransversectomy 1010 Section Tumors and Inflammation Table 1. Surgical results Author Cases Follow-up Complications/outcome/recurrence Hoshimaru et al. (1999) [18] 36 spinal cord ependymo- mas 56 months 14 improved 5 persistent deterioration 17 stabilized Conti et al. (2004) [7] 179 neurinomas 5 years total removal 174 excellent recovery 108 local recurrence 3 (malignant neurinoma) El-Mahdy et al. (1999) [9] 66 nerve sheath tumors 37 improved 3 worsened 26 stabilized Kane et al. (1999) [20] 54 intramedullary tumors 18 years in 40 patients 90% independently mobile Schick et al. (2001) [33] 197 benign spinal tumors 5 years recurrence rate: meningiomas 8.6 % neurinomas 7.7 % ependymomas 20% complications (10%): hematoma 9, hydrocephalus 4, CSF fistula 3, wound infection 2, meningitis 2 Constantini et al. (2000) [6] 164 intramedullary tumors in children and young adults 5 years 60% stabilized 15.8% improved 23.8% worsened 5-year progression-free survival was 78 % with low-grade gliomas and 30 % with high-grade gli- omas Fischer and Brotchi (1996) [14] 239 patients with low- grade intramedullary tumors 5% worsened, 50% stabilized, and 40% improved Author’s series (2004, unpublished) 79 intramedullary tumors: ependymoma 26 (33 %) Follow-up: 3monthsto 11 years complete removal with good recovery except that one patient died of respiratory insufficiency astrocytoma 20 (25 %) complete removal only in 10% but with stabiliza- tion over 3 years on average hemangioblastoma 12 (15%) complete removal with good recovery cavernous angioma 4 (5%) complete removal with stabilized residual deficits anaplastic glioblastoma 4 (5%) death within 2.5 years in spite of aggressive ther- apy including transection of the spinal cord, irra- diation, chemotherapy cauda ependymoma 3 (4%) complete removal with good recovery, one recur- rence under observation metastasis 3 (4%) primitive neuroectodermal tumors 3 (4 %) others 4 (5 %) extracavitary approach far lateral laminectomy and partial facetectomy posterolateral approach through the facet joint and pedicle transthoracic approach far lateral approach-transcondylar approach for tumors at the cervicome- dullary junction ventral corpectomy Neurinomas or neurofibromas can usually be completely excised except for the dumbbell type. Sacrifice of the affected nerve roots is often necessary and should be done with respect to the function of the nerve root ( CaseStudy1,Fig.4). Almost all meningiomas can be completely removed, with excision or coagula- tion of the dural attachment. The recurrence rate following complete resection is Intradural Tumors Chapter 35 1011 . feature of slowly growing tumors is the long history of signs and symp- toms due to the substantial plasticity of the spinal cord. The time course of symp- toms and signs is very insidious and longstanding. medullaris and filum terminale. Hemorrhage and cystic degeneration are common. Ependymomas account for 60% of glial spinal cord tumors and comprise 90% of primary tumors in the filum terminale and cauda. its flow impairment and absorption. Horner’s syndrome (enophthalmos, proptosis, myosis and loss of sweating) appears at the time of impairment of the lateral horn between C8 and T3 or of sympathetic