Spinal Disorders: Fundamentals of Diagnosis and Treatment Part 101 doc

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

a b c

Figure 2 Differential diagnosis

A differential diagnosis is mandatory because various diseases can mimick a primary spinal tumor.aT2W 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.bPreoperative T2W image andcpostoperative 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 Myxopapillary 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 with a slight female

predomi-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]

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 spRet-inal cord symptoms A highly

vascular nodule with an extensive cyst is found in around half of cases (Case

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.

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) and T2W axial (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.

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

shown in our series (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

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)

) 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-turbances are usually urogenital (less commonly anal) with difficulty in evacua-tion, retenevacua-tion, 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

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:

) bony destruction in metastasis or anaplastic tumors

) 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

and smooth in astrocytomas than in ependymomas Extramedullary tumors

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

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

Laboratory findings of CSF are supportive rather than 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

for surgical removal or it can even suffice as a treatment Further discussion on

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 position 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 ependymoangio-mas, 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 surrounddamag-ing neural structures [22] Noticeable space-occupydamag-ing

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

includes motor evoked potentials at the moment [1, 4, 5, 8, 10, 14, 19, 26, 27]

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

surgery of extramedullary tumors is usually less than 15 % Surgical results are usually curative in nerve sheath tumors, while a total recurrence rate of meningio-mas is 7 – 15 % The neurological deterioration in filum terminale ependymomeningio-mas

is more frequent, also the recurrence rate Postoperative radiotherapy 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 The5-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

Table 1 Surgical results

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:

3 months to

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 (Case Study 1, Fig 4)

Almost all meningiomas can be completely removed, with excision or

coagula-tion of the dural attachment The recurrence rate following complete reseccoagula-tion is