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Home , Central cord syndrome, Epidural abscess, Myelitis, Myelopathy, Posterior cord syndrome, Spinal cord compression

Compression and 1 3

William F. Schmalstieg and Brian G. Weinshenker

Abstract Patients with of acute require urgent neurologic evaluation focused upon the identifi cation and management of treatable disorders. MRI of the spine is the imaging modality of choice to evaluate for a compressive lesion. When cord compression is present, sur- gical treatment is usually indicated. When compression is not detected, an analysis of precise lesion localization, nonneurological clinical features, MRI fi ndings, and serologic studies narrow the . The key diagnostic considerations include demyelinating, vascular, infl amma- tory, infectious, and paraneoplastic disorders. Empiric high-dose corticos- teroid treatment is often indicated in noncompressive myelopathy; additional investigations are important to identify patients with relapsing or progressive disorders who may benefi t from preventive therapies. Patients whose symptoms continue to progress after initial immunosup- pressive treatment may benefi t from and occasionally from biopsy for defi nitive diagnosis.

Keywords CNS ¥ Demyelinating autoimmune disease ¥ Magnetic resonance imaging ¥ ¥ ¥ Spinal cord diseases ¥ Transverse

Acute myelopathies are potentially devastating etiologies of acute myelopathy are treatable, conditions that may result in irreversible loss of and rapid diagnosis and institution of appropri- mobility and control of bodily functions. Many ate treatment can prevent or reduce the extent of permanent damage to the spinal cord. Delays in the diagnosis and treatment of acute cord syn- W. F. Schmalstieg , MD (*) dromes are frequent and may contribute to loss , Mayo Clinic, of neurologic function [ 1 ] . Furthermore, some Rochester , MN , USA e-mail: [email protected] infl ammatory conditions that cause myelopathy may stabilize or remit but later relapse; patients B. G. Weinshenker , MD, FRCP(C) Neurology , Mayo Clinic, Rochester , MN , USA with such conditions may benefi t from mainte- e-mail: [email protected] nance prophylactic therapies, and therefore,

K.L. Roos (ed.), Emergency Neurology, DOI 10.1007/978-0-387-88585-8_13, 235 © Springer Science+Business Media, LLC 2012 236 W.F. Schmalstieg and B.G. Weinshenker

Fig. 13.1 Approach to diagnosis and management of acute and subacute myelopathies (NMO neuromyelitis optica; LETM longitudinally extensive ; MS ) consideration of the risk of relapse is important subacute spinal cord disorders and includes a even when spontaneous or treatment-induced diagnostic algorithm to distinguish compressive remission occurs. and noncompressive myelopathies and also to This chapter considers the clinical presenta- distinguish among the various noncompressive tion, evaluation, and management of acute and etiologies (Fig. 13.1 ). The key elements are high 13 Spinal Cord Compression and Myelopathies 237 index of suspicion and confi rmation, primarily infl ammation then leads to localized demyelina- with neuroimaging, but occasionally supported tion and frank ischemia of the cord [2 ] . by other laboratory studies. This chapter con- Vascular occlusions or other vascular anoma- cludes with treatment recommendations. lies can cause acute cord . The portion of the cord supplied by the anterior spinal artery is particularly vulnerable. Restricted fl ow of the Pathophysiology feeding vessels to this artery may produce water- shed ischemia, particularly at the terminal regions A review of spinal anatomy informs a discussion supplied by the dominant radicular artery of of the pathophysiology and clinical presentation Adamkiewicz as may occur during surgical cross- of acute disorders of the cord. The spinal cord clamping of the aorta. Other potential causes of extends between the medulla and the conus med- anterior spinal artery obstruction include aortic ullaris, the terminus of which ends opposite the dissection, atherosclerosis, cardiac embolism, L1 vertebral body. Much of the substance of the hypercoagulable states, and fi brocartilaginous cord is composed of large myelinated tracts, the embolism from intervertebral disk fragments. most clinically relevant of which include: Another uncommon but important vascular 1. Lateral corticospinal tracts carrying ipsilateral anomaly associated with myelopathy is the dural motor fi bers arteriovenous fi stula. In this condition, an abnor- 2. Spinothalamic tracts carrying contralateral mal connection of a dural artery to a vein results pain and temperature sensation in venous , resulting in damage to 3. Dorsal columns carrying ipsilateral joint posi- the cord and leading to the telltale distension of tion and vibratory sensation the epidural venous plexus that is an important The arterial vascular supply of the spinal cord radiologic sign of this entity. includes a single anterior spinal artery and two As elaborated in the section on differential posterior spinal arteries, which originate from the diagnosis, a wide variety of demyelinating, vertebral arteries. The anterior spinal artery is infl ammatory, and infectious conditions can pro- also supplied by multiple segmental arteries aris- duce intrinsic damage to the substance of the spi- ing from the thoracic and abdominal aorta. The nal cord. A detailed description of the underlying anterior spinal artery supplies the lateral corti- pathophysiology of each of these conditions is cospinal and spinothalamic tracts, whereas the beyond the scope of this text, and in many of dorsal columns are supplied by the posterior spi- these conditions the pathogenesis is poorly nal arteries. The venous drainage of the cord is understood. through the epidural venous plexus. One recent noteworthy discovery is that the The cord is surrounded by the (pia, NMO-IgG , a clinically validated bio- arachnoid, and dura mater), which are in turn marker of neuromyelitis optica (NMO), may be encircled by the vertebrae. The vertebral bodies responsible for an important portion of what had are anterior to the cord, the pedicles lateral, and been previously regarded as “idiopathic trans- the laminae and spinous processes posterior. verse myelitis.” NMO is an infl ammatory demy- In compressive lesions, such as epidural elinating disease characterized by recurrent, or metastatic disease, obstruction of the severe attacks of and longitudinally epidural venous plexus initiates spinal cord extensive transverse myelitis [ 3 ] . The target of the injury. Impairment of venous drainage causes NMO-IgG antibody is the aquaporin-4 (AQP4) vasogenic , which is in turn followed by an water channel, which is highly expressed at the infl ammatory cascade mediated, in part, by pros- astrocytic end feet of the bloodÐbrain barrier. taglandins and other infl ammatory cytokines. Current evidence suggests that this antibody is Simultaneously, the combination of external pathogenic and not merely a marker of autoim- mechanical compression and internal swelling of munity or disease severity. MRI lesions in the cord disrupts axonal conduction. Subsequent patients with NMO occur in regions known to 238 W.F. Schmalstieg and B.G. Weinshenker express high levels of AQP4 [4 ] . Additionally, Table 13.1 (continued) transfer of pooled IgG from NMO-IgG Infectious-bacterial positive patients to rats reproduces lesions similar Ð to those seen in human NMO [5, 6 ] . Antibody- – Chlamydia Ð and complement-mediated cytotoxicity to astro- Ð cytes occurs in vitro in the presence of AQP4 Ð (rare) autoantibodies and active complement and may Infectious-parasitic account for the tissue damage seen in pathologic Ð samples from patients with NMO [7 ] . Additional Ð Strongylosis mechanisms that may contribute to injury caused Infl ammatory Ð Sjögren syndrome by AQP4 specifi c autoantibodies include disrup- Ð Systemic erythematosus tion of potassium and glutamate homeostasis due Ð Wegener granulomatosis to the physical association of AQP4 with an Ð Behçet disease inward rectifying potassium channel and the excitatory amino acid transporter EAAT2. Toxic/metabolic Ð toxicity Ð Copper defi ciency Ð defi ciency (rare) Differential Diagnosis Iatrogenic Ð Radiation myelitis The differential diagnosis of acute myelopathy is Ð Postvaccination myelitis Ð Intrathecal chemotherapy extensive, including structural, vascular, demy- Neoplasia elinating, infectious, infl ammatory, neoplastic, Ð Intradural, extramedullary tumors (, and paraneoplastic conditions (Table 13.1 ). neurofi broma) Ð Intramedullary tumors (, ) Table 13.1 Etiologies of acute and subacute myelopathies Ð Lymphomatoid granulomatosis Ð Intravascular External compression Paraneoplastic myelitis Ð Metastatic spinal cord compression Ð Ð Ð Disk herniation Ð Spinal fracture Structural Ð Extramedullary hematopoiesis Ð Epidural lipomatosis External compression of the spinal cord is an Ð Atlantoaxial instability important and treatable cause of acute myelopa- Syrinx Vascular thy. Recognition of these conditions with MR Ð Spinal cord infarct imaging is usually considered straightforward. A Ð Intraspinal hematoma typical example of cord compression in the set- Ð Dural arteriovenous fi stula ting of vertebral metastasis from a primary lung Demyelinating carcinoma is displayed in Fig. 13.2 . It is essential Ð Multiple sclerosis Ð Neuromyelitis optica to have a high index of suspicion for these disor- Ð Idiopathic transverse myelitis ders as few symptoms aside from pain may be Ð Acute disseminated present initially and neurologic deterioration can Infectious-viruses occur rapidly. Ð Herpes viruses Spinal cord compression in the setting of con- Ð Ð Dengue genital stenosis and/or degenerative Ð Picornaviruses (including , poliomyelitis) disk disease usually presents with subacute or Ð chronic symptoms, although acute presentations (continued) can occur in the setting of trauma or acute disk 13 Spinal Cord Compression and Myelopathies 239

gadolinium enhancement associated with stenosis tends to be quite focal and localized to the area of maximal compression, whereas enhancement in longitudinally extensive myelitis or tumor often extends over several vertebral segments (Fig. 13.3 ) [ 8 ] . Uncommon causes of extradural compres- sion include extramedullary hematopoiesis, epi- dural lipomatosis, and atlantoaxial instability. Extramedullary hematopoiesis occurs in a num- ber of hematologic disorders and in rare circum- stances the epidural space may be involved. Reported causes include beta thalassemia, myel- odysplastic syndromes, and polycythemia vera. Symptoms typically evolve over one to several months [9 ] . Epidural lipomatosis is a condition in which excess fat deposits form in the epidural space. Spinal cord compression can occur as a consequence, particularly in patients with pre- existing spinal stenosis. Risk factors include endogenous or exogenous excess, obesity, and diabetes mellitus [ 10 ] . This condi- tion often causes slowly progressive neurologic Fig. 13.2 Thoracic spinal cord compression caused by symptoms, but there are several reports of acute metastatic lung carcinoma, sagittal T2 MRI myelopathy related to epidural fat deposition [11 ] . Atlantoaxial instability is usually associ- herniation. Magnetic resonance imaging readily ated with an underlying condition and most detects these abnormalities. commonly occurs in patients with rheumatoid Occasionally, patients with myelopathy sec- arthritis or trisomy 21 [12, 13 ] . Patients with ondary to chronic stenosis, often due to a combi- atlantoaxial dislocation may present with pro- nation of congenital and acquired causes, will gressive myelopathy or acute spinal cord have dramatic longitudinally extensive cord sig- injury. nal abnormalities on MRI. These intrinsic cord Spinal cord syrinx usually presents with a abnormalities may cause the clinician to overlook slowly progressive . an underlying spinal stenosis producing a sub- Characteristic fi ndings include early occurrence acute ischemic myelopathy due to compression, of deep, poorly localized pain followed by loss of or the apparent cord compression may be attrib- pain sensation at the level of the lesion, and pro- uted to cord edema from an intramedullary lesion gressive motor symptoms [ 14 ] . When a syrinx is rather than to the primary compressive process. present in the cervical cord, weakness appears Erroneous diagnoses of neuromyelitis optica, initially in the upper limbs as the motor pathways transverse myelitis, or spinal cord tumor may be to the arms are medial to those supplying the made in these circumstances. However, patients trunk and legs. Patients with this condition may with myelopathy secondary to stenosis usually present for acute evaluation when motor symp- develop symptoms over a period of several toms become bothersome or when painless inju- months, whereas transverse myelitis (either idio- ries, especially burns, occur. Rarely, acute spinal pathic or related to NMO) worsens to the point of cord damage due to syrinx occurs in the setting of maximal severity over days to weeks. In addition, trauma [15 ] or Valsalva maneuver [16 ] . 240 W.F. Schmalstieg and B.G. Weinshenker

Fig. 13.3 Comparison of MRI imaging in transverse myeli- point of maximal cord compression. (a ) Transverse myelitis, tis and compressive stenosis with longitudinally extensive sagittal T2 MRI. (b ) Transverse myelitis, sagittal T1 MRI intramedullary lesion; compressive stenosis is associated with gadolinium. (c ). Compressive stenosis, sagittal T2 MRI. with a focal ring pattern of gadolinium enhancement at the ( d ) Compressive stenosis, sagittal T1 MRI with gadolinium

Vascular the cord. Gadolinium enhancement is variable, and absence of enhancement in the setting of a In the absence of a compressive lesion, the sud- sudden-onset myelopathy is more suggestive of den onset of severe impairment of motor and spi- infarct than an infl ammatory process. Figures 13.4 nothalamic sensory functions with relative and 13.5 display the evolution of a typical cord preservation of dorsal column sensory modalities infarct. suggests a in the distribution of the ante- Intraspinal hematomas are uncommon. These rior spinal artery. This is a feared complication of conditions can occur as a rare but serious conse- surgical manipulation of the thoracic or abdomi- quence of , especially in patients nal aorta, and in that context is readily identifi ed. treated with anticoagulant drugs. A study of 342 However, cord infarction may occur spontane- patients who were anticoagulated with heparin after ously and occasionally without clearly identifi - lumbar puncture demonstrated a 2% risk of spinal able risk factors that aid in the diagnosis. hematoma, whereas there were no hematomas in a MRI fi ndings suggestive of anterior spinal matched cohort of patients who were not anticoagu- cord infarction include central T2 hyperintensity lated [ 17 ] . Patients with a recent history of spinal with sparing of the posterior cord and swelling of , epidural anesthesia, or coagulopathy are 13 Spinal Cord Compression and Myelopathies 241 also at risk. Hemorrhage into the subarachnoid, A high index of suspicion for spinal arterio- subdural, or epidural spaces can occur, epidural venous fi stula (AVF) is necessary as this is a treat- hematoma being the most common [ 17] . Patients able cause of progressive myelopathy. In the present with new, severe spinal pain and rapidly majority of cases, this condition produces a myel- progressive neurologic defi cits. These conditions opathy that evolves over months. Some patients can be readily identifi ed with MR imaging. present with a stepwise course with repeated epi- sodic deterioration related to upright posture or to minor exertion. Although this disorder is most common in men in the seventh decade of life, this

potentially reversible process should be considered in all patients with an otherwise unexplained pro- gressive or subacute myelopathy [ 18 ] . Abnormal high T2 signal in the cord extending into the conus and gadolinium enhancement are typical but non- specifi c MRI fi ndings of spinal dural AVF. The absence of any abnormal T2 signal is distinctly unusual in patients with dural AVF and suggests an alternate diagnosis. Presence of fl ow voids repre- senting dilation of the epidural venous plexus is a more specifi c fi nding (Fig. 13.6 ), but may be seen in less than 50% of patients on standard MRI imag- ing. Prone-supine is highly sensitive for detection of dilated epidural veins; the invasive nature of the procedure and substantial false posi- tive rate limit the usefulness of myelography as a screening tool [ 18 ] . In patients with a stepwise or Fig. 13.4 Early cord infarct with patchy T2 signal change progressive myelopathy and radiologic fi ndings and swelling of the distal spinal cord, sagittal T2 MRI suggestive of dural AV fi stula, comprehensive

Fig. 13.5 Established cord infarct with central T2 hyperintensity. (a ) Axial T2 MRI. (b ) Sagittal T2 MRI 242 W.F. Schmalstieg and B.G. Weinshenker

Fig. 13.6 Characteristic fl ow voids due to dilation of the epidural venous plexus in the setting of dural AVF, sagittal T2 MRI

spinal angiography may be warranted. Fistulae producing a progressive myelopathy may be found as high as the brainstem, and accordingly one needs to be determined to detect the abnormality in cases where the clinical and screening radiologic features strongly suggest that a fi stula is present.

Demyelinating Disease Fig. 13.7 Typical cord lesions caused by multiple sclero- Demyelinating diseases account for a substantial sis. (a ) Axial T2 MRI. (b ) Sagittal T2 MRI percentage of acute myelopathies. Distinguishing patients who have or are at risk to develop MS from those with less common demyelinating dis- 3. Extends over less than two vertebral segments orders such as NMO, acute disseminated enceph- 4. Minimal or no cord swelling is present [19 ] alomyelitis (ADEM), and idiopathic transverse In patients with spinal lesions meeting these myelitis is important for the prognosis of the criteria, a careful history regarding any previous patient and for selection of appropriate therapy to episodic neurologic symptoms may reveal a his- prevent recurrence. tory of past MS exacerbations that assist with the In a patient presenting with a new, incomplete diagnosis. MRI scan of the brain may detect typi- myelopathy the following features on spinal MRI cal brain lesions of multiple sclerosis (focal, T2 should suggest the possibility of an MS-related hyperintense lesions that are periventricular, jux- lesion (Fig. 13.7 ): tacortical, or located in the brainstem). However, 1. Clearly circumscribed, focal T2 hyperintensity nonspecifi c brain lesions are common due to 2. Affects only part of the cord in axial cross sec- defi nable (e.g., ) and nondefi nable causes tion, usually, but not exclusively in the periph- and therefore such lesions should not be assumed ery of the spinal cord to be pathognomonic of MS. Additionally, brain 13 Spinal Cord Compression and Myelopathies 243 lesions are common in NMO and do not exclude that diagnosis [20 ] . Cerebrospinal fl uid (CSF) examination is often performed in this setting, although this testing may be unnecessary in patients with a high pretest probability of having MS based on clinical and radiographic evidence. Detection of oligoclonal bands in the CSF, preferably by isoelectric focus- ing on agarose gels followed by immunodetec- tion, is predictive of eventual development of MS independent of MRI fi ndings [ 21 ] . Nevertheless, as oligoclonal bands are not present in all patients with MS and occur in other infl ammatory, infec- tious, and neoplastic conditions, presence of oli- goclonal bands should not be regarded as “diagnostic” of MS and the result of this study should not be used to guide treatment decisions in isolation. Other CSF fi ndings that should suggest a diagnosis other than MS include a nucleated cell count greater than 50/m L and an excess of neutrophils. Longitudinally extensive cord signal change extending over three or more vertebral segments is unusual in multiple sclerosis. Some authors argue for the existence of an opticospinal variant of MS in Asian patients that is distinct from NMO, and longi- Fig. 13.8 Longitudinally extensive cord signal change tudinally extensive spinal cord lesions may occur in caused by NMO, sagittal T2 MRI patients with that condition [22 ] . Nevertheless, the occurrence of longitudinally extensive transverse myelitis (LETM) in the setting of a previous history and pleocytosis exceeding 50 WBC/m L and neu- of one or more attacks of severe optic neuritis is trophilic pleocytosis occur in approximately 25% highly suspicious for NMO and should prompt the of cases in the context of an acute attack [24 ] . clinician to obtain a serum NMO-IgG antibody. The Occasional patients have CSF NMO-IgG anti- sensitivity and specifi city of this immunofl uores- bodies despite having negative results in serum cent antibody test in classic NMO are approximately [ 25 ] . 75% and >90%, respectively [3, 23 ] . Wingerchuk and colleagues have suggested Brain MRI is helpful in the evaluation of sus- the following diagnostic criteria for “defi nite pected NMO. Brain MRI lesions are common in NMO”: NMO patients. In one series of 60 NMO patients, 1. History of optic neuritis 60% had an abnormal brain MRI [20 ] . MRI 2. History of acute myelitis lesions have been reported in NMO in regions of 3. At least two of three supportive criteria the brain known to express high levels of aqua- (a) MRI demonstrating contiguous spinal porin-4, including the hypothalamus and periven- cord lesion extending over ³ 3 vertebral tricular regions [4 ] . However, brain lesions in segments (Fig. 13.8 ) NMO patients usually differ from lesions that are (b) Brain MRI at the onset of NMO symp- characteristic of MS. toms that does not satisfy diagnostic crite- CSF fi ndings in NMO differ from those of ria for MS MS; oligoclonal bands are infrequent in NMO (c) Seropositivity for NMO-IgG [23 ] 244 W.F. Schmalstieg and B.G. Weinshenker

The absence of a history of optic neuritis does Clinical features that should prompt an not exclude an NMO spectrum disorder. Some increased level of suspicion for an infectious pro- patients with an isolated LETM will subsequently cess include current or recent presence of fever, develop classic fi ndings of NMO. Others may meningismus, rash, symptoms of systemic ill- have recurrent attacks of myelitis in the absence ness, recent travel, or immunosuppression. of optic neuritis, and may have a limited form of Although nonspecifi c, CSF pleocytosis (particu- NMO. Presence of the NMO-IgG antibody in the larly if greater than 50 WBCs/m L) suggests this setting of a single episode of LETM is strongly possibility. However, patients with parainfectious predictive of subsequent relapse; one series dem- myelopathy often do not recall or have symptoms onstrated a 55% risk of further episodes of myeli- of a recent illness. In a review of 23 patients with tis and/or optic neuritis within one year in patients parainfectious myelopathy confi rmed by sero- with a LETM [26 ] . logical or CSF studies, only nine (39%) recalled Acute myelopathy may occur in the setting of symptoms consistent with an infectious process ADEM, a multifocal demyelinating disorder of in the previous month [28 ] . the CNS that typically occurs after an infectious Viruses are the most common cause of parain- syndrome or recent vaccination; it is more com- fectious myelopathy [ 28 ] . CSF PCR testing for mon in children. In the classic presentation, MRI herpes viruses ( virus 1 and 2, demonstrates multifocal gadolinium-enhancing EpsteinÐBarr virus, , cyto- CNS lesions. The most specifi c criterion that dis- megalovirus, human herpesvirus-6) is appropri- tinguishes ADEM from MS, and is required for ate in an unexplained myelopathy as these viruses the diagnosis, is [27 ] . are the most commonly identifi ed causes of Patients with a symmetric, severe acute myel- parainfectious myelopathy and may be treatable opathy (“complete transverse myelitis”) and/or with specifi c antiviral therapies [ 28 ] . A multitude isolated LETM with negative NMO-IgG may of other viruses have been implicated as causes have an isolated infl ammatory demyelinating of infectious or parainfectious myelitis, including transverse myelitis (i.e., idiopathic transverse adenoviruses, coxsackie , enteroviruses, myelitis) or another infectious, infl ammatory, or [28 ] , and dengue [29 ] . neoplastic condition. As discussed below, serum Certain viral characteristically pro- and CSF testing may reveal evidence of a parain- duce an acute fl accid with sparing of fectious cause in these patients; when such test- sensory function when involving the central ner- ing is unrevealing, clinical and radiographic vous system. Poliomyelitis is the classic example follow-up is important. In patients in this group of such a condition. This disorder is now extraor- who display ongoing clinical deterioration dinarily rare in developed countries, although beyond 3 weeks or have worsening fi ndings on importation of this disease from endemic regions MRI, biopsy of the spinal cord should be consid- [ 30] and limited person to person spread in an ered to exclude tumor or another treatable infl am- undervaccinated community have been reported matory disorder, such as . in recent years [31 ] . Similar clinical presenta- tions have been associated with epidemics of 70 (acute hemorrhagic conjunctivitis) Infectious and enterovirus 71 (hand, foot, and mouth dis- ease) [32 ] , as well as West Nile virus [ 33 ] . In a In addition to compression by an extrinsic infec- minority of cases, rabies encephalomyelitis can tious lesion such as an epidural abscess, some also present as an ascending fl accid paralysis pathogens can produce acute or subacute myel- with spinal cord signal change [34 ] . opathies by direct of the cord or by Parainfectious myelitis may occur in associa- inducing a parainfectious, presumably autoim- tion with recent bacterial infections, often with mune process. Chlamydia and Mycoplasma species [28 ] . Myelitis 13 Spinal Cord Compression and Myelopathies 245 can occur in Mycobacterium tuberculosis infection diagnosis of this disease, but this test is insensi- either due to direct involvement of the cord or on a tive and does not establish a diagnosis in isola- compressive basis in the setting of vertebral tion [40 ] . There are no other laboratory or imaging involvement (). Bacterial myelitis can fi ndings that are unique to this condition, and also occur with Treponema pallidum (syphilis) [ 35 ] accordingly the diagnosis requires presence of or burgdorferi (Lyme disease) infections other characteristic systemic features. [36 ] ; both of these presentations are uncommon. Sarcoidosis is a nonnecrotizing granulomatous Fungal and parasitic infections are rare causes infl ammatory process that can involve multiple of acute myelitis, but should be considered in organ systems. Neurological involvement occurs patients at risk due to immunosuppression and/or in approximately 5% of cases, and in those cases, travel exposures. Infections associated with acute neurologic symptoms are the initial manifestation myelopathies include schistosomiasis [37 ] , strongy- in about half [42 ] . In the absence of systemic dis- losis, candidiasis [28 ] , and blastomycosis [38 ] . ease, the diagnosis of neurosarcoidosis is often diffi cult. Spinal imaging fi ndings that may sug- gest this process include a nodular enhancing pat- I n fl ammatory tern in the parenchyma, meningeal enhancement, and nerve root enhancement. Oligoclonal bands In addition to infl ammatory demyelinating dis- in the CSF have been reported in 27Ð51% of eases, other systemic infl ammatory disorders can cases; the presence of oligoclonal bands should produce acute or subacute myelopathies. not automatically lead to a diagnosis of MS [43, Myelopathy can occur as a complication of 44 ] . Although neither sensitive nor specifi c, an Sjögren syndrome or systemic lupus erythemato- elevated serum ACE level may suggest sarcoido- sus. However, antibodies associated with these sis as well. In patients with imaging fi ndings sus- syndromes (e.g., ANA, SS-A) are encountered in picious for sarcoid and those with an otherwise patients with NMO and may occur in other unexplained myelopathy, it is helpful to search for infl ammatory demyelinating diseases. A serolog- evidence of systemic sarcoid in a lesion that could ical survey of 153 patients with NMO spectrum be biopsied (e.g., an enlarged lymph node). CT disorders found positive ANA and SS-A antibod- imaging of the chest may demonstrate evidence of ies in 44% and 16%, respectively [39 ] . hilar lymphadenopathy. Blind conjunctival biopsy Accordingly, diagnoses of lupus or Sjögren syn- occasionally demonstrates characteristic noncase- drome should not be made on the basis of anti- ating granulomatous infl ammation. In cases of body fi ndings alone in cases of acute myelopathy isolated CNS involvement, such studies will be unless specifi c diagnostic criteria for these dis- unrevealing and empiric corticosteroid treatment eases are met. for both therapeutic and diagnostic purposes is Behçet disease is a chronic, relapsing infl am- often the best approach; dramatic and sustained matory disorder characterized by recurrent oral improvement in the face of a syndrome suggestive aphthous ulcers and other systemic manifesta- of sarcoidosis is often the basis of a tentative but tions including recurrent genital ulcerations, eye, acceptable diagnosis. and skin lesions [ 40] . Spinal cord and other ner- vous system involvement occurs in a minority of patients with this condition, either due to direct Toxic/Metabolic formation of lesions in the CNS or secondary to infarct from involvement of major vascular struc- Metabolic disorders affecting the cord usually tures [41 ] . Presence of a positive pathergy test produce a chronic myelopathy, although many (development of a nodule ³ 2 mm in diameter patients will not complain of symptoms until a 24Ð48 h after subcutaneous insertion of a sterile certain level of impairment develops. In most, needle) is accepted as a supportive criterion for careful history reveals that the symptoms of 246 W.F. Schmalstieg and B.G. Weinshenker myelopathy are long-standing. Nevertheless, the onset of myelopathy after vaccination may given that the diagnosis and treatment of these be purely coincidental and recent vaccination disorders is associated with minimal risk, obtain- should not deter investigations to uncover other ing limited metabolic studies such as serum treatable causes. vitamin B12, methylmalonic acid, and copper Subacute myelopathy also may result from levels is appropriate in the setting of unexplained toxic effects of intrathecal chemotherapy with subacute or chronic myelopathies. several agents including methotrexate, doxorubi- Acute myelopathies have occurred secondary cin, vincristine, and cytarabine [45 ] . to toxic exposures from consumption of toxic dietary staples (e.g., cassava, Lathyrus sativus ) or recreational substance abuse (e.g., tricresyl phos- Neoplastic and Paraneoplastic phate toxicity from consumption of adulterated “Jamaican ginger” extract); many of these condi- Intramedullary , such as tions are of limited historical or geographic rele- and , and extramedullary, intradural vance [45 ] . An exception is myelopathy secondary tumors, such as and neurofi bromas, to nitrous oxide exposure. Nitrous oxide can pro- may become symptomatic with a subacute time duce myelopathy via irreversible oxidation of course mimicking extradural tumors or transverse cobalamin, resulting in secondary vitamin B12 myelitis. These tumors are easily visualized on defi ciency [45 ] . Individuals with preexisting sub- MRI, although they may sometimes be confused clinical vitamin B12 defi ciency are particularly with infl ammatory lesions. Biopsy is usually vulnerable. This condition continues to occur required to confi rm the diagnosis. secondary to recreational abuse [46 ] and rarely in Lymphoproliferative malignancies, such as patients receiving nitrous oxide anesthesia [47 ] lymphomatoid granulomatosis and intravascular or dental professionals working in poorly venti- lymphoma, can involve the spinal cord and lated offi ces [46 ] . In recreational users, specifi c evolve with a subacute time course. Confi dent questioning about use of nitrous oxide is impor- diagnosis requires biopsy of the CNS or other tant as users may be reluctant to admit this habit involved site, although in the case of lymphoma- and unaware of its toxic potential. toid granulomatosis the presence of oligoclonal bands and positive CSF PCR for Epstein-Barr virus increases the index of suspicion. Iatrogenic Myelitis may occur as a paraneoplastic dis- ease. The index of suspicion for a paraneoplastic Patients who have undergone radiation treatment process should be increased in patients with a for cancer can develop radiation myelitis when known history of cancer and in smokers. A serum the spinal cord is included in the radiation fi eld. evaluation for paraneoplastic autoantibodies This condition can present acutely during radia- should be considered in these circumstances. tion treatment or in a delayed fashion. In a patient Certain imaging patterns may also be suspicious with a history of cancer, it is essential to exclude for a paraneoplastic etiology; we have encoun- direct metastatic involvement of the cord prior to tered a number of patients with hyperintense T2 attributing any myelopathy to radiation effect. lesions that appear confi ned within individual Autoimmune myelitis may occur after vac- spinal tracts in this circumstance, often symmet- cinations. Classic descriptions of postvaccina- rically on both sides of the cord (Fig. 13.9 ) [49 ] . tion encephalomyelitis occurred in individuals Paraneoplastic syndromes may produce multifo- who received obsolete forms of rabies vaccina- cal involvement mimicking other tion, but postvaccination myelitis has been disorders such as NMO. In particular, collapsin reported after a host of other common vaccina- response-mediator protein-5 (CRMP-5) IgG anti- tions including infl uenza, pertussis, diphtheria- bodies can cause autoimmune myelitis and optic tetanus, MMR, and [ 48 ] . However, neuritis [50, 51 ] . 13 Spinal Cord Compression and Myelopathies 247

Fig. 13.9 Signal change in the central cord and lateral columns caused by paraneoplastic myelitis in the setting of . (a ) Axial T2 MRI. (b ) Axial T1 MRI with gadolinium

Alternate Localizations sentation of a chronic metabolic, degenerative, or infectious disorder (e.g., AIDS myelopathy, tropi- When there is no spinal cord abnormality on neu- cal spastic paraparesis due to HTLV-I) should also roimaging in the context of an apparent acute be considered, although these conditions rarely myelopathy, the responsible lesion may be else- evolve during short-term neurologic follow-up. where in the nervous system. The primary item Occasionally, patients with chronic myelopathies on the differential diagnosis in patients with bilat- do not seek medical attention despite long-stand- eral motor and sensory symptoms is an acute ing symptoms until they become associated with neuropathy such as Guillain–Barré syndrome. In functional impairment. addition to ascending weakness, fi ndings favor- ing this diagnosis include arefl exia, absence of a defi ned sensory level, and elevated protein con- Epidemiology centration in the CSF with a normal cell count. In patients with pure motor symptoms, myopathies Metastatic spinal cord compression is a common and occasionally neuromuscular junction disor- complication of advanced cancer, occurring in 2.5Ð ders can be mistaken for spinal cord disease. 6% of individuals with systemic malignancy ascer- Parafalcine space-occupying lesions (e.g., men- tained in population-based studies [ 52, 53] . In ingioma) and bilateral anterior cerebral artery approximately 20% of cases, cord compression is distribution infarcts occasionally present with the presenting manifestation of cancer [ 54 ] . bilateral lower limb weakness mimicking myel- Metastases attributable to a specifi c cancer gener- opathy as well. ally parallel the relative frequency of that cancer, However, the absence of an MRI abnormality with approximately half of cases attributable to car- should not automatically lead to the conclusion cinomas of the breast, prostate, and lung [52 ] . that the problem does not localize to the spinal However, certain malignancies including renal cell cord. Subtle imaging abnormalities such as swell- carcinoma [ 52 ] , , and lymphoma ing of the cord in the absence of signal change, as [ 54 ] are disproportionately more likely to result in occasionally seen in early cord infarct, or symp- cord compression, whereas gastrointestinal cancers, tomatic epidural lipomatosis may be missed on including colorectal and pancreatic carcinoma, are initial review. The possibility of an “acute” pre- disproportionately less likely to do so [53 ] . 248 W.F. Schmalstieg and B.G. Weinshenker

As MS is a relatively common disorder (prev- Table 13.2 Demographic factors associated with spe- alence estimated at 0.9 cases per 1,000 in the cifi c causes of myelopathy United States population [55 ] ) and the majority Metastatic spinal cord compression: prior history of of patients have imaging evidence of spinal cord malignancy, elderly patients and children; uncommon in young adults involvement even at the time of diagnosis [ 56 ] , Multiple sclerosis: median age of onset in third decade of MS is responsible for a substantial proportion of life; more common in females acute myelopathies. MS plaques in the cord often Neuromyelitis optica: relapsing form more common in result in minimal symptoms, and are asymptom- women; non-Caucasians overrepresented in US patients atic in up to two-thirds of cases [ 57 ] . Milder relative to MS myelopathic presentations with asymmetric Spinal cord infarct: increased risk with age; male sex motor and sensory involvement (i.e., “partial Dural arteriovenous fi stula: most common in seventh decade of life; male predominance transverse myelitis”) are the most common myel- Systemic lupus erythematosus/Sjögren syndrome: female opathies that are manifestations of inaugural or predominance established MS [58 ] . Behçet disease: most common in patients of Middle Other individual causes of nontraumatic, acute Eastern and Far Eastern origin; more common in males myelopathy are uncommon. For instance, retro- of Middle Eastern origin and more severe in males spective studies suggest that the incidence of Sarcoidosis: more common in women; threeÐfourfold greater risk in African Americans compared to acute transverse myelitis in patients without a Caucasians previous history of neurologic disease ranges from 1.3 to 4.6 cases per million per year [59, Table 13.3 Risk factors associated with specifi c causes 60 ] . Similarly, epidural abscess was diagnosed at of myelopathy a rate of only 2 of 10,000 hospital admissions per Cigarette smoking: metastatic spinal cord compression, year at an urban referral center [ 61 ] . Collectively, paraneoplastic myelopathy, cord infarction however, these less common entities constitute Injection drug use: epidural abscess an important group of disorders that may need Nitrous oxide abuse: myelopathy due to induced vitamin very specifi c treatment. B12 defi ciency The etiology of new-onset, noncompressive Immunosuppression: epidural abscess, other infectious myelopathy is often unclear at the time of presen- myelopathies tation. A recent French series reported that the History of cancer: metastatic spinal cord compression, toxic myelopathy with history of intrathecal chemother- etiology of acute myelopathy could not be deter- apy, radiation myelitis with history of radiotherapy mined in 101 of 170 patients at onset. Fifty-four Obesity: epidural lipomatosis percent of these patients were subsequently diag- Corticosteroid excess: epidural lipomatosis nosed with either multiple sclerosis (45 patients), GI malabsorption or surgery: myelopathy due to nutritional neuromyelitis optica (5 patients), or a connective defi ciency, including B12 and copper defi ciency tissue disease (5 patients). Many patients with Excess zinc ingestion: myelopathy due to copper defi ciency each of these disorders would likely benefi t from maintenance therapies to prevent relapse. This result highlights the importance of diagnostic less likely. Demographic features associated with testing in cases of acute noncompressive myel- selected causes of acute myelopathy are pre- opathy, as many patients with this type of presen- sented in Table 13.2 [ 18, 62Ð 65 ] . Most causes of tation have treatable disorders with potential to acute myelopathy are not restricted by demogra- result in serious future morbidity. phy, and age, gender, and ethnicity do not exclude any etiology from consideration in an individual patient. Demographics and Other Risk Factors Recognition of risk factors related to habits or other medical history is equally important. Risk Age, gender, ethnicity, and race may suggest that factors associated with particular causes of myel- a particular cause of acute myelopathy is more or opathy are listed in Table 13.3 . 13 Spinal Cord Compression and Myelopathies 249

Table 13.4 Etiologies of spinal cord syndromes Clinical Features Brown-Séquard syndrome Multiple sclerosis Syndromes Penetrating trauma Metastatic cord compression Presentations of spinal cord disease are often Epidural abscess Parainfectious myelopathy described in terms of clinical syndromes. Spinal Anterior cord syndrome cord syndromes associated with specifi c etiolo- Anterior spinal artery infarct gies are listed in Table 13.4 . Although the type of Disk herniation clinical presentation seen may help to narrow the Metastatic cord compression differential diagnosis, none of these syndromes Epidural abscess Radiation myelitis are pathognomonic for any particular condition. Trauma Accordingly, recognition of other characteristic Central cord syndrome clinical features, imaging fi ndings, and the results of other diagnostic studies are necessary for accu- Intrinsic spinal cord tumor rate diagnosis. Neuromyelitis optica Transverse myelitis Trauma Brown-Séquard Syndrome “Complete” Brown-Séquard syndrome refers to Multiple sclerosis the clinical presentation seen with hemisection of Posterior spinal artery infarct Tertiary syphilis the spinal cord. An affected patient has loss of Subacute combined degeneration due to B12 or copper motor function and dorsal column sensory modal- defi ciency ities on the side of the lesion, with pain and tem- Conus medullaris syndrome perature loss below the level of the lesion on the Disk herniation opposite side of the body due to disruption of the Metastatic cord compression Intrinsic spinal cord tumor spinothalamic tract. The complete presentation is Trauma unusual; a “partial” Brown-Séquard syndrome Dural arteriovenous fi stula with preservation of dorsal column sensory func- tion is more common. This type of asymmetric Complete cord syndrome Idiopathic transverse myelitis presentation is often seen in demyelinating dis- Trauma eases, particularly MS, but can also occur in the Metastatic cord compression early stages of a compressive lesion. Epidural abscess Hemorrhage Ischemia Anterior Cord Syndrome In this presentation, the corticospinal and spi- nothalamic tracts are injured bilaterally with preservation of dorsal column sensory functions. and impairment of motor function in the upper This syndrome is seen with infarction of the ante- limbs prior to the lower limbs and trunk. In addi- rior spinal artery, but can also occur with tion to syrinx and cord tumor, the features of compressive lesions. central cord syndrome can occur with infl amma- tory demyelinating diseases, particularly neuro- Central Cord Syndrome myelitis optica. The characteristic evolution of a central cord syn- drome in the setting of a syrinx was described Posterior Cord Syndrome earlier. Common features include deep, uncom- Isolated involvement of the dorsal columns is fortable pain, loss of pain and temperature sensa- most commonly seen in the setting of a chronic tion at the level of the lesion due to disruption of myelopathy; in the setting of ter- the crossing fi bers of the spinothalamic tracts, tiary syphilis is a classic example. This syndrome 250 W.F. Schmalstieg and B.G. Weinshenker occasionally occurs due to infarction of the than in the neck or low back. Pain that worsens at posterior spinal artery. night or with recumbent position is also sugges- tive of cord compression. Conus Medullaris Syndrome A history of prior neurological symptoms is Myelopathy confi ned to the terminal portion of often informative in the diagnosis of infl amma- the spinal cord results in fl accid paralysis of the tory demyelinating diseases. A history of previ- bladder and anal sphincters. The presentation ous episodic visual, motor, urinary, or sensory may occur as a component of a more extensive disturbances lasting greater than 24 h may sug- cord lesion involving the conus or be quite iso- gest previously unrecognized MS exacerbations. lated. There are multiple causes including com- A history of clear worsening of neurologic symp- pression, dural arteriovenous fi stula, , toms in response to heat or a reproducible “shock- and demyelination. One needs to distinguish this like” sensation traveling down the spine with presentation from a . forward fl exion of the neck (Lhermitte sign) is Compression or infl ammation of the cauda equina quite suggestive of demyelination. Paroxysmal produces lower fi ndings including tonic spasms (brief, involuntary muscle contrac- weakness and refl ex loss in the lower limbs cor- tions typically lasting from 15 to 60 s at a time) responding to the involved nerve roots as well as are a less common but highly specifi c indicator of sensory changes in the dermatomes innervated an infl ammatory demyelinating disease. A his- by involved sensory roots. Pain is usual in cauda tory of episodes of intractable vomiting or hic- equina syndrome; bowel and bladder involve- coughs is now recognized as a common harbinger ment is variable depending on the levels of NMO spectrum disorders [67, 68 ] . involved.

Complete Cord Syndrome Time Course The clinical picture of complete transection of the spinal cord at the level of the lesion (absence of Myelopathies can develop suddenly, acutely all sensory modalities and motor function below (<24 h to 3 weeks), subacutely (over weeks to the lesion) is described as the complete cord syn- months), or insidiously. Apoplectic onset of drome. This type of presentation occurs with symptoms often suggests a vascular etiology severe idiopathic transverse myelitis and is also a such as an ischemic cord infarct or occasionally a common presentation of an extradural compres- hemorrhage. Compressive lesions can also pres- sive lesion producing severe cord compression. ent abruptly, as in the case of an acute disk her- niation or a pathologic fracture in the setting of malignancy. Infl ammatory disorders usually do Symptoms not present instantaneously, but patients may awaken with new symptoms and thereby con- Although many symptoms of acute cord injury found the determination of the mode of onset. are nonspecifi c, certain symptoms are character- Many etiologies of myelopathy, such as demy- istic and suggestive of particular conditions. elinating diseases, other infl ammatory disorders, Pain is not unique to cord compression, but is and cord compression, reach maximal severity over an important “red fl ag.” In the majority of cases days to a few weeks. Other conditions that can pres- of metastatic SCC, pain precedes the onset of ent with a similar time course include parainfectious other neurologic symptoms. Pain in the thoracic myelopathy, radiation myelitis, and paraneoplastic region is particularly concerning, not only myelitis. Disorders that evolve over weeks or lon- because the majority of metastatic cord compres- ger include spinal stenosis, dural arteriovenous fi s- sions occur in this region [ 66 ] , but also because tula, chronic infections (e.g., HIV myelopathy, “benign” musculoskeletal and radicular causes of HTLV-I, tertiary syphilis), metabolic disorders, and pain in the thoracic spine are far less common intradural and intramedullary tumors. 13 Spinal Cord Compression and Myelopathies 251

CSF Examination Diagnosis A CSF examination is often the next step in the Neuroimaging, and to a lesser extent, other evaluation of a noncompressive myelopathy. CSF diagnostic studies are essential for accurate examination is usually not helpful in diagnosing the diagnosis of acute and subacute myelopathies cause of spinal cord compression and may result in given the lack of specifi city of clinical and neurologic deterioration in patients with severe demographic features. A stepwise approach to cord compression. Routine CSF studies should diagnostic testing is discussed; specifi c features include cell count with differential, glucose and suggestive of particular disorders were pre- protein concentration, oligoclonal banding, and sented earlier. cytologic examination; it is often helpful to retain spinal fl uid to allow for additional testing informed by the results of the initial screening tests. Spine MRI

MRI scan of the spine is the key diagnostic proce- Brain MRI dure in the assessment of acute cord lesions. The superiority of MR imaging in visualizing soft tissue In cases of acute, noncompressive myelopathy, makes MRI the procedure of choice in assessing brain MRI imaging is useful to detect character- infl ammatory, vascular, infectious, and metabolic istic features of demyelinating disease. In the set- myelopathies. MRI has also supplanted CT myel- ting of an asymmetric partial transverse myelitis, ography as the preferred procedure in cases of sus- presence of brain lesions consistent with MS pected cord compression. In metastatic SCC, MRI strongly suggests that the presentation is due to is equally sensitive and more specifi c than CT myel- infl ammatory demyelinating disease. In patients ography [69, 70 ] . Additionally, myelography may with a clinically isolated demyelinating syn- result in neurologic deterioration in patients with drome, the fi nding of typical MS lesions on brain severe compression who have complete block of MRI predicts an approximately 90% chance of the fl ow of myelographic dye. developing clinically defi nite MS in the future Patients with cord compression may experi- [ 71 ] . However, a normal brain MRI scan does not ence signifi cant neurologic deterioration over a exclude the diagnosis of a demyelinating disease. period of a few hours. When suspected, MRI It is also important to distinguish the typical imaging should be obtained on an emergent basis periventricular, juxtacortical, and brainstem and not delayed. If a compressive lesion is identi- lesions of MS from nonspecifi c T2 signal abnor- fi ed, defi nitive treatment with surgery or radio- malities in the deep subcortical , therapy is indicated. Although additional testing which do not have the same diagnostic implica- to identify the underlying condition causing com- tions when seen in isolation. pression is important, treatment is urgently needed and should not be delayed to obtain addi- tional testing; however, radiotherapy may not be Blood/Serology provided until a defi nitive diagnosis of cancer is obtained at the time of surgery in patients without Serum NMO-IgG antibody serology should be an established history of cancer. obtained in patients with unexplained longitudi- When abnormal signal is apparent within the nally extensive (³ 3 vertebral segments in length) substance of the cord, a review of the past his- signal abnormality regardless of whether or not a tory, clinical presentation, and imaging fi ndings patient has a past history of optic neuritis. In con- may suggest a particular diagnosis. However, in trast, patients with a history of optic neuritis and many cases further studies are necessary. partial transverse myelitis without longitudinally 252 W.F. Schmalstieg and B.G. Weinshenker extensive cord signal change are unlikely to have ideally prior to the institution of empiric antibiotic NMO; MS is a more likely diagnosis in this therapy. The yield of blood cultures in epidural context. abscess is approximately 60%, with the most com- In patients with isolated myelitis and other- mon organism being [72 ] . wise normal CNS imaging, viral serologies may yield evidence supporting a role of common pathogens associated with parainfectious myel- Other Imaging Studies opathy. CSF PCR studies may be a more reliable marker of recent infection. Detecting evidence of In patients who are unable to undergo MRI recent infection with herpes viruses is important because of implanted MRI-incompatible medical as patients may respond to specifi c antiviral ther- devices, presence of magnetic foreign bodies, or apy with acyclovir and related compounds. Even body habitus, CT myelography is an alternative in cases where a positive result does not alter the imaging modality to exclude compression. treatment strategy, fi nding evidence of a recent CT imaging of the chest, abdomen, and pelvis infection may limit the need for additional diag- may reveal an underlying cancer in cases of nostic testing. occult malignancy presenting with cord compres- When an underlying systemic infl ammatory sion. In noncompressive myelopathies that are disease is suspected, obtaining an antinuclear anti- atypical for demyelinating disease, CT imaging body (ANA), anti-double stranded DNA antibod- may also be useful to screen for lymphadenopa- ies, antibodies to extractable nuclear antigens (e.g., thy suggestive of sarcoidosis or lymphoma. SS-A), and antineutrophil cytoplasmic antibodies Gallium-67 scintigraphy occasionally reveals (p-ANCA and c-ANCA) may be useful to screen evidence suggestive of sarcoidosis when routine for systemic infl ammatory and vasculitic disor- CT imaging is negative. Positron emission tomog- ders. However, when clinical and radiographic raphy (PET) scan can detect an otherwise occult fi ndings strongly suggest an infl ammatory demy- malignancy in cases of cord compression or fi nd- elinating disease, a “positive” serologic result, ing of a positive paraneoplastic autoantibody. such as a positive ANA, is unlikely to indicate an alternate diagnosis, especially considering the nonspecifi city of this antibody. A “panel” of sero- Treatment logic markers of autoimmunity to screen for “mim- ics” of multiple sclerosis is not helpful and may be Compressive misleading given the high frequency of false posi- tive results when used as a screening test. Despite availability of MRI imaging, delays in the treatment of metastatic cord compression remain common. In one series of 301 patients, only 33% Blood/Other were ambulatory at the time of treatment, unchanged from the era prior to MRI imaging. Additional laboratory tests may be valuable in Most had experienced deterioration in motor diagnosing the cause of a compressive myelopa- function after initial presentation to a medical thy, although usually not essential to emergent practitioner before defi nitive treatment was insti- management. In cases where cord compression is tuted [1 ] . Patients who are nonambulatory often the initial manifestation of an occult cancer, pros- remain so; nearly 40% of nonambulant patients tate-specifi c antigen testing and monoclonal pro- remain unable to walk after treatment [73 ] . In tein studies of the serum and urine (often positive contrast, 80Ð100% of spinal cord compression in multiple myeloma and other plasma cell dyscra- patients who are ambulatory at the time of treat- sias) may suggest an underlying malignancy. ment initiation remain ambulatory [52, 74Ð 76 ] . When epidural abscess is considered, blood cul- Accordingly, rapid identifi cation of cord compres- tures should be obtained from two separate sites, sion and early defi nitive treatment are essential 13 Spinal Cord Compression and Myelopathies 253 for optimal outcomes. and surgi- capacity [75 ] . No specifi c radiotherapy regimen cal decompression were proven effective for treat- has been proven superior. In the United States, ment of metastatic spinal cord compression in patients often receive 30 Gy to the involved area controlled clinical trials, and the standard of care in equal doses over 10 days. Some authors have also includes radiotherapy. advocated lower doses, with doses as low as 8 Gy A single placebo-controlled trial addressed the in a single fraction appearing benefi cial in a ran- use of corticosteroids as an adjunct to radiation domized trial [80 ] . therapy in metastatic cord compression. The treat- The treatment of other causes of spinal cord ment group received 96 mg of intravenous (IV) compression is usually surgical. Although no at presentation and then 24 mg of controlled trials have addressed the issue of sur- oral dexamethasone four times daily for 3 days gical versus medical management of epidural followed by taper. At the conclusion of treatment, abscess, surgical decompression followed by 81% of the dexamethasone-treated group versus antibiotic treatment is considered the standard of 59% of the placebo-treated group were ambula- care for this condition [ 81 ] . Surgery is also indi- tory; at 6 months, 63% of patients in the treatment cated in patients with symptomatic compression group versus 33% of the placebo-treated group on the basis of degenerative spine disease and/or were ambulatory [77 ] . Two small trials compar- a congenitally narrow spinal canal. ing high-dose dexamethasone (96Ð100 mg initial IV dose) to lower doses (10Ð16 mg) did not dem- onstrate a statistically signifi cant difference in Vascular outcome between the two doses [78, 79 ] . Nevertheless, we recommend that patients with No treatment of spinal cord infarct is proven limb weakness in the setting of metastatic cord effective, and management is supportive. In compression receive an initial dose of 100 mg of patients with evidence of after dexamethasone IV followed by 16 mg daily, sub- aortic surgery, a protocol for hemodynamic aug- sequently tapered over approximately 2 weeks. mentation of the blood pressure with vasopres- Patchell and colleagues reported a random- sors and use of lumbar drainage has been ized but nonblinded trial of direct decompressive advocated. This strategy has not been validated surgery for metastatic cord compression followed in a clinical trial, but good outcomes have been by radiotherapy versus radiotherapy alone. reported with this protocol in patients presenting Patients in the surgery group were more likely to with delayed evidence of cord ischemia after sur- remain ambulatory (84% versus 57%, p 0.001) gery [ 82 ] . Similar treatment might be considered and for a longer interval (median 122 days versus in patients with early cord ischemia due to other 13 days, p 0.003) compared to the radiotherapy causes, but effi cacy has not been established. only group. In patients unable to walk prior to There are a limited number of reports of success- treatment, a higher percentage of surgically ful use of catheter guided intra-arterial throm- treated patients regained that capacity (62% ver- bolysis for cord infarction [ 83, 84 ] . The primary sus 19%, p 0.01). Patients with lymphoma were limitation of thrombolysis is the narrow window excluded as this tumor is considered highly radi- of opportunity for successful administration, osensitive, as were those who had been nonam- especially considering the diffi culties inherent in bulatory for greater than 48 h. On the basis of this determining the etiology of an acute myelopathy trial, surgery is recommended for symptomatic and excluding contraindications to thrombolysis. patients with spinal cord compression who would Dural arteriovenous fi stulae and other spinal be able to tolerate it [73 ] . cord arteriovenous malformations should be In patients who are poor surgical candidates treated with surgical or endovascular obliteration due to baseline functional status or short life of the fi stula. Improvement in functional status in expectancy, radiotherapy alone is also benefi cial these conditions can occur even when treatment in relieving pain and preserving ambulatory has been delayed for up to several years [85 ] . 254 W.F. Schmalstieg and B.G. Weinshenker

Approach to Suspected Infl ammatory In patients who stabilize or improve, assess- and Other Myelopathies ment for an underlying demyelinating disease should be conducted as described previously. Given the relative rarity of many causes of acute, Patients with features suggestive of multiple noncompressive myelopathy and the diffi cult sclerosis or a high risk of developing this condi- ethics of conducting controlled trials in patients tion should be considered for immunomodula- with devastating acute neurologic conditions, tory therapy. The institution of such therapies is there is a dearth of controlled clinical trial data not urgent and should be offered after careful for these disorders. We present a general approach consideration as to the nature of the underlying to management in which empiric, early treatment disorder, such as MS versus NMO. Patients with is instituted while additional diagnostic studies suspected MS are usually treated with interferon are conducted to refi ne the diagnosis. beta or glatiramer acetate, although other options After cord compression has been excluded by are available. Patients who meet diagnostic crite- neuroimaging, clinicians must decide whether ria for neuromyelitis optica or those with a posi- the history, clinical presentation, and imaging are tive NMO-IgG antibody are at high risk for suffi cient to defi ne a particular diagnosis. Often, additional, clinically severe episodes of demyeli- the diagnosis is not immediately apparent. In nation, and early institution of long-term immu- most of these cases, we advocate initial treatment nosuppressant therapy for patients in these with high-dose intravenous steroids (i.e., methyl- categories is indicated. Recommended therapies prednisolone 1 g IV daily for 5 days). Although include azathioprine [88 ] , mycophenolate mofetil this treatment is of unproven benefi t for many [ 89 ] , and rituximab [90 ] ; there is insuffi cient evi- causes of acute myelopathy, the treatment is dence to establish whether one of these agents is regarded to be highly effective for transverse superior as an initial treatment. myelitis of a variety of causes. Even if the diag- Patients with subacute myelopathy who are nosis of a primary infl ammatory process is incor- not improving with treatment and have no diagno- rect, corticosteroids may be benefi cial in reducing sis after a thorough search for infectious and sys- infl ammation and edema, and rarely would temic infl ammatory disorders may be candidates worsen the underlying disease process causing an for biopsy of the spinal cord; the primary goals acute myelopathy. Accordingly, most patients are to exclude malignancy and identify certain should be offered corticosteroid treatment empir- infl ammatory disorders with characteristic histol- ically when an infl ammatory myelopathy is being ogy (e.g., neurosarcoidosis). When neuroimaging considered. In cases in which infectious etiolo- is highly suggestive, empiric long-term corticos- gies are suspected, particularly bacterial and fun- teroid treatment for a presumptive diagnosis of gal infections, it is often best to defer steroid neurosarcoidosis may be appropriate without administration until the diagnosis of infection biopsy, but such decisions are diffi cult and risk can be confi rmed or refuted. missing an alternate etiology that requires differ- Patients who do not respond to initial steroid ent treatment. When a chronic infl ammatory dis- treatment and who do not have evidence of a non- order such as sarcoidosis is identifi ed, patients infl ammatory disorder, such as cord infarction, require initiation of treatment, usually with a pro- may benefi t from plasma exchange. A random- longed course of moderate dose steroids (i.e., ized, sham-controlled trial of plasma exchange in prednisone 1 mg/kg/day for six months). patients with severe attacks of acute CNS demy- elination unresponsive to high-dose steroids dem- onstrated a 42.1% rate of moderate or greater Conclusion improvement with plasmapheresis as compared to 5.9% for sham treatment [86 ] . Factors reported to The initial priority in assessment of an acute or predict a benefi cial response to plasma exchange subacute myelopathy is to obtain neuroimaging to include male sex, preservation of refl exes, and determine whether cord compression is present. early onset of treatment [87 ] . 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