00132979-201108000-00006 - mielopatías infecciosas

8/22/2019 00132979-201108000-00006 - Mielopatas Infecciosas

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Infectious

MyelopathiesJoseph R. Berger, MD, FACP, FAAN

ABSTRACT

Every genus of microorganism, as well as prions, has been associated with disease ofthe spinal cord. The spectrum of pathogens resulting in myelopathy varies with thepopulation. Myelopathy is uniquely associated with certain retroviruses, particularlyHIV type 1 and human T-cell lymphotropic virus type I, but the myelopathies that occurwith these viruses are chiefly limited to at risk populations. In the immunocompro-mised population, a diverse array of pathogens may cause spinal cord disease,especially viruses from the Herpesviridae family, most notably cytomegalovirus andvaricella-zoster virus. The prototypical myelopathy resulting from bacterial infection istabes dorsalis, but this disorder is vanishingly rare in the modern era. In developingcountries, Mycobacterium tuberculosis and schistosomiasis remain significant causesof myelopathy.

Continuum Lifelong Learning Neurol 2011;17(4):761775.

INTRODUCTION

Myelopathies consequent to an infectiousorganism are extremely diverse in their

presentations. They vary with respectto the populations most commonly af-fected, the clinical manifestations, theassociated disorders, and radiographicand laboratory features. An extensivediscussion of each of the infectiousmyelopathies is beyond the scope of thisreview, but the salient infectious myelo-pathies will be addressed by etiology.

Infectious myelopathies present invariegated manners. Those that are theconsequence of retroviruses, such asHIV, human T-cell lymphotropic virustype I (HTLV-I), and syphilis, typicallypresent in a subacutely or chronicallyprogressive manner. Associated riskfactors for the acquisition of these infec-tions often help the clinician recognizethem. Other infectious myelopathiestypically present as acute illnesses, oftenexhibit discrete sensory levels, and may

be associated with systemic features ofinfection. Fever and spinal percussion

tenderness are often observed in pa-tients with epidural abscesses. However,

the most important element to estab-

lishing the correct diagnosis is maintain-ing a high index of suspicion.

VIRAL MYELOPATHIES

A large number of viruses may causemyelitis (Table 3-1). Acute viral myelitismay present as an acute flaccid paralysis

(poliomyelitis) or as a disorder in whichlong tract involvement due to whitematter disease predominates.1 The viralinfections1 that typically present as anacute flaccid paralysis include poliovirustypes 1, 2, and 3; Coxsackievirus types Aand B; Enterovirus 71, and the Flavivi-ruses, which include West Nile virus.2

Retroviral infection with HIV and HTLVare examples of viruses that may result ina slowly progressive myelopathy in which

white matter disease predominates.

HIV Type 1

Neurologic disease is common in thesetting of HIV/AIDS. Ten percent to 20%

Address correspondenceto Dr Joseph R. Berger,740 S Limestone,Neurology DepartmentKentucky Clinic L-445,Lexington, KY 40536,[email protected].

Relationship Disclosure:Dr Berger has receivedpersonal compensation forspeaking engagements orconsulting activities with

Asphelia Pharmaceuticals,Inc., Astellas Pharma US,Inc., Bayer, EMD Serono,Inc., GlaxoSmithKline,Merck Serono, MillenniumPharmaceuticals, Inc.,Pfizer Inc., and TevaNeuroscience. Dr Bergerreceives research support

from Biogen Idec andEMD Serono, Inc.

Unlabeled Use ofProducts/InvestigationalUse Disclosure:Dr Berger reports nodisclosure.

Copyright* 2011,American Academy ofNeurology. All rightsreserved.

Review Article

761Continuum Lifelong Learning Neurol 2011;17(4):761775 www.aan.com/continuum

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.


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of individuals infected with HIV haveneurologic disorders herald their infec-tion, and ultimately more than halfdevelop some neurologic complication.

While spinal cord disease occurring in

association with AIDS has been infre-

quently observed in retrospective clinicalseries, autopsy series predating the an-tiretroviral therapy era indicate that11%3 to 22%4 have pathologic featuresof a unique spinal cord disorder first de-

scribed by Petito and colleagues.4 The

TABLE 3-1 Viral Etiologies of Myelitis

DNA RNAEnveloped Herpesviruses Togaviruses

Herpes simplex virus,types 1 and 2

Rubella virus

Varicella-zoster virusRetroviruses

Epstein-Barr virusHIV type 1

CytomegalovirusHuman T-cell lymphotropicvirus type I

Herpes simiae (B virus) Orthomyxoviruses

Poxviruses Influenza virus

Vaccinia virus Paramyxoviruses

Variola virus Measles virus

Mumps virus

Bunyaviruses

California virus

Arenaviruses

Lymphocyticchoriomeningitis virus

Rhabdoviruses

Rabies virus

Flaviviruses

West Nile virus

Tickborne encephalitis virus

Nonenveloped H epatitis B virus Picornaviruses

Coxsackievirus

Hepatitis A virus

Encephalomyocarditis virus

Echoviruses

Poliovirus types 1, 2, and 3

Other Enteroviruses

Adapted from Tyler KL, Gross RA, Cascino GD. Unusual viral causes of transverse myelitis: hepatitis A virus and

cytomegalovirus. Neurology 1986;36(6):855Y888. Copyright B1986, AAN Enterprises, Inc. All rights reserved.

Infectious Myelopathies

762 www.aan.com/continuum August 2011



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discord between clinical and patho-logic series suggests that this mye-lopathy is common but clinically un-

derrecognized. Although the clinicalpresentation of HIV-associated vacuo-lar myelopathy (Case 3-1) may overlap

with that of other myelopathies asso-ciated with HIV-1 infection (Table 3-2),the pathologic appearance is quitedistinct. Clinically, these patients fre-quently report initial paresthesia and

vague discomfort in their legs followedby leg weakness, imbalance, and gaitimpairment. In more than one-half of

patients, incontinence of bladder andbowel supervenes. Typically this myel-

opathy is seen late in the course ofHIV-1 infection. It has been described,however, as the presenting manifesta-

tion of this viral infection.6,7 Physicalexamination reveals a spastic parapare-sis in which spasticity is more prom-inent than the degree of weakness.The involvement is typically, but notalways, symmetric. Gait ataxia andlower extremity dysmetria and dyssy-nergy are seen. Although upper ex-tremity strength may be unaffectedinitially, pathologically brisk reflexes inboth upper and lower limbs are antici-

pated, unless, as is commonly the case,a superimposed peripheral neuropathy

KEY POINTS

h HIV-associated

myelopathy is

underrecognized.

h The diagnosis of

HIV-associated

myelopathy is one

of exclusion.

Case 3-1A 47-year-old man with known HIV infection of 12 years duration noteddifficulty ascending stairs in his home. He described a sense of increasingleg stiffness and in the following months developed a feeling that hislegs wanted to scissor when he walked. He was plagued by urinaryfrequency and described a sense of numbness in both feet. Ten monthsafter the onset of his initial symptoms, he began using a cane toambulate. He denied any problems with his upper extremities.Examination and self-assessment demonstrated slowing of cognition, but

this did not markedly impede his activities of daily living. He had noLhermitte sign on neck flexion and no spinal percussion tenderness.Strength and tone were normal in the upper extremities. He hadspasticity in both lower extremities with easily elicitable clonus at theankles, but lower extremity strength was normal. His gait was slow,stiff legged, and wide based. He was unable to tandem. Reflexes werebrisk in the upper extremities with bilaterally positive Hoffmann signs 3+at the knees and trace at the ankles with bilaterally positive Babinskisigns. He could not perceive a briskly struck tuning fork at the toes andexhibited a positive Romberg sign. Pinprick and temperature sensewere impaired to the midcalves. He had no sensory level to pinprickover his trunk.

A cranial MRI showed brain atrophy and multiple hyperintense signalabnormalities on T2-weighted imaging and FLAIR in deep white matter.Cervical and thoracic MRIs were normal. CSF analysis was normal. EMGand nerve conduction studies were compatible with a sensorimotorneuropathy. Laboratory studies were unrevealing, including vitamin B12level and homocysteine and methylmalonic acid levels. His CD4 count was230 cells/mm3, and his viral load was undetectable.

Comment. This man exhibits the cardinal features of HIV-associatedvacuolar myelopathy, namely a slowly progressive myelopathypredominantly involving the corticospinal tracts. As is commonly observed,he has other HIV-related neurologic problems, including cognitive deficitsand peripheral neuropathy.




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is present. Extensor plantar responsesand other features of upper motorneuron disease are observed. Sensory

examination reveals that vibratory andposition sense are disproportionatelyaffected in comparison to other sen-sory modalities. A sensory level over thetrunk should suggest an alternativediagnosis. Electrophysiologic studiesmay reveal a prolonged latency of cor-tical evoked responses following tibialnerve stimulation.

The striking pathologic findings ofHIV-associated myelopathy are loss of

myelin and microvacuolization due tointramyelin swelling that is accompaniedby lipid-laden macrophages. Axons arepreserved except in areas of marked

vacuolization (Figure 3-1), and althoughmicroglial nodules may be detected inthe spinal cord gray matter, inflamma-

tion and intranuclear viral inclusions arenot generally observed. The abnormal-ities predominate in the middle andlower thoracic cord, but the cervicalcord may be similarly affected. The lat-

eral and posterior columns are typicallyinvolved to a greater extent than theanterior columns (Figure 3-2). The pa-thology bears a strong resemblance tothat of subacute combined degenera-tion of the spinal cord.4 The patho-genesis of HIV-associated myelopathy

remains uncertain. A similar clinicopa-thologic condition has been observedin patients with cancer or other immuno-suppressive conditions in the absenceof HIV infection.8

The diagnosis of HIV-associated mye-

lopathy remains one of exclusion becausemyelopathy in HIV infection has beenassociated with many other etiologies(Table 3-1). Among the myelopathiesthat have been observed is an acutemyelitis occurring at the time of HIVseroconversion.9 Whether this is theconsequence of HIV infection of thecord or an autoimmune disorder trig-gered by the infection remains uncertain.

KEY POINT

h HIV-associated

myelopathy is often

accompanied by HIV

dementia and

HIV-associated

peripheral

neuropathy.

TABLE 3-2 Myelopathies

Associated WithHIV Infection

b Infectious Etiologies

Viral

Primary HIV infection

Acute transient myelopathyoccurring at the time ofseroconversion

Chronic progressivemyelopathy (HIV-associated

vacuolar myelopathy)Human T-cell lymphotropicvirus type I

Cytomegalovirus

Herpes simplex virus

Herpes zoster virus

Bacterial

Epidural abscess

Mycobacterium tuberculosis

Treponema pallidum

Cryptococcus neoformans

Others

Parasitic

Toxoplasma gondii

b Noninfectious Etiologies

Multiple sclerosisYlike illness

Tumors5

Plasmacytoma

Spinal cord astrocytomas

Others

Epidural hemorrhage secondaryto thrombocytopenia

Vascular injury secondary tovasculitis

Adapted from Berger JR. Medical myelopathies. In:

Herkowitz HN, Garfin SR, Eismont FJ, et al, editors.

Rothman Simeone: the spine. 5th ed. Philadelphia:

Saunders, 2006:795Y813. Copyright B2006, with

permission from Elsevier.





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Typically, MRI of the spinal cord isunremarkable, but on rare occasionshyperintense signal abnormalities onT2-weighted imaging may be observedin the affected posterior and lateral

columns.10,11 This finding is helpful inexcluding other potential etiologiessuch as lymphoma, abscess, or epidurallipomatosis. Myelography seldom addsto the diagnostic evaluation. CSF analy-

sis is important to rule out other po-tential pathogens and should includeroutine bacterial and fungal cultures andcryptococcal antigen as well as studiesfor cytomegalovirus (CMV), herpes sim-plex virus (HSV) type 1 and 2, and

varicella-zoster virus (VZV), among otherpathogens. No established therapy forHIV-associated myelopathy exists; anti-retroviral therapy does not affect thenatural history of the disorder.12 Thedisorder typically plateaus eventually.

Human T-cell LymphotropicVirus Type I

HTLV-I remains relatively rare in theUnited States; a study of volunteer blooddonors by the American Red Cross re-

vealed a seropositivity rate of 0.025%.13

However, its seroprevalence rate amongparenteral drug abusers and commercialsex workers is 25% in some communi-ties.14 Transmission of HTLV-I by blood

transfusion associated with myelopathyis well confirmed. The myelopathy thatoccurs with HTLV-I has been referred toas tropical spastic paraparesis (TSP) orHTLV-IYassociated myelopathy (HAM).Clinically, the disorder is typically aslowly progressive myelopathy develop-ing over years with symptoms of spasticlower extremity weakness and a spasticbladder predominating. Sensory abnor-

malities including paresthesia, pain, andnumbness may also be observed. Amore rapid course, with progression tothe patient becoming wheelchair de-pendent occurring over weeks tomonths, has been reported in as many

FIGURE 3-1 Microvacuolization of the posterior columnsof the spinal cord in HIV-associatedvacuolar myelopathy.

FIGURE 3-2 Demyelination in posterior, lateral, andanterior columns of the spinal cord inHIV-associated vacuolar myelopathy.




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as 8% of cases15 and appears to be morecommon in those infected by bloodtransfusion.16 It is estimated that one in

250 individuals infected with HTLV-I willdevelop HAM/TSP.17 The major patho-logic feature is chronic inflammation ofthe spinal cord characterized by peri-

vascular inflammation, macrophage in-filtration, and astrogliosis coupled withlong tract degeneration and demyeli-nation chiefly affecting the pyramidal,spinocerebellar, and spinothalamictracts extending from the upper cervicalcord to the lumbar regions.18 Various

therapeutic modalities have been used,including immunomodulatory and anti-viral strategies, but no ideal therapy hasbeen identified yet.19 As with HIV-1 in-fection, a peripheral neuropathy may beassociated with this infection.

HTLV-II, a related type C retrovirus,may rarely result in a myelopathy similarto HAM/TSP.20 The epidemiology of this

virus is somewhat different than that ofHTLV-I because the populations princi-pally affected are American Indians and

parenteral drug abusers; nonetheless, itsmode of transmission parallels that ofHTLV-I and HIV.

Herpesviruses

Immunosuppression frequently predis-poses patients to the development ofmyelopathy resulting from herpesvi-ruses. After initial infection, the VZVremains latent within the dorsal rootganglia. Following reactivation, it spreadscentrifugally along the correspondingnerves resulting in a severely painful,blistering dermatomal eruption referredto as shingles. On rare occasions whenthe thoracic dermatomes are involved,the virus may spread centripetally andresult in a necrotizing myelopathy.21 Inthe immunocompetent host, VZV mye-litis occurs within 1 to 2 weeks of theappearance of the dermatomal rash.

Very rarely, it may occur in the absence

of an observed rash. The myelitis occursat the level of the affected dermatomeand results in paraparesis. In contrast,

VZV myelopathy often occurs insidi-ously and progresses slowly in theimmunosuppressed host. The closetemporal relationship to the rash sug-gests the diagnosis, which is confirmedby the presence of VZV DNA by PCR inthe CSF or VZV antibody in the CSF. Inthese cases, treatment with IV acyclovir(10 mg/kg every 8 hours) should beinitiated.

In rare instances, usually with primary

infection, HSV-2, the etiology of genitalherpes, may cause a sacral radiculitis22 oran ascending myelitis.23 These neuro-logic complications are rarely observed

with recurrent HSV-2.24 Epstein-Barrvirus,25,26 the etiologic agent of infec-tious mononucleosis, and CMV27 mayalso result in a transverse myelitis at thetime of primary infection.

Intheimmunocompromisedhost,par-ticularly in the setting of HIV infection,CMV may result in a transverse myelitis

or a polyradiculomyelitis. In exceptionalcases, it may be observed in immuno-logically healthy individuals.28 CMVtransverse myelitis may present withparaplegia, tetraplegia, urinary retention,and sensory deficits, whereas CMV poly-radiculomyelitis typically presents as aprogressive ascending hypotonic weak-ness with hyporeflexia, paresthesia, hyp-esthesia, and early urinary retention.29

MRI findings may include a thickenedcauda equina and enhancement of theleptomeninges, dorsal roots, and caudaequina. A mixed pleocytosis or polymor-phonuclear cell predominance on CSFanalysis may suggest the diagnosis,

which can be confirmed by PCR. Whilefew controlled trials have been reported,ganciclovir is recommended in combi-

nation with foscarnet if the patient hasbeen previously treated or exhibits dis-ease progression.29 Cidofovir also hasactivity against CMV.

KEY POINTS

h Many herpesviruses

may result in a

transverse myelitis.

h The presence of a

polymorphonuclear

pleocytosis in the

appropriate clinical

context suggests

cytomegalovirus

polyradiculoneuritis.





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Enteroviruses

Enteroviruses, particularly poliovirus,can affect the spinal cord. Fortunately,

effective vaccination has made this ill-ness very rare in the Western world. Inthe United States in the recent past,approximately 10 to 15 cases of poliohave been reported yearly; most of these

were vaccine associated, although sev-eral occurred in immigrants. Paralyticpoliomyelitis is a rare complication ofpoliovirus infection (1% to 2%); mostinfections result in inapparent infection(90% to 95%) or a minor illness with

mild systemic symptoms (5% to 10%).The poliovirus has a unique predilectionto affect the anterior horn cells of thespinal cord and therefore results in alower motor neuron type of weakness,

which is characterized by a flaccid weak-

ness with wasting, fasciculations, andareflexia. Weakness may arise rapidlyover a 48-hour period or occur in adelayed fashion over weeks from thetime of infection. Sensory and sphincterfunctions are spared. Age of acquisition

of the infection determines the risk ofparalysis. Infants are rarely paralyzed,childrens risks are intermediate, andadults are much more frequently para-lyzed. Other Enteroviruses, includingCoxsackieviruses and echoviruses, mayalso result in myelitis.

West Nile Virus

West Nile virus is a mosquitoborneFlavivirus first recognized in the Westernhemisphere in 1999 when 59 infectedpersons in New York City were identi-fied.30 Following its introduction, the

virus rapidly spread widely throughoutthe United States.31 Approximately 5%of patients with symptomatic WestNile virus infection (fewer than 1 in 5infected patients display symptoms)develop severe neurologic disease, in-cluding meninigitis, encephalitis, a polio-myelitis-like acute flaccid paralysis, andother neurologic manifestations.32 The

flaccid weakness has been attributed toloss of anterior horn cells.33 It typicallymanifests during the subacute phase of

the illness and peaks in 2 to 8 days. Theweakness affects one or more limbs andis associated with flaccid tone andhyporeflexia or areflexia. Mechanical

ventilation may be required because ofrespiratory muscle weakness. MRI oftenshows cauda equina enhancement andparenchymal spinal cord and leptome-ningeal signal changes, and the CSFshows a neutrophilic leukocytosis.33

Pathologic features include perivascular

chronic inflammation and anterior horncell dropout.33

Other Viruses

While viruses may result in an acutemyelitis, they may also trigger an auto-immune transverse myelitis. Distinguish-ing an infectious from a parainfectiousdisorder can be difficult. It has beenestimated that as many as 20% to 40% ofall patients with transverse myelitis havea preceding or concurrent viral infection.

Even in instances of neuromyelitisoptica, the consequence of an antibodyto aquaporin 4, viral as well bacterialpathogens have been considered poten-tial precipitants.34

BACTERIAL MYELOPATHIESSyphilis

CNS invasion by Treponema pallidumgenerally occurs within the first year ofsyphilitic infection, and the frequency ofabnormal CSF results in untreated pa-tients with primary or secondary syph-ilis varies between 13.9% and 70%.Despite the high frequency of CNSinvasion, only about 5% of patients withsyphilis will develop clinical neurosyphi-lis if left untreated. At one time, syph-ilitic spinal cord disease, particularlytabes dorsalis, was among the mostcommon expressions of neurosyphilisand was 10 times more common thanother forms of spinal syphilis. Syphilitic




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meningomyelitis and spinal vascularsyphilis were the second and third mostcommon forms of spinal syphilis, re-

spectively. Spinal syphilis rarely occursin the absence of syphilitic involvementat other sites of the neuraxis. It hasbeen estimated that the incidence ofpure spinal syphilis is approximatelyone-fifth the incidence of cerebrospinalsyphilis.

Syphilis may affect the spinal cord in avariety of fashions.35 The pathology maybe predominantly meningovascular orparenchymatous in nature. Gummas

may grow within the substance of thecord or compress the cord by growthfrom the surrounding meninges. Theclinical picture of spinal cord compres-sion in syphilis may also arise as a resultof hypertrophic pachymeningitis or ver-tebral lesions resulting from syphiliticosteitis.

Tabes dorsalis. Tabes dorsalis(Case 3-2) is the prototypical spinalcord disorder associated with syphilis.Currently, tabes dorsalis accounts for no

more than 5% of neurosyphilis. Thelatency from infection to the develop-ment of tabes averages 10 to 15 years but

varies between 2 and 38 years. As manyas 65% of patients recall a history of

venereal infection. The disorder pre-dominantly appears in the fourth andfifth decade, with an average age of on-set of 40 years. Men are affected 10 timesmore often than women. Tabes dorsalis

has been observed, albeit rarely, as aconsequence of congenital infection.

The clinical course of tabes has his-torically been divided into three separate

phases: preataxic, ataxic, and terminal.The preataxic phase begins insidiouslyand lasts on average 3 years. Subjective

symptoms predominate, including theclassic crisis, a severe lancinating pain.The painful crisis heralds the disorder in70% of patients and is ultimately presentin 90%. Impotence and sphincter dys-function may be early features. Physicalexamination typically shows absent

reflexes, sensory impairment, positiveRomberg sign, and Argyll Robertson

Case 3-2A 54-year-old woman had noted severe painful spasms affecting her abdomen and groin 3 monthsprior to examination. The paroxysms of pain had no known precipitants and persisted despite the useof a variety of analgesic medications. She also reported that her legs were weak and heavy and thatshe had recently begun using a laxative to induce bowel movements. She had recently moved toKentucky from New York City to assist her 30-year-old daughter in caring for her child. She reportedthat at the time of her daughters birth she had been addicted to crack cocaine and in prenatal testinghad been Venereal Disease Research Laboratory (VDRL) positive. She recalls receiving one injection ofpenicillin at that time. No lumbar punctures were performed.

On examination, she had irregular, small pupils that reacted to light and accommodation. Lower

extremity strength was graded as 4+/5 and the legs were spastic, but knee and ankle jerks could notbe elicited. Plantar responses were extensor bilaterally. Her gait was spastic and ataxic and she couldnot tandem. Her gait had a slapping quality, but no footdrop was evident. Vibratory sense wasseverely impaired to the knees and she could not sense toe movement well in either foot. Rombergtest was positive.

Serum VDRL was positive at 1:64 and microhemagglutination assay was positive, providing serologicevidence of syphilis. An MRI of the cervical and thoracic cord was unremarkable. CSF analysis showed9 lymphocytes/mm3, protein of 72 mg/dL, and positive VDRL. Treatment with IV penicillin wasadministered for tabes dorsalis.

Comment. This patient had tabes dorsalis with a 30-year hiatus from the time of inadequatetreatment for syphilis.





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pupils. Hypalgesia, hyperalgesia, allo-cheiria (sensation of a stimulus in onelimb is perceived in another), pallesthe-

sia (sensation of mechanical vibration), adelay in pain perception of up to 15seconds following the application of thestimulus, and an aftersensation lasting upto 30 seconds may all be reported. Lossof deep pain sensation is evidenced bydiminished sensation to the applicationof pressure to various anatomic sites: theulnar nerve (Biernacki sign), the Achillestendon (Abadie sign), and the testicle(Pitres sign). Despite the loss of pain,

superficial tactile sensation is generallywell preserved early in the course of thedisorder.

The ataxic phase lasts between 2 and10 years and is characterized by severe,predominantly lower limb, ataxia. Gen-erally the tabetic pains worsen duringthis period. Arthropathy develops in 5%to 10% of patients because of recurrenttraumatic injury resulting from loss ofdeep pain sensation. Proprioceptive lossthat causes a slapping gait predisposes

the knee joint to this injury. The tarsaljoints, hip, ankle, and spine, as well asother joints, can be similarly involved.

The terminal phase also has an aver-age duration of between 2 and 10 years.Cachexia, leg stiffness and paralysis, andautonomic dysfunction with obstinateconstipation and bladder incontinenceare prominent. Sepsis from decubitusinfections and pyelonephritis is fre-quently the terminal event.

The classic signs of tabes dorsalis areabsentin approximately 50% of patients inthe early stages of the disease because asmany as 10% of tabes dorsalis casesremain atypical throughout their course.Other neurosyphilitic manifestations arefrequently observed with tabes dorsalis,including generalparesis, syphiliticmenin-gomyelitis, and spinal cord gummas.

The posterior spinal roots and poste-rior spinal columns of the lower spinalcord are predominantly involved in

tabes dorsalis, and pathologic examina-tion reveals leptomeningitis with de-myelination of the dorsal columns, root

entry zone, and Lissauer tract. Posteriorroots are destroyed and replaced byfibrosis.

Syphilitic meningomyelitis. In the

present era, syphilitic meningomyelitisoccurs more frequently than tabes dor-

salis. Syphilitic meningomyelitis affectspredominantly men between the ages of

25 and 40 years. The latency from theonset of the infection to the onset of

symptoms averages 6 years (range 1 to

30 years).

36

The first symptoms are asense of heaviness in the legs, generallybilaterally. Paresthesia and fleeting pains

may be reported, with little apparent sen-sory disturbance on examination. Thesymptom complex mirrors that of cer-

vical spondylotic myelopathy. Precipitate

frequency, hesitancy, and impotence arecommon. The predominant finding onneurologic examination is a spastic weak-ness in the extremities, especially thelower extremities. Muscle bulk is pre-

served, and muscle stretch reflexes areexaggerated with positive Babinskisigns. Sensory loss is slight. Occasionallya Brown-Sequard syndrome, significantamyotrophy, or a clinical picture of atransverse myelitis may complicatesyphilitic meningomyelitis. Pathologicexamination reveals thickened, inflamedmeninges predominating in the cervicalregion, with involvement of the periph-ery of the spinal cord, especially the lat-eral columns. Vascular involvement ofthe cord by both Heubner endarteritis,a syphilitic medium-sized vessel vasculi-tis, and Nissl-Alzheimer endarteritis, asyphilitic small vessel vasculitis, is seen.

Other forms of spinal syphilis. Awide variety of other syphilitic spinalcord abnormalities can be found in

the literature, including hypertrophicpachymeningitis, gummas of the spinalcord, spinal cord compression fromspinal gummas, syphilitic osteitis (or

KEY POINT

h Syphilitic meningomyelitis

is more common than

tabes dorsalis.




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syphilitic aortitis), and spinal cord in-farction from syphilitic vasculitis.

The recommended treatment of spi-

nal cord syphilis is the same as that ofother forms of neurosyphilis, namely 12to 24 million units of aqueous penicillindaily in divided doses administered every4 hours for 10 to 14 days.37 Othertreatment regimens38 using doxycycline,ceftriaxone, or erythromycin may beconsidered if the patient is intolerantof penicillin. However, these treatmentregimens are not well established intreating symptomatic neurosyphilis.

Tuberculosis

Neurologic complications of Mycobacte-rium tuberculosis remain common insome parts of the world and should al-

ways be considered in individuals whohave emigrated from these regions. It isestimated that 10 to 15 million peopleare infected with M. tuberculosis in theUnited States. The most common causeof myelopathy with tuberculosis arisesfrom skeletal involvement, namely Pott

disease or tuberculous spondylitis,which accounts for one-half of all skele-tal tuberculosis and develops in less than1% of all infected persons.39 The myco-bacteria spread to the vertebrae viablood, lymph, or direct contiguity fromthe lung. Symptoms and signs of spinalcord involvement develop slowly and in-sidiously, often without any systemic fea-tures to suggest tuberculosis. Back painpredominates in most patients. The char-acteristic roentgenographic defect is an-

terior wedging of two adjacent vertebraewith loss of the intervening disk space.The spine is enveloped by pus extrudinganteriorly from the affected vertebrae.Myelopathy typically results from pres-sure on the anterior spinal cord bycaseous or granulating tissue, inflamma-tory thrombosis of the anterior spinalartery, or injury to the cord from spinalinstability. Complete spinal cord tran-section may result from the latter insult.

Myelopathy occurring in associationwith tuberculous infection may alsooccur as a consequence of intramedul-

lary tuberculomas, intradural tuberculo-mas, and arachnoiditis that may beunassociated with bony lesions.40 Inone study of spinal tuberculosis,41 neu-rologic deficits were seen in 54% ofpatients with bony tuberculous lesions,39% of patients with intraspinal granulo-matous tissue occurring in the absenceof bony lesions, and 7% of patients withintraspinal tuberculomas.

A high index of suspicion for tuber-

culous myelopathy is required. In onestudy, only 41% of patients exhibited apositive purified protein derivative test.39

Therapy of patients with spinal tuber-culosis requires at least 12 months ofantibiotic treatment as well as surgicaldecompression in the presence of neu-rologic abnormalities.41 In the settingof intraspinal granulomatous disease

without significant bony destruction,laminectomy and debridement is ade-quate41; however, more aggressive ther-

apy is warranted when vertebral bodiesare involved. A two-stage procedure com-prised of posterior instrumental stabi-lization followed by anterior radicaldecompression permits earlier mobiliza-tion after neurologic recovery,42 althoughcomplications are common.43 Reports ofthe frequency of neurologic recovery withspinal tuberculosis vary, but functionalrecovery rates as high as 90% have beenreported.44 Patients with thoracic lesions

with severe neurologic deficits show theleast improvement, while patients withlumbar disease have the best outcomes.44

Other Forms of BacterialMyelopathy

A number of other bacterial infectionshave been associated with myelitis.On rare occasions, the spinal cordmay be seeded by bacteria leading toa suppurative myelitis with abscess for-mation. In a review by Dutton and





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Alexander,45 direct spread from adjacentinfections was most commonly ob-served; however, hematogenous dissem-

ination from endocarditis, pulmonaryinfections, and other sites was also fre-quently observed. Staphylococci, Strep-tococci, Escherichia coli, and Nocardiaare among the organisms that have beenisolated in these cases. Catscratch dis-ease resulting from Bartonella henselaehas been reported to cause a myelitis

with Brown-Sequard syndrome.46 In ad-dition to the typical meningoradicu-litis and cranial neuropathies observed

with Lyme disease, the treponemal in-fection with Borrelia burgdorferi, amyelopathy,47 and meningomyelitis48

may also occur. Rarely, Whipple diseasedue to Tropheryma whippelii can alsocause a myelopathy.49,50

Myelopathies seen in association withbacterial infection may be parainfectious.The transverse myelitis that accompaniesa bacterial infection is similar clinically andpathologically to that following viral infec-tion or vaccination. Among the reported

potential causes51,52

are scarlet fever,pertussis, whooping cough, Mycoplasmapneumonia, and pneumococcal pneumo-nia, but it is likely that transverse myelitismay follow any bacterial infection.

FUNGAL MYELOPATHIES

Isolated fungal disease of the spinalcord is rare. Certain fungi (Blastomyces,Coccidiodes, and Aspergillus) may in-

vade the spinal epidural space. Gener-ally, the spinal cord is compromised bylesions arising from a vertebral osteomye-litic focus or by those extending throughthe intervertebral foramina. Certain fungi,such as Cryptococcus neoformans, re-sult in granulomatous meningitis, whichmay lead to intraspinal or extraduralgranulomas that can compromise thespinal cord. Alternatively, these organ-isms can lead to spinal cord infarctionas a result of the associated meningo-

vascular inflammation. Aspergillosis is

generally observed only in patients whoare immunosuppressed, with leukemiaand lymphoma being common predis-

posing illnesses. Aspergillosis has beenreported to affect the spinal cord inseveral different fashions, including bycompromise of the blood supply occur-ring in association with fungal endar-teritis, by direct parenchymal infiltrationof the spinal cord, or by cord compres-

sion from osteomyelitis, paravertebralmass,53 and epidural abscess.54 Excep-tional case reports of myelopathy fromother fungi can be found, including

Candida, Histoplasma capsulatum,Pseudallescheria boydii , Cladospo-rium trichoides, and paracoccidomy-cosis, among others.

PARASITIC MYELOPATHIES

On a global scale, Schistosoma,55 partic-ularly S. haematobium and S. mansoni,represents one of the most commoncauses of infectious myelopathy. Theseorganisms are only seen in certain geo-graphic regions, namely the Far East,

South America, and Africa. A history oftravel to these regions and swimming orbathing in fresh water contaminated

with the cercariae that are released fromcertain aquatic snails may suggest the

diagnosis. The disease results from granu-lomatous involvement, typically of thelower spinal cord. The presentation maybe acute or subacute. Lower limb pain and

weakness, sensory impairment, and blad-der and bowel dysfunction are coupled

with MRI features that suggest an inflam-matory myelopathy. The CSF exhibits aninflammatory pattern with or withouteosinophils. Early diagnosis and treatmentare important for a good outcome.56

Hydatid disease, which results fromthe larval form of the canine tapeworm,Echinococcus granulosus, may causespinal intramedullary cysts or compressthe spinal cord and roots because ofbone invasion. The latter chiefly occursin the lower thoracic region.

KEY POINTS

h Bacterial and viral

infections may each

serve as a trigger

for autoimmune

transverse myelitis.

h Schistosomiasis should

always be considered in

those individuals with a

lower cord myelitis who

have traveled to regions

where the parasite

is endemic.




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Cysticercosis is the result of infectionwith the larval form of pork tapeworm,Taenia solium. It is endemic in China,

southeast Asia, India, sub-SaharanAfrica, and Latin America. Spinal cordinvolvement may complicate as manyas 5% of cases, although the brain is thepreferred site in the CNS. Cysticercosismost frequently infiltrates the subar-achnoid space, but intramedullary fluid-

filled cysts are also observed. A slowlyprogressive myelopathy implicating alesion in the cervical or thoracic spinal

cord is the typical mode of presen-tation for these lesions. Therapy withalbendazole may be effective in eradi-cating the live parasite.

Paragonimiases, a lung fluke acquiredby eating undercooked freshwater crabs,occurs chiefly in China but may be seenin other parts of the world. Spinal corddisease results from extradural, or morerarely, intradural granuloma formation.Angiostrongylus cantonensis, the mostcommon cause of eosinophilic menin-

gitis and meningoencephalitis in theworld, has also been reported to causespinal cord disease.57 In patients with

AIDS, toxoplasmosis has been reportedin rare instances to cause an abscess ofthe spinal cord.

EPIDURAL ABSCESSES

Spinal epidural abscess may present as asurgical emergency evolving rapidlyover several days or may arise more

Case 3-3A 72-year-old man with diabetes presented with fever, low back pain, a

sense of lower extremity weakness, and difficulty urinating and defecating3 weeks after undergoing prostate surgery. He stated that the back painstarted approximately 10 days ago and was accompanied by fever, chills,and sweats. He attributed the problem to the flu and treated himself withantipyretics and analgesics. A sense of weak knees and difficulty withsphincter function that developed over the preceding 24 hours promptedhim to seek medical attention. Examination was remarkable for atemperature of 38.3-C (101-F), percussion tenderness over the middleportion of his lower spine, 4/5 strength in the quadriceps and footdorsiflexors, and depressed knee and ankle jerks. Sensory perception wasimpaired to vibratory sense in distal lower extremities. An MRI showed anepidural abscess extending from L2 to L5. He recovered completelyfollowing surgical evacuation and antibiotic administration. Enterococcus

was cultured from the surgically evacuated pus.Comment. Infectious myelopathies are often diagnostically challenging.

They can present in myriad fashions, and their onset may be acute,subacute, or chronic. Pain, weakness, spasticity, sensory symptoms, orsphincter disturbances may be the dominant feature. A high index ofsuspicion is required by the clinician. Clues to the correct diagnosis areoften, but not invariably, present in the history and physical examination.

FIGURE 3-3 Epidural abscess. This midthoracic epiduralabscess shows extension over several vertebrallevels on gadolinium-enhanced MRI.





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indolently. Staphylococcus aureus isthe etiologic agent in over 50% of acutespinal epidural abscesses, although a

broad spectrum of other organismsmay be implicated.58 Infection mayspread directly from a focus of osteo-myelitis or hematogenously from adistant site, such as skin furuncles orpulmonary infections. Trauma to theback, typically very minor in nature, hasbeen reported by as many as one-thirdof individuals developing spinal epi-dural abscess (Case 3-3).59 A high de-gree of suspicion for spinal epidural

abscess should be maintained when IVdrug abusers present with fever andback pain. Patients with an acute epi-dural abscess typically have more sys-temic illness than those with vertebralosteomyelitis.60 The definitive diagnosisis based on identification of the offend-ing organism from pus from the ab-scess, although blood cultures arepositive in 60% of cases.60 MRI is thediagnostic modality of choice and gado-linium administration increases diag-

nostic sensitivity (Figure 3-3).

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