infectious myelopathy

INFECTIOUS MYELOPATHY

DR.SARATH MENON.R, MD(Med.),DNB(Med.),MNAMS

DM RESIDENT,

DEPT. OF NEUROSCIENCES

AIMS,KOCHI.

INTRODUCTION

Infections and secondary inflammatory changes

play an important role

Direct neuronal invasion

Molecular mimicry

Myelopathy- spinal cord dysfunction of any

etiology ,intrinsic or extrinsic

PRESENTATION

Acute transverse myelitis

Acute flaccid paralysis- AHC, motor roots

APPROACH

History & physical examinations

Tempo of illness

Exposure

Demographic- endemicity

Host immune status

Ancillary test

Diagnosis & Rx

PARAINFECTIOUS ETIOLOGY

30 -60% infective myelopathy preceeded by

systemic infectious process

Molecular mimicry-

cross reactivity with host antigen in spinal cord

Usually 2-4 wks after infection

Dx- CSF IgG index,OCB

Serology & specific antigen in csf /serum

Rx-

Iv steroid

Refractory cases- IVIG,cyclophosphamide or

rituximab.

CAUSATIVE AGENTS

Viral

Bacterial

Parasitic

Fungal

RETRO VIRUSES- HIV

CNS – lymphocytes,microglia

Crosses BBB

Neurotoxicity by viral proteins

Chronic pro inflammatory state

CD4 < 200- HIV – vacuolar myelopathy

HIV –VACUOLAR MYELOPATHY

Slow progressive,painless myelopathy

LL weakness,gait difficulties,spasticity,erectile

dysfunction,mild paresthesia

Urge incontinence,urgency- later

Impaired proprioception

LL disproportionately affected.

Diagnosis of exclusion in HIV + pts.

Acute presentation,spinal level ,prominent pain ,UL

prominently involved- alternate diagnosis

D/D- oppurtunistic infection,neoplasms,VB12 def.

Imaging-

Usually normal.

Spinal cord atrophy

Findings similar SACD

Microscopy-

spongy,vacuolation of myelin

lipid laden macrophages

Rx-

HAART reduced incidence

No response to ART,B12 or IVIG,steroids

13

HIV-related myelopathy. Vacuolar changes

are evident in the lateral and posterior

columns of the thoracic spinal cord.

HTLV-1 (HAM/TSP)

4% HTLV-1 will develop

Female predominance

CD8 + Tcell neurotoxicity or molecular mimicry

Clinical features

- insidious ,slow progression

- LL spasticity

- prominent bladder/bowel involvement

- UL weakness insignificant

Diagnosis

- Clinical,demographic,serology

- csf- lymphocytic pleocytosis,OCB+

Confirmation- Western blot

PCR- peripheral blood- distinction & viral load

Imaging

-Focal T2 Hyperintensity in lower cervical cord

-contrast enhancement+

- close d/d to MS

- cervical/thoracic cord atrophy

TREATMENT

No effective clinical trials to date.

Steroids

INF-alpha, cyclosporine,azathioprine- effective

early – limited evidence

HAART

ENTEROVIRUSES

Ubiquitous RNA virus

Produce acute flaccid paralysis

Poliovirus

- AHC affection

- Subsaharan Africa,middle east,Indian subcontinent

- Fever,menigismus,asymmetric flaccid paralysis of LL

proximal > distal over 2 days

- Post polio syndrome

- Slow progressive recrudescence

- Severity of initial disease

ENTEROVIRUS 71- EV 71

AFP similar to polio

Asia –pacific

Children

Fever ,rash – paralysis over 3-5 days

Mri= T2 hyperintensity in lower brainstem,cerebellum

CSF- lymphocytic pleocytosis

No specific rx

IVIG -tried

FLAVIVIRUS- WEST NILE VIRUS

Polio-like paralysis

Mosquito vector

Fever—myelitis—over 2-8 days

Flaccid paralysis, respiratory,bladder +

Risk factor

Age > 50 yrs,immunosuppression

WNV – directly affect AHC

21

West Nile virus encephalomyelitis.

A, Crosssection

of the cervical spinal cord showing

anterior horn–predominant inflammatory

infiltrate (arrows).

.

B, Higher magnification shows

destruction of anterior horn neurons with

perivascular

lymphocytic cuffing seen at lower right;

arrow indicates a

remaining neuron

Diagnosis

-peripheral leukocytosis,thrombocytopenia,transaminitis

CSF- PMN /mononclear pleocytosis,elev.protein,sug-nl

- IgM –sensitive/specific

- serology

-Spinal cord imaging-normal

- Rx

- Supportive,no specific

- anecdotal- steroids

RABIES

2/3rd –furious/encephalitic,1/3rd –dumb/paralytic

Paralytic-

GBS like presentation—encephalopathy—death

Considered in exposure to animal bite esp.bat

PCR- Skin biopsy from nape of neck-specific

Serology

Virus amplification from skin,saliva,CSF

Supportive rx.

Prophylaxis

HERPES VIRUSES-HSV1&2

HSV1 &2 – myelitis

HSV-2 related myelitis-adults

Elsberg syndrome-reactivation of HSV-2

inflammation in dorsal roots + spinal cord = radiculomyelitis

C/f :

- subacute lower extremity weakness may ascend

- Numbness or tingling in lumbosacral dermatome

- Urinary retention

Acute necrotising myelopathy- severe form seen in

immunocompromised

Flaccid paraplegia+ areflexia

Diagnosis

- CSF-lymphocytic pleocytosis with raised protein

Necrotizing myelitis- PMN leukocytosis

CSF-PCR amplification of DNA

Imaging

- Spinal cord edema

- T2 hyperintensity+CE of radicular roots & cord

Rx

- Iv acyclovir x 14 days f/b oral acyclovir /valacyclovir

- Steroids –role uncertain

- Complete recovery is posssible

- 20% cases,recur

VZV

Myeloradiculitis on reactivation-immunocompromised

Necrotising vasculitis + demyelination

Zoster preceeds, cases with no rash

Asymmetric paraparesis + sensory loss- days to wks

CSF-

Mononuclear pleocytosis ,elevated protein

Anti-VZV IgM assay in CSF-sensitive

PCR- rapid

Imaging- T2 hyperintense in cord = dermatome

Rx

iv acyclovir + steroids

CMV

Imunocompromised- HIV – CD4<100cells/microL

Lumbosacral polyradiculomyelitis-

supf.meningitis-> nerve roots & spinal cord

Necrotizing myelitis

Imaging-

cord edema+root edema+ CE

meningeal thickening+clumping of roots

CSF-

PMN pleocytosis+elev.protein+ low sugar

Rx

IV ganciclovir+ foscarnet

Poor prognosis

EBV

Children / young adults

Immunocompromised –transplant

Spectrum – aseptic meningitis

meningoencephalitis

cranial/peripheral neuritis

GBS & myelitis

Myelitis- 2-3 weeks after primary infection

flaccid paraparesis,sensory level,bladder+

CSF-

mononuclear pleocytosis,elev.protein,sugar-nl

Serology –EBV DNA

CSF-EBV DNA PCR

Imaging-

T2hyperintensity+ce+nerve thickening

Rx

- Acyclovir-little effect on clinical course

- steroids

BACTERIAL- SYPHILIS

Meningovascular-cord infraction-endarteritis-rare

Tabes Dorsalis

Post antibiotic era- less incidence

c/f-

subacute/chronic – sensory ataxia+

loss of vibration,joint position

lancinating pain+

hyperreflexia,charcot joint,AR pupil

Imaging-

cord atrophy

non enhancing T2 hyperintensity-posterior cord

SYPHILIS-OTHER FORMS OF MYELOPATHY

Hypertrophic pachymeningitis

Spinal cord Gumma

AHC

Syingomelia

Aortic aneurysm –sec AHC

Charcot vertebra-cord compression

SYHILITIC MENINGOMYELITIS

Current era, most common spinal cord d/s

Men-25-40 yrs

Avg.6yr after infection

Progressive spastic ,asymmetric paraparesis

Imaging-

T2 hyperintensity central cord +CE

DIAGNOSIS & RX

Peripheral serology+ CSF evaluation

VDRL & RPR- sensitive in early

TP-FAB- specific

CSF- mild inflammatory

- VDRL,FAB

Rx

Inj.Penicillin aqueous -12-24 mu q4h x 10-14 days

Jarisch-Herxheimer reaction

(iv steriods-premptively)

LYME DISEASE

Ixodes tick-endemic North America,Europe,Asia

Erythema migricans-initial lesion

Classic triad- facial palsy,aseptic meningitis,painful

radiculitis

Bannworth synd.-acute transverse myelitis-painful

Chronic,progressive myelopathy- other form

Diagnosis

-clinical history

-ELISA/Western blot

-CSf- Lyme specific IgM

-MRI- T2 hyperintensity+CE-root,meninges

Rx-

IV Ceftriaxone-14-28 days+ steroids

TUBERCULOSIS

MC myelopathy- Pott’s disease

Vertebral venous system

Anterior segment of thoracic & lumbar spine-collapse

Other forms-

- intramedullary/intradural tuberculomas-

(S/A myelopathic symptoms).

- granulomatous myeloradiculitis-

(rapid progressive rad.pain,paresthesia,flaccid

weakness,babinski+ ,bladder+)

- spinal artery vasculitis+ cord infarction

- ADEM

- Cord compression- vertebre,granulating tissue

DIAGNOSIS

CSF- lymphocytic pleocytosis,low sugar,very high protein

AFB,TB cultures

Mantaux test- + in 40%

MRI (Pott’s)–T1 hypo +T2 hyper +CE

Vertebre collapse+ cord compression

Granulomatous myeloradiculitis-

CE+ meningeal thickening +spinal roots

Tuberculomas-

CE+ T1 hypointense ring +T2 hyperintense central

RX

2 month HRZE/S+ 7-10 Month HR

Vertebral disease- surgical option

Lumbar disease-better prognosis

PYOGENIC BACTERIA

Vertebral osteomyelitis- collapse+ epidural abscess

Intramedullary abscess- hematogenous seeding+

Epidural abscess

- osteomyelitis- hematogenous

- Local soft tissue,viscera,instrumentation ant.epidural

- Direct seeding- post.epidural

- Risk factors+

- Thoracic +

C/F-

- Focal back pain+ muscle spasms

- Fever

- MC- S.aureus > Streptococcus > GNB

Diagnosis-

ESR,CRP

Blood culture-+ 60%

Imaging

LP –contraindicated

Rx

- Drainage

- Iv antibiotics

OTHER BACTERIAL MYELOPATHY

Bartonella- myelitis & Brown –Sequard syndrome

Whipple disease-

Parainfectious-

Mycoplasma

Pertussis

PARASITIC MYELOPATHIES

Schistosomiasis

Central America & Africa

Retrograde migration of eggs ffrom portal system to

epidural venous plexus

Subacute- low back ache- paraparesis-sensory level-

bladder/bowel++

T11 –L1 & Cauda equina

MRI-

-Cord enlargement

- intramedullary T2 hyperintensity

- lower thoracolumbar cord,conus,cauda CE

DIAGNOSIS

3 features

-Lower spinal cord or cauda

-Evidence of infection(ova in stool/urine,rectal

biopsy,serology)

-Exclusion of other causes

Peripheral Serology- ELISA,IF

CSF tests specific- Monoclonal antibodies or PCR

Tissue biopsy- gold standard

(avoided in CNS disease).

RX

Praziquantel

Concurrent steroids

Rarely, decompression- medically refractory

OTHER PARASITES

Toxoplasma gondii-

-Advanced HIV

-Parenchymal + spinal cord mass lesions

-Peripheral IgG+

- CSF-PCR(spf)

Rx-

pyrimethamine + sulfadiazine /clindamycin

folinic acid

NEUROCYSTICERCOSIS

1.2 %-5.8% cases involve spinal cord

Subarachnoid

Subarachnoid cysts migrate from basal cisterns

75% cases – intracranial NC

Csf- high proten + eosinophilia

Rx

- albendazole + steroids

- rarely,decompression.

HYDATID CYST-ECHINOCOCCUS

Spinal rare

Vertebrae,extradural or paraspinal

Cysts in other sites+

Large- mass effect,bony destruction,inflammatory

response

Imaging-cysts

Serology

Rx-

albendazole

surgical

Recurrence- norm

OTHER PARASITES

Gnathostoma spinigerum

Angiostrongylus cantonensis

FUNGAL CAUSES

Immunocompromised

Aspergillus,cryptococcus

Spinal myelopathy

- epidural abscess

- c/c arachnoiditis

- intramedullary granulomas

- frank myelitis

- vasculitis + cord infarction.

APPROACH

Clinical –

- Onset- Acute vs Subacute Vs Chronic

- Progression

- Painful vs painless

- Sensory level

- Bladder/Bowel+

CSF analysis

Imaging

ACUTE FLACCID PARALYSIS

Polio

Enteroviruses

West NileV

Leukomyelitis-(Acute)

Herpes

CMV

Borellia- rare

EBV

Rabies

LEUKOMYELITIS (SUBACUTE-CHRONIC)

Treponema

Mycoplasma

Tuberculosis

HIV/HTLV-1

Thank you