Infectious myelopathy- approach to myelopathy

1. INFECTIOUS MYELOPATHY
DR.SARATH MENON.R, MD(Med.),DNB(Med.),MNAMS
DM RESIDENT,
DEPT. OF NEUROSCIENCES
AIMS,KOCHI.

2. 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

3. PRESENTATION
 Acute transverse myelitis
 Acute flaccid paralysis- AHC, motor roots

4. APPROACH
 History & physical examinations
 Tempo of illness
 Exposure
 Demographic- endemicity
 Host immune status
 Ancillary test
 Diagnosis & Rx

6. 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.

7. CAUSATIVE AGENTS
 Viral
 Bacterial
 Parasitic
 Fungal

9. RETRO VIRUSES- HIV
 CNS – lymphocytes,microglia
 Crosses BBB
 Neurotoxicity by viral proteins
 Chronic pro inflammatory state
 CD4 < 200- HIV – vacuolar myelopathy

10. 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.

11.  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. 13
HIV-related myelopathy. Vacuolar changes
are evident in the lateral and posterior
columns of the thoracic spinal cord.

15. 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

16.  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

17. TREATMENT
 No effective clinical trials to date.
 Steroids
 INF-alpha, cyclosporine,azathioprine- effective
early – limited evidence
 HAART

18. 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

19. 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

20. 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. 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

22.  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

23. 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

24. 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

25.  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

26. 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

27. 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

28. 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

29.  Serology –EBV DNA
 CSF-EBV DNA PCR
 Imaging-
T2hyperintensity+ce+nerve thickening
Rx
- Acyclovir-little effect on clinical course
- steroids

31. 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

32. SYPHILIS-OTHER FORMS OF MYELOPATHY
 Hypertrophic pachymeningitis
 Spinal cord Gumma
 AHC
 Syingomelia
 Aortic aneurysm –sec AHC
 Charcot vertebra-cord compression

33. 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

34. 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)

35. 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

36. 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

37. 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

38. RX
 2 month HRZE/S+ 7-10 Month HR
 Vertebral disease- surgical option
 Lumbar disease-better prognosis

39. 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 +

40.  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

42. OTHER BACTERIAL MYELOPATHY
 Bartonella- myelitis & Brown –Sequard syndrome
 Whipple disease-
 Parainfectious-
Mycoplasma
Pertussis

44. 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

45. 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).

46. RX
 Praziquantel
 Concurrent steroids
 Rarely, decompression- medically refractory

47. OTHER PARASITES
 Toxoplasma gondii-
-Advanced HIV
-Parenchymal + spinal cord mass lesions
-Peripheral IgG+
- CSF-PCR(spf)
 Rx-
pyrimethamine + sulfadiazine /clindamycin
folinic acid

48. 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.

49. 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

50. OTHER PARASITES
 Gnathostoma spinigerum
 Angiostrongylus cantonensis

51. FUNGAL CAUSES
 Immunocompromised
 Aspergillus,cryptococcus
 Spinal myelopathy
- epidural abscess
- c/c arachnoiditis
- intramedullary granulomas
- frank myelitis
- vasculitis + cord infarction.

54. APPROACH
 Clinical –
- Onset- Acute vs Subacute Vs Chronic
- Progression
- Painful vs painless
- Sensory level
- Bladder/Bowel+
 CSF analysis
 Imaging

55. ACUTE FLACCID PARALYSIS
 Polio
 Enteroviruses
 West NileV
Leukomyelitis-(Acute)
 Herpes
 CMV
 Borellia- rare
 EBV
 Rabies

56. LEUKOMYELITIS (SUBACUTE-CHRONIC)
 Treponema
 Mycoplasma
 Tuberculosis
 HIV/HTLV-1

59. Thank you