Spinal cysticercosis and infectious myelopathies

a presentation about spinal NCC and other infectious myelopathies

1. Spinal Cysticercosis and other infectious myelopathies Dr. Imran Rizvi Assistant professor, Neurology KGMU

2. Outline Spinal cysticercosis (Epidemiology, clinical features, diagnosis and management) Other infectious myelopathy Tuberculosis (Non-osseous spinal tuberculosis) Viral myelopathies

3. Introduction Cysticercosis is caused by the encysted larval stage of Taenia solium. NCC : Most common parasitic infection of CNS. Spinal cysticercosis : “Uncommon presentation of a common disease.” Pure spinal cysticercosis in the absence of intracranial involvement is a realtively rare entity. Del Brutto et al. J Neurol Sci.  2013 Aug 15;331(1-2):114-7.

4. Classification

5. Epidemiology Spinal cysticercosis is relatively rare as compared to involvement of the brain. Exact incidence and prevalence: difficult to estimate. Spinal involvement: 0.25 – 5.8% of all NCC cases. Spinal cysticercosis is commonly described in association with intracranial NCC (about 80% cases). Isolated spinal involvement: Uncommon. Kim KS. Surg Neurol 1985. Dietemann JL. J Radiol 1985

6. Most common site of involvement: Thoracic/ lumbosacral Intradural Extramedullary (Subarachnoid) forms: Most common form of spinal cysticercosis. Subarachnoid forms are most commonly associated with intracranial involvement. Spinal involvement is more commonly seen in association with basal subarachnoid neurocysticercosis . Callacondo D. Neurology 2012;78:1394–1400

7. Etiopathogenesis (how spinal cord gets involved ?) Hematogenous route : The artery of Adamkiewicz. Venous route : Retrograde blood flow via venous plexus Ventriculo-ependymal route: The dilated ependymal canal allows the cysticercus to migrate from the fourth cerebral ventricle into the spinal cord. Subarachnoid route: Parasites descends to spinal cord by way of gravity.

8. Clinical features The clinical features of spinal cysticercosis depends upon The anatomic location of cyst: Intramedullary Vs. Extramedullary. Spinal level of lesion Size of the lesion Host immune reaction. Shah S, Dalvie S (2017) Cysticercosis of the Spine: A Review. Arch Parasitol 1: 110

9. Intramedullary lesions Subacute to insidious onset of partial or complete cord syndrome. Weakness Sensory disturbances. Sphincter disturbances. Spasticity, Brisk DTR, extensor plantar. Brown- sequard syndrome. Conus medullaris syndrome Del Brutto et al. J Neurol Sci.  2013 Aug 15;331(1-2):114-7.

10. Extramedullary lesions Commonly present as radiculopathy. Back pain. Lower extremity pain. Asymmetric weakness of lower limbs. Cauda equina syndrome.

11. Extramedullary cysticercosis Intramedullary cysticercosis Commonest site of involvement Lumbosacral spine Thoracic spine Commonest pathogenesis Migration through ventricular system Hematogenous dissemination Most common clinical syndrome Radiculopathy Myelopathy

12. Investigations MRI Spine. Anti cysticercal antibodies. CSF examination.

13. MRI MRI is the imaging modality of choice for the diagnosis of SC. Hypointense on T1 Hyperintense on T2 An eccentric mural nodule ( Scolex ): Hyper on T1, Hypo on T2 can be seen in about 2/3 cases Surrounding edema: Hypointense on T1 and hyperintense on T2. Ring enhancement > solid enhancement: post contrast image. Cord swelling may be seen

14. Sag T2, Axial T2 and T1+C

15. Anti-cysticercal antibodies  The serological assay of choice for the diagnosis of NCC is Enzyme-linked immunotransfer blot (EITB). But the sensitivity and specificity of EITB for diagnosis of SC is not known. EITB: Good sensitivity and specificity for 2 or more NCC involving the brain. Major drawback: Low sensitivity for detection of single lesion and calcified lesion. False positive: Endemic As most of the spinal lesions are single: Not expected to have good sensitivity. Garg RK. Neurol India 2004;52:171-7

16. Diagnosis MRI spine: Typical lesions with scolex. MRI brain: Typical lesions with scolex. Follow-up MRI after cysticidal therapy shows lesion resolution. Histopathological diagnosis following surgical excision.

17. Treatment Two types of approaches Medical management alone Surgery followed by medical management The best approach is not known: No RCTs are available. Treatment is individualized patient to patient

18. Medical treatment Cysticidal drugs along with corticosteroids. Albendazole: 15mg/Kg/Day Praziquantel: 50mg/Kg/Day Duration: 4-6 weeks Corticosteroids should be used along with cysticidal agents. Steroids are generally given for 6-8 weeks

19. Medical management can be used alone if the neurological deficit is stable or slowly progressive. Medical management can be used alone in cases of multifocal or unresectable lesions. Medical treatment should be given post operatively to prevent recurrence following surgical resection. Shah S, Dalvie S (2017) Cysticercosis of the Spine: A Review. Arch Parasitol 1: 110

20. Surgical treatment Surgical treatment leads to decompression and also leads to a histo pathological diagnosis. Indicated for rapidly worsening deficit. Extramedullary lesion: laminectomy and excision of the compressing cystic lesions. Intramedullary lesions: myelotomy and microsurgical dissection from surrounding parenchyma.

21. Other infectious myelopathies

22. Common infectious causes of myelopathies Bacterial infection Spinal epidural abscess ( Staphylococci, Streptococci, Escherichia coli) Tuberculosis Syphilis Lyme’s disease Mycoplasma (parainfectious myelitis) Viral infections Acute infectious/ parainfectious myelopathies HSV 1 and 2 VZV CMV EBV Polio and other enteroviruses. Rabies Chronic myelopathies HTLV HIV

23. Fungal infections Cryptococcus Blastomyces Coccidiodes Aspergillus Parasitic infection Cysticercosis Schistosoma Echinococcus granulosus Toxoplasma

24. Tuberculous myelopathy

25. Approximately 2% of all TB cases are spine TB. Anatomically spinal TB can involve: Vertebral body Inter vertebral disc Para vertebral soft tissues Epidural space Subdural and intra medullary involvement TB involvement of spinal cord compared to that of the brain occurs in the ratio of 1:42

26. Spectrum of spinal cord involvement due to tuberculosis Vertebral Involvement Pott's spine Non-osseous Involvement Tuberculous arachnoiditis (myeloradiculopathy) Intradural, extramedullary tuberculoma Intramedullary tuberculoma Spinal tuberculous abscess Acute myelitis Syringomyelia Along with TBM Early or Late Some times as a result of paradoxical reaction

27. Epidemiology The exact incidence and prevalence of various types of Non-osseous spinal TB is difficult to estimate. Dastur reviewed 74 paraplegia due to TB without evidence of Pott's disease and found Extradural granulomas: 64% Arachnoidal lesions: 20% Subdural/extramedullary lesions: 8% Intrameduallary lesions: 8%

28. Spinal involvement in 147 patients was reviewed tuberculous radiculomyelopathy (38.7%) Extramedullary Intradural tuberculoma (19.9%) Syringomyelia (14.9%) Intramedullary tuberculoma (9.4%) tuberculous myelitis (8.84%) Tuberculous abscess (7.2%) Infarct (1.1%).

29. Pathogenesis Spinal cord involvement can occur via Hematogenous route. Downward extension of intracranial TBM. TB lesion primarily arising in the spinal meninges . Extension from TB spondylitis. An abnormal immune reaction against mycobacterial antigen is thought to be the main pathogenic mechanism for occurrence of TB myelitis.

30. Clinical features (TB Radiculomyelopathy) Paraparesis: most common presenting complaint. Subacute areflexic paraparesis: MC manifestation. Back pain, Root pain, Parasthesia, saddle anaesthesia. Muscle wasting Loss of DTR, extensor plantar response. Cauda-conus syndrome.

31. TB Radiculomyelopathy can some times manifest paradoxically after initiation of ATT. TB Radiculomyelopathy can sometimes be asymptomatic. TB Radiculomyelopathy may manifest several years after initial TBM. It may be concomitant at the time of diagnosis or may appear as late as 30 years after tuberculous meningitis.

32. Clinical features (TB Myelitis) Acute to subacute transverse cord syndrome. Paraparesis/ Quadriparesis. Sensory involvement below a level. Bladder and bowel involvement. Commonly effects more than one spinal segment. Thoracic > cervical cord: MC site of involvement. TB myelitis is commonly associated with TBM/ TB arachnoiditis.

33. Clinical features (Spinal tuberculoma) Spinal tuberculomas: Intradural extramedullary or intramedullary. Weakness of limbs Sensory involvement Bowel and bladder involvement. Can occur paradoxically during treatment.

34. Syringomyelia It is usually a late complication of TBM. Rarely it can develop acutely. Progressive paraparesis, sensory loss and sphincter involvement.

35. Diagnosis CSF examination Neuroimaging

36. CSF examination If spinal TB is associated with TBM typical changes are lymphocytic pleocytosis, decreased glucose levels and elevated protein levels. In patients with arachnoiditis: a very high protein content (consequence of spinal block). Confirmation of diagnosis can be done by ZN staining, CSF culture and nucleic acid amplification techniques.

37. Investigation Advantage Disadvantage Microscopy (Z-N staining) Low cost. Diagnosis can be established rapidly if AFB are seen in the CSF. Turnaround time around 2 hours. Low/variable sensitivity for detection of AFB in CSF. Cannot differentiate between drug resistant and sensitive strain . Culture Culture of MTB from CSF is the gold standard for diagnosis. DST can be performed along with culture . Time consuming method (turnaround time of several weeks). Can detect only 1/3 of cases .

38. NAA tests Can rapidly detect nucleic acid of MTB in CSF. Turnaround time is just 3-6 hours. Remains positive after receiving ATT up to 1 month. Very good specificity around 100%. Sensitivity for the diagnosis of TBM around 56 %. Xpert MTB/RIF Rapid results; turnaround time around 2 hours. Can detect rifampicin resistance simultaneously. Minimal training is required to conduct the test . CSF needs to be centrifuged for best results.

39. Neuroimaging MRI is the imaging investigation of choice for evaluation of spinal TB. MRI of Spinal arachnoiditis CSF loculation Obliteration of spinal sub arachnoid space Contrast enhancement of meninges Clumping and enhancement of nerve roots irregularity of thecal sac, nodularity and thickening of nerve roots

40. Delamarter classification Group 1 Central conglomerations of cauda equine nerve roots Group 2 Peripheral clumping of nerve roots giving empty thecal sac appearance Group 3 soft tissue mass replacing subarachnoid space giving rise to a central opacity Delamarter et al. Spine ( Phila Pa 1976).1990;15:304–310.

41. MRI TB Myelitis Tuberculous myelitis appears as hyperintense on T2, isointense to hypointense on T1-weighted images and shows segmental enhancement on post-contrast images.

42. MRI tuberculoma

43. MRI TB syrinx Syringomyelia, on MRI, presents as cord cavitation that typically demonstrates CSF intensity on T1- and T2-weighted images.

44. Treatment Anti tuberculosis drugs Corticosteroids Surgery ? Intrathecal hyaluronidase

45. Anti tuberculosis treatment Treatment is based on observation studies and clinical experience rather than clinical trials. Initiation phase: HRZS/ E about 2 month Continuation phase: HR about 10 months Duration of therapy can be individualized. Corticosteroids are proven to be beneficial in TBM, but exact role of steroids in managing the spinal involvement is not known.

46. Surgery Tuberculomas: surgical excision Spinal arachnoiditis: surgical decompression Syringomyelia: syringo -peritoneal shunt placement. Exact timing and indications of surgery are not clear.

47. Viral myelopathies

48. Viral infections can cause myelopathies by 2 mechanisms Direct infection of spinal cord A parainfectious mechanism (with a presumed autoimmune pathogenesis) Clinically viral myelopathies can present with Acute transverse Myelopathy Chronic Myelopathy

49. Common viral infections presenting as acute transverse myelopathies HSV 1 and 2 VZV Epstien Bar virus Cytomegalo virus The infection with these viruses follows 3 phases. The initial acute phase: Acute febrile illness with/ without rashes/vesicles. The latent phase: The virus lies dormant in tissues for month to years The reactivation phase: Acute Myelopathy Diagnosis Commonly by PCR and/or antibody testing of the CSF, which is highly sensitive. MRI: T2 Hyperintensity in the spinal cord Treatment CMV: ganciclovir and foscarnet . VZV/ HSV: Acyclovir

50. Viruses presenting as chronic myelopathies Human T cell lymphotropic virus (HTLV) HIV

51. HTLV myelopathy Twenty million people worldwide are thought to be infected with HTLV-1. Only a small proportion of infected individuals develop myelopathy with the estimated lifetime risk being 0.25%. It is spread by sexual contact, blood transfusion, sharing of infected needles and breast feeding.

52. HTLV-1 Myelopathy= TSP Insidious onset weakness of both lower limbs. Spasticity, hyperreflexia, and extensor plantar responses. Sensory impairment usually consists of loss of vibratory sensation. Bowel and bladder dysfunction. Wheel chair dependence over time. CSF: anti HTLV antibodies

53. Myelopathies associated with HIV

54. The most common HIV associated myelopathy is vacuolar myelopathy. Usually occurs in the setting of advanced immunosuppression. C/F: lower extremity weakness, gait impairment, and bowel and bladder incontinence. O/E: Spastic paraparesis, with weakness, spasticity, hyperreflexia and extensor plantar responses. Vibratory and joint position senses are disproportionately affected compared with pinprick and temperature

55. MRI: Normal, T2 hyperintensity CSF examination is essential to rule out other infectious agents. No established therapy for HIV-associated myelopathy exists. Antiretroviral therapy does not affect the natural history of the disorder.

56. Take home message TB, Cysticercosis and viral etiologies are amongst the common causes of infectious myelopathies in our setup. They usually present with partial or complete spinal cord syndromes of acute to subacute onset. Performing an MRI brain can be sometimes helpful in reaching to a diagnosis: NCC, TB Treatment on infectious myelopathies is based on observational studies rather than RCTs.

57. Thank you