APPROACH TO NON COMPRESSIVE MYELOPATHY [Autosaved].pptx

non compressive myelopathy and its approach

1. APPROACH TO NON COMPRESSIVE MYELOPATHY DR PRAKARSH SHARMA SR NEUROLOGY

2. CASE SCENARIO 34 yr female noticed numbness of both lower limb which started circumferentially, By evening she noticed tightening around lower chest, By next day morning she had weakness of both legs unable to get up from bed, Was taken to near by hospital and was catheterized and drained large volume of urine.

3. ANATOMY OF SPINAL CORD Length: 45 cm Extend of spinal cord: From medulla to lower border of L1 in adults. Dura & arachnoid inserts at S2 level. Pia mater extends till coccyx. Filum terminale : Fibrous termination of pia mater, from conus to соссух . The lower most portion of spinal cord is known as conus. The segment just above it is called as epiconus . There are two enlargements, cervical level &Lumbar level. cervical level supplies large number of muscle in upper limb and the lumber level supplies large number of muscles in lower limb.

4. SPINAL CORD CROSS SECTION

5. Blood supply Spinal cord's blood supplied by predominantly three arteries: • Anterior spinal artery.• Posterior spinal artery.• Radicular artery. Anterior spinal artery: vertebral artery Posterior spinal artery: PICA/ vertebral segmental arteries: Forms radiculomedullary  arteries

6. MYELOPATHIES CLASSIFICATION

7. ACUTE------- WITHIN DAYS SUBACUTE------- 2-6 WEEKS CHRONIC------- > 6 WEEKS DURATION

8. Features Compressive Non compressive Bone deformity + - Bony tenderness + - Girdle like sensation + - Upper level of Sensory loss + - Root pain + - Onset and progress Gradual May be acute Bladder and bowel involvement Early Usually late(early in ATM) Symmetry Asymmetrical(U shaped) Symmetrical

9. NON COMPRESSIVE MYELOPATHY INFLAMMATORY MYELOPATHIES –MYELITIS 1 . INFECTIOUS- VIRAL, BACTERIAL ,FUNGAL PARASTIC 2. AUTOIMMUNE - SLE.SJOGREN,SARCOIDOSIS,BECHET S,MCTD 3. DEMYELINATING - MS,NMO, ADEM, POST VIRAL POST VACCINIAL 4 .PARANEOPLASTIC

10. NON INFLAMMTORY MYELOPATHIES

11. EVALUATION OF MYELOPATHY MRI WITH GADOLINIUM ENHANCEMENT CSF ANALYSIS INFECTIOUS POST INFECTIOUS AUTOIMMUNE MS RELATED SPINAL CORD INFARCTION AVM OTHER

12. Hereditary myelopathy classification 1.HSP or spastic paraplegia. 2. MND. 3. Spastic ataxia's (SPAX). 4. metabolic leukoencephalopathy.

13. HSP 2nd to 4th* decade is the common age of onset. Progressive symmetric spasticity of lower limb. Dynamic » on examination. Posterior column, bladder/sphincter may be involved Family history is present &> 70 genes involved. Pathogenesis :• Axonal transport disruption.• Impaired neuronal lipid homeostasis.• mitochondrial dysfunction.• Abnormal organelle morphogenesis. Long axons are affected first, hence involvement of lower limb> upper limb

14. . Classification of HSP :1. Pure HSP. 2 Complex: Other neurological signs. 3. Complicated: Non neurological signs. Non neurological signs: 1. Optic atrophy. 2. Retinitis pigmentosa. 3. Deafness. 4. Dementia/ intellectual disability. 5. Extrapyramidal / pseudobulbar. 6. Hypoplasia of corpus callosum. 7. Amyotrophy. 8. Peripheral neuropathy. 9. Ataxia 10. Bladder. 11.Ichthyosis. 12. Autoimmune haemolytic anemia /thrombocytopenia Evans syndrome). Genetically classified into :1. AD: most common, 1/4** sporadic, most are pure.2 AR: most complicated are AR.3. X linked

15. Adreno-myeloneuropathy ABCD I gene, X linked. Peroxisomal betaoxidation leads to accumulation of VLCFA’s. presentation:• Pure adrenal involvement. • Adrenoleukodystrophy: 4 to 8 yrs boys. • Adrenomyeloneuropathy : Adult thoracic cord + peripheral nerve. Empty lipid cleft in Schwann cells.

16. ACUTE TRANSVERSE MYELITIS

17. Epidemiology incidence - up to 3 per 100,000 patient years (0.003%) no familial or ethnic predisposition More common in females c/f symptoms typically develop over hours to days and then worsen over days to weeks. pyramidal, sensory, and autonomic dysfunction to varying degrees “band like” horizontal area of altered sensation on the neck or torso

18. Neuroimaging Excludes compressive etiology Brain MRI should be performed to determine if other demyelinating lesions within (CNS) are present ,MS AND NMO SPECIFIC LESIONS NORMAL MRI with myelopathy – - not myelopathy - Friedreich’s ataxia, motor neuron disease, vitamin B12 or copper deficiency myelopathy , hereditary spastic paraparesis , HIV,HTLV -1

19. - Csf picture: A low CSF glucose concentration - infection (fungal, bacterial, or mycobacterial ), isolated low in neurosarcoidosis carcinomatosis , ,SLE Elevated protein concentration 50% of patients with transverse myelitis CSF WBC count defines inflammatory myelitis . -CSF IL-6 has been described as a biomarker to help predict disability in acute transverse myelitis -The sensitivity of NMOIgG is 70% whereas the specificity approaches 100%.

20. -PROGNOSIS 1/3rd of patients recover with little to no sequelae , 1/3 rd a moderate degree of residual disability and 1/3rd remain severely disabled Poorer prognostic factors in acute transverse myelitis CLINICAL LABORATORY rapid progression of symptoms, -absence of csf changes back pain/ neck pain -prominent & diffuse signal mri changes Flaccidity/spinal shock, - denervation potentials on EMG Attenuation of reflexes -absent/attenuated motor& sensory Early onset amyotrophy evoked potentials

21. MANAGEMENT ACUTE MANAGEMENT – HIGH DOSE IV STEROIDS – methylprednisolone 1 gm for 3- 7 days If poor response to steroids – plasmapheresis should be offered within 15 days Has shown favourble outcome in demyelinating and autoimmune diseases SUPPORTIVE MANAGEMENT- - SPASTICITY BLADDER DYSFUNCTION GI DYSFUNCTION COMPLICATIONS DUE TO IMMOBILITY – PRESSURE SORE,DVT MALNUTRTITION,RESPIRATORY THERAPY

22. INFECTIOUS CAUSES

23. SPINAL CORD INFECTIONS WHEN TO SUSPECT SPINAL CORD INFECTION ? DEMOGRAPHIC FACTORS – residence in endemic areas,h /o exposures,blood transfusion ,chemotherapy ,transplant recipent (CMV,HHV7) CLINICAL CLUES – other systems –retina ( cmv ) pharynx( ebv ), lung ( cryptococcus,TB ), vesciles ( hsv ), erthema migrans ( lyme .s) and neurologic- meningoencephalitis,encephalopathy

24. Hiv infection MYELOPATHY can be due to HIV- itself( CD4 < 200), Herpes Zoster,Tuberculosis,HTLV-1, syphilis HIV MYELOPATHY- DIAGNOSIS OF EXCLUSION SYMMETRIC PAINLESS SPASTIC parapareis with impaired joint position vibration,Concomitant neuropathy. Pathologically – vacoular myelopathy ..spongy degeneration .,demyelination (axons relatively preserved ) Neuroimaging and csf picture is often normal ViT b12 deficiency may contribute No effective treatment ..ART may reduce the incidence

25. SYPHILIS Treponema pallidum , hiv co-infection Tabes dorsalis ,meningomyelitis, pachymenigitis,spinal vascular syphilis TABES DORSALIS- less than 5% of neurosyphilis Post columns and spinal roots, hyperreflexia Preataxic -Lightening pains of the legs, ARP Ataxic phase- sensory ataxia ,slapping gait Paralytic phase CSF VDRL 12- 14 MU OF AQUEOUS PENICILLIN G DAILY -10-14 DAYS

26. Other csf studies

27. HTLV/TSP • 30 yrs onset, slowly progressive, spastic paraparesis • Paraesthesia + painful sensory neuropathy + Bladder involvement. • mRI : Atrophy of thoracic cord • HTLV 1: Periventricular white mater hyperintensity not in HTLV 2 HTLV positive serology in blood and CSF. • CSF antibody index + OCB + PCR: more specific. • may be asymmetric, often lacking a well defined sensory level. • The only sign in the arms may be hyperreflexia after several years of illness. No definitive treatment available.

28. DEMYELINATING DISORDERS MULTIPLE SCLEROSIS - lesions are usually small (<2 vertebral segments in length) and peripheral, cause asymmetric symptoms and signs Lhermitte sign isolated proprioceptive loss of an upper extremity (‘‘sensory useless hand syndrome’’), Brown-Se´quard syndrome, or, more commonly, incomplete involvement

29. CSF oligoclonal bands (OCBs) are present in more than 90% of patients, other conditions that cause inflammation in the CNS, including NMO, paraneoplastic disorders, SLE, neurosarcoidosis , Behçet’s disease immunoglobulin ( Ig )G index is seen in more than 60%. following equation: IgG Index -(CSF IgG /albumin)/(serum IgG /albumin). Ratio -0.3 and 0.6 Subclinical optic nerve involvement on visually evoked response testing MRI brain FINDINGS predicts relapse

30. NEUROMYELITIS OPTICA Lesions are centrally located and necrotic leading to more symmetric symptoms and signs, greater disability NMO is relatively more common in Asian and African individuals, autoimmune conditions including SLE, Sjogren's syndrome, and thyroid autoimmune disorders may coexist. NMO-IgG -recently identified serum antibody highly specific (>90%) and sensitive (>70%) for NMO. Risk of developing recurrent myelitis or new onset optic neuritis in patients with an LETM was more than 50% in NMO-IgG seropositive

31. MULTIPLE SCLEROSIS NEUROMYELITIS OPTICA

32. ACUTE DISSEMINATED ENCEPHALOMYELTIS ADEM- monophasic disorder that affects the brain and occasionally the spinal cord history of preceding viral or other infectious illness. show demyelinating lesions that are generally of the same age POSTVACCINE MYELITIS -occurring in the 3 weeks following a vaccination, such as smallpox ,hepatitis B, typhoid, influenza, rubella, and tetanus

33. ACUTE IDIOPATHIC TRANSVERSE MYELITIS idiopathic nature is a diagnosis of exclusion preceding nonspecific fever, nausea possibly indicating a prior viral infection is common 16-60% of all Transverse myelitis Female preponderance Typically monophasic (1/4 th recur) may have an NMO spectrum disorder. The lesion length varies from less than one segment to the entire cord.

34. Diagnostic criteria

35. IMMUNE DISEASES Sarcoidosis - CNS involvement -5% of cases 18% presented with myelopathy Spinal cord sarcoidosis may present with paraparesis, quadriparesis, sensory changes, autonomic dysreflexia, radicular symptoms, or cauda equina syndrome. The cervical cord is affected more than other segments of the spinal cord. Pleocytosis (especially lymphocytic), elevated proteins, and sometimes low glucose are the most common abnormalities. INVX -plain films of the chest ,ACE levels specificity at 80 to 95 the sensitivity is 60%. Mri may show long segment cord change.

36. Systemic Lupus Erythematosus -1 to 2% of patients with SLE ANA , APLA antibody that is positive in 43 to 73% with myelitis patients with NMO ANA was positive in 52.6% Sjögren’s Syndrome – that 35%- spinal cord involvement, spinal along with optic neuritis can occur, mimic MS -anti ro & anti la - steroids and immunosuppresants

37. Paraneoplastic Disorders and Myelopathy subacute myelopathies MAY OCCUR BEFORE DETECTION OF CANCER search for antibodies and an underlying malignancy warranted if other etiologies for the myelopathy are not apparent often produce tract-specific involvement/TM/recurrent Ab to CRMP5 may lead to myelopathy and optic neuropathy that may mimic NMO Amphiphysin - specific antibodies raise the possibility of breast cancer. Detection and t/t of underlying cancer , immunosupression

38. Vascular BLOOD SUPPLY OF SPINAL CORD

39. Spinal cord infarction 1% of all strokes, 5% of acute myelopathies 6 th to 7 th decade Atherosclerosis , surgery of aorta, systemic hypotension, Iatrogenic causes- vertebral angiography, spinal trauma Relative hypovascularity of thoracic cord(>60% of SCI occur) Pain(often radicular) and sensory symptoms first Clinical Nadir within 12 hrs Anterior spinal atery syndrome –symmetric weakness with B/l Spinothalamic with bladder Post spinal artery ischemia –rare Frequent overlap of signs . Can be devastating and life threatening mortality rate of 20-25%

40. owl's eye sign: Seen in spinal cord infarct in vascular ischemia. Thoracic is most common site. Pyramidal tract more likely to be affected,Located in Watershed area. more energy consuming tract. more phylogeneticaly evolved Anterior spinal artery is mostly involved

41. Management High risk procedures serial neurologic assessment In Aortic manipulation –vasopressors manitain MAP>90 MRI spine –r/o compression (epidural hematoma).DWI more sensitive CSF drainage maintain CSF pressure at 10 mm Hg Antiplatelet used (trials not available)

42. Foix- Alajouanine syndrome • Subacute necrotic myelopathy. • Progressive thoracic myelopathy over weeks or months. • Extensive thrombophlebitis of spinal veins. • COPD /neoplasm.

43. METABOLIC MYELOPATHIES

44. SUBACUTE COMBINED DEGENERATION Despite widespread screening vit b12 deficency is – 15-25% of older individuals ETIOLOGY malabsorptive disorders, such as poor nutrition, atrophic gastritis, H2 antagonists and metformin, fish tapeworm. CLINICAL FEATURES:Fatigue , generalized weakness Slowly progressive myelopathy Paraparesis with hyperreflexia and spasticity Mild sensory symptoms with loss of vibration ,proprioception Bladder bowel also can occur Associated peripheral neuropathy Psychological symptoms , cognitive decline Optic neuropathy

45. diagnosis Cbc - macrocytosis ,pancytopenia .mcv (only in 40%) Vitamin b12 levels –lacks sensitivity and specificity 1/3 rd of cases with normal vit b12 levels have elevated homocysteine and MMA levels Subclinical vit b12 deficiency occurs with age Low levels with neurologic manifestations – cause and effect relation poor Tests for cause of deficiency-serum gastrin, anti intrinsic factor antibody (elevated gastrin in 30% elderly ) MRI SPINE –hyperintense T2 WEIGHTED signal in posterior and lateral columns

46. SAGGITAL T2 WEIGHTED AXIAL T2 WEIGHTED Rx-Oral or parenteral vitb12 NEUROLOGIC symptoms- high dose im 1000ug Im for 2 weeks daily f/b 1000ug monthly for 6 months

47. Nitrous oxide exposure

48. FOLATE DEFICIENCY CAN alone cause myelopathy (less common) Alcoholics, neural tube defects, GI disease, pregnancy ,drugs – trimethoprim Myelopathy, neuropathy, optic neuropathy ,cognitive decline Serum folate ,red cell folate (more reliable) serum homocysteine Oral folate 1mg tds f/b 1mg per day

49. Copper deficiency Prosthetic group for various enzymes Causes- gastric surgery, zinc toxicity ,TPN, malabsorption Clinical -Myelopathy, myeloneuropathy Diagnosis-serum ceruloplasmin, serum or urinary copper Supplementation with oral copper

50. toxic myelopathies LATHYRISM – Lathyrus sativus ,toxic amino acid(B oxalyl amino alanine ) from grass pea Spastic paraparesis with degenerative changes in spinal cord Preventable- avoid pure grass consumption, mix with cereals KONZO - poorly processed cassava SEEN IN AFRICA Spastic paraparesis

51. SMON - clioquinol was used as antiparasitic drug in Japan Subacute paraparesis with optic atrophy ORGANOPHOSPHORUS- - CAN CAUSE MYELOPATHY AND MYELONEUROPATHY Most imp content –TOCP Acute intoxication f/b latent phase of several weeks Progressive leg weakness –sensory motor neuropathy with spacticity paraparesis RBC cholinesterase

52. Other toxic myelopathies Chemotherapy induced Hepatic Myelopathy Heroin myelopathy Fluorosis

53. Radiation associated myelopathy Radiation-induced myelopathies are usually slowly progressive but may occur up to 15 years after the end of radiation treatment, Early radiation myelopathy is usually self limiting. cord swelling or enhancement may be seen initially but later atrophy simultaneous involvement of the adjacent vertebrae in the same field,

54. CONCLUSION Spinal cord can be affected by multiple etiologies. A sound clinical history, pattern of evolution, imaging, and laboratory evaluation can help ascertain diagnosis in most of the patients. “AS A RULE COMPRESSIVE ETIOLOGY IS RULED OUT FIRST”

55. REFERENCES Seminars in neurology –vol 28, Feb 2008 Seminars in neurology –vol 32, April 2012 Neurology clinics – (spinal cord diseases) feb 2013 vol 31 metabolic and toxic myelopathies –American academy of neurology 2008 infectious and inflammatory myelopathies - American academy of neurology Spinal cord syndromes- differential diagnosis in Neurology

56. Thank you