Non compressive myelopathy

brief review of diiferent causes of non compressive myelopathy and their characterstics

1. EVALUATION AND DIAGNOSIS OF NON COMPRESSIVE MYELOPATHY PRESENTED BY: DR. HIRDESH CHAWLA JUNIOR RESIDENT III

2. 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

3. TIME COURSE : Acute- within days(usually vascular, radiation, infection ) Sub acute- 2-6 weeks Chronic- more than 6 weeks( degenerative, demyelinating , sarcoidosis , dural AV fistula , metabolic , tabes dorsalis , HIV related) PHASE: Single event(most common) Multiphasic (rare)- Demyelinating , Vascular, Systemic disease EXTENT OF INVOLVEMENT: Monofocal - ATM Multifocal- ADEM,NMO,MS CLASSIFICATION

4. DISTRIBUTION: Gray matter- Poliomyelitis White matter- Leucomyelitis Whole cross sectional area- Transverse myelitis Meninges and SC- Meningomyelitis Meninges and root- Meningoradiculitis

5. Complete spinal cord : involvement of all the tracts (trauma, compression or acute transverse myelitis ). Brown Séquard syndrome: multiple sclerosis and compression. Anterior spinal cord syndrome : anterior spinal artery infarct and multiple sclerosis Posterior spinal cord syndrome : vitamin B12 or copper deficiency. Central syndrome : spino-thalamic crossing, cortico-spinal and autonomic tracts ( syringomyelia , neuromyelitis optica ). Medullary cone: sacral emerging fibres (post-viral myelitis ). Cauda equina : acute cytomegalovirus infection, polyradiculitis Tractopathies : vitamin B12 deficiency, paraneoplastic myelopathy and multiple sclerosis.

6. SACD HIV associated myelopathy Freidrich’s ataxia Tabes dorsalis MYELOPATHY WITH PERIPHERAL NEUROPATHY

7. 1. INFECTIOUS - Viral, Bacterial, Fungal and Parasitic 2. AUTOIMMUNE - SLE, Sjogren’s , Sarcoidosis , Behcet Syndrome ,MCTD, Poly Arteritis Nodosa , p ANCA positive vasculitis . 3. DEMYELINATING - MS,NMO, ADEM, Post viral post vaccinial 4 .PARANEOPLASTIC 5. ENCEPHALOMYELITIS INFLAMMATORY MYELOPATHIES

8. NON INFLAMMATORY MYELOPATHIES

9. Excludes compressive etiology. There needs to be gadolinium enhancement of the spinal cord for inflammatory pathology Brain MRI should be performed to determine if other demyelinating lesions within (CNS) are present ,MS and NMO specific lesions. NEUROIMAGING

10. NOT a myelopathy ( Guillain Barre’s , Inflammatory radiculopathy ) MRI performed during convalescence period. Friedreich’s ataxia, Motor neuron disease, Vitamin B12 or copper deficiency myelopathy , Hereditary spastic paraparesis , HIV,HTLV-1 NORMAL MRI WITH MYELOPATHY

11. IMAGING FEATURES POTENTIAL DIAGNOSIS Blood within the spinal cord(bright and dark T1 and T2 signal) Vascular malformation(cavernous angioma or dural AV fistula) Flow void within SC Dural AV fistula or AVM Central T2 signal abnormality Venous hypertension Ring enhancing lesion Infection or tumour (consider steroids to rule out inflammation process before biopsy) Fusiform lesion over >3 spinal segments NMO T2 bright lesion in white matter ,<2 SC segments,<50% of cord diameter, Rostral caudal extent MS

12. Represent extensive involvement of the spinal cord, with abnormal T2 signal traversing at least three vertebral body segments in length. Differential diagnosis NMO(typical) Multiple sclerosis- confluent short segment lesions mimicking LESC Immunological - Neurosarcoidosis,Sjogrens,SLE Behcet’s disease Paraneoplastic myelitis Post infectious Vascular - Infarction,Dural AV fistula Metabolic and radiation myelopathy LONGITUDINAL EXTENSIVE TRANSVERSE MYELITIS

13. A low CSF glucose concentration:- infection ( fungal, bacterial,or mycobacterial ), Isolated low in neurosarcoidosis , carcinomatosis , SLE CSF WBC count defines inflammatory myelitis . High immunoglobulin G index in the CSF- Inflammatory If none of these findings are present at the time of onset of symptoms, MRI and lumbar taps must be repeated two to seven days later. CSF EXAMINATION

14. Pleocytosis - Infections, Inflammations, Demyelinating disorders. Mononuclear cells in AV malformations, paraneoplastic Erythrocytosis - AVM,AVF,SLE,Behcet’s Elevated protein- Tumours , paraneoplastic , vascular, radiation. CSF normal- Delayed progressive radiation myelopathy Bizzare giant cells- vacuaolar myelopathy of HIV. Pronounced pleocytosis , normal glucose,eosinophilia - schistosomiasis CSF ANALYSIS

15. EVALUATION OF MYELOPATHY MRI WITH GADOLINIUM ENHANCEMENT CSF ANALYSIS

16. ACUTE TRANSVERSE MYELITIS

17. Incidence - up to 3 per 100,000 patient years (0.003%) Female preponderance Typically monophasic (1/4 th recur) First peak between 10-19 yrs of age and other between 30-39 yrs. Of age Symptoms typically develop over hours to days and then worsen over days to weeks(acute to subacute ) Pyramidal(flaccid paraplegia), sensory(definite sensory level), and autonomic dysfunction to varying degrees . Backache and progressive paraparesis are presenting complaints. Early bladder and bowel involvement. “band like” horizontal area of altered sensation on the TORSO and rarely on neck.(but unlike compressive-no root pain, spinal tenderness). Plantars are extensor (maybe absent in spinal shock stage) FEATURES

18. Diagnostic criteria

19. 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. MRI findings include focal and central high signal areas in T2 sequences, occupying more than two thirds of the spinal cord axially, and extending over three to four segments, generally in the thoracic spine. Spinal expansion may or may not be found and, in general, there is contrast medium enhancement, usually patch-like or diffuse. MRI findings are usually normal in 40% of cases MRI FINDINGS

21. INFECTIONS

22. INFECTIOUS CAUSES

23. 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 – Lymphadenopathy Retina (CMV), Pharynx(EBV), Lung ( cryptococcus , TB), Vesicles (HSV, Entero virus 71), Erythema migrans (Lyme’s) and Neurologic- meningoencephalitis , encephalopathy Recurrent genital infections- Behcets SPINAL CORD INFECTIONS

24. Enterovirus (Coxsackie and polio),West Nile  Anterior horn cells, motor nucleus of brainstem Herpetic Dorsal root ganglion,extensive inflammatory necrosis of SC Schistosomiasis causes intensely inflammatory and granulomatous myelitis.Diagnosed by elevated titres of Ab against schistosome . HSV-2 produces a distinctive syndrome of recurrent sacral cauda equina neuritis( lumbosacral radiculitis ) with urinary retention in association with outbreaks of genital herpes ( Elsberg’s syndrome) * Hence disturbance of function are either in sensory or motor NEURONS rather than tracts SPECIFIC FEATURES

25. Myelitis that presents as dysfunction of motor and sensory tracts is rarely viral but rather due to Non infectious inflammatory pathology BUT EXCEPTION BEING Zoster myelitis HIV associated Vacuolar myelopathy HAM(Tropical spastic paraparesis ) Dumb rabies

26. MYELOPATHY can be due to HIV - itself, Herpes Zoster , Tuberculosis, HTLV-1 HIV MYELOPATHY- DIAGNOSIS OF EXCLUSION Pathologically – vacuolar myelopathy , spongy degeneration , demyelination (axons relatively preserved) Most severe in thoracic segments with posterior and lateral columns affected diffusely SYMMETRIC PAINLESS SPASTIC paraparesis Lesions resemble SACD but B12 levels are normal HAART has no effect on myelopathy HIV INFECTION

27. Slowly progressive with UMN signs Early bladder involvement with disorder of sphincter control. Upper extremities are spared(except for lively tendon reflexes) Preserved brainstem and mentation . Posterior column and corticospinal tract in thoracic cord is most commonly involved. CSF shows –normal protein and glucose and increased HTLV-1 antibodies TROPICAL SPASTIC PARAPARESIS BY HTLV-I

28. Tabes dorsalis , meningomyelitis , pachymenigitis , spinal vascular syphilis TABES DORSALIS- less than 5% of neurosyphilis Post. columns and spinal roots Preataxic - Lightening pains of the legs, ARP, urinary incontinence Ataxic phase- sensory ataxia ,slapping gait Paralytic phase CSF shows- pleocytosis , increased protein,increase in IgG with OGB, serological tests SYPHILIS

29. POST INFECTIOUS AND POST VACCINIAL

30. Most common cause of ATM Temporal relationship to infection or vaccination Development in days to 2 weeks when patient is resolving from febrile epsiode Monophasic temporal course Varying degrees of weakness, ascending sensory symptoms, sphincter disturbances. 40% give a positive H/O infection.(EBV,CMV and Mycoplasma most common. NOT Campylobacter jejuni ) Slight asymmetric of symptoms and signs, sensory level on trunk and Babinski positive distinguishes it from GBS POSTINFECIOUS AND POSTVACCINAL

31. CSF- WBCs 10 – 100/mm3,Normal glucose, Raised protein , Pauci inflammatory also. Absent oligoclonal bands MRI – Minimal gadolinium enhancement with slight T2 signal abnormalities over 2-3 segments. POSTVACCINE MYELITIS -occurring in the 3 weeks following a vaccination, such as smallpox ,hepatitis B, typhoid, influenza, rubella, and tetanus

32. ADEM- Monophasic disorder that affects the brain and occasionally the spinal cord. History of preceding viral or other infectious illness.(not definite criteria for diagnosis) Show diffuse demyelinating lesions that are generally of the same age. Usually include encephalopathy but may also include focal or multifocal demyelinating inflammatory syndromes of the CNS such as optic neuritis and myelitis . ADEM is a differential diagnosis for isolated demyelinating syndrome, which is a more common precursor of MS in adults . ADEM symptoms include rapidly progressing encephalopathy associated with seizures or multiple neurologic deficits. The spinal cord is affected in 11% to 28% of patients, generally in the thoracic and cervical segments ACUTE DISSEMINATED ENCEPHALOMYELTIS

33. There are no diagnostic criteria, but ADEM must be suspected when one or more of the following are present : •Initial multifocal presentation with multiple symptoms. • Less than 10 years of age. • Signs and symptoms of meningoencephalitis . • Encephalopathy. • Bilateral optic neuritis. • CSF pleocytosis without oligoclonal banding. • MRI shows lesions in areas not affected by MS, such as the grey matter or the cortex. • Lesions on MRI appear larger with poorly defined edges that enhance with gadolinium

34. DEMYELINATING DISORDERS

35. Lesions are usually small (<2 vertebral segments in length) and peripheral. Cause asymmetric symptoms and signs Lhermitte sign Acute spinal MS is relatively painless and without fever and improves with residual signs. MULTIPLE SCLEROSIS

36. Polman et al. reviewed McDonald’s diagnostic criteria in 2010 and proposed the following : Space: One or more lesions with and without gadolinium enhancement in two of the following areas: periventricular , juxtacortical , infratentorial , or spinal cord. Time: One new lesion on T2 sequences or a gadolinium enhancing lesion when compared to the previous MR image, and concomitant finding of asymptomatic lesions with or without enhancement.

37. CSF oligoclonal bands (OCBs) are present in more than 90% of patients(may be absent after first attack) 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 Advanced neuroimaging such as diffusion tensor and magnetization transfer imaging may help identify the involvement of the apparently normal white matter, which is abnormal in MS and normal in ADEM.

38. On the sagittal plane, the plaques may be anterior, central or posterior. Acute lesions enhance with gadolinium, due to rupture of the blood-brain barrier. This enhancement is less in cerebral lesions. Unlike neuromyelitis optica , viral or idiopathic myelitis , in MS no black holes are visualized in the spinal cord . NAA has been has been found to be reduced on spectroscopy, in spinal cord areas that appear normal on conventional MRI. MRI FINDINGS

39. Dawson’s fingers on MRI

40. Lesions are centrally located and necrotic leading to more symmetric symptoms and signs and greater disability NMO is relatively more common in Asian and African individuals, Female preponderance with mean age of 40 yrs. Autoimmune conditions including SLE, SjoGren syndrome, and thyroid autoimmune disorders may coexist NEUROMYELITIS OPTICA

41. Combination of Optic neuritis with Myelitis also occur in: Multiple sclerosis ADEM Sjogren’s syndrome SLE Rarely with viral and bacterial infections. Paraneoplastic ( Ab to CRMP 5) DIFFERENTIALS

42. Radiological characteristics include a central longitudinal and extensive cervicodorsal lesion (three or more spinal segments) with spinal expansion, of low signal in T1 sequences and high signal in T2 sequences and patchy enhancement. It has been demonstrated that 60% of patients may have periventricular lesions (areas of high aquaporin 4 concentration). In this case, NMO is not associated with cerebral white matter lesions, and the spinal lesions are confluent and extend to multiple segments (which is infrequent in MS); Cranial nerve and cerebellar involvement is common in MS and is not present in NMO.

43. NMO- IgG -against Aquaporin 4(water channel protein)recently identified serum antibody highly specific (>90%) and sensitive (>70%) for NMO. Typically oligoclonal bands are absent(unlike in MS)

44. Acute Demyelinating Disease MRI SPINE MRI BRAIN CSF Multiple sclerosis <2 spinal segments,peripherally located,predilection for posterior and lateral funiculi White matter lesions, Dawson fingers, juxtacortical , periventricular OGB and raised IgG index NMO >3 segments, gadolinium Enhancement and cord swelling. T1 dark lesions and Bright spotty lesions In 60% of pts. Usually periventricular . sometimes hypothalamic or brainstem Prominent pleocytosis with PMN or eosinophil predominance, no OGB in 80%, normal IgG index ADEM Variable lesion length Large, confluent white matter lesions. lesions of same age Pleocytosis ..OGB and IgG index may be abnormal transiently Idiopathic transverse myelitis Variable lesion length No brain lesion Pleocytosis ..OGB and IgG index may be abnormal transiently

45. IMMUNOLOGICAL DISORDERS

46. CNS involvement -5% of cases, 18% with myelopathy Asymmetrical ascending paraparesis with bladder involvement in most patients. Subacute or chronic,relapsing , slowly progressive polyradiculopathy , myelopathy Gadolinium enhancement of active intramedullary lesions. CSF-increased cells and protein, normal glucose, increased IgG levels and activated histiocytes . Characterstic lesion is a multifocal- subpial nodular enhancement of meninges adjacent to lesion within the cord or nerve roots. CXR PA ,ACE levels specificity at 80 to 95 the sensitivity is 60%.Definitive diagnosis requires biopsy. SARCOIDOSIS

47. Systemic Lupus Erythematosus -1 to 2% of patients with SLE The most accepted hypothesis is a vascular mechanism secondary to ischemic lesions ANA , APLA antibody is positive in 43 to 73% with myelitis patients with NMO ANA was positive in 52.6% CSF shows mild lymphocytic pleocytosis . Oligoclonal bands are variable finding Sjögren’s Syndrome - 35% of cases have spinal cord involvement. Includes episodes of optic neuritis but no oligoclonal bands

48. PARANEOPLASTIC DISORDERS

49. Subacute myelopathies MAY OCCUR BEFORE DETECTION OF CANCER Amphiphysin - specific antibodies raise the possibility of breast cancer. Paraneoplastic Disorders and Myelopathy

50. Lesions are necrotic involving both grey and white matter The lesion often involves the thoracic spinal cord extending one or several contiguous segments, that shows a high-intensity signal in T2 sequences and gadolinium enhancement. In contrast,nodular enhancement seen in intramedullary metastasis or extradural mets . With cord compression There is increased protein concentration in the CSF with few mononuclear cells. No tumour cells in CSF Anti YO, Anti Tr , Anti Hu antibodies, Anti GAD and anti Amphiphysian . PARANEOPLASTIC MYELOPATHY…

51. VASCULAR

52. BLOOD SUPPLY OF SPINAL CORD Vascular

53. 1% of all strokes, 5% of acute myelopathies 6 th to 7 th decade CAUSES: Atherosclerosis , surgery of aorta, systemic hypotension, Iatrogenic causes- vertebral angiography, spinal trauma Relative hypovascularity of thoracic cord(>60% of SCI occur) Spinal cord infarction

54. Pain(often radicular ) and sensory symptoms first Clinical Nadir within 12 hrs Anterior spinal artery syndrome –symmetric weakness with B/l Spinothalamic with bladder involvement. Post. spinal artery ischemia –rare Frequent overlap of signs . Can be devastating and life threatening FEATURES

55. Arterial thrombosis: aortic surgery, spinal angiography, vasculitis , embolism, arterial dissection, hypotension, and prothrombotic states. Anterior spinal artery lesion: anterior spinal syndrome Posterior spinal artery lesion: posterior column syndrome Subcommisural artery lesion : Brown Séquard syndrome Arteriovenous fistula- Weakness with Upright posture or walking Venous infarct ETIOLOGY

56. CSF is normal, although in arteriovenous fistulas there may be higher protein concentrations without pleocytosis . Spinal MRI shows single central hyperintensity DIAGNOSIS

57. Type of vascular lesion MRI findings Anterior spinal artery occlusion Elongated pencil like lesion in anterior cord Posterior spinal artery occlusion Triangular lesion in posterior cord Subcommisural Artery Lateral cord lesion Hematomyelia Appearance of blood products, Flow voids in the cord Fibrocartilaginous disc embolism Loss of vertical IV disc height, microfractures in vertebral endplates,T2 signal abnormality AV fistulas Long spinal cord lesion extending into conus,tortuous vessels.Spinal angiogram needed to confirm

58. METABOLIC MYELOPATHIES

59. Despite widespread screening Vit . B12 deficiency is – 15-25% of older individuals ETIOLOGY :- malabsorptive disorders atrophic gastritis, H2 antagonists and metformin , fish tapeworm SUBACUTE COMBINED DEGENERATION

60. Fatigue, generalised weakness Slowly progresive myelopathy Mild sensory symptoms with loss of vibration and proprioception sense( POSTERIOR COLUMN)-First manifestation Paraparesis with hyperreflexia and spasticity (PYRAMIDAL) Bladder bowel also can occur Associated PERIPHERAL NEUROPATHY Psychological symptoms , cognitive decline Optic neuropathy Clinical features

61. 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 Diagnosis

62. MRI SPINE – hyperintense T2 WEIGHTED signal in posterior and anterolateral columns without contrast enhancement. INVERTED V SIGN

63. INVERTED V SIGN

64. Nitrous oxide exposure

65. CAN alone cause myelopathy (less common) CAUSES:- Alcoholics GI disease pregnancy drugs – trimethoprim Myelopathy , neuropathy, optic neuropathy ,cognitive decline Serum folate ,red cell folate (more reliable) and serum homocysteine levels for diagnosis FOLATE DEFICIENCY

66. Posterior and lateral columns are affected with reduced ankle reflexes Causes- Gastric surgery Zinc toxicity TPN Malabsorption Hypocupremic anemia with ringed sideroblasts with vacuolated myeloid precursors in marrow mimiking MDS Clinical - Myelopathy , myeloneuropathy Diagnosis-serum ceruloplasmin , serum or urinary copper Copper deficiency

67. 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 Toxins

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

69. Chemotherapy induced Hepatic Myelopathy Heroin Myelopathy Fluorosis Other toxic myelopathies

70. DEGENERATING MYELOPATHY

71. FAMILIAL SPASTIC PARAPLEGIA: 3 rd – 4 th decade. Can occur in 1 st decade too AD/AR/X-linked Sensory involvement is minimal,Bladder is involved late in the illness. Amyotrophy , MR, Optic atrophy, cataracts, epilepsy,peripheral neuropathy and deafness Survival is long because respiration is spared Only symptomatic therapy

72. PHYSICAL AGENTS

73. Amount of current, duration of contact, resistance offered by the skin Immediate or Delayed – few days to 6 weeks The deep white matter is the most affected since it comprises the cortex and the subcortical arcuate fibers -when high ampere current flows through body Heating of tissue, Vasocclusive changes, demyelination , fracture . Involvement of anterior spinal artery and its branches SPINAL ATROPHIC PARALYSIS - delayed ,focal muscular atrophy. gray matter affected the most.because of low voltage current Lightening injury: Arborescent marks Limbs may be pale and cold or cyanotic Late presentation of an atrophic limb paralysis Also associated with severe motor polyneuropathy ELECTRICAL INJURIES

74. Upper thoracic cord Little or no brain inv. Posterior column > lateral column Decompression in hyperbaric chamber, Symptomatic treatment CAISSON’S DISEASE

75. MC - Mediastinal irradiation for Hodgkin’s disease Early transient(3 – 6 months after )- Lhermitte sign. Disappear after few months. Spongy appearance of white matter with demyelination . Delayed progressive/Slowly evolving amyotrophy - Between 12-15 months, sensory followed by motor symptoms PAIN IS ABSENT(+ nt in spinal mets .) LESION IS EXTENSIVE in rostro caudal fashion than in vascular and demyelinating myelopathy Coagulative necrosis ,vascular changes, secondary degeneration Could be avoided if 6000 cGy over 30 – 70 days not exceeding 200cGy/day or 900cGy/week RADIATION MYELOPATHY

76. Painful root and cord symptoms Syphilis, Resistant meningitis, TB, Penicillin, Contrast, steroids, Thickening of Arachnoid , proliferation of connective tissue and adhesion between arachnoid & dura . PERSISTANT PAIN commonly in lumbofemoral regions, but weakness and atrophy are less frequent. CT/MRI contrast showing total or partial loss of spinal subarachnoid space(candle guttering). Mri shows loss of normal ring of CSF or localised loculations of CSF Degeneration of peripheral fibres of posterior and lateral column CHRONIC ADHESIVE ARACHNOIDITIS