Faculty of Medicine Siriraj Hospital Mahidol University

The Neurological Society of Thailand February 6th, 2020 Chiangrai Hospital in Systemic Diseases

Naraporn Prayoonwiwat, M.D. Division, Department of Medicine Siriraj Hospital

[email protected] 02 419 7101-2 Myelopathy An Approach Scope  Essential neuroanatomy  ascending tract  descending tract  vascular supply  Approach: differential diagnosis  clinical presentation  clinical course  etiology d NP AscendingMyelopathy tracts LateralAn spinothalamicApproach tract Scope Ventral spinothalamic tract  Essential Dorsalneuroanatomy funiculus: Fasciculus cuneatus Fasciculus gracilis P ascendingSpinoreticulothalamic tract tract  descendingSpinocerebellar tract tract  vascularCuneocerebellar supply tract  Approach:Rostrocerebellar differentialtract diagnosis  clinical presentation  clinical course  etiology d NP Brazis: Localization in Clinical Neurology 2017 Myelopathy An Approach Scope  Essential neuroanatomy P ascending tract  descending tract Sensory vascularafferent fibers supply via dorsal root Unmyelinated fiber (pain, temperature) ascend/descend few Approach:levels to synapse differential in dorsal horn diagnosis (2nd order neurons) axons decussateclinical presentationin anterior white commissure to ventrolateral clinical quadrant course as lateral spinothalamic tract ascends etiology to ventrolateral thalamus d NP Brazis: Localization in Clinical Neurology 2017 Sensory Spinothalamic tract in Tracts dorsolateral Pain and brain stem Temperature Sensation S Pathway L T C Cross midline S via anterior L commissure T Lateral Fibers ascend Spinothalamic 2-3 segments Tract S L Patten: d NP Neurological Differential Diagnosis 1996 Sensory LTC Tracts Tactile Sensation

Spinothalamic tract to VPL nucleus of thalamus Cross midline via anterior Ventral white Spinothalamic commissure Tract

d NP Myelopathy An Approach Scope  Essential neuroanatomy P ascending tract  descending tract Myelinated vascular fibers (position, supply vibration) enter dorsal funiculus medially as fasciculus gracilis (sacral > T6) laterally Approach: as fasciculus differential cuneatus (> diagnosis T6) ascend to synapse clinical 2nd order presentation neurons (nucleus gracilis, nucleus cuneatus clinical) in medulla; course decussate and ascend as medial lemniscus etiologyto ventrolateral thalamus d NP Brazis: Localization in Clinical Neurology 2017 Sensory Nucleus gracilis S Nucleus cuneatus Tracts CT L Cross midline Cervical Dorsal Column Sensation Fasciculus cuneatus L S (mid T to C) T Thoracic

Fasciculus gracilis (S, L to lower T) LS Lumbar Accurate touch, 2-point discrimination, position d NP Sacral Neuroanatomy of Cross Section: Ascending Tracts Fasciculus gracilis Fasciculus cuneatus S L Th C Dorsal spinocerebellar Th Lateral C L S corticospinal

S Ventral L Th spinocerebellar C

Lateral Ventral corticospinal spinothalamic d NP Brazis 2001 Myelopathy Descending tracts An Approach Lateral corticospinal tract Scope Ventral corticospinal tract  Essential Corticorubrospinalneuroanatomytract  ascendingVestibulospinal tract tract Reticulospinal tract P descending tract From 1o vascularmotor, lateral supply premotor and supplementary motor Approach: cortex descend differential through corona diagnosis radiata, posterior limb ofclinical internal capsule presentation, ventral midbrain, pons; 90% decussate clinical at ventral course medulla cross midline to lateral corticospinal etiology tract, 10% continue as ventral cortico- spinal tract to cross at anterior commissure (C, upper T ) d NP Brazis: Localization in Clinical Neurology 2017 CTL Medullary decussation Lateral CS Motor tract 90% Pathway L TC Cervical Ventral CS tract 10% Corticospinal Tract L Cross midline T via anterior commissure Thoracic

L d NP Lumbar Neuroanatomy of Spinal Cord Cross Section: Descending Tracts Fasciculus gracilis Fasciculus cuneatus S L Th C Dorsal spinocerebellar Th Lateral C L S corticospinal

S Ventral L Th spinocerebellar C

Lateral Ventral corticospinal spinothalamic d NP Brazis 2001 Myelopathy Arterial supply An Approach PAnterior spinal artery Scope Anterior sulcal artery  Essential neuroanatomyCircumflex artery  ascendingPPosterior tract spinal artery  descendingRadicular tract artery Radiculomedullary artery P arterial supply  Approach: differential diagnosis  clinical presentation  clinical course  etiology d NP Brazis: Localization in Clinical Neurology 2001 Neuroanatomy of Spinal Cord Arterial Supply Posterior spinal arteries Anterior spinal Radiculo arteries medullary artery of Adamkiewicz

Radicular artery

Aorta d NP Prasad S, Price RS, Karnick SM, et al. Neurology 2007;69:E41 Neuroanatomy of Spinal Cord Arterial Supply

Level Feeder C1-C4 Anterior spinal artery, no radiculo- medullary branch C5-T2 2-4 Radicular arteries from vertebral, cervical arteries T3-T8 One radiculomedullary artery, few intercostal arteries T9-S5 Radiculomedullary branches, Adamkewicz artery d NP Brazis: Localization in Clinical Neurology 2017 Vertebral artery

From costo-cervical Watershed trunk area

Aortic From T5 or T6 arch intercostal artery

Adamkewicz artery Spinal cord from left lower arterial intercostal arteries T10, T11 or T12 d NP supply Posterior spinal arteries Anterior sulcal artery Spinal Cord Segmental Arterial Supply

Circumflex artery Radiculo- medullary arteries Anterior spinal d NP artery Brazis: Localization in Clinical Neurology 2017 Neuroanatomy of Spinal Cord Arterial Supply Fasciculus gracilis Posterior spinal artery Fasciculus cuneatus

Lateral corticospinal

Lateral Anterior sulcal artery spinothalamic Anterior spinal artery d NP Brazis: Localization in Clinical Neurology 2017 Neuroanatomy of Spinal Cord Cord-Vertebra Levels C

Difference: spinal and vertebral segmentsT SpinalEssentialNo. neuroanatomySpinous process segment Versus Cord segment Cervical 8 0 (matched) Thoracic 12 T6 cord ~ T4 vertebra L

Lumbar 5 L3 cord ~ T11 vertebra S

J Emer Med Service Sacral 5 S1 cord ~ T12 vertebra 11 Nov2014 Coccygeal 1 conus medullaris ~ L1-2

d NP Brazis: Localization in Clinical Neurology 2001 Myelopathy Differential Diagnosis Differential diagnosis: acute myelopathy versus non myelopathy SignsMyelopathy strongly indicating myelopathy versus non myelopathy : Sensory level on torso : Spinal tract crossed findings (e.g., unilateral pyramidal signs with contralateral spinothalamic findings) : Spinal tract-specific sensory findings (e.g., selective spinothalamic findings with preserved dorsal column findings; suspended band of spinothalamic sensory loss) : Urinary retention Signs consistent with but not diagnostic of myelopathy : Glove-and-stocking sensory loss (consider peripheral neuropathy)

: Hyporeflexia/hypotonia (consider peripheral neuropathy)

: Unilateral or bilateral signs (consider brain or brainstem disorders) Signs suggesting alternative diagnosis

: Spasms, rather than (consider stiff-person syndrome) : Paratonic rigidity (consider frontal lobe disorder)

: Cognitive impairment (consider frontal lobe or diffuse brain disorder)

: Dysarthria and dysphagia (consider brainstem disorder, such as ) d NP Schmalstieg WF, Weinshenker BG. Neurology 2010;75;S2 Myelopathy Differential Diagnosis Extramedullary versus intramedullary Symptoms & Signs Extramedullary Intramedullary Spontaneous pain Radicular pain: lancinating Funicular (central) pain: Dermatome distribution painful dysesthesia Common, early Ill-defined Vertebral pain Common Unusual LMN signs Unusual Widespread with Segmental, if present atrophy, fasciculation UMN signs Early, present Late, present Sensory deficits Ascending progression Descending progression Dissociative sensory loss Perineal sensation Common, marked ‘Sacral sparing’ (saddle area) Sphinctor Late Early with caudal lesion involvement (conus/cauda equina) Trophic changes Unusual Common d NP Brazis PW, Masdeu JC, Biller J. Ed. Localization Clinical Neurology 2017.pp105-32 Spinal Cord Syndromes

Complete transection Brown Sequard

Central cord Anterior spinal artery d NP Brazis: Localization in Clinical Neurology 2017 Inflammatory:Spinal Post vaccine, Cord Trauma:Syndromes spinal injury (stab) post infectious, MS, NMOSD : intramedullary Trauma: spinal injury, disc tumor (primary/metastatic) herniation Inflammatory: MS, Post Vascular: epidural vaccine, post infectious (anticoagulant) Neoplasm: tumor, paraneoplastic ✔ ✔ Trauma:Complete hyperextension transection Vascular:Brown Aortic Sequarddissection, Neoplasm: intramedullary vasculitis, aortic tumor Degenerative/hereditary: Iatrogenic: Post-op spine, , hydromyeliaaorta, thoracic ; post-op spinal AVM; decompression injury ✔ Central cord ✔Anterior spinal artery d NP Brazis: Localization in Clinical Neurology 2017 Spinal Cord Syndromes

Posterolateral column Posterior column

Anterior horn Anterior horn-pyramidal tract d NP Brazis: Localization in Clinical Neurology 2017 Inflammatory:Spinal HIV vacuolar Cord Infection:Syndromes myelopathy, HTLV-1 () associated (HAM/TSP) Degenerative/hereditary: Toxic: Nitrous oxide myelo- cervical spondylosis neuropathy Vascular: posterior spinal Metabolic: B12, copper artery deficiency-related myeloneuropathy ✔Degenerative/hereditary:Posterolateral column ✔Posterior column Infection:Cervical spondylosis poliomyelitis Iatrogenic: post radiation Degenerative: amyotrophic Infection: postpolio synd lateral sclerosis (ALS) Metabolic: hexosaminidase deficiency Degenerative/hereditary: spinal✔Anterior muscular horn atrophy ✔Anterior horn-pyramidal tract d NP Brazis: Localization in Clinical Neurology 2017 Acute Myelopathy Differential Diagnosis  Neoplastic  Infectious  Vascular  Structural  Inflammatory/demyelinating/autoimmune  Toxic/metabolic  Iatrogenic  Miscellaneous

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Differential Diagnosis  Neoplastic  Etiology Clinical Pearls Metastatic epidural History cancer/myeloma, risk spinal cord factors for cancer (e.g., smoker); compression Initial cancer presentation in 20% Extramedullary History hematologic malignancy myeloid tumors Intramedullary History cancer/myeloma, risk metastasis factors for cancer Primary spinal cord Lymphoma > subacute tumors Others usually chronic

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Differential Diagnosis  Infectious Etiology Clinical Pearls Spinal epidural Immunocompromised, spinal abscess procedures Fever/chill/night sweat Intravenous drug user Intramedullary infectious

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute MyelopathyP Spinal Infection Classification Intramedullary Abscess Subdural Empyema Spinal Abscess / Empyema

Spinal Discitis Infection Spondylodiscitis Spondylitis

Paraspinal infection

Lener S, et al. Management of spinal infection: a review of the literature. d NP Acta Neurochirurgica 2018;160:487–96 Acute MyelopathyP Spinal Epidural Abscess Pathogenesis  Bacteria gain access to epidural space - contiguous spreading (1/3) - hematogenous dissemination (1/2) - source unidentified  Spinal cord injury: - direct: mechanical compression - indirect: vascular occlusion (septic thrombophlebitis)

d NP Acute MyelopathyP Spinal Epidural Abscess Predisposing conditions  Underlying disease: DM, alcoholism, HIV  Spinal abnormality/intervention: trauma, degenerative joint disease, surgery, drug injection, placement of stimulators or catheters  Potential local/systemic source of infection skin/soft tissue infection, osteomyelitis, UTI, sepsis, indwelling vascular access, IV drug use, nerve acupuncture, tattooing, epidural analgesia/nerve block d NP Acute MyelopathyP Spinal Epidural Abscess Organisms common  Staphylococcus aureus most common  Coagulase-negative staphylococci, e.g. S. epidermidis (spinal procedures, placement of catheter for analgesia, glucocorticoids, surgery)  Gram-negative bacteria, esp. E. coli (urinary tract infection) Pseudomonas aeruginosa (IV drug user)

d NP Acute MyelopathyP Spinal Epidural Abscess Organisms rare  Anaerobic bacteria  Actinomycosis  Nocardiosis  Mycobacteria  Fungi  Parasite

d NP Acute MyelopathyP Spinal Epidural Abscess Clinical features: variable progression  Stage 1: back pain at affected level  Stage 2: radicular pain radiating from involved spinal level  Stage 3: motor weakness, sensory deficit, bladder/bowel dysfunction  Stage 4: paralysis Common symptoms: back pain (3/4), fever (1/2), neurologic deficit (1/3) Level: thoracolumbar, lumbar > cervical level d NP Acute MyelopathyP Spinal Epidural Abscess Diagnosis:  Clinical: Back pain, fever, spinal cord dysfn  Imaging: MRI or CT scan with contrast

d NP Acute MyelopathyP Spinal Epidural Abscess Diagnosis:  Clinical: Back pain, fever, spinal cord dysfn  Imaging: MRI or CT scan with contrast  CSF study: parameningeal reaction (non specific)  Demonstration of organism: culture (blood, primary source, needle aspiration/biopsy Treatment:  Medical: iv antibiotics usually 6 weeks  Surgical: drain and debridement d NP Acute Myelopathy Differential Diagnosis  Intramedullary infectious myelitis Preferred Bacteria Clinical clues diagnostic test Intramedullary Surgical drainage, Systemic infection pyogenic isolation of abscess organism Borrelia Serum and CSF Tick bite burgdorferi serology Erythema migrans Lyme disease rash, polyarthritis Treponema Serum RPR (rapid pallidum plasma regain) Infarct (meningo- Syphilis CSF VDRL vascular) Mycobacterium CSF CSF Ziehl HIV tuberculosis Neelson (NZ) stain Meningomyelitis d NP FlanaganCulture, EP, Pittock TB PCRSJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Differential Diagnosis  Intramedullary infectious Preferred Virus Clinical clues diagnostic test Herpes simplex CSF PCR May be necrotizing virus HSV 1, 2 Genital/oral HSV Varicella zoster CSF PCR, IgM Zoster rash virus May cause vasculopathy Cytomegalo CMV PCR Polyradiculo- virus myelitis in HIV May be necrotizing Ebstein Barr EBV PCR Postviral immune- virus mediated myelitis d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Differential Diagnosis  Intramedullary infectious myelitis Preferred Virus Clinical clues diagnostic test West Nile virus CSF IgM Acute flaccid paralysis Enterovirus: CSF PCR Acute flaccid D68, 70, 71 paralysis Cocksackie A, B Poliovirus CSF PCR Acute flaccid paralysis

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Differential Diagnosis  Intramedullary infectious myelitis Preferred Parasite Clinical clues diagnostic test Gnathostoma Serum and CSF Ingestion of raw, spinegerum serology undercooked freshwater fish, frog, eel, reptile, bird Larva migrans Radicular pain Eosinophilia (serum/CSF)

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute MyelopathyP Parasitic Myelitis  Spinal gnathostomiasis  Gnathostoma spinegerum  History of exposure: ingest 3rd stage larva (raw fish, shrimp)  Pathogenesis: - Larva travel along spinal nerves and vessels through intervertebral foramen to enter spinal cord - Direct destruction of nervous tissue > hemorrhagic tracks, eosinophils d NP Emerging Infectious Diseases CME. 2011;17:1174-80 Acute MyelopathyP Parasitic Myelitis  Spinal gnathostomiasis  Clinical: 248 patients

Syndromes Portal of entry Clinical % Radiculomyelitis Intervertebral foramen Sharp radicular pain 55 Myelitis/Myelo along spinal nerve/vessel Spinal cord syndrome / Skull base neural foramen Severe , stiff 30 Meningo along cranial nerve/vessel neck, CN palsy, altered encephalitis consciousness, focal signs Hemorrhage - intracerebral Intravertebral/neural Headache, focal sign 8 - subarachnoid foramen Headache, stiff neck 7

d NP Emerging Infectious Diseases CME. 2011;17:1174-80 Acute MyelopathyP Parasitic Myelitis  Spinal gnathostomiasis  Clinical: - cutaneous larva migrans present in only 7% - myelopathy: radiculopathy >> acute spinal cord syndrome  Blood and CSF: eosinophilia  MRI: cord edema, multiple levels gadolinium enhancement

d NP Emerging Infectious Diseases CME. 2011;17:1174-80 Acute Myelopathy Differential Diagnosis  Intramedullary infectious myelitis Preferred Parasite Clinical clues diagnostic test Schistosomiasis Serum and CSF Swimming in fresh S. manosi serology water S. hematobium Demonstration of Lumbar pain, eggs in urine/stool numbness, weakness, urinary symptom, erectile dysfunction Eosinophilia (serum/CSF)

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute MyelopathyP Parasitic Myelitis  Spinal schistosomiasis  Uncommon  History of exposure (water contaminated with cercaria) > skin penetration  Pathology: granulomatous surrounding ova  Clinical: asymptomatic -> necrotizing TM : low back pain (radicular pain) : acute myelopathy lower thoracic to conus d NP medullaris (myeloradiculopathy) Acute MyelopathyP Parasitic Myelitis  Spinal schistosomiasis  CSF: non specific pleocytosis, eosinophilia <50% of cases; protein  MRI: : enlargement of conus medullaris : thickening of cauda equina roots : heterogeneous enhancement patterns (nodular intramedullary enhancement > granuloma, surrounding ova d NP Adeel AA. Spinal cord schistosomiasis. Sudan J Paediatr 2015;15:23-8 Acute Myelopathy Differential Diagnosis  Intramedullary infectious myelitis Preferred Virus Clinical clues diagnostic test HIV HIV serology Acute infection > at initial presentation Chronic (vacuolar myelopathy) >more common Rabies PCR from skin Bat/dog bites biopsy in neck Hydrophobia beneath hair line

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Differential Diagnosis  Vascular Etiology Clinical Pearls Epidural, subdural, Post spinal procedure, post subarachnoid traumatic, coagulopathy, small- hematoma vessel vasculitis, prior radiation Intramedullary AVM, cavernous malformation, “hematomyelia” hemorrhagic metastasis, bleeding diathesis, Osler– Weber–Rendu, prior radiation Spinal cord infarct Post aortic surgery, aortic (or vertebral artery) dissection, hypotension, vascular risk factors, endocarditis, intravascular lymphoma, thrombophilia d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute MyelopathyP Spinal Cord Infarction  Rare disorder  Incidence: about 1% of all  Mean age: 64 years old  Mechanism Diseases/procedures involving thoraco-abdominal Arterial occlusion: arteriosclerosis, embolic occlusion, vasculitis, infection, Hypoperfusion Venous infarction d NP Acute MyelopathyP Spinal Cord Infarction Anterior spinal artery occlusion  Most common of spinal cord infarction  Onset: abrupt  Back pain ~70% at level of lesion  Acute stage: flaccid paralysis, areflexia  Days >> weeks: spasticity,  Presentation bilateral > unilateral

d NP Acute Myelopathy Spinal Cord Infarction Anterior spinal artery occlusion  Neurologic findings : Deficits below level of the lesion - Loss of motor function - Loss of pain/temperature sensation : Sparing of proprioceptive, vibratory sense ‘dissociative sensory loss’ : Autonomic dysfunction - Sexual dysfunction - Bowel and bladder dysfunction d NP Acute MyelopathyP Spinal Cord Infarction Aortic surgery  Most common cause of spinal cord infarction  Occur in both open surgery and endovascular repair  Presentation: immediate after surgery, or after a period of normal neuro function

d NP Acute MyelopathyP Spinal Cord Infarction  High mortality rate  Incidence ~ 4%  Acute occlusion of branches of aorta: celiac, superior mesenteric, renal and radicular arteries  Typically involve mid-lower thoracic cord

d NP Acute Myelopathy Differential Diagnosis  Vascular  Etiology Clinical Pearls Fibrocartilaginous Young women, preceding trauma, embolism Valsalva Vascular malformation - Dural AV fistula Older men, stepwise deterioration precipitated by exercise, Valsalva - AVM/cavernous Older children/young adults malformation Usually present due to hemorrhage Venous congestive Venous anomalies of inferior vena cava

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute MyelopathyP Spinal Arteriovenous Shunt  Abnormal connections between spinal arteries and bypass network  Type: Arteriovenous fistula (AVF); dural AVF most common, usually at lower T or T-L level Arteriovenous malformation (AVM), rare; venous capillary nidus  Pathophysiology: direct cord compression (mechanical) by engorged or spinal blood flow disturbance and cord González AL, et al. Spinal AVM. In July J, Wahjoepramono EJ (ed), d NP Neurovascular Surgery 2019 Acute Myelopathy Spinal Arteriovenous Shunt  Clinical: Slow progressive myelopathy (some with recurrent symptoms) - Motor weakness (most common) - Paresthesia P- Sphincter disturbances - Acute onset of back pain or myelopathy (perimedullary/intramedullary type) - Meningeal irritation (bleeding)

Takai K. Historical changes in the classification of spinal AV shunts. d NP Neurol Med Chir (Tokyo) 2017; 57 Acute Myelopathy Spinal Arteriovenous Shunt  MRI: perimedullary AVM P- T1W, hypointense, swollen spinal cord - Diffuse T2W intramedullary lesion at central area >> cord edema (ischemia, congestion) P - Flow-void serpiginous lesion overlying cord surface

d NP Acute Myelopathy Spinal Arteriovenous Shunt  Angiogram: perimedullary AVM - demonstration of arterial feeder, capillarry nidus, draining vein

d NP Acute Myelopathy Differential Diagnosis  Structural Etiology Clinical Pearls Osteoporotic History osteoporosis vertebral collapse Steroid use Herniated disc History degenerative disc disease Prior spine surgery Atlantoaxial Down syndrome subluxation Rheumatoid arthritis Spondylosis Prior history of spine surgery Epidural Obese, corticosteroid use lipomatosis Surfer’s Novice surfers myelopathy d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Differential Diagnosis  StructuralHerniated discs Etiology Clinical Pearls Osteoporotic History osteoporosis vertebral collapse Steroid use History degenerativeC2 disc disease Herniated disc myelopathy Prior spine surgery Atlantoaxial Down syndrome subluxation Rheumatoid arthritis Spondylosis Prior history of spine surgery Epidural Obese, corticosteroidRheumatoid use lipomatosis arthritis Surfer’s Novice surfersRev Colomb Radiol. 2011; 22:1-21 myelopathy d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Differential Diagnosis  Inflammatory/demyelinating/autoimmune Etiology Clinical Pearls Neuromyelitis Females; African descent optica spectrum History of , Sjogren’s or disorder myasthenia gravis Accompanying optic neuritis or nausea/vomiting; tonic spasms/ Lhermitte’s Young Caucasian women Lhermitte’s, sensory useless hand (proprioceptive deficit) MOG-IgG myelitis Conus involvement; ADEM d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Differential Diagnosis  Inflammatory/demyelinating/autoimmune Etiology Clinical Pearls ADEM Children Recent infection/vaccination Spinal cord African-American sarcoidosis Systemic/pulmonary symptoms Connective tissue Synovitis, oral/genital ulcers disease-associated (Behcet’s disease) Paraneoplastic (can History cancer, cancer risk factors be necrotizing) (e.g., smoking) Idiopathic d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Myelopathy Myelitis Clinical manifestation: Acute or subacute spinal cord dysfunction motor: weakness (1-4 limbs) mono/para/tri/hemi/tetra-paresis sensory: sensory level autonomic: bladder, bowel, sexual Pathophysiology: interruption in ascending and descending neuroanatomical pathways in transverse plane of spinal cord. Pathology: inflammatory process d NP Acute Transverse Myelitis Cautions in Diagnosis of Acute Myelitis 1. History of spine radiation in 10 years 2. Clinical compatible with ischemic process: hyperacute onset, deficits according to vascular territory 3. Findings compatible with arteriovenous malformation 4. Serologic study compatible with connective tissue diseases 5. Clinical/laboratory study suggestive of infections (e.g. syphilis, AIDS, HTLV-1, mycoplasma or virus) 6. Clinical, MRI or laboratory study compatible with MS, NMOSD, ADEM d NP Myelitis:Spinal Differential Cord Dysfunction Diagnosis

An Approach c Presencec of spinal cord MRI lesion

LETM Partial involvement Brain MRI compatible with Brain MRI compatible with MS

NMO and not MS CSF oligoclonal bands: +ve

c c c AQP4/NMOc IgG:+ve Abnormal VEPs

Yes No Yes None

NMOSD Additional data Hi risk for MS Lo risk for MS

Dry eyes, dry Preceding Systemic Oral, genital Paraneoplastic Vaccine mouth infection ANA +ve ulcers, uveitis panel +ve SS-A/SS-B +ve

Post Post Sjogren Systemic lupus Behcet Paraneoplastic infectious vaccination syndrome erythematosus disease myelopathy d NP Acute Myelopathy Systemic Autoimmune Disease  Sjӧgren syndrome  Clinical: - Middle to elder age female - Dry eyes, dry mouth > 3 months - Acute/progressive myelopathy; 1st symptom  CSF: non specific  MRI: LETM, C-level  Immune profile: anti SS-A (Ro), anti SS-B (La) antibody, Schirmer test, lip biopsy (sialadenitis) d NP Transverse myelitis. Beh SC et al. Neurol Clin 2013;31:79-138. Acute Myelopathy Systemic Autoimmune Disease  Systemic lupus erythematosus  Clinical: - Skin, serositis, renal, hematologic - Acute myelopathy 1-3% of CNS lupus within first 5 years of disease - Recurrence 21-56%  CSF: normal/non specific; OCB rarely pos  MRI: LETM, T-level  Immune profile: ANA, anti dsDNA, antiphospholipid antibody d NP Transverse myelitis. Beh SC et al. Neurol Clin 2013;31:79-138. Acute Myelopathy Systemic Autoimmune Disease  Antiphospholipid syndrome  Clinical: - History of deep vein thrombosis - Pulmonary embolism - Multiple miscarriages - Young-onset stroke - Monophasic > recurrent myelitis:  CSF: normal  MRI: normal in ~ 40%  Immune profile: Antiphospholipid antibody d NP Transverse myelitis. Beh SC et al. Neurol Clin 2013;31:79-138. Acute Myelopathy Systemic Autoimmune Disease  Behcet disease  Clinical: - Triad: recurrent oral ulcers, genital ulcers, uveitis - More common in male - Parenchymal () - Vascular (cerebral venous thrombosis, arterial infarction) - Myelopathy: 2.5-30% C-T level subacute/progressive d NP Transverse myelitis. Beh SC et al. Neurol Clin 2013;31:79-138. Acute Myelopathy Systemic Autoimmune Disease  Behcet disease  Clinical: - Triad: recurrent oral ulcers, genital ulcers, uveitis - More common in male - Parenchymal/Vascular/Myelopathy  CSF: non specific; L or PMN; OCB neagative  MRI: LETM, can be whole cord with edema  Test: Pathergen test, HLA B5/B51

d NP Transverse myelitis. Beh SC et al. Neurol Clin 2013;31:79-138. Acute Myelopathy Systemic Autoimmune Disease  Paraneoplastic myelopathy  Clinical: - Isolated myelopathy: rare - Subacute, insidious onset (weeks-months) - Mostly women - Cancer: lung, breast (combined ~50%), kidney, thyroid, ovary, melanoma, lymphoma - May precede cancer diagnosis

Flanagan EP, et al. Paraneoplastic isolated myelopathy Clinical course d NP and neuroimaging clues. Neurology 2011;76:2089–95 Acute Myelopathy Systemic Autoimmune Disease  Paraneoplastic myelopathy  CSF: non specific; elevated IgG index  MRI: normal or LETM  Paraneoplastic auto antibody: Amphiphysin, CRMP-5 (combined ~ 60%) PCA type 1, 2 ANNA-1, ANNA-3

CRMP-5: collapsing response-mediator protein 5; PCA: Purkinje-cell cytoplasmic antibody type 1; ANNA: antineuronalnuclear antibody

Flanagan EP, et al. Paraneoplastic isolated myelopathy Clinical course d NP and neuroimaging clues. Neurology 2011;76:2089–95 Acute Myelopathy Systemic Autoimmune Disease  Idiopathic transverse myelitis  Clinical criteria (proposed 2002) - Spinal bilateral motor, sensory or autonomic dysfunction - Bilateral sensory level (symptom+sign) - Evidence of spinal inflammation MRI: gadolinium enhancement or CSF: elevated CSF cell or IgG index - Duration of symptoms 4 hours to 21 days - R/O extra-axial compression d NP Transverse Myelitis Consortium Working Group. Neurology 2002;59:499-505 Acute Myelopathy Differential Diagnosis  Toxic/metabolic  Etiology Clinical Pearls Vitamin B12 Usually chronic but present acute deficiency in setting of nitrous oxide use Lathrysm Africa, Asia Grass pea ingestion (Lathyrus sativus) Konzo Raw cassava (cyanide) ingestion Heroin Acute or subacute combined degeneration-like presentation

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute Myelopathy Metabolic Myelopathy  Subacute combined degeneration - B12 deficiency - Copper deficiency P- Nitrous oxide use > acute myelopathy  Clinical: loss of vibration, proprioception; gait ataxia (sensory ataxia); muscle weakness Usually chronic, acute in nitrous oxide use  MRI: long cord lesion, dorsal part, non enhanced; inverted V-shape Moghaddham SM, Bhatt AA. Intramedullary cord lesions. d NP Insights Imaging 2018;9:511-26 Acute Myelopathy Metabolic Myelopathy  Subacute combined degeneration - B12 deficiency - Copper deficiency P- Nitrous oxide use > acute myelopathy  Clinical: loss of vibration, proprioception; gait ataxia (sensory ataxia); muscle weakness Usually chronic, acute in nitrous oxide use  MRI: long cord lesion, dorsal part, non enhanced; inverted V-shape Moghaddham SM, Bhatt AA. Intramedullary cord lesions. d NP Insights Imaging 2018;9:511-26 Acute Myelopathy Differential Diagnosis  Iatrogenic  Etiology Clinical Pearls Radiation History of spinal irradiation Medications Cytarabine, methotrexate

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319- Acute MyelopathyP Post Radiation Myelopathy  of radiation, irreversible  History of radiation >4,000 Rad  Types > acute myelopathy > subacute/chronic progressive Acute: weeks to months; 2% of ATM; transient sensory symptoms (Lhermitte’s sign), resolved in 2-36 weeks Early late: 6 months to 2 years Late: > 2 years

d NP Sanchez AMG, et al. Diagnostic approach to myelopathy. Rev Colomb Radiol 2011; 22:1-21 Acute Myelopathy Differential Diagnosis  Miscellaneous  Etiology Clinical Pearls Electrocution Recent electrocution myelopathy Decompression Scuba divers sickness (Caisson disease) Functional Recent psychologic stressor Inconsistencies on examination

d NP Flanagan EP, Pittock SJ. Handbook Clin Neurol 2017;140: 319-