Acute Myelopathies

1. Acute Myelopathies Darrell Laudate 12/4/09 AM Report

2. Overview of Acute Myelopathy • Spinal cord dysfunction or myelopathy, can occur due to a lesion arising within the spinal cord or due to compression of the spinal cord originating outside of it • Frequently devastating, often producing quadriplegia, paraplegia, and sensory deficits • Many spinal cord diseases are reversible if recognized and treated at an early stage

3. Transverse Myelopathy vs. Myelitis • Transverse Myelopathy refers to clinical presentation of severe motor, sensory, and autonomic dysfunction (bowel, bladder, and sexual abnormalities ) below a spinal cord lesion due to any acute/ subacute process affecting the spinal cord, compressive or not • Often associated with back pain • Transverse Myelitis refers to an inflammatory process of the grey and white matter of the spinal cord

4. Transverse Myelopathies (cont.) • Localization of the lesion depends upon the level of the spinal cord involved and the extent of the involvement of the various long tracts. In some cases, there is almost total paralysis and sensory loss below the level of the lesion, others only partial loss • If cervical area is involved, all four limbs may be involved and there is risk of respiratory paralysis (segments C3,4,5 to diaphragm) • Lhermitte's sign: an electric shock-like sensation down the neck, back, or extremities that occurs with bending of the neck • Lesions of the lower cervical (C2-T1) region will cause a combination of upper and lower motor neuron signs in the upper limbs, and exclusively upper motor neuron signs in the lower limbs. • A lesion of the thoracic spinal cord (T1-12) will produce a spastic paraplegia. • A lesion of the lower part of the spinal cord (L1-S5) often produces a combination of upper and lower motor neuron signs in the lower limbs

5. Upper vs Lower Motor Neuron Lesions • Lower motor neuron lesion is a lesion which affects nerve fibers traveling from the anterior horn of the spinal cord to the relevant muscle(s)  • Associated with areflexia • leads to flaccid paralysis (paralysis accompanied by muscle loss) • Upper motor neuron lesion is a lesion of the neural pathway above the anterior horn cell or motor nuclei of the cranial nerves and are marked by: • Spasticity, increase in tone in the extensor muscles (lower limbs) or flexor muscles (upper limbs) • Clasp-knife response where initial resistance to movement is followed by relaxation • Weakness in the flexors (lower limbs) or extensors (upper limbs), but no muscle wasting • Brisk tendon jerk reflexes • Babinski or Hoffman sign is present • increase deep tendon reflex • Pronator drift • (Spinal Shock - loss of sensation accompanied by motor paralysis with initial loss but gradual recovery of reflexes • Occurs following a spinal cord injury, thus what may have looked like a lower motor neuron lesion can later reveal itself to be an upper motor lesion)

6. Important Dermatomal Landmarks • C2 - posterior half of the skull cap • C3 - area correlating to a high turtle neck shirt • C4 - area correlating to a low-collar shirt • C6 - (radial nerve) 1st digit (thumb) • C7 - (median nerve) 2nd and 3rd digit • C8 - (ulnar nerve) 4th and 5th digit, also the funny bone • T4 - nipples. • T5 - Inframammary fold. • T6/T7 - xiphoid process. • T10 - umbilicus (important for early appendicitis pain) • T12 - pubic bone area. • L1 - inguinal ligament • L4 - includes the knee caps

7. Evaluation of suspected myelopathy • Imaging is indicated in all patient with suspicion for myelopathy • MRI is generally the most appropriate study as it images the spine, paraspinal region, and spinal cord; also may reveal evidence of intrinsic lesions • most patients with suspected cord compression should have total spinal cord imaging • sole imaging of the lumber spine is often ordered with cord compression suspicion, but recall the spinal cord ends at L1, thus visualization of the spinal cord is not possible with a lumbar MRI alone • lumbar MRI is useful however to exclude cauda equina compression (lower extremity weakness and sensory and bladder disturbances without upper motor neuron signs) • Exceptions may include pts with upper and lower extremity symptoms as cervical localization is likely -> Cervical MRI

8. Other Studies • Lumbar Puncture • Serologic Studies as clinically indicated • CT myelogram may be beneficial in patients with suspected inflammatory or demyelinative lesions of the spinal cord

9. Noncompressive Myelopathies • Vascular • Arteriovenous malformation • Antiphospholipid syndrome and other hypercoagulable states • Inflammatory • Multiple sclerosis • Neuromyelitis optica (Devic’s Disease) • Transverse myelitis (idiopathic) • Sarcoidosis • Vasculitis • Infectious/Postinfectious • Viral: VZV, HSV-1 & -2, CMV, HIV, HTLV-I, enteroviruses, flaivaviruses • Bacterial and mycobacterial: Borrelia, Listeria, syphilis, Mycoplasma pneumoniae • Parasitic: schistosomiasis, toxoplasmosis • Metabolic • Vitamin B12 deficiency (subacute combined degeneration) • Copper deficiency

10. Compressive Myelopathies • Cervical spondylosis • Epidural, intradural, or intramedullary neoplasm • Epidural abscess • Epidural hemorrhage/hematoma • Herniated disc • Posttraumatic compression by fractured or displaced vertebra or hemorrhage Clinical criteria alone cannot distinguish spinal cord compression and intrinsic cord lesions

11. Acute Viral Myelitis • Two Forms • Enteroviruses (poliovirus, coxsackie virus, and enterovirus 71), Flaviviruses (West Nile virus and Japanese encephalitis virus) have been known to target the gray matter (Anterior horn cells) of the spinal cord, producing acute lower motor neuron disease.1 • usually accompanied with fever, headache, and meningismus • produces asymmetrical flaccid weakness with reduced or absent reflexes and few sensory symptoms or signs • MRI often shows hyperintensities in the anterior horns of the spinal cord on T2-weighted imaging Cerebrospinal fluid (CSF) analysis demonstrates a moderate pleocytosis • These features help to distinguish this form of viral myelitis from Guillain-Barré syndrome, which usually produces symmetric deficits, with no MRI abnormalities, and is associated with elevated CSF protein levels without pleocytosis.

12. Acute Viral Myelitis • CMV, VZV, HSV I &II, HCV, and EBV are associated with a second form of viral myelitis has clinical and diagnostic test features that are similar to transverse myelitis • Association between the myelitis and the virus is not always clear, some may represent post-infectious transverse myelitis, others, a positive polymerase chain reaction (PCR) test in the CSF suggests that the myelitis is directly related to the viral infection • Treated with Herpes zoster, HSV, and EBV myelitis are treated with intravenous acyclovir (10 mg/kg q8h) or oral valacyclovir (2 gm tid) for 10–14 days; CMV with ganciclovir (5 mg/kg IV bid) plus foscarnet (60 mg/kg IV tid), or cidofovir (5 mg/kg per week for 2 weeks).2

14. Other Infectious Myelopathies • HIV • More of a chronic myelopathy, Often found mostly in late stages of AIDS and associated with AIDS related dementia in half • slowly progressive spastic paraparesis is accompanied by loss of vibration and position sense and urinary frequency, urgency, and incontinence • CSF may show nonspecific protein elevation • ART may reverse the symptoms3 • Bacterial • Mycoplasma (acute and post infectious), Listeria monocytogenes • TB • via secondary cord compression from verterbral osteomyelitis, aka Pott’s disease • Also via compressive tuberculomas • Lyme disease • Cases have been described in which clinical and MRI features resembling acute transverse myelitis have been attributed to Lyme disease.4 • CSF in these cases typically demonstrates a lymphocytic pleocytosis and elevated protein • Schistosomiasis (in endemic areas)

15. Tabes Dorsalis (Locomotor Ataxia) • Form of tertiary neurosyphilis in which the nerves of the dorsal (or posterior) columns degenerate • Loss of sense of position (proprioception), vibration, and discriminative touch • Latency period of 3-20 years • Cardinal signs of tabes are loss of reflexes in the legs; impaired position and vibratory sense; Romberg's sign • also: • bilateral Argyll Robertson pupils • fleeting and repetitive lancinating pains, primarily in the legs • Paresthesias/ formincation • visceral crisis (Bladder disturbances, and acute abdominal pain with vomiting • personality changes, dementia, deafness, visual • skeletal musculature is hypotonic due to destruction of the sensory limb of the spindle reflex • Ataxia of the legs and (tabetic) gait due to loss of position sense occurs in half of patients

16. Tabes dorsalis (cont.) • VDRL & RPR (nontreponemal tests) may be nonreactive in late neurosyphilis • If suspcion suspicion for neurosyphilis, serum FTA-ABS or TPPA (treponemal tests) are preferred • CSF may be completely normal in tabes dorsalis, or may show mild lymphocytic pleocytosis with 10 to 50 cells/microL and protein concentrations of 45 to 75 mg/dL. • Syphilitic meningovascular myelitis can represent an earlier form of syphilis infection • focal inflammation of the meninges can secondarily affect the adjacent anterior spinal artery thus result in a CVA or spinal cord infarction • Treatment - Penicillin G 3 to 4 million units IV every four hours or 24 million units continuous IV infusion for 10 to 14 days

17. Connective tissue Associated Myelopathies • SLE • May be the initial feature but onset is usually present with other active lupus signs. • thought to be due to an arteritis, with resultant ischemic necrosis of the spinal cord • ANA, ds-DNA, anti-Sm, Anti-neuronal (may correlate with active CNS lupus) • Has been associated with antiphospholipid antibodies in some studies but not all.5 • Treatment: Prednisone (1.5 mg/kg per day), plasmapheresis, and cyclophosphamide.6 • Antiphospholipid antibodies a may also benefit with warfarin as well as steroids and immunosuppressive treatment.7 • Mixed connective tissue disease • Sjogren's syndrome (antibodies to the Ro/SSA or La/SSB) • Scleroderma (ANA, anti-Scl-70, anti-centromere (ACA), anti-RNA polymerase III, and anti-beta2-glycoprotein I antibodies) • Ankylosing spondylitis • Acute myelopathy will typically occur in the setting of fracture of ankylosed spine or atlantoaxial-axial subluxation • cauda equina sydrome rare but associated with long standing disease • Rheumatoid arthritis • atlantoaxial subluxation, atlantoaxial impaction, and/or subaxial subluxation • Rarely associated with CNS vasculitis and more rarely with myelopathy from vasculitis

18. Sarcoid • Neurosarcoidosis • Typically occur perivascularly, but they can be extramedullary or intramedullary, and can involve the cauda equina. • Occurs 5% of Sarcoid patients • MRI signal abnormalities are not specific • neurosarcoid lesions can appear similar to transverse myelitis or can resemble a tumor • CSF profile consists of variable lymphocytic pleocytosis; oligoclonal bands are present in one-third of case • Generally treated with corticosteroids and other immunomodulatory agents and can improve

19. B12 Deficiency (subacute combined degeneration of spinal cord) • Damage to peripheral nerves caused by demyelination and irreversible nerve cell death. • Symptoms include • paresthesias in the hands and feet • loss of vibration and position sensation • progressive spastic and ataxic weakness • Loss of reflexes due to an associated peripheral neuropathy in a patient who also has Babinski signs, is an important diagnostic clue • Optic atrophy and irritability or other mental changes may be prominent in advanced cases • This myelopathy tends to be diffuse rather than focal; signs are generally symmetric and reflect predominant involvement of the posterior and lateral tracts, including Romberg's sign

20. B12 deficiency (cont.) • Usually established  by the presence of decreased Vit B12 level • in the cases of low-normal B12, the presence of elevated MMA and homocysteine levels may be useful • Treatment: 1mg Cbl IM once daily for 1 week, followed by 1 mg IM every week for four weeks • if the underlying disorder persists, 1 mg every month for the remainder of the patient's life.

21. Hypocuric Myelopathy (Copper Deficiency) • Very similar to subacute combined degeneration • Progressive spasticity, severe gait abnormalities including ataxia, and a neuropathy. • Also associated with anemia and neutropenia in certain patients • More common after gastric bypass, also with zinc supplementation • Diagnosis usually confirmed with low levels of serum copper are found and often there is also a low level of serum ceruloplasmin • Symptoms are potentially reversible with copper supplementation and reversal of underlying cause

22. Multiple Sclerosis • Most common autoimmune inflammatory demyelinating disease of the CNS • Women of Northern European descent who are of child-bearing age. • Histological examination of active plaques reveals perivascular infiltration of lymphocytes (predominantly T cells) and macrophages with occasional plasma cells. Perivascular and interstitial edema may be prominent.

23. Multiple Sclerosis (cont.) • Multiple sclerosis (MS) is a clinical diagnosis. There are no clinical findings that are unique to this disorder, but some are highly characteristic • Older criteriaconsidered clinical characteristics and a number of laboratory studies • these findings were then used to place patients in categories ranging from clinically definite to laboratory supported definite to clinically probable to laboratory supported probable MS • McDonald criteria focus on a demonstration with clinical, laboratory and radiologic data of the dissemination of MS lesions in time and space, also incorporated specific MRI findings into the diagnostic scheme • A diagnosis cannot be made until other possible conditions have been ruled out and there is evidence of demyelinating events separated anatomically and in time

24. Multiple Sclerosis (cont.) • CSF • oligoclonal bands using isoelectric focusing is the most important diagnostic CSF study when determining a diagnosis of MS • 2/3 will have normal leukocyte count • >50cells/microliter occurs only rarely and should raise suspicion of alternative etiology • Will also see elevation of the CSF immunoglobulin level relative to other protein components, suggesting intrathecal synthesis, generally IgG   • MRI • Cerebral or spinal plaques that are ovoid and hyperintense on proton density and T2-weighted studies, and they are hypointense (if visible at all) on T1-weighted images. • Conventional T2-weighted MRI techniques may underestimate MS plaque size and burden, Diffusion tensor imaging and MR spectroscopy may correct this • Evoked potentials (EPs): CNS electrical events generated by peripheral stimulation of a sensory organ) • Can detect abnormal CNS function that may be clinically undetectable or help define the anatomical site of the lesion in tracts not easily visualized by imaging (e.g., optic nerves, dorsal columns).

25. Neuromyelitis optica (Devic’s Disease) • Autoimmune, inflammatory disorder in which the optic nerves and spinal cord are targeted but may also affect the brain, • Resembles multiple sclerosis (MS) as it has varying degrees of weakness or paralysis in the legs or arms, loss of sensation (including blindness), and/or bladder and bowel dysfunction. • Lesions are different from those observed in MS in that the attacks appear to be not mediated by the immune system's T cells but rather by antibodies called NMO-IgG that target aquaporin 4 of astrocytes.6 • Acts as a channel for the transport of water across the cell membrane • Found in the processes of the astrocytes that surround the blood-brain barrier, • This blood-brain barrier is weakened in Devic's disease, but it is unclear how NMO-IgG immune response leads to demyelination • Criteria: Optic neuritis, Myelitis, and one of the following: • MRI evidence of a contiguous spinal cord lesion three or more segments in length, or • Seropositivity for NMO-IgG • Treatment: Steroids, Cytoxan, PLEX, +/- Rituximab

26. Cervical Spondylosis • Chronic degenerative and hypertraphic changes that involve intervertebral disks, vertebral bodies, facet joints, and ligaments • if severe, can result in narrowing of cervical spinal canal and cause spinal cord compression • In many case series, cervical spondylotic myelopathy is the most common cause of myelopathy, particularly in older adults • Cervical Spondylotic Myelopathy • clinical syndrome associated with spondylosis but with spinal cord dysfunction • commonly in pts > 55y, perhaps most common form of myelopathy • insidious onset of numbness, parathesias in upper extremities, spastic or stiff-legged gait that is often not associated with pain • surgical decompression is generally used to treat if symptomatic, although there is no evidence from RCT proving the efficacy of this therapy7

27. Metastatic Disease to Spinal Cord • Oncologic emergency • usually requring treatment with corticosteroids (usually dexamethasone), and emergent radiation therapy or surgery • indications for decompressive surgery for metastatic epidural spinal cord compression includes: when tissue diagnosis is needed, presence of spinal instability, or tumor is known to be radioresistant • One study showed patients who underwent anterior decompressive surgical resection of metastatic epidural spinal cord compression due to cancer had better ambulatory outcomes than with radiation therapy alone.8

28. Epidural Abscess • Rare, occurring in only 1 patient per 10,000 admitted to the hospital.9 • Most common pathogen is Staphylococcus aureus, which accounts for about two-thirds of cases 9 • Typically originate via contiguous spread from infections of skin and soft tissues or as a complication of spinal surgery and other invasive procedures, including indwelling epidural catheters. • Expected back and/or radicular pain usually but not always accompanied systemic signs of infection • MRI preferred test • Requires emergent surgical decompression and antibiotic therapy are indicated to treat epidural abscess

29. Spinal Cord Infarction • Rare compared with CVA • Most frequently caused by surgical procedures and pathologies affecting the aorta • May also occur in the setting of vascular risk factors or aortic disease • Presents with sudden spinal cord dysfunction that typically corresponds to the territory of the anterior spinal artery • Weakness and pinprick loss below the level of the infarction but sparing vibration and position sense • No treatment available and prognosis is variable and dependent upon severity of presenting deficit

30. Dural AVM of Spinal Cord • Rare cause of ischemic spinal cord dysfunction • Obstructs venous outflow of the spinal cord • May progress over months to years • Surgical obliteration of the fistula can potentially reverse this condition

31. References • Solomon et al. Infectious causes of acute flaccid paralysis. Curr Opin Infect Dis. 2003 Oct;16(5):375-81 • Hauser et al. "Chapter 372. Diseases of the Spinal Cord" (Chapter): Harrison's Principles of Internal Medicine, 17e: http://www.accessmedicine.com/content.aspx?aID=2904373. • Meurs et al. Acute transverse myelitis as a main manifestation of early stage II neuroborreliosis in two patients. Eur Neurol 2004; 52:186. • Staudinger et al. Remission of HIV myelopathy after highly active antiretroviral therapy. Neurology 2000; 54:267. • Lennon et al. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J. Exp. Med. 2005. 202 (4): 473–7. • Transverse myelitis as the first manifestation of systemic lupus erythematosus or lupus-like disease: good functional outcome and relevance of antiphospholipid antibodies. AU D'Cruz DP; Mellor-Pita S; Joven B; Sanna G; Allanson J; Taylor J; Khamashta MA; Hughes GR SO J Rheumatol 2004 Feb;31(2):280-5. • Transverse myelopathy in systemic lupus erythematosus: an analysis of 14 cases and review of the literature. AU Kovacs B; Lafferty TL; Brent LH; DeHoratius RJ SO Ann Rheum Dis 2000 Feb;59(2):120-4. • Acute transverse myelopathy in systemic lupus erythematosus: clinical presentation, treatment, and outcome. AU Mok CC; Lau CS; Chan EY; Wong RW SO J Rheumatol 1998 Mar;25(3):467-73 • Porter et al. Endocrine and reproductive manifestations of sarcoidosis. QJM 2003; 96:553. • McCormick et al. Cervical Spndylotic myelopathy: make the difficult diagnosis, then refer to surgery. Cleve Clin J Med. 2003;70:899-904 • Patchell et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005;366:643. • Darouiche, RO. Spinal epidural abscess. N Engl J Med 2006; 355:2012.