Spinal Cord Injury: Infectious and Inflammatory Etiologies

INTRODUCTION

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In most high-resource countries, the three most common etiologies of non-traumatic spinal cord injury (NTSCI) include SCI caused by tumors, degenerative conditions of the spine, and vascular etiologies. In contrast, in many low-resource countries that have high levels of tuberculosis and other infectious diseases such as HIV, infectious causes are more common than degenerative and vascular etiologies.¹ Given the paucity and variability in what conditions are reported in studies of the incidence of NTSCI, the overall incidence of infectious and inflammatory causes cannot be estimated with any confidence.

NTSCI typically presents with findings similar to those seen with traumatic SCI (TSCI), specifically weakness and sensory changes below the neurologic level of injury, often accompanied by bowel and bladder or other autonomic impairments. NTSCI can also result in the same types of secondary medical complications as TSCI, including but not limited to, deep vein thrombosis, pressure ulcers, autonomic dysreflexia, pneumonia, orthostatic hypotension, spasticity, heterotopic ossification, pain, and sexual dysfunction.

This chapter will address the most common infectious and inflammatory etiologies of NTSCI seen in high-resource countries. (See Chapter 15 for myelopathies and motor neuron diseases and Chapter 17 for neoplasms). As there is widespread availability of magnetic resonance imaging (MRI) and computed tomography (CT) in high-resource countries, compressive etiologies can be easily excluded. However, since the differential diagnosis of NTSCI also includes infectious, toxic, nutritional, vascular, systemic, and paraneoplastic as well as inflammatory etiologies, many of which present similarly clinically, differentiating among these other causes of NTSCI (see Table 16–1) can be difficult and time consuming. In addition to performing a thorough history and physical examination and obtaining the requisite imaging studies, obtaining spinal fluid analysis and serological studies often is essential to make a definitive diagnosis.

Table 16–1Differential Diagnosis and Diagnostic Investigation of Nontraumatic Spinal Cord Injury

Etiology	Disease Process	Imaging and Laboratory Studies Specific for Diagnosis
Spinal column disorders	Congenital spinal stenosis	Spinal MRI CT scan
	Acquired spinal stenosis Ossification of posterior longitudinal ligament Spondylosis Spondylolisthesis
	Atlantoaxial instability Rheumatoid arthritis Down’s syndrome Osteogenesis imperfecta
	Disc prolapse
Metabolic disorders	Vitamin B₁₂ deficiency Folate deficiency	Vitamin B₁₂ and folic acid levels Methylmalonic acid Homocysteine Parietal cell and IF antibodies
	Copper deficiency	Serum copper levels Ceruloplasmin
Vascular disorder	Hemorrhage Epidural hematoma Dural AV fistula AVM with hemorrhage	Spinal MRI Spinal angiogram (if there is strong suspicion of vascular malformation and MRI findings are equivocal) Hypercoagulable investigation – protein C, protein S, antithrombin III, lupus anticoagulant, prothrombin G20210A, factor V Leiden, factor VIII, anticardiolipin antibody, fibrinogen, homocysteine
	Ischemia Dural AV fistula AVM without hemorrhage Atherosclerosis Aortic dissection Takayasu’s arteritis Atheromatous emboli Thromboemboli Venous infarction Hypotensive-hypoperfusion Fat emboli
Inflammatory and autoimmune disorders	Multiple sclerosis	See Table 16–3 Spinal and brain MRI CSF – oligoclonal bands, IgG index
	Neuromyelitis optica spectrum disorder	See Table 16–4 Spinal and brain MRI AQP4-Ab, ANA
	Transverse myelitis – idiopathic	See Table 16–7 Spinal MRI
	Acute disseminated encephalomyelitis	Spinal and brain MRI
	Collagen vascular disease Systemic lupus erythematosus (SLE) Sjogren’s disease Antiphospholipid syndrome Behcet’s disease Mixed connective tissue disease Systemic sclerosis	ANA dsDNA Antiribonucleoprotein Anti-Smith Anti-SSA Antiphospholipid antibody Rheumatoid factor Anti-scl70 (ELISA)
	Sarcoidosis	CSF – ACE Serum – soluble IL-1 receptor
	Paraneoplastic Breast carcinoma Small cell lung cancer	Anti-Ri (ANNA-2) Anti-amphiphysin IgG Anti-CRMP5 antibody
	Arachnoiditis	CT myelogram or spinal MRI
Radiation related	Radiation myelitis	Spinal MRI
Drugs and Toxins	Organophosphates	Spinal MRI Serum – acetylcholinesterase Serum – butyrylcholinesterase
	Epidural anesthesia	Spinal MRI
	Pharmacological agent Nitrous oxide Chemotherapeutic agents Sulfasalazine Tumor necrosis factor-alpha inhibitors	Spinal MRI Brain MRI Vitamin B₁₂ levels EMG/NCS
Neoplastic disorders	Extradural tumors (metastatic) Lungs Breast Gastrointestinal tract	Spinal MRI Tumor biopsy or resection
	Intradural extramedullary tumors Neurofibroma Meningioma Schwannoma Chordoma
	Intradural intramedullary tumors Astrocytoma Ependymoma Oligodendroglioma Cavernoma
Infection – viral	Retrovirus HIV HTLV	Enzyme-linked immunosorbent assay (ELISA) and Western blot HTLV-1 antibodies
	Herpes virus Herpes simplex virus (HSV) Herpes zoster Cytomegalovirus (CMG) Epstein-Barr virus (EBV)	CSF – HSV-1/2 PCR CSF – VZV PCR CSF – CMV PCR CSF – EBV PCR
	Enterovirus Poliovirus – acute Polio virus – chronic (post-polio syndrome	See Table 16–8 Spinal MRI and EMG/NCS
	West Nile virus (WNV)	WNV-specific IgM in serum or CSF
Infection – bacterial	Staphylococcus aureus Staphylococcus epidermidis Escherichia coli Pseudomonas aeruginosa Streptococcal	Blood culture
	Treponema pallidum (neurosyphilis)	CSF – VDRL Serologic assay – PRP
	Mycobacterium TB	Mantoux tuberculin skin test TB blood test QuantiFERON Acid-fast bacilli sputum or culture
	Borrelia burgdorferi (Lyme)	ELISA and Western blot – B. burgdorferi antibodies
Infection – fungal	Blastomyces Coccidioides Cryptococcus Aspergillus	Fungal culture
Infection –parasitic	Schistosomes Echinococcus granulosus Taenia solium Paragonimus	Microscopic examination of ova, larvae of adult parasites in stool Blood or other samples or identification of parasite antigens or molecular tests for parasite DNA
Motor neuron disease	Amyotrophic lateral sclerosis Primary lateral sclerosis Progressive muscular atrophy	EMG/NCS
Miscellaneous	Syringomyelia	MRI CT with contrast with delayed imaging

As a general rule, if an inflammatory (noninfectious) etiology is suspected, administration of high-dose corticosteroids is the first-line treatment. In cases where the presumed inflammation is refractory to corticosteroids, plasmapheresis, intravenous immunoglobulin (IVIG), or another immunomodulatory agent is utilized with a goal of reducing the serum concentrations of suspected autoantibodies presumably causing ongoing SCI. If an infection is suspected, targeted antimicrobial treatment is usually initiated. Because different infectious and inflammatory NTSCI may require different specific treatments, in this chapter, we will discuss the most common infectious and inflammatory causes of SCI and their treatments separately.

As the underlying cause of NTSCI is ascertained and treated, concurrent rehabilitative care should be administered. Because of the weakness, sensory loss, bowel and bladder deficits, spasticity, and secondary medical complications, those with NTSCI should optimally receive rehabilitative care at a dedicated SCI unit.² In this setting, a multidisciplinary rehabilitation team can include, but is not limited to, a physiatrist, primary care physician, neuropsychologist, neurologist, nursing, physical and occupational therapist, neuropsychiatrist, and social worker. These specialized centers deliver highly efficient and cost-effective individualized care that minimize adverse events, lower rehospitalization rates, and improve patient perception.³ Because patients presenting with NTSCI manifest symptoms similar to TSCI, rehabilitation methods are often similar. Table 16–2 outlines a comprehensive rehabilitation treatment program addressing common impairments and dysfunctions seen in SCI individuals. Treatments should include addressing the rehabilitation needs outlined for the different types of NTSCI discussed in this chapter. If there are unique rehabilitation needs based on etiology, they will be discussed in the relevant sections.

Table 16–2Spinal Cord Injury Impairments and Rehabilitation Interventions

Impairments	Rehabilitation Interventions
Weakness	Based on level of weakness, maximize level of self-care and mobility: Range of motion (ROM) Strengthening Functional training in activities of daily living (ADLs), including feeding, grooming, dressing, and bathing Locomotor training Functional electrical stimulation device Neuromuscular electrical stimulation Robot-assisted gait training Transfer training Equipment: Orthoses Gait aids Assistive devices Durable medical equipment Wheelchair and cushion Assistive technology and environmental control units
Neurogenic bladder	Initiate appropriate management to completely empty, keep patient dry, and minimize complications such as a high-pressure bladder and reflux or leakage, urinary tract infections (UTIs), strictures, and bladder stones Spinal (infrapontine-suprasacral) lesion – upper motor neuron (UMN) bladder Physical exam UMN signs including hyperreflexia, spasticity Intact bulbocavernosus reflex and anocutaneous reflex (anal wink) Testing Postvoid residual (PVR) urine measurement Urodynamic study (UDS) Different management goals Normal voiding with control Straight in-and-out catheterization (intermittent catherization [IC]) several times per day without leaking in between – preferred method if person can perform Fluid management Change frequency of IC Anticholinergic medication or beta-3 adrenergic to relax detrusor Inject detrusor with botulinum toxin Augmentation cystoplasty External condom catheter without need for intermittent catheterization – bladder reflex triggering (“balanced bladder”) Adequate penis size/shape to maintain an external catheter PVRs are <200 mL Bladder pressures are <40 cm H₂O on UDS No autonomic dysreflexia during voiding Add anti-alpha-adrenergic medication to reflex sphincter if PVR >200 mL and/or high bladder pressures (>40 cm H₂O) Diaper Indwelling catheter (transurethral versus suprapubic) Persons who have sustained high bladder pressures or high postvoid residuals and cannot IC Combination of the above Sacral/infrasacral lesion – lower motor neuron (LMN) bladder Physical exam LMN signs (muscle atrophy, depressed or absent deep tendon reflexes) Absent bulbocavernosus reflex and anocutaneous reflex (anal wink) Lower abdominal distention with palpable firm bladder Testing Postvoid residual (PVR) urine measurement Urodynamic study (UDS) Different management goals Bladder expression Straining (abdominal straining, Valsalva’s maneuver) External compression (Crede’s maneuver) Empty bladder with low residual (<200 mL) without undue strain Consider wearing pads or incontinence undergarments or artificial sphincter if still leaking between expressions Intermittent catheterization Fluid management Change frequency of catheterizations Use condom catheter or pads Consider injection of periurethral bulking agent, sling procedure, or artificial sphincter if still leaking between IC Indwelling catheter
Spasticity	Minimize the detrimental features and utilize the benefits of spasticity to maximize function, independence, and quality of life Avoid noxious stimuli, as this may exacerbate spasticity Rehabilitation therapy Positioning in bed and wheelchair Modalities – heat, cold, electrical stimulation, biofeedback Therapeutic exercise – stretching, hydrotherapy Orthotics, bracing, serial casting Oral antispasmodics Baclofen – presynaptic inhibition of interneurons via gamma-aminobutyric acid (GABA) B agonist Benzodiazepines – postsynaptic effects of GABA Alpha-2-agonists – clonidine and tizanidine Dantrolene sodium – prevent the release of calcium from the sarcoplasmic reticulum Intrathecal baclofen (ITB) Injection therapy Neurolysis with phenol or alcohol Neuromuscular junction block by preventing the release of acetylcholine with botulinum toxin Orthopedic treatments – tenotomy, tendon lengthening, myotomy, tendon transfers Neurosurgery – neurectomy, myelotomy, rhizotomy, selective dorsal rhizotomy
Neurogenic bowel	Initiate appropriate bowel program to ensure effective and efficient colonic evacuation while preventing incontinence and constipation
	Type Time of routine Frequency Interventions Medications Oral Rectal	Upper motor neuron 30–60 minutes after meals (to use gastrocolic response) Daily preferred Digital stimulation (dependent on preservation of sacral reflex) Stool softeners, bulking agents, stimulant agents, and osmotic agents taken 8–12 hours before the evacuation Stimulant suppositories or mini-enemas trigger a reflex evacuation of the colon/rectum	Lower motor neuron 30–60 minutes after meals Daily or multiple times per day if needed Digital evacuation (not dependent on sacral reflex arcs) Bulking agent (fiber) help produce a bulky formed stool Suppositories or mini-enemas are not helpful
Autonomic dysfunction Orthostatic hypotension	Maximize upright tolerance and functional activity by treating symptomatic orthostatic hypotension Physical treatments Elastic abdominal binder Lower limb compression stockings Decrease seatback angle in a recliner wheelchair from near supine gradually to full upright as tolerated Gradually raise head of bed before getting out of bed Tilt table Pharmacological treatments Salt tablets, 1–2 grams two to three times daily before meals Fludrocortisone (synthetic corticosteroid with mineralocorticoid >> glucocorticoid potency), 0.1–0.2 mg one to two times per day Midodrine (alpha 1 receptor agonist), 5–20 mg one to three times per day Droxidopa (synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase) 100–160 mg one to three times per day
Autonomic dysreflexia (AD)	Condition of imbalanced reflex sympathetic discharge in response to noxious stimuli after spinal cord injury Prevent and educate the symptoms and management of AD Clinical features Pounding headache Hypertension Profuse sweating and flushing above the level of injury Blurry vision Sudden rise in blood pressure greater than 20 mm Hg Bradycardia Treatment Sit patient upright Loosen clothing Relieve obstruction to drainage of an indwelling urinary catheter If no indwelling catheter present then catheterize If the systolic blood pressure is still 150 mm Hg or greater, administer rapidly acting and easily reversible antihypertensives such as nitropaste If the systolic blood pressure is less than 150 mm Hg, then the rectum should be manually disimpacted Search for other precipitants if symptoms persist Prophylactic treatment for those with recurrent episodes of AD can include alpha-blockade or ganglion blockade
Respiratory	Pulmonary exercises Inspiratory muscle training with threshold or resistive trainer Start at an intensity of 30–70% of maximal inspiratory pressure for a duration up to 30 minutes per session 4–6 days/week Aerobic exercise training 70–80% of maximum heart rate and occurring at least three times a week Muscle training of the clavicular portion of pectoralis major can help improved forced expiration (cough) Ten maximal isometric contractions of 6 seconds each, 5 days per week for 6 weeks Additional strategies Encourage regular sputum clearance/pulmonary hygiene Smoking cessation Sleep apnea detection/management Maintenance of general fitness/activity Immunization Influenza yearly Pneumococcal pneumonia every 5 years Atelectasis Lung expansion Use of high tidal volumes with mechanical ventilation (up to 15–20 cc/kg ideal body weight) Secretion mobilization Postural drainage Chest percussion Secretion clearance Suctioning Manually assistive cough Insufflator-exsufflator Bronchoscopy Medication Bronchodilators Mucolytics Adequate hydration
Osteoporosis	Physical measures Weight bearing ambulation or standing (standing frame or standing wheelchair if necessary FES ergometry or FES ambulation Supplements (check 250-hydroxyvitamin D levels) Calcium supplementation (at least 1500 mg/day) Vitamin D supplementation (at least 1000 IU/day) Medications Bisphosphonates – evidence not strong for prevention of bone loss in SCI population
Heterotopic ossification	Medications Bisphosphonates – etidronate disodium (20 mg/kg/day by mouth for 3–6 months) Prevents soft tissue ossification in most with only bone scan evidence Less than half with x-ray evidence of heterotopic ossification (HO) show response NSAIDs – indomethacin or other Exercises ROM exercises avoiding excessive force and muscle trauma Surgery Primary goal for removal of HO is to promote easier positioning, transfers, and ADLs Surgery should only be attempted when HO is mature and the bone scan and alkaline phosphatase are normal Wedge resection is the most common type of surgical excision Radiation Low-dose radiation has been reported to control HO and avoid recurrence following surgery It is given in a single fraction either just before or right after surgery
Pressure injury	Avoid or prevent worsening of pressure injury by monitoring skin integrity regularly, assessing the need for specialized seating/mattress, and performing appropriate and adequate pressure relief Pressure redistribution and support surfaces Bed support surfaces Use pressure-redistribution bed support surfaces for individuals who are at risk or who have pressure injuries Bed positioning Avoid positioning directly on the pressure injuries Use pillows, cushions, and positioning aids to reduce pressure on existing pressure injuries or vulnerable kin areas Avoid closed cutouts or donut-type cushions Prevent contact between bony prominences Avoid elevating the head of bed unless it is medically necessary to perform activities of daily living Reposition in bed every 2 hours Wheelchair positioning Prescribe a power weight-shifting wheelchair system for individuals who are unable to independently perform an effective pressure relief Use wheelchair tilt-in-space and/or recline devices Maintain an offloaded position from the seating surface for at least 1–2 minutes
Sexuality	Address sexual dysfunction, intimacy, and reproduction holistically and in an interdisciplinary team Psychological Identify and address issues with self-image, self-esteem, and fear of being rejected, as well as fear of and anxiety about sexual failure Erectile dysfunction Psychogenic erection or lubrication Requires sensation in T11–L2 dermatomes, and the quality of event is related to the degree of light touch and pinprick sensory preservation at this level Reflexogenic erection or lubrication Requires preservation of sacral reflex function (S4–S5) Reflexogenic erection or lubrication is generally possible if hyperactive bulbocavernosus (BC) present or if hypoactive BC is present with some preserved sensation at S4–S5 Reflexogenic erection and lubrication is lost if BC and sensation at S4–S5 is absent Treatment Oral: type 5 phosphodiesterase inhibitors Injection: vasoactive substance (alprostadil, papaverine, phentolamine) Physical device: vacuum constrictive devices Implantable devices: silicone malleable implant and inflatable implant Ejaculatory dysfunction Manual or partner masturbation Penile vibratory stimulation Electroejaculation
Community reintegration	Navigate insurance/financial issues to maximize benefits Identify and address possible barriers such as: Home care equipment Home aid and/or attendant Transportation Address adjustment to disability

MULTIPLE SCLEROSIS

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Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease that tends to affect women more than men with an approximately 2:1 ratio. The median and mean ages of MS onset are 24 and 30 years of age, respectively. The peak age of onset is about 5 years earlier for women than for men.

There are three different types of MS: relapsing remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). RRMS consists of episodes of acute worsening of neurologic function with either new symptoms or the worsening of existing symptoms, called relapses or attacks, with total or partial recovery afterward and no apparent progression of disease (no evidence of disease worsening on an objective measure of change over time, with or without relapse or new MRI activity). Relapses are caused by inflammation in the central nervous system (CNS), which damages myelin. Approximately 85% to 90% of people with MS are initially diagnosed with RRMS. However, most patients with RRMS will eventually enter a secondary progressive phase. RRMS can be further classified as active in the setting of new relapses/attacks and/or new lesions or not active with no evidence of disease activity. The course could also be classified as worsening with increased disability confirmed over a specified period following a relapse, or stable with no increased disability.

In RRMS, bowel and/or bladder symptoms at the onset are the only symptoms that have strong and consistent associations with poor prognosis. Additional factors that predict long-term disability in patients with RRMS are incomplete recovery from the first attack, a short interval between the first and second attacks, and early accumulation of disability.⁴

PPMS consists of steadily worsening neurologic function from the onset of symptoms without initial relapses or remissions. About 5% to 10% of patients with MS are diagnosed with PPMS. PPMS does not progress in a linear fashion, and often there are periods of clinical stability without progression of disease. Therefore, classification of progression is typically determined by assessing the change over a one-year period. A patient who has gradually worsened would be classified as progressing, and if stable, as not progressing. Similar to RRMS, a patient can also be classified as active or not active based on disease activity. A common indicator that is frequently used for classifying the severity and progression of MS is the Expanded Disability Status Scale (EDSS), developed by Kurtzke in 1983. The EDSS is a 10-point scale where points accumulate with greater exhibited disability.

SPMS follows an initial course of RRMS, which then becomes more steadily progressive, with or without relapses.⁵

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