Multiple Sclerosis

Introduction

• MS is an immune-mediated disease characterized by inflammation, demyelination, and axonal damage in the central nervous system.¹
• MS primarily affects young adults with a mean onset age of 28-31 years, with a female to male ratio of approximately 2:1.²
• The course of MS is characterized by exacerbations and remissions at unpredictable intervals over a period of several years.
• Progression of disability due to MS is highly variable among patients.

Pathophysiology

• Inflammation, demyelination, and axonal damage are the major pathologic mechanisms that cause clinical manifestations.³
• The characteristic neuropathology of MS is the presence of focal demyelinated plaques within the central nervous system with variable inflammation and scarring (gliosis) that can be seen on magnetic resonance imaging (MRI).
• The varying location of plaque formation dictates the clinical manifestations that patients may have.
  • Brainstem and cranial nerve involvement can lead to optic neuritis, diplopia, and trigeminal neuralgia.
  • Cerebellar involvement can cause vertigo and gait disturbances.
  • Cerebrum and spinal cord involvement causes cognitive dysfunction, limb paresthesia, motor weakness, and bladder dysfunction.
• Symptoms of MS can eventually persist and lead to severe disability from visual loss, ataxia, skeletal muscle weakness, incontinence, and paralysis.

Clinical Course

• There are two main patterns of disease with MS: relapsing-remitting and progressive disease.⁴
  • The relapsing-remitting phenotype of MS accounts for approximately 85% of cases and is defined by MS attacks (flares, relapses, exacerbations) followed by full or incomplete recovery of symptoms.
  • The progressive type is much less common and is characterized by continued deterioration over time. It can be further delineated into the primary progressive and secondary progressive type of MS.
  • Primary progressive MS is the accumulation of disease with occasional plateaus or temporary minor improvements.
  • Secondary progressive MS describes patients with relapsing-remitting disease that eventually develop worsening disease with or without additional flares.

Treatment

• The main treatment goal for an acute exacerbation of MS is to reduce the recovery time.
  • Corticosteroids are used for acute relapses for their immunomodulatory and anti-inflammatory properties to improve axonal nerve conduction, decrease edema, and restore the blood-brain barrier.⁵
  • Adrenocorticotropic hormone (ACTH) is an alternative for patients who do not respond to or tolerate corticosteroids. ACTH stimulates endogenous corticotropin production to regulate anti-inflammatory and immunomodulatory functions.
  • Plasmapheresis is considered second-line therapy for MS and aims to remove pathogenic antibodies and proinflammatory mediators from the circulatory system.
• Patients with relapsing-remitting MS should begin disease-modifying therapy (DMT) to decrease relapse rate and slow the accumulation of CNS lesions.⁶
  • High efficacy DMTs include monoclonal antibodies such as natalizumab, ocrelizumab, and ofatumumab. The main disadvantage of these therapies is the risk of severe adverse events including serious infections and breakthrough disease with cessation of therapy.
  • Low risk DMTs include interferon beta and glatiramer. The advantage of initiating therapy with these DMTs is the long-term evidence of safety and rarity of serious adverse events.

Preoperative Assessment

• A thorough history and physical examination is necessary to determine an appropriate anesthetic plan and safe postoperative management.³
• A comprehensive preoperative evaluation should assess the patient’s baseline neurological signs and symptoms, triggers, progression of disease, and medications.
• Regarding baseline impairment, MS can cause respiratory dysfunction, autonomic nervous system dysfunction, and conduction abnormalities.⁷
• The broad spectrum of medications that patients with MS can be treated which can create many potential anesthetic drug interactions perioperatively.³
  • If patients were treated with oral or intravenous corticosteroids recently for an exacerbation, the anesthesiologist should consider stress-dose steroids.
  • Muscle relaxants, specifically baclofen, can cause muscle weakness and increased sensitivity to nondepolarizing muscle relaxants.
• Preoperative testing is usually dictated by patient comorbidities.

Intraoperative Considerations

• The stress of surgery and anesthesia may worsen symptoms and incite an MS flare, but this correlation remains unpredictable.²
• An elevated body temperature has been shown to be a trigger for an exacerbation by causing conduction block in demyelinated nerves, and an increase in body temperature as little as 1 degree Celsius can cause an MS flare.¹
  • The anesthesiologist should meticulously monitor the patient’s temperature and maintain normothermia.
• Regarding general anesthesia, there is no evidence to suggest superiority between inhaled anesthetics and intravenous anesthetics.⁷
  • No complications have been reported with the use of sevoflurane, desflurane, nitrous oxide, propofol, midazolam, dexmedetomidine, ketamine, and opioids.
  • The use of premedication may be advantageous in patients with MS as stress is a reported trigger for disease exacerbation.³
  • Since patients with MS have an upregulation of nicotinic acetylcholine receptors characteristic of upper motor neuron lesions, succinylcholine should be avoided as it can cause a profound hyperkalemic response.
  • With nondepolarizing neuromuscular blockers, patients with MS may exhibit a prolonged response if they have skeletal muscle weakness.
• The concern with neuraxial anesthesia is the possibility of exposing demyelinated areas of the spinal cord with local anesthetics and their potential neurotoxic effects.
  • There are several case reports associating spinal anesthesia to MS symptom exacerbation, but there have also been studies that show no link between spinal anesthesia and relapses.⁸ MS is not a contraindication to spinal anesthesia, but the anesthesiologist should consider the possibility of inciting an MS flare.
  • Epidural anesthesia is considered a safe technique in patients with MS, and several studies in the obstetric population have shown no difference in relapse rate using epidural anesthesia.
• Peripheral nerve blocks are regarded to be safe in MS, a disease of the CNS, though studies are limited.
• Regardless of the type of anesthetic and medications used, patients may experience exacerbation of their disease postoperatively.

Postoperative Management

• Irrespective of the type of anesthetic performed and medications used, patients are at an increased risk of release in the postoperative period.
• Complications such as fever and infection have been shown to exacerbate the signs and symptoms of MS.²
• Patients with respiratory involvement at baseline are more susceptible to pulmonary issues such as atelectasis, hypoventilation, and airway obstruction.
• Blood pressure fluctuations can occur in the postoperative period in patients with autonomic nervous system involvement.
• Residual motor blockade may be more common in patients with MS.
• Vigilance is key for safe postoperative management of a patient with MS.