Neurologic/Neuromuscular Disorders

Neurologic/Neuromuscular Disorders

5.1 Cerebrovascular Disease and Stroke

Corey Amlong

Robert D. Sanders

Stroke can be a devastating sequela of the perioperative period. Patients who suffer a stroke during or after noncardiac, nonneurologic surgery have an eightfold increased risk of mortality (1). Patients who suffer a stroke during or after cardiac or major vascular surgery have a mortality rate of up to 38% (2). The morbidity associated with perioperative stroke is equally, if not more staggering. Twenty-two percent of patients who have a cerebrovascular insult, perioperatively or otherwise, will have some sort of deficit 5 years later (3). Fortunately, the incidence of perioperative stroke is relatively low (0.05% to 0.7%) in nonneurosurgical, noncardiac patients (1,4,5). However, the high mortality and burden of morbidity associated with these events makes it imperative that at-risk patients are identified preoperatively so that risk-reduction steps may be taken.

Historically, three risk factors for perioperative stroke have been identified:

  • History of prior stroke or TIA

  • Advanced age

  • Renal disease

Other risk factors are shown in Table 5.1.

Patients with preexisting cerebrovascular disease are at a greater risk for perioperative stroke. With an aging population and advances in stroke treatment, patients who have suffered a cerebrovascular event increasingly present for unrelated surgery. How long to wait between an acute cerebrovascular event and unrelated elective surgery is uncertain. Cerebral autoregulation can be altered following an ischemic event, and it is unclear how long it takes for regulatory mechanisms to normalize. Smaller studies have shown no clear correlation between the temporal relationship of a stroke and increased risk in the perioperative period (7). Larger studies suggest higher risk of adverse events in patients undergoing surgery within 9 months of a stroke (8). The balance between safety concerns and the requirement for surgery is best managed with collaboration of the neurologist, surgeon, anesthesiologist, and the patient (9).

The type of surgery is considered when risk-stratifying patients, as various surgeries are associated with differing incidence of stroke. Cardiac surgery, especially valve repair or replacement, carries the highest risk of perioperative stroke. Table 5.2 lists surgeries and their associated incidence of stroke.

TABLE 5.1 Independent Predictors of Perioperative Stroke in Large Epidemiologic Studies (1,5,6)

Atrial fibrillation

Valvular cardiac disease

Heart failure

Diabetes mellitus

Female sex

Myocardial infarction within 6 months

Prior cardiac intervention

Current dialysis

Acute renal failure (or acute on chronic renal disease)

Chronic obstructive pulmonary disease

Current smoker


TABLE 5.2 Incidence of Stroke After Various Types of Surgeries

Type of Surgery (Reference)

Incidence (%)

Coronary artery bypass grafting (CABG) (10)


Combined CABG and valve surgery (10)


Double or triple valve surgery (10)


Mitral valve replacement (10)


Aortic valve replacement (10)


Beating-heart CABG (10)


Hip arthroplasty (5)


Colectomy (5)


Appendectomy (1)


Hernia repair (1)


Hysterectomy (1)


Abdominal exploration (1)


Limb amputation (1)


Spine surgery (1)


Pancreatic surgery (1)


Preanesthetic evaluation of patients with cerebrovascular disease focuses on the cause and timing of any previous strokes or TIAs. Symptoms at the time of the event and any residual deficits such as weakness, dysarthria, and vision changes are noted. An echocardiogram, if not previously done, should be obtained to evaluate for cardioembolic sources, arrhythmias, intracardiac shunts, or valvular pathology. Any previously obtained imaging of the head and neck, including any carotid studies, should also be reviewed. Physical examination includes a basic neurologic examination with careful documentation of any deficits. Auscultation and palpation of the carotid arteries is performed to evaluate for bruits. The presence of a bruit in the setting of neurologic symptoms warrants further evaluation.

Patients with symptomatic carotid disease, or those with a history of stroke or TIA with flow-limiting carotid stenosis as a causative contributor, should avoid unrelated elective surgery until the carotid disease is addressed (see Chapter 5.2). A majority of guidelines recommend intervention such as endovascular stenting or open endarterectomy to restore flow prior to unrelated elective surgery (11). Many of these guidelines are based upon studies with patients initially enrolled decades ago. However, vast improvements in medical management have been made in that time period. These advances are not accounted for in many guidelines, and CEA or angioplasty and stenting continue to be the standard for those with symptomatic carotid disease. Recent evidence suggests that endovascular treatment may have a higher risk of adverse events when compared to endarterectomy (12), although this approach may still be preferable to an open approach for numerous other reasons.

A unique subset of patients with cerebrovascular disease are those with Moyamoya. Moyamoya is a rare vasculopathy in which patients have a progressive narrowing of their distal internal carotid arteries and/or the proximal branching vessels leading to significant stenosis or complete occlusion. The formation of many fine collateral vessels around the stenotic lesion leads to a unique appearance on imaging prompting the disease’s name. Pathophysiology and causation of the disease remain elusive. A minority of cases are associated with other systemic pathology, such as sickle cell or neurofibromatosis, and termed “Moyamoya syndrome” (13). A majority of patients present with TIA symptoms or overt ischemic stroke, although hemorrhagic stroke from rupture of the weak collateral vessels can occur (13). These patients may have preexisting deficits such as aphasia or hemiparesis. Treatments such as antiplatelet agents and surgical revascularization are aimed at reducing rates of future stroke, although success in this regard has proven to be modest (14,15).

Patients with preexisting cerebrovascular disease are often placed on an anticoagulation regimen for risk reduction. The AHA recommends patients with a history of noncardioembolic stroke be placed on an antiplatelet drug to mitigate risk of recurrence (16). Antiplatelet agents have equivalent efficacy when compared to vitamin K antagonists but with fewer side effects (16). Aspirin remains the most common agent; however, other antiplatelet agents are increasingly being used. The combination of aspirin and other antiplatelet agents for stroke risk mitigation has a higher risk of bleeding complications than aspirin alone (16). Similarly, the addition of a vitamin K antagonist to an antiplatelet agent may have added risk without added efficacy in comparison to a single antiplatelet agent. Observational studies suggest that antiplatelet agents may be protective against perioperative stroke when patients undergo cardiac surgery (17,18), but there is little evidence of such protection for noncardiac
surgery. The POISE-2 trial suggests there are no beneficial effects of antiplatelet agents for stroke prevention in patients undergoing nonneurologic, noncardiac surgery, and there may be an increased risk of bleeding (19). A discussion with the prescribing provider and surgeon before surgery regarding risks and benefits of continuing antiplatelet agents and anticoagulants in the perioperative setting is ideal but not always feasible. Patients undergoing procedures with a low risk of bleeding, such as minor dental, dermatologic, or ophthalmologic procedures or endoscopies, may safely continue their antithrombotic agents in the perioperative period. Procedures considered moderate or high risk—most notably cardiac, thoracic, intra-abdominal, or neurosurgical procedures—will likely require cessation of antithrombotic agents to mitigate risk of periprocedural bleeding. Cessation with or without bridging with LMWH or UFH should take into account the individual patient’s risk for incurring thromboembolism. Those with a CHA2DS2VASc score of >2, a stroke/TIA or VTE within the previous 3 months, or those with genetic predisposition to thromboembolism are considered higher risk (20). Ultimately, the risk of thromboembolism needs to be weighed against the risk of periprocedural bleeding. As the antithrombotic effects of many of these agents are prolonged, the decision to stop an agent may need to be made several days prior to the scheduled procedure. See Chapters 18.2 and 18.3 for further discussion of perioperative anticoagulant use.


1. Mashour G, Shanks A, Kheterpal S. Perioperative stroke and associated mortality after noncardiac, nonneurologic surgery. Anesthesiology. 2011;114:1289-1296.

2. Salazar JD, Wityk RJ, Grega MA, et al. Stroke after cardiac surgery: short- and long-term outcomes. Ann Thorac Surg. 2001;72:1195-1201.

3. Douiri A, Rudd AG, Wolfe CD. Prevalence of poststroke cognitive impairment: South London Stroke Register 1995-2010. Stroke. 2013;44:138-145.

4. Kam P, Calcroft R. Peri-operative stroke in general surgical patients. Anaesthesia. 1997; 52:879-883.

5. Bateman BT, Schumacher HC, Wang S, et al. Perioperative acute ischemic stroke in noncardiac and nonvascular surgery: incidence, risk factors, and outcomes. Anesthesiology. 2009;110:231-238.

6. Sharifpour M, Moore LE, Shanks AM, et al. Incidence, predictors, and outcomes of perioperative stroke in noncarotid major vascular surgery. Anesth Analg. 2013;116:424-434.

7. Sanders R, Bottle A, Jameson S, et al. Independent preoperative predictors of outcomes in orthopedic and vascular surgery: the influence of time interval between an acute coronary syndrome or stroke and the operation. Ann Surg. 2012;255:901-907.

8. Jorgensen MB, Torp-Pederson C, Gislason G, et al. Time elapsed after ischemic stroke and risk of adverse cardiovascular events and mortality following elective noncardiac surgery. JAMA. 2014;312:269-277.

9. Mashour GA, Moore LE, Lele AV, et al. Perioperative care of patients at high risk for stroke during or after noncardiac, nonneurologic surgery: consensus statement from the society for neuroscience in anesthesiology and critical care. J Neurosurg Anes. 2014;26:273-285.

10. Bucerius J, Gummert J, Borger M, et al. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg. 2003;75:472-478.

11. Abbott AL, Paraskevas KI, Kakkos SK, et al. Systematic review of guidelines for the management of asymptomatic and symptomatic carotid stenosis. Stroke. 2015;46:3288-3301.

12. Abbott AL, Adelman MA, Alexandrov AV, et al. Why calls for more routine carotid stenting are currently inappropriate: an international, multispecialty, expert review and position statement. Stroke. 2013;44:1186-1190.

13. Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med. 2009;360:1226-1237.

14. Kronenburg A, Braun KP, van der Zwan A, et al. Recent advances in moyamoya disease: Pathophysiology and treatment. Curr Neurol Neurosci Rep. 2014;14:423.

15. Pandey P, Steinberg GK. Neurosurgical advances in the treatment of moyamoya disease. Stroke. 2011;42:3304-3310.

16. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.

17. Cao L, Young N, Liu H, et al. Preoperative aspirin use and outcomes in cardiac surgery patients. Ann Surg. 2012;255:399-404.

18. Cao L, Silvestry S, Zhao N, et al. Effects of preoperative aspirin on cardiocerebral and renal complications in non-emergent cardiac surgery patients: A sub-group and cohort study. PLoS One. 2012;7:e30094.

19. Devereaux PJ, Mrkobrada M, Sessler DI, et al. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370:1494-1503.

20. Raval A, Cigarroa J, Chung M, et al. Management of patients on non-vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: a scientific statement from the American Heart Association. Circulation. 2017;135(10):e604-e633.

5.2 Carotid Bruit

Corey Amlong

Robert D. Sanders

The discovery of a previously undocumented carotid bruit on a preanesthetic physical examination is not uncommon. The presence of a bruit does not necessarily indicate that a patient has significant flow-limiting carotid lesions (as few as 40% do) but should certainly prompt the examiner to perform a more focused history. The patient may not realize or report neurologic symptoms; a detailed history and examination may uncover unrealized indicators of pathology. If a patient is truly asymptomatic and has no history of TIA or stroke, then the risk of perioperative stroke is fairly low and the case can proceed without further workup (1). The Framingham study indicated that the risk of stroke in patients with asymptomatic carotid stenosis, even if hemodynamically significant, is 1% to 2% annually, and there is little to no evidence indicating that patients with asymptomatic carotid stenosis are at a greater risk for perioperative stroke when having noncardiac, nonneurologic surgery (2). Pre-existing cerebrovascular disease (including stenosis of one or both carotid arteries) has been shown to be a significant risk factor for perioperative stroke in patients having cardiac surgery (3).

Atheromatous plaques are focal thickenings of the intima consisting of a variety of constituents including fat-laden immune cells, debris, and connective tissue. A core of free lipid droplets and foam cells is surrounded by a thin, smooth muscle cap. Infiltration of the lesion by immune cells from circulating blood occurs constantly, and the activation of these immune cells, with resultant release of proinflammatory cytokines, may play an important role in the natural history of plaque growth and rupture. Erosion of the endothelium or rupture of the cap exposes the prothrombotic material to circulating platelets and leads to thrombosis, which is now widely accepted as the main cause of distal ischemia.

Classically, at least since the 1995 asymptomatic carotid atherosclerosis study (4) and the 2004 European Asymptomatic Carotid Surgery Trial (5), the degree of carotid stenosis has driven the recommendation for surgical intervention based on these studies’ findings of statistically significant improvements in outcomes after CEA in patients with a certain degree of asymptomatic stenosis when compared to medical management. Numerous studies of varying degrees of quality have since been published in contrast or in agreement with this management algorithm. Proponents of medical management of asymptomatic carotid stenosis point out that the introduction and implementation of new drugs have decreased the incidence of stroke and that the risk of perioperative stroke is higher than the risk of annual stroke while being medically managed. Conversely, proponents of prophylactic CEA for asymptomatic, but significant, carotid stenosis argue that 30-day stroke risk after CEA is declining with improved surgical methodology. Additional large-scale trials are needed if updates to current recommendations are to occur. Until then, the management of patients with asymptomatic carotid disease will likely remain controversial.

Ultimately, the type of planned surgery dictates if a provider should investigate the presence or degree of carotid stenosis if a bruit is discovered. Patients having cardiac or vascular surgery are at greatest risk of perioperative stroke in the presence of significant carotid disease and may benefit from further evaluation before elective surgery. Further workup may be warranted if the surgery is expected to have large hemodynamic variability, if the head and neck are to be manipulated to a great extent, or if positioning may compromise cerebral blood flow (e.g., sitting position).

Bruits associated with symptomatic carotid disease need to be investigated. Numerous imaging modalities can elucidate the degree of stenosis and the amount of hemodynamic significance associated with stenotic plaques. Carotid arteriography remains the gold standard in evaluation of stenotic lesions but is invasive and not without risk. Advances in technique and equipment have made carotid ultrasound with Doppler imaging an acceptable first-line study despite questionable accuracy in determining degree of stenosis and inability to image intracranial circulation. See Chapter 5.1 for more information on patients with cerebrovascular disease.


1. Dodick DW, Meissner I, Meyer FB, et al. Evaluation and management of asymptomatic carotid artery stenosis. Mayo Clin Proc. 2004;79:937-944.

2. Wolf P, Kannel W, Sorlie P, et al. Asymptomatic carotid bruit and risk of stroke: The Framingham Study. JAMA. 1981;245:1442-1445.

3. Bucerius J, Gummert J, Borger M, et al. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg. 2003;75:472-478.

4. Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995;273:1421-1428.

5. Halliday A, Mansfield A, Marro J, et al; MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomized controlled trial. Lancet. 2004;363:1491-1502.

5.3 Aneurysms and Arteriovenous Malformations

Panumart Manatpon

Diana Ayubcha

W. Andrew Kofke

The incidence of cerebral aneurysms is 3.2% in adults worldwide. Only 0.25% of these will have a rupture in the future (1). Unruptured aneurysms are usually found incidentally in patients presenting with symptoms other than hemorrhage. In ruptured aneurysms, which result in a subarachnoid hemorrhage (SAH), 80% of patients complain of the worst headache of their life. Other signs of SAH include nausea, vomiting, photophobia, neck pain, and loss of consciousness. Up to 10% to 43% of patients will have a sentinel headache, days to weeks before rupture (2,3). SAH has significant morbidity with a mortality rate of 20% to 40%. About half of SAH survivors have a significant reduction in health-related quality of life (4). SAH during pregnancy most commonly occurs in the postpartum period and is less likely to be caused by aneurysms, when compared to nonparturients (5).

The goals of treatment are to prevent rupture and subsequent hemorrhage or re-hemorrhage in ruptured aneurysms. This can be accomplished by microvascular clipping or endovascular coiling. Many studies show that endovascular coiling, when compared to surgery, reduces procedural morbidity and mortality in unruptured aneurysms but also has a higher recurrence rate (1,6,7,8). The complete obliteration rate of coiling is much lower when compared to clipping. Endovascular management is more difficult in patients with aberrant anatomy (3). Ruptured aneurysms can be treated by either approach, but endovascular coiling tends to be the primary therapy. This is especially true for elderly patients and poor-grade SAH.

Cerebral AVM consist of a tangle of abnormal vessels, referred to as a nidus, connecting the high-pressure arterial system to the low-pressure venous system. AVM is the most common etiology of intracranial hemorrhage in young patients and a typical presentation includes hemorrhage (50%), seizures, and neurologic deficits. The risk of ruptured AVM is approximately 2% to 4% per year (9). Treatment approaches to AVM include surgical removal, endovascular embolization, and stereotactic radiosurgery, all depending on the location, size, and whether or not there is a hemorrhagic presentation (10).


Clinical evaluation of AVM and aneurysms includes patient history, physical examination, and a review of the disease pathology. Cerebral aneurysms are associated with several disorders, of which the most commonly associated is autosomal dominant polycystic kidney disease. Others include Ehlers-Danlos syndrome, Marfan syndrome, coarctation of the aorta, bicuspid aortic valve, pseudoxanthoma elasticum, and pheochromocytoma (1). In addition, SAH is associated with other conditions, including hypertension, diabetes mellitus, and heart disease.

SAH can cause a myriad of extracranial systemic effects. Hyponatremia is the most common electrolyte abnormality in SAH patients resulting from either cerebral salt wasting syndrome or syndrome of inappropriate antidiuretic hormone secretion (SIADH). Other electrolyte disturbances include hypokalemia, hypocalcemia, and hypomagnesemia. Intravascular volume deficit is also commonly seen in these patients. Moreover, SAH can affect myocardial function which is thought to be due to increased localized catecholamine release in the myocardium. Cardiac manifestations
include cardiac arrhythmias, prolonged QT, T wave abnormalities, Q waves, elevated troponin level, regional wall motion abnormalities, and cardiomyopathy. Further cardiac investigations such as serum cardiac enzymes and echocardiography may be indicated. Pulmonary complications, including pulmonary edema, pneumonia, and acute lung injury, can occur in up to 80% of SAH patients (11).

Patients may receive medications such as antihypertensive agents, steroids, and mannitol. Thus, serum electrolytes and glucose are obtained and appropriately treated preoperatively. Anticonvulsant medications such as phenytoin and carbamazepine can decrease the effect of nondepolarizing muscle relaxants leading to a higher dose requirement. Hemodynamics should be optimized to avoid rupture, re-bleeding, and cerebral ischemia.


1. Thompson BG, Brown RD, Jr., Amin-Hanjani S, et al. Guidelines for the management of patients with unruptured intracranial aneurysms: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46:2368-2400.

2. Suarez JI. Diagnosis and management of subarachnoid hemorrhage. Continuum (Minneap Minn). 2015;21(5 Neurocritical Care):1263-1287.

3. Connolly ES, Jr., Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43:1711-1137.

4. Manhas A, Nimjee SM, Agrawal A, et al. Comprehensive overview of contemporary management strategies for cerebral aneurysms. World Neurosurg. 2015;84:1147-1160.

5. Bateman BT, Olbrecht VA, Berman MF, et al. Peripartum subarachnoid hemorrhage: nationwide data and institutional experience. Anesthesiology. 2012;116:324-333.

6. Hoh BL, Chi YY, Lawson MF, et al. Length of stay and total hospital charges of clipping versus coiling for ruptured and unruptured adult cerebral aneurysms in the Nationwide Inpatient Sample database 2002 to 2006. Stroke. 2010;41:337-342.

7. Brinjikji W, Rabinstein AA, Nasr DM, et al. Outcomes with treatment by coiling relative to clipping of unruptured intracranial aneurysms in the United States, 2001-2008. AJNR Am J Neuroradiol. 2011;32:1071-1075.

8. McDonald JS, McDonald RJ, Fan J, et al. Comparative effectiveness of unruptured cerebral aneurysm therapies: propensity score analysis of clipping versus coiling. Stroke. 2013;44:988-994.

9. Kim H, Al-Shahi Salman R, McCulloch CE, et al. Untreated brain arteriovenous malformation: patient-level meta-analysis of hemorrhage predictors. Neurology. 2014;83:590-597.

10. Potts MB, Jahangiri A, Jen M, et al. Deep arteriovenous malformations in the basal ganglia, thalamus, and insula: multimodality management, patient selection, and results. World Neurosurg. 2014;82:386-394.

11. Lin BF, Kuo CY, Wu ZF. Review of aneurysmal subarachnoid hemorrhage-focus on treatment, anesthesia, cerebral vasospasm prophylaxis, and therapy. Acta Anaesthesiol Taiwan. 2014;52:77-84.

5.4 Myasthenia Gravis

Panumart Manatpon

Diana Ayubcha

W. Andrew Kofke

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies which attack the postsynaptic acetylcholine receptor at the neuromuscular junction. The incidence and prevalence of MG has increased, doubling in the past decade, likely the result
of improvements in epidemiologic methodology, overall patient care, and increased life expectancy (1). Patients usually present with proximal muscle weakness, which is alleviated by rest and exacerbated by activity. Up to 60% of patients present with diplopia, ptosis, or both (2). Bulbar muscles may be impaired and result in dysphagia or dysarthria. Table 5.3 shows the accepted classification based on the severity of the disease and clinical presentation of MG.

TABLE 5.3 Myasthenia Gravis Foundation of America Clinical Classification of Myasthenia Gravis

Stage I

Ocular involvement only

Stage II

Generalized mild muscle weakness

Stage IIa

Stage IIb

Predominantly affects limb and axial muscles

Predominantly bulbar and respiratory muscle involvement

Stage III

Generalized moderate muscle weakness

Stage IIIa

Stage IIIb

Predominantly limb and axial muscles

Predominantly bulbar and respiratory muscle involvement

Stage IV

Generalized severe weakness

Stage IVa

Stage IVb

Predominantly affects limb and axial muscles

Predominantly bulbar and respiratory muscle involvement

Stage V

Tracheal intubation and/or mechanical ventilation

There are medical and surgical treatment options for MG. Pyridostigmine, which is a cholinesterase inhibitor, is considered first-line therapy. If patients continue to be symptomatic, glucocorticoids are added to the medical regimen. Immunosuppressive agents (azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, and rituximab) are used when patients do not respond to current therapy, if glucocorticoid doses are excessive, or patients are unable to tolerate side effects of current regimen. Immunosuppressive agents are considered as an earlier intervention for patients with diabetes mellitus, osteoporosis, ischemic heart disease, or patients with continued significant bulbar and muscle weakness. In patients with severe bulbar and respiratory compromise, intravenous immunoglobulin (IVIG) is recommended. Plasma exchange is preferred if the risk factors (renal insufficiency, thrombotic events, and IgA deficiency) associated with anaphylaxis and IVIG are a concern (3). IVIG has comparable efficacy and duration of effect to plasma exchange (4). Thymectomy is a surgical option for patients with thymomas who are younger than 45 years old and have positive serum anti-AchR antibody. However, the benefit of this surgery is controversial in patients with nonthymomatous ocular MG (2,3).

Myasthenic patients with muscle weakness and respiratory insufficiency may be experiencing a myasthenic crisis (an exacerbation of the disease) or a cholinergic crisis (caused by cholinesterase inhibitor overdose). In a cholinergic crisis, autonomic symptoms, such as bronchospasm, sialorrhea, bronchorrhea, and diarrhea, may be present in addition to muscle weakness. Administering a single small dose of edrophonium can help distinguish myasthenic crisis from cholinergic crisis. Symptoms will show improvement in patients with myasthenic crisis, whereas symptoms will worsen in patients with cholinergic crisis (5).


Elective surgery can be performed in stable patients who have well-controlled or mild disease. Neurology is consulted preoperatively if patients need further optimization or have severe disease with significant compromise. Azathioprine inhibits phosphodiesterase in the motor nerve terminal. It enhances the effect of acetylcholine but decreases the effect of nondepolarizing neuromuscular blocking agents (NMBA). For emergency surgery, patients with a myasthenic crisis are optimized with plasma exchange or IVIG (2,3,6). The pharmacology of neuromuscular blockade and its reversal is complex in MG. The number of normal postsynaptic acetylcholine receptors is decreased. The effect of NMBA increases, whereas the effect of depolarizing agents (succinylcholine) is reduced due to fewer normal acetylcholine receptors to depolarize. Plasma cholinesterase is inhibited by therapeutic cholinesterase inhibitors. As a result, the duration of succinylcholine is increased and prolonged blockade can occur. Discontinuation of anticholinesterase inhibitors may lead to increased sensitivity to NMBA (7). Anticholinesterase inhibitors are continued perioperatively with potential intravenous administration if the patient is unable to take oral doses. The conversion ratio from intravenous to oral pyridostigmine is 1:30-90.

MG has been associated with other autoimmune diseases such as thyroiditis, hematologic autoimmune disorders, rheumatoid arthritis, and SLE (2,7). Patients are screened for these diseases preoperatively. Muscle weakness can predispose patients to respiratory infection, osteoporosis, obesity, and other conditions which may complicate the recovery period (2).

Up to 16% of patients with MG have cardiac involvement, including asymptomatic ST-T wave changes and rhythm abnormalities, myocarditis, heart failure, autonomic instability, and sudden death (7,8,9,10). Routine screening is not recommended, but electrocardiography and/or echocardiography are considered in patients with poor exercise tolerance, dyspnea, or fatigue.

The likelihood of postoperative mechanical ventilation is a concern in these patients and is assessed preoperatively (Table 5.4).

The incidence of postoperative myasthenic crisis is reported to be between 6% and 34%. Risk factors of postoperative crisis are shown in Table 5.5.

Administering high-dose glucocorticoids in the preoperative period reduces postoperative myasthenic crisis without increasing the rate of pneumonia, wound
infection, or impaired glucose tolerance (14). Other studies show the benefits of lowdose prednisolone (30 mg/day) to decrease postoperative respiratory insufficiency and the duration of mechanical ventilation (15).

TABLE 5.4 Scoring System to Predict the Need for Postoperative Ventilator Support (11)

Duration of myasthenia ≥6 years (12 points)

History of chronic respiratory disease (10 points)

Pyridostigmine dose >750 mg/day (8 points)

Vital capacity <2.9 L (4 points)

Total score of ≥10 points indicates a high chance of postoperative mechanical ventilation for at least 3 hours.

TABLE 5.5 Risk Factors for Postoperative Myasthenic Crisis (12,13)

Osserman stage equal to or higher than 2b

Previous history of myasthenic crisis

Symptoms duration >2 years

Lung resection

High preoperative anti-acetylcholine receptor antibody titer

Unstable MG after preoperative medical therapy

Body mass index >28

MG patients are at risk of aspiration due to weakness of oral and pharyngeal muscles. Aspiration prophylaxis including premedication with H2 antagonists and metoclopramide are considered. Premedication with sedatives and opioids are used with caution so as not to depress respiratory drive.


1. Carr AS, Cardwell CR, McCarron PO, et al. A systematic review of population based epidemiological studies in myasthenia gravis. BMC Neurol. 2010;10:46.

2. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14:1023-1036.

3. Sussman J, Farrugia ME, Maddison P, et al. Myasthenia gravis: Association of British Neurologists’ management guidelines. Pract Neurol. 2015;15:199-206.

4. Barth D, Nabavi Nouri M, Ng E, et al. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. 2011;76:2017-2023.

5. Blichfeldt-Lauridsen L, Hansen BD. Anesthesia and myasthenia gravis. Acta Anaesthesiol Scand. 2012;56:17-22.

6. Jamal BT, Herb K. Perioperative management of patients with myasthenia gravis: prevention, recognition, and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107:612-625.

7. Turakhia P, Barrick B, Berman J. Patients with neuromuscular disorder. Med Clin North Am. 2013;97:1015-1032.

8. Kumagai S, Kato T, Ozaki A, et al. Serial measurements of cardiac troponin I in patients with myasthenia gravis-related cardiomyopathy. Int J Cardiol. 2013;168:e79-e80.

9. Suzuki S, Utsugisawa K, Yoshikawa H, et al. Autoimmune targets of heart and skeletal muscles in myasthenia gravis. Arch Neurol. 2009;66:1334-1338.

10. Nikolic A, Peric S, Nisic T, et al. The presence of dysautonomia in different subgroups of myasthenia gravis patients. J Neurol. 2014;261:2119-2227.

11. Leventhal SR, Orkin FK, Hirsh RA. Prediction of the need for postoperative mechanical ventilation in myasthenia gravis. Anesthesiology. 1980;53:26-30.

12. Leuzzi G, Meacci E, Cusumano G, et al. Thymectomy in myasthenia gravis: proposal for a predictive score of postoperative myasthenic crisis. Eur J Cardiothorac Surg. 2014;45:e76-e88.

13. Ando T, Omasa M, Kondo T, et al. Predictive factors of myasthenic crisis after extended thymectomy for patients with myasthenia gravis. Eur J Cardiothorac Surg. 2015;48: 705-709; discussion 9.

14. Yamada Y, Yoshida S, Suzuki H, et al. Efficacy of perioperative high-dose prednisolone therapy during thymectomy in myasthenia gravis patients. J Cardiothorac Surg. 2013;8:226.

15. Kataoka H, Kiriyama T, Kawaguchi T, et al. Preoperative low-dose steroid can prevent respiratory insufficiency after thymectomy in generalized myasthenia gravis. Eur Neurol. 2014;72:228-233.

5.5 Lambert-Eaton Syndrome

Scott Stevens

Keith J. Ruskin


The presenting symptom of Lambert-Eaton is typically proximal muscle weakness in the pelvic and truncal areas. Characteristic features include bulbar dysfunction, decreased deep tendon reflexes, posttetanic potentiation of muscle contraction, and autonomic dysfunction. Muscle weakness is more significant in the morning and usually improves throughout the day due to repeated nerve stimulation. Autonomic manifestations include gastroparesis, orthostatic hypotension, urinary retention, and dry mouth.


Preanesthesia evaluation includes a comprehensive history and physical examination. A history of progressive proximal muscle weakness, in addition to gait alterations or difficulty standing from a chair, is suggestive of the disease. Patients may also complain of stiff or aching muscles. Muscle fatigue or cramping commonly occurs, especially after exercise. Sanders et al. recently described a “triple timed get-up-and-go” test that may help to assess disease severity (3). Patients with bulbar involvement or autonomic dysfunction are at increased risk for aspiration. Patients may experience respiratory muscle weakness, leading to dyspnea. Patients should also be asked about symptoms suggestive of pharyngeal weakness (e.g., difficulty swallowing), although some evidence suggests only 7% of Lambert-Eaton patients experience this symptom. Postural hypotension, a history of dry mouth, or impotence suggests autonomic dysfunction. Systemic illness can exacerbate chronic weakness, so a comprehensive history is important. Evaluation of lung function with spirometry and pulmonary function testing help to stratify the risk of postoperative respiratory complications. Although there is very little data about preoperative pulmonary function testing in patients with Lambert-Eaton syndrome, a vital capacity of less than 2.0 to 2.9 L in adults may predict the need for postoperative ventilation. Assessment of antibody burden has not been shown to be predictive of disease severity but can serve as a marker, in individual patients, of response to immunomodulation therapy. Preoperative plasmapheresis should be considered in patients with severe dysfunction.

The patient’s acetylcholine augmenting medications are continued through the perioperative period. Gastrointestinal prokinetic agents are considered in patients with autonomic dysfunction. Individuals with Lambert-Eaton are characteristically sensitive to neuromuscular blockade with both nondepolarizing and depolarizing; anesthetic techniques that avoid neuromuscular blockade or that limit their use are preferred. Patients with Lambert-Eaton syndrome who receive neuromuscular blockade and endotracheal intubation may require postoperative intubation and mechanical ventilation. They also have an increased risk of postoperative respiratory complications, around 11% (4). Antibiotics such as fluoroquinolones, aminoglycosides, and erythromycin are avoided because they potentiate neuromuscular blockade. Maintenance of normothermia and avoidance of hyperthermia can prevent exacerbation of muscle weakness (5).


1. Tarr TB, Wipf P, Meriney SD. Synaptic pathophysiology and treatment of Lambert-Eaton Myasthenic syndrome. Mol Neurobiol. 2015;52(1):456-463.

2. Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev. 2011;2:CD003279.

3. Sanders DB, Guptill JT, Aleš KL. Reliability of the triple timed-up-and-go (3TUG) test. Muscle Nerve. 2017 doi: 10.1002/mus.25700

4. Weingarten T, Araka CN, Mogensen ME, et al. Lambert-Eaton myasthenic syndrome during anesthesia: a report of 37 patients. J Clin Anesth. 2014;26:648-653.

5. Ricker K. Hertel G, Stodiek S. The influence of local cooling on neuromuscular transmission in the myasthenic syndrome of Eaton and Lambert. J Neurol. 1977;217(2):95-102.

5.6 Amyotrophic Lateral Sclerosis

Amelia Nelson

Amyotrophic lateral sclerosis (ALS) is a progressive and incurable disease characterized by degeneration, dysfunction, and eventual paralysis of upper and lower motor neurons. It is sometimes referred to by the eponym Lou Gehrig disease, for the New York Yankees baseball player who succumbed to ALS at the age of 37. The underlying etiology of ALS is not clear (1). While most cases are sporadic, 5% to 10% are familial. The diagnosis is made clinically by evaluating for upper and lower motor neuron dysfunction in multiple motor groups (see Table 5.6) (2,3).

TABLE 5.6 Signs and Symptoms of Amyotrophic Lateral Sclerosis by Motor Group

Upper Motor Neuron

Lower Motor Neuron


Stiffness and spasticity

Poor coordination

Hyperreflexia and clonus






Poor balance

Neck weakness, difficulty holding up head

Difficulty standing erect

Abdominal protuberance


Jaw spasticity and trismus



Laryngospasm (spontaneous or due to aspiration)

Pseudobulbar affect

Jaw and lip weakness (difficulty opening and closing mouth)



Voice changes (quiet, hoarse)



Weak cough



Morning headache (nocturnal hypoxemia)

Sedation and confusion (hypercarbia)

The signs and symptoms at onset and the patterns of disease progression are variable. The median time of survival after diagnosis is 3 to 5 years. Death typically results from ventilatory failure due to neuromuscular weakness. Riluzole is the only medication approved for disease modification, rather than palliation of symptoms. Its exact mechanism of action is debated, but clinical trials show modest improvement of survival time.

Patients with ALS are best served by a multidisciplinary team (neurology, pulmonology, palliative care, nutrition, social work, and physical, occupational, respiratory, and speech therapy) experienced in ALS care (4). This is also true when planning for a surgical procedure. Preoperative assessment of the ALS patient begins with characterization of the surgical plan. Advancing disease may require palliative procedures such as placement of feeding tubes or tracheotomy. Surgery may be tangentially related to the disease (long bone fracture after a fall) or not disease related (appendectomy). Context allows the anesthesiologist to prioritize further evaluation or consultation and discuss the risks and benefits of the anesthetic options. Elective and semielective procedures should be scheduled as early in the disease process as possible. Progressive muscular weakness increases risk for aspiration and can cause exquisite sensitivity to the respiratory depressants utilized perioperatively.

The history focuses on disease trajectory, current and previous physical status, ventilatory reserve, signs and symptoms of nocturnal hypoventilation, and aspiration risks. The patient is assessed for ALS-plus syndrome where the stereotypical upper and lower motor neuron findings coexist with parkinsonism, progressive supranuclear palsy, and (importantly) autonomic instability and dysfunction (5). Evaluation of the airway assesses and documents oral aperture, jaw mobility, and range of motion of the neck. Inability to elevate the palate or protrude the tongue affects the Mallampati score. Masseter spasticity can lead to severe trismus. Muscular laxity may lead to recurrent temporomandibular dislocations. Longstanding weakness of the neck extensors can lead to anterocollis, and spasticity can cause torticollis.

Ideally, individuals with ALS will have serial ventilatory assessments, starting at the time of diagnosis. ALS specialists typically monitor patients with pulmonary function tests and tests of neuromuscular strength, including upright and supine forced vital capacity (FVC) and maximum inspiratory and expiratory pressures. An FVC <50% of predicted is a marker for early ventilatory failure and need for chronic support (6). Updated studies should be done if there has been a significant change in symptoms. If indicated, the patient should be initiated on noninvasive positive pressure ventilation (NIPPV) before surgery. Patients with coexisting cardiac disease who are now physically limited need optimization of medical regimens. It is highly unlikely that additional testing is indicated given patients’ prognosis and typical life expectancy.

Preoperative laboratory work is guided by the patient’s comorbidities. An electrolyte panel and assessment of renal function is reasonable if the patient has severely impaired swallowing, weight loss, and is at risk for dehydration. Creatine phosphokinase is typically elevated due to chronic muscle wasting and should not raise concerns for myocardial injury.

Having trusted family members or friends present for the preoperative visit is useful for many reasons. Patients with advanced disease (or bulbar-predominant presentation) may have reduced verbal ability due to oropharyngeal weakness or dysarthria. Some individuals utilize writing pads or electronic devices for communication but many have self-developed shorthand codes (blinking, tapping), which close confidants are skillful at interpreting. Additionally, while traditional teaching describes
ALS as a pure motor disorder, cognitive changes are common. Many individuals with ALS demonstrate frontotemporal executive dysfunction, and a small percentage will develop frontotemporal dementia (7). Patients with ALS often have strong preferences about end-of-life care, intubation, and resuscitation. Involving family in complex discussions is ideal. Engaging the patient and his or her medical power of attorney in a dynamic discussion about mechanical ventilation when sedation and general anesthesia are under consideration is an essential part of the preoperative visit.

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Nov 14, 2018 | Posted by in ANESTHESIA | Comments Off on Neurologic/Neuromuscular Disorders

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