Acetylcholine Receptor-Positive Myasthenia Gravis in Older Patients

Acetylcholine receptor-positive myasthenia gravis (AChR-positive MG) is an autoimmune disease that leads to Fatigable weakness, often fluctuating in severity. The disease can be more subtle and more difficult to diagnose and treat in older adults, especially those over 80 years of age. As a result of increasing life expectancy, late-onset MG is becoming more apparent in the frail elderly patient who may have several comorbid illnesses and decreasing reserve. These patients are particularly poor candidates for the more toxic medications with side effects that are commonly used in the treatment of MG.

In the very old the same disease can look different. Normal aging is accompanied by a number of physical changes that affect the immune system, muscles, lungs, swallowing function, and metabolism. Therefore, it is not always easy to recognize the symptoms of the eye muscle disease. Mild ptosis, or subtle diplopia, change in hoarseness or fatigue when chewing or swallowing, may be mistaken for “normal aging” and allowed to delay diagnosis. Alternatively, these symptoms can be confused with other potentially serious conditions, such as stroke, or neurodegenerative diseases, like Parkinson’s disease, or physical deconditioning.

Recognizing illness and starting treatment promptly, with an age-related focus, can prevent many catastrophes, including serious aspiration, falls, malnutrition, and prolonged hospitalization. The goal is to control symptoms while also encouraging safe swallowing, effective breathing, continued mobility, and independence. Patients with cancer may be on immunosuppression, and avoiding drug toxicity in the elderly requires special consideration. Polypharmacy is a problem in older patients.

Why It Matters

High stakes in frailty and limited reserve

The very old patient has less “reserve”. Small changes from day to day due to breathing, swallowing or mobility can lead to a marked change in their condition. Patients with AChR-positive MG more commonly present with ocular weakness but progression to bulbar (voice, swallowing, chewing) and respiratory weakness is most commonly associated with ED visits, ICU admission and a prolonged hospital stay. A patient with MG who develops relatively minor respiratory weakness as a result of their disease can deteriorate to respiratory failure much more rapidly than the same degree of weakness would in a younger patient with MG, particularly one who has underlying chronic lung disease or heart disease such as an 85 year old patient in this report.

The “Weakening Swallow” places individuals at risk for aspiration and pneumonia, delirium, dehydration, malnutrition, and loss of function. In the elderly, a single episode of aspiration can lead to hospitalization, subsequent immobility, pressure sores, increasing dependence, and ultimately, transfer to a nursing facility. Swallowing difficulties in patients with Myasthenia Gravis (MG) vary in degree and unpredictability, making it difficult to determine whether a patient can safely ingest food and liquid. A uniform approach to the assessment of risk for such patients is therefore indicated.

Diagnosis is often delayed or missed

Myasthenia Gravis in the elderly may be frequently overlooked. MG symptoms may be misinterpreted and masked by the more common disorders of old age. Ptosis may be viewed as normal; weakness of the speech muscles may be attributed to dentures that do not fit properly, stroke, or other neurologic diseases. Fatigue in the geriatric patient may be attributed to other symptoms of anemia, depression, heart disease, etc. Geriatric patients may downplay their symptoms, because they have a decreased acuity of pain and emotion, or they may have cognitive impairment limiting their medical history.

Early diagnosis is crucial to avoid serious consequences. By being aware of patterns, doing a good history and bedside fatigue testing, and requesting early antibody testing, physicians can make the correct diagnosis earlier in the course of illness, thereby avoiding a potentially calamitous hospital stay for an avoidably prolonged illness.

Treatment benefits remain, but risks rise

Patients with AChR-positive MG generally respond well to both symptomatic and immune-directed treatments, and the risk:benefit ratio for these treatments may change in older patients. Corticosteroids can improve muscle strength but can cause many problems, including delirium, insomnia, mood changes, hyperglycemia, fluid retention, hypertension, and osteoporosis. Many MG patients are therefore treated with steroid-sparing medications that can decrease the long-term need for high doses of steroids. Many of these medications can take months to achieve their full effect, and side effects can be significant. As a result, monitoring of patients on these medications is often necessary.

Polypharmacy is a characteristic feature of the elderly. Many prescribed medications can cause interactions, as well as induce weakness. Many commonly used medications in the elderly can impair neuromuscular transmission and cause fatigue that potentially places the patient at risk for respiratory compromise, especially in the setting of concurrent sedative use or lung disease.

Crises are dangerous, but preventable

The older patient with myasthenic crisis, characterized by respiratory failure requiring ventilatory support, faces especially grave prognosis. In addition to the serious clinical problems posed by myasthenia, the older patient is particularly sensitive to the risks of intubation, prolonged ventilator stay, hospital-acquired infection, and delirium.

Prevention of severe “crises” is our main goal. This means early detection of bulbar weakness and institution of “rescue” therapy for those who require it. A plan for increasing weakness, early detection of respiratory problems, and access to NM experts when necessary is fundamental in reducing “crises” and improving quality of life.

System impact: coordination, cost, and access

Management of very old patients with MG is particularly challenging. In addition to the patient’s and family’s wishes and overall health status, a very old patient with MG is treated by a team of health care providers from several disciplines, including the neurologist, the patient’s primary care physician or geriatrician, speech-language pathologist, nutritionist, respiratory therapist, pharmacist, rehabilitation specialist, and home health care providers. These patients face a particularly hazardous transition from the hospital to rehabilitation or skilled nursing facility and then to long-term care, during which there is a significant risk of error or incorrect diagnosis of medication effects.

Targeted therapy for elderly cancer patients may yield clinical benefits; however, these treatments are very expensive and often there is a paucity of clinical data to support their use in very old, frail patients. To ensure equitable distribution of these expensive treatments to cancer patients who could benefit from them, it is essential that targeted cancer medications be distributed safely across all care settings and be accessible in a variety of locations, including rural hospitals and skilled nursing facilities that may not have an oncologist on staff.

Who It Affects

Older adults with late-onset or newly recognized MG

Patients range from 70 year olds newly diagnosed with AChR-positive MG to patients in their 80’s and 90’s with long standing disease. Some patients have been misdiagnosed for months or even years receiving a diagnosis of age appropriate symptoms or a co-morbid condition until they seek a diagnosis for symptoms that interfere with their quality of life.

Management of patients with severe exacerbations of chronic respiratory disease in the older patient can be particularly challenging, as many of these patients are treated for several chronic conditions and are often evaluated and managed by different specialists. Conditions such as heart disease, other chronic lung disease, diabetes, chronic kidney disease, history of stroke, frailty, and cognitive impairment all must be considered when deciding on a course of treatment and evaluating potential benefit from an exacerbation.

Families and caregivers

Caregivers can play a critical role in management of MG as most patients require daily monitoring of their weakness, which can be unpredictable, and need to be on schedule with daily medications. Especially the older patients need help in monitoring their symptoms, ensuring that they are eating safely, and being able to recognize the early signs of worsening of either respiratory or bulbar weakness.

In addition to the emotional toll, caring for a family member also can involve managing a multitude of services and providers from different settings, which can be overwhelming. By educating patients and their families and simplifying the care planning process, we can help reduce errors and stress while preserving independence and fostering home care whenever possible.

Clinicians across settings

Your neurologist or neuromuscular specialist can guide management regarding confirmation of diagnosis, choice of immunotherapy, and prevention of exacerbations versus relapses. Primary care providers manage competing lists of comorbidities, watch for potential MG complications, provide advice on vaccination and infection prevention, and manage for asymptomatic carriage of bacteria. Geriatric experts can provide additional advice on issues of frailty, cognitive changes, falls, and decreased function, as well as deprescribing in the elderly patient.

The Speech-Language Pathologist, Dietitian, Respiratory Therapist, Pharmacist and the Rehabilitation Team all play a crucial role in ensuring safe outcomes for older adults. Their intervention is vital to preventing poor oral intake, aspiration, hospital readmission and achieving excellent quality of life.

Health systems and payers

Other factors such as monitoring frequency, need for multidisciplinary management and occasional high cost of therapy (e.g., inpatient hospitalization for hydration/dehydration) must also be considered by administrators and payers. These factors likely affect older, less mobile patients and their caregivers differently than do coverage decisions, prior authorization requirements and access to infusion centers or home-based treatments.

What Changes

A geriatric-adapted diagnostic approach

The clinician should suspect MG in any patient with fluctuating, fatigable weakness. In very old adults, it is helpful to ask about eyes, face, voice, swallowing, and breathing. For example: • Do your eyelids droop more later in the day? • Does your speech fade with talking? • Do you choke on thin liquids when tired? • Do you get short of breath when lying flat or after speaking?

Objective confirmation of Myasthenia Gravis (MG) diagnosis should not be delayed. Antibody testing is useful in the diagnosis of MG and can help to stratify the risk of disease in patients in whom the clinical diagnosis is unclear. Electrodiagnostic testing is particularly helpful in ambiguous cases where clinical impressions are not supported. Imaging of thymic disease is useful in a subset of patients, and decisions regarding its use should be made with the patient’s age, medical goals, and potential for surgical therapy in mind.

Symptom relief with careful dosing

Patients on acetylcholinesterase inhibitors for Alzheimer disease require individualized dosing for optimal benefit and to prevent adverse effects. Patients with delayed gastric motility, patients who are underweight, and patients with renal insufficiency are particularly sensitive to adverse effects such as diarrhea, abdominal pain, sweating, bradycardia, and syncope.

Dosage should be initiated at a relatively low level and titrated to maximum therapeutic benefit as side effects (primarily cholinergic) are detected. As dose is increased, patients may report worsening of symptoms. This typically indicates either overmedication, an interacting medication, or the patient is experiencing an exacerbation of their underlying illness. The clinician should address these situations promptly.

Immunotherapy with safety-first sequencing

Corticosteroids have benefits but also many potential hazards for the very old. Strategies to safe use of corticosteroids include starting on the lowest effective dose and/or slow taper, protecting against osteoporosis, monitoring glucose and mood, and preventing infection. Some older patients might benefit from a time limited course of steroids in conjunction with a longer-term steroid-sparing strategy. In these cases, it is helpful to plan stopping points and periodic re-evaluation.

These agents may potentially offer steroid-sparing effects thereby decreasing long-term toxicity but have a delayed onset of action and can be difficult to monitor in frail patients. Older patients may be particularly prone to cytopenias, hepatotoxicity, nephrotoxicity, and infections compared with younger patients. Monitoring labs should be realistic and, ideally, scheduled in advance.

Targeted biologics: selective use and goal-based decisions

Newer targeted therapies for some cancers may provide an important clinical advance for some patients. When considering such therapy for very old patients, decisions must be made in an explicit goal-directed fashion. A therapy potentially to cost treatment and close monitoring to control swallowing in an 88-year old with recurrent aspirations and a history of repeated hospitalizations for illness affecting his ability to breathe, probably would be worth cost. An 84-year old with mild symptoms of ocular disease and increased risk of serious infection, on the other hand, likely would be contraindicated for a chance at symptom relief and would require conservative management.

Decisions about care and progress should be made based on three criteria: function, time, and risk tolerance. Patients and families should have a clear understanding of the expected return to function timeframe as well as what monitoring and infection precautions may be necessary. Additionally, patients and families need to understand what outcomes are most important to them (e.g. ability to eat safely/orally, ability to speak clearly, ability to walk safely, prevention of subsequent hospitalization).

Rescue therapies and crisis prevention pathways

Help in older patients to avoid late presentation and shorten ICU stay by identifying need for escalation plan early. E.g. worsening dysphagia, poor cough, difficulty counting change at a rate of one number per second, worsening breathlessness. Early intervention with measures to improve cough and appropriate transfer to pulmonary medicine with timely decision to commence “rescue” therapy.

MG management pathways in emergency setting need to standardize for optimal management of patients in the ED and on the inpatient wards. Suggestions include initial monitoring of respiratory status/pulmonary function, avoidance of swallowing oral intake when appropriate, cessation of medications known to worsen MG, and clear criteria for needing ICU level care.

Swallowing and nutrition become central

Bulbar weakness is a very serious disability in the very old. Therefore it is critical that swallow safety be assessed early in the geriatric patient’s trajectory and repeated as necessary. Speech-language pathology can assist in the bedside screening for risk of aspiration and in the decision to change the patient’s diet from pureed to more solid forms. Additionally, the patient and his caregivers can learn techniques to eat and drink more efficiently and in a variety of positions.

We can help prevent your child from deteriorating and learn to tolerate treatment better. Our Dietitian can help children and their families to ensure that they are eating enough protein and enough energy to prevent weight loss, dehydration and ensure that they are not lacking in any important nutrients due to fatigue. Occasionally, we may need to find some temporary nutritional supplementation to add to their diet.

Respiratory monitoring and home support

Early identification of respiratory compromise is critical. All patients and families should be empowered to recognize changes in their condition, and seek evaluation and treatment before a severe compromise develops. The use of home pulse oximetry for some patients and families may be beneficial. The respiratory care provider must remain vigilant in the assessment of patients to prevent a late crisis.

Our home-based home health care service offers home-based support with activities for daily living to prevent hospitalization, as well as telesickness follow-up, home health nursing, respiratory therapy and caregiver training for the stabilization of patients with medical needs who have difficulty visiting clinics.

Medication reconciliation and deprescribing as safety interventions

In the very old patient with MG, a medication review is not optional as many commonly prescribed medications can worsen weakness or potentially increase respiratory risk. All antimicrobials, cardiac medications, sedatives, anticholinergics and muscle relaxants should be reviewed prior to initiation or dose change and, if indicated, before discussion with the patient’s neurology team.

Deprescribing can help older individuals gain strength, wakefulness and balance. It can reduce sedative burden, decrease anticholinergic burden and facilitate safe simplification of complex medication regimens. This simplification can reduce the risk of falls, confusion and aspiration, while improving adherence to indicated medications.

Rehabilitation, falls prevention, and function

We can assist patients and families to include strategies from physical and occupational therapy to promote mobility while respecting energy levels. This may include gentle strengthening, exercises to improve endurance, energy conservation techniques, adaptive equipment and home modifications for safety and fall prevention.

Function-focused goals steer care in important directions. For many very old adults, safety in walking to the bathroom, eating, communication with loved ones, and living at home are among the top goals.

Advance care planning as routine care

Planning ahead is a form of safety for very old adults for whom such a decision might arise during an exacerbation of advanced dementia. This discussion should occur early in the illness in a calm fashion, and the very old adult and family should understand the effects of positive pressure ventilation and of intubation as well as the probability of a good outcome based on the patient’s and family’s experiences, the patient’s underlying medical conditions and the patient’s level of frailty.

Having preferences recorded can help to reduce anxiety in times of crisis and promote the delivery of person centred care for people with dementia. This is particularly important for people with severe dementia and those receiving care from multiple health professionals.

References:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12094810/ https://pubmed.ncbi.nlm.nih.gov/18567874/