A 62-year-old man with amyotrophic lateral sclerosis (ALS) is brought to the office by his family due to being withdrawn, sleeping more than normal, and having episodes of confusion. He says, "I just feel tired and have headaches sometimes, but otherwise I'm okay." The ALS was diagnosed 5 years ago. The patient has developed progressively worsening weakness of his upper and lower extremities despite riluzole therapy and now uses a wheelchair. He underwent percutaneous gastrostomy tube placement 6 months ago due to dysphagia. Temperature is 37 C (98.6 F), blood pressure is 122/68 mm Hg, pulse is 80/min, and respirations are 16/min. Physical examination shows tongue atrophy with fasciculations. The lungs are clear on auscultation bilaterally. Heart sounds are normal. The abdomen is soft and nontender with a properly positioned gastrostomy tube. Upper and lower extremity motor strength is decreased. Laboratory results are as follows:
| Complete blood count | ||
| Hemoglobin | 10.8 g/dL | |
| Platelets | 280,000/mm3 | |
| Leukocytes | 7,500/mm3 | |
| Serum chemistry | ||
| Sodium | 136 mEq/L | |
| Potassium | 3.8 mEq/L | |
| Chloride | 100 mEq/L | |
| Bicarbonate | 30 mEq/L | |
| Creatinine | 0.8 mg/dL | |
Chest x-ray shows bilateral basal atelectasis but no infiltrate, consolidation, or pleural effusion. Which of the following is the most appropriate next step in evaluation of this patient's current symptoms?
Amyotrophic lateral sclerosis | |
Clinical manifestations |
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Diagnosis |
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Treatment |
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EMG = electromyography; NIPPV = noninvasive positive pressure ventilation; PEG = percutaneous endoscopic gastrostomy. | |
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects upper and lower motor neurons throughout the body. Lower motor neuron involvement manifests as skeletal muscle weakness (due to atrophy) and fasciculations. Weakness of the diaphragm leads to paradoxical breathing (eg, abdominal expansion during expiration rather than inspiration) with poor inspiratory strength. Shallow breathing with low tidal volumes (ie, hypoventilation) results in atelectasis and respiratory insufficiency.
Respiratory insufficiency is compounded during sleep because of decreased accessory respiratory muscle activity during the REM stage, in addition to airway collapse due to relaxation of weakened pharyngeal muscles. Therefore, respiratory insufficiency may resemble obstructive sleep apnea with symptoms that include daytime fatigue and headaches. Patients can also develop cognitive impairment caused by hypercapnia (ie, chronic respiratory acidosis), as suggested by this patient's compensatory elevation in serum bicarbonate. Suspicion of respiratory insufficiency should be confirmed with arterial blood gas analysis.
Treatment focuses on improving respiratory function, which both prolongs survival and improves quality of life. Noninvasive positive pressure ventilation assists respiratory function by opening the upper airway and providing positive end-expiratory pressure to improve atelectasis.
(Choice B) Depression screening is appropriate in patients with ALS because of the psychosocial impact of living with a debilitating disease. Although symptoms of depression overlap with this patient's symptoms (eg, fatigue, sleep disturbance, social withdrawal), the presence of confusion and an elevated serum bicarbonate level should prompt assessment for respiratory insufficiency.
(Choice C) MRI of the brain is helpful for the initial diagnosis of ALS because it helps exclude other causes (eg, multiple sclerosis) of similar symptoms. However, MRI of the brain is unlikely to provide additional diagnostic information in this patient with established ALS and symptoms that suggest respiratory insufficiency.
(Choice D) Serum ammonia level can be elevated in patients with hepatic encephalopathy in the setting of advanced cirrhosis, but even in such patients determining the level is rarely helpful (hepatic encephalopathy is diagnosed based on signs and symptoms). In addition, this patient has no laboratory abnormalities to suggest cirrhosis (eg, hyponatremia, thrombocytopenia).
(Choice E) Thyroid function testing aids in the diagnosis of hypothyroidism, which can also cause fatigue and cognitive impairment. However, respiratory insufficiency in patients with hypothyroidism is typically seen only in severe disease (ie, myxedema coma), which is usually accompanied by hypothermia, hyponatremia, bradycardia, and/or hypotension.
Educational objective:
Amyotrophic lateral sclerosis can cause diaphragmatic weakness with resultant hypoventilation (ie, respiratory insufficiency). Arterial blood gas analysis should be performed to assess for hypercapnia, which is suggested by an elevated serum bicarbonate level.