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Elderly Man’s Neurologic Symptoms: Drug Overdose or Something Else?
A 79-year-old man presents to an emergency department in Corinth, Mississippi, with altered mental status. Initial assessment finds he is oriented to person and has pronounced shivering. Clinical examination findings are significant -- his temperature is 100.9°F (38.2°C) and oxygen saturation is 93% on 3-L nasal cannula.
Past medical history includes insulin-dependent diabetes mellitus and coronary artery disease status, for which the patient has undergone coronary bypass surgery.
Lab test results are notable for a white blood cell count of 13.8 x 103/µL, bands 8.0%, and hemoglobin 10.9.
Other findings:
- Blood urea nitrogen/creatinine: 38/1.4
- Creatine phosphokinase: 5,608
- Glucose: 308
- HbA1C: 9.6%
- Troponins: 2.94
Clinicians perform a chest x-ray, which reveals fractures of the left lateral 8th-9th ribs, with left lower-lobe opacification.
The patient's temperature is rechecked and found to be elevated, at 102°F (38.8°C). Clinicians treat the patient for community-acquired pneumonia and order further tests due to the elevated troponin level.
Following admission to hospital, the patient develops worsening respiratory distress, shaking tremors, and confusion, and is transferred to the intensive care unit; his troponin level remains elevated. Initial management includes lorazepam for control of tremors.
Days 3 and 4 in Hospital
Although the patient's rigors show improvement, physical examination notes clonus and a further increase in temperature to 104°F (40°C). At this point, clinicians review his medications and discover that he has been taking sertraline. This raises the possible diagnosis of serotonin syndrome, and he is started on the serotonergic receptor antagonist cyproheptadine.
By the following morning, the patient is alert and oriented, but with no memory of the previous few days. His temperature remains elevated at 101.1°F (38.3°C).
During the remainder of his time in hospital, his condition is baseline, and the other comorbid conditions are managed and under control.
The patient is discharged to a rehab facility, and sertraline is discontinued.
Discussion
Clinicians reporting this case of a 79-year-old man with altered mental status likely due to serotonin syndrome in addition to chronic medical comorbidities note the importance of physicians' consideration of serotonin syndrome as a differential diagnosis, since it is often unrecognized, and presents with symptoms that may be masked by symptoms of other comorbidities.
Serotonin syndrome, which can be fatal without timely diagnosis and treatment, may be caused by medication overdose, drug-drug interactions, or regular doses of medications. To improve the mortality associated with serotonin syndrome, it is important to consider the presenting symptoms so that prompt treatment can be provided.
Presenting symptoms for the condition are typically vague, including diaphoresis, hyperthermia, agitation, tachycardia, and mydriasis. The syndrome is also marked by neurologic symptoms, including hyper-reflexia, clonus, and tremors, more prominent in the lower extremity.
The case authors note that this patient illustrates the diagnostic difficulties that can arise when someone presents with other co-existing pathologies such as myocardial infarction and thyrotoxicosis. This patient's presentation with altered mental status and tremors -- along with lab test evidence of community-acquired pneumonia and myocardial ischemia -- led to appropriate treatment of the concomitant conditions. It was when his confusion and tremors persisted that a full neurological exam and medication review was performed, on the patient's third day of hospitalization.
Evidence of inducible clonus and the finding that the patient was taking sertraline led clinicians to add serotonin syndrome to the differential diagnosis, highlighting the importance of taking a thorough medical/medication history, ideally at the time of presentation.
However, based on suspected serotonin syndrome on the third hospitalization day, the patient was given cyproheptadine -- a situation, the case authors note, that should also have warranted consultation with a psychiatrist. However, the improvement in the patient's tremors and altered mental status following treatment with the serotonin receptor agonist does not eliminate delirium as a possible differential diagnosis, since cyproheptadine has been reported to improve this state as well.
Among the other differentials considered -- neuroleptic malignant syndrome (NMS), malignant hyperthermia, and anticholinergic toxicity -- NMS and anticholinergic toxicity were unlikely since the patient was not taking antipsychotics or anticholinergics. As well, the absence of a recent history of anesthesia reduced the likelihood of malignant hyperthermia.
The timing of symptom onset can help differentiate some similar conditions. For instance, while the onset of symptoms of malignant hyperthermia, anticholinergic toxicity, and serotonin syndrome occurs within 24 hours, neuroleptic malignant syndrome develops over a period of days to weeks.
That the patient's recent health history included myocardial ischemia and community-acquired pneumonia increased clinicians' consideration of delirium. However, there was no noted sundowning behavior and his exam findings significant for ankle clonus were more consistent with serotonin syndrome.
The patient most likely had serotonin syndrome due to his taking sertraline, and may have recently increased his dose, the case authors note, adding that there have been reported cases of serotonin syndrome due to a single medication. There have also been reported cases of serotonin syndrome associated with coronary artery disease and other heart disease. The patient met the requirements for diagnosis of serotonin syndrome using Hunter Serotonin Toxicity criteria -- i.e., history of serotonergic agent use, inducible clonus, hyperthermia, and tremor.
Conclusions
The case authors conclude that serotonin syndrome is an often overlooked diagnosis due to the similarity of the presenting symptoms with those of other pathologies. Nevertheless, it is a potentially life-threatening condition that should be considered in patients presenting with these vague neurologic symptoms.
