Transient Global Amnesia as a Possible First Manifestation of COVID-19

Abstract

Evidence of involvement of the nervous system in COVID-19 disease is accumulating. We describe a case of a 53-year-old man presented with classic syndrome of transient global amnesia with symptoms lasting less than 24 hours and mild transient unexplained fever. Workup including brain MRI, electroencephalogram, and chest X ray was negative and the patient was discharged. The day after discharge, the patient started to experience the classic respiratory and systemic COVID-19 illness and was eventually readmitted with hypoxic respiratory failure and positive COVID-19 test a week after the first hospital discharge. The case highlights the importance of neurological syndromes as presenting prodrome to the respiratory illness of COVID-19.

Case Report

A 53-year-old male pharacist was in his normal state of health when, 2 hours into the afternoon shift at the retail pharmacy he works at, his coworkers noticed that he was confused asking repetitive questions. They called his wife who brought him to the emergency department (ED) about 3 hours from symptom onset. In the ED, he was awake and alert, knew who he was and where he was but did not remember what had happened at work and how he was brought to the hospital. He was feeling lightheaded but denied fever, chills, congestion, shortness of breath, chest pain, palpitation, diaphoresis, nausea, or vomiting, recent illness or trauma, recent exposure to COVID-19 cases or other sick persons. The patient had known asthma and used various beta agonists and steroid inhalers at home. He was mildly obese (body mass index 32.7 kg/m²) and had obstructive sleep apnea (OSA) that was well managed with continuous positive airway pressure (CPAP) device but was otherwise quite healthy and active individual with no history of prior seizures, migraine, or other neurological conditions. He was an occasional alcohol drinker but was not a smoker and did not use illicit drugs. His initial vital signs showed mildly elevated blood pressure (150/87 mm Hg) but no fever (36.7°C), tachycardia, or tachypnea. His oxygen saturation was 98% on room air. Generally, he looked well with no pallor or cyanosis, no evidence of trauma, had moist oral mucosa, normal posterior pharynx, supple neck, clear lung auscultation without wheezes, rales or rhonchi, normal cardiac auscultation, strong symmetric radial pulse, soft non-tender non-distended abdomen, had no peripheral edema, and no rash. On neurological examination, he was alert and oriented to place and persons but not time or date. He was inquiring repeatedly about what was happening and how he got to the ED. Otherwise, his language function was normal and he did not have focal any neurological deficit. Electrocardiogram and head CT were obtained and were normal. Laboratory tests included complete blood count, basic metabolic profile, liver function tests, serum troponin, urinalysis, and urine drug screen. The only abnormal laboratory findings were serum sodium 134 mEq/L, serum calcium 7.9 mg/dL, and serum glucose 179 mg/dL. The ED team first called the oncall stroke neurologist and the impression was possible transient global amnesia (TGA) not stroke. The patient was admitted for observation and a brain MRI which was done overnight.

Next morning, 16 hours after symptom onset, he was noted to have a low-grade fever 37.8°C (repeat half hour later was 37.9°C).

When evaluated by general neurology (about 17 hours from symptom onset), the patient was feeling back to normal. He remembered sleeping well the night before with the help of his CPAP, waking up feeling fine in the morning, and remembered the events of the prior day including starting his work shift but nothing after that until being inside the MRI machine and feeling claustrophobic. The neurological examination including a detailed mental state examination was completely normal. His MRI was normal. Electroencephalogram (EEG) was also normal. He was diagnosed with TGA with no further neurological investigations or therapies. However, the mild fever which had started an hour before the neurological examination was unexplained. The neurologist raised the possibility of COVID-19 in a phone call with the hospitalist. However, it was felt unlikely given the lack of other classic symptoms. As a precautionary measure, a chest X ray (CXR) was ordered and showed mild patchy lingular and right infra-hilar opacities that were interpreted as atelectasis (see Figure 1). There was no consolidation or increased interstitial markings. Temperature recheck an hour later was 37.3°C and the patient was discharged home.

Figure 1.

Chest X ray done on days 2, 7, and 9 after the onset of transient global amnesia. there is progression of interstitial opacities with the first scan interpreted as bibasilar atelectasis. subsequent scans recognized as interstitial opacifications of viral pneumonia.

Two days later, the patient called and reported that he had had persistent low grade fever ranging from 37.7°C to 37.9°C and on that particular day it reached 40°C. He also reported headaches, poor appetite, body aches, chills, and fatigue, productive cough, shortness of breath, chest pain with deep breathing, and loss of smell. The patient was sent for COVID-19 testing which came back positive the next day. He was managed at home initially with symptomatic treatments and home quarantine. He was given pulse oximeter to monitor his oxygenation. Unfortunately, his symptoms worsened over the next few days and he became hypoxic which led to admission 7 days after the first hospital discharge. At the time of writing this report, the patient is in the intensive care unit with progressive hypoxic respiratory failure, thrombocytopenia, lymphocytopenia, elevated C-reactive protein, D-dimer, lactate dehydrogenase, aspartate aminotransferase levels, creatine kinase, and worsening euvolemic hyponatremia.

Discussion

COVID-19 pandemic is primary a respiratory disease, however, reports of neurological involvement have been accumulating. The spectrum of neurological diseases of COVID-19 is actively unfolding. The most comprehensive report of CNS involvement is a retrospective study of 214 patients in China.¹ Central nervous system (CNS) symptoms included dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure. Specific CNS diseases including encephalitis² and stroke³ have also been reported. This is the first report of TGA. It is important to recognize here that TGA was the presenting syndrome starting 16 hours before the first fever was detected and 2 days before any respiratory symptoms. A recently published case series of 5 patients described stroke as one of the presenting features of COVID-19³ but in our case, TGA syndrome preceded any COVID-19 systemic or respiratory symptom. It is unclear whether the viral illness triggered the TGA, either by an unknown disease-specific process or just the stress the developing infection, or the 2 conditions are unrelated and their co-occurrence was coincidental. We did not detect structural brain pathology on MRI and the EEG was completely normal. A review of the literature revealed one case of TGA attributed to herpes encephalitis⁴ although in that case, the recovery of cognitive function was not as rapid as in our case. The association between OSA and TGA has been observed before with the apnea-induced cerebral injury being the underlying pathology that predisposes to TGA.⁵ Our patient did have OSA, so if the above speculated relationship between OSA and TGA is true, he might have been predisposed to TGA. Although it is hard to ascertain an association, let alone causation, between TGA and COVID-19, this case and other cases documenting nervous system involvement in COVID-19 patients, demand recognition, vigilance, and further study. It is also worth noting that later in the course of the disease, the patient had laboratory markers of other neurologic conditions, namely myopathy and syndrome of inappropriate antidiuretic hormone secretion.

There was a 3-day delay in testing this patient because his fever was mild and transient and because his CXR that showed basilar opacifications was interpreted as atelectasis. This highlights the importance of intermittent low grade fever as a prodromal symptom of the acute severe respiratory illness, as was the case in the first COVID-19 case reported in the United States.⁶ As for the CXR, it evolved over time into multifocal interstitial opacities consistent with COVID-19 pneumonia (see Figure 1). In retrospect, one may see how all these telltale signs should have prompted an earlier testing.

Neurologists, and particularly neurohospitalists, should be on the watch and use all the safety precautions recommended by the CDC and by their local institutions, when evaluating any patient with new onset neurological conditions even if there are no symptoms suggestive of COVID-19.