Cryptococcal meningitis initially presenting with ST elevations and elevated cardiac biomarkers

Abstract

Acute neurological events are a common cause of ECG abnormalities and transient elevations in cardiac biomarkers. This case describes an uncommon presentation of cryptococcal meningitis in a non-immunosuppressed patient, presenting with altered sensorium and derangements in cardiac profile. Delay in diagnosing meningitis was avoided by paying close attention to the patient’s presenting symptoms and by pursuing non-cardiac causes of ECG changes and elevations in cardiac troponin. Expeditious treatment and involvement of the infectious disease consultant resulted in excellent clinical response without permanent neurological sequelae.

Background

Patients with acute neurological conditions are often encountered by cardiology specialists who are frequently tasked with explaining the patient’s elevated cardiac biomarkers or changes in ECG pattern. This task is seldom simple, given the coexistence of chronic cardiac pathology preceding the acute neurological insult. Compounding this issue is the alteration in cognition experienced by some of the patients, which makes obtaining a thorough history nearly impossible. Although numerous ECG alterations have previously been described in the setting of acute neurological conditions, no cases of cryptococcal meningitis causing ECG changes or rise in cardiac biomarkers have been reported.

Case presentation

A middle-aged man presented with acute onset of altered mental status. Prior to the day of presentation, the patient was at his usual state of health and had just completed his first cycle of chemotherapy for recently diagnosed throat cancer, which consisted of cisplatin, taxotere and 5-fluorouracil. On arrival to the hospital, the patient was described as confused, refusing to make eye contact and combative towards the medical staff, requiring high doses of sedative medications to ensure patient and staff safety. Initial vital signs reveal an afebrile patient with a normal blood pressure and tachycardia at 125 beats per minute. Physical examination revealed an agitated, restless and confused patient asking repetitive questions but without focal neurological deficits. Cardiac examination revealed tachycardia, without additional murmurs, rubs or gallops. Initial laboratory evaluation revealed a normal complete blood count and basic metabolic panel, with initial troponin less than 0.01 ng/mL. Initial ECG (figure 1) was concerning for ST elevations in the inferior and lateral leads. Radiographic findings included a normal head CT without evidence of bleed or mass effect. The interventional cardiologist was notified of the ECG findings, after which patient was given a full dose of aspirin and intravenous heparin. Cardiac catheterization revealed moderate ostial left anterior descending artery lesion (figure 2), with otherwise unremarkable coronary vasculature. Repeat troponin was elevated and reached a value of 1.2 ng/mL. Echocardiography was pursued, revealing a mildly depressed left ventricular ejection fraction of 50%–55%, without regional wall motion abnormalities, valvular disease or pericardial effusion. Lumbar puncture was finally performed given persistently altered mental status, which was significant for an elevated opening pressure of 32 cm of water and subsequent isolation of Cryptococcus neoformans antigen by lateral flow immunoassay. The diagnosis of cryptococcal meningitis was confirmed with growth of C. neoformans from patient’s cerebrospinal fluid (figure 3).

Figure 1.

Initial ECG revealing ST elevations in the inferior and lateral leads.

Figure 2.

Coronary angiography revealing moderate ostial left anterior descending artery stenosis.

Figure 3.

Gram-stained yeast from cerebrospinal fluid direct smear showing budding yeast cells surrounded by a capsule, diagnostic for Cryptococcus neoformans. (A) Colony growth on sheep blood agar showing glistening opaque apparance within 24–48hrs. (B) Gram stained yeast from CSF direct smear showing budding yeast cells surrounded by a capsule.

Outcome and follow-up

Treatment was begun with intravenous amphotericin B, flucytosine and serial lumbar punctures, resulting in rapid improvement in mental status. Patient’s cardiac biomarkers and ECG subsequently returned to baseline. Follow-up postdischarge revealed a neurologically intact patient, with no evidence of residual neurological deficits or alteration in cognition.

Discussion

ECG changes related to central nervous system events have been well documented, dating as far back as 1938.¹ Most commonly occurring with subarachnoid haemorrhage, ECG changes have been reported in the setting of a variety of neurological processes, including ischaemic stroke, intracranial tumours, traumatic brain injury and meningitis.² The most common ECG changes may include repolarisation abnormalities such as T wave inversion and QTc prolongation.³ Less commonly, diffuse ST elevation may occur in the absence of pericardial inflammation.³ Cardiac arrhythmias have also been reported, including bradyarrhythmias,^{4 5} atrioventricular block,⁶ sinus tachycardia and ventricular tachycardia.³ The aetiology of these ECG changes has been difficult to establish, especially given the wide variety in ECG morphologies. Earlier theories attempted to relate ECG changes to elevated intracranial pressure,⁴ but subsequent case series failed to show a correlation between ECG changes and cerebrospinal fluid pressures.^{4 7} Similarly, no association has been established between ECG changes and troponin elevation.⁸ The most prevalent theory currently described relates ECG changes to a surge in catecholamine release by the sympathetic nervous system,³ causing a phenomenon referred to as neurogenic stunned myocardium.⁹ The apical and basal portions of the myocardium are particularly vulnerable to excess catecholamines, owing to higher concentration of adrenoreceptors and greater density of sympathetic nerves in those regions.⁹ Catecholamines are released from local nerve endings in the heart,¹⁰ which may explain the presence of ST elevations in the inferior and lateral segments of the ECG. Animals infused with norepinephrine have demonstrated a similar pattern of subendocardial myocardial lesions and contraction band necrosis as patients with subarachnoid haemorrhage, supporting the theory of local myocardial catecholamine surge¹¹ and elevation in cardiac biomarkers.¹² Troponin elevations have also been described in the setting of neurological insults, including subarachnoid haemorrhage, stroke, head injury, space-occupying lesion and seizures.^{8 12} Differentiating ischaemic from neurogenic ECG changes may be difficult, especially in the early phase of injury. However, lack of evolving T wave changes and Q waves supports a neurological aetiology.¹³

This case report highlights the importance of maintaining a high index of suspicion for a neurological process in the setting of elevated cardiac biomarkers and ECG changes, especially in the presence of altered sensorium, focal neurological findings or abnormal brain imaging. This case further highlights the importance of a thorough physical examination to achieve the correct diagnosis.

Learning points.

• Acute neurological events commonly cause transient ECG changes and may elevate cardiac biomarkers.

• Cryptococcal meningitis has never previously been linked to ECG changes or elevated cardiac biomarkers.

• Neurological causes of ECG changes and elevated cardiac biomarkers should be pursued early, especially in the setting of altered sensorium, to avoid permanent neurological impairment and to avoid potentially harmful interventions.

• A thorough physical examination is fundamental early on to achieve the right diagnosis.