Herpes simplex virus type 1 (HSV-1) is the most common cause of life-threatening sporadic encephalitis globally, with an annual incidence of 2 to 4 cases per 1,000,000 persons [1,2]. It has a bimodal distribution, commonly affecting patients younger than 20 years due to a primary infection and older than 50 years due to reactivation of a latent infection, with both sexes equally affected [3,4]. HSV-1 encephalitis (HSE) usually presents acutely, but a few cases with subacute onset have also been reported [5]. A prodromal phase of fever, malaise, headache, and nausea often precedes more severe neurologic symptoms including altered mental status, seizures, and focal neurologic deficits [3]. Early recognition and treatment with acyclovir is of critical importance, as untreated HSE has a mortality rate of 70% [6]. To the best of our knowledge, only a few cases of HSE with subacute onset have been reported, and even fewer have described an initial manifestation of autonomic nervous system symptoms. Herein, we present a case of subacute HSE admitted to the emergency department because of an episode of syncope with concomitant bradycardia on electrocardiography performed at admission.

An 82-year-old man with a history of ischemic stroke presented to the emergency department because of an episode of syncope with secondary nasal trauma. Relevant history included a few presyncope episodes that had occurred during the prior week. On examination, the patient’s vital signs were as follows: blood pressure, 129/61 mmHg; heart rate, 45 beats/min; oxygen saturation, 96%; and body temperature, 36.0 ºC. Upon admission, there was no evidence of focal neurologic deficit, and the patient was fully place-person-time oriented. He underwent brain computed tomography (CT) without any evidence of pathology (Figure 1A). All routine investigations including complete blood count (white blood cell, 6,900/μL; normal range, 4,000–10,000/μL) and blood chemistry (C-reactive protein, 0.4 mg/dL; normal range, <0.5 mg/dL) were normal. Electrocardiogram (ECG) revealed sinus bradycardia (heart rate, 45 beats/min), echocardiogram was performed (left ventricular ejection fraction, 55%–60%; tricuspid regurgitation ++, mitral regurgitation ++), and the patient was immediately admitted to the cardiac intensive care unit for pacemaker implantation. On the first day of hospitalization, the patient was febrile (38.5 ºC). Although bradycardia was not reversed with the administration of isoprenaline, pacemaker implantation was postponed due to fever. Because of desaturation and fever, the patient underwent neurological assessment (Glasgow Coma Scale [GCS] 15/15, no focal neurologic deficits) and received antibiotic therapy with ceftriaxone because lower respiratory tract infection was suspected. On hospitalization day 4, the patient was still febrile and unresponsive to antibiotic therapy. Neurological reassessment revealed subtle lip twitching, a muscle strength of 4+/5 of the left upper limb according to the manual muscle testing scale, and time disorientation. The patient was transferred to the neurology department. Encephalogram during wakefulness was performed, showing diffuse slowing of background activity and periodic lateralized epileptiform discharges consisting of sharp waves and slow waves over the right temporal/parietal lobe (Figure 2). The patient underwent immediate repetitive brain CT, which showed gray and white matter abnormalities in the right temporal lobe (Figure 1B). Because of the focal neurologic signs and the findings of both electroencephalogram and CT, lumbar puncture was subsequently performed. Cerebrospinal fluid (CSF) analysis revealed a protein level of 74 mg/dL, a glucose level of 60 mg/dL (serum level, 115 mg/dL), and a total cell count of 78 cells/μL (80% lymphocytes); cultures were sterile. Cytological analysis of the fluid was negative for malignancy, and the cell morphology was consistent with an inflammatory process (probable chronic viral infection). CSF was sent for polymerase chain reaction for herpes simplex virus (HSV) and was found to be positive for HSV-1 DNA. As soon as the HSV infection was suspected, the patient received treatment with acyclovir for viral infection and levetiracetam as an anticonvulsant medication. After levetiracetam administration, bradycardia was gradually reversed; however, despite acyclovir administration, clinical status deteriorated rapidly. On day 6, the patient was alert, able to execute simple commands, and showed left-sided mild VII cranial nerve palsy of central origin, left-sided hemianopsia, left-sided lower limb monoparesis, left-sided plantar extensor reflex, and dysphagia. Brain magnetic resonance imaging with intravenous administration of gadolinium showed a non-enhancing, increased T2-weighted signal intensity lesion (evident in the T2-weighted modalities with and without CSF-signal suppression) in the right temporal/parietal lobe (Figure 3). On day 7, the patient was comatose (GCS 8/15; E=2, M=5, V=1). Three days later, he passed away.

Ethical approval was obtained from the Scientific Council of Army Equity Fund Hospital (No. 6080/12-06-2025), in accordance with the Declaration of Helsinki. Written informed consent was obtained from the patient’s relatives for publication of this case report and any accompanying images.

HSE is associated with significant morbidity and mortality. Even with early diagnosis and treatment, mortality is estimated to be between 20% and 30% [7-9]. HSE clinical features typically include a prodromal phase with nonspecific symptoms like fever, headache, malaise, nausea, and vomiting, followed by acute or subacute encephalopathy with focal neurologic deficits, seizures, and altered mental status or coma [10]. In our case, the patient presented to the emergency department because of an episode of syncope. Before the patient’s admission to the neurology department, he underwent extensive cardiological evaluation in the cardiac intensive care unit, with 24-hour monitoring of vital signs and ECG. Since no other pathology except sinus bradycardia was found, pacemaker implantation was recommended. His relatives mentioned some presyncope episodes during the week preceding his admission to the hospital, while episodes of short-term disorientation during the past month were attributed to the patient’s age. Nevertheless, there were no other symptoms to raise suspicion of encephalitis. Only after day 4 of hospitalization did neurological reassessment reveal focal neurologic signs, necessitating transfer to the neurology department.

To the best of our knowledge, HSE with subacute progression has rarely been described in the literature, and only three cases exhibited syncope as the initial clinical manifestation [4,11]. The etiology of sinus node dysfunction in the context of HSE is not fully understood but seems to be the result of central nervous system (CNS) dysfunction rather than primary cardiac injury [11]. Although bradycardia is often attributed to cardiac arrhythmia, sick sinus syndrome, or obstructive cardiac lesions, this case highlights the importance of considering other causes of syncope, including metabolic or CNS-related origins, even when cardiac abnormalities are present. CNS pathologies leading to bradycardia and syncope as the sole manifestation include epilepsy, cardiovascular accident, space-occupying lesions, raised intracranial pressure, and head trauma [12]. The central neurocircuitry controlling the heart rate is very complex, involving many different regions such as the brainstem, thalami, hypothalamus, amygdala, and insular cortices. Whereas the effects of cardiovascular disease on the nervous system have been widely studied, our understanding of the effects of neurological disorders on the cardiovascular system is relatively recent [13,14]. In our case, the patient presented with subacute-onset HSE and dysautonomia as the initial manifestation. The heart-brain axis most probably induced bradycardia in the context of seizure activity. Bradycardia was reversed only after levetiracetam administration; it did not respond to isoprenaline. Increased heart rate has been reported to occur in 64% to 100% of temporal lobe seizures, while bradycardia has been reported to occur in only a small percentage of cases and has been described as ictal bradycardia syndrome [15-17]. The exact pathophysiology leading to ictal bradycardia syndrome is not fully understood. Potential mechanisms include increased parasympathetic activity or disrupted sympathetic activity caused by ictal activity. Ictal discharges, especially those of the temporal lobe origin, can spread to the brain regions involved in autonomic control, influencing the parasympathetic and sympathetic outputs to the heart. The insular cortex, amygdala, anterior cingulate cortex, hypothalamus, and brainstem nuclei are part of the above-described “brain-heart axis” [13]. A previous report described a case of ictal asystole secondary to suspected HSE [18]. Our case highlights the importance of determining the underlying cause of syncope according to the published guidelines of the European Society of Cardiology [19]. Despite the normal neurologic examination and initial brain imaging, a broader investigation of the patient, including neurological reassessment and timely lumbar puncture, as soon as bradycardia did not respond to sympathomimetic drug administration, could have led to earlier HSE diagnosis. It should be noted that, despite the response to anticonvulsant therapy, the patient’s overall condition deteriorated rapidly. The key determinant of clinical response and reduction of morbidity in HSE is the timely administration of antiviral medication. Anticonvulsants have been proven beneficial when administered adjunctively to ameliorate epileptic manifestations [20]. Prompt and effective treatment with antiviral agents is crucial for achieving favorable outcomes.

This case highlights the importance of early recognition of the atypical subacute course of HSE and its possible presentation in the emergency department as an acute cardiologic event. Early diagnosis is crucial, as prompt initiation of antiviral therapy may lead to neurological recovery, while treatment delays often lead to mortality.