A 53-year-old female recently received a diagnosis of Glioblastoma Multiform and underwent surgical resection twice, first in June 2022 and then again in August 2022, due to disease relapse. Her treatment plan included sessions of radiation therapy, Dexamethasone, and Temozolomide. Her post-operative recovery was uneventful, but her family brought her to the emergency department 1 month after her second surgery due to fever, acute confusion, blurry vision, right-sided weakness, and an inability to walk. During her hospitalization, her condition deteriorated further. She experienced seizures that necessitated sedation and intubation, and subsequently, she was initiated on high-dose antimicrobials due to suspicion of post-neurosurgical meningitis.

Upon admission, her initial investigations were unremarkable except for hyponatremia, with sodium levels measuring 126 mmol. Additionally, a CT scan of her brain revealed post-surgical changes without any other concerning abnormalities. In response to her seizure episode, an electroencephalogram was performed, which identified moderate encephalopathy and disturbances in cerebral activity in the right temporoparietal region, accompanied by active epileptic discharges. Despite medical intervention, the patient’s condition persisted, and a follow-up electroencephalogram showed refractory seizure activity, leading to several antiepileptic medications. Subsequent magnetic resonance imaging (MRI) of her brain indicated increased hyperintensity and diffusion restriction signals in the right temporal lobe, right mesial temporal structure, insular cortex, inferior frontal lobe, and cingulate gyrus, raising suspicions of viral encephalitis (Fig. 1). The results of the cerebrospinal fluid analysis after 3 days of antimicrobial treatment for meningitis are shown in Table 1.

Upon analyzing the patient's brain MRI, increased hyperintensity and diffusion restriction signals were observed in several areas, including the right temporal lobe, right mesial temporal structure, insular cortex, inferior frontal lobe, and cingulate gyrus, leading to suspicions of viral encephalitis

Microbiological studies on this CSF, including common bacterial and viral pathogens causing meningitis, were positive for Herpes simplex 1 PCR (Fig. 2).

Microbiological results of the CSF sample, including common bacterial and viral pathogens causing meningitis, were positive for Herpes simplex 1

Acyclovir at a dosage of 10 mg per kg every 8 hours was added to her antimicrobial regimen. The patient’s level of consciousness remains depressed, and she continues to run a low-grade fever despite receiving antiviral and antibacterial therapy. There has been no improvement in her level of consciousness during this period. A follow-up magnetic resonance imaging (MRI) was conducted after 10 days of acyclovir treatment; unfortunately, her consciousness level did not improve. The MRI report indicated the progression of right hemispheric encephalitis with features suggestive of associated meningitis. The distribution of parenchymal injury is consistent with herpetic encephalitis, along with the progression of high-grade glioma and persistent entrapment of the left temporal horn (Fig. 3).

This MRI figure shows that the distribution of parenchymal injury is consistent with herpetic encephalitis, along with the progression of high-grade glioma and persistent entrapment of the left temporal horn

As a result of the MRI findings, the case was reassessed by a multidisciplinary team, which included experts from neurology, neurosurgery, infectious diseases, and oncology. The consensus was to perform a repeat lumbar puncture to assess for any neurovascular complications related to HSV encephalitis, especially since the patient’s level of consciousness did not improve. The repeated cerebrospinal fluid (CSF) analysis showed no pleocytosis, and the repeated Herpes simplex PCR was negative. Metagenomics testing was conducted to assess for possible mutant HSV, considering the reported progression on her follow-up MRI. Her antiviral agents were modified to Foscarnet while awaiting the results of the metagenomics test. She completed more than 14 days of Foscarnet treatment and 21 days of acyclovir.

Metagenomics analysis revealed the presence of Para-echovirus (with a coverage of 10.6%), along with other infective agents, including Raistonia pickettii, Burkholderia cepcia complex, Elizabethkingia anopheles, and Pseudomonas sstatzeri (Table 1). The patient was already receiving antibacterial treatment that covered all these pathogens, but unfortunately, her level of consciousness did not improve. Subsequent follow-up MRI scans showed a worsening of FLAIR imaging hyperintensity in the right temporal, parietal, and frontal lobes, suggesting herpetic encephalitis. Signs of laminar necrosis along the cortex of the temporal and parietal lobes were also observed, along with an increase in the dimensions of the recurrent necrotic mass (GBM) and worsening surrounding vasogenic edema and mass effect. These findings indicate an advanced stage of HSV encephalitis and a recurrence of her underlying malignancy. Despite ongoing medical care, the patient’s clinical status did not improve, and her treating oncologist eventually gave her a poor prognosis. Consequently, she was transferred back to her home country.

Parechovirus can cause infections in humans, particularly in infants and young children. It was initially identified in the 1950s, but it was not until the 1990s that it gained recognition as a significant cause of neonatal sepsis and central nervous system (CNS) infections. Subsequent studies have demonstrated that parechoviruses can lead to a wide range of clinical conditions, spanning from mild respiratory infections to severe CNS infections such as meningitis or encephalitis. While parechovirus infections are generally self-limiting and mild, severe cases can result in long-term complications or even death. Consequently, understanding the patterns of parechovirus transmission and the clinical features of infection is crucial for effective diagnosis and treatment [7,8,9,10]. Diagnosis of PeV in pediatrics typically achieved with nucleic acid amplification testing in CSF and stool samples. Specific platforms for rapid molecular diagnostics include PeV in meningitis multiplex polymerase chain reactions, such as the total nucleic acid isolation kit (Roche Diagnostics, Mannheim, Germany) [1].

One study examined the prevalence of Parechovirus in adults in the Netherlands. Out of more than 10,000 clinical samples, approximately 11 samples tested positive for PeV by PCR. Among these patients, 8 were found to be immunocompromised and developed disseminated disease with infections lasting for more than 3 months. This indicates that immunocompromised individuals, whether due to an underlying medical condition or immunosuppressive therapy, are at a higher risk of developing a more severe form of Parechovirus infection and experiencing prolonged shedding of the virus [7].

In 2018, a noteworthy case of Human Parechovirus (PeVs) encephalitis in adults was reported, featuring a complex presentation of refractory status epilepticus [11]. As far as our current knowledge goes, there have been no documented cases of Human Parechovirus (PeVs) encephalitis among adults in Saudi Arabia. The treatment for Parechovirus in pediatric and adult patients is primarily supportive management, as there are no available antiviral therapies.