Authors: Esraa Alsaadi, Saja Karaja, William Borghol, Marah Abou Hala, Anas Jouhar
Categories: Case Report, Meningoencephalitis, Tuberculosis, Seizures, Herpes simplex virus (HSV), Case report
Source: Journal of Medical Case Reports
Authors: Esraa Alsaadi, Saja Karaja, William Borghol, Marah Abou Hala, Anas Jouhar
Herpes simplex encephalitis is the most common form of encephalitis, while tuberculous meningitis is a rare condition accounting for less than 1% of all tuberculosis cases. Since the symptoms are similar in both diseases, differentiating between them is a clinical challenge, even after performing cerebrospinal fluid analysis, as the final diagnosis remains based on the specific investigations that were unusually positive for both diseases in our patient, which have not been reported previously, making this case the first in medical literature on this subject.
A 45-year-old Syrian male patient presented with fever, headache, and generalized seizures with decreased cognitive function. He was referred to the emergency department, where radiological investigations and other tests revealed concurrent infection with herpes simplex encephalitis and tuberculous meningitis with tuberculous brain abscesses confirming involvement of the brain parenchyma by both infections. The patient was treated with intravenous acyclovir, antituberculosis regimen, and anticonvulsants, resulting in notable clinical improvement. However, he experienced a tonic–clonic seizure, complicated by aspiration pneumonia, and later developed acute respiratory failure and succumbed to his condition on the 21st day of hospitalization.
Although the presentations of herpes simplex encephalitis and tuberculous meningitis are similar, clinicians should not exclude one diagnosis when the other is confirmed, as both conditions can coexist in the same patient, as our case report demonstrates.
Herpes simplex encephalitis (HSE) represents the most prevalent cause of acute encephalitis, with the varicella-zoster virus (VZV) following closely behind [1, 2]. The annual incidence of HSE is estimated to range from 1 to 2.5 cases per million individuals, and the mortality rate is significantly elevated in untreated cases, with figures reaching approximately 70%. Fortunately, this mortality rate can be reduced to between 11% and 19% with the initiation of prompt antiviral therapy. Nonetheless, even among patients who receive treatment with acyclovir, mortality rates can still be as high as 30%, accompanied by substantial morbidity [1, 2]. Tuberculous meningitis (TBM), a severe form of tuberculosis (TB), accounts for roughly 1% of all TB infections [3]. Patients diagnosed with TBM commonly present with classical symptoms, including headache, fever, and neck stiffness. A hallmark pathological feature of TBM is the presence of thick exudates, particularly prominent in the basilar meninges, which can complicate diagnostic efforts due to the disease’s relative rarity and diverse clinical manifestations [2, 4, 5]. Furthermore, tuberculous brain abscesses, although rare, represent a distinct manifestation of central nervous system (CNS) TB, characterized by encapsulated pus collections containing viable tubercular bacilli, yet lacking evidence of tuberculous granuloma [6]. These brain abscesses are observed in approximately 4–8% of immunocompetent patients with CNS TB infections [7]. Differentiating between encephalitis caused by TB and that induced by herpes simplex virus poses significant challenges, particularly given the overlapping clinical and laboratory characteristics, especially in cerebrospinal fluid (CSF) profiles. This situation underscores the necessity for accurate and refined diagnostic methods [4, 5, 8]. In this report, we present the first known case of a male patient exhibiting concurrent infections in the brain involving both tuberculosis and herpes simplex virus.
This is a case report of a 45-year-old Syrian male with a medical history significant for poorly controlled hypertension and type 2 diabetes mellitus, both previously managed with oral pharmacotherapy of unspecified agents, which he independently discontinued. The patient had no history of smoking, alcohol consumption, or recreational drug use. He had a notable familial predisposition to hypertension, affecting both his father and brother. He presented to the emergency department with a 4-week history of persistent fever, headache, and progressively worsening generalized fatigue and malaise. These symptoms remained refractory to prior empiric treatment, including a 1-week course of ceftriaxone (1 g twice daily) and acetaminophen (1 g three times daily), without clinical improvement. The patient experienced four generalized tonic–clonic seizures, each lasting over 5 minutes, with an interval of about 3 minutes between episode. Upon initial examination, he was found to be unconscious, exhibiting a Glasgow Coma Scale (GCS) score of 3. The patient’s vital signs at presentation were notable, with a blood pressure of 160/110 mmHg, tachycardia with a heart rate of 107 beats per minute, a respiratory rate of 17 breaths per minute, a low-grade fever of 37.9 °C, and an oxygen saturation of 92% on room air. Capillary blood glucose was markedly elevated at 270 mg/dL. Owing to his critical condition, the patient was urgently transferred to the intensive care unit (ICU) and subsequently intubated for airway protection. Further neurological assessment revealed dilated pupils, hypotonia, weak deep tendon reflexes, and an extensor plantar response, with no evidence of neck stiffness. Aside from these findings, the general clinical examination did not reveal any additional abnormalities. The differential diagnoses considered in this case included viral meningoencephalitis, subacute meningitis, and brain abscess. Despite the administration of intravenous anticonvulsants such as diazepam, phenytoin, and valproic acid infusions, the seizures persisted until general anesthesia was achieved with an infusion of midazolam. Initial laboratory investigations indicated elevated C-reactive protein (CRP) levels, while metabolic panels remained within normal limits. A non-contrast computed tomography (CT) scan of the brain yielded no significant abnormalities (Fig. 1). CSF analysis revealed turbidity, an elevated total cell count with predominant lymphocytic pleocytosis, increased protein levels, and decreased glucose levels.Fig. 1Computed tomography of the brain showing no significant abnormalities
Treatment was initiated with antibiotics [vancomycin (1 g × 2/day), ceftriaxone (2 g × 2/day), and antiviral acyclovir (750 mg × 3/day)], after which extubation occurred 48 hours post-administration of midazolam, resulting in the cessation of seizures and a noted improvement in the patient’s level of consciousness (the patient exhibited drowsiness and partial responsiveness, with spontaneous movement observed in all four limbs. Plantar reflexes were flexor bilaterally). Polymerase chain reaction (PCR) analysis of CSF revealed a positive detection for herpes simplex virus (HSV) DNA type 1. Electroencephalography (EEG) was not conducted owing to the absence of an EEG machine in the intensive care unit of our hospital. Furthermore, investigations were undertaken to evaluate for subacute meningitis, including fungal, tuberculous, and brucellosis meningitis in the CSF. Subsequent imaging through contrast-enhanced magnetic resonance imaging (MRI) of the brain revealed hyperintensities in the bilateral cerebellum, as well as in the superficial and deep white matter and basal ganglia. Notably, the imaging findings demonstrated ring enhancement indicative of multiple brain abscesses, accompanied by basal meningeal enhancement (Fig. 2).Fig. 2Contrast-enhanced magnetic resonance imaging of the brain demonstrating hyperintensities in both superficial and deep white matter, as well as the bilateral basal ganglia (a, b, c) in the fluid-attenuated inversion recovery sequence. The images also reveal ring enhancement within the superficial and deep white matter and the basal ganglia (d, e), along with ring enhancement observed in the left (f) and right (g) cerebellum. In addition, basal meningeal enhancement is noted in the T1-weighted contrast sequence (h, i)
Direct examination for Koch’s bacillus, fungal elements, and Cryptococcus antigen yielded negative results; however, GeneXpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay performed on CSF was positive for Mycobacterium tuberculosis, with no rifampicin resistance detected. In response, antitubercular therapy (isoniazid 300 mg/day, rifampicin 600 mg/day, pyrazinamide 2000 mg/day, and ethambutol 1200 mg/day), including dexamethasone, was promptly initiated, resulting in notable clinical improvement following a negative fungal culture outcome. Nevertheless, on the 15th day of hospitalization, the patient experienced a tonic–clonic seizure, complicated by aspiration pneumonia, necessitating reintubation and management with levetiracetam and thiopental infusions. Despite achieving control of the seizure activity (no myoclonic jerks, pupils were reactive and symmetrical, and plantar reflexes were flexor), there was no corresponding improvement in the level of consciousness. A repeat CT scan of the brain on the 15th day of hospitalization revealed no significant changes (Fig. 3).Fig. 3Computed tomography of the brain did not show any changes
Further microbiological evaluation of sputum cultures identified the growth of Streptococcus, which demonstrated sensitivity to colistin, leading to an adjustment of the therapeutic regimen. Despite these interventions, the patient’s condition continued to deteriorate, culminating in multi-organ failure and cardiogenic shock, which ultimately resulted in mortality on the 21st day of hospitalization. The repeat CT scan of the brain disclosed grossly dilated ventricles (Fig. 4), and owing to persistent hemodynamic instability, neurosurgical intervention was deemed impractical. Ultimately, the patient developed acute respiratory failure and succumbed to his condition (Fig. 5 shows the graphical timeline).Fig. 4Computed tomography of the brain showing grossly dilated ventricle (a, b)
Encephalitis is a serious neurological disorder characterized by inflammation within the parenchyma of the CNS, resulting from the direct or indirect effects of various pathogenic factors on the brain [1, 2]. Among the different types of encephalitis, HSE is the most prevalent form of acute encephalitis, with an annual incidence of approximately 1–2.5 cases per million individuals. HSE is particularly life-threatening, as untreated cases can exhibit mortality rates as high as 70%. However, with timely and appropriate treatment, this rate can significantly decrease to between 11% and 19% [1, 2, 9]. In contrast, TBM is relatively uncommon, despite the high prevalence of TB in developing countries, affecting about 1% of all TB cases. The rarity of TBM presents a diagnostic challenge, which is further complicated when attempting to distinguish it from HSE owing to overlapping laboratory and clinical features associated with both conditions [2, 6]. This complexity highlights the importance of precise diagnostic measures to ensure proper identification and treatment for patients experiencing these severe neurological disorders. HSE is characterized by acute symptoms such as headache, fever, and nausea, and it may progress to more severe neurological manifestations such as seizures and changes in cognition and personality [9]. In contrast, the manifestations of TBM include the traditional signs and symptoms of meningitis in general, such as headache, fever, and neck rigidity, noting that the sign of neck rigidity may be absent in the early stages. In advanced and untreated stages, a patient with TBM may experience a significant deterioration in consciousness with a GCS of 10 or less, seizures, hemiparesis, and involvement of cranial nerves [4, 5]. Returning to our patient’s symptoms, we found that he suffered from most of these symptoms, including fever, headache, and prolonged generalized seizures, along with severe cognitive deterioration, with a GCS of 3 before seizure treatment, which rose to a GCS of 8 after seizure treatment with appropriate anticonvulsants. CSF analysis is important in diagnosing both diseases, as both share many CSF findings, such as pleocytosis with lymphocytic predominance, elevated protein levels, and a slight difference in glucose levels. The glucose level significantly decreases in TBM, while it remains normal in HSE, with a potential increase in red blood cells (RBCs) due to hemorrhagic necrosis in HSE. Upon conducting a CSF analysis for our patient, we found similar results in terms of elevated cell count with lymphocytic predominance, elevated protein levels, and low glucose levels without a significant increase in RBCs. Neuroimaging is also an important adjunct in diagnosis. Although CT is typically the first radiological investigation, it often does not show significant changes, especially in the early stages of both diseases. MRI, however, is a more accurate and sensitive imaging modality. MRI with contrast typically shows hydrocephalus with meningeal enhancement and basal exudate in TBM and may reveal tuberculomas or infarctions. In HSE, the MRI shows hyperintense lesions reflecting white matter changes. These findings closely resemble the neuroimaging results obtained for our patient, characterized by meningeal enhancement at basal meninges, white matter lesions (hyperintense lesions), and ring enhancement suggesting a tuberculous brain abscess, which is a rare complication of CNS TB. The definitive diagnosis for HSE is made using PCR, while GeneXpert testing serves as the definitive diagnosis for TBM. The Xpert MTB/RIF assay is a rapid, automated system based on PCR technology. It is used to detect Mycobacterium tuberculosis and rifampicin resistance. This test provides accurate results within just 2 hours. Studies have shown that its sensitivity for diagnosing TBM ranges from 50% to 86%, while its specificity ranges from 90% to 98%. The diagnostic accuracy can be influenced by factors such as CSF sample volume and whether centrifugation is performed prior to testing [10, 11]. Notably, in our case, both diagnostic tests were positive. Treatment is primarily based on the administration of intravenous acyclovir for HSE and conventional antituberculous therapy with corticosteroids for TBM to reduce the risk of persistent neurological disorders and mortality rates; both treatments were administered to our patient [5, 6, 9]. According to our knowledge and literature review, we found that our case is the first documented occurrence of simultaneous TBM and HSE in medical literature. We found only one case report published in 2020 describing a double infection of the brain with tuberculosis and herpes zoster [6]. In our case, TBM was accompanied by HSE, making this report the first of its kind. Moreover, what makes this case even more unique is the formation of a tuberculous abscess as a complication of TBM, indicating that both infections affected the brain parenchyma of the patient.Fig. 5Timeline depicting rapid clinical Admission with initial intubation and therapy on Day 1; improvement with extubation on Day 3; initiation of anti-tubercular treatment on Day 5;deterioration with seizures on Day 15; and fatal multi-organ failure by Day 21
In light of this case, we contend that a clinical suspicion of either TBM or HSE necessitates immediate investigation and should not lead to delays in treatment. Moreover, upon confirming one diagnosis, it is essential to continue further investigations until the alternative diagnosis is either confirmed or ruled out, particularly in immunosuppressed individuals. Comprehensive exploration of all differential diagnoses for acute and subacute meningitis is imperative in similar cases to ensure that no potential etiologies are overlooked. Considering the significant morbidity and mortality associated with these infections, early diagnosis and prompt initiation of treatment are crucial for enhancing patient outcomes. Conversely, delays in seeking medical attention are associated with poorer prognoses.