A 26-year-old female undergraduate presented to critical care medicine with a 29-day history of fever accompanied by mental and behavioral disorders. The body temperature rose, thus leading to a coma and intermittent convulsions during the last 28 days. Also, there was no significant personal history.
Before admission, she had received treatment in two hospitals. Her CSF sample was colorless, and routine analysis indicated total cells are 2/mm3, with 50% leukocytes, total protein and glucose levels were 0.341 g/L and 2.8 mmol/L, and CSF cultures were negative for bacterial and fungal organisms. Normal findings were obtained from the autoimmune encephalitis examination and cranial CT. EEG expressed irregular activity with epileptiform discharge in the anterior temporal and bilateral frontal areas. HHV-7 DNA was detected in the mNGS of CSF, she was diagnosed with meningitis and/or encephalitis in other hospitals, and then acyclovir was added. Sputum cultures were Acinetobacter baumannii and Burkholderia cepacia. After an active medical intervention, the body temperature was lower than the initial state, but progressive deterioration of the level of consciousness was uncontrolled and then led to a requirement for mechanical ventilation.
On admission, a physical examination revealed that she was unconscious and underwent mechanical ventilation via tracheostomy. Also, she had a fever, lung crackles, neck stiffness, and unconscious limb convulsions. A lumbar puncture was performed, and CSF pressure was 252 mm H2O. The patient was empirically treated with ganciclovir, meropenem, tigecycline, micafungin, corticoids, glycerol fructose, midazolam, levetiracetam, topiramate, perampanel, clonazepam, phenobarbital. On the third evolution day, mechanical ventilation mode was converted to oxygen inhalation mode, and her condition improved.
Furthermore, anti-ANA-IgG in serum was mildly positive, but a wide spectrum of antibodies (anti-nRNP, anti-Sm, anti-SS-A, anti-Ro-52, anti-SS-B, anti-Scl-70, anti-Jo-1, anti-ACA, anti-AnuA, anti-AHA, anti-ARPA, anti-AMA-M2, anti-PCNA, anti-PM-Scl100, anti-HHV-1-IgG, anti-HHV-2-IgG, anti-Toxo-IgM, anti-CMV-IgM, anti-Rubella-IgM) in serum were normal. To check the brain function, unfortunately, her cranial CT was negative, MRI was not performed because she had been wearing a dental appliance. The second mNGS of CSF indicated Enterococcus faecium and anti-Aspergillus-IgG in the blood were positive. Thus, we added contezolid and voriconazole to alleviate the previous treatment. On the 18th day of admission, her body temperature was up again, combined with primary epilepsy, lumbar puncture was performed, and CSF pressure was 210 mmH2O, but the CSF cultures and CSF mNGS were negative, then the blood antibodies (anti-HHV-1-IgG, anti-HHV-2-IgG, anti-Toxo-IgG, anti-CMV-IgG, anti-Rubella-IgG) was normal. With the treatment adjustment, the body temperature returned to normal, and the Glasgow Coma Score (GCS) was 15 points (E4, V5, M6). However, her memory ability was damaged, and she was transferred to a rehabilitation hospital for better treatment. Suddenly her body temperature rose again, accompanied by generalized epilepsy, then returned to our hospital the following day. The 4th CSF mNGS indicated HHV-1, EEG expressed irregular activity with a slow wave in the temporal and bilateral frontal areas, urine culture was Klebsiella pneumoniae, the patient was treated with contezolid, corticoids, levetiracetam, topiramate, Perampanel, Clonazepam, amika, ganciclovir. As time passed, her memory ability improved quickly, and she could eat by herself. Whereas she often felt choking when she ate chewy food, but the result of the gastroscopy indicated normal, to some extent implying she had a psychological disorder. Finally, with the help of humanistic concern and antiepileptic drugs, the patient recovered completely after two months.
The diagnostic evaluation of HHV-7 encephalitis needs to be guided by epidemiologic laboratory tests, imaging examinations, and clinical proof. The information is as follows. For the first line of investigation, HHV-7 DNA was detected in CSF, but there was no abnormal personal history (information provided by her relatives). For the second line of investigation, on day 1, the respiratory pathogen spectrum (Legionella, Mycoplasma pneumonia, Chlamydia pneumonia, Respiratory syncytial virus, Adenovirus, Influenza virus A, Parainfluenza virus, Coronavirus) were negative. However, Influenza-virus-B-IgM in serum was positive. Hepatitis viruses (Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis E), Treponema pallidum, and Human immunodeficiency virus were negative, and sputum cultures were Acinetobacter baumannii and Burkholderia cepacia, we added antibiotics. On day 3, tubercle bacillus was negative, and bacterial cultures in the blood and CSF were negative. On day 7, a wide spectrum of blood antibodies (anti-nRNP, anti-Sm, anti-SS-A, anti-Ro-52, anti-SS-B, anti-Scl-70, anti-Jo-1, anti-ACA, anti-AnuA, anti-AHA, anti-ARPA, anti-AMA-M2, anti-PCNA, anti-PM-Scl100) were negative, anti-ANA-IgG was mildly positive, its titers were more than 1:100. However, these indications had no high specificity for the diagnostic of the disease. On day 8, Neisseria meningitides and Cryptococcal neoformans(serum and CSF) were also negative, then a wide spectrum of CSF antibodies (anti-HHV-1-IgG, anti-HHV-2-IgG, anti-Toxo-IgM, anti-CMV-IgM, anti-Rubella-IgM) was negative. Third line investigation, the cranial CT was negative, but the MRI was not performed because the dental appliance affected the result. Finally, on day 8, Enterococcus faecium was detected in the mNGS CSF, and we added contezolid combined with clinical proof. Then the mNGS of CSF indicated HHV-1 on day 33. The patient was treated with ganciclovir for about 6 weeks intermittently.