A 39-year-old male patient was admitted to the Department of Emergency Medicine, the Second Hospital of Shanxi Medical University on May 12th, 2020, due to chief complaints of fever for more than 10 days and disturbance of consciousness accompanied by convulsions for 2 days.
The patient developed intermittent fever before May 1st, 2020 (the specific time was unknown), the highest temperature was ~37.5 C, accompanied by chest tightness. The conditions were unresponsive to self-administered oral anti-inflammatory drugs. Diarrhea occurred on May 7th, and the conditions gradually deteriorated. On May 10th, the temperature elevated to 39 C, accompanied by headache, confusion, and inability to answer questions correctly.
The patient had a history of intermittent "low fever" for 7-8 years. Due to his suspected "rheumatoid arthritis," the patient had taken oral medications (Chinese patent medicines and hormones, but the specific details were unknown) irregularly for many years. The patient had been married for 10 years without children. His wife was in good health and claimed that her reproductive system examination showed no abnormalities.
When admission, the patient was admitted to the ICU of the Department of Neurology for further diagnosis and treatment.
Physical examinations on admission showed the body temperature at 40 C, pulse at 120 beats/min, respiration rate at 20 times/min, blood pressure at 120/70 mmHg, blood oxygen saturation at 96%, and assisted ventilation. Nervous system examinations indicated moderate coma. The pupils were equal in size and roundness with a diameter of ~0.3 cm, and the light reflex was normal. His muscular tone of four limbs slightly increased. Meningeal irritation signs were positive, and bilateral pathological signs were negative.
The patient was uncooperative with the rest physical examinations. Related biochemical and imaging examinations were also tested. Emergency blood gas analysis showed pH at 7.457, PCO2 at 28.9 mmHg, and PO2 at 97.7 mmHg. Routine blood test showed WBC counts at 12.34 x 109/L, RBC counts at 4.30 x 1012/L, hemoglobin concentration at 118.0 g/L, platelet counts at 258.00 x 109/L, and C-reactive protein at 277.20 mg/L. Head CT did not reveal any obvious abnormalities, while chest CT showed mild pneumonia of the lower lobes.
Initial treatments included ice blanket and ice cap for physical cooling, empirical antiviral and antibacterial therapies, intravenous administration of gamma-globulin to improve immunity, elimination of autoimmune antibodies, rehydration, and other symptomatic and supportive treatment. At 23:18 of that night, the patient manifested sudden convulsions of the four limbs, loss of consciousness, lockjaw, and ocular gaze to the left. After intravenous injection of 10 mg diazepam, ocular gaze, limb stiffness, and convulsion stopped, but strong limb struggling occurred. Propofol was then administered for sedation purpose, followed by tracheal intubation, tracheotomy, and assisted ventilation. Subsequently, propofol combined with midazolam, meanwhile, antiviral, antibacterial, physical cooling, fluid rehydration, and other therapies were provided, but the temperature still elevated intermittently, up to 41 C.
Relevant laboratory examinations were completed: Blood coagulation series showed prothrombin time control at 13.50 S, prothrombin time measurement at 12.7 S, D-dimer at 1,892 ng/ml. Procalcitonin was tested at 3.53 ng/ml. ESR was at 120.00 mm/h. IgG was at 15.70 g/L, IgA was <0.0667 g/L, IgM at 0.53 g/L. Mycobacterium tuberculosis antibody test and sputum acid-fast bacillus smear showed negative. Blood biochemistry showed Urea at 7.62 mmol/L, creatinine at 75.43 mumol/L, potassium at 3.83 mmol/L, sodium at 143.00 mmol/L, chlorine at 112.00 mmol/L, creatine kinase isoenzyme MB at 0.42 ng/mL, myoglobin at 103.02 ng/mL, hypersensitive troponin at 0.02 ng/mL, B-type natriuretic peptide at 38.38 pg/ml, ALT at 23.10 U/L, AST at 48.20 U/L, albumin at 24.20 g/L, and LDL at 2.43 mmol/L. Thyroid function showed Serum T3 3.75 pmol/L, serum free T4 12.71 pmol/L, highly sensitive serum TSH 0.76 mIU/L; 8. Folic acid 21.08 nmol/L, vitamin B12 252.00 pmol/L. CSF examination showed high pressure, WBC counts at 680 x 106/L, microscopic multinuclear cells at 81%, microscopic lymphocytes at 19%, RBC counts 170 x 106/L, gamma-globulin test (+), glucose at 0.69 mmol/L (2.2-3.9), chlorine at 124 mmol/L, and CSF proteins at 3.28 g/L (0.08-0.43).
CSF virus series (human cytomegalovirus and EB virus) and ink staining (Cryptococcus and Mycobacterium tuberculosis) showed negative. CSF immunoglobulin showed IgG at 1250.00 mg/L, IgA at 0.91 mg/L, and IgM at 4.37 mg/L. Autoimmune encephalitis autoantibody, paraneoplastic syndrome autoantibody, and central nervous system demyeling antibody of CSF and blood were tested. The results of CSF were positive/weakly positive, while the blood results were all negative (Figures 1, 2). The CSF and blood samples of the patient were also sent for PACEseq metagenomic next-generation sequencing (mNGS) detection (Hugobiotech, Beijing, China). L. monocytogenes was identified in both CSF and blood, with the specific sequence number of 1,629 and 8, respectively (Figure 3).
Based on the patient's symptoms, extra information was added according to the inquiry into the medical history of family members. The patient usually did not pay much attention to oral hygiene. He brushed teeth irregularly, and often ate food directly out of the refrigerator. He felt oral discomfort 2 days before disease onset. The patient had repeatedly instilled tobramycin eye drops due to eye discomfort, and often squeezed multiple acne on the face by himself. The past medication history included the use of a large amount of oral drugs for the treatment of rheumatoid arthritis, without seeking formal medical treatments, instead, he often searched the Internet for medicines on his own and orally administered more than 10 drugs (including non-steroidal hormonal anti-inflammatory drugs). Therefore, this patient had a history of ingesting unclean food and facial infection, as well as the use of multiple drugs including glucocorticoids. This could lead to a weakened and compromised immunity, causing L. monocytogenes invasion into the central nervous system.
The patient was finally diagnosed as Listeria meningoencephalitis with secondary epilepsy and status epilepticus, bilateral pneumonia, and perhaps rheumatoid arthritis. Thus, adjusted treatments including ampicillin and rifampicin in combination with meropenem, linezolid, and acyclovir were given. Anti-epileptic therapy, dehydration to reduce cerebral edema, and intravenous infusion of globulin symptomatic and supportive treatments were also provided.
After 10 days of treatments, the patient symptoms partially improved. The consciousness gradually regained. Seizures did not recur. His temperature gradually decreased. However, the patient's responsiveness was unsatisfactory. In the meantime, new problems emerged. Despite temperature decline, low fever persisted for a long time, fluctuating at 37.5-38.0 C, and ESR continued to be around 110 mm/h. Neurological examination showed suspicious paralysis of limbs and ophthalmoplegia: despite the consciousness, the patient was unable to speak due to tracheotomy or follow the sound, both eyes was able to move leftward, but the left eye outreached poorly, both pupils was equal in size and roundness with a diameter of 0.3 cm, light reflex was normal, muscle tone of the upper limbs slightly increased, while muscle tone of the lower limbs was basically normal, there was no voluntary movement of the four limbs even under strong stimulation, and bilateral pathological signs were negative. During treatment, the patient developed severe anemia, which met the indication for blood transfusion, unfortunately, repeated blood matching failed.
On May 25th, 500 mg methylprednisolone pulse therapy was added. On the next day, the patient's symptoms significantly relieved. Both hands could raise off the bed, and muscle contraction of both lower limbs was observed. During the following more than 10 days of treatments (the protocol was the same as above), the patient's symptoms gradually improved. The temperature decreased to normal. The patient regained consciousness and was able to speak. His muscle tone of four limbs reached level 4, and ophthalmoplegia gradually alleviated. Repeated examinations of CSF routine and biochemistry gradually returned normal. ESR gradually decreased to normal level.
On June 28th, mNGS result reported the number of specific sequences of L. monocytogenes decreased to 136. Subsequent re-examinations of MRI (T1, T2, FLAIR, DWI, ADC) showed bilateral frontal and parietal cortex necrosis and meningoencephalitis (Figure 4). The patient was instructed to strengthen rehabilitation training. Reexamination of the CSF on July 12th reported mononuclear cell proliferation, L. monocytogenes, and autoimmune antibody (-). Since the follow-up to present, small oral dose of hormone was regularly administered, and the disease has not recurred.