New Findings, Classification and Long-Term Follow-Up Study Based on MRI Characterization of Brainstem Encephalitis Induced by Enterovirus 71

Abstract

Background: To report the diversity of MRI features of brainstem encephalitis (BE) induced by Enterovirus 71. This is supported by implementation and testing of our new classification scheme in order to improve the diagnostic level on this specific disease.

Methods: Neuroimaging of 91 pediatric patients who got EV71 related BE were hospitalized between March, 2010 to October, 2012, were analyzed retrospectively. All patients underwent pre- and post-contrast MRI scan. Thereafter, 31 patients were randomly called back for follow-up MRI study during December 2013 to August 2014. The MRI signal patterns of BE primary lesion were analyzed and classified according to MR signal alteration at various disease stages. Findings in fatal and non-fatal cases were compared, and according to the MRI scan time point during the course of this disease, the patients' conditions were classified as 1) acute stage, 2) convalescence stage, 3) post mortem stage, and 4) long term follow-up study.

Results: 103 patients were identified. 11 patients did not undergo MRI, as they died within 48 hours. One patient died on 14th day without MR imaging. 2 patients had postmortem MRI. Medical records and imaging were reviewed in the 91 patients, aged 4 months to 12 years, and two cadavers who have had MRI scan. At acute stage: the most frequent pattern (40 patients) was foci of prolonged T1 and T2 signal, with (15) or without (25) contrast enhancement. We observed a novel pattern in 4 patients having foci of low signal intensity on T2WI, with contrast enhancement. Another pattern in 10 patients having foci of contrast enhancement without abnormalities in T1WI or T2WI weighted images. Based on 2 cases, the entire medulla and pons had prolonged T1 and T2 signal, and 2 of our postmortem cases demonstrated the same pattern. At convalescence stage, the pattern observed in 4 patients was foci of prolonged T1 and T2 signal without contrast enhancement. Follow-up MR study of 31 cases showed normal in 26 cases, and demonstrated foci of prolonged T1 and T2 signal with hyper-intensity on FLAIR in 3 cases, or of prolonged T1 and T2 signal with hypo-intensity on FLAIR in 2 cases. Most importantly, MR findings of each case were thoroughly investigated and classified according to phases and MRI signal alteration.

Conclusions: This study has provided enhanced and useful information for the MRI features of BE induced by EV71, apart from common practice established by previous reports. In addition, a classification scheme that summarizes all types of features based on the MRI signal at the four different stages of the disease would be helpful to improve the diagnostic level.

Fig 1. Loctation of primary lesion.

The diagram showed the location of primary lesion of brainstem encephalitis induced by EV71, which was a longitudinal lesion at the posterior junction region of the pons and medulla oblongata.

Fig 2. Acute stage typeⅠ.Female, 3 years old, on the 9th day of the disease.

Sagittal MR images revealed a longitudinal lesion at the posterior junction region of the pons and medulla oblongata, with prolonged T1 (A, white arrow) and prolonged T2 (B, black arrow) signal, without enhancement (C, white arrow). See follow-up study in Fig 9.

Fig 3. Acute stage type Ⅱ.

Male 20 months old. Sagittal T1WI (A) appeared normal. A patchy lesion with prolonged T2 signal was revealed on sagittal T2WI (B, black arrow), with mild enhancement (C, white arrow).

Fig 4. Acute stage type Ⅲ, Female, 2.5 years old, on the 7th day of the disease.

There was no abnormal signal at the brainstem seen from sagittal T1WI (A) and T2WI (B); Post-contrast sagittal T1WI demonstrated a patchy, moderate enhancement region (C, white arrow).

Fig 5. Acute stage type IV, Male, 6 months old, on the 6th day of the disease.

There was no abnormal signal at the brainstem seen from sagittal T1WI (A). T2WI showed a hypo-intensive lesion at the posterior junction region of the pons and medulla (B, black arrow), which had moderate enhancement (C, white arrow).

Fig 6. Acute stage type V, Male, 28 months old, on the 11th day of the disease.

Whole brain stem was involved in this case, from midbrain to medullar oblongata, demonstrating as prolonged T1 (A) and prolong T2 signal (B, black arrow), without enhancement (C). This subject was hospitalized in PICU for 20 days, and final discharged. Follow-up study showed that there were neurologic sequealae, presenting as irregular breath and extremities tremor during sleeping.

Fig 7. Convalescence Stage, Male, 4 years old, on the 28th day of the disease.

MR images showed there is a longitudinalmalacia cavity at the posterior junction region of the pons and medulla, with prolonged T1 (A, white arrow) and prolonged T1 (B, black arrow) signal, without enhancement (C, white arrow). This subject had had impaired function of breath and recurrent pneumonia after discharge.

Fig 8. Postmortem stage, Male, 37 months old, on the 2nd day of the disease.

Sagittal FALIR (A, black arrow) and axial T2WI (B, black arrow) showed the whole posterior portion of the brainstem was involved, demonstrating hyper-intensive signal, with restricted diffusion (C, black arrow).

Fig 9. Follow-up study of previous case (Female, 6 years 8 months old,from Fig 2) in 3 years 8 months.

Sagittal MR images revealed the lesion was smaller while compared with Fig 2, demonstrating prolonged T1 (A, white arrow) and prolonged T2 (B, black arrow) signal, and hyper-intensive signal on FLAIR(C, white arrow). This subject had special neurological sequelae, which were irregular breath and involuntary extremity tremor during sleeping at night.