European Review for Medical and Pharmacological Sciences

2020; 24: 10708-10711

A girl with acute encephalitis followed by acutecerebellitis/cerebellopathy
G. IMATAKA1, K. WAKE2, S. YOSHIHARA1
Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan
Department of Emergency and Critical Care Medicine, Dokkyo Medical University, Tochigi, Japan

12Abstract. – OBJECTIVE: The purpose of thisstudy is to bring attention to a case of acute encephalitis not concurrent with acute cerebellitis.
CASE PRESENTATION: Five days after onsetof common cold symptoms, a 17-months-old girlsuffered convulsions, vomiting and respiratory arrest. On exam, she had pharyngeal inflammation, brisk deep tendon reflexes, respiratory acidosis, leukocytosis, negative rapid antigen tests, and segmental pneumonia. Brain CT
and MRI/MRA were negative, and EEG was consistent with acute encephalitis. Following hypothermic therapy, methylprednisolone pulse therapy and cefotaxime, she recovered. Four days
after discharge, she sustained limb and truncal
ataxia associated with normal EEG, followed bybilateral intention tremor. Blood and CSF chemistry and cell counts were normal. Brain MRI revealed high intensity signals in the dentate nuclei and enhancement in the cerebellar whitematter, suggestive of acute cerebellitis/cerebellopathy. SPECT imaging showed reduced
blood flow in the cerebellum, right thalamus andbrain stem. Following short-term administrationof g-globulin and prednisolone, she regained
her ability to sit and, eventually, to walk. Fourmonths after initial presentation, her brain MRI
was normal. No relapse has occurred in 5 years.
CONCLUSIONS: The uncommon sequentialdevelopment of acute encephalitis followed byacute cerebellitis suggests an immune-mediated cerebellar ataxia.
Key Words:
Acute cerebellitis, Acute encephalitis, Ataxia, Children, Cerebellopathy, Immune-mediated cerebellar
ataxia.

Introduction
Acute cerebellitis is a rare inflammatory syndrome with the majority of cases described inyoung, previously healthy children1-3. It can be
a complication of systemic infections1-7 and is10708

characterized by acute onset of cerebellar signs
and symptoms (such as ataxia, intention tremor
or dysarthria) often accompanied by fever, altered mental status and characteristic imaging
abnormalities of the cerebellum1-3,8-10. There isno established treatment, but some cases havebeen treated with intravenous immunoglobulin
or steroids1-3. Some children presenting with acutecerebellitis are occasionally found to have concurrent inflammation in other parts of the brain(encephalitis)11-17. Herein, we present the rare andunique case of a young child with acute encephalitis who subsequently developed acute cerebellitis/cerebellopathy and was successfully treated.
Case Presentation
Patient was 17-months-old when she was admitted to the hospital for the first time sufferingfrom an acute encephalopathy. She had no abnormalities at birth, and the family history did notshow any prior complications. On day 5 after theonset of a common cold with no gastrointestinal
symptoms, she suffered from partial convulsions
followed by recurrent vomiting, which led to respiratory arrest for about 15 minutes. During her
stay in the emergency department, her consciousness level was eye opening 2, verbal response 2
and motor response 3 in Glasgow coma scale.
Later, she was admitted to the intensive careunit, and was kept under artificial mechanicalrespiration. Physical findings included injectedpharyngeal mucosa and brisk accelerated deep
tendon reflex in the upper and lower limbs. Bloodgas and hematological analyses showed that thepH, PCO2, WBC, and CRP values were 7.173,63.4 mmHg, 21,600/mm3, and 3.3 mg/dl, respectively. Rapid antigen test including influenza A/Bvirus, rota virus, group A streptococcus andmycoplasma were negative. A cerebrospinal fluid(CSF) test showed that the cell count and proteinlevel were 52/3 and 15 mg/dl, respectively. ChestCorresponding Author: George Imataka MD, Ph.D., B.Phil, LL.B., PGDBA; e-mail: geo@dokkyomed.ac.jp

A girl with acute encephalitis followed by acute cerebellitis/cerebellopathy

X-ray revealed right upper segmental pneumonia.
Brain computed tomography did not reveal any
abnormalities and brain MRI/MRA results werenormal. Electroencephalograms (EEG) showedasymmetric high-amplitude d waves on both left
and right sides, which was suggestive of an acuteencephalitis (Figure 1). She was treated with35.0 degree’s mild brain hypothermic therapy
combined with methylprednisolone steroid pulse
therapy for 3 days (with a hypothermia durationof 72 hours). Continuous intravenous injection of
midazolam, D-mannitol, cefotaxime sodium, andother needed agents was performed. 99m-Tc ECD
single photon emission computed tomography(SPECT) did not reveal any abnormalities on day
12. MRI showed a slight atrophy in the frontal
region on day 13. Improvement in the symptoms
was observed, and the patient was discharged onday 14.
Four days after discharge (day 18), she sufferedfrom ataxia of the limbs and trunk, EEG wasperformed but no abnormalities were detected.
On day 23, we observed that patient was unable
to maintain the sitting position while developing
cerebellum symptoms. At the second admission,
the consciousness level was normal, intention
tremor on both hands was noted. Blood cellcounting as well as blood biochemistry analysis
were both normal. The CSF cell count was 32/3,
and the protein level was 24 mg/dl. She tested
negative for the oligoclonal band. Brain MRI
results (T2-weighted FLAIR images) revealed ahigh signal intensity in the bilateral cerebellar
deep white matter areas, at the dentate nucleusof the cerebellum, and in the subcortical whitematter areas of the right parietal/occipital lobes.
In addition, the cerebellar white matter and deep
white matter, marked enhancement effects wereobserved (Figure 2A, B). Thus, the MRI find-Figure 2. MRI and SPECT imaging. A, B, on day 23,
MRI FLAIR images revealed high signal intensity in thebilateral cerebellar deep white matter, dentate nucleus andsubcortical white matter of the right parietal/occipital lobes.
C, D, on day 37, SPECT showed decreases blood flow in thecerebellum, right thalamus and brain stem.

ings suggested acute cerebellitis/cerebellopathy.
At this point (on day 24) we administrated 400
mg/kg of g-globulin for 5 days alongside with 2
mg/kg/day prednisolone. The patient regains her
ability to sit normally on day 29. SPECT results
on day 37 showed a decline in blood flow in thecerebellum, right thalamus, and brain stem (Figure 2C, D). Thereafter, ataxia of the limbs andtrunk symptoms were improved gradually. Patient was able to walk and was discharged on day
48. Four months after the initial onset, brain MRI
confirmed the disappearance of all abnormal signal intensities in the cerebellum. There has been
no relapse during 5 year of follow-up.

Discussion

Figure 1. EEG recorded asymmetric high-amplitude dwaves.

Acute cerebellitis is characterized by acutecerebellar ataxia or dysfunction attributable to a
recent or concurrent infectious illness, or rarely
a recent vaccination, associated with MRI evidence of predominant cerebellar inflammation2.
It occurs in previously well children, usually
under 6 years of age2. The clinical features ofacute cerebellitis at presentation include in decreasing frequency (55%-15%) somnolence or10709

G. Imataka, K. Wake, S. Yoshiharacoma, ataxia, headache, nausea, vomiting, fever,dysarthria, mutism, gait disturbance, dysmetria
and seizure2. The majority of cases are attributed to post infective inflammation based on theclinical presentation. Of the cases in which apathogen was found, most were due to viral(e.g., rotavirus11-15, Epstein-Barr virus, varicellazoster, influenza A and B6), bacterial (e.g., Streptococcus7) and mycoplasmal (e.g., Mycoplasma
pneumoniae5) infections1-4. A minority of casesof postimmunization acute cerebellitis have beenreported (e.g., vaccination for varicella, influenza) without evidence of systemic infection2.
Also, the rates of cerebellitis after vaccination aremuch lower than in association with infection18.
The pathogenic mechanisms through which systemic infections may cause specific neurologicaldisorders have not been definitively established
but are believed to be autoimmune2,19. An immune-mediated pathogenesis is also suggested by
the paucity of causative pathogen detected in thepatients’ CSF. Auto-antibodies possibly involvedin cerebellar inflammation have been detectedin the serum and/or CSF of patients with acutecerebellitis and include antibodies against glutamate receptor delta 2 (predominantly expressedon cerebellar Purkinje cells)7,20, gangliosides (inM. pneumoniae cases)21,22 and centrosomes (pericentrin; in varicella cases)23. Clinically, the mostsensitive imaging modality for assessing cerebral
and cerebellar inflammation is MRI1-3,8. Various
patterns of cerebellar inflammation have beenreported, including inflammation of the dentate
nuclei and hemispheres. Single-photon emission
computed tomography (SPECT) imaging may reveal the presence of reduced cerebellar blood flowin acute cerebellitis2,9,10. Serology may demonstrate elevate infection or inflammation biomarkers, but CSF analyses and cerebral EEG areoften non-contributory1-3. Most patients respondto medical management consisting of intravenous
administration of immunoglobulins, steroids(e.g., methylprednisolone), antiviral agents (i.e.,acyclovir) and broad-spectrum antibiotics1-3. The
majority of patients improve within 2 weeks, butcerebellar ataxia may take months to resolve andlong-term neurological disabilities and occasional
deaths have been reported1-3.
Some children presenting with acute cerebellitis are occasionally found to have concurrent
inflammation in other parts of the brain (encephalitis). Examples of acute cerebellitis concurrent
with encephalitis include cases of rotavirus gastroenteritis11-15, rhinovirus16 or with an unknown
10710

etiology17. In the present case, acute encephalitis
with possible brainstem involvement developed
first, as suggested by the patient’s convulsion
and respiratory arrest and EEG abnormalities
without MRI evidence of cerebral or cerebellar
inflammation. Only 4 days after her recovery anddischarge did she demonstrate cerebellar signs
and symptoms evidenced by limb and truncal
ataxia, bilateral intention tremor, difficulty sitting
and walking. Imaging abnormalities detected in
the cerebellum by MRI and SPECT imaging wereconsistent with a diagnosis of acute cerebellitis/cerebellopathy. Attempts at identifying the etiologic agent by rapid antigen test (influenza A/Bvirus, rotavirus and Group A streptococcus) andCSF oligoclonal band test were inconclusive.
The temporal dissociation of acute encephalitis
followed by acute cerebellitis suggests an immune-mediated cerebellar ataxia. Only in a report of two patients with rotavirus gastroenteritis
have the symptoms of acute encephalitis subsided
before the cerebellar signs (mutism, slow speechand dysarthria) became evident and a brain MRI
showed cerebellar involvement11. However, thepresent case does not support rotavirus as theetiology and presents a different spectrum ofcerebellar signs.

Conclusions
The sequential development of acute encephalitis followed by acute cerebellitis/ cerebellopathy in this child is uncommon. A process ofimmune-mediated cerebellar ataxia is supported
by its response to immunoglobulin and steroid
therapy.
Conflict of Interest

The Authors declare that they have no conflict of interests.

References1) Kornreich L, Shkalim -Zemer V, L evinsky Y, A bdallahW, G anelin -Cohen E, Straussberg R. Acute cerebellitis in children: a many-faceted disease. J Child
Neurol 2016; 31: 991-997.
2) Emelifeonwu JA, Shetty J, K aliaperumal C, G allo P,Sokol D, Soleiman H, K andasamy J. Acute cerebellitis in children: a variable clinical entity. J Child
Neurol 2018; 33: 675-684.
3) Yildirim M, Gocmen R, Konuskan B, Parlak S, Yalnizo glu D, A nlar B. Acute cerebellitis or postinfectious

A girl with acute encephalitis followed by acute cerebellitis/cerebellopathy

4)
5)
6)
7)
8)

9)

10)

11)

12)

13)

cerebellar ataxia? Clinical and imaging features inacute cerebellitis. J Child Neurol 2020; 35: 380388.
Nussinovitch M, Prais D, Volovitz B, Shapiro R, A mir
J. Post-infectious acute cerebellar ataxia in children. Clin Pediatr 2003; 42: 581-584.
G ayatri N, Tyagi A, M ahadevan U. Acute hydrocephalus in a child with mycoplasma cerebellitis. BrainDev 2009; 31: 618-621.
Hackett I, O’Sullivan R, Zaid AA, Rea D, Walsh S.
Acute cerebellitis associated with dual influenza A(H1N1) and B infection. Ir Med J 2013; 106: 87-88.
Uchizono H, Iwasa T, Toyoda H, Takahashi Y, Komada Y. Acute cerebellitis following hemolytic streptococcal infection. Ped Neurol 2013; 49: 497-500.
Rossi A, M artinetti C, Morana G, Severino M, Torto ra D. Neuroimaging of infectious and inflammatory diseases of the pediatric cerebellum and brainstem. Neuroimaging Clin N Am 2016; 26: 471-487.
Daaboul Y, Vern BA, Blend MJ. Brain SPECT imaging and treatment with IVIg in acute post-infectious cerebellar ataxia: case report. Neurol Res
1998; 20: 85-88.
Nagamitsu S, M atsuishi T, Ishibashi M, Yamashita
Y, Nishimi T, Ichikawa K, Yamanishi K, K ato H. Decreased cerebellar blood flow in postinfectious
acute cerebellar ataxia. J Neurol Neurosurg Psychiatry 1999; 67: 109-112.
Shiihara T, Watanabe M, Honma A, K ato M, Mori ta Y, Ichiyama T, M aruyama K. Rotavirus associatedacute encephalitis/encephalopathy and concurrent cerebellitis: report of two cases. Brain Dev
2007; 29: 670-673.
Kobayashi S, Negishi Y, A ndo N, Ito T, Nakano M,Togari H, Wakuda M, Taniguchi K. Two patients withacute rotavirus encephalitis associated with cerebellar signs and symptoms. Eur J Pediatr 2010;
169: 1287-1291.
Kubota T, Suzuki T, K itase Y, K idokoro H, Miyajima Y,
Ogawa A, Natsume J, Okumura A. Chronological diffusion-weighted imaging changes and mutism inthe course of rotavirus-associated acute cerebellitis/cerebellopathy concurrent with encephalitis/encephalopathy. Brain Dev 2011; 33: 21-27.

14) Mori T, Morii M, Kuroiwa Y, Hotsubo T, Fuse S, Tsustumi H. Rotavirus encephalitis and cerebellitis
with reversible magnetic resonance signal changes. Pediatr Int 2011; 53: 252-255.
15) Paketçi C, Edem P, Okur D, Sarıoğlu FC, Güleryüz H,Bayram E, Kurul SH, Yiş U. Rotavirus encephalopathy with concomitant acute cerebellitis: report ofa case and review of the literature. Turk J Pediatr
2020; 62: 119-124.
16) Hazama K, Shiihara T, Tsukagoshi H, M atsushigeT, Dowa Y, Watanabe M. Rhinovirus-associatedacute encephalitis/encephalopathy and cerebellitis. Brain Dev 2019; 41: 551-554.
17) Zhang YQ, Chen D, Zou YF, H uang M, J ia XY. Lesions more than cerebellum in a puerpera ofacute cerebellitis: concurrent encephalitis, nota subtype of ADEM. Clin Case Rep 2013; 1: 1619.
18) van der M aas NAT, Vermeer - de Bondt PE, de Melker H, K emmeren JM. Acute cerebellar ataxia in theNetherlands: a study on the association with vaccinations and varicella zoster infection. Vaccine2009; 27: 1970-1973.
19) Joubert B, Rostásy K, Honnorat J. Immune-mediated ataxias. Handb Clin Neurol. 2018; 155: 313332.
20) Shiihara T, K ato M, Konno A, Takahashi Y, Hayasaka
K. Acute cerebellar ataxia and consecutive cerebellitis produced by glutamate receptor delta2 autoantibody. Brain Dev. 2007; 29: 254-256.
21) Komatsu H, Kuroki S, Shimizu Y, Takada H, Takeuchi
Y. Mycoplasma pneumoniae meningoencephalitis and cerebellitis with antiganglioside antibodies. Pediatr Neurol. 1998; 18: 160-164.
22) Hanzawa F, Fuchigami T, Ishii W, Nakajima S, K awamu ra Y, Endo A, A rakawa C, Kohira R, Fujita Y, Taka hashi S. A 3-year-old boy with Guillain-Barré syndrome and encephalitis associated with Mycoplasma pneumoniae infection. J Infect Chemother. 2014; 20: 134-138.
23) Fritzler MJ, Zhang M, Stinton LM, R attner JB.
Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar
ataxia. BMC Pediatr. 2003; 3: 11.

10711