Neuroimaging Spectrum of Enterovirus Central Nervous System Infections in a Pediatric Population

Abstract

Background and Objective

Enteroviral infections range from self-limiting illnesses to severe neurological disorders. A thorough review of published literature reveals few studies highlighting the neuroimaging findings of such cases; however, none have been published from the Indian subcontinent. The present study analyzes the varied imaging and clinical spectrum of microbiologically proven cases of encephalomyelitis due to enterovirus in a tertiary care institute in northern India.

Methods and Materials

This prospective study was conducted at a tertiary care institute in north India, and included 23 cases that presented with variable neurological symptoms of central nervous system infection and were found to have enterovirus, confirmed using reverse transcriptase-polymerase chain reaction. All these patients had undergone a brain magnetic resonance imaging (MRI). MRI spine was done depending on the symptoms of the patients. Imaging analysis was done by two experienced neuroradiologists.

Results

Fever was the most common presenting symptom, followed by altered sensorium and seizures. In neuroimaging, we found ganglio-capsular (13 cases, 56%), brain stem (7, 30%), cerebral hemisphere (6, 26%), and spinal cord (3, 13.04%) involvement.

Conclusion

Basal ganglia and brainstem involvement was a common pattern seen in our cases, unlike the previously reported pattern of predominant posterior fossa structure involvement. As the pattern and site of both the spinal cord and the brain differ from previously published literature, further analysis would be needed to confirm the cause of such findings.

Keywords

enterovirus infections - viral encephalitis - Picornaviridae - neuroimaging - magnetic resonance imaging

Introduction

Enteroviral encephalomyelitis represents a significant challenge in pediatric neurology and infectious disease management. Enterovirus (EV) is transmitted by the oral–fecal pathway. Following an intestinal infection, the infection first grows in the small intestine's lymph nodes or pharynx before spreading to other body organs. Common clinical signs include fever, moderate pharyngitis, irritation, and respiratory symptoms, along with systemic symptoms including headache, vomiting, and occasionally diarrhea.[1] On the other hand, EV 71-caused hand, foot, and mouth disease exhibits more severe clinical presentations, including meningoencephalomyelitis, poliomyelitis-like paralytic illness, and brainstem encephalitis, which are among the most common neurologic sequelae.[1] The rapid clinical progression and potential for long-term sequelae underscore the critical need for prompt and accurate diagnosis. In this context, magnetic resonance imaging (MRI) has emerged as an indispensable diagnostic tool, offering high-resolution insights into the anatomical and pathological alterations associated with the disease.[2]

Conventional MRI techniques have significantly enhanced our ability to detect subtle changes in brain parenchyma. Characteristic imaging findings in enteroviral encephalomyelitis often include hyperintense lesions in the brainstem, cerebellum, and spinal cord. A comprehensive review by Abdelgawad et al[3] highlights these typical patterns in pediatric brain infections, reinforcing the utility of MRI in differentiating viral etiologies.[3] Similarly, a pictorial essay by Jayaraman et al emphasizes the varied imaging spectrum of viral encephalitis, illustrating how MRI can be used to distinguish enteroviral encephalomyelitis from other causes of central nervous system (CNS) infections.[4]

Furthermore, regional studies have begun to shed light on the epidemiological and imaging nuances of the disease. For instance, research from India indicates an evolving spectrum of acute encephalitis syndrome (AES), where EVs, although representing a minor fraction, contribute to significant morbidity.[5] These findings suggest that regional variations may influence both clinical presentations and imaging characteristics, necessitating tailored diagnostic approaches.

Between 2000 and 2010, there was a significant shift in the AES spectrum in India. Among AESs, Japanese encephalitis (JE) virus has been recognized in the majority of cases (5–35%), followed by herpes simplex virus (HSV) and EVs (0.1–33%). With an increase in non-JE outbreaks caused by Chandipura virus and Nipah virus, EVs are also being increasingly detected in these cases.[6] In India, not many studies have been conducted to detect the presence of EV in patients with neurological diseases. Beig et al have reported viral etiology in 21.8% patients from Uttar Pradesh, India, with acute febrile encephalopathy, of which, EV-A71 was found to be the most severe with 42% cases and 50% mortality rate.[7]

Few viruses display characteristic MRI changes. The neonatal HSV shows T2 hyperintensities in the basal ganglia and the thalamus, with hemorrhages seen better as blooming in the susceptibility-weighted imaging (SWI). HSV in older patients affects the medial temporal lobe and the limbic system. There is relative sparing of the basal ganglia. The Epstein–Barr virus (EBV) encephalitis commonly involves the basal ganglia and thalamus.

Previous studies have been conducted, especially in cases of outbreak settings. In the past decade, the evidence from India has focused on microbiological and epidemiological aspects of encephalitis in general and especially outbreaks.[4] [5] [8] [9] [10] The present study is a case series from a tertiary care institute in north India, discussing the spectrum of imaging findings in microbiologically proven cases of EV—the first one done in an Indian setting, as per our best understanding.

Materials and Methods

This prospective descriptive study was conducted at our institute from October 2022 to September 2024. This study was approved by the Institutional Ethics Committee of our institute (ref. no- INT/IEC/2023/SPL-986). The methods were performed in accordance with the principles of the Declaration of Helsinki. The study included children between 1 month and 12 years of age with suspected CNS viral infection (AES, aseptic meningitis, and acute flaccid paralysis as per the relevant case definitions)[11] admitted to our institute within 7 days of onset of symptoms. All these patients had undergone neuroimaging at our institute. Cases where organisms other than EV were isolated were excluded from the analysis.

Specimen Collection and Testing

The cerebrospinal fluid (CSF), throat swab, and rectal swab/stool samples were collected from the enrolled children by trained staff following standard operating procedures, only after obtaining written consent from their parent or legal guardian. The specimens were immediately transferred to the clinical laboratory in the cold chain (4°C) for further investigations. The stool samples were processed as per World Health Organization (WHO) guidelines. The samples were stored in aliquots at −80°C till tested. Using the Insta NX Mag16Plus Automated Nucleic Acid Extractor (HiMedia, India), viral RNA was extracted, which was subjected to “one-step real-time reverse transcriptase-polymerase chain reaction (PCR) targeting the 5′-UTR gene” as described previously.[12] All samples with a Cq value of ≤34 and an observable sigmoid graph on real-time PCR run were reported as positive. Genotyping of positive samples was performed by targeting the viral protein 1 (VP1) region as described previously.[13] [14] The PCR product of around 370 bp was gel-purified using HiYield Gel/PCR purification kit (Real Biotech Corporation, Taiwan) and subjected to Sanger sequencing. The sequence analysis was done using “GeneStudio (version 2.2.0.0)” and “Bioedit sequence alignment editor (version 7.2.5)” software. The nucleotide sequences were used to identify the EV genotype using NCBI BLAST and the EV genotyping tool.[15]

Diagnostic Interpretation

Depending on clinical sample types in which evidence of enteroviral infection was identified, the etiology was considered as “definitive, probable, or possible” as described in [Table 1].[16]

Table 1 Diagnostic classification of enterovirus real-time RT-PCR-positive cases (n = 23)

Diagnostic category	Definition[16]	Clinical sample tested	Enterovirus real-time PCR positive
Definite	“Enterovirus detection in CSF and absence of other viruses in CSF or blood”	CSF	02 (8.6%)
Possible	“Enterovirus detection in either throat swab or rectal swab/stool and absence of other viruses in CSF or blood“	Throat swab	02 (8.6%)
		Rectal swab/stool	12 (52.1%)
Probable	“Enterovirus detection in throat swab and rectal swab/stool and absence of other viruses in CSF or blood”	Both throat swab and rectal swab/stool	7 (30%)

Abbreviations: CSF, cerebrospinal fluid; RT-PCR, reverse transcription-polymerase chain reaction.

Clinical Evaluation

Every patient had a thorough clinical evaluation, with the documentation of vitals, general physical examination, and symptoms, such as altered sensorium, fever, and seizure (together with several episodes and seizure pattern), as found from the electronic medical records. As much as possible, a thorough neurological examination was performed on each patient. Every patient had a fundus examination to check for the existence of papilledema.

Laboratory Investigations

All patients underwent basic blood counts and renal and liver function tests. Additionally, an electrocardiogram, abdominal ultrasound, and chest X-ray were performed. Patients without a contraindication had their CSF sent for cell counts and microbiological (culture and staining) and biochemical investigations (sugar, protein, albumin).

Imaging Evaluation

The patients underwent MRI brain with or without spine imaging, depending on whether they had suspicion of spinal cord involvement or not. All children under 5 years or those unable to remain still underwent sedation with oral Triclofos 0.5 mL/kg, and if required, i.v. Ketamine was given in doses of 1 mg/kg, maximum up to two times, or i.v. Midazolam 0.1 mg/kg for the first dose and 0.05 mg/kg for the second and third doses, maximum up to three doses. A 3 Tesla MRI scanner was used to perform the scan (Phillips, The Netherlands) using the following sequences: T1 3D SPGR (pre- and post-gadolinium contrast), T2-weighted fast spin echo, T2-FLAIR, diffusion-weighted imaging (DWI), and SWI. The whole spine screening protocol included T1 post-contrast and T2 sequences. Weight-based intravenous gadolinium (Gd-DTPA) was used unless contraindicated. Two neuroradiologists (having 15 and 5 years of experience in evaluating brain MRI) independently reviewed all MRI studies and scored the presence or absence of signal abnormalities in each predefined region (basal ganglia, brainstem, cerebral cortex, etc.). Inter-reader agreement for each region was quantified using Cohen's kappa statistic (κ), calculated as [(Po − Pe)/(1 − Pe)]/(1 − Pe), where “Po” indicates observed proportion of agreement and “Pe” expected agreement by chance (calculated from the marginals). Interobserver variability was assessed using a generalized κ statistic and percentage of agreement was calculated for multiple size strata with interpretation using the table given by Landis and Koch in 1977 as “poor (<0.00), slight agreement (0.0–0.20), fair (0.21–0.40), moderate (0.41–0.60), substantial (0.61–0.80), and almost perfect (0.81–1.00) agreement based on the respective kappa scores.”

Data were entered and stored in MS excel. The involvement in the brain was divided into five categories, including basal ganglia, corpus callosum, capsular region, posterior fossa, cerebral white/gray matter, and spinal cord involvement. Additional points like the absence or presence of diffuse restriction, hemorrhage, and meningeal enhancement were also recorded.

Results

Twenty three cases met the inclusion criteria, out of which 15 (65.2%) were male and the rest were female. Their ages ranged from 2 months to 11 years, with the median (interquartile range) being 24 months (11–60 months). There were 17 cases (73.9%) below the age of 5 years. The children had varied clinical presentations, as given in [Table 2]. Out of the total 23 cases, 4 cases had no significant findings. In the rest of the cases, the spectrum of brain MRI findings is described in [Table 3].

Table 2 Different symptoms with which the case presented

Clinical presentation	Frequency
Fever	20
Vomiting	10
Encephalopathy/altered sensorium	10
Seizures	10 (8 GTCS, 1 focal seizure)
Decreased/abnormal body movement	8
Lethargy/generalized weakness	4
Cough	3
Coryza	2
Loose stool	3
Poor feeding, limb weakness, tremors, right-sided paucity of movements, inability to move LL, change in voice, leg pain	1 each

Abbreviations: GTCS, general tonic-clonic seizure; LL, lower limb.

Table 3 Spectrum and pattern of MRI findings

Structure involved		Frequency
Basal ganglia ( n  = 13)	Caudate	6
	Putamen	6
	Globus pallidus	5
	Subthalamic nuclei	2
	Thalamus	7
Capsule ( n  = 3)	External capsule	3
	Claustrum	2
Posterior fossa ( n  = 7)	Dorsal midbrain	6
	Ventral midbrain	2
	Dorsal pons	6
	Ventral pons	1
	Dorsal medulla	2
	Ventral medulla	1
	Cerebellum	1
Cerebral ( n  = 6)	Frontal	4
	Parietal	4
	Temporal	3
	Occipital	3
Spinal cord ( n  = 3)	Thickening and enhancement of the cauda equina nerve roots	2
	Diffuse spinal cord involvement	1

Abbreviation: MRI, magnetic resonance imaging.

Possible and Probable Diagnosis

Two of the CSF samples tested positive for EV (8.6%), which is above the average positivity reported previously ([Table 1]). Such a low positivity can be justified owing to the transient positivity of EVs in CSF samples.[17] Furthermore, none of the 23 cases had positive bacterial cultures. Further discussion is provided in the Limitations section. A possible diagnosis was made in 60% (14/23) cases, while 7 cases (30%) had probable EV infection based on virus detection in both throat swab and rectal swab/stool samples ([Table 3]), where either rectal swab/stool or throat swab was positive. Different EV types, including five cases (21%) of Enterovirus A (Coxsackievirus A16, Enterovirus A71, Enterovirus A76), three cases (13%) of Enterovirus B (Enterovirus B80, Echovirus E7, and Echovirus 14), and seven cases (30%) of Enterovirus C (Coxsackievirus A4, Coxsackievirus A22, Coxsackievirus A1), were isolated.

Case–Control Analysis of Anatomical Involvement

To determine if the observed patterns of CNS involvement were specific to EV encephalitis, the case group was compared with a control group of 23 pediatric patients who underwent neuroimaging for various neurological conditions, which tested negative for EV in stool/rectal or nasal swab. The case and control groups were well-matched, with no significant difference in sex distribution (15 male cases vs. 10 male controls, p = 0.245) or age stratification (17 cases <5 years vs. 12 controls <5 years, p = 0.245).

A direct comparison between the EV encephalitis cases and the control group revealed a highly statistically significant association between EV infection and involvement of the basal ganglia/thalamus (p = 0.003). Lesions in this region were observed in 13 of 23 cases (56.5%) compared with only 3 of 23 controls (13.0%). Conversely, cerebral involvement was significantly less frequent in the EV group than in the control group (26.1 vs. 65.2%, p = 0.011). No significant differences were found for posterior fossa or spinal cord involvement.

Discussion

The most common pattern of involvement was involvement of deep gray matter nuclei, followed by posterior fossa involvement. There was substantial agreement (κ = 0.63) overall for the area of brain involvement. Posterior fossa had the maximum inter-reader agreement (0.75, substantial agreement), while the spinal cord had the least (0.50, moderate agreement).

Most Common Pattern

Ganglio-capsular predominant pattern: among the basal ganglia structures, the thalamus (30%), followed by the caudate nucleus, was most frequently involved (26.5%). Basal ganglia involvement, which is a more common site of involvement for pathogens like EBV, varicella zoster virus, dengue virus, JE virus, Cryptococcus, and tuberculosis,[18] rather unusual for EV, was found to be the most common site of involvement in the present study. Previously, only one case of lower portion of globus pallidus involvement out of a case series of five[2] has been reported in the literature. Although thalamic involvement has been previously reported in a total of three cases,[19] [20] it was found in over 30% of our cases ([Fig. 1e]). We found two cases of claustrum involvement ([Fig. 1a, b]), which has been previously reported only in chronic enteroviral encephalomyelitis in immunocompromised patients.[21] Both patients with signal changes in the claustrum had an acute-onset neurological deterioration.

Fig. 1 Gangliocapsular involvement—axial FLAIR (A) and T2-weighted images (B) of a 2-year-old child with a 5-day history of fever, vomiting, and paucity of movement in all four limbs showed altered signal in the bilateral basal ganglia (R > L) and the fronto-parieto-occipital lobes (not shown) with associated diffusion restriction (C) and absence of susceptibility changes on SWI (D); case of a 1-year-old child who developed fever, watery diarrhea, and status epilepticus showed T2 (E) and FLAIR (F) hyperintensity in the B/L basal ganglia and the right thalamus, along with diffusion restriction in the corresponding region (G) and absence of susceptibility changes on SWI (H). SWI, susceptibility-weighted imaging.

Posterior Fossa Involvement—Second Most Common Pattern

Among the posterior fossa structures, the dorsal pons ([Fig. 2a, c, e, g]) involvement has been found to be the most common site of brainstem involvement in previous studies,[3] [22] [23] as well as in the current analysis. In our series of cases, whenever the pontine tegmentum was involved, there were concurrent signal changes noted in the tegmentum of the midbrain as well ([Fig. 2b]). Cerebellum, when involved, did not show isolated involvement and was always involved with brainstem and cortex involvement. Other pathogens, e.g., Burkholderia, after nasopharyngeal mucosal colonization, also show retrograde spread to the brainstem, leading to neuromelioidosis and rhombencephalitis, as well as spread of micro-abscesses along longitudinal white matter and commissural tracts.[18]

Fig. 2 Posterior fossa involvement in enterovirus encephalomyelitis: (A–D) axial T2 MRI (A, B) of a 2-year-old boy who developed fever, uttering of nonmeaningful words, and abnormal body movements showed signal changes on T2W (A, B) in tegmentum of pons (A) and mid-brain (B) with associated diffusion restriction (C), and absent changes on SWI (D); (E–H) an 8-month-old child who presented with 3-day history of fever, cough, and coryza showed areas of FLAIR hyperintensity in the pons (E) and mid-brain (F) along with diffusion restriction (G), with no susceptibility artifacts on SWI (H). MRI, magnetic resonance imaging; SWI, susceptibility-weighted imaging; T2W, T2-weighted.

Third Most Common Pattern—Cerebral White and Gray Matter Predominant

Six cases consisted of cerebral white/gray matter involvement. Although cerebral involvement in the form of diffusion restriction in white or gray matter is mostly seen in the “P-A-R-E-C-H” group of pathogens (conveniently mnemonic for “Parechovirus, Adenovirus, Rotavirus, EV, Chikungunya, and HSV”).[18] In differential diagnosis for white matter changes in the absence of DWI changes, congenital “TORCH infections (toxoplasma, other, rubella, cytomegalovirus, and HSV)” should be considered.[18] Cerebral involvement in the form of white matter signal changes was reported by Li et al in two cases of EV presenting in acute stages.[20] Moreover, cerebral involvement has also been described in chronic cases where cystic encephalomalacic changes were seen developing over the course of 1 year.[24] We found that when the cerebral hemispheres were involved, it was always associated with diffusion restriction. Pure involvement of either cerebral white or gray matter was not noted in our analysis.

Spinal Cord Involvement

A total of six patients underwent spine screening, out of which 50% had a normal study. There has always been a possibility of the spread of the virus by neural pathways, leading to the distribution of inflammation seen in the brain.[25]

Diffuse central cord signal changes were seen in one case, a 2-year-old male child who developed paucity of movement of all limbs on day 4 of illness, which on examination revealed flaccid paralysis without fecal incontinence. The changes on MRI were localized to the cervicodorsal region ([Fig. 3a–c]), and have been previously described as one of the patterns of spinal cord involvement.[23] [25] The other pattern of spinal cord involvement we noted was enhancement of the cauda equina nerve roots ([Fig. 3e, f, h]) (n = 2), which has been seen previously in both acute[2] (only one case reported till date as per our understanding) and subacute settings.[25] Bilateral/unilateral ventral horn or root involvement of the cervical cord or the thoracic spinal cord is the overall most common imaging manifestation of enteroviral radiculomyelitis.[26] However, such a pattern of involvement was not seen in our analysis.

Fig. 3 Spinal cord involvement: a 2-year-old child with a 5-day history of fever, vomiting, and altered sensorium with paucity of movement of all four limbs showed a long segment T2 (A) and DIR (C) hyperintensity in the cervico-dorsal spinal cord without any significant post-contrast enhancement (B); in a 3- (D–F) and a 2-year-old (G–I) child with a 2-day history of bilateral lower limb weakness that progressed to inability to move the legs or sit, contrast-enhanced magnetic resonance imaging (MRI) of the spine showed cauda equina nerve root enhancement, seen in the sagittal (E and H) and axial (F) T1W post-contrast images, with no definite signal changes on T2-weighted images (D and G). DIR, double inversion recovery; SWI, susceptibility-weighted imaging; T1W, T1-weighted.

Associated Findings

Classical bilateral thalamic involvement with central diffusion restriction in viral encephalitis is described as the “double-donut” sign[27] described in dengue, herpes simplex, rabies, and West Nile virus encephalitis.[27] Such a finding was seen in our analysis in one of the cases. Communicating hydrocephalus was seen in four of our cases, where it was associated with CSF ooze (n = 1), cerebral/cerebellar atrophy (n = 1), and white matter paucity with benign enlargement of the subarachnoid space. A 9-year-old male patient, who was homozygous for HbS (sickle cell anemia), was found to have deep medullary vein thrombosis in the left frontal parietal white matter region.

Comparison with Regional EV Strains and Previous Studies

It is difficult to precisely document regional EV strain in India due to the presence of limited studies done on EV outbreaks in India.[8] The present literature states that EV 71 is less commonly seen in India, where coxsackievirus B5, echovirus 19, EV-A89, and EV-A76 are more commonly found.[8] Thus, the typical rhombencephalitis form of involvement seen in EV-A71 might not be evident from our study ([Table 4]). [Table 5] shows the comparison of the present study with previous studies on EV CNS infections. It is important to note the low detection in CSF in most of the studies.

Table 4 Subtype of enterovirus and regional variation

Feature	Predominant serotypes/species	Primary clinical syndrome	Key neurological manifestations	Reported severity/morality	References
India (Uttar Pradesh)	EV-A (EV-89, EV-76), EV-B (CBV5, ECV19)	Acute encephalitis syndrome (AES)	Encephalitis	High case fatality reported in outbreaks	[8] [30]
Asia-Pacific	EV-A (EV-A71, various subgenogroups)	Hand, foot, and mouth disease (HFMD)	Brainstem encephalitis (rhombencephalitis)	High mortality in severe cases, often from neurogenic pulmonary edema	[31]
Europe	EV-B (Echovirus 30, Echovirus 11)	Aseptic meningitis, neonatal sepsis	Aseptic meningitis	Generally lower mortality, but high morbidity/mortality in neonatal sepsis outbreaks	[32]
The Americas	EV-D (EV-D68)	Severe respiratory illness	Acute flaccid myelitis (AFM)	Severe respiratory failure; long-term paralysis in AFM survivors	[25]

Table 5 Comparison of the present analysis with previously published literature on enterovirus CNS infections

Study (year)	Cases that underwent MRI (N)	CSF virology yield, N (%)	Basal ganglia (N)	Brainstem (N)	Cerebral (N)	Spinal cord (N)	Ref.
Shen et al (1999)	20	Either of throat/rectal/ CSF immunoblot	2	15	0	3	[19]
Jang et al (2012)	5	1 (25%)	1	3	1	1	[2]
Abdelgawad et al (2016)	25	8 patients by virus culture from the rectum, throat, and CSF; rest by clinical + MRI findings	0	18 (5 cases were normal)	0	2	[3]
Li et al (2012)	35	Positive nucleic acid from a sample of pharyngeal swab, stool, CSF	1	21	7	10	[20]
Le et al (2010)	194	4 (2.1%)	NR	NR	NR	NR	[16]
Choi et al (2011)	42	3 (7.1%)	NR	NR	NR	NR	[1]
Present study (2025)	23	2 (8.6%)	13	7	6	3

Abbreviations: CSF, cerebrospinal fluid; MRI, magnetic resonance imaging.

Clinical Follow-Up and Long-Term Implications

While the acute phase of EV encephalitis commands immediate clinical attention, the long-term trajectory of survivors is of equal importance. Of the 23 children, 1 patient (4.3%) died, and the 22 survivors were discharged with a wide spectrum of neurological deficits and complex care requirements. This aligns with broader literature, indicating that encephalitis can lead to incomplete recovery in a majority of pediatric patients, with sequelae including epilepsy, developmental delay, and learning disabilities.[28]

The follow-up data from this cohort reveal a challenging post-encephalitis landscape. A significant portion of survivors (7 of 22, or 31.8%) were discharged with persistent and difficult-to-manage seizures, requiring multiple anti-epileptic medications. Motor deficits were also common, affecting at least 6 of the 22 survivors (27.3%), with presentations ranging from dystonia and hyperkinetic movements to significant weakness necessitating ongoing physical therapy. The most severe cases required intensive interventions such as tracheostomy (one case), VP shunts (one case), and immunomodulatory therapies, including intravenous immunoglobulin, steroids, and plasma exchange, underscoring the profound systemic impact of the initial infection in at least 4 of the 22 survivors (18.2%).

Follow-up neuroimaging in a subset of patients (3 of 22, or 13.6%) confirmed the structural basis for these long-term deficits, revealing persistent lesions (one case), diffuse cerebral atrophy combined with delayed myelination (one case), and new-onset spinal cord involvement (one case). Atrophy as a post-encephalitic complication in EV has been reported previously to occur in the brain stem and upper cord.[28] Severe atrophy with cystic encephalomalacia has also been seen, as reported previously.

The experience of this cohort powerfully illustrates that EV encephalitis is frequently not a self-limiting event but the beginning of a chronic neurological condition. Even in cases without classic encephalitis, EV CNS infections can lead to long-term developmental concerns. The significant sequelae observed—ranging from refractory epilepsy to permanent motor and respiratory compromise—are consistent with outcomes reported for severe EV infections, particularly EV-A71.

Limitations

This study lacked imaging follow-up in most but three of the cases, which can give insight into the disease progression/resolution and any short-term complications. We could not determine serotype directly from CSF or blood; genotyping was performed on throat/rectal specimens only, as low yield of EV in CSF is well documented with ∼0–5% positivity.[23] [29] “Throat swab samples in virus transportation medium are considered to be the most useful specimens” in terms of the rate of virus detection and availability, as per the WHO.[30] Moreover, they say “Enterovirus can be shed in the stool for several weeks and stool (rectal swab) samples are also appropriate clinical specimens for virus detection and/or isolation.”[30]

Implication

Keeping in mind the greater instances of atypical radiological findings in microbiologically confirmed cases of EV in the pediatric population, in a single center in northern India, more research are needed to confirm if these findings are consistent in a larger population.

Conclusion

In India, after the introduction of JE virus under the universal immunization program in some endemic states, there is a relative increase in prevalence of non-JE virus encephalitis, such as enteroviral encephalomyelitis. In contrast to conventional published literature from around the globe, the radiological findings in our series show a greater involvement of basal ganglia getting involved instead of the rhombencephalitis seen typically. Other atypical findings include a double-donut sign of diffusion restriction that is commonly seen in dengue or JE encephalitis. EV, like the now-eradicated poliovirus (which belongs to the same family, Picornaviridae), shows a similar pattern of spinal cord involvement. However, we found that the myelitis due to EV infection shows enhancement and thickening of the cauda equina nerve roots, a pattern described in Guillain–Barré syndrome or chronic inflammatory demyelinating polyneuropathy.

Conflict of Interest

None declared.

Ethical Approval

This study has been approved by the institutional ethics committee. All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Patients' Consent

Informed consent has been taken from parents/legal guardians of the participants of the study.

^# These authors contributed equally.

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Publication History

Article published online:
05 February 2026