A case of autonomic dysfunction in infantile idiopathic longitudinally extensive transverse myelitis
Article information
Abstract
Longitudinally extensive transverse myelitis (LETM) is a rare but severe inflammatory spinal cord disorder in infants. Autonomic dysfunction (AD), though recognized in high cord lesions, is rarely described in infantile idiopathic LETM and may reflect extensive involvement. We report an 11-month-old infant who developed acute flaccid quadriparesis, bulbar dysfunction, respiratory failure, and marked AD following a febrile illness. The infant was initially managed as Guillain-Barré syndrome and received intravenous immunoglobulin therapy without clinical improvement. Subsequent magnetic resonance imaging revealed a longitudinally extensive spinal cord lesion consistent with LETM. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation, while myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies were negative. The infant developed severe AD requiring supportive care, with gradual recovery after high-dose intravenous methylprednisolone. This case underscores AD as a marker of extensive spinal cord involvement and a predicting of a severe disease course.
Introduction
Acute transverse myelitis is an uncommon but severe inflammatory disorder of the spinal cord that may manifest as longitudinally extensive transverse myelitis (LETM), a magnetic resonance imaging (MRI)-defined phenotype characterized by a spinal cord lesion extending over 3 or more contiguous vertebral segments (1,2). It is also rare in infancy and often presents as a rapidly progressive neurological emergency (3). Clinical features depend on the level of lesion and may include flaccid paralysis, bulbar dysfunction, respiratory compromise, or autonomic dysfunction (AD). Although the AD is recognized in high cord lesions (3,4), it is rarely described in infants with idiopathic LETM.
We report an 11-month-old boy with antibody-negative LETM presenting with acute flaccid weakness, bulbar involvement, respiratory failure, and AD. This case highlights that unexplained AD in a case of acute transverse myelitis can be an early indicator of extensive spinal cord involvement, such as LETM. Written informed consent was obtained from his legal guardians for publication of the clinical details and accompanying images. Ethical clearance was waived for case reports by the institutional ethics committee of the Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital as per the Indian Council of Medical Research guidelines.
Case
An 11-month-old previously healthy male presented to the emergency department with high-grade fever accompanied by upper respiratory tract symptoms. Approximately 12 hours after the onset of fever, his parents noticed motor weakness of the left leg, manifested as reduced spontaneous movements. Within a few hours, the weakness progressed to involve the right leg. Over the subsequent 2 days, the weakness ascended to involve the truncal musculature, resulting in an inability to sit without support. The infant later developed a shrill cry and dysphagia, with gurgling sounds noted during feeding.
The infant was the first-born offspring of a non-consanguineous marriage with an uneventful antenatal, perinatal, and neonatal history. He was born at a gestational age of 39 weeks via spontaneous vaginal delivery with a birth weight of 2.8 kg, and had shown normal developmental milestones such as the ability to crawl and stand with support prior to illness onset. There was no history of spinal dysraphism, previous surgery, or significant medical illness.
The infant presented to the emergency department with the following vital signs: blood pressure, 95/71 mmHg; heart rate, 130 beats/minute; respiratory rate, 40 breaths/minute; temperature, 38.3 °C, and oxygen saturation 88% on room air. He showed mild respiratory distress with subcostal retractions, necessitating high-flow nasal cannula (HFNC) support. Otherwise, his respiratory examination was unremarkable. Cardiovascular and abdominal examinations were unremarkable with good peripheral pulses.
Neurological examination showed generalized hypotonia with muscle power graded as 3/5 in both arms, 2/5 and 1/5 in the right and left legs, respectively (Table). Deep tendon reflexes were absent, plantar responses were mute, and a weak gag reflex indicated bulbar involvement. There was no history of seizures, abnormal gaze, trauma, recent vaccination, rash, or gastroenteritis.
Timeline of illness
A presumptive diagnosis of Guillain-Barré syndrome (GBS) was considered based on the presence of generalized hypotonia, absent deep tendon reflexes, and mute plantar responses. Lumbar puncture was performed to exclude meningitis, showing a cerebrospinal fluid (CSF) profile as follows: protein, 173 mg/dL (reference value, 20–80); glucose, 65 mg/dL (40–80); and leukocytes, 1 cell/mm3. In view of the CSF profile consistent with albuminocytologic dissociation, the infant was transferred to the high dependency unit and started on intravenous immunoglobulin at a total dose of 2 g/kg over 2 days. However, following completion of the therapy, no improvement was observed in the weakness. The infant continued to require the use of HFNC. Subsequent CSF cultures and viral polymerase chain reaction panel turned out sterile or negative through day 3.
MRI of the spine performed on day 5 proved longitudinally extensive central T2 hyperintensities involving the cervical, thoracic, and lumbar spinal cord, with ventral thecal sac enhancement extending from T12 to L5 and mild thickening of the cauda equina, consistent with LETM (Figures 1 and 2). Serum myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 antibodies, obtained on day 6 and reported on day 8, were negative, supporting a diagnosis of idiopathic LETM. Brain MRI was unremarkable with no evidence of optic nerve abnormalities. There was no clinical evidence of the optic nerve involvement; however, visual evoked potentials could not be performed given the infant’s age. He was initiated on high-dose intravenous methylprednisolone (30 mg/kg/day) from day 6 to 10 after the MRI confirmation, followed by oral prednisolone (2 mg/kg/day) from day 11 to 24, with gradual tapering over the subsequent 4 weeks.
Magnetic resonance imaging of the spine performed on day 5. (A) Sagittal T2-weighted image demonstrates the longitudinally extensive central spinal cord hyperintensity extending from the lower thoracic cord to the conus medullaris (black arrows). (B) Sagittal post-contrast T1-weighted fat-suppressed image shows the smooth ventral dural enhancement with mild enhancement and thickening of the cauda equina (white arrow). (C) Sagittal short tau inversion recovery image confirms the extensive thoracolumbar spinal cord hyperintensity (black arrows) as well as mild thickening of the cauda equina (white arrow).
Sequential axial T2-weighted magnetic resonance imaging demonstrating the central hyperintense lesions involving more than 50% of the cross-sectional area of the spinal cord (arrows).
In the meantime, on day 2–3, the infant developed AD characterized by fluctuating heart rate, intermittent hypertension, diaphoresis, and urinary and bowel retention. Oral clonidine was started for hemodynamic control, and manual and pharmacological measures were implemented for bladder and bowel management. Owing to bulbar weakness and impaired swallowing, nasogastric feeding was continued as part of supportive care.
Following the initial high-dose methylprednisolone therapy, the infant showed progressive improvement in the bulbar and respiratory function over day 8–9, allowing successful weaning from the HFNC and resumption of oral feeding by day 12. Autonomic parameters stabilized, supplemental oxygen was discontinued, urinary bladder function returned to normal, and bowel evacuation was achieved with laxative support.
Partial motor recovery was observed by day 13. At discharge on day 16, the infant showed slight improvement in the motor strength of both arms and legs, with muscle power of 3/5–4/5 in the arms and 2/5 in both legs. Higher mental functions were normal, and bulbar function had recovered completely. Autonomic function remained stable on oral tapering dose of clonidine.
On 1-week follow-up after the discharge, the infant showed gradual improvement in the tone and motor power of the legs, with the better trunk control and ability to sit with minimal support. Deep tendon reflexes and plantar responses gradually reappeared during recovery, with no evidence of spasticity. However, independent standing or walking had not yet been achieved at 6-week follow-up. Physiotherapy and neuro-rehabilitation were continued on an outpatient basis, and clonidine was gradually tapered and discontinued. There were no further episodes of AD, and no recurrence of neurological symptoms or new deficits was noted. Further long-term follow-up was unavailable, as the family resided in a remote area and was unable to attend subsequent follow-ups.
Discussion
LETM in infants is rare and often masquerades as GBS, particularly when presenting with acute flaccid paralysis, areflexia, bulbar dysfunction, and AD. The etiology may be infectious, postinfectious, autoimmune, or demyelination such as neuromyelitis optica spectrum disorder and MOG-associated diseases. However, a subset of patients remains seronegative for both MOG and aquaporin-4 antibodies, and is categorized as having idiopathic LETM as our patient (3).
AD is a recognized but underreported complication of acute transverse myelitis, particularly in children. It may manifest as fluctuating heart rate, labile blood pressure, temperature dysregulation, and bladder and bowel dysfunction (5,6). In our patient, the AD manifested as variable heart rate, intermittent hypertension, diaphoresis, irritability, and bladder and bowel retention during the acute phase, requiring intensive monitoring and pharmacologic control with clonidine. Such manifestations likely reflect extensive myelitis involving the intermediolateral cell columns or descending autonomic tracts, and may be associated with a more severe clinical course and poorer neurological outcomes. The reported frequency of AD ranges from 7.5% in the acute phase to as high as 90% in chronic traumatic spinal cord injury (4). Although AD is well documented in traumatic or neoplastic etiologies (7,8), only isolated reports exist in demyelinating or idiopathic myelitis, particularly in infants.
The initial diagnosis of GBS in this case underscores the clinical overlap among acute flaccid paralysis syndromes in infancy. The diagnostic process was further confounded by the presence of albuminocytologic dissociation and mild contrast-enhancing cauda equina thickening. However, the characteristic MRI findings were more consistent with LETM (Figures 1 and 2). Previous reports have shown that LETM may occasionally present with mild pleocytosis and elevated CSF protein concentrations, resulting in diagnostic overlap with peripheral neuropathies such as GBS (9). However, marked CSF protein elevation is uncommon in LETM and should prompt evaluation for infectious, neoplastic, or obstructive etiologies (3). The non-availability of age-appropriate nerve conduction studies further delayed early diagnostic clarification in this case. The lack of clinical improvement following intravenous immunoglobulin therapy, together with the characteristic MRI findings, ultimately established the diagnosis of LETM. Early initiation of high-dose corticosteroid therapy remains the cornerstone of management and is associated with improved neurological outcomes (9).
Suthar et al. (10) described the heterogeneous clinical presentation, severity, and outcomes of pediatric acute transverse myelitis, noting that cervical spinal cord involvement is associated with a more severe disease and higher risk of respiratory compromise. Similarly, Chandrasekar et al. (11) demonstrated considerable variability in the clinical manifestations, etiologies, treatment responses, and outcomes of LETM, highlighting it as a spectrum rather than a uniform disease entity. Our case mirrors these observations, with the extensive cervical spinal cord involvement resulting in profound motor weakness, respiratory failure, and AD, yet achieving a meaningful neurological recovery following early aggressive immunotherapy. This case highlights the diagnostic challenge posed by LETM in infancy, particularly when it mimics GBS. Prompt recognition of AD as an early clue to LETM, together with early spinal MRI and timely immunotherapy, was pivotal in establishing the diagnosis and achieving favorable neurological outcomes.
Notes
Author contributions
Conceptualization: MN
Methodology, Data curation, Formal analysis, Investigation, and Validation: all authors
Visualization: MN and BP
Writing-original draft: VA, RJ, and MN
Writing-review and editing: MN and BP
All authors read and approved the final manuscript.
Conflicts of interest
No potential conflicts of interest relevant to this article were reported.
Funding sources
No funding source relevant to this article was reported.
Acknowledgments
We are deeply grateful to the patient’s parents for their cooperation, trust, and consent in sharing the details of this case for academic and clinical learning purposes. We sincerely acknowledge the support of the Department of Radiology for their valuable contributions in the diagnosis and management of this case. During the preparation of this manuscript, the authors used ChatGPT (OpenAI) to improve the language, grammar, and readability of the text.