Pediatr Radiol (2015) 45:244–257 DOI 10.1007/s00247-014-3225-4
PICTORIAL ESSAY
Longitudinally extensive myelopathy in children Danielle Eckart Sorte & Andrea Poretti & Scott D. Newsome & Eugen Boltshauser & Thierry A. G. M. Huisman & Izlem Izbudak
Received: 11 March 2014 / Revised: 9 August 2014 / Accepted: 27 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract When children present with acute myelopathy manifested by sensory, motor, or bowel and bladder symptoms, MRI of the neuraxis with contrast agent is the most important imaging study to obtain. Although occasionally normal, MRI often demonstrates signal abnormality within the spinal cord. Classically, longitudinally extensive transverse myelitis (≥3 vertebral bodies in length) has been described with CME activity This article has been selected as the CME activity for the current month. Please visit the SPR Web site at www.pedrad.org on the Education page and follow the instructions to complete this CME activity. D. E. Sorte Division of Interventional Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, MD, USA A. Poretti : T. A. G. M. Huisman Section of Pediatric Neuroradiology, Division of Pediatric Radiology, The Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, MD, USA S. D. Newsome Department of Neurology, Division of Neuroimmunology, Johns Hopkins University, Baltimore, MD, USA E. Boltshauser Department of Neuropediatrics, University of Zurich, Zurich, Switzerland I. Izbudak (*) Section of Pediatric Neuroradiology, Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, 600 N. Wolfe St., Phipps B-126-B, Baltimore, MD 21287-0842, USA e-mail: [email protected]
neuromyelitis optica (NMO), but alternative diagnoses should be considered. This pictorial essay reviews the differential diagnoses that may present with longitudinally extensive spinal cord signal abnormalities. Multiple inflammatory, infectious, vascular, metabolic and neurodegenerative etiologies can present with a myelopathy. Thus, radiologists can assist in the diagnosis by familiarizing themselves with the spectrum of diseases in childhood that result in longitudinally extensive signal abnormalities in the absence of trauma. Keywords Neuromyelitis optica . Transverse myelitis . Longitudinally extensive transverse myelitis . Acute disseminated encephalomyelitis . Spinal cord . Myelopathy . Magnetic resonance imaging . Child
Introduction Intramedullary spinal cord lesions in children are rare but can result in profound morbidity. Establishing an accurate diagnosis is critical for pediatric patients who present with myelopathy. We explore the differential diagnoses of children who present with longitudinally extensive, intramedullary MRI signal abnormality in the spinal cord and myelopathy. We prefer to use the term longitudinally extensive myelopathy (LEM) because “myelitis” implies inflammation only. Traditionally, longitudinally extensive transverse myelitis (LETM) was described in the setting of neuromyelitis optica (NMO); however other inflammatory, infectious, vascular, metabolic and degenerative disorders can have a similar MRI appearance and clinical presentation [1–3]. Intramedullary tumors, relatively common in the pediatric population, can mimic LEM. Radiation myelitis can also present with LEM. Although trauma can produce similar longitudinally extensive signal abnormality (variable T2 signal and possible T1hyperintensity), the clinical history usually leads to the correct
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diagnosis of cord contusion; therefore, this topic is not reviewed here. Longitudinally extensive signal abnormality on MRI, or its commonly used clinical correlate LETM, is defined as T2hyperintense intramedullary signal in the spinal cord with craniocaudal extent spanning three or more vertebral body heights. On axial images the signal abnormality may involve the central cord with sparing of the periphery or the entire cross-sectional cord, the anterior horns, the lateral columns or the dorsal columns, or demonstrate patchy, randomly distributed signal abnormality [4]. The clinical classification of central nervous system (CNS) inflammatory disorders is evolving but we use the most recent pediatric consensus criteria (Table 1) [5]. The most common inflammatory diseases (primarily demyelinating diseases) that affect the spinal cord are immune-mediated, including multiple sclerosis (MS), neuromyelitis optica (NMO), acute disseminated encephalomyelitis (ADEM), and idiopathic and post-infectious/ post-vaccination transverse myelitis [6]. There is radiographic and clinical overlap for many of these entities [1, 3, 7]. Rare but other treatable causes of LEM such as infectious myelitis or spinal cord ischemia should be considered and excluded [2, 8]. Tumor should be referred for histopathological diagnosis via resection or biopsy when radiologic and clinical findings are predominately suggestive of a tumor. Herein, we present a pictorial essay illustrating common and rare causes of myelopathy in children.
Evaluation algorithm and imaging protocols When a patient presents with an acute myelopathy (neurogenic bladder and bowel dysfunction, sensory or motor deficits, or pain) with or without encephalopathy, contrast-enhanced spine MRI should be performed as soon as possible and before a lumbar puncture. Contrast-enhanced brain MRI is needed to document intracranial findings at presentation (e.g., demyelinating lesions), exclude stroke, and evaluate for emergencies such as herpes encephalitis. Contrast-enhanced spine MRI should be performed to exclude cord compression by an epidural hematoma, bone or disc, or tumor, in addition to evaluating spinal cord signal changes [9]. Compressive myelopathy is a surgical emergency and is not discussed in this review. Spine and brain MRI findings are summarized in Table 2 [10]. Spinal cord imaging should include T1, contrast-enhanced T1, T2, short tau inversion recovery (STIR) and, whenever possible, diffusion tensor imaging (DTI) [11]. If there is strong suspicion for spinal cord infarction or a vascular malformation after MRI, catheter digital subtraction spinal angiography (DSA) may be considered. During DSA, rotational angiography or flat-panel CT are used to characterize vascular lesions at our institution [12]. MRI of the brain should include standard T1, contrast-enhanced T1, T2, fluid attenuation inversion recovery (FLAIR) and DWI sequences. At our institution the MRI examinations are performed at either 1.5-T or 3-T magnet strength scanners from different manufacturers: Intera or Achieva (Philips Healthcare, Best, the Netherlands), GE (GE Healthcare, Milwaukee, WI), and
Table 1 International Pediatric Multiple Sclerosis Study Group criteria 2013 revisions* Disorder
2013 criteria*
Neuromyelitis optica (NMO)
Both required (not simultaneously) • Optic neuritis • Acute myelitis 2 of 3 supportive criteria • Contiguous spinal cord MRI lesion ≥3 vertebral segments • Brain MRI does not meet criteria for MS • Anti-aquaporin-4 IgG seropositive status Multiple sclerosis (MS) Any of the following • Two or more CNS clinical events without encephalopathy separated by more than 30 days • Single clinical event and MRI features meet McDonald criteria for DIS and DIT, only for children ≥12 and without an ADEM onset • ADEM followed after 3 months by a clinical event without encephalopathy, with new brain lesions consistent with MS on MRI Acute disseminated encephalomyelitis • A first polyfocal clinical CNS event with presumed inflammatory cause (ADEM) • Encephalopathy than cannot be explained by fever is present • MRI shows diffuse, poorly demarcated, >1–2-cm lesions involving predominately the cerebral white matter; rare if any T1-hypointense lesions; deep gray matter lesions can be present • No new symptoms, signs, or MRI findings 3 months after an incident of ADEM Clinically isolated syndrome (CIS) • A first monofocal or multifocal CNS demyelinating event without encephalopathy unless due to fever • Transverse myelitis can represent CIS * Adapted with permission from [5] CNS central nervous system, DIS dissemination in space, DIT dissemination in time, IgG immunoglobulin G
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Table 2 MRI features of diagnoses that present with longitudinally extensive myelopathy Diagnosis
Brain MRI
Spine MRI
Idiopathic transverse myelitis (ITM) Acute disseminated encephalomyelitis (ADEM) Neuromyelitis optica (NMO) Multiple sclerosis (MS)
T2 bright signal, usually >3 vertebral bodies in length T2 bright signal, usually >3 vertebral bodies in length
Acute viral myelitis Spinal cord infarct
Normal Large subcortical and deep white matter lesions. No T1-hypointense lesions 68% with brain lesions Well-demarcated lesions in the periventricular, juxtacortical, infratentorial white matter. T1 dark areas later Usually unaffected Normal
Vascular malformations
Normal
Vitamin deficiencies Tumors
Normal Normal
Radiation myelitis
Normal
T2 bright, characteristically LETM Short, eccentric lesions characteristic. Longitudinally extensive more likely in chronic MS, associated with cord atrophy T2 bright, cord swelling, enhancement T2 bright signal, may be normal in first 24 h, DWI/DTI is more sensitive Intradural flow voids, intramedullary flow voids, rarely hemorrhage, enhancing vessels Dorsal and lateral white matter T2 bright, no enhancement Marked cord expansion, usually enhances [10]. Hemorrhage or calcifications T2 bright, may enhance, T1 hyperintense vertebrae
DTI diffusion tensor imaging, DWI diffusion-weighted imaging, LETM longitudinally extensive transverse myelitis
Avanto, Trio, Verio, Aera, or Skyra, (Siemens Healthcare, Erlangen, Germany). Our protocols use weight-based dosing of Magnevist or Gadavist (Bayer, Whippany, NJ). As an example, the following cervical spine MRI protocol with diffusion tensor imaging might be used, including a sagittal T1-W sequence with repetition time (TR) 404 ms and echo time (TE) 12 ms, matrix size 320×240, field of view (FOV) 22×22 cm and section thickness/spacing 3.0/3.3 mm; an axial T2-W sequence with TR/TE 5,180/98 ms, matrix size 320×240, FOV 20×20 cm and section thickness/spacing 4.0/4.4 mm; a sagittal short tau inversion recovery (STIR) sequence with TR/TE 4,570/61 ms, inversion recovery (IR) 160 ms, section thickness/spacing 3.0/3.3 mm, FOV 22×22 cm and matrix size 256×192; and a diffusion tensor multishot echoplanar sequence with b values of 750 to 1,000. When interpreting an MRI in a child with myelopathy, the radiologist must first establish the absence of cord compression and then seek the most likely diagnosis. The acuity of symptom onset, age of the patient, spine imaging findings, brain imaging, cerebrospinal fluid and serum laboratory values, and associated abnormalities will help narrow the differential diagnosis (Table 3, [13–19]). Occasionally, the initial MRI is normal. Repeat imaging may be helpful in this setting.
Differential diagnosis: inflammatory Neuromyelitis optica Neuromyelitis optica (NMO), previously known as Devic’s disease, is a severe CNS inflammatory disease that is autoimmune in nature and targets the spinal cord and optic nerves
(Fig. 1) [20]. NMO was once thought to be a severe form of multiple sclerosis; however its clinical, radiologic and pathological features differ greatly. NMO is underreported, although more recently a highly specific serological marker for NMO, NMO-IgG (anti-aquaporin-4 antibodies), allows more accurate diagnosis (sensitivity 70–80% and specificity >99%) [21, 22]. The finding of LETM was originally described in neuromyelitis optica. Diagnostic criteria developed to help aid in the diagnosis of NMO were revised in 2006 [23]. The 2013 pediatric-revised criteria (Table 1) require an individual to have two absolute criteria present (optic neuritis and acute myelitis), and at least two of three supportive criteria (LETM, NMO-IgG seropositive status, and/or brain MRI that does not meet criteria for multiple sclerosis) to make a definitive diagnosis [5, 23, 24]. Brain lesions can be present in the supratentorial regions or brainstem (typically around the fourth ventricle or hypothalamus), a departure from older criteria [25]. If an individual experiences a suspected inflammatory longitudinally extended myelopathy, serum testing for NMO-IgG is recommended at first presentation [26]. Acute disseminated encephalomyelitis (ADEM) ADEM has significant overlap in its imaging appearance with NMO and pediatric MS (Fig. 2) [5, 8]. The presence of encephalopathy, defined as behavioral changes such as confusion or excessive irritability or altered level of consciousness (lethargy or coma) is required to confidently diagnose ADEM. The adult diagnostic criteria were revised in 2007 [27]. The 2013 pediatric diagnostic criteria (Table 1) [5] require all of the following: encephalopathy not explained by fever, a polyfocal CNS clinical event and brain MRI with
Bimodal peaks in children (0–2 years and 5–17 years) [13]
Idiopathic transverse myelitis (ITM)
Usually adults unless cardiac Not reported Sudden arrest or systemic hypotension Bimodal, infants and adolescents Rare; spinal cord AVM most Sudden if intramedullary common (44%), followed by hemorrhage, more insidious perimedullary AVF (24%) [19] if venous steal or mass effect Much more common in adults Incidence not known in children Slowly progressive Depends on treatment, usually Normal reversible Children and young adults Rare, 35% of intraspinal tumors Insidious (high-grade have a Related to treatment are intramedullary shorter prodrome with mean 4.5 months) Related to radiation, no other Early up to 10% following spinal Early, mild form: 2–6 months Early form usually resolves Elevated protein, not helpful in specific age irradiation, after radiation; late severe over several months, late diagnosis late is exceedingly rare form 6–12 months after progresses inexorably radiation
Spinal cord infarct
AVF arteriovenous fistula, AVM arteriovenous malformation, CSF cerebrospinal fluid, IgG immunoglobulin G, PCR polymerase chain reaction
Radiation myelitis
Tumors
Vitamin deficiencies
Vascular malformations
Varies geographically, much less Hours to days, may be common than ITM associated with fever
Oligoclonal IgG bands (8–92% positive in children) and pleocytosis (33–73% of children) [18] Variable PCR-positive for specific organism, protein and cell count markedly elevated 50% recover in adults, pediatric Normal or mildly elevated protein duration unknown Depends on treatment Normal or mildly elevated protein
Unknown
Multiple sclerosis (MS)
Variable
Pleocytosis and elevated protein. May be normal
Abnormal in half. Lymphocytosis and elevated protein
CSF
Acute viral myelitis
3
recover, 1 3 moderate disability, 1 3 severe disability [14] 2–4 weeks 1
Clinical course
Progressive or relapsing/ remitting Children more likely to present Relapsing-remitting typical with isolated optic neuritis in children
Variable
Encephalopathy 4–13 days after infection or vaccination
Progression to nadir between 4 h and 21 days
Symptom onset
Older children and young adults 0.032–3.1 per 100,000, 0.5 new per million per year [16] 5% of cases
PICTORIAL ESSAY
Longitudinally extensive myelopathy in children Danielle Eckart Sorte & Andrea Poretti & Scott D. Newsome & Eugen Boltshauser & Thierry A. G. M. Huisman & Izlem Izbudak
Received: 11 March 2014 / Revised: 9 August 2014 / Accepted: 27 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract When children present with acute myelopathy manifested by sensory, motor, or bowel and bladder symptoms, MRI of the neuraxis with contrast agent is the most important imaging study to obtain. Although occasionally normal, MRI often demonstrates signal abnormality within the spinal cord. Classically, longitudinally extensive transverse myelitis (≥3 vertebral bodies in length) has been described with CME activity This article has been selected as the CME activity for the current month. Please visit the SPR Web site at www.pedrad.org on the Education page and follow the instructions to complete this CME activity. D. E. Sorte Division of Interventional Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, MD, USA A. Poretti : T. A. G. M. Huisman Section of Pediatric Neuroradiology, Division of Pediatric Radiology, The Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, MD, USA S. D. Newsome Department of Neurology, Division of Neuroimmunology, Johns Hopkins University, Baltimore, MD, USA E. Boltshauser Department of Neuropediatrics, University of Zurich, Zurich, Switzerland I. Izbudak (*) Section of Pediatric Neuroradiology, Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, 600 N. Wolfe St., Phipps B-126-B, Baltimore, MD 21287-0842, USA e-mail: [email protected]
neuromyelitis optica (NMO), but alternative diagnoses should be considered. This pictorial essay reviews the differential diagnoses that may present with longitudinally extensive spinal cord signal abnormalities. Multiple inflammatory, infectious, vascular, metabolic and neurodegenerative etiologies can present with a myelopathy. Thus, radiologists can assist in the diagnosis by familiarizing themselves with the spectrum of diseases in childhood that result in longitudinally extensive signal abnormalities in the absence of trauma. Keywords Neuromyelitis optica . Transverse myelitis . Longitudinally extensive transverse myelitis . Acute disseminated encephalomyelitis . Spinal cord . Myelopathy . Magnetic resonance imaging . Child
Introduction Intramedullary spinal cord lesions in children are rare but can result in profound morbidity. Establishing an accurate diagnosis is critical for pediatric patients who present with myelopathy. We explore the differential diagnoses of children who present with longitudinally extensive, intramedullary MRI signal abnormality in the spinal cord and myelopathy. We prefer to use the term longitudinally extensive myelopathy (LEM) because “myelitis” implies inflammation only. Traditionally, longitudinally extensive transverse myelitis (LETM) was described in the setting of neuromyelitis optica (NMO); however other inflammatory, infectious, vascular, metabolic and degenerative disorders can have a similar MRI appearance and clinical presentation [1–3]. Intramedullary tumors, relatively common in the pediatric population, can mimic LEM. Radiation myelitis can also present with LEM. Although trauma can produce similar longitudinally extensive signal abnormality (variable T2 signal and possible T1hyperintensity), the clinical history usually leads to the correct
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diagnosis of cord contusion; therefore, this topic is not reviewed here. Longitudinally extensive signal abnormality on MRI, or its commonly used clinical correlate LETM, is defined as T2hyperintense intramedullary signal in the spinal cord with craniocaudal extent spanning three or more vertebral body heights. On axial images the signal abnormality may involve the central cord with sparing of the periphery or the entire cross-sectional cord, the anterior horns, the lateral columns or the dorsal columns, or demonstrate patchy, randomly distributed signal abnormality [4]. The clinical classification of central nervous system (CNS) inflammatory disorders is evolving but we use the most recent pediatric consensus criteria (Table 1) [5]. The most common inflammatory diseases (primarily demyelinating diseases) that affect the spinal cord are immune-mediated, including multiple sclerosis (MS), neuromyelitis optica (NMO), acute disseminated encephalomyelitis (ADEM), and idiopathic and post-infectious/ post-vaccination transverse myelitis [6]. There is radiographic and clinical overlap for many of these entities [1, 3, 7]. Rare but other treatable causes of LEM such as infectious myelitis or spinal cord ischemia should be considered and excluded [2, 8]. Tumor should be referred for histopathological diagnosis via resection or biopsy when radiologic and clinical findings are predominately suggestive of a tumor. Herein, we present a pictorial essay illustrating common and rare causes of myelopathy in children.
Evaluation algorithm and imaging protocols When a patient presents with an acute myelopathy (neurogenic bladder and bowel dysfunction, sensory or motor deficits, or pain) with or without encephalopathy, contrast-enhanced spine MRI should be performed as soon as possible and before a lumbar puncture. Contrast-enhanced brain MRI is needed to document intracranial findings at presentation (e.g., demyelinating lesions), exclude stroke, and evaluate for emergencies such as herpes encephalitis. Contrast-enhanced spine MRI should be performed to exclude cord compression by an epidural hematoma, bone or disc, or tumor, in addition to evaluating spinal cord signal changes [9]. Compressive myelopathy is a surgical emergency and is not discussed in this review. Spine and brain MRI findings are summarized in Table 2 [10]. Spinal cord imaging should include T1, contrast-enhanced T1, T2, short tau inversion recovery (STIR) and, whenever possible, diffusion tensor imaging (DTI) [11]. If there is strong suspicion for spinal cord infarction or a vascular malformation after MRI, catheter digital subtraction spinal angiography (DSA) may be considered. During DSA, rotational angiography or flat-panel CT are used to characterize vascular lesions at our institution [12]. MRI of the brain should include standard T1, contrast-enhanced T1, T2, fluid attenuation inversion recovery (FLAIR) and DWI sequences. At our institution the MRI examinations are performed at either 1.5-T or 3-T magnet strength scanners from different manufacturers: Intera or Achieva (Philips Healthcare, Best, the Netherlands), GE (GE Healthcare, Milwaukee, WI), and
Table 1 International Pediatric Multiple Sclerosis Study Group criteria 2013 revisions* Disorder
2013 criteria*
Neuromyelitis optica (NMO)
Both required (not simultaneously) • Optic neuritis • Acute myelitis 2 of 3 supportive criteria • Contiguous spinal cord MRI lesion ≥3 vertebral segments • Brain MRI does not meet criteria for MS • Anti-aquaporin-4 IgG seropositive status Multiple sclerosis (MS) Any of the following • Two or more CNS clinical events without encephalopathy separated by more than 30 days • Single clinical event and MRI features meet McDonald criteria for DIS and DIT, only for children ≥12 and without an ADEM onset • ADEM followed after 3 months by a clinical event without encephalopathy, with new brain lesions consistent with MS on MRI Acute disseminated encephalomyelitis • A first polyfocal clinical CNS event with presumed inflammatory cause (ADEM) • Encephalopathy than cannot be explained by fever is present • MRI shows diffuse, poorly demarcated, >1–2-cm lesions involving predominately the cerebral white matter; rare if any T1-hypointense lesions; deep gray matter lesions can be present • No new symptoms, signs, or MRI findings 3 months after an incident of ADEM Clinically isolated syndrome (CIS) • A first monofocal or multifocal CNS demyelinating event without encephalopathy unless due to fever • Transverse myelitis can represent CIS * Adapted with permission from [5] CNS central nervous system, DIS dissemination in space, DIT dissemination in time, IgG immunoglobulin G
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Table 2 MRI features of diagnoses that present with longitudinally extensive myelopathy Diagnosis
Brain MRI
Spine MRI
Idiopathic transverse myelitis (ITM) Acute disseminated encephalomyelitis (ADEM) Neuromyelitis optica (NMO) Multiple sclerosis (MS)
T2 bright signal, usually >3 vertebral bodies in length T2 bright signal, usually >3 vertebral bodies in length
Acute viral myelitis Spinal cord infarct
Normal Large subcortical and deep white matter lesions. No T1-hypointense lesions 68% with brain lesions Well-demarcated lesions in the periventricular, juxtacortical, infratentorial white matter. T1 dark areas later Usually unaffected Normal
Vascular malformations
Normal
Vitamin deficiencies Tumors
Normal Normal
Radiation myelitis
Normal
T2 bright, characteristically LETM Short, eccentric lesions characteristic. Longitudinally extensive more likely in chronic MS, associated with cord atrophy T2 bright, cord swelling, enhancement T2 bright signal, may be normal in first 24 h, DWI/DTI is more sensitive Intradural flow voids, intramedullary flow voids, rarely hemorrhage, enhancing vessels Dorsal and lateral white matter T2 bright, no enhancement Marked cord expansion, usually enhances [10]. Hemorrhage or calcifications T2 bright, may enhance, T1 hyperintense vertebrae
DTI diffusion tensor imaging, DWI diffusion-weighted imaging, LETM longitudinally extensive transverse myelitis
Avanto, Trio, Verio, Aera, or Skyra, (Siemens Healthcare, Erlangen, Germany). Our protocols use weight-based dosing of Magnevist or Gadavist (Bayer, Whippany, NJ). As an example, the following cervical spine MRI protocol with diffusion tensor imaging might be used, including a sagittal T1-W sequence with repetition time (TR) 404 ms and echo time (TE) 12 ms, matrix size 320×240, field of view (FOV) 22×22 cm and section thickness/spacing 3.0/3.3 mm; an axial T2-W sequence with TR/TE 5,180/98 ms, matrix size 320×240, FOV 20×20 cm and section thickness/spacing 4.0/4.4 mm; a sagittal short tau inversion recovery (STIR) sequence with TR/TE 4,570/61 ms, inversion recovery (IR) 160 ms, section thickness/spacing 3.0/3.3 mm, FOV 22×22 cm and matrix size 256×192; and a diffusion tensor multishot echoplanar sequence with b values of 750 to 1,000. When interpreting an MRI in a child with myelopathy, the radiologist must first establish the absence of cord compression and then seek the most likely diagnosis. The acuity of symptom onset, age of the patient, spine imaging findings, brain imaging, cerebrospinal fluid and serum laboratory values, and associated abnormalities will help narrow the differential diagnosis (Table 3, [13–19]). Occasionally, the initial MRI is normal. Repeat imaging may be helpful in this setting.
Differential diagnosis: inflammatory Neuromyelitis optica Neuromyelitis optica (NMO), previously known as Devic’s disease, is a severe CNS inflammatory disease that is autoimmune in nature and targets the spinal cord and optic nerves
(Fig. 1) [20]. NMO was once thought to be a severe form of multiple sclerosis; however its clinical, radiologic and pathological features differ greatly. NMO is underreported, although more recently a highly specific serological marker for NMO, NMO-IgG (anti-aquaporin-4 antibodies), allows more accurate diagnosis (sensitivity 70–80% and specificity >99%) [21, 22]. The finding of LETM was originally described in neuromyelitis optica. Diagnostic criteria developed to help aid in the diagnosis of NMO were revised in 2006 [23]. The 2013 pediatric-revised criteria (Table 1) require an individual to have two absolute criteria present (optic neuritis and acute myelitis), and at least two of three supportive criteria (LETM, NMO-IgG seropositive status, and/or brain MRI that does not meet criteria for multiple sclerosis) to make a definitive diagnosis [5, 23, 24]. Brain lesions can be present in the supratentorial regions or brainstem (typically around the fourth ventricle or hypothalamus), a departure from older criteria [25]. If an individual experiences a suspected inflammatory longitudinally extended myelopathy, serum testing for NMO-IgG is recommended at first presentation [26]. Acute disseminated encephalomyelitis (ADEM) ADEM has significant overlap in its imaging appearance with NMO and pediatric MS (Fig. 2) [5, 8]. The presence of encephalopathy, defined as behavioral changes such as confusion or excessive irritability or altered level of consciousness (lethargy or coma) is required to confidently diagnose ADEM. The adult diagnostic criteria were revised in 2007 [27]. The 2013 pediatric diagnostic criteria (Table 1) [5] require all of the following: encephalopathy not explained by fever, a polyfocal CNS clinical event and brain MRI with
Bimodal peaks in children (0–2 years and 5–17 years) [13]
Idiopathic transverse myelitis (ITM)
Usually adults unless cardiac Not reported Sudden arrest or systemic hypotension Bimodal, infants and adolescents Rare; spinal cord AVM most Sudden if intramedullary common (44%), followed by hemorrhage, more insidious perimedullary AVF (24%) [19] if venous steal or mass effect Much more common in adults Incidence not known in children Slowly progressive Depends on treatment, usually Normal reversible Children and young adults Rare, 35% of intraspinal tumors Insidious (high-grade have a Related to treatment are intramedullary shorter prodrome with mean 4.5 months) Related to radiation, no other Early up to 10% following spinal Early, mild form: 2–6 months Early form usually resolves Elevated protein, not helpful in specific age irradiation, after radiation; late severe over several months, late diagnosis late is exceedingly rare form 6–12 months after progresses inexorably radiation
Spinal cord infarct
AVF arteriovenous fistula, AVM arteriovenous malformation, CSF cerebrospinal fluid, IgG immunoglobulin G, PCR polymerase chain reaction
Radiation myelitis
Tumors
Vitamin deficiencies
Vascular malformations
Varies geographically, much less Hours to days, may be common than ITM associated with fever
Oligoclonal IgG bands (8–92% positive in children) and pleocytosis (33–73% of children) [18] Variable PCR-positive for specific organism, protein and cell count markedly elevated 50% recover in adults, pediatric Normal or mildly elevated protein duration unknown Depends on treatment Normal or mildly elevated protein
Unknown
Multiple sclerosis (MS)
Variable
Pleocytosis and elevated protein. May be normal
Abnormal in half. Lymphocytosis and elevated protein
CSF
Acute viral myelitis
3
recover, 1 3 moderate disability, 1 3 severe disability [14] 2–4 weeks 1
Clinical course
Progressive or relapsing/ remitting Children more likely to present Relapsing-remitting typical with isolated optic neuritis in children
Variable
Encephalopathy 4–13 days after infection or vaccination
Progression to nadir between 4 h and 21 days
Symptom onset
Older children and young adults 0.032–3.1 per 100,000, 0.5 new per million per year [16] 5% of cases
