Mimics and Rare Presentations of Pediatric Demyelination





This article reviews the features that should prompt consideration of diseases that mimic acquired demyelinating syndromes and multiple sclerosis using vignettes to highlight unusual clinical and radiologic features. Cases of transverse myelitis, spinal infarction, acute disseminated encephalomyelitis, fever-induced refractory epileptic encephalopathy in school-aged children, small-vessel vasculitis, Griscelli syndrome type 2, cysticercosis, vitamin B12 deficiency, and chronic relapsing inflammatory optic neuropathy are presented.


Key points








  • Demyelination of the optic nerves, spine, and brain may occur as a monophasic or transiently multiphasic illness without chronic relapsing demyelination typical of multiple sclerosis (MS). To date, no biomarker or magnetic resonance (MR) imaging pattern reliably identifies such individuals.



  • Asymptomatic brain lesions outside of the optic nerve or spinal cord strongly favor MS.



  • Anterior horn cell involvement can be prominent in both vascular and demyelinating disorders of the spinal cord.



  • Diffusion restriction can be detected in the spinal cord but it is not pathognomonic for infarction in this region; diffusion restriction within the cord has been reported in transverse myelitis.



  • Ring enhancement differentials include infections, granulomatous disease and neoplasms, but can be seen in patients with demyelination. Open-ring enhancement is more typical of demyelinating lesions. When open-ring sign is present in the brain, demyelination is much more likely than neoplasm or infection.




Introduction


Acquired demyelinating syndromes (ADS) of the central nervous system (CNS) are characterized by acute neurologic deficits, magnetic resonance (MR) imaging findings of focal or multifocal areas of abnormal signal on T2-weighted images in the brain, optic nerves, or spinal cord, and a response to corticosteroids. The clinical features of ADS relate to the localization of areas of inflammation. Common ADS presentations include optic neuritis (ON), transverse myelitis (TM), brainstem syndromes, polyfocal neurologic deficits, and polyfocal deficits accompanied by encephalopathy (termed acute disseminated encephalomyelitis [ADEM]). For some patients, ADS occurs as a monophasic illness, whereas for others it represents the first clinical manifestation of multiple sclerosis (MS). Table 1 provides a diagnostic evaluation for children suspected of having an acquired demyelinating syndrome or MS.



Table 1

Diagnostic evaluation for children evaluated for suspected acquired demyelinating syndromes and multiple sclerosis
































The following investigations should be performed, as clinically indicated:
MR imaging Brain MR imaging in all children
Spine MR imaging in all children with clinical spine involvement
Orbital MR imaging for children with visual loss
The following MR imaging sequences are suggested:
FLAIR or T2-weighted sequences in at least 2 planes
Pre- and postgadolinium T1-weighted images
Diffusion-weighted sequences
Evoked potentials VEPs
SSEPs
Laboratory screening for NMO and MAS Serum NMO IgG
CSF NMO IgG (if serum negative)
Ferritin
Triglycerides
Infection screening CBC + differential
Serum viral serologies (EBV, mycoplasma, HSV serology)
VDRL
Lyme disease (seasonal)
Cysticercosis (based on travel to endemic areas only)
HTLV (based on travel to endemic areas only)
Endocrine TSH, T4, anti-TPO antibodies if Hashimoto encephalopathy is a consideration
Mitochondrial lactate serum + CSF Pyruvate; if higher than normal lactate, calculate lactate to pyruvate ratio
DNA studies, skin and muscle biopsy if mitochondrial disease strongly suspected
Rheumatologic disease ESR, CRP
ANA, dsDNA
Anticardiolipin and antiphospholipid antibodies
Angiotensin-converting enzyme
CXR (if sarcoidosis is strongly suspected)
Nutritional Vitamin B12 (serum)
25-hydroxyvitamin D (25(OH)D)
CSF studies Glucose
Lactate
Protein
Cell count
Culture and sensitivity, Gram stain when appropriate
Oligoclonal bands (compared with concurrently obtained serum) a
CSF viral cultures + PCR herpesviruses
Cytology (if indicated)

Abbreviations: ANA, antinuclear antibody; CBC, complete blood count; CRP, C-reactive protein; CSF, cerebrospinal fluid; CT, computed tomography; CXR, chest radiograph; DNA, deoxyribonucleic acid; dsDNA, double-stranded deoxyribonucleic acid; EBV, Epstein-Barr virus; ESR, erythrocyte sedimentation rate; FLAIR, fluid-attenuated inversion recovery; HSV, herpes simplex virus; HTLV, human T-lymphotropic virus; IgG, immunoglobulin G; MAS, macrophage activation syndrome; NMO, neuromyelitis optica; PCR, polymerase chain reaction; SSEP, somatosensory evoked potential; T4, thyroxine test; TPO, Thyroid peroxidase; TSH, thyroid-stimulating hormone; VDRL, venereal disease research laboratory; VEP, visual evoked potential.

a The accuracy of oligoclonal band measurement depends on the diagnostic test used and on the experience of the laboratory performing the test. Isoelectric focusing has the highest sensitivity.



Although well characterized clinically and radiologically, the clinical features of acute demyelination are not specific. Clinicians must be alert to other neurologic disorders with similar signs. The diagnosis of monophasic ADS and MS requires exclusion of other diagnoses. Table 2 highlights some of the MR imaging features that should prompt clinicians to consider diagnoses other than ADS and MS. This article reviews the features that should prompt consideration of diseases that mimic ADS and MS, using vignettes to highlight unusual clinical and radiologic features.



Table 2

MR imaging red flags for the diagnosis of children with acquired demyelinating syndromes
















MR imaging Leptomeningeal enhancement SVcPACNS
Infection
Tumor
HLH
Leptomeningeal enhancement is not a feature of MS in adults, and emerged as a red flag for vasculitic or malignant processes in the pediatric cohort
Lesion expansion Tumor
Lymphoma
PML
Sarcoidosis
Increased size of T2 lesions on serial imaging is well recognized in MS, although this should always prompt consideration of malignancy. Increasing size of a white matter–predominant lesion without lesion enhancement in a patient treated with immunosuppressant therapy (or a patient with known HIV) should prompt consideration of PML. PML is a risk for MS patients exposed to more intense immunosuppressive therapies
Hemorrhage ANE
Stroke
Cerebellitis
AHLE
Large-vessel CNS vasculitis
SVcPACNS
Although susceptibility-weighted imaging reveals tiny microfoci of hemosiderin in MS patients, hemorrhage large enough to be visible on conventional MR imaging sequences is not a feature of ADS or MS, and should prompt consideration of disorders in which the cerebral vasculature is specifically involved

Abbreviations: ADS, acquired demyelinating syndrome; AHLE, acute hemorrhagic leukoencephalitis; CNS, central nervous system; HIV, human immunodeficiency virus; HLH, hemophagocytic lymphohistiocytosis; MS, multiple sclerosis; PML, progressive multifocal leukoencephalopathy; SVcPACNS, small-vessel childhood primary angiitis of the central nervous system.


Typical features of pediatric demyelination on MR imaging


As detailed in the article elsewhere in this issue by Verhey and colleagues, MR imaging plays an increasingly important role in the diagnosis of monophasic ADS and MS. The MR imaging appearance of childhood MS is characterized by multiple white matter lesions, which are of increased signal on T2-weighted and fluid-attenuated inversion recovery (FLAIR)-weighted images. Lesions may enhance with administration of gadolinium. However, enhancement may be absent even in acute lesions. Areas of hypointensity on T1-weighted images may reflect acute lesions or areas of long-standing regional tissue loss. Younger children often exhibit larger and more diffuse, bilateral white matter lesions with ill-defined borders that are frequently confluent at disease onset. Despite the important role played by MR imaging in the diagnosis of ADS and MS, it must be used in conjunction with clinical features.


Distinguishing acute demyelination from acute vascular insult in the spinal cord


Acute neurologic deficits prompt consideration of vascular occlusion and cerebral or spinal cord infarction, key differentials of ADS. In patients with infarction, the rapid development over minutes to hours of maximal deficit favors vascular occlusion. However, acute deficits can occur in patients with ADS, particularly those with TM. MR imaging lesions that conform to specific vascular distributions in the brain or anterior spinal artery of the spinal cord would support vascular causes. As emphasized by the following 2 vignettes, distinguishing vascular from demyelinating disease can be difficult.



CLINICAL VIGNETTE


An 11-year-old girl presented with acute onset of back pain, shooting pain down her legs, loss of bowel and bladder control, and 4-limb weakness that developed over 1 to 2 hours. Weakness then worsened progressively to complete paralysis over the next 5 days with concomitant respiratory failure. MR imaging of the spine on day of onset revealed a focal hyperintensity on T2-weighted images in the anterior aspect of the cervical cord, more prominently involving the anterior horn cells, extending from the C3 level to the T2/T3 level with no diffusion restriction ( Fig. 1 A, B). Repeat MR imaging on day 5 showed expansion of the cord from C3 to T2. MR imaging of the brain was normal. Spinal fluid analysis revealed a normal protein and cell count. Serum coagulation profile was normal.




Fig. 1


Axial T2 image ( A ) on day of onset of symptoms shows focal hyperintensity in the anterior horn cells bilaterally. There was no diffusion restriction (not shown). Sagittal T2 image ( B ) on the same day shows the longitudinal extent of the abnormal signal in the anterior portion of the cord. Sagittal T2 image 18 months after onset ( C ) show residual hyperintensity with associated volume loss in the upper spinal cord.


The prominent back pain and initial rapid progression prompted consideration of spinal cord infarct, whereas the subsequent progressive worsening and delayed spinal cord expansion favored a demyelinating process. The extensive lesion length led to serologic evaluation for aquaporin-4 antibodies (results were negative), as longitudinally extensive TM is a core feature of neuromyelitis optica (NMO). Treatment with corticosteroids did not lead to neurologic improvement. Plasma exchange (PLEX) was initiated, and within 48 hours she was able to breathe independently. A course of 5 exchanges was completed. After 5 weeks in the intensive care unit (ICU), she was discharged to a rehabilitation hospital where she continued inpatient treatment for 4 months. Eighteen months after onset, she has moderate hand weakness and minor bladder-control issues, but has regained all lower extremity and proximal upper limb strength. Follow-up MR imaging reveals residual intramedullary T2 hyperintensity with associated volume loss of the upper cervical cord ( Fig. 1 C). Recovery and symptoms were ultimately deemed to be consistent with severe TM.



CLINICAL VIGNETTE


A 14-year-old girl developed acute-onset bilateral lower extremity weakness, numbness, and bladder incontinence that progressed to maximal initial deficit over the course of 2 hours. Her history was remarkable for a mild back injury that occurred 5 months prior during training for competitive gymnastics. At presentation to hospital, examination was remarkable for flaccid tone and absent reflexes in the lower extremities, bilateral lower limb weakness, and a sensory level at T4/5. MR imaging of the spine demonstrated spinal cord swelling in the distal lumbar to sacral segments with abnormal intramedullary signal ( Fig. 2 A) and diffusion restriction ( Fig. 2 B, C). In addition, a disc herniation was noted at T12-L1 level (see Fig. 2 A). Spinal fluid analysis was unremarkable. The focal disc protrusion and diffusion restriction imaged on MR raised the possibility of fibrocartilaginous disc embolism. Treatment included low molecular weight heparin for possible anterior spinal artery stroke and a 5-day course of intravenous methylprednisolone to address a possible inflammatory component. Three days after onset, when performing a Valsalva maneuver in the context of constipation, she developed acute worsening of her lower limb weakness, leading to complete paraplegia. MR imaging demonstrated extension longitudinally of abnormal T2 signal hyperintensity from T11 to the mid L1 level ( Fig. 2 D), and extension transversely to involve the anterior horn cells ( Fig. 2 E). The diffusion-weighted images again showed some restriction of diffusion. The patient was discharged to a rehabilitation hospital for 4 months of inpatient treatment, has experienced minimal improvement, and remains wheelchair dependent. The very rapid progression to maximal deficit, prior history of back pain, MR imaging evidence of disc herniation, and poor recovery favor a diagnosis of fibrocartilaginous embolic spinal cord infarct.


Jan 3, 2022 | Posted by in NEUROLOGICAL IMAGING | Comments Off on Mimics and Rare Presentations of Pediatric Demyelination
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