Supplementary Table 1 Existing literature of radiological findings associated with Balό’s concentric sclerosis.
Reference / Clinical characteristics and treatment / Conventional neuroimaging (T1-weighted and T2-weighted) / Diffusion-weighted imaging (DWI) / Magnetic resonance spectroscopy (MRS)Spiegel M et al. (1989)1 / Presentation: 39-year-old man with mental deficits, mild spastic tetraparesis, dysarthria, left central facial palsy and gait disturbances
Treatment: intravenous methylprednisolone
Outcome: improved gait, facial palsy and mental deficit / Initial imaging: multiple concentric white matter lesions consistent with BCS
10 weeks later: reduction in the size and number of the lesions / Not performed / Not performed
Hanemann CO et al. (1993)2 / Presentation: 32-year-old woman with left hemiparesis, urinary retention, fatigue and mental slowing
Diagnosis: biopsy-proven BCS
Treatment: intravenous dexamethasone followed by mitoxantrone
Outcome: improvement in disability / Initial imaging: hypointense concentric lesions in right frontal, left occipital and left centroparietal lobes
6 weeks later: reduction in size of all lesions
6 months later: additional reduction in all lesions; no enhancement / Not performed / Not performed
Revel MP et al. (1993)3 / Presentation: 22-year-old woman with progressive left hemiparesis and right lateral gaze palsy
Treatment: intravenous methylprednisolone followed by oral taper
Outcome: mild left hemiparesis 6 months later / Initial imaging: multiple high signal foci with alternating low and high signal areas; one lesion enhanced / Not performed / Not performed
Revel MP et al. (1993)3 / Presentation: 27-year-old man with right hemiparesis and dysarthria
Treatment: none
Outcome: spontaneous recovery within 10 days; right facial paresis 3 months later / Initial imaging: periventricular white matter hyperintensities with concentric foci / Not performed / Not performed
Tersegno MM and Reich DR (1993)4 / Presentation: 32-year-old woman with sudden left paresthesias
Diagnosis: autopsy-proven BCS
Treatment: steroids
Outcome: clinical progression followed by death 1 year later / Initial imaging: large right parietal mass with concentric rings and peripheral enhancement
8 months later: bilateral frontal lesions with concentric rings; atrophy in region of initial lesion / Not performed / Not performed
Gharagozloo et al. (1994)5 / Presentation: 32-year-old woman with progressive left hemiparesis hemiplegia, and left homonymous heminanopsia over 2 weeks
Diagnosis: autopsy-confirmed BCS
Treatment: intravenous steroids
Outcome: initial improvement followed by increasing weakness and apathy with relentless progression until death 1 year after symptom onset / Initial imaging: large right parietal lesion with mass effect and marginal enhancement
Approximately 9 months later: multiple large lesions with concentric ring appearance / Not performed / Not performed
Louboutin JP and Elie B (1995)6 / Presentation: 16-year-old boy with acute bilateral visual impairment, headache, ataxia, right hemisensory loss, alteration of consciousness, and vertigo
Diagnosis: biopsy-proven BCS
Treatment: intravenous prednisone (initially), followed by intravenous cyclophosphamide and ACTH (after worsening), followed by azathioprine (maintenance)
Outcome: mild improvement after steroids followed by worsening to include left hemiparesis; further improvement after cyclophosphamide and ACTH and sustained improvement after starting azathioprine / Initial imaging: multiple white matter lesions of varying size with concentricity in a 3cm right frontal lesion
4 months later: all lesions smaller; concentric pattern still evident in right frontal lesion
16 months after presentation: loss of concentric pattern
2 years after presentation: one new lesion near right occipital horn / Not performed / Not performed
Chen CJ et al. (1996)7 / Presentation: 27-year-old woman with rapidly progressive right hemiparesis
Diagnosis: biopsy-proven BCS
Treatment: none
Outcome: nearly complete recovery after 3 months with no weakness after 1 year / Initial imaging: multiple concentric white matter lesions
10 days later: bifrontal alternating isointense and hypointense or hyperintense rings with partial enhancement
20 days later: concentric lesion with partial enhancement in frontal lobe
3 months later: marked resolution of all lesions / Not performed / Not performed
Chen CJ et al. (1996)8 / Presentation: 54-year-old man with unsteady gait, progressing to hiccups, slurred speech and choking within 2 weeks
Treatment: corticosteroids for 2 weeks
Outcome: full recovery after 2 weeks of therapy; stable at 8 month follow-up / Initial imaging: multiple round lesions in a concentric or mosaic pattern with mild rim enhancement / Not performed / Not performed
Morioka C et al. (1996)9 / Presentation: 22-year-old man with nausea and vomiting, bowel and bladder incontinence, quadriparesis, and altered level of consciousness
Treatment: glycerin (initially) followed by prednisone (after second MRI)
Outcome: normalization of function except for residual euphoria and severe cognitive abnormalities at 3 weeks; after treatment with steroids had mild cognitive dysfunction / Initial imaging: concentric patterns of low signal lesions with enhancement
3 weeks later: enlarged lesions with presumed necrosis on T1-weighted MRI
9 weeks later: regression of hyperintensities with concentric lesions
16 weeks later: lesions were "remarkably" improved / Not performed / Not performed
Sekijima Y et al. (1997)10 / Presentation: 28-year-old woman with confusion and impaired level of consciousness, progressive gait disturbance, aphasia, right leg weakness, and right homonymous hemianopsia
Treatment: intravenous methylprednisolone then oral taper followed by plasmapheresis
Outcome: marked improvement in symptoms; no further demyelinating events 3 years after onset of symptoms / 12 days after onset: multiple lesions with ‘fried egg’ appearance; no enhancement
21 days after onset: slight enlargement of existing lesions; some with enhancing concentric rings
53 days after onset: regression of lesions with no enhancement / Not performed / Not performed
Kim MO et al.
(1997)11 / Presentation: 52-year-old woman with right hemiparesis
Diagnosis: biopsy-proven BCS
Treatment: intravenous dexamethasone
Outcome: gradual resolution of hemiparesis over 5 months; no further events after 17 months / Initial imaging: multiple white matter lesions with marginal enhancement
14 days later: increased size of initial lesion / Not performed / Initial: decrease in NAA:Cr ratio, increased Cho:Cr ratio, elevated lipid peak
9 months later: Decreased lipid peak, increased myoinositol peak, no significant changes in NAA:Cr or Cho:Cr ratios
Murakami Y et al. (1998)12 / Presentation: 4-year-old boy with headaches, drowsiness, and right hemiparesis
Treatment: intravenous dexamethasone
Outcome: complete resolution of symptoms in two weeks / Initial imaging: concentric enhancing lesions in centrum semiovale and occipital lobes
3 weeks later: non-enhancing hyperintensities in occipital lobe
6 months later: non-enhancing hyperintensities in occipital lobe / Not performed / Not performed
Singh S et al.
(1999)13 / Presentation: 45-year-old woman with cognitive decline, seizures and abnormal limb movements
Treatment: intravenous methylprednisolone and intravenous immunoglobulin (IVIg) followed by high-dose intravenous methylprednisolone and azathioprine
Outcome: slight improvement after 1 month, followed by slowly progressive worsening / Initial imaging: multiple concentric lamellar rings in left frontal, temporal and parietal lobes, with additional lesions in corpus callosum
9 months later: reduction in lesion size and absence of concentric layers / Not performed / Not performed
Singh S et al.
(1999)13 / Presentation: 38-year-old man with alexia, aphasia and right hemiparesis
Treatment: dexamethasone and plasmapheresis followed by oral steroids and azathioprine
Outcome: mild cognitive recovery after treatment; no long-term follow-up reported / Initial imaging: left frontal lesion consisting of alternating concentric rings and surrounding edema with peripheral enhancement
6 weeks later: reduction in lesion size with persistent rings and widening of lamellae / Not performed / Not performed
Ng SH et al.
(1999)14 / Presentation: 56-year-old woman with right-sided weakness, dysarthria and gait abnormalities
Treatment: oral prednisolone followed by slow taper
Outcome: resolution of hemiparesis after 1 month; subsequent recurrence of right hand clumsiness / Initial imaging: left frontoparietal lesions with edema and concentric ring enhancement; right frontal subcortical lesion with concentric rings and enhancing lamellae
12 months later: persistence of concentric ring pattern in left frontoparietal cortex / Not performed / Not performed
Chen CJ et al. (1999)15 / Presentation: 27-year-old woman with right hemiparesis and memory impairments
Diagnosis: biopsy-proven BCS
Treatment: not reported
Outcome: no clinical relapse after 1 year / Initial imaging: frontoparietal lesions with concentric rings; outer two to three layers had incomplete enhancement / Not performed / Not performed
Chen CJ et al. (1999)15 / Presentation: 56-year-old woman with right hemiparesis and dysphagia
Diagnosis: biopsy-proven BCS
Treatment: not reported
Outcome: no clinical relapse after 1 year / Initial imaging: frontoparietal lesions with multiple lamellae that enhanced / Not performed / Not performed
Chen CJ et al. (1999)15 / Presentation: 22-year-old man with tetraparesis and confusion
Treatment: not reported
Outcome: no clinical relapse after 1 year / Initial imaging: multiple concentric lesions with enhancement
2 weeks later: outward expansion of lesions with loss of internal enhancement but new peripheral enhancement / Not performed / Not performed
Chen CJ et al. (1999)15 / Presentation: 42-year-old man with left hemiparesis
Treatment: not reported
Outcome: no clinical relapse after 2 years / Initial imaging: frontoparietal and temporal rings without enhancement / Not performed / Not performed
Chen CJ et al. (1999)15 / Presentation: 33-year-old woman with left hemiplegia
Treatment: not reported
Outcome: no clinical relapse after 1 year / Initial imaging: frontoparietal lesions with enhancement of all layers except at the margins.
1 month later: new hypointensity in frontal lobe within one lesion / Not performed / Not performed
Manelfe C et al. (1999)16 / Presentation: 44-year-old man with rapid onset of cerebellar and ‘hemispheric’ symptoms and signs
Treatment: mitoxantrone
Outcome: improvement in the subsequent months without complete resolution (some remaining ataxia, arm incoordination, and memory and attention deficits) / Initial imaging: multifocal superficial and deep white matter lesions, some of which enhanced in a ring-like manner; rare gray matter involvement (insula, caudate, putamen) / Not performed / Not performed
Iannucci G et al. (2000)17 / Presentation: 31-year-old with weakness
Treatment: not reported
Outcome: not reported / Initial imaging: two lesions with alternating concentric rings with an intermediate ring that enhanced
4 months later: coalescence of lesion / Initial imaging:
diffusivity values (x 10-3 mm2/s):
center, 1.234;
inner ring, 1.295;
intermediate ring, 1.099; outer ring, 1.146 / Not performed
Caracciolo JT et al. (2001)18 / Presentation: 34-year-old woman with seizures and expressive aphasia
Diagnosis: biopsy-proven BCS
Treatment: not reported
Outcome: not reported / Initial imaging: concentric demyelinating lesion in left frontal lobe with enhancing concentric rings / Not performed / Not performed
Karaarslan E et al. (2001)19 / Presentation: 52-year-old man with ataxia, left hemiparesis and confusion
Diagnosis: biopsy-proven BCS
Treatment: not reported
Outcome: residual left hemiparesis and no further events after 3 years / Initial imaging: concentric rings in right centrum semiovale with focal peripheral enhancement
13 months later: residual concentric lesion / Not performed / Not performed
Karaarslan E et al. (2001)19 / Presentation: 20-year-old woman with left hemiparesis
Treatment: corticosteroids
Outcome: no further relapses after 6 months / Initial imaging: concentric rings adjacent to right lateral ventricle with prominent peripheral enhancement / Not performed / Not performed
Karaarslan E et al. (2001)19 / Presentation: 48-year-old man with aphasia
Treatment: intravenous methylprednisolone
Outcome: mild clinical improvement after 1 month / Initial imaging: multiple white matter lesions with an enhancing left concentric
temporoparietal lesion
1 month later: no new lesions
4 years later: no new lesions; gliosis within old lesions / Not performed / Not performed
Karaarslan E et al. (2001)19 / Presentation: 38-year-old man with dysarthria, dysphagia and fatigue
Treatment: intravenous methylprednisolone
Outcome: normal neurological examination after 4 years without further clinical events / Initial imaging: multiple white matter lesions with concentric enhancing pattern
3 weeks later: multiple concentric lesions with no enhancement / Not performed / Not performed
Karaarslan E et al. (2001)19 / Presentation: 15-year-old woman with left hemiparesis
Treatment: intravenous methylprednisolone
Outcome: improvement with no further events after 6 months / Initial imaging: concentric lesion in right centrum semiovale / Not performed / Initial:
increased Cho:Cr ratio, decreased NAA:Cr ratio; possibly increased lipid and lactate peaks
Chen CJ et al. (2001)20 / Presentation: 37-year-old woman with right face and hand numbness and weakness
Treatment: not reported
Outcome: no further events at 8 months / Initial imaging: frontoparietal lesions with marginal enhancement / Not performed / Initial: decreased NAA:Cr ratio, increased Cho:Cr ratio
7 months later: incomplete improvement
Chen CJ et al. (2001)20 / Presentation: 56-year-old woman with progressive right hemiparesis and dysphagia
Treatment: not reported
Outcome: no further events at 1 year / Initial imaging: frontoparietal lesions with concentric ring enhancement / Not performed / Initial: decreased NAA:Cr ratio and increased Cho:Cr peak
14 months later: persistent abnormalities
Chen CJ et al. (2001)20 / Presentation: 42-year-old man with progressive left hemiparesis and concentration problems
Treatment: not reported
Outcome: no further events at 2 years / Initial imaging: frontoparietal and temporal lesions with no enhancement / Not performed / Initial: decreased NAA:Cr ratio, increased choline:Cr ratio
8 months later: incomplete improvement
Chen CJ et al. (2001)20 / Presentation: 33-year-old woman with left hemiplegia
Treatment: not reported
Outcome: no further events at 1 year / Initial imaging: frontoparietal lesions with concentric rings and marginal enhancement / Not performed / Decreased NAA/Cr ratio, increased choline/Cr peak
Two months later:
limited improvement
Kastrup O et al. (2002)21 / Presentation: 43-year-old man with inattention, memory deficits, and right-sided clumsiness
Treatment: intravenous prednisolone
Outcome: gradual improvement of symptoms / Initial imaging: right parietal lesion with concentric rings and mild surrounding edema; marked contrast enhancement of lamellae
4 weeks later: confluence of lesions with patchy enhancement / Not performed / Not performed
Gu J et al. (2003)22 / Presentation: 35-year-old man with left hemiparesis
Treatment: repeated courses of intravenous dexamethasone
Outcome: mild clinical improvement after first steroid course and nearly complete restoration of strength after second course of steroids / Initial imaging: multiple concentric rings in right frontal, parietal and temporal lobes with no enhancement
1 month after symptoms: concentric rings remaining
3 years after presentation: small, non-specific, plaque-like lesion remained / Not performed / Not performed
Gu J et al. (2003)22 / Presentation: 38-year-old woman with bifacial paresis, quadriplegia, apathy and seizures
Treatment: corticosteroids
Outcome; death resulting from pulmonary embolism / Initial imaging: concentric rings with no enhancement / Not performed / Not performed