---
title: "Neurological involvement in localized scleroderma: clinical features and neuroimaging patterns"
id: "frontiers-in-immunology-9-neurological-involvement-in-localized-scleroderma-a-systematic-review-of"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-9-neurological-involvement-in-localized-scleroderma-a-systematic-review-of"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1921069"
published_at: "2026-09-15T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Neurological involvement in localized scleroderma: clinical features and neuroimaging patterns
## Provenance & Clinical Metadata
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- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1921069)
- **Published At:** 2026-09-15T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This systematic review assessed neurological involvement in **localized scleroderma (LoS)** across 242 publications covering nearly 3,500 patients. The review included case reports, case series, and cohort studies identified from PubMed, Embase, and Cochrane (1947–2025). - Central nervous system (CNS) manifestations were common. The most frequently reported CNS symptoms were **headache/migraine** (384 cases) and **epilepsy** (203 cases); hemiparesis, stroke, vomiting/nausea and developmental retardation were also reported. - Meta-analysis of 16 cohorts (2,913 patients) produced a random-effects pooled prevalence for headache/migraine of 13.2% (95% CI 6.2%–23.9%) and for epilepsy of 6.5% (95% CI 2.7%–14.0%). Headache/migraine appeared more frequent in Parry–Romberg syndrome (PRS) and ECDS+PRS than in en coup de sabre (ECDS); epilepsy prevalence was similar across subtypes. - Peripheral nervous system (PNS) involvement included paresthesia (61 cases), cranial nerve involvement (46 cases across multiple cranial nerves), facial pain (25 cases), peripheral neuropathy (8 cases) and other motor or sensory findings. - Psychiatric symptoms were reported but less common overall; anxiety (18 cases), depression (16), cognitive impairment (13) and photophobia (13) were among the observed neuropsychiatric features. Pooled prevalence for psychiatric symptoms was low (0.3%, 0.0%–1.5%). - **Neuroimaging** (MRI and CT) revealed a range of abnormalities. On MRI, the most frequent findings were **T2 white matter hyperintensity** (174 cases), brain atrophy (86), abnormal gyral pattern (46), gliosis and ventricular dilatation. On CT the most common abnormalities included brain calcification, skull atrophy and white matter hypodensity. - MRI cohort meta-analysis (11 cohorts, 411 patients) estimated T2 white-matter hyperintensities prevalence at 15.0% (7.0%–27.3%) and noted higher frequency in the ECDS+PRS subgroup (27.1%). Brain atrophy was less frequent (4.0%, 0.5%–19.4%); abnormal gyral patterns were rare with imprecise estimates. - Other reported imaging findings included hemorrhage, cystic lesions, gliosis, leptomeningeal enhancement, aneurysm/vascular malformation, cerebral infarction/ischemia, grey-matter abnormalities and calcifications. - Complementary tests such as electroencephalography (EEG) and cerebrospinal fluid (CSF) analysis were reported and should be selectively performed when clinically indicated. - The authors conclude neurological involvement in LoS is common, especially in craniofacial subtypes (ECDS, PRS). They recommend performing **MRI** in all craniofacial LoS patients at diagnosis, with or without neurological symptoms. - Mechanisms remain incompletely defined; proposed contributors include immune-mediated inflammation, vasculopathy, fibrosis and tissue disruption. Multidisciplinary evaluation and individualized immunomodulatory management are often required.
## Clinical Analysis & Structured Key Points
Frontiers | Neurological involvement in localized scleroderma: a systematic review of clinical manifestations and neuroimaging findings SYSTEMATIC REVIEW article Front. Immunol. , 15 September 2026 Sec. Multiple Sclerosis and Neuroimmunology Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1921069 Published in Frontiers in Immunology Multiple Sclerosis and Neuroimmunology 7 impact factor 11.3 citescore Part of a Research Topic Neuroinflammation and immune mechanisms in brain disorders Submission open 7597 views 9 articles Editor & Reviewers Edited by W W Wei Wang Reviewed by D Z Dan Zhang E K Elif KILIÇ KÖNTE Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Figure 4 View in article Table 1 Number of cases with different central nervous system symptoms in patients with localized scleroderma. View in article Table 2 Number of cases with different peripheral nervous system symptoms in patients with localized scleroderma. View in article Table 3 Number of cases with psychiatric symptoms in patients with localized scleroderma. View in article Table 4 Number of cases with abnormalities on brain MRI in patients with localized scleroderma. View in article Table 5 Number of cases with abnormalities on head CT in patients with localized scleroderma. View in article Table 6 Other complementary examination results of patients with localized scleroderma. View in article SYSTEMATIC REVIEW article Front. Immunol. , 15 September 2026 Sec. Multiple Sclerosis and Neuroimmunology Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1921069 Neurological involvement in localized scleroderma: a systematic review of clinical manifestations and neuroimaging findings Y C Yuming Chong 1 † W M Wangfei Mo 2 † C D Congcong Deng 3 † N Y Nanze Yu 1 Z X Zenan Xia 1 * X L Xiao Long 1 * 1. Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China 2. Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China 3. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China See more Article metrics View details Abstract Background: Localized scleroderma (LoS) is an autoimmune disorder leading to skin sclerosis and subcutaneous tissue atrophy. Apart from the disfiguring craniofacial lesions, the extracutaneous involvement in LoS has been increasingly recognized and studied. Among all, neurological involvement is common and worth special attention. Objectives: This systematic review summarizes the neurological symptoms, neuroimaging findings, and other complementary examination results of LoS. Methods: Records were retrieved using keywords related to the disease, neurological symptoms, and neurological examinations. After excluding irrelevant literature, case reports, case series, and cohort studies were included. A statistical analysis was performed, focusing on central and peripheral nervous system symptoms, neuroimaging manifestations, and other complementary examination results. Results: A total of 242 topic-related publications reporting data on nearly 3,500 patients were finally included. The top ranked central nervous system symptoms of LoS were headache and migraine, epilepsy, and hemiparesis. Headache/migraine were more frequent in Parry-Romberg syndrome than in en coup de sabre , whereas epilepsy was broadly comparable across subtypes. The top peripheral nervous system symptoms were paresthesia, cranial nerve involvement, and facial pain. The top five most common manifestations on MRI were T2 white matter hyperintensity lesion, brain atrophy, abnormal gyral pattern, gliosis, and ventricular dilatation. The top three most common manifestations on CT were brain calcification, skull atrophy, and white matter hypodensity. Other complementary examinations, including electroencephalography and cerebrospinal fluid test should be selectively performed if necessary. Conclusion: Neurological involvement was common among LoS patients. Attention should be paid to the neurological manifestations of LoS at their first visit. It is recommended to perform MRI scanning for all craniofacial LoS patients, with or without neurological symptoms, at the time of diagnosis. Introduction Localized scleroderma (LoS) is a rare autoimmune disorder, mainly leading to skin sclerosis and subcutaneous tissue atrophy ( 1 , 2 ). A population-based study in Olmsted County, USA, from 1960 to 1993 estimated an incidence rate per 10–000 population of 0.27, with an annual increase of 3.6% ( 3 , 4 ). A female predominance of 2.4 to 4.2:1 was also reported ( 5 ). LoS can occur at any age, and about one-third of cases begin in childhood ( 6 ). The mean age at onset of juvenile localized scleroderma is 6.4 to 8.7 years, and onset at birth has been reported, while the mean age at onset in adult is about 45 years ( 6 , 7 ). According to the Mayo classification, LoS can be divided into five subtypes: plaque morphea, generalized morphea, bullous morphea, linear morphea, and deep morphea ( 8 ). En coup de sabre (ECDS) is a subtype of linear morphea characterized by a linear lesion on the forehead or frontal scalp. The lesions on the scalp are usually accompanied by irreversible hair loss. Progressive facial hemiatrophy (PFH), also known as Parry-Romberg syndrome (PRS), frequently overlaps with ECDS ( 9 , 10 ). It is a special and severe type in which lesions have extended to half of the face, leading to hemifacial atrophy of skin, subcutaneous tissue, muscle, and bone ( 11 ). The diagnosis of LoS is often based on clinical manifestations and/or skin biopsy. Systematic and topical medications are used to control disease progression. Topical medications include glucocorticoid preparations, topical calcipotriol ointment, and tacrolimus ointment. Systematic medications include anti-inflammatory drugs and immunosuppressants. After the disease reaches a stable stage, surgical treatment such as autologous fat transplantation and skin flap transplantation can be considered to restore soft tissue volume. LoS may present as a remission-relapse course. It could recur even after many years of quiescence, especially in linear morphea of limbs ( 12 ). And juvenile patients may experience multiple relapses in adulthood ( 13 ). In recent years, evidence from cohort studies has shown that LoS, traditionally regarded as a cutaneous autoimmune disorder, can involve a range of neurological involvement, particularly in craniofacial variants such as ECDS and PRS ( 14 – 17 ). Manifestations range from headaches, seizures, and cognitive or psychiatric symptoms to neuroimaging abnormalities affecting the cerebral parenchyma, ventricular system, and meninges ( Figure 1 ). The mechanisms remain incompletely defined but may involve immune-mediated inflammation, vasculopathy, fibrosis, and disruption of adjacent tissues. Recognition of neurological complications is important because symptoms can precede, accompany, or follow skin disease. Multidisciplinary assessment, neuroimaging, and individualized immunomodulatory management are often required to optimize outcomes in clinical practice. This is a systematic review to comprehensively summarize the neurological symptoms and neuroimaging findings of LoS. Figure 1 Schematic diagram of neurological involvement of localized scleroderma. SSc: systemic sclerosis. Methods This systematic review was reported in accordance with the PRISMA guidelines. This review focused on LoS and its neurological involvement including clinical symptoms, neuroimaging findings, and complementary examinations. A literature search was performed in PubMed, Embase, and Cochrane Library using the following terms: Disease-related terms: “localized scleroderma” OR “en coup de sabre” OR “morphea” OR “Parry Romberg” OR “Parry–Romberg” OR “progressive facial hemiatrophy” OR “progressive hemifacial atrophy” Symptom-related terms: “brain” OR “neurological symptom*” OR “neurologic symptom*” OR “neurological involvement*” OR “neurologic involvement*” OR “neurological manifestation*” OR “neurologic manifestation*” OR “aneurysm*” OR “aneurysmal” OR “cognitive impairment*” OR “memory” OR “seizure*” OR “epilepsy” OR “headache” OR “depression” OR “anxiety” OR “mood disorder*” OR “neuropsychiatric” OR “psychosis” OR “neuropathy” OR “neuropathologic” OR “peripheral nerve*” OR “cranial nerve*” OR “carpal tunnel syndrome” OR “ulnar entrapment” OR “tarsal tunnel syndrome” OR “mononeuropathy” OR “polyneuropathy” OR “radiculopathy” OR “myelopathy” OR “autonomic nervous system” OR “nervous system” Complementary examination-related terms: “magnetic resonance imaging” OR “MRI” OR “magnetic resonance angiography” OR “MRA” OR “computed tomography” OR “CT” OR “electroencephalography” OR “EEG” OR “electromyography” OR “EMG” OR “neuroimaging” The search was limited to studies published between 1947 to 2025. Only English publications were included. Manual screening was performed by two independent authors (Y.C. and W.M.) to exclude irrelevant articles and literature without detailed information for analysis. Neurological symptoms, neuroimaging manifestations, and complementary examination results were summarized. For each eligible cohort study or case series, the number of affected patients and the number assessed were extracted for main neurological symptoms and neuroimaging abnormalities. Overall analyses included all eligible cohorts, while subgroup analyses were restricted to explicitly reported ECDS, PRS, and ECDS+PRS cohort. Pooled prevalences and 95% confidence intervals were calculated using the Wilson score method. Pooled prevalences were estimated separately for each outcome and subgroup using a random-effects binomial–normal generalized linear mixed model with a logit link, fitted by maximum likelihood. Results A total of 336 publications were identified for screening ( Figure 2 ). After excluding non-English records, records that could not be retrieved, and irrelevant literature, 248 articles went into further analysis. Six of them were excluded because they lacked sufficient information for data extraction and quantitative analysis. Finally, this review included a total of 242 publications for review, comprising case reports, case series, and cohort studies, summing up nearly 3,500 patients ( 18 – 227 ). Figure 2 Flow diagram for this systematic review. Neurologic symptoms Central nervous system (CNS) involvement is common among patients with LoS ( Table 1 ). Headache/migraine was the most frequently reported CNS symptom, presenting in 384 patients, followed by epilepsy occurring in 203 cases. Other central nervous system symptoms, including hemiparesis, stroke, vomiting and nausea, and developmental retardation were also common. Other symptoms included vertigo, facial palsy, automatic activity, impaired memory, hearing loss, tinnitus, etc. Table 1 Rank Symptom Events Reference 1 Headache/migraine 384 ( 18 – 78 ) 2 Epilepsy 203 ( 18 , 20 , 22 , 26 – 29 , 31 – 35 , 37 , 38 , 40 , 43 , 46 – 49 , 52 – 55 , 57 , 58 , 60 , 63 , 65 , 69 , 70 , 73 , 76 , 77 , 79 – 157 ) 3 Hemiparesis 40 ( 32 , 44 , 47 , 49 , 60 , 61 , 63 , 72 – 74 , 84 , 93 , 101 – 103 , 105 , 108 , 111 , 113 , 115 , 116 , 119 , 125 , 127 , 129 , 138 , 148 , 150 , 153 , 154 , 158 – 165 ) 4 Developmental retardation 14 ( 48 , 65 , 101 , 121 , 129 , 130 , 139 , 143 , 148 , 150 , 164 , 166 ) 5 Stroke 13 ( 18 , 27 , 33 , 34 , 42 , 53 , 72 , 82 , 86 , 88 , 167 , 168 ) 6 Vertigo 12 ( 53 , 71 , 78 , 79 , 84 , 88 , 100 , 102 , 104 , 148 ) Facial palsy 12 ( 49 , 54 , 58 , 82 , 102 , 130 , 131 , 156 , 169 – 171 ) 8 Impaired memory 8 ( 55 , 58 , 79 , 97 , 107 , 142 , 166 , 167 ) 9 Tinnitus 7 ( 18 , 61 , 102 ) 10 Dysphagia 6 ( 41 , 49 , 124 , 131 ) Hearing loss 6 ( 30 , 78 , 160 , 162 , 167 , 172 ) 12 Impaired visuospatial function 4 ( 32 , 52 , 58 , 97 ) Ataxia 4 ( 32 , 79 , 158 , 173 ) 14 Dysarthria 3 ( 131 , 143 , 173 ) 15 Mirror movement 1 ( 109 ) Number of cases with different central nervous system symptoms in patients with localized scleroderma. Sixteen cohort studies/case series (2,913 patients) contributed to the neurological-symptom meta-analysis ( Figure 3 . Supplementary Table 1 ) ( 18 , 23 , 27 , 28 , 32 , 35 , 37 , 48 , 49 , 58 , 70 , 102 , 126 , 130 , 134 , 208 ). Headache/migraine was the most frequently reported manifestation, with a random-effects pooled prevalence of 13.2% (95% CI, 6.2%–23.9%), followed by epilepsy at 6.5% (2.7%–14.0%). Headache/migraine appeared more frequent in PRS (28.1%) and ECDS+PRS (21.1%) than in ECDS (19.2%), whereas pooled epilepsy estimates were broadly comparable across subtypes (11.7%–15.4%). Pooled prevalence data of other main neurological symptoms were shown in Supplementary Table 1 . Figure 3 Random-effects pooled prevalence of neurological symptoms in localized scleroderma: overall and subtype-specific analysis. (A) Headache/migraine; (B) Epilepsy; (C) Psychiatric symptom. ECDS, en coup de sabre ; PRS, Parry-Romberg syndrome. Peripheral nervous system (PNS) involvement can also be observed in patients with LoS ( Table 2 ). A total of 61 cases were identified with paresthesia, the most common peripheral nervous system symptom. Reported paresthesia (sensory disturbance) included unilateral paresthesia, hypoesthesia, dysesthesia, numbness, and heaviness. Cranial nerve involvement was described in 46 cases, making it the second most common symptom. Among other peripheral nervous system involvement, facial pain and peripheral neuropathy were reported in 25 and 8 cases, respectively. Table 2 Rank Symptom Events Reference 1 Paresthesia 61 ( 18 , 27 , 29 , 34 , 38 , 42 , 47 , 50 , 53 – 55 , 58 , 60 , 66 , 72 – 74 , 76 , 83 , 93 , 98 , 102 , 107 , 132 , 148 , 153 , 156 , 158 , 160 , 171 , 172 , 174 – 181 ) 2 Cranial nerve involvement 46 2nd (Optic nerve) 6 ( 137 , 156 , 181 – 184 ) 3rd (Oculomotor nerve) 7 ( 54 , 76 , 130 , 131 , 141 , 151 , 184 ) 4th (Trochlear nerve) 3 ( 76 , 79 , 130 ) 5th (Trigeminal nerve) 9 ( 49 , 64 , 131 , 152 , 172 , 174 , 185 – 187 ) 6th (Abduction nerve) 8 ( 54 , 78 , 82 , 128 , 130 , 131 , 188 , 189 ) 7th (Facial nerve) 11 ( 49 , 66 , 69 , 87 , 130 , 141 , 169 , 188 , 190 , 191 ) Unspecified 2 ( 27 ) 3 Facial pain 25 ( 18 , 192 – 194 ) 4 Peripheral Neuopathy 8 ( 70 , 102 , 128 , 130 , 171 ) 5 Myalgia 7 ( 48 , 58 , 65 , 155 , 157 , 165 , 171 ) 6 Facial spasm 6 ( 49 , 191 , 194 – 196 ) 7 Myopathy 2 ( 197 ) Alien-hand syndrome 2 ( 52 , 162 ) 9 Cervical sympathetic hyperactivity 1 ( 192 ) Number of cases with different peripheral nervous system symptoms in patients with localized scleroderma. Psychiatric symptoms can also be been observed in LoS patients ( Table 3 ). Among them, anxiety (18 cases) was the most common symptom, followed by depression (16 cases), cognitive impairment (13 cases), and photophobia (13 cases). The pooled prevelence meta-analysis showed psychiatric symptoms were less common (0.3%, 0.0%–1.5%) in LoS patient population ( Figure 3 ). Table 3 Rank Symptom Events Reference 1 Anxiety 18 ( 24 , 27 , 42 , 52 , 79 , 84 , 91 , 97 , 142 , 198 , 199 ) 2 Depression 16 ( 27 , 36 , 42 , 52 , 57 , 84 , 95 , 97 , 98 , 102 , 130 , 199 ) 3 Cognitive impairment 13 ( 33 , 52 , 58 , 65 , 79 , 84 , 93 , 97 , 111 , 125 , 153 , 166 , 167 ) Photophobia 13 ( 38 , 40 , 53 , 56 , 73 , 160 , 179 , 186 , 190 , 200 , 201 ) 5 Sleep disturbance 9 ( 53 , 91 , 199 ) 6 Appetite change 8 ( 52 , 56 , 199 ) 7 Behavioral disorders 7 ( 52 , 58 , 70 , 79 , 139 ) 8 Irritability 6 ( 26 , 53 , 65 , 97 , 124 , 139 ) Phonophobia 6 ( 38 , 53 , 73 , 186 , 190 , 201 ) 10 Auditory hallucinations 5 ( 52 , 148 , 156 , 157 ) 11 Visual hallucinations 3 ( 27 , 52 , 53 ) 12 Obsessive–compulsive disorder 2 ( 27 , 198 ) 13 Agoraphobia 1 ( 99 ) Oppositional behaviour 1 ( 121 ) Somnolent 1 ( 63 ) - Unspecified 10 ( 23 , 130 ) Number of cases with psychiatric symptoms in patients with localized scleroderma. Neuroimaging findings MRI and CT were the key neuroimaging methods to evaluate the neurological involvement in LoS. MRI scans in patients with LoS reveal a diverse range of typical abnormalities ( Table 4 ). T2 white matter hyperintensity was found in 174 cases, making it the most common feature on MRI. Brain parenchyma atrophy (86 cases), abnormal gyral patten (46 cases), hemorrhage (24 cases), and ventricular dilatation (24 cases) were also reported, followed by brain calcification (23 cases), gliosis (23 cases), cystic lesion (19 cases), blurring white-gray matter (16 cases), aneurysm & vascular malformation (14 cases), cerebral infarction & ischemia (13 cases), grey matter abnormality (12 cases), and leptomeningeal enhancement (11 cases). Table 4 Rank Manifestation Events Reference 1 T2 white matter hyperintensity 174 ( 20 , 22 , 26 , 27 , 29 – 34 , 37 , 38 , 40 – 43 , 47 – 50 , 52 – 55 , 58 – 60 , 66 , 67 , 69 , 71 – 74 , 79 – 89 , 91 – 94 , 97 , 98 , 101 – 103 , 105 , 107 , 110 , 111 , 113 , 116 – 118 , 120 – 123 , 126 , 129 – 134 , 138 , 142 – 144 , 146 , 148 , 153 , 154 , 158 , 159 , 161 – 163 , 165 , 172 – 175 , 180 , 183 , 189 , 194 , 201 – 211 ) 2 Brain atrophy 86 ( 18 , 24 , 26 , 27 , 31 , 32 , 34 , 41 , 43 , 48 , 49 , 52 , 55 , 65 , 66 , 82 – 84 , 88 , 98 , 101 – 104 , 107 , 108 , 111 , 115 , 117 – 120 , 125 , 127 , 129 , 131 , 134 , 138 , 139 , 143 , 149 , 152 , 161 , 162 , 164 , 166 , 173 , 174 , 193 , 205 , 208 , 212 – 217 ) 3 Abnormal gyral pattern 46 ( 24 , 27 , 29 , 31 , 32 , 40 , 47 , 49 , 50 , 54 , 58 , 60 , 73 , 74 , 83 , 97 , 111 , 129 , 131 , 132 , 134 , 142 , 146 , 148 , 153 , 166 , 174 , 205 ) 4 Hemorrhage 24 ( 18 , 20 , 22 , 34 , 38 , 49 , 56 , 60 , 63 , 72 , 81 , 87 , 92 , 93 , 100 , 103 , 106 , 172 , 174 , 204 ) Ventricular dilatation 24 ( 26 , 29 , 31 , 73 , 82 – 84 , 97 , 102 , 107 , 111 , 119 , 130 – 132 , 138 , 139 , 148 , 153 , 166 , 174 , 205 , 207 ) 6 Calcification 23 ( 20 , 27 , 31 , 34 , 39 , 40 , 42 , 47 , 58 , 60 , 102 , 103 , 105 , 130 , 134 , 149 , 211 , 218 ) Gliosis 23 ( 31 , 34 , 37 , 84 , 88 , 101 , 104 , 111 , 120 , 137 , 148 , 162 , 175 , 182 , 183 , 219 ) 8 Cystic lesion 19 ( 18 , 26 , 31 , 38 , 44 , 55 , 83 , 87 , 137 , 148 , 175 , 207 ) 9 Blurring white-gray matter 16 ( 74 , 83 , 130 , 132 , 134 , 148 ) 10 Aneurysm & vascular malformation 14 ( 59 , 61 , 63 , 68 , 70 , 84 , 104 , 147 , 179 , 180 , 189 , 220 ) 11 Cerebral infarction & ischemia 13 ( 56 , 63 , 72 , 82 , 129 , 159 , 165 , 167 , 168 , 174 , 180 , 186 , 212 ) 12 Grey matter abnormality 12 ( 32 , 49 , 112 ) 13 Leptomeningeal enhancement 11 ( 27 , 32 , 47 , 50 , 73 , 74 , 146 , 204 ) 14 Edema 10 ( 31 , 44 , 47 , 52 , 54 , 87 , 105 , 112 ) 15 Encephalomalacia 9 ( 38 , 49 , 82 , 87 , 102 , 182 , 183 ) 16 Cortex thickening 8 ( 31 , 50 , 52 , 54 , 74 , 83 , 148 ) 17 Cavernoma 7 ( 27 , 60 , 80 , 92 , 175 , 218 ) Vasculitis 7 ( 56 , 59 , 70 , 94 , 102 , 126 ) 19 Demyelination 4 ( 55 , 102 , 211 ) Lateral ventricle asymmetry 4 ( 49 , 221 ) Tumor 4 ( 47 , 126 , 210 , 222 ) 22 Agenesis of corpus callosum 3 ( 97 , 108 , 154 ) 23 Porencephaly 2 ( 27 , 150 ) Subdural effusion 2 ( 131 , 135 ) 25 Cavum septum pellucidum 1 ( 198 ) Number of cases with abnormalities on brain MRI in patients with localized scleroderma. Eleven MRI cohorts (411 patients) were included in the neuroimaging meta-analysis ( Figure 4 , Supplementary Table 2 ) ( 18 , 27 , 32 , 37 , 48 , 49 , 58 , 102 , 130 , 134 , 208 ). T2 white-matter hyperintensities were the most prevalent MRI abnormality overall (15.0%, 7.0%–27.3%) and were most frequent in the ECDS+PRS subgroup (27.1%, 8.2%–45.2%). Brain atrophy was less common overall (4.0%, 0.5%–19.4%), while abnormal gyral patterns were rare and imprecisely estimated (0.9%, 0.0%–12.3%). Pooled prevalence data of other main neuroimaging abnormalities were shown in Supplementary Table 2 . Figure 4 Random-effects pooled
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