Localized scleroderma (LoS) is an autoimmune skin disorder that primarily causes skin sclerosis and subcutaneous tissue atrophy. Beyond disfiguring craniofacial lesions, extracutaneous involvement — notably neurological complications — has gained recognition. This systematic review synthesized published data on neurological symptoms, neuroimaging findings, and complementary examinations in LoS to inform clinical recognition and evaluation.
The review aimed to summarize clinical neurological manifestations, describe neuroimaging patterns on MRI and CT, report results from other tests (EEG, CSF, EMG) and provide pooled prevalence estimates where data permitted.
A literature search was performed in PubMed, Embase, and the Cochrane Library using disease-specific, symptom-related, and complementary examination–related terms. The search covered 1947–2025 and was restricted to English-language publications. Two authors performed manual screening to exclude irrelevant records and reports without extractable data.
Included study types comprised case reports, case series, and cohort studies. Data extracted included numbers of affected patients for key neurological symptoms and neuroimaging abnormalities. For pooled prevalence analyses the authors used a random-effects binomial–normal generalized linear mixed model with a logit link and maximum likelihood estimation; pooled prevalences and 95% confidence intervals were calculated via the Wilson score method.
Across 242 publications encompassing nearly 3,500 patients, central nervous system (CNS) involvement was reported frequently. The most commonly documented CNS symptoms were headache/migraine (384 cases) and epilepsy (203 cases). Other reported CNS features included hemiparesis, stroke, vomiting and nausea, developmental delay, vertigo, facial palsy, impaired memory, hearing loss, tinnitus, dysphagia, impaired visuospatial function, ataxia, dysarthria and rarer signs such as mirror movement.
Sixteen cohort studies or case series (2,913 patients) were included in the neurological symptom meta-analysis. The random-effects pooled prevalence for headache/migraine was 13.2% (95% CI, 6.2%–23.9%), and for epilepsy was 6.5% (95% CI, 2.7%–14.0%). Subgroup analyses suggested headache/migraine were more frequent in Parry–Romberg syndrome (PRS, 28.1%) and combined ECDS+PRS cohorts (21.1%) than in en coup de sabre (ECDS, 19.2%), whereas pooled epilepsy prevalence was broadly comparable across subtypes.
These findings highlight that headaches and seizures are among the most common neurologic presentations in LoS and that craniofacial variants may carry higher headache burden.
Peripheral nervous system (PNS) involvement was observed but less extensively reported than CNS manifestations. The most common PNS symptom was paresthesia (61 cases), described as unilateral paresthesia, hypoesthesia, dysesthesia, numbness, or a sense of heaviness. Cranial nerve involvement was documented in 46 cases, affecting multiple cranial nerves including optic, oculomotor, trochlear, trigeminal, abducens and facial nerves. Facial pain (25 cases), peripheral neuropathy (8 cases), myalgia, facial spasm, myopathy and isolated syndromes such as alien-hand were also reported.
Psychiatric and cognitive symptoms were recorded in a smaller number of patients. Anxiety (18 cases), depression (16), cognitive impairment (13) and photophobia (13) were among the most frequent neuropsychiatric presentations. In pooled analysis psychiatric symptoms were uncommon overall (0.3%, 0.0%–1.5%).
MRI and CT were the principal modalities used to evaluate structural and parenchymal involvement.
On MRI, a wide spectrum of abnormalities was reported. The most frequent MRI feature was T2 white matter hyperintensity (174 cases). Other MRI findings included brain parenchymal atrophy (86 cases), abnormal gyral pattern (46), hemorrhage, ventricular dilatation, calcification, gliosis, cystic lesions, blurring of the white–gray matter interface, aneurysm and vascular malformations, cerebral infarction/ischemia, grey matter abnormalities and leptomeningeal enhancement among others.
Eleven MRI cohorts (411 patients) were included in a neuroimaging meta-analysis. T2 white-matter hyperintensities had a pooled prevalence of 15.0% (95% CI, 7.0%–27.3%), with higher frequency in ECDS+PRS cohorts (27.1%). Brain atrophy was less common overall (4.0%, 0.5%–19.4%) and abnormal gyral patterns were rare and imprecisely estimated.
CT findings reported across studies included brain calcification, skull atrophy and white matter hypodensity among the more prevalent changes, though specific pooled CT prevalences were not detailed in the parts of the source text provided here.
The range of imaging abnormalities — from focal white matter changes and atrophy to hemorrhage, calcification and leptomeningeal enhancement — reflects heterogeneous pathologic processes reported in LoS, including inflammation, vascular involvement, gliosis and chronic tissue loss.
Complementary tests documented in the literature include electroencephalography (EEG), cerebrospinal fluid (CSF) analysis and electrophysiology (EMG). These examinations were variably reported and are recommended to be performed selectively, guided by clinical presentation (for example EEG in seizures, CSF when inflammatory or infectious processes are considered). The source emphasizes selective use rather than routine performance for all patients.
This systematic review consolidates evidence that neurological involvement in LoS is not rare and covers a broad clinical and imaging spectrum. Craniofacial subtypes, notably ECDS and PRS, appear particularly associated with neurologic manifestations and a higher burden of imaging abnormalities. The mechanisms proposed in the literature include immune-mediated inflammation, vasculopathy, fibrosis and disruption of adjacent tissues, though definitive pathogenetic pathways remain incompletely defined.
Clinically, headaches and seizures are key signals warranting neurological evaluation. Neuroimaging, primarily MRI, frequently identifies white matter lesions, atrophy and other focal parenchymal or vascular changes that may guide management and follow-up. Multidisciplinary assessment and individualized immunomodulatory therapy are often required in patients with significant neurologic involvement.
Neurological complications are common in LoS and can precede, accompany or follow cutaneous disease. Based on the assembled evidence, the authors recommend performing MRI scanning for all craniofacial LoS patients at diagnosis, regardless of whether neurological symptoms are present. Complementary tests such as EEG and CSF analysis should be used selectively according to clinical indications. Early recognition, multidisciplinary evaluation and individualized management are emphasized to optimize outcomes.
The review incorporated a heterogeneous body of literature including case reports and series, which can introduce reporting bias. Not all imaging and clinical outcomes were uniformly reported across studies. Some pooled estimates had wide or imprecise confidence intervals, particularly for less common findings. Specific numeric details for certain CT pooled prevalences and for several complementary examination outcomes were not reported in full in the provided source text.