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J Clin Neurol
J Clin Neurol
JCN
Journal of Clinical Neurology (Seoul, Korea)
1738-6586
2005-5013
Korean Neurological Association

39227340
10.3988/jcn.2024.0057
Letter to the Editor
Recurrent Seizures in a Case of Linear Scleroderma En Coup de Sabre
https://orcid.org/0009-0004-0434-9223
Ahn Soo Hyun a
https://orcid.org/0000-0003-2881-0366
Lee Han Sang a
https://orcid.org/0009-0003-8920-2273
Yeom Seunghan a
https://orcid.org/0000-0001-8064-6749
Park Kyung-Il ab
a Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
b Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
Correspondence: Kyung-Il Park, MD, PhD. Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, 152 Teheran-ro, Gangnam-gu, Seoul 06236, Korea. Tel +82-2-2112-5756, Fax +82-2-2112-5635, ideopki@gmail.com
9 2024
24 7 2024
20 5 545547
25 1 2024
07 4 2024
07 5 2024
Copyright © 2024 Korean Neurological Association
2024
Korean Neurological Association
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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pmcDear Editor,

Linear scleroderma en coup de sabre (LScs) is a chronic connective-tissue disease of unknown etiology that is associated with increased collagen production and fibrosis of the involved tissues in the head or face.12 LScs mainly involves the dermis and subcutaneous tissue, but extracutaneous manifestations may also be present.1 Here we describe a case of LScs with central nervous system (CNS) involvement presenting with recurrent seizures.

A 30-year-old female was admitted to the electroencephalogram (EEG) monitoring unit due to recurrent new-onset seizures. Her semiology was consistent with generalized tonic–clonic seizure with preceding left arm weakness. The initial neurological examination showed no abnormal signs. A physical examination revealed two linear streaks of cutaneous indurations on the right forehead, which extended to linear alopecia in the frontoparietal area (Fig. 1A). The patient had been diagnosed as LScs based on the presence of this cutaneous lesion in her 20s, but was not taking any medication. The lesion had been stable in recent years, and the patient had never previously undergone neuroimaging. Her past medical history revealed hypertension and diabetes mellitus, while her family history was unremarkable.

Brain magnetic resonance imaging (MRI) revealed multiple T2-weighted high-signal-intensity lesions in the right frontal, parietal, and temporal lobes, which occupied 0.58% of the entire brain parenchyma according to a volumetric analysis performed using a locally developed NeuRoi software package (Fig. 1B and C). A few microbleeds were combined within the lesion, with subtle gadolinium enhancement (Fig. 1D and E). This prompted clinical suspicion of LScs with CNS involvement, and further extensive evaluations were performed to exclude other differential diagnoses. EEG findings were negative for focal slowing and epileptiform discharges. The cerebrospinal fluid (CSF) profile was within the normal limits with negative cytology, making encephalitis less likely. Serum and CSF synaptic autoantibodies against NMDAR, AMPAR, DPPX, LGI1, CASPR2, and GABA-B receptors were negative. Serological screening for markers of rheumatic diseases and systemic vasculitis were negative except for an ANA titer of 1:160. Transfemoral cerebral angiography did not produce any findings consistent with vasculitis or venous thrombosis. A diagnosis of lymphoma was made less likely by negative findings from a bone marrow examination, fluorine-18 fluorodeoxyglucose positron-emission tomography, skin-punch biopsy, and systemic screening for malignancy.

A final diagnosis of LScs with CNS involvement was made. The patient was treated with intravenous methylprednisolone and was discharged on oral prednisolone as well as levetiracetam. One month later she reported being free of all neurological symptoms at the outpatient clinic. Follow-up brain MRI revealed a decrease in lesion size, and oral prednisolone was held. While the patient remained symptom-free, follow-up brain imaging at 27 months showed an increase in lesion size (Fig. 1B). A brain biopsy was considered, but this was deferred due to the lesion being near the primary motor cortex and a high risk of hemorrhage. After a comprehensive re-evaluation the diagnosis remained unchanged, and a single course of intravenous immunoglobulin was administered. Three-month follow-up brain MRI showed no significant increase in lesion extent, but methotrexate was initiated due to transient symptoms of left hemibody paresthesia. This treatment decreased the frequency of sensory symptoms, and at the last follow-up she was symptom-free.

Neurological complications are the most common extracutaneous manifestations in LScs, with epilepsy being the most frequently reported.3 In patients with neurological symptoms, brain MRI reveals one or more T2-weighted high-signal-intensity lesions in about 90% of patients, and such lesions can occur before cutaneous lesions become evident.34 There have also been reports of lesions in asymptomatic patients, and brain MRI is recommended in LScs patients to screen for CNS involvement.56

The longitudinal course of CNS lesions in response to treatment remains unclear in the literature. There have been individual case reports of lesion progression, but these cases improved after adequate treatment with immunosuppressants.789 A few cases have shown relapsing symptoms, some in which immunotherapy was not initially provided,810 and some even in the context of immunotherapy, requiring treatment to be escalated.47 One case showed aggravation of symptoms after discontinuation of immune suppressants, but neuroimaging data at the time of relapse were not reported.10 There have been only a few reports on serial neuroimaging findings of LScs patients, and the available information on treatments remains inadequate.45 The present case is the first to illustrate the chronological changes in neuroimaging findings in response to treatment.

There are currently no specific recommendations to guide immunotherapy in LScs patients, and treatment is generally not decided until after significant neurological symptoms occur. The present case shows that even after successful immunotherapy, the disease may progress when treatment is discontinued. Such progression may precede neurological symptoms, and radiological evaluations may aid the early detection and thus lead to prompt medical interventions.

Availability of Data and Material

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Fig. 1 Physical and imaging findings of the patient. A: Scleroderma lesions. Two linear streaks of cutaneous indurations were evident on the right forehead, extending from underneath the right eyebrow to above the hairline. Linear alopecia was present in the right frontoparietal area. B: Results from a volumetric analysis of serial brain MRI performed using a locally developed NeuRoi software package. High-signal-intensity lesions in axial T2-weighted FLAIR images were selected and measured. The x-axis shows the imaging date on a nonlinear scale, and the y-axis shows the lesion volume as a percentage of the entire parenchymal volume. An initial decrease in lesion volume was observed in response to corticosteroid therapy, followed by a subclinical increase in extent after discontinuing immunotherapy. C–E: Initial brain MRI findings. C: T2-weighted FLAIR sequences showing multiple high-signal-intensity lesions (arrows) in the right frontal, parietal, and temporal lobes. D: Susceptibility-weighted imaging sequences showing multiple microbleeds (arrows). E: Postenhanced T1-weighted sequences showing subtle nodular enhancement (arrows) at some of the microbleeds. FLAIR, fluid-attenuated inversion recovery; IV, intravenous; MRI, magnetic resonance imaging; PO, per os.

Ethics Statement: This study was approved by the Seoul National University Hospital Institutional Review Board (IRB no. H-2306-181-1443). This report conforms to the Declaration of Helsinki, and explicit written consent was obtained from the patient.

Author Contributions: Conceptualization: Soo Hyun Ahn, Kyung-Il Park.

Supervision: Kyung-Il Park.

Validation: Kyung-Il Park.

Visualization: Soo Hyun Ahn.

Writing—original draft: Soo Hyun Ahn.

Writing—review & editing: all authors.

Conflicts of Interest: The authors have no potential conflicts of interest to disclose.

Funding Statement: None
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1 Careta MF Romiti R Localized scleroderma: clinical spectrum and therapeutic update An Bras Dermatol 2015 90 62 73
2 Amaral TN Marques Neto JF Lapa AT Peres FA Guirau CR Appenzeller S Neurologic involvement in scleroderma en coup de sabre Autoimmune Dis 2012 2012 719685 22319646
3 Amaral TN Peres FA Lapa AT Marques-Neto JF Appenzeller S Neurologic involvement in scleroderma: a systematic review Semin Arthritis Rheum 2013 43 335 347 23827688
4 Kister I Inglese M Laxer RM Herbert J Neurologic manifestations of localized scleroderma: a case report and literature review Neurology 2008 71 1538 1545 18981376
5 Appenzeller S Montenegro MA Dertkigil SS Sampaio-Barros PD Marques-Neto JF Samara AM Neuroimaging findings in scleroderma en coup de sabre Neurology 2004 62 1585 1589 15136686
6 Knobler R Moinzadeh P Hunzelmann N Kreuter A Cozzio A Mouthon L European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, part 1: localized scleroderma, systemic sclerosis and overlap syndromes J Eur Acad Dermatol Venereol 2017 31 1401 1424 28792092
7 Magro CM Halteh P Olson LC Kister I Shapiro L Linear scleroderma “en coup de sabre” with extensive brain involvement—clinicopathologic correlations and response to anti-Interleukin-6 therapy Orphanet J Rare Dis 2019 14 110 31096996
8 Nguyen K Atty C Ree A Linear scleroderma en coup de sabre presenting with seizures Radiol Case Rep 2020 15 2164 2170 32952756
9 Unterberger I Trinka E Engelhardt K Muigg A Eller P Wagner M Linear scleroderma “en coup de sabre” coexisting with plaque-morphea: neuroradiological manifestation and response to corticosteroids J Neurol Neurosurg Psychiatry 2003 74 661 664 12700315
10 Stone J Franks AJ Guthrie JA Johnson MH Scleroderma “en coup de sabre”: pathological evidence of intracerebral inflammation J Neurol Neurosurg Psychiatry 2001 70 382 385 11181863
