Recurrent Seizures in a Case of Linear Scleroderma En Coup de Sabre

Dear 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.¹,² 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.

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.

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.³,⁴ There have also been reports of lesions in asymptomatic patients, and brain MRI is recommended in LScs patients to screen for CNS involvement.⁵,⁶

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.⁷,⁸,⁹ A few cases have shown relapsing symptoms, some in which immunotherapy was not initially provided,⁸,¹⁰ and some even in the context of immunotherapy, requiring treatment to be escalated.⁴,⁷ 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.⁴,⁵ 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.