title: Neurologic involvement in scleroderma: a systematic review.
abstract: OBJECTIVE
  To perform a systematic review of neurologic involvement in Systemic sclerosis (SSc) and Localized Scleroderma (LS), describing clinical features, neuroimaging, and treatment.
  
  
  METHODS
  We performed a literature search in PubMed using the following MeSH terms, scleroderma, systemic sclerosis, localized scleroderma, localized scleroderma "en coup de sabre", Parry-Romberg syndrome, cognitive impairment, memory, seizures, epilepsy, headache, depression, anxiety, mood disorders, Center for Epidemiologic Studies Depression (CES-D), SF-36, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9 (PHQ-9), neuropsychiatric, psychosis, neurologic involvement, neuropathy, peripheral nerves, cranial nerves, carpal tunnel syndrome, ulnar entrapment, tarsal tunnel syndrome, mononeuropathy, polyneuropathy, radiculopathy, myelopathy, autonomic nervous system, nervous system, electroencephalography (EEG), electromyography (EMG), magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA). Patients with other connective tissue disease knowingly responsible for nervous system involvement were excluded from the analyses.
  
  
  RESULTS
  A total of 182 case reports/studies addressing SSc and 50 referring to LS were identified. SSc patients totalized 9506, while data on 224 LS patients were available. In LS, seizures (41.58%) and headache (18.81%) predominated. Nonetheless, descriptions of varied cranial nerve involvement and hemiparesis were made. Central nervous system involvement in SSc was characterized by headache (23.73%), seizures (13.56%) and cognitive impairment (8.47%). Depression and anxiety were frequently observed (73.15% and 23.95%, respectively). Myopathy (51.8%), trigeminal neuropathy (16.52%), peripheral sensorimotor polyneuropathy (14.25%), and carpal tunnel syndrome (6.56%) were the most frequent peripheral nervous system involvement in SSc. Autonomic neuropathy involving cardiovascular and gastrointestinal systems was regularly described. Treatment of nervous system involvement, on the other hand, varied in a case-to-case basis. However, corticosteroids and cyclophosphamide were usually prescribed in severe cases.
  
  
  CONCLUSIONS
  Previously considered a rare event, nervous system involvement in scleroderma has been increasingly recognized. Seizures and headache are the most reported features in LS en coup de sabre, while peripheral and autonomic nervous systems involvement predominate in SSc. Moreover, recently, reports have frequently documented white matter lesions in asymptomatic SSc patients, suggesting smaller branches and perforating arteries involvement.
authors.affiliation: Rheumatology Division, Faculty of Medical Science, State University of Campinas, Campinas, Brazil; Rheumatology Lab, Faculty of Medical Science, State University of Campinas, Campinas, Brazil.
authors.forename: Tiago Nardi
authors.initials: TN
authors.lastname: Amaral
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Peres
authors.forename: Aline Tamires
authors.initials: AT
authors.lastname: Lapa
authors.forename: João Francisco
authors.initials: JF
authors.lastname: Marques-Neto
authors.forename: Simone
authors.initials: S
authors.lastname: Appenzeller
mesh_terms: D006801:Humans; D009422:Nervous System Diseases / Q000150:complications* / Q000503:physiopathology; D012594:Scleroderma, Localized / Q000150:complications* / Q000503:physiopathology; D012595:Scleroderma, Systemic / Q000150:complications* / Q000503:physiopathology