Cutaneous Manifestation in Neurological Disorders: A Systematic Review of Observational Studies (Preprint)

BACKGROUND Cutaneous manifestations are increasingly recognized as serving as important indicators of several neurological disorders because of the shared mechanisms between the two conditions. This systematic review aims to synthesize the available observational evidence on cutaneous manifestations related to neurological disorders. OBJECTIVE To systematically review and synthesize observational evidence on the relationship between cutaneous manifestations and neurological disorders, highlighting their role as early indicators of underlying neurological pathology. METHODS This is a systematic review conducted in accordance with PRISMA guidelines across different electronic databases from inception up to 2023. Study selection, extraction of data, and quality assessment were performed independently by two reviewers. RESULTS The review included 30 studies published between 1964 and 2023, including a total sample of 9472 (1172 cases and 8300 controls), mostly as case reports, and representing diverse geographic regions. Pigmentary disorders were the most common reported cutaneous manifestations (N=17 studies), particularly among patients with congenital neurocutaneous disorders. Most of the cutaneous symptoms were reported before or at the onset of neurological symptoms. The shared embryological origins, neural crest cell migration defects, immune-mediated processes, or chronic inflammatory pathways were the most proposed pathophysiological mechanisms related to the two conditions. CONCLUSIONS This review indicated that cutaneous manifestations are common and clinically relevant across different neurological disorders and frequently serve as early markers of underlying neurological pathology.