Fractures beyond spasms: Progressive encephalomyelitis with rigidity and myoclonus associated with GABA-linked bone fragility
Abstract
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and severe form of stiff-person spectrum disorders, typically associated with painful spasms, brainstem involvement, and autonomic dysfunction. Previous reports have described fractures as an uncommon but recognized complication of PERM, typically attributed to mechanical stress from recurrent spasms; however, disrupted γ- aminobutyric acid (GABA)ergic signaling may also impair bone metabolism. We report a 53-year-old man with seronegative PERM who developed vertebral and pelvic fractures without trauma during hospitalization. Immunotherapy with intravenous immunoglobulin, methylprednisolone, and rituximab improved neurological symptoms, but spasticity persisted. Bone turnover markers remained persistently elevated and bone healing was delayed even 6 months after the fractures. Introduction of intrathecal baclofen resulted in marked reduction of spasticity, normalization of bone markers, improvement in bone mineral density, and radiographic evidence of fracture healing. This case suggests that impaired GABAergic signaling in PERM may contribute to high-turnover bone metabolism and skeletal fragility, in addition to mechanical stress. Awareness of this potential complication is important, as early initiation of immunotherapy combined with GABA-enhancing therapy may improve both neurological and skeletal outcomes.
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