Menopause is under-recognized as a biological and sociocultural contributor to brain health, and scientific understanding of the impact that the menopausal transition has on the brain is minimal. This knowledge gap is particularly detrimental for women who live with neurological conditions. We lack sufficient data to understand the experience of women with established neurological conditions during perimenopause, the mechanisms associated with postmenopausal changes in disease course and how to improve management of neurological conditions in a sex-specific way. Furthermore, approximately two thirds of women experience cognitive concerns during the menopausal transition. Although earlier menopause is associated with a greater risk of cognitive decline, the influence of the menopausal transition on subsequent risk of neurological conditions remains unclear. In this Roadmap, we identify key areas in which research is limited and highlight historical and scientific challenges that have hindered progress in understanding brain health in the context of menopause. To address these challenges, we consider existing knowledge and propose priorities and future research directions to advance our understanding of the relationship between menopause and neurological health and disease.

Primary (genetic) pediatric dystonia, characterized by sustained or intermittent muscle contractions that cause abnormal movements or postures, affects 16.4 in 100,000 children worldwide. It can be caused by various factors, including pathogenic variants in genes such as TOR1A, associated with DYT-TOR1A dystonia. In this report, we present the case of a toddler with DYT-TOR1A treated with deep brain stimulation (DBS) because of his early-onset, rapidly progressive, and refractory status dystonicus. Genetic testing confirmed a maternally inherited pathogenic variant in TOR1A, c.907_909del (p.Glu303del). His dystonia was refractory to multiple optimized medications and continuous infusions. Ultimately, DBS surgery to the bilateral globus pallidus interni (GPi) provided symptomatic relief of his status dystonicus. His atypical presentation and young age made it difficult to predict expected outcomes. Thus, he required unique planning considerations before placement of bilateral GPi DBS. This case highlights challenges in symptom management, anticipatory guidance, and treatment expectations in the complex and refractory condition of status dystonicus for a young patient with DYT-TOR1A.

A 79-year-old man with metastatic Merkel cell carcinoma undergoing cancer-directed treatment was admitted to the hospital with 1 week of bilateral upper and lower extremity tremor and nearly continuous involuntary facial movements. These abnormal movements of his face, head, and limbs were exacerbated by purposeful movement. Examination revealed dysarthria with tremulous speech, intention tremors of the head and all extremities, distally diminished vibration sense with hyporeflexia, bilateral upper extremity dysdiadochokinesis, bilateral lower extremity dysmetria on heel-to-shin testing, and truncal ataxia. MRI of the brain showed no acute abnormalities. CSF and serum testing showed evidence of CNS inflammation with a CSF lymphocytic pleocytosis and elevated total protein. Diagnosis was ultimately made using serum and CSF studies. Here, we discuss the differential diagnosis of 2 weeks of diffuse intention tremor, involuntary facial movements, and ataxia. We discuss the workup, diagnosis, acute and nonacute management of this condition, as well as important clinical points regarding the broader category into which this diagnosis falls.