Coexistence of relapsing-remitting multiple sclerosis and Huntington’s disease: a rare overlap of neuroinflammatory and neurodegenerative disorders

Abstract

Case Presentation: A 36-year-old man with a family history of Huntington’s disease (HD) (affected father) presented with progressive imbalance and sensory symptoms. The patient was previously asymptomatic until 2021, when he developed right-sided ataxia and gaze-evoked nystagmus. At that time, no formal diagnosis was established; he received pulse corticosteroid therapy with incomplete recovery and remained without neurological follow-up for three years. During this period, the patient experienced clinical progression and the development of new lesions. In August 2024, he was hospitalized with dizziness, gait instability, headache, nausea, and hand paresthesia. Examination was consistent with cerebellar syndrome. He received five days of pulse therapy with partial improvement. MRI revealed multiple periventricular, juxtacortical, and infratentorial lesions, including the cerebellar peduncles and cervical spinal cord with gadolinium enhancement, fulfilling the McDonald criteria for a definitive diagnosis of relapsing-remitting MS (RRMS). Natalizumab was initiated, achieving satisfactory control of new relapses. However, during follow-up, the patient tested positive for anti-JCV antibodies, and treatment was later switched to cladribine. Despite inflammatory stability, the patient developed a dysexecutive syndrome and orofacial tics, alongside an increased frequency of falls due to involuntary movements. Hyperkinetic features, including chorea and tic-like movements, became prominent. Given the family history and atypical progression for MS alone, genetic testing was performed after shared decision-making, confirming HTT gene expansion with 47 CAG repeats and establishing the HD diagnosis. The patient remained clinically stable under cladribine but continued to exhibit cognitive impairment and persistent involuntary movements, consistent with HD progression. Discussion: This case illustrates a rare coexistence of RRMS and HD, with few cases reported worldwide. MS is an inflammatory demyelinating disease with multifocal white matter lesions, while movement disorders are uncommon. The progressive hyperkinetic symptoms and family history supported investigation for HD, an autosomal dominant neurodegenerative disorder caused by CAG expansion in the HTT gene. There is limited evidence on shared pathophysiology or interaction between these conditions. The diagnostic challenge in this overlap lies in distinguishing which symptoms arise from inflammatory demyelination versus neurodegeneration. The emergence of a dysexecutive syndrome and choreiform movements in a patient with a family history of HD should prompt genetic screening. Final Comments: This case emphasizes the rare coexistence of RRMS and HD and the importance of considering concurrent diagnoses in patients with atypical features and relevant family history. The lack of evidence on disease interaction underscores the need for further research and personalized management.