Speakers - 2026

Title: An Unexpected Rhythm: Adult Onset Alexander Disease Presenting with Palatal Myoclonus

Abstract

Adult-onset Alexander disease (AOAD) is a rare neurodegenerative leukodystrophy caused by mutations in the glial fibrillary acidic protein (GFAP) gene. Compared with the infantile form, adult-onset disease often presents with subtle and heterogeneous neurological manifestations, making diagnosis particularly challenging. We present a clinically diagnosed case of AOAD in a patient with progressive palatal myoclonus and cerebellar ataxia, highlighting the diagnostic complexity and importance of recognizing characteristic clinical and radiological findings.

The patient experienced a slowly progressive neurological syndrome characterized by palatal myoclonus, gait ataxia, mild dysphagia with intermittent nasopharyngeal aspiration, and progressive functional decline. MRI demonstrated characteristic medullary and upper cervical spinal cord atrophy, strongly supporting the diagnosis of adult-onset Alexander disease despite negative GFAP genetic testing, which is recognized in a proportion of clinically typical cases.

During the disease course, the patient developed recurrent episodes of sepsis, anaemia, odynophagia, and significant nutritional deterioration. While dysphagia contributed to aspiration risk, multidisciplinary assessment suggested that poor oral intake was multifactorial, with psychosocial factors also playing an important role. Nutritional management required close collaboration between neurology, speech and language therapy, dietetics, palliative care, and primary care to determine the appropriate timing of enteral feeding while balancing quality-of-life considerations.

Further neurological evaluation identified an asymmetric patchy sensory neuropathy on nerve conduction studies, prompting investigations for alternative or concurrent pathologies, including paraneoplastic syndromes and systemic vasculitis. Additional investigations included ANCA and paraneoplastic antibody testing, nutritional screening, evaluation for infective endocarditis, and MRI of the whole spine to exclude other causes of neurological deterioration.

This case demonstrates the broad clinical spectrum of adult-onset Alexander disease and emphasizes the importance of integrating clinical findings with characteristic neuroimaging when genetic testing is inconclusive. It also illustrates the challenges of managing systemic complications in patients with progressive neurodegenerative disorders and highlights the value of multidisciplinary care in optimizing diagnosis, treatment, nutritional support, and patient outcomes.

Audience Takeaways:

Following this presentation, participants will be able to:

• Recognize the characteristic clinical features of adult-onset Alexander disease, including palatal myoclonus and progressive cerebellar ataxia.
• Identify the hallmark MRI findings of medullary and upper cervical spinal cord atrophy that support diagnosis, even when GFAP genetic testing is negative.
• Develop an evidence-based differential diagnosis for palatal myoclonus, including neurodegenerative, paraneoplastic, vascular, inflammatory, and structural causes.
• Appreciate the role of multidisciplinary management in addressing dysphagia, malnutrition, recurrent infections, and palliative care needs.
• Apply a systematic approach to investigating atypical neurological deterioration by considering concurrent neuropathies, vasculitic disorders, and paraneoplastic syndromes.

Benefits to the Audience:

This presentation will increase awareness of a rare but clinically important neurological disorder and provide practical diagnostic strategies that can shorten time to diagnosis. Attendees will gain insight into interpreting characteristic MRI findings, managing complex systemic complications, coordinating multidisciplinary care, and recognizing when additional investigations are warranted despite an established neurodegenerative diagnosis. The case also provides valuable teaching material for clinicians, educators, and researchers interested in rare neurological diseases.