A New Era for Huntington’s Disease Care: 2026 AAN Key Takeaways

Huntington’s Disease (HD) represents one of the most challenging neurodegenerative conditions in modern medicine. For healthcare providers, managing HD requires more than just a deep understanding of neurology. Managing HD demands a holistic perspective that balances motor, psychiatric, and cognitive symptoms. As presented at the 2026 AAN Annual Meeting in Chicago by Dr. Victor Sung, Director of the University of Alabama at Birmingham (UAB) HD Center of Excellence, the “Treatment of HD – The Present” is focused on aggressive symptomatic management while preparing for a future defined by disease-modifying therapies.

Expert Insights into Modern Management, Staging, and the Multi-Disciplinary Approach

Managing Huntington’s Disease (HD) requires addressing the “HD Triad” of motor, cognitive, and psychiatric symptoms. While chorea is the most recognizable sign, psychiatric issues like depression and high suicide risk often cause the greatest caregiver burden. Clinical practice recognizes three main phenotypes: motor-predominant, mixed motor/behavioral, and pre-manifest. Treatment has evolved with the HD-Integrated Staging System (HD-ISS), which uses biological landmarks such as CAG repeat length (>40) and brain volume reduction to track progression from Stage 0 to Stage 3. For chorea, VMAT2 inhibitors like tetrabenazine, deutetrabenazine, and valbenazine are first-line therapies. Choosing between them depends on dosing needs—ranging from TID to once-daily—and side effect profiles such as sedation or depression.

Management must be multidisciplinary, involving PT/OT, speech therapy, and social work to mitigate functional decline. Current guidelines also emphasize managing non-motor symptoms like apathy and agitation through environmental modifications and pharmacological adjustments. Ultimately, early “research care” via clinical trials remains the gold standard for management while awaiting disease-modifying breakthroughs.

Why It Matters

The Burden of the HD Triad

Huntington’s Disease is characterized by the HD Triad, a relentless combination of motor, cognitive, and psychiatric symptoms. Understanding this triad is critical because it dictates the patient’s functional decline. While chorea is the most recognized motor hallmark, affecting approximately 90% of patients, it is often the psychiatric and cognitive components that cause the greatest caregiver burden and early loss of independence.

• Motor Symptoms: Chorea impacts gait, coordination, speech, and swallowing. However, the movement disorder also encompasses tics, dystonia, and a hallmark slowing of smooth pursuit and saccades.
• Cognitive Symptoms: Patients face executive dysfunction that inexorably progresses to full-scale dementia.
• Psychiatric/Behavioral Symptoms: Depression and OCD are found in 30-80% of patients. Perhaps most critically for providers, HD carries a significantly elevated suicide risk and high levels of impulsivity, irritability, and apathy

In the absence of current disease-modifying therapies (DMTs), symptomatic treatment is our primary tool to maintain quality of life. As clinicians, our role is to mitigate the functional impact of these symptoms across all Activities of Daily Living (ADLs).

Who It Affects

A Spectrum of Phenotypes

HD does not present uniformly. Clinical practice typically encounters three distinct phenotypes that require tailored approaches:

1. The Motor-Predominant Phenotype

These patients, often mid-manifest, present primarily with chorea and physical clumsiness. A classic case involves a 44-year-old mechanic noticing trouble at work. For these individuals, the focus is on VMAT2 inhibitors to control involuntary movements and prolong their ability to remain in the workforce. Even mild chorea can have a massive impact on voluntary tasks, often hidden by the patient’s own disease unawareness (anosognosia).

2. The Mixed Motor/Non-Motor Phenotype

Younger patients may present with more aggressive behavioral issues. A 27-year-old prodromal patient might lose their job due to irritability or lashing out rather than motor failure. In these cases, the use of atypical antipsychotics (like risperidone) serves a dual effect, treating both the chorea and the psychiatric aggression.

3. The Pre-manifest / Early Manifest Candidate

These individuals are often highly aware of their genetic status and are actively seeking clinical trials. For a 47-year-old with 41 CAG repeats and subtle motor signs (TMS of 6), management is less about heavy medication and more about “research care,” psychological support, and sleep hygiene to preserve their current function while awaiting DMT breakthroughs.

What Changes

The New Frontier of Staging and Treatment

The clinical understanding of HD staging has undergone a paradigm shift. We are moving away from simple “Pre-manifest vs. Manifest” toward the HD-Integrated Staging System (HD-ISS).

Redefining the Disease Course

Under the HD-ISS, we now recognize stages based on biological and clinical landmarks:

• Stage 0: Genetic confirmation (CAG ≥ 40) with no clinical changes.
• Definition: Individuals who have the genetic marker for HD
• Clinical Status: Classified as Premanifest HD
• Stage 1: Biomarkers of pathogenesis (reduction in Putamen and Caudate volume).
• Definition: Evidence of underlying brain changes before clinical symptoms emerge
• Clinical Status: Primarily falls under Premanifest HD
• Stage 2: Emergence of clinical signs or symptoms (Total Motor Score changes).
• Definition: The onset of detectable motor or cognitive changes
• Clinical Status: Classified as Prodromal HD
• Stage 3: Functional change (decline in Total Functional Capacity).
• Definition: The disease begins to impact the patient’s daily functional abilities
• Progression: This stage is further subdivided into mild, moderate, and severe functional decline
• Clinical Status: Classified as Manifest HD (corresponding to traditional Shoulson-Fahn Stages)

The Chorea Treatment Landscape

Treatment for chorea has expanded significantly. FDA-approved VMAT2 inhibitors now include tetrabenazine (short half-life, TID dosing), deutetrabenazine (medium half-life, BID dosing), and the recently approved valbenazine (long half-life, once-daily dosing). While antipsychotics remain common due to low cost and dual effects, evidence-based guidelines from the AAN and EHDN emphasize VMAT2 inhibitors as first-line therapy for isolated chorea due to their superior evidence base (Grade A/Level B evidence).

Chorea Treatment Decision Tree

1. Assessment: Determine if chorea requires treatment. - Criteria: Chorea is significant on its own (Total Maximal Chorea (TMC) score in the 15–20 range) OR it is mild but represents a significant percentage of the Total Motor Score (TMS). 2. Initial Selection: If treatment is indicated, assess behavioral symptoms. - Pathway: If there are no significant behavioral symptoms, start with a VMAT2 inhibitor. 3. Financial Consideration: Assess the patient’s financial options. - Action: If financially viable, prioritize starting with a novel VMAT2 inhibitor (VMAT2i). 4. Final Drug Selection: Choose the specific novel VMAT2i. - Decision Factors: Select between deutetrabenazine and valbenazine based on the patient’s specific need for rapid efficacy and the drug’s adverse effect (AE) profile.

HD Genetic Testing Guidelines Comparison

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The Multi-Disciplinary Standard of Care

No neurologist can manage HD alone. The broad impact of the disease requires a team-based approach, modeled by the HDSA Centers of Excellence. This team must include:

• PT/OT/Speech Therapy: To manage gait and swallowing risks.
• Social Workers: Critical for navigating disability applications and long-term care.
• Dietitians: To combat the high metabolic demand and weight loss associated with the disease.
• Psychotherapists: To provide the emotional support necessary to navigate the “Life Milestones” (marriage, family, job loss) that are complicated by the disease.

2018 EHDN/HSG Expert-Based Consensus Guidelines

1) Agitation

• Identify and treat comorbid medical conditions that may precipitate acute agitation.
• As a preventative strategy, promptly treat irritability, other coexisting psychiatric symptoms, and sleep disturbances.
• Modify environmental factors that may contribute to agitation.

2) Anxiety

• Treat coexisting psychiatric symptoms or comorbid medical conditions.
• Modify environmental factors that may contribute to anxiety.

3) Apathy

• Differentiate apathy from the impaired ability to perform motor or cognitive tasks.
• Consider dose reduction of medications.
• Treat coexisting depression, as it may contribute to apathy.

4) Psychosis

• Identify and treat comorbid medical conditions that can precipitate the acute onset of psychotic symptoms.
• Treat coexisting psychiatric symptoms of HD.
• Modify external environmental factors that may contribute to the distress caused by psychotic symptoms.

5) Sleep Disorders

• Treat potential contributing factors to sleep disturbance in HD.
• Assess and adjust dosing schedules of medications that may contribute to sleep disturbances.

“Research care is clinical care”

For patients in the early stages, participating in trials isn’t just about the future of science. Participating in clinical trials provides a level of monitoring and specialized attention that is the gold standard for HD management today.

Conclusion

Huntington’s Disease management is an evolving field. By identifying the specific phenotype of the patient, utilizing the latest VMAT2 inhibitors, and embracing the Integrated Staging System, healthcare providers can offer more than just symptom control; they can offer a roadmap. As we await the arrival of therapies targeting somatic expansion and mHtt lowering, our priority remains clear: comprehensive, multi-disciplinary care that preserves the dignity and independence of the patient for as long as possible.

Reference

1. “Treatment of HD – The Present” by Victor Sung, MD (2026). UAB HD Center of Excellence | Heersink School of Medicine.
2. Tabrizi SJ, Schobel S, Gantman EC, et al. A biological classification of Huntington’s disease: the Integrated Staging System. Lancet Neurol. 2022;21(7):632-644. doi:10.1016/S1474-4422(22)00120-X
3. Anderson KE, van Duijn E, Craufurd D, et al. Clinical Management of Neuropsychiatric Symptoms of Huntington Disease: Expert-Based Consensus Guidelines on Agitation, Anxiety, Apathy, Psychosis and Sleep Disorders. J Huntingtons Dis. 2018;7(3):355-366. doi:10.3233/JHD-180293