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Project Aim:
1 - To change the current diagnostic criteria to include cognitive, psychiatric, behavioral, and vegetative decline for diagnosis via the UHDRS.
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UHDRS Q80 should be changed: Q80 diagnostic criteria (Motor, Cognitive, Behavioral, and Functional components) do you believe with a confidence level ≥99% that this participant has manifest HD? (0 = No, 1 = Yes)
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Confidence level ≥99% should be changed to ≥50%
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2 - If a patient has an expanded CAG (mutation above normal range) and expresses cognitive, psychiatric, behavioral, or vegetative decline, the patient should receive a diagnosis of Huntington's disease. A diagnosis for patients with these symptoms of Huntington's disease will facilitate the necessary supports and services they need.
Current Diagnostic Criteria for Huntington's Disease:
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Does not meet the needs of our patients and families.
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Excludes a large group of our patients who do not express overt motor symptoms (chorea).
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Does not effectively support our patients who have manifested: psychiatric, cognitive, behavioral, and vegetative symptoms of Huntington’s disease.
How did Project CHANGE begin?
Patients / Family Feedback:
The endeavor and goal to change the diagnostic criteria for Huntington’s disease are driven by patients and families worldwide. WeHaveAFace.org, and its Senior Medical Advisor, Dr. Herwig Lange (George Huntington Institute of Germany), asked the international Huntington’s disease community to participate in an anonymous survey on October 13, 2020. The survey was shared via social media platforms (Facebook, Twitter, LinkedIn, Instagram, etc.), WeHaveAFace Global Times (electronic newspaper), WeHaveAFace TV, and WeHaveAFace global email database.
The Survey Question: “Should the diagnostic criteria for Huntington's disease be reviewed and updated?”
*In the survey, "other symptoms" pertain to depression, anxiety, behavioral issues, mood swings, physical abuse, social issues, alcohol/drug issues, suicidal thoughts/actions, apathy, sexual promiscuity, inability to hold employment/problems at work, etc.*
Results:
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Over 5,000 of our patients/caregivers participated, and saturation was reached via early review of data on November 15, 2020; however, the survey remained open until January 7, 2021, for additional data collection.
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Overall: 95% of our patients and families surveyed agreed that the diagnostic criteria for Huntington’s disease should be reviewed and updated.
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Participating countries: USA, Canada, Mexico, England, Scotland, Ireland, Germany, Finland, Australia
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See survey results and read comments from our patients and families.
Dr. Hugh Rickards, Professor of Neuropsychiatry (National Centre for Mental Health, Birmingham, England), brought up a fundamental question for our patients and families. With Dr. Rickards’ question in mind, the international group continued to move this mission forward and published an anonymous poll on March 1, 2021. The poll was shared via social media platforms (Facebook, Twitter, Instagram, and email).
Dr. Rickards’s question was: “Why is a diagnosis of Huntington's disease important to you?"
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On March 7, 2021, over 4,000 individuals within the international Huntington’s community voiced their opinion and participated. The poll closed on March 15, 2021.
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Participating countries: USA, Canada, Mexico, England, Scotland, Ireland, France, Germany, Netherlands, Italy, Australia, and Spain.
Chart expressing Huntington’s disease community polling results:
Data from the three lowest polled responses:
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My parent did not/will not get tested, but I want to know.
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To participate in studies and trials.
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To plan to have biological children.
Project CHANGE!
Petition Results
Once the new proposal was completed, we brought the new clinical diagnostic criteria recommendations to our global population. Via a petition, we asked patients, caregivers, family, friends, and our HD medical professionals to sign the petition if they agreed with the updated recommendations. We were not surprised by the results! Please review them below.
Diagnosis
Project CHANGE partnering HD organizations and medical professionals wish to underscore that a diagnosis of Huntington's disease is not for everyone. This is not our aim. We fully understand and recognize the implications of a diagnosis.
Based on our global polls and petition feedback, Dr. Herwig Lange (George Huntington Institute, Germany) created a proposal of recommendations for new clinical diagnostic criteria for Huntington's disease. This proposal will benefit patients with a diagnosis of Huntington's disease when it is needed. We are pleased that a project of this magnitude was driven by the perspectives of our global Huntington's disease community. Decision-making on any diagnostic criteria must include the population being served.
Recommendations for New Clinical Diagnostic Criteria of Huntington’s Disease
This proposal was written by Dr. Herwig Lange (George Huntington Institute, Germany), and supported by: Dr. Thomas Bird (Founder of University of Washington HDSA Center of Excellence), Dr. Travis Cruickshank (Edith Cowan University, Perth Australia), Dr. Matthias Dose (founder of Huntington-Zentrum Süd, Munich, Germany). Dr. Clare Eddy (Birmingham and Solihull Mental Health NHS Foundation Trust, England), Dr. Jane Paulsen (University of Wisconsin-Madison), Dr. Hugh Rickards (University of Birmingham, England), Dr. Adolf Weindl (Technische Universität München, Munich, Germany),
Project CHANGE International Support Network
Without the support and participation from the Huntington's community, nothing can change. Therefore, it is paramount that patients and families take the lead in bringing about the changes we need. We are also pleased that many HD organizations and medical professionals are supporting this initiative. Together we can better the lives of our Huntington's patients and families.
Dr. Herwig Lange (George Huntington Institute), Dr. Ralf Reilmann (George Huntington Institute), James Valvano (WeHaveAFace), Louise Vetter (HDSA), Debra Lovecky (HDSA), Dr. Jane Paulsen (University of Wisconsin, Madison), Dr. Hugh Rickards (National Centre for Mental Health, Birmingham), Dr. Travis Cruickshank (Edith Cowan University), Mayke Oosterloo (Maastricht University Medical Center, NL), Dr. Thomas Bird (HDSA CoE, University of Washington), Dr. Roger Barker (University of Cambridge, UK), Dr. Raymund A. C. Roos (Leiden University Medical Centre, NL), Debbi Fox-Davis (HDReach.org), Donaji Toledo, (AMEH - La Asociación Mexicana de la Enfermedad de Huntington), Tatiana Henrique, (ABH – Associação Brasil Huntington), Cath Stanley, (HDA - Huntington's Disease Association), Frances Saldana, (HDCare.org), Dr. Clare Eddy, (Birmingham and Solihull Mental Health NHS Foundation Trust).
Project Support
Video Testimonies
The following information underscores the importance of Project CHANGE
What is Huntington’s Disease?
It is important to define Huntington’s disease. As per the National Institute of Neurological Disorders and Stroke (NINDS), "Huntington's disease (HD) is an inherited disorder that causes brain cells, called neurons, to die in various areas of the brain, including those that help to control voluntary (intentional) movement. Symptoms of the disease, which gets progressively worse, include uncontrolled movements (called chorea), abnormal body postures, and changes in behavior, emotion, judgment, and cognition. People with HD also develop impaired coordination, slurred speech, and difficulty feeding and swallowing. HD typically begins between ages 30 and 50. An earlier onset form called juvenile HD occurs under age 20. Its symptoms differ somewhat from adult onset HD and include rigidity, slowness, difficulty at school, rapid involuntary muscle jerks called myoclonus, and seizures. More than 30,000 Americans have HD. Huntington’s disease is caused by a mutation in the gene for a protein called huntingtin. The defect causes the cytosine, adenine, and guanine (CAG) building blocks of DNA to repeat many more times than is normal. Each child of a parent with HD has a 50-50 chance of inheriting the HD gene. A child who does not inherit the HD gene will not develop the disease and generally cannot pass it to subsequent generations. A person who inherits the HD gene will eventually develop the disease. HD is generally diagnosed based on a genetic test, medical history, brain imaging, and neurological and laboratory tests."
*NINDS description of HD is incomplete as it does not include the malfunction and loss of glial cells (cells essential to support and protect neurons), which are more frequent in the brain than neurons. The NINDS description also lacks information about the damage to cortical areas of the brain, leading to psychiatric, cognitive, and behavioral problems. These problems with HD are more relevant to patients and families in their everyday functions than motor symptoms (chorea), as per the feedback from our international survey.
Although a definition of Huntington’s disease can be found on the websites of every HD lay organization, HD Center, HD Healthcare Center, etc., to truly comprehend what Huntington’s disease is, it is paramount to have the insights and life experiences of patients, caregivers, and families who are directly affected. It is also imperative that the voices of Huntington’s patients, caregivers, and families are heard. These warriors are the natural experts! Sadly, the challenge that patients and families experience is receiving a diagnosis of Huntington’s disease when needed. The global Huntington’s community has spoken, and it is time to have the current diagnostic criteria changed to benefit the needs and lives of patients and families.
Note: As per EHDN (European Huntington Disease Network), a meeting took place in Vienna (2019) – a redefining of JHD (Juvenile-onset HD) was accepted. The publication (January 2019) is now defined as Pediatric Huntington’s disease. Read paper
Understanding why the current diagnostic criteria for Huntington's disease must be changed.
The American Academy of Neurology (AAN), and the Movement Disorder Society, have not effectively procured the support and needs of our Huntington’s patients and families. We all must come together for the betterment of our community.
The PREDICT HD study, conducted over twelve years and funded by the NINDS (National Institute of Neurological Disorders and Stroke), found that behavioral and cognitive changes occur decades before the movement disorder, yet neurologists have been slow at best in incorporating the research into their practice and diagnosis. PREDICT HD looked specifically at recognizing early HD with the expectation that data would assist in the development of disease-modifying therapies.
Another point to consider is the recent updating of the diagnostic criteria for ALS (amyotrophic lateral sclerosis), which sought to improve the early diagnosis of the disease when clinical symptoms were minimal so affected patients could access various therapies and sustain a higher quality of life. The consensus group agreed that ALS was a progressive disorder. The new definition of ALS is Progressive motor impairment, documented by history or repeated clinical assessment, preceded by normal motor function. Upper and lower motor neuron dysfunction in at least one body region (in the same body region if only one body region is involved), or lower motor neuron dysfunction in at least two body regions. Investigation finds that excluded alternative disease processes.
This new definition raises a few points for diagnosing Huntington’s disease - it is a progressive disease leading to impairment in one or more of three distinct spheres – behavior, cognition, motor – that can be documented by history or repeated clinical assessment. But unlike ALS, at what point does each of those spheres meet a minimum measure of impairment? If a Huntington’s patient is gene-positive, is 50% impairment in one or more spheres adequate for a diagnosis? The TFC (Total Functional Capacity) scale, created by Shoulson and Fahn, 1979, and then adopted by the HSG in 1996), is the main assessment tool of functional status in HD clinical care and research. It has been used as the primary outcome measure in several clinical trials in manifest HD.
However, as per the TFC – the scale was designed to assess progression of HD in patients with manifest disease and accordingly emphasizes self-care, mobility, and independence. Is the TFC a reliable tool to assess this degree of impairment? How can documentation by healthcare providers be standardized so impairment observed/documented over time is reliable?
What effect does a diagnosis have for our patients who are gene positive? Does knowing with a 50% certainty provide a greater or lesser benefit to the individual? Will it make a significant difference in the choices our patients and families make? If a survey of the HD community supports the benefit of a definitive diagnosis with 50% certainty, then the voice of the patients and families must be included in any modifications made to diagnostic criteria. Some of the resistance to change is mired in paternal attitudes that persist in the medical community.
It doesn’t seem to matter if the physician is younger or older, many still cling to the idea that the patient doesn’t have sufficient knowledge to form an opinion even when the family may be actively educating the healthcare provider about Huntington’s disease in order to obtain a diagnosis.
Earlier diagnosis would open access to therapies that could improve the quality of life of our community, but the flip side of an earlier diagnosis might be denial of access to clinical trials. The Huntington’s community wants this to be considered since we are still lacking any real therapy.
Training for neurologists in movement disorders, including Huntington’s disease, has not changed significantly in over twenty-five years – since the gene was actually located. Neurologists are still taught that HD is a movement disorder first, and other symptoms follow.
This specific topic on how little training medical professionals receive regarding Huntington’s disease was outlined within the 2019 award-winning documentary – “The Purple Road” (29:44 – 30:50), by WeHaveAFace.org.
As of 2019 what we found were the following:
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Medical Schools: most often only 1-2 hours, mostly on biology and genetics of HD.
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Internal Medicine for Family Practice Residency Training: at best, 1-2 hours.
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Neurology Residency Training: only a few hours unless the trainee specifically requests it.
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The Movement Disorder Fellowship Training: for many programs, this is still only a few hours, even in centers that have HD-specific clinics.
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Psychiatry Fellowship Training: many programs offer no training in HD.
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Post-Graduate Continuing Education: hasn’t been offered before 2010.
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It is hard to get doctors to attend a course in HD, including Movement Disorder Neurologists, even when it is free.
Additional proof for necessary changes to take place was expressed in our first award-winning documentary - "The Huntington's Disease Project: Removing the Mask." The documentary took on the most sensitive subject matter relating to Huntington's disease. At that time it was taboo to remove the mask on topics that were hidden for decades (psychiatric, cognitive, behavioral, and vegetative), listed above. It was time to let patients and caregivers openly discuss what truly happens to patients and families - unsensored.
It has been noted that some neurologists are reluctant to diagnosis HD in the absence of movements since they continue to believe that there is little that can be done for the patient. As per the publication, “A Physician’s Guide to the Management of HD,” by the HDSA (Huntington’s Disease Society of America), observational studies have demonstrated that changes can occur prior to the development of motor symptoms. In fact, “A Physician’s Guide to the Movement of HD” notes that cognitive changes have been observed in 40% of individuals studied and are detectable in more than 70% of those close to a diagnosis of manifest HD. Several studies have suggested that cognitive and behavioral impairments are greater sources of impaired functioning than the movement disorder in persons with HD, both in the workplace and at home. Yet neurologists will not diagnosis without the movement disorder.
Published papers call for a review of current diagnostic criteria for Huntington's disease
Mark Guttman, MD, FRCPC - Center for Movement Disorders
"Individuals at risk for HD are given a clinical diagnosis of the disease only after they have developed motor abnormalities. Clinicians, families and patients are aware that changes occur in many nonmotor domains, including cognition and behaviour, years before the motor-dependent clinical diagnosis is made in some individuals. Longitudinal observational studies have identified that there are many changes that occur before the clinical diagnosis of HD. Researchers postulate that these changes should be considered part of the pathological process of HD. Since these changes have occurred before clinical diagnosis using motor criteria, to date it has been difficult to categorize them and to determine their relevance when planning clinical trials and dealing with regulatory agencies. Using the concept of a patient converting from a presymptomatic state to being diagnosed with HD as an endpoint of clinical trials creates considerable methodological problems. Furthermore, if this is to be the only focus of disease modifying research in HD, we will lose the opportunity to modify the underlying disease process in the earliest stages of the condition. We propose a different conception of HD as the spectrum of clinical manifestations that includes the earliest symptoms as part of HD even before diagnosis by current diagnostic criteria. The paradigm shift is to change the focus of clinical research from the concept of preventing the transition of subjects from a "preclinical" to "diagnosed with HD" state to altering the progression of HD throughout the entire spectrum of the disease."
As per the Journal of the Neurological Sciences - "Mild cognitive impairment and dementia in motor manifest Huntington's disease: Classification and prevalence" - "In patients with HD, there are neurodegenerative changes that involve the cerebral cortex, striatum, subcortical white matter, hippocampus, cerebellum, and brainstem [4]. These degenerative changes can lead to a variety of cognitive impairments in HD [5]. In premotor-HD, which is the stage before the onset of motor symptoms in genetically confirmed HD patients [6], early functional brain impairments in medial and dorsolateral prefrontal cortical networks may occur before cortical or striatal atrophy are evident [7–9]. Subsequently, when the motor abnormalities emerge, structural striatal and thalamic atrophy often plays a role in executive dysfunction [10,11]." Read Article.
Mild Cognitive Impairment as an Early Landmark in Huntington’s Disease
"Seven hundred and sixty-eight prodromal HD participants had completed all six cognitive tasks, had MRI, and underwent longitudinal assessments. Over half (i.e., 54%) of the participants had MCI at study entry, and half of these had single-domain MCI. Compared to participants with intact cognitive performances, prodromal HD with MCI had higher genetic burden, worsened motor impairment, greater brain atrophy, and a higher likelihood of estimated HD onset. Prospective longitudinal study of those without MCI at baseline showed that 48% had MCI in subsequent visits and data visualization suggested that single-domain MCI, two-domain MCI, and dementia represent appropriate cognitive impairment staging for HD gene-mutation carriers. Findings suggest that MCI represents an early landmark of HD and may be a sensitive enrichment variable or endpoint for prodromal clinical trials of disease modifying therapeutics." - Read Article.
Ying Zhang 1, Junyi Zhou 2, Carissa R. Gehl 3, Jeffrey D. Long 3,4, Hans Johnson 3,5,
Vincent A. Magnotta 3,6, Daniel Sewell 4, Kathleen Shannon 7 and Jane S. Paulsen 7*
Cognitive Impairment in Huntington Disease: Diagnosis and Treatment
"Cognition has been well characterized in the various stages of Huntington disease (HD) as well as in the prodrome before the motor diagnosis is given. Although the clinical diagnosis of HD relies on the manifestation of motor abnormalities, the associated impairments have been growing in prominence for several reasons. First, research to understand the most debilitating aspects of HD has suggested that cognitive and behavioral changes place the greatest burden on families, are most highly associated with functional decline, and can be predictive of institutionalization. Second, cognitive impairments are evident at least 15 years prior to the time at which motor diagnosis is given. Finally, cognitive decline is associated with biological markers such as brain atrophy, circulating levels of brain-derived neurotrophic factors, and insulin-like growth factor 1. Efforts are now underway to develop valid and reliable measures of cognition in the prodrome as well as in all stages of HD so that clinical trials can be conducted using cognitive outcomes. Cognitive measures have excellent potential both for the early detection of HD in persons with genetic risk and as sensitive outcomes in clinical trials. Cognitive impairment is evident decades before motor diagnosis is given, and diagnostic criteria for HD should be revisited to keep clinical practice in concert with research findings. Cognitive tools for clinical trials are needed, and much cognitive research remains to be done to assure that reliable, valid, and feasible cognitive measures are available to detect changes secondary to interventions in HD." Jane S. Paulsen - Read Article.
Since the rollout of Project CHANGE, we have witnessed a forward-thinking approach toward diagnosing patients who suffer from cognitive, psychiatric, behavioral, and vegetative decline. Although it is a step in the right direction, it is imperative to have more supportive documentation that aligns with the needs of our patients and families.
