The diagnosis and treatment of choreoa and tardive dyskinesia related to Huntington's disease in adults was explained at this summit forum

The first Deuterium Tetrabenazine China-West International Summit Forum ended successfully, and we reviewed the wonderful content
together.

In the field of movement disorders, there is a common direction of neurology and psychiatry, that is, extrapyramidal diseases, in which hypotonia-hyperkinesthesia, with Huntington's disease (HD) and tardive dyskinesia (TD) as the main representative diseases
.

With the approval of deuterated tetrabenazine tablets (trade name: Titan), new treatments have been provided for adult HD-related chorea, adult patients with HD and TD at home and abroad, making it possible
to further improve their quality of life.
On October 29, 2022, the first Deuterium Tetrabenazine China-West International Summit Forum was successfully held in Chengdu, where many experts in neurology and psychiatry at home and abroad shared their experience in TD and HD treatment, opening up a smooth life path
for more patients.
This article summarizes and organizes the main hot topics of this summit forum, collects the essence, and shares it with readers
.

Experts at home and abroad collide in thinking, and HD and TD diagnosis and treatment experience is coming

This summit forum brought together neurologists and psychiatrists, top experts and scholars from home and abroad to share clinical experience and jointly explore more suitable diagnosis and treatment solutions
for HD and TD patients.

HD is an autosomal dominant neurodegenerative disorder that typically presents with a triad of motor disorders, cognitive impairment, and psychobehavioral abnormalities
.
Movement disorders in HD include involuntary movements, which typically present with chorea-like symptoms, and dystonia, loss of postural reflexes, bradykinesia, and muscle rigidity; Involuntary motor symptoms can affect patients' voluntary movement, and the latter often affects quality of life more than the former, including slurred speech, dysphagia, unsteady walking, balance disorders, etc
.

More than 90% of patients with HD develop chorea-like symptoms, which can occur at different stages
of the course of HD.
Selective vesicle monoamine transporter 2 (VMAT2) inhibitors can be used in patients with chorea-like symptoms, and deuterated tetrabenazine has been shown to significantly reduce the maximum choreaa (TMC) score (4.
4 points) [^1], with a low
incidence of adverse effects.

In addition to HD, neurologists may also be exposed to TD patients
.
The pathophysiology of TD has not been fully elucidated and may be related to DA receptor upregulation and hypersensitivity (Figure 1), abnormal γ-aminobutyric acid (GABA) neuronal function, and cholinergic dysfunction ^[2].

TD is generally considered difficult
.
Studies have shown that lowering or discontinuing antipsychotic medications has a limited effect on relieving TD [^3], and switching from first-generation antipsychotics to second-generation antipsychotics does not improve TD ^[4].

Fig.
1 Mechanism of postsynaptic dopamine receptor upregulation and hypersensitivity response triggering TD

With the deepening of research and the continuous development of drugs, the treatment of TD has experienced the stage of no drug availability to drug finding, and deuterium tetrabenazine provides a new method
for the treatment of TD.
The 2013 American Academy of Neurological Disorders (AAN) guidelines do not have a Class A recommendation for TD ^[5].

The 2018 updated AAN guidelines state that the novel selective VMAT2 inhibitors deuterated tetrabenazine and valbenazine are recommended for the treatment of TD based on significant evidence (Class I) ^{support [6].}

The 2021 American Psychiatric Association (APA) guidelines for schizophrenia recommend (1B) that patients with schizophrenia who develop moderate to severe or disabling TD associated with antipsychotic therapy should be treated
with a VMAT2 reversible inhibitor.
In patients with moderate to severe or disabling TD associated with antipsychotic therapy, VMAT2 inhibitors significantly reduce movement signs and symptoms
of dyskinesia.
These drugs may also be effective against other late-onset ^{syndromes [7].}

Clinical trials of deuterated tetrabenazine have been reported
abroad.
Results of ARM-TD studies (Figure 2) showed that deuterated tetrabenazine significantly reduced AIMS scores at 12 weeks and was well tolerated in patients with moderate to severe TD ^[8].

The AIM-TD study showed (Figure 3) that deuterated tetrabenzazine 24 mg/day and 36 mg/day significantly reduced involuntary activity levels in patients with TD with good safety and tolerability ^[9].

In addition, a study published in 2019 showed that deuterated tetrabenazine reduced AIMS scores after 80 weeks of treatment with a good safety profile (Figure 4) ^[10].

Figure 2 Primary endpoint of the ARM-TD study [8].

Figure 3 Primary endpoint of the AIM-TD study [9].

Fig.
4 Deuterated tetrabenazine can reduce AIMS score after 80 weeks of treatment and has a good safety profile [10].

Based on evidence-based medical evidence, in April 2017, the US FDA approved deuterium tetrabenazine tablets for marketing
.
China continues to pay attention to deuterated tetrabenazine tablets, and in May 2020, it approved the marketing of deuterated tetrabenzazine tablets for the treatment of HD-related chorea, as well as TD, and is the second country
to approve the marketing of deuterated tetrabenazine tablets.

Multidisciplinary collaboration to provide a full range of services for patients

Dopamine-regulated abnormal mental disorders and movement disorders have a common disease mechanism, so the diagnosis and treatment of HD and TD patients often require neurologists, psychiatrists and other physicians to adopt a multidisciplinary diagnosis and treatment (MDT) mode to work together to provide patients with all-round and integrated services
.
The MDT model is a treatment model
in which multidisciplinary experts discuss cases of a certain disease or a system of disease and develop the best treatment plan for patients on the basis of comprehensive opinions of various disciplines.

Clinically, dyskinesia disorders may present similarly, and differential diagnosis is particularly important
in patients with HD or TD.
In particular, when the patient presents with dyskinesia or atypical course of disease, has a family history of other motor or neurodegenerative diseases (eg, HD), has other neurologic or systemic medical signs and symptoms, and has an unexpected therapeutic response to the movement disorder, intolerance, or resistance, a multidisciplinary physician is required to confirm the diagnosis
.

Among them, neurologists can provide important support for the differentiation of TD from Parkinson's tremor, HD, and Wilson's disease.

Patients with Parkinson's disease often mistake TD for tremor during the course of the disease, but the regularity and frequency of tremor help to make the differential diagnosis, and tremor in TD is irregular, while parkinson's disease tremor is rhythmic
.
Chorea-like hyperactivity symptoms in early HD may be similar to TD presentations, but family history, symptoms, and cognitive function can help in the differential diagnosis (Figure 5).

Wilson's disease is an autosomal recessive copper metabolism disorder disease, the clinical manifestation is mainly mental symptoms and liver symptoms two aspects, Wilson disease perioral movement is very typical, but usually presents a tendency to dystonia; And dysarthria, drooling, and K-F ring are common in Wilson's disease, but not in TD, which is the key
point of identification.

Figure 5 Differential diagnosis of TD and HD

The big coffee said, concentrated

At the summit forum, the discussion session of the big coffee pushed the whole meeting to a climax
.
Experts from different cities gathered to discuss
hot topics related to TD and HD.
The panelists emphasized:

(1) Under the background of the current normalization of the COVID-19 epidemic, in view of the difficulty of patients seeking medical treatment offline, HD/TD patients can be managed daily through
online appointment video diagnosis and treatment, high-resolution video condition assessment, etc.

(2) Clinicians should pay more attention to TD, pay attention to early identification of TD, and be proficient in TD assessment tools, early diagnosis and timely use of deuterated tetrabenazine, reduce or stop anti-acetylcholine drugs, which will help patients benefit and promote the improvement
of the overall function of TD patients.

(3) Even the same disease has different manifestations in different systems in the clinic, so the differential diagnosis and treatment of diseases require multidisciplinary collaboration
.
The multidisciplinary diagnosis and treatment model will effectively avoid the situation of "blind people touching elephants" and bring benefits
to HD and TD patients.

(4) According to evidence-based medical recommendations, deuterium tetrabenazine can help improve the symptoms of HD and TD patients, and will comprehensively consider the patient's disease characteristics, socioeconomic factors and other aspects in clinical application, and require doctors and patients to make joint decisions
.

(5) It is necessary to pay attention to patient education, guide patients to have reasonable expectations for disease treatment, communicate the onset time and side effects of drugs to patients and families in detail, encourage patients and their families to adhere to treatment, and improve treatment compliance
.

Finally, the participating experts concluded that the emergence of deuterium tetrabenazine has brought hope for the treatment of HD and TD, making it possible
to have drugs for these two types of diseases.
In the future, the pathological mechanism of HD and TD is still worthy of continuous exploration by clinicians and researchers, and it is believed that with the advancement of technology, our understanding of HD and TD will continue to deepen.

[1] Frank S, Testa C M, Stamler D, et al.
Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial[J].
JAMA, 2016,316(1):40-50.

Sun Zhenxiao,Sun Yuxin,Yu Xiangfen[J].
China Licensed Pharmacist,2016,13(03):34-41.
)

[3] Mentzel CL, Bakker PR, van Os J,et al.
J Clin Psychiatry.
2017 Mar; 78(3):e279-e285.

[4] Bhidayasiri R, Jitkritsadakul O, Friedman JH, et al.
J Neurol Sci.
2018 Jun 15; 389:67-75.

[5] Bhidayasiri R, Fahn S, Weiner WJ, et al.
Neurology.
2013 Jul 30; 81(5):463-469.

[6] Bhidayasiri R, Jitkritsadakul O, Friedman JH, et al.
J Neurol Sci.
2018 Jun 15; 389:67-75.

[7] Keepers GA, Fochtmann LJ, Anzia JM, et al.
3rd ed.
American Psychiatric Association Publishing; 2021.

[8] Fernandez HH, Factor SA, Hauser RA,et al.
.
Neurology.
2017 May 23; 88(21):2003-2010.

[9] Anderson KE, Stamler D, Davis MD, et al.
2017 Aug; 4(8):595-604.

[10] Fernandez HH, Stamler D, Davis MD,et al.
J Neurol Neurosurg Psychiatry.
2019 Dec; 90(12):1317-1323.

*This article is for scientific information provided only to healthcare professionals and does not represent the views of the platform