Voluntary Inhibitory Control of Chorea: A Case Series

ABSTRACT

Background

Volitional control of involuntary movements has so far been considered a hallmark of tic disorders. However, modulation of involuntary movements can also be observed in other hyperkinesias.

Cases

Here, we present 6 patients with chorea able to suppress their involuntary movements, on demand. In 3 of them, surface electromyography was used to quantify degree of suppression and confirmed a reduction of muscle activity up to 68%, during volitional control.

Conclusion

This observation represents a first step toward a description of a new clinical feature in choreic syndromes and an opportunity to redefine the role of volitional inhibition in hyperkinetic movement disorders.

https://onlinelibrary.wiley.com/page/journal/23301619/homepage/mdc312907-sup-v001_1.htm

Chorea consists of irregular movements flowing from one body part to another in a non‐patterned fashion. Because choreic movements in Huntington's disease (HD) are not preceded in the EEG by a Bereitschaftspotential, they are classified as involuntary.1, 2

Although volitional inhibition is usually considered as the main feature that distinguishes tics from other involuntary movement disorders, there have been previous reports in which patients could suppress chorea.2, 3 Indeed, temporary and partial suppression of chorea can be observed while patients perform semipurposeful activities, although, in some cases, this is difficult to distinguish from incorporation of the chorea into an apparently volitional movement (parakinesia).

The aim of this article is to provide further evidence for the volitional control of chorea in 6 patients. Surface electromyography (EMG) was used to quantify degree of suppression in 3 of them.

Case Series

Case 1

This 82‐year‐old gentleman was referred for a 3‐year history of involuntary movements and memory difficulties, which started after a trip to Malaysia. On examination, he presented with generalized chorea, along with some dystonic features of his arms, which he was able to control for several seconds when asked. His past medical history was unremarkable, apart from aortic valve replacement at the age of 72.

Although he was investigated extensively, the cause of the chorea remained unknown.

Indeed, there were no significant abnormalities on brain MRI. Laboratory and genetic tests for HD, chromosome 9 open reading frame 72 (C9orf72), spinocerebellar ataxia type 17 (SCA17), and dentatorubral‐pallidoluysian atrophy (DRPLA) were normal. There was no history of infective contact during his trip to Malaysia, and screening for Whipple's disease and syphilis was negative. He had no past medical history of antipsychotic or antiemetic drug use or a family history of neurological disorders. When he was a child, he had tonsillitis attributed to Streptococcal infections. However, we ruled out Sydenham's chorea and other autoimmune/paraneoplastic conditions. He passed away 2 months after admission, because of a stroke.

Case 2

One year previously, a 49‐year‐old, right‐handed lady noticed involuntary movements of the legs, with the tendency of turning in while walking. Later, the hands became involved with her fingers curling and twisting. However, she was partially able to control them, and when concentrating on other tasks, the movements subsided. She also reported a recent onset of episodes of “violent” involuntary movements at night, while she was awake. She has had depression and anxiety for 10 years preceding the onset of chorea and had a positive family history of depression, anxiety, and dementia. On examination, clear choreic movements were observed. Polysomnography excluded that the paroxysmal attacks at night were epileptic in origin, and they were thought to be functional. Genetic screening revealed a mutation in the TBP gene consistent with a diagnosis of SCA17 (50 CAG/CAA repeats).

Case 3

This 64‐year‐old lady developed late‐onset generalized chorea at the age of 56. She had a possible family history of involuntary movements, given that her mother, who died at the age of 65 because of a heart attack, probably had a similar symptomatology late in life. Clinically, there were involuntary movements involving her limbs, square wave jerks in eyes primary position, and a suggestion of nystagmus in extreme gaze. The patient was able to stop her involuntary movements for a period of time. Memory, mood, and sleep were not affected. She was investigated for HD, DRPLA, C9orf72, and SCA1, 2, 3, 6, and 17, which were all negative. She was also screened for anti‐nuclear antibody, anti‐neutrophil cytoplasmic antibody, coeliac disease antibodies, and full blood count cell and acanthocytes, with no significant outcome.

Case 4

A 77‐year‐old right‐handed woman was admitted following acute onset of involuntary movements involving the left hemibody and hemiface. On examination, the patient presented with abrupt, jerky movements mainly involving proximal joints of the left limbs and left facial grimacing. There was additional paratonia together with brisk reflexes, as well as mild dystonic posturing of the left limbs. Gait was unsteady, and tandem gait could not be performed. The patient was able to suppress the involuntary choreoballistic movements, which could also be modulated by contralateral maneuvers such as finger tapping. Cognitive assessment proved mild deterioration.

Blood tests revealed severe hyperglycaemia (>500 mg/mL). MRI showed a chronic vascular encephalopathy and a hyperintensity in T₁‐weighted images in the right caudate. A diagnosis of nonketotic hyperglycemic chorea (NKHC) was then confirmed. She was treated with tetrabenazine, with a significant improvement of her choreiform movements. Nevertheless, mild dyskinesias persisted at 18 months of follow‐up.

Case 5

Eight years previously, a 54‐year‐old, right‐handed lady had experienced onset of walking difficulty, imbalance and falls, and involuntary movements involving her face and limbs. She also had depression, personality and behavioral changes, together with progressive cognitive deterioration. Her grandmother, mother, and brother were all affected by generalized “twitching.” On examination, she presented with choreic movements involving all the body. She was partially able to control them, and when concentrating on other tasks, the movements could stop for a few seconds and then re‐emerge. She had also some facial grimacing. There was evidence of gaze and motor impersistence on eye movements and tongue examination. Her gait was broad‐based. Analysis of the TBP gene eventually showed 43 CAG/CAA repeats, consistent with a diagnosis of SCA17.

Case 6

A 53‐year‐old man developed progressive walking difficulties with balance impairment and marked postural instability. Over the previous 6 months, he had developed dysarthria, clumsiness in the upper limbs with involuntary movements, and memory impairment. He was able to suppress his involuntary movements completely. The patient's grandmother suffered from a similar condition, and his mother had symptoms of dementia. On examination, the patient presented with hypomimia, whereas eye movements disclosed broken pursuit. He had bradykinesia and mild apraxia. Additionally, he presented with generalized chorea especially in the trunk and upper extremities, associated with dystonia. His gait was broad‐based, and he could not walk in tandem. Molecular analysis of the Huntingtin gene showed an abnormally expanded 43 CAG repeats, consistent with a molecular diagnosis of HD.

Surface EMG Recording

In cases 1, 2, and 3, activity from the muscles clinically more affected by chorea at rest was recorded by bipolar Ag‐AgCl surface EMG electrodes. EMG recording was performed in two conditions: (1) free to move and (2) during suppression of the involuntary movements on demand. The recording was performed for 60 to 80 seconds. Methods and data analysis are detailed in Supporting Information Text S1. Clinical features and electrophysiological results are summarised in Table 1. Figure 1 shows EMG recording of case 3.

Table 1.

Clinical features and electrophysiological results

A. Clinical Features (N = 6)
Age (years)	65.6 ± 13.6
Disease duration (years)	4.3 ± 4.6
Diagnosis	HD (1), NKHC (1), SCA17 (2), nondetermined choreic syndrome (2)

B. Surface EMG (N = 3)
Case #	Case 1	Case 2	Case 3
Degree of suppression	35%	32%	68%

For part A, data are mean ± SD; in brackets: number of patients affected.

SD, standard deviation.

Figure 1.

EMG recording of case 3 during free to move condition on the left column (A,C,E,G), and involuntary movements’ suppression condition on the right column (B,D,F,H). ECR, extensor carpi radialis; SCM, sternocleidomastoid; Trap, trapezius.

Discussion

In 1989, Koller and Biary reviewed the extent to which patients with a variety of different movement disorders could volitionally suppress or reduce their movements.3 They pointed out that all types of movement (tremor, chorea, and tics) could be reduced, but the extent of control varied between them: tics were suppressible in 100% of cases, whereas only 2% of patients with essential tremor could suppress their tremor.3 Fifty percent of patients were able to reduce their chorea.3

In this case series, we present a heterogeneous group of patients able to voluntary control their choreic movements, when asked. In 3 patients, EMG recording confirmed a reduction in muscle activity up to 68% during suppression (Fig. 1).

Oppositely to tics, which are discrete involuntary movements, chorea consists of a more continuous muscle activity and an estimation of the “number of movements” in chorea would certainly be impractical. Therefore, with the intent of estimating the reduction of global involuntary movements, we used the root mean square of the EMG signal (see Supporting Information Text S1), which reflects the recruitment of muscle fibers during contraction, for a given period of time. Our results showed a global reduction of EMG root mean square, reflecting a global suppression of involuntary muscle activity.

In contrast to tic disorders, none of our patients experienced any sense of relief and no transient increase in severity of chorea when the suppression was stopped, suggesting a difference in conscious awareness of the processes leading to expression of tics versus chorea. On the other hand, similarly to tics, it seems that this was not a blanket suppression of all movement, given that a selective inhibition of chorea could also be observed when diverting attention away from the movements (i.e., while performing other tasks).4

Shibasaki and colleagues previously noted that patients affected by chorea‐acanthocytosis were able to reduce or completely suppress the involuntary movements during tasks or on demand, whereas the same tasks enhanced the movements in 3 subjects with HD, clinically diagnosed but not genetically confirmed.2 Nevertheless, here we report on a case of genetically confirmed HD who could voluntarily control his choreic movements.

Although tics and chorea are different types of involuntary movements, the mechanisms that could participate in volitional control of tics may be relevant to volitional suppression of chorea.5 The basal ganglia are involved in selection of appropriate actions from a range of competing responses through patterns of activity in the direct and indirect pathways, and it has been proposed that both tics and chorea result from dysfunction of these circuits.6, 7 Experiments show that tic suppression involves activation of frontal areas of the cortex coupled with reduced activity in basal ganglia, implying that input to basal ganglia from frontal areas may be able temporarily to compensate for this problem.8 One possible mechanism is that implicated in reactive inhibition in healthy individuals. If volunteers attempt to suppress an action that has already been initiated, activity in the inferior frontal gyrus may excite the subthalamic nucleus and directly increase inhibitory output of the internal pallidal segment to thalamus and sensorimotor cortex and abort ongoing motor plans.9 However, reactive inhibition is a phasic response and may well be rather different to the continuing tonic suppression of involuntary movements we describe here. Nevertheless, it could potentially explain why tics are more suppressible than other involuntary movements. In fact, it could be that perception of premonitory urge engages the phasic suppression of reactive inhibition, which adds to, and increases the effectiveness of, ongoing levels of tonic inhibition.

Further investigations are certainly needed to clarify the mechanisms underlying chorea suppression.

One limit of the study is the small number of patients involved in the EMG recording. EMG was recorded in two conditions, which differed only by a simple instruction. Thus, we can exclude that the observed suppression of chorea was attributed to changes in brain state caused by further cognitive, emotional, or motor variables. Nevertheless, we did not test patients’ perception of movements subsiding when performing other tasks. The ability to modulate involuntary movements and their attenuation while doing other tasks (which can resemble distractibility) might be evocative of functional disorders.10 However, the diagnosis of functional movement disorders is based on the presence of positive signs, other than “distractibility,” and specific elements on the neurological examination, such as inconsistency (i.e., changing patterns over time), incongruence (i.e., a clinical phenomenology discordant with recognized organically determined patterns), sudden onset of the symptoms, increase in involuntary movements with attention, and excessive fatigue or demonstration of effort.10 Although we cannot disclose the presence of incongruence in our patients, given that the ability to suppress choreic movements is still not an accepted pattern, the absence of elements supporting a positive diagnosis of functional disorder and the presence of specific clinical features or genetic tests confirmed the diagnosis of chorea.

In conclusion, based on our cases, various types of chorea with both primary and secondary causes can be, to some extent, controlled by effort of will. However, whether and to which extent the ability to suppress involuntary movements is present in every form of chorea is still an open question. Nevertheless, in clinical practice, the ability of choreic patients to volitionally decrease their movements should not be misinterpreted as evidence of psychogenicity.3 Conversely, recognition of suppressibility might be a key point to address these patients to strategies such as cognitive‐behavioral training.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.

R.B.: 1B, 1C, 3A

A.L.: 1B, 1C, 3A

B.B.: 3B

K.S.: 1C, 3B

L.R.: 1C, 3B

J.C.R.: 3B

M.Z.: 3B

K.P.B.: 1A, 3B

Disclosures

Ethical Compliance Statement: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The patients have given written and informed consent for online publication of their videos. The authors confirm that the approval of an institutional review board was not required for this work.

Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest.

Financial Disclosures for previous 12 months: K.P.B. holds research grants from NIHR RfPB, MRC Wellcome Strategic grant (Ref. No.: WT089698), and PD UK (Ref. No.: G‐1009) and has received honoraria/financial support to speak/attend meetings from GSK, Boehringer Ingelheim, Ipsen, Merz, Sun Pharma, Allergan, Teva, Lundbeck, and Orion pharmaceutical companies. K.P.B. receives royalties from Oxford University Press and a stipend for Movement Disorders Clinical Practice (MDCP) editorship.

Supporting information

Text S1. Methods and data analysis of EMG recording.

Video S1. All the cases are shown at rest and during suppression of the involuntary movements on demand.