An analysis of the efficacy of botulinum neurotoxin type a in treating cervical dystonia

Abstract

BACKGROUND:

The first-line treatment for cervical dystonia (CD) consists of repeated intramuscular injections of botulinum toxin (BoNT). However, the efficacy in some patients may be unsatisfactory and they may discontinue treatment.

OBJECTIVE:

To examine the factors associated with the maximum rate of remission in patients with CD after initial botulinum neurotoxin type A (or botulinum toxin type A abbreviated as BTX-A or BoNT-A) treatment.

METHODS:

Patients with CD who received BoNT-A injections were evaluated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Tsui scale, with follow-up endpoints lasting until the start of the second injection. Patients who did not receive a second injection of BoNT-A were followed up for at least 5 months. The maximum remission rates were determined using the lowest Tsui and TWSTRS total scores during the follow-up period. We obtained basic information about these patients such as age, gender, duration of disease, presence of additional disease, types of torticollis, presence of anxiety, depression, tremors, single-photon emission computed tomography (SPECT) findings, injected dose, and so on from their medical records.

RESULTS:

A total of 70 patients with CD participated in this study, with males comprising 35.7% (25 individuals) with an average age of 45 $\pm$ 14 years old. The duration of disease was an independent risk factor for determining whether a complete remission has been attained using the Tsui scale (odds ratio [OR] $=$ 0.978, 95% confidence interval [CI]: 0.959–0.997, $P=$ 0.026). The optimal cut-off point for predicting patients who were unable to achieve complete remission based on duration of disease was 7.5 months (AUG $=$ 0.711). Patients with CD with additional disease had greater difficulty achieving complete remission than those with CD alone based on TWSTRS assessments ( $P=$ 0.049). During the study, approximately 17% of all participants reported experiencing adverse reactions that lasted between 1 to 3 weeks before disappearing.

CONCLUSION:

BoNT is an effective and safe method for treating CD. The maximum remission rates of patients after their first injections are influenced by the duration of their disease. Thus, treatment using BoNT injections must be administered as soon as possible.

Keywords

Botulinum neurotoxin (BoNT)cervical dystonia efficacy maximum remission rate spasmodic torticollis

1. Introduction

Cervical dystonia (CD) is characterized by a constant or sporadic contraction of the neck muscles, and involves abnormal neck and/or head movements and gestures, with or without head tremors and lifting of the shoulder. There are many treatments available [1, 2], and first-line treatment for CD consists of repeated intramuscular injections of botulinum toxin (BoNT) [3]. The efficacy in some patients may be unsatisfactory and they may discontinue treatment. The first BoNT injection is of utmost importance because the willingness of a patient to continue treatment is directly related to how well the first injection works and whether it meets the expectations of the patient. Determining the factors influencing BoNT efficacy and accurately predicting its efficacy after the first injection can provide clinicians with a reference and increase patient compliance with subsequent treatment. According to studies, treatment non-response is the biggest barrier to BoNT satisfaction [4]. Other immediate barriers include adverse effects, a rapid decline in treatment efficacy, and inexperienced treating physicians. The results of a 24-year case-control study revealed that the coexistence of neck pain and oromandibular dystonia decreased long-term treatment satisfaction in patients with CD [5]. However, these studies are either long-term or use the remission rate between baseline and a specific follow-up date (e.g., 2 weeks, 1 month) as the evaluation index. They are limited in their ability to assess optimal efficacy because the time it takes for patients to achieve optimal response varies. In this paper, we used the maximum remission rate as the assessment index, with the lowest scores during follow-up serving as the assessment endpoints. We calculated the maximum remission rate and analyzed the influencing factors related to the maximum remission rate to provide a reference for clinicians.

2. Methods

2.1 Research design and participants

In this retrospective study, patients with CD hospitalized or visiting the Second Hospital of Hebei Medical University between June 2020 and June 2022 were analyzed. Inclusion criteria: (1) Patients diagnosed with CD according to the Chinese Expert Consensus on Diagnosis of Dystonia (2020 Edition) [6]; (2) Patients who complied with the treatment and signed informed consent voluntarily; (3) Patients without any significant organic disease. Exclusion criteria: (1) Patients who did not comply with the treatment; (2) Patients with insufficient follow-up data. All patients received BoNT injections guided by electromyography (Natus Nicolet EDX EMG, America) and ultrasound (GE Healthcare, LOGIQ S8). This study was approved by the Ethics Committee of the Second Hospital of Hebei Medical University.

2.2 Data collection

Using outpatient and inpatient medical records and imaging data, we obtained demographic and clinical data for each study participant, including age, gender, duration of disease, presence of additional disease, type of torticollis, presence of anxiety, depression, tremors, single photon emission computed tomography (SPECT) findings, and injection dose. Two categorizing approaches were used to classify the types of torticollis: based on the collum-caput concept (COL-CAP) [7] and based on whether a patient presented with one torticollis type or two or more torticollis types. Using the former method, there were 11 types: laterocollis, laterocaput, torsion neck, torsion head, anterocollis, anterocaput, retrocollis, retrocaput, horizontal displacement, longitudinal displacement, and mixed types (two or more types at once); using the latter method, there were two types: single and combined. Only 18 participants were subjected to an analysis of anxiety and depression, as only these 18 participants had complete data from anxiety and depression assessments. The anxiety and depression template scale of the hospital served as the basis for the evaluations [8]. Patients with a score $>$ 7 were diagnosed with anxiety and depression. Follow-up commenced after the initial BoNT injection. Participants were instructed to record videos regularly and when they were feeling well. Follow-up endpoint was the beginning of the second injection. Patients who did not receive a second BoNT-A injection were followed up for a minimum of five months.

2.3 Assessment indexes

The symptoms of the patients were evaluated using the TWSTRS and Tuis scale prior to treatment and during follow-up hospital visits. Maximum remission rates were computed based on the lowest scores on the Tsui scale and TWSTRS during the follow-ups. Maximum remission rate $=$ ((the score prior to treatment-the lowest score)/the score prior to treatment) $\times$ 100%. The efficacy of the treatment was evaluated based on previously published criteria [9]: 0–10%: ineffective; 11–50%: partial remission; 51–80%: high level of remission; 81–100%: complete remission.

2.4 Statistical methods

Statistical analysis was performed using SPSS 26, with measurement data expressed as mean $\pm$ standard deviation and enumeration data expressed as number of cases (%). The $t$ -test for two independent samples was used to compare two sets of normally distributed data; the Mann-Whitney test was used to compare two sets of non-normally distributed data; and the Kruskal-Wallis H test was used to compare multiple sets of non-normally distributed data. Using binary logistic regression, independent risk factors that could determine whether complete remission had been achieved based on the Tsui scale, were analyzed. The optimal cutoff value was determined using an ROC (receiver operating characteristic) curve. Spearman’s rank correlation was utilized to analyze the correlation between duration of disease and the presence of additional diseases, torticollis types, anxiety, depression, and tremors in patients with CD. $P<$ 0.05 indicated a statistically significant difference.

3. Results

3.1 General clinical characteristics of patients in the ineffective, partial remission, high level of remission, and complete remission groups

We enrolled 70 patients with CD in this study, and the average maximum remission rates for Tsui and TWSTRS were (61.4 $\pm$ 33.9) % and (60.3 $\pm$ 31.2) %, respectively. Table 1 contains the general clinical information. There were statistically significant differences between the four maximum remission rates of TWSTRS based on the index of whether a patient had an additional disease in addition to CD ( $P=$ 0.049). Patients with CD alone were more likely to experience remission than those with CD and additional diseases.

3.2 General clinical characteristics of patients with complete and non-complete remission

In order to analyze the differences between the complete and non-complete remission groups, the

Table 1
Descriptions of general statistics for the four remission rates

General clinical data		Tsui score					TWSTRS				$p$
		Ineffective ( $n=$ 10)	Partial remission ( $n=$ 16)	High level of remission ( $n=$ 20)	Complete remission ( $n=$ 24)		Ineffective ( $n=$ 3)	Partial remission ( $n=$ 25)	High level of remission ( $n=$ 19)	Complete remission ( $n=$ 23)
Female		4 (8.9%)	12 (26.7%)	11 (24.4%)	18 (40.0%)	0.197	0 (0.0%)	18 (40.0%)	10 (22.2%)	17 (37.8%)	0.342
Age	$\leqslant$ 20	1 (25.0%)	0 (0.0%)	1 (25.0%)	2 (50.0%)	0.254	1 (25.0%)	0 (0.0%)	1 (25.0%)	2 (50.0%)	0.390
	21–30	2 (40.0%)	1 (20.0%)	1 (20.0%)	1 (20.0%)		0 (0.0%)	3 (60.0%)	0 (0.0%)	2 (40.0%)
	31–40	1 (4.8%)	9 (42.9%)	1 (4.8%)	10 (47.6%)		0 (0.0%)	6 (28.6%)	5 (23.8%)	10 (47.6%)
	41–50	1 (5.9%)	2 (11.8%)	7 (41.2%)	7 (41.2%)		0 (0.0%)	5 (29.4%)	8 (47.1%)	4 (23.5%)
	51–60	3 (23.1%)	1 (7.7%)	5 (38.5%)	4 (30.8%)		1 (7.7%)	7 (53.8%)	1 (7.7%)	4 (30.8%)
	$>$ 60	2 (20.0%)	3 (30.0%)	5 (50.0%)	0 (0.0%)		1 (10.0%)	4 (40.0%)	4 (40.0%)	1 (10.0%)
With comorbidities		5 (35.7%)	2 (14.3%)	3 (21.4%)	4 (28.6%)	0.173	2 (14.3%)	6 (42.9%)	4 (28.6%)	2 (14.3%)	0.049^*
Duration of	$\leqslant$ 3	2 (11.1%)	4 (22.2%)	2 (11.1%)	10 (55.6%)	0.234	0 (0.0%)	6 (33.3%)	3 (16.7%)	9 (50.0%)
disease	3–12 (excluding 3)	2 (11.1%)	4 (22.2%)	5 (27.8%)	7 (38.9%)		0 (0.0%)	7 (38.9%)	5 (27.8%)	6 (33.3%)
(months)	12–48 (excluding 12)	3 (17.6%)	4 (23.5%)	4 (23.5%)	6 (35.3%)		1 (5.9%)	6 (35.3%)	4 (23.5%)	6 (35.3%)
	$>$ 48	3 (17.6%)	4 (23.5%)	9 (52.9%)	1 (5.9%)		2 (11.8%)	6 (35.3%)	7 (41.2%)	2 (11.8%)
Torticollis	Laterocollis	0 (0.0%)	0 (0.0%)	0 (0.0%)	1 (100.0%)	0.150	0 (0.0%)	0 (0.0%)	0 (0.0%)	1 (100.0%)	0.112
type	Laterocaput	0 (0.0%)	2 (66.7%)	1 (33.3%)	0 (0.0%)		0 (0.0%)	1 (33.3%)	1 (33.3%)	1 (33.3%)
	Torsion neck	2 (11.1%)	5 (27.8%)	6 (33.3%)	5 (27.8%)		0 (0.0%)	8 (44.4%)	6 (33.3%)	4 (22.2%)
	Torsion head	1 (8.3%)	2 (16.7%)	3 (25.0%)	6 (50.0%)		0 (0.0%)	3 (25.0%)	2 (16.7%)	7 (58.3%)
	Retrocollis	1 (100.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)		1 (100.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)
	Retrocaput	2 (50.0%)	1 (25.0%)	0 (0.0%)	1 (25.0%)		1 (25.0%)	1 (25.0%)	1 (25.0%)	1 (25.0%)
	Anterocollis $+$	0 (0.0%)	0 (0.0%)	0 (0.0%)	2 (100.0%)		0 (0.0%)	0 (0.0%)	0 (0.0%)	2 (100.0%)
	Anterocaput
	Mixed types	4 (13.8%)	6 (20.7%)	10 (34.5%)	9 (31.0%)		1 (3.4%)	12 (41.4%)	9 (31.0%)	7 (24.1%)
Traditional	Torsion	3 (9.7%)	7 (22.6%)	9 (29.0%)	12 (38.7%)	0.233	0 (0.0%)	11 (35.5%)	8 (25.8%)	12 (38.7%)	0.318
classification	Lateral tilt	0 (0.0%)	2 (50.0%)	1 (25.0%)	1 (25.0%)		0 (0.0%)	1 (25.0%)	1 (25.0%)	2 (50.0%)
of torticollis	Retroversion	3 (60.0%)	1 (20.0%)	0 (0.0%)	1 (20.0%)		2 (40.0%)	1 (20.0%)	1 (20.0%)	1 (20.0%)
	Mixed type	4 (13.3%)	6 (20.0%)	10 (33.3%)	10 (33.3%)		1 (3.3%)	12 (40.0%)	9 (30.0%)	8 (26.7%)
Torticollis	Simplex type	6 (15.0%)	10 (25.0%)	10 (25.0%)	14 (35.0%)	0.824	2 (5.0%)	13 (32.5%)	10 (25.0%)	15 (37.5%)	0.476
classification	Combined type	4 (13.3%)	6 (20.0%)	10 (33.3%)	10 (33.3%)		1 (3.3%)	12 (40.0%)	9 (30.0%)	8 (26.7%)
With anxiety		1 (12.5%)	3 (37.5%)	2 (25.0%)	2 (25.0%)	0.548	1 (12.5%)	1 (12.5%)	3 (37.5%)	3 (37.5%)	0.849
With depression		0 (0.0%)	2 (40.0%)	2 (40.0%)	1 (20.0%)	0.358	0 (0.0%)	1 (20.0%)	3 (60.0%)	1 (20.0%)	0.918
With tremors		2 (10.0%)	4 (20.0%)	7 (35.0%)	7 (35.0%)	0.588	1 (5.0%)	4 (20.0%)	7 (35.0%)	8 (40.0%)	0.197
With SPECT		2 (15.4%)	4 (30.8%)	1 (7.7%)	6 (46.2%)	0.863	1 (7.7%)	2 (15.4%)	5 (38.5%)	5 (38.5%)	0.360
Dose		340.0 $\pm$ 107.5	353.1 $\pm$ 99.1	365.5 $\pm$ 96.9	396.9 $\pm$ 124.2	0.622	333.3 $\pm$ 57.7	336.4 $\pm$ 79.3	392.1 $\pm$ 137.7	401.2 $\pm$ 117.7	0.479

ineffective, partial remission, and high level of remission groups were combined to form the non-complete remission group. There were statistically significant differences between patients whose maximum remission rate on the Tsui scale reached the level of complete remission based on duration of disease ( $P=$ 0.021). In contrast, there was no statistically significant difference between the two groups for any other variable. No factor was found to predict whether a patient could achieve complete remission using TWSTRS (Table 2).

Table 2

Description of general statistics for complete and non-complete remission

General clinical data		Tsui score			TWSTRS		$p$
		Non-complete remission ( $n=$ 46)	Complete remission ( $n=$ 24)		Non-complete remission ( $n=$ 47)	Complete remission ( $n=$ 23)
Female		27 (60.0%)	18 (40.0%)	0.180	28 (62.2%)	17 (37.8%)	0.243
Age	$\leqslant$ 20	2 (50.0%)	2 (50.0%)	0.152	2 (50.0%)	2 (50.0%)	0.336
	21–30	4 (80.0%)	1 (20.0%)		3 (60.0%)	2 (40.0%)
	31–40	11 (52.4%)	10 (47.6%)		11 (52.4%)	10 (47.6%)
	41–50	10 (58.8%)	7 (41.2%)		13 (76.5%)	4 (23.5%)
	51–60	9 (69.2%)	4 (30.8%)		9 (69.2%)	4 (30.8%)
	$>$ 60	10 (100.0%)	0 (0.0%)		9 (90.0%)	1 (10.0%)
With comorbidities		10 (71.4%)	4 (28.6%)	0.617	12 (85.7%)	2 (14.3%)	0.101
Duration of	$\leqslant$ 3	8 (44.4%)	10 (55.6%)	0.021^*	9 (50.0%)	9 (50.0%)	0.122
disease	3–12 (excluding 3)	11 (61.1%)	7 (38.9%)		12 (66.7%)	6 (33.3%)
(months)	12–48 (excluding 12)	11 (64.7%)	6 (35.3%)		11 (64.7%)	6 (35.3%)
	$>$ 48	16 (94.1%)	1 (5.9%)		15 (88.2%)	2 (11.8%)
Torticollis	Laterocollis	0 (0.0%)	1 (100.0%)	0.210	0 (0.0%)	1 (100.0%)	0.100
type	Laterocaput	3 (100.0%)	0 (0.0%)		2 (66.7%)	1 (33.3%)
	Torsion neck	13 (72.2%)	5 (27.8%)		14 (77.8%)	4 (22.2%)
	Torsion head	6 (50.0%)	6 (50.0%)		5 (41.7%)	7 (58.3%)
	Retrocollis	1 (100.0%)	0 (0.0%)		1 (100.0%)	0 (0.0%)
	Retrocaput	3 (75.0%)	1 (25.0%)		3 (75.0%)	1 (25.0%)
	Anterocollis $+$	0 (0.0%)	2 (100.0%)		0 (0.0%)	2 (100.0%)
	Anterocaput
	Mixed types	20 (69.0%)	9 (31.0%)		22 (75.9%)	7 (24.1%)
Traditional	Torsion	19 (61.3%)	12 (38.7%)	0.832	19 (61.3%)	12 (38.7%)	0.597
classification	Lateral tilt	3 (75.0%)	1 (25.0%)		2 (50.0%)	2 (50.0%)
of torticollis	Retroversion	4 (80.0%)	1 (20.0%)		4 (80.0%)	1 (20.0%)
	Mixed type	20 (66.7%)	10 (33.3%)		22 (73.3%)	8 (26.7%)
Torticollis	Simplex type	26 (65.0%)	14 (35.0%)	0.885	25 (62.5%)	15 (37.5%)	0.343
classification	Combined type	20 (66.7%)	10 (33.3%)		22 (73.3%)	8 (26.7%)
With anxiety		6 (75.0%)	2 (25.0%)	0.897	5 (62.5%)	3 (37.5%)	0.965
With depression		4 (80.0%)	1 (20.0%)	0.891	4 (80.0%)	1 (20.0%)	0.322
With tremors		13 (65.0%)	7 (35.0%)	0.937	12 (60.0%)	8 (40.0%)	0.424
With SPECT		7 (53.8%)	6 (46.2%)	0.321	8 (61.5%)	5 (38.5%)	0.636
Dose		355.7 $\pm$ 98.2	396.9 $\pm$ 124.2	0.369	358.7 $\pm$ 107.8	401.2 $\pm$ 117.7	0.494

3.3 Analysis of factors affecting whether a patient could reach complete remission based on the Tsui scale

The ability of a patient to achieve complete remission was significantly related to the patient’s age (OR $=$ 0.962, 95% CI: 0.925–1.000, $P=$ 0.047) and duration of disease (OR $=$ 0.976, 95% CI: 0.956–0.996, $P=$ 0.019), and was not related to other factors. According to the results of a multivariate regression analysis that included variables with $P<$ 0.15, after adjusting for age and dose, disease duration (OR $=$ 0.978, 95% CI: 0.959–0.997, $P=$ 0.026) remained independently associated with whether a patient could achieve complete remission according to the Tsui scale (Table 3).

Table 3
Logistic regression of factors influencing patient remission based on the Tsui scale

	Univariate logistic regression			Multivariate logistic regression
	OR	95% CI	$p$	OR	95% CI	$p$
Gender	2.111	0.707–6.308	0.181	–	–	–
Age	0.962	0.925–1.000	0.047^∗	0.968	0.923–1.015	0.179
Diagnosis	0.720	0.200–2.595	0.615	–	–	–
Duration of disease	0.976	0.956–0.996	0.019^∗	0.978	0.959–0.997	0.026^∗
Torticollis type	1.077	0.397–2.925	0.884	–	–	–
Anxiety	0.750	0.081–6.958	0.800	–	–	–
Depression	1.200	0.094–15.260	0.888	–	–	–
Tremors	1.045	0.352–3.107	0.937	–	–	–
Dose	1.003	0.999–1.008	0.136	1.003	0.998–1.008	0.259

^∗p< 0.05 was statistically significant.

3.4 ROC curve when patients were predicted to be unable to achieve complete remission on the Tsui scale based on the index of duration of disease

When duration of disease was used to determine the remission status of patients, the area under the ROC curve, optimal cutoff value, sensitivity, and specificity for patients who were unable to achieve complete remission were 0.711% ( $P=$ 0.004), 7.5%, 69.6%, and 67.7%, respectively (Fig. 1).

Figure 1.

ROC curve for duration of disease and maximum remission rate on the Tsui scale.

3.5 How duration of disease relates to torticollis types, tremors, anxiety, depression, and whether a patient with CD had an additional disease

Duration of disease was weakly negatively correlated with torticollis types (single and combined) ( $P=$ 0.040, $r=-$ 0.246) and weakly positively correlated with the index of whether patients with CD had additional diseases ( $P=$ 0.033, $r=$ 0.255). No correlation was observed between duration of disease and tremors ( $P=$ 0.633), anxiety ( $P=$ 0.464), or depression ( $P=$ 0.311).

3.6 Side effects

In this study, a total of 12 patients experienced side effects, with 6 of them (50%) experiencing symptoms of weakness such as neck weakness, difficulty raising their heads, and even generalized weakness, 3 (25%) experiencing dysphagia, 2 (17%) experiencing injection site pain, and 1 (8%) experiencing injection site soreness. All patients scored $<$ 5 on a scale that rated the severity of pain from 0 (not painful) to 10 (most painful). All these side-effect symptoms appeared approximately one to three weeks after BoNT injection and lasted approximately one to three weeks before disappearing.

4. Discussion

There were statistically significant differences in duration of disease when using the Tsui scale to determine whether a patient achieved complete remission, and there were statistically significant differences in the index of whether a patient had additional diseases to CD between patients with varying degrees of remission based on the TWSTRS. A binary logistic regression analysis revealed that duration of disease was an independent risk factor for whether a patient could achieve complete remission on the Tsui scale (OR $=$ 0.978, 95% CI: 0.959–0.997, $P=$ 0.026), as well as a good predictor for patients who were unable to achieve complete remission (AUG $=$ 0.711), with an optimal cut-off point of 7.5 months.

4.1 How can the duration of disease affect efficacy?

4.1.1 Duration of disease affects the progression of disease

On the basis of the Tsui score (OR $=$ 0.978, 95% CI: 0.959–0.997, $P=$ 0.026), we found that duration of disease was an independent risk factor for whether a patient could achieve complete remission. According to previous research, following the development of CD, the longer the delay in administering BoNT, the worse the long-term prognosis of BoNT therapy, and subsequent injections were unable to compensate for the disease progression prior to BoNT therapy [10]. The results of our study suggest a similar conclusion. The disease may progress and new phenotypes may emerge as the duration of the disease increases. The complexity of CD may increase with duration of disease, even when BoNT therapy is ongoing [10]. According to research, simple CD may progress to segmental dystonia in some patients [11], thereby complicating the condition, as demonstrated by our study. According to our findings, there is a degree of positive correlation between duration of disease and the index of whether a patient had additional dystonia at other sites or additional diseases. To be more specific, the longer the duration of disease, the greater the likelihood that patients experience additional dystonia at other sites or diseases besides CD. In addition, there is a correlation between the duration of disease and the condition of patients with two or more types of torticollis; despite being a weak correlation, this shows the progression of the disease.

4.1.2 Duration of disease and tremors

Based on TWSTRS, there was no significant difference in duration of disease between the maximum remission rates. This may be because duration of disease has a greater effect on tremors, and tremor is an index in the Tsui score but not in the TWSTRS score. According to research, patients with a longer duration of CD are more likely to experience severe head tremors [12, 13]. Antelmi et al. found that patients with CD with tremors had a longer average duration of disease (17 years) than those without tremors (14 years), although this difference was not statistically significant [14]. This was confirmed by a later analysis of 1,608 patients with CD using the Dystonia Alliance Database, which found that patients with CD with tremors had longer durations than patients with CD without tremors [15]. We found no evidence in this study that the presence or absence of tremors could affect the efficacy of BoNT injections as measured by the Tsui scale. After conducting an analysis, we found no evidence of a correlation between the presence or absence of tremors and the duration of disease. This could be the result of a small sample size. In this study, 27.1% of patients with CD experienced head tremors, which is less than previous research findings (57.6%) [16]. This could also be the result of population bias resulting from the small sample size. In future studies, we plan to use a larger sample size, evaluate tremors in a more objective manner and refine the types of tremors that patients experience.

4.2 How BoNT efficacy differs between patients with CD and patients with CD with additional diseases

According to our research on the differences in BoNT efficacy between patients with CD and patients with CD with additional diseases, there was a statistically significant difference in the maximum remission rates in TWSTRS between patients with CD and patients with CD with additional diseases, but no statistically significant difference in the indexes in each subscale (therefore, the results of each subscale are not presented in this article). Whether a patient had additional diseases besides CD had no significant effect on the subscale indexes. This influence only manifested itself under overall cumulative assessment. There were index differences in each subscale between patients with CD and patients with CD with additional diseases, but they were not significant ( $P=$ 0.049). In this study, additional dystonia at other sites in patients with CD had certain effects on their cervical muscles, which in turn affected the efficacy of BoNT. However, there was no statistically significant difference between the maximum remission rates on the Tsui scale for patients with CD with various additional diseases. This may be due to the more refined index classification in TWSTRS, which makes it more sensitive to differences – it covers obstacles in daily life, pain, and so on and is more detailed in the assessments of torticollis severity, making it more sensitive to any differences. According to the findings of our study, the condition of patients with CD with additional diseases has certain effects on their quality of life, which eventually influences the overall efficacy of their treatment. Therefore, when diagnosing and treating patients, clinicians should conduct comprehensive treatments by considering the underlying conditions of patients and evaluating their symptoms and condition improvements in a reasonable and comprehensive manner.

4.3 The impacts of anxiety and depression

According to research, significant mood disorders such as anxiety and depression can have a substantial impact on the quality of life of a patient but are unrelated to disease severity [17]. No evidence was found in this study that anxiety and depression could influence the maximum remission rate. The lack of statistical significance in our study could be attributable to a number of factors, including the limited size of the sample pool and the TWSTRS’ assessment of the quality of life of patients.

4.4 Treatments for unsatisfactory efficacy

4.4.1 Accurate diagnoses

An accurate diagnosis is essential for effectiveness. Genetic testing has received increasing attention in recent years. Early genetic testing improves the diagnostic and therapeutic efficacy of doctors. In the striatum, for instance, genetic variants such as GCH1, which encodes guanosine triphosphate cyclohydrolase 1, primarily affect presynaptic dopaminergic signaling pathways. These patients are more likely to respond positively to dopaminergic drugs [18]. Based on genetic testing, we determined that one patient who visited the hospital’s botulinum toxin outpatient department had dopamine-responsive dystonia. The patient was given the appropriate medications but no botulinum toxin injection. Genetic testing revealed that another patient had a mutation in the PLA2G6 gene, which manifested as PLA2G6-associated dystonia-parkinsonism. The BoNT treatment yielded poor efficacy for this patient. Therefore, reasonable conclusions should be made regarding the effectiveness of BoNT in such patients.

4.4.2 Effect of disease subtypes on efficacy

The influence of CD subtypes on efficacy cannot be overlooked. Certain types of CD are more likely to cause non-motor symptoms than others. As shown by previous research, the lateral-and-head phenotype is associated with an increased risk of neck pain, whereas the neck phenotype was associated with the lowest risk [19]. The lack of positive results in this study may be due to the small sample size.

4.4.3 Accurately assess the target muscle and improve injection technique

Before administering BoNT-A injection, clinicians should evaluate CD more precisely to ensure the correct selection of the target muscle and to determine an appropriate dose. The results of a randomized, double-blind study indicated that SPECT improves the efficacy of BoNT in the treatment of CD, and it may become a valuable tool for facilitating BoNT injection [20]. When comparing patients who underwent SPECT and those that did not, there was no discernible difference in efficacy. However, the use of SPECT increased the ratio of complete remission patients to non-complete remission patients. In addition, electromyography and ultrasound can assist in determination of the injection site, which can improve the injection techniques of physicians.

4.5 Adverse effects

We discovered that patients experienced more severe side effects following the first injection, but that these side effects diminished with subsequent treatments. As additional injections are administered, the dose becomes more rational, and patients tend to feel better. Although side effects are common, they are typically mild and brief in duration. After multiple years of treatment, patients continue to benefit from repeated BoNT injections [21].

5. Conclusion

In this study, the factors influencing the maximum remission rate were analyzed in order to aid clinicians in determining the maximum remission rates for patients undergoing treatment. Limitations of this study: As a retrospective study with a small sample size, this research was unable to determine causality because it only examined the efficacy of BoNT in the period following the first injection. For further investigation, studies with larger sample sizes and multiple injections should be conducted.

In conclusion, the duration of disease can influence the maximum remission rates following initial BoNT injections to some degree. For maximum efficacy, BoNT should be administered to patients as soon as possible.

Footnotes

Conflict of interest

The authors declare no conflict of interest.

Funding

This study was supported by the Hebei Medical Application Technology Tracking Project (No. GZ2022013).

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An analysis of the efficacy of botulinum neurotoxin type a in treating cervical dystonia

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Methods

2.1 Research design and participants

2.2 Data collection

2.3 Assessment indexes

2.4 Statistical methods

3. Results

3.1 General clinical characteristics of patients in the ineffective, partial remission, high level of remission, and complete remission groups

3.2 General clinical characteristics of patients with complete and non-complete remission

Table 1 Descriptions of general statistics for the four remission rates

Table 3 Logistic regression of factors influencing patient remission based on the Tsui scale

3.6 Side effects

4. Discussion

4.1 How can the duration of disease affect efficacy?

4.1.1 Duration of disease affects the progression of disease

4.1.2 Duration of disease and tremors

4.2 How BoNT efficacy differs between patients with CD and patients with CD with additional diseases

4.3 The impacts of anxiety and depression

4.4 Treatments for unsatisfactory efficacy

4.4.1 Accurate diagnoses

4.4.2 Effect of disease subtypes on efficacy

4.4.3 Accurately assess the target muscle and improve injection technique

4.5 Adverse effects

5. Conclusion

Footnotes

Conflict of interest

Funding

References

Table 1
Descriptions of general statistics for the four remission rates

Table 3
Logistic regression of factors influencing patient remission based on the Tsui scale