Correlation between head tremble and the severity of Parkinson’s disease

Abstract Introduction Parkinson's (PD) is a common degenerative disease of the central nervous system. It affects more than 6 million individuals worldwide. The typical clinical manifestations include static tremor, slow movement, and unstable posture. However, the correlation between head tremor and the severity of PD remains unclear. Methods In the current study, 18 patients and 18 healthy subjects were recruited to undergo a phonation test. Noldus facereader 7.0 software was used to analyze the range of head trembling between the two groups. Results The data revealed that patients with PD had significant differences in the x‐, y‐, and z‐axis of head movement with respect to the specific pronunciation syllables compared with the normal group. Moreover, the head movement of the patients with PD was positively correlated with the severity of the disease in the single, double, and multiple syllable tests. In the phonetic test, the head displacement of patients with PD was significantly greater than that of healthy individuals, and the displacement range was positively correlated with the severity of the disease. Conclusion These pieces of evidence suggested that the measurement of head displacement assists the early diagnosis and severity of the disease.


| BACKG ROU N D
Parkinson's disease (PD) is the second most common neurodegenerative disease and its prevalence has been projected to double over the next 30 years. Linder et al. reported an annual incidence of 18.8 cases/100,000, and the mean age of onset was 70. 6

years in
Sweden. 1 Previous studies identified about 150,000 prevalent cases (prevalence = 2.30/1000 population) and 25,000 incident cases (incidence = 0.39/1000 person-years) in 2010 in France. 2 Furthermore, 680,000 individuals with PD, aged ≥45-year-old, were recorded in 2010, and the number rose to approximately 930,000 in 2020 and will rise to 1,238,000 in 2030 based on the US Census Bureau population projections. 3 In China, a multiethnic developing country with the largest population in the world is stepping into an aging era. 4 The average prevalence of PD in China was about 3.8756% in Han population (≥50-year-old). 5 It is estimated that by 2030, Chinese PD patients will increase to 4.94 million, accounting for half of the worldwide PD patients. 6 The upcoming demographic shift toward older individuals in western nations would require efforts to project the healthcare burden over the coming decades, especially for diseases, such as Alzheimer's disease and PD, with increasing incidence corresponding to age. The projected increase in dementia has been referred to as a "rising tide," emphasizing the sheer volume of this problem and warnings of public health challenges. Similarly, in China, the population of neurodegenerative disease will increase over time and cast a huge burden on the economics and healthcare system.
The body posture of the patient becomes stooped, and axial and limb rigidity with or without cogwheel phenomenon is noted with a tendency for a shuffling gait and lack of arm swing while walking.
Bradykinesia may lead to expressionless face (hypomimia), and the amplitudes of handwriting become small (micrographia). About 80% of the limbs have tremors, and most commonly, a resting pill-rolling type of tremor in the hands. The pill-rolling relates to the tendency of the contact between the thumb and the index finger and perform a circular movement (Jankovic). 7 Dystonia is a motor symptom in PD. It describes a sustained muscular contraction frequently accompanied by abnormal movements, postures, or both. This might rarely be a prediagnostic symptom in PD. The typical prediagnostic dystonias include unilateral equinovarus foot position, upper arm-forearm or forearmhand flexion, writer's cramp, oromandibular dystonia, torticollis, or different combinations of these symptoms (Tolosa and Compta). 8 Rigidity in PD means stiff, inflexible, and painful muscles all over the body but prominently in the trunk, head, and extremities, along with regular cramps and pain. Thus, rigidity is one of the primary features of PD. 9 With the progression of PD, patients experience varied speech problems, such as hoarseness and weakness, during communication.
Also, the normal speech of PD patients is altered. The most commonly reported speech problems are sudden fast or slow speech, hoarseness, imperfect talk, monotonous or nasal voice, tremorous and stuttering speech, and also difficulty in initiating the speech. 10 In the phonetic test, the head displacement of PD patients was significantly greater than that of healthy individuals, and the displacement amplitude was positively correlated with the severity of the disease. Furthermore, the measurement of head displacement assisted the early diagnosis and severity of the disease. Presently, only a few studies have reported the correlation between the severity of PD and the early cranial tremor. Break et al. hypothesized that the pathological staging of PD can be divided into six stages. In stages 3 and 4, substantia nigra, deep mesencephalic nuclei, and anterior cerebral lobes were involved, resulting in the motor symptoms of PD. The specificity of early olfactory disorders, sleep disorders, and other non-motor symptoms could lead to missed clinical diagnosis. Conversely, head shaking is a specific motor symptom. This study aimed to decipher an accurate degree of head shaking to help the early recognition of PD as an auxiliary diagnosis in the clinic.

| Ethics statement
The study was approved by the Institute of Institutional Review Board and by the Ethics Committee of Chengdu Medical College. All participants provided written informed consent. Patients with PD fulfilled the following inclusive criteria 1 : idiopathic PD and no other neurological defects 2 ; movement fluctuations that respond satisfactorily to L-dopa ("ON-OFF" effect) 3 ; no previous psychiatric problems or cognitive decline.

| Measurement of head tremor during the phonation test
The candidates were invited to participate in the phonation test in a light-stable, suitable, and quiet room. The vowels "a," "o," and "e" were selected to form the monosyllable, double syllable, and multiple syllables. When the test sample was pronounced, the airflow from the lungs strike the vocal cords through the glottis, making them vibrate evenly. For more details of the phonation test cards, see the online supporting file. Then, the trill air flows through the mouth and makes different sounds through the adjustment of the tongue and lips. A detailed phonation test protocol was utilized as described previously 11 as an active exercise that coordinates the movements of other parts. Consequently, the built-in camera in the laptop was used to record the head tremor and detailed facial expressions. Finally, Facereader 7.0 software was used to analyze the head tremor. 12

| Statistical analysis
The data were recorded and stored in Excel files, and Stata 15.0 was used for statistical analysis. The HY scale and UPDRS III were expressed as the mean (standard deviation) and analyzed by two-tailed Student's t-test. Also, age was compared between the two groups using two-tailed Student's t-test. Sex, profession, alcohol consumption, and education were compared using the chi-square test. The head tremor between the PD patients and healthy subjects was compared using two-tailed Student's t-test. Spearman's rank correlation coefficient was used to analyze the correlation between head tremor and PD severity. p < 0.05 indicated statistically significant difference.

| Head tremor in female patients in the PD and control groups
Among the 26 phonation test samples, significant differences were observed in the 2-24, 26 syllables between the PD group and the controls in the x-axis trajectory direction (p < 0.05), while no significant difference was detected in 1 and 25 syllables (p > 0.05). Furthermore, significant differences were detected in all the 26 syllables between the PD group and the controls in the y-axis trajectory direction (p < 0.05). Moreover, significant differences were observed in the 3-9, 12-14, 16, 19, 21-24, and 26 syllables between the PD group and controls in the z-axis trajectory direction (p < 0.05).

| Correlation between head tremor and disease severity in PD males in phonetic tests
The Also, a positive and negative correlation was established between head tremor in x-/y-/z-axis and UPDRS-III scale (p < 0.05). Tremor is one of the typical motor symptoms of PD. The primary clinical feature of tremor is a postural or action tremor at 5-12 Hz frequency with symmetrical presentation that involves the hands, head ("yes-yes" or "no-no"), and voice. 13 In this study, the head tremor was stimulated through the phonation test, and the head movement track in the x-, y-, and z-axis directions were recorded. syllables between PD and normal people (p < 0.05; Table 3).    Conversely, the head tremor belongs specifically to the motor symptoms. Taken together, the present study aimed to provide an accurate degree of head tremor and contribute to the early recognition of PD as an auxiliary diagnosis in the clinic.

| CON CLUS ION
In the phonetic test, PD patients showed typical displacement compared with normal individuals, and the displacement amplitude was positively correlated with the severity of the disease. This study determined an accurate degree of cranial tremor, which is valuable for the early detection of PD.

TA B L E 5
Correlation between head tremor and disease severity of female PD patients

| Limitation
The present study has some limitations. First, the sample size was small. Second, although patients in this study stopped levodopa before speech testing, they were still using other anti PD drugs and were in the "on" phase.

ACK N OWLED G M ENT
We thank Dr. Kun Huang for the valuable suggestions about the robust acoustic parameters extract software and the Department of Neurology of Chengdu Medical College for logistic support.

CO N FLI C T O F I NTE R E S T S
The authors declare that they have no competing interests.

DATA AVA I L A B I L I T Y S TAT E M E N T
All data would be made available upon reasonable request.