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Internal tremor in Parkinson's disease, multiple sclerosis, and essential tremor

      Highlights

      • Internal tremor (IT) is a common disorder only reported once before.
      • IT was found in 33% of consecutive PD, 36% of multiple sclerosis and 55% of essential tremor patients.
      • We conclude that IT is common in these three populations but confirmation is needed.
      • IT needs also to be evaluated in healthy controls.

      Abstract

      Objective

      Internal tremor (IT) is a poorly recognized symptom that has been described in Parkinson's disease (PD). Described as a feeling of tremor in the extremities or trunk without actual movement, ITs are not debilitating but can be bothersome to patients. The origin of the sensation is unknown., and ITs may be prevalent in other diseases than PD. The present study sought to expand knowledge about IT by confirming their presence in PD, and determining their prevalence in Multiple Sclerosis (MS), and Essential Tremor (ET).

      Methods

      A survey was developed in order to determine the prevalence of IT in PD, MS, and ET and to learn what associations with various disease characteristics were present. The survey was administered to 89 consecutive PD, 70 MS, and 11 ET patients.

      Results

      ITs were found to be a prevalent symptom in all three disorders (32.6% of PD, 35.9% of MS, and 54.5% of ET subjects reported experiencing ITs). ITs were found to be associated both with the subjects' perceived levels of anxiety and the presence of visible tremors.

      Conclusion

      ITs appear to be a common symptom in all three disorders studied. These results need to be confirmed and compared to appropriate control populations.

      Keywords

      1. Introduction

      “Internal tremor” (IT) was first described by Shulman et al. as a sensation of tremor in the extremities or trunk that produces no visible movement [
      • Shulman L.
      • Singer C.
      • Bean J.
      • Weiner W.
      Internal tremor in patients with Parkinson's disease.
      ]. Our clinical impression is that Parkinson disease (PD) patients report IT as though it was a physical movement, but when queried describe the lack of actual movement [
      • Watts R.
      • Mandir A.
      • Ahn K.
      • Juncos J.
      • Zakers G.
      • Freeman A.
      Electrophysiologic analysis of early Parkinson's disease.
      ]. In the only report on IT, Shulman et al. found that a sensation of IT was present in about 44% of PD patients and only 6% of a control population [
      • Shulman L.
      • Singer C.
      • Bean J.
      • Weiner W.
      Internal tremor in patients with Parkinson's disease.
      ]. Patients with normal neurological exams are sometimes evaluated in movement disorders clinics for this purpose.
      Explanations for the increased prevalence in PD are unknown. Shulman et al. found a correlation between patients with anxiety and presence of IT but many patients with IT did not suffer from anxiety. It is unknown whether or not the presence of a preexisting anxiety disorder increased the risk of IT or if IT contributed to the anxiety [
      • Shulman L.
      • Singer C.
      • Bean J.
      • Weiner W.
      Internal tremor in patients with Parkinson's disease.
      ]. Other studies have suggested that IT sensations are caused by actual tremors; Watts et al., 1991 suggests that PD patients without observable tremors may experience subclinical muscle tremors which may be a physical cause of IT [
      • Watts R.
      • Mandir A.
      • Ahn K.
      • Juncos J.
      • Zakers G.
      • Freeman A.
      Electrophysiologic analysis of early Parkinson's disease.
      ,
      • Raudino F.
      Non motor off in Parkinson's disease.
      ].
      We are unaware of studies investigating IT in multiple sclerosis (MS) patients or essential tremor (ET) patients. MS was chosen because of anecdotal information that IT was a common symptom in MS patients (personal communication). ET was chosen because of the hallmark visible tremor. The present study was completed to determine the prevalence of IT in PD, MS and ET, and to determine its relationship to anxiety and to visible tremor.

      2. Methods

      Subjects were consecutively recruited from one movement disorders clinic and one MS clinic. Subjects met criteria for the diagnosis of idiopathic PD, essential tremor or multiple sclerosis and were deemed competent to provide their own informed consent and to answer all questions in the protocol. Patients exhibiting dementia or psychiatric disorders that were severe enough to make their responses to questions unreliable were not invited. Dementia was assessed using DSM-V criteria for dementia assessed at the office visit [
      • American Psychiatric Association
      Diagnostic and Statistical Manual V.
      ]. No formal dementia screening was completed; only patients who passed the physician's assessment for dementia were invited to participate. Patients who did not pass this assessment were not recorded. Those whose English was not sound were also excluded. Only patients who indicated they had time to participate in the interview at the time of their visit were invited to participate.
      IT was defined as “a feeling of tremor, shaking, or vibration in the body that is not associated with an actual movement”. Survey questions (see appendix for list of questions) assessed the location of the IT, when the tremors began in relation to the symptoms of the patient's PD/ET/MS, how many days per week the tremor occurred, how long each episode lasted, and what the patient was doing/feeling that the subject felt specifically brought on the tremor and what the subject did to alleviate the tremor. Patients with visible tremors were asked if the IT felt the same or different than the visible tremors, and were asked to describe the difference. PD subjects received two extra questions on the survey asking whether or not PD medication alleviated the IT and whether or not the IT was associated with “off periods” of their medication. Patients who reported IT were asked whether or not they experienced burning, tingling, numbness, or aching along with the IT. All patients, regardless of whether or not they reported IT, were asked if they had a history of resting, visible tremors and were asked to rate their general level of anxiety on a scale from 0 to 10. Formal mental status testing was not performed.
      Additional information collected through patient records following the interview consisted of age, gender, duration of disease, and current medications.
      Data was analyzed using SPSS 20.
      Patients who were seen by a physician that day also received tremor scores extracted from the Unified Parkinson Disease Rating Scale (UPDRS) part III, scores for PD [summed scores of items for rest tremor and separate score for sustention/action tremor], sustention/action tremors (head, voice, arm, and leg) for ET, and Expanded Disability Status Scale (EDSS) score for MS evaluated by the physician.

      3. Results

      Eighty nine consecutive patients with PD, 73 with MS, and 11 with ET, seen in the movement disorders and MS clinics, were asked to participate. Eighty eight Parkinson's disease patients, 70 multiple sclerosis patients, and 11 essential tremor patients agreed to participate in the study after written informed consent was obtained. One PD and three MS patients refused to participate. The survey was administered orally by a single researcher, and answers were provided orally by the patient. Interviews were completed in person following the subject's appointment with the physician or during their natalizumab infusions in the case of some MS patients.
      Twenty nine of 89 PD subjects, 32.6%, 54.5% of ET patients (6/11), and 35.9% of MS patients (26/70) reported experiencing IT. Forty-eight percent of these individuals (29/61) reported feeling IT in their hands and arms, 44% (27/61) reported feeling it in their legs or feet, and 57% (35/61) reported feeling tremors in their head, neck, chest, or stomach. Significantly more MS subjects felt IT in their feet and legs than PD subjects (χ: 8.927, df = 1, p = 0.003). Age and duration of disease were not significantly related to the prevalence of IT neither in the collective group nor within each separate disease. Out of the types of medications analyzed for significance (dopamine agonists, benzodiazepines, antidepressants, monoamine oxidase inhibitors, narcotics, anti-epileptics, and natalizumab) none were found to be significantly related to the prevalence of IT. Sixty-seven percent reported that IT symptoms started after disease symptoms had begun, with 88% of those beginning over a year after disease symptoms.
      Subjects experiencing visible tremors were significantly more likely to experience IT. 72/163 PD and MS subjects reported experiencing visible tremors; 44% (32/72) of these subjects reported IT while 29% (26/91) of the subjects without visible tremors reported IT (χ: 5.186, df = 1, p = 0.023). There was no significant relationship between higher UPDRS scores or EDSS scores in PD and MS subjects, respectively, and the prevalence of IT. Sixteen of 28 PD (54%) subjects reported that PD medications did not reduce IT while 43% (12/28) reported that they did. The frequency of IT was variable. Thirty-two percent reported once a day, 29% reported 2–3 times a week, and 39% reported 4–7 times a week. The length of each IT episode was variable: 13% of subjects reported them lasting seconds, 53% reported minutes, and 34% reported hours. No significant differences were found between different disorders and these items.
      There was a significant difference between PD and MS subjects who experienced IT in terms of what they thought led to the tremor (χ: 7.246, 2 df, p = 0.27). 12/27 PD subjects believed the IT were caused by anxiety/nervousness while only 3/26 MS subjects believed so. 12/27 PD and 17/26 MS subjects were unsure of what started the tremor. The remaining members of each group mentioned other etiologies, such as exercise. Significantly more PD subjects than MS subjects believed that exercise alleviated the IT (χ: 10.904, df = 1, p = 0.012). When asked directly if the subject believed the IT sensations were associated with anxiety, significantly more PD patients believed so than MS (χ: 6.434, df = 1, p = 0.040). Of the individuals who believed their IT was associated with anxiety, significantly more PD subjects believed that their IT began mostly when they were feeling anxious (χ: 19.783, df = 1, p = <0.001). However, both groups reported that their IT would worsen if they were anxious (17/22 PD patients & 10/12 MS patients). No conclusions could be drawn concerning the ET subjects due to the small sample size.
      MS subjects with IT reported significantly higher anxiety levels than MS subjects without IT, with an average 1.9 higher on the 10-point scale (χ: 4.365, df = 1, p = 0.038). PD subjects with IT reported about 0.3 points higher on average (4.9 vs. 4.6) compared to non-IT PD subjects.

      4. Discussion

      The results of our survey suggest that IT is a common sensation in PD, MS, and ET. We did not measure IT in control populations, but Shulman et al. found a prevalence of 6% in a control population for PD.1 There is no data on the prevalence of IT in other populations. While the prevalence of IT in our PD population (32.6%) is lower than Shulman found (44%), nevertheless it is a commonly present sensation. In addition, it seems just as prevalent in the MS population (35.9%). Despite the increased prevalence of IT in the legs of MS patients, it seems that the other aspects of IT are very similar between PD and MS patients. Neither group had a relationship between their ages, duration of disease, or medications with prevalence of IT, nor was there any relationship between their respective disease severity scores and prevalence of IT.
      Our results do not suggest an etiology for the sensation and without data from control populations we cannot even be certain that the prevalence of IT is increased in any of these disorders. Significantly more subjects who reported visible tremors also reported experiencing IT, consistent with the belief that IT may simply be a subclinical physical tremor. On the other hand, IT often is felt in internal organs which cannot tremor. A large number of PD patients believed that anxiety caused their IT when asked in a free response form, and when asked directly about anxiety a significant number of PD patients believed anxiety both led to and worsened their IT. While some MS patients indicated they believed anxiety led to their IT, others instead suggested a number of causes such as exercise and relaxation with no true majority response. Despite this, we observed a very significant increase in self-reported anxiety scores in MS subjects with IT compared to MS patients without IT (1.9 points on a 10-point scale), even higher than the difference between the two PD groups (only a difference of 0.3) even though the PD groups were able to articulate the relationship. It is worth noting that PD subjects in general reported an average of 0.4 points higher than MS patients on self-reported anxiety, but the very large gap between the MS IT group and the non-IT group suggests that anxiety may also be playing a role in IT in the MS population even though the patients do not realize it.
      We are aware of several important weak points in our study, primarily the absence of control groups. We also had no validated instrument for rating IT, as this was only the second study we are aware of and the instrument from the first was not available. The number of ET patients was small, reflecting their low prevalence in this clinic. We did not administer a validated anxiety scale because we considered this a pilot trial. Subjects were interviewed with their family or friends present, if the subject so desired which may have influenced how questions were answered.
      We did confirm Shulman et al.'s observation that IT is common in PD and also that it was equally or more common in two other disorders that commonly have tremor, MS and ET. We believe, based on personal experience (JHF, SR) that patients often do not discriminate in their reporting of tremors and that doctors will assume that a bothersome tremor at home reflects a visible tremor that might respond to an increase in medication, when the tremor may in fact be an IT, whose response to most types of treatment is unknown.1
      We would like to stress the preliminary nature of this article, especially considering the very small population of ET patients available for surveying. Our observations need to be replicated in studies that include control populations. We believe that IT may be a common syndrome in PD, MS and ET. In addition, we believe that IT may be present in the general population as well, but at this time cannot speculate on whether or not it might be increased in neurological disorders not discussed here. Of particular importance, future work should investigate IT in other tremulous disorders such as those drug induced tremors seen in patients taking antipsychotics, valproic acid, lithium, etc.

      Acknowledgment

      Lisa Shulman, MD, for helpful criticism, and Peter Riskind, MD, whose observations triggered the study.

      Appendix A. Supplementary data

      References

        • Shulman L.
        • Singer C.
        • Bean J.
        • Weiner W.
        Internal tremor in patients with Parkinson's disease.
        Mov. Disord. 1996; 11: 3-7
        • Watts R.
        • Mandir A.
        • Ahn K.
        • Juncos J.
        • Zakers G.
        • Freeman A.
        Electrophysiologic analysis of early Parkinson's disease.
        Neurology. 1991; 41: 44-48
        • Raudino F.
        Non motor off in Parkinson's disease.
        Acta Neurol. Scand. 2001; 104: 312-315
        • American Psychiatric Association
        Diagnostic and Statistical Manual V.
        American Psychiatric Press, Washington, D.C2014