Functional Tremor Misdiagnosed as Parkinson’s Disease in a Geriatric Patient

Affiliations:
¹Department of Cardiology, Kelowna General Hospital, British Columbia, Canada
²Department of Family Medicine, University of Alberta, Canada
³Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada

Abstract: Tremor, a common involuntary movement disorder, is associated with numerous neurological disorders and neurodegenerative diseases. It is also a hallmark feature of Parkinson’s disease (PD). As the causes of tremor are heterogeneous, clinicians should take the time to distinguish the etiology of the tremor to ensure that patients are being treated appropriately, especially when pharmacologic management is employed. In this case report, the authors describe an elderly woman whose PD was diagnosed after a traumatic incident. After 20 years of living with the PD diagnosis and taking a regimen of carbidopa/levodopa, the healthcare team determined that the patient’s tremor was not from the PD, and carbidopa/levodopa was eventually discontinued without tremor recurrence or any other signs of PD. This case highlights how reevaluation of existing diagnoses can result in reduced medication use and improved health outcomes. It also emphasizes the role of interdisciplinary efforts and the importance of providing seamless transitional care.

Key words: Functional tremor, neurological disorders, psychogenic tremor, Parkinson’s disease.
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Tremor is one of the most prevalent involuntary movement disorders encountered by clinicians. The causes of tremor are heterogeneous, hence the type of tremor needs to be distinguished.¹ In the elderly patient, Parkinson’s disease (PD) is the most common organic cause of tremor, and, generally, clinicians are often familiar with a PD diagnosis and management; however, there are numerous other categories of tremor besides parkinsonian, including essential, dystonic, cerebellar, functional (psychogenic), orthostatic, and physiologic. Functional tremors are widely prevalent, and their diagnosis should be considered in patients with emotional triggers or an atypical presentation.¹

In this article, we describe the case of functional tremor misdiagnosed as Parkinson’s disease in a geriatric patient, which resulted in decades of unnecessary treatment with carbidopa/levodopa subsequently causing adverse drug effects. Our case illustrates that in complex geriatric patients with multiple comorbidities and polypharmacy, diagnoses should be re-evaluated on a regular basis, unnecessary medications should be tapered and discontinued, and symptoms relating to drug-related side effects should always be considered. Ultimately, the patient’s healthcare team should involve multiple disciplines and focus on seamless care transitions. The case report is followed by a brief overview of the physiology, epidemiology, diagnosis, and treatment of functional tremor in older patients.  

Case Presentation

An 85-year-old woman who did not speak English was referred to a multidisciplinary geriatric outpatient clinic specializing in comprehensive geriatric assessment. The multidisciplinary team responsible for the patient’s care consisted of a geriatrician, a pharmacist, a nurse, an occupational therapist, and an administrative assistant. Some portions of the assessment were completed with family members present, consistent with comprehensive geriatric assessment procedures, and to assist with some interpretation. The patient was referred by her family physician for uncontrolled pain, burning mouth syndrome (BMS), and insomnia. Her medical history included PD, BMS, neuropathic leg pain, osteoarthritic back pain, hypertension, gastroesophageal reflux disease, osteopenia, cholelithiasis, hiatal hernia, basal cell carcinoma of the nose, delirium (2 years prior), and previous bilateral cataract surgery. She was taking the following medications: carbidopa/levodopa controlled release (CR), two 50/200 mg tablets in the morning and at noon and one 50/200 mg tablet at night; long-actingpropranolol, 80 mg daily; pregabalin, 50 mg twice daily; ramipril, 5 mg daily; furosemide, 20 mg daily; lansoprazole, 30 mg daily; two tablets of sennosides daily; docusate calcium, 480 mg daily; risperidone, 0.25 mg daily; and one or two tablets of a codeine/caffeine/acetaminophen combination every 4 hours as needed (she took 6-8 tablets daily). She was a lifelong nonsmoker and reported no alcohol use.

This patient received a diagnosis of PD and was initiated on carbidopa/levodopa 19 years before her current presentation by her family physician. Her parkinsonian symptoms (ie, a resting right hand tremor) began after her son-in-law was murdered. She became increasingly housebound after this incident and stopped participating in social activities; this isolation worsened after the death of her husband 5 years later. Since her PD diagnosis, two different neurologists in a movement disorder clinic had seen her. Four years prior to her current presentation, one neurologist observed an occasional resting right hand tremor, mild cogwheeling, and rapid alternating finger and finger-to-nose movements. Due to inconsistencies on physical examination and symptoms consistent with mild tardive dyskinesias (ie, frequent blinking, protruding lip movements), the neurologist suggested discontinuing carbidopa/levodopa and observing for remerging PD symptoms to confirm the diagnosis. At the time, she was not on risperidone and other reversible medication-related causes of tremor had been ruled out; however, there was no record of this plan being implemented. A second neurologist saw the patient 2 years later, noted similar inconsistencies, and suggested idiopathic PD in the differential diagnosis.

During her current presentation at the geriatric clinic, the patient’s vital signs were normal. A neurological examination revealed grossly normal cranial nerves II-XII, with normal tone and sensation with no observed tremor. Her gait was slow, with no shuffling, festination, or propulsion. A musculoskeletal examination revealed generalized burning and pain, especially in the legs. A review of systems was otherwise unremarkable. Routine blood work, including a complete blood count, electrolytes, creatinine, folate, vitamin B₁₂, thyroid-stimulating hormone, and iron studies, were all within normal limits.

On physical examination, the geriatrician could not discern any signs of PD, which is atypical given the duration of her PD diagnosis (over 20 years). The underlying condition should have progressed to a more advanced stage with increased functional impairment, such as inability to mobilize; autonomic, psychiatric, and motor complications should have been more apparent as well. The pharmacist noted that the dose of levodopa had not been increased over the years, which is also inconsistent with dopaminergic drug therapy in a progressive condition such as idiopathic PD.

At the clinic, risperidone was discontinued; it was started 2 years prior for an episode of delirium. The carbidopa/levodopa dose was decreased to 50/200 mg three times daily. With regard to the BMS that was diagnosed 5 years earlier, it was unclear whether the etiology was due to the PD, anxiety because of her previous traumatic life events, or another cause. Pregabalin was continued given that it is approved for the treatment of generalized anxiety disorder in Europe and because it was providing the patient with some pain relief. For her osteoarthritic pain, the codeine/caffeine/acetaminophen combination was tapered, discontinued, and replaced with regular acetaminophen.

During three monthly follow-up visits to the clinic, the patient’s carbidopa/levodopa dose was tapered by 50% monthly until discontinued. She did not report increased rigidity, difficulty walking, or tremor. She even reported feeling better than before; she was still experiencing BMS, although the symptoms had significantly improved since her first visit. The dose of pregabalin had been titrated up for symptomatic relief, while balancing the risk of side effects (eg, weight gain); at the time, she was still taking pregabalin 50 mg twice daily. It was unclear if propranolol had been prescribed for tremor; therefore, the dose was decreased from 80 mg daily to 60 mg, tapering by 20 mg monthly until discontinued.

The patient’s last clinic visit was 1 year after her initial geriatric assessment. All of her Parkinson’s medications had been discontinued and she did not exhibit any signs of PD. She reported functioning very well at home and was subsequently discharged from the geriatric clinic.

Discussion

Functional (psychogenic) movement disorders (FMDs) comprise a wide spectrum of functional neurological disorders, of which functional tremor (FT) is the most common and accounts for 55% of FMDs.^2,3 The term functional refers to a “disturbance in functioning” of the nervous system.³ The term implies that the cause is functional rather than neurological, and its cause may not be due to psychiatric illness alone.³ Other terms used to describe FMDs include psychogenic, nonorganic, conversion disorder, and somatization disorder. The terms psychogenic and conversion may carry negative connotations, hence the current preferred terminology is functional, which indicates the disease process follows more of a neurobiopsychosocial model.⁴

Pathophysiology and Epidemiology of Functional Movement Disorders
The pathophysiology of FMDs is poorly understood.³ These disorders were historically considered an abnormal psychiatric state rather than an organic disorder attributable to a lesion or dysfunction of the nervous system. However, recent literature has challenged this belief, and a FMD may be diagnosed in the absence of a psychiatric trigger.^1-3,5 It has been increasingly noted that there is a complex interplay of other factors, such as genetic susceptibility and neurobiological factors that may also play a role in its pathogenesis.⁴ The lack of understanding of the pathophysiology has also resulted in difficulties in unifying the terminology and definitions, which directly affects accurate diagnosis and treatment.³

The prevalence of FMDs ranges between 1% and 9% of all neurological diagnoses and accounts for between 2% and 20% of all patients seen in specialized movement disorder clinics.^3,5,6 The prevalence is difficult to estimate given the lack of a consistent case definition.³ FMDs occur more often in women, with a mean age of onset of 43 years (range 37-50 years), and an average duration of 4.6 years.^2,3,6,7  

Diagnosis of Functional Tremor
FT poses a diagnostic and therapeutic challenge for neurologists and psychiatrists alike.^3,8 A thorough history is important, as it can elucidate relevant neurological or psychological causes.^1,2 A variety of diagnostic criteria exist for FMDs, including the Fahn-Williams criteria⁹; a modified version of the Fahn-Williams criteria¹⁰; the Shill-Gerber criteria¹¹; and the Gupta-Lang criteria.^3,12 The Fahn-Williams and Shill-Gerber criteria have poor to moderate interrater reliability; good agreement has only been shown when the diagnosis is “clinically definite” versus “probably” or “possible.”³ A modified version of Fahn’s criteria for psychogenic tremor may be a useful, concise, diagnostic tool for clinicians (Table 1).¹⁰

Although the diagnosis of FT has been historically considered a diagnosis of exclusion, specific diagnostic signs include variability, distractibility, co-activation sign, and entrainment.^1,2,7,12,13 Routine blood tests should be drawn to exclude reversible causes of tremor, including complete blood counts; liver, kidney and thyroid function tests; and serum copper and ceruloplasmin (to exclude Wilson’s disease). Diagnostic imaging should include computed tomography scan or magnetic resonance imaging to rule out a structural lesion; dopamine transport single-photon emission computed tomography (SPECT) or fluorodopa positron emission tomography scans may also be used to differentiate FT from parkinsonian tremors.^2,12 If available, tremor analysis via electromyography or electroencephalography may also be helpful.^2,13 

Symptoms of FT may present suddenly and are commonly precipitated by emotionally stressful life events (eg, divorce or a death in the family), physical trauma pending compensation or litigation (eg, work-related injuries), or sexual abuse.^2,6,7 As the majority of patients with FT also have coexisting depression or anxiety disorders, a psychiatric assessment may be beneficial; however, a psychopathology is not always present in patients with FT.^4,6 FT may also be common in those who have witnessed an organic form of the disorder (eg, healthcare providers or family members of patients with FT).²

Clinical Features of Functional Tremor
FT may present with multiple complex movements that mimic various organic abnormal involuntary movements (Table 2).⁶ FT often presents as a combination of resting and intentional or postural tremors that often involves the hand (84%), leg (28%), or may be generalized (20%)^1,5,7; the fingers are rarely involved, unlike in PD.^2,5,4 The onset is often abrupt (73%), with a static (46%) or fluctuating course (17%).^1,2 Symptoms may progress rapidly and become severe very quickly, unlike the slow progressive course of most organic movement disorders.³ Patients may also report complete remission followed by sudden recurrences.³

The frequency of FT is usually less than 6 Hz, but variability in tremor amplitude, frequency, and direction is commonly seen in FT.^2,6 Tremor frequencies may increase with attention and decrease with distraction. In one study, patients with FT were twice as likely to direct visual attention towards the tremor compared with those with organic tremor.¹⁴ The frequency may differ by more than 1.5 to 2.0 Hz between different limbs, whereas organic tremors rarely vary by such large frequencies.^2,7 Distractibility results when there is a change in the frequency and amplitude of the original tremor after a long period of observation or when the patient is distracted (eg, performing mental calculations)^2,7,14; the tremor typically worsens during examination.³ Coactivation is elucidated by passively moving tremor-affected joints and feeling for cocontraction of antagonist muscles in the affected limb.³

In FT, there is active resistance against passive movement resulting in fluctuations in tone or exacerbation of tremor.⁷ However, if the patient allows for passive movements until the increased tone is broken down, the tremor will often resolve; this is different than in rigidity or spasticity, when muscles cannot be completely relaxed with instruction or maneuvering.^1,7 Entrainment is determined by asking the patient to maintain a tapping motion in an uninvolved body part at a different frequency than the original tremor. As it is difficult to maintain two different voluntary frequencies, FT will change to the frequency of the uninvolved limb.¹

Due to differences in tremor generation in FT, no single measure has enough sensitivity nor specificity to differentiate FT from other forms of organic tremors.³ However, the diagnosis can be elucidated based on discordance with diagnostic criteria of organic tremors and the inconsistency of the symptoms over time.^4,13

Treatment of Functional Tremor
Patients with FT will typically receive a variety of diagnoses and undergo various treatments before a diagnosis is established.^1,12 A patient’s acceptance of the functional diagnosis is crucial for treatment to be successful, and it may be beneficial to discuss the diagnosis after a physician-patient relationship has been established.^5,6,15,16 The diagnosis should be presented to the patient in a positive, nonjudgemental fashion, emphasizing the fact that the tremor disorder is not due to an organic cause, and therefore remission may be possible.^2,4,16 A recent case report demonstrated that showing or explaining FT physical signs to the patient may convince him or her of the diagnosis and increase the likelihood of treatment success.¹⁶

Even when the diagnosis is elucidated, the treatment of FT is challenging and requires a multidisciplinary approach.⁷ As soon as a definitive diagnosis is known, treatment with a combination of therapies should be initiated, including pharmacotherapy (eg, antidepressants, anxiolytics), psychotherapy, stress management, biofeedback, hypnosis, and relaxation techniques; a combination of the aforementioned treatments have shown variable success.^1,4-6,12 Placebo therapy has not been shown to be effective and should be avoided due to ethical reasons and the potential deterioration of the practitioner-patient relationship.⁷ Optimal treatment should also involve the discontinuation of unnecessary tests, medications, and surgical interventions.^3,13 

Prognosis
Patients with FMDs may have a quality of life that is similar to or worse than patients with PD.¹⁷ Generally, treatment success of FT is variable, with poor response to medications.^1,2,5,7 Patients with better outcomes tend to be younger at diagnosis; in good physical health; with concomitant psychiatric illness, but do not have other somatoform complaints; and a shorter duration of disease (<6 months).^2,5,6,18 Patients who are resistant to the diagnosis or treatment, who present with an insidious onset of symptoms, who have a longer duration of symptoms (>6 months), and who have a history of smoking tend to have worse outcomes.^5,6 If untreated, FT may remit spontaneously in 10% to 20% of patients, but FMDs have been generally reported to persist in 65% to 95% of patients, continuing to result in moderate to severe disability.^6,18,19

Conclusion

This case illustrates a geriatric patient who was subjected to two decades of dopaminergic treatment due to a misdiagnosed tremor. The diagnosis of an FMD was elucidated from a thorough history, appropriate follow-up, implementation of specialist suggestions, and a team-based assessment. This case also highlights the challenges in diagnosing FMDs in complex older patients. Geriatric patients pose diagnostic challenges due to atypical presentation of illness, presence of comorbidities, underlying cognitive dysfunction, language barriers, and the involvement of multiple caregivers and medical providers. Many conditions or symptoms may be confused with normal physiologic changes associated with aging and are therefore underinvestigated. It is important to re-evaluate diagnoses in older adults, especially if the diagnosis is uncertain or the symptoms are inconsistent; treatment modalities should also be re-evaluated frequently. A multidisciplinary healthcare team is integral in maintaining seamless care for the older adult patient in determining mutual, patient-centered treatment plans and serving as an advocate for the patient’s overall health and wellbeing.

References

1. Bhidayasiri R. Differential diagnosis of common tremor syndromes. Postgrad Med J. 2005;81(962):756-762.
2. Bhatia KP, Schneider SA. Psychogenic tremor and related disorders. J Neurol. 2007;254(5):569-574.
3. Edwards MJ, Bhatia KP. Functional (psychogenic) movement disorders: merging mind and brain. Lancet Neurol. 2012;11(3):250-260.
4. Czarnecki K, Hallett M. Functional (psychogenic) movement disorders. Curr Opin Neurol. 2012;25(4):507-512.
5. Peckham EL, Hallett M. Psychogenic movement disorders. Neurol Clin. 2009;27(3):801-819.
6. Hinson VK, Haren WB. Psychogenic movement disorders. Lancet Neurol. 2006;5(8):695-700.
7. Thomas M, Jankovic J. Psychogenic movement disorders: diagnosis and management. CNS Drugs. 2004;18(7):437-452.
8. Kranick SM, Gorrindo T, Hallett M. Psychogenic movement disorders and motor conversion: a roadmap for collaboration between neurology and psychiatry. Psychosomatics. 2011;52(2):109-116.
9. Fahn S, Williams DT. Psychogenic dystonia. Adv Neurol. 1988;50:431-455.
10. Deuschl G, Koster B, Lucking CH, Scheidt C. Diagnostic and pathophysiological aspects of psychogenic tremor. Mov Disord. 1998;13(2):294-302.
11. Shill H, Gerber P. Evaluation of clinical diagnostic criteria for psychogenic movement disorders. Mov Disord. 2006;21(8):1163-1168.
12. Gupta A, Lang AE. Psychogenic movement disorders. Curr Opin Neurol. 2009;22(4):430-436.
13. Schrag A, Lang AE. Psychogenic movement disorders. Curr Opin Neurol. 2005;18(4):399-404.
14. van Poppelen D, Saifee TA, Schwingenschuh P, et al. Attention to self in psychogenic tremor. Mov Disord. 2011;26(14):2575-2576.
15. Friedman JH, LaFrance WC Jr. Psychogenic disorders: the need to speak plainly. Arch Neurol. 2010;67(6):753-755.
16. Stone J, Edwards M. Trick or treat? Showing patients with functional (psychogenic) motor symptoms their physical signs. Neurology. 2012;79(3):282-284.
17. Anderson KE, Gruber-Baldini AL, Vaughan CG, et al. Impact of psychogenic movement disorders versus Parkinson’s on disability, quality of life, and psychopathology. Mov Disord.2007;22(15):2204-2209.
18. McKeon A, Ahlskog E, Bower JH, Josephs KA, Matsumoto JY. Psychogenic tremor: long-term prognosis in patients with electrophysiologically confirmed disease. Mov Disord. 2009;24(1):72-76.
19. Feinstein A, Stergiopoulos V, Fine J, Lang AE. Psychiatric outcome in patients with a psychogenic movement disorder: a prospective study. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(3):169-176.

Disclosures: Dr. Sadowski reports a research grant from Pfizer Canada, Inc. The other authors report no relevant financial relationships.

Address correspondence to: Cheryl A. Sadowski, PharmD, Associate Professor, University of Alberta,3-171 Edmonton Clinic Health Academy,11405-87 Ave, Edmonton, Alberta, Canada T6G 1C9; cherylas@ualberta.ca