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|NI FEATURE: THE QUEST - COMMENTARY
|Year : 2017 | Volume
| Issue : 5 | Page : 1083-1090
Review of tremor in Parkinson's disease and atypical parkinsonian disorders
Pooja Mailankody, M Netravathi, Pramod Kumar Pal
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
|Date of Web Publication||6-Sep-2017|
Pramod Kumar Pal
Department of Neurology, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None
Rest tremor (RT), a cardinal feature of Parkinson's disease (PD) is often accompanied by other types of tremor such as action tremor, which includes postural tremor, kinetic tremor, re-emergent tremor (ReT), and orthostatic tremor (OT). Literature on other tremors of PD, especially ReT and OT, is scarce. Tremor can be present in any of the atypical parkinsonian disorders such as progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. RT can even be the presenting symptom of these disorders. The objective of this review is to provide a comprehensive review of lesser known tremors in PD and to critically look at the prevalence of tremor in atypical Parkinsonian disorders.
Keywords: Action tremor, atypical Parkinsonian disorders, orthostatic tremor, parkinson's disease, prevalence
Key Message: The lesser known tremors in Parkinson's disease have been highlighted. The characteristics of tremors in atypical parkinsonian disorders have also been elucidated.
|How to cite this article:|
Mailankody P, Netravathi M, Pal PK. Review of tremor in Parkinson's disease and atypical parkinsonian disorders. Neurol India 2017;65:1083-90
Tremor is defined as a rhythmical, involuntary oscillatory movement of a body part. Rest tremor (RT) is one of the key features of Parkinson's disease (PD). In addition to RT, patients with PD can also have an action tremor (AT), which includes postural tremor (PT), kinetic tremor (KT), re-emergent tremor (ReT), and orthostatic tremor (OT).,,, More than 90% of the patients with PD have PT.,
According to Litvan's definition, atypical parkinsonian disorders are those which progress rapidly, show a poor or transient response to dopaminergic therapy, and are accompanied by atypical features like early autonomic failure, postural instability, vertical gaze palsy, pyramidal, or cerebellar signs. The atypical Parkinsonian disorders are progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and dementia with Lewy bodies (DLB). Though not a cardinal manifestation, tremor can be present in any of these atypical parkinsonian disorders. There is sparse information on the clinical heterogeneity of tremor in these disorders. The objective of this article is to review the literature on different types of tremor in PD (excluding RT) and the prevalence of tremor in atypical parkinsonian disorders.
| » Materials and Methods|| |
Data for this review were identified by searching PubMed with the terms "Parkinson's disease," "re-emergent tremor," "orthostatic tremor," "progressive supranuclear palsy," "multiple system atrophy," "corticobasal degeneration," "dementia with Lewy bodies," " Parkinsonism More Details," "tremor," "rest tremor," "postural tremor," "action tremor," "intention tremor," "jerky tremor," "clinical," and "clinicopathological." Articles were included only if they were written in English and full texts were available. References from 1985 to 2015 were considered, including case reports and natural history, clinical, clinicopathological, and neurophysiological studies, summarizing rates of occurrence, tremor characteristics in patients with PD and atypical parkinsonian disorders.
Tremor, a key manifestation of PD, is found in more than 80% of the autopsy proven cases. Of the four cardinal manifestations of PD, tremor is the one which least responds to levodopa. The severity of tremor does not correlate with that of rigidity and bradykinesia.
RT of PD is classically described as pill rolling type with a frequency between 4 and 6 Hz.,, The tremor disappears at the beginning of a voluntary movement and increases on mental stress such as counting backwards and anxiety. The intensity of tremor can even decrease with increasing rigidity. When RT persists for more than 2 years without any other parkinsonian features, it is called monosymptomatic tremor at rest or benign tremulous parkinsonism. The most common site of RT is the upper limb. In a study of 81 patients with PD and clinically visible tremor, Zimmermann et al., found RT of the upper limbs in 83%, legs in 42%, head in 17%, tongue in 13%, and face in 12%.
Five patients with PD and RT of the head were reviewed by Roze et al. Two of them had head tremor as the initial manifestation. Isolated RT of the head as a presenting symptom of PD was described in a case report by Gan et al. Both the frequency and response of tremor to levodopa were consistent with typical RT of PD. Patients with PD can have jaw tremor that is usually characterized by up and down movement of the jaw.,
AT, defined as tremor produced by voluntary muscle contraction, includes postural and kinetic tremor (KT). The AT of PD has a prevalence of 92%. Intention tremor is classified under KT. Electrophysiological studies have shown that AT contributes to both weakness and bradykinesia in patients with PD., AT can be present even in the absence of RT and at times be more severe than RT., AT is directly correlated with motor disability. Louis et al., studied 197 patients with PD to delineate the clinical correlates of AT. They excluded patients with re-emergent tremor (ReT). It was found that AT score had the best correlation with the RT scores, ipsilateral more than contralateral. There was no association of the severity of AT with age, age of onset, or disease duration. The different types of ATs seen in PD are PT, KT, and OT.
According to Deuschl, the PT of PD has a frequency greater than that of RT (by > 1.5 Hz) and can exist either in isolation or in combination with RT. This tremor is regarded as more incapacitating than the severe RT. Among the 50 patients evaluated by Koller et al., 92% had PT. More than 80% of the patients evaluated by Milanov et al., had PT. Jankovic et al., postulated that this tremor could be either an enhanced physiological tremor or a co-existent ET. In a retrospective case series by Chaudhuri et al., it was found that 13 patients presenting with asymmetrical PT developed PD after an average period of 19.2 years. This suggests that isolated PT could be the presenting feature of PD.
KT occurs during any voluntary movement. In a study of 870 patients with PD, 47% of the patients had marked to severe KT as evidenced by the evaluation of their spiral drawings. Among the patients recruited, 29 had neither RT nor PT. However, 12 among these 29 patients had KT during spiral drawing despite the absence of RT and PT. Wenzelburger et al., analyzed KT during the reach-to-grasp movement in 13 patients with tremor predominant PD. Among the 12 patients who had KT, it was found that the frequency of the tremor in the terminal period is higher than that of RT and PT. The authors postulated that KT was nothing but an enhanced physiological tremor.
Sternberg et al., studied 50 patients of PD and 50 patients of ET to look at the phenomenology of PT. They found that the PT in PD is distal involving the metacarpo-phalangeal joints rather than the proximal wrist and elbow joints. Though KT was present in 78% of the patients, intention tremor was found only in 4% of the patients with PD. The tremor ratings on Archimedes spiral drawings were significantly lower in patients with PD.
The term ReT was first coined by Jankovic in 1999 in a short report titled "Re-emergent tremor of PD." Jankovic, in the same paper, has variably called this an RT and a "PT with latency." Subsequently, authors have called it RT that emerges after a variable latency., In 1989, Koller et al., observed that in some patients, PT appears after a delay of several seconds and hypothesized that it could be due to resetting of RT. Among the 18 patients evaluated by Jankovic et al., 12 patients had ReT and the mean latency was 9.4 s. The frequency of ReT was found to be the same as that of RT. ReT was found in 4–66% of patients with tremor predominant PD.,, The duration of latency for the tremor to re-emerge ranges from 0.79 to 13 s.,,,,, A ReT of the tongue also has been reported in the literature.
Orthostatic tremor and pseudo-orthostatic tremor
Leu-Semenescu studied 11 PD patients with tremulousness of the lower limbs; 4 were found to have fast OT with a frequency of 13–18 Hz (same as that of primary OT); and 3 were found to have slow OT with a frequency of 4–6 Hz (same as that of RT). One patient with fast OT and all patients with slow OT were found to have co-existent RT in upper limb. However, RT and slow OT never co-existed in lower limbs. Even though the amplitude may come down, the frequency remains unchanged with levodopa treatment in fast OT., The fast OT responded to clonazepam in Leu-Semenescu's series. The slow OT showed a good response to levodopa. The term "Pseudo-Orthostatic Tremor" was used by Thomas et al., to describe the dopa-responsive, 6–7 Hz tremor that occurred in four patients on standing, who later developed parkinsonism. Of these four patients, two had genetic forms of PD (Parkin and Pink 1 gene mutations) and all had abnormalities on dopamine transporter imaging consistent with PD. Levodopa responsive leg tremor or pseudo-orthostatic tremor could also suggest parkin gene mutation.,, Four members in a Spanish family presented with leg tremor of which three patients later developed akinetic rigid syndrome. All of them had a good response to levodopa. DNA analysis showed mutation of the parkin gene in these four patients.
Tremor associated with dystonia or "dystonic tremor" has been described in patients with a clinical diagnosis of PD, both in young and adult patients with PD.,,, In adults, the imaging studies revealed that they had no evidence of dopaminergic deficit and hence they were considered to have a diagnosis of Scans Without Evidence of Dopaminergic Deficit (SWEDDs). Task or position specificity, thumb extension type of tremor, presence of head tremors, and absence of fatiguing of repetitive movements are the features characteristic of SWEDDs., A 5-year follow-up study of 16 patients with asymmetric upper limb tremor associated with dystonia showed that only a minority of patients (12.5%) developed decreased nigrostriatal uptake on DaT scan. Dystonia may also be present in early onset PD with or without associated tremor.
In a questionnaire-based study, Shulman et al., found that 44% of PD patients had a sensation of internal tremor, which was closely associated with anxiety. Internal tremor was present at rest in 30% of the patients and during anxiety in 64% of the patients. It was unrelated to the Unified Parkinson's Disease Rating Scale (UPDRS) score, Hoehn and Yahr (H&Y) stage, duration of the disease, or the presence of observable tremor. Also, there was poor response to levodopa.
Progressive supranuclear palsy
PSP is a gradually progressive atypical Parkinsonism with the age of onset usually after 40 years. It is characterized by vertical supranuclear gaze palsy, nuchal rigidity, and postural instability with falls., According to Golbe et al., minimal or absent tremor was one of the diagnostic criteria required for diagnosis of PSP. A review of literature by Kristensen  in 1985 suggested that tremor in PSP is an exception. Later in 1996, Litvan et al., proposed a new criteria, which did not include tremor in the characteristics of PSP. The prevalence of tremor is high in PSP and can range from 6 to 44%.,,,,,,,,, It may even be one of the initial manifestations. The tremor is mostly symmetrical and its presence is associated with longer duration of survival in patients with PSP., The frequency of tremor in PSP was found to be lower (3 Hz) than that of parkinsonian RT (usually 4–6 Hz). Around 10–12% of the patients with ET were found to have PSP in some autopsy series., OT as the presenting symptom of PSP has been reported. Resting tremor of the jaw and symptomatic palatal tremor also have been reported in PSP.,,, The prevalence of different types of tremor in PSP found in different studies have been described in [Table 1].
Multiple system atrophy
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder in which parkinsonism is accompanied by cerebellar, pyramidal, and/or autonomic features. In addition to RT, PT, and intention tremor, an irregular jerky PT may be seen , [Table 2]. PT is the most common type of tremor in MSA.,,,,
RT can be present in 12–53% of patients with MSA.,,,,,,,,,,,,, A recent review by Kaindlstorfer et al., pointed out that the characteristic jerky PT in MSA does not satisfy the criteria for tremor and hence the term minipolymyoclonus might be more suitable on electrophysiological grounds.
Tison et al., found that 50% of the patients had tremor at their initial visit (10 months after the presenting symptom) and 62% developed it on follow-up. Among the tremor types, PT was the most frequent and RT was more often atypical (fast, irregular, myoclonic or present during action, posture, or intention) rather than pill rolling. Typical pill rolling RT was documented in 12% of the patients with MSA, whereas it was found in 74% of patients with PD. Thirty-two percent of the patients developed intention tremor after a follow-up of 62 months compared to the 2% who had it at the initial visit, which was probably secondary to cerebellar involvement. On the contrary, two other longitudinal studies found that the progression of the disease had no impact on the occurrence or severity of MSA.,
Both RT and PT were found to be more frequent in MSA-P (with Parkinsonian features) than with MSA-C (with cerebellar features).,,, The results of both the European and Japanese studies were similar with respect to RT and intention tremor. However, the frequency of PT was found to be lesser in MSA-P as compared to MSA-C in the Japanese cohort (10.1% of MSA-C and 8.7% of MSA-P patients) contrary to the European group.,,,, Jerky PT was found to be more common in MSA-P than MSA-C., Intention tremor was found to be more common in MSA-C than MSA-P. However, patients with MSA-P were also found to have intention tremor.,
In a retrospective study of 16 patients who primarily presented with unilateral lower limb RT, Hellmann et al., found that four patients had a diagnosis of MSA. Palatal tremor has been reported in MSA.
A patient of MSA can present with RT as an initial manifestation and even have the typical pill rolling type of tremor, which may lead to an erroneous diagnosis of PD. The poor response of tremor to levodopa in MSA as compared to PD is not a useful criterion for making a diagnosis.
CBD is a clinicopathological entity characterized by asymmetric rigidity, apraxia, alien hand, dystonia, and parkinsonism. Irregular RT, pill rolling type of RT, and coarse AT can be seen in patients with CBD ,,, [Table 3].
Dementia with Lewy bodies
Dementia with Lewy bodies (DLB) is clinically characterized by parkinsonism, dementia, visual hallucinations, and fluctuating cognition. RT is less common in DLB according to the recent criteria. The frequency of RT can be as high as 87% in DLB ,,, [Table 4]. An association of DLB and OT has also been noted.,
Overflow of tremor is a characteristic feature of DLB. In terms of frequency of tremor and response to treatment, RT of DLB is similar to that of PD. Lesser severity of disease and better scores on cognitive testing in patients with tremor suggest that tremor in DLB is a predictor of good prognosis.
| » Conclusions|| |
This article highlights some of the lesser known tremors in PD. We have also tried to elucidate the characteristics of tremors in atypical parkinsonian disorders. ReT is an entity which needs to be better characterized in terms of both phenomenology and electrophysiology. Levodopa responsive pseudo-OT of the leg should raise the suspicion of parkin gene mutation. RT, though classically described as a core feature of PD, can be a presenting feature in other atypical parkinsonian disorders as well. RT was found in 6–44% of patients with PSP, 12–53% of patients with MSA, 19–21% of patients with CBD, and 40–87% of patients with DLB. This challenges the specificity of RT as a cardinal sign of PD. Presence of RT implies a better prognosis in PSP, MSA, and DLB. Irregular jerky tremor is a characteristic feature of MSA. "Overflow" of tremor is a phenomenon that has been described in DLB.
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[Table 1], [Table 2], [Table 3], [Table 4]
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