The authors have studied 53 patients with essential tremor, focusing its clinical and epidemiological aspects. There were familial history in 37.70% of all cases, prevailing in females (56.60%) and white people (69.80%); nevertheless this difference can not be assured from the statistical point of view due to lack of population data. We agreed that the main incidence of this syndrome occurred beyond the 5th decade, specially during the 6th and 7th decades. Topographically, we could observe that the hand tremor predominated, with an incidence of 96.20% of the total number of cases, followed by head tremor (28.30%), voice tremor (16.99%), leg tremor (11.30%), tongue tremor (3.78%) and trunk tremor (1.88%). These focal tremors were seldom observed alone and we noted frequent association with hand tremor.
OBJECTIVE: To characterize the olfactory identification in 40 essential tremor (ET) patients, with the University of Pennsylvania 12 Smell Identification Test (UPSIT), to correlate UPSIT scores to clinical and epidemiological data and to compare it to 89 aged matched controls. METHOD: Patients were assessed using ET Clinical Scale of Evaluation and UPSIT. RESULTS: In patients with ET, the UPSIT medium score was 9.10, similar to the control group (9.11), which was also observed in all age groups. ET severity did not correlate to UPSIT scores. CONCLUSION: This study demonstrated normality of olfactory identification on ET, qualifying UPSIT to be an important tool on tremor differential diagnosis of undetermined origin.
Tremor in essential tremor (ET) and Parkinson’s disease (PD) usually present specific electrophysiologic profiles, however amplitude and frequency may have wide variations. Objective: To present the electrophysiologic findings in PD and ET. Method: Patients were assessed at rest, with posture and action. Seventeen patients with ET and 62 with PD were included. PD cases were clustered into three groups: predominant rest tremor; tremor with similar intensity at rest, posture and during kinetic task; and predominant kinetic tremor. Results: Patients with PD presented tremors with average frequency of 5.29±1.18 Hz at rest, 5.79±1.39 Hz with posture and 6.48±1.34 Hz with the kinetic task. Tremor in ET presented with an average frequency of 5.97±1.1 Hz at rest, 6.18±1 Hz with posture and 6.53±1.2 Hz with kinetic task. Seven (41.2%) also showed rest tremor. Conclusion: The tremor analysis alone using the methodology described here, is not sufficient to differentiate tremor in ET and PD.
Intravenous thymoxamine reduced the power of essential tremor but increased that of physiological and isoprenaline-induced tremor. These findings indicate that essential and physiological tremor have dissimilar pathophysiological mechanisms. They also suggest that central adrenergic mechanisms are involved in the pathophysiology of essential tremor and that isoprenaline-induced tremor is not a good model of essential tremor. Furthermore, alpha-adrenoceptor blockers may be a useful therapy for essential tremor.
Amplitude/frequency characteristics of postural hand tremor in 59 patients with bilateral essential tremor of various degrees of severity were assessed using accelerometric recordings and spectral analysis. Intra-subject comparisons of tremor characteristics between the more and less affected hands were used to control for variability of tremor due to age factors and intersubject differences in amplitude and frequency. Statistical analysis distinguished three different patient groups. Some patients had low amplitude (less than 0.1-0.015 cm) tremor in the less affected limb (which tended to be 7 Hz or more in frequency in the young) and a larger amplitude tremor in the more affected hand which was 1 Hz or more lower in frequency. Other subjects had either bilaterally small or bilaterally large amplitude tremors of similar frequencies. These findings imply that there is a downwards step in frequency between symptomatic tremors of small and large amplitude. The amplitude and frequency of the small amplitude tremors were unrelated but frequency declined with age. The frequency of the large amplitude tremor was generally determined by amplitude but a wide range of amplitudes were compatible with similar frequencies. The frequency of large amplitude tremor also declined with age. It was concluded that there are two types of essential tremor...
Essential tremor is the most common movement disorder and has an unknown etiology. Here we report that γ-aminobutyric acidA (GABAA) receptor α1–/– mice exhibit postural and kinetic tremor and motor incoordination that is characteristic of essential tremor disease. We tested mice with essential-like tremor using current drug therapies that alleviate symptoms in essential tremor patients (primidone, propranolol, and gabapentin) and several candidates hypothesized to reduce tremor, including ethanol; the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801; the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA); the GABAA receptor modulators diazepam, allopregnanolone, and Ro15-4513; and the L-type Ca2+ channel antagonist nitrendipine. Primidone, propranolol, and gabapentin reduced the amplitude (power) of the pathologic tremor. Nonsedative doses of ethanol eliminated tremor in mice. Diazepam, allopregnanolone, Ro15-4513, and nitrendipine had no effect or enhanced tremor, whereas MK-801 and CCPA reduced tremor. To understand the etiology of tremor in these mice, we studied the electrophysiological properties of cerebellar Purkinje cells. Cerebellar Purkinje cells in GABAA receptor α1–/– mice exhibited a profound loss of all responses to synaptic or exogenous GABA...
stimulation has been proposed to treat disabling tremor. The aims of
this multicentre study were to evaluate the efficacy and the morbidity
of thalamic stimulation in a large number of patients with parkinsonian
or essential tremor. METHODS—One hundred
and eleven patients were included in the study and 110 were
implanted either unilaterally or bilaterally. Patients were evaluated
with clinical scales, before and up to 12 months after surgery. RESULTS—Upper
and lower limb tremor scores were reduced in both groups. Eighty five
per cent of the electrodes satisfied the arbitrary criteria of two
point reduction in rest tremor reduction in the parkinsonian tremor
group and 89% for postural tremor reduction in the essential tremor
group. In the parkinsonian tremor group, limb akinesia and limb
rigidity scores were moderately but significantly reduced. Axial scores
were unchanged. In the essential tremor group, head tremor was
significantly reduced only at 3 months and voice tremor was
non-significantly reduced. Activities of daily living were improved in
both groups. Changes in medication were moderate. Adverse effects
related to the surgery were mild and reversible. CONCLUSIONS—Thalamic
stimulation was shown to be an effective and relatively safe treatment
for disabling tremor. This procedure initially applied in a very
limited number of centres has been successfully used in 13 participating centres.
Forehead tremor has only been reported in two patients with essential tremor, one with rhythmic tremor and the other with dystonic tremor. We report 4 new patients with essential tremor who present a 4–6 Hz frontal tremor registered by electromyography and unusual features like frontal tremor preceding limb tremor or unilateral involvement. Frontal tremor is present in some patients with essential tremor, sometimes preceding limb tremor. Treatment with botulinum toxin may be useful.
Classic essential tremor is a clinical syndrome of action tremor in the upper limbs (at least 95% of patients) and less commonly the head, face/jaw, voice, tongue, trunk, and lower limbs, in the absence of other neurologic signs. However, the longstanding notion of that essential tremor is a monosymptomatic tremor disorder is being challenged by a growing literature describing associated disturbances of tandem walking, personality, mood, hearing and cognition. There is also epidemiologic, pathologic and genetic evidence that essential tremor is pathophysiologically heterogeneous. Misdiagnosis of essential tremor is common because clinicians frequently overlook other neurologic signs and because action tremor in the hands is caused by many conditions, including dystonia, Parkinson disease and drug-induced tremor. Thus, essential tremor is nothing more than a syndrome of idiopathic tremulousness, and the challenge for researchers and clinicians is to find specific etiologies of this syndrome.
Growing clinical, neuro-imaging and post-mortem data have implicated the cerebellum as playing an important role in the pathogenesis of essential tremor. Aside from a modest reduction of Purkinje cells in some post-mortem studies, Purkinje cell axonal swellings (torpedoes) are present to a greater degree in essential tremor cases than controls. Yet a detailed study of more subtle morphometric changes in the Purkinje cell axonal compartment has not been undertaken. We performed a detailed morphological analysis of the Purkinje cell axonal compartment in 49 essential tremor and 39 control brains, using calbindin D28k immunohistochemistry on 100-µm cerebellar cortical vibratome tissue sections. Changes in axonal shape [thickened axonal profiles (P = 0.006), torpedoes (P = 0.038)] and changes in axonal connectivity [axonal recurrent collaterals (P < 0.001), axonal branching (P < 0.001), terminal axonal sprouting (P < 0.001)] were all present to an increased degree in essential tremor cases versus controls. The changes in shape and connectivity were significantly correlated [e.g. correlation between thickened axonal profiles and recurrent collaterals (r = 0.405, P < 0.001)] and were correlated with tremor duration among essential tremor cases with age of onset >40 years. In essential tremor cases...
High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor...
Essential tremor is a common disorder that lacks molecular targets for therapeutic development. T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in essential tremor. We therefore tested whether compounds that antagonize T-type calcium channel currents suppress tremor in two mouse models that possess an essential tremor-like pharmacological response profile. Tremor was measured using digitized spectral motion power analysis with harmaline-induced tremor and in the GABAA receptor α1 subunit-null model. Mice were given ethosuximide, zonisamide, the neuroactive steroid (3β,5α,17β)-17-hydroxyestrane-3-carbonitrile (ECN), the 3,4-dihydroquinazoline derivative KYS05064, the mibefradil derivative NNC 55-0396, or vehicle. In non-sedating doses, each compound reduced harmaline-induced tremor by at least 50% (range of maximal suppression: 53–81%), and in the GABAA α1-null model by at least 70% (range 70–93%). Because the T-type calcium channel Cav3.1 is the dominant subtype expressed in the inferior olive, we assessed the tremor response of Cav3.1-deficient mice to harmaline, and found that null and heterozygote mice exhibit as much tremor as wild-type mice. In addition...
Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly...
Die therapeutische tiefe Hirnstimulation hat sich in den letzten Jahren beim idiopathischen Parkinsonsyndrom und beim Essentiellen Tremor zu einer potenten therapeutischen Option mit zunehmender Bedeutung entwickelt. Obwohl die klinische Effektivität dieses operativen Verfahrens inzwischen belegt werden konnte, sind die neurophysiologischen Mechanismen der Therapie aktuell Gegenstand intensiver Forschung. In diesem Kontext bietet die neuronale Synchronisation ein attraktives Konzept zur Beschreibung der Konnektivität von zerebralen Schlüsselstrukturen innerhalb eines pathologischen tremorassoziierten motorischen Netzwerks. So wurden in der vorliegenden Arbeit neuronale und neuromuskuläre Synchronisation zwischen Nucleus subthalamicus / Nucleus ventralis intermedius thalami (STN / Vim), Kortex (M1) und den Effektoren Musculus abductor pollicis brevis / Musculus interosseus dorsalis primus (APB / FDI) beschrieben und deren gezielte Modulation durch therapeutische Stimulation und operative Mikroläsion in vier perioperativen Untersuchungsbedingungen untersucht: ein Tag vor Operation [D0], ein Tag nach Operation [D1], acht Tage nach Operation ohne Stimulation [D8StimOff] und mit Stimulation [D8StimOn]. Dabei wurden in allen Bedingungen EEG und EMG abgeleitet...
Deep brain stimulation (DBS) is a neurosurgical treatment, which has proven useful in treating Parkinson's disease. This systematic review assessed the safety and effectiveness of DBS for another movement disorder, essential tremor. All studies concerning the use of DBS in patients with essential tremor were identified through searching of electronic databases and hand searching of reference lists. Studies were categorized as before/after DBS or DBS stimulation on/off to allow the effect of the stimulation to be analyzed separately to that of the surgery itself. A total of 430 patients who had received DBS for essential tremor were identified. Most of the reported adverse events were mild and could be treated through changing the stimulation settings. Generally, in all studies, there was a significant improvement in outcomes after DBS compared with baseline scores. In addition, DBS was significantly better in testing when the stimulation was turned on, compared with stimulation turned off or baseline. Based on Level IV evidence, DBS is possibly a safe and effective therapy for essential tremor.; Eliana Della Flora, Caryn L. Perera, Alun L. Cameron, and Guy J. Maddern
Objectives: Determine the effect of contraction type and intensity, inertial loading, and visual feedback on various measures of hand tremor in subjects with essential tremor. Methods: Study 1. Twenty-three ET subjects and 22 controls held their hand in an outstretched position while supporting various submaximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Hand postural tremor and wrist extensor neuromuscular activity (EMG) were recorded. Study 2. Twenty-one ET subjects and 22 controls applied isometric wrist extension contractions with and without visual feedback. Various submaximal contraction intensities were evaluated (5%, 10%, 20% and 30% MVC). Force production and EMG were recorded. Study 3. Twenty-one ET subjects and 22 healthy controls performed slow wrist extension-flexion movements while supporting various submaximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Angular displacement and EMG were recorded. Results: Study 1. Inertial loading resulted in a reduction in postural tremor in ET subjects. The largest reduction in tremor amplitude occurred at the 15% load, which was associated with spectral separation of the mechanical reflex and central tremor component. Despite an increase in overall neuromuscular activity with inertial loading...
The pathophysiology of essential tremor (ET) is not clearly understood but is thought to involve multiple brain regions. The purpose of this study was to describe in greater detail head tremor in ET and to investigate the possible relationship between head and hand tremor.
Ten ET subjects were recruited (1 male, 9 female) and compared to three control subjects (1 male, 2 female). Head and hand tremors were recorded simultaneously with surface electromyography (EMG) of the wrist extensors and various neck muscles, laser displacement sensors (hand tremor), a load cell (hand tremor) and an accelerometer (head tremor). While seated, subjects performed four tasks: 1) constant force (10% maximum) wrist extensions (with and without visual feedback); maintenance of the hands in a horizontal posture against gravity while 2) seated upright in a chair, 3) seated in a reclined chair (20° backward, head not supported); and 4) seated upright in a chair and producing steady submaximal hip adduction forces.
Head tremor spectral peaks were found between 3.5 and 7 Hz in neck muscle EMG and the accelerometer signal. Wrist tremor (EMG and kinematic data) was slightly higher in frequency with a range of 4 -10 Hz. Of the ten ET subjects recruited for this study...
Objective: To determine the effects of head position and of different postural control demands on head tremor measures in participants with essential tremor.
Methods: Seventeen participants with essential tremor (ET) of the head and 17 control participants took part. Individuals held their heads in varying degrees of rotation, flexion, and extension. Subsequently, individuals sat and stood in different postures, incorporating different foot placements (feet apart and together), surfaces (solid and foam), and vision conditions (eyes open and closed). Neck muscle activity was recorded from three muscles bilaterally (trapezius, sternocleidomastoid, splenius capitis). Three-dimensional head and thorax positions were recorded using an Optotrak system, and head angular velocity with respect to thorax was calculated by differentiating tilt-twist angles. Fourier analysis was used to determine tremor power.
Results: ET participants showed sharp peaks at their tremor frequency in spectral plots of kinematic data, whereas CN participants did not. Electromyography data was too noisy for frequency analysis. ET participants displayed increased tremor power in head positions 25° from neutral compared to neutral and positions 50° from neutral. Tremor power increased with increasing difficulty of posture for both participant groups. Removal of vision resulted in decreased tremor power in ET participants; power was significantly decreased in the easier postures...
Previous reports have suggested that essential tremor (ET) represents a risk factor for the development of Parkinson's disease (PD). Patients with long-standing ET who develop PD tend to have a tremor-dominant subtype. To further clarify this association, we examined patients from kindreds with autosomal dominant ET who had signs of isolated PD but did not meet criteria for overlapping ET. We identified 22 patients with PD meeting these diagnostic criteria, and 90% (20 of 22) had tremor-predominant subtype of PD. Unilateral rest tremor was the presenting symptom in 15 of 22 patients, bradykinesia or rigidity in 5 of 22, and gait problems in 2 of 22. Postural tremor was relatively mild, and the severity of kinetic tremor tightly correlated with rest tremor (r = 0.83, P < 0.001). Tremor-dominant subtype of PD in patients with a positive family history of ET suggests that these patients have inherited a genetic susceptibility factor for tremor, which affects the motor phenotype of PD.
The occurrence of Parkinson's disease and of essential tremor was examined in the parents and siblings of 52 Parkinson's disease patients with onset before the age of 45 years. The expected numbers of cases with Parkinson's disease or essential tremor were calculated according to the age and sex specific incidence rates of Parkinson's disease and essential tremor in the general population. Among the parents, there was one case of Parkinson's disease (expected 1.2), and 10 cases of essential tremor (expected 5.4); among the siblings there were two cases of Parkinson's disease (expected 0.7), and three cases of essential tremor (expected 5.3). The observed and expected incidence of Parkinson's disease or essential tremor were not significantly different. This does not support the inheritance of early-onset Parkinson's disease, or the association of Parkinson's disease with essential tremor.