Isolated vertical head tremor: A diagnostic challenge

The aim of this study was to investigate the somatosensory temporal discrimination threshold in patients with essential tremor (sporadic and familial) and to evaluate whether somatosensory temporal discrimination threshold values differ depending on the body parts involved by tremor. We also investigated the somatosensory temporal discrimination in patients with isolated voice tremor. We enrolled 61 patients with tremor: 48 patients with essential tremor (31 patients with upper limb tremor alone, nine patients with head tremor alone, and eight patients with upper limb plus head tremor; 22 patients with familial vs. 26 sporadic essential tremor), 13 patients with isolated voice tremor, and 45 healthy subjects. Somatosensory temporal discrimination threshold values were normal in patients with familial essential tremor, whereas they were higher in patients with sporadic essential tremor. When we classified patients according to tremor distribution, somatosensory temporal discrimination threshold values were normal in patients with upper limb tremor and abnormal only in patients with isolated head tremor. Temporal discrimination threshold values were also abnormal in patients with isolated voice tremor. Somatosensory temporal discrimination processing is normal in patients with familial as well as in patients with sporadic essential tremor involving the upper limbs. By contrast, somatosensory temporal discrimination is altered in patients with isolated head tremor and voice tremor. This study with somatosensory temporal discrimination suggests that isolated head and voice tremors might possibly be considered as separate clinical entities from essential tremor.

The Timing of Tremor: A Biological Clock in Essential Tremor

Background: Mild and transient head tremor may sometimes be observed in otherwise tremor-free relatives of essential tremor (ET) cases, although its prevalence is unclear. A diagnostic question is whether this transient, isolated head tremor, often observed as no more than a wobble, is an early manifestation of ET or whether it is a normal finding. A direct comparison with controls is needed.Methods: Two hundred and forty-one first-degree relatives of ET cases (FD-ET) and 77 spousal controls (Co) were enrolled in a study of ET. Each underwent a detailed evaluation that included a tremor history and videotaped neurological examination. None of the enrollees reported tremor, had a prior diagnosis of ET, or had significant tremor on screening spirals. All videotaped examinations were initially reviewed by a movement disorder neurologist blinded to subject type, and among those with head tremor on examination, co-reviewed by two additional movement disorders neurologists.Results: Twenty-six (10.8, 95% Confidence interval [CI] = 7.5–15.3%) of 241 FD-ET vs. 2 (2.6, 95% CI = 0.7–9.0%) of 77 Co had isolated, transient head tremor (odds ratio = 4.54, 95% CI = 1.05–19.57, p = 0.04). No enrollee had significant upper extremity tremor and none met inclusion criteria for ET based on the presence of upper extremity tremor. With one exception, head tremor occurred during or after phonation. It was always transient (generally a single back and forth wobble) and rare (observed briefly on one or two occasions during the videotaped examination) and had a faster frequency, lower amplitude and a different quality than voluntary head shaking.Conclusion: The basis for the observed isolated head tremor is unknown, but it could be an early feature of ET in ET families.Indeed, one-in-ten otherwise unaffected first-degree relatives of ET cases exhibited such tremor. To a far lesser extent it was also observed in “unaffected” controls. In both, it is likely a sign of early, emerging, undiagnosed ET, although follow-up studies are needed to confirm this. If it were ET, it would indicate that the prevalence of ET may be considerably higher than previously suspected.

Essential tremor (ET) still remains a clinical diagnosis. Nonetheless, it is misdiagnosed in 30 to 50% of cases. There are a number of areas of diagnostic uncertainty. One of these is isolated head tremor, on which published data are limited and at variance. We studied the prevalence of isolated head (i.e., neck) tremor in ET in two population-based studies (Turkey and New York) and a large clinical sample (New York); these 583 ET cases all received the same detailed tremor examination. Head tremor with mild arm tremor occurred in a very small percentage of cases in each sample (1.9-3.1%, overall 2.7%). Nearly all of them were women. Head tremor in the complete absence of arm tremor was not observed in any cases (0.0%). These clinical data may be of value to clinicians in practice settings and researchers in phenotyping efforts in the emerging field of ET genetics.

Essential tremor (ET) is the most common tremor disorder in adults. In addition to upper limbs, the tremor in ET may also involve head, jaw, voice, tongue, and trunk. Though head tremor (HT) is commonly present in patients with ET, large comparative studies of ET patients with HT (HT+) and without HT (HT-) are few. To determine whether ET with HT is a distinct clinical subtype by comparing ET patients with and without HT, a chart review of 234 consecutive patients with ET attending the neurology clinics of the National Institute of Mental Health and Neurosciences, India, was done. A movement disorder specialist confirmed the diagnosis of ET in all patients using the National Institutes of Health collaborative genetic criteria. HT was present in 44.4% of the patients. Comparison between HT+ and HT- showed that the HT+ group patients: (1) were older, (2) had later onset of tremor, (3) had unimodal distribution of age at onset with a single peak in the fifth decade, (4) had more frequent voice tremor, and (5) were more likely to have mild cervical dystonia. HT was part of presenting symptoms in nearly two thirds of the ET patients and in the rest it was detected during clinical examination. Several demographic and clinical variables suggest that ET patients with HT have a distinct clinical phenotype.

Head tremor poses diagnostic problems, especially when present as an isolated or predominant symptom. To assess how maneuvers activating upper limb postural tremor can help differentiate head tremor in essential tremor (ET) from dystonic tremor (DT) in cervical dystonia. 48 patients with head tremor (25 ET, 23 DT), underwent clinical examination and accelerometric evaluation of head and upper limb tremor during routine tremor-inducing tasks. While accelerometric power and clinical scores of head tremor did not significantly differ between patient groups, task-induced variations revealed distinctions. ET patients exhibited increased head tremor power and clinical scores during forward outstretched and lateral wing-beating arm positions, unlike DT patients. Coherence between head and upper limb tremor remained consistent. Tremor stability index showed no significant differences. Task-induced changes in head tremor could aid in distinguishing between ET and DT. Further research is needed to refine diagnostic approaches for head tremor.

The medical treatment available for patients with essential tremor (ET) is often inadequate. Furthermore, the efficacy of the medical treatments currently available for patients with ET of cranial nerve areas is less satisfactory than that of the medical treatments available for patients with ET involving the upper extremities. This pilot study was performed to evaluate whether zonisamide (ZNS) is effective in the treatment of patients with isolated head tremor. All subjects with isolated head tremor were randomly treated with either ZNS or propranolol. After a washout period, the subjects were switched to the alternative drug. ZNS was found to be more effective in the treatment of patients with isolated head tremor than propranolol. No severe adverse effects were reported with either ZNS or propranolol. ZNS may be more useful than propranolol for the treatment of ET patients with head tremor.

There is clinical variability in essential tremor (ET), but it is not clear whether this variability is because of the existence of distinct clinical subtypes of ET (ie, forms of ET that may differ in their etiology, rate of progression, or response to treatment). To examine in a group of ET cases the age of onset, anatomic distribution, and rate of progression of tremor, and to look for associations between these factors. Cases of ET were ascertained from a community (n = 60) and a tertiary referral clinic (n = 55) in northern Manhattan, New York, NY. All subjects underwent an interview and videotaped tremor examination. Rate of progression was estimated based on the tremor severity and reported disease duration at the time of evaluation. Age of onset was bimodally distributed in clinic cases. There were differences in the anatomic distribution of the tremor (arm tremor only vs head and arm tremor vs isolated head tremor). Rate of progression was distributed exponentially; there was a large cluster of subjects with slower rates of progression, and a smaller number who had faster rates. There was an association between age of onset and rate of progression (r = 0.46-0.50, P<.002); cases with older age of onset (>60 years) progressed more rapidly (P<.001). In addition, upper limb tremor progressed more slowly among those with concomitant head tremor (P =.03). Essential tremor is not a homogeneous condition. There are differences in age of onset, anatomic distribution of tremor, and rate of progression. The ET in several groups of patients in this study (those with age of onset >60 years and those without head tremor) progressed more rapidly, suggesting that these ET cases may define distinct clinical subtypes. These subtypes should be further assessed for etiologic and genetic heterogeneity as well as differences in responsiveness to therapeutic agents. Arch Neurol. 2000;57:1194-1198

Essential and dystonic head tremor: More similarities than differences

Longitudinal evaluation of patients with isolated head tremor

P 104 - Head and hand tremor measurement and analysis for the differentiation between essential and dystonic tremors

Propranolol is used as the first-line treatment in essential tremor and it has also been proposed as a treatment for tremor in dystonia. However, several issues remain uncertain. For example, it is still not clear whether propranolol exerts a beneficial effect on head tremor. Moreover, no studies have investigated whether the effect of propranolol on head and upper limb tremor in essential tremor differs from that in dystonia. We aimed to assess the effects of propranolol on tremor in different body parts in essential tremor and in patients with tremor and dystonia. Twenty-nine patients with head and upper limb tremor were enrolled in the study, 14 with essential tremor, and 15 with dystonia. Participants underwent a clinical and kinematic analysis of tremor in two sessions, i.e., without (baseline) and 'on therapy' with propranolol. We found that head tremor was more severe in patients with dystonia, while upper limb tremor was more evident in patients with essential tremor (P < 0.05). Propranolol had no effect on head tremor in either group (all Ps > 0.05), but it did reduce upper limb tremor in patients with essential tremor. The present study demonstrates differential effects of propranolol on head and upper limb tremor in patients with essential tremor. The lack of effect on head and upper limb tremor in patients with dystonia suggests that the pathophysiological mechanisms underlying tremor in these two conditions and in different body parts may be distinct.

Essential tremor (ET) is a common movement disorder, and approximately 50% of the cases are inherited as an autosomal dominant trait.[1] The incidence of ET increases with age, may manifest at any age (childhood to adulthood), and those with a positive family history have an earlier age of onset.[2] The tremor involves mainly the upper limbs distally and is postural or kinetic type. The less common parts involved with tremor are the head, lower limbs, voice, tongue, face, and the trunk. The tremor amplitude increases with time, and patients experience difficulty in writing, eating, holding objects and doing fine motor tasks, dressing, and speaking.[3] Although ET usually does not reduce life expectancy or cause other symptoms, many patients have severe psychosocial disability.[3] Tremor often increases with anxiety, stress, and in situations involving interaction with others. Patients with head and voice tremor often suffer severe embarrassments, and may develop depression. ET should be differentiated from the other types of tremors, especially tremor of Parkinson's disease, tremor associated with hyperthyroidism, and dystonic tremor of head in patients with isolated head tremor. Once a diagnosis is made, the severity of functional and psychosocial disabilities should be assessed by objective scales, which will help to determine the need for pharmacotherapy. The management of a patient with ET includes (a) behavioral techniques and physical therapy, (b) medical therapy, and (c) surgical treatment. The patient should be explained about the disease, the long-term outcome, and what the therapies can achieve. All therapies are essentially symptomatic and will not cure or change the course of the disease. If there is minimal functional disability, the patient need not take treatment. Even if the tremor is controlled by medical therapy, stress and anxiety can increase the symptoms. An outline of the management of ET is given in Figure 1.Figure 1: A flow chart showing the steps in the management of essential tremorBehavioral Techniques and Physical Therapy Not all patients with ET will need treatment with drugs. Treatment depends on the severity of tremor, the body part affected, and the occupation of the patients. It is also determined by the degree of social disability. In patients with less disabling tremor, certain behavioral techniques and physical therapy may be useful. These include relaxation therapies and reducing emotional stress, using the less disabled hand to write or eat, using wrist weights[2] and minimizing exposure to tremorogenic foods (eg, caffeine) and drugs (eg, sympathomimetics). Medical Treatment Treatment schedules When it is decided to start medical treatment, it can be of 2 types: Intermittent treatment: On an as-needed or scheduled basis. This is recommended when the patient is distressed mainly in social gatherings or prior to an important social activity. A half to 2 tablets of propranolol (20 mg) can be administered 30 min to 1 h before a social activity or the anxiety-provoking event, which increases tremor. Alternatively, a benzodiazepine, such as lorazepam or clonazepam can be administered prophylactically. However, as the benzodiazepines can cause central nervous system adverse events and also have abuse potential, they need to be administered judiciously. Although routine use of alcohol is not recommended, in patients with alcohol responsive tremors, judicial use of a small amount of alcohol prior to select social activities, such as social dinner, can be considered. As long-term suppressive therapy: In patients who need long-term therapy, the following drugs have proved to be useful with varied efficacy and levels of recommendations, based on the class of evidence. Drugs of choice β-Blockers, most commonly propranolol, and primidone are the drugs of choice for treatment of ET. Both these agents have level A recommendation, and either can be used for initial treatment of ET[4] depending on the concurrent medical conditions, and potential side effects. Propranolol (β-2 blocker) Treatment should be initiated at 10 mg once daily and gradually titrated (eg, every 3–7 days) to 20 mg twice daily. Elderly individuals may need a lower dose (eg, 10 mg twice daily), while for those who are tolerating well, propranolol can be increased up to 240 mg/day in divided doses. Improvement occurs in approximately 50%–60% of the patients, the greatest improvement being for hand tremor, and the least for head or voice tremor. Long-acting preparations of propranolol also have a similar efficacy. Ten to 15 percent of the responders may develop tolerance after a year of treatment.[5] Side effects include light headedness, fatigue, impotence, bradycardia, and reduced blood pressure. Relative contraindications to propranolol are severe heart failure, conduction blocks, hyperactive airway disease, depression, and diabetes. Primidone The efficacy of primidone for managing ET appears to be similar to propranolol[5] and it can be an initial therapy, although most often this is started after the failure of propranolol to control ET satisfactorily. Currently, this drug is not easily available in India. The treatment is initiated at the lowest possible dose and gradually titrated up to avoid side effects, which often appear. When a 50 mg tablet or an oral suspension preparation (50 mg/mL) is available (not available in India), it can be started at 12.5 mg at bedtime and slowly titrated upward (increments by 12.5 mg every week) to the dose when desirable tremor control is achieved without significant side effects. Most patients achieve an optimal tremor control at 250 mg/day, although higher doses up to 750–1000 mg/day may sometimes be required. When a patient requires a lower dose, once daily dosing may be adequate; with higher dosage, the drug should be given in 3 divided dosages. In India, since only 250 mg tablets are available, the treatment is usually started with one-quarter of a tablet (or even smaller if feasible) at bedtime, and gradually increased by one-quarter every week, till the tremor control is achieved (the final dose may be given in 3 divided dosages). When the patient cannot tolerate any increment of dosage, he may continue the previous dosage for a longer time, and then try further increment of dosage. The most common side effect of primidone is sedation and drowsiness, and the other common side effects being nausea, vomiting, dizziness, ataxia, confusion, vertigo, and acute toxic reaction. Patients on primidone should have a complete blood count before starting the treatment and again every 6–12 months, as it has been reported, although rarely, to cause red cell hypoplasia, aplasia, agranulocytosis, and megaloblastic anemia. It is contraindicated during pregnancy, lactation, and in patients having porphyria and hepatic and renal dysfunctions. Combination therapy When monotherapy with propranolol or primidone does not adequately control limb tremor, these 2 drugs can be used in combination. It has been shown that there may be an added beneficial effect without an increase in side effects.[4] Other drugs The following drugs have lower level (level B or C) recommendations for treating ET, and should be tried (add on or monotherapy) in patients not adequately responding to propranolol or primidone, or when there are prominent side effects: Benzodiazepines This group of drugs, which probably augments GABA activity, can be used as add-on treatment for ET. Alprazolam (0.125–3 mg/day), clonazepam (0.5–6 mg/day), lorazepam (1–10 mg/day), and diazepam (1–10 mg/day) can be considered in patients with significant worsening of tremor due to anxiety or emotional stress. Clonazepam may be particularly useful for treatment of orthostatic tremor, a rare variant of ET.[6] The drugs should be used with caution because of their abuse potential, side effects of drowsiness and fatigue, and possible withdrawal symptoms following abrupt discontinuance. Gabapentin Gabapentin (structure similar to GABA) can be used as a monotherapy or as an add-on therapy for treatment of ET.[7–9] It is started at 300 mg 3 times daily, and titrated up to 1200–1800 mg/day. The drug is usually well tolerated with few side effects (sedation, irritability, ataxia, weight gain). Topiramate Topiramate (blocks sodium channels and potentiates GABA activity) has been shown to be effective in reducing ET (monotherapy or add-on therapy).[10–12] It is started at 25–50 mg at bedtime and titrated up to 400 mg/day. Side effects include suppression of appetite, weight loss, and paresthesias. Further studies are required to prove its efficacy in ET. Zonisamide Zonisamide (acts on sodium and calcium channels) has been reported to be useful in ET, especially for tremors of voice, face, tongue, and head.[13] It is initiated at 25 mg at bedtime and gradually increased to 200 mg/day. Side effects include sleepiness, fatigue, headache, and paresthesias. The drug can be used as monotherapy or add-on therapy of ET in those who have unsatisfactory response to other antitremor medications at maximally tolerated dosage. Further studies are required to determine the efficacy of zonisamide in ET. Other drugs There are reports of possible beneficial effects of pregabalin (starting at 50 mg/day and escalated to 600 mg/day), atenolol (50-150 mg/day) , sotalol (75–200 mg/day), nadolol (120–240 mg/day), clozapine (6–75 mg/day), and nimodipine (120 mg/day) in ET. Clozapine is recommended only for refractory cases of limb tremor in ET[1415] and patients should be monitored for agranulocytosis. Further studies are required to prove the efficacy of these drugs. Botulinum Toxin In medically refractory cases of ET, injections of Botulinum Toxin-A in the tremorogenic muscles (preferably under electromyographic guidance for selecting the muscles) may be useful[4]. The injection has been shown to be useful for limb, head, and voice tremor.[16–20] Side effects include temporary weakness of the injected muscles and breathlessness, dysphagia, and hoarseness following treatment for voice tremor. Botulinum toxin injection should be performed only by a trained and experienced neurologist. Surgical Treatment Surgical treatment for ET is reserved for those selected patients who have severe tremor not adequately controlled by medical therapy. Contralateral thalamotomy (VIM nucleus) or deep brain stimulation (DBS) of the thalamus are highly effective in reducing tremor.[21–22] In India, the choice between thalamotomy and DBS is primarily dictated by the availability of expertise and the cost of DBS. Bilateral thalamotomy is not recommended due to its adverse side effects. Therefore, in those who cannot afford DBS, unilateral thalamotomy contralateral to the most severely affected side is recommended. In patients who can afford DBS, bilateral DBS is recommended to suppress tremor of both sides. There is contradictory evidence that bilateral DBS may be useful for suppressing head and voice tremor. Side effects are more frequent with bilateral DBS. In summary, ET is a disorder, which can lead to a significant morbidity in some patients, especially functional disability. The approach to management should be guided by the severity of tremor, the parts of the body involved, occupation of the patient, and physical and social disability.

Isolated head tremor (IHT) is a pathological condition characterized by tremor of the head without dystonic posturing or tremor in other parts of the body. In the past, head tremor was commonly referred to as essential tremor because it is very common in families of patients with essential tremor and may precede hand tremor. Several recent observations cast doubt on this theory. The irregular character of the tremor, the low efficacy of the drugs used for essential tremor and the use of botulinum neuroprotein type A with good response point to the dystonic character of the tremor. Neurophysiological evidence for a relationship between IHT and dystonia includes an altered somatosensory temporal discrimination threshold, metabolic changes according to DAT spectrography (positron emission spectrography to determine changes in dopamine levels) and a change in the blink reflex.

Patients with Huntington disease may be unaware of their chorea and patients with Parkinson disease often do not recognize or endorse their medication-induced dyskinesias. 1, 2 Head tremor occurs in essential tremor (ET),3, 4 yet patients in our experience are often unaware of it. While this phenomenon is anecdotally noted, it has not been formally documented or studied systematically. To broadly sample ET in different settings, we selected cases from three settings: a tertiary-referral center (largest sample),5 a population-based study in Manhattan,6 and a brain repository.7 As expected, cases differed in several respects (Table). Using the same clinical questionnaire, each case was asked whether he/she sometimes has a head tremor. A 20 minute videotaped tremor examination was performed, which included assessments of arm and head tremors (including sitting facing the camera, sustained phonation, reading aloud, finger-nose-finger maneuver, drinking, using a spoon, stand facing camera, and walking). The videotape was reviewed (E.D.L.); arm tremors were rated using a 0 –3 scale.8 Head tremor was rated as absent (0), mild or equivocal (1), intermittent yet clearly present (2), moderate (3), or severe (4). Table Demographic and clinical features of ET cases in each of the three ET case samples In the tertiary-referral center, 119/320 (37.2%) ET cases had head tremor on examination (≥ 1); 46/119 (38.7%) did not report having head tremor. Most false negatives asked the interviewer, “do you see a head tremor now?” When told “yes”, they uniformly commented that they were unaware of this (e.g., “I don’t notice it”). By contrast to head tremor, of 298 ET cases with dominant hand tremor while writing on examination (rating ≥ 1), only 60 (20.1%) did not report having hand tremor while writing (OR 0.40, 95% CI 0.25 – 0.64; i.e., ET cases were 2.5 times less likely to report head tremor than handwriting tremor). Patients may under-report tremor because of embarrassment; however, when we restricted analyses to 129 ET cases who reported that they were not embarrassed by tremor, 21/43 (48.8%) with head tremor did not report their head tremor. When we restricted analyses to 78 ET cases who had moderate or severe head tremor on examination, approximately one-quarter (18/78 [23.1%]) did not report head tremor (as compared to only 12/150 [8.0%] cases with moderate to severe handwriting tremor who did not report their handwriting tremor, OR 3.45, 95% CI 1.56 – 7.61). Based on these findings, we consider that failure to report head tremor was not merely due to having mild head tremor. In the population-based sample, 13/106 (12.3%) cases had head tremor on examination; 7/13 (53.8%) did not report having head tremor. In the brain repository, 92/170 (54.1%) cases had head tremor on examination, but 30/92 (32.6%) did not report having head tremor. In each setting, one-third to one-half of ET cases did not report the presence of head tremor. These same cases were two to three times more likely to report their hand tremor than their head tremor. One possibility is ET cases failed to report head tremor because they were poor historians or were embarrassed. However, they reported hand tremor with reasonably high validity and, among those who were unembarrassed by their tremor, nearly one-half did not report their head tremor. A second consideration is cognitive impairment.1 This is unlikely; in our largest sample (tertiary-referral clinic), cases with cognitive impairment (Telephone Interview for Cognitive Status9 <31) were excluded. Third, even when head tremor impedes a skilled task (e.g., while shaving), patients are often unsure whether this is due to shaky hands or a shaky head. A final possibility is that cases were actually unaware of their head tremor. Indeed, when their tremor was pointed out to them, false negatives uniformly stated that they were unaware of it. A lack of internal feedback about a movement may lessen self-awareness of that movement. 1, 2 Whether, from a proprioceptive vantage point, patients have a subjective experience of head tremor, is not clear. For example, with some types of oscillatory cranial movements (e.g., patients with congenital nystagmus, who rarely experience oscillopsia10) perceptual stability (i.e., lack of awareness of nystagmus) may be achieved through a reduced sensitivity to the motion or the use of other signals to cancel the effects of the movements (i.e., a spatial constancy feedback loop).11 Whether a similar mechanism is operative in ET cases with head tremor deserves future investigation.