Essential Tremors (Movement Disorder).pptx

Detailed description about essential tremors

1. Movement Disorders (Essentials Tremors) Komal Antil Master of Sciences in Nursing (Neurosciences Nursing) All India Institute of Medical Sciences, New Delhi

2. Movement disorders (extrapyramidal disorders) impair the regulation of voluntary motor activity without directly affecting strength, sensation, or cerebellar function. They include hyperkinetic disorders associated with abnormal, involuntary movements and hypokinetic disorders characterized by poverty of movement. Movement disorders result from dysfunction of deep subcortical gray matter structures termed the basal ganglia.

3. Tremors A tremor is a rhythmic oscillatory movement best characterized by its relationship to voluntary motor activity , that is, according to whether it occurs at rest, during maintenance of a particular posture, or during movement. Tremor that occurs when the limb is at rest is generally referred to as static tremor or rest tremor . If present during sustained posture , it is called a postural tremor ; although this tremor may continue during movement, movement does not increase its severity. When present during movement but not at rest, it is generally called an intention or kinetic tremor . Both postural and intention tremors are also called action tremors.

4. Familial or Benign Essential Tremors

5. Introduction Most common cause of action tremor in adults. classically involves the hands and is brought out by arm movement and sustained antigravity postures, affecting common daily activities such as writing, drinking from a glass, and handling eating utensils. slowly progressive and can also involve the head, voice, and, uncommonly, the legs. It often has a familial basis with an autosomal dominant mode of inheritance . At least three gene loci have been implicated; in some cases (ETM1), the disorder is related to a polymorphism in the D3 dopamine receptor gene (DRD3).

6. Criteria for diagnosis of essential tremor Core criteria Secondary criteria Exclusion criteria • Bilateral action tremor of the hands and forearms (but not resting tremor • Absence of other neurologic signs , with the exception of cogwheel phenomenon • With or without tremor in other locations (head, voice, lower limbs) • Long duration (>3 years) • Positive family history • Beneficial response to alcohol • Isolated focal tremors (voice, head) • Orthostatic tremor with frequency >12 Hz • Task- and position-specific tremors • Sudden onset and stepwise deterioration References: 1. Bain P, Brin M, Deusch| G, et al. Criteria for the diagnosis of essential tremor. Neurology 2000; 54(11 Suppl 4):S7. 2. Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremors from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord 2018; 33:75.

7. Goals & Expectations Treatment of ET is symptomatic , and no disease-modifying therapies are available. The degree of tremor control provided by medications varies among patients and often depends on the dose of the agents used, tremor severity, and a patient's individual response to the chosen agent. Patients with mild tremor may experience complete tremor suppression with available therapies . However, the goal of therapy for most patients is to reduce tremor severity enough to prevent disability while minimizing medication side effects. It is important to explain to patients that tremor will worsen over time, and that increased doses and second-line therapies will likely be required. Tremor progression is not indicative of an alternate diagnosis such as Parkinson disease as long as no additional signs or symptoms emerge

8. Differentiating Parkinson disease and essential tremor Clinical features Parkinson disease tremor Essential tremor Age at onset >50 years Bimodal 2nd & 6th decade Sex Male > Female Male= Female Family history ~10-15% ~ 50 percent Asymmetry +++ + Frequency 4-6 Hz 6-12 Hz Character At rest Postural, Kinesthetic Supination- Pronation Flexion-extension Distribution Hands, legs, chin, tongue Hands, head, voice Associated features Bradykinesia, rigidity, postural instability, micrographia Mild gait disorder or cerebellar signs in a minority Modified with permission from: Jankovic J. Essential tremor: Clinical characteristics. Neurology 2000; 54(11 Suppl 4):S21. Copyright © 2000 Lippincott Williams & Wilkins.

9. Treatment approach Exacerbating and mitigating factors — When possible, medications or other substances (eg, caffeine ) that could be exacerbating tremor should be discontinued ; at times, doing this will suffice to control tremor , even if temporarily. Alcohol is well-known to reduce tremor in many patients with ET and often has an effect in modest amounts (eg, a half to one glass of wine ). Some patients find this effect useful in social situations .

10. Medications, toxins, and other substances associated with enhanced physiologic tremor Class Examples Antiarrythmic drugs Amiodarone Antidepressant drugs SNRIs, SSRIs, tricyclics Antiseizure medications Bromides, carbamazepine, lacosamide, lamotrigine, phenytoin, valproic acid Beta agonists Albuterol, terbutaline Glucocorticoids Dexamethasone, prednisone Mood stabilizers Lithium Other medications Cyclosporine, tacrolimus, theophylline Other substances Caffeine, cocaine, nicotine Sympathomimetics Amphetamine salts, epinephrine, methylphenidate Thyroid hormone Levothyroxine Toxins Arsenic, cyanide, DDT, lead, lindane, manganese, mercury, naphthalene, toluene SNRIs: serotonin-norepinephrine reuptake inhibitors; SSRIs: selective serotonin reuptake inhibitors; DDT: dichlorodiphenyltrichloroethane.

11. Management of essential tremors Management of essential tremor (ET) is symptomatic . Goal of pharmacotherapy : To reduce tremor severity enough to mitigate disability while minimising side effects. Before starting medication, assess tremor severity distribution (limb, head, voice) impact on activities of daily living degree of functional and social disability. Inquire about common fears and concerns (eg, Parkinson disease). Review and eliminate exacerbating factors, when possible. Dosing in this algorithm is for oral administration in adults with normal kidney function.

12. Criteria for pharmacotherapy Drug treatment should be offered to patients with ET who have intermittent or persistent disability caused by tremor. Mild ET and little or no tremor-related disability — usually do not require treatment. Patients with frequent/daily symptoms — Propranolol , a nonselective beta adrenergic blocker, and primidone , an anti seizure medication, are each considered first-line therapies for ET, and they have equivalent efficacy. The choice between these agents is based on side effect profiles, concomitant medications, and comorbidities. For ET that does not respond adequately to monotherapy with either propranolol or primidone , the two drugs can be used together. Switching from one to the other is also a reasonable strategy if either agent is poorly tolerated. Several additional drugs or classes of drugs have more limited evidence of benefit for ET but can be tried as second-line agents, either alone or in combination with a first-line therapy. These include topiramate , benzodiazepines, and gabapentin .

13. Administration and efficacy Propranolol — Propranolol is the best-studied beta blocker for ET. Beta blockers are thought to impact tremor severity through action on adrenoreceptors in a deep compartment within muscle spindles. In mice, propranolol has been shown to modulate the spiking activity of Purkinje cells and cerebellar nuclei neurons.

14. Propranolol Dose and formulation – The usual starting dose of propranolol for ET is 60 or 80 mg daily (divided two to four times per day for immediate-release). If a starting dose lower than 60 mg is desired due to comorbidities or advanced age, the immediate-release formulation can be used initially. The dose may be increased as needed at ≥1-week intervals up to a usual maximum of 360 mg daily . The mean end-titration dose of propranolol for ET in nine trials was approximately 185 mg per day. Single doses of immediate-release propranolol taken in anticipation of social situations that are likely to exacerbate tremor are useful in some patients. A single starting dose of 10 or 20 mg is suggested, which may be reasonably effective within an hour of taking the dose.

15. Side effects – Side effects attributable to propranolol , including lightheadedness, fatigue, impotence, and bradycardia, occurred in 12 to 66 percent of patients in clinical trials. As an example, one open-label study reported that such side effects led to discontinuation in 4 of 23 patients (17 percent) taking propranolol. Propranolol is relatively contraindicated in the presence of heart block, unstable heart failure, asthma, and type 1 diabetes mellitus. Propranolol

16. Primidone — Primidone is an anti seizure medication that is metabolized to phenobarbital and phenylethylmalonamide . The mechanism of action for ET is unknown, and neither metabolite appears to influence tremor when used alone. Primidone is used less commonly than propranolol but has similar efficacy and is a reasonable alternative first-line agent for ET. Primidone is a potent inducer of hepatic microsomal metabolizing enzymes. Thus, drug-drug interactions should be checked before primidone is added to existing medications. Primidone

17. Dose – Start primidone at 25 mg (one-half of the available 50 mg tablet) once daily before sleep. The dose should be titrated up carefully over several weeks as tolerated and according to therapeutic response. One suggested regimen is to titrate in 25 mg increments every three to seven days to a maximum of 250 mg at night, according to response and side effects. Sedation is usually the limiting factor with rapid titration or higher doses. Titration can be even slower for older adults. The medication should be withdrawn if there is no benefit using 250 mg each night . If there is a partial response at 250 mg nightly, the titration can continue up to 750 mg nightly as tolerated. The mean end-titration dose of primidone for ET in three trials was approximately 480 mg/day. Primidone

18. Side effects – Side effects from primidone are typically more severe at treatment initiation and may include sedation, drowsiness, fatigue, depression, nausea, vomiting, ataxia, malaise, dizziness, unsteadiness, confusion, vertigo, and an uncommon acute toxic reaction. Primidone may be better tolerated in patients with epilepsy in whom hepatic enzymes have been induced by the previous administration of phenobarbital or other antiseizure medications. Primidone

19. Second-line therapies Propranolol plus primidone — Propranolol plus primidone is preferred second-line strategy for patients with inadequate benefit on first-line therapy, when possible, based on side effects and comorbidities. The combined use of these drugs is possibly more effective than either drug alone.

20. 2. Topiramate Topiramate — Topiramate , when used at doses >200 mg/day, is effective for reducing limb tremor associated with ET and improving functional disability, but its use is associated with a relatively high rate of adverse effects. Avoid use in adults >70 years of age due to risk of cognitive side effects. Dose and side effects – The initial dose of topiramate is 25 mg once or twice a day, followed by weekly increases of 25 to 50 mg per day as tolerated up to a goal dose of at least 200 mg per day and a maximum total dose of 400 mg per day. The most common treatment-limiting adverse events in trials of topiramate for ET included paresthesias, reduced appetite, weight loss, somnolence, concentration/attention difficulty, and memory difficulty.

21. 3. Benzodiazepines Benzodiazepines — Benzodiazepines are widely used because of the usually mistaken belief that tremor is due to anxiety . Be that as it may, in patients in whom tremor is aggravated by anxiety, an anxiolytic may partially reduce tremor. Caution is urged with the use of benzodiazepines for ET because of the potential for abuse and dependence , as well as the potential for drug discontinuation to cause withdrawal symptoms (including seizures) and tremor rebound . These problems make benzodiazepines a second-line choice for the chronic treatment of ET . The two benzodiazepines that have been studied for ET are alprazolam and clonazepam .

22. Cont.. Alprazolam may be useful for the treatment of limb tremor associated with ET in select patients, although high-quality data are lacking. Two small clinical trials found that alprazolam, 0.125 to 3 mg/day , was associated with an improvement in clinical rating scales of 25 to 34 percent compared with placebo. Side effects included mild sedation and fatigue . A tremor reduction of 69 and 76 percent (according to electromyography [EMG] data recorded at 40 and 80 minutes, respectively, after a dose of alprazolam) was documented in a study involving eight patients. Clonazepam is occasionally used for the treatment of limb tremor associated with ET, although data are mixed. One clinical trial found that clonazepam 0.5 to 6 mg/day significantly reduced tremor, while another study found that clonazepam 0.4 to 4 mg/day was ineffective and resulted in a 40 percent study completion rate due to drowsiness.

23. 4. Gabapentin Gabapentin — Gabapentin as monotherapy has anti tremors effects in some patients with ET, but supporting data are very limited. Dose and side effects – If using gabapentin for ET, start with initial dose of 100 to 300 mg three times daily , using the low end of the range for older adult patients. The dose can be titrated upwards as tolerated, typically by increasing the total daily dose by 300 mg every four to seven days . An effective range is not well established for ET, but 1200 mg daily was used in the only monotherapy trial. Gabapentin may have fewer side effects than primidone but can cause sleepiness, dizziness, and gait unsteadiness, particularly in older adults.

24. Refractory Tremor Adaptive devices — Several different devices are being developed to noninvasively modulate and/or compensate for tremor severity. All patients with ET may find benefit from adaptive devices, but patients with disabling tremor who either are not candidates for other treatment modalities or have suboptimal tremor control with them may be the best candidates for these technologies.

25. Adaptive devices Neuromodulation – In a randomized, sham-controlled pilot study involving 23 blinded subjects, noninvasive median and radial nerve stimulation resulted in an improvement in the Archimedes spiral drawing task. Subsequent studies, including a larger sham-controlled trial in 77 patients and other open-label, lower quality studies, suggest that noninvasive neuromodulation therapy used repeatedly at home in 40-minute sessions is safe and improves patient-rated function and accelerometer-based tremor measurements during use of the device and for up to an hour afterwards.

26. Biomechanical loading – Biomechanical loading refers to either the external application of force on a tremulous limb or the facilitation of antagonist muscle contraction within the limb to reduce tremor . At least two small research projects have explored different wearable robots to effectively suppress tremor. One of the studies examined a robotic exoskeleton that applied forces to tremulous limbs, and the other was a neuroprosthesis capable of providing transcutaneous neurostimulation. Adaptive devices

27. Tremor cancellation devices – Commercially available tremor-canceling devices aim to facilitate activities such as eating in patients with hand tremor. In a double-blind study involving 15 study subjects, a noninvasive handheld device using Active Cancellation of Tremor (ACT) technology was shown to reduce tremor amplitude and severity for eating and transferring tasks. The device used consists of a spoon or other utensil attachment, a motion-generating platform, a controller/sensor, and a power source. Adaptive devices

28. Local vibrational therapy – A small, uncontrolled study of a local hand-arm vibration device producing vibrations in the 8 to 18 Hz frequency range was found effective in some of the study subjects. Adaptive devices

29. Botulinum toxin Botulinum toxin — Botulinum toxin (BoNT) injections have shown variable benefits in trials for hand, voice, and head tremor and are associated with dose-dependent risk of weakness in the injected muscles. However, they are endorsed by an International Parkinson and Movement Disorder Society (MDS) evidence-based review as possibly useful in clinical practice with specialized monitoring. BoNT therapy -patients who cannot tolerate or are uninterested in trying oral medications for tremor.

30. Cont… Patient selection — The best candidates for upper limb injections are patients whose tremor amplitude is mild enough to respond to low doses of BoNT type A (BoNT-A) or patients with severe and disabling upper limb tremor who would prefer hand weakness over tremor. Although reversible once the effects of BoNT wear off, hand weakness can be disabling while present, particularly when the dominant hand is affected. Only experienced limb injectors should administer this procedure. For head and vocal tremor, there are also trade-offs between benefits and side effects. BoNT-A for voice tremor is associated with side effects that include breathiness, hoarseness, and swallowing difficulty, and common side effects with head tremor injections include dysphagia and neck weakness, stiffness, and/or pain. BoNT for vocal tremor is best administered by an otolaryngology specialist with expertise in treating ET.

31. References Familial, or Benign, Essential Tremor Benito-León J, Louis ED. Essential tremor: emerging views of a common disorder. Nat Clin Pract Neurol. 2006;2:666-678. Deng H, Le W, Jankovic J. Genetics of essential tremor. Brain. 2007;130:1456-1464. Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of patients with essential tremor. Lancet Neurol. 2011;10:148-161. Elble RJ. Characteristics of physiologic tremor in young and elderly adults. Clin Neurophysiol. 2003;114:624-635. Flora ED, Perera CL, Cameron AL, Maddern GJ. Deep brain stimulation for essential tremor: a systematic review. MovDisord. 2010;25:1550-1559. Lorenz D, Deuschl G. Update on pathogenesis and treatment of essential tremor. Curr Opin Neurol. 2007;20:447-452. Louis ED. Essential tremor: evolving clinicopathological concepts in an era of intensive post-mortem enquiry. Lancet Neurol. 2010; 9:613-622. Pahwa R, Lyons KE. Essential tremor: differential diagnosis and current therapy. Am J Med. 2003;115:134-142. Sadeghi R, Ondo WG. Pharmacological management of essential tremor. Drugs. 2010;70:2215-2228. Sethi KD. Tremor. Curr Opin Neurol. 2003;16:481-485. Zesiewicz TA, Elble RJ, Louis ED, et al. Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology. Neurology. 2011;77:1752-1755. Zesiewicz TA, Chari A, Jahan I, Miller AM, Sullivan KL. Overview of essential tremor. Neuropsychiatr Dis Treat. 2010;6:401-418.

32. THANKS Do you have any questions ? For Query: [email protected]