disequilibrium) are common when treatment is started. Th erefore a starting dose of 62.5 mg or less in the evening is recommended. Fatigue is a common and sometimes dose-limiting sid e eff ect of primidone. Propranolol is usually favored over primidone in young patients without any evidence of hea rt disease or bronchial asthma. Side eff ects such as bradycardia, syncope, fatigue, and er ectile dysfunc- tion may be dose-limiting. Treatment should start with 20 \200\22360 mg/ da y, and the dose should be increased gradually. Total daily doses of 60 \200\223240 mg are a dequate in most responders (73). If one of the fi rst-line drugs does not suffi ciently imp rove tremor it should be increased to the maximally tolerated dosage. Th e two drugs can be combined if required. Second-line drugs (Table 16.2) include topiramate and gabapentin (73). Alprazolam showed co mparable eff ects to fi rst-line medication in less rigorous trials, but as it is a benzodi azepine it is not recom- mended for long-term treatment because of its addictive potential. Studies with selective beta-blockers (e.g. atenolol, sotalol) have shown less benefi cial eff ects than the non-selective beta-blocker pro- pranolol (73). Injection of botulinum tox in in hand muscles has been successfully used for hand tremor, but symptomatic hand weaknes s in 30 \200\22370% of patients limits its use (77). In patients with advanced ET, intentio n tremor can cause serious disability. Th ompson and co-workers (78) showed that clonazepam can specifi cally improve action tremor compared with propranolol. Other tremors Enhanced physiological tremor Th e term enhanced physiological tremor (EPT) r efers to a tremor with the frequency and activation characteristics of normal physi- ologic al tremor but with a larger amplitude when all other causes of tremor are excluded. It is a visible postural and action tremor which can be troublesome, particularly on action. Th er e are many causes for the enhancement of tremor (Table 16.3), among which drugs are the mos t common (Table 16.4). Th e exclusion of other neurological symptoms or diseases that could cause tremor is mandatory for the diagnosis (41). For tremors of unknown origin, the labor atory tests summarized in Table 16.5 may be considered. Moreover, in the case Head and voice tremor are usually less suppressed than hand tremor with drug therapy (73). Improvements of 30 \200\22350% in head tremor with propranolol and primidone have been repo rted in sev- eral studies (79, 80). For severe head tremors, particularly when an intention tremor is present, patients may require bilateral DBS which can reduce head tremor by up t o 75% (81 \200\22386). Treatment of voice tremor with propranolol and methazolamide did not show a positive eff ec t (87). Results for laryngeal botulinum toxin injections for voice tremor are confl icting. Typical side eff ects are a weak voice, coughing, and dysphagia (88, 89). Oxford Textbook of Movement Disorders 168 Table 16.4 Drugs with tremor as a possible side e \200 ect Group Beta-adrenergic drugs Example Fenoterol, salbutamol Phosphodiesterase inhibitors Th eophylline, ca \200 eine i . V.op m V v.o.d Anti-arrhythmic drugs Amiodarone, mexiletine, procainamide i i . c . V Calcium-channel inhibitors Nifedipine, amlodipine Ce.pc Immunotherapy Ciclosporin, tacrolimus, interferon Antidepressants Tricyclic antidepressants, SSRIs Cp.i.p Lithium Zi H2 Neuroleptics, antidopaminergics Haloperidol, metoclopramide Ra.prl Antiepileptics Valproate, lamotrigine Zi L.m Anti-infective agents Co-trimoxazole, amphotericin B, vidarabine Sth Str.pd.i G L Hormone therapy Th yroxine, calcitonin, progesterone, corticosteroids Tm Ni II Table 16.5 Recommended laboratory tests for postural and action tremors of unknown origin L aboratory value Th yroid (T 3 , T 4 , TSH) Electrolytes (Na + , K + , Ca 2+ , Cl \200\223 ) Question Hyperthyroidism Fig. 16.3 Targets for the standard treatment of tremor (73). Th e standard target is the nu cleus ventrointermedius of the thalamus (Vim, gray dot) and the region below the Vim, the r adiation pre-lemniscalis (Ra.prl, black dot). Less established targets are the caudal zona incerta (Zi, dark green dot) and the subthalamic nucleus (Sth, light green dot). Sth is the standard target for Parkinson \200\231s disease. Sth, corpus subthalamicum; Ra.prl, radiat io pre-lemniscalis; H 2 , ampus forelii, pars H 2 ; V.o.d, nucleus ventro-oralis dorsalis; V.op, nucleus ventro-oralis posterior; Vim.i, nucleus ventrointermedius internus; V.c.i, nu cleus ventrocaudalis internus; Ce.pc, nucleus centralis parvocellularis; Cp.i.p, capsula in terna crus posterior; Str.pd.i, striae pedunculi interni; Tm, nucleus tuberomammillaris; L, lemniscus; L.m, lemniscus medialis; Ni, nucleus niger; Zi, zona incerta; G, fasciculus gra cilis; II, opticus. Hypocalcaemia, hypokalaemia, metabolic alteration Liver enzymes (GGT, GOT, GPT, CE) Alcoholic disease, Wilson disease (hepatocerebral degeneration) Glucose Hypoglycaemia Immuno-electrophoresis Neuropathy in paraproteinaemia, neuropathic tremor If clinically suspected Serum ceruloplasmin, copper in 24 hour urine Wilson disease Table 16.3 Causes of enhanced physiological tremor Drugs Toxicological diagnostics Arsenic, bismuth, mercury, lead poisoning, alcohol-related, medication withdrawal Neuroleptics, metoclopramide, antidepressants (tricyclics), lithium, cocaine, alcohol, symp athomimetics, steroids, valproate, anti-arrhythmics (amiodarone), thyroid hormones, cytosta tics, immunodepressants anxiety is common and may be problematic for performing artists or people who need a high a ccuracy of dexterity, such as surgeons. It is thought to be mediated via increased sympathe tic tone which results in a beta-adrenergically driven sensitization of the muscle spindles , increasing the gain in the refl ex loops (94). A similar ori- gin via the sympathetic ner vous system has been proposed for the tremor in refl ex sympathetic dystrophy. Metabolic ab normalities, drugs and toxins, or withdrawal from such substances are common causes of EPT. Th e pathophysiology may be peripheral or central, depending on the cause. Toxins Mercury, lead, manganese, alcohol, DDT, lindan Metabolic disturbances Hyperthyroidism, hyperparathyroidism, hypoglycaemia, hepatic encephalopathy, magnesium de \201 ciency, hypocalcaemia, hyponatraemia Others Anxiety, fatigue, sympathetic re \202 ex dystrophy, withdrawal of alcohol or drugs of an undiagnosed, new onset tremor syndrome without discern- ible cause, a brain MRI scan is recommended if the symptoms are unilateral, since focal lesions can produce tremor. As both EPT and early ET are unaccompanied by other obvi- ous neurological symptoms, they a re diffi cult to distinguish. Th e positive family history in ET, its chronic course, and t he lack of an overt cause for the tremor are important clues. Sometimes the diagnosis can o nly be made aft er having observed the patient for an extended time period. EPT is usually bilateral and thus any tremor presenting unilaterally, even with a high frequency and a pur e pos- tural component, must be suspected to be a symptomatic tremor. Spectral analysis of accelerometry and EMG signal data can be helpful in demonstrating a centrally driven compon ent in ET (95). A frequency below 8 Hz, which can be seen in the very early stage of ET, fa vors ET rather than EPT (96). A recent study found the prevalence of EPT to be 9.5% in sub- jects over 50 years of age. E PT was much more common than ET (3.06%), parkinsonian tremor (2.05%) or Parkinson \200\231s disease (4.49%) (4). Th ere are no studies available on the natural history of the conditi on. Th e pathophysiological mechanism may be either activation of the refl ex loops (e.g. h yperthyroidism) or activation of a central oscillator which is related to physiological tre mor (93) caused, for example, by drugs. Th e causes of an enhancement of one or both of the physiological tremor components are div erse. Trembling with excitement, fear, or CHAPTER 16 Essential tremor and other tremors 169 Treatment Depending on the etiology of EPT, addressing the potential under- lying cause is always the fi rst step. Th ere are only a few studies that have reported on symptomatic tre atment of EPT. Treatment of thy- rotoxic tremor is recommended with propranolol (<160 mg da ily) but other beta-blockers, namely atenolol (<200 mg daily), metopro- lol (<200 mg daily) , acebutolol (<400 mg daily), oxprenolol (<160 mg daily), nadolol (<80 mg daily, and molol (<20 mg daily), have similar eff ects (97). Other treatment recommendations are based solel y on expert opinion. A single dose of a beta-blocking agent (e.g. propranolol 10 \200\22360 mg) 30 minutes before a stressful situa- tion is recommended to suppress transient tremor that is known to interfere with important (e.g. professional) activities in a predis- posed subject. Table 16.6 Treatment of parkinsonian tremor 1. Dopaminergic therapy Levodopa, dopamine agonists at dosages used for the treatment of akinesia and rigidity 2. Anticholinergics Bornaprine 3 \227 2 mg to 3 \227 4 mg Biperidine 3 \227 2 mg to 3 \227 4 mg Trihexyphen idyl 3 \227 2 mg to 3 \227 4 mg Metixene 3 \227 5 mg to 3 \227 10 mg Benztropine 3 \227 2 mg Procyclidine 3 \227 5 to 3 \227 10 mg 3. Propranolol/primidone Propranolol 3 \227 20 to 3 \227 60 mg Primidone 62.5 \200\223750 mg 4. Amantadine 3 \227 100 to 3 \227 150 mg 5. Clozapine <12.5 mg to 3 \227 25 mg 6. Bilat eral DBS of the STN or GPi (for selected cases Vim) Parkinsonian tremor Th e most common and classic parkinsonian tremor is a rest tremor or a combination of a rest and a postural/kinetic tremor with the same frequency (type I PD trem or) (41). Th e tremor frequency is mostly above 4 Hz. Higher frequencies (of up to 9 Hz) ca n occur in early PD. Th e asymmetric rest tremor is suppressed during move- ment and recurs in some posture conditions. Clinically this type I tremor aff ects the upper and lower lim bs and the face. Occasionally the tremor can start in the lower extremities. (107) are an option if dopaminergic therapy is not suffi ciently eff ect ive. Dosing of all drugs is summarized in Table 16.6. Stereotactic surgery can be considered in patients with a dis- abling tremor. All three tar gets of deep brain stimulation for PD (subthalamic nucleus (STN), globus pallidus internus (GPi), and ventrointermedius nucleus of the thalamus (Vim)) are effi cacious (109 \200\2231 12). STN and GPi stimulation also improve akinesia and rigidity, but Vim stimulation only i mproves tremor. Th erefore Vim stimulation is reserved for selected cases only, mainly elde rly patients with a stable course of tremor-dominant PD. In some patients the posture/kinetic tremor has a higher fre- quency (>1.5 Hz) that is non- harmonically related to the rest tremor (type II PD tremor) (41), if this is present. It is unknown whether the postural tremor is part of a co-existing essential tremor or a specifi c feature of PD tremor. An isolated postural and kinetic tremor with a frequency of 4 \200 \2239 Hz may be seen (type III PD tremor), particularly in PD subjects with predominant aki nesia and rigidity (41). Th is has been related to rigidity (98) and can be dem- onstrated particularly during fi nger movements (99). Th e majority of patients with PD have the clas sic parkinsonian rest tremor (type I PD tremor). For pragmatic therapy, the fi rst decision is to determine clin- ically if the PD tremor sy ndrome has a higher-frequency postural component (type II PD tremor). In this case, non-dop aminergic treatment with propranolol or primidone is recommended. Two standard situations o f complicated PD tremor will be considered: the de nov o patient and the advanced patient w ith drug-resistant tremor. Treatment Studies with PD tremor as the main outcome measure are rare, but the tremor items of the Unifi ed Parkinson \200\231s Disease Rating Scale pro- vide an estimate of the anti -tremor eff ect of these interventions. In the de nov o patient tremor may need more time to improve during the dosing-in period th an akinesia and rigidity. Th erefore the amount of dopaminergic treatment should be geared to address akinesia and rigidity. When akinesia and rigidity are ade- quately treated with a dopamine agonist or levodopa, it is advis- able to wait for another 2 months before speci fi cally targeting the tremor because this symptom can improve further with time. If a sign ifi cant tremor is still present, anticholinergic treatment is an option for the younger pa tient or an increase in dopaminergic treatment for the elderly. Amantadine is mostly ineff ective, but can be tried. Clozapine in low dose (6.75 \200\2237.5 mg) may be con- sidered, with adequate monitoring for potential side eff ects (par- ticularly agranulocytosis). If t his is not eff ective, very high doses of levodopa can be tried, but otherwise DBS is the n ext option to be considered. Levodopa is an effi cient drug against parkinsonian tremor. Th is has recently been confi r med in the ELLDOPA trial (100). All dopamine agonists have a signifi cant anti-tremor eff e ct, and a specifi c study addressed this issue for pramipexole, but there is no compelling evidence that any dopamine agonist has a better anti-tremor eff ect than the others (101 \200\223103). Anticholinergic drugs can improve rest tremor, but cognitive adverse eff ects limit their u se, especially in older patients. A small pathological series (104) which has yet to be con fi rmed suggested that patients with previous anticholinergic therapy showed more tau patho logy. Th e clinical side eff ects of anticholinergic treatment are considered to be reversi ble. Clozapine is eff ective against PD tremor (105), but is mainly used for otherwise drug -resistant trem- ors, especially when those patients have concomitant hallucina- tions. Ama ntadine is a poorly studied second-line drug for tremor with limited effi cacy. Budipine is well studied and eff ective (106), but may cause cardiac arrhythmias and is available only in some European countries. In cases with a signifi cant postural/kinetic tremor (type II PD tremor) propranolol (107, 108) and primidone In the advanced patient treatment-refractory tremor may occur in the OFF period and may req uire further smoothing of dopaminergic treatment with levodopa, dopamine agonists and/or CO MT inhibitors. If tremor continues to be a problem, despite oth- erwise treated OFF periods , the fi rst step is usually to increase the total dose of dopaminergic treatment. Th is is oft en limited by dys- kinesias; tremor may abate, but at the expense of severe dykinesias . Oxford Textbook of Movement Disorders 170 In this situation anticholinergic treatment is almost never used but clozapine may be consi dered. STN or GPi DBS may be a very worthwhile option in selected cases. form of task-specifi c tremor. It has a frequency of 5 \200\2237 Hz and can be subdivided i nto type A (task-induced tremor) and type B (positionally sensitive tremor) (119). Th e pat hophysiology is unknown. Highly skilled and over-learned tasks, in combina- tion with an in dividual \200\231s disposition, may lead to a task-specifi c tremor (119). Th ere is contro versy as to whether PWT is a vari- ant of essential tremor, a focal dystonia, or a separate nosological entity (41, 119, 127). Dystonic tremor Dystonic tremor is an entity which is under debate and diff erent defi niti ons have been proposed (113, 114). Its pathophysiology is largely unknown (115). Typical dy stonic tremor occurs in a body region aff ected by dystonia. It is defi ned (115) as a post ural/kinetic tremor not usually seen during complete rest. At onset, and some- times during the course of the disease, dystonic tremor is focal and limited to one or a few extremitie s, with irregular amplitude and variable frequencies (mostly below 7 Hz). However, some pat ients exhibit focal tremors even without overt signs of dystonia. Th ey have been included as dystonic tremor (116) because some later develop evidence of dystonia. Special forms of dystonic tremor are task-specifi c in nature, such as dystonic voice tremor (117) or dys- t onic writing tremor (118, 119). Jaw tremor and dystonia has been proposed as a specifi c en tity (120). Other task-specifi c tremors include highly trained tasks, typically in musicians and athletes. Alcohol reduces the tremor in some patients. Treatment Controlled studies are not available. Th e treatment is escalated according to th e specifi c needs of the patient. Pharmacotherapy with propranolol or primidone has been re commended. Other therapeutic options include sensory and motor training (128 \200\223130) a s well as personalized tools like special writing pencils (131). In 50% of patients injecti ons of botulinum toxin can reduce the tremor signifi cantly (132, 133). Vim DBS for task-sp ecifi c tremor is experimental (134). Th e prevalence of dystonic tremor is unknown. In one cross- sectional study 20% of patient s with primary or secondary dystonia (121) suff ered from tremor. Tremor is more common in cervical dystonia (122). Cerebellar tremor syndromes Cerebellar tremor is a symptomatic tremor with an intention com - ponent as the most prominent sign. For diagnosis of a cerebellar tremor, the following co nditions have to be satisfi ed (41): Antagonistic gestures can lead to a reduction of the tremor amplitude in patients with dyst onic tremor. Th is is frequently seen in dystonic head tremor or tremulous spasmodic tortic ollis (123). As this sign is absent in essential head tremor it can be an impor- tant diff erential diagnostic clue for head tremors in which the dys- tonic posture is not immediatel y obvious. Other important, but less specifi c, diff erential diagnostic clues are the foca l nature and relatively low frequency of dystonic tremor. Th e tremor associated with dysto nia is more diffi cult to separate from ET, especially when the accompanying dystonia has n ot evolved completely. Dopamine transporter imaging may be necessary to separate parkinsoni an tremor from dystonic tremor (124). pure or dominant intention tremor (unilateral or bilateral); \227\206 tremor frequency mainly below 5 Hz; \227\206 postural tremor may be present, but no rest tremor. \227\206 Titubation is another tremulous manifestation of cerebellar dis- ease, and is a low-frequen cy oscillation (around 3 Hz) of the head and trunk depending on postural innervation (135). Depending on the etiology a full spectrum of cerebellar symptoms and signs may be present. Cerebellar tremor syn- dromes are most frequently caused by multiple sclerosis (136). Other causes include chronic alcohol toxicity, trauma, or degen- erative cerebellar disorder (e. g. spinocerebellar ataxias). Tremor in fragile X-associated tremor \200\223ataxia syndrome (FXTAS) is mostly a postural and intention tremor, and gait ataxia is usually present in th ese patients (137). Treatment No controlled study of oral medication is available. A positive eff ect of propra nolol or anticholinergics has been reported in case series of dystonic head tremor. Th e ef fi cacy of botulinum toxin for dystonic head tremor and tremulous spasmodic dysphonia is we ll documented (51). A double-blind study has also documented the effi cacy of botulinum tox in for hand tremor (77), but the use of this agent for this indication is limited because o f associated paresis. Dystonic tremor in the setting of segmental or generalized dystonia h as been successfully treated with DBS of the pallidum in a control- led study (125). Stimul ation of the ventrolateral thalamus can also alleviate the tremor, but may occasionally lea d to worsening of the dystonia. Tremor associated with dystonia may respond to medica- tion used for classic ET. Treatment Pharmacotherapy of cerebellar tremor is oft en disappointing. Studies with cholin omimetic compounds (e.g. physostigmine, lecithin) have shown improvement in some patients, but failed to demonstrate ben- efi t in the majority. Isoniazid failed to show signifi cant results (138). 5-Hydroxytryptophan (5-HTP) has been found to be eff ective in some patient s (139, 140). Open-label studies or single-case observa- tions have shown favorable results with amantadine, propranolol, clonazepam, carbamazepine, tetrahydrocannabiol, and trihexyp he- nidyl. Levetiracetam (50 mg/kg/day) was benefi cial in a pilot trial (141). Cannabis is not eff ective (142). Probably the greatest sympto- matic improvement is obtained with eit her DBS of the thalamus or thalamotomy (143 \200\223145) but the functional benefi t can wo rsen over time, particularly in patients with multiple sclerosis (146). Task-speci \201 c tremor Task-specifi c tremor (TST) is a form of action tremor that occur s when a person performs a specifi c task, for example writing, speak- ing, or playing an i nstrument (41, 126). TST oft en occurs with dysto- nia and may share common pathophysiologi cal mechanisms. Orthostatic tremor Orthostatic tremor (OT) is a rare tremor characterized by an unsteady st ance because of a high-frequency tremor of the legs TST is labeled as uncomplicated if tremor occurs only dur- ing the task, and complicated if it has a tendency to generalize to other tasks. Primary writing tremor (PWT) is the most c ommon CHAPTER 16 Essential tremor and other tremors 171 (147, 148). OT usually begins aft er the fourth decade, and women (50 years) seem to be aff ected earlier than men (60 years). In most cases the origin is unknown or idiopathic, alth ough some patients have been reported with a positive family history. So far no candi- date genes have been identifi ed. Some authors have reported OT in advanced Parkinson \200\231s disease (149, 150). brainstem-innervated muscles (leading to oscillopsia in case of eye muscle involvement) or extremity muscles can also be aff ected (172). SPT typically follows a brainstem or cerebel lar lesion aft er a variable delay (173, 174) and is oft en associated with a cerebellar sy ndrome (175). Essential palatal tremor (EPaT) occurs without any overt central nervous pathology and is c haracterized by rhythmic movements of the soft palate (tensor veli palatini), usually with an associated ear click. Th e tensor contraction is visible as a movement of the roof of th e palate. Extremity or eye muscles are not involved. Clinical features of patients with OT include unsteadiness on standing, which rarely may ca use falls. A mild gait ataxia in older patients has been described. Sitting and walking are unaff ected. Patients try to avoid standing still. No obvious tremor is seen on visual ins pection, but tremor can be palpated or auscultated in leg muscles. OT must be separated fro m the stance tremors of ET, PD, or cerebellar tremors. Th e pathophysiology of SPT is considered to be abnormal discharges of the inferior olive. Th e pathophysiology of EPaT is unknown. OT is diagnosed by electromyography of the quadriceps mus- cle, with surface electrodes sho wing the pathognomonic 13 \200\22318 Hz burst discharges while standing, which mostly cease when sitting (151, 152). An extremely rare variant of slow orthostatic tremor has been des cribed (153, 154). Treatment Th e disability of patients with SPT is mostly due to other clinical symptoms rel ated to the underlying cerebellar lesion. Th e rhyth- mic palatal movement in SPT does not cause discomfort or dis- ability for the patient, except when the eyes are involved or when there is an extremity tremor. Oscillopsia is a diffi cult complaint to treat. Single cases have been described with a favorable response to clonazepam. Other oral drugs which have b een proposed are trihexyphenidyl and valproate. Botulinum toxin has been used to treat osci llopsia. Th e toxin can either be injected into the retrobul- bar fat tissue or individual eye muscles can be targeted selectively (176, 177). No controlled studies are available. We have found that this treatment is helpful for some patients, but is not always accept- abl e for long-term use because of its limited eff ect. In the treatment of extremity tremors, single cases have been reported to respond to clonazepam (178) or trihexiphenidyl (179). Treatment Th erapy of OT is oft en challenging. First-line therapy includes gabapentin (120 0 \200\2232400 mg/day) and clonazepam (1.5 \200\2236 mg/day) (155, 156). Alternatively, pri midone (62.5 \200\223500 mg/day) may be used. Although a mild dopaminergic defi cit has bee n found in some patients, levodopa does not seem to be an eff ective therapy (157). Bilater al Vim DBS has been described in single-case reports with OT (158, 159), and spinal stimula tion has also been successful in some patients (160). Both treatments need further evaluati on. Holmes tremor and thalamic tremor Holmes tremor is a combination of rest, postural, and int ention tremors with a low frequency (<4 Hz) (41, 161, 162). It is a symp- tomatic tremor, t ypically developing aft er a lesion in the brainstem. Diff erent names have been used in th e past (rubral tremor, midbrain tremor, Benedikt \200\231s syndrome). Such a lesion may be due to stroke, neoplasm, cystic degeneration, operative lesion, or cavernoma. Th e pathophy siology is explained by a \200\230double-hit \200\231 disruption of both nigrostriatal dop aminergic and cerebellothalamic systems (163, 164), causing the combination of a parkinsoni an rest tremor and a cerebellar intention tremor. Some patients with Holmes tremor may have additional dystonia. Th e only complaint by patients with EPaT is the ear click. A number of medications have be en reported to be successful \200\224val- proate (180), trihexyphenidyl (179), and fl unari zine (181). Recently, sumatriptan has been found to be eff ective in a few patients (182, 1 83) but was unsuccessful in others (184). Th e most established current therapy is injectio n of botulinum toxin into the tensor veli palatini muscle (185). Tremor syndromes in peripheral neuropathy Several peripheral neuropathies may present with tremor. Th e tremors are mostly postural and action in nature. Th e frequency in hand muscl es can be lower than in proximal arm muscles. Dysgammaglobulinaemia and chronic infl ammato ry demyelinat- ing neuropathy are the acquired neuropathies presenting most fre- quently wi th tremor (186). A similar type of tremor can be observed in around 40% of patients with he reditary motor and sensory neu- ropathy (HMSN) (187). Th alamic tremor is an entity which can present with the same symptoms of rest and intentio n tremor as a Holmes tremor. However, additional symptoms, such as dystonia, jerky movement s, or a sensory disturbance, are also found. Th e cause is a lesion of the lateral thalamus , which is most oft en ischaemic. Treatment No controlled trials are available. Levodopa and dopamine agonists are helpful in some patients (164). Anticholinergics, propranolol, clonazepam, primidone, and levetiracet am have also been described as being effi cacious (165 \200\223168). Some patients may bene fi t from Vim DBS (169). Treatment No specifi c therapies have been reported to be benefi cial for this type of trem or. Successful treatment of the underlying neuropathy can improve the tremor in some patien ts (186). We have found propranolol and primidone at similar dosages as used in essential t remor to be helpful for some patients. Some patients have been successfully implanted with DBS electrodes (188). Palatal tremor syndromes Palatal tremors are rare tremor syndromes and can be separated int o two forms (170, 171). Psychogenic tremors Psychogenic tremors have diverse clinical presentations and are a speci fi c variant of psychogenic movement disorders (see Chapter 31). Symptomatic palatal tremor (SPT) is characterized by rhyth- mic movements of the soft palat e (levator veli palatini), clinically visible as a rhythmic movement of the edge of the pal ate. Other Oxford Textbook of Movement Disorders 172 Most of them are action tremors, but they oft en show very unusual combinations of rest/pos tural and intention tremors (189). Sudden onset and sometimes spontaneous remission are oft en reported. On clinical examination the \200\230entrainment maneuver \200\231 (i.e. chan ges of amplitude and frequency of the trembling limb) is observed when an external rhythm i s imitated by the patient with the other arm. Some patients have a positive \200\230co-act ivation sign \200\231 which is evaluated like rigidity testing at the wrist. Variable volun tary-like force exer- tion can be felt in both movement directions (41). Some patients have a history of somatization or additional unrelated (psychogenic) neurological symptoms and signs (41). 14. Vilarino-Guell C, Ross OA, Wider C, et al. LINGO1 rs9652490 is asso- ciated with essent ial tremor and Parkinson disease. Parkinsonism Relat Disord 2010; 16 : 109 \200\2231 1 . 15. Clark LN, Park N, Kisselev S, Rios E, Lee JH, Louis ED. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet 2010; 18 : 838 \200\2234 3 . 16. Wilms H, Sievers J, Deuschl G. Animal models of tremor. Mov Disord 1999; 14 : 557 \200\2237 1 . 17. Louis ED, Zheng W, Jurewicz EC, et al. Elevation of blood beta-carbolin e alkaloids in essential tremor. Neurology 2002; 59 : 1940 \200\2234 . 18. Fekete R, Jankovic J. Revisiting the relationship between essential tremor and Parkinson \200\231s disease. Mov Disord 2011; 26 : 391 \200\2238 . 19. Adler CH, Shill HA, Beach TG. Essential tremor and Parkinson \200\231s disease: Among psychogenic movement disorders, tremor is the most common diagnosis (50%) (190). Elec trophysiological tests can help in the diff erential diagnosis (see Chapter 5 for more deta ils) (191 \200\223193). lack of a link. Mov Disord 2011; 26 : 372 \200\2237 . 20. Rajput AH, Rozdilsky B, Ang L, Rajput A. Clinicopathologic observations in essential tr emor: report of six cases. Neurology 1991; 41 : 1422 \200\2234 . 21. Rajput A, Robinson CA , Rajput AH. Essential tremor course and dis- ability: a clinicopathologic study of 20 case s. Neurology 2004; 62 : 932 \200\2236 . 22. Louis ED. Essential tremor: evolving clinicopa thological concepts in an era of intensive post-morte m enquiry. Lancet Neurol 2010; 9 : 61 3 \200\2232 2 . 23. Erickson-Davis CR, Faust PL, Vonsattel JP, Gupta S, Honig LS, Louis ED. \200\230Hairy baskets \200\231 associated with degenerative Purkinje cell changes in esse ntial tremor. J Neuropathol Exp Neurol 2010; 69 : 262 \200\2237 1 . Treatment Studies of treatment of psychogenic tremor are rare (194). Antidepressants may be helpful (195). Psychotherapy is helpful in only a minority of patients. We recommend physi otherapy, aiming to avoid co-contraction of the muscles during voluntary movement. In addit ion, propranolol may be administered at medium or high dosages to desensitize the muscle sp indles which are necessary to maintain the clonus mechanism in these patients. Conclusive d ata on the prognosis and long-term outcome in these patients are lack- ing, but the prognos is is generally believed to be poor (196). 24. Louis ED, Yi H, Erickson-Davis C, Vonsattel JP, Faust PL. Structural study of Purkinje cell axonal torpedoes in essential tremor. Neurosci Lett 2009; 450 : 287 \200\2239 1 . 25. Louis ED, Faust PL, Vonsattel JP, et al. Torpedoes in Parkinson \200\231s disease, Alzh eimer \200\231s disease, essential tremor, and control brains. Mov Disord 2009; 24 : 1600 \200\2235 . 26. Louis ED. Essential tremors: a family of neurodegenerative disorders? References 1. Louis ED, Ferreira JJ. How common is the most common adult move- ment disorde r? Update on the worldwide prevalence of essential tremor. Mov Disord 2010; 25 : 534 \200 \2234 1 . Arch Neurol 2009; 66 : 1202 \200\2238 . 27. Louis ED, Vonsattel JP. Th e emerging neuropathology of essential tremor. Mov Disord 2008; 23 : 174 \200\2238 2 . 28. Axelrad JE, Louis ED, Honig LS, et al. 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