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Home , Essential tremor, Paralysis, Synkinesis, Tremor

Journial of , , and , 1972, 35, 365-372 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.35.3.365 on 1 June 1972. Downloaded from

Clinical manifestations of essential

EDMUND CRITCHLEY From the Royal Infirmary, Preston

SUMMARY A clinical study of 42 patients with is presented. In the case of 12 patients the family history strongly suggested an autosomal dominant mode of transmission, in four the mode of inheritance was indeterminate, and the remaining 26 patients were sporadic cases without an established genetic basis. The tremor involved the upper extremities in 41 patients, the head in 25, lower limbs in 15, and trunk in two. Seven patients showed involvement of speech. Variations were found in the speed and regularity of the tremor. Leg involvement took a variety of forms: (1) direct involvement by tremor; (2) a painful limp associated with forearm tremor; (3) associated dyskinetic movements; (4) ; (5) foot clubbing; and (6) evidence of peroneal muscular atrophy. Several minor symptoms hyperhidrosis, , dyskinetic movements, and ataxia-were associated with essential tremor. Other features were linked phenotypically to the and system degenerations. Apart from minor alterations in tone, expression, and arm swing, features of were notably absent. Protected by copyright. Essential tremor has been recognized as an or- much variation. It is occasionally present at rest ganic peculiarity of the , mimick- and inhibited by action, but is more usually de- ing neurotic and neural disorders with equal creased or absent at rest and present on volun- facility. Many synonyms-for example, benign, tary increase in muscle tonus, as in holding a limb hereditary, and senile tremor-describe its varied in a definite position (static, sustained-postural presentation. Dana (1887) regarded 'hereditary' or attitude tremor) and in active movement tremor as a hitherto undescribed form of motor (kinetic or ). It may be accentu- neurosis, and observed that it resembles to some ated on approaching a goal in point-to-point extent the tremor of agitans, still more movement (terminal tremor) (Davis and Kunkle, a simple neurasthenic tremor, and was not ac- 1951). In its mildest form the tremor diathesis companied by paralysis or any other disturbance may be no more than a kind of exaggeration of of nervous function. Others commented on its physiological tremor (Kreiss, 1912) properly resemblance to hysteria (Antony and Rouvillois, managed by explanation and reassurance (Davis

1899) and to (Bergamesco, and Kunkle, 1951), or it may be so severe as to http://jnnp.bmj.com/ 1907; Dromard, 1908), but many disorders- require stereotactic (Bertrand, notably, neuroses, inebriety, drug- Hardy, Molina-Negro, and Martinez, 1969). induced , diabetic tremors, , and With the discovery of biogenic transmitter path- thyrotoxicosis may be simulated by essential ways for pathological tremors the need for a tremor. fuller review of the clinical manifestations of Parkinson (1817) and Charcot (1876) dis- essential tremor has become more interesting and tinguished between the tremors of paralysis agi- more urgent. on September 30, 2021 by guest. tans and the senile variant of essential tremor. Both types of tremor characteristically affect the PRESENT STUDY upper limbs. The Parkinsonian tremor involves alternating activation of opposing groups of The present study is based upon a personal series of the axis of the is at 42 patients in North Lancashire. Originally a group muscles along limb, present of 16 patients was selected with sufficient disability rest and disappears with activity. That ofessential to justify a crossover trial of hydro- tremor, regardless of age of onset, is seen pre- chloride in the treatment of tremor (Cox, Critchley, dominantly in the distal parts of the upper limb Schnieden, and Williams, 1971). This study was (Poirier, 1970), is more or less rhythmical, either carried out in parallel with a clinical assessment of fine or coarse, with a rate of 4 to 12 Hz. There is tremor in a group of Parkinsonism patients receiving 365 366 Edmund Critchley J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.35.3.365 on 1 June 1972. Downloaded from

Levodopa. Both groups were repeatedly examined TABLE 2 and monitored by a battery of standardized per- CLINICAL SIGNS formance tests and by serial tremor recordings using a Grass Parkinsonism transducer. The remaining 26 Family history Group I Group I1 Group III Total patients include three originally excluded from the Signs (parent +) (others) (lone) nos. therapeutic trial because their symptoms were so No associated 2 1 13 16 mild that therapy was considered unnecessary. Associated 2 0 4 6 from the Minimal Where possible, other affected members Parkinsonism 5 1 8 14 families of these unrelated propositi were examined Associated and and the findings used to substantiate the manifesta- Parkinsonism 3 2 1 6 tions of the propositus; but owing to the diversity of background and origin of the patients-two were Totals 12 4 26 42 Pakistani, two Jewish, two Irish, and one of Polish extraction-no attempt was made to examine all family members. There were 30 males and 12 females with an age- with maintenance of the typical Parkinsonism range from 16 to 72 years (average 49 years). These posture, with the arms extended and with finger- propositi were divided into three genetic groups: nose movement. Particular attention was also given to the presence of associated neuropathic GROUP I. FAMILIES WITH SECONDARY CASES AND ONE traits. The findings were then classified to assess PARENT AFFECTED 12 cases; four of these involved three generations. The parents of one proband were the presence of minimal signs of Parkinsonism first cousins and her father, two children, sister, and and of associated traits (Table 2). sister's daughter were affected.

CHARACTERISTICS OF TREMOR Marshall (1962)Protected by copyright. GROUP II. FAMILIES WITH NO AFFECTED PARENT BUT established two different patterns of upper limb SIBLINGS, PARENT'S SIBLINGS OR GRANDPARENTS tremor for essential tremor. The majority of AFFECTED Four cases: (1) half-sister with Parkin- patients had tremors which described a smooth, sonism; (2) uncle with Parkinsonism; (3) sibling wave form, indistinguishable from that with essential tremor; and (4) grandmother with regular Parkinsonism. seen in Parkinsonism. The frequency of tremor followed the age pattern for physiological tremor GROUP III. SOLITARY CASES 26 cases; including one when the duration was held constant. The other adopted child. With two patients there was evidence patients showed small irregularities in the pat- of other genetically determined traits-namely, tern and Bertrand et al. (1969a) demonstrated premature whitening of hair and clubbed feet. with photokinetic and electromyographic tech- Combining these three groups, the mean age of niques that these incoordinated movements onset of symptoms was 35 years (Table 1). lacked many of the characteristics of tremor. The present series contains many examples of CLINICAL FINDINGS and the tremor forms both the smooth irregular http://jnnp.bmj.com/ but within each of these groups there are broad The clinical examination resembled that used for distal in- the examination of Parkinsonism patients. Tone variations. Those with predominantly movement of the volvement, with striking digital tremor, were was examined by passive usually the more irregular, often with a terminal and by passive movement about the wrists and When a elbows simultaneously, with and without re- increment or a sustained-postural flap. from movement of the gross and seemingly isolated irregular movement inforcement synkinetic was made it took the form of a speedily executed observed at rest, on September 30, 2021 by guest. opposite arm. The tremor was rapid but faulty adjustment. In one individual it was possible to observe continuous sideways jerking of the right forearm and a rhythmic TABLE 1 movement of the left forearm. Involvement of AGE OF ONSET OF SYMPTOMS the whole limb was most common in those with a smoother more regular tremor of the Parkin- Onset ofsymptoms (by decade) sonism type. The speed of tremor was indepen- 0-9 10-19 20-29 20-39 40-49 50-59 60 + (no.) (no.) (no.) (no.) (no.) (no.) (no.) dent of the wave form and both smooth and were in some instances fast 7 7 7 8 5 6 irregular tremors 2 (between 8 to 10 Hz) and in others slow (though Clinical manifestations of essential tremor 367 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.35.3.365 on 1 June 1972. Downloaded from not usually below 5 Hz). Fast tremors were more others did not. The men usually found spirits common than slow tremors in the ratio 3:2. most helpful but it was not uncommon for a lady Much variation was observed in the response to say that two pints of beer or a glass of stout to cold, nervousness, , fatigue, and emotion. helped best of all. A fine task might result in an exaggeration of the Handwriting was often affected by the tremor tremor or, contrariwise, there might be an and influenced by emotional factors. One amplification of disability when lifting or carry- patient showed micrographia, but typically the ing heavy objects. The tremor often varied writing was large, untidy, and indecipherable. according to the time of day thus, I.B. found Some patients were able to write neatly provided her tremor most incapacitating in the morning, they pressed harder so as to limit the size of the not immediately on rising but when she came to script and prevent sudden, jerky movements of wash and dress, and E.F. had no trouble during the pen. Commonly they would avoid writing in the day but stopped evening visits to his office to public, putting things aside for signature until prepare ahead as fatigue made him dithery and feeling particularly well. An art teacher, D.S., he could no longer decipher his notes the next had to give up her employment because she was morning. For some patients the inability to no longer able to draw a straight line or teach socialize was particularly distressing, involving pen-lettering, and a pensioner, W.G., could not such functions as speaking in public, shaking sign his book to draw his allowance. hands, eating, drinking, or even holding a glass in a communal place. A 39 year old school PARTS OF BODY INVOLVED IN TREMOR Tremor of teacher, A.H., complained that when meeting the upper extremities was seen in all patients but men at interviews they would 'take her wrongly' one (a mild case with titubation), was bilateral in assuming that they were having a startling 32, confined to the right side in seven and to the Protected by copyright. emotional effect upon her as they shook her left in two. Not infrequently other parts of the hand. In such situations the relief afforded by body were involved in tremor and responded to is readily recognized, so much so that it the same influences as did upper limb tremor. has been loosely regarded as an invariable or Titubation was seen in 25 patients, taking the even pathognomonic feature of essential tremor. form in most of a sideways movement, some- In the present series 19 patients found the effect times fine and rapid and sometimes slower and of small quantities of alcohol beneficial but six coarse; and on passive neck movement a little http://jnnp.bmj.com/ .A. 1. -,"k. P .?, .*:"-.g .- --, ...O.

FIGURE. P.N., aged 70, written with affected right

*/ , ...... 2.t ...... :...... A..S hand, and (below) taught to on September 30, 2021 by guest. write with left hand.

46--j4s t X y.t .8 g ; x v -t..= ...... 4t^.4X 8.r ...... ;.cA ;- } ; . 368 Edmund Critchley J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.35.3.365 on 1 June 1972. Downloaded from cogwheel tremor was often felt. Four patients exacerbation of the tremor was accompanied by showed titubation with evidence of torsion heavy nocturnal sweating. His mother and sister also as described by Larsson and Sjogren had tremors. spasm may begin with tremor He had a masklike expression, no glabellar tap (1960). Torsion abnormality and an alternating strabismus. There and, in pedigrees with this disease, siblings and was a moderately rapid, coarse, alternating tremor other relatives may have tremor as their only in both arms and at rest all four limbs were on the symptom. The evolution of torsion spasm was move. His head was not involved. Only with syn- observed in one patient, F.K., a housewife aged kinesis was there any suggestion of a change in tone. 45 years. She had been under observation with a mild head tremor, which worsened with emotion 2. A variable, painful limp with mild symptoms and made her self-conscious on occasions, for 81 of tremor elsewhere. years. Then her head started to draw to the left H.P., a male aged 45 years, had complained of an with exacerbations of tremor. This tendency odd gait accompanied by pain behind the right ankle lasted a few months and finally the tremor ceased for more than 20 years. When walking his foot turns but she continued to carry her head at an angle. in and he had to reinforce his footwear with steel 191 van bars. The limp is lessened if he relaxes or has been Several series (cf. Nettleship, 1; Bogaert resting, or takes a little alcohol, and is definitely and Savitsch, 1937) have included families with worse in front of strangers. He discovered from an tremor-. These patients probably be- aunt that his father had had a similar limp, but no long to a subgroup of essential tremor. In the other member of the family is affected. present series nystagmus was not seen though On examination, there were a few rapid move- many patients displayed a slight hesitancy in ments of the right eye on looking to the right and reaching fixation and one, J.L., aged 26, who also with posturing he showed a mild, rapid tremor of the had facial twitching, complained of slowness in right arm. The tone was increased in the right armProtected by copyright. focusing. A faciolabial tremor was present in with , but the reflexes were physiological only one patient but speech difficulties, related to and symmetrical and cerebellar tests were well per- in seven One formed. His walk was at first ungainly with a tendency tremor, were present patients. to stub his right foot but as he gained confidence in spoke with a thin whistle, another stammered, the examination the limp lessened and he showed no and five had slurring of speech; one patient difficulty walking on his toes, heels, or heel-to-toe. claimed that amantadine loosened him up, helped his speech, and helped swallowing. In- 3. Irregular dyskinetic movements associated volvement of the trunk may also occur and was with tremor. present in two patients, one of whom, A.B., a J.W., aged 35 years, developed a tremor in her male aged 58, had a 10 year history of tremor right hand in 1966. There has been a recent exacerba- with shaking of both hands, titubation, and on tion and the tremor is worse when she is carrying examination showed vertical movements of the anything or is watched. She cannot drink from a full musculature of the abdominal wall. cup and her writing has become large and untidy. Alcohol quietens the tremor. Her husband com- A in the present series was the http://jnnp.bmj.com/ striking finding plains that she twitches during and she says occurrence of symptoms in the lower extremities that her right foot keeps shaking when she dances. in 15 out of the 42 patients. Involvement of the She shows a mild titubation and compound lower limbs, though mentioned as a feature of tremors of the right hand and leg with an intention exceptional cases by Flatau (1908), Velander element. She is ataxic on heel-shin coordination, but (1931), Critchley (1949), and Larsson and there were no other cerebellar signs. Cerebrospinal Sjogren (1960), has rarely been regarded as a con- fluid, serum copper oxidase and serum protein tremor, and in no series of bound iodine are all normal. When given placebo in comitant of essential on September 30, 2021 by guest. unrelated individuals have so many cases been the double-blind trial, she felt that the tablets were reported. This involvement may take a number too strong and continued for the third and fourth of week on half dosage. Amantadine did not help but forms. she is greatly relieved by mephenesin. 1. Spread of tremor from other parts of the J.L., aged 26, is a former professional runner. His body as described by Flatau (1908). mother had Parkinsonism late in life but no other J.D., a 67 year old factory inspector, could not member of the family exhibits any tendency to date the onset of his tremor but had had basal meta- tremor. Four years ago his right leg began to throw bolic rate (BMR) estimations in 1924 and in 1944, out when walking and started to drag so that he and by 1959 his tremor was so bad as to affect would wear out the toe-cap. He now has difficulty at shaving, writing, and eating in public. A recent times in putting his left foot to the ground and his Cliniical mamifestations of essential tremor 369 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.35.3.365 on 1 June 1972. Downloaded from balance has deteriorated. The tremor is more severe tended to stagger, raising the left foot higher than down the left side and affects his head, legs and usual. There was no relevant family history. hands. It is inconstant, for at home he manages well, He has a slight stammer, accompanied by dresses himself, and writes neatly, but in company he tremor. There is a tremor of the outstretched hands cannot. He could not take a tray of drinks into an and a rapid titubation without nystagmus. The limb assembled gathering unless he, himself, had had a tremor is most marked in his right arm and tone is few drinks beforehand. slightly increased by comparison with the left. His He has a fine titubation and a variable, rapid blood pressure is 180/100 mmHg. He has wasting tremor of his left arm and leg. His right arm is un- below the knees, vasomotor changes, and clubbed affected until he tries to light a match or build with feet. The ankle jerks are absent and the knee jerks blocks. His grip is strong. Tone is slightly increased obtained with difficulty. in his neck and arms but the reflexes are not exag- gerated and both plantar reflexes are flexor. His gait ADDITIONAL FEATURES The association of hyper- is clumsy with a widened base. hidrosis and essential tremor, as seen in patient J.D., was originally described by Kreiss (1912). 4. Tremnor of the upper limbs with an ataxic Another patient, D.S., complained of profuse gait. sweating and knotty cramps. Her family history J.W. and J.L. showed some ataxia. With the next was particularly involved. patient this feature was so severe that it is probably D.S., an art mistress aged 43 years, developed a advisable to regard him as having a double diagnosis tremor of the right hand when aged 14 and three of essential tremor and multiple sclerosis. years ago the tremor spread to involve the left hand. J.S., a clerk aged 56 years, had transient double It worsens when she is harassed and she has difficulty vision when aged 21 years and a provisional diag- holding a cup and saucer in company. Her inability nosis was made of multiple sclerosis. In action in to draw and teach calligraphy has already been Protected by copyright. 1944 he became paraplegic, was diagnosed as having commented upon. Sometimes the tremor will lesson shellshock but this was later amended to multiple if she takes alcohol. She once received thyroid ex- sclerosis. He recovered completely. Five years ago tract and obtained a temporary diminution of the (1965) he had further trouble with his left leg and tremor thereby. hands and experienced difficulty in writing. His Her parents were first cousins and her father had mother and maternal grandmother had essential cramps and tremor. All three children, now aged 20, tremor and he found that his own tremor was im- 18, and 16 years, have tremors: the eldest started at proved by taking spirits, though it often worsened 14, the second had 'chorea' at 10 and has since had a two days later. tremor, and the third developed a tremor soon after He had a fixed expression and turned slowly. her 16th birthday. A sister has cramps but no There was a bilateral attitudinal tremor of the upper tremor, but her 23 year old daughter (the proband's extremities without a terminal increment and with- niece) has had a tremor from the age of 16 years. All out alterations in the tone or reflexes. He was helped affected individuals complain of profuse sweating. by amantadine but after three months the effect D.S. appears depressed, emotionally flat, and tends wore off. The placebo had no effect but mephenesin to obesity. The tremor is most marked when the has proved beneficial. arms are outstretched and it bears a resemblance to http://jnnp.bmj.com/ . There is no alteration in tone. Serum mag- 5. Other abnormalities which suggest a con- nesium, copper oxidase, cholesterol, PBI, pCO2, and tinuity with other de- liver function tests are normal. generations. The electrocardiograms (ECGs) taken on Two patients from the present series had those patients included in the therapeutic trial clubbed feet-an association with essential were analysed by Dr. Perez and Dr. Logan of the tremor previously described by Kreiss (1912). department of Cardiology, Victoria Hospital, on September 30, 2021 by guest. Another patient had evidence of peroneal Blackpool, for evidence suggestive of associated muscular atrophy in addition to essential tremor. cardiomyopathies. No consistent abnormality was present from one a F.B., a male aged 53 years, attended the neuro- and, apart ECG in logical clinic for many years with bilateral clubbing patient known to have ischaemic heart disease, of his feet due to peroneal muscular atrophy. In 1968 they were within normal limits. he presented with transient ischaemic attacks due to vascular insufficiency and cervical spondylosis and METABOLIC STUDIES There was no common six months ago started to stammer and shake his head pattern of metabolic disturbance. Glycosuria and arms when excited. He complained that the was seen in three patients. One had muscles of the right leg vibrated at times and that he mellitus, another a lag storage glucose tolerance 370 Edmund Critchley J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.35.3.365 on 1 June 1972. 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curve, and the third a low renal threshold. Three THE PLACE OF TREATMENT Caution must be patients were hypertensive and five others had properly exercised in attempting to treat a con- labile systolic readings. One patient, treated dition which may be lifelong and in which the with amantadine, developed proptosis and lid- ultimate prognosis qua incapacity is considerably lag. Her protein bound iodine (PBI) was elevated better than it is in Parkinsonism; but not in- at 13-3 ,g/ml. At a lower dose of amantadine her frequently the patient finds that the tremor is clinical state improved and the PBI subsequently seriously interfering with his life (Kelly, 1965). In fell to 6-7 ,ug/ml. Many patients had had estima- childhood, school failure may result from an in- tions made of their PBI and in some cases high ability to write properly due to the tremor (Ford, normal values (8-10 ,ug/ml.) were observed but 1966). Adults may develop neuroses-for ex- they remained euthyroid. ample, being unable to have their hair cut in These patients, who represented a minority of public (Blacker, Bertrand, Martinez, Hardy, and the total series, formed so heterogeneous a Molina-Negro, 1968; also F.W. from the present group that it is reasonable to suppose that the series)-or have to leave their occupation be- metabolic disturbance was incidental, or if in any cause of incapacity arising as a direct result of way causal, dependent upon the activation of a their tremor-A.S. could not continue in his post strong latent tendency. Nevertheless, in two as airport comptroller as his tremor worsened patients the coexistence of an essential tremor whenever an aircraft landed awkwardly; a lorry- and a metabolic disturbance presented diagnostic driver, F.R., experienced difficulty pulling the difficulties: steering wheel round sharp corners and in fixing 1. W.G., aged 72 years, had a long history of the ropes and tarpaulin over his load; and a tool- trembling beginning before 1939 and affecting both maker, R.F., retired prematurely at 56 years of arms, particularly the right. In the past two years he age because he was unable to use a screwdriver.Protected by copyright. has been unable to take tea in a cafe or to sign his Two patients were invalided out of the armed name on official forms and has developed a mild forces, and several others, working as salesmen . He volunteered that the only time he gets or business executives, sought treatment because relief is if he has two pints of beer, after which he the tremor was damaging their prospects of pro- feels champion. motion. His blood pressure was 170/100 mmHg and had The most been at this level for many years. In 1967 he was successful drug for intermittent use found to have glycosuria in a diabetic detection drive in the control of tremor is mephenesin. Kelly and in 1970 showed a lag storage glucose tolerance claims that, provided the patient can tolerate curve. His PBI was 5-3 ,ug/ml. Benzhexol did not help mephenesin in a sufficiently large dose, the and amantadine worsened the tremor. He had a tremor can be suppressed in 70 to 80% of cases digital tremor of an action and sustained-postural for about 20 to 30 minutes at a time. The two type without reflex or tone change. patients for whom this form of treatment seemed 2. G.H., aged 64 years, had been a diabetic re- appropriate both responded well. For more pro- ceiving insulin for 20 years, had had two gastrectomy longed control the results are less satisfactory. http://jnnp.bmj.com/ operations and was treated with streptomycin in 1959 Fifteen out of 26 patients found amantadine for pulmonary tuberculosis. Eight months ago his as with out of 14 hands started shaking. There was a family history of beneficial compared five who diabetes and also a family history, separate from responded to placebo and six out of 12 who were this, of tremor affecting his mother and maternal helped by chlordiazepoxide. grandmother. drugs were of help in only four out of 10 patients He shakes his hand, head, and mouth and oc- and alcohol was helpful in 19 out of 25. Neither

casionally his right arm. He has difficulty writing and Levodopa (used in two patients) nor tetrabena- on September 30, 2021 by guest. shaving and sometimes has to put things aside for zine (four patients) was found to be of value. signing until he is feeling particularly well. If he takes alcohol he finds the tremor is better. RELATIONSHIP OF ESSENTIAL TREMOR TO PARKIN- He showed bilateral , an inexpressive face, a SONISM The frequency with which the two con- little cogwheel tremor in his neck and, with re- is illustrated Hoehn inforcement, an alteration in tone in his arms. The ditions are confused by and tremor was rapid with brisk reflexes and without Yahr's (1967) study of the natural history of true rigidity or bradykinesia. The blood pressure was Parkinsonism. From the total group of 856 170/100 mmHg. His writing was improved on patients they found it necessary to exclude 54 amantadine 200 mg daily and he was able to carry patients-15 because of incorrect information or out his offices as a priest with less embarrassment. inaccurate diagnosis and 39 because they were Clinical manifestations of essential tremor 371 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.35.3.365 on 1 June 1972. Downloaded from found to have essential or familial tremor with 1969). A further longitudinal separation may be 'none of the classical signs of Parkinsonism'. arrived at from the natural history of the two Thus approximately 4-500 of patients referred as conditions. Essential tremor arises as an exag- having Parkinsonism had essential tremor. In the geration of physiological tremor (Kreiss, 1912) present series four patients came with a diagnosis with episodic increases in amplitude occurring of Parkinsonism, compared with 103 patients against a background of tremor of the same seen personally over the same period correctly frequency but of lower amplitude (Marshall, diagnosed as having Parkinsonism. The per- 1962). As the malady worsens, there is much centage figure corresponds with that of Hoehn variation in the regularity of the wave form and and Yahr; but, out of a total of 42 patients seen in the severity and spread of the tremor; thus with essential tremor, less than 10% were in- patients may present different types of tremor, correctly labelled as Parkinsonism. Most patients either concomitantly or in succession, as the were referred for diagnosis and treatment, two disease progresses (Poirier, 1970). It is this syn- were considered to have multiple sclerosis, three dromic variation which makes the experimental anxiety states, and one thyrotoxicosis. These simulation of essential tremor so fallible. observations contrast with the study of 14 cases Peripheral mechanisms concerned in the pro- of benign essential tremor (Davis and Kunkle, duction of physiological tremor have been ex- 1951), the majority of whom had previously re- tensively studied and it is held that many forms ceived the diagnosis of paralysis agitans. of metabolic tremor result from activation of peripheral ,B- receptors (Marsden, DISCUSSION Foley, Owen, and McAllister, 1967). Activation The evidence for an autosomal dominant form of these receptors may account for the tremors of essential tremor (Davis and Kunkle, 1951; of thyrotoxicosis, anxiety states, and hyper- Protected by copyright. Larsson and Sjogren, 1960) is conclusive and tension; but blockade is not many of the patients in the present study con- of consistent therapeutic value in the treatment form to this mode of inheritance. Sporadic cases of essential tremor. The same receptors are in- are well recognized and by no means rare volved in hypoglycaemic tremor but their role in (Marshall, 1962). Their interpretation is open to diabetic tremor-seen in a small percentage of dispute. In 1949 Macdonald Critchley felt it diabetic subjects-is poorly understood. An probable that more than one type of inheritance alternative explanation, frequently advanced, is was concerned but it could be that sporadic that this tremor arises as a result of the prema- cases arise where the predisposition to essential ture atherosclerosis of the diabetic subject, des- tremor is inherited as a dominant gene and the pite the evidence ofCharcot (1876), Barker (1939), degree of penetrance is variable; thus Jager and and Critchley (1956) that tremor is a rare mani- King (1955) found many instances of hereditary festation of the ageing process, Furthermore, it tremor which would have been overlooked on is reasonable to assert that, apart from the con- the basis of history taking. The hypothesis of a dition of 'arteriosclerotic' Parkinsonism, in http://jnnp.bmj.com/ genetic predisposition or 'inferiority of the ner- which atherosclerotic changes are seen in the vous system' (Kreiss, 1912) would explain how, central nervous system concurrently with cellular in some cases, a subclinical metabolic or vascular changes and enzymic depletion, it is paren- derangement could result in an irreversible chymatous, not arteriosclerotic, degeneration tremor diathesis by exploitation of an intrinsic which results in tremor. defect, for example, through an impairment of a To many authors (cf. Davis and Kunkle, 1951;

dampening mechanism concerned in the control Jager and King, 1955) essential tremor is a on September 30, 2021 by guest. of physiological tremor as suggested by Marshall monosymptomatic condition; but the more (1962). widely based series (Critchley, 1949; Larsson and Advances in the histochemistry (Birkmayer Sjogren, 1960; and Bertrand et al., 1969b) agree and Hornykiewicz, 1961) and therapy of Parkin- in that 'the presence of associated neurological sonism have made the separation of essential signs (e.g. ) in addition to tremor from Parkinsonism less dependent upon tremor does not necessarily negate the diagnosis an arbitrary clinical differentiation as pro- of essential tremor' (Blacker et al., 1968). The pounded by Hoehn and Yahr (1967), even evidence presented by Larsson and Sjogren re- though the histological basis of essential tremor lates to a closed community-namely, a Swedish is still unknown (Herskovits and Blackwood, parish in which, with two exceptions, all 210 372 Edmund Critclhley J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.35.3.365 on 1 June 1972. Downloaded from cases could be traced back to four ancestral Birkmayer, W., and Hornykiewicz, 0. (1961). Der L-3, 4-Dioxyphenylalanin (= DOPA)-Effekt bei der Parkinson- couples. Additional neurological symptoms Akinese. Wiener Klinische Wochenschrift, 73, 787-788. were found in 17 out of 81 cases. They also ob- Blacker, H. M., Bertrand, C., Martinez, N., Hardy, J., and of spasmus mobilis type which Molina-Negro, P. (1968). Hypotonia accompanying the served rigidity neurosurgical relief of essential tremor. Journal of Nervous was inconstant and of relatively slight degree. In and Mental Diseases, 147, 49-55. 16 cases the gait was stiff but there were no Bogaert, L. van, and Savitsch, E. de (1937). Sur une maladie congenitale et her6dofamiliale comportant un tremble- symptoms of akinesia or any tendency to pul- ment rythmique de la tete, des globes oculaires, et des sion. It is possible that in Larsson and Sjogren's membres superieurs. Encephale, 32, 113-139. somewhat inbred population the additional Charcot, J. M., cf. Bourneville, D. M. (1876). Du tremble- ment senile. Progres Medicine, 4, 815-816. neuropathic features represented the chance Cox, B., Critchley, E. M. R., Schnieden, H., and Williams, association of genes, but additional neurological C. (1971). Some pharmacological actions of amantadine signs associated with essential tremor are also hydrochloride and its effects on experimental and clinical tremor. Paper read at the International Symposium on seen in random cases and Critchley (1949) found Tremor. Sarajevo, Yugoslavia. it necessary to refer to essential tremor and its Critchley, M., and Greenfield, J. G. (1948). Olivo-ponto- cerebellar atrophy. Brain, 71, 343-364. clinical variants. In the present series particular Critchley, M. (1949). Observations on essential (heredo- attention was paid to minimal signs of Parkin- familial) tremor. Brain, 72, 113-139. sonism and to additional neurological factors. Critchley, M. (1956). Neurologic changes in the aged. Journal of Chronic Diseases, 3, 459-477. These signs were frequently observed. No Dana, C. L. (1887). Hereditary tremor, a hitherto undescribed patients, however, showed a positive glabellar form of motor neurosis. American Journal of Medical tap phenomenon and no manifestations were Sciences, 94, 386-393. Davis, C. H. Jr., and Kunkle, E. C. (1951). Benign essential more striking than those referred to by Larsson (heredofamilial) tremor. Archives of Internal Medicine, 97, and Sjogren. Neither the signs of Parkinsonism 808-816.

were more Dromard, G. (1908). Tremblement hereditaire rappelant celuiProtected by copyright. nor the other neurological signs de la sclerose en plaques. Encephale, 3, 2me semestre, 45-53. prevalent in the inherited or sporadic groups. Flatau, G. (1908). Ueber hereditairen essentiellen Tremor. The relationship ofthe associated neurological Archiv fiir Psychiatrie und Nervenkrankheiten, vereinigt and mit Zeitschrift fiir die gesamte Neurologie und Psychiatrie, signs seen in patients with essential tremor 44, 306-340. the ataxias has been subject to much discussion, Ford, F. R. (1966). Diseases ofthe Nervous System in Infancy, notably by Macdonald Critchley. Critchley and Childhood, and Adolescence, 5th edition, p. 296. Thomas: Springfield, Ill. Greenfield (1948) held that in some cases essential Herskovits, E., and Blackwood, W. (1969). Essential (familial, tremor might represent a forme fruste of a pre- hereditary) tremor: a case report. Journal of Neurology, senile atrophy such as olivopontocerebellar Neurosurger.y, and Psychiatry, 32, 509-511. Hoehn, M. M., and Yahr, M. D. (1967). Parkinsonism: onset, atrophy. It is more probable that these con- progression and mortality. Neurology (Minneap.), 17, ditions are the result of quite different genes, al- 427-442. though the clinical (phenotypic) manifestations Jager, B. V., and King, T. (1955). Hereditary tremor. Ar- chives of Internal Medicine, 95, 788-793 often show similarities or overlap. Kelly, R. (1965). Tremor. In Encyclopaedia of General Prac- tice, vol. 6, pp. 210-216. Edited by G. F. Abercrombie and Butterworths: London. I wish to thank Professor H. Schnieden and Dr. P. K. R. M. S. McConaghey. http://jnnp.bmj.com/ Thomas for advice in the preparation of the manu- Kreiss, Ph. (1912). Ober hereditaren Tremor. Deutsche Zeitschriftfur Nervenheilkunde, 44, 111-123. script. Larsson, T., and Sj6gren, T. (1960). Essential tremor. A clinical and genetic population study. Acta Psychiatrica et REFERENCES Neurologica Scandinavica, 36, Suppl. 144. D. A. and Mc- Antony and Rouvillois (1899). Tremblement essentiel avec Marsden, C. D., Foley, T. H., Owen, L., Allister, R. G. (1967). Peripheral P-adrenergic receptors stigmates d'hyst6rie. Revue Neurologique, 7, 386. 53-65. Barker, L. F. (1939). Ageing from the point of view of the concerned with tremor. Clinical Science, 33, clinician. Problems ofAgeing, pp. 717-742. Edited by E. V. Marshall, J. (1962). Observations on essential tremor. Journal Cowdry. Williams and Wilkins: Baltimore. of Neurology, Neurosurgery, and Psychiatry, 25, 122-125. on September 30, 2021 by guest. Bergamasco, I. (1907). Intorno ad un caso di tremore Nettleship, E. (1911). On some cases of hereditary nystagmus. essenziale simulante in parte il quadro della sclerosi Transactions of the Ophthalmological Society of the United multipla. Rivista di Patologia Nervosa e Mentale, 12, 4-9. Kingdom, 31, 159-202. Bertrand, C., Hardy, J., Molina-Negro, P., and Martinez, Parkinson, James (1817). An Essay on the Shaking Palsy. S. N. (1969a). Optimum physiological target for the arrest Whittingham and Rowland: London. of tremor. Third Symposium on Parkinson's Disease, held at Poirier, L. J. (1970). Recent views on tremors and their treat- the Royal College of Surgeons of Edinburgh, pp. 251-259. ment. In Modern Trends in Neurology, 5. Pp. 80-85. Edited Livingstone: Edinburgh. by D. Williams, Butterworths: London. Bertrand, C., Hardy, J., Molina-Negro, P., and Martinez, Velander, F. G. H. (1931). Arftlighetsstudier inom tvenne S. N. (1969b). Tremor of attitude. Confinia Neurologica, 31, slakter med hereditar tremor. Nordisk Medicinsk Tidskrift, 37-41. 3, 102-108.