Journal ofNeurology, Neurosurgery, 1090 and Psychiatry 1991;54:1090-1092 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.12.1090 on 1 December 1991. Downloaded from Familial dystonic choreoathetosis with myokymia; a sleep responsive disorder

Edward Byrne, Owen White, Mark Cook

Abstract Case histories (Thefamily tree is shown in the A family is present:ed with paroxysmal figure) dystonic choreoathettosis transmitted as a Case II was born in Scotland near Edinburgh dominant trait over:five generations. The and emigrated to Australia in her early 20s and family is unusual in the marked respon- worked as a nurse maid. Her daughter (II4) siveness of the episodles to short periods of remembers her mother as having the same type sleep in several me embers, in the very of attacks that she herself had. No information variable age of onselt, and in the associa- is available about the age of onset. Case I 1 tion with prominentt myokymia in some migrated to Australia, circa 1880. She had eight cases. These overlalp features suggest a children but information is available only on link between paroxysmal dystonic II6 and her descendants. choreoathetosis and familial paroxysmal Case I16 was the sixth of eight children. She with myokymia. began to get of her limbs as a child and they persisted all through her life, probably getting less severe with age. She died aged 56, Familial disorders wiLth paroxysmal abnor- cause of death unknown. malities of motor regullation include paroxys- Case IIII was the first child of III6, a girl, mal kinesigenic choreoathetosis where sudden died at the age of five and had no known movement, the anticip)ation of movement or neurological problems. The second child, a son startle, may precipitate episodes of shortlived (III2), is alive and well at the age of 80 with no choreoathetosis,I and rarer paroxysmal dys- known The third child St Vincent's Hospital, tble neurological problems. Melbourne tonic choreoathetosisM vhere trigger factors are (II13), a boy, was asymptomatic until the age of Department of less well-defined and episodes usually more 40. At that age, he began to notice facial Neurology protracted.2 The paro)Kysmal choreoathetoses tightness followed by sometimes, E Byrne grimacing M Cook are considered to be diistinct from the familial but not always, provoked by excitement or and its the most Monash Medical periodic ataxia syndroi me3 variant, the tension. Facial grimacing was Centre, Melbourne, syndrome of familial paroxysmal ataxia and prominent feature of the early attacks but from Australia continuous myokymia1.4 In this report we the beginning he was also aware of uncontrol- Department of present a family witi h autosomal dominant movement of his limbs the arms Neurology lable affecting c this took the http://jnnp.bmj.com/ 0 White paroxysmal dystonic horeoathetosis where a more than the legs. In early attacks history of rapid of episodes very with controllable Correspondence to: alleviattion by form of muscle stiffening Professor Byrne, Neurology short periods of p in several members jerking movements developing in later attacks. Department, St Vincent's sleel Hospital, Fitzroy, suggests a link with atbnormal sleep mechan- These were of a choreoathetoid type. Both Melbourne 3065, Australia isms and a finding of myokymia in several sides were equally affected. The attacks have Received 13 February 1991. members suggest overl lap with other paroxys- shown no tendency to become less frequent Accepted 10 April 1991 mal syndromes. over the years and generally they last until the patient falls asleep. He has a warning of a on September 23, 2021 by guest. Protected copyright. feeling of tightness in his muscles before the fully evolved attack begins which enables him to withdraw into his own room. He can always fall asleep almost immediately, even when an 1I attack begins in the middle of the day, and finds 7 8 that a few minutes of sleep is sufficient to abolish the attack completely. He feels he must to abolish an attack. III fall asleep completely Episodes have not been provoked by alcohol, 4 caffeine, startle or sudden movement. The patient developed maturity-onset diabetes in IV his late 50s and in his early 70s developed 6 numbness in his feet. He had a stroke in his 70s which resulted in weakness of the left hand. On examination, aged 76, he had mild global V weakness of the left hand in keeping with the 1 2 3 4 5 6 8 9 10 history of stroke. There was evidence of a distal

Figure Family tree showing affected cases (black) and un affected cases (white). sensory neuropathy with depression of pin- Information is incomplete in the second generations of thefamily in Australia. (Shaded prick and vibration sense over his feet and cases) CasesIIII andI V4 died in childhood. proprioceptive impairment in the toes. Ankle Familial dystonic choreoathetosis with myokymia: a sleep responsive disorder 1091 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.12.1090 on 1 December 1991. Downloaded from

reflexes were absent. Occasional for 30-60 minutes. In episodes where attacks were evident in the anterior tibial muscles and are alleviated without falling asleep, he has gastrocnemii bilaterally. No myokymia was noticed that the alleviation of symptoms is evident either clinically or with electromyo- instantaneous and occurs at a point just before graphic studies. sleep. Attacks tend to occur in the afternoon Case III4 The fourth child of II6, a girl, and early evening. As a teenager, he would began to get attacks at the age ofnine or 10 with regularly go to sleep at 6 or 7 pm and would uncontrollable movements of her limbs and have recovered by 10 pm. In his early 40s, he face. She would have a feeling of apprehension became aware ofa feeling ofloss ofstrength and before the attacks began enabling her to retire muscle flickering in his thighs. to her room and although the attacks were quite On examination at the age of 45, he had frequent other family members did not know choreoathetoid movements of the legs which she had them until after the birth of an affected were infrequent but which he said tended to niece when she recognised that the niece's follow attacks of the type described above and episodes were similar to her own. The attacks which could persist for several days. Post- were more frequent during periods of tension contraction myokymia was prominent in the and are alleviated by rest. Rest on a bed for a quadriceps, femoris muscles bilaterally. Power, few minutes improved the episodes. She deep tendon reflexes and sensation were isolates herself until the attack passes off. The normal and nerve conduction studies revealed episodes are associated with a feeling of dis- no abnormalities. Muscle histology and a comfort and she is unable to sleep. lysosomal enzyme battery were normal. Case IVI The eldest child of patient III3, a Case V6 A 14 year old boy, the son of IV2 girl, had stiffening of the neck and trunk developed attacks of uncontrollable limb muscles as a small baby. At the age of eight movements similar to those described by his months, she began to get episodes with father in his early teenage years. He tried to hyperextension of the neck and trunk, flexion ignore the mild attacks. With severe attacks, of the elbows, wrists and fingers. These attacks the only means of relief is to fall asleep. On lasted some minutes and occurred on a daily examination between attacks, he had evidence basis. As she got older, her parents used to ofprominent myokymia ofa much more severe avoid telling her beforehand if the family were type than that seen in his father which affected going out as this always precipitated attacks. the right arm and leg predominantly through- The episodes with retrocollis got less severe in out the period of examination without respite. early adult life. Excitement, or alcohol He indicated that the severity of this symptom intake triggered some attacks. She has a waxed and waned but that it was with him to premonition that an attack is building up which some extent most of the time. enables her to lie down in privacy. She doesn't actually fall asleep but waits the attack out. A regular nap in the afternoon reduces the Discussion frequency of attacks. If she stands in one place The inheritance pattern in this Australian for any length oftime, this can both initiate and family is clearly autosomal-dominant in keep- compound symptoms. She has four children, ing with most published reports of familial all well. paroxysmal choreoathetosis"' although Mount

Case IV2 The index case developed muscle and Reback's original report suggested a reces- http://jnnp.bmj.com/ spasms as a boy at the age of 13 or 14 affecting sive transmission.2 Onset in infancy, as in case the legs and arms together. When asked to IVI, is well recognised with reports as early as describe his earlier attacks, he mimicked dys- one week'0 and attacks usually beginning in tonic posturing of the hands with flexion of the childhood. The range of ages of onset in this elbows and wrists and splaying of the fingers family is striking with congenital, childhood, and inversion and plantar flexion of the ankles. adolescent and adult onset cases all clearly The dystonic posturing would wax and wane documented. Onset as late as 40, as in case III3 for several hours and was alleviated only by has not been previously reported although on September 23, 2021 by guest. Protected copyright. sleep. As he got older, he became aware than an Lance has reported an atypical case with onset emotional stimulus such as watching some- in the early 20s.6 The clinical features of the thing unpleasant on television, or a movie, attacks in the family we describe are typical could precipitate attacks and that they were with a vague prodrome often with a feeling of more likely to occur when physically tired. muscle stiffening recognised in the earliest Stress is a potent trigger factor. The episodes report2 and involvement of the face, arm and were never precipitated by startle or sudden legs in variable combinations. Episodes lasted movement. The episodes became both less from a few minutes to several hours. No frequent and less severe as he entered the consistent pattern of precipitation can be fourth decade. identified in the few reported families but Episodes are rapidly terminated by a short sudden movement or startle are not precipi- sleep, and the patient finds it easy to fall asleep tating features distinguishing this disorder when he has an attack regardless of the time of from paroxysmal kinesigenic choreoathetosis. day. As he has got older, he has found that he Precipitation with alcohol, coffee and tea have can sometimes alleviate attacks if he achieves a been reported and the relationship with state of deep relaxation without actually falling or excitement as in the index case in this study asleep. He has a craving for food when he has is also recognised." Although attacks in other attacks and if he eats (usually cereal) it assists families have been alleviated by lying down, the him to relax more deeply. He typically sleeps rapid relief of symptoms by short periods of 10929Byrne, White, Cook J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.12.1090 on 1 December 1991. Downloaded from

sleep which characterised several of our cases myokymia included myokymia in some mem- has not previously been stressed. This was bers, the length of the episodes, and a tendency particularly striking with one of our subjects for abolition of attacks by sleep. A previous who found that he could instantly fall asleep in report of paroxysmal dystonic choreoathetosis the midst of an attack, at whatever time it in a patient from a family with familial ataxia"6 occurred, and that after sleeping for one to two suggests some overlap between these syn- minutes he would usually awake with the dromes. episode completely over. Failure to respond to Clearly, several different paroxysmal anticonvulsant medication distinguishes par- movement disorders can be distinguished on oxysmal dystonic choreoathetosis from parox- the basis of precipitating factors, clinical ysmal kinesigenic choreoathetosis. Myokymia features and length of episodes and response to has not been reported previously in any family treatment. The existence of cases with overlap with paroxysmal dystonic choreoathetosis to features, however, raises the possibility that our knowledge but was a prominent feature in these different clinical phenotypes may two patients in our family. represent different expressions of a single Several families with prominent myokymia gene defect, a situation not uncommon in in a setting of familial paroxysmal kinesigenic neurological illness. The striking response to ataxia have been reported.4 12-14 This syndrome sleep in several of the cases reported here is the is characterised by attacks with unsteadiness of most unique characteristic of this family and gait and limbs and shaking of the head and may provide some clues on the patho- limbs often with a feeling of stiffness in the face physiology of the disorder. and hands. Abrupt change of position usually provokes episodes as in paroxysmal kinesigenic choreoathetosis. The feeling of tightness that some subjects with this syndrome complain of 1 Kertesz A. Paroxysmal kinesigenic choreoathetosis, an as episodes are evolving, resembles that often entity within the paroxysmal choreoathetoses; description of 10 cases including 1 autopsy. Neurology 1967;17: complained of in paroxysmal dystonic choreo- 680-90. . In occasional cases, such as case III- 2 Mount LA, Reback S. Familial paroxysmal choreoathetosis: preliminary report on a hitherto undescribed clinical 25 in the study of Brunt et al,'4 attacks can last syndrome. Arch Neurol 1940;44:841-6. for many hours and be terminated by sleep. 3 Farmer TW, Mustian VM. Vestibulocerebellar ataxia; a newly defined hereditary syndrome withperiodicmanifes- Myokymia in this syndrome is often not very tations. Arch Neurol 1963;8:471-80. prominent and does not affect all family mem- 4 Van Dyke DH, Griggs RC, Murphy MJ, Goldstein MN. Hereditary myokymia and periodic ataxia. J Neurol Sci bers. 14 The fine rippling myokymia which 1975;25:109-18. characterises this disorder resembles that seen 5 Forssman H. Hereditary disorder characterised by attacks of muscular contractions induced by alcohol among other in our patients. factors. Acta Med Scand 1961;170:517. The syndrome of periodic familial ataxia is 6 Lance JW. Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes. Ann Neurol another entity that merits consideration.5 15 1977;2:285-93. This syndrome resembles our cases in the long 7 Weber MB. Familial paroxysmal dystonia. J Neur Ment Dis 1967;145:221-6. duration of attacks and the tendency for 8 Richards RN, Barnett HJM. Paroxysmal dystonic episodes to occur with tiredness but differs in choreoathetosis: a family study and review of the literature. Neurology 1968;18:461-9. the absence of nystagmus in our cases and the 9 Tibbles JAR, Barnes SE. Paroxysmal dystonic choreoath- presence of dystonic and athetoid features etosis of Mount and Reback. Pediatrics 1980;65:149-51.

10 Walker ES. Familial paroxysmal dystonic choreoathetosis; a http://jnnp.bmj.com/ rather than ataxia. neurological disorder simulating psychiatric illness. Johns The family presented in this report exhibits Hopkins Med J 1981;148:108-13. 11 Pruntek H, Monniger P. Therapeutic aspects of kinesigenic paroxysmal choreoathetosis affecting face and paroxysmal choreoathetosis and familial paroxysmal limbs with episodes lasting from minutes to choreoathetosis of the Mount Reback type. J Neurol 1980;230:163-9. hours and in some members rapidly relieved by 12 Hanson PA, Martinez CB, Cassidy R. Contractures, contin- sleep often after a very short time. There was uous muscle discharges and titubation. Ann Neurol 1977;1:120-4. no precipitation by sudden movement or startle 13 Gancher ST, Nutt JG. Autosomal dominant ;

distinguishing this disorder from familial a heterogenous syndrome. Movement Disorders 1986; on September 23, 2021 by guest. Protected copyright. 1:239-53. paroxysmal kinesigenic ataxia and continuous 14 Brunt ERP, Van Weerden TW. Familial paroxysmal kin- myokymia and also from paroxysmal kinesi- esigenic ataxia and continuous myokymia. Brain 1990;113:1361-82. genic choreoathetosis. The episodes were 15 Griggs RC, Moxley RT, Lafrance RA, McQuillen J. atypical for familial periodic ataxia, and nystag- Hereditary paroxysmal ataxia: response to acetazolamide. Neurology 1978;28:1259-64. mus was not a feature. Features which overlap 16 Mayeux R, Fahn S. Paroxysmal dystonic choreoathetosis in with the syndrome of paroxysmal ataxia and a patient with familial ataxia. Neurology 1982;32:1184-6.