3223Journal of Neurology, Neurosurgery, and Psychiatry 1992;55:322-324

SHORT REPORT J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.4.322 on 1 April 1992. Downloaded from Familial hypokalaemic periodic paralysis in Finland

I M Kantola, L T Tarssanen

Abstract carried out on both asymptomatic and sympto- Seven families with familial hypokalaemic matic family members. This is a rectangular 30 periodic paralysis were found in Finland. minute, 100 W bicycle exercise test. During Nine of the 103 asymptomatic family the exercise the rise in the plasma potassium members studied had abnormal results on concentration is monitored. According to our a potassium exercise test. The overall results, a rise in concentration of < 05 mmol/ prevalence of familial hypokalaemic peri- 1 or the ratio rise in concentration: pulse rise odic paralysis in Finland was 0-41100 000. < 0 090 suggests the diagnosis of hypoka- Carbohydrate intake and hard exercise laemic periodic paralysis. were the most important triggers of paralytic attacks. Half of the patients reported having attacks at least once a Results month. Seven patients reported cardiac Seven families with familial hypokalaemic peri- symptoms (especially bradycardia) dur- odic paralysis were found in Finland. In these ing attacks. Permanent muscular weak- families 21 living (15 men and six women) and ness was not prominent. 11 dead (six men and five women) patients with certain paralytic attacks with hypokalae- mia were noted. In the seven families 171 Familial hypokalaemic periodic paralysis is a living (80 men and 91 women) and 119 dead rare disease of undetermined cause charac- (65 men and 54 women) asymptomatic adult terised by transient attacks of hypotonic paral- family members were found. Of these 171 ysis ofvarying severity, occurring at intervals of family members 103 (49 men and 54 women) days to years in otherwise healthy people. were investigated, but not the remainder for Usually there is hypokalaemia during attacks. various reasons. Nine asymptomatic family Attacks may be precipitated by glucose members (five men and four women) showed infusion, high carbohydrate meal, emotional the same low potassium rise in the exercise test excitement, and severe muscular exertion. The as seen in symptomatic family members.2

attacks usually begin at puberty and cease at Muscle biopsies were performed on four of http://jnnp.bmj.com/ the age of 50-60 years. The mode of inherit- them. Typical dilated sarcoplasmic reticulum ance is thought to be autosomal dominant. was seen in all cases. Attacks are more common in males.' Most of the patients had been born in We determined the number of families with central Finland or Savo. Members of two hypokalaemic periodic paralysis in Finland and families were born in southwest Finland. The described their characteristics. mean (SD) age at onset ofparalytic attacks was 12 (5) years (range 6-23 years). This was lower in females (6 5 (0 5) years) than in males (15 5 on September 29, 2021 by guest. Protected copyright. Patients and methods (3 5) years). The intensity of the disease The number of families with familial hypoka- seemed to vary from one family to another. laemic periodic paralysis was determined by One patient had > 9 attacks a month, three using a special questionnaire which was sent to had 4-8 a month, eight had 1-3 a month, two chief physicians in the departments of medi- had 1-2 a year, and seven had less frequent Department of Medicine, University cine and neurology in all university hospitals, attacks. Hospital, Turku, central hospitals, and district hospitals in The attacks began in the legs in five patients, Finland Finland. If no response was received hospitals the arms in two, and in both in 14. No facial or I M Kantola were personally contacted. The family mem- eye muscle paralysis was reported. Five Departnent of bers were interviewed by the investigator. The reported permanent mild muscular Medicine, Central patients Hospital, Mikkeli, families were traced as far back as the members weakness in the extremities, which did not Finland could remember. Population registers were not affect their ability to work. L T Tarssanen used. A special questionnaire to obtain infor- One patient had a permanent cardiac pace- Correspondence to: mation about the age at onset, the maker and aortic valve one other Dr Kantola, Department of patient's prosthesis; Medicine, Turku University frequency and severity of paralytic attacks, any had familial hypercholesterolemia. Physical Hospital, SF-20520 Turku, mus- examination of the other revealed no Finland. possible provocative factors, permanent patients cular and the effect of pregnancy or Received 16 March 1990 weakness, cardiovascular, endocrinological, gastro- and in revised form 29 May was given to patients with paralytic attacks. intestinal abnormalities. Tendon reflexes were 1990. examination was on all normal. Muscle was reduced to MRC Accepted 18 September Physical performed power 1991 participants. A potassium exercise test2 was grade 4 in one patient and normal in all others. Familial hypokalaemic periodic paralysis in Finland 323

Five patients experienced constipation during but the ratio seemed to vary considerably from J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.4.322 on 1 April 1992. Downloaded from their severest attacks. Three of them had also one family to another. In some families the difficulties in urinating. One patient had poly- gene was completely non-penetrant in women uria after the attacks. Seven reported cardiac whereas in another women were affected more symptoms (especially slow pulse rate) during than men. This variability may explain the severe attacks. Five had respiratory symptoms, variable penetrance observed in earlier stud- most of them difficulties in coughing up ies.' 4-6 Our families were concentrated mainly secretions. One patient described breathing in two districts. This concentration may be due difficulties as if the diaphragm did not move at to the fact that in the past Finnish people did all. not move much from one place to another, and A variety offactors triggered paralysis. These the families may have one common pro- included carbohydrate intake (11), hard exer- genitor. cise (eight), eating sweets and chocolate (five), The age at onset differed considerably evening meals (four), irregular meals (three), between men and women. Johnsen' did not cold (two), fatigue (two), and rainy weather find this kind of difference in Danish patients. (one). One reported an increased frequency of Four of the Finnish patients belonged to the attacks during pregnancy; another had no same family, and possibly the early beginning attacks during pregnancy but had attacks of the paralytic attacks was characteristic to nearly every night after delivery. Three patients that specific family. The frequency of paralytic had no difficulties during pregnancy and breast attacks may vary not only from one patient to feeding. another but also in each patient at different Twelve patients had used potassium, seven periods of his or her life. ' 7 In Finnish patients acetazolamide, and two dichlorphenamide as no variation in paralytic attacks was seen in medication. Eight of the 12 patients found severe forms of the disease, the patients having potassium useful as a prophylactic agent had weekly attacks during the whole of their against attacks, three patients found no differ- disease. The disease seems to be milder in ence, and one found it useful only during Finland than in Denmark because about one attacks. Acetazolamide had been useful for five third of the Finnish patients but only one tenth patients as a prophylactic agent. Two patients of the Danish patients' had had only one or who had no benefit from acetazolamide were two paralytic attacks. transferred to dichlorphenamide, and their Although many of the patients described paralytic attacks almost stopped. Four of the slow pulse rate during attacks, only one had 21 patients had not had attacks for 10-20 had life threatening bradycardia. No other years. They had had their last attack at the age cases of hypokalaemic periodic paralysis with of 21-40 years. We confirmed the inheritance ventricular arrhythmias89 were found in to be autosomal dominant. The penetrance Finland. was weak. The male preponderance was 1 -9: 1, Kramer et allo suggested that cardiomyop- varying from one family to another. athy might be a complication of hypokalaemic periodic paralysis, but we found no signs of decreased cardiovascular working capacity Discussion during the exercise test.

According to our results the prevalence of The factors eliciting paralysis were similar in http://jnnp.bmj.com/ familial hypokalaemic periodic paralysis in both Finnish and Danish patients.4 Patients Finland is 0-4/100 000. Possibly as knowledge should be warned against taking large of the disease increases so will the prevalence, carbohydrate-rich meals before going to bed. as was seen from the Danish numbers. The Also hard exercise and cold, rainy weather prevalence in Denmark was calculated as seem to precipitate attacks. No regular changes 0-8/100 000 in 1959 by Sagild3 and in the pattern of attacks were seen during 1*25/10 000 in 1978 byJohnsen.'We probably pregnancy or breast feeding. There is no reason found almost all known Finnish patients to advise against pregnancy for women with on September 29, 2021 by guest. Protected copyright. because the hospitals where the questionnaire familial hypokalaemic periodic paralysis. was sent should know all patients with this kind Almost half of our patients had used potas- of rare diagnosis. Possibly, however, some sium prophylactically with good success, patients may be incorrectly diagnosed-for although others have reported its failure to example, some psychiatric diagnosis as seen in prevent attacks." 12 Its success in our patients Denmark.' may be due to the milder form of the disease in Nine asymptomatic family members were Finland. Acetazolamide also seemed to sup- found who had abnormal results on the patho- press the paralytic attacks better than potas- logical potassium exercise test but no paralytic sium, although the patients who used acet- attacks. Four showed vacuolisation in a muscle azolamide were more seriously affected by the biopsy specimen. According to these results disease. In two patients acetazolamide was not about 9% of asymptomatic family members effective and both of them were transferred to might be carriers ofthe hypokalaemic periodic dichlorphenamide, which suppressed their paralysis gene. One of our cases would have attacks almost totally. This confirms an earlier been classified as sporadic if the potassium report,'3 which suggested that if acetazolamide exercise test had not been available. If families is not effective dichlorphenamide should be are traced back far enough or if accurate used. enough diagnostic methods for family inves- The prevalence of permanent muscular tigation are used no sporadic cases exist. weakness varies from one study to another. We found a preponderance among males, Baruma et al4 reported some kind of muscular 324 Kantola, Tarssanen

4 Buruma OJS, Bots GTAM, Went LN. Familial hypokalemic weakness in all subjects investigated. It has periodic paralysis. Arch Neurol 1985;42:28-31. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.4.322 on 1 April 1992. Downloaded from been shown that ifthe muscle power decreases, 5 Talbott JH. Periodic paralysis. A clinical syndrome. Medi- cine (Baltimore) 1941;20:85-143. carbonic anhydrase treatment might improve 6 Woratz G. Hypokalamische paroxysmale Lahmung. Munch the muscle strength between attacks." 14 Med Wschr 1965;46:2318-23. 7 Zabriskie EG, Frantz AM. Familial periodic paralysis. Bull According to subjective information perma- Neurol Inst NY 1932;2:57-74. nent muscular weakness seemed to be no 8 Levitt LP, Rose UI, Dawson DM. Hypokalemic periodic paralysis with arrhythmia. N Engl Med 1972;286: problem in Finnish patients, probably because 253-4. only half of them had regular annual attacks. 9 Stubbs WA. Bidirectional ventricular tachycardia in familial hypokalaemic periodic paralysis. Proc Roy Soc Med 1976;69:223-4. This study was financially supported by grants from City of Research 10 Kramer LD, Cole JP, Messenger JC, Ellestad MH. Cardiac Turku, Research Foundation of Muscle Diseases, dysfunction in a patient with familial hypokalemic period- Foundation of Duodecim, Research and Science Foundation of ic paralysis. Chest 1979;75:189-92. Farmos Oy, and the stipend funds of the University ofTurku. 11 Griggs RC, Engel WK, Resnick JS. Acetazolamide treat- ment of hypokalemic periodic paralysis. Ann Intern Med 1970;73:39-48. 12 Resnick JS, Engel WK, Griggs RC, Stam AC. Aceta- 1 Johnsen T. Familial periodic paralysis with hypokalaemia. zolamide prophylaxis in hypokalemic periodic paralysis. Dan Med Bull 1981;28:1-27. N Engl Med 1968;278:582-6. 2 Tarssanen LT, Kantola IM, Huikko ME. Serum potassium 13 Dalakas MC, Engel WK. Treatment of "permanent" muscle exercise test in the diagnosis of familial periodic paralysis. weakness in familial hypokalemic periodic paralysis. Acta Neurol Scand 1983;68:30-3. Muscle Nerve 1983;6:182-6. 3 Sagild V. Hereditary transient paralysis with special reference to 14 Thompson AJ, Hutchinson M. Myopathy in hypokalaemic the metabolism of potassium. Copenhagen: Munksgaard, periodic paralysis: reversal with acetazolamide. Ir Med 1959. Dissertation. 1984;77:171-2. http://jnnp.bmj.com/ on September 29, 2021 by guest. Protected copyright.