ltal. J. Neurol. Sci. 13.'589-592, 1992
Autonomic nervous system function in myotonic dystrophy Pierangeli G., Lugaresi A., Contin M., Martinelli P., Montagna P., Parchi P., Verlicchi A., Cortelli P. lstituto di Neurologia, Universitd di Bologna
Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group.
Key Words: Myotonic dystrophy - - cardiovascular reflex - - autonomic nervous system - - catecholamines
Introduction
Subjects and methods
Myotonic Dystrophy (MD) is a multisystem disease transmitted in autosomal dominant fashion, marked by myotonia, muscular weakness, atrophy and characteristic electromyographic abnormalities [10, 11]. Clinical features known to be associated with autonomic nervous system (ANS) dysfunction such as orthostatic hypotension, gastrointestinal motility disorders, cardiac arrhythmias, ventilatory, bladder and sexual disturbances are common in MD [9, 12]. ANS activity in MD patients has been investigated by studying pupillary function, cardiovascular reflexes and plasma catecholamine levels [1, 4, 7, 13-15]. The results of these studies have been contradictory; some authors suggested a primary involvement of ANS in MD and others a defective function of the target organs. This study aimed to assess whether signs of subclinical ANS dysfunction in MD patients can be revealed by means of cardiovascular reflexes and the evaluation of NA and A plasma levels.
We studied 12 patients, 6 males and 6 females, with mild to moderate MD. The severity of the disease was classified on the basis of the patient's ability to perform everyday activities. 5 cases were sporadic, the other 7 came from 3 families. The mean age of patients was 36 + _ 15 years (range 1562). Clinical diagnosis was confirmed by EMG studies. Clinical history and physical examination were negative for signs of autonomic dysfunction. None of the patients had diabetes, hypertension, renal or endocrine disease. Patients were compared with 23 age ( 3 6 _+ 15 years, range 14-67) and sex (12 males and 11 females) matched controls. All subjects had normal glucose tolerance test and sodium and potassium plasma levels. Studies were performed in a temperature-controlled (23+- 1~ C) clinical investigation room. We monitored: systemic blood pressure (automatic sphygmomanometer), heart rate (precordial elec-
Received 7 November 1991 - Accepted 30 April 1992
589
The halian Journal of Neurological Sciences
trodes), thoracic breathing (strain-gauge), oronasal breathing (thermistor). Blood sample were drawn from an indwelling intravenous cannula in a forearm vein for measurement of plasma NA and A by means of high pressure liquid chromatography with electrochemical detection [2]. Autonomic function studies: 1) Beat to beat heart rate variability: recording 150 R-R intervals in basal conditions. We considered: mean and standard deviation (SD) of 150 successive R-R intervals, the SD of the differences between one R-R interval and the next (Mean-square successive difference; MSSD) and the maximum change with respect to the mean of R-R intervals expressed as a percentage (N%). 2) Head-up tilt test: After 30 rain of resting supine the patients were moved by means of a tilting table with footrest from the supine to the erect position (65 ~ for 10 min. Blood pressure and heart rate were measured every minute. Venous blood was sampled for the determination of plasma NA and A 5 and 1 rain before the test, at the 10th rain of standing and 5 min after returning to a supine position. The variations from the basal values of systolic and diastolic blood pressure, heart rate, NA and A plasma levels were measured. 3) Valsalva manoeuvre: the patients were asked to blow into a mouthpiece attached to a mercury manometer to maintain a pressure of 40 mmHg for 12 sec. We calculated the ratio of the longest RR interval after the manoeuvre (within about 20 beats) to the shortest R-R interval during the manoeuvre (Valsalva ratio; VR).
4) Deep breathing: the heart rate variation was recorded during deep breathing (6 breaths/min for 2 min). The following parameters were considered: the heart rate variation (AHR) calculated using the 10 longest R-R intervals during expiration and the 10 shortest R-R intervals during inspiration, and the ratio of the mean R-R interval during inspiration to the mean R-R interval during expiration (I/E). 5) Cold pressor test: patients were requested to immerse a hand in water at 4 ~ C for 2 rain. Blood pressure and heart rate were measured every minute. Venous blood was sampled for the determination of plasma NA and A levels 5 and 1 rain before the test and at the 2rid rain during the test. The variations from the basal value of systolic and diastolic blood pressure, heart rate, NA and A plasma levels were measured. 6) Lying d o w n : the patients were requested to maintain the erect position for 20 sec and then quickly lie down and stay supine breathing regularly. We calculated the ratio of the longest R-R interval during the 5 beats before lying down to the shortest R-R interval during the 10 beats after lying down (standing to lying ratio; S/L).
Statistics Results are presented as mean _+SD. The differences between MD patients and controls were compared by a Mann Whitney test. Variables were considered to be significant if p < 0.05.
TABLE I. Cardiovascular and catecholamine responses to tilt test and to cold pressor test (Mean +_SD TILT TEST SBP (mmHg) Basal Tilt MD
110+13
108+13
DBP (mmHg) Basal Tilt
HR (bts/min) Basal Tilt
NA (pg/ml) Basal Tilt
A (pg/ml) Basal Tilt
66_+11
68_+10
67_+12
81_+10
181_+87 398_+89
28_+17
64_+65
69_+7
73+8
68+8
83+9
185+89
378+138
20_+10
36+18
Cold P.
Basal
Cold P.
n-ll 36_+16 yrs
CONTROLS
114_+14 117_+8
n = 23 36_+15 yrs
Cold P.
Basal
COLD PRESSOR TEST Cold P. Basal Cold P. Basal
110_+13 136_+12
66_+10
87_+14
66_+9
75-+10
157-+34 204-+58
30_+24
34_+20
113_+7
68+7
79_+6
65+6
71_+6
123+56
19§
31+23
Basal MD n=12 36_+16 yrs
CONTROLS n-23 36 + 15 yrs
125_+12
164+34
SBP = systolic blood pressure; DBP - diastolic blood pressure; HR - heart rate; NA - noradrenaline; A - adrenalin.
590
Pierangeli G.: D)'sautononda in myotonic elvstrophy
TABLE 11. Heart rate variability" in supine resting condition and response to Valsalva manoeuvre, deep breathing and lying down MD
Age
Sex
R-R variability SD
MSSD
Valsalva VR
Deep breathing HR I/E
Lying down S/L
1 2 3 4 5 6 7 8 9
20 25 28 51 15 21 23 48 48
Mean_+SD Controls n=23 Mean_+SD
M M M M F F F F F
40 28 66 94 28 140 34 30 34
24 12 54 52 16 130 18 24 9
2.41 1.88 2,73 2.2 2.2 2.47 2.03 1.59 1.65
21 25 11 13 21 20 14 5 7
1,28 1,39 1,24 1,23 1,26 1.38 1.21 1.11 1.11
1.25 1.31 1.59 1.22 1.22 1.25 1.17 1.12 1.11
36_+16
55_+39
38_+38
2.13_+0,38
15_+7
1.24_+0.09 1.25+0.15
36_+15
44_+23
23+_20
1.86_+0.25
19_+7
1,34+0.17 1.30_+0.15
SD = Standard deviation of 150 R-R c o n s e c u t i v e intervals; M S S D = M e a n - s q u a r e successive differences; VR = Valsalva ratio AHR = Heart rate variation; I / E = Inspiration/Expiration ratio; S / L = S t a n d i n g / L y i n g ratio,
Results Table I shows the results of the tilt test and cold pressor test, One patient was excluded from analysis because he had a vaso-vagaI syncope preceded by lightheadedness and sudden visual loss in the 8th minute of tilt. There was no statistically significant difference between MD patients and controls. Table II shows the results of the heart rate variability test, the Valsalva manoeuvre, deep breathing and lying down. 3 patients were excluded because they showed cardiac arrhythmias which made R-R interval analysis impossible. No differences were found between patients and controls.
Discussion As a group MD patients showed normal orthoand parasympathetic cardiovascular function. Blood pressure, heart rate and responses to the tilt test showed a normal function of the overall bar-
oreflex arc. Catecholamine plasma levels in basal conditions and during the tilt test confirmed an integrated sympathetic activity [8]. Cardiovascular and catecholamine responses to the cold pressor test confirmed the integrity of the efferent sympathetic pathways [3]. There was no difference between MD patients and controls in tests evaluating the parasympathetic function. The reduction of sinus arrhythmia found in the two oldest MD patients does not point to an impaired parasympathetic function because the response to other tests (Valsalva manoeuvre, lying down) exploring the same system were normal. However in these cases we speculate that the impaired respiratory arrhythmia could be related to a defective ventilatory drive, which has already been described during sleep in MD [5, 6]. Our study showing normal ANS control of cardiovascular reflexes in normoglycemic MD patients suggests that the clinical signs which have been related to ANS dysfunction could depend on an altered function of the target organs such as smooth muscle.
Acknowledgement: We thank Mrs B. Trer~ and Mr G. Barletta for technical assistance, Mrs A. Collins and Mrs A. Pollini for assistance with the manuscript.
Sommario Nei pazienti affetti da Distrofia Miotonica si riscontrano spesso sintomi che suggeriscono un'alterata funzione del Sistema Nervoso Vegetativo. Abbiamo sottoposto a valutazione dei riflessi cardiovascolari e dei livelli ematici di catecolamine (adrenalina e noradrenalina) in condizioni basali, in posizione supina e dopo Io stimoto ortostatico e "coM-pressor'" 12 pazienti affetti da Distrqfia Miotonica. L'analisi statistica dei dati non ha mostrato differenze fra i pazienti e un gruppo di controllo comparabile per sesso ed et& 591
The Italian Journal of Neurological Sciences
Address reprint requests to: Dr. Giulia Pierangeli Clinica Neurologica Via U. Foscolo, 7 - 40123 B o l o g n a
References [1] AMINOFF M.J., BECKLEY D.J., MCILROY M.B.: Autonomic function in myotonic dystrophy. Arch. Neurol. 42:16, 1985. [2] ANTON A.H., SAVRE D.F.: A stucly of the factors affecting the aluminum oxidetrihydroxyindole procedure for the analysis of catecholamines. J. Pharmacol. Exp. Ther. 138:360-375, 1962. [3] BANNISTER R., MATHIAS C.J.: Testing autonomic reflexes. In: Bannister R., ed. Autonomic failure - A Textbook of Clinical Disorders of the Autonomic Nervous System, 2nd ed. Oxford, Oxford University Press, 1988:289-307. [4] BIRD T.D., REEMAN A.M., PFEIFER M.: Autonomic nervous system function in genetic neuromuscular disorders: hereditary motor-sensory neuropathy and myotonic dystrophy. Arch. Neurol. 41:43-46, 1984. [5] CIRIGNOTTA F., MONDINI S., ZUCCONI M., et al.: Sleep-related breathing impairment in myotonie dystrophy. J. Neurol. 235:80-85, 1987. [61 COCCAGNA G., MARTINELLI P., LUGARESI E.: Sleep and alveolar hypoventilation in myotonic dystrophy. Acta Neurol. Belg. 82:185-194, 1982. [7] DEN HE1JER J.C., VAN DUK J.G., BOLLEN
592
[8]
[9] [10] [11] [12] [13] [14]
[15]
W.L.E.M. et al.: Assessment of autonomic function in myotonic dystrophy. J. Neurol. Neurosurg. Psychiatry 54: 531-534, 1991. GOLDSTEIN D.S., MCCARTY R., POLINSKY RJ., KOPIN I.J.: Relationship between plasma norepinephrine and sympathetic neural activity. Hypertension 5:552-559, 1983. HARDIN W.B., GAY A.J.: The phenomenon of benign areflexia. Neurology 15:613-621, 1973. HARPER P.S.: Myotonic Dystrophy. Philadelphia, W.B. Saunders, 1979. HARPER P.S.: The genetics of muscular dystrophies. Prog. Med. Genet. 6:53-90, 1985. MAAS Q., PATERSON A.S.: Dystrophia myotonica as a generalized disease. Monatschr. Psychiatr. Neurol. 113:79-99, 1947. MECHLER F., MASTAGLIA F.L.: Vascular adrenergic receptor responses in skeletal muscle in myotonic dystrophy. Ann. Neurol. 9:157-162, 1981. OLOFSSON B.O., NIKLASSON U., FORSBERG H. et al.: Assessment of autonomic nerve function in myotonic dystrophy. J. Auton. Nerv. Syst. 29:187192, 1990. THOMPSON K.S., VAN ALLEN M.W., VON NOORDEN G.K.: The pupil in myotonic dystrophy. Invest Ophthalmol. Vis. Sci. 3:325-328, 1964.
Autonomic nervous system function in myotonic dystrophy Pierangeli G., Lugaresi A., Contin M., Martinelli P., Montagna P., Parchi P., Verlicchi A., Cortelli P. lstituto di Neurologia, Universitd di Bologna
Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group.
Key Words: Myotonic dystrophy - - cardiovascular reflex - - autonomic nervous system - - catecholamines
Introduction
Subjects and methods
Myotonic Dystrophy (MD) is a multisystem disease transmitted in autosomal dominant fashion, marked by myotonia, muscular weakness, atrophy and characteristic electromyographic abnormalities [10, 11]. Clinical features known to be associated with autonomic nervous system (ANS) dysfunction such as orthostatic hypotension, gastrointestinal motility disorders, cardiac arrhythmias, ventilatory, bladder and sexual disturbances are common in MD [9, 12]. ANS activity in MD patients has been investigated by studying pupillary function, cardiovascular reflexes and plasma catecholamine levels [1, 4, 7, 13-15]. The results of these studies have been contradictory; some authors suggested a primary involvement of ANS in MD and others a defective function of the target organs. This study aimed to assess whether signs of subclinical ANS dysfunction in MD patients can be revealed by means of cardiovascular reflexes and the evaluation of NA and A plasma levels.
We studied 12 patients, 6 males and 6 females, with mild to moderate MD. The severity of the disease was classified on the basis of the patient's ability to perform everyday activities. 5 cases were sporadic, the other 7 came from 3 families. The mean age of patients was 36 + _ 15 years (range 1562). Clinical diagnosis was confirmed by EMG studies. Clinical history and physical examination were negative for signs of autonomic dysfunction. None of the patients had diabetes, hypertension, renal or endocrine disease. Patients were compared with 23 age ( 3 6 _+ 15 years, range 14-67) and sex (12 males and 11 females) matched controls. All subjects had normal glucose tolerance test and sodium and potassium plasma levels. Studies were performed in a temperature-controlled (23+- 1~ C) clinical investigation room. We monitored: systemic blood pressure (automatic sphygmomanometer), heart rate (precordial elec-
Received 7 November 1991 - Accepted 30 April 1992
589
The halian Journal of Neurological Sciences
trodes), thoracic breathing (strain-gauge), oronasal breathing (thermistor). Blood sample were drawn from an indwelling intravenous cannula in a forearm vein for measurement of plasma NA and A by means of high pressure liquid chromatography with electrochemical detection [2]. Autonomic function studies: 1) Beat to beat heart rate variability: recording 150 R-R intervals in basal conditions. We considered: mean and standard deviation (SD) of 150 successive R-R intervals, the SD of the differences between one R-R interval and the next (Mean-square successive difference; MSSD) and the maximum change with respect to the mean of R-R intervals expressed as a percentage (N%). 2) Head-up tilt test: After 30 rain of resting supine the patients were moved by means of a tilting table with footrest from the supine to the erect position (65 ~ for 10 min. Blood pressure and heart rate were measured every minute. Venous blood was sampled for the determination of plasma NA and A 5 and 1 rain before the test, at the 10th rain of standing and 5 min after returning to a supine position. The variations from the basal values of systolic and diastolic blood pressure, heart rate, NA and A plasma levels were measured. 3) Valsalva manoeuvre: the patients were asked to blow into a mouthpiece attached to a mercury manometer to maintain a pressure of 40 mmHg for 12 sec. We calculated the ratio of the longest RR interval after the manoeuvre (within about 20 beats) to the shortest R-R interval during the manoeuvre (Valsalva ratio; VR).
4) Deep breathing: the heart rate variation was recorded during deep breathing (6 breaths/min for 2 min). The following parameters were considered: the heart rate variation (AHR) calculated using the 10 longest R-R intervals during expiration and the 10 shortest R-R intervals during inspiration, and the ratio of the mean R-R interval during inspiration to the mean R-R interval during expiration (I/E). 5) Cold pressor test: patients were requested to immerse a hand in water at 4 ~ C for 2 rain. Blood pressure and heart rate were measured every minute. Venous blood was sampled for the determination of plasma NA and A levels 5 and 1 rain before the test and at the 2rid rain during the test. The variations from the basal value of systolic and diastolic blood pressure, heart rate, NA and A plasma levels were measured. 6) Lying d o w n : the patients were requested to maintain the erect position for 20 sec and then quickly lie down and stay supine breathing regularly. We calculated the ratio of the longest R-R interval during the 5 beats before lying down to the shortest R-R interval during the 10 beats after lying down (standing to lying ratio; S/L).
Statistics Results are presented as mean _+SD. The differences between MD patients and controls were compared by a Mann Whitney test. Variables were considered to be significant if p < 0.05.
TABLE I. Cardiovascular and catecholamine responses to tilt test and to cold pressor test (Mean +_SD TILT TEST SBP (mmHg) Basal Tilt MD
110+13
108+13
DBP (mmHg) Basal Tilt
HR (bts/min) Basal Tilt
NA (pg/ml) Basal Tilt
A (pg/ml) Basal Tilt
66_+11
68_+10
67_+12
81_+10
181_+87 398_+89
28_+17
64_+65
69_+7
73+8
68+8
83+9
185+89
378+138
20_+10
36+18
Cold P.
Basal
Cold P.
n-ll 36_+16 yrs
CONTROLS
114_+14 117_+8
n = 23 36_+15 yrs
Cold P.
Basal
COLD PRESSOR TEST Cold P. Basal Cold P. Basal
110_+13 136_+12
66_+10
87_+14
66_+9
75-+10
157-+34 204-+58
30_+24
34_+20
113_+7
68+7
79_+6
65+6
71_+6
123+56
19§
31+23
Basal MD n=12 36_+16 yrs
CONTROLS n-23 36 + 15 yrs
125_+12
164+34
SBP = systolic blood pressure; DBP - diastolic blood pressure; HR - heart rate; NA - noradrenaline; A - adrenalin.
590
Pierangeli G.: D)'sautononda in myotonic elvstrophy
TABLE 11. Heart rate variability" in supine resting condition and response to Valsalva manoeuvre, deep breathing and lying down MD
Age
Sex
R-R variability SD
MSSD
Valsalva VR
Deep breathing HR I/E
Lying down S/L
1 2 3 4 5 6 7 8 9
20 25 28 51 15 21 23 48 48
Mean_+SD Controls n=23 Mean_+SD
M M M M F F F F F
40 28 66 94 28 140 34 30 34
24 12 54 52 16 130 18 24 9
2.41 1.88 2,73 2.2 2.2 2.47 2.03 1.59 1.65
21 25 11 13 21 20 14 5 7
1,28 1,39 1,24 1,23 1,26 1.38 1.21 1.11 1.11
1.25 1.31 1.59 1.22 1.22 1.25 1.17 1.12 1.11
36_+16
55_+39
38_+38
2.13_+0,38
15_+7
1.24_+0.09 1.25+0.15
36_+15
44_+23
23+_20
1.86_+0.25
19_+7
1,34+0.17 1.30_+0.15
SD = Standard deviation of 150 R-R c o n s e c u t i v e intervals; M S S D = M e a n - s q u a r e successive differences; VR = Valsalva ratio AHR = Heart rate variation; I / E = Inspiration/Expiration ratio; S / L = S t a n d i n g / L y i n g ratio,
Results Table I shows the results of the tilt test and cold pressor test, One patient was excluded from analysis because he had a vaso-vagaI syncope preceded by lightheadedness and sudden visual loss in the 8th minute of tilt. There was no statistically significant difference between MD patients and controls. Table II shows the results of the heart rate variability test, the Valsalva manoeuvre, deep breathing and lying down. 3 patients were excluded because they showed cardiac arrhythmias which made R-R interval analysis impossible. No differences were found between patients and controls.
Discussion As a group MD patients showed normal orthoand parasympathetic cardiovascular function. Blood pressure, heart rate and responses to the tilt test showed a normal function of the overall bar-
oreflex arc. Catecholamine plasma levels in basal conditions and during the tilt test confirmed an integrated sympathetic activity [8]. Cardiovascular and catecholamine responses to the cold pressor test confirmed the integrity of the efferent sympathetic pathways [3]. There was no difference between MD patients and controls in tests evaluating the parasympathetic function. The reduction of sinus arrhythmia found in the two oldest MD patients does not point to an impaired parasympathetic function because the response to other tests (Valsalva manoeuvre, lying down) exploring the same system were normal. However in these cases we speculate that the impaired respiratory arrhythmia could be related to a defective ventilatory drive, which has already been described during sleep in MD [5, 6]. Our study showing normal ANS control of cardiovascular reflexes in normoglycemic MD patients suggests that the clinical signs which have been related to ANS dysfunction could depend on an altered function of the target organs such as smooth muscle.
Acknowledgement: We thank Mrs B. Trer~ and Mr G. Barletta for technical assistance, Mrs A. Collins and Mrs A. Pollini for assistance with the manuscript.
Sommario Nei pazienti affetti da Distrofia Miotonica si riscontrano spesso sintomi che suggeriscono un'alterata funzione del Sistema Nervoso Vegetativo. Abbiamo sottoposto a valutazione dei riflessi cardiovascolari e dei livelli ematici di catecolamine (adrenalina e noradrenalina) in condizioni basali, in posizione supina e dopo Io stimoto ortostatico e "coM-pressor'" 12 pazienti affetti da Distrqfia Miotonica. L'analisi statistica dei dati non ha mostrato differenze fra i pazienti e un gruppo di controllo comparabile per sesso ed et& 591
The Italian Journal of Neurological Sciences
Address reprint requests to: Dr. Giulia Pierangeli Clinica Neurologica Via U. Foscolo, 7 - 40123 B o l o g n a
References [1] AMINOFF M.J., BECKLEY D.J., MCILROY M.B.: Autonomic function in myotonic dystrophy. Arch. Neurol. 42:16, 1985. [2] ANTON A.H., SAVRE D.F.: A stucly of the factors affecting the aluminum oxidetrihydroxyindole procedure for the analysis of catecholamines. J. Pharmacol. Exp. Ther. 138:360-375, 1962. [3] BANNISTER R., MATHIAS C.J.: Testing autonomic reflexes. In: Bannister R., ed. Autonomic failure - A Textbook of Clinical Disorders of the Autonomic Nervous System, 2nd ed. Oxford, Oxford University Press, 1988:289-307. [4] BIRD T.D., REEMAN A.M., PFEIFER M.: Autonomic nervous system function in genetic neuromuscular disorders: hereditary motor-sensory neuropathy and myotonic dystrophy. Arch. Neurol. 41:43-46, 1984. [5] CIRIGNOTTA F., MONDINI S., ZUCCONI M., et al.: Sleep-related breathing impairment in myotonie dystrophy. J. Neurol. 235:80-85, 1987. [61 COCCAGNA G., MARTINELLI P., LUGARESI E.: Sleep and alveolar hypoventilation in myotonic dystrophy. Acta Neurol. Belg. 82:185-194, 1982. [7] DEN HE1JER J.C., VAN DUK J.G., BOLLEN
592
[8]
[9] [10] [11] [12] [13] [14]
[15]
W.L.E.M. et al.: Assessment of autonomic function in myotonic dystrophy. J. Neurol. Neurosurg. Psychiatry 54: 531-534, 1991. GOLDSTEIN D.S., MCCARTY R., POLINSKY RJ., KOPIN I.J.: Relationship between plasma norepinephrine and sympathetic neural activity. Hypertension 5:552-559, 1983. HARDIN W.B., GAY A.J.: The phenomenon of benign areflexia. Neurology 15:613-621, 1973. HARPER P.S.: Myotonic Dystrophy. Philadelphia, W.B. Saunders, 1979. HARPER P.S.: The genetics of muscular dystrophies. Prog. Med. Genet. 6:53-90, 1985. MAAS Q., PATERSON A.S.: Dystrophia myotonica as a generalized disease. Monatschr. Psychiatr. Neurol. 113:79-99, 1947. MECHLER F., MASTAGLIA F.L.: Vascular adrenergic receptor responses in skeletal muscle in myotonic dystrophy. Ann. Neurol. 9:157-162, 1981. OLOFSSON B.O., NIKLASSON U., FORSBERG H. et al.: Assessment of autonomic nerve function in myotonic dystrophy. J. Auton. Nerv. Syst. 29:187192, 1990. THOMPSON K.S., VAN ALLEN M.W., VON NOORDEN G.K.: The pupil in myotonic dystrophy. Invest Ophthalmol. Vis. Sci. 3:325-328, 1964.
