Europ. Neurol. 13: 273-284 (1975)
A Case of Late Onset Lipid Storage Myopathy Electromyographic. Histochemical and Ultrastructural Findings
P. P inelli, M. P oloni, G. Nappi and R. Scelsi Clínica Malattie Nervöse e Mentall, and Istituto d¡ Anatomía Patológica, Università di Pavia. Pavia
Key Words. Late onset myopathy • Lipid storage myopathy • Type I fibre atro phy • Prednisone therapy Abstract. A 65-year-old woman showed the clinical picture of a myogenic my opathy, confirmed electromyographically. Detailed histopathological, histochemical and ultrastructural studies were performed on deltoid and quadriceps femoris biop sy specimens. Many muscle fibres were found to contain vacuolar spaces with lipid droplets: perivascular inflammatory changes were also observed. The affected fibres were consistently type I. Under the electron microscope the fibres contained large numbers of lipid droplets, usually next to normal mitochondria. A slight improve ment occurred after prednisone therapy.
Received: June 15, 1974; accepted: August 17, 1974.
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In the past few years a group of chronic myopathies characterized by accumulation of fat within muscular fibres have been described and rec ognized as ‘lipid storage myopathy’ [2, 3, 5, 8, 13]. In some cases abnor mal muscle mitochondria may exist [4], but in others the presence of an extramitochondrial defect of lipid metabolism is assumed. The cases ob served so far began in juvenile or middle age, with elinical and electromy ographic features similar to those of polymyositis, but with a striking ex cess of lipids in muscle fibres; clinical, electromyographic and morpholog ical disorders responded favourably to treatment with steroids. In this paper a case of lipid storage myopathy of late onset, with some peculiar features, will be reported and discussed.
274
P lNELLl/POLON l/N APPl/SCELSI
Case Report The patient, a 62-year-old female, was first admitted to the Neuropathological Institute in January 1973. No incidence of the disease in relatives was found. In the remote history there was thyroid enlargement at the age of 46, associated with a transitory hyperthyroidism; at about the same age she began to experience some dif ficulty in walking and raising her arms above her head. These symptoms responded to prednisone, given at moderate dosages. There were four episodes characterized by decrease in muscular strength and painful hypersensitivity with scapuloperoneal distribution. Each lasted about 3-5 months, with some phases of improvement in between of more than 1 year of duration. She also reported an abnormal fatigue af ter effort, although she never had cramps or dysphagia. On examination the patient showed striking atrophy at both girdles with severe weakness of the tibioperoneal muscles, intrinsic muscles of the feet and deltoid mus cles; the quadriceps muscles, biceps and triceps brachii were relatively unaffected. The muscle stretch reflexes were absent and no sensory deficit was present. There was no other evidence of neurological disturbance and the general physical exami nation was entirely normal. A provisional diagnosis of chronic polymyositis was suggested and the patient underwent the investigations detailed below.
Usual laboratory tests. On admission the usual laboratory tests on blood and urine gave normal results (erythrocytes, hemoglobin, leuko cytes, blood glucose, blood urea nitrogen, antistreptolysin O titre, C-reactive protein, erythrocyte sedimentation rate, sodium, potassium, Wasserman). The cerebrospinal fluid was normal; protein-bound iodine, free thy roxine and unsaturated thyroxine-binding globulin were in the normal range. Plasma ‘muscle’ enzymes. On admission serum lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) showed a marked rise; glutam ic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT) and aldolase levels were only slightly increased. The values of serum enzymes before and following 4 weeks of prednisone administra tion (100 mg on alternative days) are indicated in table I. Lipid measurements. Fasting blood samples were drawn before and af ter 3 weeks of feeding with an isocaloric diet (1,400 cal/day), high in car bohydrates (20% of the calories as protein, 20% as fat and 60% as car bohydrates). Triglycerides and cholesterol were determined; lipoprotein electrophoresis was performed on each sample. The values obtained are reported in table II.
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Results
A Case of Late Onset Lipid Storage Myopathy
275
Table I. Serum enzymes levels on admission and following 4 weeks prednisone (100 mg on alternate days) administration Enzymes
Normal values, mU/ml
Patients' values, mU/ml before therapy after therapy
Aldolase SGOT SGPT CPK LDH
0.9-2.5 12 12 50 115
5.7 71 32 547 1,093
0.6 13 9 35 210
Table II. Plasma lipid measurements before and after a diet high in carbohydrates Investigations
Normal values, mg %
Patients’ values, mg % standard values after high carbohydrate diet
Triglycerides Cholesterol ^-Lipoproteins Pre-/f a Chilomicrons
80-140 150-240 45-65 0-10 25-40 0-20
157 232 47.5 15.0 37.5 5.0
187 248 40.3 15.5 44.3 4.5
Plasma insulin response. Plasma insulin and blood glucose responses to oral glucose (0.75 g/kg) and to intravenous tolbutamide (1 g) tolerance tests, were studied. The results, before and after the diet, are included in the normal range. Electromyographic findings. EMG investigations have been performed with Adrian’s needles according to the usual techniques. Activity at rest: Fibrillation potentials were not found in affected mus cles. A marked insertion activity was derived from the short extensor of the toes alone but no spontaneous activity was continuously recorded.
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A slight hypertriglyceridemia was present, associated with an increase in plasma /(-lipoproteins, especially those of low density, as in type IV hy perlipoproteinemia of F redrickson et al. [10]; after the diet there was a slight increase in triglycerides and cholesterol, with a readjustement of the lipoprotein pattern.
276
P i n e l u / P o l o n i / N ai’p i /S c e l si
V.
Total duration, msec
Total duration, msec
2
Voluntary activity at minimum graded effort: It was difficult to record a regular discharge of single potentials from the muscles examined; in fact there was some interference between the potentials of different MU with resulting polyphasic patterns. On the other hand, in three attempts indi vidual MU polyphasic action potentials could not be obtained for inclu sion in the measured potentials. Therefore the calculated percentage of polyphasic action potentials may be regarded as definitely too low. Voluntary activity at maximum effort: An interference pattern was ob tained in spite of the relatively low muscular strength. In the right biceps and in the short extensor of the toes the maximum amplitude of the inter ference pattern was about 1 mV; in the deltoid muscle 1.5 mV; in the left short extensor and in both quadriceps 4 mV. MU parameters: The measurement of MU potentials generally gave mean amplitude and duration values lower than the normal, with an in creased number of polyphasic potentials. However, in some muscles, es pecially in the brachial biceps and to a lesser extent in the right short ex tensor of the toes and deltoid, the differences from the normal values were more marked, with a regular distribution (fig. 1), while in the quad riceps a large percentage of MU potentials with normal values was found (fig. 2). The strength-duration relation determined in this muscle showed an increased irregularity with chronaxie values of 0.8 msec.
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Fig.l. Histograms of MU polyphasic action potentials (hatched area) recorded from biceps brachii (open area), n = 37. Fig. 2. Histograms of MU polyphasic action potentials (hatched area) recorded from quadriceps femoris (open area), n = 28.
A Case of Late Onset Lipid Storage Myopathy
277
Fig. 3. Cross-section of deltoid muscle showing empty vacuoles in many fibres; some fibres are more severely affected than others. HE paraffin section. X 190.
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M response: Right SPE stimulation at the popliteal cavity and at the dorsal ankle gave a measurement of maximum motor conduction velocity of 44.1 m/sec, corresponding to 47.8 m/sec at 37 C; on the left side it was 47.5 m/sec, corresponding to 49 m/sec at 37 °C. By Erb’s point stim ulation a M response from deltoids with 4 msec latence, 3.5 mV ampli tude, 10 msec duration (non-maximal) was recorded; from brachial biceps a response of 6.3 msec latency, 4.6 mV amplitude and 13 msec duration was recorded. Muscle biopsy. Histopathological and histochemical observations were made on biopsies taken from the deltoid and quadriceps femoris muscles. Tissues were fixed in formaldehyde solution for paraffin sections, and frozen in isopentane cooled to 160 C with liquid nitrogen for histochemi cal preparations, according to previously described procedures [1, 7]. Paraffin sections showed a marked variation in size of fibres; a lot of ab normal empty spaces and vacuoles from less than 1 to 5 /
A Case of Late Onset Lipid Storage Myopathy Electromyographic. Histochemical and Ultrastructural Findings
P. P inelli, M. P oloni, G. Nappi and R. Scelsi Clínica Malattie Nervöse e Mentall, and Istituto d¡ Anatomía Patológica, Università di Pavia. Pavia
Key Words. Late onset myopathy • Lipid storage myopathy • Type I fibre atro phy • Prednisone therapy Abstract. A 65-year-old woman showed the clinical picture of a myogenic my opathy, confirmed electromyographically. Detailed histopathological, histochemical and ultrastructural studies were performed on deltoid and quadriceps femoris biop sy specimens. Many muscle fibres were found to contain vacuolar spaces with lipid droplets: perivascular inflammatory changes were also observed. The affected fibres were consistently type I. Under the electron microscope the fibres contained large numbers of lipid droplets, usually next to normal mitochondria. A slight improve ment occurred after prednisone therapy.
Received: June 15, 1974; accepted: August 17, 1974.
Downloaded by: Vanderbilt University Library 129.59.95.115 - 1/13/2019 7:26:28 PM
In the past few years a group of chronic myopathies characterized by accumulation of fat within muscular fibres have been described and rec ognized as ‘lipid storage myopathy’ [2, 3, 5, 8, 13]. In some cases abnor mal muscle mitochondria may exist [4], but in others the presence of an extramitochondrial defect of lipid metabolism is assumed. The cases ob served so far began in juvenile or middle age, with elinical and electromy ographic features similar to those of polymyositis, but with a striking ex cess of lipids in muscle fibres; clinical, electromyographic and morpholog ical disorders responded favourably to treatment with steroids. In this paper a case of lipid storage myopathy of late onset, with some peculiar features, will be reported and discussed.
274
P lNELLl/POLON l/N APPl/SCELSI
Case Report The patient, a 62-year-old female, was first admitted to the Neuropathological Institute in January 1973. No incidence of the disease in relatives was found. In the remote history there was thyroid enlargement at the age of 46, associated with a transitory hyperthyroidism; at about the same age she began to experience some dif ficulty in walking and raising her arms above her head. These symptoms responded to prednisone, given at moderate dosages. There were four episodes characterized by decrease in muscular strength and painful hypersensitivity with scapuloperoneal distribution. Each lasted about 3-5 months, with some phases of improvement in between of more than 1 year of duration. She also reported an abnormal fatigue af ter effort, although she never had cramps or dysphagia. On examination the patient showed striking atrophy at both girdles with severe weakness of the tibioperoneal muscles, intrinsic muscles of the feet and deltoid mus cles; the quadriceps muscles, biceps and triceps brachii were relatively unaffected. The muscle stretch reflexes were absent and no sensory deficit was present. There was no other evidence of neurological disturbance and the general physical exami nation was entirely normal. A provisional diagnosis of chronic polymyositis was suggested and the patient underwent the investigations detailed below.
Usual laboratory tests. On admission the usual laboratory tests on blood and urine gave normal results (erythrocytes, hemoglobin, leuko cytes, blood glucose, blood urea nitrogen, antistreptolysin O titre, C-reactive protein, erythrocyte sedimentation rate, sodium, potassium, Wasserman). The cerebrospinal fluid was normal; protein-bound iodine, free thy roxine and unsaturated thyroxine-binding globulin were in the normal range. Plasma ‘muscle’ enzymes. On admission serum lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) showed a marked rise; glutam ic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT) and aldolase levels were only slightly increased. The values of serum enzymes before and following 4 weeks of prednisone administra tion (100 mg on alternative days) are indicated in table I. Lipid measurements. Fasting blood samples were drawn before and af ter 3 weeks of feeding with an isocaloric diet (1,400 cal/day), high in car bohydrates (20% of the calories as protein, 20% as fat and 60% as car bohydrates). Triglycerides and cholesterol were determined; lipoprotein electrophoresis was performed on each sample. The values obtained are reported in table II.
Downloaded by: Vanderbilt University Library 129.59.95.115 - 1/13/2019 7:26:28 PM
Results
A Case of Late Onset Lipid Storage Myopathy
275
Table I. Serum enzymes levels on admission and following 4 weeks prednisone (100 mg on alternate days) administration Enzymes
Normal values, mU/ml
Patients' values, mU/ml before therapy after therapy
Aldolase SGOT SGPT CPK LDH
0.9-2.5 12 12 50 115
5.7 71 32 547 1,093
0.6 13 9 35 210
Table II. Plasma lipid measurements before and after a diet high in carbohydrates Investigations
Normal values, mg %
Patients’ values, mg % standard values after high carbohydrate diet
Triglycerides Cholesterol ^-Lipoproteins Pre-/f a Chilomicrons
80-140 150-240 45-65 0-10 25-40 0-20
157 232 47.5 15.0 37.5 5.0
187 248 40.3 15.5 44.3 4.5
Plasma insulin response. Plasma insulin and blood glucose responses to oral glucose (0.75 g/kg) and to intravenous tolbutamide (1 g) tolerance tests, were studied. The results, before and after the diet, are included in the normal range. Electromyographic findings. EMG investigations have been performed with Adrian’s needles according to the usual techniques. Activity at rest: Fibrillation potentials were not found in affected mus cles. A marked insertion activity was derived from the short extensor of the toes alone but no spontaneous activity was continuously recorded.
Downloaded by: Vanderbilt University Library 129.59.95.115 - 1/13/2019 7:26:28 PM
A slight hypertriglyceridemia was present, associated with an increase in plasma /(-lipoproteins, especially those of low density, as in type IV hy perlipoproteinemia of F redrickson et al. [10]; after the diet there was a slight increase in triglycerides and cholesterol, with a readjustement of the lipoprotein pattern.
276
P i n e l u / P o l o n i / N ai’p i /S c e l si
V.
Total duration, msec
Total duration, msec
2
Voluntary activity at minimum graded effort: It was difficult to record a regular discharge of single potentials from the muscles examined; in fact there was some interference between the potentials of different MU with resulting polyphasic patterns. On the other hand, in three attempts indi vidual MU polyphasic action potentials could not be obtained for inclu sion in the measured potentials. Therefore the calculated percentage of polyphasic action potentials may be regarded as definitely too low. Voluntary activity at maximum effort: An interference pattern was ob tained in spite of the relatively low muscular strength. In the right biceps and in the short extensor of the toes the maximum amplitude of the inter ference pattern was about 1 mV; in the deltoid muscle 1.5 mV; in the left short extensor and in both quadriceps 4 mV. MU parameters: The measurement of MU potentials generally gave mean amplitude and duration values lower than the normal, with an in creased number of polyphasic potentials. However, in some muscles, es pecially in the brachial biceps and to a lesser extent in the right short ex tensor of the toes and deltoid, the differences from the normal values were more marked, with a regular distribution (fig. 1), while in the quad riceps a large percentage of MU potentials with normal values was found (fig. 2). The strength-duration relation determined in this muscle showed an increased irregularity with chronaxie values of 0.8 msec.
Downloaded by: Vanderbilt University Library 129.59.95.115 - 1/13/2019 7:26:28 PM
Fig.l. Histograms of MU polyphasic action potentials (hatched area) recorded from biceps brachii (open area), n = 37. Fig. 2. Histograms of MU polyphasic action potentials (hatched area) recorded from quadriceps femoris (open area), n = 28.
A Case of Late Onset Lipid Storage Myopathy
277
Fig. 3. Cross-section of deltoid muscle showing empty vacuoles in many fibres; some fibres are more severely affected than others. HE paraffin section. X 190.
Downloaded by: Vanderbilt University Library 129.59.95.115 - 1/13/2019 7:26:28 PM
M response: Right SPE stimulation at the popliteal cavity and at the dorsal ankle gave a measurement of maximum motor conduction velocity of 44.1 m/sec, corresponding to 47.8 m/sec at 37 C; on the left side it was 47.5 m/sec, corresponding to 49 m/sec at 37 °C. By Erb’s point stim ulation a M response from deltoids with 4 msec latence, 3.5 mV ampli tude, 10 msec duration (non-maximal) was recorded; from brachial biceps a response of 6.3 msec latency, 4.6 mV amplitude and 13 msec duration was recorded. Muscle biopsy. Histopathological and histochemical observations were made on biopsies taken from the deltoid and quadriceps femoris muscles. Tissues were fixed in formaldehyde solution for paraffin sections, and frozen in isopentane cooled to 160 C with liquid nitrogen for histochemi cal preparations, according to previously described procedures [1, 7]. Paraffin sections showed a marked variation in size of fibres; a lot of ab normal empty spaces and vacuoles from less than 1 to 5 /
