Muscle biopsies from two patients revealed that numeroustype 2 fibers contained large abnormal areas filled with cylindrical spirals. The cytochemical profile of these cylindrical spirals was sufficiently characteristic that they could be distinguished from tubular aggregates. Their electron microscopic appearance was unmistakable. Their origin and significance are uncertain. The diverse nature of the patients' conditions (cramps and malignancy, and an unusual form of spinocerebellar degeneration) indicate that these abnormal structures are not disease specific. MUSCLE & NERVE
2:282-287
1979
CYLINDRICAL SPIRALS IN HUMAN SKELETAL MUSCLE STIRLING CARPENTER, MD, GEORGE KARPATI, MD, YVES ROBITAILLE, MD, and CALVIN MELMED, MD
T h e abriornial structures which are the subject of this article were found in the skeletal musclc cclls of two patients on muscle biopsy. On cryostat sections, they were prominent; by electron microscopy, they had a peculiar and characteristic form consisting of' cylindrical spirals. We are not aware of any previous report of this unusual morphological finding. A prccise description will aid future recognition. CLINICAL DATA Case 1, A 2Lyear-old man had suffered for many years
from increasingly severe muscle cramps in the legs, which occurred arter exercise arid at night, atid which caused pain that outlasted the cramps. A lymphmytic lyrriphoina had k e r i diagrivsed by lymph node biopsy two years earlier. T h e lymphoma was effectively treated with cyclophosphamide, prednisone, and cyclic chlorambucil. One year folloiving the discowry of the lymphonla, a
Frorn the Departments of Neurology-Neurosurgery and Pathology McGill University the Montreal Neurological Institute (Drs Carpenter and Kar pati), and the Jewish General Hospital (Ors Robitaille and Mdmed) Mon treal Quebec Canada Acknowledgments This work was supported in part by the Medical Research Council of Canada The Muscular DystroDhy Association of Canada and the Killam Memorial Fund of the Montreal Neurological Institute Address reprint requests to Dr Carpenter at the Montreal Neurological Institute 3801 University St Montreal, Quebec, Canada H3A 284 Received for publication November 9 1978 accepted for publication February 2 1979 0148-639X102040282 $00 OO/O 0 1979 Houghton Mifflin Professional Publishex
282
Cylindrical Spirals
rectal carcinoma was found; this was treated by an abdomino-perineal resection. On examination, the patient showed normal strength in all muscles and normal tendon reflexes. There was a mild distal impairment of pain perception in the hands. EMG was normal. Muscle cramps were no^ relieved by clantrolene or diazepam. Case 2. This 53-year-old man has a family hist.ory of a
gait disorder. He had sufrered from progressive ataxia of gait for 15 years. On examination, he showed cercbellar ataxia affecting trunk arid gait, mild bilateral pes cavus, some increased muscle tone in the extremities, and brisk tendon reflexes. Plantar responses were flexor. A11 modalities o f sensation were preserved. He took 110 medication. EMG was normal, as was motor nerve conduction velocity in the right peroneal nerve. Sensory potentials of the right sural nerve were of lower amplitude than normal. A clinical diagnosis was made of an unusual form of heredofamilial spinoccrebellar degeneration. MATERIALS AND METHODS
Biopsies were performed on the left gastrocnemius muscle, left sural nerve, and later on the left biceps muscle of patient 1, and on the left gastrocnemius muscle of patient 2. A batt.cry of histochemical techniques was applied to cryostat sections.FFrom the biceps biopsy of patient 1, scveral 2- x 5-mm fresh pieces of muscle were treated in a horseradish peroxidase loading solution, according to the method of Mokri and Engel.'O From these specimens, transverse and longitudinal cryostat sect.ions
MUSCLE & NERVE
JuliAug 1979
were prepared and observed for peroxidase activity by the method of Graham and Karn0vsky.j Separate portions of each biopsy were removed in an isometric clamp and fixed in 2% glutaralclehyde in cacodylate buffer. Epoxy resin-embedded sections were examined by phase microscopy and electron microscopy. RESULTS
T h e same abnormality was prominent in all biopsies. The most extensive involvement was in the biceps muscle of paticnt 1, where approximately 30% of the muscle fibers contained abnormal structures. ‘They consisted of sharply delimited clusters of small granules, or occasionally rings about 1 p m in diameter (fig. IA, B, and C), which appeared bright red with the modified trichome stain. These presumably correspond to transversely cut cylindrical tubules (vide infra). At times, a cluster of somewhat larger bluish granules surrounded the area of red granules (fig. lC), presumably corresponding to obliquely sectioned cylindrical tubules. The clusters varied in length from 10 to 300 pm; their transverse diameter measured between 5 and 30 pm. T h e fibers harboring these structures were invariably of type 2 (fig. 2A arid B) and were of normal size. Muscle cell nuclei were often found in the midst of the abnormal areas (fig. 1C). With NADH-tetrazolium reductase (NADH-TR), the abnormal structures appeared brown, indicating monoformazan deposition (fig. 2A). They showed 110 activity of succinic dehydrogenase. Periodic acid -Schiff reagent stained them lightly. In the blocks which had been loaded with horseradish peroxidase, there was no trace of entry of peroxidase into the abnormal areas. I n the gastrocnemius biopsy of patient 1, an occasional mildly atrophic muscle fiber was present. Histochemistry.
Numerous groups of abnormal cylindrical structures, which stained darkly with paraphenylenediamine, were seen in the tnuscle fibers (figs. 3 and 4). Each cylinder was about 1 p m in diameter and 10 pin long. Most were oriented parallel t o the long axis of the muscle fiber. Epoxy Resin Histology.
Electron Microscopy. When viewed at low power on transverse sections, the cylinders appeared as roughly rounded profiles composed of alternating dark and clear zones (fig. 5). On higher magnification, each cylinder was composed of a thin band of cytoplasm enclosed between membranes, spiraling toward a rounded central cytoplasmic
Cylindrical Spirals
Figure I . Cryostat sections from the b!ceps biopsy of patient I . (A) Several muscle flbers harbor single or multiple abnormal regions at their periphery which stamed bright red on the original preparation. (B) At higher power in an internally situated abnormal region. individuai granules and annulets can be resolved. In the center of the accumulation, the granules stained red; on the periphery, they appeared dark purple. (C) Three muscle celi nuclei are present within an abnormal area (arrow). Modified tnchrorne, bars = 70 pm.
MUSCLE & NERVE
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283
Figure 3. Semithin epoxy resin section from patient 7. On longitudinal section, cylindrical spirals are seen forming two collections of dark elongated structures near the edge of the muscle fiber. One mass surrounds a nucleus (white arrows). Paraphenylenediamine, phase optics, bar = 10 p n
Figure 2 . Cryostat sections from patient 1 . {A) Almost every type 2 fiber in the field contains one or more abnormal regions (arrows) which stained brown. The peripheries of some collections are bordered by a darker staining line. NADH-TR. (B) The unstained areas on the periphery and occasionally in the center of the dark type 2 fibers contain the cylindrical spirals (four examples marked by arrows). Myofibrillar A TPase, pH 9.3 preincubation. bars = 10 p.m.
area (fig. 6). Coriversely, they could be considered to be formed from the spiral development of an electron-lucent membrane-bound cistern. The rounded cytoplasmic area in the center of each cylinder contained glycogen-like particlcs and sometimes small rounded vesicles. Although the spiral shape was common to all these structures, the width of the cistern separating the cytoplasmic bands varied from place to place, reflecting distortion and compression of the structure (fig. 7). On longitudinal section, the central cytoplasmic area was seen
284
Cylindrical Spirals
Figure 4 Patient I (preparation similar to that in figure 3) Cylindrical spirals (arrow) in cross section appear as a collection of distinct round profiles Bar = 10 p.m
to be continuous with the surrounding cytoplasm at its ends (fig. 8). 'I'he cisterns closest to t h e center generally extended slightly farther longitudinally than those near the periphery of the structure. A new cisternal wrapping \\-as occasionally added along the length of the cylinder. Oblique views tended to produce smudgy irriages of the mcmbranes. Both right-handed and left-handed spirals could be seen adjacent to each other. The diameter of the cylinders varied from 50 to 110 n m . The number of spiral lariiellae varied from 9 to 15. The cytoplasmic bands, when seen clearly in profile, varied in width froin 18 to 24 nm. The limiting membranes \\-ere approxirriatcly 7 r i m in thickness arid showed the usual trilaminar membrane structure. The cisterns varied
MUSCLE & NERVE
JuliAug 1979
considerably in width from 17 to 28 nm. When cytoplasmic bands were in close apposition, an interniediate line 3-nm wide appeared in place of a cistern (fig.7) and was separated from the mcmbrane by a spac:e 4..?-nm thick. On tangential section of the membranes, no suggestion of periodicity could be seen (fig. 9). Slight dilatation of cisterns of sarcoplasmic reticulum was noted in all biopsies. 111 the first biopsy of patient I , three patches of typical tubular aggregatcs were found, although they were not in proximity to any of the cylindrical spirals. In the biopsy of‘ patient 2, certain fibers contained subsarcolemmal mitochondria1 aggregates; the prcsence of intramitochondrial crystalloids was noted in some of these fibers. DISCUSSION Figure 5. Gastrocnemius biopsy. patient 7 . This electron micrograph shows a subsarcolemmal cluster of cylindrical spirals cut in cross section. Bar = 0.5 c.
‘I’he cylindrical spirals (CSs) had a characteristic appearance by histochemistry and electron microscopy. On cryostat aectiori, there was some resemblance to tubular aggregates in the general size and shape of the a c c ~ m u l a t i o n but , ~ ~ within ~ the
Figure 6 This electron micrograph from patient 1 shows cylindr/cal spirals cut transversely Their spiral construction is evident Trilaminar membranes can be seen in places bordering the cytoplasmic bands Bar = 0 7 p r i
Cylindrical Spirals
MUSCLE & NERVE
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285
figure 7. This electron micrograph from patient 1 shows a cylindrical spiral in cross section. Where lateral deformation has caused cytoplasmic bands to come in contact with one another, an intermediate line appears. White arrow shows one such line. Bar = 0.1 prn.
clusters of CSs, one could often resolve the annular shape of transversely cut individual cylinders. Furthermore, with NADH-TR reaction, tubular aggregates appear dark blue, indicating complete reduction of nitroblue tetrazolium to diformazan. while CSs only produce monoformazan, which is brown. Various membranous whorls are encountered in muscle disease^.',^-^ Almost without exception, these appear far less organized than the CSs. CSs bear some resemblance to the spheromembranous bodies produced in experimental muscle by vincristine,2’12 but those tend to have a spherical shape. CSs are clearly different from the “concentric laminated bodies,” “concentric parallel tubules,” and
286
Cylindrical Spirals
Figure 8. In longitudinal and oblique section from patient 1 , parts of at least three cylindrical spirals can be seen. The central cytoplasmic core (two are labeled C) contains glycogen. The staggered arrangement of the ends of cisterns is visible. Bar = 0.1 pm.
“laminated membranous bodies” which were illustrated by Mair and The origin of CSs remains obscure. The failure of horseradish peroxidase to enter the structures suggests that they d o not communicate with the t-tubule system o r with the extracellular space, While some dilatation of the lateral cisterns of the sarcoplasmic reticulum was seen, no connection between sarcoplasmic reticulum and the CSs could be demonstrated. The exclusive occurrence of CSs in type 2 fibers is consistent with the possibility that they develop from a normal membrane system of the muscle cell, since tubular aggregates-which also occur exclusively in type 2 fibers in diverse disease situations-are believed to originate from
MUSCLE & NERVE
JuliAug 1979
Figure 9. No suggestion of periodicity is seen where the membranes of the cylindrical spirals are cut obliquely. Patient 2, bar = 0.1 pn.
lateral cisterns of the sarcoplasmic reticulum4 and can be produced in vitro by anoxic conditions." The occurrence of CSs in patients with markedly different clinical syndromes, without any ohvious common denominator, suggests that they represent yet another response of skeletal muscle cells t o some injury or metabolic disarrangement
which is not disease specific. It also remains unknown whether CSs in themselves can cause any significant dysfunction of muscle fibers that could lead to symptoms. Recognition of cylindrical spirals as a characteristic structure may increase our alertness to their occurrence and may lead, in time, to some knowledge of their significance.
REFERENCES
1 . Carpentcr S, Karpati G, Heller I , Eisen A: Inclusion body niyositis: a distinct variety of idiopathic inflamniatory mvopathy. Neurology (Minneap) 28:8-17, 1978. 2. Clarke JTR, Karpati G, Carpenter S, Wolfe LS: The effect of vincristine on skeletal muscle in the rat: a correlativc histochemical, ultrastructural and chemical study. J Neuropathol ExpNeurol 31:247-266, 1972. 3. Engel WK: Mitochondria1 aggregates in muscle disease. J Historhem Cytochem 12:46-48, 1970. 4. Engel WK, Bishop DU', Cunningham GG: Tubular aggregates in type I1 muscle fibers. Ultrastructural and histochemical correlation. J Crltru.rtmct RPS 31 :507-525, 1970. 5. Graham RC Jr, Karnovsky MJ: 'The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. JHi.rtorh~mCytochem 14:291-302, 1966. 6 . Karpati G, Carpenter S, Eisen A, Aube M, Diniauro S : The adult form of acid nialvase (a-1 ,.l-glucosidase) deficiency. Ann iVeurol 1:276-280, 1977.
Cylindrical Spirals
7. McDonald RD. Engel AG: Experimental chloroquirie myopathy. J Neuropathol Exp Neurol 28:479-498, 1970. 8. hlair WGP, T o m e FMS: Atlas ifthe Ultrastructure ofDisea.wd Human M u d e . Edinburgh and London, Churchill Livingstone, 1972. 9. Markland O N , DAgostino AN: Ultrastructural changer induced in muscle tibers by colchicine. Arch Meurol 24:72-82, 1971. 10. Mokri B, Engel AG: Duchenne dystrophy: electron microscopic findings pointing to a basic or early abnormality in thc plasma mcmhrane of the muscle fiber. Nevroloa (Minneap) 25:1111-1120, 1975. 11. Schiaffino S, Severin E, Caritini M, Sartore S: Tubular aggregates induced by anoxia in isolated rat cell muscle. La6 Invest 37~223-228, 1977. 12. Slotwiner P, Sung SA, Anderson PJ: Spheromemhranous degeneration of muscle induced hy vincristine. Arch N e u d 15:172-176. 1966.
MUSCLE & NERVE
Jul/Aug 1979
287
2:282-287
1979
CYLINDRICAL SPIRALS IN HUMAN SKELETAL MUSCLE STIRLING CARPENTER, MD, GEORGE KARPATI, MD, YVES ROBITAILLE, MD, and CALVIN MELMED, MD
T h e abriornial structures which are the subject of this article were found in the skeletal musclc cclls of two patients on muscle biopsy. On cryostat sections, they were prominent; by electron microscopy, they had a peculiar and characteristic form consisting of' cylindrical spirals. We are not aware of any previous report of this unusual morphological finding. A prccise description will aid future recognition. CLINICAL DATA Case 1, A 2Lyear-old man had suffered for many years
from increasingly severe muscle cramps in the legs, which occurred arter exercise arid at night, atid which caused pain that outlasted the cramps. A lymphmytic lyrriphoina had k e r i diagrivsed by lymph node biopsy two years earlier. T h e lymphoma was effectively treated with cyclophosphamide, prednisone, and cyclic chlorambucil. One year folloiving the discowry of the lymphonla, a
Frorn the Departments of Neurology-Neurosurgery and Pathology McGill University the Montreal Neurological Institute (Drs Carpenter and Kar pati), and the Jewish General Hospital (Ors Robitaille and Mdmed) Mon treal Quebec Canada Acknowledgments This work was supported in part by the Medical Research Council of Canada The Muscular DystroDhy Association of Canada and the Killam Memorial Fund of the Montreal Neurological Institute Address reprint requests to Dr Carpenter at the Montreal Neurological Institute 3801 University St Montreal, Quebec, Canada H3A 284 Received for publication November 9 1978 accepted for publication February 2 1979 0148-639X102040282 $00 OO/O 0 1979 Houghton Mifflin Professional Publishex
282
Cylindrical Spirals
rectal carcinoma was found; this was treated by an abdomino-perineal resection. On examination, the patient showed normal strength in all muscles and normal tendon reflexes. There was a mild distal impairment of pain perception in the hands. EMG was normal. Muscle cramps were no^ relieved by clantrolene or diazepam. Case 2. This 53-year-old man has a family hist.ory of a
gait disorder. He had sufrered from progressive ataxia of gait for 15 years. On examination, he showed cercbellar ataxia affecting trunk arid gait, mild bilateral pes cavus, some increased muscle tone in the extremities, and brisk tendon reflexes. Plantar responses were flexor. A11 modalities o f sensation were preserved. He took 110 medication. EMG was normal, as was motor nerve conduction velocity in the right peroneal nerve. Sensory potentials of the right sural nerve were of lower amplitude than normal. A clinical diagnosis was made of an unusual form of heredofamilial spinoccrebellar degeneration. MATERIALS AND METHODS
Biopsies were performed on the left gastrocnemius muscle, left sural nerve, and later on the left biceps muscle of patient 1, and on the left gastrocnemius muscle of patient 2. A batt.cry of histochemical techniques was applied to cryostat sections.FFrom the biceps biopsy of patient 1, scveral 2- x 5-mm fresh pieces of muscle were treated in a horseradish peroxidase loading solution, according to the method of Mokri and Engel.'O From these specimens, transverse and longitudinal cryostat sect.ions
MUSCLE & NERVE
JuliAug 1979
were prepared and observed for peroxidase activity by the method of Graham and Karn0vsky.j Separate portions of each biopsy were removed in an isometric clamp and fixed in 2% glutaralclehyde in cacodylate buffer. Epoxy resin-embedded sections were examined by phase microscopy and electron microscopy. RESULTS
T h e same abnormality was prominent in all biopsies. The most extensive involvement was in the biceps muscle of paticnt 1, where approximately 30% of the muscle fibers contained abnormal structures. ‘They consisted of sharply delimited clusters of small granules, or occasionally rings about 1 p m in diameter (fig. IA, B, and C), which appeared bright red with the modified trichome stain. These presumably correspond to transversely cut cylindrical tubules (vide infra). At times, a cluster of somewhat larger bluish granules surrounded the area of red granules (fig. lC), presumably corresponding to obliquely sectioned cylindrical tubules. The clusters varied in length from 10 to 300 pm; their transverse diameter measured between 5 and 30 pm. T h e fibers harboring these structures were invariably of type 2 (fig. 2A arid B) and were of normal size. Muscle cell nuclei were often found in the midst of the abnormal areas (fig. 1C). With NADH-tetrazolium reductase (NADH-TR), the abnormal structures appeared brown, indicating monoformazan deposition (fig. 2A). They showed 110 activity of succinic dehydrogenase. Periodic acid -Schiff reagent stained them lightly. In the blocks which had been loaded with horseradish peroxidase, there was no trace of entry of peroxidase into the abnormal areas. I n the gastrocnemius biopsy of patient 1, an occasional mildly atrophic muscle fiber was present. Histochemistry.
Numerous groups of abnormal cylindrical structures, which stained darkly with paraphenylenediamine, were seen in the tnuscle fibers (figs. 3 and 4). Each cylinder was about 1 p m in diameter and 10 pin long. Most were oriented parallel t o the long axis of the muscle fiber. Epoxy Resin Histology.
Electron Microscopy. When viewed at low power on transverse sections, the cylinders appeared as roughly rounded profiles composed of alternating dark and clear zones (fig. 5). On higher magnification, each cylinder was composed of a thin band of cytoplasm enclosed between membranes, spiraling toward a rounded central cytoplasmic
Cylindrical Spirals
Figure I . Cryostat sections from the b!ceps biopsy of patient I . (A) Several muscle flbers harbor single or multiple abnormal regions at their periphery which stamed bright red on the original preparation. (B) At higher power in an internally situated abnormal region. individuai granules and annulets can be resolved. In the center of the accumulation, the granules stained red; on the periphery, they appeared dark purple. (C) Three muscle celi nuclei are present within an abnormal area (arrow). Modified tnchrorne, bars = 70 pm.
MUSCLE & NERVE
JuliAug 1979
283
Figure 3. Semithin epoxy resin section from patient 7. On longitudinal section, cylindrical spirals are seen forming two collections of dark elongated structures near the edge of the muscle fiber. One mass surrounds a nucleus (white arrows). Paraphenylenediamine, phase optics, bar = 10 p n
Figure 2 . Cryostat sections from patient 1 . {A) Almost every type 2 fiber in the field contains one or more abnormal regions (arrows) which stained brown. The peripheries of some collections are bordered by a darker staining line. NADH-TR. (B) The unstained areas on the periphery and occasionally in the center of the dark type 2 fibers contain the cylindrical spirals (four examples marked by arrows). Myofibrillar A TPase, pH 9.3 preincubation. bars = 10 p.m.
area (fig. 6). Coriversely, they could be considered to be formed from the spiral development of an electron-lucent membrane-bound cistern. The rounded cytoplasmic area in the center of each cylinder contained glycogen-like particlcs and sometimes small rounded vesicles. Although the spiral shape was common to all these structures, the width of the cistern separating the cytoplasmic bands varied from place to place, reflecting distortion and compression of the structure (fig. 7). On longitudinal section, the central cytoplasmic area was seen
284
Cylindrical Spirals
Figure 4 Patient I (preparation similar to that in figure 3) Cylindrical spirals (arrow) in cross section appear as a collection of distinct round profiles Bar = 10 p.m
to be continuous with the surrounding cytoplasm at its ends (fig. 8). 'I'he cisterns closest to t h e center generally extended slightly farther longitudinally than those near the periphery of the structure. A new cisternal wrapping \\-as occasionally added along the length of the cylinder. Oblique views tended to produce smudgy irriages of the mcmbranes. Both right-handed and left-handed spirals could be seen adjacent to each other. The diameter of the cylinders varied from 50 to 110 n m . The number of spiral lariiellae varied from 9 to 15. The cytoplasmic bands, when seen clearly in profile, varied in width froin 18 to 24 nm. The limiting membranes \\-ere approxirriatcly 7 r i m in thickness arid showed the usual trilaminar membrane structure. The cisterns varied
MUSCLE & NERVE
JuliAug 1979
considerably in width from 17 to 28 nm. When cytoplasmic bands were in close apposition, an interniediate line 3-nm wide appeared in place of a cistern (fig.7) and was separated from the mcmbrane by a spac:e 4..?-nm thick. On tangential section of the membranes, no suggestion of periodicity could be seen (fig. 9). Slight dilatation of cisterns of sarcoplasmic reticulum was noted in all biopsies. 111 the first biopsy of patient I , three patches of typical tubular aggregatcs were found, although they were not in proximity to any of the cylindrical spirals. In the biopsy of‘ patient 2, certain fibers contained subsarcolemmal mitochondria1 aggregates; the prcsence of intramitochondrial crystalloids was noted in some of these fibers. DISCUSSION Figure 5. Gastrocnemius biopsy. patient 7 . This electron micrograph shows a subsarcolemmal cluster of cylindrical spirals cut in cross section. Bar = 0.5 c.
‘I’he cylindrical spirals (CSs) had a characteristic appearance by histochemistry and electron microscopy. On cryostat aectiori, there was some resemblance to tubular aggregates in the general size and shape of the a c c ~ m u l a t i o n but , ~ ~ within ~ the
Figure 6 This electron micrograph from patient 1 shows cylindr/cal spirals cut transversely Their spiral construction is evident Trilaminar membranes can be seen in places bordering the cytoplasmic bands Bar = 0 7 p r i
Cylindrical Spirals
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285
figure 7. This electron micrograph from patient 1 shows a cylindrical spiral in cross section. Where lateral deformation has caused cytoplasmic bands to come in contact with one another, an intermediate line appears. White arrow shows one such line. Bar = 0.1 prn.
clusters of CSs, one could often resolve the annular shape of transversely cut individual cylinders. Furthermore, with NADH-TR reaction, tubular aggregates appear dark blue, indicating complete reduction of nitroblue tetrazolium to diformazan. while CSs only produce monoformazan, which is brown. Various membranous whorls are encountered in muscle disease^.',^-^ Almost without exception, these appear far less organized than the CSs. CSs bear some resemblance to the spheromembranous bodies produced in experimental muscle by vincristine,2’12 but those tend to have a spherical shape. CSs are clearly different from the “concentric laminated bodies,” “concentric parallel tubules,” and
286
Cylindrical Spirals
Figure 8. In longitudinal and oblique section from patient 1 , parts of at least three cylindrical spirals can be seen. The central cytoplasmic core (two are labeled C) contains glycogen. The staggered arrangement of the ends of cisterns is visible. Bar = 0.1 pm.
“laminated membranous bodies” which were illustrated by Mair and The origin of CSs remains obscure. The failure of horseradish peroxidase to enter the structures suggests that they d o not communicate with the t-tubule system o r with the extracellular space, While some dilatation of the lateral cisterns of the sarcoplasmic reticulum was seen, no connection between sarcoplasmic reticulum and the CSs could be demonstrated. The exclusive occurrence of CSs in type 2 fibers is consistent with the possibility that they develop from a normal membrane system of the muscle cell, since tubular aggregates-which also occur exclusively in type 2 fibers in diverse disease situations-are believed to originate from
MUSCLE & NERVE
JuliAug 1979
Figure 9. No suggestion of periodicity is seen where the membranes of the cylindrical spirals are cut obliquely. Patient 2, bar = 0.1 pn.
lateral cisterns of the sarcoplasmic reticulum4 and can be produced in vitro by anoxic conditions." The occurrence of CSs in patients with markedly different clinical syndromes, without any ohvious common denominator, suggests that they represent yet another response of skeletal muscle cells t o some injury or metabolic disarrangement
which is not disease specific. It also remains unknown whether CSs in themselves can cause any significant dysfunction of muscle fibers that could lead to symptoms. Recognition of cylindrical spirals as a characteristic structure may increase our alertness to their occurrence and may lead, in time, to some knowledge of their significance.
REFERENCES
1 . Carpentcr S, Karpati G, Heller I , Eisen A: Inclusion body niyositis: a distinct variety of idiopathic inflamniatory mvopathy. Neurology (Minneap) 28:8-17, 1978. 2. Clarke JTR, Karpati G, Carpenter S, Wolfe LS: The effect of vincristine on skeletal muscle in the rat: a correlativc histochemical, ultrastructural and chemical study. J Neuropathol ExpNeurol 31:247-266, 1972. 3. Engel WK: Mitochondria1 aggregates in muscle disease. J Historhem Cytochem 12:46-48, 1970. 4. Engel WK, Bishop DU', Cunningham GG: Tubular aggregates in type I1 muscle fibers. Ultrastructural and histochemical correlation. J Crltru.rtmct RPS 31 :507-525, 1970. 5. Graham RC Jr, Karnovsky MJ: 'The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. JHi.rtorh~mCytochem 14:291-302, 1966. 6 . Karpati G, Carpenter S, Eisen A, Aube M, Diniauro S : The adult form of acid nialvase (a-1 ,.l-glucosidase) deficiency. Ann iVeurol 1:276-280, 1977.
Cylindrical Spirals
7. McDonald RD. Engel AG: Experimental chloroquirie myopathy. J Neuropathol Exp Neurol 28:479-498, 1970. 8. hlair WGP, T o m e FMS: Atlas ifthe Ultrastructure ofDisea.wd Human M u d e . Edinburgh and London, Churchill Livingstone, 1972. 9. Markland O N , DAgostino AN: Ultrastructural changer induced in muscle tibers by colchicine. Arch Meurol 24:72-82, 1971. 10. Mokri B, Engel AG: Duchenne dystrophy: electron microscopic findings pointing to a basic or early abnormality in thc plasma mcmhrane of the muscle fiber. Nevroloa (Minneap) 25:1111-1120, 1975. 11. Schiaffino S, Severin E, Caritini M, Sartore S: Tubular aggregates induced by anoxia in isolated rat cell muscle. La6 Invest 37~223-228, 1977. 12. Slotwiner P, Sung SA, Anderson PJ: Spheromemhranous degeneration of muscle induced hy vincristine. Arch N e u d 15:172-176. 1966.
MUSCLE & NERVE
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287
