Acta Neuropathologica
Acta Neuropathol. (Berl.) 47, 169-174 (1979)
:~) Springer-Verlag 1979
Original Works Fenestrated Blood Vessels in Human Skeletal Muscle N. R. G h a t a k a n d D. N o c h l i n Department of Pathology (Nenropathology), Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
S u m m a r y . In a fine s t r u c t u r a l study o f 32 skeletal muscle biopsies, rare e x a m p l e s o f f e n e s t r a t e d b l o o d vessels (FV) were f o u n d in three cases. In view o f similar o b s e r v a t i o n s r e p o r t e d in a case o f D u c h e n n e m u s c u l a r d y s t r o p h y , it is suggested t h a t F V albeit rare m a y occur in skeletal muscle at least u n d e r p a t h o l o g i c conditions. These a b e r r a n t F V m a y be derived f r o m a d j a c e n t dermis a n d / o r e p i n e u r i u m which are k n o w n to c o n t a i n o c c a s i o n a l FV. A l t e r n a t i v e l y , the occurrence o f fenestrae m a y reflect a nonspecific a l t e r a t i o n in pre-existing c o n t i n u o u s e n d o t h e l i u m . The significance, if any, o f their presence in skeletal muscle is u n k n o w n .
Case 2. A biopsy of the quadriceps muscle was obtained from a 5month-old female child with a clinical diagnosis of WerdnigHoffmann disease. Case 3. A biopsy of gastrocnemius muscle was obtained from a 8month-old male child with generalized hypotonia. The remaining biopsies were classified as follows: Normal or mild nonspecific changes (6), Duchenne and other types of dystrophy (5), denervation atrophy (8), polymyositis (3), nemaline myopathy (3), mitochondrial myopathy (3) and McArdle's disease (1). Small portions of muscles were fixed in 4 ~oglutaraldehyde within 10 min after removal and processed for electron microscopy in the usual manner. In each case at least 5 blocks of tissue were examined and the number of small blood vessels (capillaries and venules) encountered ranged from 20 to 50. Some selected blocks were studied by serial sectioning.
Key words: B l o o d vessels - F e n e s t r a t e d e n d o t h e l i u m - Endothelial pores muscle
-
Endothelium
-
Skeletal
The b l o o d vessels s u p p l y i n g skeletal muscle are characteristically lined by n o n f e n e s t r a t e d e n d o t h e l i u m . D u r i n g a fine s t r u c t u r a l study o f muscle biopsies we p a i d special a t t e n t i o n to the v a s c u l a t u r e a n d f o u n d rare e x a m p l e s o f f e n e s t r a t e d b l o o d vessels (FV). D e s p i t e extensive m o r p h o l o g i c i n v e s t i g a t i o n o f skeletal muscle, this feature has n o t been e m p h a s i z e d previously. In this r e p o r t we discuss o u r findings in view o f the recent interest in a b e r r a n t F V in the n e r v o u s system u n d e r certain p a t h o l o g i c conditions.
Materials and Methods Biopsies of limb muscles from 32 patients were studied. Three cases in which FV were found are briefly described. Case l. This is a 27-year-old man with long history of muscle weakness. A diagnosis of Charcot-Marie-Tooth disease was made on the basis of clinical features and family history. A biopsy of the gastrocnemius muscle was performed.
Results Case 1. The m a j o r changes consisted o f d e n e r v a t i o n a t r o p h y a c c o m p a n i e d by certain m y o p a t h i c features. T y p i c a l e n d o t h e l i a l f e n e s t r a t i o n was seen in 2 o f 35 vessels (Fig. 1). The pores measures a b o u t 7 0 n m in d i a m e t e r a n d were b r i d g e d b y a d i a p h r a g m . B o t h F V were seen in the vicinity o f an i n t r a m u s c u l a r nerve c o n t a i n i n g a single m y e l i n a t e d axon. Case 2. The muscle s h o w e d d e n e r v a t i o n a t r o p h y characteristically seen in W e r d n i g - H o f f m a n n disease. A m o n g 42 b l o o d vessels, 3 s h o w e d f e n e s t r a t i o n (Fig. 2). These vessels o c c u r r e d in the interstitial connective tissue a n d were n o t r e l a t e d to nerve fibers. Case 3. T h e r e was a slight degree o f v a r i a b i l i t y in the size o f the muscle fibers. N o specific p a t h o l o g i c changes were noted. A t o t a l o f 22 vessels were studied one o f which was f e n e s t r a t e d (Fig. 3). This vessel was situated next to n o r m a l - a p p e a r i n g muscle fibers. A variable degree o f e n d o t h e l i a l a t t e n t u a t i o n was seen in an o c c a s i o n a l vessel in several cases. S o m e o f these areas closely r e s e m b l e d i s o l a t e d fenestrae (Fig. 4). A n u m b e r o f b l o o d vessels n e a r i n t r a m u s c u l a r nerves were e n c o u n t e r e d n o n e o f w h i c h was fenestrated.
0001-6322/79/0047/0169/$1.20
170
Acta Neuropathol. (Berl.) 47 (1979)
Fig. 1. a Two fenestrated blood vessels (V) adjacent to an intramuscular nerve (Case 1). x 5,280. b Higher magnification of endothelial pores indicated by arrows, x 48,000
Discussion Whether the FV in Case 1 were intrinsic to the intramuscular nerve or the muscle tissue itself remains uncertain. In either case, their presence must be considered as an unusual feature since the blood vessels accompanying intramuscular nerves are not known to be of fenestrated type. In addition to the typical FV in three cases, the occasional observation of focal endothelial attenuation resembling pores, is of interest.
However, such isolated zones may very well be the result of adjoining pinocytotic vesicles at the luminal and abluminal surfaces of the endothelium rather than true pores. Vascular morphology in normal and pathologic human skeletal muscles has been studied in detail (Vracko, 1970; Mair and Tom6, 1972; Musch et al., 1975; Mfikitie, 1977; Reske-Nielson et al., 1977). However, to our knowledge, the presence of FV has been reported only recently in a study dealing with the
N. R. Ghatak and D. Nochlin- Fenestrated Blood Vessels in Human Skeletal Muscle
t71
Fig. 2. A fenestrated blood vessel in the interstitium of muscle. Arrows indicate typical pores (Case 2). x 19,200
vascular structure in Duchenne muscular dystrophy (Koehler, 1977). O f 5 cases studied, only 3 FV were found in a single case in which about 900 vessels were examined. The author also mentioned of 2 other cases of non-Duchenne dystrophy with rare FV. A similar phenomenon has been reported in rat skeletal muscle (Hammersen, 1966; Korneliussen, 1975). The FV were observed close to the muscle fibers as well as in the perimysial connective tissue. Korneliussen (1975) esti-
mated that enditheliaI fenestrae, both isolated and in groups, occurred in one of about 60 capillaries in all 9 animals studied. On careful search in the present study, we found a small number of FV in 3 of 32 cases. F r o m these observations it would seem that FV, although distinctly rare, may occur in skeletal muscle in humans and perhaps in other species as well. Clearly, such vessels may not be included in the samples selected for electron microscopic study or they may be easily
172
Acta Neuropathol. (Berl.)47 (1979)
Fig. 3. An intramuscular capillary showing fenestrae (arrows) in case 3. x 18,000
overlooked. This may explain why their presence in skeletal muscles had gone undetected in the past. The presence of FV in human muscle observed so far seems to be limited to pathologic conditions of dissimilar nature thus suggesting a nonspecific phenomenon like that described in the endoneurium of peripheral nerves. Fenestrated endothelium has been observed in the endoneurial vessels in leprosy (Boddingius, 1977), focal chronic demyelinating neuropathy and in scar tissue following infarction (Johnson, 1977). Since the endoneurial vessels are known to be relatively impermeable to various protein tracers it has been suggested that the FV may play a pathogenetic role in some cases presumably by disrupting the blood-nerve barrier (Johnson, 1977; Asbury and Johnson, 1978). However, a similar role of the rare F V in muscles would seem doubtful since muscle capillaries are normally perme-
able to protein tracers (Simonescu et al., 1975; Wissig and Williams, 1978). It should be mentioned that endothelial fenestrae have been observed in normal sensory and autonomic ganglia (Anzil et al., 1976; Jacobs et al., 1976; Asbury and Johnson, 1978) as well as in the epineurium of peripheral nerves (Olsson, 1975). The presence of aberrant FV is perhaps best exemplified in a variety of intracranial neoplasms. Hirano and his associates (1972, 1973, 1974, 1975) have studied this phenomenon which seems to be responsible at least in part for the breakdown of blood-brain barrier and subsequently edema associated with these tumors. The origin of these specialized blood vessels supplying the neoplastic tissue is not clear. The newly formed FV in most instances seem to be derived from the neighboring cerebral or meningeal vessels which are
N. R. Ghatak and D. Nochlin : Fenestrated Blood Vessels in Human Skeletal Muscle
173
Fig. 4a and b. Focal attenuation of capillary endothelium resembling pores (arrows). a • 33,320; b x 41,160
characteristically nonfenestrated. It has been postulated that the neoplastic process may be an important factor in inducing such vascular alteration (Hirano and Matsui, 1975). On the other hand, the FV in such tumors, as craniopharyngioma or optic nerve glioma may be derived from the vessels supplying the hypothalamus or hypophysis some of which are normally fenestrated. It is difficult to account for the presence of FV in non-neoplastic conditions involving muscles and peripheral nerves. Two possibilities similar to those sug-
gested in neoplastic conditions might be considered. Conceivably, fenestrae may occur in the pre-existing continuous endothelium as a nonspecific alteration somehow induced by the pathologic process or by some other unknown factors (Korneliussen, 1975; Anzit et al., 1976). Alternatively, they may be derived from certain adjacent tissues that normally contain FV. Indeed FV have been described in the dermis of the skin (Takada and Hattori, 1972) and the epineurium of peripheral nerves (Olsson, 1975). It seems reasonable to assume that occasional FV in skeletal muscles and
174 p e r h a p s also i n the e n d o n e u r i u m r e p r e s e n t a n i n g r o w t h o f these vessels f r o m a d j a c e n t d e r m i s a n d / o r epin e u r i u m especially u n d e r p a t h o l o g i c c o n d i t i o n s . W h a t e v e r the e x p l a n a t i o n , the p r e s e n c e o f a b e r r a n t F V in skeletal m u s c l e is a n i n t e r e s t i n g p h e n o m e n o n alt h o u g h its significance, if a n y , is difficult to ascertain.
Acknowledgement. The author thanks Dr. Edward E. Isaacs, Department of Neurology, Medical College of Virginia, for providing most of the muscle biopsy specimens.
References Anzil, A. P., Blinzinger, K., Herrlinger, H. : Fenestrated blood capillaries in rat cranio-spinal sensory ganglia. Cell Tissue Res. 167, 563-567 (1976) Asbury, A. K., Johnson, P. C.: Pathology of peripheral nerve. Philadelphia: Saunders 1978 Boddingius, J. : Ultrastructural changes in blood vessels of peripheral nerves in leprosy neuropathy. II. Borderline, borderlinelepromatous, and lepromatous leprosy patients. Acta Neuropathol. (Bed.) 40, 2 1 - 3 9 (1977) Hammersen, F. :Poren- und Fensterendotheliender Kapillaren in der Skeletmuskulatur der Ratte. Z. Zellforsch. 69, 296-310 (1966) Hirano, A., .Zimmerman, H. M. : Fenestrated blood vessels in a metastatic renal carcinoma in the brain. Lab. Invest. 26, 465-468 (1972) Hirano, A., Ghatak, N. R., Zimmerman, H. M. : Fenestrated blood vessels in craniopharyngioma. Acta Neuropathol. (Berl.) 26, 171-176 (1973) Hirano, A., Ghatak, N. R., Becker, N. H., Zimmerman, H. M. : A comparison of the fine structure of small blood vessels in intracranial and retroperitoneal malignant lymphomas. Acta Neuropathol. (Bed.) 27, 93-104 (1974) Hirano, A., Matsui, T. : Vascular structures in brain tumors, ttuman Pathol. 6, 611-621 (1975)
Acta Neuropathol. (Berl.) 47 (1979) Jacobs, J. M., Macfarlene, R. M., Cavanagh, J. B. : Vascular leakage in the dorsal root ganglia of the rat studied with horseradish peroxidase. J. Neurol. Sci. 29, 95-107 (1976) Johnson, P. C. : Fenestrated endothelium in human peripheral nervous system. J. Neuropathol. Exp. Neurol. 36, 607 (1977) Koehler, J. : Blood vessel structure in Duchenne muscular dystrophy. 1. Light and electron microscopic observations in resting muscle. Neurology (Minneap.) 27, 861- 868 (1977) Korneliussen, H.: Fenestrated blood capillaries and lymphatic capillaries in rat skeletal muscle. Cell Tissue Res. 163, 169-174 (1975) Mair, W. G. P., Tom6, F. M. S. : Atlas of the ultrastructure of diseased human muscle. Edinburgh, London: Churchill Livingstone 1972 M~ikitie, J. : Skeletal muscle capillaries in intermittent claudiction. Arch. Pathol. Lab. Med. 101, 500-503 (1977) Musch, B. C., Papapetropolous, T. A., McQueen, D. A., Hudgson, P., Weightman, D. : A comparison of the ultrastructure of small blood vessels in normal, denervated, and dystrophic human muscle. J. Neurol. Sci. 26, 221-234 (1975) Olsson, Y. : Vascular permeability in the peripheral nervous system in peripheral neuropathy, Vol. 1. Dyck, P.J., Thomas, P. K., Lambert, E. H. (eds.). Philadelphia: Saunders 1975 Simionescu, N., Simionescu, M., Palade, G. E.: Permeability of muscle capillaries to small heme-peptides. Evidence for the existence of patent transendothelial channels. J. Cell Biol. 64, 586- 607 (1975) Takada, M., Hattori, S. : Presence of fenestrated capillaries in the skin. Anat. Rec. 173, 213-220 (1972) Vracko, R. : Skeletal muscle capillaries in diabetics. A quantitative analysis. Circulation 41, 271-283 (1970) Reske-Nielsen, E., Harmsen, A., Vorre, P. : Ultrastructure of muscle biopsies in recent, short-term and long-term juvenile diabetes. Acta Neurol. Scand. 55, 345-362 (1977) Wissig, S., Williams, M. C. : Permeability of muscle capillaries to microperoxidase. J. Cell Biol. 76, 341- 359 (1978) Received March 19, 1979 / Accep ted April 26, 1979
Acta Neuropathol. (Berl.) 47, 169-174 (1979)
:~) Springer-Verlag 1979
Original Works Fenestrated Blood Vessels in Human Skeletal Muscle N. R. G h a t a k a n d D. N o c h l i n Department of Pathology (Nenropathology), Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
S u m m a r y . In a fine s t r u c t u r a l study o f 32 skeletal muscle biopsies, rare e x a m p l e s o f f e n e s t r a t e d b l o o d vessels (FV) were f o u n d in three cases. In view o f similar o b s e r v a t i o n s r e p o r t e d in a case o f D u c h e n n e m u s c u l a r d y s t r o p h y , it is suggested t h a t F V albeit rare m a y occur in skeletal muscle at least u n d e r p a t h o l o g i c conditions. These a b e r r a n t F V m a y be derived f r o m a d j a c e n t dermis a n d / o r e p i n e u r i u m which are k n o w n to c o n t a i n o c c a s i o n a l FV. A l t e r n a t i v e l y , the occurrence o f fenestrae m a y reflect a nonspecific a l t e r a t i o n in pre-existing c o n t i n u o u s e n d o t h e l i u m . The significance, if any, o f their presence in skeletal muscle is u n k n o w n .
Case 2. A biopsy of the quadriceps muscle was obtained from a 5month-old female child with a clinical diagnosis of WerdnigHoffmann disease. Case 3. A biopsy of gastrocnemius muscle was obtained from a 8month-old male child with generalized hypotonia. The remaining biopsies were classified as follows: Normal or mild nonspecific changes (6), Duchenne and other types of dystrophy (5), denervation atrophy (8), polymyositis (3), nemaline myopathy (3), mitochondrial myopathy (3) and McArdle's disease (1). Small portions of muscles were fixed in 4 ~oglutaraldehyde within 10 min after removal and processed for electron microscopy in the usual manner. In each case at least 5 blocks of tissue were examined and the number of small blood vessels (capillaries and venules) encountered ranged from 20 to 50. Some selected blocks were studied by serial sectioning.
Key words: B l o o d vessels - F e n e s t r a t e d e n d o t h e l i u m - Endothelial pores muscle
-
Endothelium
-
Skeletal
The b l o o d vessels s u p p l y i n g skeletal muscle are characteristically lined by n o n f e n e s t r a t e d e n d o t h e l i u m . D u r i n g a fine s t r u c t u r a l study o f muscle biopsies we p a i d special a t t e n t i o n to the v a s c u l a t u r e a n d f o u n d rare e x a m p l e s o f f e n e s t r a t e d b l o o d vessels (FV). D e s p i t e extensive m o r p h o l o g i c i n v e s t i g a t i o n o f skeletal muscle, this feature has n o t been e m p h a s i z e d previously. In this r e p o r t we discuss o u r findings in view o f the recent interest in a b e r r a n t F V in the n e r v o u s system u n d e r certain p a t h o l o g i c conditions.
Materials and Methods Biopsies of limb muscles from 32 patients were studied. Three cases in which FV were found are briefly described. Case l. This is a 27-year-old man with long history of muscle weakness. A diagnosis of Charcot-Marie-Tooth disease was made on the basis of clinical features and family history. A biopsy of the gastrocnemius muscle was performed.
Results Case 1. The m a j o r changes consisted o f d e n e r v a t i o n a t r o p h y a c c o m p a n i e d by certain m y o p a t h i c features. T y p i c a l e n d o t h e l i a l f e n e s t r a t i o n was seen in 2 o f 35 vessels (Fig. 1). The pores measures a b o u t 7 0 n m in d i a m e t e r a n d were b r i d g e d b y a d i a p h r a g m . B o t h F V were seen in the vicinity o f an i n t r a m u s c u l a r nerve c o n t a i n i n g a single m y e l i n a t e d axon. Case 2. The muscle s h o w e d d e n e r v a t i o n a t r o p h y characteristically seen in W e r d n i g - H o f f m a n n disease. A m o n g 42 b l o o d vessels, 3 s h o w e d f e n e s t r a t i o n (Fig. 2). These vessels o c c u r r e d in the interstitial connective tissue a n d were n o t r e l a t e d to nerve fibers. Case 3. T h e r e was a slight degree o f v a r i a b i l i t y in the size o f the muscle fibers. N o specific p a t h o l o g i c changes were noted. A t o t a l o f 22 vessels were studied one o f which was f e n e s t r a t e d (Fig. 3). This vessel was situated next to n o r m a l - a p p e a r i n g muscle fibers. A variable degree o f e n d o t h e l i a l a t t e n t u a t i o n was seen in an o c c a s i o n a l vessel in several cases. S o m e o f these areas closely r e s e m b l e d i s o l a t e d fenestrae (Fig. 4). A n u m b e r o f b l o o d vessels n e a r i n t r a m u s c u l a r nerves were e n c o u n t e r e d n o n e o f w h i c h was fenestrated.
0001-6322/79/0047/0169/$1.20
170
Acta Neuropathol. (Berl.) 47 (1979)
Fig. 1. a Two fenestrated blood vessels (V) adjacent to an intramuscular nerve (Case 1). x 5,280. b Higher magnification of endothelial pores indicated by arrows, x 48,000
Discussion Whether the FV in Case 1 were intrinsic to the intramuscular nerve or the muscle tissue itself remains uncertain. In either case, their presence must be considered as an unusual feature since the blood vessels accompanying intramuscular nerves are not known to be of fenestrated type. In addition to the typical FV in three cases, the occasional observation of focal endothelial attenuation resembling pores, is of interest.
However, such isolated zones may very well be the result of adjoining pinocytotic vesicles at the luminal and abluminal surfaces of the endothelium rather than true pores. Vascular morphology in normal and pathologic human skeletal muscles has been studied in detail (Vracko, 1970; Mair and Tom6, 1972; Musch et al., 1975; Mfikitie, 1977; Reske-Nielson et al., 1977). However, to our knowledge, the presence of FV has been reported only recently in a study dealing with the
N. R. Ghatak and D. Nochlin- Fenestrated Blood Vessels in Human Skeletal Muscle
t71
Fig. 2. A fenestrated blood vessel in the interstitium of muscle. Arrows indicate typical pores (Case 2). x 19,200
vascular structure in Duchenne muscular dystrophy (Koehler, 1977). O f 5 cases studied, only 3 FV were found in a single case in which about 900 vessels were examined. The author also mentioned of 2 other cases of non-Duchenne dystrophy with rare FV. A similar phenomenon has been reported in rat skeletal muscle (Hammersen, 1966; Korneliussen, 1975). The FV were observed close to the muscle fibers as well as in the perimysial connective tissue. Korneliussen (1975) esti-
mated that enditheliaI fenestrae, both isolated and in groups, occurred in one of about 60 capillaries in all 9 animals studied. On careful search in the present study, we found a small number of FV in 3 of 32 cases. F r o m these observations it would seem that FV, although distinctly rare, may occur in skeletal muscle in humans and perhaps in other species as well. Clearly, such vessels may not be included in the samples selected for electron microscopic study or they may be easily
172
Acta Neuropathol. (Berl.)47 (1979)
Fig. 3. An intramuscular capillary showing fenestrae (arrows) in case 3. x 18,000
overlooked. This may explain why their presence in skeletal muscles had gone undetected in the past. The presence of FV in human muscle observed so far seems to be limited to pathologic conditions of dissimilar nature thus suggesting a nonspecific phenomenon like that described in the endoneurium of peripheral nerves. Fenestrated endothelium has been observed in the endoneurial vessels in leprosy (Boddingius, 1977), focal chronic demyelinating neuropathy and in scar tissue following infarction (Johnson, 1977). Since the endoneurial vessels are known to be relatively impermeable to various protein tracers it has been suggested that the FV may play a pathogenetic role in some cases presumably by disrupting the blood-nerve barrier (Johnson, 1977; Asbury and Johnson, 1978). However, a similar role of the rare F V in muscles would seem doubtful since muscle capillaries are normally perme-
able to protein tracers (Simonescu et al., 1975; Wissig and Williams, 1978). It should be mentioned that endothelial fenestrae have been observed in normal sensory and autonomic ganglia (Anzil et al., 1976; Jacobs et al., 1976; Asbury and Johnson, 1978) as well as in the epineurium of peripheral nerves (Olsson, 1975). The presence of aberrant FV is perhaps best exemplified in a variety of intracranial neoplasms. Hirano and his associates (1972, 1973, 1974, 1975) have studied this phenomenon which seems to be responsible at least in part for the breakdown of blood-brain barrier and subsequently edema associated with these tumors. The origin of these specialized blood vessels supplying the neoplastic tissue is not clear. The newly formed FV in most instances seem to be derived from the neighboring cerebral or meningeal vessels which are
N. R. Ghatak and D. Nochlin : Fenestrated Blood Vessels in Human Skeletal Muscle
173
Fig. 4a and b. Focal attenuation of capillary endothelium resembling pores (arrows). a • 33,320; b x 41,160
characteristically nonfenestrated. It has been postulated that the neoplastic process may be an important factor in inducing such vascular alteration (Hirano and Matsui, 1975). On the other hand, the FV in such tumors, as craniopharyngioma or optic nerve glioma may be derived from the vessels supplying the hypothalamus or hypophysis some of which are normally fenestrated. It is difficult to account for the presence of FV in non-neoplastic conditions involving muscles and peripheral nerves. Two possibilities similar to those sug-
gested in neoplastic conditions might be considered. Conceivably, fenestrae may occur in the pre-existing continuous endothelium as a nonspecific alteration somehow induced by the pathologic process or by some other unknown factors (Korneliussen, 1975; Anzit et al., 1976). Alternatively, they may be derived from certain adjacent tissues that normally contain FV. Indeed FV have been described in the dermis of the skin (Takada and Hattori, 1972) and the epineurium of peripheral nerves (Olsson, 1975). It seems reasonable to assume that occasional FV in skeletal muscles and
174 p e r h a p s also i n the e n d o n e u r i u m r e p r e s e n t a n i n g r o w t h o f these vessels f r o m a d j a c e n t d e r m i s a n d / o r epin e u r i u m especially u n d e r p a t h o l o g i c c o n d i t i o n s . W h a t e v e r the e x p l a n a t i o n , the p r e s e n c e o f a b e r r a n t F V in skeletal m u s c l e is a n i n t e r e s t i n g p h e n o m e n o n alt h o u g h its significance, if a n y , is difficult to ascertain.
Acknowledgement. The author thanks Dr. Edward E. Isaacs, Department of Neurology, Medical College of Virginia, for providing most of the muscle biopsy specimens.
References Anzil, A. P., Blinzinger, K., Herrlinger, H. : Fenestrated blood capillaries in rat cranio-spinal sensory ganglia. Cell Tissue Res. 167, 563-567 (1976) Asbury, A. K., Johnson, P. C.: Pathology of peripheral nerve. Philadelphia: Saunders 1978 Boddingius, J. : Ultrastructural changes in blood vessels of peripheral nerves in leprosy neuropathy. II. Borderline, borderlinelepromatous, and lepromatous leprosy patients. Acta Neuropathol. (Bed.) 40, 2 1 - 3 9 (1977) Hammersen, F. :Poren- und Fensterendotheliender Kapillaren in der Skeletmuskulatur der Ratte. Z. Zellforsch. 69, 296-310 (1966) Hirano, A., .Zimmerman, H. M. : Fenestrated blood vessels in a metastatic renal carcinoma in the brain. Lab. Invest. 26, 465-468 (1972) Hirano, A., Ghatak, N. R., Zimmerman, H. M. : Fenestrated blood vessels in craniopharyngioma. Acta Neuropathol. (Berl.) 26, 171-176 (1973) Hirano, A., Ghatak, N. R., Becker, N. H., Zimmerman, H. M. : A comparison of the fine structure of small blood vessels in intracranial and retroperitoneal malignant lymphomas. Acta Neuropathol. (Bed.) 27, 93-104 (1974) Hirano, A., Matsui, T. : Vascular structures in brain tumors, ttuman Pathol. 6, 611-621 (1975)
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