LETTERS TO THE EDITOR
NEUROGENIC MUSCLE WEAKNESS IN CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA (CPEO) Muscle weakness i i i c l i r o i i i c . pr.ogrcssivc cxxtcrn;il ophtlialrnoplegia (C:PF.O) 1ias l)et:ri artributcd to mitochondr-iaI disease i r i rnuscIe. I.' We rcport ;ui exariipie ot ricurogrriic.mtiscle wrakncss oc:c:urr-ingin CPEO, wliicli has not berii previously documentctl. T w o brothcl-s, ages 38 arid 30 ycal-s. had progr-cssivc cxterrial ct~,htIialriiopl~~gi;i, iietin)st'iisory 1ie;ii.ing loss, gynccomastia, prim;n-y lesticular fhilurc, r-orl-colic dcgcricriitiori, optic at~,opIiy,and kcr;ttopathy. 111 their e;n-ly 20s, slowly progressive iiiuscle weakness and atrophy in a 1~i'"doiiiiiiiiiillylilnb-girdlc clistrihutioti I ~ t l dcvclopetl. ('I'lie o~~Iitli;iltiiologi~. ;ispects ot the c ~ s c s are 1-eported elsewhct c.'")Muscic stretch reflexes were absent in ~ h clegs and clirninishetl in the arms. 'l'hcrc was 110 spasticity. M ~ ~ s c lcrcatinc e kinasc lcvcls wc'i-c corisisteri~lynormal i i i Ijotli bi otlicrs.
The younger brother, who was more severely aflccted, had had left vastus latcralis rnusclc biopsy studies at the age of' 27, which showed 21 mild tiilrscle fibertype grouping. N o ragged-red fibers a d no other histochemical abnormalities were found. N o abnormal rnitochoncltia were found on electron microscopic examjnation. A~ialyscs of glyculytic cnzymcs arid cytoc~irorneoxiclase were IIuring the next three years, tnore inuscle weakness arid atrophy had developed. 1Iis gait wits watldling. Muscle strength testing showed both proxim;tl Icg miiscles a n d foot extensor muscles t o be 4.0 and the proxinial arm muscles to hc 4.5 011 the Medical Researc.h Council scale. I)isr;il cx11-rinity rnuscles were norrnal in strength. Lumbosacral MKI studies showed mild degenerativc disk disc;ise. Motor and sensory nerve conduction studies of the upper and lower extremities w e r e iwmial. ?'lie needlc clcctrodc cxaniination i.evealecl tiotmal insertional activity and no spontai~eotisactivity. Motor
FIGURE 1. A prominent muscle fiber type grouping, consistent with chronic neurogenic atrophy. NADH stain x 50.
MUSCLE & NERVE
December 1990
1183
unit potentials in both lower extremity muscles WCI-c moderately diminished in riurriher and were firing at a rapid rate; they were polyphasic and moderately to markedly increased in duration and amplitude. T h e upper extremity muscles showed mild but similar changes. Biopsy studies of I he right vastus lateralis niuscle showed occasional small group atrophy arid proniirient muscle fiber type grouping (Fig. 1 ). l r i additiori, there were scattered ragged-red fibers. Electron niicroscopic examination revealed abnormal mitochondria characterized by paracrystalline inclusioits. In the older brother, who was less severely affected than the younger brother, electromyography (EMC;) revealed similar, but milder motor unit potential changes on needle electrode examination of both upper and lower extremities. He declined muscle biopsy studies. T h e mitochondrial abrioi-malities found in rnusc:le biopsies arid "myopathic:" changes seen in EMC, studies in some patients are usually the main features of mitochondrial myopathy in C:PE0.4 O u r patients certainly had more than mitochondrial myopathy. There were significant chronic neurogenic motor unit potential changes on EMG and marked chronic denervation atrophy in the muscle biopsy, indicating that lower rnotor neurons, their axons, or both are also affected in a chronic fashion, causing limb-girdle muscle weakness. Our cases thus suggest that mitochondrial disease involves the lower motor neuron as well as many other different organs.5
Michael J. Schwarttman, DO* Hiroshi Mitsumoto, MD* Robert W. Shields, Jr., MD* Melinda L. Estes, MDt David M. Meister, MD# Gregory S. Kosmorsky, DO$ Departments of *Neurology, TPathology, and +Ophthalmology The Cleveland Clinic Foundation 9500 Euclid Avenue, Cleveland, Ohio 44195 I . DiMaur-o S, Bonilla E, Zeviani M, Makagawa M , I k V i v o DC: Mitorhondrial inyopathies. Arm N w r d 1985;I7:52 1 538. 2. Kamieniccka Z,Schrrialbruch H: Neuroniuscular disorders with ahnortnal musclc mitochondria. Znl Ii071 Cy(d 1980; 6 5 3 2 1 -357. 3. Kosmorsky GS, Mcisler DM, Sheeler LA, et al: Farriilial ophthalmoplegia-plus syndrome with rorrical endothclial tiisorder. Naurr,-opklltcilmt,log 1989;5:2? 1-277. 4 . Mitsumoto H, Aprillc JR, Wray SII, Nemni R, Uraclley WG: Chronic progressive external ophthalmoplegia: Clinical, rnotptiologic, arid biochcrnical studies. Nawolo,q 1983; -
33:452-461.
5. Zeviani M , Honilla E, 13cVivo 1)C, DiMauro S: Mitochondrial diseases. Neurol Clzn 198!3;7:123- 156.
STEROID-RESPONSIVE MICROVASCULITIS IN POLYMYALGIA RHEUMATICA I have read the recent article by Bromberg et at' with great interest. If I understood it correctly, in order to explain the impressive clinical and electi-omyographic
1184
improvement of' their 2 patients with polyrriyalgia rlieumatica (PMK) following steroid trcatmriit, the authors have hypothesized a stcroid-responsi\ie rriicrovasculitis that resulted in ischemic damage to the axoils of the motor nerve tertiiinal brariches. I have nevcr- experienced treating I'M K paticn t s whose elcctrodiagriostic cxaniiriations a r d o r muscle biopsics revealed any abnormalities. However, sincc a strong clinical association between I'M K and giant cell arteritis cannot be dcnied, 1 havc tliought that the symptoms of PMK might be an expression of' ari underlying vasculitis not always clinically cvident, ;IS had beer1 suggested by Paullcy a n d Hughes7 some 30 years ago. Accordingly, I take ii special interest i n the recent coricept that a vasculitis involving the nutrient vessels o r the V;IS;Z nervorum plays a crucial role iri the pathologic mechariisrris of the peripheral neuropathics iri giant cell artei-itis.'." having exmiined the yield of laboHellmarin et ratory evaluatioris for occult vasculitis iri their m o i i o neuritis multiplex patients, have pointed out that oiiethird of the untreated patients (ie, 3 of 10 cases) with rnorioneuritis multiplcx of ail unknowii origin irnproved spuittaneoiisly. Further, as Chuaiig ct al.' have mentioned, I makc i t ;I rule to first try a rrnristeroidal anti-inflammatory drug alone, in patients with PMR without clinical vascular syrnptorris o r signs, cspecially for those whosc tcmporal artery biopsies W C I Y found 1.0 be normal. Sonic of these patients I i a v e showri a good hut gl-adual response t n this therapy, in coritrast to the dramatic responsr that is oftcn seeii to thc use of a s t r roid. 'Thus, the possibility exists that an assumcd, uriderlying rnicrovasculitis of' PMK dies Out in the coursc 01' time, aiid that the use of stcroid therapy merely augtrierits the implwverrient 01' the vasculitis. For many y a r s , most of the vasculitic syndi-oiiies werc thought t o be, at least in part, caused by i I r i r n u n o pathogenic rncchariisms. Foremost among these mechanisnis is the irnmune complex model, whcreby antigenantibody complexes either circulate and are deposited in the vesscl walls o r are fomied in situ at the are;! o f iriflammation." 'IIierefixe, I would be intei-csteci iii ixiving furthcr information ;illout the serum levcls of the irriniunoglobulins, the coiriplcmerits, arid thc itniiiune complexes with 1-efcrence t o the 2 reportcd cases b y Bromberg et al, if these levels have been itivestigatccl during the course ot' the steroid therapy. I also would like t o learri the detailed data that resultctl f ' r u i i i the light and electron microscopic examination of' the intramuscular vasa nervorum. since 1 rim irrtrigucd b y tlie suppositiori" that the natural history of the nc~irologic: findings in patierits with small vesscl vasculitis lirriiterl t o the peripheral nervous system car1 be detected simply by an exarninalioii of large scctioris o l the nerve. Hideto Akama, MD Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanornachi, Shinjuku-ku, Tokyo 160, Japan
MUSCLE & NERVE
December 1990
1.
Brombcrg MB,Donofrio PI.), Scgal BM: Stcroid-responsive elcct.romyographic abnoriiialkies in polymydgk rhcumatica. M u r c k N m e 1990;13:138-141.
~ Ilundcr
NEUROGENIC MUSCLE WEAKNESS IN CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA (CPEO) Muscle weakness i i i c l i r o i i i c . pr.ogrcssivc cxxtcrn;il ophtlialrnoplegia (C:PF.O) 1ias l)et:ri artributcd to mitochondr-iaI disease i r i rnuscIe. I.' We rcport ;ui exariipie ot ricurogrriic.mtiscle wrakncss oc:c:urr-ingin CPEO, wliicli has not berii previously documentctl. T w o brothcl-s, ages 38 arid 30 ycal-s. had progr-cssivc cxterrial ct~,htIialriiopl~~gi;i, iietin)st'iisory 1ie;ii.ing loss, gynccomastia, prim;n-y lesticular fhilurc, r-orl-colic dcgcricriitiori, optic at~,opIiy,and kcr;ttopathy. 111 their e;n-ly 20s, slowly progressive iiiuscle weakness and atrophy in a 1~i'"doiiiiiiiiiillylilnb-girdlc clistrihutioti I ~ t l dcvclopetl. ('I'lie o~~Iitli;iltiiologi~. ;ispects ot the c ~ s c s are 1-eported elsewhct c.'")Muscic stretch reflexes were absent in ~ h clegs and clirninishetl in the arms. 'l'hcrc was 110 spasticity. M ~ ~ s c lcrcatinc e kinasc lcvcls wc'i-c corisisteri~lynormal i i i Ijotli bi otlicrs.
The younger brother, who was more severely aflccted, had had left vastus latcralis rnusclc biopsy studies at the age of' 27, which showed 21 mild tiilrscle fibertype grouping. N o ragged-red fibers a d no other histochemical abnormalities were found. N o abnormal rnitochoncltia were found on electron microscopic examjnation. A~ialyscs of glyculytic cnzymcs arid cytoc~irorneoxiclase were IIuring the next three years, tnore inuscle weakness arid atrophy had developed. 1Iis gait wits watldling. Muscle strength testing showed both proxim;tl Icg miiscles a n d foot extensor muscles t o be 4.0 and the proxinial arm muscles to hc 4.5 011 the Medical Researc.h Council scale. I)isr;il cx11-rinity rnuscles were norrnal in strength. Lumbosacral MKI studies showed mild degenerativc disk disc;ise. Motor and sensory nerve conduction studies of the upper and lower extremities w e r e iwmial. ?'lie needlc clcctrodc cxaniination i.evealecl tiotmal insertional activity and no spontai~eotisactivity. Motor
FIGURE 1. A prominent muscle fiber type grouping, consistent with chronic neurogenic atrophy. NADH stain x 50.
MUSCLE & NERVE
December 1990
1183
unit potentials in both lower extremity muscles WCI-c moderately diminished in riurriher and were firing at a rapid rate; they were polyphasic and moderately to markedly increased in duration and amplitude. T h e upper extremity muscles showed mild but similar changes. Biopsy studies of I he right vastus lateralis niuscle showed occasional small group atrophy arid proniirient muscle fiber type grouping (Fig. 1 ). l r i additiori, there were scattered ragged-red fibers. Electron niicroscopic examination revealed abnormal mitochondria characterized by paracrystalline inclusioits. In the older brother, who was less severely affected than the younger brother, electromyography (EMC;) revealed similar, but milder motor unit potential changes on needle electrode examination of both upper and lower extremities. He declined muscle biopsy studies. T h e mitochondrial abrioi-malities found in rnusc:le biopsies arid "myopathic:" changes seen in EMC, studies in some patients are usually the main features of mitochondrial myopathy in C:PE0.4 O u r patients certainly had more than mitochondrial myopathy. There were significant chronic neurogenic motor unit potential changes on EMG and marked chronic denervation atrophy in the muscle biopsy, indicating that lower rnotor neurons, their axons, or both are also affected in a chronic fashion, causing limb-girdle muscle weakness. Our cases thus suggest that mitochondrial disease involves the lower motor neuron as well as many other different organs.5
Michael J. Schwarttman, DO* Hiroshi Mitsumoto, MD* Robert W. Shields, Jr., MD* Melinda L. Estes, MDt David M. Meister, MD# Gregory S. Kosmorsky, DO$ Departments of *Neurology, TPathology, and +Ophthalmology The Cleveland Clinic Foundation 9500 Euclid Avenue, Cleveland, Ohio 44195 I . DiMaur-o S, Bonilla E, Zeviani M, Makagawa M , I k V i v o DC: Mitorhondrial inyopathies. Arm N w r d 1985;I7:52 1 538. 2. Kamieniccka Z,Schrrialbruch H: Neuroniuscular disorders with ahnortnal musclc mitochondria. Znl Ii071 Cy(d 1980; 6 5 3 2 1 -357. 3. Kosmorsky GS, Mcisler DM, Sheeler LA, et al: Farriilial ophthalmoplegia-plus syndrome with rorrical endothclial tiisorder. Naurr,-opklltcilmt,log 1989;5:2? 1-277. 4 . Mitsumoto H, Aprillc JR, Wray SII, Nemni R, Uraclley WG: Chronic progressive external ophthalmoplegia: Clinical, rnotptiologic, arid biochcrnical studies. Nawolo,q 1983; -
33:452-461.
5. Zeviani M , Honilla E, 13cVivo 1)C, DiMauro S: Mitochondrial diseases. Neurol Clzn 198!3;7:123- 156.
STEROID-RESPONSIVE MICROVASCULITIS IN POLYMYALGIA RHEUMATICA I have read the recent article by Bromberg et at' with great interest. If I understood it correctly, in order to explain the impressive clinical and electi-omyographic
1184
improvement of' their 2 patients with polyrriyalgia rlieumatica (PMK) following steroid trcatmriit, the authors have hypothesized a stcroid-responsi\ie rriicrovasculitis that resulted in ischemic damage to the axoils of the motor nerve tertiiinal brariches. I have nevcr- experienced treating I'M K paticn t s whose elcctrodiagriostic cxaniiriations a r d o r muscle biopsics revealed any abnormalities. However, sincc a strong clinical association between I'M K and giant cell arteritis cannot be dcnied, 1 havc tliought that the symptoms of PMK might be an expression of' ari underlying vasculitis not always clinically cvident, ;IS had beer1 suggested by Paullcy a n d Hughes7 some 30 years ago. Accordingly, I take ii special interest i n the recent coricept that a vasculitis involving the nutrient vessels o r the V;IS;Z nervorum plays a crucial role iri the pathologic mechariisrris of the peripheral neuropathics iri giant cell artei-itis.'." having exmiined the yield of laboHellmarin et ratory evaluatioris for occult vasculitis iri their m o i i o neuritis multiplex patients, have pointed out that oiiethird of the untreated patients (ie, 3 of 10 cases) with rnorioneuritis multiplcx of ail unknowii origin irnproved spuittaneoiisly. Further, as Chuaiig ct al.' have mentioned, I makc i t ;I rule to first try a rrnristeroidal anti-inflammatory drug alone, in patients with PMR without clinical vascular syrnptorris o r signs, cspecially for those whosc tcmporal artery biopsies W C I Y found 1.0 be normal. Sonic of these patients I i a v e showri a good hut gl-adual response t n this therapy, in coritrast to the dramatic responsr that is oftcn seeii to thc use of a s t r roid. 'Thus, the possibility exists that an assumcd, uriderlying rnicrovasculitis of' PMK dies Out in the coursc 01' time, aiid that the use of stcroid therapy merely augtrierits the implwverrient 01' the vasculitis. For many y a r s , most of the vasculitic syndi-oiiies werc thought t o be, at least in part, caused by i I r i r n u n o pathogenic rncchariisms. Foremost among these mechanisnis is the irnmune complex model, whcreby antigenantibody complexes either circulate and are deposited in the vesscl walls o r are fomied in situ at the are;! o f iriflammation." 'IIierefixe, I would be intei-csteci iii ixiving furthcr information ;illout the serum levcls of the irriniunoglobulins, the coiriplcmerits, arid thc itniiiune complexes with 1-efcrence t o the 2 reportcd cases b y Bromberg et al, if these levels have been itivestigatccl during the course ot' the steroid therapy. I also would like t o learri the detailed data that resultctl f ' r u i i i the light and electron microscopic examination of' the intramuscular vasa nervorum. since 1 rim irrtrigucd b y tlie suppositiori" that the natural history of the nc~irologic: findings in patierits with small vesscl vasculitis lirriiterl t o the peripheral nervous system car1 be detected simply by an exarninalioii of large scctioris o l the nerve. Hideto Akama, MD Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanornachi, Shinjuku-ku, Tokyo 160, Japan
MUSCLE & NERVE
December 1990
1.
Brombcrg MB,Donofrio PI.), Scgal BM: Stcroid-responsive elcct.romyographic abnoriiialkies in polymydgk rhcumatica. M u r c k N m e 1990;13:138-141.
~ Ilundcr
