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Ischemic Monomelic Neuropathy: An Under-Recognized Complication of Hemodialysis Access
Ischemic Monomelic Neuropathy: An Under-Recognized Complication of Hemodialysis Access Robert J. Hye, MD, and Yehuda G. Wolf MD, San Diego, California
During the past 3 years six episodes of ischemic monomelic neuropathy (IMN) have been identified in five patients as a complication of upper extremity dialysis grafts. All patients had long-standing insulin-dependent diabetes, peripheral neuropathy, and brachial artery graft origins, whereas 60% had peripheral vascular disease. Five episodes occurred immediately after graft placement, whereas one was due to a graft-related thromboembolus. Diagnostic delay was common with initial findings attributed to anesthesia, positioning, or surgical trauma. Electrophysiologic studies showed underlying diabetic neuropathy with severe multifocal neuropathy distal to the grafts. Digital pressure indices were reduced but there was no critica~ ischemia. In three cases ischemia was completely corrected with improvement in one. One patient had proximal balloon angioplasty with no improvement and of the two untreated patients, one improved slightly. Ischemic monomelic neuropathy is a rare but disabling complication of dialysis access in diabetic uremic patients. Its occurrence is unpredictable and diagnostic delay is common. Correction of ischemia is indicated but usually does not improve the neuropathy. Prevention requires further research to more accurately characterize the patients at risk. (Ann Vasc Surg 1994;8:578-582.)
Broadened indications, as well as increasing age and survival of the population with chronic renal failure, have resulted in an increased necessity for hemodialysis access in patients with advanced atherosclerosis and complications of diabetes. As a consequence, ischemic complications of arteriovenous fistulas and grafts are being encountered with increasing frequency. ~'2 Although thromboembolic complications are well known, ischemia in this setting is more often d u e to a "steal syndrome" or "venous sink" phen o m e n o n where the access diverts blood into the
From the Department of Surgery, University of California, San Diego, Calif. Presented at the Twelfth Annual Meeting of tile Southern California Vascular Surgical Society, Coronado, Calif., September 17-19, 1993. Reprint requests: Robert J. Hye, MD, UCSD Medical Center, 200 W. Arbor Dr., San Diego, CA 92103-8401.
578
low-resistance venous system at the expense of distal arterial perfusion. Two clinical syndromes can occur as a result. The first is the typical presentation of distal ischemic rest pain with mild sensory loss that may progress to tissue loss and muscle weakness and is correctable by a number of techniques. 2-4 The second is the more serious, disabling, and often irreversible occurrence of severe sensorimotor dysfunction without tissue necrosis distal to the arterial anastomosis termed "ischemic monomelic neuropathy" (IMN) by Wilbourn et al? Although these syndromes share many features, patients with "steal syndrome" have more severe ischemia with less neurologic dysfunction and symptoms resolve with correction of the ischemia. IMN, on the other hand, is characterized by abrupt, severe, often irreversible motor nerve dysfunction in the setting of mild-tomoderate ischemia. The pathogenesis is thought to be due to ischemia that is transient or insufficient to cause muscle or skin necrosis but results
Vo[. 8, No. 6 1994
in severe ischemic n e r v e injury in susceptible patients. Over the p a s t 3 years six episodes of I M N related to dialysis access h a v e b e e n d i a g n o s e d in five patients at our i n s t i t u t i o n a n d provide the basis for this report.
MATERIAL AND METHODS B e t w e e n July 1990 a n d J u l y 1993, five p a t i e n t s w e r e identified by the surgical services at University of California San Diego Medical Center a n d the San Diego Veterans A d m i n i s t r a t i o n Medical Center as h a v i n g six episodes of I M N as a consequence of dialysis graft p l a c e m e n t or as a c o m plication of dialysis access. The chronic h e m o d i alysis p o p u l a t i o n at the t w o i n s t i t u t i o n s n u m b e r s b e t w e e n 90 a n d 100 persons, 40% of w h o m are diabetic. A p p r o x i m a t e l y 80 surgical p r o c e d u r e s are p e r f o r m e d a n n u a l l y for h e m o d i a l y s i s access. All cases w e r e a s s o c i a t e d w i t h PTFE grafts origin a t i n g f r o m the brachial a r t e r y - f o u r in the forea r m a n d two ha the u p p e r arm. The diagnosis w a s m a d e o n clinical g r o u n d s alone in t w o i n s t a n c e s a n d w i t h adjunctive vascular l a b o r a t o r y a n d electrophysiologic studies ( e l e c t r o m y o g r a p h y / n e r v e c o n d u c t i o n velocity [EMG/NCV] ) in the other four. The clinical basis for diagnosis w a s severe sens o r i m o t o r d y s f u n c t i o n w i t h o u t a p p a r e n t limbt h r e a t e n i n g ischemia. Vascular l a b o r a t o r y criteria w e r e u s e d in c o n j u n c t i o n w i t h electrophysiologic studies w i t h t h e criteria b e i n g the a b s e n c e of critical i s c h e m i a (digital p r e s s u r e index > 0.3) associated w i t h the characteristic EMG/NCV p a t t e r n suggestive of a x o n - l o s s lesions of m o t o r a n d sensory nerves. T r e a t m e n t w a s at the discretion of the individual surgeon. Follow-up w a s o b t a i n e d b y c h a r t review a n d p a t i e n t interviews.
CASE R E P O R T S Case 1. A 64-year-old man with a 30-year history of insulin-dependent diabetes, poorly controlled hypertension, severe peripheral vascular disease, cerebrovascular disease, and diabetic nephropathy underwent placement of an 8 rmn PTFE right upper arm brachial artery to axillary vein graft. Two previous forearm grafts had failed early as a result of extensive arterial disease. Shortly after surgery the patient complained of "stiffness" and coldness in the right hand that was initially attributed to edema and the effects of anesthesia. Subsequently, profound weakness of the intrinsic hand musculature and a wrist drop were noted. Electrophysiologic studies performed 6 weeks after graft placement showed severe IMN involving the median, ulnar, and radial nerves just below the elbow
Ischemic monomelic neuropathy 579
and contralateral sensorimotor polyneuropathy. Segmental pressure indices in the fingers were 0.3. Arteriography revealed a proximal axillary artery stenosis that was dilated with improvement in digital indices to 0.5 but improvement in motor function was minimal. The graft was not revised or ligated because of limited access sites and the patient died 2 years later without ever showing significant improvement. Case 2. A 62-year-old m a n with insulin-dependent diabetes for more than 20 years, diabetic retinopathy, and nephropathy underwent placement of a 6 m m PTFE graft between the left brachial artery and the antecubital vein in the forearm. Postoperatively he complained of pain and weakness in the hand that was initially attributed to either intraoperative positioning or a complication of the axillary block. Persistence of symptoms after 4 weeks led to an evaluation in the vascular laboratory that showed digital pressure indices of 0.75. Electrophysiologic studies showed severe distal denervation in the left forearm consistent with IMN as well as proximal and contralateral sensorimotot polyneuropathy. No treatment was instituted because the neuropathy was believed to be nonreversible. At 3 months no improvement was noted and the patient was subsequently lost to follow-up. Case 3. A 51-year-old w o m a n with insulin-dependent diabetes for 8 years underwent placement of a 6 m m PTFE left forearm brachial artery to antecubital vein dialysis graft. When seen 7 days later she complained of pain, coolness, and edema in the hand. Examination revealed severe sensory loss and weakness of the intrinsic hand musculature with moderate weakness of wrist extension. The graft was hgated on postoperative day 8 and over the course of 6 weeks her strength improved to approximately 80% of that in the contralateral hand. Case 4. A 64-year-old m a n with insulin-dependent diabetes for 22 years, diabetic retinopathy, and peripheral neuropathy had a 6 m m PTFE graft placed between the right brachial artery and the antecubital vein. The day after surgery he complained of pain and weakness in his right hand. Examination revealed a cool viable hand with virtual complete loss of wrist extension and intrinsic muscle function. Arteriography was performed and showed a 50% stenosis at the site of proximal clamp placement. The graft was ligated on postoperative day 2 and patch angioplasty was performed on the proximal stenotic segment. Postoperative digital pressure indices were 0.8, and electrophysiologic studies showed denervation of radial, ulnar, and median innervated musculature distal tO the graft consistent with IMN. Further investigation disclosed a history of similar but milder symptoms in the left hand after placement of a graft with the same anatomic configuration 2 years earlier. This had subsequently improved but electrophysiologic studies confirmed the presence of ldss severe IMN in that arm as well. At 4 months' follow-up there was minimal improvement in the right hand despite intensive physical therapy. Case 5. A 56-year-old w o m a n with a 25-year
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Table I. Clinical characteristics of patients w i t h IMN Patient
Age (yr)
Sex
Diabetic complications
Insulin dependent fir)
Vascular d i s e a s e
1 2 3 4 (a and b) 5
64 62 51 64 56
M M F M F
N,K R,N,K ?N,K R,N,K R,N,K
30 20 8 22 25
Yes Yes No Yes No
R = retinopathy; N =
neuropathy; K = nephropathy.
Table II. T r e a t m e n t and o u t c o m e o f patients w i t h IMN Patient
T i m e to d i a g n o s i s
1 2 3 4a 4b 5
6 wk 4 wk 7 days 1 day 2 yr 4 days
Diagnostic criteria
EMG/NCV EMG/NCV Clinical EMG/NCV EMG/NCV Clinical
history of insulin-dependent diabetes, diabetic retinopathy, nephropathy, and peripheral neuropathy developed a cool, numb, paralyzed hand when her left upper arm brachial artery to brachial vein dialysis graft thrombosed. Coincidental bilateral lower extremity deep venous thrombosis was diagnosed and heparin therapy was begun. Her hand was thought to be viable and perfusion improved clinically but the hand remained profoundly weak. An arteriogram obtained on hospital day 4 showed brachial artery thromboembolus but attempted lytic therapy was only partly successful. Surgical thromboembolectomy restored normal perfusion but there was minimal improvement in neurologic function 6 weeks after the procedure. Metastatic ovarian cancer had been discovered and she died shortly thereafter. Summaries of the clinical characteristics of the patients in this report, their treatment, and outcomes are provided in Tables I and II.
DISCUSSION IMN is a rare complication of dialysis access in diabetic patients. Most case reports appear in the n e u r o l o g y literature a n d IMN is rarely m e n t i o n e d in surgical reports or vascular access textbooks. Nevertheless, it appears to be a distinct clinical e n t i t y identified by p r o f o u n d neurologic impairm e n t in the setting of only m i l d - t o - m o d e r a t e ischemia.
Treatment
Outcome
Proximal angioplasty None Graft ligation Graft ligation None Embolectomy
Unimproved Unimproved Significant improvement Unimproved Moderate improvement Unimproved
The initial description of w e a k n e s s in the muscles i n n e r v a t e d by the radial, ulnar, a n d median nerves in two patients following p l a c e m e n t of a forearm dialysis graft was provided by Bolton et al. 6 in 1979. S u b s e q u e n t reports by other investigators described the d e v e l o p m e n t of IMN in a total of 16 additional patients, all of w h o m h a d l o n g - s t a n d i n g diabetes mellitus and grafts originating f r o m the brachial artery. 1'5"7'~ S y m p t o m s were usually present i m m e d i a t e l y after surgery but the diagnosis was often delayed w i t h findings being a t t r i b u t e d to anesthetic complications, patient positioning, or surgical trauma. The retrospective n a t u r e of this review and the fact that patients were m a n a g e d by n u m e r o u s individuals resulted in a n o n u n i f o r m a p p r o a c h to diagnosis and t r e a t m e n t . Nevertheless, the six cases described in our experience display the same clinical features as those in prior reports including the lack of i m p r o v e m e n t in m o s t instances even w i t h correction of the ischemic insuit. Three of our five patients had evidence of p e r i p h e r a l vascular disease including upper ex, tremity involvement, as did m a n y of the patients in the prior reports. 8 It is logical to conclude t h a t patients w i t h proximal occlusive arterial disease m a y be predisposed to this complication, alt h o u g h it is certainly seen in the absence of discernible o c d u s i v e lesions as well.
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The clinical findings of IMN following dialysis graft placement are distinct and consist of pain and paresthesia in the hand and arm with weakness of muscles innervated by the three major nerves of the forearm. Complete paralysis of the intrinsic hand musculature is common, usually with less severe but disabling weakness in wrist flexion and extension. Although the hands of affected persons show signs of diminished perfusion, tissue necrosis is not seen and digital pressure indices are generally not consistent with limb threat. In the patients in w h o m we measured upper extremity pressures, only one was near a critical level with a digital index of 0.3. The other patients had no clinical signs of threatened tissue loss. When electrophysiologic studies are obtained they characteristically show unobtainable sensory nerve action potentials and slowed motor conduction velocities consistent with axonal sensorimotor polyneuropathy in the unaffected extremities of these persons. These are the typical findings of diabetic polyneuropathy. Needle electrodes inserted into affected muscles generally reveal evidence of severe acute denervation that is maximal distally. These findings were present in all three of our patients who were studied. Although ischemic neuropathy is a well-known sequela of acute ischemia, the profound unexpected neuropathy seen in these patients with only moderate ischemia is striking. The uniform presence of long-standing diabetes mellitus and diabetic neuropathy clearly suggests that the preexisting neuropathy is responsible for an increased sensitivity to ischemia. Arterial occlusive disease is also common and may be a predisposing factor. Although the exact cause of diabetic polyneuropathy remains unproved, recent studies implicate nerve ischemia as a significant component. 9'~~It is likely that preexisting ischemia and damage to neural tissue are responsible for lowering the threshold for ischemic injury in these persons. IMN has not been described in patients with grafts originating distal to the brachial artery despite the fact that severe hand ischemia is occasionally seen in these patients. Since the ischemia is confined to the hand in most of these persons, it is likely that any consequent ischemic neuropathy -would be far more subtle in presentation than in. patients with more proximal graft origins and nerve ischemia. Experimental models of ischemic neuropathy suggest that there are "watershed" zones of perfusion in peripheral
lschemic monomelic neuropathy 581
nerves, ll Such areas in the region supplied by the distal brachial artery may also be a factor in the development of IMN. Whether the temporary ischemia that occurs during arterial occlusion while the graft is being constructed or the subsequent less severe ischemia that is due to the diversion of blood flow into the graft is a more critical factor is not known. The crucial issues for the surgeon who cares for these patients are prevention and management. The percentage of patients with diabetes in the chronic hemodialysis population ranges from 20% to 40% depending on the unit. Most of these patients will have some degree of peripheral neuropathy and m a n y have peripheral vascular disease. Many surgeons prefer to originate dialysis grafts from the brachial artery in these patients because of diseased radial and ulnar arteries, yet most of these patients do not develop IMN. It would be interesting to evaluate this population with electrophysiologic and vascular noninvasive studies preoperatively to attempt to identify predictors of IMN. We have designed and plan to institute such a study. Data regarding the exact incidence of this condition are lacking because of underdiagnosis and misdiagnosis. In the reported cases diagnostic delay was common and most were only diagnosed after evaluation by a neur010gist. It is also possible that underreporting occurs because most surgeons and nephrologists do not distinguish IMN as an entity distinct from other ischemic complications of dialysis grafts. Although a "venous sink" or "steal syndrome" and IMN may merely represent opposite ends of a spectrum of ischemic complications of dialysis access, our experience suggests it is possible to make the distinction on the basis of clinical and electrophysiologic data. In the recent report by Ballard et al. 1 the incidence of IMN was only 3%, w h e r e a s ischemia due to a "steal syndrome" was four times more common. Our own experience is similar with only five patients diagnosed with IMN over 3 years. No systematic study of the diabetic dialysis population has been undertaken to determine whether {here is a spectrum of severity of IMN with the reported cases representing only one extreme. Current data do not allow predictions of which patients are likely to develop IMN but do identify patients with long-standing diabetes with peripheral neuropathy and vascular disease as the population at risk. Preoperative noninvasive arterial assessment should be considered in patients with
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diabetes and avoidance of limbs or correction of blood flow in those with documented occlusive lesions may be of benefit. Optimal management of these patients includes an awareness of the risk, avoidance of the dominant arm whenever possible, serious consideration of peritoneal dialysis, and careful postoperative assessment for any evidence of IMN. The use of tapered grafts is not likely to have an impact on the development of IMN because arterial diameter is the most important determinant of flow, and experimentally flow in 4 • 7 m m tapered grafts is no different from that in 6 m m grafts. ~2'~3Additionally, if transient ischemia during clamping is an important causative factor, there is no reason to believe tapered grafts would lessen the likelihood of IMN. When IMN is identified, immediate correction of ischemia, usually by graft ligation, should be undertaken. This underscores the importance of careful neurologic assessment of the operated extremity in the immediate postoperative period. It must be recognized that m a n y patients will not improve and most will have some permanent motor dysfunction. Among the three patients in this series in w h o m total correction of ischemia was performed, significant improvement was noted in only one. Correction of ischemia was documented in six of the previously reported cases with significant improvement noted in two. Although the small numbers and variations in management make conclusions difficult, all reported cases in which improvement was noted were treated within 2 weeks of onset. Elimination of IMN ultimately requires more accurate characterization of the patients at greatest risk. A careful prospective study of the population with diabetic renal failure including those undergoing arterial noninvasive and electrophysiologic testing may be of benefit and should be performed. Variability in blood supply to the nerves and arterial disease patterns may ultimately prove to be more important than the degree of neuropathy and the extent of arterial disease.
CONCLUSION IMN is a rare but devastating complication of hemodialysis access in uremic diabetic patients. The presence of peripheral neuropathy, longstanding diabetes, and peripheral vascular disease are predictors of risk. Severe neurologic dysfunction out of proportion to the degree of ischemia in the affected extremity is the hallmark of the condition and differentiates it from the "steal syndrome." Recognition should lead to immediate correction of any ischemia with the realization that most patients will be left with residual neurologic impairment.
REFERENCES 1. Ballard JL, Bunt TJ, Malone JM. Major complications of angioaccess. Am J Surg 1992;164:229-232. 2. Schanzer H, Skladany M, Haimov M. Treatment of angioaccess-induced ischemia by revascularization. J Vase Surg 1992; 16:861-866. 3. Jendrisak MD, Anderson CB. Vascular access in patients with arterial insufficiency. Ann Surg 1990;212:187-193. 4. Jain IGM, Simoni EJ, Munn JS. A new technique to correct vascular steal secondary to hemodialysis grafts. Surg Gynecol Obstet 1992;175:183-184. 5. Wilbourn AJ, Furlan AJ, Hulley W, et al. Ischemic monomelic neuropathy. Neurology 1983;33:447-451. 6. Bolton CF, Driedger AA, Lindsay RM. Ischemic neuropathy in uremic patients caused by bovine arteriovenous shunts. J Neurol Neurosurg Psychiatry 1979;42:810-814. 7. Wytrzes L, Markley HG, Fisher M, et al. Brachial neuropathy after brachial artery-antecubital vein shunts for chronic hemodialysis. Neurology 1987;37:1398-1400. 8. Riggs JE, Moss AH, Labosky DA, et al. Upper extremity ischemic monome]ic neuropathy: A complication of vascular access procedures in uremic diabetic patients. Neurology 1989;39:997-998. 9. Dyck PJ, Karnes JL, O'Brien P, et al. The spatial distribution of fiber loss in diabetic potyneuropathy suggests ischemia. Ann Neurol 1986;I9:440-449. 10. Johnson PC, Doll SC, Cromey DW. Pathogenesis of diabetic neuropathy. Ann Neurol 1986;19:450-457. 1t. Kelly CJ, Augustine C, Rooney BP, et al. An investigation of the pathophysiology of ischemic neuropathy. Eur J Vasc Surg 1991;5:535-539. 12. Sumner DS. Hemodynamics and pathophysiology of arteriovenous fistulas. In Rutherford RB, ed. Vascular Surgery, 3rd ed. Philadelphia: WB Saunders, 1989, pp 1007-1032. 13. Fillinger MF, Reiwitz ERI Schwartz RA, et al. Graft geometry and venous intimal-medial hyperplasia in arteriovenous loop grafts. J Vasc Surg 1990;11:556-566.
During the past 3 years six episodes of ischemic monomelic neuropathy (IMN) have been identified in five patients as a complication of upper extremity dialysis grafts. All patients had long-standing insulin-dependent diabetes, peripheral neuropathy, and brachial artery graft origins, whereas 60% had peripheral vascular disease. Five episodes occurred immediately after graft placement, whereas one was due to a graft-related thromboembolus. Diagnostic delay was common with initial findings attributed to anesthesia, positioning, or surgical trauma. Electrophysiologic studies showed underlying diabetic neuropathy with severe multifocal neuropathy distal to the grafts. Digital pressure indices were reduced but there was no critica~ ischemia. In three cases ischemia was completely corrected with improvement in one. One patient had proximal balloon angioplasty with no improvement and of the two untreated patients, one improved slightly. Ischemic monomelic neuropathy is a rare but disabling complication of dialysis access in diabetic uremic patients. Its occurrence is unpredictable and diagnostic delay is common. Correction of ischemia is indicated but usually does not improve the neuropathy. Prevention requires further research to more accurately characterize the patients at risk. (Ann Vasc Surg 1994;8:578-582.)
Broadened indications, as well as increasing age and survival of the population with chronic renal failure, have resulted in an increased necessity for hemodialysis access in patients with advanced atherosclerosis and complications of diabetes. As a consequence, ischemic complications of arteriovenous fistulas and grafts are being encountered with increasing frequency. ~'2 Although thromboembolic complications are well known, ischemia in this setting is more often d u e to a "steal syndrome" or "venous sink" phen o m e n o n where the access diverts blood into the
From the Department of Surgery, University of California, San Diego, Calif. Presented at the Twelfth Annual Meeting of tile Southern California Vascular Surgical Society, Coronado, Calif., September 17-19, 1993. Reprint requests: Robert J. Hye, MD, UCSD Medical Center, 200 W. Arbor Dr., San Diego, CA 92103-8401.
578
low-resistance venous system at the expense of distal arterial perfusion. Two clinical syndromes can occur as a result. The first is the typical presentation of distal ischemic rest pain with mild sensory loss that may progress to tissue loss and muscle weakness and is correctable by a number of techniques. 2-4 The second is the more serious, disabling, and often irreversible occurrence of severe sensorimotor dysfunction without tissue necrosis distal to the arterial anastomosis termed "ischemic monomelic neuropathy" (IMN) by Wilbourn et al? Although these syndromes share many features, patients with "steal syndrome" have more severe ischemia with less neurologic dysfunction and symptoms resolve with correction of the ischemia. IMN, on the other hand, is characterized by abrupt, severe, often irreversible motor nerve dysfunction in the setting of mild-tomoderate ischemia. The pathogenesis is thought to be due to ischemia that is transient or insufficient to cause muscle or skin necrosis but results
Vo[. 8, No. 6 1994
in severe ischemic n e r v e injury in susceptible patients. Over the p a s t 3 years six episodes of I M N related to dialysis access h a v e b e e n d i a g n o s e d in five patients at our i n s t i t u t i o n a n d provide the basis for this report.
MATERIAL AND METHODS B e t w e e n July 1990 a n d J u l y 1993, five p a t i e n t s w e r e identified by the surgical services at University of California San Diego Medical Center a n d the San Diego Veterans A d m i n i s t r a t i o n Medical Center as h a v i n g six episodes of I M N as a consequence of dialysis graft p l a c e m e n t or as a c o m plication of dialysis access. The chronic h e m o d i alysis p o p u l a t i o n at the t w o i n s t i t u t i o n s n u m b e r s b e t w e e n 90 a n d 100 persons, 40% of w h o m are diabetic. A p p r o x i m a t e l y 80 surgical p r o c e d u r e s are p e r f o r m e d a n n u a l l y for h e m o d i a l y s i s access. All cases w e r e a s s o c i a t e d w i t h PTFE grafts origin a t i n g f r o m the brachial a r t e r y - f o u r in the forea r m a n d two ha the u p p e r arm. The diagnosis w a s m a d e o n clinical g r o u n d s alone in t w o i n s t a n c e s a n d w i t h adjunctive vascular l a b o r a t o r y a n d electrophysiologic studies ( e l e c t r o m y o g r a p h y / n e r v e c o n d u c t i o n velocity [EMG/NCV] ) in the other four. The clinical basis for diagnosis w a s severe sens o r i m o t o r d y s f u n c t i o n w i t h o u t a p p a r e n t limbt h r e a t e n i n g ischemia. Vascular l a b o r a t o r y criteria w e r e u s e d in c o n j u n c t i o n w i t h electrophysiologic studies w i t h t h e criteria b e i n g the a b s e n c e of critical i s c h e m i a (digital p r e s s u r e index > 0.3) associated w i t h the characteristic EMG/NCV p a t t e r n suggestive of a x o n - l o s s lesions of m o t o r a n d sensory nerves. T r e a t m e n t w a s at the discretion of the individual surgeon. Follow-up w a s o b t a i n e d b y c h a r t review a n d p a t i e n t interviews.
CASE R E P O R T S Case 1. A 64-year-old man with a 30-year history of insulin-dependent diabetes, poorly controlled hypertension, severe peripheral vascular disease, cerebrovascular disease, and diabetic nephropathy underwent placement of an 8 rmn PTFE right upper arm brachial artery to axillary vein graft. Two previous forearm grafts had failed early as a result of extensive arterial disease. Shortly after surgery the patient complained of "stiffness" and coldness in the right hand that was initially attributed to edema and the effects of anesthesia. Subsequently, profound weakness of the intrinsic hand musculature and a wrist drop were noted. Electrophysiologic studies performed 6 weeks after graft placement showed severe IMN involving the median, ulnar, and radial nerves just below the elbow
Ischemic monomelic neuropathy 579
and contralateral sensorimotor polyneuropathy. Segmental pressure indices in the fingers were 0.3. Arteriography revealed a proximal axillary artery stenosis that was dilated with improvement in digital indices to 0.5 but improvement in motor function was minimal. The graft was not revised or ligated because of limited access sites and the patient died 2 years later without ever showing significant improvement. Case 2. A 62-year-old m a n with insulin-dependent diabetes for more than 20 years, diabetic retinopathy, and nephropathy underwent placement of a 6 m m PTFE graft between the left brachial artery and the antecubital vein in the forearm. Postoperatively he complained of pain and weakness in the hand that was initially attributed to either intraoperative positioning or a complication of the axillary block. Persistence of symptoms after 4 weeks led to an evaluation in the vascular laboratory that showed digital pressure indices of 0.75. Electrophysiologic studies showed severe distal denervation in the left forearm consistent with IMN as well as proximal and contralateral sensorimotot polyneuropathy. No treatment was instituted because the neuropathy was believed to be nonreversible. At 3 months no improvement was noted and the patient was subsequently lost to follow-up. Case 3. A 51-year-old w o m a n with insulin-dependent diabetes for 8 years underwent placement of a 6 m m PTFE left forearm brachial artery to antecubital vein dialysis graft. When seen 7 days later she complained of pain, coolness, and edema in the hand. Examination revealed severe sensory loss and weakness of the intrinsic hand musculature with moderate weakness of wrist extension. The graft was hgated on postoperative day 8 and over the course of 6 weeks her strength improved to approximately 80% of that in the contralateral hand. Case 4. A 64-year-old m a n with insulin-dependent diabetes for 22 years, diabetic retinopathy, and peripheral neuropathy had a 6 m m PTFE graft placed between the right brachial artery and the antecubital vein. The day after surgery he complained of pain and weakness in his right hand. Examination revealed a cool viable hand with virtual complete loss of wrist extension and intrinsic muscle function. Arteriography was performed and showed a 50% stenosis at the site of proximal clamp placement. The graft was ligated on postoperative day 2 and patch angioplasty was performed on the proximal stenotic segment. Postoperative digital pressure indices were 0.8, and electrophysiologic studies showed denervation of radial, ulnar, and median innervated musculature distal tO the graft consistent with IMN. Further investigation disclosed a history of similar but milder symptoms in the left hand after placement of a graft with the same anatomic configuration 2 years earlier. This had subsequently improved but electrophysiologic studies confirmed the presence of ldss severe IMN in that arm as well. At 4 months' follow-up there was minimal improvement in the right hand despite intensive physical therapy. Case 5. A 56-year-old w o m a n with a 25-year
580
Annals of Vascular Surgery
Hye and Wolf
Table I. Clinical characteristics of patients w i t h IMN Patient
Age (yr)
Sex
Diabetic complications
Insulin dependent fir)
Vascular d i s e a s e
1 2 3 4 (a and b) 5
64 62 51 64 56
M M F M F
N,K R,N,K ?N,K R,N,K R,N,K
30 20 8 22 25
Yes Yes No Yes No
R = retinopathy; N =
neuropathy; K = nephropathy.
Table II. T r e a t m e n t and o u t c o m e o f patients w i t h IMN Patient
T i m e to d i a g n o s i s
1 2 3 4a 4b 5
6 wk 4 wk 7 days 1 day 2 yr 4 days
Diagnostic criteria
EMG/NCV EMG/NCV Clinical EMG/NCV EMG/NCV Clinical
history of insulin-dependent diabetes, diabetic retinopathy, nephropathy, and peripheral neuropathy developed a cool, numb, paralyzed hand when her left upper arm brachial artery to brachial vein dialysis graft thrombosed. Coincidental bilateral lower extremity deep venous thrombosis was diagnosed and heparin therapy was begun. Her hand was thought to be viable and perfusion improved clinically but the hand remained profoundly weak. An arteriogram obtained on hospital day 4 showed brachial artery thromboembolus but attempted lytic therapy was only partly successful. Surgical thromboembolectomy restored normal perfusion but there was minimal improvement in neurologic function 6 weeks after the procedure. Metastatic ovarian cancer had been discovered and she died shortly thereafter. Summaries of the clinical characteristics of the patients in this report, their treatment, and outcomes are provided in Tables I and II.
DISCUSSION IMN is a rare complication of dialysis access in diabetic patients. Most case reports appear in the n e u r o l o g y literature a n d IMN is rarely m e n t i o n e d in surgical reports or vascular access textbooks. Nevertheless, it appears to be a distinct clinical e n t i t y identified by p r o f o u n d neurologic impairm e n t in the setting of only m i l d - t o - m o d e r a t e ischemia.
Treatment
Outcome
Proximal angioplasty None Graft ligation Graft ligation None Embolectomy
Unimproved Unimproved Significant improvement Unimproved Moderate improvement Unimproved
The initial description of w e a k n e s s in the muscles i n n e r v a t e d by the radial, ulnar, a n d median nerves in two patients following p l a c e m e n t of a forearm dialysis graft was provided by Bolton et al. 6 in 1979. S u b s e q u e n t reports by other investigators described the d e v e l o p m e n t of IMN in a total of 16 additional patients, all of w h o m h a d l o n g - s t a n d i n g diabetes mellitus and grafts originating f r o m the brachial artery. 1'5"7'~ S y m p t o m s were usually present i m m e d i a t e l y after surgery but the diagnosis was often delayed w i t h findings being a t t r i b u t e d to anesthetic complications, patient positioning, or surgical trauma. The retrospective n a t u r e of this review and the fact that patients were m a n a g e d by n u m e r o u s individuals resulted in a n o n u n i f o r m a p p r o a c h to diagnosis and t r e a t m e n t . Nevertheless, the six cases described in our experience display the same clinical features as those in prior reports including the lack of i m p r o v e m e n t in m o s t instances even w i t h correction of the ischemic insuit. Three of our five patients had evidence of p e r i p h e r a l vascular disease including upper ex, tremity involvement, as did m a n y of the patients in the prior reports. 8 It is logical to conclude t h a t patients w i t h proximal occlusive arterial disease m a y be predisposed to this complication, alt h o u g h it is certainly seen in the absence of discernible o c d u s i v e lesions as well.
Vol. 8, No. 6 1994
The clinical findings of IMN following dialysis graft placement are distinct and consist of pain and paresthesia in the hand and arm with weakness of muscles innervated by the three major nerves of the forearm. Complete paralysis of the intrinsic hand musculature is common, usually with less severe but disabling weakness in wrist flexion and extension. Although the hands of affected persons show signs of diminished perfusion, tissue necrosis is not seen and digital pressure indices are generally not consistent with limb threat. In the patients in w h o m we measured upper extremity pressures, only one was near a critical level with a digital index of 0.3. The other patients had no clinical signs of threatened tissue loss. When electrophysiologic studies are obtained they characteristically show unobtainable sensory nerve action potentials and slowed motor conduction velocities consistent with axonal sensorimotor polyneuropathy in the unaffected extremities of these persons. These are the typical findings of diabetic polyneuropathy. Needle electrodes inserted into affected muscles generally reveal evidence of severe acute denervation that is maximal distally. These findings were present in all three of our patients who were studied. Although ischemic neuropathy is a well-known sequela of acute ischemia, the profound unexpected neuropathy seen in these patients with only moderate ischemia is striking. The uniform presence of long-standing diabetes mellitus and diabetic neuropathy clearly suggests that the preexisting neuropathy is responsible for an increased sensitivity to ischemia. Arterial occlusive disease is also common and may be a predisposing factor. Although the exact cause of diabetic polyneuropathy remains unproved, recent studies implicate nerve ischemia as a significant component. 9'~~It is likely that preexisting ischemia and damage to neural tissue are responsible for lowering the threshold for ischemic injury in these persons. IMN has not been described in patients with grafts originating distal to the brachial artery despite the fact that severe hand ischemia is occasionally seen in these patients. Since the ischemia is confined to the hand in most of these persons, it is likely that any consequent ischemic neuropathy -would be far more subtle in presentation than in. patients with more proximal graft origins and nerve ischemia. Experimental models of ischemic neuropathy suggest that there are "watershed" zones of perfusion in peripheral
lschemic monomelic neuropathy 581
nerves, ll Such areas in the region supplied by the distal brachial artery may also be a factor in the development of IMN. Whether the temporary ischemia that occurs during arterial occlusion while the graft is being constructed or the subsequent less severe ischemia that is due to the diversion of blood flow into the graft is a more critical factor is not known. The crucial issues for the surgeon who cares for these patients are prevention and management. The percentage of patients with diabetes in the chronic hemodialysis population ranges from 20% to 40% depending on the unit. Most of these patients will have some degree of peripheral neuropathy and m a n y have peripheral vascular disease. Many surgeons prefer to originate dialysis grafts from the brachial artery in these patients because of diseased radial and ulnar arteries, yet most of these patients do not develop IMN. It would be interesting to evaluate this population with electrophysiologic and vascular noninvasive studies preoperatively to attempt to identify predictors of IMN. We have designed and plan to institute such a study. Data regarding the exact incidence of this condition are lacking because of underdiagnosis and misdiagnosis. In the reported cases diagnostic delay was common and most were only diagnosed after evaluation by a neur010gist. It is also possible that underreporting occurs because most surgeons and nephrologists do not distinguish IMN as an entity distinct from other ischemic complications of dialysis grafts. Although a "venous sink" or "steal syndrome" and IMN may merely represent opposite ends of a spectrum of ischemic complications of dialysis access, our experience suggests it is possible to make the distinction on the basis of clinical and electrophysiologic data. In the recent report by Ballard et al. 1 the incidence of IMN was only 3%, w h e r e a s ischemia due to a "steal syndrome" was four times more common. Our own experience is similar with only five patients diagnosed with IMN over 3 years. No systematic study of the diabetic dialysis population has been undertaken to determine whether {here is a spectrum of severity of IMN with the reported cases representing only one extreme. Current data do not allow predictions of which patients are likely to develop IMN but do identify patients with long-standing diabetes with peripheral neuropathy and vascular disease as the population at risk. Preoperative noninvasive arterial assessment should be considered in patients with
582
Annals of Vascular Surgery
Hye and Wo~
diabetes and avoidance of limbs or correction of blood flow in those with documented occlusive lesions may be of benefit. Optimal management of these patients includes an awareness of the risk, avoidance of the dominant arm whenever possible, serious consideration of peritoneal dialysis, and careful postoperative assessment for any evidence of IMN. The use of tapered grafts is not likely to have an impact on the development of IMN because arterial diameter is the most important determinant of flow, and experimentally flow in 4 • 7 m m tapered grafts is no different from that in 6 m m grafts. ~2'~3Additionally, if transient ischemia during clamping is an important causative factor, there is no reason to believe tapered grafts would lessen the likelihood of IMN. When IMN is identified, immediate correction of ischemia, usually by graft ligation, should be undertaken. This underscores the importance of careful neurologic assessment of the operated extremity in the immediate postoperative period. It must be recognized that m a n y patients will not improve and most will have some permanent motor dysfunction. Among the three patients in this series in w h o m total correction of ischemia was performed, significant improvement was noted in only one. Correction of ischemia was documented in six of the previously reported cases with significant improvement noted in two. Although the small numbers and variations in management make conclusions difficult, all reported cases in which improvement was noted were treated within 2 weeks of onset. Elimination of IMN ultimately requires more accurate characterization of the patients at greatest risk. A careful prospective study of the population with diabetic renal failure including those undergoing arterial noninvasive and electrophysiologic testing may be of benefit and should be performed. Variability in blood supply to the nerves and arterial disease patterns may ultimately prove to be more important than the degree of neuropathy and the extent of arterial disease.
CONCLUSION IMN is a rare but devastating complication of hemodialysis access in uremic diabetic patients. The presence of peripheral neuropathy, longstanding diabetes, and peripheral vascular disease are predictors of risk. Severe neurologic dysfunction out of proportion to the degree of ischemia in the affected extremity is the hallmark of the condition and differentiates it from the "steal syndrome." Recognition should lead to immediate correction of any ischemia with the realization that most patients will be left with residual neurologic impairment.
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