Observations were made on the occurrence of peripheral neuropathy in a series of 139 patients admitted to a chronic dialysis program over a 10-year period. Evidence of neuropathy was obtained in approximately 50% of these patients over the total period. Once dialysis was instituted, distal paresthesiae evident before the inception of dialysis tended to clear rapidly. Occurrence of the symptom of “restless legs” correlated positively with the presence of neuropathy. Persistent neuropathy was more commonly sensory than motor, and its features were consistent with a predominant loss of large myelinated fibers. This analysis suggests that multiple factors may be involved in the origin of uremic neuropathy. MUSCLE 8 NERVE
1:396-399
1978
SCREENING FOR PERIPHERAL NEUROPATHY IN PATIENTS TREATED BY CHRONIC HEMODIALYSIS P. K. THOMAS, DSc, MD
W h e n the first group of 20 patients was accepted for chronic hemodialysis treatment at the Royal Free Hospital in London, 15 showed evidence of peripheral neuropathy. and in 2 it was found to be severe.13 Because criteria for admission to chronic dialysis programs have since become more discriminating, severe neuropathy is now infrequently encountered. However, peripheral neuropathy remains a continuing cause of discomfort and disability in patients on such treatment. Since uremic neuropathy may be improved by increased or, more effectively, by successful renal transplantation,4 early recognition of peripheral nerve involvement assumes some importance. T h e clinical features of uremic neuropathy have previously been discussed by Asbury, Victor, and Adams,’ by Tenckhoff et a],” by Nielsen,14 as well as by others, and thus they need not be reviewed here. Callaghan’ commented on the occurrence of “restless legs” (Ekbom’s syndrome) as a significant symptom, whereas Nielsen14 found that this symptom was reported with equal frequency by patients with and without neurop-
From the Royal Free Hospital, London, England Financial support from the Medical Research Council is gratefully acknowledged The patients were kindly referred by Dr W R Cattell and Dr L Baker Address reprint requests to Professor Thomas at the Department of Neurological Science, Royal Free Hospital, Pond Street, London NW3 2QG, England 0148-639X/0105/0396$00 OW0 1978 Houghton Mifflin Professional Publishers
396
Uremic Neuropathy
athy. Preswick and Jeremy,Is as well as later authors, commented o n the presence o f subclinical neuropathy in patients with chronic renal failure-that is, the occurrence of nerve conduction abnormalities in the absence of symptoms or signs of neuropathy. MATERIALS AND METHODS
This article assesses the occurrence of peripheral neuropathy in patients admitted for treatment by chronic hemodialysis over the past 10 years at St. Leonard’s Hospital, London. Cases with conditions that might cause neuropathy (other than uremia) were excluded. T h e series comprised 139 patients, 93 of whom were male and 46 of’ whom were female. T h e age range at the time of admission to the program was 20 to 54 years, with a mean of 36.7 for males and 35.9 for females. T h e longest follow-up period was 10 years, and patients were assessed annually unless particular reasons arose that warranted more frequent examination. All cases were assessed clinically by a single observer (P. K. Thomas), and motor nerve conduction velocity was measured in the peroneal nerve with recordings from the extensor digitorum brevis, except when this muscle was completely denervated. I n the earlier period of the study, peroneal nerve action potentials were also recorded; subsequently, conduction was examined in the sural nerve. Surface temperature over the distal part of the limb at the time of the recordings was not less than 32°C. O u r findings with respect to changes in nerve conduction during chronic hemodialysis have been reported previously” and will not be included here.
MUSCLE & NERVE
Sept/Oct 1978
Table 1. Symptoms of peripheral neuropathy in patients on chronic hemodialysis. Number of patients (%)” Initial Asymptomatic Weakness Numbness Paresthesiae “Restless legs”
117 (84.2) 2 (1.4) 2 (1.4) 10 (7.2) 10 (7.2)
During 74
(77.1) 2 (2.1) 1 (1.0) 4 (4.2) 14 (14.6)
Total
Final
75 (53.2) 4 (2.8) 3 (3.1) 14 (10.1) 24 (17.3)
79 (82.3) 1 (1.0) 3 (3.1)
0
(0)
10 (10.4)
”Lee-hand columns do not add up to total sample number, and right-hand columns do not add up to 700%. because of symptom overlap and loss of some patients to follow-up
RESULTS Symptoms of Neuropathy. Table 1 shows, in the first
paired column, an analysis of the symptoms of peripheral neuropathy exhibited by patients at the time of admission to the program, the percentage values being given in parentheses. Symptoms of neuropathy were present in approximately 1576, sensory symptoms occurring more frequently. The second paired column indicates the number of patients who developed symptoms during the follow-up periods as well as those who were asymptomatic, with the combined total indicated in the third paired column. Thus, throughout the entire period, approximately 25% displayed symptoms of neuropathy at one time or another. Only 3% complained of muscle weakness, but paresthesiae, which were usually ,of a tingling nature, were noted in approximately 10% of patients. “Restless legs” was a symptom in as many as 17’%,and has a significant association with neuropathy. Table 2 shows whether clinical or subclinical neuropathy was present at the time of any examination when the patient was experiencing “restless legs.” A chi square test demonstrated a statistically significant association hetween this symptom and neuropathy ( p = .01). Muscle cramps were a frequent complaint, usually at the time of dialysis, and have not been assessed. Signs of Neuropathy. Table 3 shows, in the first paired column, a breakdown of the numbers of patients with signs of peripheral neuropathy at the time of admission to the program. The second paired column indicates those who developed signs during the follow-up period, and the combined total is indicated in the third. Initially, approximately 25% displayed some signs of neuropathy. Including those who developed signs during the followup period, approximately 50% exhibited signs at some time. Weakness was evident in less than 5%, whereas depression or loss of ankle jerks developed in about 25%, and depression or loss of knee jerks occurred in 12%. Sensory loss was most frequently observed for vibration and was detected in 1076, with joint-position sense and light touch less often affected, pain and temperature being involved the least. Sex Distribution. In most of the previous series, a greater vulnerability to uremic neuropathy has been noted among males than among females.14However, the pres-
Uremic Neuropathy
Table 2. “Restless legs” in patients on chronic hemodialysis.
Neuropathy Clinical Subclinical Total Without neuropathy
Affected
Unaffected
13 8 21 3
48 36 84 53
ent series contained only a slight excess of affected males. Of the 93 male patients, 45 (48.4%) were affected, whereas of the 46 females, 19 (41.3%) displayed evidence of peripheral neuropathy. A chi square test showed no significant difference ( p > .05). Final Assessment. T h e final paired column in table 1
shows the frequency of symptoms at the time of the last assessment before the analysis reported here. Comparison with the first paired column reveals that the proportion of cases with symptoms is virtually identical to that at the initial assessment. Reduced numbers in the final assessment result from the fact that it includes patients who have not yet had their second annual appraisal, and excludes those who were assessed only once because of death or successful renal transplantation. If only those patients who have had more than one assessment are considered, the proportions remain approximately the same. T h e pattern of distribution of individual symptoms remains constant, with the striking exception of paresthesiae, which were initially present in 7% hut were absent in the final assessment. Usually, the tingling (or, rarely, burning) paresthesiae that occurred in the feet-and sometimes also in the handscleared rapidly once treatment was instituted. This did not seem to be the case with the symptom of “restless legs”: it appeared for the first time in some patients who were already receiving dialysis. The final paired column in table 3 gives the number of patients with signs of peripheral neuropathy at the final assessment. A slightly smaller proportion of PAtients displayed signs at the final assessment than initially, but the distribution showed no striking difference, although muscle weakness at the time of acceptance tended to improve with dialysis. This was most evident in one patient (case 10 in Thomas et alls), who had a
MUSCLE & NERVE
SepVOct 1978
397
Table 3. Signs of peripheral neuropathy in patients on chronic hemodialysis. Number of patients (%)a
None Weakness 5 wasting Tendon reflex loss or depression Knee Ankle Sensory loss Light touch Pain and temperature Joint position Vibration
Initial
During
Total
100 (67.11) 4 (2.9)
68 (70.1) 2 (2.1)
68 (48.9) 6 (4.3)
69 1
8 (5.8) 19 (13.7)
9 (9.4) 18 (18.8)
‘17 37
(12.2) (26.6)
9 20
4 (2.9) 2 (1.4) 5 (3.6) 14 (10.1)
0 0 1 13
2 0 4 12
(1.4) (0) (2.9) (8.6)
2 2 1 2
(2.1) (2.1) (1.0) (2.1)
Final
”Left-hand columns do not add up to total sample number, and right-hand cdumns do not add up to TOO%, because of symptom overlap and loss of some patients to follow-up.
proposed that recovery of nerve conduction velocity is biphasic, with an initial rapid phase succeeded by a more gradual one. He has suggested that the former phase is related to recovery from a “toxic” impairment of axon Focal Nerve Lesions. During the follow-up period, five membrane function, and the latter to recovery from a patients developed evidence of focal peripheral nerve structural neuropathy involving a combination of axonal lesions; these excluded any that were attributable to the degeneration and segmental demyelination. The mechinsertion of shunts or to the establishment of arterioanism responsible for the occurrence of “restless legs” venous fistulae. Three developed local lesions of the may differ from that of the distal paresthesiae in view common peroneal nerve and one meralgia paresthetica; of its different behavior. That patients may develop an one developed the carpal tunnel syndrome, confirmed almost pure motor neuropathy, as occurred in one paby nerve conduction studies, on the side with an antetient in this series, also suggests either variation in the brachial arteriovenous fistula. Sensory symptoms in the hand were precipitated by dialysis, and the condition was metabolic insult or differences between patients in the selective vulnerability of motor and sensory fibers. relieved by surgical decompression of the nerve. The clinical features of the more persistent symptoms of neuropathy (vibration, joint-position, and tactile DISCUSSION sensory loss) are consistent with a predominant loss of As initially predicted by Asbury, Victor, and Adams,l the larger myelinated fibers; rarely is there loss of pain and temperature sensibility. Despite some initial reports uremic neuropathy is likely to be a sequel of a metabolic to the contrary, it is now clear that uremic neuropathy disturbance related to chronic renal insufficiency. Iminvolves a distal axonal degeneration that generally afprovement by dialysis or renal transplantation suggests fects larger myelinated fibers to a greater extent than the operation of a retained metabolite, the nature of smaller, with relative sparing of unmyelinated axons.8’18 which remains elusive. Clearly, this metabolite has a molecular weight exceeding that of urea or ~ r e a t i n i n e , ’ ~ One personally observed case (not in the present series) developed a gross sensory neuropathy with severe loss and some researchers have surmised that it may be in of sense ofjoint position, vibration, and tactile sensation, the “middle molecular weight” range.3*6Suggestions that myoinositol may be responsible7 have not been conbut with sparing of pain, temperature sensation, and motor power. This led to prominent involuntary movefirmed.12J6 The most recent contender is parathyroid ments of the pseudoathetoid type and sensory ataxia. hormone,’ although, as Avram and his coworkers admit, The occurrence of five instances of focal peripheral the correlation they detected between elevated parathyroid hormone levels and decreased motor nerve connerve lesions in this series supports the contention of duction velocity might be related to some other correNielsen14 that uremic neuropathy, like certain other neuropathies, exhibits an abnormal susceptibility to lated factor that influences peripheral nerve function. pressure palsies. Our patient with the carpal tunnel synThis analysis of the features of peripheral neuropdrome, as in the cases reported by Harding and Le athy in patients receiving chronic hemodialysis suggests fan^,^ described aggravation of her symptoms by dithat the causal mechanisms may be multiple. With dialysis, the tingling paresthesiae felt distally in the limbs alysis. These authors have argued that a vascular steal produced by the shunt may lead to the development of tend to subside rapidly. Whether these sensations result symptoms at the time of dialysis if the nerve is already from overt structural changes in nerve or from alteracompromised by compression in the carpal tunnel. tions in membrane function is uncertain. Nielsen14 has severe symmetrical and almost purely motor neuropathy initially, which slowly recovered almost completely.
398
Uremic Neuropathy
MUSCLE & NERVE
Sept/Oct 1978
REFERENCES
1 . Asbury AK, Victor M, Adams RD: Uremic neuropathy. Arch Neurol 8:413-428, 1963. 2. Avram MM, Feinfeld DA, Huatuco AH: Search for the uremic toxin: decreased motor-nerve conduction velocity and elevated parathyroid hormone in uremia. N EnglJ MeQ 298:lOOO-1003, 1978. 3. Babb AL, Popovich RP, Christopher TG, Scribner BH: The genesis of the square meter-hour hypothesis. Trans Am Soc ArtifIntern Organs 17:81, 1971. 4. Bolton CF, Baltzan MA, Baltzan RB: Effects of renal transplantation on uremic neuropathy. A clinical and electrophysiologic study. N E n g l J Med 284:1170-1175, 1971. 5. Callaghan N: Restless legs syndrome in uremic neuropathy. Neurology (Minneap) 16:359-361, 1966. 6. Christopher TG, Camebi V, Harker LA, Hurst PE, Popovich RP, Babb AL, Scribner BH: A study of hemodialysis with lowered dialysate flow rate. Tram Am Soc Artif Zntern Organs 17:92, 1971. 7. DeJesus PV, Clements RS, Winegrad AI: Hypermyoinositolemic polyneuropathy in rats. A possible mechanism for uremic polyneuropathy. J Neurol Sn‘ 21 :237-249, 1974. 8. Dyck, PJ, Johnson WJ, Lambert EH, O’Brien PC: Segmental demyelination secondary to axonal degeneration in uremic neuropathy. Mayo Clzn Proc 46:400-431, 1971. 9. Harding AE, Le Fanu J: Carpal tunnel syndrome related to antebrachial Cimino-Brescia fistula. J Neurol Neurosurg Psychiatry 40:511-513, 1977.
Uremic Neuropathy
10. Heron JR, Konotey-Ahulu FID, Shaldon S, Thomas PK: Nerve conduction in chronic renal failure treated by dialysis. Excerpta Med Int Cong Ser 103: 138-140, 1965. 1 1 . Jebsen RH, Tenckhoff H, Honet JC: Natural history of uremic polyneuropathy and effects of dialysis.N En91J Med 277:327-333, 1967. 2. Jefferys JGR, Palmano KP, Sharma AK, Thomas PK: Influence of dietary myoinositol on nerve conduction and phospholipids in normal and diabetic rats. J Neurol Neurosurg Psychzatry 41:333-339, 1978. 3. Konotey-Ahulu FID, Baillod R, Comty CM, Heron JR, Shaldon S, Thomas PK: Effect of periodic dialysis on the peripheral neuropathy of end-stage renal failure. Br Med J 2:1212-1215, 1965. 14. Nielsen VK: The peripheral nerve function in chronic renal failure: a survey. Acta Med Scand (Suppl) 573: 1-32, 1974. 15. Preswick G, Jeremy D: Subclinicalpolyneuropathy in chronic renal failure. Lancet 2:731-732, 1964. 16. Reznek RH, Salway JG, Thomas PK: Plasma-myoinositol levels in uraemic neuropathy. Lancrt 1:675-676, 1977. 17. Tenckhoff HA, Boen ST, Jebsen RH, Spiegler JH: Polyneuropathy in chronic renal insufficiency.JAMA 192:11211124, 1965. 18. Thomas PK, Hollinrake K, Lascelles RG, O’Sullivan DJ, Baillod RA, Moorhead JF, Mackenzie JC: The polyneuropathy of chronic renal failure. Brain 94:761-780, 1971.
MUSCLE & NERVE
SepVOct 1978
399
1:396-399
1978
SCREENING FOR PERIPHERAL NEUROPATHY IN PATIENTS TREATED BY CHRONIC HEMODIALYSIS P. K. THOMAS, DSc, MD
W h e n the first group of 20 patients was accepted for chronic hemodialysis treatment at the Royal Free Hospital in London, 15 showed evidence of peripheral neuropathy. and in 2 it was found to be severe.13 Because criteria for admission to chronic dialysis programs have since become more discriminating, severe neuropathy is now infrequently encountered. However, peripheral neuropathy remains a continuing cause of discomfort and disability in patients on such treatment. Since uremic neuropathy may be improved by increased or, more effectively, by successful renal transplantation,4 early recognition of peripheral nerve involvement assumes some importance. T h e clinical features of uremic neuropathy have previously been discussed by Asbury, Victor, and Adams,’ by Tenckhoff et a],” by Nielsen,14 as well as by others, and thus they need not be reviewed here. Callaghan’ commented on the occurrence of “restless legs” (Ekbom’s syndrome) as a significant symptom, whereas Nielsen14 found that this symptom was reported with equal frequency by patients with and without neurop-
From the Royal Free Hospital, London, England Financial support from the Medical Research Council is gratefully acknowledged The patients were kindly referred by Dr W R Cattell and Dr L Baker Address reprint requests to Professor Thomas at the Department of Neurological Science, Royal Free Hospital, Pond Street, London NW3 2QG, England 0148-639X/0105/0396$00 OW0 1978 Houghton Mifflin Professional Publishers
396
Uremic Neuropathy
athy. Preswick and Jeremy,Is as well as later authors, commented o n the presence o f subclinical neuropathy in patients with chronic renal failure-that is, the occurrence of nerve conduction abnormalities in the absence of symptoms or signs of neuropathy. MATERIALS AND METHODS
This article assesses the occurrence of peripheral neuropathy in patients admitted for treatment by chronic hemodialysis over the past 10 years at St. Leonard’s Hospital, London. Cases with conditions that might cause neuropathy (other than uremia) were excluded. T h e series comprised 139 patients, 93 of whom were male and 46 of’ whom were female. T h e age range at the time of admission to the program was 20 to 54 years, with a mean of 36.7 for males and 35.9 for females. T h e longest follow-up period was 10 years, and patients were assessed annually unless particular reasons arose that warranted more frequent examination. All cases were assessed clinically by a single observer (P. K. Thomas), and motor nerve conduction velocity was measured in the peroneal nerve with recordings from the extensor digitorum brevis, except when this muscle was completely denervated. I n the earlier period of the study, peroneal nerve action potentials were also recorded; subsequently, conduction was examined in the sural nerve. Surface temperature over the distal part of the limb at the time of the recordings was not less than 32°C. O u r findings with respect to changes in nerve conduction during chronic hemodialysis have been reported previously” and will not be included here.
MUSCLE & NERVE
Sept/Oct 1978
Table 1. Symptoms of peripheral neuropathy in patients on chronic hemodialysis. Number of patients (%)” Initial Asymptomatic Weakness Numbness Paresthesiae “Restless legs”
117 (84.2) 2 (1.4) 2 (1.4) 10 (7.2) 10 (7.2)
During 74
(77.1) 2 (2.1) 1 (1.0) 4 (4.2) 14 (14.6)
Total
Final
75 (53.2) 4 (2.8) 3 (3.1) 14 (10.1) 24 (17.3)
79 (82.3) 1 (1.0) 3 (3.1)
0
(0)
10 (10.4)
”Lee-hand columns do not add up to total sample number, and right-hand columns do not add up to 700%. because of symptom overlap and loss of some patients to follow-up
RESULTS Symptoms of Neuropathy. Table 1 shows, in the first
paired column, an analysis of the symptoms of peripheral neuropathy exhibited by patients at the time of admission to the program, the percentage values being given in parentheses. Symptoms of neuropathy were present in approximately 1576, sensory symptoms occurring more frequently. The second paired column indicates the number of patients who developed symptoms during the follow-up periods as well as those who were asymptomatic, with the combined total indicated in the third paired column. Thus, throughout the entire period, approximately 25% displayed symptoms of neuropathy at one time or another. Only 3% complained of muscle weakness, but paresthesiae, which were usually ,of a tingling nature, were noted in approximately 10% of patients. “Restless legs” was a symptom in as many as 17’%,and has a significant association with neuropathy. Table 2 shows whether clinical or subclinical neuropathy was present at the time of any examination when the patient was experiencing “restless legs.” A chi square test demonstrated a statistically significant association hetween this symptom and neuropathy ( p = .01). Muscle cramps were a frequent complaint, usually at the time of dialysis, and have not been assessed. Signs of Neuropathy. Table 3 shows, in the first paired column, a breakdown of the numbers of patients with signs of peripheral neuropathy at the time of admission to the program. The second paired column indicates those who developed signs during the follow-up period, and the combined total is indicated in the third. Initially, approximately 25% displayed some signs of neuropathy. Including those who developed signs during the followup period, approximately 50% exhibited signs at some time. Weakness was evident in less than 5%, whereas depression or loss of ankle jerks developed in about 25%, and depression or loss of knee jerks occurred in 12%. Sensory loss was most frequently observed for vibration and was detected in 1076, with joint-position sense and light touch less often affected, pain and temperature being involved the least. Sex Distribution. In most of the previous series, a greater vulnerability to uremic neuropathy has been noted among males than among females.14However, the pres-
Uremic Neuropathy
Table 2. “Restless legs” in patients on chronic hemodialysis.
Neuropathy Clinical Subclinical Total Without neuropathy
Affected
Unaffected
13 8 21 3
48 36 84 53
ent series contained only a slight excess of affected males. Of the 93 male patients, 45 (48.4%) were affected, whereas of the 46 females, 19 (41.3%) displayed evidence of peripheral neuropathy. A chi square test showed no significant difference ( p > .05). Final Assessment. T h e final paired column in table 1
shows the frequency of symptoms at the time of the last assessment before the analysis reported here. Comparison with the first paired column reveals that the proportion of cases with symptoms is virtually identical to that at the initial assessment. Reduced numbers in the final assessment result from the fact that it includes patients who have not yet had their second annual appraisal, and excludes those who were assessed only once because of death or successful renal transplantation. If only those patients who have had more than one assessment are considered, the proportions remain approximately the same. T h e pattern of distribution of individual symptoms remains constant, with the striking exception of paresthesiae, which were initially present in 7% hut were absent in the final assessment. Usually, the tingling (or, rarely, burning) paresthesiae that occurred in the feet-and sometimes also in the handscleared rapidly once treatment was instituted. This did not seem to be the case with the symptom of “restless legs”: it appeared for the first time in some patients who were already receiving dialysis. The final paired column in table 3 gives the number of patients with signs of peripheral neuropathy at the final assessment. A slightly smaller proportion of PAtients displayed signs at the final assessment than initially, but the distribution showed no striking difference, although muscle weakness at the time of acceptance tended to improve with dialysis. This was most evident in one patient (case 10 in Thomas et alls), who had a
MUSCLE & NERVE
SepVOct 1978
397
Table 3. Signs of peripheral neuropathy in patients on chronic hemodialysis. Number of patients (%)a
None Weakness 5 wasting Tendon reflex loss or depression Knee Ankle Sensory loss Light touch Pain and temperature Joint position Vibration
Initial
During
Total
100 (67.11) 4 (2.9)
68 (70.1) 2 (2.1)
68 (48.9) 6 (4.3)
69 1
8 (5.8) 19 (13.7)
9 (9.4) 18 (18.8)
‘17 37
(12.2) (26.6)
9 20
4 (2.9) 2 (1.4) 5 (3.6) 14 (10.1)
0 0 1 13
2 0 4 12
(1.4) (0) (2.9) (8.6)
2 2 1 2
(2.1) (2.1) (1.0) (2.1)
Final
”Left-hand columns do not add up to total sample number, and right-hand cdumns do not add up to TOO%, because of symptom overlap and loss of some patients to follow-up.
proposed that recovery of nerve conduction velocity is biphasic, with an initial rapid phase succeeded by a more gradual one. He has suggested that the former phase is related to recovery from a “toxic” impairment of axon Focal Nerve Lesions. During the follow-up period, five membrane function, and the latter to recovery from a patients developed evidence of focal peripheral nerve structural neuropathy involving a combination of axonal lesions; these excluded any that were attributable to the degeneration and segmental demyelination. The mechinsertion of shunts or to the establishment of arterioanism responsible for the occurrence of “restless legs” venous fistulae. Three developed local lesions of the may differ from that of the distal paresthesiae in view common peroneal nerve and one meralgia paresthetica; of its different behavior. That patients may develop an one developed the carpal tunnel syndrome, confirmed almost pure motor neuropathy, as occurred in one paby nerve conduction studies, on the side with an antetient in this series, also suggests either variation in the brachial arteriovenous fistula. Sensory symptoms in the hand were precipitated by dialysis, and the condition was metabolic insult or differences between patients in the selective vulnerability of motor and sensory fibers. relieved by surgical decompression of the nerve. The clinical features of the more persistent symptoms of neuropathy (vibration, joint-position, and tactile DISCUSSION sensory loss) are consistent with a predominant loss of As initially predicted by Asbury, Victor, and Adams,l the larger myelinated fibers; rarely is there loss of pain and temperature sensibility. Despite some initial reports uremic neuropathy is likely to be a sequel of a metabolic to the contrary, it is now clear that uremic neuropathy disturbance related to chronic renal insufficiency. Iminvolves a distal axonal degeneration that generally afprovement by dialysis or renal transplantation suggests fects larger myelinated fibers to a greater extent than the operation of a retained metabolite, the nature of smaller, with relative sparing of unmyelinated axons.8’18 which remains elusive. Clearly, this metabolite has a molecular weight exceeding that of urea or ~ r e a t i n i n e , ’ ~ One personally observed case (not in the present series) developed a gross sensory neuropathy with severe loss and some researchers have surmised that it may be in of sense ofjoint position, vibration, and tactile sensation, the “middle molecular weight” range.3*6Suggestions that myoinositol may be responsible7 have not been conbut with sparing of pain, temperature sensation, and motor power. This led to prominent involuntary movefirmed.12J6 The most recent contender is parathyroid ments of the pseudoathetoid type and sensory ataxia. hormone,’ although, as Avram and his coworkers admit, The occurrence of five instances of focal peripheral the correlation they detected between elevated parathyroid hormone levels and decreased motor nerve connerve lesions in this series supports the contention of duction velocity might be related to some other correNielsen14 that uremic neuropathy, like certain other neuropathies, exhibits an abnormal susceptibility to lated factor that influences peripheral nerve function. pressure palsies. Our patient with the carpal tunnel synThis analysis of the features of peripheral neuropdrome, as in the cases reported by Harding and Le athy in patients receiving chronic hemodialysis suggests fan^,^ described aggravation of her symptoms by dithat the causal mechanisms may be multiple. With dialysis, the tingling paresthesiae felt distally in the limbs alysis. These authors have argued that a vascular steal produced by the shunt may lead to the development of tend to subside rapidly. Whether these sensations result symptoms at the time of dialysis if the nerve is already from overt structural changes in nerve or from alteracompromised by compression in the carpal tunnel. tions in membrane function is uncertain. Nielsen14 has severe symmetrical and almost purely motor neuropathy initially, which slowly recovered almost completely.
398
Uremic Neuropathy
MUSCLE & NERVE
Sept/Oct 1978
REFERENCES
1 . Asbury AK, Victor M, Adams RD: Uremic neuropathy. Arch Neurol 8:413-428, 1963. 2. Avram MM, Feinfeld DA, Huatuco AH: Search for the uremic toxin: decreased motor-nerve conduction velocity and elevated parathyroid hormone in uremia. N EnglJ MeQ 298:lOOO-1003, 1978. 3. Babb AL, Popovich RP, Christopher TG, Scribner BH: The genesis of the square meter-hour hypothesis. Trans Am Soc ArtifIntern Organs 17:81, 1971. 4. Bolton CF, Baltzan MA, Baltzan RB: Effects of renal transplantation on uremic neuropathy. A clinical and electrophysiologic study. N E n g l J Med 284:1170-1175, 1971. 5. Callaghan N: Restless legs syndrome in uremic neuropathy. Neurology (Minneap) 16:359-361, 1966. 6. Christopher TG, Camebi V, Harker LA, Hurst PE, Popovich RP, Babb AL, Scribner BH: A study of hemodialysis with lowered dialysate flow rate. Tram Am Soc Artif Zntern Organs 17:92, 1971. 7. DeJesus PV, Clements RS, Winegrad AI: Hypermyoinositolemic polyneuropathy in rats. A possible mechanism for uremic polyneuropathy. J Neurol Sn‘ 21 :237-249, 1974. 8. Dyck, PJ, Johnson WJ, Lambert EH, O’Brien PC: Segmental demyelination secondary to axonal degeneration in uremic neuropathy. Mayo Clzn Proc 46:400-431, 1971. 9. Harding AE, Le Fanu J: Carpal tunnel syndrome related to antebrachial Cimino-Brescia fistula. J Neurol Neurosurg Psychiatry 40:511-513, 1977.
Uremic Neuropathy
10. Heron JR, Konotey-Ahulu FID, Shaldon S, Thomas PK: Nerve conduction in chronic renal failure treated by dialysis. Excerpta Med Int Cong Ser 103: 138-140, 1965. 1 1 . Jebsen RH, Tenckhoff H, Honet JC: Natural history of uremic polyneuropathy and effects of dialysis.N En91J Med 277:327-333, 1967. 2. Jefferys JGR, Palmano KP, Sharma AK, Thomas PK: Influence of dietary myoinositol on nerve conduction and phospholipids in normal and diabetic rats. J Neurol Neurosurg Psychzatry 41:333-339, 1978. 3. Konotey-Ahulu FID, Baillod R, Comty CM, Heron JR, Shaldon S, Thomas PK: Effect of periodic dialysis on the peripheral neuropathy of end-stage renal failure. Br Med J 2:1212-1215, 1965. 14. Nielsen VK: The peripheral nerve function in chronic renal failure: a survey. Acta Med Scand (Suppl) 573: 1-32, 1974. 15. Preswick G, Jeremy D: Subclinicalpolyneuropathy in chronic renal failure. Lancet 2:731-732, 1964. 16. Reznek RH, Salway JG, Thomas PK: Plasma-myoinositol levels in uraemic neuropathy. Lancrt 1:675-676, 1977. 17. Tenckhoff HA, Boen ST, Jebsen RH, Spiegler JH: Polyneuropathy in chronic renal insufficiency.JAMA 192:11211124, 1965. 18. Thomas PK, Hollinrake K, Lascelles RG, O’Sullivan DJ, Baillod RA, Moorhead JF, Mackenzie JC: The polyneuropathy of chronic renal failure. Brain 94:761-780, 1971.
MUSCLE & NERVE
SepVOct 1978
399
