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July2007 Vol.44 Issue:      2 Table of Contents
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Evaluation of The Clinical and Neurophysiologic Parameters of Peripheral Nerve Functions in Uremic Egyptian Patients

Lobna Ibrahim Sultan

Department of Neurology, Alexandria University



ABSTRACT

Polyneuropathy (PNP) is one of the most frequent neurological manifestations of chronic renal failure (CRF). Uremic neuropathy has attracted great interest, however, some debate is still present about many of its aspects. The aim of the present work was to study the prevalence and the patterns of peripheral neuropathy in Egyptian CRF patients treated with and without dialysis. Also to establish which of the electrophysiologic parameters are the most sensitive in demonstrating PNP. Patients and Methods: Forty CRF patients were enrolled in this study (21 males, 19 females) with average age 43.64±11.5 years. They were divided into two equal groups according to the scheduled treatment protocol: the hemodialysis group [HG] and conservative group [CG]. The study also included 20 volunteers as a control group. Electrophysiological parameters for motor and sensory evaluation of nerve functions were executed. Motor conduction studies were performed for the median, ulnar, tibial and peroneal nerves. F wave studies were done for the aforementioned nerves. Sural, ulnar and radial sensory conduction nerve studies as well as H reflex study were also included. The severity of polyneuropathy were graded on clinical basis using total clinical neuropathy score [TNSc] as well as both clinical and electrophysiological basis using total neuropathy score [TNSr]. Results: The prevalence of PNP was 65% in the HG and 60% in the CG with no significant difference between them. The overall prevalence of PNP in CRF patients was 62.5%. It was commoner and severer in males than females. It was evident clinically in 37.5%. No significant difference was found between the clinical and electrophysiological severity of PNP in both groups. The TNSr showed only mild to moderate PNP. The pattern of uremic neuropathy was axonopathic affecting the sensory fibers more than the motor ones, distal more than proximal portions of peripheral nerves. Both large and small fibers populations were affected but with large fiber predominance. Peroneal and sural nerves showed the highest rate of pathologic electrophysiologic parameters (62.5% each), followed by the tibial nerve (60%). The least affected nerves were the radial and median (20% & 27.5%respectively) followed by the ulnar and facial nerves (32.5% each). H reflex latency, peroneal minimal F latency as well as both sural nerve peak latency and sensory nerve action potential (SNAP) showed a 100% sensitivity in detecting PNP. Followed by tibial minimal F latency, peroneal compound motor action potential (CMAP) amplitude and sural nerve conduction velocity (CV) (96% sensitivity each). Then came the tibial CMAP amplitude and peroneal CV (92% sensitivity reciprocally). A positive correlation was found between blood urea, serum creatinine, serum potassium and severity of PNP. More close negative correlation was found between creatinine clearance, hemoglobin concentration and uremic neuropathy. The study revealed that neither the prevalence nor the severity of uremic neuropathy were related to the patient’s age, nature of the underlying kidney disease or duration of dialysis treatment. Conclusion: The prevalence of PNP in CRF patients is still considerable despite of the considerable awareness of the problem and the recent advancement in treatment. Hyperkalemia emerges as a contributing factor to the development of neuropathy as well as urea and creatinine levels seem to act synergistically with other potential neuro toxins. The most sensitive electrophysiologic parameters were abnormalities in H reflex latency, sural nerve parameters and F wave minimal latency of the peroneal and tibial nerves. (Egypt J. Neurol. Psychiat. Neurosurg., 2007, 44(2): 473-487)




INTRODUCTION

 

Described at the end of the 19th century, investigated from the development of dialysis since 1960, peripheral neuropathy occurs almost constantly in patients with CRF. Uremic neuropathy attracted great interest and became an important issue since the advent of long term hemodialysis and renal transplantation programs for the treatment of terminal uremia. This is because the occurrence of neuropathy has been one of the limiting factors in their success.1

The reported incidence of uremic neuropathy showed a great variability and may reach up to 100% of cases with CRF depending on the used diagnostic criteria.2 The major questions concerning the mechanism of production of neuropathy still remain unanswered, although many mechanisms have been implicated. The most widely accepted mechanism is that accumulation of slowly dialyzable middle molecules (500- 2000 Daltons) which may include methylguanidine, parathyroid hormones, B2 microglobulin and myoinositol, can be correlated with the degree of neurotoxicity.3

In patients with CRF abnormal electrophysiological study of the peripheral nerves may be present in the absence of symptoms and physical findings of neuropathy.3 Electrophysiological techniques are performed to quantify the demyelinating and axonal lesions, to verify the long term adequacy of dialysis, and to observe improvement after kidney transplantation.1

Peripheral nerve involvement in patients with chronic renal failure is important from the rehabilitation point of view. Neuropathy adds more disability to these patients. It also may affect the function and quality of life in them. In view of these facts it looks important to study the peripheral nerve function in patients with chronic renal failure to disclose the magnitude of peripheral nerve impairment in these patients. This is essential for proper assessment of their disability and subsequent rehabilitation.

The aim of this work was two-fold: first, to study the prevalence and the patterns of peripheral neuropathy in CRF patients with and without dialysis. Second, to assess the sensitivity of the various electrophysiologic parameters in detection of uremic neuropathy.

 

MATERIALS AND METHODS

 

The study included 40 CRF patients divided into two groups according to the scheduled treatment protocol. The hemodialysis group (HG) included 20 patients (9 females& 11 males). Their mean age was 43.27±11.5 years. All of them received 3 hemodialysis sessions per week. The conservative group (CG) included 20 patients (10 females & 10 males). Their mean age was 44.8±11.4 years. The mean durations of their kidney disease were 72.3±43 months for HG and 64.9±39 months for CG.

Twenty normal volunteers served as controls and were matching in age & sex to the patients.

 

A-      Clinical assessment:

A full history taking with special emphasis on cause, onset, duration of kidney disease and duration of hemodialysis (for HG). Detailed neurological history with particular reference to presence of risk factors for polyneuropathy and to the occurrence of symptoms indicating peripheral neurological damage. Patients with other possible causes indicating peripheral neuropathy such as diabetes, alcoholism, amyloidosis or other systemic illness were excluded. No medications known to affect nerve function were taken by these subjects. Each patient was alert, fully oriented, cooperative and responsive during all phases of testing.

Complete neurological examination was done with special emphasis on peripheral nerves examination.

 

B-      Laboratory investigations:

The following laboratory investigations were performed for every patient before electrophysiological examination: complete blood count, fasting and 2 hours post-prandial blood sugar, liver function tests. Patients with abnormal results were excluded from the study. Renal function tests (blood urea, serum creatinine and clearance tests). Serum electrolytes for sodium, potassium, bicarbonate and phosphorus were estimated (pre and post dialysis in HG group).

 

C-      Imaging studies: Abdominal ultrasound was done for nephropathy grading. Cervical and lumbosacral plain X rays were obtained for screening spinal disorders that may cause radiculopathy.

 

D-      Electrophysiologic evaluation: were done by using ComperioTM EMG/EP machine and Neuropack Nihon Koden® Machine.

*     Motor nerve conduction studies for the facial, median, ulnar, femoral, common peroneal and tibial nerves. The assessed parameters were the distal latency (DL), amplitude of the compound muscle action potential (CMAP), (peak to peak), duration of CMAP, nerve conduction velocity. Except for the facial and femoral nerves where the NCV were not recorded because stimulation was done at only one site.

*     Sensory nerve conduction studies for the ulnar, radial and sural nerves. The onset latency, peak latency, amplitude of sensory nerve action potential (SNAP) (peak to peak) and nerve conduction velocity (NCV) were the recorded sensory parameters.

*     F wave study for all nerves examined by motor study.

*     Gastro-soleus H reflex study.

 

Distal latency, nerve action potential and F waves determination were measured as described by Stalberg and Falck4 and Falck et al.5.

For dialysis patients, the electrophysiological study was done the day next to dialysis session.

For clinical and electrophysiological case definition and identification of polyneuropathy, we used the guidelines of the report of American Academy of Neurology, in conjunction with the American Association of Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation.6

Reduced version of the total neuropathy score (TNSr)7 and clinical total neuropathy score (TNSc)8 were used for quantification and grading of polyneuropathy. Modified criteria of Albert and Kelley was used for determining if the polyneuropathy is primarily demyelinating in nature.

For determining large and small fibre involvement, the clinical criteriae proposed by Lefaucher and Creange were applied.9

 

RESULTS

 

Out of the 40 CRF patients, polyneuropathy was evident in 62.5%. Fifteen patients (37.5%) had clinical evidence of polyneuropathy. In 10 patients (25%), it was only detected electrophysiologically. No significant differences was found in the prevalence of polyneuropathy between CRF patients whether treated conservatively or by hemodialysis (Table 1).

The mean TNSr was significantly higher in males than females (20.35±10.37 & 9.0±8.29 respectively). (Table 2)

There was also high significant difference in the mean TNSr between patients with kidney disease less than 5 years, 5-10 years and more than 10 years (2.5±0.7, 13.85±10.4 and 24.3±7.5 respectively). Neither patient's age, nor nature of underlying kidney disease was associated with occurrence of polyneuropathy.

The duration of dialysis in the polyneuropathy HG didn't differ significantly from those without neuropathy (Table 2).

A significant positive correlation was found between the level of blood urea, serum creatinine, serum potassium and degree of polyneuropathy. On the other hand, negative significant correlation occurred between creatinine clearance, hemoglobin concentration and severity of neuropathy (Fig. 1). No correlation was found between the other tested biochemical parameters and the presence or absence of neuropathy.

Motor conduction parameters (Table 3)

CRF patient and controls showed statistical significant difference between them in all the motor conduction parameters of the tibial, peroneal and facial nerves.

No significant difference in the mean ulnar distal motor latency, CMAP amplitude or CV among the studied groups, as well as the mean latency of the femoral nerve.

Regarding median nerve, it showed a significant difference in all its motor conduction parameters between HG and controls. While, it showed a significant difference in only the mean CMAP between the CG and controls. The mean median latency showed significant differences between both HG & CG.

 

Sensory conduction study parameters (Table 4)

Significant differences were found in the mean peak latency SNAP amplitude and CV of the sural nerve between CRF groups and controls.

For the ulnar nerve, significant difference was only found in the SNAP amplitude between both CRF groups versus controls (51.78±18.0, 54±16.3 versus 66.72±12.0 µV) (p=0.005). No significant differences were found in the ulnar peak latency and CV

For the radial nerve, no significant differences were found between it’s sensory conduction parameters in the CRF patients and controls

 

Late response parameters (Table 5):

F wave parameters of peroneal and median nerves showed a highly significant difference between HG and CG at one side and controls on the other side.

Although the conventional motor study parameters of the ulnar nerve didn't show a significant difference between patients and controls, (Table 3) yet F wave minimal latency showed a significant difference between them.

A highly significant difference was also found in the mean minimal F wave latency of the tibial nerve between each of patients groups and controls.

The mean H reflex latency showed a very high significant difference between patients groups and controls.

Significant predominance of large fibre affection was found in the uremic neuropathy patients. Non of them had sole manifestations of small fiber affection (Table 6).

By comparing the ratio of the proximal and distal amplitude and area of CMAP of all motor nerve examined no significant difference was found between patients with neuropathy and controls (Table 7).


 

 Table 1. The prevalence of polyneuropathy in the studied groups.         

 

 

Cases defined clinically

c2

P

Subclinical neuropathy

Cases defined clinically and electrophysiologically

c2

P

No.

Percent

no.

Percent

no.

Percent

Hemodialysis group

8

40%

0.417

0.519

5

25%

13

65%

0.1

0.744

Conservative group

7

35%

5

25%

12

60%

Total

15

37.5%

 

10

25%

25

62.5%

 

 

 

 

 Table 2. Correlation between clinical variables and severity of polyneuropathy.

Clinical variable

CRF patients

Test of significance

Total neuropathy score

Mean±SD

Test of significance

With Neuropathy

Without Neuropathy

Age group

 

 

 

 

 

20 –

4

5

c2 = 4.33

P = 0.114

19.00±9.59

F = 0.49

P = 0.618

35 –

10

8

14.00±11.22

< 50 years

11

2

18.36±11.71

Sex

 

 

 

 

 

Male (n=21)

17

4

c2 = 6.42

20.35±10.37

t = 2.93

Female (n=19)

8

11

P = 0.01

9.00±8.29

P = 0.01

Duration of kidney disease

 

 

 

 

 

Less than 5 y

2

11

c2 = 19.5

P = 0.000

2.5±0.7

H = 10.23

P = 0.006

5y to less than 10 y

14

4

13.85±10.4

< 10 years

9

0

24.33±7.51

Duration of dialysis in HG (n=20)

 

 

 

 

 

Less than 5 y

9

4

c2 = 0.29

P = 0.589

16.3±11.4

U = 14

P = 0.53

5 years or more

4

3

20.5±11.8

Causes of kidney disease

 

 

 

 

 

Autoimmune

0

1

c2 = 6.04

P = 0.41

 

H = 0.87

P = 0.92

Hypertension

9

5

14.22±12.87

Polycystic kidney

2

2

15.5±17.67

Obstructive nephropathy

4

0

21.7±3.3

Pyelonephritis

2

1

18.5±14.84

Drug induced

0

1

 

Not determined

8

5

16.87±11


 

Fig. (1): A scatter and dot graphs showing the correlations between the degree of polyneuropathy

(Total neuropathy score; TNSr) and biochemical parameters of patients.

Table 3. Motor conduction parameters of the studied groups.

 

 

Hemodialysis group

Conservative group

Control group

F

P

Mean±SD

Mean±SD

Mean±SD

Median

 

 

 

 

 

Latency (msec)

4.22 ± 1.08

3.14 ± 0.57

3.12 ± 0.44

13.8

0.000

Amplitude (mv)

9.58 ± 3.30

12.7 ± 5.5

15.7 ± 3.3

9.14

0.000

CV (m/sec)

51.1 ± 3.9

55.57 ± 6.82

60.0 ± 3.88

15.68

0.000

Ulnar

 

 

 

 

 

Latency (msec)

2.7 ± 0.49

2.58 ± 0.52

2.4 ± 0.36

1.78

0.1

Amplitude (mv)

13.79 ± 3.36

13.83 ± 3.49

15.92 ± 2.12

2.97

0.059

CV (m/sec)

56.94 ± 6.13

57.65 ± 6.46

61.45 ± 4.10

3.03

0.056

Tibial

 

 

 

 

 

Latency (msec)

5.26 ± 1.15*

5.06 ± 1.04*

4.26 ± 0.42

6.38

0.003

Amplitude (mv)

11.27 ± 6.04*

12.37 ± 5.00*

16.93 ± 3.4

7.32

.0002

CV (m/sec)

42.6 ± 4.4*

42.9 ± 5.35*

47.90 ± 2.67

9.7

0.000

Peroneal

 

 

 

 

 

Latency (msec)

5.44 ± 1.00*

5.43 ± 1.27**

4.6 ± 0.70

4.14

0.020

Amplitude (mv)

3.59 ± 2.47*

3.76 ± 2.48**

7.55 ± 1.41

20.7

0.000

CV (m/sec)

43.55 ± 4.94*

43.52 ± 4.18**

49.22 ± 2.11

13.77

0.000

Facial

 

 

 

 

 

Latency (msec)

3.51 ± 0.70

3.41 ± 0.67

2.9 ± 0.34

5.04

0.01

Amplitude (mv)

2.88 ± 0.67

2.85 ± 0.74

3.43 ± 0.57

4.35

0.01

Femoral

 

 

 

 

 

Latency (msec)

4.89 ± 0.99

5.0 ± 0.92

4.56 ± 0.98

1.1

0.33

Amplitude (mV)

11.68 ± 3.29

11.51 ± 3.1

13.69 ± 1.7

3.6

0.03

*   Response was absent in 1 case                                           ** Response was absent in 2 cases

CV= conduction velocity, msec = milli second, mV= milli volt

 

Table 4. Sensory conduction parameters of the studied groups.

 

 

Hemodialysis group

Conservative group

Control group

F

P

Mean ± SD

Mean ± SD

mean ± SD

Ulnar

 

 

 

 

 

Latency (msec)

2.90 ±0.30

2.85 ± 0.32

2.7 ± 0.19

2.64

0.080

Amplitude (µv)

51.78 ± 18.0

54.0 ± 16.32

66.72 ± 12.0

5.28

0.008

CV (m/sec)

54.65 ± 5.42

54.52 ± 5.43

57.7 ± 2.7

2.92

0.062

Radial

 

 

 

 

 

Latency (msec)

2.46 ± 0.30

2.49 ± 0.33

2.31 ± 0.22

2.19

0.120

Amplitude (µv)

42.21 ± 19.53

40.48 ± 15.24

52.23 ± 12.82

3.09

0.053

CV (m/sec)

56.35 ± 6.01

56.54 ± 6.02

60.13 ± 3.98

3.08

0.054

Sural

 

 

 

 

 

Latency (msec)

3.93 ± 0.64*

3.98 ± 0.76**

3.00 ± 0.55

11.26

0.000

Amplitude (µv)

10.67 ± 4.64*

9.84 ±n 3.82**

14.92 ± 1.53

12.72

0.000

CV (m/sec)

40.1 ± 5.92*

39.86 ± 5.40**

46.48 ± 2.52

11.59

0.000

*   Response was absent in 7 case       ** Response was absent in 6 cases              µv =microvolt

Table 5. Comparison between late response parameters in the studied groups.

 

Late response parameters

Hemodialysis group

Conservative group

Control group

F

P

Mean±SD

Mean±SD

Mean±SD

F- Wave

Median nerve

 

 

 

 

 

Latency (msec)

29.53 + 3.80

26.71 ± 2.81

25.11 ± 1.96

11.43

0.000

Persistence

89.0 ± 12.93

98.5 ± 2.85

98.25 ± 2.93

9.55

0.000

Ulnar nerve

 

 

 

 

 

Latency (msec)

28.83 ± 3.79

28.48 ± 3.54

26.38 ± 1.82

3.46

0.038

Persistence

93.88 ± 18.0

98.0 ± 4.97

99.0 ± 2.05

1.24

0.296

Tibial nerve

 

 

 

 

 

Latency (msec)

52.03 ± 5.01

50.47 ± 7.81

45.39 ± 3.91

7.05

0.002

Persistence

93.5 ± 22.71

87.5 ± 29.2

100 ± 0.0

1.71

0.190

Peroneal nerve

 

 

 

 

 

Latency (msec)

54.0 ± 5.37*

50.76 ± 7.13**

45.67 ± 3.71

10.85

0.000

Persistence

38.5 ± 28.7*

44.25 ± 41.07**

77.25 ± 20.8

8.91

0.001

Gastro-soleus H-Reflex

 

 

 

 

 

Latency (msec)

33.75 ± 3.4*

34.0 ± 4.2*

28.65 ± 2.0