Volume 2, Issue 7 (Autumn 2016)                   Caspian.J.Neurol.Sci 2016, 2(7): 41-48 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Saeidi M, Raftari S, Roudbary S, Rezaeitalab F, Hatamian H. Peripheral Neuro Electrodiagnostic Abnormalities in Patients with Multiple Sclerosis: A Cross Sectional Study. Caspian.J.Neurol.Sci. 2016; 2 (7) :41-48
URL: http://cjns.gums.ac.ir/article-1-130-en.html
1- Associate Professor of Neurology, Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2- Neurologist, Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3- Associate Professor, Neurology Department of Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
4- Assistant Professor of Neurology, Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Rezaeitalabf@mums.ac.ir
5- Professor, Department of Neurology, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
Full-Text [PDF 636 kb]   (545 Downloads)     |   Abstract (HTML)  (1118 Views)
Full-Text:   (275 Views)

ABSTRACT

Background: Multiple sclerosis (MS) is known to affect essentially the central nervous system; however, peripheral nerve involvement, as an additional cause of disability, has been recently noticed.

Objectives: This study was aimed to perform detailed electrodiagnostic assessments in MS patients to evaluate peripheral nervous system involvement.

Materials and Methods: A total of eighty MS patients were evaluated for probable peripheral nerves involvement in a cross sectional study from August 2012 to August 2013.Patients with evidence of radiculopathy, diabetes, uremia, and anemia or cobalamin deficiency had been excluded. Clinical disability was ascertained by applying Expanded Disability Status Scale (EDSS) score. All electrodiagnostic assessment was performed by a single expert operator. Demographic parameters and paraclinical findings including MRI plaques were recorded. The data were analyzed in SPSS version 19applying the paired t-test and Mann-Whitney U test.

Results: The sural nerves showed the most consistent finding of abnormal conduction velocity (30%). The most frequent amplitude disturbance was observed in the peroneal nerves (10%). We did not find a significant association between abnormal findings and EDSS or MRI plaques (p<0.05). Patients with raised latency of the sensory nerves were younger than those with normal figures (p<0.05). Also, patients with prolonged disease were more likely to show peripheral nerve disturbances (p<0.05).

Conclusion: Peripheral nerve involvement was seen in MS patients, without significant relationship with physical disability and MRI plaques. On the other hand, disease duration, age and male gender were associated with peripheral nerve abnormalities.

Keywords: Electromyography; Multiple Sclerosis; Peripheral Nervous System

Introduction

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease and the most significant cause of disability in young adults. Its most important pathological finding is the plaques of the central nerve system, with distinct areas of the demyelination in white matter of the central nerve system and relative axonal preservation [1]. Tissue damage and neurological symptoms are supposed to be the results of immune mechanisms that target myelin antigens in the central nervous system (CNS) [2].

In addition to the involvement of the CNS, demyelination of the peripheral nerve system has been observed in 5% to 74% of patients that may be due to similar pathogenesis affecting both peripheral and central nerves system [3,4,5]. With nerve conduction studies (NCS), peripheral nerve lesion can be determined by nerve conduction velocity, distal latency, and amplitude of Compound Muscle Action Potential (CMAP) or Sensory Nerve Action Potential (SNAP). In this manner, the damage of the myelin sheet results in raised distal latency and decreased nerve conduction velocity, while decline in CMAP and SNAP amplitude represents axonal damage [6].

Because of a wide range of reported abnormalities, we aimed to investigate NCS changes of the peripheral nerves in MS patients with emphasis on the duration of disease, age and disability. Also, this study examined the relationship between peripheral nerve disturbance and MRI plaques, which has not been reported.

Materials and Methods

The proposal of this prospective cross sectional study was approved by the ethics committee of Mashhad University of Medical Sciences. We studied 88 MS patients who referred from the neurology clinic of Qaem hospital, Mashhad, Northern east of Iran since August 2012 to August 2013. The diagnosis was confirmed based on the 2010 McDonald MS Diagnostic Criteria. The patients were investigated for diabetes mellitus, anemia, uremia, vitamin B12 deficiency or rheumatologic diseases through laboratory tests. Individuals with above conditions or with a history of trauma or surgery in the limbs, neck and lumbar spine, also myopathic findings and evidence of radiculopathy or carpal tunnel syndrome in the electrodiagnostic tests were excluded from the study.

Ultimately, a total of 80 patients completed the study. Written informed consent was provided by each participant.

Their disabilities were assessed according to the Expanded Disability Status Scale (EDSS) score through a precise neurological examination and recorded. According to clinical course, the types of MS were determined: relapsing remitting (RR), secondary progressive (SP), primary progressive (PP), and progressive relapsing (PR). Demographic information such as age, gender, and duration of the disease was recorded. They were placed in three age related groups: under 30, 31 to 40, and more than 41 years old. Next, they underwent nerve conduction studies of the ulnar, median, tibial, peroneal and sural nerves on both sides by EMG/NCV system, (1 Nihon Kohden Neuropack S1 MEB 2300 A / in Japan).  Also, the number of plaques and the involved areas of the brain and spinal cord were calculated based on Magnetic Resonance Imaging (MRI)s   taken   during  the  previous year. After data collection and entry, the statistical software SPSS-19 was used to analyze the data and the paired t-test and Mann-Whitney U test were applied to compare the significance of variables. P-value less than 0.05 were considered as the significant difference level.

Results

The sample comprised of 80 MS patients, 15 male (18.8%) and 65 female (81.2%). The mean age of the participants was 31±7.5 year. The most common age group was younger than 30 years (47.5%). The most common type was relapsing remitting (RR) with 91.5%, followed by PR and SP. Mean duration of the disease was 47.1±5.1 months.

The average number of MRI plaques was 6.6±3.1and mean EDSS score was 1.3±0.43.

The mean amplitude, latency, and velocity of the sensory and motor nerves of the upper and lower limbs have been presented in table 1.Accordingly, among upper limb nerves, the most frequent disturbance of latencies and amplitudes were related to the ulnar nerves (15% and 6.2%, respectively), and of velocity was detected in the median nerves (20% of the motor branches and 25% of the sensory branches). In the lower limbs, abnormal latencies and amplitudes of the motor nerves were more prevalent in the peroneal nerves (16.25% and 10%, retrospectively) and disturbance of velocity was more commonly presented in the tibial nerves (27.5%).

Table 1. Electrodiagnostic findings of the peripheral nerves among MS patients

Motor nerve

Sensory nerve

Nerve

Index

Mean ± SD

Normal range

The number

of patients with abnormal finding (%)

Mean ± SD

Normal range

The number

of patients with abnormal finding (%)

Median

Amplitude (µV)

6.3± 2.5

≥ 4.0

2 (2.5)

39.3 ± 18.1

≥20

4(5)

Latency (ms)

4.2 ± 0.63

≤ 4.4

5(6.2)

3.1± 0.81

≤ 3.5

12 (15)

Velocity (ms)

49± 5.6

≥ 49

16 (20)

51± 6.1

≥ 50

20 (25)

Ulnar

Amplitude (µV)

9.1 ± 1.8

≥ 7.0

5(6.2)

34.8 ± 18.2

≥17

2 (2.5)

Latency (ms)

3.1± 0.6

≤ 3.3

12 (15)

2.9 ± 0.44

≤ 3.1

10 (12.5)

Velocity (ms)

48.4 ± 6.7

≥ 49

12 (15)

57.1±8.2

≥ 50

18 (22.5)

Peroneal

Amplitude (µV)

3.9  ±1.1

≥ 3

8(10)

-

-

Latency (ms)

5.7±1.09

≤ 6.5

13 (16.25)

-

-

Velocity (m/s)

50.2  ± 9.1

≥ 44

20 (25)

-

-

Tibial

Amplitude (µV)

7.1± 3.6

≥ 4

4 (5)

-

-

Latency (ms)

4.9 ±1.05

≤ 5.8

7 (8.7)

-

-

Velocity (ms)

47.4±7.6

≥ 41

22 (27.5)

-

-

Sural

Amplitude (µV)

-

-

10.1±5.2

≥6

8 (10)

Latency (ms)

-

-

4.1± 0.81

≤4.4

13 (16.2)

Velocity (ms)

-

-

45.2 ± 7.1

≥ 40

24 (30)

SD=Standard Deviation. The normal values arequotedfrom the reference text book (6)

We also examined the relationship between electrodiagnostic findings and gender, duration of the disease, MRI plaques and EDSS scores; the results are shown in table 2 to 6. According to this, there was a significant gender differences in favor of women in the frequency of amplitude disturbances of the examined motor nerves. The other electrodiagnostic findings did not differs statistically in the different sexes (Table 2).

Table 2. The relationship between gender and abnormal findings of the nerves

Nerve

Index

Males

With abnormal motor test (%)

Females

 with abnormal motor test (%)

Fisher Exact Test  p-value

Males

with abnormal sensory test (%)

Females

with abnormal sensory test (%)

Fisher Exact Test  p-value

Median

Amplitude

0 (0)

2 (2.5)

0.002

1 (1.1)

4 (5)

0.001

Latency

2 (2.5)

3 (3.7)

0.213

5(6.2)

7 (8.7)

0.168

Velocity

6 (7.5)

10 (12.5)

0.412

8 (10)

12 (16)

0.107

Ulnar

Amplitude

1 (1.1)

4 (5)

0.001

0

2 (2.5)

0.002

Latency

3 (3.7)

7 (8.7)

0.441

4 (5)

8 (10)

0.174

Velocity

5(6.2)

7 (8.7)

0.301

7 (8.7)

11(13.75)

0.168

Tibial

Amplitude

0 (0)

4 (5)

<0.000

-

-

-

Latency

2 (2.5)

5 (6.2)

0.558

-

-

-

Velocity

10 (12.4)

12 (16)

0.174

-

-

-

Peroneal

Amplitude

2 (2.5)

6 (7.5)

0.023

-

-

-

Latency

4(5)

9 (11.1)

0.168

-

-

-

Velocity

12 (16)

8 (10)

0.107

-

-

-

Regarding age, the patients with and without abnormal amplitude of sensory and motor upper limb nerves was in similar ranges. The average ages of patients with normal and abnormal latency of all motor nerves were similar except for the ulnar and the tibial nerves. Among the sensory nerves, patients with abnormal latencies of the median, ulnar, and sural nerves were significantly younger than those with normal figures. The other abnormal parameters were not showed to be related to age (Table 3).

Table 3. The relationship between age and abnormal findings of the nerves

Motor nerve

Sensory nerve

Nerve

Electrodignostic finding

Mean

age± SD years

T test

p-value

Mean

age± SD years

T test

p-value

Median

Normal

29.8±6.5

0.764

31.7±7.4

0.033

Abnormal

27.8± 5.5

-

26.5±5.5

-

Ulnar

Normal

32.1±6.3

0.016

32.3±6.3

0.002

Abnormal

28±4.3

-

24.5±5.4

-

Peroneal

Normal

30.1±4.1

0.868

-

-

Abnormal

29.8 ±6.5

-

-

-

Tibial

Normal

31.8±5.6

0.001

-

-

Abnormal

27.3±3.91

-

-

-

Sural

Normal

-

-

31.4±7.8

0.016

Abnormal

-

-

28.1±3.2

-

Furthermore, data analysis showed that the average period of the disease was similar among patients with normal and abnormal amplitudes. However, it was significantly higher in patients with the following findings: abnormal amplitude of the sural and sensory median, increased latency of   the motormedian, ulnar, tibial and peroneal nerves, and raised latency of the sensory median nerves. The average duration of disease in patients with abnormal velocity of the all nerves was significantly more than those with normal velocity, except for the sural, the sensory ulnar and the motor tibial nerves (Table 4).

Table 4. The association between electrodiagnostic findings of motor nerves and duration of MS

Motor nerve

                        Sensory nerve

Nerve

Index

Electrodiagnostic finding

Mean years of disease ± SD

p-value

Electrodiagnostic finding

Mean years of disease ± SD

p-value

Median

Amplitude

Normal

5.8 ± 3.4

0.235

Normal

5.7 ± 3.3

0.026

Abnormal

6.5 ± 2.5

Abnormal

6.4 ± 2.1

-

Latency

Normal

5.4 ± 3.1

0.001

Normal

5.4 ± 3.2

<0.0001

Abnormal

9.4 ± 3.1

Abnormal

9.1 ± 3.2

Velocity

Normal

4.1 ± 2.8

0.007

Normal

4.8 ± 3.2

0.008

Abnormal

6.6 ± 3.3

Abnormal

6.1 ±2.3

Ulnar

Amplitude

Normal

5.7 ± 3.3

0.033

Normal

5.8 ± 3.4

0.382

Abnormal

7.1 ± 3.3

Abnormal

8.0

Latency

Normal

5.4 ± 3.3

0.041

Normal

5.7 ± 3.3

0.745

Abnormal

8.1 ± 3.1

Abnormal

6.8 ± 3.4

Velocity

Normal

4 ± 2.2

0.002

Normal

5.3± 3.5

0.001

Abnormal

6.8 ± 3.5

Abnormal

3.5 ± 1.5

Peroneal

Amplitude

Normal

5.7 ± 3.4

0.237

Normal

-

-

Abnormal

7.1 ± 3.3

Abnormal

-

Latency

Normal

5.5 ± 3.3

0.004

Normal

-

-

Abnormal

8.2 ± 3.5

Abnormal

-

Velocity

Normal

4.9 ± 2.7

0.007

Normal

-

-

Abnormal

6.7 ± 3.4

Abnormal

-

Tibial

Amplitude

Normal

5.8 ± 3.4

0.23

Normal

-

-

Abnormal

6.4 ±2.5

Abnormal

-

Latency

Normal

5.7 ± 3.3

0.03

Normal

-

-

Abnormal

8.1 ± 2.3

Abnormal

-

Velocity

Normal

6.4 ± 3.3

0.201

Normal

-

-

Abnormal

5.2 ± 3.1

Abnormal

-

Sural

Amplitude

Normal

-

-

Normal

5.4 ± 3.1

<0.000

Abnormal

-

Abnormal

10.1 ± 2.2

Latency

Normal

-

-

Normal

5.8  ±3.3

0.218

Abnormal

-

Abnormal

6.4 ± 3.3

Velocity

Normal

-

-

Normal

6.5 ± 3.3

0.001

Abnormal

-

Abnormal

4.8 ± 3.1

SD=Standard Deviation

There was no relationship between electrodiagnostic findings and the average number of MRI plaques and mean EDSS score (Table 5 and 6).

Table 5. The association between electrodiagnostic findings and the number of MRI plaques in MS patients

Motor nerve

Sensory nerve

Nerve

Electrodiagnostic finding

Mean number of plaques ± SD

p-value

Electrodiagnostic finding

Mean years of disease ± SD

p-value

Median

Normal

6.3 ± 3.0

0.37

Normal

6.7 ± 3.1

0.188

Abnormal

7.3 ± 3.4

Abnormal

3.7 ± 2.5

Ulnar

Normal

6.2 ± 2.8

0.101

Normal

6.5 ± 3.1

0.121

Abnormal

7.8 ± 3.6

Abnormal

10

Peroneal

Normal

6.2 ± 2.7

0.98

Normal

-

-

Abnormal

7.2 ± 3.3

Abnormal

-

Tibial

Normal

6.3 ± 2.6

0.581

Normal

-

-

Abnormal

6.9 ± 3.6

Abnormal

-

Sural

Normal

-

-

Normal

6.7 ± 3.3

<0.0001

Abnormal

-

Abnormal

5.2 ± 3.3

Discussion

The most common abnormality in this study was found in the NCV of the sural nerves (30%), followed by the tibial nerves (27.5%). The reported abnormalities of the peripheral nerves are various in the previous studies. For example, NCV abnormalities were reported in 29.4% of MS patients by Gartzenk et al. [7] and in only 5% by Misawa et al. [3]. In Shefner's study, 9 patients out of 14 showed normal amplitude and velocity [8]. In Pogonzelski's study, 74% of sufferers had at least one abnormality of the electrodiagnostic parameters that was not shown to be related to age, sex, and duration of the disease [5], while in our study some of the electrodiagnostic disturbances were seen in younger ages. In Ayromlu's study, abnormal amplitude (22.5%) and velocity of the motor nerves (33%) were common, while the frequency of abnormal velocity of the sensory nerves was not more common compared with the normal population [9].

In a study conducted by Anlar et al. the most common electrodiagnostic abnormality was low amplitude of ulnar and sural nerves that were detected in 16.5% of MS patients. Again, this research did not show any relationship between peripheral nerve disorders and MS signs, neurologic deficits and gender [10]. In contrast, the present study showed that abnormal amplitude  of some of the peripheral nerves was seen more in male patients, while velocity and latency disturbances did not differ with gender. Besides, it was observed that the longer duration of MS disease, the higher the frequency of some abnormal findings, specially delayed latencies of all motor nerves and the sensory median nerve.

On the other hand, the amplitude disturbances in our study, did not accompany a higher number of MRI plaques. Also, the EDSS scores were not related to electrodiagnostic parameters. Hence, we did not find an association between peripheral nerve affection and disability related to MS. Sarova-Pinhas et al. also showed no relationship between NCS findings and disability among MS patients [11], to best of our knowledge, the present study is the only one that analyzed the correlation between MRI plaques and NCS abnormalities.

Altogether, peripheral nerve involvements have been reported to be between 5 to 74 percent in MS patients [3,5,7,9,10]. This wide range of frequency may be attributed to genetic diversity or different sample sizes and inclusion/exclusion criteria. In the other Iranian study (Ayromlu et al.), the frequency of abnormalities was near to our study [9], which may be explained by genetic factors or common    environmental   agents  that  affect both peripheral and central nervous system. These findings may support some aspect of currently proposed pathophysiology of MS disease. On the other hand, based on the aim of the studies, the results are different. For instance, the lowest figure (5%) represented only significant demyelinating polyneuropathy reported by Misawa et al. [3], while the highest figure (74%) belonged to the Pogonzelski's study, showed any subclinical lesions of the peripheral nervous system in MS [5]. Also, sample size may justify the different results. Anlar et al.’ study with 20 subjects reported 16.5% abnormalities, while Gartzen et al. study with a sample size similar to our study (54 subjects) found 29.6% abnormal findings [7].

 In general, it seems that younger patients suffering from MS for longer periods of time are more susceptible to develop some peripheral nerve disorders, especially for delayed latencies of the motor ulnar and tibial, and the sensory median nerves. In addition, the presence of peripheral nerve abnormalities in some MS patients may open a window to understanding the nature of the demyelinating process in this disease.

Conclusion

This study showed that abnormalities of the peripheral nerve system occurred regardless of MRI plaques or EDSS. On the other hand, disease duration, age and gender were associated with some peripheral nerve abnormalities. 

Acknowledgments

 The authors appreciate the cooperation of electrodignostic staff in Qaem hospital and the neurology department of Mashhad University of Medical Sciences.

Conflict of Interest

The authors have no conflict of interest. 

References

  1. Bradly WG, Robert B, Gerald M, Jankovic J. Neurology in Clinical Practice. 5th ed. Philadelphia: Butterworth-Heinemann: Elsevier; 2008.
  2. Serafini B, Rosicarelli B, Franciotta D, Magliozzi R, Reynolds R, Cinque P, et al. Dysregulated Epstein-Barr Virus Infection in the Multiple Sclerosis Brain. J Exp Med 2007; 204(12):2899-912.
  3. Misawa S, Kuwabara S, Mori M, Hayakawa S, Sawai S, Hattori T. Peripheral Nerve Demyelination in Multiple Sclerosis. Clin Neurophysiol 2008; 119(8):1829-33.
  4. Confavreux C, Vukusic S, Adeleine P. Early Clinical Predictors and Progression of Irreversible Disability in Multiple Sclerosis: an Amnesic Process. Brain 2003; 126(Pt 4):770-82
  5. Pogorzelski R, Baniukiewicz E, Drozdowski W. Subclinical Lesions of Peripheral Nervous System in Multiple Sclerosis Patients. Neurol Neurochir Pol 2004; 38(4):257-64.
  6. Shapiro B, Pretson D. Electromyography and Neuromuscular disorders. 3th ed. London: Elsevier; 2013.
  7. Gartzen K, Katzarava Z, Diener HC, Putzki N. Peripheral Nervous System Involvement in Multiple Sclerosis. Eur J Neurol 2011; 18(5):789-91.
  8. Shefner JM, Carter JL, Krarup C. Peripheral Sensory Abnormalities in Patients with Multiple Sclerosis. Muscle and Nerve 1992; 15(1):73-6.
  9. Ayromlou H, Mohammad-Khanli H, Yazdchi-Marandi M, Rikhtegar R, Zarrintan S, Golzari SE, Ghabili K. Electrodiagnostic Evaluation of Peripheral Nervous System Changes in Patients with Multiple Sclerosis. Malays J Med Sci 2013; 20(4):32-8.
  10. Anlar O, Tombul T, Kisli M. Peripheral Sensory and Motor Abnormalities in Patients with Multiple Sclerosis. Electromyogr Clin Neurophysiol 2003;43(6):349-51.
  11. Sarova-Pinhas I, Achiron A, Gilad R, Lampl Y. Peripheral  Neuropathy in Multiple Sclerosis: a Clinical and Electrophysiologic Study. Acta Neurol Scand 1995;91(4):234-8.

  1. Hidasi E, Diószeghy P, Csépány T, Mechler F, Bereczki D. Peripheral Nerves Are Progressively Involved in Multiple Sclerosis-a Hypothesis from a Pilot Study of Temperature Sensitized Electroneurographic Screening. Medical Hypotheses 2009; 72(5):562-6.
  2. Warabi Y, Yamazaki M, Shimizu T, Nagao M. Abnormal Nerve Conduction Study Findings Indicating the Existence of Peripheral Neuropathy in Multiple Sclerosis and Neuromyelitis Optica. Biomed Res Int 2013; 2013:Article ID 847670.

  1. Grana EA, Kraft GH. Electrodiagnostic Abnormalities in Patients with Multiple Sclerosis. Arch Phys Med Rehabil 1994; 75(7):778-82.

15. Petajan JH. Electromyographic Findings in Multiple Sclerosis: Remitting Signs of Denervation. Muscle Nerve 1982;5(9S):S157-60.

Type of Study: Research | Subject: Special
Received: 2017/01/5 | Accepted: 2017/01/5 | Published: 2017/01/5

Add your comments about this article : Your username or Email:
Write the security code in the box

© 2017 All Rights Reserved | Caspian Journal of Neurological Sciences

Designed & Developed by : Yektaweb