|Year : 2016 | Volume
| Issue : 3 | Page : 179-183
Phrenic neuropathy in comparison with peripheral neuropathy in patients with chronic renal failure on hemodialysis
Ahmed Abohagar1, Yossri Ashour1, Mohamed Negm1, Abdelnasser Mourad2, Mohamed Hegazy1
1 Department of Neuropsychiatry, Suez Canal University, Ismailia, Egypt
2 Department of Neuropsychiatry, Banha University, Banha, Egypt
|Date of Submission||16-Apr-2015|
|Date of Acceptance||02-Jun-2016|
|Date of Web Publication||27-Oct-2016|
Department of Neuropsychiatry, Suez Canal University, Ismailia
Source of Support: None, Conflict of Interest: None
Background Uremia-induced phrenic neuropathy may account for diaphragmatic involvement in patients with end-stage renal disease who are on dialysis.
Objective The aim of this study was to assess the occurrence of phrenic neuropathy and its relationship with hyperkalemia and frequency of dialysis in patients with chronic renal failure on dialysis.
Patients and methods The study included 27 patients with chronic renal failure on dialysis and 27 controls. All patients and controls were subjected to history taking, neurological examination, laboratory tests, neurophysiological study of phrenic and peripheral nerves, and scales to assess the severity of symptoms and disability caused by peripheral neuropathy.
Results Of the 27 patients, 70.4% had phrenic motor neuropathy, 33.4% had median motor neuropathy, 48.2% had median sensory neuropathy, 40.8% had peroneal motor neuropathy, and 66.7% had peroneal sensory neuropathy with highly statistically significant difference in neuropathy between patients and controls. Infrequent dialysis was the cause of bilateral mixed (44.4%) and axonal (33.3%) phrenic motor neuropathy. Bilateral mixed phrenic motor neuropathy was more frequent in the hyperkalemia group (31.2%).
Conclusion Phrenic neuropathy is a frequent complication in chronic renal failure patients on dialysis, especially in those with hyperkalemia and undergoing infrequent dialysis.
Keywords: end-stage renal disease, peripheral neuropathy, phrenic neuropathy
|How to cite this article:|
Abohagar A, Ashour Y, Negm M, Mourad A, Hegazy M. Phrenic neuropathy in comparison with peripheral neuropathy in patients with chronic renal failure on hemodialysis. Egypt J Neurol Psychiatry Neurosurg 2016;53:179-83
|How to cite this URL:|
Abohagar A, Ashour Y, Negm M, Mourad A, Hegazy M. Phrenic neuropathy in comparison with peripheral neuropathy in patients with chronic renal failure on hemodialysis. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2021 Apr 20];53:179-83. Available from: http://www.ejnpn.eg.net/text.asp?2016/53/3/179/193087
| Introduction|| |
Peripheral neuropathy induced by uremia commonly occurs in patients with end-stage renal disease (ESRD) on dialysis ; its incidence ranges from 15 to 85% ,.
During dialysis, numerous uremic toxins with various cytotoxic activities accumulate, causing peripheral neuropathy, in which the cell bodies of neurons remain intact but the axons are affected . Peripheral nerve dysfunction was related to an interference with the nerve axon membrane function and inhibition of Na+/K+-activated ATPase by toxic factors in uremic serum ,. Hyperkalemia, which is primarily responsible for uremic depolarization, can contribute to the development of neuropathy ,,.
As a part of peripheral neuropathy, uremia-induced isolated or bilateral phrenic neuropathy may account for diaphragmatic involvement in uremic patients . This may be suspected from the complaint of dyspnea on exertion, or orthopnea.
| Aim of the work|| |
The aim of this study was to assess phrenic neuropathy in patients with chronic renal failure who were on regular dialysis with regard to peripheral neuropathy and identify the relationship between hyperkalemia and frequency of dialysis with the occurrence of phrenic neuropathy.
| Patients and methods|| |
The study included 27 patients with chronic renal failure who were on dialysis, and 27 controls. All patients and controls were subjected to thorough history taking, including symptoms of chronic kidney disease, frequency of dialysis, common symptoms of peripheral neuropathy, and dyspnea on effort as a symptom of phrenic neuropathy. Clinical neurological examination and laboratory investigations were conducted on all studied groups and included serum creatinine and potassium levels (hyperkalemia is considered when serum potassium level exceeds 5.5 mEq/l).
The Overall Neuropathy Limitations Scale (ONLS)  and the Modified Medical Research Council Dyspnea Scale (MMRCDS)  were used to assess the severity of symptoms and disability.
The ONLS consisted of 12 questions on the severity of symptoms. Items are rated as arm scale, which ranges from 0 to 5, and leg scale, which ranges from 0 to 7. The MMRCDS consists of four grades to describe shortness of breath [Table 1],[Table 2],[Table 3].
Nerve conduction studies were carried out using Nihon Kohden Neuropack machine software (model MEB_9200K; Japan). We performed motor nerve conduction study of phrenic nerves, motor and sensory nerve conduction study of both median nerves, and bilateral motor and sensory nerve conduction study of both peroneal nerves.
Patients’ data were coded and entered using SPSS, version 16. Quantitative variables were summarized as mean, SD, and range. Comparison between groups was made using the independent-sample t-test for normally distributed quantitative variables and the nonparametrical Mann–Whitney test for non-normally distributed qualitative variables. Correlation was determined using Pearson’s correlation to test for linear relation between quantitative variables. The correlation coefficient denotes whether the correlation is direct or inverse. P values of 0.05 or less were considered statistically significant (confidence interval period 95%) and highly significant at the level of 0.01.
| Results|| |
This study included 54 individuals: 27 patients and 27 healthy controls. Each group was subdivided on the basis of age (18–30 years, 31–40 years, 41–50 years, and > 50 years) and sex. Most of the patients and controls were in the 18–30-year age group (44.5 and 55.5%, respectively) and most belonged to the male sex (59 and 55.5%, respectively) with no statistically significant difference. Of the 27 patients, 70.4% had phrenic motor neuropathy, 33.4% had median motor neuropathy, 48.2% had median sensory neuropathy, 40.8% had peroneal motor neuropathy, and 66.7% had peroneal sensory neuropathy. None of the 27 controls had phrenic motor neuropathy, whereas 11.2% had median motor neuropathy, 15% had median sensory neuropathy, 7.5% had peroneal motor neuropathy, and 15% had peroneal sensory neuropathy [Table 4]. There was a highly statistically significant difference in the type of neuropathy.
There was significant statistical difference between patients and controls with regard to phrenic motor neuropathy at age 31–40 years in the form of unilateral mixed neuropathy and at age above 50 years in the form of bilateral mixed neuropathy. There was significant statistical difference between patients and controls as regards median motor neuropathy at age greater than 50 years in the form of bilateral mixed neuropathy, whereas there was median motor neuropathy among controls at age 31–40 years in the form of bilateral demyelinating neuropathy. There was no significant statistical difference between patients and controls regarding median sensory neuropathy. There was significant statistical difference between patients and controls regarding peroneal motor neuropathy at age 41–50 and above 50 years in the form of bilateral mixed neuropathy, whereas there was peroneal motor neuropathy among controls at age 41–50 and above 50 years in the form of unilateral and bilateral demyelinating neuropathy. There was significant statistical difference between patients and controls with regard to peroneal sensory neuropathy at age 18–30 years in the form of unilateral and bilateral mixed neuropathy, whereas there was peroneal sensory neuropathy among controls at age 41–50 years in the form of unilateral demyelinating and mixed neuropathy.
Infrequent dialysis causes bilateral mixed (44.4%) and axonal (33.3%) phrenic motor neuropathy, bilateral mixed median motor neuropathy (33.3%), and bilateral mixed median sensory neuropathy (55.6%) with significant statistical difference. Infrequent dialysis also causes equal bilateral axonal and mixed (44.4%) peroneal motor neuropathy and bilateral mixed peroneal sensory neuropathy (100%) with significant statistical difference in the frequency of dialysis between the two groups.
Bilateral mixed phrenic motor neuropathy was more frequent in the hyperkalemia group (31.2%) with significant statistical difference. In contrast, bilateral mixed median motor neuropathy (25%), bilateral mixed median sensory neuropathy (37.5%), bilateral mixed peroneal motor neuropathy (31.2%), and bilateral mixed peroneal sensory neuropathy (56.2%) showed no significant statistical difference in the hyperkalemia group.
Dyspnea was studied using the Modified Medical Research Council Scale (MMRCS). Unilateral neuropathy causes mainly dyspnea grade 1 and 2, whereas bilateral neuropathy causes dyspnea grade 3 and 4, with significant statistical difference [Table 5].
|Table 5: Phrenic motor neuropathy and Modified Medical Research Council Dyspnea Scale|
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Disability in the upper limbs was studied using the ONLS. Unilateral neuropathy causes mainly limitation of grade 1 in both upper limbs, whereas bilateral neuropathy causes limitations of grades 2, 3, and 4, with significant statistical difference [Table 6].
|Table 6: Median motor neuropathy and arm score Overall Neuropathy Limitation Score among cases|
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Disability in the lower limbs was studied using ONLS. Neuropathy causes no limitation, whereas bilateral neuropathy causes disability of grades 2 and 3, with significant statistical difference [Table 7].
|Table 7: Peroneal motor neuropathy and leg score Overall Neuropathy Limitation Score among cases|
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| Discussion|| |
Peripheral neuropathy is a common complication in patients with advanced chronic renal failure. Among the peripheral nerves that can be affected is the phrenic nerve . In the present study the rate of phrenic motor neuropathy was 70.4% among ESRD patients, in keeping with previous studies ,.
In our present study, patients with ESRD on hemodialysis had a mean phrenic nerve latency of 8.3 ± 0.9 ms, detected unilaterally or bilaterally, which was highly significantly prolonged than in controls (6.1 ± 0.3 ms). Zifko et al.  stated that patients with chronic renal failure had prolonged right and left phrenic nerve latencies. The prolonged latency could be due to the presence of phrenic nerve neuropathy, which was explained by Dyck et al. , Thomas and Eliasson  and Krishnan et al. to be due to primary axonal degeneration with secondary segmental demyelination.
In the patient group, the mean phrenic nerve amplitude was 40 ± 20 μV, which was significantly lower than that in the control group (597 ± 140 μV). The reduced amplitude generally denotes either axonal degeneration with loss of motor units or advanced myopathy .
Phrenic neuropathy was present in 93% of hyperkalemic ESRD patient on hemodialysis. Krishnan and Kiernan  stated that latency was reduced in 75% of hyperkalemic ESRD patients. The degree of depolarization correlates with serum potassium, suggesting that chronic hyperkalemic depolarization plays an important role in the development of nerve dysfunction in patients with chronic renal failure. Prolonged exposure to hyperkalemia in ESRD patients is due to the postdialysis rebound of K+, which is a well-recognized phenomenon , with hyperkalemia typically recurring within 6 h of a dialysis session owing to re-equilibration between intracellular and extracellular fluid compartments . Such prolonged hyperkalemia may cause disruption of normal ionic gradients, which are essential for axonal survival , activating damaging Ca2+-mediated processes and leading to axonal loss .
In the present study, all patients with infrequent dialysis had peroneal motor neuropathy, whereas 88.8% had median motor neuropathy and almost 100% had sensory neuropathy of both nerves. The prevalence of phrenic motor neuropathy was 100% with infrequent dialysis. In the patient group peroneal nerve conduction velocity was abnormally higher than median nerve conduction velocity (peroneal motor neuropathy was 11%, whereas median motor neuropathy was 9%, and peroneal sensory neuropathy was 18%, whereas median sensory neuropathy was 13%), consistent with the lower limb predisposition to neuropathy. Previous studies have demonstrated these abnormalities to be a sensitive marker of neuropathy in patients with uremia . Mansouri et al.  have discovered significant increase in the amplitude of the tested peripheral nerves (sensory median and peroneal nerves) following a single session of hemodialysis. In contrast, Laaksonen et al.  stated no significant change in any of the neurophysiological parameters following a single hemodialysis.
No symptoms were seen in 10% of patients with median motor neuropathy in the present study, whereas 40% had symptomatic nondisabling neuropathy and 60% had disabling neuropathy. In studying the peroneal nerve 16.6% of patients with peroneal motor neuropathy had no symptoms, 25% of patients had symptomatic nondisabling neuropathy, and 58% of patients had disabling neuropathy. Aggarwal et al.  observed that neurological symptoms increased steadily with a rise in serum creatinine. The Nerve Conduction Velocity NCVs decreased significantly with increase in serum creatinine levels. Most of the patients (70%) had uremic polyneuropathy, 6% had asymptomatic neuropathy, 51% had symptomatic nondisabling neuropathy, and 13% had disabling neuropathy.
In this study, 57.8% of patients had unilateral phrenic motor neuropathy leading to nondisabling dyspnea, whereas 42% of patients had bilateral phrenic motor neuropathy leading in disabling dyspnea.
| Conclusion|| |
Phrenic neuropathy with subsequent respiratory dysfunction is a frequent complication in chronic renal failure patients on dialysis especially in those with hyperkalemia and undergoing infrequent dialysis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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