Neurophysiologic Study in Children with End Stage Renal Disease on Regular Hemodialysis

INTRODUCTION

The Kidney Disease and Outcome Quality Initiative (K/DOQI) working group of the National Kidney Foundation of the United States defines chronic kidney disease (CKD) as structural or functional kidney abnormalities (abnormal urine analysis, imaging studies, or histology) that last at least three months with or without decreased glomerular filtration rate (GFR), or GFR was less than 60ml /min/1.73 m2 surface area¹_. Renal failure is accompanied with numerous of neurological issues, including cerebrovascular disorders, cognitive impairment, uremic encephalopathy, peripheral neuropathy, and myopathy²_. Uremic encephalopathy is a pure brain disease that occurs in individuals with

acute or chronic renal failure when creatinine clearance (Cr Cl) values fall below 15 ml/min ³_. Electroencephalogram (EEG) is useful in uremic encephalopathy; it may be of diagnostic value, EEG

showing generalized slowing that becomes more severe as the condition worsen⁴_. In CKD, the EEG demonstrates irregular low voltage, a weakening of the posterior dominant alpha rhythm, and theta bursts on occasion. Long bursts of bilateral, simultaneous slow and sharp waves, sometimes known as spike waves, are common. These alterations are maintained by dialysis, which is both effective and long-lasting⁵. Chronic kidney disease is associated with peripheral nerve damage, which is a well-known consequence. (CKD)⁶. Uremic neuropathy is quite frequent in people with CKD, with incidence rates of 60–90 percent in dialysis patients. Neuropathy that is clinically significant is usually a late consequence that only affects individuals with end-stage renal failure.⁷ In CKD; the development of a myopathy produces proximal muscular weakening and atrophy, primarily in the lower limb muscles. Uremic myopathy is characterised by glomerular filtration rates of less than 25 ml/min and has been linked to fatigability and decreased exercise capacity. Because electromyography and creatine kinase values are usually normal, the diagnosis is based mostly on clinical evidence.⁸-⁹

This work was aimed to demonstrate the neurophysiologic changes using EEG, NCV and EMG in children with CKD on regular hemodialysis and to correlate these changes with duration of dialysis and duration of disease.

PATIENTS AND METHODS

A cross sectional study was done on 30 children with chronic kidney disease on regular hemodialysis. Patients were selected from the Pediatric Nephrology Unit at Al-Azhar University Hospitals according to certain inclusion and exclusion criteria. Patients included in this study their age ranged from (6-18) year and there were on regular hemodialysis for more than 1 year.

 They were 16 males and 14 females, mean age (13.50 ± 2.96year). Patients having primary central or peripheral nervous system disease from congenital or other causes than CKD, patients have systemic disease affecting nervous system and patients receiving medication affecting nervous system were excluded from the study.

Ethical consideration

All studied participants were had to complete prenatal history, development history, onset and course of ESRD, previous medication, family history of similar condition, detailed family history of genetic disease, duration of dialysis, history of drug intake, history of bone affection and neurological clinical, complete physical examination. Investigations in form of CBC, serum urea, serum creatinine, serum potassium, serum sodium, parathyroid hormone, serum phosphorus, alkaline phosphatase, serum calcium were done. Nerve conduction (NC), electromyography (EMG) and electroencephalography (EEG) were done to participants.

Neurophysiological Studies:

A)   Nerve Conduction Study and Electromyography:

Neurophysiology investigations as nerve conduction, including sensory and motor assessment, as well as electromyography, were performed on all patients in the current study. In lower limb, the tibial and peroneal nerves on both sides (motor) and (sensory) were evaluated. Upper limb with median and ulnar nerves (motor and sensory) in one limb only away from arterio-venous fistula. The tibialis anterior muscle in lower limb and the biceps muscle in upper limb were also investigated.

B) Electroencephalogram:

Compumedlcs e series equipment was used to do the EEG in a quiet room.  The 21-channel EEGs were recorded under normal settings (rest, hyperventilation, and light stimulation); children were observed while lying down with their eyes closed for the duration of the study. EEG data from 19 scalp electrodes were recorded for 20 minutes using the International 10—20 System and an average reference.

Statistical analysis of the data

The IBM SPSS software programme version 20.0 was used to examine the data that was supplied into the computer. (IBM Corporation, Armonk, NY). Numbers and percentages were used to represent categorical data. The Chi-square test was used to look into the relationship between the categorical variables. When the expected cell counts were fewer than 5, the Monte Carlo correction test was used instead. The Shapiro-Wilk test was used to check for normality in continuous data. Range (minimum and maximum), mean, standard deviation, and median were used to express distributed data. For regularly distributed quantitative data, the student t-test was employed to compare two groups. For not regularly distributed quantitative variables, the Mann Whitney test was employed to compare two groups. The diagnostic performance of the markers was determined using the Receiver Operating Characteristic Curve (ROC), with an area greater than 50% indicating acceptable performance and an area more than 100% indicating the best performance for the test. The significance of the acquired results was assessed at a 5% level of significance.

RESULTS

Our results showed clinical data of 30 patients; 16 males and 14 females with mean age of (13.50 ± 2.96). 25 patients were on regular hemodialysis for less than 5 years. Most common causes of chronic kidney disease were congenital kidney and ureter malformation followed by glomerular diseases and unknown etiology (table 1). Five cases showed abnormalities (slowing background). One case of the six patients who showed epileptic discharge has as well slow background (and this case is one of the five cases who showed slow background). EMG showed no abnormalities. NCV showed normal 14 patients, 14 patients with axonal polyneuropathy and 2 patients with demyelinating polyneuropathy (table 2). Laboratories findings of patients(with exception of S. sodium) are abnormal when compared to the reference ranges for biochemical parameters (Nelson textbook of Pediatrics 20^th edition) showed in (table3). There was positive correlation between nerve conduction velocity findings and duration of disease, moreover there was positive correlation between NCV changes and both potassium and phosphorus other parameters showed no definite correlation with NCV findings (table 4).No significant difference was found between findings in EEG & NCV showed in (table 5).

ROC curve showed positive correlation between nerve conduction finding and both; duration of disease, serum potassium, and serum phosphorus (16 abnormal versus 14 normal).

Table 1: Clinical data of studied patients (n = 30). Our results showed clinical data of 30 patients; 16 males and 14 females with mean age of (13.50 ± 2.96). 25 patients were on regular hemodialysis for less than 5 years. Most common cause of chronic kidney disease was congenital kidney and ureter malformation followed by glomerular diseases and unknown etiology.

Table 2: Distribution of the Studied cases according to electroencephalography, electromyography and nerve conduction velocity (n = 30). Five cases showed abnormalities (slowing background). One case of the six patients who showed epileptic discharge has as well slow background (and this case is one of the five cases who showed slow background). EMG showed no abnormalities. NCV showed normal fourteen patients, fourteen patients with axonal polyneuropathy and two patients with demyelinating polyneuropathy.

Table 3: Descriptive analysis of the Studied cases according to laboratory investigations (n = 30; SD: Standard deviation). Laboratories findings of patients (with exception of S. sodium) are abnormal when compared to the reference ranges for biochemical parameters (Nelson textbook of pediatrics 20th edition).

Table 4: Relation between NCV and EEG with different parameters. There was positive correlation between nerve conduction velocity findings and duration of disease, moreover there was positive correlation between NCV changes and both potassium and phosphorus other parameters showed no definite correlation with NCV findings. (SD: Standard deviation; t: Student t-test; U: Mann Whitney test; c2:  Chi square test ; MC: Monte Carlo; p: p value for comparing between the studied groups; *: Statistically significant at p ≤ 0.05).

Table 5: Relation between nerve conduction velocity and electroencephalogram. (c²:  Chi square test; p: p value for comparing between the studied groups.

Table 6: Validity (AUC, sensitivity, specificity) for D.O.D (years), serum potassium and Serum phosphorus to discriminate Abnormal NCV patients (n = 16 vs. 14). No significant difference was found between findings in EEG & NCV. AUC: (Area Under a Curve; p value: Probability value; CI: Confidence Intervals; NPV: Negative predictive value; PPV: Positive predictive value; *: Statistically significant at p ≤ 0.05; #Cut off was choose according to Youden index).

Fig 1: A: ROC curve for duration of disease (years) to discriminate Abnormal NCV patients (n = 16 vs. 14). B: ROC curve for serum k to discriminate Abnormal NCV patients (n = 16 vs. 14). C: ROC curve for serum P to discriminate Abnormal NCV patients (n = 16 vs. 14). ROC curve showed positive correlation between nerve conduction finding and both; duration of disease, serum potassium, and serum phosphorus (16 abnormal versus 14 normal).