Abnormalities in event-related potential and brainstem auditory evoked response in children with nocturnal enuresis

Brain & Development 24 (2002) 681–687 www.elsevier.com/locate/braindev

Original article

Abnormalities in event-related potential and brainstem auditory evoked response in children with nocturnal enuresis q Akin Iscan a,*, Yasar Ozkul b, Dogan Unal c, Mustafa Soran d, Mahmut Kati e, Senay Bozlar b, Akif Himmet Karazeybek d a

Department of Child Neurology, University of Dokuz Eylul, Mehmet Efe Sok Ozcelik B Sitesi 51/13 Balcova, Izmir, Turkey b Department of Neurology, Faculty of Medicine, University of Harran, Sanlıurfa, Turkey c Department of Urology, Faculty of Medicine, University of Harran, Sanlıurfa, Turkey d Department of Pediatrics, Faculty of Medicine, University of Harran, Sanlıurfa, Turkey e Department of Psychiatry, Faculty of Medicine, University of Harran, Sanlıurfa, Turkey Received 18 January 2002; received in revised form 16 April 2002; accepted 13 May 2002

Abstract To evaluate central nervous system functioning involvement in nocturnal enuresis, P300 and N200 event-related brain potentials and brainstem auditory-evoked potentials (BAER) were assessed in a group of 35 enuretic boys aged 7–9 years. The measurements of enuretic group were compared to those of age and sex matched non-enuretics. P300 latency in the enuretic group was significantly longer than in nonenuretic group (420 ms at parietal scalp (Pz), 414 ms at central scalp (Cz) versus 386 ms at Pz, 376 ms at Cz; P , 0:01 and P , 0:01, respectively). Both enuretic and non-enuretic subjects were divided into three subgroups his age. There was no significant difference in terms of both P300 amplitude and N200 latency and N200 amplitude between non-enuretic age subgroups. But, P300 latency over central scalp in 8 years old non-enuretic subgroup was significantly longer than in 9 years old non-enuretic subgroup (P , 0:01). No significant difference was found in latency and amplitude of P300 and N200 latency between enuretic subgroups. However, N200 amplitude at Cz in 8 years old enuretic subgroup was significantly lower than both in 7 years old enuretic subgroup and in 9 years old enuretic subgroup (P , 0:01 and P , 0:01, respectively). There were significant topographical differences in latency and amplitude of P300 and in N200 latency in enuretic age subgroups, only. There was no significant difference in interpeak latencies I–III, I–V and III–V and wave latencies I, III and V of BAERs between enuretic group and non-enuretic subgroup. Longer interpeak and wave latencies of BAERs were found both in 8 years old enuretic subgroup and 8 years old non-enuretic subgroup. Conclusion: Longer P300 latency in primer enuretics compare to non-enuretics is an evidence of a maturational delay of central nervous system functioning. q 2002 Elsevier Science B.V. All rights reserved. Keywords: P300 latency; Enuresis nocturna

1. Introduction Nocturnal enuresis is frequently diagnosed among school children and an important psychosocial problem affecting millions of children and parents [1,2]. It is a familial condition with complex inheritance patterns. The hypothesis that enuresis represents developmental

q The study was presented at Seventh Child Neurology Congress of Meditterrenian Countries, 30 May–1 Jun, 2001, Istanbul, Turkey. * Corresponding author. Tel.: 190-232-278-6379; fax: 190-232-2781128. E-mail address: [email protected] (I. Akin).

delay or maturation lag in central nervous system development was well supported by a number of clinical observations. A significantly higher proportion of bedwetting is observed in children who are also delayed in walking and talking, a significant number of children with primary enuresis display retardation in skeletal maturation [3,4]. A maturational delay in electroencephalography (EEG) records central nervous system functions have also been reported enuretics [5]. Recently, an electrophysiological evidence of dismaturation in central nervous system functioning has been shown in nocturnal enuretics [6]. Nocturnal enuresis are merely an expression of neurophysiological immaturity and the achieving dryness is a sequential part of the child’s general development.

0387-7604/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S 0387-760 4(02)00077-3

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Event related potentials (ERPs) have been found to be related to cognitive function. Many studies on ERPs have been conducted, focusing especially on the P300 component. It is considered to reflect the stimulus evaluation time, or the updating of the working memory [7]. P300 latency of ERPs decreases with age in childhood, suggesting physiological hypofunctioning of central nervous system. On the other hand, primary enuresis is also considered to be associated with maturational delay in central nervous system functions. Thus, the current study was planned on the base of a hypothesis that ERPs of a enuretic child who especially has unable to night-time sphincter control even during school age period (such as 7–9 years) will differ from that of non-enuretic one. Brainstem auditory evoked potentials (BAEPs) is a surface-recorded series of electrical potentials emanating from the tracts and nuclei of the auditory pathway. BAEPs are generated by the auditory nerve and brainstem in response to a ‘click’ stimulus. The components of this series of potential waves have been numbered I–VII. One special feature of brainstem auditory-evoked potentials (BAER) is the dependence on maturation [8]. We hypothesized that BAER shows different pattern in enuretics compare with non-enuretics. It has been reported that enuretics have higher incidence of EEG abnormalities compare with non-enuretics [5]. In addition to ERPs and BAERs, we also examined EEG records of enuretic children.

2. Patients and methods A detailed history about maturation and defecation was obtained from participating children’s parents. Non-organic enuresis was defined with regard to The 10th Revision of International Classification of Mental and Behavioural Disorders (ICD-10) [9]. To eliminate the age dependent factor in event related potentials, the age range was selected as such narrow range. Inclusion criteria: (a) age 7–9 years; (b) male sex (to eliminate sex effect); (c) primary enuresis; (d) no daytime incontinence; (e) no evidence of systemic disease; (f) no evidence of intestinal parasitic infection on stool examination (to exclude cases with segonder enuresis result from parasitic infection); (g) minimum of four wet nights per week for last 3 months (only higher frequency of nocturia might be associated with a hypofunctioning in central nervous system resulting an alteration in event related potentials); and (h) no previous treatment for enuresis. Blood and serum analysis included complete blood count, eritocyt sedimentation rate, C-reactive protein, urea, creatinin, glucose (no abnormality was found in these analysis). An urine analysis, urine culture and stool microscopy were performed in all enuretics. If an enuretic boy had an additional abnormality which may cause a secondary enuresis such as urinary tract infection, intestinal parasitic infection and urinary calculus, he was excluded from the study. A

careful ultrasonographic screening of urinary system was also performed in all enuretic subjects. Ultrasonographic examination of a boys required intravenous pyelograhy, and eventually he was diagnosed as enuresis plus ureteropelvic junction stricture. During the study period, a total of 46 consecutive enuretic boys fulfilled inclusion criteria. Five of 46 cases refused participation to the study. An informed consent was obtained from remaining 41 participants. Thus, 41 enuretic cases were included in this study. After that, six cases were excluded from the trial: Two of six cases refused some obligatory laboratory test, remaining four cases had enuresis nocturna plus an additional disease: One enuresis plus urinary tract infection plus ascaris lumbriciodes, one enuresis plus renal calculus and oxuriasis, one enuresis plus ureteropelvic stricture, and remaining one case enuresis plus ascaris lumbriciodes. Thus, enuretic group eventually consisted of 35 enuretic boys. The control group was composed of 31 non-enuretic healthy boys. They had applied to outpatient clinic of Harran University Hospital for an immunization for hepatitis B. After a complete history and physical examination, the boys fulfilling the inclusion criteria for control subjects were included into study.

2.1. Event related potentials Event related potentials were recorded at in a sound-proof room with a Dantec Keypoint V2,02 electroneurograph (Denmark). ERPs were recorded at Cz and Pz with gold cup electrodes, referred to linked earlobes with a forehead ground. The impedance between electrode and scalp was less than 5000 ohm. The filter bandpass was 0.5–50 Hz, sensitivity 10 mV, and analysis time was 500 ms. The subjects pressed a switch held in the dominant hand each time they detected a target tone. The responses were averaged. The stimuli were given until 30 target trials were achieved. The signals were 1 kHz standard, and 2 kHz target tones presented through head phones at 60 dB above-hearing level having 10 ms rise/fall and 100 ms plateau times. These two types of stimuli were presented alternatively and irregularly. The interstimulus interval was randomly varied between 1 and 3.3 s. The probability of the target stimulus with 1 kHz tone was 15% and the other 85% were non-target stimuli. Before recording, the hearing ability of the subjects was tested to confirm that they could distinguish target from the non-target tone. The largest negative peak appearing between 180 and 360 ms and the largest positive peak between 250 and 500 ms on the ERP waveform in response to the target stimuli were designated as N200 and P300 components, respectively. The latencies of N200 and P300 were measured relative to the onset of the stimulus. Both P300 and N200 were measured both at Cz and Pz.

A. Iscan et al. / Brain & Development 24 (2002) 681–687

2.2. Brain-stem auditory evoked potentials The stimulation consisted of 90 ms square pulses presented monoaurally through headphones at an intensity of 60 dB above hearing level and a frequency of 8/s. Auditory brainstem responses were obtained by averaging a differently recorded EEG signal (Cz vertex; Ai, ipsilateral earlobe; ground, forehead). The bandwidth was 0.1–3 kHz. The signals averaged on-line. The averaging epoch was 10 ms. The stimulus was given until 1050 trials without artifacts were collected. As it is generally agreed that waves I, III and V are constant and reproducible markers in the response, only these waves were studied. The latencies of waves I, III and V were measured from the onset of the stimulus. The latencies of waves I, III and V were measured from the onset of the stimulus. Interpeak latencies I–III, III–V and I–V were calculated. 2.3. Statistical analysis Significance of differences between the mean of the

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control and enuretic groups was determined by Student’s t-test. Statistical differences between subgroups were tested using Kruskal–Wallis one way analysis of variance, followed by Mann–Whitney U-test for post hoc comparisons of median values. Wilcoxon Rank Sum test (for related groups) were used to compare medians; and a P value, ,0.01 was accepted significant. 3. Results The data from 35 enuretic boys aged 7–9 years and 31 age and sex matched non-enuretic controls were given in Table 1. No significant difference was found in terms of the mean age, height and body weight between enuretic group and non-enuretic group (P , 0:01). The mean P300 latency in enuretic group was significantly higher than that in nonenuretic group. No significant difference was found in terms of P300 amplitude, P300 latency and N200 amplitude between enuretic group and non-enuretic group. Reaction

Table 1 The P300 and N200 event-related brain potentials and brainstem auditory-evoked potentials (BAER) of 35 enuretic boys aged 7–9 years and of sex and age matched non-enuretic 31 controls Enuretic (n ¼ 35) mean (SD)

Non-enuretic (n ¼ 31) mean (SD)

Statistical analysis ab

Age (year)

7.97 (0.79)

7.9 (0.79)

NS

Height (cm)

124 (4.69)

123 (5.78)

NS

Weight (kg)

24.5 (3.43)

25.5 (3.05)

NS

P300 at Pz Latency (ms) Amplitude (mV)

420 (57.2) 19.1 (8.41)

386 (47.7) 19.6 (7.66)

P , 0.01 NS

P300 at Cz Latency (ms) Amplitude (mV)

414 (52.6) 17.9 (7.8)

376 (52.7) 17.2 (7.8)

P , 0.01 NS

N200 at Pz Latency (ms) Amplitude (mV)

259 (29.3) 8.75 (3.87)

262 (27.4) 7.48 (2.73)

NS NS

N200 at Cz Latency (ms) Amplitude (mV)

265 (31.2) 8.54 (2.28)

265 (29.9) 8.14 (3.19)

NS NS

2.02 (0.08) 4.14 (0.14) 6.25 (0.16)

1.99 (0.12) 4.09 (0.13) 6.15 (0.26)

NS NS NS

2.12 (0.16) 2.12 (0.11) 4.24 (0.15)

2.08 (0.15) 2.33 (1.43) 4.16 (0.22)

NS NS NS

886 (67)

849 (83)

NS

BAEPs Wave I latency (ms) Wave III latency (ms) Wave V latency (ms) Interpeak latency (ms) I–III III–V I–V Reaction time (ms) a b

Student’s t-test was used for statistical analysis. P , 0.01 was accepted statistically significant.

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Table 2 The event-related brain potentials and brainstem auditory-evoked responses of 35 primary enuretic a Statistical analysis bc

Enuretic subgroups (n ¼ 35) 7 years old (n ¼ 11) I

8 years old (n ¼ 14) II

9 years old (n ¼ 10) III

I versus II

I versus III

II versus III

P300 at Pz (A) Latency (ms) (B) Amplitude (mV)

437 (329–477) 16.1 (8.59–28.5)

405 (331–511) 18.7 (13.3–36.7)

402 (387–506) 23.5 (13–35.9)

NS NS

NS NS

NS NS

P300 at Cz (C) Latency (ms) (D) Amplitude (mV)

435 (342–479) 16.3 (3.64–30.1)

398 (333–491) 23.3 (8.78–30.2)

404 (343–512) 13.8 (11.4–24.7)

NS NS

NS NS

NS NS

N200 at Pz (E) Latency (ms) (F) Amplitude (mV)

277 (224–283) 7.7 (4.53–12.8)

263 (216–333) 8.74 (4.2–13.4)

226 (217–265) 11 (4.7–19)

NS NS

NS NS

NS NS

N200 at Cz (G) Latency (ms) (H) Amplitude (mV)

287 (223–293) 10.6 (4.69–13.7)

267 (218–334) 6.89 (4.69–9.1)

235 (219–268) 9.34 (7.78–10.4)

NS P , 0.01

NS NS

NS P , 0.01

BAEPs Wave I latency (ms) Wave III latency (ms) Wave V latency (ms) Interpeak latency (ms) I–III III–V I–V

1.97 (1.88–2.17) 4.13 (3.9–4.24) 6.1 (5.9–6.51)

2.03 (1.85–2.15) 4.22 (4.15–4.51) 6.38 (6.18–6.53)

2.05 (1.98–2.07) 4.02 (3.95–4.14) 6.24 (6.18–6.31)

NS P , 0.001 NS

NS NS NS

NS P , 0.001 NS

2.12 (1.95–2.2) 2.02 (1.92–2.27) 4.14 (3.95–4.41)

2.21 (2.05–2.46) 2.08 (2–2.24) 4.3 (4.23–4.54)

1.97 (1.9–2.14) 2.28 (2.15–2.25) 4.19 (4.13–4.31)

NS NS P , 0.01

NS NS NS

P , 0.001 P , 0.01 P , 0.01

Reaction time (ms)

859 (740–986)

901 (840–989)

889 (846–955)

NS

NS

NS

Statistical Analysis cd A versus C B versus D E versus G F versus H

NS NS P , 0.01 NS

NS NS NS NS

P , 0.01 P , 0.01 NS NS

a b c d

Variables were shown as median (min-max). Mann–Whitney U-test was used for statistical analysis. P , 0.01 was accepted statistically significant. Wilcoxon Signed Ranks Test was used for statistical analysis.

time of enuretic group did not significantly differ from that of non-enuretic group. To evaluate the effect of age factor on ERPs and BAERs 35 enuretic boys were divided by age into three different subgroups: 7 years old enuretic subgroup, 8 years old enuretic subgroup and 9 years old enuretic subgroup. The nonenuretic boys were similarly divided by age into three subgroups. Tables 2 and 3 demonstrates ERPs, BAERs and reaction time obtained in each subgroup. No significant difference was found in latency and amplitude of P300 between enuretic subgroups (Table 2). No significant difference was found between non-enuretic subgroups, with the exception of a significantly shorter P300 latency at Cz in 9 years old non-enuretic subgroup compare to 7 years old nonenuretic subgroup (P , 0:01) (Table 3). Statistical analysis indicated that lower N200 amplitude at Cz in 8 years old enuretic subgroup compare to 7 years old enuretic subgroup and to 9 years old enuretic subgroup (6.89 versus 10.6 and

9.34 mV, respectively) (Table 2). There was no significant difference both in N200 latency and in N200 amplitude between non-enuretic subgroups (Table 3). The topographical difference in terms of P300 wave and N200 wave within each age subgroup was investigated. For each parameter, a statistical analysis of difference between measured value of the parameter over Cz and that measured value of the same parameter over Pz was made (Tables 2 and 3). None of the non-enuretic subgroups had a significant topographical difference both in P300 wave and N200 wave. Whereas, 9 years old enuretic subgroup had a significant topographical difference both in latency and amplitude of P300 wave; this enuretic subgroup had also a shorter P300 latency and a higher P300 amplitude at Pz (P , 0:01, both in latency and amplitude of P300). On the other hand, the only significant topographical difference in terms of N200 latency was noted within 7 years old enuretic subgroup; this enuretic subgroup had a longer N200 latency at Cz compare to Pz.

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Table 3 The event-related brain potentials and brainstem auditory-evoked potentials of 31 non-enuretic boys a Statistical analysis bc

Non-enuretic subgroups (n ¼ 31) 7 years old (n ¼ 11) I

8 years old (n ¼ 12) II

9 years old (n ¼ 8) III

I versus II

I versus III

II versus III

P300 at Pz (A) Latency (ms) (B) Amplitude (mV)

427 (302–492) 20.6 (6.22–27.3)

380 (323–411) 19.5 (8.95–22.4)

378 (382–418) 24.6 (11.3–37.5)

NS NS

NS NS

NS NS

P300 at Cz (C) Latency (ms) (D) Amplitude (mV)

422 (320–485) 20 (2.79–26.1)

369 (308–435) 15.1 (8.6–29.7)

322 (294–417) 17.7 (11.5–26)

NS NS

NS NS

P , 0.01 NS

N200 at Pz (E) Latency (ms) (F) Amplitude (mV)

267 (224–306) 7.2 (4.5–8.9)

272 (237–295) 7.78 (5.1–11.5)

251 (204–287) 5.72 (4.6–14.4)

NS NS

NS NS

NS NS

N200 at Cz (G) Latency (ms) (H) Amplitude (mV)

277 (223–308) 9.18 (4.7–13.2)

272 (238–298) 8.84 (4.19–13.7)

250 (202–288) 4.8 (4.69–13.2)

NS NS

NS NS

NS NS

BAEPs Wave I latency (ms) Wave III latency (ms) Wave V latency (ms) Interpeak latency I–III (ms) III–V (ms) I–V (ms)

2.08 (2–2.22) 4.1 (3.95–4.24) 6.18 (5.85–6.84)

1.92 (1.83–2.05) 4.2 (3.88–4.32) 6.21 (5.9–6.4)

2 (1.7–2.05) 4 (3.92–4.09) 5.97 (5.72–6.24)

P , 0.001 NS NS

NS NS NS

NS NS NS

2 (1.92–2.18) 2.13 (1.87–9.98) 4.1 (3.85–4.69)

2.2 (2–2.37) 2.1 (1.8–2.17) 4.22 (4.07–4.49)

1.98 (1.8–2.24) 1.98 (1.8–2.15) 3.98 (3.93–4.14)

P , 0.01 NS NS

NS NS NS

P , 0.01 NS P , 0.001

Reaction time (ms)

883 (711–921)

901 (749–934)

799 (657–981)

NS

NS

NS

Statistical analysis cd A versus C B versus D E versus G F versus H

NS NS NS NS

NS NS NS NS

NS NS NS NS

a b c d

Variables were shown as median (min-max). Mann–Whitney U-test was used for statistical analysis. P , 0.01 was accepted statistically significant. Wilcoxon Signed Ranks Test was used for statistical analysis.

Brainstem auditory evoked responses measured in enuretic and non-enuretic groups were documented in Table 1. No significant difference in wave (I, III, V) and interpeak latency (I–III, III–V and I–V) between enuretic and nonenuretic group was found. A significantly longer wave III latency and interpeak latency I–V was observed in 8 years old enuretic subgroup compare to younger and older enuretic subgroups (Table 2). Interpeak latency I–III was significantly longer in 8 years old enuretic subgroup than that in 9 years old enuretic subgroup. Whereas, interpeak latency III– V of 8 years old enuretic subgroup was significantly shorter than that in 9 years old enuretic subgroup. EEG records revealed no abnormality.

4. Discussion ERPs have related to cognitive function. P300 latency of

ERPs decreases with age in childhood, by maturation. The BAEP is a neurophysiological study that provides functional information about the auditory system and brainstem [10,11]. This study reports cross-sectional data on ERPs and BAERs in primary enuresis. The main finding of this study was a prolonged P300 latency in nocturnal enuresis, while N200 remain normal. N200 component has been reported to related to stimulus classification and stimulus deviance, while the P300 has been described to reflect stimulus evaluation and context updating [12–14]. The P300 component is used as an objective measurement of cognitive function. It is well known that there are a negative correlation between age and P300 latency in childhood: P300 latency during childhood decreases with age, reaching it’s mature value after or during the second decade of life. Allison et al. [15] have investigated the developmental and aging changes in somatosensory auditory and visual evoked potentials in

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286 normal subjects ranging in age from 4 to 95 years. The authors reported that increased conduction time in somatosensory cortex, visual cortex and brain-stem auditory pathways play an important role in the genesis of age associated change in P300 latency. In the study of Von Gontard et al. [6], has also been indicated a general developmental (neuromotor) delay in addition to specific dysfunction of the brain stem in primary enuretic children. Steinhausen and Gobel [4] have investigated the developmental and family history, psychiatric diagnoses, and specific delays in development of 386 enuretic children attending to a child psychiatric clinic. The authors reported that an overrepresentation of delayed developmental milestones in enuretics compared to nonenuretics. In present study, only a reliable history of sitting and walking could be obtained. We did not find any significant difference in terms of both sitting history and walking history between enuretics and non-enuretics (data not shown). It is clear that neurodevelopmental history of participants were not defined only sitting and walking history. Therefore, longer P300 latency in enuretics reflects an expression of neurophysiological immaturity which might be together with neurodevelopmental delay or without. The study by Longstaffe et al. [16] described that the selfconcept of enuretic children was disturbed and attentional performance was deteriorated. They found that children’s self-concept, social thought and attention improved with the treatment. On the other hand, it has been showed that nocturnal enuresis affects the sequence of normal social, emotional, cognitive, or motor development via psychosocial stress [1]. We did not assess the psychosocial factors in enuretic subjects. So, we have no clue of disturbed selfconcept and/or decreased attentional performance and/or psychosocial stress in enuretic subjects in this study. Therefore, we do not know whether psychosocial factors might contributed the P300 latency prolongation of the enuretic boys or not. A recent study [17] has reported that P300 was linked to attentional performance with low working memory demands rather than to effortful working memory updating, retrieval from memory stores, or mild cognitive impairment. Low attentional performance and/or low working memory or a combination of many factor affecting P300 generation may led to longer P300 latency in enuretics. Kawauchi et al. [5] have analyzed the number of sleep spindles and delta waves during EEG in enuretics. Authors reported that there was no decrease in the number of sleep spindles and delta waves before the nocturnal urination in a great majority of enuretics. They concluded that an immaturity in the function of the thalamus might be a cause of the arousal dysfunction in nocturnal enuresis. P300 wave is a complex potential arising from multiple generators, including cortical and subcortical structures, the hipocampus, thalamus, and the mesencephalic reticuler formation [18]. The dysfunctioning in one or more structure in this complex may contribute to the prolongation of P300. Thus, a functional delaying of brain functioning, for example thalamic function rather than brain-stem may contribute to the

prolongation of P300 in our enuretics with a normal BAERs suggesting no evidence of maturational delay in brain-stem auditory pathways functioning. The P300 latency was tended to be decrease with aging in childhood has been reported in previous studies [19,20]. We also did not find in terms of P300 latency between age subgroup, except one comparison: Nine years old enuretic group have had a significantly shorter P300 latency than that of 7 years old enuretic subgroup (322 versus 369 ms, P , 0:01). The difference in terms of P300 amplitude between age subgroups was statistically analyzed: As in shown by previous reports [19–22], no significant difference was found in this study (Tables 2 and 3). The topographical feature of P300 amplitude and P300 latency was also investigated in our study. As in the study of Sangal [22] we found that both P300 latency and amplitude was not changed by side of scalp in non-enuretics (Table 3). But, statistical analysis in terms of P300 latency and P300 amplitude between enuretic subgroup was revealed a significant difference: 9 years old enuretic subgroup have had significantly longer P300 latency and lower P300 amplitude over central scalp compare to that over parietal scalp (Table 2). This finding in our study is the opposite of Johnson [21] that found higher P300 activity over central scalp compare to that over parietal scalp in healthy female subjects. The different topographical P300 activity in older enuretics in our study was not reported previously. An another clue in the present study is no evidence of a change in N200 latency with aging for this age range, 7–9 years (Table 2). It has been showed that the N200 latency decreases as the age increases [23–26]. We found no significant change in terms of N200 latency between age subgroups. But, N200 amplitude at Cz in 8 years old enuretic subgroup was significantly lower than both that of 7 years old enuretic subgroup and 9 years old enuretic subgroup in present study (Table 2). In our study, as in the study of Enoki and coworkers [25], N200 amplitude was higher in younger age group (7 years old enuretic subgroup) compare to older group (8 years old enuretic subgroup). But, in contrast to Enoki et al, we found significantly higher N200 amplitude in older subgroup (9 years old enuretic subgroup) compare to younger subgroup (8 years old enuretic subgroup). In summary, N200 amplitude was not changed with aging in non-enuretics, whereas some controversial changes in N200 amplitude was changed with aging in enuretics (Tables 2 and 3). The BAEP is a neurophysiological study that provides functional information about the auditory system and brainstem [11]. We did not find any significant difference in terms of wave latency and of interpeak latencies between enuretic group and nonenuretic group (Table 1). But, there were significant difference in terms of BAEP between age subgroups (Tables 2 and 3): Wave latency III and interpeak latency I–III and I–V in 8 years old enuretic subgroup were longer comparing to both younger (7 years old enuretic subgroup) and older (9

A. Iscan et al. / Brain & Development 24 (2002) 681–687

years old enuretic subgroup) enuretic subgroup. Eight years old non-enuretic subgroup had also longer interpeak latencies I–III and I–V compare to other non-enuretic age subgroup (Table 2). In the study of Jiang [27] has been found that the maturation of waveform and interpeak latencies in BAERs begins from birth and is completed between the ages of 9 months and 3 years. The meaning of longer wave III latency and interpeak intervals of I–III and I–V in 8 years old subgroup compare to younger and to older subgroup in this study remains unclear.

[9]

[10]

[11] [12] [13]

5. Conclusions The present study shows that primary nocturnal enuresis is associated with longer P300 latency of event related potentials, while N200 latency may remain normal. Longer P300 latency is an evidence of a maturational delay of central nervous system functioning in enuretic boys. Enuretics had also some topographical differences in P300 latency and amplitude compare to non-enuretics, reflecting some different pattern in generation of P300 component.

[14]

[15]

[16]

[17]

[18]

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