Autonomic nervous system in individuals with cerebralpalsy: a controlled study

Maria C. Ferreira1,2, Carlos Pastore

3, Rodrigo Imada

3, Renata Guare

4, Mariana Leite

4, Dalva Poyares

5,

Maria T. Santos6

1Universidade Cruzeiro do Sul; 2Universidade Paulista; 3Instituto do Coracao, Hospital das Clınicas, Universidade de Sao Paulo;4Universidade Cruzeiro do Sul; 5Psychobiology Department, Universidade Federal de Sao Paulo; 6Persons with Disabilities Division,Universidade Cruzeiro do Sul, Sao Paulo, SP, Brazil

BACKGROUND: Disturbances in homeostatic functions

have been observed in individuals with cerebral palsy (CP),

possibly resulting from autonomic dysfunction. Salivary

flow rate and saliva composition are controlled by the

autonomic nervous system, and CP individuals exhibit

alterations in salivary parameters that suggest autonomic

impairment. This study aimed to investigate cardiac para-

meters as indicative of autonomic disturbances, possibly

associatedwithsalivarychangesobserved inCPindividuals.

METHODS: Ninety individuals with CP were compared

with 35 sibling volunteers with no neurological damage

(CG). Twenty-four-hour ECG ⁄ Holter monitoring (SEER�

Light; GE Medical Systems, Milwaukee, WI, USA) and

12-lead electrocardiographic recordings were performed

on the CP and control groups. Total saliva was collected,

and the salivary flow rate and total protein concentration

were determined.

RESULTS: Cerebral palsy (CP) individuals presented a

significant reduction in salivary flow rate (P < 0.01) and

increased protein concentrations (P < 0.01) compared to

CG. Twenty-four-hour Holter ECG analysis showed dif-

ferences for high frequency (HF), low frequency (LF) and

LF ⁄ HF ratio between the groups, with the CP group

presenting higher HF and LF values and lower LF ⁄ HF.

Electrocardiographic parameters showed a statistically

significant difference for heart rate, and its correlates,

and mean corrected QT interval between the groups

studied (P < 0.05). Snoring was frequent among CP

patients. ECG and autonomic changes were indepen-

dently associated with CP.

CONCLUSION: Individuals with cerebral palsy present

cardiovascular changes principally manifested as disturbed

sympathovagal balance. These autonomic dysfunctions

could contribute to the salivary changes observed.

J Oral Pathol Med (2011) 40: 576–581

Keywords: cerebral palsy; saliva; salivary gland

Introduction

Cerebral palsy (CP) describes a group of chronicdisorders that involves movement and posture develop-ment, often accompanied by epilepsy, secondary mus-culoskeletal problems and disturbances of sensation,perception, cognition, communication and behavior. Itis the most common cause of severe physical disability inchildhood (1), with an estimated prevalence of 2.4 per1000 children (2).

Alterations in salivary flow rate and biochemicalparameters of whole saliva have been described inindividuals with CP (3–6), together with reducedsalivary flow rate (3) with variation in sodium andpotassium concentrations (4), reduction in digestiveand antimicrobial enzymes activities, such as amylaseand peroxidase (5), increased sialic acid concentrationsthat could be related to increased saliva viscosity (5) anddelayed recovery of salivary pH, involving compromisedability to buffer exogenous acid (6).

Both salivary flow rate and saliva composition arecontrolled by the autonomic nervous system (ANS) (7).Cholinergic fibers that are active in the salivary glandsrelease acetylcholine, which binds to M1 and M3muscarinic receptors. Such stimuli on muscarinic recep-tors promote increased salivary output by increasingwater and electrolyte liberation. Sympathetic fibersdischarge noradrenaline, which in turn promotes therelease of more protein into the salivary flow rate (7).

Evaluation of cardiac neural regulation providesuseful information not only of sympathetic or parasym-pathetic activity but also regarding the functionalintegrity of the central nervous system (CNS) (7).Impaired psychomotor development is often precededby major intraventricular hemorrhage or periventricular

Correspondence: Maria T. Santos, Persons with Disabilities Divi-sion, Universidade Cruzeiro do Sul, Rua Constantino de Souza, 454,room 141, Sao Paulo, SP, Brazil 04605-001. Tel: 55 11 9972 2301,Fax: 55 11 3287 5770, E-mails: drsantosmt@yahoo.com.br, mtbrs@hotmail.comAccepted for publication January 10, 2011

J Oral Pathol Med (2011) 40: 576–581

ª 2011 John Wiley & Sons A/S Æ All rights reserved

wileyonlinelibrary.com/journal/jop

doi: 10.1111/j.1600-0714.2011.01008.x

Journal of

Oral Pathology & Medicine

leukomalacia and CNS functional competence impactson a wide range of physiological system abnormalities(8). Heart rate variability (HRV) is a helpful clinicaltool, providing concomitant information regardingANS and CNS functional integrity (9).

Some studies have suggested autonomic abnormalityassociated with cerebral palsy. During the tilt test, HRVvalues similar to those verified in normal individualswere observed in individuals with CP (10–12); however,the modulation effects on autonomic function weredisturbed resulting in unbalance sympathovagal activity,with decreased sympathetic response after stress (10–12).Disturbances in homeostatic functions were alsoobserved in CP individuals and clinically, the prevalenceof bladder and bowel dysfunction, possibly resultingfrom autonomic dysfunction (13).

As individuals with CP exhibit alterations in salivaryparameters suggestive of autonomic impairment, it washypothesized that central autonomic dysfunction is partof CP physiopathology. The aim of this study was toinvestigate autonomic disturbances by analyzing cardiacparameters. It was also hypothesized that these potentialautonomic changes are related to salivary alterations inCP individuals compared to their siblings.

MethodsStudy designNinety patients diagnosed with CP who were referred tothe Lar Escola Sao Francisco rehabilitation center, anon-governmental organization that provides schooling,healthcare and social services to handicapped children inSao Paulo, Brazil, were consecutively included in thisstudy. The inclusion criteria were individuals with aclinical medical diagnosis of cerebral palsy (Interna-tional Classification of Diseases and Related HealthProblems 10th, ICD-10), aged 3–15 years, of either sex,showing absence of seizures for at least 30 days prior toinclusion in the study and whose parents ⁄ carers pro-vided informed consent. The exclusion criteria were (i)previous surgical procedure for saliva control; (ii) use ofdrugs that would interfere with saliva secretion (anti-cholinergic and neuroleptic drugs, benzodiazepines) atleast 7 days prior to potential inclusion in the study; (iii)previous history of cardiac diseases, clinically confirmedby a cardiologist or echocardiograph evaluations.

The patients’ medical records were reviewed fordemographic and clinical data, including sex, age, bodymass index (BMI), and drugs used continuously, and thepresence of snoring during sleep was questioned.

The control group (CG) was composed of 35individuals who were sibling volunteers, matched byage (3–15 years). None of these individuals presentedany systemic condition nor had they taken any medica-tion in the 15 days prior to the study tests.

This protocol was reviewed by the Human ResearchEthics Committee and approved by the Federal Uni-versity of Sao Paulo Institutional Review Board (IRB)under protocol no. 1034 ⁄ 06. After being informed of theaim of the investigation, written informed consent forparticipation and publication was obtained from the

adult responsible for each child ⁄ individual who agreedto participate in the study.

Echocardiographic analysesPrevious history of cardiac diseases was determined byechocardiograph evaluations for the exclusion criteria.CP and control individuals were submitted to M-modeand B-mode (two-dimensional) echocardiography, usinga Sequoia 512 system equipped with a 2.5- to 4.0-MHzmultifrequency model 3V2c transducer (Acuson; Moun-tain View, CA, USA). The echocardiographic variablesassessed were left atrial and left ventricular volumes,systolic function using the modified biplane Simpsonrule, and LV mass, to exclude severe cardiac disease.

Saliva collectionAt least 2 h after the previous meal, unstimulated wholesaliva was collected from CP individuals (n = 60) andcontrols (n = 16) between 8 and 10 AM, to minimizethe circadian rhythm effects, using slight suctionthrough a soft plastic catheter. Saliva produced in thefirst 10 s was discarded, and the subsequent saliva wascollected for exactly 5 min in a graduated cylinder tocalculate the initial flow rate (ml ⁄min). During thecollection period, all individuals remained comfortablyseated in a ventilated, well-lit room. If a child did notpermit saliva collection, he or she was excluded. Salivarytotal protein concentration was estimated by the Brad-ford method (14) using bovine serum albumin asstandard.

HRV analysesTwenty-four hour ECG Holter monitoring (SEER�

Light, GE Medical Systems, Milwaukee, WI, USA) wasperformed on the individuals from the CP (n = 60) andcontrol (n = 16) groups. Subsequently, the data wereprocessed and analyzed by a 250-Hz sampling frequency(GE MARS 7.1 equipment with MARS 7.1; GEMedical System software).

For the HRV analyses, time and frequency domainindexes were used. Time domain indices are derivedfrom temporal variations in cycles or from percentageoscillations observed between consecutive cardiac cycles.The time domain indices used were SDNN (standarddeviation of all NN intervals during the 24-h recording)and pNN50 (percentage of intervals greater than 50 msdifferent from the preceding interval). Only the normalto normal, NN intervals (the length between twosuccessive heart beats) over a period of at least 18 h ofanalyzable signal were analyzed using the time domainmethod (15).

Power spectral analysis of the HRV was calculatedwithin the three frequency bands: very low frequency(VLF: 0.0033–0.04Hz), which may reflect the activity ofthe renin-angiotensin-aldosterone system, although itsrole remains unclear (16); low frequency (LF: 0.04–0.15 Hz), which reflects modulation in the sympatheticand parasympathetic tone by baroreflex activity (17);and high frequency (HF: 0.15–0.40 Hz), which reflectsrespiratory modulation of RR intervals with the efferentimpulses on the cardiac vagus nerve (18). In addition,

ANS in individuals with cerebral palsy

Ferreira et al.

577

J Oral Pathol Med

the total power (TP: 0–0.40Hz) and the ratio of LF toHF power were calculated, a measure that has been usedas an indicator of sympathovagal balance.Heart rate variability (HRV) analysis was performed

using time (SDNN and pNN50) and frequency (VLF,HF, LF and HF ⁄LF ratio) domain indices for the entire24-h recording.

12-Lead ElectrocardiographyTwelve-lead electrocardiographic recordings of 4 · 3formats were performed on CP individuals (n = 90) andcontrols (n = 35) on Cardiofax ECG-9620 (NihonKohden, Tokyo, Japan) equipment, at a speed of25 mm ⁄ s and 10 mV gain, with individuals in the supineposition in a quiet environment. A cardiologist analyzedall the recordings, while blinded to clinical data. TheECG variables obtained were heart rate, PR interval,QRS duration, QT interval, P-wave axis (SAP), QRSaxis (SAQRS), T-wave axis (SAT), RR interval, andmanual measurements of maximum and mean correctedQT intervals (QTc).

Statistical analysisThe data are presented as mean values ± standarddeviation (SD). The Mann–Whitney test was used tocompare BMI, salivary parameters, HRV, and ECGvariables between independent groups. The chi-squareand Fisher’s exact tests were used to analyze categoricalvariables. The Kruskal–Wallis test was used to comparesalivary parameters and HRV variables among theneuroabnormality type and clinical patterns of move-ment of the CP types. Spearman’s correlation coeffi-cients were computed between two variables. Twologistic regression models were built considering QTcand LF ⁄HF as dependent variables and group condi-tion, anticonvulsant drug use and the presence ofsnoring as explicative variables. All statistics wereperformed using the SPSS statistical software, version17.0 (SPSS, Chicago, IL, USA), and statistical softwareMedCalc, version 9.0.1. A statistically significant differ-ence was set at P < 0.05.

ResultsDescriptive characteristicsThe descriptive characteristics of the 90 individuals withCP (age range 3–15 years) and 35 controls (age range 3–15 years) are presented in Table 1. Eighteen individualswith CP were excluded from the initial sample (108),because three presented previous history of cardiacdiseases, five previous surgical procedures for salivacontrol, and 10 were unable to maintain continued useof the 24-h ECG ⁄Holter device for a period of 24 h. Nosignificant differences in age and sex were observedbetween groups evaluated. BMI was significantly lowerand the presence of snoring significantly higher amongCP individuals (P < 0.05).

Salivary resultsCerebral palsy (CP) individuals presented a significantreduction in salivary flow rate and an increase in protein

concentrations compared to the CG (P < 0.01), asverified in the results presented in Table 2.

No statistically significant differences were observedwhen salivary flow rate was compared among spasticquadriplegic (n = 22; 0.54 ± 0.31), spastic diplegic(n = 21; 0.56 ± 0.34), and dyskinetic (n = 12;0.49 ± 0.21) individuals (P = 0.391, Kruskal–Wallistest). When total protein was compared among the samegroups, again, no significant differences were observedamong spastic quadriplegic (2.48 ± 0.82), spastic diple-gic (2.39 ± 0.73), and dyskinetic (2.45 ± 0.65) individ-uals (P = 0.364, Kruskal–Wallis test). The spastichemiplegic (n = 1) and ataxic (n = 4) individuals werenot included in the salivary flow rate and total proteincomparison, because of the small number of individualswith these types of neuromotor abnormality.

HRV resultsResults from the 24-h Holter ECG analysis (Table 3)showed a statistically significant difference for HF andnearly significance differences for LF and LF ⁄HFbetween the groups (P < 0.05). The CP group pre-sented higher HF and LF values and lower LF ⁄HFcompared to controls. The others HRV parametersstudied revealed no differences.

Table 1 Descriptive characteristics of individuals from cerebral palsy(CPG) and control (CG) groups

Individual variablesCPG

(n = 90)CG

(n = 35) P value*

Sex, n (%)Female 32 (35.6) 18 (51.4) 0.519a

Male 58 (64.4) 17 (48.4)Age, mean [±SD] years 9.3 ± 3.1 8.9 ± 3.3 0.628b

Neuromotor abnormality typeSpastic 68 (75.6) 0Dyskinetic 16 (17.8) 0Ataxic 6 (6.6) 0

Clinical patterns of movementQuadriplegia 31 (45.6) 0Diplegia 31 (45.6) 0Hemiplegia 6 (8.8) 0

Anticonvulsive drugs, n (%)Yes 32 (35.5) 0 0.016*c

No 58 (64.5) 35 (100)BMI 15.1 ± 1.9 16.4 ± 2.8 0.034*b

SnoringYes 71 (78.9) 2 (5.7)No 19 (21.1) 33 (94.3) <0.001*a

BMI, body mass index.The data were compared by the achi-square test, bMann–Whitney test,cFisher’s exact test, *P < 0.05.

Table 2 Mean (±SD) values for flow rate (ml ⁄min) and proteinsconcentration from the cerebral palsy and control groups

Variable CPG (n = 60) CG (n = 16) P value*

Salivary flow rate 0.54 ± 0.36 0.82 ± 0.37 0.001*Protein concentration 2.44 ± 0.70 1.93 ± 0.30 0.001*

*Mann–Whitney test comparing the cerebral palsy group (CPG) andcontrol group (CG), *P < 0.050.

ANS in individuals with cerebral palsy

Ferreira et al.

578

J Oral Pathol Med

When LF ⁄HF was compared among spastic quadri-plegic (n = 22; 1.23 ± 0.23), spastic diplegic (n = 21;1.29 ± 0.19), and dyskinetic (n = 12; 1.14 ± 0.22)individuals, no significant differences were observedamong the groups studied (P = 0.102, Kruskal–Wallistest). The spastic hemiplegic (n = 1) and ataxic (n = 4)individuals were not included in the comparison,because of the small number of individuals with thesetypes of neuromotor abnormality.

ECG resultsThe ECG results are presented in the Table 4. Compar-ison between the CP and CG groups regarding ECGparameters showed a significant difference for heart rate,PR interval, QRS duration, SAQRS, RR, QT, and meanQTc (P < 0.05). The remaining ECG parameters didnot achieve significance.

When the CP group was divided according toprevious use or not of anticonvulsant drugs, thecomparison between these subgroups revealed no dif-ference for maximum and mean corrected QT intervals(P = 0.503 and 0.101, respectively).

Significant positive correlations were obtained be-tween BMI and heart rate (RS = 0.315; P = 0.001) andBMI and salivary flow rate (RS = 0.221; P = 0.014).

Cerebral palsy (CP) was independently associatedwith QTc and LF ⁄HF imbalance, when controlled forsnoring or use of anticonvulsant medications (P = 0.01and 0.02, respectively).

Discussion

The aim of this study was to evaluate cardiac parametersoften used as indicative of functional autonomic activityand their possible correlation with salivary alterations inindividuals with cerebral palsy. To our knowledge, thisis the first study to demonstrate cardiac alterations,autonomic dysfunction among CP children and adoles-cents, using ECG recordings and salivary parameteralterations when compared to sibling controls.

The characteristics of the CP population studied aresimilar to those reported in the literature showing agreater number of spastic individuals, followed bydyskinetic and rare cases of ataxic individuals (19). Asexpected, CP individuals were thinner compared to theirsiblings, because of oral-motor dysfunction, i.e., diffi-culty in chewing and swallowing and the presence ofprimitive pathological reflexes, such as suckle-swallow,rooting, gagging, and biting, which interfere in theirfeeding skills, reflecting in feeding competencies thatinfluence nutritional status in CP (20).

Certain parameters are indicative of cardiac risk,including BMI (21), obstructive sleep apnea and snoring(22). In this study, observation verified that CP individ-uals presented reduced BMI, but significantly highersnoring frequency, in agreement with a previous report(23). It is hypothesized that the snoring condition in CPmay be because of upper-airway and facial muscle tonusalterations, as well as poor head posture control,described only in individuals without neurologicaldamage (24). However, in the present study, snoringwas not associated with any of the ANS or cardiacalterations observed.

Twenty-four-hour ECG recordings are particularlyuseful for risk stratification regarding a variety ofpathological conditions, but can also be useful forquantifying autonomic dysfunction (15), although pre-vious studies seem to have rarely focused on ANSfunction of CP individuals. However, it is a simple, non-invasive method for assessing ANS activity, particularlyin a sample of CP individuals who sometimes do notcollaborate while being examined.

Although the HRV results showed nearly significantdifferences for LF and sympathovagal imbalancebetween the groups studied, it should be emphasizedthat they are clinically relevant for CP group, particu-larly if these patients would be under stressing condi-tions, such as dental treatment. Even though statisticaldifferences were not high, the possible cause of thedifferences observed for the sympathovagal balance inthe general motor function of the CP individuals,represented by their neuromotor abnormality type(spasticity and dyskinesia) and clinical patterns ofmovement (quadriplegic and diplegic), could be relatedto the degree and the extension of the areas of cerebrallesions.

Table 3 Mean (±SD) values for HRV parameters of 24-h recordingfrom the cerebral palsy (CPG) and control (CG) groups

Variable CPG (n = 60) CG (n = 16) P value*

HR Max (bpm) 158.22 ± 16.08 161.25 ± 14.88 0.499HR mean (bpm) 96.92 ± 10.79 92.50 ± 11.50 0.101HR min (bpm) 57.75 ± 10.86 54.56 ± 8.45 0.131SDNN (ms) 107.60 ± 38.09 121.13 ± 33.96 0.139pNN50 (%) 15.05 ± 12.15 17.04 ± 9.25 0.282VLF (ms2) 33.18 ± 10.25 29.99 ± 7.39 0.143HF (ms2) 24.11 ± 9.82 18.79 ± 6.42 0.023*LF (ms2) 29.14 ± 11.07 24.77 ± 7.00 0.063*LF ⁄HF 1.24 ± 0.22 1.39 ± 0.33 0.051*Total power 86.43 ± 29.67 73.54 ± 19.78 0.177

HR, Heart rate; HF, High frequency; VLF, Very Low frequency; LF,Low frequency; LF ⁄HF, ratio of LF component to HF component.Mann–Whitney test comparing the cerebral palsy group (CPG) andcontrol group (CG), *P < 0.050.

Table 4 Mean (±SD) values for ECG parameters from the cerebralpalsy and control groups

Variable CPG (n = 90) CG (n = 36) P value*

Heart rate (bpm) 104.34 ± 20.30 84.17 ± 13.27 <0.001*PR interval (ms) 128.48 ± 14.72 138.11 ± 15.09 0.026*QRS duration (ms) 77.36 ± 8.65 82.0 ± 8.69 0.007*SAP (�) 41.11 ± 22.85 37.37 ± 17.32 0.349SAQRS (�) 46.23 ± 26.38 59.71 ± 25.38 0.039*QT 332.42 ± 31.07 361.25 ± 27.82 <0.001*SAT (�) 34.23 ± 29.15 42.85 ± 17.11 0.171RR 598.48 ± 127.71 722.64 ± 109.64 <0.001*Maximum QTc (ms) 442.36 ± 25.18 433.25 ± 23.25 0.408Mean QTc (ms) 418.05 ± 18.40 408.83 ± 19.35 0.018*

SAP, P-wave axis; SAQRS, QRS axis; SAT, T-wave axis.Mann–Whitney test comparing the cerebral palsy group (CPG) andcontrol group (CG), *P < 0.050.

ANS in individuals with cerebral palsy

Ferreira et al.

579

J Oral Pathol Med

Considering both the saliva analysis and HRV results,the findings suggest that an ANS imbalance existstoward a sympathetic predominance, which may explainthe results described in the literature regarding salivaryparameter alterations (3–6).The measurement of HRV can be classified into time

and frequency domain analyses. The time domainanalysis is a general measure of the ANS balance,whereas the frequency domain analysis permits thestudy of the sympathetic and parasympathetic contri-butions of autonomic control with some degree ofseparation (15). HRV has been evaluated in CPindividuals (10–12), but only over a very short periodduring the tilt test. The differential of the present studywas the results obtained for HRV measured by 24-hHolter ECG analysis, which monitors cardiac functionin relation to daily activity.Some studies (10–12) have tried to document auto-

nomic disorders in CP individuals using HRV analysis,involving studies conducted both at rest and understress. Isolated values obtained either at rest or understress revealed no significant differences; however, therewas a significant difference in response to stress inCP individuals presenting a smaller increase in theLF ⁄HF ratio than that of the control groups, whichmight indicate the existence of an autonomic responsedeficit in the CP group (10), probably due to a ceilingeffect. The disturbed sympathovagal balance observed inthe CP group in the present study might be the result ofinitial the brain lesion (10), and it is indicative that theCP individuals present higher sympathetic (LF) andparasympathetic (HF) activity, resulting in low modu-lation (LF ⁄HF), because they are at the upper limit ofsympathetic activity.As the pathway of saliva secretion is under autonomic

control and somatosensory and visceral afferents ofcranial nerves terminate in the tractus solitarius andsalivatory nuclei in the medulla oblongata, the secretionof saliva is stimulated by the action of neurotransmittersof the ANS, and the final composition of saliva is relatedto the stimuli origin, i.e., sympathetic or parasympa-thetic (7). The increased protein concentration andreduced salivary flow rate observed for the CP groupcould be the result of b-adrenergic activation. In fact,increased heart rate in the ECG and increased LF in24-h ECG recordings were verified, which suggests apredominance of the sympathetic response. Weacknowledge that HRV is an estimate of the ANStonus to the heart and whether it reflects peripheralANS tonus is a matter for further discussion (10).The electrocardiogram results showed an enlargement

of the mean QTc interval and a trend toward enlarge-ment of the maximum QTc interval in the CP group. Ithas been demonstrated in the literature that this findingis linked to increased risk of cardiac arrhythmias anddeath (25).Improved medical care for individuals with CP has

increased their survival rates, with approximately 85%achieving a 20-year survival rate, which remains alower survival outlook than in the general population.Many more deaths are caused by respiratory system

diseases among those dying in their 20 and 30 s thanwould be expected in the CP population. For thoseindividuals who die in their 40 and 50 s, the increase indeaths is caused by diseases of the circulatory system.More deaths than expected in this age-group arecaused by diseases of the nervous system (26). Recog-nizing and preventing the underlying mechanismsinfluencing cardiovascular comorbidities in these pa-tients may prevent early deaths and increase awarenessconcerning the risks of anesthetics and other medica-tions when treating medical conditions among CPindividuals.

The importance of the findings of this study isreflected directly in the dental treatment of individualswith CP, because they are at risk of cardiovascularevents. The dental surgeon must be alert to factors thatmay increase the risk of cardiovascular problems inindividuals with cerebral palsy, such as knowledge of thepsychotropic drugs used by these individuals continu-ously, possible drug interactions with anesthetic drugs,the need for pain control and the duration of the sessionowing to the spasticity of masticatory muscles. More-over, other factors are responsible for the release ofendogenous catecholamines, such as fear, anxiety, dif-ficulty in communication and expression of pain anddiscomfort of buccodental origin.

Based on these findings, it can be concluded thatindividuals with cerebral palsy present an increasedcardiovascular risk, a disturbed sympathovagal balancethat could contribute to the salivary secretion alterationsobserved. Further studies must be conducted to inves-tigate the possible correlations between the disturbedsympathovagal balance, oromotor function, hydrationstatus and ⁄ or impairment of salivary gland functions incerebral palsy individuals.

References

1. Rosenbaum P, Paneth N, Leviton A, et al. A report: thedefinition and classification of cerebral palsy April 2006.Dev Med Child Neurol Suppl 2007; 109: 8–14.

2. Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M,Chaudhuri AR, Zalutsky R. How common are the‘‘common’’ neurologic disorders? Neurology 2007; 68:326–37.

3. Santos MT, Guare R, Leite MF, Ferreira MC, Nicolau J.Does the neuromotor abnormality type affect the salivaryparameters in individuals with cerebral palsy? J OralPathol Med 2010; 39: 770–4.

4. Siqueira WL, Rodrigues Santos MT, De Oliveira E,Nicolau J. Comparison of electrolyte concentrations inwhole saliva of individuals with and without cerebralpalsy. Quintessence Int 2007; 38: 301–6.

5. Rodrigues Santos MT, Siqueira WL, Nicolau J. Amylaseand peroxidase activities and sialic acid concentration insaliva of adolescents with cerebral palsy. Quintessence Int2007; 38: 467–72.

6. Siqueira WL, Santos MT, Elangovan Simoes A, Nicolau J.The influence of valproic acid on salivary pH in childrenwith cerebral palsy. Spec Care Dentist 2007; 27: 64–6.

7. Proctor GB, Carpenter GH. Regulation of salivary glandfunction by autonomic nerves. Auton Neurosci 2007; 133:3–18.

ANS in individuals with cerebral palsy

Ferreira et al.

580

J Oral Pathol Med

8. Felderhoff-Mueser U, Buhrer C. Clinical measures topreserve cerebral integrity in preterm infants. Early HumDev 2005; 81: 237–44.

9. Doussard-Roosevelt JA, Porges SW, Scanlon JW, AlemiB, Scanlon KB. Vagal regulation of heart rate in theprediction of developmental outcome for very low birthweight preterm infants. Child Dev 1997; 68: 173–86.

10. Yang TF, Chan RC, Kao CL, et al. Power spectrumanalysis of heart rate variability for cerebral palsy patients.Am J Phys Med Rehabil 2002; 81: 350–4.

11. Kerppers I, Arisawa AL, Oliveira VF, Sampaio MM,Oliveira S. Heart rate variability in individuals withcerebral palsy. Arch Med Sci 2009; 5: 45–50.

12. Park ES, Park CI, Cho SR, Lee JW, Kim EJ. Assessmentof autonomic nervous system with analysis of heart ratevariability in children with spastic cerebral palsy. YonseiMed J 2002; 43: 65–72.

13. Veugelers R, Benninga MA, Calis EA, et al. Prevalenceand clinical presentation of constipation in children withsevere generalized cerebral palsy. Dev Med Child Neurol2010; 52: e216–21.

14. Bradford MM. A rapid and sensitive method for thequantitation of microgram quantities of protein utilizingthe principle of protein-dye binding. Anal Biochem 1976;72: 248–54.

15. European Society of Cardiology and The North AmericanSociety of Pacing and Electrophysiology. Heart ratevariability. Standards of measurement, physiologicalinterpretation, and clinical use. Task Force of the Euro-pean Society of Cardiology and the North AmericanSociety of Pacing and Electrophysiology. Eur Heart J1996; 17: 354–81.

16. Bonaduce D, Marciano F, Petretta M, et al. Effects ofconverting enzyme inhibition on heart period variability inpatients with acute myocardial infarction. Circulation1994; 90: 108–13.

17. Bloomfield DM, Kaufman ES, Bigger JT Jr, Fleiss J,Rolnitzky L, Steinman R. Passive head-up tilt and activelystanding up produce similar overall changes in autonomicbalance. Am Heart J 1997; 134: 316–20.

18. Bloomfield DM, Magnano A, Bigger JT Jr, RivadeneiraH, Parides M, Steinman RC. Comparison of spontaneous

vs. metronome-guided breathing on assessment of vagalmodulation using RR variability. Am J Physiol Heart CircPhysiol 2001; 280: H1145–50.

19. Mcmanus V, Guillem P, Surman G, Cans C. SCPE work,standardization and definition: an overview of the activ-ities of SCPE: a collaboration of European CP registers.Zhongguo Dang Dai Er Ke Za Zhi 2006; 8: 261–5.

20. Dos Santos MT, Nogueira ML. Infantile reflexes and theireffects on dental caries and oral hygiene in cerebral palsyindividuals. J Oral Rehabil 2005; 32: 880–5.

21. Lehman SJ, Massaro JM, Schlett CL, O’DonnelL CJ,Hoffmann U, Fox CS. Peri-aortic fat, cardiovasculardisease risk factors, and aortic calcification: the Framing-ham Heart Study. Atherosclerosis 2010; 210: 656–61.

22. O’Driscoll DM, Foster AM, Ng ML, et al. Acute cardio-vascular changes with obstructive events in children withsleep disordered breathing. Sleep 2009; 32: 1251–2.

23. Shintani T, Asakura k, Ishi K, Yoshida M, Kataura A,Ogasawara H. Obstructive sleep apnea in children withcerebral palsy. Nippon Jibiinkoka Gakkai Kaiho 1998; 101:266–71.

24. Schwab R, Kuna S, Remmers JE. Anatomy and physiol-ogy of upper airway obstruction. In: Kryger M, Roth T,Dement W eds Principles and practice of sleep medicine.Philadelphia: Elservier, 2005; 983–1000.

25. Rana BS, Lim PO, Naas AA, et al. QT interval abnor-malities are often present at diagnosis in diabetes and arebetter predictors of cardiac death than ankle brachialpressure index and autonomic function tests. Heart 2005;91: 44–50.

26. Hemming K, Hutton JL, Pharoah PO. Long-term survivalfor a cohort of adults with cerebral palsy. Dev Med ChildNeurol 2006; 48: 90–5.

Acknowledgements

This study was supported by the Fundacao de Amparo a Pesquisa do

Estado de Sao Paulo (FAPESP) under protocol number 08 ⁄ 00960-6. Theauthors gratefully acknowledge Nelson Samesina, Cesar J Grupi and

Jaqueline Wagenfuhr for their professional support in this study.

ANS in individuals with cerebral palsy

Ferreira et al.

581

J Oral Pathol Med