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Dtsch Arztebl Int. 2011 June; 108(25): 426±431.

Published online 2011 June 24. doi: 10.3238/arztebl.2011.0426 PMCID: PMC3139414

Copyright notice Review Article

Early Detection of Hearing Impairment in Newborns and InfantsMartin Ptok, Prof. Dr. med. Dr. med. h. c. *1 1Klinik und Poliklinik für Phoniatrie und Pädaudiologie, Medizinische Hochschule Hannover *Klinik und Poliklinik für Phoniatrie und Pädaudiologie Medizinische Hochschule Hannover Carl-Neuberg-Str. 1,30625 Hannover, Germany ; Email: [email protected] Received August 17, 2010; Accepted March 24, 2011.

See "Hearing²the Gateway to Speech and Cognition" on page 425.

y Other Sections

Abstract

Background

1±2 out of 1000 newborns have markedly impaired hearing.Methods

Review of the pertinent literature, which was retrieved with a selective search of the

following databases: NHS EED (Economic Evaluation Database), HTA (Health Technology

Assessment), DARE (Database of Abstracts of Reviews on Effectiveness), Clinical Trials,

CDSR (Cochrane Database of Systematic Reviews), and PubMed.

Results

The current scientific evidence favors universal neonatal hearing screening (UNHS) for the

early detection of hearing impairment. UNHS is best performed in two stages: firstmeasurement of otoacoustic emissions and then automated assessment of the brainstem

auditory evoked response. To be effective, UNHS programs must have a high coverage

rate, high sensitivity and specificity, and proper tracking with a low rate of loss to follow-up.

Children with positive screening tests for hearing impairment should undergo confirmatory

testing as soon as possible and then receive the appropriate treatment. Early intervention is

particularly critical for speech acquisition.

Conclusion

The early detection and treatment of hearing impairment in newborns and infants has abeneficial effect on language acquisition.

y Other Sections



Hearing plays a key part in learning to talk. Without speech and hearing it is difficult for

interpersonal relationships to develop and thrive. In earlier times children who did not react

to acoustic stimuli and were able neither to understand speech nor to acquire it

spontaneously encountered severe discrimination, being dismissed as simple-minded or

worse. As late as 1950, the standard policy was to wait until a hearing-impaired child hadlearned to speak proficiently before prescribing an individually designed hearing aid. The

intention was to protect the hearing-impaired child from its own imperfect speech. Early

detection of impaired hearing thus seemed superfluous, since in any case a hearing aid

would not be prescribed until later (1).

Growth in understanding of the functional and morphological maturation of the auditory

system and of the complexities of emotional and social development in children, coupled

with advances in hearing technology, have led to a fundamental change in attitude. Today,

it is axiomatic that hearing impairment should be detected and treatment initiated as early

as possible. Following a ruling by the Federal Joint Committee (Gemeinsamer Bundesausschuss) that came into effect on 1 January 2009, all newborn children in

Germany are entitled to hearing screening (2). Universal newborn hearing screening

(UNHS) is either recommended or already practiced and legally regulated (nationally or

regionally) (4) in many other European nations, e.g., Austria (e1), Great Britain (e2), Italy

(e3), and France (e4), as well as in various countries in Asia (e5) and in the whole of the

USA (3).

In deciding whether to establish a system for early detection of hearing impairment in

newborns and infants, a range of questions had and have to be answered, for example:

y Will screening of newborn children always detect hearing impairment? How high are

the sensitivity and specificity of UNHS? What proportion of newborns are screened?

How high is the rate of children who have conspicuous findings but are lost to follow-

up? Is it better to screen all newborns or only those with risk factors?

y What benefits does early detection of hearing impairment bring? Do children in

whom hearing impairment is detected early by UNHS develop better than those who

do not undergo UNHS and whose hearing problems are discovered later?

y What potential risks are involved in newborn hearing screening, e.g., by

unnecessarily alarming parents whose children have a false-positive result?y How soon and with what degree of certainty can confirmatory tests be carried out

after a positive screening result? How quickly can treatment be initiated after

confirmation of the diagnosis? Is it better to start treatment immediately or later?

Before these questions can be considered, however, two other issues have to be resolved:



y Quality: What type of hearing impairment is involved (e.g., middle ear impairment,

inner ear impairment, unilateral or bilateral impairment)?

y Quantity: What is the degree of hearing impairment (e.g., expressed as hearing loss

in decibels)?

This article describes how these questions can be answered or have already been

answered.

y Other Sections

Methods

A selective search of the literature (checklist at www.prisma-statement.org) was carried out

in the following databases:

y NHS EED (Economic Evaluation Database)y HTA (Health Technology Assessment) or DARE (Database of Abstracts of Reviews

on Effectiveness) (http://www.crd.york.ac.uk/crdweb; last accessed on 16 August

2010)

y Clinical Trials (http://clinicaltrials.gov/ct2/search; last accessed on 17 August 2010)

y CDSR (Cochrane Database of Systematic Reviews)

(http://www2.cochrane.org/reviews; last accessed on 17 August 2010)

y PubMed/Medline (last accessed on 16 August 2010)

A search on the terms ³infant´, ³newborn´, ³child´, ³pediatric´, ³paediatric´, ³hearing loss´,³hearing impairment´, and ³deafness´ yielded 21 135 results. Restriction to the years 2007

to 2010 identified 3146 evaluable publications.

The reason for excluding earlier studies was that those before 2007 were covered in an

extremely thorough survey by the Institute for Quality and Efficiency in Health Care (I nstitut

für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) (5). Further restriction to

publications including the terms ³clinical trial´ or ³comparative study´ narrowed the sample

down to 379 studies.

Screening of the abstracts of all 379 publications was followed by full-text analysis of thestudies featuring empirical data.

Prevalence

Different studies broadly agree that one or two of every 1000 newborns have a hearing

impairment that on current evidence warrants treatment or observation, i.e., permanent

hearing loss with a lowering of the absolute threshold of hearing for speech perception by at



least 35 dB (e6 ± e8). To date, the UNHS study groups have concentrated on detecting such

hearing impairments as early as possible (1).

y Other Sections

Classification of hearing disorders

The term ³hearing impairment´ is of little practical use without further qualification. It is

advisable to classify disorders of hearing according to:

y Quality and location

y Cause

y Severity.

Quality and location

The hearing process can be divided into sound conduction, transformation of sound waves

into bioelectrical signals, and neural processing. A hearing disorder may involve only one or

a combination of these functions. Hearing impairments can thus be classified as follows:

y Impairments of conduction (defective transport of sound waves from the external

environment to the inner ear)

y Sensory impairment (defective sensation and transformation of stimuli between the

base of the stapes and the first neuron of the auditory nerves)

y Retrocochlear and central hearing impairment and auditory perception disorders

(defective transmission, processing, and perception of stimuli)y Combined hearing impairments.

Particularly important in the context of early detection of hearing disorders in newborns and

infants are conductive and sensory impairments, together with auditory neuropathy, which is

occasionally included among the central hearing impairments.

Causes

As with other sensory impairments, there are hereditary and non-hereditary or congenital

and pre-, peri-, or postnatal causes of hearing disorders. While the cause of conductive

hearing loss can usually be identified relatively simply (e.g., by means of otoscopy in the

case of tympanic effusion or accumulation of earwax), even thorough diagnostic

investigation fails to uncover the reason for around half of the cases of inner ear hearing

impairment in childhood. Approximately 50% of severe hearing impairments arising in the

inner ear are thought to be hereditary in origin. The precise causes of central auditory

perception disorders cannot be established.



Severity

Classification of severity is usually based on the average hearing loss in the frequency

range of normal speech. Thus the hearing impairment is described solely in terms of the

absolute threshold of hearing. However, the principal function of hearing is to detect rapid

changes of frequency and intensity in acoustic signals above the threshold, and thus tounderstand speech. The conventional adult classification according to speech

comprehension (speech audiometric determination of whole-word comprehension and

hearing loss for numbers) is not applicable to newborns and infants. Moreover, such a

classification provides only a ³snapshot´ of hearing ability. Intermittent hearing impairments

(e.g., in children with recurring tympanic effusions) must also be considered as significant

disorders. In such cases it may be beneficial to record how often episodes of hearing

impairment occur over an extended period of time, e.g., a year, and then to decide how best

to proceed.

Even precise classification according to the results of routine speech audiometric testingdoes not do justice to central hearing impairments and auditory perception disorders.

y Other Sections

Diagnosis of hearing disorders in early childhood

Diagnosis of hearing disorders in newborns and infants is generally a two-stage process. As

described above, the current standard is UNHS, followed immediately by confirmatory

diagnostic evaluation as appropriate.

Universal newborn hearing screening

The various studies on UNHS have either measured otoacoustic emissions (OAE) (e9) or

performed automated auditory brainstem response (AABR) audiometry, or both. In two-

stage screening, OAE measurement is followed by AABR audiometry. In one very thorough

analysis, Wolff et al. found that the reported sensitivity of OAE measurement varied from

50% to 100% and the specificity from 49% to 97% (6). A weakness of OAE measurement is

that it does not detect fluctuating hearing impairments or those due to auditory neuropathy

(e9 ± e12). A controlled study carried out in the UK employed two-stage screening: The

estimated sensitivity (no follow-up of screening-negative children, assumption of at least afew false negatives) was 91.7% (95% confidence interval [CI] 0.742 to 0.977), the specificity

98.5% (95% CI 0.983 to 0.987) ([7, 8], evaluated by [6]).

From the practical clinical viewpoint, neither OAE measurement nor AABR audiometry is

simple to perform. Although the equipment has become much easier to use (Figure), it is



advisable for the tests to be conducted by well-trained and experienced staff, and also to

keep the referral rate reasonably low.

Figure 1 Hearing screening with a handheld touch-screen device capable of both

measurement of transitory evoked otoacoustic emissions (TOAE) and

automated auditory brainstem response (AABR) audiometry

Another criterion of the quality of UNHS is the coverage rate, i.e., the proportion of

newborns screened. Varying figures are reported in the literature. Green, for example,

found that 95% of newborns were screened in the states of the USA in which UNHS was

compulsory by law, against only 26% in the remaining states (9).

Whenever screening arouses suspicion of hearing impairment, the child concerned mustundergo confirmatory diagnostic evaluation; the rate of loss to follow-up of a UNHS program

should be kept as low as possible. To this end, functioning central registries must be set up

(e13). These centers should ideally maintain registers of children who have not been

screened and children with a conspicuous screening result. The screening center can then

track these children and ensure that the required investigations are instigated. Despite the

recommendations of the Federal Joint Committee, Germany is not yet completely covered

by such tracking centers for UNHS.

Selective screening of newborns with specific risk factors has been discussed as an

alternative to UNHS (Box). These children have an up to 10 times higher risk of suffering animpairment of hearing that requires treatment (1% to 2% instead of 0.1% to 0.2%).

However, around half of all hearing-impaired children exhibit no risk factors and would

therefore not be among those screened. For this reason, selective screening is no longer

recommended.

BOX. Hearing impairment in early childhood: signs and risk factors (11)

y Concern on the part of parents/guardians regarding the hearing, speech

development, or general development of their child

y Family history of permanent hearing impairment in childhoody Stay of more than 5 days in the neonatal intensive care unit, possibly including the

need for ventilation, extracorporeal membrane oxygenation, assisted breathing,

administration of ototoxic drugs or loop diuretics, and hyperbilirubinemia requiring

transfusion

y Intrauterine infections such as cytomegalovirus, herpes, rubella, syphilis, and

toxoplasmosis



y Craniofacial anomalies, including malformation of the earlobe, auditory canal, or

auricular appendages and anomalies of the auditory pit and petrosa

y External signs that may indicate a syndrome involving sensorineural hearing loss or

permanent conductive hearing loss, e.g., a white forelock

y

Syndromes involving immediate, progressive, or late-onset hearing loss, such asneurofibromatosis, osteopetrosis, and Usher syndrome; other complexes associated

with hearing disorders are Waardenburg, Alport, Pendred, and Jervell-Lange-Nielsen

syndromes

y Neurodegenerative diseases such as Hunter syndrome or sensorimotor

neuropathies such as Friedreich ataxia and Charcot-Marie-Tooth syndrome

y Demonstration in culture of infections associated with sensory hearing loss, including

bacterial or viral (especially herpes or varicella) meningitis

y Head injury, particularly fractures of the skull base or petrosa requiring inpatient

treatment

y Chemotherapy

y Otitis media recurring frequently or persisting for more than 3 months

It is advisable for newborns with specific risk factors, e.g., those who have been treated for

more than 5 days in a neonatal intensive care unit or required ventilation, to be referred for

immediate AABR screening or go straight to (confirmatory) diagnostic evaluation. An

American committee of experts recommends that children with risk factors (box) be

monitored/examined regularly for 3 years (10, 11).

UNHS is worthwhile only if (a) the diagnosis is confirmed and treatment instigated withoutdelay and (b) these measures then have a positive impact on patient-relevant endpoints,

i.e., if hearing-impaired children who are diagnosed early develop better with regard to

speech acquisition than those whose hearing disorders are detected and treated later. No

relevant prospective randomized trials have been conducted for ethical and moral reasons,

but cohorts with and without UNHS have been compared. Sininger et al. found that final

diagnosis and commencement of treatment were some 24 months earlier in hearing-

impaired children who had undergone UNHS than in those who had not been screened

(e14). The few studies on receptive speech skills (speech comprehension) show a

significant benefit of UNHS; regarding expressive speech skills, there was at least a trend

towards better development in UNHS children (for example [76, 12 ± 14]). Wolff et al. are

quite right to point out that the clinical significance of these advantages is unclear (6) (see

also [e15]); however, the findings of the DECIBEL Collaborative Study Group indicate that

newborn hearing screening is superior to distraction audiometry in the ninth month of life not

only in terms of development of social behavior, gross motor skills, and both receptive and



expressive speech skills, but also with regard to quality of life as assessed by questionnaire

(15).

The potential drawbacks of UNHS include unnecessary alarming of the parents in the case

of false-positive findings. However, studies have failed to confirm any such disadvantages.

Since UNHS (as desired) leads²or is intended to lead²to early detection and thus to

prompt treatment, the risks and drawbacks of early treatment can be counted as (late)

disadvantages of UNHS. Case studies and case reports have described an increased rate

of meningitis in children who receive a cochlear implant (CI) at an early age. Reefhuis et al.

reported incidence of 138.2 cases per 100 000 person-years, 30 times higher than in a

comparative cohort (e16). It must be pointed out, however, that most reports describe the

use of a CI electrode that is now no longer employed.

Although the data do not permit definitive conclusions, it is currently not thought that UNHS

entails any risks that might lead to it being discredited.

y Other Sections

Confirmatory diagnostic evaluation

If UNHS indicates that a child may have a hearing impairment, complementary

investigations to confirm the diagnosis should be instigated as soon as possible. These

examinations should be able to definitively confirm or exclude hearing impairment, and if a

hearing disorder is present they should provide precise qualitative and quantitative

characterization (e17). For the above-mentioned reasons this is practically impossible;

however, confirmatory diagnostic procedures can describe hearing impairment, in the sense

of permanent hearing loss of 35 dB or more, well enough for appropriate treatment to be

instigated.

Pedaudiology

Hearing tests can fundamentally be divided into subjective and objective examinations. In

subjective tests a sound stimulus is offered and the examiner observes and evaluates the

child¶s reaction. Objective hearing tests are not truly objective, but are termed so because

they do not require cooperation by the child. The auditory stimulus is presented (semi-

)automatically, and simultaneously specific neurobiological reactions are registered (16).

Declau et al. (17) published data on confirmatory diagnostic evaluation after positive UNHS

in a large group of children: Of 170 children with a positive UNHS result (corresponding to

ca. 87 000 newborns screened), 5 had a tympanic effusion that regressed during the

observation period. Permanent hearing impairment was confirmed in 116 children, bilateral

in 68 cases and unilateral in the other 48 neonates. The average absolute threshold of



hearing was 70 to 80 dB nHL. The initial (screening) AABR result was confirmed in full in

60.4% of cases. Interestingly, 11.6% of the newborns thought to have a unilateral hearing

impairment on UNHS were found to have a bilateral impairment when assessed in more

detail.

Objective hearing tests were used for confirmatory audiological diagnosis, but no subjective

tests. This is regrettable, because even in young children subjective hearing tests yield

results that help to decide how best to proceed.

y Other Sections

Conclusion and perspective

Overall, the studies that have been carried out to date indicate that properly conducted

UNHS followed by a functioning program of observation for children affected by hearing

impairments yields positive results with regard to speech and general development. Therisks and drawbacks of UNHS seem slight.

Nevertheless, the data on early detection of hearing impairment in newborns and infants are

not very robust: Further research is clearly required. Besides the full-scale implementation

of UNHS, the most important single measure for the practical realization of early detection

of hearing impairments in newborns and infants in Germany seems to be the installation of

a system of tracking centers covering the whole country. In the next few years we must on

the one hand consider whether the rate of false-positive UNHS results can be reduced by

improved assessment of the middle ear status (e18, e19). On the other hand, particularly

thinking about future early interventions, we must investigate the potential utility of hybrid

screening schemes, combining audiological testing with genetic screening (e.g., 35delG in

GJB2/connexin mutation [e20, e21] or congenital cytomegalovirus infection [e22,e23]).

Key Messages.

y The current scientific evidence supports the demand for universal newborn hearing

screening (UNHS) conducted by carefully trained personnel.

y

A functioning system for registering and tracking both non-screened children andthose with a conspicuous screening result is of crucial importance.

y Two-stage (or combined) screening yields better results than measurement of

otoacoustic emissions alone; however, children exhibiting specific risk factors should

immediately undergo AABR screening or (confirmatory/excluding) diagnostic

evaluation.



y Conspicuous findings on screening should be swiftly followed by confirmatory

diagnostic assessment and, if indicated, treatment.

y On the available evidence, the risks and disadvantages of UNHS are slight.

Acknowledgments

Translated from the original German by David Roseveare.

Footnotes

The author declares that no conflict of interest exists.

y Other Sections

References

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2 . Bekanntmachung eines Beschlusses des Gemeinsamen Bundesausschusses über eine Änderung der Kinder-

Richtlinien. www .g-ba.de/downloads/39-26 1-68 1 /2008 -06 -19-K inder -H%C 3%B6rscreening_BAnz .pdf . Einführung

eines Neugeborenen-Hörscreenings vom 19. Juni 2008.

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services? P ublic H ealth Re p. 2010;125:199±207. [PMC free article] [PubMed]

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Sur g. 2010;18:399±404. [PMC free article] [PubMed]

5 . IQWiG (ed.) Abschlussbericht S05 -0 1. Köln: Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen

(IQWiG); 2007. Früherkennungsuntersuchung von Hörstörungen bei Neugeborenen.

6 . Wolff R, Hommerich J, Riemsma R, Antes G, Lange S, Kleijnen J. Hearing screening in newborns: Systematic

review of accuracy, effectiveness, and effects of interventions after screening. Arch Dis C hild . 2010;95:130±

135. [PubMed]

7 . Kennedy C, McCann D, Campbell MJ, Kimm L, Thornton R. Universal newborn screening for permanent childhood

hearing impairment: An 8-year follow-up of a controlled trial. Lancet .2005;366:660±662. [PubMed]

8 . Controlled trial of universal neonatal screening for early identification of permanent childhood hearing impairment.

Wessex universal neonatal hearing screening trial group. Lancet .1998;352:1957±1964. [PubMed]

9. Green DR, Gaffney M, Devine O, Grosse SD. Determining the effect of newborn hearing screening legislation: An

analysis of state hearing screening rates. P ublic H ealth Re p. 2007;122:198±205.[PMC free article] [PubMed]

10 . Joint Committee on Infant Hearing, American Academy of Audiology, American Academy of Pediatrics, American

Speech-Language-Hearing Association, Directors of Speech and Hearing Programs in State Health and Welfare

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hearing. P ediatrics. 2000;106

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impairment. J AMA. 2010;304:1701±1708. [PubMed]

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e1. Weichbold V, Nekahm-Heis D, Welzl-Muller K. Evaluation of the austrian newborn hearing screening

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Abstract

Pain is one of the most misunderstood, under diagnosed, and under treated/untreated

medical problems, particularly in children. One of the most challenging roles of medical

providers serving children is to appropriately assess and treat their pain. New JCAHO

regulations regard pain as ³the fifth vital sign´ and require caregivers to regularly assessand address pain. Pain being a personal experience, many different terms are used to

describe different sensations. Assessment of pain in children is linked to their level of

development. Children of the same age vary widely in their perception and tolerance of

pain.

Keywords: Pain in children, Neglected and unaddressed, Barriers to pain assessment and

management

y Other Sections

INTRODUCTION

Every child will experience pain at one time or another, whether it is from everyday bumps

and bruises, or due to more chronic conditions such as headaches, gastrointestinal

problems, or diabetes. In fact, as many as 40% of children and adolescents complain of

pain that occurs at least once weekly, and chronic pain affects at least 15%±20% of

children. Just as chronic pain is more prevalent in women than men, girls report more pain

than boys.[1]

Pediatric pain stems from a wide range of chronic conditions- usually muscle, bone, or joint

pain, headaches, or abdominal pain-and require pain management. But the medical

community has not placed the same emphasis on pain management for pediatric patients

as it has for adults and seniors. Each year, 1.5 million children have surgery, and many

receive inadequate pain relief and in 20% of cases, the pain becomes chronic. Of children

aged 5±17 years, 20% suffer headaches.[2] . More than one-third of children complain of

abdominal pain lasting two weeks or longer.[3] Juvenile arthritis, which causes joint

inflammation and aches, affects nearly 250,000 people under the age of 16 years.[4]

If left unaddressed, chronic pain can affect children in ways that will follow them throughout

their lives. They can develop emotional and psychological scars from their pain that cantaint future choices concerning their lives and health care. Untreated pain in childhood also

can lead to chronic pain in adulthood and old age[5]

y Other Sections

BE AN ADVOCATE FOR YOUR CHILD¶S PAIN MANAGEMENT



Pain is truly both a physical and an emotional experience perceived and processed by the

brain, it is a real health problem as well. Each child has different pain perception, and the

meaning of pain is also different from child to child. The goal of treatment is to decrease the

intensity of pain and make the child feel better. For acute pain, this goal is often met

successfully. But chronic pain-pain lasting for at least three months or more-has a differenteffect on the nervous system and needs to be treated differently. Perhaps one of the most

difficult challenges professionally. Perhaps one of the most difficult challenges

professionally and emotionally is learning to handle pain in pediatric patients. It is

sometimes a necessary part of our work to inflict pain during procedures, immunizations,

and other treatments. In the past, there was a relative lack of accountability for providing

pain relief. Culture has changed as evidenced by the New JCAHO (Joint Commission on

Accreditation of Healthcare Organizations) regulations which regard pain as ³the fifth vital

sign´ and require caregivers to regularly assess and address pain.[6] However, pain

remains one of the most misunderstood, under diagnosed, and Under treated/untreated

medical problems in children.

WHY IS PEDIATRIC PAIN NEGLECTED?

Pediatric pain is neglected and undertreated for several reasons:

1. Children and adults react differently when it comes to pain.

2. Doctors focus on the source rather than the symptom. Many physicians become so

focused on determining what is causing a child¶s pain that they fail to perform pain

management.

3. Some physicians do not understand pediatric pain management.

y Other Sections

TELL±TALE SIGNS OF PAIN IN CHILDREN

Certain behaviors can alert you to your child¶s pain, even if the child can not properly

express it himself. These include:

y Favoring one arm or leg over the other.

y A decrease in physical activity.y Changes in appetite or sleep pattern.

y Avoiding contact with other children.

y Crankiness, irritability, or unruly behavior.

y Nonverbal expressions of pain such as gasping, wincing, or frowning.

y Physical cues like dull eyes, flushed skin, rapid breathing, or sweating.



neonate into the role of ³biologic machine´ rather than a human being capable of

perceiving, responding to, and interacting with his or her environment.

3. Assumptions on the part of patients as well as caregivers affect pain assessment.

Many children will deny pain because of fear of disappointing caregivers or fear of an

injection.4. Many health care providers also at least subconsciously believe that they, rather

than the child, can accurately judge a child¶s pain experience. They may attribute a

child¶s distractibility to absence of pain. This perception represents a

misunderstanding of the powerful roles of distraction and comforting in the

attenuation or relief of pain.

5. We still expect children to react to pain with some predictable, visible signs such as

sweating, tachycardia, wincing, crying, jerking away, and muscle tension. The

absence of these typical signs may be considered as adaptation on the part of the

child.

CAN¶T CHILDREN CATEGORIZE PAIN?

There are several categories of pain. One of the most common is that which is associated

with a disease state (e.g., arthritis, sickle-cell disease) or that which is associated with an

observable physical injury or trauma (e.g., burns, fractures). Some of the most challenging

conditions involve pain that is not associated with a well-defined or specific disease state or

physical injury (e.g., tension headaches, recurrent abdominal pain). Pain may also be

caused by the medical provider (e.g., circumcisions, injections). Pain may be caused by

habits and behaviors as well (e.g., abdominal pain related to intake of alcohol or spicy

foods, and so on).

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A DEVELOPMENTAL APPROACH TO ASSESSMENT±NEONATES,

TODDLERS, AND SCHOOL GOING KIDS

To accurately assess pain in children, the medical care-giver must tailor assessment

strategies to the child¶s developmental level. Several factors modify pain perceptions

including age, cognition, sex, previous pain experience, temperament, cultural and family

factors, and situational factors. There are three widely used categories of behavioral

indicators of pain: global rating scales (GRS) behavioral observation scales (BOS). and

indirect measures, GRS rely on the assessment of predictable behavioral indicators of pain

such as crying, wincing, or screaming. Indirect measures of pain may be assessed by

requests for medication, or ³well´ behavior such as playing. We know, however, that

requests for pain medication are not reliably linked to pain intensity. BOS focus on the



documentation of specific behaviors indicative of pain. Physiologic measures (e.g., heart

rate and blood pressure) are helpful as adjuncts to behavioral observation, but are neither

sensitive nor specific pain indicators.

Neonates

There is no easy or scientific way to tell how much pain an infant is having. BOS and

physiologic measures can be difficult to interpret. Neonates may manifest pain by crying or

being silent, wiggling, or being still. The infant may make faces or not. The cry of pain in the

neonate is quite distinctive. Primary caregivers easily distinguish and interpret cries.

Toddlers

Reports of caregivers can be invaluable in pain assessment in the toddler age group. The

fear factor is a large contributor to experience of pain in this and the school-age group.

Toddlers may become very quiet and inactive while in pain or may become very active.

Parents report that ³they aren¶t acting like they normally do.´ Interpreting toddlers¶ behavior may be difficult due to exacerbating factors such as separation anxiety, memory of previous

painful experiences, and physical restraint. Sometimes toddlers manifest their pain and fear

by aggressive outbursts.[10]

School-age children

School-age children are more accurate in communicating about their pain. By age 8 years,

children can very reliably describe location of pain. Symptom scales and self-report tools

are appropriate for most children 4 years of age and older. Children older than 8 years who

understand the concept of order or number can use a Numeric Rating Scale or a HorizontalWord ± Graphic Rating Scale. Pain diaries may be helpful in the school age group. School-

age children also exhibit self-control when they are experiencing pain. They may not report

pain in an attempt to show bravery.[11]

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DISCUSSION

If pain is not addressed and treated early on, it can greatly impact a child¶s quality of life by

interfering with mood, sleep, appetite, school attendance, academic performance, and

participation in sports and other extracurricular activities. Further, if unrelieved, childhood

pain can enhance a child¶s vulnerability to pain later in life. Early experiences such as pain

are associated with multiple alterations in the adult brain in a number of animal models.

Repeated exposure to pain may cause altered pain sensitivity, anxiety, stress disorders,

hyperactivity, and attention deficit disorder, impaired social skills, and patterns of self-

destructive behavior.[8] It is essential that healthcare providers begin to recognize pediatric



pain so that appropriate strategies can be devised to target and reduce children¶s distress

and pain-related disability. Unaddressed pain can also result in significant financial stress

for families who not only have to cover healthcare expenses, but who may also have to

miss work to care for a sick child. Inadequate prevention and relief of pediatric pain are still

widespread. Many obstacles exist to providing appropriate pain care to children andadolescents.

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CONCLUSION

Children are particularly responsive to pain-controlling strategies that involve their

imaginations and senses of play. Sensory and procedural information coupled with

behavioral techniques can be used to distract children away from painful procedures and to

decrease fear and anxiety.

All patients in pain can benefit from well-chosen use of psychologic techniques. This

approach in children must take into account the developmental level of the child.

Approaches as simple as covering the wound or as involved as play therapy may be used.

It is wise to keep children with their caregivers if at all possible. With proper guidance,

parents assist with distracting the child and reinforcing the suggestions of the medical team.

Developing a calm, patient, understanding approach to the needs of the child and his or her

caregivers can markedly enhance the encounter.

In spite of so much understanding about pediatric pain management, the sad reality is that

pediatric pain management research has not been effectively translated into routine clinical

practice.

Footnotes

Source of Support: Nil

Conflict of Interest: None declared

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REFERENCES

1. Goodman JE, McGrath PJ. The epidemiology of pain in children and adolescents: A review. P ain.1991;46:247±

64. [PubMed]

2 . Zeltzer LK, Schlank CB. New York NY: HarperCollins; 2005. Conquering Your Child¶s Chronic Pain: A

Pediatrician¶s Guide for Reclaiming a Normal Childhood.



3. Chronic Abdominal Pain in Childhood: Diagnosis and Management. Retrieved from American Academy of Family

P hysicians. Available from: http://www.aafp.org/afp/990401ap/1823.html.

4. Juvenile Arthritis. from American Academy of Orthopaedic Surgeons. Website: Available

from:http://orthoinfo.aaos.org/topic.cfm?topic=A00075.

5 . Zeltzer LK, Anderson CT, Schechter NL. Pediatric Pain: Current status and new directions. C urr P robl P ediatr . 1990;20:415±86.

6 . McCaffery M. Pain relief for the child: Problem areas and selected non-pharmacologic methods.P ediatric

Nurs. 1977;3:11±6.

7 . Scanlon JW. Appreciating neonatal pain. Adv P edi . 1991;38:317±31.

8 . Anand KJ, Scalzo FM. Can adverse neonatal experiences alter brain development and subsequent behavior? Biol

Neonate. 2000;77:69±82. [PubMed]

9. Paris P. Pain management in the child. 1987;5:699-707. Emer g Med C lin North Am. 1987;5:699±707. [PubMed]

10 . Kuttner L. Management of young children¶s acute pain and anxiety during invasive medical

procedures. P ediatrician. 1989;16:39±44. [PubMed]11. Rivera WB. Practical points in the management of postoperative pediatric pain. J P ost Anesth Nurs. 1991;6:40±

2. [PubMed]

Ischemic Stroke in Infants and Children: Practical Management inEmergencySara Ciccone,* Michela Cappella, and Caterina Borgna-PignattiDepartment of Clinical and Experimental Medicine-Pediatrics, University of Ferrara, 44121 Ferrara, Italy*Sara Ciccone: Email: [email protected]

Academic Editor: Halvor NaessReceived September 23, 2010; Revised April 27, 2011; Accepted May 2, 2011.This is an open access article distributed under the Creative Commons Attribution License, which permits

unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

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Abstract

Stroke is a rare disease in children, with an estimated incidence 13/100000 and a significant

impact on morbidity and mortality. Clinical presentation and risk factors, present in almost

half of pediatric patients, are not the same as in adults. The diagnosis of stroke in children is

often delayed because signs and symptoms can be subtle and nonspecific. History and

clinical examination should exclude underlying diseases or predisposing factors.

Neuroimaging is crucial in defining diagnosis. Other tests might be necessary, according to

the clinical picture. We present here the most recent practical directions on how to diagnose

and manage arterial stroke in children, according to different international guidelines on the

subject.



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1. Introduction

The World Health Organization (WHO) defines stroke as ³a clinical syndrome of rapidly

developing focal or global disturbance of brain function lasting >24 hours or leading to deathwith no obvious nonvascular cause´ [1]. This definition should be integrated by a reference

to neuroimaging, at present considered essential to define the neurovascular origin of

symptoms. A modern definition could be ³a clinical syndrome characterized by (1) a

neurological deficit related to the perfusion territory of a cerebral artery and (2)

neuroradiological evidence of an ischemic lesion´ [2, 3].

Transient ischemic attacks (TIAs) are defined as ³a sudden, focal neurologic deficit that

lasts for less than 24 hours, of presumed vascular origin, confined to an area of the brain or

eye perfused by a specific artery´ [4]. In childhood, on the contrary, even in the presence of

transient symptoms, imaging often shows a cerebral infarction [5].

Strokes are classically divided in primarily ischemic or hemorrhagic. While adult strokes are

prevalently ischemic (80%) and due to atherosclerosis, in childhood up to 45% of strokes

are hemorrhagic and are associated with a wide spectrum of risk factors [6].

The estimated incidence of ischemic stroke in children older than 28 days of life is variable

[7 ±9] but, according to a large prospective, population study, it averages 13/100.000 for all

strokes, 7.9/100.000 for ischemic strokes, and 5.1 for hemorrhagic strokes [8].

Approximately 20% of children die after an ischemic stroke while more than 50% of those

surviving present neurological sequelae, most commonly hemiparesis [7, 9]. The cumulativestroke recurrence rate has been reported to be 15% at 1 year, and 19% at 5 years [ 10], and

up to 41% at 5 years [11].

A risk factor is present in almost half of the children at the time of stroke [12] (Table 1).

Common risk factors in childhood are congenital heart disease, sickle cell disease,

infections, and various prothrombotic conditions [13 ±15]. The most common cause of stroke

in children is probably heart disease, detected in 19% of children with arterial thrombosis

(Canadian Pediatric Ischemic Stroke Registry) [16]. Recent studies underline the

importance of infection: it seems that at least a third of cases of childhood stroke occur insuch a context. A fifth of the children with ischemic infarction of unknown origin has a

history of prior chickenpox [16 ±18].



Table 1 Risk factors for pediatric stroke.

In about 80% of children with arterial stroke, arterial imaging is abnormal [12].

The purpose of this paper is to provide practical up-to-date directions on how to diagnose

and manage arterial stroke in children (1 month±18 years), in an emergency department.

Neonatal stroke is not included because of its peculiar characteristics.

In preparing this work we followed the most recent guidelines on arterial stroke in childhood

(Pediatric Stroke Working Group, 2004; American College of Chest Physicians, 2004; Italian

Society of Pediatrics, 2007; American Stroke Association, 2008).

Additionally, a literature review was made, analyzing relevant articles on the subject, up to

August, 2010 by searching Pubmed, EMBASE, Cochrane Library and in bibliographies of

relevant articles. Search terms were ³stroke,´ ³emergency,´ ³child,´ ³childhood,´

³management.´

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2. Diagnosis

2.1. Clinical Presentation

The clinical presentation of stroke differs depending on age, involved artery, and cause

[19, 20].

While in infancy symptoms are usually aspecific, in older children, the most frequent

presenting symptoms are focal neurologic deficits such as hemiplegia or a gross, focal

motor deficit [21].

Symptoms according to the involved artery are listed in Table 2. The vascular territory of the

middle cerebral artery is the most frequently affected.



Table 2 Clinical presentation of stroke depending on the involved

artery.

2.2. Differential Diagnosis

Diagnosis of stroke in children is often delayed because signs and symptoms can be subtle

and nonspecific, such as mild single limb weakness, incoordination, and sensory

disturbances, initially attributed to causes other than stroke [22].

In a child presenting with an acute neurologic deficit, before a diagnosis of ischemic stroke

is made, other cerebrovascular diseases (hemorrhagic stroke, cerebral venous sinus

thrombosis) need to be considered.

Frequent causes of acute hemiplegia are Todd's palsy, where focal seizures usually

precede monoparesis or hemiplegia, and hemiplegic migraine, in which hemiplegia is

preceded by visual or sensitive disorders and followed by headache. It is also necessary to

exclude meningoencephalitis, generally associated with fever, headache and altered

consciousness.

Acute neurologic deficits may be caused by tumors, central nervous system disorders

including acute disseminated leukoencephalitis, cerebellitis, reversible posterior

leukoencephalopathy, alternating hemiplegia, metabolic disorders, epilepsy, and

psychogenic diseases [23].

2.3. Early Investigations (on Presentation)

The first step to detect a stroke is including this option in the differential diagnosis of an

acutely ill child. Early diagnosis allows prompt starting of appropriate therapy.

2 .3.1. H istory

Clinical history should include ethnic origin, the presence of sickle cell disease or congenital

heart disease, head or neck trauma (associated with intracranial hemorrhage and

dissection), recent infection (especially chickenpox), vasculitis and blood disorders [19], as

well as cerebrovascular diseases, coagulopathies, or immunologic disorders among first-

degree relatives.

How and how rapidly symptoms develop is of major importance. Up to a third of children

who have had a stroke have a history of recent events consistent with TIAs [24].

2 .3.2 . P hysical Examination



A complete physical and neurologic examination, including monitoring of vital parameters,

will identify neurologic damages and allow presumptive diagnosis of the brain vessel

involved. Signs of systemic diseases that increase the risk of stroke should be looked for.

2 .3.3. I mag ing Studies

Non-contrast computed tomography (CT) can be performed promptly and quickly in

emergency. It can adequately exclude hemorrhagic stroke or parenchymal abnormalities

that produces a mass effect, and it may reveal a low-density lesion in arterial ischemic

stroke and cerebral venous sinus thrombosis. However, CT is usually normal within the first

12 hours after the onset of symptoms [6]. It should be requested whenever magnetic

resonance (MR) is not available [19].

MR, in fact, is the ³gold standard´ imaging modality for the investigation of arterial ischemic

stroke in infants and children [25] due to its greater sensitivity and specificity. MR is useful

to differentiate stroke from ³stroke mimics´ but it is rarely available in emergency [26]. Thediagnostic efficiency of MR can be further improved by perfusion techniques, that quantify

relative cerebral blood flow, volume, and transit time by the use of bolus administration of

gadolinium-based contrast material [5, 27,28].

MR with diffusion weighting is very useful in accurately identifying regions of early ischemia

and infarction [26]. MR angiography is a noninvasive procedure that detects large vascular

abnormalities [29], and it is as effective as cerebral angiography in identifying large

ischemic lesions [30]. MR angiography is a reasonable alternative to conventional

arteriography in most patients [31, 32]. If the pattern of brain injury could be consistent with

venous infarction, emergency vascular imaging should include MR venography. In fact, 10%of hemorrhagic strokes in children are secondary to cerebral venous sinus thrombosis [6].

Vascular imaging of the extracranial circulation, such as cervical MRA or Doppler

ultrasound, should also be performed, particularly if the history is suggestive of a cervical

arterial dissection.

2 .3.4. Other I nvesti g ations

Complete blood cell count, iron studies, prothrombin time, partial thromboplastin time,

sedimentation rate, and antinuclear antibodies could be useful [19].

2.4. Second-Line Investigations (after 48 Hours as Indicated)

Once stroke has been diagnosed, several studies may be helpful for the ongoing evaluation

and management of the patient.



Electrocardiogram and transthoracic or transesophageal echocardiogram are always

necessary in all children with known or suspected congenital heart disease who have had a

stroke [20, 33].

Echocardiography may be helpful to diagnose patent foramen ovale; this abnormality can

be up to four times greater in children with stroke with undetermined etiology than in the

general population [34].

The diagnosis of some conditions, including extracranial arterial dissection, particularly

involving the posterior circulation, and small-vessel vasculitis, is difficult using MR

angiography alone. In these circumstances, catheter cerebral angiography is sometimes

required. However, catheter cerebral angiography is an invasive procedure, not commonly

performed in children, and it has similar diagnostic yield as MR combined with MR

venography and MR arteriography [6].

Conventional angiography can be necessary in order to identify moyamoya syndrome [19].

Hemoglobin electrophoresis and urine drug screening, particularly for sympathomimetics

may be indicated. A full evaluation for thrombophilia is reasonable in all children with stroke.

It should include evaluation of protein C and protein S deficiency, antithrombin III, heparin

cofactor II, plasminogen, von Willebrand's antigen, factor VIII, factor XII, factor V Leiden,

activated protein C resistance, prothrombin 20210 gene, serum homocysteine, methylene-

tetra-hydro-folate-reductase, lipoprotein (a), and antiphospholipid antibodies [35 ±37]. When

indicated on the basis of clinical suspicion, more extensive diagnostic testing, such as

cerebrospinal fluid analysis, lipid profile, Varicella-Zoster and human immunodeficiency

virus, and screening for metabolic disorders might be performed. However, in the majority of

cases, the results of these studies will not have an impact on emergency care [19]. We

suggest a flow chart for diagnosis of ischemic stroke in emergency (see Figure 1).

Figure 1 Flowchart: diagnosis of ischemic stroke in emergency.

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3. Management in Emergency

Guidelines based on strong evidence for the acute care of childhood stroke do not exist,

with the exception of sickle cell disease. Therefore, treatment recommendations for

ischemic stroke in children are extrapolated from adult guidelines.

Children with early acute ischemic cerebral stroke need to be admitted to a clinical unit

where continuous monitoring is possible. Only in selected cases treatment in intensive care

units is needed [38, 39].

3.1. Supportive Care

The general approach in emergency includes simple measures such as maintenance of

respiratory and cardiovascular functions, aggressive treatment of infection, seizures and

fever, maintenance of normoglycemia and normovolemia [20,40], and oxygen

supplementation to keep SaO2 > 95% during the first 24 hours after stroke [41]. Medical or

surgical treatment of intracranial hypertension, when present, is important, because children

have higher risk of tonsillar herniation due to cerebral edema. Hyperventilation is a short

term solution that should be used for imminent herniation until a definitive therapy, such as

decompressive neurosurgery, can be offered [40, 42, 43].

3.2. Anticoagulant Therapy and Antiplatelet Agents

The choice between anticoagulant and antiplatelet agents is controversial and there are few

data to guide this decision in children [44].

As anticoagulation therapy, both unfractionated heparin and low molecular weight heparin(LMWH) have been used in children with AIS. Current guidelines recommend

anticoagulation in children with proven arterial dissection or cardioembolic stroke or during

the diagnostic evaluation period, until a cardiac source or an arterial dissection has been

excluded [42]. Heparin should be used in children thought to have a high risk of recurrence

and a low risk of secondary hemorrhage [5, 45].

According to the international literature, LMWH at the dose of 1 mg/kg every 12 hours

represents a safe initial therapy for ischemic stroke in infants and children. Hemorrhagic

stroke needs to be excluded before starting treatment [46 ±49]. Low molecular weight

heparin offers several advantages over standard unfractionated heparin and oralanticoagulants: lower risk of heparin-induced thrombocytopenia, fewer drug interactions,

fewer adverse effects on bone when given long term, and lower cost. Furthermore, LMWH

is administered subcutaneously, and it demonstrates predictable age-dependent

pharmacokinetics and less need for monitoring, thus reducing the need for multiple

venipunctures [46]. Enoxaparin (1mg/kg subcutaneously for children more than 2 months of

age, or 1.5 mg/kg for infant less than 2 months of age) is the most frequently used LMWH in



children [47]. In children with cardiac embolism or vascular dissection, LMWH is

administered for 3 to 6 months [50].

Concerning antiplatelets, even in absence of randomized clinical trials for the use of aspirin

in the acute treatment of AIS in children, most experts agree that this drug use is

reasonable for secondary stroke prevention. Standard dosage of 1 to 5mg/kg/day for a

minimum of 3 to 5 years from the acute event is recommended as secondary prevention

[50]. The increased risk of Reye's syndrome should be considered. Clopidogrel has been

used at dosages of about 1 mg/kg per day in children unable to take aspirin [42, 51].

Thrombolysis with tissue plasminogen activator (tPA) is not currently used and the Royal

College of Physicians, AHA Stroke Council, and ACCP guidelines do not recommend it. In

fact, the diagnosis of stroke in children is usually made after the time interval required for

intravenous or intraarterial tPA thrombolysis (3 hours and 6 hours after stroke onset, resp.)

[3, 52 ±54].The International Paediatric Stroke Study group recommends that thrombolysis should not

be used unless it is part of randomised control trial [55, 56].

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4. Hemorrhagic Stroke

Hemorrhagic stroke is as common as arterial ischemic stroke with an estimated incidence of

1.5±2.9 per 100.000 children per year [41]. It includes spontaneous intraparenchymal

hemorrhage and nontraumatic subarachnoid hemorrhage.

Structural lesions are the most common causes of intraparenchymal hemorrhages in a

population-based cohort [57]. Brain tumors (27%) and arteriovenous malformations (17%)

are the most frequent. Medical etiologies are less common. Coagulopathies (13%) include

various causes of thrombocytopenia, hemophilia and von Willebrand's disease, sickle cell

anemia (6%), hypertension (10%), and infections (6%). Intraparenchymal hemorrhages of

idiopathic origin are also frequent (23%).

Non-traumatic subarachnoid hemorrhages are most often caused by intracranial

aneurysms. Ruptured aneurysms account for 10% of intracranial hemorrhages in children.The incidence of subarachnoid hemorrhage is increased in various congenital and

hereditary conditions such as cerebral artero-venous malformations, cardiac disorders

(coarctation of the aorta, bacterial endocarditis, and atrial myxoma), autosomal dominant

polycystic kidney disease, connective tissue abnormalities (Marfan's syndrome,

fibromuscular dysplasia, and Ehlers-Danlos type IV), hematological disorders (sickle cell



disease, G6PD deficiency, and thalassemia), phakomatoses (neurofibromatosis type 1,

especially following radiation therapy and tuberous sclerosis) [58].

Headache or vomiting due to raised intracranial pressure, seizures and focal neurologic

deficits are the presenting symptoms in children [41]. During evaluation of pediatric stroke it

is mandatory to exclude an acute intraparenchymal bleeding. To this end non-contrast TC

should be performed.

Treatment of hemorrhagic stroke requires a multidisciplinary team management with

neurological and neurosurgical care.

Management options in hemorrhagic stroke fall into two categories: general efforts to

stabilize the patient and measures to reduce the risk of rebleeding [5].

Surgical management is controversial, and there is no evidence that surgical evacuation of

a supratentorial intraparenchymal hematoma is beneficial at any age [59, 60]. However,evacuation of a rapidly expanding hematoma causing cerebral herniation may be of benefit

[6]. Surgical or endovascular obliteration of aneurysms and artero-venous malformations is

effective for many individuals, but stereotactic radiotherapy is being used increasingly in

children with artero-venous malformations that are small or difficult to approach surgically.

Several large retrospective studies have shown that stereotactic radiotherapy is safe and

effective for the treatment of children with an artero-venous malformation [61, 62].

Treatment of coagulation defects and hematologic disorders should reduce the risk of

subsequent hemorrhage. Emergency splenectomy is indicated for intraparenchymal

bleeding associated with idiopathic thrombocytopenic purpura. Other importantcomplications of non-traumatic subarachnoid hemorrhage that require treatment are

hydrocephalus, vasospasm, and hyponatremia [5].

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5. Stroke in Sickle Cell Disease

The most common hematologic risk factor for stroke is sickle cell disease (SCD). Eight

percent of patients younger than 19 years will develop a stroke. In this group the highest

rate of first ischemic stroke is in children between 2 and 5 years of age while hemorrhagicstroke affects adults aged 20 to 30 years. Both familial and environmental factors seem to

be involved in the occurrence of stroke [19]. In the absence of therapy recurrence of stroke

is as high as 40% [63].

Small infarctions have been found on MR in 20 to 35% of children with SCD in the absence

of symptoms [64, 65]. These so-called ³silent infarcts,´ predominantly located in frontal and



parietal cortical, subcortical, and border-zone areas are associated with deterioration in

cognitive function and with an increased risk of clinically symptomatic stroke [66, 67].

Stroke may also be due to large vessel vasculopathy that generally involves the middle

cerebral artery territory. Some individuals develop progressive vasculopathy of the

intracranial internal carotid artery and of its distal collateral vessels, a picture called

moyamoya syndrome. Small infarctions typically involve the basal ganglia and the deep

white matter within the anterior circulation.

Risk factors for stroke in SCD are summarized in Table 3.

Table 3 Risk factors for stroke in sickle cell disease.

5.1. Prevention

The presence of high cerebral blood flow velocity as measured by transcranial Doppler (TD)

identifies patients at high risk of primary prevention.

In healthy children, the velocity in the middle cerebral artery is around 90 cm/s while in SCD

children it is 130±140 cm/s. Stroke risk is high when velocity is >200cm/s.

A randomized trial (Stroke Prevention Trial in Sickle Cell Anemia: STOP) compared periodic

blood transfusion with standard care in 130 children with SCD who were selected for high

stroke risk on the basis of TD results. The trial was halted because of the high number of

strokes in the standard-care arm compared with the transfusion-treated group (11 versus 1),

in whom the risk of stroke was reduced from 10% to <1% per year [68].

The current National Heart, Lung, and Blood Institute of the National Institutes of Health

(NHLBI) recommendation is to evaluate children between 2 and 16 years with SCD using

TD at 6 month intervals. If velocity is >200 cm/s, confirmed after a control performed few

weeks later, chronic transfusion therapy should be started [63] and should not be

discontinued even if TD normalizes (as demonstrated by the randomized controlled trial

STOP II [5]).

5.2. Therapy

The treatment of acute ischemic infarction resulting from SCD includes intravenous

hydration and exchange transfusion to keep HbS <30% and Hb between 10±12.5g/dL [69].

Exchange transfusion avoids the theoretical risk of increasing blood viscosity that could

accompany a rapid increase of the hematocrit [5].



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6. Conclusions

Stroke is relatively rare in children, except, as mentioned, in sickle cell disease. It

represents, however, one of the ten ³top causes´ of childhood death. Its relatively raritycauses a lack of awareness that cerebrovascular disease occurs in children. Furthermore,

risk factors and clinical presentation are distinctive compared to adults. For these reasons

diagnosis is often delayed. It has been estimated that 48±72 hours frequently elapse

between the onset of symptoms and diagnosis [70].

When evaluating a child with stroke, several tests, including imaging studies, are helpful to

confirm the diagnosis, to differentiate hemorrhagic from ischemic stroke, and to guide the

emergency management.

No uniform approach exists for the treatment of childhood stroke. Until data based onrandomized pediatric clinical trials will be available, treatment recommendations for the

acute care of children with stroke will continue to be extrapolated from adult guidelines.

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Int J Otolaryngol. 2011; 2011: 487532.

Published online 2011 June 28. doi: 10.1155/2011/487532 PMCID: PMC3133014

Copyright © 2011 Dimitrios G. Balatsouras et al.

Study of Allergic Rhinitis in ChildhoodDimitrios G. Balatsouras, 1 * George Koukoutsis, 1 Panayotis Ganelis, 1 AlexandrosFassolis, 1 George S. Korres, 2 and Antonis Kaberos 1 1ENT Department, Tzanion General Hospital of Piraeus, Afentouli 1 & Zanni, 18536 Piraeus, Greece2ENT Department, Atticon University Hospital of Athens, 1 Rimini Str., Haidari, 12462 Athens, Greece*Dimitrios G. Balatsouras: Email: [email protected]

Academic Editor: R. L. DotyReceived February 13, 2011; Accepted April 28, 2011.This is an open access article distributed under the Creative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

y Other Sections

Abstract

Allergic rhinitis is common among children and quite often represents a stage of the atopic

march. Although sensitization to food and airborne allergens may appear in infancy and

early childhood, symptoms of the disease are usually present after age 3. The aim of this



study was to determine the most frequent food and indoor and outdoor respiratory allergens

involved in allergic rhinitis in children in the region of Piraeus. The study was performed in

the outpatient clinic of otolaryngologic allergy of a general hospital. Fifty children (ranged 6±

14 ) with symptoms of allergic rhinitis and positive radioallergosorbent test (RAST) for IgE

antibodies or skin prick tests were included in the study. Thirty six (72%) of the subjects of the study had intermittent allergic rhinitis. The most common aeroallergens determined

were grass pollens and Parietaria, whereas egg and milk were the food allergens identified.

The detection of indoor and outdoor allergens in the region of Piraeus, based on skin prick

tests and RAST tests, showed high incidence of grasses and food allergens, which is

similar to other Mediterranean countries.

y Other Sections

1. Introduction

Allergic rhinitis is one of the most common disorders, which affects 5±40% of population,

according to various reports [1, 2]. It may be classified as persistent and intermittent allergic

rhinitis, depending on the frequency of symptoms. It presents a high morbidity because it

affects social life, professional activities, and, especially in children, school performance [3].

Allergic rhinitis is common among children and quite often represents a stage of the atopic

march [4]. Although sensitization to food and airborne allergens may appear in infancy and

early childhood, symptoms of the disease are usually present after age 3. The aim of this

study was to determine the most frequent respiratory and food allergens as a cause of

allergic rhinitis in children in the region of Piraeus.

y Other Sections

2. Materials and Methods

We examined 50 children who presented with allergic rhinitis in the outpatient clinic of

otolaryngologic allergy, belonging to the ENT department of our hospital. The age of the

patients ranged from 6 to 14 years (mean 10.7 2.1), and they were all living in the region

of Piraeus. Diagnosis was on the basis of a history of allergic rhinitis, either seasonal or

perennial, on the findings of clinical examination and on the presence of positiveradioallergosorbent (RAST) test for IgE antibodies (RAST-CAP-FEIA, Pharmacia, Uppsala,

Sweden). All children were tested in a series of allergens, including grasses, cereales,

parietaria, urtica, tree allergens (Olea euro pea,C y pressus sem pervirens, P inus pinea,

and P o pulus alba), dust mites, animal dander and food allergens. The RAST results were

classified, as Class 1 (low level of specific IgE), Class 2 (moderate level), Class 3 (high

level), and Class 4 (very high level) [5]. In a group of 12 older children, skin-prick tests were



also performed. Details of this procedure are reported elsewhere [6]. The skin prick tests

were considered positive if the mean wheal diameter was 3 mm or larger.

y Other Sections

3. Results and Discussion

The main clinical and demographic features of our patients are shown in Table 1. Twenty-

nine patients were females and 21 males. Severity of rhinitis was mild in 19 patients (38%)

and moderate/severe in the remaining 31 (62%), according to the criteria of ARIA [7]. Thirty-

seven (74%) of the children suffered from other allergic diseases as well, including

childhood asthma, allergic conjunctivitis, and atopic dermatitis.

Table 1 Clinical and demographic features of our patients.

Thirty six (72%) of the subjects of the study had intermittent allergic rhinitis, owed to pollen

aeroallergens, with a mean of 2 allergens per patient (Tables (Tables22 and and3).3). Nine

patients (18%) were sensitized to one allergen, 17 patients (34%) were sensitized to two

and 10 patients (20%) to three allergens. The remaining 14 (28%) children suffered from

persistent rhinitis, owed mainly to nonpollen aeroallergens and to food allergens. A mean of

1.5 allergens per patient was found in this group (Tables (Tables22 and and4).4). Seven(14%) of them were sensitized to one allergen, and another 7 patients (14%) were

sensitized to two allergens. The mean values of total serum IgE were 449.7 ( 336.9) kU/L in

the first group (patients with intermittent disease) and 934.2 ( 765.8)kU/L in the second

group (patients with persistent disease), presenting significant variability (Table 1). The rate

of agreement between the results of the skin prick tests when performed and the results of

RAST was high (Table 2). There was no consistent correlation between severity of allergic

rhinitis and RAST classes, suggesting that probably antibody levels are only one of the

factors that determine symptom severity [8].

Table 2 Types of allergens, RAST classes, and skin reaction.



Table 3 Positive RAST (and skin prick test when performed) to

various allergens in intermittent allergic rhinitis.

Table 4 Positive RAST (and skin prick test when performed) to

various aeroallergens and food allergens in persistent

allergic rhinitis.

Allergic rhinitis is a significant clinical problem in children. In the Mediterranean region there

are characteristic climatic conditions, such as mildness of winter and poor rainfall during thesummer, that facilitate the growing of a typical vegetation with production of allergenic

pollen [1]. Rich and long pollinic seasons are, thus, favored, and the pollen grains of various

plants can reach high atmospheric concentrations, causing severe clinical symptoms of

rhinoconjunctivitis and asthma. The prevalence of allergic rhinitis in children in the

Mediterranean countries has been reported to range from 9.4% to 16.8% [2, 9]. However,

more than 40% of the children reported allergic rhinoconjunctivitis symptoms in the past

[2, 10]. Most prevalent allergic plants with known clinical significance are

grasses, P arietaria and Olea euro paea.

P arietaria was the most important allergenic pollen in the children of our study. This is

an Urticacea plant characteristic of Mediterranean flora, which has been found to be the

most common cause of allergy in the Mediterranean countries, either in adults or in children

[11]. D'Amato and Lobefalo [12] in a study conducted in Naples, foundP arietaria as the

most common allergen in adults, and Kontothanasi et al. [6], in a study of allergens in adult

patients in western Athens, which is a neighbouring region to ours, reported this allergen as

the second most common after Graminae, and especially Dactilis g lomerata. Other species

of Urticaea and C ereales were less commonly determined allergens in the subjects of our

study.

From the trees, we found Olea euro peae to be the most common aeroallergen,

whereas C y pressus sem pervirens, P inus pinea, and P o pulus alba were less frequently

identified. Olive trees are, only occasionally, found in the surroundings, but air currents

carry their pollen from suburban areas. Olea euro peae is a major tree producing allergenic

pollen in the Mediterranean area [12, 13], and the same has been reported for cypress [14]

and the other implicated trees [15].



In our study, most pollen aeroallergens were associated with intermittent rhinitis, whereas

hypersensitivity in nonpollen allergens was associated with persistent rhinitis. We found

house dust and mites (Dermato phag oides pteronyssinus andDermato phag oides farinae)

the most common allergens and this agrees to previous reports in Mediterranean countries.

According to Verini et al. [13] a high incidence of positive reactions to Dermato phag oides pt and fa was found, exceeding 70%. Furthermore, Ramadan et al. [16] found a high

incidence of mites in Lebanon. Lower rates were reported in other studies, as in the

investigation by Erel et al. [17] in which an incidence of 20% was found in Turkey. Positivity

to dog and cat allergens is of lower incidence, especially in countries where keeping house

pets is not a common practice [16]. Food allergy as a potentially important factor in the

pathogenesis of allergic rhinitis should, also, be noticed [18]. We found only two cases with

allergy owed to egg and milk, but further investigation of a large number of children for food

allergy is warranted.

Finally, we should mention that we found a mean of 2 allergens per patient in intermittentrhinitis and a mean of 1.5 allergens per patient in persistent rhinitis. Polysensitization has

been also reported elsewhere, as in the study of Verini et al. [13], in which only 12% of

children in a central Italian area were monosensitized, whereas the remaining were

sensitized to 2-3 (56%) or even more allergens.

4. Conclusions

In conclusion, the detection of indoor and outdoor allergens in the region of Piraeus, based

on skin prick tests and RAST tests, showed high incidence of grasses and food allergens,

which is similar to other Mediterranean countries. Our results reflect the specialcharacteristics of the region of Piraeus, which has a high population density and is polluted

from industries, the port, and the heavy traffic. However, our subjects originated also from

the country of the surrounding region, two nearby islands, and the rural area of Trizinia,

resulting in the variety of allergens identified from our investigation.

y Other Sections

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