Standardizedassessment of behaviorand adaptive livingskills in juvenileneuronal ceroidlipofuscinosis

Heather Adams* PhD;Elisabeth A de Blieck MPA CCRC;Jonathan W Mink MD PhD;Frederick J Marshall MD;Jennifer Kwon MD MPH, University of Rochester School ofMedicine and Dentistry, Rochester, NY;Leon Dure MD, Department of Pediatrics, University ofAlabama-Birmingham, Birmingham, AL;Paul G Rothberg PhD;Denia Ramirez-Montealegre MD;David A Pearce, University of Rochester School of Medicineand Dentistry, Rochester, NY, USA.

*Correspondence to first author at Pediatric ClinicalResearch Office, Box 777, University of Rochester MedicalCenter, 601 Elmwood Avenue, Rochester, NY 14642, USA.E-mail: heather_adams@urmc.rochester.edu

We obtained information about the behavioral, psychiatric, andfunctional status of 26 children (13 males, 13 females) withjuvenile neuronal ceroid lipofuscinosis (JNCL; mean age 12y3mo [SD 3y 4mo]; range 6y 9mo to 18y 8mo). Twenty-fivechildren had visual impairment and 18 were known to have apositive seizure history before enrollment. Parents completedthe Child Behavior Checklist, Scales of Independent Behavior –Revised, and a structured interview to assess obsessive–compulsive symptoms. Participants exhibited a broad range ofbehavioral and psychiatric problems, rated as occurringfrequently and/or as severe in more than half of the sample.Males and females did not differ with regard to the number ofbehavioral and psychiatric problems. Children were also limitedin their ability to perform activities of daily living, includingself-care, hygiene, socialization, and other age-appropriatetasks. Results provide a quantitative baseline for behavioral andpsychiatric problems and functional level in JNCL, againstwhich further decline can be measured. Longitudinalassessment of behavioral and psychiatric symptoms andfunctional abilities is continuing and will provide much-neededdata on the natural history of JNCL.

The neuronal ceroid lipofuscinoses are fatal, autosomal reces-sive, lysosomal storage diseases. Core symptoms include blind-ness, seizures, cognitive and motor decline, and prematuredeath (Rider and Rider 1999). Although the neuronal ceroidlipofuscinoses are rare, the major childhood variants (infantile,typical onset 6mo–2y; late infantile, typical onset 2–4y; andjuvenile, typical onset 5–8y) are the most frequent neurode-generative disorders of childhood, affecting approximately 8out of 100 000 worldwide (Santavuori et al. 2000). Variants ofneuronal ceroid lipofuscinosis are distinguished clinically byage of onset and by the rate and sequence of symptom progres-sion. Juvenile neuronal ceroid lipofuscinosis (JNCL) is themost prevalent childhood variant, with symptom onset typical-ly between 4 and 10 years of age. Most children survive intotheir second or third decade (Hofmann et al. 1999). Currently,treatment for all neuronal ceroid lipofuscinosis variants issymptomatic rather than neuroprotective.

Continuing work has greatly expanded genetic and biochem-ical knowledge of the NCLs (Weimer et al. 2002). Behavioraland psychiatric problems in JNCL have also been described,including aggression, anxiety, depression, and hallucinations(Boustany and Filipek 1993, Lauronen et al. 1999, Bäckmanet al. 2001). A partly retrospective survey of two JNCL groupsreported many patients with aggression, mood disturbances,and hallucinations or delusions (Santavuori et al. 1993). Arecent study of Finnish children with JNCL was consistent withearlier reports: investigators found a large number of psychi-atric problems in affected children (Bäckman et al. 2005).Females had significantly more problems in selected areas thanmales, but exhibited different problems depending upon thesource; parents reported more anxious/depressed symptomsand teachers reported greater social problems in females thanin males. Further research is necessary to determine whetherthese sex differences are consistent across other groups ofaffected children, and also how such differences might beexplained. Moreover, work is needed to clarify the behavioraland psychiatric phenotype of JNCL. With the exception of thatin Bäckman et al. (2005), there is little quantitative informationon the incidence and severity of these problems in JNCL.

We have developed a Unified Batten Disease Rating Scale(UBDRS) to quantify physical, behavioral, and functional aspectsof JNCL in a neurological exam setting (Marshall et al. 2005).We initiated the current study in conjunction with theUBDRS to further characterize the natural history of neu-ropsychological and behavioral and psychiatric symptoms ofJNCL, and to describe changes in affected children’s capacity toemploy everyday adaptive skills (e.g. feeding and self-care).In this continuing study we conduct biannual assessments ofbehavioral, psychiatric, and adaptive functioning in childrenwith JNCL. Our ultimate goal is to improve our understand-ing of the natural history of JNCL, which will be essential forevaluating future candidate therapies to prevent, retard, orreverse its devastating effects. We report here the baselinedata for the behavioral and psychiatric status and adaptivefunctioning of 26 children diagnosed with JNCL.

MethodsPARTICIPANTS

Twenty-six children and their parents completed baselineassessment for this longitudinal study. Participants wererecruited via the Batten Disease Support and ResearchAssociation (BDSRA) in Reynoldsberg, Ohio. A subset (n=13)

Developmental Medicine & Child Neurology 2006, 48: 259–264 259

See end of paper for list of abbreviations.

also participated in the UBDRS project (Marshall et al. 2005).Data collection and initial recruitment began with direct,face-to-face interviews at the BDSRA annual meeting in 2004.Subsequent recruitment was via the BDSRA website(www.bdsra.org) and newsletter; this lead to further data col-lection by telephone interviews and post. Parents completedstandardized forms rating their child’s behavioral and psychi-atric functioning and adaptive skills. At the BDSRA meeting,children who could attend, could provide verbal responses,and were not fatigued (n=6) also completed a brief assessmentto estimate verbal intellectual ability (Wechsler 2003). Fourobtained the lowest score possible, and scores of the remain-ing two children were mildly impaired and within the averagerange respectively. All parents provided written informed per-mission for their child’s participation in this study, which wasapproved by the University of Rochester Medical CenterInstitutional Review Board.

MEASURES

Child Behavior Checklist (CBCL)

The CBCL is a standardized behavior rating scale with excel-lent psychometric properties (Achenbach and Rescorla 2001).Parents rated 112 problem behaviors as follows: 0=‘not true’,1=‘somewhat/sometimes true’, 2=‘very true/often true’.We examined global problems on the CBCL Internalizing,Externalizing, and Total Problems scales. We also examinedCBCL subscales to identify symptom clusters consideredproblematic for these children. We excluded the SomaticComplaints subscale (physical problems without a medicalcause) because parents reported JNCL-related symptoms (e.g.‘eye problems’). All CBCL scales are reported as age- and sex-standardized T scores (mean 50 [SD 10]).

Children’s Yale-Brown Obsessive Compulsive Scale

The Children’s Yale-Brown Obsessive Compulsive Scale(Goodman et al. 1991) is a reliable and valid structured interviewevaluating the content, frequency, and severity of obsessive andcompulsive symptoms (Scahill et al. 1997). Parents describedtheir child’s obsessive and compulsive symptoms and rated the

severity of any recent (during the past month) symptoms on a 5-point scale (range: 0=none, 4=incapacitating).

Scales of Independent Behavior – Revised (SIB-R)

To assess functional abilities, we used the SIB-R (Bruininks etal. 1996), Short Form for Visually Impaired Individuals. TheSIB-R is an age-standardized test of functional abilities andmaladaptive behaviors. It provides an index of overall func-tioning (Relative Mastery Index; RMI), the level of supportrequired to meet daily tasks, and the frequency and severityof eight specific maladaptive behaviors summarized acrossthree general domains.

ResultsAll statistical analyses were performed with SPSS (version12.0). Mean age of the sample was 12 years 3 months (SD 3y4mo; range 6y 9mo to 18y 8mo). There were 13 males and 13females. All children were Caucasian except one who wasbiracial. Eighteen children had a positive seizure history (sixwithout seizures, two unknown). All had clinical symptomsof JNCL except one child who was asymptomatic at this base-line assessment. Mean age of symptom onset was 5 years 7months (SD 1y 3mo; range 3y 6mo to 7y; n=21). Among 17symptomatic children, vision loss was their first symptom(behavior problems, n=4; unknown, n=4). All participantsexcept the asymptomatic child had some degree of visionloss. In 13 children also undergoing the UBDRS examina-tion, vision loss was rated independently by three neurolo-gists on a 5-point scale (0=normal; 4=blind; Marshall et al.2005). The modal rating for all but one child (12/13) was nobetter than ‘light/dark perception only’. In the remaining 13participants (data collected by phone or post), all parentsanswered affirmatively when asked if their child had experi-enced visual loss. Thirteen children were homozygous forthe common deletion in the CLN3 gene. The common dele-tional mutation in the CLN3 gene was analyzed by usingmethodology previously described by this research group(Rothberg et al. 2004). Two children were heterozygous forthe deletion with a novel mutation. Eleven children hadJNCL by clinical and/or electron microscope criteria, buteither they had not been studied by DNA analysis for CLN3mutations, or genetic status was provided solely by parentalreport.

BEHAVIORAL AND PSYCHOLOGICAL FUNCTIONING

Parents of 24 out of 26 children completed the CBCL. Meansand standard deviations for T scores on all CBCL scales arepresented in Table I. We defined CBCL problems as occur-ring at the ‘borderline’ range cutoff on the CBCL Problemscales and subscales (T scores of at least 60 and 65 respective-ly). The borderline range captures problems that do notmeet clinical significance but are nevertheless a source ofconcern. Mean CBCL Total Problems fell within this border-line range (mean 63.3 [SD 8.7]). Twelve children had at leastborderline elevations in Internalizing Problems, and 13 hadat least borderline elevations in Externalizing Problems.Nineteen children had at least borderline clinical eleva-tions in CBCL Total Problems. Neither chronological agenor symptom duration was significantly correlated withCBCL Total Score. We also re-examined group mean T scoresafter excluding the asymptomatic participant. This partici-pants’ scores were within the clinically normal range, but

260 Developmental Medicine & Child Neurology 2006, 48: 259–264

Table I: T scores for Child Behavior Checklist (Achenbachand Rescorla 2001) scales (n=24)

Scale Mean T score SD Range

Problem ScaleInternalizing Problems 58.3 8.9 33–70Externalizing Problems 59.4 9.2 41–75Total Problems 63.3a 8.7 38–74

SubscaleAnxious/Depressed 54.0 4.0 50b–65Withdrawn/Depressed 57.4 6.8 50–73Somatic Complaints 64.4 7.6 50–80Social Problems 64.3 8.3 50–79Thought Problems 69.4c 8.4 50–85Attention Problems 62.8 9.1 50–83Rule-Breaking Behavior 55.7 6.4 50–70Aggressive Behavior 62.9 8.7 50–81

aFor Problem Scales, borderline range is T=60–63 (84th to 90th centile). bChild Behavior Checklist subscales are truncated atlower end of scale at T=50. cFor subscales, borderline range isT=65–69 (93rd to 97th centile).

there were no appreciable group differences in any CBCLscales when this data was excluded (all differences less than1.5 points). Thus, this participant’s data were included for allsubsequent analyses.

CBCL subscales offer a higher level of detail on the compo-nent parts of global internalizing and externalizing problemareas. The mean Thought Problems score was elevated withinthe borderline clinical range (Table II). CBCL subscales withthe highest frequencies of borderline or clinical elevationswere: Thought Problems, Social Problems, Attention Prob-lems, and Aggressive Behavior. Table II shows the number ofchildren rated as within normal, borderline, and clinical cutoffranges for CBCL subscales. Finally, using the t-test for indepen-dent samples, we did not find significant sex differences on anyCBCL scale.

The specific pattern of individual problems within thisunique disease group was also of interest. We examined thefrequency with which parents endorsed individual CBCL items(excluding Somatic Complaints items). Participants were ratedas exhibiting many individual problems, often at rates com-parable to those of clinically referred samples. Notably, the

CBCL item ‘obsessions’ obtained was endorsed for 21 of the24 children. Table III lists the top 20 problem items endorsedby parents.

The SIB-R was completed for 25 children. Fifteen children

Behavioral Symptoms in Juvenile Neuronal Ceroid Lipofuscinosis Heather Adams et al. 261

Table II: Numbers of children scoring in normal, borderline,and clinical ranges on Child Behavior Checklist (CBCL)subscales

CBCL subscale Number of children

Normal Borderlinea Clinicalb

Anxious/Depressed 24 1 0Withdrawn/Depressed 20 4 1Social Problems 10 11 4Thought Problems 4 9 12Attention Problems 14 7 4Rule-breaking Behavior 22 3 0Aggressive Behavior 15 7 3

aFor subscales, borderline range is T=65–69 (93rd to 97th centile).bFor subscales, clinical range is T>70 (more than 97th centile).

Table IV: Numbers of children scored for severity of maladaptive behaviors on Scales of Independent Behavior – Revised (n=25)

Behavior domain Severity category

Normal Marginally serious Moderately serious Serious Very serious

Internalizeda,b 15 9 0 0 0Asocialc 10 5 9 1 0Externalizedd 17 6 2 0 0

aTwenty-five children completed the SIB-R; however, data were missing on one item (self-harmful behavior) for one participant.bInternalized, Internalized Maladaptive Behavior domain, comprising three behavior items: Hurtful to self, Unusual or repetitive habits,Withdrawn or inattentive behavior.cAsocial, Asocial Maladaptive Behavior domain, comprising two behavior items: Socially offensive, Uncooperative behavior.dExternalized, Externalized Maladaptive Behavior domain, comprising three behavior items: Hurtful to others, Destructive to property,Disruptive behavior.

Table III: Numbers of children with top 20 problem items in Child Behavior Checklist (CBCL) identifiedby parents (n=24)

CBCL problem item Sometimes/somewhat true Very true/often true

Can’t get his/her mind off certain thoughts; obsessions 9 12Acts too young for his/her age 9 11Demands a lot of attention 9 11Argues a lot 13 7Speech problem 5 14Talks too much 8 11Stubborn, sullen, or irritable 13 6Picks nose, skin, or other parts of body 11 7Clings to adults or too dependent 12 6Sudden changes in mood or feelings 12 6Temper tantrums or hot temper 13 5Bites fingernails 10 7Inattentive or easily distracted 13 4Whining 13 4Disobedient at home 14 3Can’t concentrate, can’t pay attention for long 8 8Impulsive or acts without thinking 10 6Unusually loud 7 8Repeats certain acts over and over; compulsions 8 7Fails to finish things he/she starts 13 2

were rated as having Asocial Maladaptive Behavior problems.Nine children had Internalizing Maladaptive Behaviors. Eightwere ranked with marginally or moderately serious Extern-alizing Maladaptive Behavior problems. Table IV summarizesthe number of children ranked within each severity categoryfor SIB-R Maladaptive Behavior domains.

For specific SIB-R behavior ratings, ‘uncooperative behav-iors’ were rated with high frequency, occurring one to six times aweek in eight children, and at least once daily in eight otherchildren. Furthermore, parents of 15 children indicated thatuncooperative behaviors caused a moderate or severe prob-lem. Frequency and severity ratings for each SIB-R behaviorproblem area are shown in Figure 1.

OBSESSIVE AND COMPULSIVE SYMPTOMS

Parents of 25 children completed the Children’s Yale-BrownObsessive Compulsive Scale. Although obsessive and compul-sive symptoms spanned a broad content range, several themeswere common. Seven children were preoccupied with reli-gious figures or themes, and/or death, although not all knewtheir diagnosis or prognosis. Other obsessions centered onfears about animals or imaginary characters (sometimes pro-voked by visual hallucinations; n=5), contamination (n=3),physical appearance (n=2), and anticipated events (n=4).

Many children were described as routine-bound and ritu-alistic. Nine engaged in repetitive questioning or discussion,or insisted that routines be performed in a certain sequence.

Children also engaged in ordering/arranging or counting items(n=5), hoarding (n=1), and repetitive checking (n=2). Parentsalso described non-compulsive but repetitive or stereotypicbehaviors, such as echolalic speech, clasping/threading fingerstogether, stroking items, shredding paper by hand, picking atone’s own skin, or playing with one’s hair.

Obsessive and compulsive severity rankings were com-pleted by parents of children experiencing recent (duringthe past month) obsessive (n=14) and compulsive (n=8)symptoms. Many of these children were rated as spendingminimal time (less than 1h daily) engaged in obsessions(n=8) or compulsions (n=5). Most parents reported thatchildren experienced between none to a moderate level ofdistress over their obsessive thoughts (n=13). Five childrenexperienced at least a moderate or higher level of distressrelated to the interruption of compulsive behaviors. Six chil-dren were rated as having moderate to severe difficulty inexpending effort to resist compulsions, and six had severe orextreme difficulty in controlling or suppressing compulsivebehaviors. Median obsessive and compulsive severity rank-ings are provided in Table V.

ACTIVITIES OF DAILY LIVING SKILLS

The mean overall SIB-R RMI was more than 2 SDs belowage-expected norms (mean 69.9 [SD 41.9]; range 0–168).However, this value may overestimate functioning in oursample, because floor effects of the measure meant that the

262 Developmental Medicine & Child Neurology 2006, 48: 259–264

Figure 1: Scales of Independent Behavior – Revised: (a,b) frequency and (c,d) severity of selected behavior problems.

a

Nr

of p

artic

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ts

Never <1mo 1–3mo 1–6wk 1–10d >1h

Hurtful to self

Hurtful to others

Destructive to property

Disruptive behavior

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16

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8

4

0

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20

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Never <1mo 1–3mo 1–6wk 1–10d >1h

Nr

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24

20

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4

0

Hurtful to self

Hurtful to others

Destructive to property

Disruptive behavior

Not a problem Mild Moderate Severe Extremeproblem problem problem problem

Nr

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0Not a problem Mild Moderate Severe Extreme

problem problem problem problem

Unusual/repetitive behavior

Socially offensive behavior

Withdrawal/inattention

Uncooperative behavior

b

c d

Unusual/repetitive behavior

Socially offensive behavior

Withdrawal/inattention

Uncooperative behavior

four lowest-functioning children could not even be assignedRMI scores. RMI was significantly inversely correlated withboth children’s age (r=–0.71, p<0.001) and with symptomduration (r=–0.58, p<0.001). However, age and symptomduration were also highly positively correlated (r=0.93,p<0.001).

We also examined the SIB-R Support score, which was cal-culated for 25 children. It reflects the extent to which supportis needed to perform daily activities, and includes informationfrom both adaptive-level (RMI) and all maladaptive behaviors.Only two participants required None to Infrequent support.The remaining children (n=22) required some level of sup-port in performing daily activities: intermittent (n=5), limited(n=11), frequent (n=2), extensive (n=3), and pervasive (n=1).

RELATIONSHIPS BETWEEN SYMPTOM SEVERITY, FUNCTIONAL SKILLS,AND SYMPTOM DURATION

A higher CBCL Total Problems score was associated with worseadaptive functioning as measured by the SIB-R RMI (r=–62,p<0.01). JNCL symptom duration was inversely related toadaptive functioning (SIB-R RMI; r=–58, p<0.01) but not tooverall behavioral and psychiatric symptoms on the CBCLTotal Problems scale.

DiscussionThe present study found many behavioral and psychiatricproblems in children with JNCL. On the CBCL, problemsspanned areas of socialization, inattention, aggression, and oddthoughts and behaviors. Symptom duration was not associat-ed with overall CBCL-rated behavioral and psychiatric problemsat this baseline assessment, but our longitudinal design willprovide an opportunity to track changes in these symptomsover time.

We partly replicated CBCL findings from another recentstudy of JNCL, obtaining remarkably similar CBCL subscalescores (Bäckman et al. 2005). However, we did not find sexdifferences. Additional research is necessary to clarify this,because the extant literature is now balanced between onepositive and one negative finding. We did use a more recentversion of the CBCL (from 2001) in comparison to Bäckmanet al. (2005; CBCL 1991 version). The two versions are highlycorrelated (r=0.87–0.99; Achenbach and Rescorla 2001 ) but

we do recognize that CBCL results may diverge because ofupdates to item content and the standardization sample.

Detailed assessment of childhood obsessive and compul-sive symptoms involves querying both parent and child(Goodman et al. 1991). Although parents were directly inter-viewed (either in face-to-face or via telephone sessions) regard-ing their children’s behavior, we could not interview part-icipants directly, because cognitive impairment precluded self-appraisal of symptoms. On the basis of parent descriptions,however, the current sample’s obsessive and compulsive sym-ptoms seem distinct from obsessive-compulsive disorder. First,obsessive-compulsive disorder is characterized by unwantedobsessive and compulsive symptoms (Scahill et al. 1997). Bycontrast, most participants were not disturbed by obsessiveand compulsive symptoms, although some became distressedwhen symptoms were interrupted. Second, in obsessive–com-pulsive disorder, compulsions are often performed to mini-mize anticipated, unrealistic harm, or reduce discomfort fromobsessions. However, participants’ compulsions, non-compul-sive stereotypies, and their need for routine were not goal-directed. Rather, they seemed the behavioral analog of echo-lalic speech and perseverative thoughts. This perseverativestyle has been described previously in JNCL (Hofman et al.1999), but more work is needed to distinguish it from what isseen in many other conditions, including developmental delay,autism, and some psychiatric and neurological disorders (Bod-fish et al. 2000). Finally, some obsessive fears were apparentlyprovoked by visual hallucinations, which have been previouslyreported in JNCL (Lanska and Lanska 1993, Santavuori et al.1993, Bäckman et al. 2001). Cognitively impaired JNCL chil-dren may be unable to differentiate between frightening hallu-cinations and real events, and consequently may ruminateabout these fearful perceptions, despite parental reassurances.

This study is the first to quantify functional skills in JNCL.Most children required at least some support with tasks ofdaily living, and longer symptom duration was associated withreduced functional skills. This is not surprising, given thatmotor, speech, and cognitive abilities needed for daily inde-pendence tasks each deteriorate as JNCL progresses. Overallbehavioral and psychological problems were also inverselyrelated to adaptive functioning. Overall, SIB-R results under-score the potential burden for parents or carers, who musthelp affected children to perform these tasks.

There are several limitations of this study. Only the SIB-Rwas developed specifically for use in visually impaired per-sons. Unfortunately, there are few psychometrically soundtools for evaluating visually impaired children. The diversityof visually impaired children, who vary in terms of comorbidconditions, and the timing, etiology, and degree of theirvision loss and visual impairment, create challenges forestablishing test norms or identifying control groups. We rec-ognize the need to develop normative data for blind, neuro-logically intact children that will serve as a benchmark forperformance in the population of visually impaired childrenwith JNCL or other neurodegenerative diseases.

Although lacking norms for visually impaired children, theCBCL has many strengths. It is extensively researched and tran-slated, and has been validated internationally on more than11000 children (Achenbach and Rescorla 2001). Of particularinterest to us is the established use of the CBCL in northernEuropean countries, where the prevalence of JNCL is highest(see, for example, Novik 1999). Vision loss, seizures, and

Behavioral Symptoms in Juvenile Neuronal Ceroid Lipofuscinosis Heather Adams et al. 263

Table V: Median rankings for severity of behaviors rated onChildren’s Yale-Brown Obsessive Compulsive Scale

Behavior Median Range

Obsessions (n=14)Time spent on obsessions 1.0 1–4Interference by obsessions 1.0 0–3Distress experienced because of obsessions 2.0 0–3Resistance to obsessions (effort) 2.0 0–4Control over obsessions (success) 2.0 0–4

Compulsions (n=8)Time spent on compulsions 1.0 1–2Interference by compulsions 0.5 0–2Distress experienced because of compulsions 2.0 0–4Resistance to compulsions (effort) 4.0 1–4Control over compulsions (success) 3.0 0–4

Scoring: 0=none, 1=mild, 2=moderate, 3=severe, 4=extreme.

intellectual impairment are each independently associatedwith behavioral and functional deficits in congenitally andadventitiously blind children without JNCL (Hatton et al. 1997,McHugh and Lieberman 2003) and it has been estimated thatmore than one-half of visually impaired children are also intel-lectually delayed (Mervis et al. 2002). Children with seizure dis-orders are likewise at risk for behavioral and psychiatricdifficulties (Hoare and Kerley 1991, Dunn and Austin 1999).Finally, in children with intellectual delays, behavioral prob-lems may occur at three to four times the rate of that in childrenwith average intellectual ability (cognitively intact children);higher rates of psychiatric disturbance are also reported (Lovelland Reiss 1993). In the present study, direct assessment ofintellectual function was not possible for many participants,and our study design did not include queries about academicplacement. However, in a subset of children we have demon-strated cognitive impairment, although there are too few dataat present to determine an association between cognitive func-tion and behavioral problems in JNCL.

ConclusionThe current results provide a standardized assessment of thebehavioral, psychiatric, and functional difficulties that affectchildren with JNCL. Additional research is also needed tounderstand how these difficulties are associated with specificaspects of disease progression, and how such symptoms relateto caregiver burden. Our ongoing, longitudinal research willtrack changes in behavioral and psychiatric problems and func-tional skills over time. Information on the natural history ofJNCL can inform better day-to-day management of behavioral,psychiatric, and functional difficulties of affected children, andwill help to measure change in these symptoms reliably whenfuture candidate therapies become available.

DOI: 10.1017/S0012162206000570Accepted for publication 11th July 2005.

Acknowledgements

This research was supported by a grant from the Luke and Rachel Batten Foundation and was conducted with permissionfrom the BDSRA. We thank the children and parents whoparticipated in this research for their time and efforts, and alsoLance Johnston (Executive Director of the BDSRA) and JaredBenedict, who provided assistance in coordinating assessments atthe 2004 BDSRA meeting.

ReferencesAchenbach TM, Rescorla LA. (2001) Manual for the ASEBA School-

Age Forms and Profiles. Burlington, VT: University of Vermont,Research Center for Children, Youth, and Families.

Bäckman ML, Åberg LE, Aronen ET, Santavuori PR. (2001) Newantidepressive and antipsychotic drugs in juvenile neuronalceroid lipofuscinoses – a pilot study. Eur J Paediatric Neurology

5: 163–166.Bäckman ML, Santavuori PR, Åberg LE, Aronen ET. (2005)

Psychiatric symptoms of children and adolescents with juvenileneuronal ceroid lipofuscinosis. J Intellect Disabil Res 49: 25–32.

Bodfish JW, Symons FJ, Parker DE, Lewis MH. (2000) Varieties ofrepetitive behavior in autism: comparisons to mental retardation.J Autism Dev Disord 30: 237–243.

Boustany R-M, Filipek P. (1993) Seizures, depression and dementiain teenagers with Batten’s Disease. J Inherit Metab Dis 16: 252–255.

Bruininks RH, Woodcock RW, Weatherman RE, Hill BK. (1996)Scales of Independent Behavior – Revised: Comprehensive

Manual. Itasca, IL: Riverside.Dunn DW, Austin JK. (1999) Behavioral issues in pediatric epilepsy.

Neurology 53: S96-S100.

Goodman WK, Price LH, Rasmusen SA, Riddle MA, Rapoport JL.(1991) Children’s Yale-Brown Obsessive Compulsive Scale.

Second Revision. New Haven, CT: Yale Child Study Center.Hatton DD, Bailey DB Jr, Burchinal MR, Ferrell KA. (1997)

Development growth curves of preschool children with visionimpairments. Child Dev 68: 788–806.

Hoare P, Kerley S. (1991) Psychosocial adjustment of children with chronic epilepsy and their families. Dev Med Child Neurol

33: 201–215.Hofman I, Kohlschütter A, Santavuori P, Gottlob I, Goebel HH,

Lake BD, Schutgens RBH, Greene NDE, Leung K-Y, Mitchison HM,Munroe PB, Taschner PEM. (1999) CLN3 Juvenile NCL.In: Goebel HH, Mole SE, Lake BD, editors. The Neuronal Ceroid

Lipofuscinoses (Batten Disease). Amsterdam: IOS Press. p 55–73.Hofmann SL, Das AK, Yi W, Lu J-Y, Wisniewski KE. (1999)

Genotype–phenotype correlations in neuronal ceroidlipofuscinosis due to palmitoyl-protein thioesterase deficiency.Mol Genet Metab 66: 234–239.

Lanska DJ, Lanska MJ. (1993) Visual ‘release’ hallucinations injuvenile neuronal ceroid-lipofuscinosis. Pediatr Neurol

9: 316–317.Lauronen L, Munroe PB, Järvelä I, Autti T, Mitchison HM, O’Rawe AM,

Gardiner RM, Mole SE, Puranen J, Häkkinen AM, Kirveskari E,Santavuori P. (1999) Delayed classic and protracted phenotypesof compound heterozygous juvenile neuronal ceroidlipofuscinosis. Neurology 52: 360–365.

Lovell RW, Reiss AL. (1993) Dual diagnoses: psychiatric disorders indevelopmental disabilities. Pediatr Clin N Am 40: 579–592.

Marshall FJ, de Blieck EA, Mink JW, Dure L, Adams H, Messing S,Rothberg PG, Levy E, McDonough T, DeYoung J, Wang M,Ramirez-Montealegre D, Kwon JM, Pearce DA. (2005) A clinicalrating scale for Batten disease: reliable and relevant for clinicaltrials. Neurology 65: 275–279.

Mervis CA, Boyle CA, Yeargin-Allsopp M. (2002) Prevalence andselected characteristics of childhood vision impairment. Dev Med

Child Neurol 44: 538–541.McHugh E, Lieberman L. (2003) The impact of developmental

factors on stereotypic rocking of children with visualimpairments. J Visual Impair Blindness 97: 453–474.

Novik TS. (1999) Validity of the Child Behaviour Checklist in aNorwegian sample. Eur Child Adolesc Psychiatry 8: 247–254.

Rider JA, Rider DL. (1999) Thirty years of Batten Disease research:present status and future goals. Mol Genet Metab 66: 231–233.

Rothberg P, Ramirez-Montealegre D, Frazier S, Pearce D. (2004)Homogeneous polymerase chain reaction nucleobase quenchingassay to detect the 1-kbp deletion in CLN3 that causes Battendisease. J Mol Diagn 6: 260–263.

Santavuori P, Lauronen L, Kirveskari E, Åberg L, Sainio K, Autti T.(2000) Neuronal ceroid lipofuscinoses in childhood. Neurol Sci

21: S35–S41.Santavuori P, Linnankivi T, Jaeken J, Vanhanen S-L, Telakivi T,

Heiskala H. (1993) Psychological symptoms and sleepdisturbances in neuronal ceroid-lipofuscinoses (NCL). J Inherit

Metab Dis 16: 245–248.Scahill L, Riddle M, McSwiggin-Hardin M, Ort S, King R, Goodman W,

Cicchetti D, Leckman J. (1997) Children’s Yale-Brown ObsessiveCompulsive Scale: reliability and validity. J Am Acad Child

Adolesc Psychiatry 36: 844–852.Wechsler D. (2003) Wechsler Intelligence Scale for Children –

Fourth Edition (WISC-IV). San Antonio, TX: The PsychologicalCorporation.

Weimer JM, Kriscenski-Perry E, Elshatory Y, Pearce DA. (2002) Theneuronal ceroid lipofuscinoses. Mutations in different proteinsresult in similar disease. Neuromol Med 1: 111–124.

264 Developmental Medicine & Child Neurology 2006, 48: 259–264

List of abbreviations

BDSRA Batten Disease Support and Research AssociationCBCL Child Behavior ChecklistJNCL Juvenile neuronal ceroid lipofuscinosisRMI Relative Mastery IndexSIB-R Scales of Independent Behavior – RevisedUBDRS Unified Batten Disease Rating Scale