A clinical rating scale for Batten disease

Marshall, Frederick J.; Blieck, Elisabeth A. de; Mink, Jonathan W.; Dure, Leon S.; Adams, Heather; Messing, Susan; Rothberg, Paul G.; Levy, E.; McDonough, Tracy A.; DeYoung, Jay; Wang, M.; Ramirez-Montealegre, Denia; Kwon, Jennifer M.; Pearce, David A.

doi:10.1212/01.wnl.0000169019.41332.8a

Cited by 89 publications

(118 citation statements)

References 29 publications

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“…All participants except the asymptomatic child had some degree of vision loss. In 13 children also undergoing the UBDRS examination, vision loss was rated independently by three neurologists on a 5-point scale (0=normal; 4=blind; Marshall et al 2005). The modal rating for all but one child (12/13) was no better than 'light/dark perception only'.…”

Section: Resultsmentioning

confidence: 99%

“…Participants were recruited via the Batten Disease Support and Research Association (BDSRA) in Reynoldsberg, Ohio. A subset (n=13) 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.…”

Section: Participantsmentioning

confidence: 99%

“…We have developed a Unified Batten Disease Rating Scale (UBDRS) to quantify physical, behavioral, and functional aspects of JNCL in a neurological exam setting (Marshall et al 2005). We initiated the current study in conjunction with the UBDRS to further characterize the natural history of neuropsychological and behavioral and psychiatric symptoms of JNCL, and to describe changes in affected children's capacity to employ everyday adaptive skills (e.g.…”

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confidence: 99%

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Standardized assessment of behavior and adaptive living skills in juvenile neuronal ceroid lipofuscinosis

Adams

Blieck

Mink

et al. 2006

Developmental Medicine &Amp; Child Neurology

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We obtained information about the behavioral, psychiatric, and functional status of 26 children (13 males, 13 females) with juvenile neuronal ceroid lipofuscinosis (JNCL; mean age 12y 3mo [SD 3y 4mo]; range 6y 9mo to 18y 8mo). Twenty-five children had visual impairment and 18 were known to have a positive seizure history before enrollment. Parents completed the Child Behavior Checklist, Scales of Independent BehaviorRevised, and a structured interview to assess obsessivecompulsive symptoms. Participants exhibited a broad range of behavioral and psychiatric problems, rated as occurring frequently and/or as severe in more than half of the sample. Males and females did not differ with regard to the number of behavioral and psychiatric problems. Children were also limited in their ability to perform activities of daily living, including self-care, hygiene, socialization, and other age-appropriate tasks. Results provide a quantitative baseline for behavioral and psychiatric problems and functional level in JNCL, against which further decline can be measured. Longitudinal assessment of behavioral and psychiatric symptoms and functional abilities is continuing and will provide much-needed data on the natural history of JNCL.

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Section: Resultsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

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confidence: 99%

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Standardized assessment of behavior and adaptive living skills in juvenile neuronal ceroid lipofuscinosis

Adams

Blieck

Mink

et al. 2006

Developmental Medicine &Amp; Child Neurology

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“…We developed the Unified Batten Disease Rating Scale (UBDRS) to measure disease progression in JNCL. 11 We used the UBDRS to evaluate and quantify disease burden in 82 subjects with JNCL from 2002 through 2010, the largest cohort of patients with JNCL reported to date.…”

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confidence: 99%

Quantifying physical decline in juvenile neuronal ceroid lipofuscinosis (Batten disease)

Kwon¹,

Adams²,

Rothberg³

et al. 2011

Neurology

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Objective: To use the Unified Batten Disease Rating Scale (UBDRS) to measure the rate of decline in physical and functional capability domains in patients with juvenile neuronal ceroid lipofuscinosis (JNCL) or Batten disease, a neurodegenerative lysosomal storage disorder. We have evaluated the UBDRS in subjects with JNCL since 2002; during that time, the scale has been refined to improve reliability and validity. Now that therapies are being proposed to prevent, slow, or reverse the course of JNCL, the UBDRS will play an important role in quantitatively assessing clinical outcomes in research trials. Methods:We administered the UBDRS to 82 subjects with JNCL genetically confirmed by CLN3 mutational analysis. Forty-four subjects were seen for more than one annual visit. From these data, the rate of physical impairment over time was quantified using multivariate linear regression and repeated-measures analysis. Results:The UBDRS Physical Impairment subscale shows worsening over time that proceeds at a quantifiable linear rate in the years following initial onset of clinical symptoms. This deterioration correlates with functional capability and is not influenced by CLN3 genotype. Conclusion:The UBDRS is a reliable and valid instrument that measures clinical progression in JNCL. Our data support the use of the UBDRS to quantify the rate of progression of physical impairment in subjects with JNCL in clinical trials. Neurology The neuronal ceroid lipofuscinoses (NCLs) are degenerative, autosomal recessive storage diseases with common clinical and pathologic features, including blindness, seizures, dementia, motor decline, and lysosomal accumulation of autofluorescent material (ceroid and lipofuscin).1 The NCLs are categorized by genetic etiology. The juvenile form of neuronal ceroid lipofuscinosis (JNCL), also called Batten disease, is the most prevalent NCL. Clinically, JNCL begins with progressive visual loss between 4 and 8 years of age, followed by seizures, then loss of motor coordination and dementia between 10 and 12 years. Death occurs by the third or fourth decade. 1,2 JNCL is due to mutations of the CLN3 3 gene that encodes a ubiquitously expressed protein of unknown function localized to the lysosomal membrane 4,5 ; modeling studies suggest a role in substrate trafficking. 5,6 Most cases of JNCL are caused by an approximately 1-kb deletion in the CLN3 3,7 gene, encompassing exons 7 and 8. Approximately 74% of patients with JNCL are homozygous for this common deletion, and 22% are compound heterozygotes for this deletion and another CLN3 mutation.8 There are no mutations consistently associated with better prognosis. 8 -10 From the University of Rochester (J.M.K., H.A., P.G.R., E. With biological advances, there is hope for rational therapies to prevent, slow, or reverse the course of JNCL. We developed the Unified Batten Disease Rating Scale (UBDRS) to measure disease progression in JNCL.11 We used the UBDRS to evaluate and quantify disease burden in 82 subjects with JNCL from 2002 through 2010...

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“…The scale for each item studied ranges from 0 (most severe) to 3 (normal). Marshall et al [70,71] developed clinical assessment tools, referred to as the Unified Batten Disease Rating Scale, to measure the severity and progression of CLN3 disease, juvenile based on motor assessment, behavior and functional capability. It is time to adopt one or two scales that will be applied internationally to fully understand NCL disease in the 21 st Century and to have accurate data against which the effect of new therapeutic treatments can be assessed.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Approaches to the Challenge of Neuronal Ceroid Lipofuscinoses

Kohan¹,

Cismondi²,

Oller-Ramírez³

et al. 2011

CPB

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The Neuronal Ceroid Lipofuscinoses (NCLs) are lysosomal storage diseases (LSDs) affecting the central nervous system (CNS), with generally with recessive inheritance. They are characterized by pathological lipofuscin-like material accumulating in cells. The clinical phenotypes at all onset ages show progressive loss of vision, decreasing cognitive and motor skills, epileptic seizures and premature death, with dementia without visual loss prominent in the rarer adult forms. Eight causal genes, CLN10/CTSD, CLN1/PPT1, CLN2/TPP1, CLN3, CLN5, CLN6, CLN7/MFSD8, CLN8, with more than 269 mutations and 49 polymorphisms (http://www.ucl.ac.uk/ncl) have been described. Other NCL genes are hypothesized, including CLN4 and CLN9; CLCN6, CLCN7 and possibly SGSH are under study. Some therapeutic strategies applied to other LSDs with significant systemic involvement would not be effective in NCLs due to the necessity of passing the blood brain barrier to prevent the neurodegeneration, repair or restore the CNS functionality. There are therapies for the NCLs currently at preclinical stages and under phase 1 trials to establish safety in affected children. These approaches involve enzyme replacement, gene therapy, neural stem cell replacement, immune therapy and other pharmacological approaches. In the next decade, progress in the understanding of the natural history and the biochemical and molecular cascade of events relevant to the pathogenesis of these diseases in humans and animal models will be required to achieve significant therapeutic advances.

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A clinical rating scale for Batten disease

Abstract: The Unified Batten Disease Rating Scale (UBDRS) is a reliable instrument that effectively tests for neurologic function in blind and demented patients. In its current form, the UBDRS is useful for monitoring the diverse clinical findings seen in Batten disease.

Cited by 89 publications

References 29 publications

Standardized assessment of behavior and adaptive living skills in juvenile neuronal ceroid lipofuscinosis

Standardized assessment of behavior and adaptive living skills in juvenile neuronal ceroid lipofuscinosis

Quantifying physical decline in juvenile neuronal ceroid lipofuscinosis (Batten disease)

Therapeutic Approaches to the Challenge of Neuronal Ceroid Lipofuscinoses

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