JNNP: Development of a Novel Clinical Examination Scale for Measuring Creutzfeldt-Jakob Disease Severity

Human prion diseases are a group of universally fatal neurodegenerative diseases caused by the autocatalytic, misfolding of constitutively expressed prion proteins (PrPC) into disease-associated assemblies, including a protease-resistant form designated PrPSc (~85% of event cases), hereditary (10%–15%), and acquired (<1%) subtypes
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The median clinical duration of sporadic Creutzfeldt-Jakob disease (sCJD) from symptom onset is 4 months, although the recognized disease course varies from short weeks to years

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Well-designed clinical rating scales are necessary to interpret and manage this variability, by providing quantitative measures of disease-specific changes, as clinical trial eligibility and stratification criteria, outcome measures, or for prognostic modeling

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The management paper presents the Medical Research Council Prion Disease Rating Scale (MRC Scale), a validated functional outcome measure of disease progression in sCJD, obtained through brief nursing staff interviews

The MRC scale was developed using Rasch modeling, a form of item response modeling

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This article was published in the Journal of Neurology, Neurosurgery & Psychiatry .

The National Prion Surveillance Cohort (NPMC) protocol was published, and upon enrollment, each patient underwent a comprehensive clinical assessment, including a standardized neurological examination and bedside neuropsychological panel (short-term cognitive examination (SCE)), MMSE and MRC scale
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Assessments were repeated at home visits every 4 to 8 weeks, and the MRC scale was repeated remotely every 2 weeks based on clinical rate of change

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Diagnosis Cognition and motor scale scores and cognitive/motor ratios were subsequently calculated for all other patients with any form of prion disease recruited to NPMC between October 2008 and December 2016

Also included are other composite or functional items that can also capture impairments in one or more motor pathways, such as eye movements, gait, and mobility

Final Cognitive and Motor Scale

 

The Cognitive Item Bank originally consisted of items from the Cognitive Short Test

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Attempts to mitigate this by limiting the final scale to six items, and including in the final pool the item with the largest pooled normalized effect size between two consecutive patient assessments to maximize confidence in the minimum number of assessments.

They can be done within minutes at the bedside as part of a normal neurocognitive exam

Longitudinal changes in motor and cognitive scales between first and second assessments 

Two validated, disease-specific, clinician-examined-based scoring scales were developed for patients with sCJD using the Rasch model, reflecting disease progression in the cognitive and motor systems
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Both scales can be completed in minutes, avoid jargon or abstract scoring systems, and require no special equipment
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They used items commonly assessed in routine neurological and bedside cognitive examinations
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The Comprehensive Examination Scale score provides a single measure of clinical progression at the bedside
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These scales complement the function-oriented MRC scales and have a variety of potential uses
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Objective quantification of motor and cognitive impairment in prion disease should add valuable clinical tools to patient assessment in formal clinical trials and routine neurological practice
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Differences in the speed and extent of motor and cognitive impairment help to stratify patient phenotypes that progress at different rates, thereby providing more accurate prognostic information for patients and their families
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Differences in the speed and extent of motor and cognitive impairment help to stratify patient phenotypes that progress at different rates, thereby providing more accurate prognostic information for patients and their families
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Differences in the speed and extent of motor and cognitive impairment help to stratify patient phenotypes that progress at different rates, thereby providing more accurate prognostic information for patients and their families
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These two new sCJD motor and cognitive scales and composite examination scales should prove useful in objectively measuring phenotypic and clinical changes in future clinical trials and patient stratification
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This statistical approach could help overcome barriers to assessing clinical changes in rapidly progressive multisystem disease with limited patient follow-up
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NihatA ,MokTH ,OddH NihatANihat MokTHMok OddHOdd, et alDevelopment of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob diseaseJournal of Neurology, Neurosurgery & PsychiatryPublished Online First:12 January 2022.
 Published Online First: doi:10.
1136/jnnp-2021-327722doi:

 

 

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