Researchers Develop, Validate New Scale to Assess CMT Severity in Very Young Children

Researchers have developed a new scale to assess disease severity in infants with Charcot-Marie-Tooth disease (CMT). The final version of the Charcot-Marie-Tooth disease Infant Scale (CMTInfS) is easy to use and very reliable to evaluate disease outcomes for early-onset CMT and other types of nerve disorders.

The study supporting that assessment, “Development and validation of the Charcot-Marie-Tooth Disease Infant Scale,” was published in BRAIN.

CMT is the most common heritable disease that affects the peripheral nervous system — the network of nerves responsible for controlling movement and sensation in the limbs. The disease can be caused by different genetic mutations and manifest at different ages, depending on the particular type and sub-type.

Several CMT types start in the first years of life, which may be the best time window to act in order to avoid disease progression and further clinical complications.

“Carefully validated, sensitive and reliable functional outcome measures to assess the effectiveness of interventions are vital for the success of clinical trials [in young children and infants with CMT],” the researchers from the University of Sydney and collaborators wrote.

Although several outcome measures, such as the Rasch-modified CMT Neuropathy Score (CMTNSv2-R) and the CMT Pediatric Scale (CMTPedS), have been implemented in clinical trials involving older children and adults with CMT, there are no specific tools especially designed to assess disease severity in children younger than three years old.

In this study, researchers set out to develop and validate the CMTInfS as a functional clinical assessment tool to measure CMT severity in young children and infants with CMT.

A total of 128 children — 26 with a confirmed diagnosis of CMT, seven “at risk” of CMT, and 95 healthy controls — from newborn to four years old were recruited to participate in the study through the National Institutes of Health (NIH)-funded Inherited Neuropathies Consortium (INC).

The final version of the CMTInfS based on a pool of 15 items “capturing gross and fine motor development and sensation, [including] lower limb involvement, hand dexterity and coordination, strength, balance and mobility,” was used on all children.

Mathematical analysis revealed the CMTInfS was suited to evaluate disease severity among children with CMT. In addition, statistical analysis demonstrated the CMTInfS had an high intra-rater and inter-rater reliability, that is, repeated scores from the same patient in different periods of time and scores attributed by different evaluators were all consistent.

The new scale also was capable to distinguish between healthy children and those with CMT, producing scores that were in agreement with those obtained through the CMTPedS.

“[T]he final version of the CMTInfS requires 20 [minutes] to administer and is a reliable and sensitive 15-item functional outcome measure for early onset CMT and related neuropathies. The CMTInfS will be implemented in natural history studies to understand the rate of progression at the earliest stages of disease in preparation for therapeutic trials of early interventions,” the researchers wrote.