Updated Kumamoto scale to aid doctors in monitoring ATTRv
New scale has clearer definitions, better symptom and organ involvement scoring
Specialists in Scandinavia have updated the Kumamoto scale, a tool long used to monitor the progression of hereditary transthyretin amyloidosis (ATTRv), a group of diseases that includes familial amyloid polyneuropathy (FAP).
The revised scale introduces clearer definitions and more precise scoring for symptoms and organ involvement, while still being practical for day-to-day clinical use.
“We believe that our revision has significantly improved the Kumamoto scale,” making it a “reliable and easy-to-use clinical tool for monitoring ATTRv,” wrote the researchers, who said the “scale is not fully comprehensive since some disease manifestations are not included” and has not yet been validated in this patient population. The study, “Introducing a revised version of the Kumamoto scale as an easy-to-use clinical tool for monitoring multisystemic changes in hereditary transthyretin amyloidosis,” was published in the Orphanet Journal of Rare Diseases.
In ATTRv, mutations in the TTR gene lead to a faulty transthyretin protein being produced that’s prone to forming toxic clumps, or amyloid deposits, in tissues. When these aggregates accumulate primarily in the nerves outside the brain and spinal cord, the disease is called FAP. This form of the disease can affect sensory function, movement, and autonomic processes, or involuntary body functions such as blood pressure, digestion, and bladder control. FAP symptoms range from numbness and weakness to dizziness, and bowel and urinary problems.
In ATTRv with cardiomyopathy, amyloid deposits mostly build up in the heart, leading to thickened walls, irregular rhythms, and eventual heart failure.
Over the past decade, treatments capable of slowing or halting ATTRv progression have been introduced, but responses among patients can vary. Monitoring symptoms and organ function regularly is critical for guiding care and optimizing outcomes.
Revising the Kumamoto scale
The Kumamoto scale, first introduced in 1997 in Japan, was one of the earliest tools for measuring disease severity in ATTRv. It covers four domains — sensory loss, motor weakness, autonomic symptoms, and major organ involvement. Each domain is scored from zero to 24, for a maximum of 96 points, with higher scores indicating more severe disease.
The scale has been used in clinical trials and to evaluate the outcome of a liver transplant in certain FAP patients. Clinics in Sweden have used it routinely for ATTRv patients since 2020 and Danish guidelines recommend it in following FAP patients on disease-modifying treatments.
“Having used the scale at the clinic in recent years, we have noticed that some elements of the scale could benefit from slight adjustments,” wrote researchers from Sweden, Denmark, and Norway who agreed on refinements for making the Kumamoto scale more precise, standardized, and easier to use in everyday practice. The revised scale standardizes sensory testing methods using a thermal device set at 25 C (about 77 F) to assess a person’s ability to detect cold temperatures, a Neuropen with a NeuroTip for pinprick pain, and cotton for light touch.
To better detect the spread of nerve damage, each limb is now divided into five anatomical levels rather than three, allowing for subtler and more accurate assessment of sensory loss. Also, the sensory evaluation of the trunk and head was adjusted to follow the typical pattern of nerve damage, which starts at the midline of the chest and then spreads out toward the sides.
Where motor function had been inconsistently assessed, it’s now standardized with the Medical Research Council scale for each of four standard movements — lifting the foot toward the shin, knee extension, elbow flexion, and lifting the back of the hand upward.
Autonomic symptoms are also assessed more thoroughly. Gastrointestinal involvement (GI) now covers both diarrhea and constipation, which is an early sign of GI dysfunction. Orthostatic hypotension, that is, a drop in blood pressure that can cause dizziness or fainting when standing from a lying position, is also measured more precisely, with a narrower range of blood pressure change between positions.
Urinary issues should be assessed with bladder scans to measure residual urine after double voiding, a technique to help ensure the bladder is as empty as possible. Organ involvement, specifically of the kidneys, is also now more clearly defined.
While the scale’s subtotal and total scores remain unchanged, scoring of some specific items changed, the researchers said.
“We believe that the revised Kumamoto scale is a reliable and easy-to-use clinical tool for monitoring ATTRv amyloidosis that is suitable for use in clinical trials,” the researchers wrote. “If combined with selected disease biomarkers, nutritional status, and functional status scales [related to both nerve and heart damage], it offers a comprehensive clinical assessment of ATTRv patients.” While no validation studies have been conducted yet, they do plan to assess the variability in scores between patients and between repeated measurements in the same patient.
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