Handwriting Can Help Identify Asymptomatic Huntington’s, Study Suggests

Analysis of handwriting movements using a pen tablet and specialized software can accurately distinguish people with Huntington’s disease who are still asymptomatic from those without the disease, a new study suggests.

The findings also reveal that certain stroke features differ significantly between healthy individuals and patients who are already experiencing Huntington’s symptoms.

The research, “Handwriting Movement Abnormalities in Symptomatic and Premanifest Huntington’s Disease,” was published in the journal Movement Disorders Clinical Practice.

Handwriting abnormalities in Huntington’s patients were last reported nearly 20 years ago, and included longer stroke duration and greater variability in stroke velocity. Among questions still unanswered is whether assessing handwriting movements can help detect abnormalities in the asymptomatic (premanifest) stage of Huntington’s and serve as a predictor of disease progression.

To investigate, researchers at University of California San Diego tested whether handwriting abnormalities were associated with clinical features in symptomatic patients, and if such abnormalities could distinguish asymptomatic Huntington’s patients from healthy controls.

The team asked participants to complete five simple tasks: draw simple loops left to right (a string of “l” letters in cursive writing), complex loops (“lleellee”), rapid overlay circles, and spirals, and write the sentence “Today is a nice day.”

Participants used a Wacom digitizing tablet, a device often used by artists to draw on a computer screen. The tablet has a special pen and is sensitive to the level of applied pressure, mimicking traditional drawing on paper. Handwriting traces were recorded and analyzed using a specialized software called MovAlyzeR.

The study involved 38 symptomatic patients (mean age of 55 years), 30 asymptomatic individuals at risk for symptomatic disease (45 years), and 25 healthy controls (44 years).

Results revealed significantly longer and more variable stroke duration, as well as decreased handwriting smoothness, and increased and more variable pen pressures in the handwriting of Huntington’s patients compared with the handwriting of the healthy controls.

Longer stroke duration was associated with greater Penney burden of pathology (BOP) and CAG × age product, two measures of disease progression. Of note, the CAG × age product is calculated by multiplying the number of CAG repeats by the patient’s age.

CAG repeats are the genetic abnormality in people with Huntington’s. Patients may have 36 to more than 120 of these repeats of three DNA building blocks (cytosine, adenine, and guanine) in their HTT gene. The longer this region is, the earlier the symptoms appear and the more severe the disease.

Data also showed that analysis of certain handwriting features could distinguish asymptomatic patients from controls with 85% accuracy, 90% sensitivity, and 80% specificity. These included greater variability in stroke amplitude, velocity and pen pressure, higher levels of pen pressure, longer stroke durations, and lower velocities for combinations of handwritten circles, sentences, and spirals.

“These findings support the clinical utility of dynamic measures of handwriting kinematics as a potential early behavioral biomarker in [Huntington’s],” the researchers wrote.

However, they cautioned that these results require confirmation, especially those in asymptomatic patients, and that studies in larger groups are still needed.