Gait phenotype in Batten disease: A marker of disease progression.

BACKGROUND

Gait impairment and its etiologic correlate has not previously been subject of special attention in Batten disease.

METHODS

In the present review, the clinical picture of gait phenotype during Batten disease course accompanied by descriptions of the known concomitant patho-anatomical changes is presented.

RESULTS

In CLN1 a non-rhythmic gait is seen around 1-1½ years of age. Shortly after, postural hypotonia and exaggerated tendon reflexes develop. The disease reaches a burnt-out stage during the third year of age and subsequently the children are almost without voluntary movements. The existing literature indicates that gait phenotype in CLN1 is caused by early involvement of the spinal interneurons followed by impact of the cortex and the cortico-spinal tracts. The earliest walking abnormality in children with CLN2 is a clumsy, ataxic, and spastic gait, which is in accordance with the existing imaging and histologic studies showing early involvement of the cerebellum and the cortico-spinal pathways. In CLN3, a reduction in walking speed is present at the age of 7-8 years. It occurs simultaneously with a reduction in the white matter microstructure and brain connectivity networks. Functional impairment of the basal ganglia contributing to a parkinsonian gait phenotype occurs in the mid-teens. In the late teens and early twenties involvement of the peripheral nerves, neurogenic musculoskeletal atrophy, loss of tendon reflexes and postural control are seen.

CONCLUSION

The progressively impaired gait function in Batten disease is related to timing of damage of distinct areas of the nervous system depending on subtype and is a powerful marker of disease progression.