BACKGROUND: Ataxia-Teleangiectasia (A-T) is a rare neurodegenerative disorder characterized by progressive cerebellar degeneration. Till few years ago only supportive care was available to improve the neurological function in A-T patients. Even though A-T remains an incurable disease, we recently demonstrated a drug dependent amelioration of neurological signs in A-T patients during a short-term treatment with oral betamethasone. AIMS: The aim of this study is to evaluate whether the steroid induced motor performance changes in A-T are associated with functional magnetic resonance imaging (fMRI) modifications. This represents a preliminary pilot study, which requires a validation on a larger cohort of patients. METHODS: Six A-T patients received a 10-days cycle of oral betamethasone at 0.03 mg/kg/day. fMRI studies were carried out at T0 and at the end of the cycle. The neurological evaluation was performed through the Scale for the Assessment and Rating of Ataxia (SARA) quantification. The fMRI protocol was a block design with alternating epochs of rest and prono-supination of the dominant (right) hand. RESULTS: The voxel-based comparison showed a remarkable increase in the number of activated voxels within the motor cortex under the on-therapy condition as compared with the cortical activity under baseline condition in the 2 patients who completed the study protocol. CONCLUSIONS: Changes in motor performance in A-T patients treated with betamethasone are coupled with an increase in the activation in relevant cortical areas, thus suggesting that in A-T patients steroid treatment could improve motor performance facilitating cortical compensatory mechanisms.
BACKGROUND:Ataxia-Teleangiectasia (A-T) is a rare neurodegenerative disorder characterized by progressive cerebellar degeneration. Till few years ago only supportive care was available to improve the neurological function in A-Tpatients. Even though A-T remains an incurable disease, we recently demonstrated a drug dependent amelioration of neurological signs in A-Tpatients during a short-term treatment with oral betamethasone. AIMS: The aim of this study is to evaluate whether the steroid induced motor performance changes in A-T are associated with functional magnetic resonance imaging (fMRI) modifications. This represents a preliminary pilot study, which requires a validation on a larger cohort of patients. METHODS: Six A-Tpatients received a 10-days cycle of oral betamethasone at 0.03 mg/kg/day. fMRI studies were carried out at T0 and at the end of the cycle. The neurological evaluation was performed through the Scale for the Assessment and Rating of Ataxia (SARA) quantification. The fMRI protocol was a block design with alternating epochs of rest and prono-supination of the dominant (right) hand. RESULTS: The voxel-based comparison showed a remarkable increase in the number of activated voxels within the motor cortex under the on-therapy condition as compared with the cortical activity under baseline condition in the 2 patients who completed the study protocol. CONCLUSIONS: Changes in motor performance in A-Tpatients treated with betamethasone are coupled with an increase in the activation in relevant cortical areas, thus suggesting that in A-Tpatientssteroid treatment could improve motor performance facilitating cortical compensatory mechanisms.
Authors: Harvey Perez; May F Abdallah; Jose I Chavira; Angelina S Norris; Martin T Egeland; Karen L Vo; Callan L Buechsenschuetz; Valentina Sanghez; Jeannie L Kim; Molly Pind; Kotoka Nakamura; Geoffrey G Hicks; Richard A Gatti; Joaquin Madrenas; Michelina Iacovino; Peter J McKinnon; Paul J Mathews Journal: Elife Date: 2021-11-01 Impact factor: 8.713