Steroid-induced improvement of neurological signs in ataxia-telangiectasia patients.

A recent clinical observation reported on a dramatic improvement of neurological symptoms following short-term betamethasone administration in a child affected with ataxia-teleangiectasia (A-T). The aim of this study was to extend this observation to additional A-T patients followed at a single Immunodeficiency Center. Six consecutive patients (three males; mean age 16.3 years, range 5-30 years) were enrolled into this monocentric before-after trial. A cycle of oral betamethasone at the dosage of 0.1 mg/kg/day was administered for 10 days. The neurological evaluation was performed through the Scale for the Assessment and Rating of Ataxia. Overall, five of the six patients exhibited a clear amelioration of the neurological performances. Only in two patients, a slight amelioration persisted 7 days after the therapy withdrawal, whilst in the other patients the score reached approximately the pre-treatment value at the end of the therapy. Twenty-eight of the 46 evaluated neurological items (60%) improved during therapy. The speech disturbance, finger chase and nose-finger test showed the more significant improvement. The clinical amelioration was inversely correlated with the level of cerebellum atrophy, as revealed by the magnetic resonance. Our data indicate that neurological signs in A-T are susceptible of beneficial pharmacological intervention even years after the disease onset

Steroid-induced improvement of neurological signs in ataxia-telangiectasia patients

A recent clinical observation reported on a dramatic improvement of neurological symptoms following short-term betamethasone administration in a child affected with ataxia-teleangiectasia (A-T). The aim of this study was to extend this observation to additional A-T patients followed at a single Immunodeficiency Center. Six consecutive patients (three males; mean age 16.3 years, range 5-30 years) were enrolled into this monocentric before-after trial. A cycle of oral betamethasone at the dosage of 0.1 mg/kg/day was administered for 10 days. The neurological evaluation was performed through the Scale for the Assessment and Rating of Ataxia. Overall, five of the six patients exhibited a clear amelioration of the neurological performances. Only in two patients, a slight amelioration persisted 7 days after the therapy withdrawal, whilst in the other patients the score reached approximately the pre-treatment value at the end of the therapy. Twenty-eight of the 46 evaluated neurological items (60%) improved during therapy. The speech disturbance, finger chase and nose-finger test showed the more significant improvement. The clinical amelioration was inversely correlated with the level of cerebellum atrophy, as revealed by the magnetic resonance. Our data indicate that neurological signs in A-T are susceptible of beneficial pharmacological intervention even years after the disease onset. © 2008 The Author(s)

Efficacy of very-low-dose betamethasone on neurological symptoms in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is a non-curable neurodegenerative disorder, associated with progressive neurological dysfunction, oculocutaneous telangiectasia, immunodeficiency, predisposition to cancer and radiosensitivity. A recent study documented improvement in neurological symptoms after a short-term therapy with betamethasone in patients with A-T. Aim of this study was to evaluate the minimum therapeutically effective dosage of betamethasone on neurological symptoms of A-T. Methods: Six responsive patients with A-T, received two 20-day cycles of oral betamethasone at 0.01 and 0.03 mg/kg/day (10% and 30% of the previously used full dosage), each followed by a 20-day washout period. Clinical and laboratory evaluations were carried out at T0 and at the end of each cycle. Neurological assessment was performed through the Scale for the Assessment and Rating of Ataxia (SARA). The glucocorticoid-induced leucine zipper (GILZ) and glucocorticoid receptor (GR) RNA expression were evaluated before and during the trial through real-time PCR. Results: SARA scores significantly improved in all patients at the dosage of 0.03 mg/kg/day. In particular, three patients exhibited an improvement in 5/8 variables and two patients of 7 and 8 variables, respectively. Furthermore, the clinical improvement was already evident after the lower dosage. The basal GILZ and GR RNA expression were significantly lower in patients than in controls. GILZ expression increased in all patients after the beginning of the therapy, whereas no correlation between GR and the response was found. Conclusion: Our data indicate that betamethasone is effective in A-T at a minimal dosage and that GILZ may be a useful biomarker of the clinical response. This study provides Class IIIA evidence that betamethasone at very low dosage is effective in improving neurological signs of patients affected with ataxia-telangiectasia