Response to amoxicillin and perampanel in infantile Alexander disease
Por:
Boronat, S, Turon-Viñas, E, Mac Manus, N, Diaz-Gomez, A, Vicente, M, Ros-Castelló, V, Sierra-Marcos, A
Publicada:
6 nov 2024
Ahead of Print:
1 nov 2024
Resumen:
Type I Alexander disease (AxD) presents with paroxysmal neurodegeneration, refractory epilepsy, and encephalopathy in the first years of life and is associated with a poor prognosis. Although there is no treatment, mild symptomatic improvement has been reported in one case of adult Alexander treated with ceftriaxone, given its interaction with the mutant glial fibrillary acid protein (GFAP) responsible for the disease's pathogenesis. We describe a patient presenting with irritability starting at 2 months of age, initially attributed to gastroesophageal reflux. A ventriculoperitoneal shunt was placed at 3 months of age due to hydrocephalus secondary to aqueduct stenosis detected through an MRI scan, but the irritability persisted. At 5 months, a new brain MRI was performed due to irritability worsening, onset of abnormal ocular movements and seizures. In addition genetic testing was performed. AxD was diagnosed due to the mutation c.716G>A (p.Arg239His) in GFAP. Since irritability had worsened and had not responded to levomepromazine, treatment with amoxicillin (80 mg/kg/day) was attempted to modulate glutamate levels. The patient showed a striking improvement of irritability in 48 h that persisted over the next months. The patient had frequent daily seizures which did not respond to valproate, clonazepam, or phenobarbital. Perampanel, a postsynaptic AMPA receptor antagonist, was added to phenobarbital and he was seizure free for more than 3 months. Drugs modulating glutamate levels in the central nervous system, including beta-lactam antibiotics and perampanel, may have an important role in the symptomatic treatment of AxD and other neurodegenerative diseases where glutamatergic excitotoxicity is a pathogenic determinant.
Filiaciones:
Boronat, S:
UAB, Hosp Santa Creu i Sant Pau, Pediat Neurol Unit, Barcelona, Spain
Turon-Viñas, E:
UAB, Hosp Santa Creu i Sant Pau, Pediat Neurol Unit, Barcelona, Spain
Mac Manus, N:
UAB, Hosp Santa Creu i Sant Pau, Pediat Neurol Unit, Barcelona, Spain
Diaz-Gomez, A:
UAB, Hosp Santa Creu i Sant Pau, Pediat Neurol Unit, Barcelona, Spain
Vicente, M:
UAB, Vall dHebron Hosp Barcelona, Neurophysiol Unit, Barcelona, Spain
Ros-Castelló, V:
UAB, Hosp Santa Creu i Sant Pau, Epilepsy Unit, Barcelona, Spain
Sierra-Marcos, A:
UAB, Hosp Santa Creu i Sant Pau, Epilepsy Unit, Barcelona, Spain
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