Folinate responsive encephalopathy with ascending spastic paraplegia, torsion dystonia, epilepsy and involvement of the autonomous nerves system

Abstract

Hereditary spastic paraplegia with associated central nervous system involvement is a rare, heterogeneous group of diseases with poor prognosis and without knowledge about basic mechanisms. Patients are treated symptomatically and live span is limited by the common problems of neurodegenerative diseases. There are single reports about folinate responsiveness. Case report: We report about a young Indian woman, who after normal development until age of 12 years, developed ascending spastic paraplegia, first loosing the ability to walk and urinary bladder control. During the next year she developed severe torsion dystonia with hundreds of episodes a day, followed by the loss of swallowing. Needing gastric tube feeding over 6 month, she received jejunostomy due to pylorospasm, and showed retrograde intestinal transport. Subsequently she had myoclonic and focal seizures, but she did not impair intellectually. Extensive diagnostic approaches in various international institutes including metabolic workup, CFS and genetic analysis, MRS, spinal MRI, L-DOPA PET, muscle, skin and intestinal biopsies, neurophysiology and psychological testing revealed normal results. cMRI showed slight atrophy and EEG revealed flattening and triphasic waves as unspecific signs of encephalopathy. FDG-PET demonstrated an increase in glucose metabolism in the basal ganglia during torsion- dystonia episodes. Antidystonic/antiepileptic treatment with baclophen, clonazepam, trihexephenydil, terabenzaine, gabapentine and levetirazetam hardly could control dystonia and epilepsy. Due to severe spastic paraplegia she was fixed to bed over 6 years, just able to move here left arm and speak. Encouraged by a report of folinate responsive spastic paraplegia we started with 15mg folinic acid per day. During the following month the now 18 years old woman seamed to impair intellectually and after 6 month of folinate treatment developed hallucinations during a pneumonia. The called psychiatrist diagnosed acute delirium and recommended the withdrawal of the antichoniergic medication. Trihexephenidyl was withdrawn stepwise without negative consequence, what as tried before resulted in massive dystonia. Subsequently withdrawal of total medication had no consequence but resulted in increasing mobility, ability to eat, swallow, intestinal motility and bladder function. Finally, besides 15mg folinate, 2 month of medication she was able to walk free. Now about 2½ years after starting folinate treatment she is visiting school again living a nearly normal live just having some residual joint contractions. EEG pattern normalized.