Valproate associated non-hyperammonaemic encephalopathy: delayed onset after X years stable dose with full recovery[HC1]
Caruna-Galizia, Elizabeth1; Isaacs, Jeremy1; Cock, Hannah R1,2.
1Atkinson Morley Regional Neuroscience Centre, St Georges University Hospitals NHS Foundation Trust, London SW17 0QT
2Institute of Medical & Biomedical Education, St Georges University of London, SW17 0RE
Presenting Authoru: Elizabeth Caruna-Galizia, Speciality Trainee Neurology[HC2]
Non-hyperammonaemic parkinsonism, with or without cognitive impairment, is a rare adverse effect of sodium valproate therapy. We present the case of a 60 year old lady who developed a progressive akinetic-rigid syndrome with ataxia and cognitive impairment that resolved on cessation of valproate and review the relevant literature.
Case report: The patient had been on a stable dose of valproate for many x years [HC3]for the management of a generalized seizure disorder. Phenytoin had been withdrawn X months prior to presentation recently been withdrawn and she remained seizure-free. Her new symptoms progressed over X[HC4] months. Extensive blood tests including antineuronal and paraneoplastic antibodies (negative) and ; Investigation of her symptoms included serum ammonia and valproate levels (normal limits) identified no other cause., which were within normal limits. Her EEG showed generalized slow wave and an MRI showed mild generalized atrophy. Hypothesising that this might be a delayed onset valproate, perhaps precipitated by withdrawal of phenytoin elevating valproate levels, she was admitted for Rapid rapid substitution of valproate with levetiracetam. Her rigidity, bradykinesia, tremor and ataxia resolved within a week; Her score on the Adenbrooks Cognitive Examination-which was X on admission, had improved to X by day and on follow up X months she now reports no concerns. led to resolution of rigidity, bradykinesia, tremor and ataxia[HC5]. Serial cognitive assessments showed dramatic improvement.
Discussion & Conclucions: Twenty-sevenReversible disorders of motor function, gait and cognition attributable to Valproate are well described in the literature, though most present much earlier in treatment or as a result of a known dose escalation, typically within weeks or months adult[HC6] patients have been described in the literature presenting with parkinsonism attributed to sodium valproate{Mahmoud, 2011 #8804}{Armon, 1996 #8803}. In these cases and case series symptoms developed weeks to years after starting valproate. Given the insidious progression of symptoms and lack of association with valproate dosage, drug levels or presence of hyperammonaemia, a low index of suspicion is needed to make the diagnosis of valproate-associated encephalopathy in patients presenting with an extra-pyramidal syndrome. As in our case, withdrawal of valproate led to dramatic recovery over weeks to months in almost all reported cases. The mechanism by which valproate gives rise to a parkinsonian syndrome, with or without cognitive impairment, remains unknown but is likely to be multifactorial and mediated through its effects on mitochondrial metabolism and inhibition of GABA degradation within the nigrostriatal pathway.
[HC1]Ideally need something a bit catchier but which conveys the interesting message (the v. delayed onset.
[HC2]You need to add you presenting author office hours phone number, email and a fax number.
[HC3]How many – I recal something like 15-20years, which is the unusual thing about this case, and that there was no dose change
[HC4]I think it was 4-6 months? Check in letters.
[HC5]Need a bit more detail re timescales; assessments (e.g. ACE-R improved from X to X within days, normal by x)
[HC6]It’s more than this –