Persistent cerebellar ataxia with cerebellar cognitive affective syndrome due to acute phenytoin intoxication: A case report

Phenytoin is one of the commonly used antiepileptic drugs. The common dose dependent and reversible neurological side effects of phenytoin are nystagmus, diplopia, dysarthria, ataxia, incoordination, chorioathetosis, orofacial dyskinesias and drowsiness. Persistent cerebellar dysfunction with cerebellar atrophy is a well known complication of long term phenytoin use. There are several mechanisms proposed including hypoxia due to frequent seizures or toxic effects of phenytoin on cerebellar Purkinje cells. However, irreversible cerebellar dysfunction following acute phenytoin intoxication is rare. We report a 20 year old female who presented with nystagmus, dysarthria, limb and truncal ataxia with orofacial dyskinesias and chorea. She also had cognitive and affective symptoms in the form of reduced attention, slow responses, lalling speech, blunting of affect, inappropriate laughter, reduced self care and executive dysfunction. The symptoms started 2 weeks following the initiation of phenytoin 300mg/ day, given prophylactically following left basal ganglia bleed. Her serum phenytoin was in toxic range, hence phenytoin was stopped. Her PET scan revealed bilateral cerebellar hypometabolism. At 6 months follow up, she had persistent ataxia with cognitive and affective dysfunction and follow up MRI showed diffuse cerebellar atrophy. The clinical and radiological fi ndings suggest that acute phenytoin intoxication is responsible for persistent ataxia and cerebellar cognitive affective syndrome. Neurology Asia 2013; 18(1) : 107 – 111 Address correspondence to: Dr. Meena Gupta, DM (Neurology), Director, Professor Department of Neurology, 5th Floor, Academic Block, G.B. Pant Hospital, JLN Marg, New Delhi -110002 (India). Tel: 09718599301, 011232324242 ext.5501, 01123231298, Email: [email protected] INTRODUCTION Phenytoin (PHT) is one of the commonly used antiepileptic drugs. It is known to have neurological, hematological, metabolic and endocrinal side effects. The common neurological side effects of PHT include nystagmus, diplopia, ataxia, incoordination, chorioathetosis, orofacial dyskinesias and drowsiness. At higher levels ophthalmoplegia and encephalopathy may be seen. The symptoms are dose dependent and are usually reversible but persistent effect on CNS, most commonly as cerebellar dysfunction may be seen with prolonged use. Irreversible cerebellar dysfunction is a well known complication of chronic PHT toxicity, but is rarely seen following acute intoxication. We report a 20 year old female patient who developed persistent ataxia with cerebellar cognitive affective syndrome following acute PHT intoxication. CASE REPORT A 20 year old right handed female with a history of right hemiplegia due to left basal ganglia bleed 8 weeks back; referred to us with tremulousness in left upper limb, slurring of speech, blurring of vision, excessive sleep and imbalance while sitting and standing since last 6 weeks. Her weight was less than 40 kg and she was on PHT 300 mg/ day for seizure prophylaxis, however there was no history of any seizures. She was on PHT for 2 weeks prior to the onset of neurological symptoms and for a total of 8 weeks before presentation. There was no history of hypertension, at the time of stroke her BP was 130/80 mm of Hg and at the time of presentation to us BP was 110/70 mm of Hg. She denied any history of illicit / recreational drug use. At the time of presentation her general physical examination was normal. On neurological examination she was conscious, oriented but excessively sleepy. She had differential Neurology Asia March 2013 108 right hemiparesis with right facial palsy. Her cerebellar examination revealed scanning speech, bilateral horizontal gaze evoked nystagmus, titubation, severe generalized hypotonia with severe limb, truncal and gait ataxia. She also had extrapyramidal features including orofacial dyskinesia, chin tremor, and choriform movement of the tongue and left hand. Considering a possibility of PHT toxicity we did her serum PHT level, which was found to be markedly elevated at 55 microgram/ml (therapeutic range 10-20 microgram/ml). Her electroencephalogram (EEG) showed diffuse slowing of background activity without any epileptiform discharges. (Figure 1a) As the patient did not have any seizures, PHT was rapidly tapered off. Her repeat EEG performed a week later showed normal background activity (Figure 1b). After stopping PHT she was more awake and alert. On detailed higher mental function evaluation she had cognitive and affective changes in the form of reduced attention span, slow to respond, lalling speech, childish behaviour, blunting of affect with inappropriate laughter, reduced self care, executive dysfunction as lack of planning and initiation, defi cient abstract thinking and working memory. A diagnosis of acute cerebellar dysfunction with orofacial dyskinesia and chorea with cerebellar cognitive affective syndrome due to acute PHT intoxication in a case of right hemiparesis due to left gangliocapsular bleed was made. Her non-contrast CT brain (done at the time of ictus) showed acute bleed in left gangliocapsular area with mass effect. (Figure 2) We investigated for the cause of her intracranial bleed. Her routine Figure 1. EEG on admission (a) was showing diffuse slowing of background activity. Repeat EEG (b) was normal. Figure 2. Non contrast CT brain showing acute bleed in left gangliocapsular area with mass effect.