Pearls and Oy-sters: Vitamin B₆ deficiency presenting with new-onset epilepsy and status epilepticus in a patient with Parkinson disease

Pearls

• Pyridoxine (vitamin B₆) deficiency is a treatable cause of new-onset epilepsy and status epilepticus in patients with Parkinson disease (PD).

• Long-standing high-dose carbidopa-levodopa intake in the setting of gastroparesis or poor nutritional intake may contribute to pyridoxine deficiency in patients with PD.

Oy-sters

• Unrecognized pyridoxine deficiency in patients with PD could lead to epilepsy and status epilepticus.

• There is no evidence to support dietary avoidance of pyridoxine in patients with PD who are treated with carbidopa-levodopa.

Case report

An 83-year-old woman with hypertension, coronary artery disease, and PD developed recurring paroxysmal events consistent with multifocal motor and nonmotor epileptic seizures with and without secondary generalization. Repeated EEG studies revealed multifocal epileptiform discharges or electrographic seizures. Brain MRI and CSF studies were unremarkable.

Over the next 6 months, her epileptic seizures became progressively more frequent despite treatment with oral levetiracetam (1,000 mg twice daily, 29.45 mg/kg/d), topiramate (100 mg twice daily, 2.95 mg/kg/d), phenytoin (150 mg twice daily, 4.42 mg/kg/d), and lorazepam (0.5 mg daily). She presented to the emergency department at our institution after several recurrent seizures without return to her neurologic baseline. Despite initial administration of 2 mg IV lorazepam, the patient had 1 additional focal motor seizure requiring 2 more mg of IV lorazepam. Her levetiracetam dose was increased to 1,500 mg twice daily (44 mg/kg/d) after a loading IV dose of 1,000 mg. Clinical seizures ceased, but she required intubation for airway protection. Her health care proxy agreed to intubation despite a previous advanced directive given the potential reversibility of her current condition. Despite her antiepileptic medication levels being therapeutic, continuous video-EEG monitoring persistently showed occasional electrographic seizures and frequent multifocal epileptiform discharges (figure).

Figure Scalp EEG recording examples in this patient with Parkinson disease and pyridoxine deficiency causing new-onset epilepsy and status epilepticus

Frequent, independent, multifocal epileptiform discharges (arrows) are shown with maximal amplitudes on the (A and C) right frontal (Fp2 electrode), (A and C) left frontotemporal (FT9 electrode), (B and D) midline (Fz/Cz electrodes), and (B and D) right frontotemporal regions (FT10/F8 electrodes). EEG activity was recorded with scalp electrodes positioned according to the 10–20 international system. Signals from (A and B) average referential and (C and D) bipolar montages were recorded at a sample rate of 500 Hz, sensitivity of 7 μV/mm, high-frequency filter of 70 Hz, and low-frequency filter of 1 Hz. Panels A (average referential montage) and C (bipolar montage) correspond to the same time epoch. Panels B (average referential montage) and D (bipolar montage) correspond to the same time epoch.

Her dopaminergic regimen for PD treatment had remained stable for the previous 2 years. Her medications included 1 tablet of carbidopa/levodopa 25/100 mg controlled release and 2 tablets of carbidopa/levodopa 25/100 mg immediate release taken together 7 times per day (2,100 mg/d), pramipexole 1.5 mg per mouth 3 times daily, and amantadine 100 mg per mouth daily. Her total levodopa-equivalent daily dose was 2,475 mg. According to her health care proxy, the patient had developed progressively worsening symptoms consistent with gastroparesis and unintended weight loss of 9 kg over the 6 months before seizure onset. Furthermore, the proxy reported that she had been specifically trying to avoid pyridoxine (vitamin B₆) in her diet after learning about the potential reduction of levodopa efficacy in a support group. Unfortunately, the patient and her health care proxy had not discussed this decision with any of her physicians.

Laboratory studies confirmed the suspicion of pyridoxine deficiency. She had very low serum pyridoxine (<5 nmol/L, normal 20–125 nmol/L), low serum folate (4.2 ng/mL, normal >4.6 ng/mL), normal serum vitamin B₁₂ (1,060 pg/mL, normal 232–1,245 pg/mL), and high serum homocysteine (19 μmol/L, normal 0–15 μmol/L) levels. Pyridoxine replacement was started at 20 mg/d IV with immediate improvement in her mental status, resolution of electrographic seizures, and marked reduction in the frequency of epileptiform discharges. Unfortunately, the patient did not tolerate extubation due to severe laryngeal stenosis and, along with her health care proxy, decided not to be reintubated, subsequently passing away.