Cannabinoids were used to successfully treat epileptic seizures in a patient with Batten’s disease for whom conventional therapies alone failed, according to a case report, suggesting cannabinoids should be investigated further as a possible treatment of seizures.
The report, “Successful treatment of cannabinoid administration for refractory epilepsy in Batten disease: about a case,describes the case of a 25-year-old man with Batten’s disease who was admitted to a hospital in Cyprus with severe seizure activity. It was published in the journal Neurological sciences.
Before being admitted to hospital, the patient had had eight to 12 seizures a day, which had increased to 50 a day at the time of admission.
The patient’s brain scans and lab tests were normal, although an electroencephalogram (EEG), which measures electrical activity in the brain, showed a high susceptibility to seizures.
Prior to admission, he was taking 1000 mg of Keppra (levetiracetam) twice daily, 400 mg of valproic acid (sodium valproate) and 125 mg of Lamictal (lamotrigine). He also used zonisamide suppositories (100 mg in the morning and 150 mg in the evening) and 10 mg of diazepam as needed.
All drugs were administered through a percutaneous endoscopic gastrostomy (PEG), which is a feeding tube inserted into the stomach.
Doctors first gave diazepam intravenously (IV), but by day seven his seizure rate had increased to 80 a day and he was moved to an intensive care unit.
There the patient was intubated and sedated with a mixture of propofol, midazolam and fentanyl.
Doctors switched her Keppra and valproic acid to IV rather than PEG and added phenytoin IV three times a day. He continued to receive Lamictal and Zonisamide via PEG.
Despite these measures, her seizures continued at 60 per day, with up to 10 episodes of five to 45 seconds each occurring within an hour.
At 22 days, her seizures were still uncontrollable, despite a tracheotomy – a tube surgically placed through the neck into the trachea to help with breathing – and an increase in sedatives and antiepileptic treatment, including the addition of Onfi (clobazam ).
The seizure activity continued despite the addition of phenobarbital, then worsened when the patient developed a respiratory infection and fever, although this was successfully treated with antibiotics.
On day 27, when an EEG detected a seizure while the patient was on mechanical ventilation, specialist consultants advised palliative care, used to provide comfort in life-threatening cases without effective remedies.
At this point, the patient’s parents, after reading the available literature, requested that cannabinoid treatment be included in their son’s therapy.
Approval was given and treatment started with two drops daily of a solution (from Tilray Canada) containing 25 mg/mL delta9-tetrahydrocannabinol (THC) and 0.5 mg/mL cannabidiol (CBD). CBD is the non-psychoactive compound derived from the cannabis plant, while THC is the compound that causes mood-altering (psychotropic) effects.
This dose was increased by one drop daily for five days, at which time the seizures began to lessen. As treatment progressed, the patient regularly discontinued sedatives and mechanical ventilation.
Eight days after starting cannabinoid therapy, the formulation was changed to two drops three times a day of a 3% CBD oil, with a gradual increase in dose.
Seven days later, he started a regimen of 10% CBD oil and THC oil with an initial dose of 10 drops each three times a day via PEG (equivalent to 2.5 mg/kg /day of CBD and 0.15 mg/kg/day of THC).
The seizure activity decreased steadily, which allowed the patient to stop taking midazolam.
Three weeks after the start of the cannabinoid treatment, the patient no longer had seizures and could stop taking diazepam and Onfi while gradually decreasing the phenobarbital.
At 60 days, he was mobile in his wheelchair and continued to breathe on his own via the tracheostomy. After remaining seizure-free, he was finally released on the 73rd day.
At the time of his discharge, he was prescribed 17 drops of 10% CBD oil and 11 drops of THC four times a day (equivalent to 5.6 mg/kg/day of CBD and 1.4 mg/kg/ THC day); 1500 mg of Keppra, 400 mg of valproic acid and 100 mg of zonisamide twice a day; and 90 mg of phenobarbital three times a day via PEG.
Antiepileptic blood levels and liver function tests were stable after starting cannabinoid therapy.
He remained seizure-free except for sporadic myoclonic jerks in his palms for the next three months.
His doses of THC, valproic acid, and phenobarbitol continued to taper, and six months after discharge he was weaned from zonisamide and the tracheostomy was removed.
“The case of our patient with refractory epilepsy in Batten disease confirms the efficacy of cannabinoids in refractory epilepsy,” the authors wrote. “Further experimental studies in the spectrum of neuronal ceroid lipofuscinosis disorders are needed to validate these findings.”
