A Pediatric Patient With Autism Spectrum Disorder and Epilepsy Using Cannabinoid Extracts as Complementary Therapy

A Case Report

Juliana Andrea Ponton; Kim Smyth; Elias Soumbasis; Sergio Andres Llanos; Mark Lewis; Wilhelm August Meerholz; Robert Lawrence Tanguay

Disclosures

J Med Case Reports. 2020;14(162) 

In This Article

Case Presentation

A 15-year-old boy, of South African descent, is presented with a long-standing history of social and communicative challenges dating back to early childhood, including difficulties in appropriate use of facial expressions, eye contact, and gestures to regulate social interaction (see Figure 1 for patient's timeline). He has a history of difficulty in establishing and maintaining relationships, although he has been able to establish some friendships. His mother notes a history of selective mutism dating back to age 3. He has areas of fixated interests and some ritualized behaviors that on assessment were below the threshold for a diagnosis of obsessive-compulsive disorder. In 2016, he was formally diagnosed as having ASD by a specialized organization in British Columbia (BC), the Interior Health Children's Assessment Network (IHCAN), with supporting evidence from Autism Diagnostic Interview – Revised (ADI-R) and the Autism Diagnostic Observation Schedule 2 (ADOS-2). He does well academically and there are no cognitive concerns. Sometimes he shows aggressive behaviors towards his mother and other relatives.

Figure 1.

Patient's timeline depicting important dates and events. ACH Alberta Children's Hospital, ADI-R Autism Diagnostic Interview – Revised, ADOS-2 Autism Diagnostic Observation Schedule 2, ASD autism spectrum disorder, AQ Autism Spectrum Quotient (Adult), BC British Columbia, BMI body mass index (calculated by Du Bois method), CBD cannabidiol, CBE cannabidiol-based extract, CSHQ Children's Sleep Habits Questionnaire (Abbreviated), CYMH Child and Youth Mental Health, IHCAN Interior Health Children's Assessment Network, OCD obsessive-compulsive disorder, THC delta-9-tetrahydrocannabinol, upset stomach gastrointestinal side effects, VAS visual analog scale, VPA valproic acid. VAS severity for overall anxiety, social anxiety, aggressiveness and irritability, 0 = least severe, 10 = most severe. VAS for talkativeness, 0 = quiet, 10 = very talkative. VAS for focus, 0 = unfocused, 10 = focused

He was diagnosed as having epilepsy characterized by focal seizures at age 7 at an emergency department service in BC and was subsequently treated by his pediatrician and a pediatric neurologist at the Alberta Children's Hospital (ACH). He was initially prescribed carbamazepine for seizures which was stopped in 2015 due to side effects (upset stomach), followed by clobazam (stopped in 2016 due to suicidal ideation) and valproic acid (VPA) (stopped in 2017 due to alopecia, tremor, and reflux). The latter also caused a significant weight gain of approximately 13 kg in 1 year, resulting in a calculated body mass index (BMI) with the Du Bois method of 25.5 kg/m2. He is currently on lamotrigine for seizures, lorazepam for breakthrough seizures, melatonin for insomnia, riboflavin, ranitidine, magnesium, and orally administered CBE 0.2 mL (4 mg of CBD and 0.1 mg twice a day). No therapy had been tried for behavioral symptoms, although his mother mentioned that VPA and lamotrigine were also prescribed for their effect on mood.

He is currently in psychotherapy at the Child and Youth Mental Health (CYMH) clinic in BC for his selective mutism and anxiety disorder diagnosed by psychiatrists in the same province. He has also had sleep difficulties since 2016. His perinatal history is unremarkable. His birth followed a full-term pregnancy and was uncomplicated except for a required caesarean section due to macrosomia (> 4000 g) and macrocephaly (his mother does not remember the measurement), and subsequent hospitalization for neonatal jaundice. No genetic syndrome was suspected; no genetic testing was ever done. He met expected neurodevelopmental milestones for his age. His mother and grandmother have a history of depression and anxiety. There is other familial history of eating disorders and alcoholism, but no history of genetic syndromes.

In mid-2017, his parents consulted a medical cannabis physician from Caleo Health to assess the suitability of cannabis-based medicines as adjunctive or replacement therapy for seizures. At the time, a physical examination and laboratory findings were normal. A neurologic examination was unremarkable; mental status – awake, alert, cooperative; cranial nerves – normal; motor – normal tone, bulk, strength, and reflexes in upper and lower extremities, proximal and distal, deep tendon reflexes 2+ symmetric. A skin examination was unremarkable, there were no hypopigmented macules, café-au-lait macules, neurofibromas, or axillae ephelides. A long-term (48-hour) electroencephalogram done in 2016 did not record any epileptogenic potentials; magnetic resonance imaging (MRI) showed no intracranial abnormalities and a computed tomography (CT) scan of his head was normal (2015). Laboratory results done mid-2017 were normal: complete blood count and differential, vitamin B12, creatinine, sodium, potassium, calcium, magnesium, total bilirubin, albumin, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transferase, alanine aminotransferase, and triacylglycerol lipase. He had low ferritin (11 μg/L) but normal hemoglobin (159 g/L), due to starting a vegetarian diet, which was followed up by the family physician.

He had not had a clinical seizure in 6 months (last seizure in March 2017). Medications at the time of initiation of CBE were: lamotrigine 200 mg twice a day for seizures, lorazepam 1 mg sublingual (SL)/buccal as necessary, infrequently used for seizures, melatonin 6 mg for sleep initiation, riboflavin 400 mg administered orally once daily, magnesium 1 tablet administered orally once daily, and ranitidine 150 mg twice a day. When asked for symptom severity on a visual analog scale (VAS) (0 = least severe, 10 = most severe), his mother reported overall anxiety, social anxiety, aggressiveness, and irritability severity, at 10/10, 10/10, 6/10, and 9/10, respectively. On VAS to assess for talkativeness (0 = quiet, 10 = very talkative) in social situations, the mother reported 0/10. On VAS for concentration (0 = unfocused, 10 = very focused), 4/10 was reported. In regards to sleep, the mother stated he was sleeping approximately 5 to 6 hours, and was having trouble falling asleep. After the initial assessment, his parents gave consent to start therapy and CBE was prescribed (60 mL bottle of 1:20 CBE – 0.001% THC and 0.02% CBD), from CanniMed, with an olive oil carrier. His parents were instructed to administer 0.1 mL twice a day (2 mg CBD and 0.1 mg THC) and increase by 0.1 mL (2 mg CBD and 0.1 mg THC) per dose if no effects were shown to a maximum of 0.5 mL (10 mg CBD and 0.5 mg THC) per dose.

In December 2017, after 3 months of the CBE prescription, his mother increased the dose to 0.2 mL twice a day (4 mg CBD and 0.2 mg THC) as the family noted only mild improvements in anxiety symptoms. In August 2018, a medical cannabis follow-up was conducted. At 0.2 mL twice a day for almost 9 months, our patient's family reported an improvement of 7 points for overall and social anxiety and irritability, and 6 points on aggressiveness on their respective VAS. Talkativeness improved by 4 points and focus by 2 points. In February 2020, another medical cannabis follow-up was conducted and positive effects were still evident at the same dose. When the mother was asked to complete the Children's Sleep Habits Questionnaire (CSHQ) Abbreviated, she stated that he slept 7 hours and only had trouble falling asleep in his own bed as he resists going to bed. No side effects were reported (nausea/vomiting, diarrhea, headaches, euphoria, feeling high, anxiety, panic attacks, palpitations, somnolence during the day or drowsiness). Laboratory results remained normal and low ferritin was corrected. He began to initiate and reciprocate conversations with acquaintances he had previously been unable to speak to (for example, doctors, community members). He became more motivated and energetic, starting his own vegetarian diet and exercise programs, ultimately losing 6.4 kg after starting CBE for a calculated BMI of 21.33 kg/m2. He was able to start his first part-time job helping customers and interacting with them. He was instructed to fill out the self-administered Adult AQ which resulted in a normal score of 10 as shown in Table 1. His mother stated he now also has a girlfriend. Recently, his mother started weaning him off CBE to go on a trip and noted an immediate change. He became more irritable and aggressive.

In discussion with their neurologist, the family decided to wean lamotrigine while remaining on CBE (0.2 mL twice a day – 4 mg CBD and 0.2 mg THC). Unfortunately, there was a recurrence of seizures and lamotrigine was titrated back to the full 200 mg twice a day dose.

Currently, our patient remains on the same medication as mentioned above, as well as low dose of CBE. He has maintained the positive effect on his behavioral symptoms, anxiety, sleep, and social deficits on CBE 1:20 ratio, 0.2 mL twice a day (4 mg CBD and 0.2 mg THC) and no side effects have been reported.

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