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Abstract: Use of Medicinal Cannabis (Cannabidiol) in Tuberous Sclerosis Complex Epilepsy (TSC) in Mexico.

Observational, descriptive cross-sectional study.

 

Dr. Carlos G. Aguirre Velázquez.

Summary

The experience of parents and patients with the use of medicinal Cannabis or Cannabidiol (CBD) in epilepsy secondary to the Tuberous Sclerosis Complex (TSC) in Mexico was explored through an online structured survey. 105 entries were obtained to the survey, 58 cases are reported that meet the inclusion criteria. Forty-seven (47) children and adolescents from 5 months to 18 years of age and eleven (11) adults over 18 years of age. The distribution by sex is 52% male and 48% female. 70.6% present some epileptic syndrome: Lennox-Gastaut syndrome (LGS) 20,

West Syndrome (SW) 20 and 6 Myoclonic-Astatic Epilepsy (AME). With a diagnosis of Epilepsy

Refractory (ER) in 22 (38%). 78% receive polypharmacy with more than 2 anticonvulsants. 10 cases (17.2%) receive treatment with medicinal Cannabis. CBD has reported a decrease in seizures in 7 (70%) cases; moderately to important in 6 (60%), discrete 1, unchanged 1, and no cases free of seizures or with increased seizures. No serious adverse events were reported, in 4 cases (40%) they were mild with increased appetite and sleep disturbances. Parents report improvement in quality of life parameters; emotional state, cognition, sleep, and eating.

Keywords: Epilepsy, Tuberous sclerosis, Medicinal cannabis, Cannabidiol.

Introduction

Tuberous Sclerosis Complex (TSC) is an autosomal dominant neurocutaneous syndrome of variable expression with multisystem involvement; where the skin, brain, eyes, kidneys, and heart are commonly affected by hamartomatous, malformations or tumor lesions. The incidence is 1: 9,400 to 10,000 births. There are mutations in the TSC1 Cr9 and TSC2 Cr16 genes that synthesize the hamartin and tuberin proteins that act as tumor suppressors in the Rapamycin mTOR system. Seizures are the most common neurological symptom of TSC in 85%, seizures are refractory to anticonvulsants in 63% (Morton, 2008). The generalized type is the most frequent with infantile spasms in 68% of cases in childhood. Tonic and atonic seizures and atypical absences may also occur, especially in patients with a pattern of slow paroxysmal spike-slow wave complexes ≤2.5 Hz on the EEG, which constitutes Lennox-Gastaut Syndrome (LGS) (Pellock, Dodson, & Bourgeois, 2008). Generalized tonic-clonic seizures replace previous seizures with advancing age and there is usually great variability in the seizure pattern (Franz, 1998).

Several mechanisms have been proposed by which CBD may have anticonvulsant effects (Wetly, Luebke & Gidal, 2014). CBD’s ability to block the mTOR pathway and its antioxidant and anti-inflammatory properties are of great interest as a potential new treatment for TSC and refractory epilepsy (Chesher and Jackson, 1974). In Mexico, for several years there has been a movement of parents and patients with epilepsy requesting these treatments and many already use some of these CBD products.

Hussain, Zhou, and Jacobson (2015) in a survey of 117 parents of children with refractory epilepsy due to LGS and Infantile Spasms reported improvement in an average treatment time of 6.8 months, with an average dose of 4.3 mg/kg/day of CBD. Devinsky, Marsh, and Friedman (2016) publish the result of the first prospective and multicenter open clinical trial with the use of a pharmaceutical product (Epidiolex®) based on a cannabinoid – 99% Cannabidiol (CBD) in 162 children with refractory epilepsy, in This study reported an average reduction of motor seizures of 36.5% and an adequate safety profile. Hess, Moody, and Geffrey (2016) in an expanded access protocol used CBD as an adjunct treatment in patients with drug-resistant epilepsy secondary to TSC. The response rate was 50% at 3 months of treatment and a mean reduction of 48.8% in the frequency of seizures. There are no controlled studies published in our country about the effectiveness and safety of the use of medicinal Cannabis (CBD) in epilepsy or TSC.

Recently (Aguirre-Velázquez, 2017) published the first observational study on the use of medicinal cannabis in Mexico in 43 cases of pediatric refractory epilepsy. Parents reported an 81% improvement in the frequency, intensity, and duration of seizures and quality of life parameters. In this study, there are 3 cases of Tuberous Sclerosis Complex and refractory epilepsy that used some form of medicinal Cannabis. The purpose of this work is to describe the experience of parents and patients with the use of CBD in epilepsy secondary to TSC in our country.

Methodology

An online survey was conducted that explored the experience of parents and patients with the use of cannabidiol (medicinal Cannabis) in children and adults with epilepsy secondary to Tuberous Sclerosis Complex (TSC) in Mexico. A commercial online SurveyMonkey® software (www.surveymonkey.com) was used, acquiring a license with options to elaborate unlimited questions of various types; open, closed, multiple-choice and with filters in a package of invitations by email and/or links for social networks or web pages. The system captures individual responses and automatically produces a report with basic statistics. The information is stored under security standards in SuperNAP and InterNAP ®.

The survey was designed with 35 questions and 1 open opinion in 3 sections. An informed consent and confidentiality clause was included at the beginning for personal data requesting acceptance. The sections were: 1) Personal data. 2) Information about tuberous sclerosis. 3) Information on epilepsy and its treatment.

The survey was distributed for 30 days, April 14 to May 14, 2017, to parents of children and patients in 4 Facebook groups- 1) Asociación POR GRACE AC, dedicated to sharing information on the use of medicinal cannabis to treat seizures of their children. 2) Asociación Mexicana de Esclerosis Tuberosa A.C., group of parents and TSC patients. 3) Welcome to Holland, the parents’ group for the dissemination of medicinal cannabis in epilepsy. 4) NPI Neurology and Comprehensive Psychology, page of a private medical group. The criteria for the invitation were: 1) Diagnosis of tuberous sclerosis complex and epilepsy under treatment. Participation was voluntary and by self-selection. The inclusion criteria were: Children, adolescents, or adults of both sexes with a confirmed diagnosis of TSC by clinical criteria and/or laboratory, imaging, genetic, or biopsy of lesions. Residence in Mexico. The exclusion criteria were; cases without a diagnosis of TSC and/or without seizures and incomplete surveys. Cases of residents in other countries outside of Mexico were not included.

An automated report of all the information from 104 surveys was obtained, leaving 58 surveys for analysis. An Excel® 2013 package was used to obtain statistical data with measures of central tendency, absolute and percentage data to generate tables and graphs.

Results

58 surveys were analyzed, the ages of the group varied in a range from 2.4 to 29 years, with a mean of 9.9 years and S.D. 7.1 years. There was a slight predominance of males (52%) in this group, 10.3% had a hereditary family history for TSC. The diagnosis of TSC was made more frequently in the infant stage (0 to 2 years) in 58.6% by different methods, various specialists, and care centers; 75.8% had imaging and EEG studies, only by clinical history criteria 10.3%. Genetic confirmation by TSC1 and TSC2 in 6 cases (10.3%) and 2 (3.4%) by biopsy of lesions.

The onset of epilepsy predominated in the range from newborn to 2 years (70%), the diagnosis of some epileptic syndrome was established in 36 cases (72.7%) and some cases reported several epileptic syndromes in their evolution. Refractory epilepsy was declared in 38% of cases.

The predominant seizures were generalized in 63.6% of types; Myoclonic, atonic, tonic, and tonic-clonic, followed by atypical absences and infantile spasms. Focal seizures were reported in 20.7%, cases with mixed seizures 15.5%. They received polypharmacy of 3 to 8 anticonvulsants 34 (68%) and more than 10 anticonvulsants 4 (8%).

There were 10 cases with medicinal Cannabis (Cannabidiol) treatment, the most used product was RSHO-X in 6 cases, 2 artisan products, 1 Gummy CBD, and 1 Nanko.

The results indicate a significant decrease in seizures in 60% of cases (80-100%). No seizure-free or exacerbation-free cases were reported with CBD. The doses of CBD varied from 0.7 to 19 mg / Kg/day (= 4.1 mg / Kg/day), in artisan products, it is not possible to obtain a dosage. Mild adverse effects occurred.

Parents report changes in quality of life parameters with medicinal Cannabis (CBD) treatment.

Conclusions
The experience of parents and patients with the use of medicinal Cannabis (CBD) is positive for having an improvement in the frequency, intensity, and duration of seizures secondary to TSC. Likewise, they report an improvement in general parameters of quality of life. This therapeutic resource is already available in our country and at a moderate cost in relation to other treatments. Controlled studies with greater statistical solidity are required to support the use of Cannabidiol (medicinal Cannabis) in epilepsy secondary to TSC.

If you wish to consult the full study in its English version, you can do so at the following link:

http://www.journalrepository.org/media/journals/JAMMR_64/2017/Oct/Velazquez23122017JAMMR36585.pdf

Presentación del Dr. Carlos Aguirre

Posted by Por GRACE on Thursday, October 12, 2017







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