Cannabidiol Elevates Mechanistic Target of Rapamycin Inhibitor Levels in Patients With Tuberous Sclerosis Complex.

Abstract:

BACKGROUND:The mechanistic target of rapamycin inhibitors everolimus and sirolimus have activity against multiple manifestations of tuberous sclerosis complex and are approved to treat astrocytomas, angiomyolipomas, lymphangioleiomyomatosis, and epilepsy. Cannabidiol is a novel antiepileptic medication. There is lack of information regarding drug-drug interactions between mechanistic target of rapamycin inhibitors and cannabidiol in clinical practice. METHODS:We reviewed patients with tuberous sclerosis complex who were treated with a mechanistic target of rapamycin inhibitor (everolimus, sirolimus) and cannabidiol. Clinical information, mechanistic target of rapamycin inhibitor and cannabidiol dosing, concomitant antiepileptic drugs, as well as laboratory and adverse events were reviewed before and after initiation of cannabidiol. RESULTS:A total of 25 patients were treated with cannabidiol and a mechanistic target of rapamycin inhibitor (18 everolimus, seven sirolimus). All mechanistic target of rapamycin inhibitor levels were drawn as troughs. Levels were significantly higher in 76% patients after cannabidiol treatment (P = 0.0003). Median change from baseline was +9.8 ng/mL for everolimus and +5.1 ng/mL for sirolimus. Adverse events occurred in 40%, with diarrhea being the most frequent adverse event occurring in three patients. No severe adverse events occurred during the treatment period. CONCLUSIONS:Cannabidiol resulted in increased serum levels of everolimus and/or sirolimus. Some patients experienced doubling or tripling of their mechanistic target of rapamycin inhibitor trough following the addition of cannabidiol. In some cases, this resulted in clinical toxicity, as well as laboratory abnormalities. Awareness of this interaction can lead clinicians to evaluate serum levels and other safety laboratory studies more closely, and thereby avoid potentially significant adverse effects. In patients known to be prone to mechanistic target of rapamycin inhibitor toxicity, preemptive reduction in dose may be warranted upon initiation of cannabidiol.

journal_name

Pediatr Neurol

journal_title

Pediatric neurology

authors

Ebrahimi-Fakhari D,Agricola KD,Tudor C,Krueger D,Franz DN

doi

10.1016/j.pediatrneurol.2019.11.017

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

59-61

eissn

0887-8994

issn

1873-5150

pii

S0887-8994(19)30955-5

journal_volume

105

pub_type

杂志文章
  • Rethinking the Magnetic Resonance Imaging Findings in Early Rasmussen Encephalitis: A Case Report and Review of the Literature.

    abstract:OBJECTIVE:We present a child with Rasmussen encephalitis and highlight the pitfalls of diagnosis when magnetic resonance imaging (MRI) is negative for atrophy. We review the literature regarding this issue, introduce the FreeSurfer software as a potential means of noninvasive diagnosis, and discuss methods for prompt a...

    journal_title:Pediatric neurology

    pub_type: 杂志文章,评审

    doi:10.1016/j.pediatrneurol.2015.12.004

    authors: Holec M,Nagahama Y,Kovach C,Joshi C

    更新日期:2016-06-01 00:00:00

  • EEG correlation of improvement in hemolytic-uremic syndrome after plasma infusion.

    abstract::We report a previously undescribed electroencephalographic pattern of epochs of diffuse delta background (85-240 sec) alternating with epochs of classic "burst suppression" (90-270 sec) in a 13-month-old girl with hemolytic-uremic syndrome. A dramatic electroencephalographic improvement was evident on continuous monit...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/0887-8994(90)90120-p

    authors: Pascual-Leone A,Dhuna AK,Janousek ST,Talwar D

    更新日期:1990-07-01 00:00:00

  • Neurofibromatosis type 1 associated with moyamoya syndrome in children.

    abstract:BACKGROUND:Vascular abnormalities in neurofibromatosis type 1 may arise anywhere in the cardiovascular system, and cerebrovascular involvement is the predominant feature of moyamoya syndrome. Because neurofibromatosis type 1 is a neurocutaneous disorder and routine follow-up with cranial MRI is not standard practice in...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2013.04.007

    authors: Duat-Rodríguez A,Carceller Lechón F,López Pino MÁ,Rodríguez Fernández C,González-Gutiérrez-Solana L

    更新日期:2014-01-01 00:00:00

  • Cortical atrophy and cognitive performance in infantile nephropathic cystinosis.

    abstract::A group of children and adolescents with infantile nephropathic cystinosis underwent cognitive testing and were examined for cortical atrophy using magnetic resonance imaging or computed tomography. Ten of 11 patients demonstrated cortical atrophy. A consistent pattern of lower cognitive performance was found in patie...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/0887-8994(90)90004-k

    authors: Nichols SL,Press GA,Schneider JA,Trauner DA

    更新日期:1990-11-01 00:00:00

  • Recurrent Fat Embolic Strokes in a Patient With Duchenne Muscular Dystrophy With Long Bone Fractures and a Patent Foramen Ovale.

    abstract:BACKGROUND:Individuals with Duchenne muscular dystrophy have an increased risk of long bone fractures. Such fractures are sometimes associated with brain dysfunction due to fat embolism syndrome, although this syndrome has seldom been documented in muscular dystrophy patients. PATIENT DESCRIPTION:We describe a child w...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2016.05.013

    authors: Bugnitz CJ,Cripe LH,Lo WD,Flanigan KM

    更新日期:2016-10-01 00:00:00

  • The influence of excessive chewing gum use on headache frequency and severity among adolescents.

    abstract:BACKGROUND:Excessive gum-chewing is underreported as a headache precipitant in children and adolescents. We evaluated the influence of daily excessive gum-chewing in older children and teenagers with chronic headache, emphasizing the impact of habit discontinuation and its reintroduction. METHODS:Patients with chronic...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2013.08.015

    authors: Watemberg N,Matar M,Har-Gil M,Mahajnah M

    更新日期:2014-01-01 00:00:00

  • Multiplex ligation-dependent probe amplification to subtelomeric rearrangements in idiopathic intellectual disability in Colombia.

    abstract:BACKGROUND:A cause cannot be determined in 30% to 50% of patients with intellectual disability. Determining the etiology of intellectual disability is important and useful for pediatric neurologists, geneticists, pediatricians, and patients' families because it allows assessment of recurrence risk, appropriate genetic ...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2013.10.017

    authors: Medina A,Piñeros L,Arteaga C,Velasco H,Izquierdo A,Giraldo A,Espinosa E

    更新日期:2014-03-01 00:00:00

  • Brain death secondary to arteriovenous hemangioma of the forearm.

    abstract::We describe the association of brain death in an infant with a large cutaneous hemangioma of the forearm. The irreversible cerebral injury is presumed to be secondary to cerebral hypoperfusion as a result of a combination of systemic hypotension and a systemic vascular "steal" phenomenon caused by the cutaneous hemang...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/0887-8994(90)90083-d

    authors: Hamvas A,Perlman JM,Volpe JJ

    更新日期:1990-01-01 00:00:00

  • Neuroimaging features in a neonate with rhizomelic chondrodysplasia punctata.

    abstract::Rhizomelic chondrodysplasia punctata is a rare genetic disorder of peroxisomal metabolism that is characterized clinically by shortening of the proximal limbs, cataracts, a characteristic facial appearance, failure to thrive, and psychomotor retardation. This report describes a newborn with a severe phenotype whose ne...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2007.07.006

    authors: Goh S

    更新日期:2007-11-01 00:00:00

  • Prevalence of tics in schoolchildren in central Spain: a population-based study.

    abstract::Tic disorders constitute a neurodevelopmental disorder of childhood. This study sought to determine the prevalence of tic disorders in a school-based sample. A randomized sample of 1158 schoolchildren, based on clusters (classrooms) in the province of Burgos (Spain), was identified on a stratified sampling frame combi...

    journal_title:Pediatric neurology

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.pediatrneurol.2011.03.003

    authors: Cubo E,Gabriel y Galán JM,Villaverde VA,Velasco SS,Benito VD,Macarrón JV,Guevara JC,Louis ED,Benito-León J

    更新日期:2011-08-01 00:00:00

  • Neuroimaging in the evaluation of children and adolescents with intractable epilepsy: II. Neuroimaging and pediatric epilepsy surgery.

    abstract::The costs of epilepsy encompass all aspects of life, including medical, educational, and psychosocial. Adults with intractable epilepsy who undergo epilepsy surgery and have seizure-free outcomes still have significant barriers in the attainment of improved quality of life. For this reason, there is increasing interes...

    journal_title:Pediatric neurology

    pub_type: 杂志文章,评审

    doi:10.1016/s0887-8994(97)00170-7

    authors: Zupanc ML

    更新日期:1997-09-01 00:00:00

  • Association of the nicotinic receptor beta 2 subunit and febrile seizures.

    abstract::The nicotinic acetylcholine receptors are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. Mutations in neuronal nicotinic acetylcholine receptor beta 2 subunit have been associated with autosomal dominant nocturnal frontal lobe epilepsies. A major challenge is t...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2003.08.001

    authors: Peng CT,Chou IC,Li CI,Hsu YA,Tsai CH,Tsai FJ

    更新日期:2004-03-01 00:00:00

  • Acute cerebellar swelling in varicella encephalitis.

    abstract::A 4-year-old male developed encephalitis 2 weeks after the onset of varicella. During his evaluation neuroradiologic procedures documented cerebellar edema and demyelination. Cerebrospinal fluid titers confirmed varicella encephalitis. To our knowledge, this patient is the first reported with focal cerebellar edema, a...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/0887-8994(88)90054-9

    authors: Hurst DL,Mehta S

    更新日期:1988-03-01 00:00:00

  • Ryanodine myopathies without central cores--clinical, histopathologic, and genetic description of three cases.

    abstract:BACKGROUND:Mutations in ryanodine receptor 1 gene (RYR1) are frequent causes of myopathies. They classically present with central core disease; however, clinical variability and histopathologic overlap are being increasingly recognized. PATIENTS:Patient 1 is a 15-year-old girl with mild proximal, four-limb weakness fr...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2014.04.024

    authors: Rocha J,Taipa R,Melo Pires M,Oliveira J,Santos R,Santos M

    更新日期:2014-08-01 00:00:00

  • Acquired microcephaly in blepharophimosis-ptosis-epicanthus inversus syndrome because of an interstitial 3q22.3q23 deletion.

    abstract:BACKGROUND:Blepharophimosis-ptosis-epicanthus inversus syndrome is an autosomal dominant condition because of mutations or deletions of the FOXL2 gene. Microcephaly is not associated with FOXL2 mutations but has been reported in individuals with chromosome 3q deletions, which include the FOXL2 gene and other contiguous...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2014.01.055

    authors: Dean SJ,Holden KR,Dwivedi A,Dupont BR,Lyons MJ

    更新日期:2014-06-01 00:00:00

  • The Utilization of Nerve Transfer for Reestablishing Shoulder Function in the Setting of Acute Flaccid Myelitis: A Single-Institution Review.

    abstract:BACKGROUND:Acute flaccid myelitis (AFM) is a rare disease of young children. The typical presentation involves acute-onset flaccid paralysis in one or more extremities with a nonspecific viral prodrome. Long-term outcomes demonstrate that functional recovery plateaus around six to nine months. The purpose of this study...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2020.06.016

    authors: Paziuk TM,Tadley M,Aversano M,Kozin SH,Zlotolow DA

    更新日期:2020-10-01 00:00:00

  • Rett syndrome: clinical and electrophysiologic aspects.

    abstract::Rett syndrome is a neurodevelopmental disorder that almost exclusively affects females. The clinical course as well as the electroencephalogram pattern are characteristic and have been correlated to the clinical stages of the disease. Sixty to 70 percent of the patients develop epilepsy. The aim of this retrospective ...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2006.10.003

    authors: Moser SJ,Weber P,Lütschg J

    更新日期:2007-02-01 00:00:00

  • Hemiconvulsion-hemiplegia-epilepsy syndrome associated with CACNA1A S218L mutation.

    abstract::Hemiconvulsion-hemiplegia-epilepsy syndrome involves sudden and prolonged unilateral seizures, followed by transient or permanent hemiplegia and epilepsy during infancy or early childhood. Some patients with familial hemiplegic migraine and demonstrating the S218L mutation in CACNA1A experience severe attacks with uni...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2011.04.010

    authors: Yamazaki S,Ikeno K,Abe T,Tohyama J,Adachi Y

    更新日期:2011-09-01 00:00:00

  • Dandy-Walker cyst associated with occipital meningocele.

    abstract::Dandy-Walker cyst associated with occipital meningocele is very rare. Only 12 patients have been reported. We report a female infant with Dandy-Walker cyst and occipital meningocele whose diagnosis was suspected antenatally by in utero ultrasonography. At birth, head circumference was normal for 37 weeks gestation. Sh...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/0887-8994(89)90071-4

    authors: Suzuki Y,Mimaki T,Tagawa T,Seino Y,Ohmichi M,Sugita N,Morimoto K,Yoshimine T

    更新日期:1989-05-01 00:00:00

  • Clinical features of developmental disability associated with cerebellar hypoplasia.

    abstract::Sporadic nonsyndromic cerebellar hypoplasia is a radiological diagnosis with clinical features and a relation with developmental disability that are presently not known. Through a retrospective review of a comprehensive standardized computerized database containing more than 2,500 patients examined consecutively by a ...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/s0887-8994(96)00220-2

    authors: Shevell MI,Majnemer A

    更新日期:1996-10-01 00:00:00

  • Recurrent intracranial ependymoma in children: salvage therapy with oral etoposide.

    abstract::Chronic oral VP-16 (etoposide) is a chemotherapy regimen with a wide application in oncology and documented efficacy against germ cell tumors, lymphomas, Kaposi's sarcoma, and primary brain tumors. This study was performed to assess the toxicity and activity of chronic oral etoposide in the management of children with...

    journal_title:Pediatric neurology

    pub_type: 临床试验,杂志文章

    doi:10.1016/s0887-8994(00)00249-6

    authors: Chamberlain MC

    更新日期:2001-02-01 00:00:00

  • Methylphenidate effects on global and complex measures of EEG.

    abstract::Methylphenidate (MPH) effects on global and complex measures of electroencephalography were examined in boys with attention-deficit-hyperactivity disorder between the ages of 9 and 11 years. Electroencephalogram (EEG) data were collected separately from the administration of a continuous performance task and were eval...

    journal_title:Pediatric neurology

    pub_type: 临床试验,杂志文章

    doi:10.1016/s0887-8994(99)00052-1

    authors: Lubar JF,White JN Jr,Swartwood MO,Swartwood JN

    更新日期:1999-09-01 00:00:00

  • Short term effects of valproate on infantile spasms.

    abstract::Although valproic acid (VPA) is used to treat infantile spasms, VPA's efficacy in infantile spasms has not been determined in a controlled study. This study evaluated the effect of VPA on infantile spasms in patients who had not responded to adrenocorticotropin (ACTH) and corticosteroid therapy. The hypotheses were te...

    journal_title:Pediatric neurology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/0887-8994(85)90006-2

    authors: Dyken PR,DuRant RH,Minden DB,King DW

    更新日期:1985-01-01 00:00:00

  • Overstimulation of nerve growth factors in postinfectious and autoimmune diseases.

    abstract::Nerve growth factor (NGF) in cerebrospinal fluid was measured by ELISA in ten children with postinfectious diseases and in five children with diseases suggested to be of autoimmune etiology. Three groups of patients were studied: (1) those with moderately elevated concentrations (50.67 +/- 17.02 pg/mL, mean and SEM), ...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/s0887-8994(97)00204-x

    authors: Riikonen RS,Söderström S,Korhonen LT,Lindholm DB

    更新日期:1998-03-01 00:00:00

  • Subclinical rhythmic EEG discharge of adults: SREDA in two children.

    abstract::Subclinical rhythmic electroencephalogram (EEG) discharge is an uncommon rhythmic EEG pattern that has been reported to occur in adults. It is thought to be a nonspecific finding with little clinical significance. This article reports this EEG pattern in two children and suggests it be called subclinical rhythmic EEG ...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/s0887-8994(01)00238-7

    authors: Nagarajan L,Gregory PB,Hewitt IK,Gubbay SS,Parry TS

    更新日期:2001-04-01 00:00:00

  • Idiopathic unilateral paralysis of the palate in childhood.

    abstract::Idiopathic soft palate paralysis is an isolated clinical entity of unknown cause. Typical clinical features are sudden onset, rhinolalia, and nasal escape of fluids from the ipsilateral nostril. The disorder affects mainly male children at the ages of 2 to 3 years and resolves spontaneously. This report presents a 5-y...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2005.02.014

    authors: Alp H,Tan H,Altunkaynak S,Orbak Z

    更新日期:2005-08-01 00:00:00

  • Pathophysiology and neuroprotection of global and focal perinatal brain injury: lessons from animal models.

    abstract:BACKGROUND:Arterial ischemic stroke occurs more frequently in term newborns than in the elderly, and brain immaturity affects mechanisms of ischemic injury and recovery. The susceptibility to injury of the brain was assumed to be lower in the perinatal period as compared with childhood. This concept was recently challe...

    journal_title:Pediatric neurology

    pub_type: 杂志文章,评审

    doi:10.1016/j.pediatrneurol.2015.01.016

    authors: Titomanlio L,Fernández-López D,Manganozzi L,Moretti R,Vexler ZS,Gressens P

    更新日期:2015-06-01 00:00:00

  • The effect of topiramate on body weight and ghrelin, leptin, and neuropeptide-Y levels of prepubertal children with epilepsy.

    abstract:BACKGROUND:Weight loss is one of the most frequent side effects of topiramate treatment. The aim of our study was to investigate the effect of topiramate on body mass index, serum glucose, insulin, cortisol, leptin, and neuropeptide-Y levels and the role of these variables on the pathogenesis of weight loss in prepuber...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/j.pediatrneurol.2014.05.001

    authors: Ozcelik AA,Serdaroglu A,Bideci A,Arhan E,Soysal Ş,Demir E,Gücüyener K

    更新日期:2014-08-01 00:00:00

  • Parry-Romberg syndrome associated with Adie's pupil and radiologic findings.

    abstract::We describe Adie's pupil and radiologic changes related to Parry-Romberg syndrome in a child who presented with facial hemiatrophy with no neurologic deficit. We suggest that cerebral lesions in Parry-Romberg syndrome without neurologic symptoms must be carefully investigated. ...

    journal_title:Pediatric neurology

    pub_type: 杂志文章

    doi:10.1016/s0887-8994(01)00333-2

    authors: Aynaci FM,Sen Y,Erdöl H,Ahmetoğlu A,Elmas R

    更新日期:2001-11-01 00:00:00

  • Congenital alopecia, seizures, and psychomotor retardation in three siblings.

    abstract::Three siblings, devoid of hair at birth, had an unusual autosomal recessive disorder characterized by universal congenital alopecia, microcephaly, seizures, psychomotor retardation, and severe growth failure. Metabolic and chromosome studies were normal. Skin biopsies disclosed immature hair follicles, some of which w...

    journal_title:Pediatric neurology

    pub_type: 杂志文章,评审

    doi:10.1016/0887-8994(87)90037-3

    authors: Wessel HB,Barmada MA,Hashida Y

    更新日期:1987-03-01 00:00:00