Constipation, antiepileptic drugs, and gingivitis in children and adolescents with cerebral palsy

Ferreira, Ana Cristina Fernandes Maria; Mayer, Márcia Pinto Alves; Kawamoto, Dione; Santos, Maria Teresa Botti Rodrigues

doi:10.1111/ipd.12488

Cited by 17 publications

(24 citation statements)

References 28 publications

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“…GMFCS is stratified into five levels of body mobility: Level I (walking without limitations), Level II (walking with limitations), Level III (walking using a hand-held mobility device), Level IV (self-mobility with limitations), and Level V (transported in a wheelchair) (6). Our previous studies demonstrated that out of 254 subjects, 50 (19.7%) had GMFCS I, II, or III while 204 (80.3%) presented GMFCS IV or V (7)(8)(9). Notably, epilepsy prevalence increases in spastic CP subjects at the highest GMFCS classifications (IV and V) (10).…”

Section: Introductionmentioning

confidence: 99%

“…Constipation is caused by multiple factors including: (1) reduced intake of fiber and liquids (responsible for the digestive system functioning) (11), (2) central nervous system damage (12), (3) mobility reduction (13), (4) and/or the use of antiepileptic drugs (AEDs) (11,14). In subjects using AEDs the incidence of gut constipation is elevated (7). Other side effects co-occurring with gastrointestinal complications include oral dysbiosis, gingival bleeding (GB), and an increase of systemic inflammation (15).…”

Section: Introductionmentioning

confidence: 99%

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The Impact of Oral-Gut Inflammation in Cerebral Palsy

et al. 2021

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Background: Oral-gut inflammation has an impact on overall health, placing subjects at risk to acquire chronic conditions and infections. Due to neuromotor disturbances, and medication intake, cerebral palsy (CP) subjects present intestinal constipation, impacting their quality of life (QOL), We aimed to investigate how oral inflammatory levels predicted gut phenotypes and response to therapy.Methods: A total of 93 subjects aging from 5 to 17 years were included in the study, and assigned into one of the 4 groups: CP with constipation (G1, n = 30), CP without constipation (G2, n = 33), and controls without CP with constipation (G3, n = 07) and without CP and without constipation (G4, n = 23). In addition to characterizing subjects' clinical demographics, medication intake, disease severity levels, salivary cytokine levels [TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-10], and Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Statistical significance was evaluated by Shapiro-Wilks, Student's T-Test, ANOVA, and ANCOVA analysis.Results: Salivary proinflammatory cytokines were highly correlated with the severe form of gut constipation in G1 (P < 0.001), and out of all cytokines IL-1β levels demonstrated highest correlation with all gut constipation (P < 0.05). A significant relationship was found between the type of medication, in which subjects taking Gamma-Aminobutyric Acid (GABA) and GABA+ (GABA in association with other medication) were more likely to be constipated than the other groups (P < 0.01). Cleary salivary inflammatory levels and gut constipation were correlated, and impacted QOL of CP subjects. G1 presented a lower QOL mean score of CPCHILD (49.0 ± 13.1) compared to G2 (71.5 ± 16.7), when compared to G3 (88.9 ± 7.5), and G4 (95.5 ± 5.0) (P < 0.01). We accounted for gingival bleeding as a cofounder of oral inflammation, and here were no differences among groups regarding gender (P = 0.332) and age (P = 0.292).Conclusions: Collectively, the results suggest that saliva inflammatory levels were linked to gut constipation, and that the clinical impact of medications that controlled gut was reliably monitored via oral cytokine levels, providing reliable and non-invasive information in precision diagnostics.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Impact of Oral-Gut Inflammation in Cerebral Palsy

et al. 2021

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“…The first study, which evaluated the association between intestinal constipation, use of antiepileptic drugs (AEDs), and gingivitis in subjects with spastic CP, was published by our work group (Figure 2) [35]. It was clearly demonstrated an association between intestinal constipation and the use of GABA antiepileptic drugs (phenobarbital, primidone, benzodiazepines including diazepam, lorazepam, and clonazepam; topiramate, felbamate, ezogabine); GABA transporter tiagabine GABA transaminase (vigabatrin); synaptic release machinery SV2A (levetiracetam, brivaracetam α2δ gabapentin, gabapentin enacarbil, pregabalin).…”

Section: Epilepsymentioning

confidence: 99%

Brain Injury and Neuroinflammation of the Gut-Brain Axis in Subjects with Cerebral Palsy

Ferreira¹,

Freire²,

Siqueira³

et al. 2021

Advancement and New Understanding in Brain Injury

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Cerebral Palsy (CP) is a limiting deficiency, characterized by a permanent neuromotor disorder which affects movements, resulting in non-progressive lesions of the immature brain during the neuro psychomotor stages. Epidemiological studies of premature births correlated with the presence of high levels of inflammation in the umbilical cord, amniotic fluid, and fetal blood, being that one of the most relevant underlying physiopathological mechanisms includes inflammation and intra-amniotic infection, with inflammatory response and damage to the developing brain. Recently attributed to the excessive production of cytokines, CP inflammation is mostly modulated through diet restriction, intestinal dysfunction, and drug intake. The high prevalence of convulsive crises in individuals with CP (77%) on its own does not bring about post inflammatory and post convulsive cytokine synthesis, treated with antiepileptic medication. In these individuals, there is high incidence of intestinal constipation (47%), besides oral dysbiosis, gingival bleeding and even greater increase in chronic inflammation. The dysbiosis causes an increase in mucous permeability (leaky-gut) of the gut-brain axis, and increase in seric endotoxin, demonstrating a persistent inflammatory state, and supporting the emergence of new side effects, which can become the object of future research.

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“…Constipation may be caused by multiple components including: 1) reduced intake of fiber and liquids (responsible for the digestive system functioning) [13], 2) central nervous system damage [14], 3) mobility reduction [15], 4) and/or the use of AEDs [13,16]. In subjects using AEDs the incidence of constipation is elevated [7]. Other side effects co-occurring with the gastrointestinal complications include oral dysbiosis, gingival bleeding (GB), and increase of systemic inflammation [17].…”

Section: Introductionmentioning

confidence: 99%

“…GMFCS is stratified into five levels of body mobility: Level I (walks without limitations), Level II (walks with limitations), Level III (walks using a hand-held mobility device), Level IV (self-mobility with limitations) and Level V (transported in a wheelchair) [6]. Our previous studies demonstrated that out of 254 subjects, 50 (19.7%) subjects had GMFCS I, II or III while 204 (80.3%) presented GMFCS IV or V [7–9]. These proportion results reflect on the population of this current cohort.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Inflammatory Factors Influencing Constipation and Quality of Life in Cerebral Palsy

Acf

Freire

et al. 2019

Preprint

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Introduction: Intestinal constipation is a clinical consequence, secondary to neuromotor disturbances, which acts on subjects with cerebral palsy (CP). The aim of this study was to investigate the factors influencing constipation and the quality of life (QOL) of CP subjects. Materials and methods: We recruited a total of 63 subjects aging from 5-17 years with spastic CP who received physical rehabilitation. The subjects were divided into two groups including with and without constipation. Subjects were assigned into one of the 4 groups (G1-4) based on the prevalence of 1) CP and 2) Constipation. Subjects were assigned as CP with constipation (G1), CP without constipation (G2), and controls without CP with constipation (G3) and without CP and without constipation (G4). Subject demographics, use of antiepileptic drugs (AEDs), motor function, caregiver priorities and child health index of life with disabilities (CPCHILD) were included. In addition to medical metadata, a subset of subjects was evaluated for oral and systemic inflammation through gingival bleeding and serum cytokine levels (TNF-alpha, IL-1 beta, IL-6, IL-8, IL-10) respectively. Statistical significance was evaluated by ANOVA One-Way (parametric data) and Kruskal Wallis (non-parametric data). Results: A significant relationship was found between the type of medication and constipation. Subjects taking GABA and GABA+ (GABA in association with other medication) were more likely to be constipated than the other groups (P < 0.01). Additionally, quality of life was directly correlated with constipation; subjects in G1 presented the lower mean score of CPCHILD (49.0 SD13.1) compared to G2 (71.5 SD 16.7) when compared to G3 (88.9 SD 7.5), and G4 (95.5 SD5.0) (P < 0.01). Inflammation was more severe for patients in G1 (P < 0.001). There were no differences among groups regarding gender (P = 0.332) and age (P = 0.292). Conclusions: Our results suggest that constipation was mostly affected by the use of certain antiepileptic drugs, namely GABA. This showed a direct detrimental effect on CP quality of life, which was influenced by inflammatory cytokines and the dosage and type of AEDs.

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Constipation, antiepileptic drugs, and gingivitis in children and adolescents with cerebral palsy

Cited by 17 publications

References 28 publications

The Impact of Oral-Gut Inflammation in Cerebral Palsy

The Impact of Oral-Gut Inflammation in Cerebral Palsy

Brain Injury and Neuroinflammation of the Gut-Brain Axis in Subjects with Cerebral Palsy

Clinical and Inflammatory Factors Influencing Constipation and Quality of Life in Cerebral Palsy

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