Intrathecal baclofen for multiple sclerosis related spasticity: A twenty year experience

Sammaraiee, Yezen; Yardley, Martin; Keenan, Liz; Buchanan, Katrina; Stevenson, VL; Farrell, Rachel

doi:10.1016/j.msard.2018.10.009

Cited by 31 publications

(27 citation statements)

References 25 publications

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“…The exact dosage utilized in the test injection was based on clinical expertise with the goal to effectively alleviate spasticity without compromising ambulation or transfer abilities. 10 The dose was finalized on the morning of the test based on clinical evaluations by a physiatrist and a physical therapist (PT). The patients were counseled extensively on the risks, benefits and goals for ITB treatment.…”

Section: Methodsmentioning

confidence: 99%

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Long-term outcomes of intrathecal baclofen in ambulatory multiple sclerosis patients: A single-center experience

et al. 2020

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Background: Intrathecal baclofen (ITB) is traditionally reserved for non-ambulatory patients. Objective: To investigate outcomes of ITB in ambulatory multiple sclerosis (MS) patients. Methods: Changes in outcome measures were estimated by a mixed effect model, while the complication rate was calculated using a logistic regression. Predictors of non-ambulatory status were identified by Cox model. Results: In all, 256 patients received an ITB test injection and 170 underwent ITB surgery. Aggregate Modified Ashworth Scale (MAS) scores for the ambulatory ITB cohort decreased from 13.5 ± 6.96 to 4.54 ± 4.18 at 5 years ( p < 0.001). There was no significant change in walking speed 1 year post ITB surgery (0.45 m/second ± 0.30 vs 0.38 m/second ± 0.39, p = 0.80) with 77.8% of patients remaining ambulatory which decreased to 41.7% at year 5. Longer MS disease duration (hazard ratio (HR): 1.04; 95% confidence interval (CI): 1.01–1.07; p = 0.018) and lower hip flexor strength (HR: 0.40; 95% CI: 0.27–0.57; p < 0.001) predicted non-ambulatory status after surgery. Complications were more likely in the ambulatory cohort (odds ratio (OR): 3.30, 95% CI: 2.17–5.02; p = 0.017). Conclusion: ITB is effective for ambulatory MS patients without compromising short-term walking speed, although a higher complication rate was observed in this cohort.

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Section: Methodsmentioning

confidence: 99%

“…As such, there is a concern that reducing spasticity in these ambulatory patients could compromise their future physical function. 8–11…”

Section: Introductionmentioning

confidence: 99%

Long-term outcomes of intrathecal baclofen in ambulatory multiple sclerosis patients: A single-center experience

et al. 2020

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“…This is mitigated to a certain extent by receptor reserve so that even if only a few receptors are available, they will still be sufficient for a significant biological effect. Reassuringly, baclofen, a GABA(B) receptor agonist that activates the Gi cascade shows sustained long-term efficacy when used to treat spasticity (Sammaraiee et al, 2019).…”

Section: Chemogeneticsmentioning

confidence: 99%

Optogenetic and chemogenetic therapies for epilepsy

Walker

Kullmann

2020

Neuropharmacology

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“…[8][9][10] It is implicated in neurological and neuropsychiatric disorders, including spasticity, epilepsy, pain, addiction, and anxiety. 11,12 GABA B receptor is an important target for two drugs on the market, baclofen used to treat spasticity in multiple sclerosis patients 13 and alcoholism, 14 and GHB used for treating narcolepsy. 15 Moreover, recent studies have revealed the GABA B receptor can be the target of auto-antibodies epilepsies and encephalitis.…”

Section: Introductionmentioning

confidence: 99%

Structural basis for distinct quality control mechanisms of GABA _B receptor during evolution

Zhang

Xue

et al. 2020

FASEB j.

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Cell surface trafficking of many G protein-coupled receptors is tightly regulated. Among them, the mandatory heterodimer GABA B receptor for the main inhibitory neurotransmitter, γ-aminobutyric acid (GABA), is a model. In mammals, its cell surface trafficking is highly controlled by an endoplasmic reticulum retention signal in the C-terminal intracellular region of the GB1 subunit that is masked through a coiled-coil interaction with the GB2 subunit. Here, we investigate the molecular basis for the export of its homolog in Drosophila melanogaster that regulates the circadian rhythm and sleep. In contrast to mammals, the endoplasmic retention signal is carried by GB2, while GB1 reaches the cell surface alone. NMR analysis showed that the coiled-coil domain that controls GABA B heterodimer formation is structurally conserved between flies and mammals, despite specific features. These findings show the adaptation of a similar quality control system during evolution for maintaining the subunit composition of a functional heterodimeric receptor.

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Intrathecal baclofen for multiple sclerosis related spasticity: A twenty year experience

Cited by 31 publications

References 25 publications

Long-term outcomes of intrathecal baclofen in ambulatory multiple sclerosis patients: A single-center experience

Long-term outcomes of intrathecal baclofen in ambulatory multiple sclerosis patients: A single-center experience

Optogenetic and chemogenetic therapies for epilepsy

Structural basis for distinct quality control mechanisms of GABA _B receptor during evolution

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Intrathecal baclofen for multiple sclerosis related spasticity: A twenty year experience

Cited by 31 publications

References 25 publications

Long-term outcomes of intrathecal baclofen in ambulatory multiple sclerosis patients: A single-center experience

Long-term outcomes of intrathecal baclofen in ambulatory multiple sclerosis patients: A single-center experience

Optogenetic and chemogenetic therapies for epilepsy

Structural basis for distinct quality control mechanisms of GABA B receptor during evolution

Contact Info

Product

Resources

About

Structural basis for distinct quality control mechanisms of GABA _B receptor during evolution