Intraventricular Baclofen Research Articles

Intraventricular baclofen for intractable spasticity and secondary dystonia: a frame-based stereotactic approach and case series

ObjectiveIntraventricular baclofen has been reported as an alternative to intrathecal baclofen for managing refractory spasticity and dystonia in some circumstances. In this report, we described a frame-based stereotactic approach for precisely positioning of the infusion catheter into the third ventricle.Material and methodsHigh resolution contrast-enhanced anatomical MR sequences was acquired prior to surgery for pre-planning. Catheter trajectory was planned to pass from the lateral ventricle to the third ventricle through the Foramen of Monro. The surgical procedure was adapted from the frame-based deep brain stimulation surgery. The Touch-Loc kit (SceneRay, China) was used to temporarily secure the catheter in place during the surgery. From July 2022 to December 2022, three patients suffering from intractable spasticity and/or secondary dystonia received IVB successfully using the described technique.ResultsNo severe adverse events, including death, intracranial hemorrhage, infection, catheter migration or fracture, were documented at the last follow-up (range: 12‒24 months). Transient side effects included mild nausea following the initiation of infusion or the increase in infusion rate. All three patients responded to the IVB.ConclusionsThe described frame-based stereotactic technique for IVB catheter implant is feasible and could be quickly mastered by neurosurgeons in related fields. Larger prospective cohorts with longer follow-up periods are necessary to further evaluate the long-term safety and efficacy of this procedure.

History and evolution of surgical treatment for spasticity: a journey from neurotomy to selective dorsal rhizotomy.

The evolution of neurosurgical approaches to spasticity spans centuries, marked by key milestones and innovative practitioners. Probable ancient descriptions of spasmodic conditions were first classified as spasticity in the 19th century through the interventions of Dr. William John Little on patients with cerebral palsy. The late 19th century witnessed pioneering efforts by surgeons such as Dr. Charles Loomis Dana, who explored neurotomies, and Dr. Charles Sherrington, who proposed dorsal rhizotomy to address spasticity. Dorsal rhizotomy rose to prominence under the expertise of Dr. Otfrid Foerster but saw a decline in the 1920s due to emerging alternative procedures and associated complications. The mid-20th century saw a shift toward myelotomy but the revival of dorsal rhizotomy under Dr. Claude Gros' selective approach and Dr. Marc Sindou's dorsal root entry zone (DREZ) lesioning. In the late 1970s, Dr. Victor Fasano introduced functional dorsal rhizotomy, incorporating electrophysiological evaluations. Dr. Warwick Peacock and Dr. Leila Arens further modified selective dorsal rhizotomy, focusing on approaches at the cauda equina level. Later, baclofen delivered intrathecally via an implanted programmable pump emerged as a promising alternative around the late 1980s, pioneered by Richard Penn and Jeffrey Kroin and then led by A. Leland Albright. Moreover, intraventricular baclofen has also been tried in this matter. The evolution of these neurosurgical interventions highlights the dynamic nature of medical progress, with each era building upon and refining the work of significant individuals, ultimately contributing to successful outcomes in the management of spasticity.

Intraventricular baclofen for palliative management of acquired generalized dystonia in pediatric patients: a case series and literature review.

Dystonia represents a significant source of disability in children. Generalized dystonia, which involves multiple body regions, leads to impaired mobility and motor function, resulting in substantial challenges in daily activities. Surgical treatments are used when medical treatments fail. Intrathecal baclofen (ITB) or deep brain stimulations (DBS) are the most employed surgical therapies. When these options are not feasible or ineffective, some authors have explored the use of intraventricular baclofen (IVB). In this report, we present four cases of pediatric patients with generalized dystonia who underwent treatment with IVB, resulting in notable improvements. To further explore the potential of this treatment modality, we conducted a comprehensive literature review. The findings from our study provide a comprehensive overview that can guide palliative management in similar cases.

Spasticity and movement disorders in cerebral palsy.

To review the neurosurgical treatments of children with movement disorders associated with cerebral palsy (CP) during the previous decades, up to the present day. An extensive literature review was undertaken to identify important publications about this subject. My experience treating children with these disorders over the past three decades was included in the individual sections. Peripheral neurotomies have been developed for children with focal spasticity. For those with spastic paraparesis, selective lumbar rhizotomies were developed, and for those with spastic quadriparesis, intrathecal baclofen infusions were developed. Both effectively alleviate spasticity in the affected extremities. Generalized dystonia associated with CP has been treated with deep brain stimulation with mild improvement, but treatment with intrathecal baclofen and intraventricular baclofen improve those movements markedly. No effective treatment has been reported for children with athetoid CP. For those with choreiform CP, deep brain stimulation may be effective but intrathecal baclofen does not appear to be. Treatment of children with movement disorders associated with CP increased slowly in the 1970s and 1980s but accelerated rapidly in the 1990s with the introduction of lumbar dorsal rhizotomies and intrathecal baclofen. In the last 30years, tens of thousands of children with spasticity and movement disorders associated with CP have been treated by pediatric neurosurgeons, and their care has become an integral component of current pediatric neurosurgical practice.

Deep brain stimulation and intrathecal/intraventricular baclofen for glutaric aciduria type 1: A scoping review, individual patient data analysis, and clinical trials review.

Glutaric aciduria type 1 (GA1) is an autosomal recessive disease frequently leading to dystonia. Deep brain stimulation (DBS), intrathecal baclofen (ITB), and intraventricular baclofen (IVB) are the current interventional treatment options for refractory dystonia. We performed a scoping review, individual patient data (IPD) analysis, and clinical trials review to summarize the existing literature on these interventions in this population, characterize outcomes, and suggest directions for future investigation. PubMed, Embase, and Scopus were searched following PRISMA guidelines. IPD were extracted from studies providing IPD for GA1 patients. ClinicalTrials.gov was reviewed. Of 139 articles, 7 studies with 10 patients were included. In study-level data, 2/4 (50.0%) DBS studies found no improvement in dystonia and 3/3 (100%) on baclofen found decreased dystonia and enteral medication regimen. In the IPD analysis, four studies with 5 patients (2 IVB, 2 DBS, 1 ITB) were included. The average percent reduction in dystonia was 29.9% ± 32.5% (median:18%, IQR:18%-29.2%). Function improved in 4 (80.0%) patients. All patients with reported changes in enteral dystonia-related medication regimen (3/3, 100%) reported reduction in medication usage. No patients (0%) had perioperative complications. Mean follow-up length was 14.8 ± 12.2 months. No interventional clinical trials were found. ITB, IVB, and DBS represent present neuromodulatory approaches for the treatment of GA1. ITB and IVB reduce dystonia, while DBS has a heterogeneous effect. ITB and IVB improved function and reduced enteral medication regimens. These findings must be viewed with caution considering limited data and a serious risk of bias. Further large-scale studies are necessary to determine indications for ITB, IVB, and DBS and elucidate treatment algorithms.

Prepontine baclofen catheter placement: A case report and technical illustration

BackgroundIntrathecal baclofen (ITB) is used for medically refractory spasticity and dystonia. There are times when intraventricular baclofen (IVB) is used as a last resort for patients who cannot tolerate or cannot receive intrathecal baclofen through a traditional route. We present a patient with a history of cerebral palsy and multiple ITB and IVB revisions who presented with medically refractory spasticity and severe autonomic storming. Other options are needed for patients with persistent autonomic storming, dystonia and spasticity following IVB and spinal intrathecal baclofen treatment. MethodsWe propose a technical variation and case illustration of a prepontine catheter placement through an endoscopic third ventriculostomy. Through this approach, a ventricular catheter was used to deliver baclofen into the intrathecal space. ResultsFollowing the procedure, the patient showed improvement in Ashworth score and autonomic storming. ConclusionThis technique could provide an alternative and superior therapeutic option to traditional catheter placement for intrathecal baclofen delivery.

Management of hypertonia in cerebral palsy.

The review provides an update on the treatment of hypertonia in cerebral palsy, including physical management, pharmacotherapy, neurosurgical, and orthopedic procedures. Serial casting potentiates the effect of Botulinum neurotoxin A injections for spasticity. Deep brain stimulation, intraventricular baclofen, and ventral and dorsal rhizotomy are emerging tools for the treatment of dystonia and/or mixed tone. The long-term results of selective dorsal rhizotomy and the timing of orthopedic surgery represent recent advances in the surgical management of hypertonia. Management of hypertonia in cerebral palsy targets the functional goals of the patient and caregiver. Treatment options are conceptualized as surgical or nonsurgical, focal or generalized, and reversible or irreversible. The role of pharmacologic therapies is to improve function and mitigate adverse effects. Further investigation, including clinical trials, is required to determine the role of deep brain stimulation, intraventricular baclofen, orthopedic procedures for dystonia, and rhizotomy.

Intraventricular baclofen therapy in refractory secondary dystonia-Indication, methodology, safety, and first results

Intraventricular baclofen therapy in refractory secondary dystonia-Indication, methodology, safety, and first results

Intraventricular baclofen as an alternative to intrathecal baclofen for intractable spasticity or dystonia: outcomes and technical considerations

The aim of this study was to identify the benefits of intraventricular baclofen (IVB) therapy for the treatment of intractable spasticity or dystonia in a subset of patients who had experienced multiple revisions while receiving intrathecal baclofen (ITB) therapy. The authors reviewed the charts of 22 consecutive patients with intractable spasticity or dystonia who initially underwent ITB therapy, subsequently suffered multiple revisions during ITB therapy, and ultimately received IVB therapy, all during a 12-year period from November 1998 to October 2010. The intraventricular catheters were positioned in the lateral ventricle, aided by stereonavigation. The surgical revision rate (the average number of surgical revisions per average number of follow-up years) during ITB therapy was 0.84, and was 0.50 during IVB therapy. The most frequent complication requiring surgical revision during ITB therapy was catheter occlusion, followed by pump malfunction/pump pocket issues, and infection. The most frequent complication requiring surgical revision during IVB therapy was infection, followed by catheter misplacement/migration. Four patients suffered infection that required removal of their intraventricular catheter, and currently have no baclofen system. Some of these patients had a history of increasing revisions with increasing frequency during ITB therapy. Such a history puts them at risk for spinal arachnoiditis, a condition that complicates further ITB therapy. For such patients, the authors believe that IVB therapy may be a beneficial therapeutic option, given that the surgical revision rate was lower for IVB than for ITB. Intraventricular baclofen may be a cost-effective option for patients with mounting revisions during ITB therapy.

Stereotactic endoscopic placement of third ventricle catheter for long-term infusion of baclofen in patients with secondary generalized dystonia

Continuous infusion of baclofen is a treatment option for severe generalized dystonia. Catheter insertion within the third ventricle has been described as an alternative to standard intrathecal placement to maximize intracranial concentrations of baclofen. The authors describe their experience with a novel technique for stereotactic endoscopic insertion of baclofen infusion catheters in the third ventricle in 3 patients with severe secondary generalized dystonia. Insertion was successful in all 3 patients, and all of them experienced significant improvement in dystonia scores on the Barry-Albright Dystonia Scale. Follow-up ranged from 5.5 to 7 months (mean 6 months), and no mechanical complications or CSF leaks were observed. The stereotactic endoscopic insertion of a baclofen infusion catheter into the third ventricle appears to be a safe method for continuous intraventricular baclofen infusion in patients with generalized secondary dystonia.

Intraventricular vs Intrathecal Baclofen for Secondary Dystonia

Intrathecal baclofen (ITB) is an effective treatment for secondary dystonia. However, in many patients with dystonia, placement of an intrathecal catheter is difficult because of anatomic anomalies or spinal fusion. Intraventricular baclofen (IVB) has been shown to be an effective alternate route for drug delivery in a small series of patients. To present the largest series of IVB cases to date and to compare the complication rate with that of a concurrent cohort of ITB cases. The senior author's series of IVB cases were reviewed. All contemporaneous cases of ITB for dystonia were reviewed as a control group. Data were collected by retrospective medical records review. Thirty IVB patients and 33 ITB patients were identified. Mean follow-up was 15 and 16 months, respectively. IVB patients were younger, were more commonly underweight, and had more severe dystonia, although no difference between groups was significant. Eleven patients (37%) in the IVB group and 16 patients (48%) in the ITB group experienced complications. Kaplan-Meier survival analysis showed an odds ratio of 0.67 (95% confidence interval, 0.30-1.48; P = .31) in favor of IVB. Adjusting for age and underweight status yielded an odds ratio of 0.64 (95% confidence interval, 0.29-1.42; P = .27) in favor of IVB. There were 7 catheter or leak-related complications in the ITB group and 2 in the IVB group (P = .15). This study shows that IVB is as safe as ITB. There may be a lower risk of catheter or leak-related complications with IVB, although this study was too small to show significance.

Technique for insertion of intraventricular baclofen catheters

Intraventricular baclofen (IVB) infusion has been used recently to treat secondary dystonia. Techniques of catheter implantation have not been thoroughly described. The object of this study was to describe a technique developed in the past 6 years to implant intraventricular catheters for baclofen infusion. Thirty-one patients underwent endoscopic placement of intraventricular catheters for IVB, primarily patients whose anatomy made implantation of intrathecal catheters difficult or inappropriate. Using the technique described, catheters were successfully inserted into the desired ventricular location in each patient. Catheters remained in the desired location in 29 of 31 cases. Catheters can be inserted into the cerebral ventricles for infusion of baclofen. The technique described herein has been associated with few complications.

Intraventricular baclofen for dystonia: techniques and outcomes

The aim of this study was to evaluate the use of intraventricular baclofen (IVB) for the treatment of severe generalized secondary and heredodegenerative dystonia. Nine children and 1 adult with severe dystonia unresponsive to multiple oral medications were treated with IVB. Intraventricular catheters were positioned endoscopically in the third ventricle. Eight of the 10 patients responded to IVB; their mean dystonia scores on the Barry-Albright dystonia scale decreased from 23 to 8. The 2 patients who did not respond had not responded to previous high doses of intrathecal baclofen. No adverse side effects related to IVB occurred. One child developed a pump infection that required pump removal, 1 developed a CSF infection that cleared after antibiotic administration, and 1 developed ventriculomegaly that required a shunt placement. Intraventricular baclofen is an effective method of infusing baclofen to treat severe, generalized secondary dystonia, and, at times, heredodegenerative dystonia. The site of baclofen's activity when treating dystonia may be at the cortical level, and intraventricular infusion may result in higher baclofen concentrations over the cortex than intrathecal infusion. Additional studies are necessary to determine whether IVB is effective at lower doses than those used with intrathecal baclofen administration.

Long-term intraventricular baclofen infusion in beagles

This study was designed to evaluate the clinical and histopathological effects of long-term (3-month) intraventricular baclofen (IVB) infusion in beagle dogs. Catheters were inserted stereotactically into the lateral ventricles of nine dogs and were connected to implanted Synchromed II pumps. Saline solution (control animals) and IVB (experimental animals) were infused continuously. The IVB dosages ranged from 100 to 1000 microg/day. An IVB infusion of 135 microg/day or less throughout a 3-month period was associated with no adverse side effects in any animal. Infusion of 150 microg/day produced overt seizures in one dog and produced adverse side effects in another; a reduction in the dosage given to these animals to 135 microg/day was tolerated with no adverse effects. Infusion of IVB at a dosage of 250, 500, or 1000 microg/day caused lethal toxicity within the first 4 days of infusion. Histopathological specimens obtained at necropsy revealed no ventricular or subependymal changes in animals receiving an IVB dosage of 135 microg/day or less. Intraventricular baclofen infusion in beagles has dose-related toxicity; however, no clinical or neurological toxicity was evidenced at clinically tolerated dosages (< or =135 microg/day) throughout 3 months of infusion.

Intraventricular baclofen infusion for dystonia

Two children with generalized dystonia were given continuous intraventricular baclofen (IVB) infusions. The first was a 12-year-old girl with mixed dystonia and spasticity caused by methylmalonic aciduria whose spinal anatomy precluded administration of intrathecal baclofen (ITB). The second was an 11-year-old boy whose dystonia was associated with cerebral palsy and had not improved significantly in response to conventional ITB treatment. The girl improved dramatically with IVB; the boy experienced no greater improvement from IVB than from ITB. No adverse effects were noted in either child during 2 to 6 months of infusion. These are the first reports of the use of IVB in this clinical setting. The results warrant additional investigation.

γ-Amino Butyric Acid Type B Receptors Stimulate Neutrophil Chemotaxis during Ischemia-Reperfusion

Serine/threonine kinase Akt, or protein kinase B, has been shown to regulate a number of neutrophil functions. We sought to identify Akt binding proteins in neutrophils to provide further insights into understanding the mechanism by which Akt regulates various neutrophil functions. Proteomic and immunoprecipitation studies identified gamma-amino butyric acid (GABA) type B receptor 2 (GABA(B)R2) as an Akt binding protein in human neutrophils. Neutrophil lysates subjected to Akt immunoprecipitation followed by immunoblotting with anti-GABA(B)R2 demonstrated Akt association with the intact GABA(B)R. Similar results were obtained when reciprocal immunoprecipitations were performed with anti-GABA(B)R2 Ab. Additionally, GABA(B)R2 and Akt colocalization was demonstrated by confocal microscopy. A GABA(B)R agonist, baclofen, activated Akt and stimulated neutrophil-directed migration in a PI3K-dependent manner, whereas CGP52432, a GABA(B)R antagonist blocked such effects. Baclofen, stimulated neutrophil chemotaxis and tubulin reorganization in a PI3K-dependent manner. Additionally, a GABA(B)R agonist failed to stimulate neutrophil superoxide burst. We are unaware of the association of GABA(B)R with Akt in any cell type. The present study shows for the first time that a brain-specific receptor, GABA(B)R2 is present in human neutrophils and that it is functionally associated with Akt. Intraventricular baclofen pretreatment in rats subjected to a stroke model showed increased migration of neutrophils to the ischemic lesion. Thus, the GABA(B)R is functionally expressed in neutrophils, and acts as a chemoattractant receptor via an Akt-dependent pathway. The GABA(B)R potentially plays a significant role in the inflammatory response and neutrophil-dependent ischemia-reperfusion injury such as stroke.