Intrathecal Baclofen Therapy

Intrathecal Baclofen Therapy

Intrathecal baclofen was first introduced in 1985 to manage childhood hypertonia. There has been an evolution in thought as to how candidates should be identified and what forms of hypertonia respond to this treatment.


Intrathecal baclofen (ITB) treatment is considered a powerful tool in the management of severe spasticity in neurological conditions such as multiple sclerosis, cerebral palsy, and traumatic spinal cord injury and brain injury.

Intrathecal baclofen (ITB) has been known to reduce spasticity which did not respond to oral medications and botulinum toxin treatment.

Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump.

For spasticity of spinal cord origin, ITB Therapy via an implantable infusion system should be reserved for patients unresponsive to oral baclofen or those who experience intolerable CNS side effects at effective doses. Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal baclofen therapy.

Berntsson et al., reported the potential beneficial effects of ITB treatment in patients with hereditary ataxia who also suffer from spasticity/spasms 1).

Screening test

A successful trial may confirm predetermined goals, which may include improved mobility/positioning, decreased time/improved independence for activities, less home exercise, better wheelchair tolerance, decreased caregiver time, improved sleep, and reduced pain, or may modify goals and expectations. Individuals should not be tested in the presence of active medical issues (e.g., MS exacerbations, active urinary tract infection, nonhealing wounds). Oral antispasmodics can be weaned before trial if a goal is to eliminate them. The standard baclofen test dose is a 50-mcg bolus, 25 mcg in very small children or patients who rely on spasticity for mobility. Patients unresponsive to the standard dose may require 75 mcg or 100 mcg; 24 hours should elapse between bolus doses. Cardiopulmonary parameters should be checked frequently during the first two hours postinjection, and spasticity measures assessed at least twice within four hours. Observation continues until the patient is stable and recovers from hypertonia. Adverse events include spinal headaches, nausea/vomiting, urinary retention, hypotension, seizures, drowsiness/sedation, respiratory depression, and coma. Before implantation, team members must discuss starting dose, drug concentration, delivery mode, pump size and location, and catheter tip placement. Patients/caregivers should understand the commitment necessary for ITB therapy 2).

Adverse events

Adverse events (AEs) related to intrathecal baclofen (ITB) therapy in adults, was relatively low. This has to be balanced against the clinical, functional and quality of life improvements, which are expected from ITB therapy 3).

This therapy is contraindicated in patients who are hypersensitive to baclofen. Implantation of the infusion system is contraindicated if the patient is of insufficient body size, requires a pump implant deeper than 2.5 cm, or, in the presence of spinal anomalies or active infection.

The most frequent drug adverse events vary by indication but include: hypotonia (34.7%), somnolence (20.9%), headache (10.7%), convulsion (10.0%), dizziness (8.0%), urinary retention (8.0%), nausea (7.3%), and paresthesia (6.7%). Pump system component failures leading to pump stall, or dosing/programming errors may result in clinically significant overdose or underdose. Acute massive overdose may result in coma and may be life threatening.

The most frequent and serious adverse events related to device and implant procedures are catheter dislodgement from the intrathecal space, catheter break/cut, and implant site infection including meningitis. Electromagnetic interference (EMI) and Magnetic resonance imaging (MRI) may cause patient injury, system damage, operational changes to the pump, and changes in flow rate.

Case series

The objective of a study of Berntsson et al., from Sweden was to assess the effectiveness of the ITB in patients with inherited ataxia suffering from severe painful spasms and/or spasticity.

A total of 5 patients with spinocerebellar ataxia 3 or 7 or Friedreich’s ataxia were included in this observational multicenter study. The patients were interviewed and completed outcome measures assessing pain (The Brief Pain Inventory), fatigue (Fatigue Severity Scale), and life satisfaction (LiSAT-9) before and 1 year after the treatment. Spasticity (Modified Ashworth Scale) and spasm frequency (SPFS) were measured objectively for each patient.

The mean treatment time was 1.9 years. Evaluation of established standard forms revealed symptomatic relief from spasticity, spasms, pain, and fatigue in addition to improved body posture, sleep, and life satisfaction after ITB treatment.

They reported the potential beneficial effects of ITB treatment in patients with inherited ataxia who also suffer from spasticity/spasms. ITB treatment indication in neurological disorders allows for extension to the treatment of spasticity/ spasms in patients with hereditary ataxia 4).


A study aimed to investigate beneficial and adverse effects of Intrathecal Baclofen (ITB) bolus injection and pump therapy in patients with cerebral palsy (CP) and to compare outcomes to patients with acquired brain injury such as traumatic brain injury and cerebral hypoxia. ITB test trials were performed in 37 patients (19 CP and 18 acquired brain injury). Based on ambulatory function, CP patients were divided into 2 groups: 11 patients with nonambulatory CP and 8 patients with ambulatory CP. Change of spasticity was evaluated using the Modified Ashworth Scale. Additional positive or negative effects were also evaluated after ITB bolus injection. In patients who received ITB pump implantation, outcomes of spasticity, subjective satisfaction and adverse events were evaluated until 12 months post-treatment. After ITB bolus injection, 32 patients (86.5%) (CP 84.2% versus acquired brain injury 88.9%) showed a positive response of reducing spasticity. However, 8 patients with CP had negative adverse effects. Particularly, 3 ambulatory CP patients showed standing impairment and 1 ambulatory CP patient showed impaired gait pattern such as foot drop because of excessive reduction of lower extremity muscle tone. Ambulatory CP patients received ITB pump implantation less than patients with acquired brain injury after ITB test trials (P = .003 by a chi-squared test). After the pump implantation, spasticity was significantly reduced within 1 month and the effect maintained for 12 months. Seventeen patients or their caregivers (73.9%) were very satisfied, whereas 5 patients (21.7%) suffered from adverse events showed no subjective satisfaction.

ITB therapy was effective in reducing spasticity in patients with CP and acquired brain injury. Before ITB pump implantation, it seems necessary to perform the ITB bolus injection to verify beneficial effects and adverse effects especially in ambulatory CP 5).


In a single center study Motta et al investigated the complications occurring before and after the introduction of the new Ascenda intrathecal catheter (Medtronic Inc.) in pediatric patients treated with intrathecal baclofen therapy (ITB) for spasticity and/or dystonia.

This was a retrospective review of 508 children who had received ITB, 416 with silicone catheters in the 13 years between September 1998 and September 2011 and 92 with Ascenda intrathecal catheters in the 3 years between September 2011 and August 2014. The authors evaluated major complications such as infections, CSF leaks treated, and problems related to the catheter or pump, and they compared the 2 groups of patients who had received either a silicone catheter or an Ascenda catheter implant. RESULTS One hundred twenty patients in the silicone group (29%) and 1 patient in the Ascenda group (1.1%; p < 0.001) had a major complication. In the silicone group 23 patients (5.5%) were affected by CSF leakage and 75 patients (18%) experienced 82 catheter-related events, such as occlusion, dislodgment, disconnection, or breakage, which required catheter replacement. In the Ascenda group, only 1 patient (1.1%) was affected by CSF leakage. CONCLUSIONS To the authors’ knowledge, this study is the first in the literature to compare the performance of the new Ascenda catheter, introduced in 2011, with the traditional silicone catheter for intrathecal drug infusion. In their analysis, the authors found that the Ascenda catheter can reduce major complications related to the catheter after ITB pump implantation. Further investigation is necessary to expand on and confirm their results 6).

Case reports

The case of a young woman who received intrathecal baclofen therapy (ITB) and subsequently became pregnant and had a normal delivery. A 28-year-old woman with flexion myelopathy had anterior decompression with fusion at C4/5 and C5/6 levels. Clinical symptoms improved after surgery. However, when she was 29 years old, her symptoms steadily advanced to Modified Ashworth Scale 3 spasticity level in the lower legs, with pain in both of them and urinary retention tendency. Since a 25 μg intrathecal baclofen injection improved her symptoms, an ITB pump system was implanted. After surgery, lower limb spasticity and urinary retention improved. Two years after ITB pump implantation, the patient married and became pregnant. The patient intended to have normal delivery but the induction of labor was ineffective and childbirth was completed by Cesarean section with lumbar anesthesia. The infant’s Apgar score was 8 at 1 min and 9 at 5 min, and birth-weight was 2,704 g. We measured the baclofen concentration in the patient’s breast milk using high-performance liquid chromatography/tandem mass spectrometry. The level of baclofen in the breast milk was very low (0.617 ng/ml) and the predicted pharmacological effect on the infant was judged to be negligible. No withdrawal symptoms or muscle tone abnormalities were found after birth. Our findings indicate that ITB therapy could be considered for young women with severe spasticity, even if they plan to have children 7).

A report describes the successful management of painful spasms in a 65-year-old woman with Friedreich’s ataxia (FA) via intrathecal baclofen (ITB) therapy following unsuccessful medical treatments.

To Kalyvas et al., knowledge, this is the third reported case in the literature. Unfortunately, the pathophysiological characteristics of muscle spasms in FA are not well explored and understood while the therapeutic mechanisms of the different treatments are rather vague. Taking into consideration the suggested spinal atrophy in FA, the clinical resemblance of FA and chronic spinal injury muscle spasms, together with the rapid ITB therapy effectiveness in alleviating FA muscle spasms, they attempted to suggest a putative pathophysiological mechanism acting at the spinal level and possibly explained by the presence of independent spinal locomotor systems producing muscle spasms. Specifically, overexcitement of these centers, due to loss of normal regulation from upper CNS levels, may result in the uncontrolled firing of secondary motor neurons and may be the key to producing muscle spasms. However, further research under experimental and clinical settings seems to be necessary 8).


1) , 4)

Berntsson SG, Gauffin H, Melberg A, Holtz A, Landtblom AM. Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms. Stereotact Funct Neurosurg. 2019 Mar 14:1. doi: 10.1159/000497165. [Epub ahead of print] PubMed PMID: 30870851.

Boster AL, Bennett SE, Bilsky GS, Gudesblatt M, Koelbel SF, McManus M, Saulino M. Best Practices for Intrathecal Baclofen Therapy: Screening Test. Neuromodulation. 2016 Aug;19(6):616-22. doi: 10.1111/ner.12437. Epub 2016 Jul 19. Review. PubMed PMID: 27434115.

Borrini L, Bensmail D, Thiebaut JB, Hugeron C, Rech C, Jourdan C. Occurrence of adverse events in chronic intrathecal baclofen infusion: a one-year follow-up study of 158 adults. Arch Phys Med Rehabil. 2014 Jan 6. pii: S0003-9993(14)00003-3. doi: 10.1016/j.apmr.2013.12.019. [Epub ahead of print] PubMed PMID: 24407102.

Yoon YK, Lee KC, Cho HE, Chae M, Chang JW, Chang WS, Cho SR. Outcomes of intrathecal baclofen therapy in patients with cerebral palsy and acquired brain injury. Medicine (Baltimore). 2017 Aug;96(34):e7472. doi: 10.1097/MD.0000000000007472. PubMed PMID: 28834868.

Motta F, Antonello CE. Comparison between an Ascenda and a silicone catheter in intrathecal baclofen therapy in pediatric patients: analysis of complications. J Neurosurg Pediatr. 2016 Jun 24:1-6. [Epub ahead of print] PubMed PMID: 27341610.

Hara T, Nakajima M, Sugano H, Karagiozov K, Hirose E, Goto K, Arai H. Pregnancy and Breastfeeding during Intrathecal Baclofen Therapy – A Case Study and Review. NMC Case Rep J. 2018 Jun 25;5(3):65-68. doi: 10.2176/ eCollection 2018 Jul. PubMed PMID: 30023142; PubMed Central PMCID: PMC6048348.

Kalyvas AV, Drosos E, Korfias S, Gatzonis S, Themistocleous M, Sakas DE. Intrathecal Baclofen Therapy for Painful Muscle Spasms in a Patient with Friedreich’s Ataxia. Stereotact Funct Neurosurg. 2018 Jun 8:1-4. doi: 10.1159/000489220. [Epub ahead of print] PubMed PMID: 29886479.

Fourth ventricle outlet obstruction

Fourth ventricle outlet obstruction

The fourth ventricle outlet obstruction (FVOO) is a rare but well-established cause of obstructive tetra-ventricular hydrocephalus, characterizing with dilatation or large cerebrospinal fluid collection of the foramen of Magendie and foramen of Luschka.

Hydrocephalus is classified as noncommunicating and communicating based on whether all ventricular and subarachnoid spaces are communicating. Although the diagnosis between the two different states is crucial, it is difficult in certain conditions. In particular, communicating hydrocephalus and noncommunicating hydrocephalus owing to fourth ventricle outlet obstruction are highly misdiagnosed.

In FVOO, cerebrospinal fluid (CSF) is blocked at the fourth ventricle outlets by a membranous structure in the absence of any additional obstructive organic pathologies. Various terms for referring to FVOO have been used in previous reports, such as fourth ventricle/ventricular outlet obstruction 1) 2) 3) 4), fourth ventricular outflow obstruction 5), membranous obstruction of the fourth ventricle outlet 6) , obstruction of Magendie’s and Luschka’s foramina 7) , obstruction of fourth ventricular exit8) and primary obstruction of the fourth ventricle outlets 9). Far distal obstructive hydrocephalus is a term that includes Dandy Walker or Arnold Chiari malformation, membranous obstruction or fourth ventricle and intercisternal external obstruction of the CSF 10).


The etiology and pathogenesis of FVOO are unclear, although some cases present with a history of meningitis or intraventricular hemorrhage.

In children, it is usually the consequence of posterior cerebral fossa malformations; while in adult, the occlusion is rather acquired than congenital, mostly linked to an inflammatory process, intraventricular hemorrhagehead traumabrain tumors or Arnold-Chiari malformation. However, idiopathic FVOO is extremely rare, and only 6 such cases have been reported in the English literature.

Bai et al., described an extraordinarily rare case of idiopathic FVOO in a 15-year-old patient successfully treated with direct microsurgical excision of the obstruction membrane. Furthermore, the clinical characteristics and treatment for this rare disease were investigated and reviewed 11).


CT ventriculography in infants, and CT cisternography in elder children, may assist to differentiate between FVOO and communicating hydrocephalus. The importance of these tests is for children with MRI suggestive of FVOO related hydrocephalus, but with no clear demonstration of the obstruction site. The implication of this differentiation may be for deciding between treatment of hydrocephalus with a ventriculoperitoneal shunt or with an endoscopic third ventriculostomy 12).


Third ventricle-fourth ventriculostomy is by far the most frequently used technique for cannulation of the aqueduct in a trapped fourth ventricle. In reported cases of , they have introduced a silicone tube stent from below after accessing the fourth ventricle through a small suboccipital craniectomy, ascending it on the aqueduct in order to reach the third ventricle. Management of this infrequently isolated fourth ventricle, but communicated with the rest of ventricular system, remains a challenge for neurosurgeons. Lack of knowledge of the pathophysiology makes it difficult to treat a problem that we do not understand 13).

ETV is a viable option for treatment of patients with FVOO. The high failure rate in infants younger than 6 months of age suggests that ventriculoperitoneal shunting is a favorable option in this age group, rather than ETV. Isolated fourth ventricle is uncommon after ETV in hydrocephalus attributable to FVOO 14).

Suehiro et al., reported the use of neuroendoscopic third ventriculostomy to treat successfully both hydrocephalus and syringomyelia associated with fourth ventricle outlet obstruction. A 27-year-old woman presented with dizziness, headache, and nausea. Magnetic resonance (MR) imaging demonstrated dilation of all ventricles, downward displacement of the third ventricular floor, obliteration of the retrocerebellar cerebrospinal fluid (CSF) space, funnellike enlargement of the entrance of the central canal in the fourth ventricle, and syringomyelia involving mainly the cervical spinal cord. Cine-MR imaging indicated patency of the aqueduct and an absent CSF flow signal in the area of the cistema magna, which indicated obstruction of the outlets of the fourth ventricle. Although results of radioisotope cisternography indicated failure of CSF absorption, neuroendoscopic third ventriculostomy completely resolved all symptoms as well as the ventricular and spinal cord abnormalities evident on MR images. Neuroendoscopic third ventriculostomy is an important option for treating hydrocephalus in patients with fourth ventricle outlet obstruction15).

Case series

Three patients who were 21, 53, and 68 years of age presented with either headaches (isolated or associated with raised intracranial pressure) or vertigo, or a combination of gait disorders, sphincter disorders, and disorders of higher functions. In each case, magnetic resonance (MR) imaging demonstrated hydrocephalus involving the four ventricles (mean transverse diameter of third ventricle 14.15 mm; mean sagittal diameter of fourth ventricle 23.13 mm; and mean ventricular volume 123.92 ml) with no signs of a Chiari Type I malformation (normal posterior fossa dimensions, no herniation of cerebellar tonsils). The diagnosis of obstruction was confirmed using ventriculography (in two patients) and/or MR flow images (in two patients). All patients presented with marked dilation of the foramen of Luschka that herniated into the cisterna pontis. All patients were treated using ETV. No complications were observed. All three patients became asymptomatic during the weeks following the surgical procedure and remained stable at a mean follow-up interval of 36 months. Postoperative MR images demonstrated regression of the hydrocephalus (mean transverse diameter of third ventricle 7.01 mm; mean sagittal diameter of fourth ventricle 16.6 mm; and mean ventricular volume 79.95 ml), resolution of dilation of the foramen of Luschka, and good patency of the ventriculostomy (flow sequences). These results confirm the existence of hydrocephalus caused by idiopathic fourth ventricle outflow obstruction without an associated Chiari Type I malformation, and the efficacy of ETV for this rare indication 16).

Case reports

Duran D, Hadzipasic M, Kahle KT. Mystery Case: Acute hydrocephalus caused by radiographically occult fourth ventricular outlet obstruction. Neurology. 2017 Jan 31;88(5):e36-e37. doi: 10.1212/WNL.0000000000003555. PubMed PMID: 28138085 17).

A 66-year-old woman with gait disturbance and incontinence caused by hydrocephalus underwent ventriculoperitoneal shunt surgery. After 9 months, her fourth ventricle became enlarged and could not be controlled by lowering the shunt pressure. Magnetic resonance imaging (MRI) demonstrated obstruction at the foramen of Magendie, foramina of Luschka, and the cerebral aqueduct. Endoscopic surgery for aqueduct plasty with third ventriculostomy was planned. Because the aqueduct was observed to open spontaneously, only the standard third ventriculostomy was performed. When MRI findings were reviewed retrospectively, an unnatural space was observed between the lower cranial nerves and cerebellar hemisphere that grew along with the fourth ventricular enlargement. This space was determined by MRI cisternography to be the cystic membrane ballooning out from the foramen of Luschka. The primary hydrocephalus likely resulted from fourth ventricle outlet obstruction.

Enlargement of the whole ventricular system with an expanded space between the lower cranial nerves and cerebellar hemisphere can be caused by fourth ventricle outlet obstruction. In such cases, preoperative evaluation of anatomic architecture and cerebrospinal fluid obstruction using MRI cisternography is essential and leads to a successful endoscopic strategy 18).

A 3-year old boy without any remarkable medical history presented with a headache and vomiting. Computed tomography (CT) images, which had incidentally been taken 2 years previously due to a minor head injury, showed no abnormality. Magnetic resonance imaging on admission showed tetra-ventricular hydrocephalus associated with the dilatation of the fourth ventricle outlets, without any obstructive lesions. However, CT ventriculography, involving contrast medium injection through a ventricular catheter, suggested mechanical obstruction of the cerebrospinal fluid (CSF) at the fourth ventricle outlets. Thus, the patient was diagnosed with FVOO and ETV was performed; the hydrocephalus was subsequently resolved. Although hydrocephalus recurred 1 year postoperatively, re-ETV for the highly stenosed fenestration successfully resolved this condition.

ETV should be considered for FVOO treatment, particularly in idiopathic cases without CSF malabsorption 19).

A 15-year-old girl with amenorrhea and a several-week history of headache. After the diagnosis of membranous obstruction of the foramen of Magendie suggested by MRI, suboccipital craniotomy for removal of the membrane was carried out. The patient made an excellent postoperative recovery, and postoperative phase-contrast MRI demonstrated patent cerebrospinal fluid (CSF) pathways at the level of the foramina of Magendie and Luschka. We believe that this case is of interest because of the unequivocal evidence on MRI studies of the occlusion of the foramen of Magendie preoperatively, and because of the dramatic postoperative MRI findings demonstrating the effectiveness of the surgical procedure both in terms of ventricular size and CSF flow characterization 20).


1) , 13)

Ferrer E, de Notaris M. Third ventriculostomy and fourth ventricle outlets obstruction. World Neurosurg. 2013 Feb;79(2 Suppl):S20.e9-13. doi: 10.1016/j.wneu.2012.02.017. Epub 2012 Feb 10. Review. PubMed PMID: 22381846.
2) , 14)

Mohanty A, Biswas A, Satish S, Vollmer DG. Efficacy of endoscopic third ventriculostomy in fourth ventricular outlet obstruction. Neurosurgery. 2008 Nov;63(5):905-13; discussion 913-4. doi: 10.1227/01.NEU.0000333262.38548.E1. PubMed PMID: 19005381.
3) , 12)

Roth J, Ben-Sira L, Udayakumaran S, Constantini S. Contrast ventriculo-cisternography: an auxiliary test for suspected fourth ventricular outlet obstruction. Childs Nerv Syst. 2012 Mar;28(3):453-9. doi: 10.1007/s00381-011-1639-y. Epub 2011 Nov 29. PubMed PMID: 22124573.
4) , 15)

Suehiro T, Inamura T, Natori Y, Sasaki M, Fukui M. Successful neuroendoscopic third ventriculostomy for hydrocephalus and syringomyelia associated with fourth ventricle outlet obstruction. Case report. J Neurosurg. 2000 Aug;93(2):326-9. PubMed PMID: 10930021.
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Karachi C, Le Guérinel C, Brugières P, Melon E, Decq P. Hydrocephalus due to idiopathic stenosis of the foramina of Magendie and Luschka. Report of three cases. J Neurosurg. 2003 Apr;98(4):897-902. PubMed PMID: 12691419.
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Huang YC, Chang CN, Chuang HL, Scott RM. Membranous obstruction of the fourth ventricle outlet. A case report. Pediatr Neurosurg. 2001 Jul;35(1):43-7. Review. PubMed PMID: 11490191.

Carpentier A, Brunelle F, Philippon J, Clemenceau S. Obstruction of Magendie’s and Luschka’s foramina. Cine-MRI, aetiology and pathogenesis. Acta Neurochir (Wien). 2001;143(5):517-21; discussion 521-2. PubMed PMID: 11482704.

Choi JU, Kim DS, Kim SH. Endoscopic surgery for obstructive hydrocephalus. Yonsei Med J. 1999 Dec;40(6):600-7. PubMed PMID: 10661039.

Longatti P, Fiorindi A, Martinuzzi A, Feletti A. Primary obstruction of the fourth ventricle outlets: neuroendoscopic approach and anatomic description. Neurosurgery. 2009 Dec;65(6):1078-85; discussion 1085-6. doi: 10.1227/01.NEU.0000360133.29217.44. PubMed PMID: 19934967.

Oertel JM, Mondorf Y, Schroeder HW, Gaab MR. Endoscopic diagnosis and treatment of far distal obstructive hydrocephalus. Acta Neurochir (Wien). 2010 Feb;152(2):229-40. doi: 10.1007/s00701-009-0494-z. Epub 2009 Aug 26. PubMed PMID: 19707715.

Bai J, Yu Q, Sun X, Xiao H, Wang K, Sun F, Sui Q. Hydrocephalus Due to Idiopathic Fourth Ventricle Outflow Obstruction. J Craniofac Surg. 2019 Mar 6. doi: 10.1097/SCS.0000000000005314. [Epub ahead of print] PubMed PMID: 30865115.

Duran D, Hadzipasic M, Kahle KT. Mystery Case: Acute hydrocephalus caused by radiographically occult fourth ventricular outlet obstruction. Neurology. 2017 Jan 31;88(5):e36-e37. doi: 10.1212/WNL.0000000000003555. PubMed PMID: 28138085.

Shimoda Y, Murakami K, Narita N, Tominaga T. Fourth Ventricle Outlet Obstruction with Expanding Space on the Surface of Cerebellum. World Neurosurg. 2017 Apr;100:711.e1-711.e5. doi: 10.1016/j.wneu.2017.01.088. Epub 2017 Jan 31. PubMed PMID: 28153613.

Ishi Y, Asaoka K, Kobayashi H, Motegi H, Sugiyama T, Yokoyama Y, Echizenya S, Itamoto K. Idiopathic fourth ventricle outlet obstruction successfully treated by endoscopic third ventriculostomy: a case report. Springerplus. 2015 Sep 30;4:565. doi: 10.1186/s40064-015-1368-x. eCollection 2015. PubMed PMID: 26543700; PubMed Central PMCID: PMC4627988.

Dentatorubrothalamic tract

Dentatorubrothalamic tract

The dentatothalamic tract (or dentatorubrothalamic tract) is a tract which connects the dentate nucleusand the thalamus while sending collaterals to the red nucleus.

The term “dentatorubrothalamocortical” is sometimes used to emphasize termination in the cerebral cortex.

The dentatothalamic tract or dentatorubrothalamic tract (DRTT) originates from the dentate nucleus in the cerebellum and terminates in the contralateral ventral lateral nucleus (VL) of the thalamus after decussating to the contralateral red nucleus. Identification of the DRTT is difficult due to the fact that it is a long, multisynaptic, neural tract crossing to the opposite hemisphere.

The dentato-rubro-thalamic tract (DRTT) regulates motor control, connecting the cerebellum to the thalamus. This tract is modulated by deep brain stimulation in the surgical treatment of medically refractory tremor, especially in essential tremor, where high-frequency stimulation of the thalamus can improve symptoms. The DRTT is classically described as a decussating pathway, ascending to the contralateral thalamus. However, the existence of a nondecussating (i.e. ipsilateral) DRTT in humans was recently demonstrated, and these tracts are arranged in distinct regions of the superior cerebellar peduncle.

Petersen et al., hypothesized that the ipsilateral DRTT is connected to specific thalamic nuclei and therefore may have unique functional relevance. The goals of this study were to confirm the presence of the decussating and nondecussating DRTT pathways, identify thalamic termination zones of each tract, and compare whether structural connectivity findings agree with functional connectivity. Diffusion-weighted imaging was used to perform probabilistic tractography of the decussating and nondecussating DRTT in young healthy subjects from the Human Connectome Project(n = 91) scanned using multi-shell diffusion-weighted imaging (270 directions; TR/TE = 5500/89 ms; spatial resolution = 1.25 mm isotropic). To define thalamic anatomical landmarks, a segmentation procedure based on the Morel stereotactic atlas of the human thalamus was employed, and DRTT targeting was quantified based on the proportion of streamlines arriving at each nucleus. In parallel, functional connectivity analysis was performed using resting-state functional MRI (TR/TE = 720/33 ms; spatial resolution = 2 mm isotropic). It was found that the decussating and nondecussating DRTTs have significantly different thalamic endpoints, with the former preferentially targeting relatively anterior and lateral thalamic nuclei, and the latter connected to more posterior and medial nuclei (p < 0.001). Functional and structural connectivity measures were found to be significantly correlated (r = 0.45, p = 0.031). These findings provide new insight into pathways through which unilateral cerebellum can exert bilateral influence on movement and raise questions about the functional implications of ipsilateral cerebellar efferents 1).

Pineda-Pardo et al., published a cohort of 24 essential tremor patients before and 3 months after unilateral transcranial magnetic resonance guided focused ultrasound targeting at the posteroventral part of the VIM. Microstructural changes along the dentatorubrothalamic tract (DRTT) were quantified by means of probabilistic tractography, and later related to the clinical improvement of the patients at 3-months and at 1-year after the intervention. In addition the changes along two neighboring tracts, that is, the corticospinal tract and the medial lemniscus, were assessed, as well as the relation between these changes and the presence of side effects. Thalamic lesions produced local and distant alterations along the trajectory of the DRTT, and each correlated with clinical improvement. Regarding side effects, gait imbalance after thalamotomy was associated with greater impact on the DRTT, whereas the presence of paresthesias was significantly related to a higher overlap between the lesion and the medial lemniscus. This work represents the largest series describing the microstructural changes following transcranial MR-guided focused ultrasound thalamotomy in essential tremor. These results suggest that clinical benefits are specific for the impact on the cerebello-thalamo-cortical pathway, thus reaffirming the potential of tractography to aid thalamotomy targeting 2).

Diffusion tensor imaging was performed at 1.5-T using a synergy-L sensitivity encoding head coil. DRTTs were obtained by selection of fibers passing through three regions of interest (the dentate nucleus, the superior cerebellar peduncle, and the contralateral red nucleus) from 41 healthy volunteers. Probabilistic mapping was obtained from the highest probabilistic location at 2.3 mm above the anterior commissure-posterior commissure level.

DRTTs of all subjects, which originated from the dentate nucleus, ascended through the junction of the superior cerebellar peduncle and the contralateral red nucleus and then terminated at the VL nucleus of the thalamus. The highest probabilistic location for the DRTT at the thalamus was compatible with the location of the VL nucleus.

Kwon et al identified the DRTT in the human brain using probabilistic tractography. Our results could be useful in research on movement control 3)

The dentatorubrothalamic tract (DRTT) is the major efferent cerebellar pathway arising from the dentate nucleus (DN) and decussating to the contralateral red nucleus (RN) and thalamus. Surprisingly, hemispheric cerebellar output influences bilateral limb movements. In animals, uncrossed projections from the DN to the ipsilateral RN and thalamus may explain this phenomenon. The aim of a study was to clarify the anatomy of the dentatorubrothalamic connections in humans.

Meola et al applied advanced deterministic fiber tractography to a template of 488 subjects from the Human Connectome Project (Q1-Q3 release, WU-Minn HCP consortium) and validated the results with microsurgical dissection of cadaveric brains prepared according to Klingler’s method.

The authors identified the “classic” decussating DRTT and a corresponding nondecussating path (the nondecussating DRTT, nd-DRTT). Within each of these 2 tracts some fibers stop at the level of the RN, forming the dentatorubro tract and the nondecussating dentatorubro tract. The left nd-DRTT encompasses 21.7% of the tracts and 24.9% of the volume of the left superior cerebellar peduncle, and the right nd-DRTT encompasses 20.2% of the tracts and 28.4% of the volume of the right superior cerebellar peduncle.

The connections of the DN with the RN and thalamus are bilateral, not ipsilateral only. This affords a potential anatomical substrate for bilateral limb motor effects originating in a single cerebellar hemisphere under physiological conditions, and for bilateral limb motor impairment in hemispheric cerebellar lesions such as ischemic stroke and hemorrhage, and after resection of hemispheric tumors and arteriovenous malformations. Furthermore, when a lesion is located on the course of the dentatorubrothalamic system, a careful preoperative tractographic analysis of the relationship of the DRTT, nd-DRTT, and the lesion should be performed in order to tailor the surgical approach properly and spare all bundles 4).



Petersen KJ, Reid JA, Chakravorti S, Juttukonda MR, Franco G, Trujillo P, Stark AJ, Dawant BM, Donahue MJ, Claassen DO. Structural and functional connectivity of the nondecussating dentato-rubro-thalamic tract. Neuroimage. 2018 Aug 1;176:364-371. doi: 10.1016/j.neuroimage.2018.04.074. Epub 2018 May 4. PubMed PMID: 29733955; PubMed Central PMCID: PMC6002752.

Pineda-Pardo JA, Martínez-Fernández R, Rodríguez-Rojas R, Del-Alamo M, Hernández F, Foffani G, Dileone M, Máñez-Miró JU, De Luis-Pastor E, Vela L, Obeso JA. Microstructural changes of the dentato-rubro-thalamic tract after transcranial MR guided focused ultrasound ablation of the posteroventral VIM in essential tremor. Hum Brain Mapp. 2019 Mar 13. doi: 10.1002/hbm.24569. [Epub ahead of print] PubMed PMID: 30865338.

Kwon HG, Hong JH, Hong CP, Lee DH, Ahn SH, Jang SH. Dentatorubrothalamic tract in human brain: diffusion tensor tractography study. Neuroradiology. 2011 Oct;53(10):787-91. doi: 10.1007/s00234-011-0878-7. Epub 2011 May 3. PubMed PMID: 21547376.

Meola A, Comert A, Yeh FC, Sivakanthan S, Fernandez-Miranda JC. The nondecussating pathway of the dentatorubrothalamic tract in humans: human connectome-based tractographic study and microdissection validation. J Neurosurg. 2015 Oct 9:1-7. [Epub ahead of print] PubMed PMID: 26452117.
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