MR-guided focused ultrasound in pediatric neurosurgery: current insights, technical challenges, and lessons learned from 45 treatments at Children's National Hospital.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) is an evolving technology with numerous present and potential applications in pediatric neurosurgery. The aim of this study was to describe the use of MRgFUS, technical challenges, complications, and lessons learned at a single children's hospital. METHODS: A retrospective analysis was performed of a prospectively collected database of all pediatric patients undergoing investigational use of MRgFUS for treatment of various neurosurgical pathologies at Children's National Hospital. Treatment details, clinical workflow, and standard operating procedures are described. Patient demographics, procedure duration, and complications were obtained through a chart review of anesthesia and operative reports. RESULTS: In total, 45 MRgFUS procedures were performed on 14 patients for treatment of diffuse intrinsic pontine glioma (n = 12), low-grade glioma (n = 1), or secondary dystonia (n = 1) between January 2022 and April 2024. The mean age at treatment was 9 (range 5-22) years, and 64% of the patients were male. With increased experience, the total anesthesia time, sonication time, and change in core body temperature during treatment all significantly decreased. Complications affected 4.4% of patients, including 1 case of scalp edema and 1 patient with a postprocedure epidural hematoma. Device malfunction requiring abortion of the procedure occurred in 1 case (2.2%). Technical challenges related to transducer malfunction and sonication errors occurred in 6.7% and 11.1% of cases, respectively, all overcome by subsequent user modifications. CONCLUSIONS: The authors describe the largest series on MRgFUS technical aspects in pediatric neurosurgery at a single institution, comprising 45 total treatments. This study emphasizes potential technical challenges and provides valuable insights into the nuances of its application in pediatric patients.

Hand Dystonia after Focused Ultrasound Thalamotomy in Essential Tremor.

INTRODUCTION: Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for drug-resistant tremor. The most frequent side effects are ataxia, gait disturbance, paresthesias, dysgeusia, and hemiparesis. Here, we report the first case of thalamic hand dystonia rapidly occurring after MRgFUS thalamotomy of the ventral intermediate nucleus (V.im). CASE PRESENTATION: MRgFUS thalamotomy was performed in a 60-year-old left-handed patient for his disabling medically refractory essential tremor. The intervention resulted in a marked reduction of his action tremor. However, the patient developed an unvoluntary abnormal posture in his left hand a few days after the procedure with difficulty holding a cigarette between his fingers. Brain MRI revealed the expected MRgFUS lesion within the right V.im as well as an extension of the lesion anteriorly to the V.im in the ventro-oralis nucleus. Tractography showed that the lesion disrupted the dentato-rubro-thalamic tract as expected with a lesion suppressing tremor. However, the lesion also was interrupted fibers connecting to the superior frontal and pre-central cortices (primary motor cortex, premotor cortex, and supplementary area). We hypothesized that the interventional MRgFUS thalamotomy was slightly off target, which induced a dysfunction within the cortico-striato-thalamo-cortical network and the cerebello-thalamo-cortical pathway reaching a sufficient threshold of basal ganglia/cerebellum circuitry interference to induce dystonia. CONCLUSION: This rare side effect emphasizes the risk of imbalance within the dystonia network (i.e., basal ganglia-cerebello-thalamo-cortical circuit) secondary to V.im thalamotomy.

Pharmacological and neurosurgical management of cerebral palsy and dystonia: Clinical practice guideline update.

Dystonia, typically characterized by slow repetitive involuntary movements, stiff abnormal postures, and hypertonia, is common among individuals with cerebral palsy (CP). Dystonia can interfere with activities and have considerable impact on motor function, pain/comfort, and ease of caregiving. Although pharmacological and neurosurgical approaches are used clinically in individuals with CP and dystonia that is causing interference, evidence to support these options is limited. This clinical practice guideline update comprises 10 evidence-based recommendations on the use of pharmacological and neurosurgical interventions for individuals with CP and dystonia causing interference, developed by an international expert panel following the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The recommendations are intended to help inform clinicians in their use of these management options for individuals with CP and dystonia, and to guide a shared decision-making process in selecting a management approach that is aligned with the individual's and the family's values and preferences.

Outcomes of Unilateral Pallidotomy in Focal and Hemidystonia Cases: A Single-Blind Cohort Study.

BACKGROUND: The role of deep brain stimulation in the treatment of dystonia has been widely documented. However, there is limited literature on the outcome of lesioning surgery in unilateral dystonia. OBJECTIVE: We restrospectively reviewed our cases of focal and hemidystonia undergoing unilateral Pallidotomy at our institute to evaluate the short-term and long-term outcome. METHODS: Patients who underwent radiofrequency lesioning of GPi for unilateral dystonia between 1999 and 2019 were retrospectively reviewed. All patients were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Dystonia Disability Scale (DDS) preoperatively at the short term follow-up (<1 year) and at long-term follow-up (2-7.5 years). Video recordings performed at these time points were independently reviewed by a blinded movement disorders specialist. RESULTS: Eleven patients were included for analysis. The preoperative, short-term, and long-term follow-up motor BFMDRS and DDS scores were 15.5 (IQR [interquartile range]: 10.5, 23.75) and 10.5 (IQR: 6.0, 14.5); 3.0 (IQR: 1.0, 6.0, P = 0.02) and 3.0 (IQR: 3.0, 8.0, P = 0.016); and 14.25 (IQR: 4.0, 20.0, P = 0.20) and 10.5 (IQR: 2.0, 15.0, P = 0.71) respectively. For observers B, the BFMDRS scores at the same time points were 19 (IQR: 12.5, 27.0), 7.5 (IQR: 6.0, 15.0, P = 0.002), and 21 (IQR: 7.0, 22.0, P = 0.65) respectively. The improvement was statistically significant for all observations at short-term follow-up but not at long-term follow-up. CONCLUSION: Pallidotomy is effective for hemidystonia or focal dystonia in the short term. Continued benefit was seen in the longer term in some patients, whereas others worsened. Larger studies may be able to explain this in future.

Neurosurgical management of non-spastic movement disorders.

BACKGROUND: Non-spastic movement disorders in children are common, although true epidemiologic data is difficult to ascertain. Children are more likely than adults to have hyperkinetic movement disorders defined as tics, dystonia, chorea/athetosis, or tremor. These conditions manifest from acquired or heredodegenerative etiologies and often severely limit function despite medical and surgical management paradigms. Neurosurgical management for these conditions is highlighted. METHODS: We performed a focused review of the literature by searching PubMed on 16 May 2023 using key terms related to our review. No temporal filter was applied, but only English articles were considered. We searched for the terms (("Pallidotomy"[Mesh]) OR "Rhizotomy"[Mesh]) OR "Deep Brain Stimulation"[Mesh], dystonia, children, adolescent, pediatric, globus pallidus, in combination. All articles were reviewed for inclusion in the final reference list. RESULTS: Our search terms returned 37 articles from 2004 to 2023. Articles covering deep brain stimulation were the most common (n = 34) followed by pallidotomy (n = 3); there were no articles on rhizotomy. DISCUSSION: Non-spastic movement disorders are common in children and difficult to treat. Most of these patients are referred to neurosurgery for the management of dystonia, with modern neurosurgical management including pallidotomy, rhizotomy, and deep brain stimulation. Historically, pallidotomy has been effective and may still be preferred in subpopulations presenting either in status dystonicus or with high risk for hardware complications. Superiority of DBS over pallidotomy for secondary dystonia has not been determined. Rhizotomy is an underutilized surgical tool and more study characterizing efficacy and risk profile is indicated.

[Efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome].

Objective: To evaluate the efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome. Methods: The Clinical data of 56 patients with Meige syndrome in the Department of Pain Medicine, Affiliated Hospital of Jiaxing University from June 2019 to January 2023 were retrospectively analyzed [19 males and 37 females, aged 42-76 (58.6±8.3) years], including 51 cases of blepharospasm, 3 cases of oromandibular dystonia and 2 cases of blepharospasm concomitant with oromandibular dystonia. CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves was performed on different types of Meige syndrome. And the efficacy and complications of the technique were observed. Results: Fifty-one patients with blepharospasm Meige syndrome underwent CT-guided radiofrequency of facial nerve through bilateral stylomastoid foramen punctures, the symptoms of blepharospasm disappeared completely, leaving bilateral mild and moderate facial paralysis symptoms. Three patients with oral-mandibular dystonia underwent CT-guided radiofrequency therapy by bilateral foramen ovale puncture of mandibular branches of trigeminal nerve, masticatory muscle spasm disappeared, the patients had no difficulty opening the mouth, and the skin numbness in bilateral mandibular nerve innervation area was left. Two cases of Meige syndrome with blepharospasm concomitant with oromandibular dystonia were treated by radiofrequency of facial nerve and mandibular branch of trigeminal nerve, and all symptoms disappeared. The patients were followed up for 1-44 months after the operation, and the symptoms of mild and moderate facial paralysis disappeared at (3.2±0.8) months after the operation, but the numbness did not disappear. Three patients with blepharospasm recurred at the 14, 18 and 22 months after the operation, respectively, while the rest cases did not recur. Conclusions: According to different types of Meige syndrome, CT-guided partial radiofrequency ablation of responsible cranial nerves can effectively treat the corresponding type of Meige syndrome. The complications are only mild and moderate facial paralysis which can be recovered, and/or skin numbness in the mandibular region.

[Methods and results of neurosurgical treatment of cerebral palsy]. / Metody i rezul'taty neirokhirurgicheskogo lecheniya detskogo tserebral'nogo paralicha.

Treatment of spastic syndrome and muscular dystonia in patients with cerebral palsy is a complex clinical problem. Effectiveness of conservative treatment is not high enough. Modern neurosurgical techniques for spastic syndrome and dystonia are divided into destructive interventions and surgical neuromodulation. Their effectiveness is different and depends on the form of disease, severity of motor disorders and age of patients. OBJECTIVE: To evaluate the effectiveness of various methods of neurosurgical treatment of spasticity and muscular dystonia in patients with cerebral palsy. MATERIAL AND METHODS: We To evaluate the effectiveness of various methods of neurosurgical treatment of spasticity and muscular dystonia in patients with cerebral palsy.analyzed literature data in the PubMed database using the keywords «cerebral palsy¼, «spasticity¼, «dystonia¼, «selective dorsal rhizotomy¼, «selective neurotomy¼, «intrathecal baclofen therapy¼, «spinal cord stimulation¼, «deep brain stimulation¼. RESULTS: Effectiveness of neurosurgery was higher for spastic forms of cerebral palsy compared to secondary muscular dystonia. Destructive procedures were the most effective among neurosurgical operations for spastic forms. Effectiveness of chronic intrathecal baclofen therapy decreases in follow-up due to secondary drug resistance. Destructive stereotaxic interventions and deep brain stimulation are used for secondary muscular dystonia. Effectiveness of these procedures is low. CONCLUSION: Neurosurgical methods can partially reduce severity of motor disorders and expand the possibilities of rehabilitation in patients with cerebral palsy.

Neurosurgical management of elevated tone in childhood: interventions, indications and uncertainties.

Elevated tone (hypertonia) is a common problem in children with physical disabilities. Medications intended to reduce tone often have limited efficacy, with use further limited by a significant side effect profile. Consequently, there has been growing interest in the application of Neurosurgical Interventions for the Management of Posture and Tone (NIMPTs). Three main procedures are now commonly used: selective dorsal rhizotomy (SDR), intrathecal baclofen (ITB) and deep brain stimulation (DBS). This review compares these interventions, along with discussion on the potential role of lesioning surgery. These interventions variably target spasticity and dystonia, acting at different points in the distributed motor network. SDR, an intervention for reducing spasticity, is most widely used in carefully selected ambulant children with cerebral palsy. ITB is more commonly used for children with more severe disability, typically non-ambulant, and can improve both dystonia and spasticity. DBS is an intervention which may improve dystonia. In children with certain forms of genetic dystonia DBS may dramatically improve dystonia. For other causes of dystonia, and in particular dystonia due to acquired brain injury, improvements following surgery are more modest and variable. These three interventions vary in terms of their side-effect profile and reversibility. There are currently populations of children for who it is unclear which intervention should be considered (SDR vs ITB, or ITB vs DBS). Concerns have been raised as to the equity of access to NIMPTs for children across the UK, and whether the number of surgeries performed each year meets the clinical need.

Cerebellar Cortex Stimulation for Acquired Dystonia: A Case Report and Review of Its Role in Modern Surgical Practice.

BACKGROUND: Cerebral palsy (CP) is a common cause of acquired dystonia, which can lead to significant interference with quality of life and societal participation. In the last two decades, the surgical treatment of dystonia has primarily focused on deep brain stimulation targeting the basal ganglia and thalamic circuits. However, stimulation of the basal ganglia has generally been less effective in acquired combined forms of dystonia, including dystonic CP. These limitations, along with growing evidence for the role of the cerebellum in the pathophysiology of dystonia, have led to renewed interest in the cerebellum as a target for therapeutic stimulation in dystonia. Nevertheless, there are very few contemporary studies demonstrating its use. We present the case of a patient with generalized dystonia due to dyskinetic CP who was successfully treated with stimulation of the cerebellar cortex in the modern era. We also review the evidence underpinning targeting of the cerebellum in surgical therapy for dystonia and examine the latest reports of this approach in the surgical literature. SUMMARY: The patient derived significant improvement in the control of her dystonic symptoms, with a reduction in her BFMDRS score from 83 to 25. No complications were observed during more than 3 years of postoperative follow-up. Since the turn of the 21st century, there have been only 7 reports of cerebellar stimulation for dystonia, recruiting a total of 18 patients. These studies have exclusively targeted deep brain structures, making the present report of cortical cerebellar stimulation particularly unique. KEY MESSAGES: In the 21st century, cerebellar stimulation has predominantly been a second-line treatment for dystonia, after the failure of DBS targeting more mainstream loci within the thalamus and globus pallidus. However, there is increasing recognition of the role of the cerebellum in movement disorders, with multiple convergent lines of evidence supporting its involvement in dystonia pathophysiology. The cerebellum is worthy of greater consideration as a target for neurostimulation in dystonia, particularly in cases of acquired etiology.

Long-Term Outcomes of Deep Brain Stimulation for Pediatric Dystonia.

BACKGROUND: Deep brain stimulation (DBS) has been utilized for over two decades to treat medication-refractory dystonia in children. Short-term benefit has been demonstrated for inherited, isolated, and idiopathic cases, with less efficacy in heredodegenerative and acquired dystonia. The ongoing publication of long-term outcomes warrants a critical assessment of available information as pediatric patients are expected to live most of their lives with these implants. SUMMARY: We performed a review of the literature for data describing motor and neuropsychiatric outcomes, in addition to complications, 5 or more years after DBS placement in patients undergoing DBS surgery for dystonia at an age younger than 21. We identified 20 articles including individual data on long-term motor outcomes after DBS for a total of 78 patients. In addition, we found five articles reporting long-term outcomes after DBS in 9 patients with status dystonicus. Most patients were implanted within the globus pallidus internus, with only a few cases targeting the subthalamic nucleus and ventrolateral posterior nucleus of the thalamus. The average follow-up was 8.5 years, with a range of up to 22 years. Long-term outcomes showed a sustained motor benefit, with median Burke-Fahn-Marsden dystonia rating score improvement ranging from 2.5% to 93.2% in different dystonia subtypes. Patients with inherited, isolated, and idiopathic dystonias had greater improvement than those with heredodegenerative and acquired dystonias. Sustained improvements in quality of life were also reported, without the development of significant cognitive or psychiatric comorbidities. Late adverse events tended to be hardware-related, with minimal stimulation-induced effects. KEY MESSAGES: While data regarding long-term outcomes is somewhat limited, particularly with regards to neuropsychiatric outcomes and adverse events, improvement in motor outcomes appears to be preserved more than 5 years after DBS placement.

Combined Unilateral Radiofrequency Lesioning of the Motor Thalamus, Field of Forel, and Zona Incerta: A Series of Cases With Dystonia.

BACKGROUND: Dystonia is a group of disorders characterized by involuntary slow repetitive twisting movements and/or abnormal posture. Surgical options such as neuromodulation through deep brain stimulation and neuroablative procedures are available for patients who do not respond to conservative treatment. OBJECTIVE: To present our series of patients with dystonia who were treated with stereotactic combined unilateral radiofrequency lesioning of the motor thalamus, field of Forel, and zona incerta. METHODS: Medical records of 50 patients with dystonia who were treated with unilateral combined lesions were reviewed. Outcomes of the surgical procedure were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (with movement and disability subscales) and Unified Parkinson's Disease Rating Scale-tremor items. RESULTS: Based on the symptoms, patients were categorized as having generalized dystonia (34%), hemidystonia (30%), and dystonic tremor (DT) (36%). Primary/idiopathic dystonia, primary genetic/hereditary dystonia, and secondary dystonia accounted for 16%, 4%, and 80% of patients, respectively. The mean follow-up duration was 156.2 ± 88.9 mo. The overall improvement in the Burke-Fahn-Marsden Dystonia Rating Scale scores (movement and disability, respectively) was 57.8% and 36.4% in generalized dystonia, 60.0% and 45.8% in hemidystonia, and 65.6% and 56.8% in DT. Patients with DT showed an 83.3% improvement in mean Unified Parkinson's Disease Rating Scale tremor score. Patients with cerebral palsy showed mean improvements of 66.7% in movement scores and 50.8% in disability scores. No mortality or major morbidity was observed postoperatively. CONCLUSION: Stereotactic radiofrequency unilateral combined thalamotomy, campotomy, and zona incerta lesions may be an effective surgical alternative for patients with dystonia, especially those with secondary dystonia resistant to deep brain stimulation.

Should the Globus Pallidus Targeting Be Refined in Dystonia?

BACKGROUND AND STUDY AIMS: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective therapy for primary generalized and focal dystonias, but therapeutic success is compromised by a nonresponder rate of up to 20%. Variability in electrode placement and in tissue stimulated inside the GPi may explain in part different outcomes among patients. Refinement of the target within the pallidal area could be helpful for surgery planning and clinical outcomes. The objective of this study was to discuss current and potential methodological (somatotopy, neuroimaging, and neurophysiology) aspects that might assist neurosurgical targeting of the GPi, aiming to treat generalized or focal dystonia. METHODS: We selected published studies by searching electronic databases and scanning the reference lists for articles that examined the anatomical and electrophysiologic aspects of the GPi in patients with idiopathic/inherited dystonia who underwent functional neurosurgical procedures. RESULTS: The sensorimotor sector of the GPi was the best target to treat dystonic symptoms, and was localized at its lateral posteroventral portion. The effective volume of tissue activated (VTA) to treat dystonia had a mean volume of 153 mm3 in the posterior GPi area. Initial tractography studies evaluated the close relation between the electrode localization and pallidothalamic tract to control dystonic symptoms.Regarding the somatotopy, the more ventral, lateral, and posterior areas of the GPi are associated with orofacial and cervical representation. In contrast, the more dorsal, medial, and anterior areas are associated with the lower limbs; between those areas, there is the representation of the upper limb. Excessive pallidal synchronization has a peak at the theta band of 3 to 8 Hz, which might be responsible for generating dystonic symptoms. CONCLUSIONS: Somatotopy assessment of posteroventral GPi contributes to target-specific GPi sectors related to segmental body symptoms. Tractography delineates GPi output pathways that might guide electrode implants, and electrophysiology might assist in pointing out areas of excessive theta synchronization. Finally, the identification of oscillatory electrophysiologic features that correlate with symptoms might enable closed-loop approaches in the future.

The minimal clinically important change in the motor section of the Burke-Fahn-Marsden Dystonia Rating Scale for generalized dystonia: Results from deep brain stimulation.

BACKGROUND: The minimal clinically important difference (MCID) describes the smallest change in an outcome that is considered clinically meaningful. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) is the most frequently rating scale assessing the efficacy of deep brain stimulation therapy (DBS) for dystonia. To expand our understanding, we evaluated the MCID thresholds for the BFMDRS motor subscale (MS) using physician-reported outcomes. METHODS: We assessed the MCID thresholds for the BFMDRS using movement disorder specialist ratings of videotapes from patients with genetically determined dystonia (Tor1A and THAP1) who underwent bilateral globus pallidum internum (GPi) DBS. We calculated the effect size of the BFMDRS-MS change and determined the MCID thresholds using the Clinical Global Impression of Change (CGIC). RESULTS: Twelve participants with a median age at DBS of 44.5 (range:27-68) had baseline and follow-up BFMDRS-MS with a median post-DBS follow-up of 5.5 years. Based on descriptive analysis, patients with good improvement after DBS according to the CGIC [8/12 (67%)] had a median BFMDRS-MS score reduction of 77% [Interquartile range (IQR):66.2;91.0) with an effect size of 0.39, and those with non-improvement [4/12 (33%)], had a median BFMDRS-MS score reduction of 62% (IQR:36.6;83.6). CONCLUSIONS: Our MCID estimates can be utilized in clinical practice in judging clinical relevance. However, further larger, powered studies are needed to simultaneously determine and compare MCID using patient and physician-reported outcomes in segmental and generalized dystonia in genetic and non-genetic populations.

Are we on the right track in DBS surgery for dystonic head tremor? Polymyography is a promising answer.

The clinical benefit of Deep Brain Stimulation (DBS) is associated with electrode positioning accuracy. Intraoperative assessment of clinical effect is therefore key. Evaluating this clinical effect in patients with dystonic head tremor, as opposed to limb tremor, is challenging because the head is fixed in a stereotactic frame. To clinically assess head tremor during surgery, surface electromyography (EMG) electrodes were bilaterally applied to the sternocleidomastoid and cervical paraspinal muscles. This case shows that intraoperative polymyography is an easy and useful tool to assess the clinical effect of DBS electrode positioning.

The actual use of directional steering and shorter pulse width in selected patients undergoing deep brain stimulation.

INTRODUCTION: Directional deep brain stimulation (DBS) and pulse with <60µs increase side-effects threshold, enlarging the therapeutic window. However, new systems allowing these advanced features are more expensive and often available only for a limited number of patients in some centers. It is unknown how many and which DBS patients actually need the advanced features because of an insufficient improvement with standard parameters. METHODS: We included in the analysis all patients with Parkinson's disease, dystonia and tremor who were selected to receive implantation of advanced DBS systems based on specific preoperative or intraoperative clinical features. RESULTS: After a median follow-up of 15 months, 54.9% of the 51 patients implanted with directional leads were using the advanced features in one or both leads (n = 42 leads, 42%), meaning these leads were programmed either with directional stimulation (n = 9, 9%), a shorter pw (n = 20, 20%) or both (n = 13, 13%). This included 92% of patients implanted in the Vim, 44% of those implanted in the STN, and 40% of those implanted in the GPi. CONCLUSIONS: DBS systems with advanced features may be particularly indicated for selected patients based on some clinical characteristics and the chosen target. This data may help clinicians allocate resources in a more informed way.

High-fidelity transmission of high-frequency burst stimuli from peripheral nerve to thalamic nuclei in children with dystonia.

High-frequency peripheral nerve stimulation has emerged as a noninvasive alternative to thalamic deep brain stimulation for some patients with essential tremor. It is not known whether such techniques might be effective for movement disorders in children, nor is the mechanism and transmission of the peripheral stimuli to central brain structures understood. This study was designed to investigate the fidelity of transmission from peripheral nerves to thalamic nuclei in children with dystonia undergoing deep brain stimulation surgery. The ventralis intermediate (VIM) thalamus nuclei showed a robust evoked response to peripheral high-frequency burst stimulation, with a greatest response magnitude to intra-burst frequencies between 50 and 100 Hz, and reliable but smaller responses up to 170 Hz. The earliest response occurred at 12-15 ms following stimulation onset, suggesting rapid high-fidelity transmission between peripheral nerve and thalamic nuclei. A high-bandwidth, low-latency transmission path from peripheral nerve to VIM thalamus is consistent with the importance of rapid and accurate sensory information for the control of coordination and movement via the cerebello-thalamo-cortical pathway. Our results suggest the possibility of non-invasive modulation of thalamic activity in children with dystonia, and therefore the possibility that a subset of children could have beneficial clinical response without the need for invasive deep brain stimulation.

Pharmacological and neurosurgical interventions for individuals with cerebral palsy and dystonia: a systematic review update and meta-analysis.

AIM: To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia. METHOD: Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE. RESULTS: Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis. INTERPRETATION: Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis.