Marsden Dystonia Research Articles

Efficacy of the Hegab temporomandibular joint splint in treating patients diagnosed with dystonia with or without systemic involvement: A report of 14 cases

Dystonia is a neurological motor disorder characterised by involuntary and uncontrollable muscle contractions, tension, twisting, and tremors. The aim of the present study was to analyse the improvement in dystonic contractions in patients with dystonia following the use of a Hegab temporomandibular joint splint (HTS). The Fahn-Marsden Dystonia Movement Scale (DMS) and Disability Scale were used in the current study to evaluate dystonia. An HTS with a thickness ranging from 4 to 6 mm was used to treat the patients enrolled in the study. The final sample comprised 14 patients (10 female and four male) with mean (range) ages of 35.64 (18 to 55) years. Pre-treatment DMS ranged from 6.5 to 57 mean (SD) 18.21 (13.38). At the end of the study, DMS ranged from 0 to 15 mean (SD) 3.14 (3.86). Statistical analysis of the differences between pre-treatment and post-treatment DMS showed a significant decrease in DMS at the end of the treatment period (p = 0.0001). Regarding the disability scale, pre-treatment disability scale ranged from 7 to 18 mean (SD) 9.46 (3.02). At the end of the study, DMS ranged from 0 to 3 mean (SD) 1.46 (1.13). There was a statistically highly significant decrease in the Disability Scale at the end of the treatment period (p value ≤ 0.0001). This study suggests that the HTS can be considered an effective treatment modality for dystonia, as it significantly decreases both the DMS and the Disability scale.

Zinc for GNAO1 encephalopathy: Preclinical profiling and a clinical case

De novo pathogenic variants in GNAO1-the gene encoding the major neuronal G protein Gαo-cause pediatric encephalopathies and other neurological deficiencies largely refractory to available therapies. Zn2+ emerged to restore guanosine triphosphate hydrolysis and cellular interactions of pathogenic Gαo; dietary zinc salt supplementation improves lifespan and motoric function in a Drosophila disease model. Using biochemical, animal, and first-in-human studies, we provide support for the patient stratification and application of zinc acetate in GNAO1-associated disorders. We show that 16 different pathogenic missense variants cluster in three distinct groups in their responsiveness to Zn2+, and we provide the safety study in a mouse disease model. We further describe treatment of a 3-year-old patient with the common pathogenic GNAO1 variant c607G>A, p.Gly203Arg with oral 50mg zinc (in the form of zinc acetate) daily, as applied in Wilson's disease. During 11months of treatment, the patient shows cessation of daily dyskinetic crises, improved Burke-Fahn Marsden Dystonia Rating Scale movement score, reduction in epileptic seizures, and an excellent safety profile. Our findings warrant a large-scale clinical trial and might set the new standard of care for GNAO1-related disorders. This work was funded by the Russian Science Foundation (grant #21-15-00138) and GNAO1 España.

Anterior capsulotomy combined with subthalamic nucleus deep brain stimulation for tardive dystonia

BackgroundDeep brain stimulation (DBS) has been reported as a therapy option for the motor dysfunction of severe tardive dystonia (TD). The major psychiatric diseases, however, are contraindications to DBS treatment in TD patients. MethodsSix severe, medically refractory TD patients undergoing bilateral anterior capsulotomy combined with bilateral subthalamic nucleus (STN)-DBS treatment were studied retrospectively at two time points: pre-operation, and 1–3 years post-operation. Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) was used to assess the dystonia and disability. Depressive, anxiety, psychiatric symptoms, and Quality of Life (QoL) were evaluated using the 17-item Hamilton Depression Scale (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive and Negative Syndrome Scale (PANSS), and 36-item Short-Form Health Survey (SF-36), respectively. ResultsAfter receiving the combination treatment for 25 ± 11.6 months (range, 12–41 months), significant clinical symptom improvements were reported in TD patients. BFMDRS motor and disability scores were ameliorated by 78.5 ± 32.0% (p = 0.031) and 76.5 ± 38.6% (p = 0.031), respectively. The HAMD-17 and HAMA-14 scores were reduced by 60.3 ± 27.9% (p = 0.007) and 60.0 ± 24.6% (p = 0.009), respectively. Furthermore, the PANSS scores of the comorbidity schizophrenia TD patients decreased by 58.1 ± 6.0% (p = 0.022), and the QoL improved by 59.7 ± 14.1% (SF-36, p = 0.0001). During the research, there were no notable adverse effects or problems. ConclusionBilateral anterior capsulotomy combined with bilateral STN-DBS may be an effective and relatively safe treatment option for severe TD comorbid with major psychiatric disorders.

The use of flexible botulinum toxin type A inter-injection intervals after removal of deep brain stimulation due to infection in patient with DYT-THAP1 (DYT6)

Deep brain stimulation of globus pallidus internus is a safe and effective method of treatment of isolated generalized dystonia. Abrupt discontinuation of stimulation can lead to a sharp increase in the severity of the condition with a significant increase in the risk of dystonic status. Correction of the condition by selecting conservative therapy is often insufficient. Based on the description of a clinical observation, we demonstrated the possibility of effective use of flexible botulinum toxin type A inter-injection intervals after removal of deep brain stimulation due to infection in patient with DYT-THAP1 (DYT6). Due to the high risk of formation of antibodies to botulinum toxin type A when using short intervals, as well as when using high doses, preference was given to a drug with proven low immunogenicity — incobotulotoxin A. Incobotulotoxin A was administered once a month in a total dose of 400 units to various muscle groups (head, neck, trunk, limbs). At the time of publication, the duration of follow-up was six months, six procedures were performed, a total of 2,400 units of incobotulotoxin A. No significant side effects were noted. Evaluation of the effectiveness of the therapy was carried out by calculating the points of the Burke–Fahn–Marsden Dystonia Rating Scale. There was a decrease from 34 points (the indicator at the time of termination of neurostimulation) to 13.5 points (after six months of therapy). The therapy allowed the patient to maintain motor activity during the waiting period for repeated deep brain stimulation.

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

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. We restrospectively reviewed our cases of focal and hemidystonia undergoing unilateral Pallidotomy at our institute to evaluate the short-term and long-term outcome. 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. 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. 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.

Subthalamic deep brain stimulation for primary dystonia: defining an optimal location using the medial subthalamic nucleus border as anatomical reference.

Although the subthalamic nucleus (STN) has proven to be a safe and effective target for deep brain stimulation (DBS) in the treatment of primary dystonia, the rates of individual improvement vary considerably. On the premise of selecting appropriate patients, the location of the stimulation contacts in the dorsolateral sensorimotor area of the STN may be an important factor affecting therapeutic effects, but the optimal location remains unclear. This study aimed to define an optimal location using the medial subthalamic nucleus border as an anatomical reference and to explore the influence of the location of active contacts on outcomes and programming strategies in a series of patients with primary dystonia. Data from 18 patients who underwent bilateral STN-DBS were retrospectively acquired and analyzed. Patients were assessed preoperatively and postoperatively (1 month, 3 months, 6 months, 1 year, 2 years, and last follow-up after neurostimulator initiation) using the Toronto Western Spasmodic Torticollis Rating Scale (for cervical dystonia) and the Burke-Fahn-Marsden Dystonia Rating Scale (for other types). Optimal parameters and active contact locations were determined during clinical follow-up. The position of the active contacts relative to the medial STN border was determined using postoperative stereotactic MRI. The clinical improvement showed a significant negative correlation with the y-axis position (anterior-posterior; A+, P-). The more posterior the electrode contacts were positioned in the dorsolateral sensorimotor area of the STN, the better the therapeutic effects. Cluster analysis of the improvement rates delineated optimal and sub-optimal groups. The optimal contact coordinates from the optimal group were 2.56 mm lateral, 0.15 mm anterior, and 1.34 mm superior relative to the medial STN border. STN-DBS was effective for primary dystonia, but outcomes were dependent on the active contact location. Bilateral stimulation contacts located behind or adjacent to Bejjani's line were most likely to produce ideal therapeutic effects. These findings may help guide STN-DBS preoperative planning, stimulation programming, and prognosis for optimal therapeutic efficacy in primary dystonia.

Blood neurofilament light chain as a surrogate marker for dystonia.

Dystonia is a heterogeneous movement disorder, and it remains unclear whether neurodegeneration is involved. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. We aimed to investigate whether plasma NfL levels were elevated and associated with disease severity in patients with dystonia. We enrolled 231 unrelated dystonia patients (isolated dystonia n = 203; combined dystonia n = 28) and 54 healthy controls from movement disorder clinics. Clinical severity was evaluated using the Fahn Marsden Dystonia Rating Scale, the Unified Dystonia Rating Scale, and the Global Dystonia Rating Scale. Blood NfL levels were measured by single-molecule array. Plasma NfL levels were significantly higher in those with generalized dystonia compared to those with focal dystonia (20.1 ± 8.8 vs. 11.7 ± 7.2 pg/mL; p = 0.01) or controls (p < 0.01), while the level was comparable between the focal dystonia group and controls (p = 0.08). Furthermore, the dystonia combined with parkinsonism group had higher NfL levels than the isolated dystonia group (17.4 ± 6.2 vs. 13.5 ± 7.5 pg/mL; p = 0.04). Notably, whole-exome sequencing was performed in 79 patients and two patients were identified as having likely pathogenic variants: one had a heterozygous c.122G>A (p.R41H) variant in THAP1 (DYT6) and the other carried a c.1825G>A (p.D609N) substitution in ATP1A3 (DYT12). No significant correlation was found between plasma NfL levels and dystonia rating scores. Plasma NfL levels are elevated in patients with generalized dystonia and dystonia combined with parkinsonism, suggesting that neurodegeneration is involved in the disease process of this subgroup of patients.

Cranial geometry in patients with dystonia and Parkinson’s disease

Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = − 0.282, p = 0.016). The Burke–Fahn–Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms.

The Safety to Switch from Constant Voltage to Constant Current with a Mixed Internal Pulse Generator in Deep Brain Stimulation

Abstract Background: Deep brain stimulation (DBS) is an efficient modality for the treatment of movement disorders. Differing from the constant voltage (CV)-DBS devices, constant current (CC)-DBS devices may allow more precise stimulation of the target brain regions since they are less influenced by impedance. If internal pulse generators (IPGs) of DBS devices are required to be connected with electrodes of different brands, employing proper adapters is necessary. Such connected DBS devices are called mixed or hybrid devices. Objectives: As there is sparse information about the clinical mixed devices, we studied their safety and efficacy. Materials and Methods: Clinical scores of 13 patients implanted with mixed DBS devices were determined with the Unified Parkinson’s Disease Rating Scale (UPDRS) in Parkinson’s disease (PD) (n = 10) and with the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) in dystonia (n = 3). Patient satisfaction was assessed with the Timmerman questionnaire. The Clinical Global Impression Improvement (CGI-I) Scale was also evaluated. Results: Patients’ overall satisfaction was considerably higher with mixed devices. The UPDRS and BFMDRS clinical scores did not significantly differ after switching to a mixed DBS device. Three patients before the DBS switch suffered from side effects under the CV mode. These patients got rid of the side effects in their follow-up with a reduction in pulse width values. Discussion: Mixed devices working in CC mode are well tolerated with high patient satisfaction. Conclusion: Besides patient satisfaction, mixed IPGs are also considered safe.

Obsessive–compulsive symptoms are negatively correlated with motor severity in patients with generalized dystonia

We aimed to clarify the correlations between motor symptoms and obsessive–compulsive symptoms and between the volumes of basal ganglia components and obsessive–compulsive symptoms. We retrospectively included 14 patients with medically intractable, moderate and severe generalized dystonia. The Burke–Fahn–Marsden Dystonia Rating Scale and Maudsley Obsessional Compulsive Inventory were used to evaluate the severity of dystonia and obsessive–compulsive symptoms, respectively. Patients with generalized dystonia were divided into two groups; patients whose Maudsley Obsessional Compulsive Inventory score was lower than 13 (Group 1) and 13 or more (Group 2). Additionally, the total Maudsley Obsessional Compulsive Inventory scores in patients with dystonia were significantly higher than normal volunteers’ scores (p = 0.025). Unexpectedly, Group 2 (high Maudsley Obsessional Compulsive Inventory scores) showed milder motor symptoms than Group 1 (low Maudsley Obsessional Compulsive Inventory scores) (p = 0.016). “Checking” rituals had a strong and significant negative correlation with the Burke–Fahn–Marsden Dystonia Rating Scale (ρ = − 0.71, p = 0.024) and a strong positive correlation with the volumes of both sides of the nucleus accumbens (right: ρ = 0.72, p = 0.023; left: ρ = 0.70, p = 0.034). Our results may provide insights into the pathogenesis of obsessive–compulsive disorder and dystonia.

Micro lesion effect of pallidal deep‑brain stimulation for meige syndrome

To analyse the microlesion effect (MLE) in the globus pallidus interna (GPi) of deep brain stimulation (DBS) in patients with Meige syndrome. Thirty-two patients with primary Meige syndrome who underwent GPi-DBS in this study. Burke–Fahn–Marsden Dystonia Rating Scale scores (BFMDRS-M) were obtained for the evaluation of clinical symptoms at 3 days before DBS (baseline), 24 h after DBS surgery, once weekly for 1 month until electrical stimulation, 6 months postoperatively and 12 months after surgery. Twenty-seven patients had MLE after GPi-DBS. The mean time of BFMDRS-M scores maximal improvement from MLE was 35.9 h postoperatively (range, 24–48 h), and the mean scores improved by 49.35 ± 18.16%. At 12 months after surgery, the mean BFMDRS-M scores improved by 50.28 ± 29.70%. There was a positive correlation between the magnitude of MLE and the motor score at 12 months after GPi-DBS (R2 = 0.335, p < 0.05). However, there was no correlation between the duration of MLE and DBS improvement. Most Meige syndrome patients who underwent GPi-DBS and had MLE benefited from MLE. For Meige syndrome, MLE might be a predictive factor for patient clinical symptom improvement from DBS.

Long-Term Outcomes of Deep Brain Stimulation in Pantothenate Kinase-Associated Neurodegeneration-Related Dystonia.

ObjectiveTo investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN).MethodsWe reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre- and postoperative Burke–Fahn–Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected. Descriptive analysis was performed for BFMDRS-M scores, BFMDRS-D scores, and the orofacial, axial, and limb subscores of the BFMDRS-M at 6–12, 24–36, and 60–72 months postoperatively.ResultsFive classic-type, four atypical-type, and one unknown-type PKAN cases were identified. The mean preoperative BFMDRS-M score was 92.1 for the classic type and 38.5 for the atypical or unknown type, with a mean BFMDRS follow-up of 50.7 months and a clinical follow-up of 69.0 months. The mean improvements in BFMDRS-M score were 11.3%, 41.3%, and 30.5% at 6–12, 24–36, and 60–72 months, respectively. In four patients with full regular evaluations until 60–72 months, improvements in the orofacial, axial, and limb subscores persisted, but the disability scores worsened from 24–36 months post-operation compared to the baseline, mainly owing to the aggravation of eating and feeding disabilities.ConclusionThe benefits of GPi-DBS on dystonia may persist for more than 5 years in PKAN. The effects on patients’ subjective disability may have a shorter duration despite improvements in dystonia owing to the complex manifestations of PKAN.

Acupuncture for dystonia in brain-type Wilson's disease with internal retention of damp heat pattern: A randomized clinical trail针刺治疗湿热内蕴型肝豆状核变性脑型肌张力障碍-随机临床试验

ObjectiveTo observe the clinical efficacy of acupuncture on dystonia in brain-type Wilson's disease (WD) with internal retention of damp heat pattern. MethodsA total of 60 patients with WD dystonia with internal retention of damp heat pattern were randomized into acupuncture and medication groups using a random number table, with 30 participants in each group. All patients had a low-copper diet and consumed dimercaptopropanesulfonate sodium (DMPS) for copper excretion. In the acupuncture group, on the base of the same treatment as that given to the medication group, acupuncture was applied at Băihuì (百会GV20), Shéntíng (神庭GV24), Chéngjiāng (承浆CV4), Jiānyú (肩髃LI5), Nàoshū (臑俞SI10), Wàiguān (外关TE5), Nèiguān (内关PC6), Shŏusānlĭ (手三里LI10), Hégŭ (合谷LI4), Yángxī (阳溪LI5), Huántiào (环跳GB30), Bìguān (髀关ST31), Yánglíngquán (阳陵泉GB34), Fēnglóng (丰隆ST40), Zúsānlĭ (足三里ST36), Sānyīnjiāo (三阴交SP6), Xuánzhōng (悬钟GB39), and Xíngjiān (行间LR2). Before and 24 days after treatment, the modified Ashworth scale (MAS) and Burke–Fahn–Marsden dystonia rating scale (BFMDRS) were used to evaluate dystonia symptoms.The allocation scheme was concealed for the outcome assessors. ResultsThe data of 30 cases were analyzed in each group.Before treatment, the MAS score difference between the acupuncture and medication groups was not statistically significant (P > 0.05). Compared with the score before treatment, the MAS score was lower significantly in both the acupuncture group (2.63 ± 0.76 vs 4.50 ± 0.78) and medication group (3.30 ± 0.65 vs 4.40 ± 0.77) after treatment (both P < 0.05). After treatment, the MAS score in the acupuncture group was significantly lower than that in the medication group (P < 0.01). Before treatment, the BFMDRS score was not significantly different between the two groups (P > 0.05). Compared with the score before treatment, the BFMDRS score was significantly lower in both the acupuncture (64.97 ± 14.26 vs 85.23 ± 16.99) and medication groups (11.33 ± 2.60 vs 75.40 ± 16.25) after treatment (both P < 0.05). The BFMDRS score of the acupuncture group was lower than that of the medication group after treatment (P < 0.05).During treatment, 1 case had allergic reaction of DMPS in the acupuncture group, manifested as reddish skin and skin rashes, and the allergic symptoms disappeared after anti-allergic treatment. There was no any adverse reaction in the medication group. ConclusionCombined treatment with acupuncture and Western medication is significantly effective against dystonia in brain-type WD with internal retention of damp heat pattern.

Metabolic Imaging of Deep Brain Stimulation in Meige Syndrome.

ObjectivesThe subthalamic nucleus (STN) has been shown to be a safe and effective deep brain stimulation (DBS) surgical target for the treatment of Meige syndrome. The aim of this study was to compare changes in brain metabolism before and 6 months after STN-DBS surgery.MethodsTwenty-five patients with primary Meige syndrome underwent motor function assessment, including the Burke–Fahn–Marsden Dystonia Rating Scale movement (BFMDRS-M) and disability subscale (BFMDRS-D) and positron emission tomography with an 18[F]-fluorodeoxyglucose scan before and 6 months after STN-DBS surgery. For the voxelwise metabolic change assessment, the p-value was controlled for multiple comparisons using the familywise error rate.ResultsThere was a significant decrease in BFMDRS-M scores 6 months after STN-DBS, from 10.02 ± 3.99 to 4.00 ± 2.69 (p < 0.001). The BFMDRS-D scores also decreased significantly from 4.52 ± 2.90 to 0.64 ± 1.29 (p < 0.001). In the left hemisphere, hypermetabolism was found in the occipital lobe, superior parietal gyrus, postcentral gyrus and thalamus. In the right hemisphere, hypermetabolism was found in the lentiform nucleus, precuneus and precentral gyrus in patients with Meige syndrome receiving DBS. In addition, the bilateral inferior temporal gyrus and middle frontal gyrus exhibited glucose hypermetabolism.ConclusionOur findings indicate that STN-DBS has a significant effect on metabolic level in the brain, which may be an important mechanism for the treatment of Meige syndrome using STN-DBS.

Unilateral pallidothalamic tractotomy at Forel's field H1 for cervical dystonia.

BackgroundNeurosurgical ablation of Forel's field H1 for cervical dystonia, which is currently abandoned, was formerly used in the 1960s–1970s. Regardless of the lack of neuroimaging modalities and objective evaluation scales, the reported efficacy was significant. Although recent studies have reappraised the ablation of the pallidothalamic tract at Forel's field H1 for Parkinson's disease, the efficacy for cervical dystonia has not been investigated well.MethodsData of 35 patients with cervical dystonia who underwent unilateral pallidothalamic tractotomy at Forel's field H1 were retrospectively analyzed. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores, the neck score of the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), and adverse events were evaluated preoperatively and at the last available follow‐up period.ResultsThe mean clinical follow‐up period was 13.9 ± 6.5 months. The mean TWSTRS total scores were 34.3 ± 14.0 preoperatively and 18.4 ± 16.5 at the last available follow‐up period (46.4% improvement, p < 0.0001). The BFMDRS neck score also improved significantly from 6.2 ± 2.9 preoperatively to 2.8 ± 2.8 at the last available follow‐up period (55.0% improvement on the neck score, p < 0.0001). Reduced hand dexterity in seven patients, hypophonia in five patients, dysarthria in four patients, and executive dysfunction in one patient were confirmed as adverse events at the last available follow‐up evaluation. One patient had postoperative hemorrhage.ConclusionThe current study confirmed significant improvement in TWSTRS total scores and BFMDRS neck scores at the 13.9‐month follow‐up after unilateral pallidothalamic tractotomy. The pallidothalamic tract in Forel's field H1 is expected to be an alternative treatment target for cervical dystonia.

Long-term effects of pallidal deep brain stimulation in tardive dystonia: a follow-up of 5–14 years

IntroductionPallidal DBS is an established treatment for severe isolated dystonia. However, its use in disabling and treatment-refractory tardive syndromes (TS) including tardive dyskinesia and tardive dystonia (TD) is less well investigated and long-term data remain sparse. This observational study evaluates long-term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with medically refractory TS.MethodsWe retrospectively analyzed a cohort of seven TD patients with bilateral GPi-DBS. Involuntary movements, dystonia and disability were rated at long-term follow-up (LT-FU) after a mean of 122 ± 33.2 SD months (range 63–171 months) and compared to baseline (BL), short-term (ST-FU; mean 6 ± 2.0 SD months) and 4-year follow-up (4y-FU; mean 45 ± 12.3 SD months) using the Abnormal Involuntary Movement Scale (AIMS) and the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), respectively. Quality of life and mood were evaluated using the SF36 and Beck Depression Index (BDI) questionnaires, respectively.ResultsAt LT-FU patients had improved by 73% ± 14.2 SD in involuntary movements and 90% ± 1.0 SD in dystonia. Mood had improved significantly whereas quality of life remained unchanged compared to baseline. No serious long-lasting stimulation-related adverse events (AEs) were observed. Three patients of this cohort presented without active stimulation and ongoing symptom relief at long-term follow-up after 3–10 years of continuous DBS.ConclusionPallidal DBS is a safe and effective long-term TD treatment. Even more interesting, three of our patients could stop stimulation after several years of DBS without serious relapse. Larger studies need to explore the phenomenon of ongoing symptom relief after DBS cessation.

Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?

Background: The pathogenesis of dystonia is remarkably diverse. Some types of dystonia, such as DYT5 (DYT-GCH1) and tardive dystonia, are related to dysfunction of the dopaminergic system. Furthermore, on pathological examination, cell loss in the substantia nigra (SN) of patients with dystonia has been reported, suggesting that impaired dopamine production may be involved in DYT5 and in other types of dystonia.Objectives: To investigate functional dopaminergic impairments, we compared patients with dystonia and those with Parkinson's disease (PD) with normal controls using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and dopamine transporter single photon emission computed tomography (DAT SPECT).Methods: A total of 18, 18, and 27 patients with generalized or segmental dystonia, patients with PD, and healthy controls, respectively, were examined using NM-MRI. The mean area corresponding to NM in the SN (NM-SN) was blindly quantified. DAT SPECT was performed on 17 and eight patients with dystonia and PD, respectively. The imaging data of DAT SPECT were harmonized with the Japanese database using striatum phantom calibration. These imaging data were compared between patients with dystonia or PD and controls from the Japanese database in 256 healthy volunteers using the calibrated specific binding ratio (cSBR). The symptoms of dystonia were evaluated using the Fahn–Marsden Dystonia Rating Scale (FMDRS), and the correlation between the results of imaging data and FMDRS was examined.Results: The mean areas corresponding to NM in the SN (NM-SN) were 31 ± 4.2, 28 ± 3.8, and 43 ± 3.8 pixels in patients with dystonia, PD, and in healthy controls, respectively. The mean cSBRs were 5 ± 0.2, 2.8 ± 0.2, 9.2 (predictive) in patients with dystonia, PD, and in healthy controls, respectively. The NM-SN area (r = −0.49, p < 0.05) and the cSBR (r = −0.54, p < 0.05) were inversely correlated with the FMDRS. There was no significant difference between the dystonia and PD groups regarding NM-SN (p = 0.28). In contrast, the cSBR was lower in patients with PD than in those with dystonia (p < 0.5 × 10−6).Conclusions: Impairments of the dopaminergic system may be involved in developing generalized and segmental dystonia. SN abnormalities in patients with dystonia were supposed to be different from degeneration in PD.

Surgical Management for Dystonia: Efficacy of Deep Brain Stimulation in the Long Term.

Introduction: Dystonia is a movement disorder substantially affecting the quality of life. Botulinum Neurotoxin (BoNT) is used intramuscularly as a treatment for dystonia; however, not all dystonia patients respond to this treatment. Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease (PD) and essential tremor, but it can help in dystonia as well. Objectives: We studied a total of 67 dystonia patients who were treated with DBS over a period of 7 years to find out the long-term efficacy of DBS in those patients. First, we calculated patient improvement in post-surgery follow-up programs using the Global Dystonia Severity scale (GDS) and Burke–Fahn–Marsden dystonia rating scale (BFMDRS). Secondly, we analyzed the scales scores to see if there was any statistical significance. Methods: In our study we analyzed patients with ages from 38 to 78 years with dystonia who underwent DBS surgery between January 2014 and December 2020 in four different centers (India, Kuwait, Egypt, and Turkey). The motor response to DBS surgery was retrospectively measured for each patient during every follow-up visit using the GDS and the BFMDRS scales. Results: Five to 7 years post-DBS, the mean reduction in the GDS score was 30 ± 1.0 and for the BFMDRS score 26 ± 1.0. The longitudinal change in scores at 12 and 24 months post-op was also significant with mean reductions in GDS and BFMDRS scores of 68 ± 1.0 and 56 ± 1.0, respectively. The p-values were <0.05 for our post-DBS dystonia patients. Conclusions: This study illustrates DBS is an established, effective treatment option for patients with different dystonias, such as generalized, cervical, and various brain pathology-induced dystonias. Although symptoms are not completely eliminated, continuous improvements are noticed throughout the post-stimulation time frame.

Globus Pallidus Internus Deep Brain Stimulation Using Frame-Based vs. Frameless Stereotaxy in Dystonia: A Single-Center Experience.

Objective: Bilateral globus pallidus internus deep brain stimulation (GPi-DBS) is an established and effective therapy for primary refractory dystonia. However, the comparison of frameless vs. frame-based DBS surgery technique is still controversial. This retrospective study aims to compare the clinical outcome of two GPi-DBS surgical techniques for patients affected by primary generalized or multi-segmental dystonia.Methods: For lead's stereotaxic placement, 10 patients underwent frame-based surgery and the other 10 subjects DBS surgery with a frameless technique. Clinical features were evaluated at baseline and 6 and 12 months after surgery by means of the Burke–Fahn–Marsden Dystonia Rating Scale.Results: Frame-based GPi-DBS and frameless stereotaxic group revealed a comparable clinical outcome with no surgical complications.Conclusions: Frameless technique is safe and well-tolerated by patients and showed similar effectiveness of the frame-based stereotaxic surgery during GPi-DBS for primary dystonia. Notably, it could be a valid alternative solution because of the great advantage in improving the patient's discomfort during awake surgery.

Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia.

Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% (p < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD.