Dystonia Score Research Articles

Efficacy of Oral Trihexyphenidyl Plus Clonazepam Versus Trihexyphenidyl for the Treatment of Dystonia in Children With Dystonic Cerebral Palsy: An Open-Label Randomized Controlled Trial

BackgroundTrihexyphenidyl and clonazepam are commonly used to treat dystonia in children with cerebral palsy (CP). However, there is a notable gap in the literature when it comes to studies that combine these first-line agents for the management of dystonia. MethodsThis open-label, randomized controlled trial aimed to compare the efficacy of adding oral clonazepam to trihexyphenidyl (THP + CLZ) versus using trihexyphenidyl alone (THP) in reducing the severity of dystonia, as measured by the Barry-Albright Dystonia (BAD) score. The study was conducted over a 12-week therapy period in children with dystonic CP aged two to 14 years. ResultsEach group enrolled 51 participants. The THP + CLZ group showed significantly better improvement in dystonia severity at 12 weeks compared with the THP group alone (−4.5 ± 2.9 vs −3.4 ± 1.7, P = 0.02). Furthermore, the THP + CLZ group exhibited superior improvement in the severity of choreoathetosis, upper limb function, pain perception by the child, and quality of life, with P values of 0.02, 0.009, 0.01, and 0.01, respectively. The number of participants experiencing treatment-emergent adverse events was comparable in both groups (P = 0.67). Importantly, none of the participants in any of the groups reported any serious adverse events. ConclusionA combination of oral THP + CLZ proves to be more efficacious than using THP alone for the treatment of dystonic CP in children aged two to 14 years in terms of reducing the severity of dystonia.

Genome sequencing reanalysis increases the diagnostic yield in dystonia

PurposeWe investigated the contribution of genomic data reanalysis to the diagnostic yield of dystonia patients who remained undiagnosed after prior genome sequencing. MethodsProbands with heterogeneous dystonia phenotypes who underwent initial genome sequencing (GS) analysis in 2019 were included in the reanalysis, which was performed through gene-specific discovery collaborations and systematic genomic data reanalysis. ResultsInitial GS analysis in 2019 (n = 111) identified a molecular diagnosis in 11.7 % (13/111) of cases. Reanalysis between 2020 and 2023 increased the diagnostic yield by 7.2 % (8/111); 3.6 % (4/111) through focused gene-specific clinical correlation collaborative efforts [VPS16 (two probands), AOPEP and POLG], and 3.6 % (4/111) by systematic reanalysis completed in 2023 [NUS1 (two probands) and DDX3X variants, and a microdeletion encompassing VPS16]. Seven of these patients had a high phenotype-based dystonia score ≥3. Notable unverified findings in four additional cases included suspicious variants of uncertain significance in FBXL4 and EIF2AK2, and potential phenotypic expansion associated with SLC2A1 and TREX1 variants. ConclusionGS data reanalysis increased the diagnostic yield from 11.7 % to 18.9 %, with potential extension up to 22.5 %. While optimal timing for diagnostic reanalysis remains to be determined, this study demonstrates that periodic re-interrogation of dystonia GS datasets can provide additional genetic diagnoses, which may have significant implications for patients and their families.

Targeting Sensory Systems in the Treatment of Dystonia: Outcomes from a Case Series

Substantial scientific evidence has been gathered on the pathophysiology of dystonia, leading to proposed theoretical treatment protocols for rehabilitating patients with this disorder. This study aimed to assess patient outcomes following the application of novel functional neurology treatment protocols based on basic neuroscience research. A consecutive case series of patients diagnosed with dystonia and treated in a private practice setting was studied for their response to neural rehabilitation techniques based on published basic neuroscience research. Sensory stimulation techniques including non-invasive spinal cord stimulation, vestibular nerve neuromodulation based on targeted skull vibration and stimulation of reciprocal inhibitory nerve activity of dystonic muscles was used as novel add on therapy to standard care. The subjects included 6 cases of cervical dystonia and 3 cases of more generalized dystonia. The proposed rehabilitation procedures were explained in detail to the patients, including the investigational nature of these procedures, and written informed consent was obtained from each patient prior to treatment. Based on the comparison of total dystonia scores upon admission and prior to treatment with total dystonia scores at the completion of a course of care, all 9 patients in this case series demonstrated improvement in their dystonic symptoms after treatment. The group average pre-treatment dystonia score was 11.4, while the post-treatment group averaged dystonia score was 5.2 points. This represents a moderate, but clinically important improvement in global dystonia scores in a series of 9 patients treated in a private practice setting. Considering that dystonia is highly resistant to treatment, the improvement seen in this case series suggests that the methods involved warrant further investigation in a more formal research setting. The clinically meaningful improvements (approximately 50% for the group average) seen in these cases argue for more research into the role of the sensory systems in both the pathophysiology and treatment of dystonic conditions.

Acute Dystonia Associated with Low-Dose Aripiprazole in a Male Child: A Case Report

Aripiprazole is a newer anti-psychotic agent with low liability for Extrapyramidal Symptoms (EPS). Acute dystonia develops due to a lack of dopamine, resulting in a relative overactivity of cholinergic neurons. In the past, cases of Aripiprazole-induced acute dystonia have been reported more frequently among adults than children. Here, the authors present a case in which acute dystonia developed at a very low dose (2 mg) of Aripiprazole. The case involves a 10-year-old boy diagnosed with Oppositional Defiant Disorder (ODD) who exhibited aggressive behaviour and irritability. Aripiprazole (2 mg) was initiated for treatment, but after five days, the patient developed excessive sleepiness, slurred speech, oculogyric crisis, and torticollis, indicative of acute dystonia. To rule out any organic causes, a detailed assessment and investigations were conducted, including complete blood counts, liver and kidney function tests, serum calcium, electrolytes, ceruloplasmin, blood copper levels, slit-lamp examination for Kayser-Fleischer ring, and electroencephalography, which did not reveal any significant organic conditions. Aripiprazole was discontinued, and Promethazine was administered. The dystonia score on the Unified Dystonia Rating Scale (UDRS) decreased from 10 to 0 in 5 days, indicating complete resolution of dystonia. Naranjo’s causality assessment score was seven, reflecting the probable association of aripiprazole with acute dystonia. This case emphasises the importance of monitoring for adverse reactions to anti-psychotic medications, particularly in paediatric patients, and the need for prompt recognition and management of adverse effects to ensure patient safety and treatment efficacy. To the best of our knowledge, this is the first case report of acute dystonia in a child at such a low dose of Aripiprazole. Clinicians should be vigilant for the emergence of such significant adverse effects of commonly used drugs.

Clinical and genetic profile of patients with dystonia: An experience from a tertiary neurology center from India

BackgroundThe genetics of dystonia have varied across different ethnicities worldwide. Its significance has become more apparent with the advent of deep brain stimulation. ObjectiveTo study the clinico-genetic profile of patients with probable genetic dystonia using whole exome sequencing (WES). MethodsA prospective, cross-sectional study was conducted from May 2021 to September 2022, enrolling patients with dystonia of presumed genetic etiology for WES. The study compared genetically-determined cases harboring pathogenic/likely-pathogenic variants (P/LP subgroup) with the presumed idiopathic or unsolved cases. ResultsWe recruited 65 patients (males, 69.2%) whose mean age of onset (AAO) and assessment were 25.0 ± 16.6 and 31.7 ± 15.2 years, respectively. Fifteen had pathogenic/likely-pathogenic variants (yield = 23.1%), 16 (24.6%) had variants of uncertain significance (VUS), 2 were heterozygous carriers while the remaining 32 cases tested negative (presumed idiopathic group). The P/LP subgroup had a significantly younger AAO (16.8 ± 12.3 vs 31.3 ± 17.0 years, p = 0.009), longer duration of illness (10.9 ± 10.3 vs 4.8 ± 4.3 years, p = 0.006), higher prevalence of generalized dystonia (n = 12, 80.0% vs n = 10, 31.3%, p = 0.004), lower-limb onset (n = 5, 33.3% vs n = 1, 3.1%, p = 0.009), higher motor (p = 0.035) and disability scores (p = 0.042). The classical DYT genes with pathogenic/likely pathogenic variants included 3 cases each of TOR1A, and KMT2B, and single cases each of SGCE, EIF2AK2, and VPS16. Non-DYT pathogenic/likely-pathogenic cases included PINK1, PANK2, CTSF, POLG, MICU1, and TSPOAP1. ConclusionsThe yield of WES was 23.1% among cases of probable genetic dystonia. Pathogenic or likely pathogenic variants in TOR1A, KMT2B, and SGCE genes were commoner. The absence of family history emphasizes the importance of accurate assessment of clinical predictors before genetic testing.

Glutaric Aciduria Type 1: Comparison between Diffusional Kurtosis Imaging and Conventional MR Imaging.

Routine MR imaging has limited use in evaluating the severity of glutaric aciduria type 1. To better understand the mechanisms of brain injury in glutaric aciduria type 1, we explored the value of diffusional kurtosis imaging in detecting microstructural injury of the gray and white matter. This study included 17 patients with glutaric aciduria type 1 and 17 healthy controls who underwent conventional MR imaging and diffusional kurtosis imaging. The diffusional kurtosis imaging metrics of the gray and white matter were measured. Then, the MR imaging scores and diffusional kurtosis imaging metrics of all ROIs were further correlated with the morbidity scores and Barry-Albright dystonia scores. The MR imaging scores showed no significant relation to the morbidity and Barry-Albright dystonia scores. Compared with healthy controls, patients with glutaric aciduria type 1 showed higher kurtosis values in the basal ganglia, corona radiata, centrum semiovale, and temporal lobe (P < .05). The DTI metrics of the basal ganglia were higher than those of healthy controls (P < .05). The fractional anisotropy value of the temporal lobe and the mean diffusivity values of basal ganglia in glutaric aciduria type 1 were lower than those in the control group (P < .05). The diffusional kurtosis imaging metrics of the temporal lobe and basal ganglia were significantly correlated with the Barry-Albright dystonia scores. The mean kurtosis values of the anterior and posterior putamen and Barry-Albright dystonia scores were most relevant (r = 0.721, 0.730, respectively). The mean kurtosis values of the basal ganglia had the best diagnostic efficiency with area under the curve values of 0.837 for the temporal lobe, and the mean diffusivity values of the basal ganglia in glutaric aciduria type 1 were lower than those in the control group (P < .05). The diffusional kurtosis imaging metrics of the temporal lobe and basal ganglia were significantly correlated with the Barry-Albright dystonia scores. The mean kurtosis values of the anterior and posterior putamen and Barry-Albright dystonia scores were most relevant (r = 0.721, 0.730, respectively). The mean kurtosis values of the basal ganglia had the best diagnostic efficiency with area under the curve values of 0.837. Diffusional kurtosis imaging provides more comprehensive quantitative information regarding the gray and white matter micropathologic damage in glutaric aciduria type 1 than routine MR imaging scores.

Trihexyphenidyl in young children with dystonic cerebral palsy: A single arm study.

The incidence of dystonic cerebral palsy causing significant morbidity is on the rise. There is a paucity of evidence for the management of dystonia in children. Forty-one children aged 6 months-5 years with predominantly dystonic cerebral palsy were started on a predetermined protocol of trihexyphenidyl (0.25-0.52 mg/kg) and followed up at 3, 6 and 12 weeks. Dystonia severity, motor function and developmental age at baseline and 12 weeks were compared using the Global Dystonia Scale (GDS), the Gross Motor Function Measure (GMFM), and Fine Motor/Perceptual Subscale of the Early Developmental Profile-2. Thirty-four children completed the entire 12 weeks of intervention. The mean age of participants was 25±11 months. A significant decrease in median total dystonia scores on the GDS was observed post-intervention (74.5 to 59, p < 0.0001), and 64% of participants gained motor milestones. GMFM scores increased significantly from a median of 19.8% pre-intervention to 26.5% post-intervention (p < 0.0001). There was improvement in the fine motor domain as compared to the baseline (p < 0.0001). The number of children classified at Gross Motor Function Classification System levels 1 and 2 increased to 47.05% from 5.88% in the pre-intervention group. Trihexyphenidyl significantly improved dystonia, motor function and development in children with dystonic cerebral palsy in this study. Additional studies are needed to clarify its role in larger numbers of children with this condition.

Transient dystonia correlates with parkinsonism after 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine in nonhuman primates.

Unilateral internal carotid artery 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion in non-human primates produces transient contralateral hemi-dystonia followed by stable contralateral hemi-parkinsonism; the relationship between dystonia and parkinsonism remains unclear. We hypothesized that transient dystonia severity following MPTP correlates with parkinsonism severity. In male Macaca nemestrina (n = 3) and M. fascicularis (n = 17) we administered unilateral intra-carotid MPTP, then correlated validated blinded ratings of transient peak dystonia and delayed parkinsonism. We also correlated dystonia severity with post-mortem measures of residual striatal dopamine and nigral neuron counts obtained a mean 53 ± 15 days following MPTP, after resolution of dystonia but during stable parkinsonism. Median latency to dystonia onset was 1 day, and peak severity 2.5 days after MPTP; total dystonia duration was 13.5 days. Parkinsonism peaked a median of 19.5 days after MPTP, remaining nearly constant thereafter. Peak dystonia severity highly correlated with parkinsonism severity (r[18] = 0.82, p < 0.001). Residual cell counts in lesioned nigra correlated linearly with peak dystonia scores (r[18] = -0.68, p=<0.001). Dystonia was not observed in monkeys without striatal dopamine depletion (n = 2); dystonia severity correlated with striatal dopamine depletion when residual nigral cell loss was less than 50% ([11] r = -0.83, p < 0.001) but spanned a broad range with near complete striatal dopamine depletion, when nigral cell loss was greater than 50%. Our data indicate that residual striatal dopamine may not reflect dystonia severity. We speculate on mechanisms of transient dystonia followed by parkinsonism that may be studied using this particular NHP MPTP model to better understand relationships of transient dystonia to nigrostriatal injury and parkinsonism.

Prediction of Preoperative Scale Score of Dystonia Based on Few-Shot Learning

As a neurological disease, dystonia mainly has symptoms including muscle stiffness, dyskinesia, tremor, muscle spasm, etc. Dystonia score plays an important role in targeted auxiliary diagnosis, treatment plan design, and follow-up evaluation of patients. In this paper, the feature information of brain lateralization is extracted from electroencephalography (EEG) signals by clustering method, while information on time domain, frequency domain, and time sequence are extracted from EEG signals and electromyography (EMG) signals. Various deep-learning models are used to predict dystonia scores. Experiments show that this method can effectively predict dystonia based on the quantitative indicators extracted from few-shot neural signals. The methodology in this paper can help doctors judge the disease more accurately, make personalized treatment plans, and assist in monitoring the treatment effect.

Cerebral and cerebellar white matter tract alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN)

BackgroundTo examine structural connectivity of white matter tracts in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) dystonia and identify those ones which correlate negatively to severity of symptoms. MethodsIn a group of 41 patients suffering from PKAN dystonia and an age- and gender-matched control group, white matter tractography was carried out, based on diffusion tensor imaging magnetic resonance data. Postprocessing included assessment of Quantitative Anisotropy (QA) using q-space diffeomorphic reconstruction in order to reduce influence of iron accumulation in globus pallidus of patients. ResultsWhole brain tractography presented significantly reduced QA values in patients (0.282 ± 0.056, as compared to controls (0.325 ± 0.046, p < 0.001). 9 fiber clusters of tracts correlated negatively to the dystonia score of patients: the middle cerebellar peduncle and the tracts of both cerebellar hemispheres as well as corpus callosum, forceps minor, the superior cortico-striate tracts and the superior thalamic radiations of both cerebral hemispheres (False Discovery Rate FDR = 0.041). ConclusionThe finding of a reduced global structural connectivity within the white matter and of negative correlation of motor system-related tracts, mainly those between the basal ganglia, cortical areas and the cerebellum, fits well to the concept of a general functional disturbance of the motor system in PKAN.

Intestinal Decontamination Therapy for Dyskinesia and Motor Fluctuations in Parkinson's Disease

Parkinson's disease is neurodegenerative disorder with an initial robust response to levodopa. As the disease progresses, patients frequently develop dyskinesia and motor fluctuations, which are sometimes resistant to pharmacological therapy. In recent years, abnormalities in gut microbiota have been identified in these patients with a possible role in motor manifestations. Dysbiosis may reduce levodopa absorption leading to delayed “On” or “no-On” states. Among 84 consecutive patients with PD, we selected 14 with levodopa-induced dyskinesia and motor fluctuations with a Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part IV ≥ 8 points following a trial of pharmacological adjustment 2–3 months prior to study enrollment or adjustments in deep brain stimulation therapy. Patients received treatment with sodium phosphate enema followed by oral rifaximin and polyethylene glycol for 7 and 10 days, respectively. Evaluations between 14 to 21 days after starting treatment showed improvement in MDS-UPDRS-IV (P = 0.001), including duration (P = 0.001) and severity of dyskinesia (P = 0.003); duration of medication “Off”-state (P = 0.004); functional impact of motor fluctuations (P = 0.047) and complexity of motor fluctuations (P = 0.031); no statistical improvement was observed in “Off” dystonia (P = 0.109) and total motor scores (P = 0.430). Marked to moderate improvement in dyskinesia was observed in 57% of cases with blinded evaluation of videos. About 80% of patients perceived moderate to robust improvement at follow-up. A therapeutic strategy aimed at decontamination of intestines showed benefit in motor fluctuations and dyskinesia. Further studies should confirm and clarify the mechanism of improvement observed in these patients.

Unilateral pallidothalamic tractotomy for akinetic-rigid Parkinson's disease: a prospective open-label study.

Neurosurgical ablation is an effective treatment for medically refractory motor symptoms of Parkinson's disease (PD). A limited number of studies have reported the effect of ablation of the pallidothalamic tract for PD. In this study, the authors evaluated the safety and efficacy of unilateral pallidothalamic tractotomy for akinetic-rigid (AR)-PD. Fourteen AR-PD patients, who were enrolled in this prospective open-label study, underwent unilateral pallidothalamic tractotomy. The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and Part IV (dyskinesia and dystonia) scores and levodopa equivalent daily dose (LEDD) were evaluated at baseline and at 3 and 12 months postoperatively. Of the 14 patients enrolled in the study, 4 were lost to follow-up and 10 were analyzed. The total MDS-UPDRS Part III score significantly improved from 45 ± 4.6 at baseline to 32.9 ± 4.8 at 12 months postoperatively (p = 0.005). Contralateral side rigidity and bradykinesia significantly improved from 4.4 ± 0.5 and 10.4 ± 1.5 at baseline to 1.7 ± 0.4 (p = 0.005) and 5.2 ± 1.4 (p = 0.011) at 12 months, respectively. While posture significantly improved with a 20% reduction in scores (p = 0.038), no significant improvement was found in gait (p = 0.066). Dyskinesia and dystonia were improved with a 79.2% (p = 0.0012) and 91.7% (p = 0.041) reduction in scores, respectively. No significant change was found in the LEDD. Hypophonia was noted in 2 patients, eyelid apraxia was noted in 1 patient, and a reduced response to levodopa, which resulted in an increase in the daily dose of levodopa, was noted in 3 patients. No serious permanent neurological deficits were observed. Unilateral pallidothalamic tractotomy improved contralateral side rigidity and bradykinesia, dyskinesia, and dystonia in patients with AR-PD. Clinical trial registration no.: UMIN000031138 (umin.ac.jp).

Changes in Cerebral Gray and White Matter in Patients with Pantothenate Kinase-Associated Neurodegeneration: A Long-Term Magnetic Resonance Imaging Follow-Up Study.

ObjectiveTo determine the volume changes in gray and white matter during a long-term follow-up in patients suffering from pantothenate kinase-associated neurodegeneration (PKAN).MethodsMagnetic resonance imaging was repeated in 13 patients and 14 age-matched controls after a mean interval of more than 7 years. T1-weighted sequences were evaluated by fully automated atlas-based volumetry, compared between groups and correlated with disease progression.ResultsThe patients did not show generalized cerebral atrophy but did show a significantly faster volume reduction in the globus pallidus during follow-up (between -0.96% and -1.02% per year, p < 0.05 adjusted for false discovery rate) than controls, which was significantly related to the progression in their dystonia scores (p = 0.032).ConclusionThe volume loss in the globus pallidus over time—together with the accumulation of iron known as the “tiger’s eye”—supports the pathophysiologic concept of this nucleus as a center of inhibition and its severe malfunction in PKAN.

Quality of Life in Newly Diagnosed Patients With Parkin-Related Parkinson's Disease.

Introduction: Mutations in the Parkin gene are the most common cause of autosomal recessive early-onset Parkinson's disease (PD). However, little is known about the quality of life (QoL) in Parkin-related PD. Here, we investigated the patterns of QoL in newly diagnosed Parkin-related PD patients.Methods: Newly diagnosed PD patients (diagnosis made within 12 months) who had an age of onset (AOO) below 40 and underwent a PD-related genetic testing, were recruited (n = 148). Among them, 24 patients carried bi-allelic variants in Parkin (PD-Parkin) and 24 patients did not have any known causative PD mutations, or risk variants (GU-EOPD). The clinical materials, relevant factors and determinants of QoL were analyzed.Results: PD-Parkin patients had a younger AOO (p = 0.003) and longer disease duration (p = 0.005). After adjustment for AOO and disease duration, more dystonia (p = 0.034), and worse scores of non-motor symptoms including Beck depression inventory (BDI, p = 0.035), Epworth sleepiness scale (ESS, p = 0.044), and subdomains of depression/anxiety (p = 0.015) and sleep disorders (p = 0.005) in Non-motor symptoms questionnaire, were found in PD-Parkin comparing with GU-EOPD. PD-Parkin patients had poorer QoL (adjusted p = 0.045), especially in the mobility (adjusted p = 0.025), emotional well-being (adjusted p = 0.015) and bodily discomfort dimensions (adjusted p = 0.016). BDI scores (p = 0.005) and ESS scores (p = 0.047) were significant determinants of QoL in PD-Parkin.Conclusion: Newly diagnosed PD-Parkin patients showed worse QoL. More depression and excessive daytime sleepiness predicted worse QoL. For clinicians, management of depression and excessive daytime sleepiness is suggested to better improve QoL in patients with Parkin mutations.

Reliability and Validity of the Dyskinesia Impairment Scale in Children and Young Adults with Inherited or Idiopathic Dystonia.

Background: The Dyskinesia Impairment Scale (DIS) is a new assessment scale for dystonia and choreoathetosis in children and youth with dyskinetic cerebral palsy. Today, the Burke–Fahn–Marsden Dystonia Rating Scale (BFM) is mostly used to assess dystonia in children with inherited dystonia. The aim of this study was to assess reliability and validity of the DIS in children and youth with inherited or idiopathic dystonia. Methods: Reliability was measured by (1) the intraclass correlation coefficients (ICCs) for inter-rater and test-retest reliability, as well as (2) standard error of measurement (SEM) and minimal detectable difference (MDD). For concurrent validity of the DIS-dystonia subscale, the BFM was administered. Results: In total, 11 males and 9 females (median age 16 years and 7 months, range 6 to 24 years) were included. For inter-rater reliability, the ICCs for the DIS total score and the dystonia and choreoathetosis subscale scores were 0.83, 0.87, and 0.71, respectively. For test-retest reliability, the ICCs for the DIS total score and the dystonia and choreoathetosis subscale scores were 0.95, 0.88, and 0.93, respectively. The SEM and MDD for the total DIS were 3.98% and 11.04%, respectively. The Spearman correlation coefficient between the dystonia subscale and the BFM was 0.88 (p < 0.01). Conclusions: Good to excellent inter-rater, test-retest reliability, and validity were found for the total DIS and the dystonia subscale. The choreoathetosis subscale showed moderate inter-rater reliability and excellent test-retest reliability. The DIS may be a promising tool to assess dystonia and choreoathetosis in children and young adults with inherited or idiopathic dystonia.

Pallidotomy for Dystonia.

Deep brain stimulation (DBS) is currently the preferred surgical treatment for various movement disorders. Pallidotomy is an effective procedure for patients with dystonia and Parkinson's disease and was the surgical treatment of choice before the advent of DBS. However, it can be the preferred modality in immunocompromised patients and those patients who cannot afford DBS due to financial constraints. Hypophonia, dysarthria and dysphagia are the most significant complications of bilateral pallidotomy. The aim of this study was to present the surgical technique and nuances involved in bilateral simultaneous pallidotomy in a patient with generalized dystonia. A 30-year male with primary generalized dystonia presented to us with preoperative Burke-Fahn-Marsden (BFM) Dystonia Rating Scale of 24. After acquiring preoperative volumetric 3T MRI and stereotactic CT, bilateral pallidotomy was done under general anesthesia. There were no procedure related complications. At two months of follow-up, his BFM dystonia score improved from 24 to 4.5. Appropriately acquired volumetric MRI, meticulous planning and meticulously performed surgical procedure can help in achieving good outcome and minimize the complications.

F147. RESTING STATE NETWORKS ALTERATION IN PANTOTHENATE-KINASE ASSOCIATED NEURODEGENERATION (PKAN)

BackgroundWhile functional MRI and PET studies have shown altered task-related brain activity in PKAN, we want to find such differences also in the resting state (RS).Here we used ICA based analysis to investigate RS fMRI data to compare connectivity of 11 well known networks (Auditory, Cerebellum, Default Mode Network (DMN), Exectutive Control, Fronto-parietal 1, Fronto-parietal 2, Salience, Sensorimotor, Visual1, Visual2, Visual3 network) between patients with PKAN and healthy controls suggesting deficits in related neuropsychological functions.MethodsWe obtained RS fMRI series (3T, 3x3x3mm resolution, 45 slices, TR 2s, 300 volumes) in 17 PKAN patients but 3 were discarded because of excessive movement, (mean age 17.2a±7.1) on stable medication and 15 healthy controls (22.5a±8.3).Subjects were asked to lie in the scanner keeping eyes closed with no further specific instructions. Data were pre-processed; we applied FSL MELODIC (pICA) yielding IC, we used FIX to auto-classify ICA components which represent artifacts and an automated routine to select for each subject the component matching the anatomical definition of resting state networks.SPM12 was used for second level analysis, we used two sample t-test to compare networks functional connectivity between groups. In addition, we used multiple regression to correlate RS networks activity components with Dystonia score.ResultsOur method reliably identified all networks in every control and patients. We found significant differences in the anatomical pattern of areas. Patients showed decreased functional connectivity in comparison to healthy controls in portions of Fronto-parietal 1, Fronto-parietal 2 and Visual1 networks; in addition, patients showed increased functional connectivity in comparison to healthy controls in portions of Cerebellum, DMN, Executive Control, Salience and Visual1 networks. Finally, significant correlation was found between dystonia score and functional connectivity of Cerebellum, Fronto-parietal1, Fronto-parietal2, Salience, Sensorimotor and Visual2 networks.DiscussionWell known resting state networks were reliable identified from RS fMRI in PKAN patients. The differences in anatomical distribution point to possible alterations in functional connectivity in PKAN, which suggests disruption in cerebellum, DMN, fronto-parietal, salience and visual activity. Correlations with dystonia suggest a direct relation to motor items, which would support a clinical significance of altered RS networks activity.

Upper Limb Function, Kinematic Analysis, and Dystonia Assessment in Children With Spastic Diplegic Cerebral Palsy and Periventricular Leukomalacia.

Assessment of upper limb function, kinematic analysis, and dystonia in patients with spastic diplegia cerebral palsy and periventricular leukomalacia. Seven children with spastic diplegia cerebral palsy and 8 controls underwent upper limb kinematics. Movement duration, average and maximum linear velocity, index of curvature, index of dystonia, and target accuracy and stability were analyzed. In the patients with spastic diplegia, Gross Motor Function and Manual Ability Classification Systems were determined, and spasticity and dystonia were rated using the Modified Ashworth and the Burke-Fahn-Marsden Dystonia scales respectively. Children with spastic diplegia demonstrated a tendency toward higher index of dystonia reflecting overflow, higher index of curvature, lower velocities, and poor target accuracy and stability. All patients showed clinical evidence of dystonia in the upper limbs. Dystonia scores correlated with the Manual Ability Classification System (r = 0.86, P = .01) and with the index of dystonia (r = 0.82, P = .02). Children with spastic diplegia cerebral palsy present dystonia in the upper limbs. This is functionally relevant and can be measured with kinematic analysis.

Impaired Bed Mobility: Quantitative Torque Analysis With Axial Inertial Sensors

To develop a practical objective method for home assessment of a patient's ability to turn in bed. Nocturnal parameters and torque of self-turning in bed from 17 PD couples were assessed and compared using a wearable axial sensor for two nights in their homes. The torque of axial rotation which indicates the ability of PD patients to turn in bed was significantly less than their spouses (p < 0.001). Significant correlations were observed between the torque of turning in bed and total unified Parkinson's Disease Rating Scale score (r = 0.71; p = 0.001), and total Nocturnal Akinesia Dystonia and Cramp score (r = 0.634; p = 0.006). Our study confirms a decreased ability in turning in PD.

How well do Parkinson's disease patients turn in bed? Quantitative analysis of nocturnal hypokinesia using multisite wearable inertial sensors

BackgroundNocturnal hypokinesia/akinesia is a distressing symptom in patients with Parkinson's disease (PD). However, it is difficult to accurately monitor these symptoms based on clinical interviews alone. ObjectivesTo quantitatively compare nocturnal movements of PD patients with their spouses by using multisite inertial sensors and to correlate these parameters with disease severity scores. MethodsNocturnal movements in 19 PD couples (mild-moderate stage) were assessed and compared using wearable sensors (limbs and trunk) for one night at their homes. Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, number of getting out of bed, and limb movements. Each activity was compared to sleep diary, and video recording for accuracy. ResultsPD patients significantly had fewer rolling over (p = 0.048), turned with smaller degree (p = 0.007), less velocity (p = 0.011), and acceleration (p < 0.001), but had more episodes of getting out of bed (p = 0.03, nocturia) when compared to their spouses. Moderate and significant correlations were observed between the mean duration of rolling over and the Unified Parkinson's Disease Rating Scale-Axial score, and Nocturnal Akinesia Dystonia and Cramp Score. The number of leg movements (predominant side) significantly correlated with REM behavior disorder single-question screen. Episodes of nocturia correlated with total and bedtime levodopa equivalent dose. Several other correlations were also observed. ConclusionOur study was able to demonstrate quantitatively the presence of nocturnal hypokinesia in PD patients. This problem correlated with daytime axial motor and nonmotor symptoms. Treatment strategy for PD should be based on a comprehensive review of both day- and nighttime symptoms.