Regional structural abnormalities in thalamus in idiopathic cervical dystonia.

BACKGROUND: The thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD); however, the nature of alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD. METHODS: Structural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analysed in patients with iCD. RESULTS: Compared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group. CONCLUSION: This study highlights the neurobiological mechanisms of iCD related to thalamic volume changes.

Topological alterations in white matter anatomical networks in cervical dystonia.

BACKGROUND: Accumulating neuroimaging evidence indicates that patients with cervical dystonia (CD) have changes in the cortico-subcortical white matter (WM) bundle. However, whether these patients' WM structural networks undergo reorganization remains largely unclear. We aimed to investigate topological changes in large-scale WM structural networks in patients with CD compared to healthy controls (HCs), and explore the network changes associated with clinical manifestations. METHODS: Diffusion tensor imaging (DTI) was conducted in 30 patients with CD and 30 HCs, and WM network construction was based on the BNA-246 atlas and deterministic tractography. Based on the graph theoretical analysis, global and local topological properties were calculated and compared between patients with CD and HCs. Then, the AAL-90 atlas was used for the reproducibility analyses. In addition, the relationship between abnormal topological properties and clinical characteristics was analyzed. RESULTS: Compared with HCs, patients with CD showed changes in network segregation and resilience, characterized by increased local efficiency and assortativity, respectively. In addition, a significant decrease of network strength was also found in patients with CD relative to HCs. Validation analyses using the AAL-90 atlas similarly showed increased assortativity and network strength in patients with CD. No significant correlations were found between altered network properties and clinical characteristics in patients with CD. CONCLUSION: Our findings show that reorganization of the large-scale WM structural network exists in patients with CD. However, this reorganization is attributed to dystonia-specific abnormalities or hyperkinetic movements that need further identification.

Cervical motion alterations and brain functional connectivity in cervical dystonia.

INTRODUCTION: Evaluating the neural correlates of sensorimotor control deficits in cervical dystonia (CD) is fundamental to plan the best treatment. This study aims to assess kinematic and resting-state functional connectivity (RS-FC) characteristics in CD patients relative to healthy controls. METHODS: Seventeen CD patients and 14 age-/sex-matched healthy controls were recruited. Electromagnetic sensors were used to evaluate dystonic pattern, mean/maximal cervical movement amplitude and joint position error with eyes open and closed, and movement quality during target reaching with the head. RS-fMRI was acquired to compare the FC of brain sensorimotor regions between patients and controls. In patients, correlations between motion analysis and FC data were assessed. RESULTS: CD patients relative to controls showed reduced mean and maximal cervical range of motion (RoM) in rotation both towards and against dystonia pattern and reduced total RoM in rotation both with eyes open and closed. They had less severe dystonia pattern with eyes open vs eyes closed. CD patients showed an altered movement quality and sensorimotor control during target reaching and a higher joint position error. Compared to controls, CD patients showed reduced FC between supplementary motor area (SMA), occipital and cerebellar areas, which correlated with lower cervical RoM in rotation both with eyes open and closed and with worse movement quality during target reaching. CONCLUSIONS: FC alterations between SMA and occipital and cerebellar areas may represent the neural basis of cervical sensorimotor control deficits in CD patients. Electromagnetic sensors and RS-fMRI might be promising tools to monitor CD and assess the efficacy of rehabilitative interventions.

Hypertrophy of the Spinalis Cervicis Muscle in Cervical Dystonia.

Background: Botulinum neurotoxin A (BoNT) is the first line treatment for cervical dystonia (CD) and treatment outcome significantly depends on the correct identification of the muscles involved. Phenomenology shown: In a case with insufficient response to BoNT treatment further work up with magnetic resonance imaging (MRI) of the neck revealed a hypertrophic spinalis cervicis muscle, that is not commonly involved in CD. Educational value: This highlights the use of MRI for muscle selection in treatment refractory CD cases.

Experience with the management of 2599 cases of congenital muscular torticollis and a multicenter epidemiological investigation in 17 hospitals in China.

BACKGROUND: Congenital muscular torticollis (CMT) is a common musculoskeletal disease affecting infants and young children. If CMT is not treated correctly and timely, it can lead to limited head and neck movements, head and neck deviation, and abnormal posture. In order to improve patients' symptoms and alleviate the negative impact of the disease on their lives, we are committed to exploring the treatment of CMT. METHODS: The general clinical and ultrasonographic data of 2599 children with CMT who received standardized treatment at Shenzhen Children's Hospital from 2004 to 2020 were retrospectively reviewed. According to given treatment, children with CMT were divided into the physiotherapy group, physiotherapy combined with glucocorticoid treatment group, and surgical treatment group. We divided children with CMT into local mass, uniform thickening, and atrophy according to ultrasound features. General clinical information, treatment, and ultrasound examination data in each group were compared. Additionally, electronic medical records of 2344 patients admitted due to CMT in 17 tertiary children's hospitals of China's Futang Research Center of Pediatric Development (FRCPD) from 2015 to 2019 were retrospectively analyzed. Data on sex, age, year of admission and discharge, and treatment costs during hospitalization were extracted from the first medical record pages according to the ICD codes. The data were assessed for normality using the Kolmogorov-Smirnov test. Depending on the data distribution, they were analyzed using parametric tests, such as the t-test, or non-parametric tests. Qualitative data are expressed as percentages (%) and analyzed using the chi-square or Fisher's exact probability test, with α = 0.05 as the test level. P < 0.05 was considered to be indicative of a statistically significant difference. RESULTS: Three types of CMT were defined based on sternocleidomastoid muscle ultrasound examination characteristics: local mass, uniform thickening, and atrophy. Age at first diagnosis was 69.21 ± 108.41 days in local mass type group, 216.85 ± 324.09 days in uniform thickening group, and 417.88 ± 739.05 days in atrophy- type group; while age at first physiotherapy use was 94.06 ± 206.49 days, 255.00 ± 430.62 days, 540.92 ± 1059.29 respectively. The children included in local mass type group have shown a high success rate of conservative treatment, with a rate of 7.5% of children underwent surgery. Age at first diagnosis was 112.44 ± 224.12 days in the physiotherapy group, 115.87 ± 144.86 days in the physiotherapy combined with glucocorticoid treatment subgroup, whereas the age at first physiotherapy use was 137.38 ± 312.11 and 196.91 ± 344.26 days respectively. In the observation period (2015-2019) the mean age at surgery for CMT in 17 tertiary children's hospitals of the FRCPD was 50 months. Overall, 663 children with CMT were 1-2 years of age, accounting for the largest proportion (28.3%). Followed by 417 individuals (17.8%) were 7-14 years of age, indicating that there are still more children with CMT receiving surgical treatment later. CONCLUSIONS: Early diagnosis and treatment are essential to improve the conservative treatment success rate and achieve good prognosis in children with CMT. Our team's concept for treating CMT is as follows: after diagnosing the children, we will adopt the standardized protocol of treatment, with physiotherapy combined with the injection of glucocorticoid drugs and SCM release surgery, when needed. This program has a high conservative treatment success rate and may facilitate the achievement of better prognosis and reduced teratogenicity rate.

Neck stiffness and bone osteolytic lesion in a 3-years old child: a case report.

BACKGROUND: Neuroblastoma is the most frequent extracranial solid tumor occurring in childhood, representing approximately 28% of all cancers diagnosed in infants. Signs and symptoms of neuroblastoma vary with the site of development of the tumor and can mimic other diseases due to its extreme clinical variability. However, torticollis is not reported in the medical literature as a leading symptom of neuroblastoma. CASE PRESENTATION: Here we report the case of a 3 years-old girl with fever and neck stiffness. Blood tests revealed a mild anemia and a rise in inflammatory markers. CT-scan showed a solid, heterogeneous, predominantly hypodense surrenal mass with eccentric calcification and extensive inhomogeneity of the vertebral metamers. Blood tests revealed raised serum levels of Neuron-Specific Enolase. At the 24-hours urine collection urinary catecholamines were greatly increased. A course of chemotherapy for neuroblastoma was promptly started with immediate clinical improvement. CONCLUSIONS: This case shows that the presence of torticollis could be a chief complaint of neuroblastoma. To our knowledge, neuroblastoma is not mentioned among life-threatening underlying conditions of torticollis in most recent literature reviews.

Assessment of axial rotation movement in cervical dystonia using cone-beam computed tomography.

BACKGROUND: Cervical dystonia is a neurological disorder characterized by involuntary muscle contractions and abnormal postures of the head and neck. Botulinum neurotoxin injection is the first-line treatment. Imaging determination of the cervical segments involved (lower or upper according to the torticollis-torticaput [COL-CAP] Classification) is an aid in determining the muscles to be injected. We aimed to clarify the impact of dystonia on posture and rotational movement of cervical vertebrae in the transverse plane. METHODS: A comparative study was conducted in a movement disorders department. Ten people with cervical dystonia and 10 matched healthy subjects (without cervical dystonia) were recruited. 3-D images of posture and cervical range of motion in axial rotation in the sitting position were recorded by using a cone-beam CT scanner. Range of rotational motion of the upper cervical spine from the occipital bone to fourth cervical vertebra was measured and compared between the two groups. FINDINGS: The head posture analysis showed that the total cervical spine position was more significantly distant from the neutral position for people with dystonia than healthy subjects (p = 0.007). The rotational range of motion of the cervical spine was significantly lower in cervical dystonia participants than in healthy subjects for the total (p = 0.026) and for upper cervical spine (p = 0.004). INTERPRETATION: We demonstrated, by means of cone-beam CT, that the disorganization of movements due to cervical dystonia affected the upper cervical spine and mostly the atlantoaxial joint. The involvement of rotator muscles at this cervical level should be considered more in treatments.

Does Pallidal Physiology Determine the Success of Unilateral Deep Brain Stimulation in Cervical Dystonia?

Pallidal deep brain stimulation is a well-known surgical treatment for cervical dystonia. The resolution of dystonia typically requires bilateral pallidal stimulation, but in some instances, unilateral stimulation has been successful. In such instances, generally, the stimulated hemisphere was contralateral to the dystonic sternocleidomastoid, but rarely it was ipsilateral. We sought for the physiological features that determine the basis for success and laterality of deep brain stimulation for cervical dystonia with prominent torticollis. We found that pallidal physiology such as high burst to tonic ratio and significant interhemispheric differences in the neuronal firing rate and regularity are critical determinants of successful treatment with unilateral deep brain stimulation. We also found that higher lateralized differences in pallidal physiological parameters predict more robust improvement. In three out of four patients, the stimulation of the hemisphere ipsilateral to the dystonic sternocleidomastoid muscle was effective. These patients did not have any structural brain abnormalities on clinically available imaging studies. One patient responded to the unilateral deep brain stimulation in the hemisphere contralateral to the dystonic sternocleidomastoid. This patient had a structural putamen lesion on brain MRI. These results provide objective parameters determining the success of pallidal deep brain stimulation for treatment of cervical dystonia. The results also depict differences in the pallidal physiology in patients where ipsilateral versus contralateral deep brain stimulation was effective.

Fixel-Based Analysis Reveals Whole-Brain White Matter Abnormalities in Cervical Dystonia.

BACKGROUND: Cervical dystonia (CD) is a form of isolated focal dystonia typically associated to abnormal head, neck, and shoulder movements and postures. The complexity of the clinical presentation limits the investigation of its pathophysiological mechanisms, and the neural networks associated to specific motor manifestations are still the object of debate. OBJECTIVES: We investigated the morphometric properties of white matter fibers in CD and explored the networks associated with motor symptoms, while regressing out nonmotor scores. METHODS: Nineteen patients affected by CD and 21 healthy controls underwent diffusion-weighted magnetic resonance imaging. We performed fixel-based analysis, a novel method evaluating fiber orientation within specific fiber bundles, and compared fiber morphometric properties between groups. Moreover, we correlated fiber morphometry with the severity of motor symptoms in patients. RESULTS: Compared to controls, patients exhibited decreased white matter fibers in the right striatum. Motor symptom severity negatively correlated with white matter fibers passing through inferior parietal areas and the head representation area of the motor cortex. CONCLUSIONS: Abnormal white matter integrity at the basal ganglia level may affect several functional networks involved, for instance, in motor preparation and execution, visuomotor coordination, and multimodal integration. This may result in progressive maladaptive plasticity, culminating in overt symptoms of dystonia. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Clinical features of cervical dystonia patients classified by the COL-CAP concept and treated with ultrasound-guided botulinum neurotoxin.

Background and purpose:

Cervical dys­tonia (CD) is the most common form of focal dystonias, where the identification of the involved muscles, the determination of optimal botulinum neurotoxin A (BoNT-A) dose per muscle injection, and precise tar­ge­ting may be challenging. The aim of the current study is to compare local centre data with international data, enabling the iden­tification of population and me­tho­do­­lo­gical factors behind the differences, there­by further improvement of the care of Hun­ga­rian patients with CD.

The data of all consecutive CD patients, who were injected with BoNT-A at the botulinum neurotoxin outpatient clinic at the Department of Neurology, University of Szeged between 11 August and 21 Sep­tember 2021, were retrospectively col­lected and analysed in a cross-sectional manner. The frequency of the involved muscles, determined by the application of the collum-caput (COL-CAP) concept, and the parameters for the BoNT-A formulations, injected via ultrasound (US)-guidance, were calculated and compared with available international data.

In the current study, 58 patients (19 males and 39 females) were involved with mean age of 58.4 (± SD 13.6, range 24-81) years. The most common subtype was torticaput (29.3%). Tremor affected 24.1% of patients. The most injected muscles were trapezius (56.9% of all cases), followed by the levator scapulae (51.7%), splenius capitis (48.3%), sternocleidomastoid (32.8%), and semispinalis capitis (22.4%). The injected mean doses per patient were 117 ± SD 38.5 (range: 50-180) units for onaBoNT-A, 118 ± SD 29.8 (range: 80-180) units for incoBoNT-A, and 405 ± SD 162 (range: 100-750 units) for aboBoNT-A.

Although there were several similarities between the results of the current and the multicentre studies, all were carried out using the COL-CAP concept and US-guided BoNT-A injections, authors should pay attention to better distinction of torti-forms and the more frequent injection of especially the obliquus capitis inferior, mainly in cases with no-no tremor.

Spontaneous spinal epidural hematoma in a toddler presenting with torticollis: case report and literature review.

INTRODUCTION: Spontaneous spinal epidural hematoma (SSEH) is a rare entity, especially in toddlers and infants. The nonspecificity of its presenting symptoms in children may be a source of delayed diagnosis. CASE DESCRIPTION: We report the case of a 20-month-old young boy without medical history who presented with irreducible torticollis, worsened a few days later by severe tetraplegia and respiratory distress. Spinal magnetic resonance imaging (MRI) showed a posterior epidural hematoma, extending from C3 to T1 and compressing the spinal cord. An urgent decompressive surgery via an extensive laminectomy and evacuation of the clot was performed. The patient demonstrated a partial neurological recovery on follow-up. CONCLUSION: SSEH is a rare and serious condition that may compromise the functional and vital prognosis of the patient, hence the importance of prompt diagnosis and urgent treatment.

Iron accumulation and axonal damage of cerebellum in idiopathic cervical dystonia.

BACKGROUND AND PURPOSE: Postmortem brain study indicated that cerebellar Purkinje cell (PC) loss might be a pathological finding in patients with inherited and idiopathic cervical dystonia (ICD). The analysis of conventional magnetic resonance imaging brain scans failed to yield support for this finding. Previous studies have identified that iron overload can be the consequence of neuron death. The objectives of this study were to investigate iron distribution and demonstrate changes in axons in the cerebellum, providing evidence for PC loss in patients with ICD. METHODS: Twenty-eight patients with ICD (20 females) and 28 age- and sex-matched healthy controls were recruited. A spatially unbiased infratentorial template was applied to perform cerebellum optimized quantitative susceptibility mapping and diffusion tensor analysis based on magnetic resonance imaging. Voxel-wise analysis was performed to assess cerebellar tissue magnetic susceptibility and fractional anisotropy (FA) alterations, and the clinical relevance of these findings was investigated in the patients with ICD. RESULTS: Increased susceptibility values revealed by quantitative susceptibility mapping in the right lobule CrusI, CrusII, VIIb, VIIIa, VIIIb and IX were found in the patients with ICD. A reduced FA value was found across almost all the cerebellum; an FA value of the significant clusters within the right lobule VIIIa significantly correlated with the motor severity of patients with ICD (r = -0.575, p = 0.002). CONCLUSIONS: Our study provided evidence for cerebellar iron overload and axonal damage in patients with ICD, which may indicate PC loss and related axonal changes. These results provide evidence for the neuropathological findings in patients with ICD and further highlight the cerebellar involvement in the pathophysiology of dystonia.

[Atlantoaxial rotatory subluxation - a cause of torticollis in children]. / Atlantoaxial subluxation kan vara en orsak till tortikollis hos barn.

Atlantoaxial rotatory subluxation is an important differential diagnosis in young children with torticollis. The condition rarely results in neurological deficits. Radiological examinations such as computer tomography (CT) and magnetic resonance imaging (MRI) are useful to determine the diagnosis. It is important for doctors in all areas of healthcare to be aware of the condition, as persistent problems or surgery can be avoided by early detection and treatment.

C2 semisegmented hemivertebra - a rare anomaly presenting with torticollis.

BACKGROUND: Cervical hemivertebrae are extremely rare anomalies which usually present with restriction of neck movements and torticollis in childhood. Hemivertebrae within the craniovertebral junction have only been reported once previously in the literature. We report a case of semisegmented C2 vertebra presenting in a young adult with cervical pain and torticollis with no other associated anomalies. CASE DESCRIPTION: A 21-year-old lady presented with a history of neck pain for the past 10 days and longstanding torticollis with head tilt to the left. Computed tomographic scan of the cervical spine revealed a semisegmented hemivertebra located laterally between the C1 lateral mass and C2 on the right side which was not associated with any other bony anomalies, scoliosis or atlantoaxial dislocation. Conservative treatment with physical therapy was the chosen therapeutic strategy. CONCLUSION: Hemivertebrae within the craniovertebral junction are exceedingly rare anomalies which may present with pain and deformity in childhood and are an important cause of congenital torticollis which may be associated with other spinal, craniofacial, cardiac or renal anomalies.

Role of supplementary motor area in cervical dystonia and sensory tricks.

Sensory trick is a characteristic feature of cervical dystonia (CD), where a light touch on the area adjacent to the dystonia temporarily improves symptoms. Clinical benefit from sensory tricks can be observed before tactile contact is made or even by imagination. The supplementary motor area (SMA) may dynamically interact with the sensorimotor network and other brain regions during sensory tricks in patients with CD. In this study, we examined the functional connectivity of the SMA at rest and during sensory trick performance and imagination in CD patients compared to healthy controls using functional magnetic resonance imaging. The functional connectivity between the SMA and left intraparietal sulcus (IPS) region was lower in CD patients at rest and it increased with sensory trick imagination and performance. SMA-right cerebellum connectivity also increased with sensory trick imagination in CD patients, while it decreased in healthy controls. In CD patients, SMA connectivity increased in the brain regions involved in sensorimotor integration during sensory trick performance and imagination. Our study results showed a crucial role of SMA in sensorimotor processing during sensory trick performance and imagination and suggest the IPS as a novel potential therapeutic target for brain modulation.

Therapeutic Efficacy and Prediction of 18F-FDG PET/CT-Assisted Botulinum Toxin Therapy in Patients With Idiopathic Cervical Dystonia.

PURPOSE: This study aimed to investigate the therapeutic efficacy of 18F-FDG PET/CT-assisted botulinum toxin (BTX) injection therapy and predictive PET findings in relation to a good response in patients with idiopathic cervical dystonia (ICD). MATERIALS AND METHODS: A total of 78 patients was enrolled from November 2007 to July 2018. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was determined at baseline and 4 weeks after BTX injection guided by electromyography and PET/CT. The number of hypermetabolic muscles, the highest SUVmax among hypermetabolic muscles, and the total SUVmax of hypermetabolic muscles were evaluated as pretreatment PET parameters. A good response was defined as a reduction rate ≥30% and a point decrease ≥15 of the TWSTRS total score. RESULTS: Half of the subjects showed a good response. Good responders had significantly higher baseline TWSTRS scores than poor responders (total score, P < 0.001; severity, P < 0.001; disability, P < 0.001; pain, P = 0.026). Good responders also had significantly higher numbers of hypermetabolic muscles and BTX-injected hypermetabolic muscles (P < 0.001, both). In multivariable analysis, the baseline TWSTRS disability subscale score and the number of BTX-injected hypermetabolic muscles were significant predictors for good response (P = 0.001 and P = 0.028). The aforementioned 3 PET parameters were positively correlated with the baseline TWSTRS scores. In addition, PET/CT well detected dystonic deep cervical muscles. CONCLUSIONS: FDG PET/CT-assisted BTX injection therapy showed good therapeutic efficacy in ICD patients. The numbers of hypermetabolic cervical muscles and BTX-injected hypermetabolic muscles may be helpful in predicting a good response.

Does Ultrasound Guidance Improve the Effectiveness of Neurotoxin Injections in Patients with Cervical Dystonia? (A Prospective, Partially-Blinded, Clinical Study).

AIM: The aim of this study was to evaluate the efficacy of ultrasound guidance (US) in the treatment of cervical dystonia (CD) with botulinum neurotoxin type A (BoNT-A) injections in comparison to anatomical landmarks (AL). To date, US is routinely used in many centers, but others deny its usefulness. MATERIALS AND METHODS: Thirty-five patients (12 males, 23 females) with a clinical diagnosis of CD were included in the study. Intramuscular administration of BoNT-A was performed using either US guidance, or with AL, in two separate therapeutic sessions. The efficacy of BoNT-A administration was assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), Tsui modified scale, Craniocervical Dystonia Questionnaire (CDQ-24) and Clinical Global Impression-Improvement scale (CGI-I). Additionally, patients at therapeutic sessions were digitally recorded and evaluated by two blinded and independent raters. RESULTS: A significant decrease in total TWSTRS, severity subscale TWSTRS, Tsui score, and CDQ-24 was found in both the AL and US group; however, in the TWSTRS disability and pain subscales, a significant decrease was found only in the US group. Moreover, US guided treatment also resulted in a greater decrease in TWSTRS, Tsui score and CDQ-24 compared to anatomical landmarks use only. CONCLUSIONS: US guidance might be helpful in improving the results of BoNT-A injections in cervical dystonia, reducing associated pain and disability; however, more studies are needed to evaluate its clinical efficacy.

Structural and functional brain abnormalities in idiopathic cervical dystonia: A multimodal meta-analysis.

BACKGROUND: Neuroimaging studies have identified both brain structural and functional abnormalities in patients with idiopathic cervical dystonia (iCD), but often yield diverse results. We aim to find the specific and common neurostructural/functional abnormalities in iCD by conducting separate and multimodal meta-analyses across structural and functional neuroimaging studies. METHODS: A systematic literature search was conducted to identify relevant publications. Separate meta-analysis for whole-brain voxel-based morphometry (VBM) studies and for functional imaging studies, and a multimodal meta-analysis across VBM and functional studies in iCD were conducted using anisotropic effect size-based signed differential mapping. RESULTS: We included twenty-seven studies, including nine structural datasets comprising 152 iCD patients and 188 healthy controls, and seventeen functional datasets describing 352 iCD patients and 296 healthy controls. The multimodal analysis showed overlap between anatomic and functional changes in bilateral precentral and postcentral gyri, bilateral paracentral lobules, right supplementary motor area, bilateral median cingulate/paracingulate gyri, right caudate nucleus and thalamus, right cerebellum and lingual gyrus. We also found gray matter alterations alone in bilateral dorsolateral superior frontal gyri, left middle temporal gyrus, right inferior parietal gyrus, and left cerebellum; and altered functional activity alone in right fusiform gyrus, bilateral precuneus. CONCLUSION: The current meta-analyses revealed significant conjoint and dissociated brain structural and functional abnormalities in iCD, and emphasized the involvement of cortico-thalamo-basal ganglia circuit and cerebellum.