Stimulation-Induced Dyskinesia After Subthalamic Nucleus Deep Brain Stimulation in Patients With Meige Syndrome.

OBJECTIVES: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is increasingly used to treat Meige syndrome (MS) and markedly improves symptoms. Stimulation-induced dyskinesia (SID), which adversely affects surgical outcomes and patient satisfaction, may, however, occur in some patients. This study attempts to explore possible causes of SID. MATERIALS AND METHODS: Retrospectively collected clinical data on 32 patients who underwent STN-DBS between October 2016 and April 2019 were analyzed. Clinical outcomes were assessed pre- and post-surgery, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS). Patients were divided into a dyskinesia group and a non-dyskinesia group, according to whether or not they experienced persistent SID during follow-up. The coordinates of the active contacts were calculated from post-operative computerized tomography or magnetic resonance imaging, using the inter-commissural line as a reference. At final follow-up, the main stimulatory parameters for further study included pulse width, voltage, and frequency. RESULTS: At final follow-up (mean = 16.3 ± 7.2 months), MS patients had improved BFMDRS total scores compared with pre-surgical scores (mean improvement = 79.0%, p < 0.0001). The mean improvement in BFMDRS total scores in the dyskinesia (n = 10) and non-dyskinesia (n = 22) groups were 81.6 ± 8.8% and 77.9 ± 14.2%, respectively. The mean minimum voltage to induce dyskinesia was 1.7 ± 0.3 V. The programmed parameters of both groups were similar. When compared with the non-dyskinesia group, active stimulatory contact coordinates in the dyskinesia group were inferior (mean left side: z = -2.3 ± 1.7 mm vs. z = -1.2 ± 1.5 mm; p = 0.0282; mean right side: z = -2.7 ± 1.9 mm vs. z = -2.3 ± 1.7 mm; p = 0.0256). The x and y coordinates were similar. CONCLUSION: STN-DBS is an effective intervention for MS, providing marked improvements in clinical symptoms; SID may, however occur in the subsequent programming control process. Comparing patients with/without dyskinesia, the active contacts were located closer to the inferior part of the STN in patients with dyskinesia, which may provide an explanation for the dyskinesia.

Movement Disorder in Wilson Disease: Correlation with MRI and Biomarkers of Cell Injury.

To report the phenomenology of movement disorder (MD) in neurological Wilson disease (NWD), and correlate these with MRI, and biomarkers of oxidative stress, excitotoxicity, and inflammation. Eighty-two patients were included, and their phenomenology of MD was categorized. The severity of dystonia was assessed using the Burke-Fahn-Marsden score, and chorea, athetosis, myoclonus, and tremor on a 0-4 scale. The MRI changes were noted. Serum glutamate, cytokines, and oxidative stress markers were measured. Movement disorders were noted in 78/82 (95.1%) patients and included dystonia in 69 (84.1%), chorea in 31 (37.8%), tremor in 24 (29.3%), parkinsonism in 19 (23.2%), athetosis in 13 (15.9%), and myoclonus in 9 (11.0%) patients. Dystonia was more frequently observed in the patients with thalamic (76.8 vs 23.2%), globus pallidus (72.0 vs 28.0%), putamen (69.5 vs 30.5%), caudate (68.3 vs 31.7%) and brainstem (61.0 vs 39.0%) involvement, and tremor with cerebellar involvement (37.5 vs 5.2%). The median age of onset of neurological symptoms was 12 (5-50) years. WD patients had higher levels of malondialdehyde (MDA), glutamate, and cytokines (IL-6, IL-8, IL-10, and TNFα) and lower levels of glutathione and total antioxidant capacity (TAC) compared with the controls. Serum glutamate, IL-6, IL-8, and plasma MDA levels were increased with increasing neurological severity, while glutathione and TAC levels decreased. The severity of dystonia related to the number of MRI lesions. MD is the commonest neurological symptoms in WD. Oxidative stress, glutamate, and cytokine levels are increased in WD and correlate with neurological severity.

Neurological Soft Signs Predict Auditory Verbal Hallucinations in Patients With Schizophrenia.

Neurological soft signs (NSS) are well documented in individuals with schizophrenia (SZ), yet so far, the relationship between NSS and specific symptom expression is unclear. We studied 76 SZ patients using magnetic resonance imaging (MRI) to determine associations between NSS, positive symptoms, gray matter volume (GMV), and neural activity at rest. SZ patients were hypothesis-driven stratified according to the presence or absence of auditory verbal hallucinations (AVH; n = 34 without vs 42 with AVH) according to the Brief Psychiatric Rating Scale. Structural MRI data were analyzed using voxel-based morphometry, whereas intrinsic neural activity was investigated using regional homogeneity (ReHo) measures. Using ANCOVA, AVH patients showed significantly higher NSS in motor and integrative functions (IF) compared with non-hallucinating (nAVH) patients. Partial correlation revealed that NSS IF were positively associated with AVH symptom severity in AVH patients. Such associations were not confirmed for delusions. In region-of-interest ANCOVAs comprising the left middle and superior temporal gyri, right paracentral lobule, and right inferior parietal lobule (IPL) structure and function, significant differences between AVH and nAVH subgroups were not detected. In a binary logistic regression model, IF scores and right IPL ReHo were significant predictors of AVH. These data suggest significant interrelationships between sensorimotor integration abilities, brain structure and function, and AVH symptom expression.

The relationship between neuroimaging and motor outcome in children with cerebral palsy: A systematic review - Part A. Structural imaging.

BACKGROUND: Conventional Structural Magnetic Resonance Imaging (sMRI) is a mainstay in Cerebral Palsy (CP) diagnosis. AIMS: A systematic literature review was performed with the aim to investigate the relationship between structural brain lesions identified by sMRI and motor outcomes in children with CP. METHODS: Fifty-eight studies were included. The results were analysed in terms of population characteristics, sMRI (classified according to Krägeloh-Mann & Horber, 2007), gross and fine motor function and their interrelation. OUTCOMES: White matter lesions were the most common brain lesion types and were present in 57.8 % of all children with uCP, in 67.0 % of all children with bCP and in 33 % of the group of mixed subtypes. Grey matter lesions were most frequently registered in children with dyskinesia (n = 42.2 %). No structural anomalies visualized by sMRI were reported in 5.7 % of all cases. In all lesion types, an equal distribution over the different gross motor function classification system categories was present. The included studies did not report sufficient information about fine motor function to relate these results to structural imaging. CONCLUSIONS AND IMPLICATIONS: The relationship between brain structure and motor outcome needs to be further elucidated in a representative cohort of children with CP, using a more standardized MRI classification system.

Suprasellar Cyst Presenting With Bobble-Head Doll Syndrome.

BACKGROUND: Bobble-head doll syndrome is a rare neurological syndrome presenting with repetitive anteroposterior head movements. It is usually associated with expansile cystic lesions in the third ventricular region. CASE DESCRIPTION: An 8-year-old boy presented with involuntary bobbling head movements. Magnetic resonance imaging of the brain revealed an extensive suprasellar cyst resulting in obstructive hydrocephalus. Endoscopic ventriculo-cysto-cisternostomy resulted in improved clinical outcome. CONCLUSIONS: Endoscopic ventriculo-cysto-cisternostomy is an effective, less-invasive technique in the treatment of suprasellar cysts that results in resolution of the bobbling head movements.

Expanding the Phenotype: Neurodevelopmental Disorder, Mitochondrial, With Abnormal Movements and Lactic Acidosis, With or Without Seizures (NEMMLAS) due to WARS2 Biallelic Variants, Encoding Mitochondrial Tryptophanyl-tRNA Synthase.

BACKGROUND: WARS2 encodes a tryptophanyl tRNA synthetase, which is involved in mitochondrial protein synthesis. Biallelic mutations in WARS2 are rare and have been associated with a spectrum of clinical presentations, including neurodevelopmental disorder with abnormal movements, lactic acidosis with or without seizures (NEMMLAS). CASE PRESENTATION: Here we present the case of an 8-year-old girl with ataxia and parkinsonism with periventricular white matter abnormalities on magnetic resonance imaging (MRI) and global developmental delay. The initial investigations revealed an elevated lactate level. Extensive metabolic testing, including a muscle biopsy, was inconclusive. Cerebrospinal fluid (CSF) neurotransmitter levels were low; however, a trial of levodopa was unremarkable. The chromosomal microarray and initial ataxia gene panel was normal. Zinc supplementation for a heterozygous variant of unknown significance in the CP gene on the ataxia exome panel was not effective in treating her symptoms. Reanalysis of the ataxia exome panel highlighted biallelic mutations in WARS2, which lead to the diagnosis of neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS). This lead to parental genetic testing, redirected therapy, and helped to expand the symptomology of this rare condition. CONCLUSION: Here we emphasize the importance of imminent and repeat expanded genetic testing to ensure early diagnosis and treatment for rare pediatric disorders. The patient is being trialed on a mitochondrial cocktail in an attempt to compensate for defects in mitochondrial protein synthesis associated with this variant. Longitudinal monitoring of disease manifestation will help establish the currently unknown natural history of this condition.

Distúrbio de movimento por conta de estado hiperosmolar não cetótico em idosa: relato de caso / Movement disorder caused by hyperosmolar hyperglycemic state in an older adult: a case report

O diabetes e suas complicações constituem as principais causas de mortalidade precoce na maioria dos países. O envelhecimento da população e a crescente prevalência da obesidade e do sedentarismo, além dos processos de urbanização, são considerados os principais fatores responsáveis pelo aumento da incidência e da prevalência do diabetes mellitus (DM) em todo o mundo. Este relato de caso objetiva descrever a presença de distúrbio do movimento em idoso por conta do estado hiperosmolar não cetótico. A combinação de hemicoreia-hemibalismo, hiperglicemia não cetótica e envolvimento dos gânglios da base em exames de imagem é considerada uma síndrome única. Os distúrbios do movimento em estado hiperosmolar não cetótico apresentam resposta terapêutica satisfatória com o uso de neurolépticos e controle glicêmico adequado. A escassez de trabalhos publicados proporciona subdiagnósticos clínico e laboratorial, interferindo no prognóstico e no acompanhamento dos pacientes.

Diabetes mellitus (DM) and its complications constitute the leading causes of early mortality in most countries. Population aging and the growing prevalence of obesity and sedentary lifestyles, in addition to spreading urbanization, are considered the main drivers of the increasing incidence and prevalence of DM worldwide. This case report describes the acute onset of movement disorder in an older woman secondary to hyperosmolar hyperglycemic state (HHS). The combination of hemichorea­hemiballismus, HHS, and evidence of basal ganglia involvement on neuroimaging is considered a unique syndrome. Movement disorders secondary to HHS respond satisfactorily to administration of neuroleptic agents and proper glycemic control. The lack of published studies on this pathologic entity may lead to clinical and laboratory underdiagnosis, with negative impacts on patient prognosis and follow-up.

An unusual presentation of bobble-head doll syndrome in a patient with hydranencephaly and Chiari 3 malformation.

Bobble-head doll syndrome is a rare movement disorder that is usually associated with lesions involving the third ventricle. It is characterised by stereotypical rhythmic up-and-down or side-to-side head movements. The pathophysiology and anatomical basis for this unusual manifestation is still a subject of intense scrutiny. The syndrome has never been described in a patient with both hydranencephaly and Chiari type 3 malformation. We describe a 2-year-old female patient who presented with congenital hydrocephalus, an occipital encephalocele and rhythmic bobbling of the head. Imaging investigation revealed a Chiari type 3 malformation and hydranencephaly. The patient was taken to theatre for a ventriculoperitoneal shunt insertion, and at day 3 post operatively, the patient had a markedly decreased head circumference and a decrease in the frequency of the bobbling of the head. A further review at 2 weeks showed that the bobbling of the head had ceased. Although the pathophysiology of bobble-head doll syndrome is yet to be fully understood, there has been postulation of either a third ventricular enlargement or a cerebellar dysfunction to explain bobble-head doll syndrome. Our case illustrates that the pathophysiology is most likely multifactorial as illustrated by the fact that by just addressing the high intracranial pressure with a shunt was sufficient to treat the condition.

A case of new PCDH12 gene variants presented as dyskinetic cerebral palsy with epilepsy.

Here we report a Japanese patient with new compound heterozygous truncating variants in the PCDH12 gene. As compared to the previously reported families who had congenital microcephaly, intrauterine growth retardation, intracranial calcification, and neonatal seizure associated with dysplasia of the midbrain-hypothalamus-optic tract, the present patient showed no midbrain-hypothalamus dysplasia or congenital/postnatal microcephaly, but dyskinetic cerebral palsy and severe intellectual disability as well as multifocal epilepsy. To understand phenotypic spectrum associated with PCDH12 variants, more reports are needed.

A preliminary exploration of plain-film radiography in scapular dyskinesis evaluation.

BACKGROUND: Evaluation of scapular dyskinesis is of clinical interest because it is believed to be associated with pathologies of the shoulder. This study investigated the feasibility of plain-film radiography in evaluating scapular dyskinesis. METHODS: Subjects with unilateral disorders of the shoulder (n = 186) who underwent plain-film radiography of bilateral scapulae were divided into 4 categories of scapular dyskinesis patterns according to the Kibler classification and analyzed. Coracoid upward shift distance (CUSD), length of the scapular spine line (LSS), and scapular upward rotation angle (SURA) were measured on the radiographs. Intrarater and inter-rater reliability were tested, and the characteristics of these parameters in each type were analyzed. The differences (d) between bilateral scapulae (d-CUSD, d-LSS, and d-SURA) among the 4 categories were compared. RESULTS: Intrarater and inter-rater reliability were excellent for all parameters. Significant differences between the scapulae were observed in CUSD in type I and in LSS in type II categories. No significant difference in any of the parameters was found in type III. Compared with the other categories, d-CUSD in type I and d-LSS in type II were significantly larger. The cutoff values of d-CUSD and d-LSS were 1.1 mm and 1.2 mm, respectively. No significant difference in d-SURA was found among the 4 categories. CONCLUSIONS: The measurement of CUSD, LSS, and SURA on plain-film radiography had excellent reliability. d-CUSD and d-LSS were characteristic parameters of type I and type II, respectively; however, type III had no distinguishing characteristics among the parameters.

Three-dimensional scapular dyskinesis in hook-plated acromioclavicular dislocation including hook motion.

BACKGROUND: The purpose of this study is to analyze the 3-dimensional scapular dyskinesis and the kinematics of a hook plate relative to the acromion after hook-plated acromioclavicular dislocation in vivo. Reported complications of acromioclavicular reduction using a hook plate include subacromial erosion and impingement. However, there are few reports of the 3-dimensional kinematics of the hook and scapula after the aforementioned surgical procedure. METHODS: We studied 15 cases of acromioclavicular dislocation treated with a hook plate and 15 contralateral normal shoulders using computed tomography in the neutral and full forward flexion positions. Three-dimensional motion of the scapula relative to the thorax during arm elevation was analyzed using a computer simulation program. We also measured the distance from the tip of the hook plate to the greater tuberosity, as well as the angular motion of the plate tip in the subacromial space. RESULTS: Decreased posterior tilting (22° ± 10° vs 31° ± 8°) in the sagittal plane and increased external rotation (19° ± 9° vs 7° ± 5°) in the axial plane were evident in the affected shoulders. The mean values of translation of the hook plate and angular motion against the acromion were 4.0 ± 1.6 mm and 15° ± 8°, respectively. The minimum value of the distance from the hook plate to the humeral head tuberosity was 6.9 mm during arm elevation. CONCLUSIONS: Acromioclavicular reduction using a hook plate may cause scapular dyskinesis. Translational and angular motion of the hook plate against the acromion could lead to subacromial erosion. However, the hook does not seem to impinge directly on the humeral head.

The Pioneering and Unknown Stereotactic Approach of Roeder and Orthner from Göttingen. Part II: Long-Term Outcome and Postmortem Analysis of Bilateral Pallidotomy in the Pre-Levodopa Era.

Before the advent of levodopa, pallidotomy was initially the most effective treatment for Parkinson disease, but it was soon superseded by thalamotomy. It is widely unknown that, similar to Leksell, 2 neurologists from Göttingen, Orthner and Roeder, perpetuated pallidotomy against the mainstream of their time. Postmortem studies demonstrated that true posterior and ventral pallidoansotomy sparing the overwhelming mass of the pallidum was accomplished. This was due to a unique and individually tailored stereotactic technique even allowing bilateral staged pallidotomies. In 1962, the long-term effects (3-year follow-up on average) of the first 18 out of 36 patients with staged bilateral pallidotomies were reported in great detail. Meticulous descriptions of each case indicate long-term improvements in parkinsonian rigidity and associated pain, as well as posture, gait, and akinesia (e.g., improved repetitive movements and arm swinging). Alleviation of tremor was found to require larger lesions than needed for suppression of rigidity. No improvement in speech, drooling, or seborrhea was observed. By 1962, the team had operated 13 patients with postencephalitic oculogyric crises with remarkable results (mean follow-up: 5 years). They also described alleviation of nonparkinsonian hyperkinetic disorders (e.g., hemiballism and chorea) with pallidotomy. The reported rates for surgical mortality and other complications had been remarkably low, even if compared to those reported after the revival of pallidotomy by Laitinen in the post-levodopa era. This applies also to bilateral pallidotomy performed with a positive risk-benefit ratio that has remained unparalleled to date. The intricate history of pallidotomy for movement disorders is incomplete without an appreciation of the achievements of the Göttingen group.

Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders.

Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations.

MRI for the diagnosis of scapular dyskinesis: a report of two cases.

Scapular dyskinesis describes the altered position of the scapula and/or abnormal movements of the scapulothoracic joint. It is caused by bony anatomical variations, bursitis, tumors, and muscular pathological conditions including loss of innervation and fibrosis. Scapular dyskinesis is just as often subclinical as it is symptomatic, and as the periscapular anatomical changes may not result in patient symptoms, a precise diagnosis of the etiology and pathophysiology has been a challenge. Scapular bony prominence is a common etiology of scapular dyskinesis, but does not always result in morbidity. We report a case of a 39-year-old man in whom an extensive MRI with fluid-sensitive imaging sequences covering the whole of the scapula was beneficial in diagnosing the inflammation adjacent to the bony deformity, which confirmed the etiology of scapular dyskinesis. Furthermore, in a 41-year old man without any anatomical variances, a similar MRI showed inflammation at the subscapular fossa that suggested altered scapular kinematics. An arthroscopic debridement of the lesion improved the symptoms. MRI in conjunction with plain radiographs, CT and physical examination enabled a precise diagnosis of the etiology. Fluid-sensitive MR images are important in defining the presence of inflammation, and are beneficial in determining the pathological significance of findings through other diagnostic measures.

Hemiballismus as a complication of an intratumoral chemotherapy catheter.

We report an unusual case of delayed bilateral, right greater than left hemiballismus in a 15-year-old female patient with a history of a craniopharyngioma 2years following the insertion of a right intratumoral chemotherapy catheter. Following cyst decompression, the catheter was found to have changed position, traversing the basal ganglia structures, namely the right subthalamic nucleus. Her movement disorder near-completely resolved immediately following removal of the catheter. A review of the current literature and proposed pathophysiological mechanisms are discussed.

Revisit to scapular dyskinesis: three-dimensional wing computed tomography in prone position.

BACKGROUND: Three-dimensional (3D) wing computed tomography (CT) showed a high inter-rater reliability in assessing scapular dyskinesis. METHODS: The 330 scapular movements of 165 patients were classified into 4 types by 7 blinded observers. Then, 3D wing CT was performed with patients prone, and 4 blinded observers measured 5 angles, consisting of upward rotation (UR) superior translation (ST), anterior tilting (AT), protraction (PRO), and internal rotation (IR). The inter-rater reliability (IRR) of 2 methods was calculated, and cutoff values were determined for the 5 angles on the 3D wing CT images. RESULTS: The IRR was 0.783 for the observational method of scapular dyskinesis and 0.981 for 3D wing CT in the prone position. UR and ST angles were significantly larger in type 3 more than in the other types (P < .001, P < .001), and the AT angle showed a similar pattern in type 1 (P < .001). The PRO angle was significantly larger in types 1, 2, and 3 more than in type 4 (P < .001, P < .001, P = .013), and the IR angle was significantly larger in type 2 more than in the other types (P < .001). The cutoff values of the 5 angles were UR, 117°; ST, 90°; AT, 8°; PRO, 99°; and IR, 51°. The UR angle showed a significant correlation with glenohumeral internal rotation deficit (odds ratio, 0.436; P = .029) and the IR angle with MDI (odds ratio, 8.947; P = .048). CONCLUSION: The patients with a high UR angle showed a low rate of glenohumeral internal rotation deficit and those with a high IR angle had a high rate of the MDI in affected shoulder by the determinant of the cutoff value of the 5 angles. LEVEL OF EVIDENCE: Level III, development of diagnostic criteria with nonconsecutive patients, diagnostic study.

How to assess scapular dyskinesis precisely: 3-dimensional wing computer tomography--a new diagnostic modality.

BACKGROUND: Aberrations in scapular motion are believed to be associated with the presence of shoulder or elbow pathologies. There are many methods to evaluate scapular kinematics, but they have certain limitations. Nevertheless, it is believed that appropriate rehabilitation for each type of scapular dyskinesis is important. METHODS: Eighty-nine athletes were videotaped and seven blinded observers categorized scapular dyskinesis into 4 types, which was followed by 3-dimensional (3D) wing computer tomography (CT). Four blinded examiners evaluated 5 angles [upward rotation (UR), internal rotation (IR), anterior tilting (AT), superior translation (ST), and protraction (PRO)] on the 3D wing CT. Inter-rater reliability (IRR) was calculated for both the methods. CT scan measurements were compared with the 4 observational types to establish the validity. RESULTS: The IRR with observational assessment of scapular dyskinesis into 4 types was good, 0.780. The 3D wing CT analysis had a very high IRR, 0.972. There was a statistically significant correlation between observational assessment and 3D wing CT analysis. The UR angle, ST angle in type 3 scapular dyskinesis, and AT angle in type 1 scapular dyskinesis were increased as compared with those in the other types of scapular dyskinesis. All these measurements were made in the resting position of the scapula. CONCLUSION: The 3D wing CT analysis allows precise quantification of a position associated with scapular dyskinesis. Therefore, 3D wing CT can be considered as an alternative method for assessing scapular dyskinesis.

The association of Chiari type III malformation and Klippel-Feil syndrome with mirror movement: a case report.

Basically Chiari type III malformation is a combination of encephalocele with of brain stem and cerebellar abnormality. Although Klippel-Feil syndrome may be associated with other congenital anomalies, this syndrome is mainly associated with varying degrees of cervical vertebral fusion anomalies. In this study, we reported the association of Chiari type III malformation and Klippel-Feil syndrome with the mirror movement by imaging studies. The main involvement in Chiari type III malformation and Klippel-Feil syndrome is in the craniocervical junction. In such a small area, the emergence of these complex pathologies in our case was remarkable. Our patient had reconstruction surgery of the posterior fossa and his encephalocele was excised successfully. Hydrocephaly and/or deterioration in the functions of other posterior fossa structures have not been seen in the patient's follow-up.

Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D(2) receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.