Putamen Nucleus Research Articles

Cortical thickness and subcortical volume abnormalities in male crack-cocaine users

Crack-cocaine offers a higher risk of abuse than intranasal and intravenous use of cocaine. Yet, current treatments remain disappointing and our understanding of the mechanism of crack-cocaine neurotoxicity is still incomplete. Magnetic resonance images studies on brain changes of crack-cocaine addicts show divergent data. The present study investigated gray matter (GM) abnormalities in crack-cocaine dependents (n = 18) compared to healthy controls (n = 17). MRI data was analysed using FreeSurfer and voxel-based morphometry (VBM). FreeSurfer analysis showed that CD had decreased cortical thickness (CT) in the left inferior temporal cortex (lTC), left orbitofrontal cortex (lOFC) and left rostro frontal cortex (lRFC), enlargement in left inferior lateral ventricle, and smaller GM volume in right hippocampus and right ventral diencephalon. VBM analysis showed that CD had significantly decreased GM volume in left Putamen and left nucleus accumbens. Furthermore, we found a negative correlation between duration of crack-cocaine use and lTC CT. These results provide compelling evidence for GM abnormalities in CD and also suggest that duration of crack-cocaine use may be associated with CT alterations.

An open-label, positron emission tomography study of the striatal D2/D3 receptor occupancy and pharmacokinetics of single-dose oral brexpiprazole in healthy participants

PurposeThe aim of this Phase 1, open-label, positron emission tomography (PET) study was to determine the degree of striatal D2/D3 receptor occupancy induced by the serotonin–dopamine activity modulator, brexpiprazole, at different single dose levels in the range 0.25–6 mg.MethodsOccupancy was measured at 4 and 23.5 h post-dose using the D2/D3 receptor antagonist [11C]raclopride. The pharmacokinetics, safety and tolerability of brexpiprazole were assessed in parallel.ResultsFifteen healthy participants were enrolled (mean age 33.9 years; 93.3% male). Mean D2/D3 receptor occupancy in the putamen and caudate nucleus increased with brexpiprazole dose, leveled out at 77–88% with brexpiprazole 5 mg and 6 mg at 4 h post-dose, and remained at a similar level at 23.5 h post-dose (74–83%). Estimates of maximum obtainable receptor occupancy (Omax) were 89.2% for the putamen and 95.4% for the caudate nucleus; plasma concentrations predicted to provide 50% of Omax (EC50) were 8.13 ng/mL and 7.75 ng/mL, respectively. Brexpiprazole area under the concentration–time curve (AUC∞) and maximum plasma concentration (Cmax) increased approximately proportional to dose. No notable subjective or objective adverse effects were observed in this cohort.ConclusionBy extrapolating the observed single-dose D2/D3 receptor occupancy data in healthy participants, multiple doses of brexpiprazole 2 mg/day and above are expected to result in an efficacious brexpiprazole concentration, consistent with clinically active doses in schizophrenia and major depressive disorder.Trial registrationClinicalTrials.gov NCT00805454 December 9, 2008.

Neurological Manifestations of Wilson's Disease: Pathophysiology and Localization of Each Component.

Wilson’s disease (WD) is an autosomal recessive disease that presents mainly with hepatic, neurological, and psychiatric manifestations. Neurological manifestations have been described in the past. Nevertheless, the pathophysiology and the clinical relevance of these manifestations have not been described in great detail in the medical literature. We aim to consolidate the knowledge about the neurological manifestations of WD and present the pathophysiology of each neurological manifestation of the disease. We will give a brief definition, the provenance, and the pathophysiology of the neurological conditions. We collected data from the National Library of Medicine (PubMed) using regular keywords and medical subject headings. Studies were selected applying the following inclusion/exclusion criteria: (1) studies that used exclusively human subjects, (2) papers published in English, and (3) papers from 1990 onward. The exclusion criteria were (1) studies that used animals, (2) papers not published in English, and (3) papers published before 1990. Additional studies were included via reference lists of identified papers and related articles featured in PubMed and Google Scholar.Copper toxicity is the principal factor for brain degeneration seen in WD. Parkinsonism seen in WD has been associated with a nigrostriatal dopaminergic deficit. Resting tremor may have the same pathophysiology as parkinsonism. Action tremor is related to an accumulation of copper in the cerebellum's vermis and hemispheres. At the same time, essential tremor can be explained due to affection of the dentate nucleus. Choreoathetosis is produced due to increased activity of the direct pathway. We did not find specifically associated pathophysiology related to dysarthria. We assume that multiple parts of the brain are involved in that problem. Putamen nucleus damage is the leading cause that explains dystonia seen in WD along with the globus palidus. We did not find a specific localization for seizures in WD, but the pathology seems to be related to decreased levels of B6 and direct toxicity of copper on the brain.

P.427 Effect of autogenic training on brain activity in migraineurs without aura

Migraine is one of the most prevalent neurological disorders which is suggested to be associated with dysfunctions of the central nervous system. The purpose of the present study was to detect the altered functional connectivity architecture in the large-scale network of the whole brain in migraine without aura (MWoA). Meanwhile, the brain functional hubs which are targeted by MWoA could be identified. A new voxel-based method named functional connectivity density (FCD) mapping was applied to resting-state functional magnetic resonance imaging data of 55 female MWoA patients and 44 age-matched female healthy controls (HC). Comparing to HC, MWoA patients showed abnormal short-range FCD values in bilateral hippocampus, bilateral insula, right amygdale, right anterior cingulate cortex, bilateral putamen, bilateral caudate nucleus and the prefrontal cortex. The results suggested decreased intraregional connectivity of these pain-related brain regions in female MWoA. In addition, short-range FCD values in left prefrontal cortex, putamen and caudate nucleus were significantly negatively correlated with duration of disease in MWoA group, implying the repeated migraine attacks over time may consistently affect the resting-state functional connectivity architecture of these brain hubs. Our findings revealed the dysfunction of brain hubs in female MWoA, and suggested the left prefrontal cortex, putamen and caudate nucleus served as sensitive neuroimaging markers for reflecting the disease duration of female MWoA. This may provide us new insights into the changes in the organization of the large-scale brain network in MWoA.

Quantitative susceptibility mapping shows lower brain iron content in children with autism.

To explore the application of quantitative susceptibility mapping (QSM) of brain iron content in children with autism. For the control group, 40 normal children aged 2-3, 3-4, 4-5, and 5-6years were prospectively selected from June 2018 to December 2018, with equal numbers of males and females in each age group. For the study group, 40 children with autism aged 2-3, 3-4, 4-5, and 5-6years were prospectively selected from January 2019 to October 2019; once again, there were equal numbers of males and females in each age group. All children received routine head MRI scans and enhanced T2*-weighted angiography (ESWAN) sequence scans, and the ESWAN sequence images were processed by software to obtain magnetic susceptibility maps. The regions of interest (ROIs) of the frontal white matter, frontal gray matter, thalamus, red nucleus, substantia nigra, dentate nucleus, globus pallidus, putamen nucleus, caudate nucleus, pons, and splenium of the corpus callosum were selected, and the magnetic susceptibility values were measured. The differences in magnetic susceptibility between the two groups were compared in children at the same age. For the children aged 2-3years, the magnetic susceptibility values in the caudate nucleus, dentate nucleus, and splenium of the corpus callosum in the study group were lower than those in the control group (p < 0.05). For the children aged 3-4, 4-5, and 5-6years, the magnetic susceptibility values in the frontal white matter, caudate nucleus, red nucleus, substantia nigra, dentate nucleus, and splenium of the corpus callosum in the study group were lower than those in the control group (p < 0.05). The brain iron content of children with autism is lower than that of normal children. This study protocol was registered at the Chinese clinical trial registry (registration number: ChiCTR2000029699; http://www.chictr.org.cn/searchprojen.aspx ). • In this study, the brain iron content of normal children and children with autism was compared to identify the differences, which provided a new objective basis for the early diagnosis of children with autism. • This study examined the iron content values in various brain regions of normal children aged 2-6years in this region and established a reference range for iron content in various brain regions of normal children in one geographical area, providing a reliable and objective standard for the diagnosis and treatment of some brain diseases in children. • The results of this study indicate that the brain iron content of preschool children with autism is lower than that of normal preschool children.

Cerebello-basal ganglia connectivity fingerprints related to motor/cognitive performance in Parkinson's disease

IntroductionThe role of the cerebellum in Parkinson's disease (PD) has attracted increasing attention; however, the role of functional connectivity (FC) between the basal ganglia and particular cerebellar subregions remains to be elucidated. We aimed to clarify the FC and its contribution to motor and cognitive performances in patients with PD. MethodsWe included 99 patients with PD and 99 age- and sex-matched healthy controls in this study. We created a cerebellar functional parcellation by performing cerebellum-only independent component analysis. Using the functional parcellation map, we performed seed-based connectivity analysis using each region as a seed and extracted the mean correlation coefficients within the thalamus and basal ganglia, including the caudate, pallidum, putamen and subthalamic nucleus. We examined the group differences and correlations with the motor and general cognitive scores. In addition, we conducted a mediation analysis to clarify the relationship among FC, motor severity, and cognition. ResultsThe PD group showed decreased FC between a wide range of cerebellar subregions and the basal ganglia. Motor severity was correlated with FC between the subthalamic nucleus and posterior Crus I/II, and general cognitive performance scores correlated with FC between the caudate nucleus and medial-posterior part of the Crus I/II (p < 0.05, corrected for multiple comparisons). The cerebello-caudate network had a direct effect on cognitive performance (p = 9.0 × 10−3), although partially mediated by motor performance (p = 8.2 × 10−3). ConclusionFC between cerebellar Crus I/II and divergent basal ganglia related to motor and cognitive performance in PD.

Performance evaluation of a novel multi-pinhole collimator for dopamine transporter SPECT

There is a tradeoff between spatial resolution and count sensitivity in SPECT with conventional collimators. Multi-pinhole (MPH) collimator technology has potential for concurrent improvement of resolution and sensitivity in clinical SPECT of ‘small’ organs. This study evaluated a novel MPH collimator specifically designed for dopamine transporter (DAT) SPECT with a triple-head SPECT camera. Count sensitivity was measured with a 99mTc point source placed on the lattice points of a 1 cm grid covering the whole field-of-view (FOV). Spatial resolution was assessed with a Derenzo type hot rod phantom. An anthropomorphic striatum phantom was scanned with total activity representative of a typical patient scan and different striatum-to-background activity concentration ratios. Recovery of striatum-to-background contrast was assessed by the contrast-recovery-coefficient. Measurements were repeated with double-head SPECT with fan-beam or low-energy-high-resolution-high-sensitivity (LEHRHS) collimators. A patient referred to DAT SPECT because of suspicion of Parkinson’s disease was scanned with both LEHRHS and MPH collimators after a single tracer injection. The axial MPH sensitivity profile was approximately symmetrical around its peak, although it was shifted 7 cm towards the patient to simplify positioning. Peak sensitivity of the triple-head MPH system in the center of the FOV was 620 cps MBq−1 compared to 225 cps MBq−1 for the double-head fan-beam system. Sensitivity of the MPH system decreased towards the edges of the FOV. The full width of the sensitivity profile at 200 cps MBq−1 was 21 cm transaxially and 11 cm axially. In MPH SPECT of the Derenzo phantom all rods with ≥ 5 mm diameter were clearly visible. MPH SPECT improved striatal contrast recovery by ≥ 20% compared to fan-beam SPECT. The patient scan demonstrated good image quality of MPH SPECT with almost PET-like delineation of putamen and caudate nucleus. SPECT with dedicated MPH collimators provides considerable improvement of the resolution-sensitivity tradeoff in DAT SPECT compared to SPECT with fan-beam or LEHRHS collimators.

Discrete finger sequences are widely represented in human striatum

Research in primates and rodents ascribes the striatum a critical role in integrating elementary movements into unitary action sequences through reinforcement-based learning. Yet it remains to be shown whether the human striatum represents action sequence-specific information. Young right-handed volunteers underwent functional magnetic resonance imaging while they performed four discrete finger sequences with their right hand, consisting of five button presses. Specific finger sequences could be discriminated based on the distributed activity patterns in left and right striatum, but not by average differences in single-voxel activity. Multiple bilateral clusters in putamen and caudate nucleus belonging to motor, associative, parietal and limbic territories contributed to classification sensitivity. The results show that individual finger movement sequences are widely represented in human striatum, supporting functional integration rather than segregation. The findings are compatible with the idea that the basal ganglia simultaneously integrate motor, associative and limbic aspects in the control of complex overlearned behaviour.

Expression of GPR55 and either cannabinoid CB1 or CB2 heteroreceptor complexes in the caudate, putamen, and accumbens nuclei of control, parkinsonian, and dyskinetic non-human primates.

Endocannabinoids are neuromodulators acting on specific cannabinoid CB1 and CB2 G-protein-coupled receptors (GPCRs), representing potential therapeutic targets for neurodegenerative diseases. Cannabinoids also regulate the activity of GPR55, a recently "deorphanized" GPCR that directly interacts with CB1 and with CB2 receptors. Our hypothesis is that these heteromers may be taken as potential targets for Parkinson's disease (PD). This work aims at assessing the expression of heteromers made of GPR55 and CB1/CB2 receptors in the striatum of control and parkinsonian macaques (with and without levodopa-induced dyskinesia). For this purpose, double blind in situ proximity ligation assays, enabling the detection of GPCR heteromers in tissue samples, were performed in striatal sections of control, MPTP-treated and MPTP-treated animals rendered dyskinetic by chronic treatment with levodopa. Image analysis and statistical assessment were performed using dedicated software. We have previously demonstrated the formation of heteromers between GPR55 and CB1 receptor (CB1-GPR55_Hets), which is highly expressed in the central nervous system (CNS), but also with the CB2 receptor (CB2-GPR55_Hets). Compared to the baseline expression of CB1-GPR55_Hets in control animals, our results showed increased expression levels in basal ganglia input nuclei of MPTP-treated animals. These observed increases in CB1-GPR55_Hets returned back to baseline levels upon chronic treatment with levodopa in dyskinetic animals. Obtained data regarding CB2-GPR55_Hets were quite similar, with somehow equivalent amounts in control and dyskinetic animals, and with increased expression levels in MPTP animals. Taken together, the detected increased expression of GPR55-endocannabinoid heteromers appoints these GPCR complexes as potential non-dopaminergic targets for PD therapy.

Quantitative Measurement of Metal Accumulation in Brain of Patients With Wilson's Disease.

Currently, no study has evaluated metal accumulation in the brains of patients with Wilson's disease by using quantitative susceptibility mapping at 3T MRI. The objectives of this study were to qualitatively and quantitatively evaluate changes in magnetic susceptibility and R2* maps in deep gray matter nuclei to discriminate Wilson's disease patients from healthy controls and to evaluate their sensitivities in diagnosing Wilson's disease. Magnetic susceptibility and R2* maps and conventional T1-weighted, T2-weighted, and T2-weighted fluid-attenuated inversion recovery images were obtained from 17 Wilson's disease patients and 14 age-matched healthy controls on a 3T MRI scanner. Differences between Wilson's disease and healthy control groups in susceptibility and R2* values in multiple deep nuclei were evaluated using a Mann-Whitney U test and receiver operating characteristic curves. The correlations of susceptibility and R2* values with Unified Wilson's Disease Rating Scale score were also performed. Magnetic susceptibility and R2* can effectively distinguish different types of signal abnormalities. Magnetic susceptibility and R2* values in multiple deep nuclei of Wilson's disease patients were significantly higher than those in healthy controls. Magnetic susceptibility value in the substantia nigra had the highest area under the curve (0.888). There were positive correlations of the Unified Wilson's Disease Rating Scale score with susceptibility values in the caudate nucleus (r = 0.757, P = 0.011), putamen (r = 0.679, P = 0.031), and red nucleus (r = 0.638, P = 0.047), as well as R2* values in the caudate nucleus (r = 0.754, P = 0.012). Quantitative susceptibility mapping at 3T could be a useful tool to evaluate metal accumulation in deep gray matter nuclei of Wilson's disease patients. © 2020 International Parkinson and Movement Disorder Society.

In vivo absolute quantification of striatal and extrastriatal D2/3 receptors with [123I]epidepride SPECT

Background[123I]epidepride is a high-affinity radiotracer used in single-photon emission computed tomography (SPECT) imaging of the D2/3 receptors. It binds with high affinity to striatal and extrastriatal receptors. Nevertheless, its slow kinetics in the striatum impedes quantification in this region. Thus, an approach that would allow a simultaneous quantification of both striatal and extrastriatal D2/3 receptors would be of interest for preclinical and clinical SPECT neuroimaging. We describe a partial saturation protocol that allows us to produce an in vivo Scatchard plot and thus estimate Bavail and appKd separately in both striatal and extrastriatal regions, through a single dynamic SPECT session. To validate this approach, a multi-injection protocol is used for the full kinetic modeling of [123I]epidepride using a two-tissue compartment, 5-parameter model (2T-5k).MethodsEighteen male rats were used. Binding parameters were estimated using the multi-injection protocol. Various simulations were performed to estimate the optimal conditions for the partial saturation protocol, which was applied at the region and voxel level. The results of the partial saturation study were compared to those obtained with the 2T-5k model. To illustrate the interest of the partial saturation approach, we performed a preliminary study of the effect of a chronic, subcutaneous administration of haloperidol (1 mg/kg/day), a D2 receptor antagonist, on the Bavail of [123I]epidepride in the rat striatum.ResultsA series of simulations demonstrated that a mass of 3 ug/kg of unlabeled epidepride allows the formation of an in vivo Scatchard plot. The partial saturation study led to robust estimations of Bavail in all brain regions that highly correlated (r = 0.99) with the corresponding values from the multi-injection study. A chronic haloperidol treatment resulted in a 17.9% increase in the Bavail values in the left Caudate Putamen nucleus (CP) (p = 0.07) and a 13.8% increase in the right CP (p = 0.12).ConclusionA partial saturation method allowed the robust quantification of D2/3 receptors in striatal and extrastriatal D2/3 receptors with a single-scan approach. This approach may be applied in the mapping of the D2/3 receptor in translational biological studies and potentially, in clinical SPECT imaging.

Striatal volumes as potential biomarkers in Eating Disorders: A pilot study.

Differences in bulimic and impulsive behaviours in Eating Disorders (ED) have been associated with cortico-striatal circuit dysfunction at a neurobiological level. We sought to investigate neo-striatal volume as a biomarker in ED subgroups as well as the possible relationship with trauma history. We studied 24 female patients: Anorexia Nervosa AN (n=8), Bulimia Nervosa BN (n=9), comorbid ED with borderline personality disorder (EDc; n=7), and a group of Healthy Controls (n=19). Binge eating behaviours and impulsivity scales were used to characterize our sample as well as Trauma Questionnaires and Magnetic resonance imaging (MRI) volumetric manual measurements of caudate and putamen nuclei (striatum). Our preliminary results showed a significantly larger left putaminal volume in AN compared to the other three groups [C (p=0.008), BN (p<.001) and EDc (p=.001)] and a smaller right putaminal volume in EDc compared to controls (p=.045) and AN (p=.039). Some negative correlations were found between bilateral putaminal volumes and self-reported general and early traumatization scores. This pilot study suggested that striatal volumes might differentiate AN from BN and EDc at a neurobiological level with implications for treatment strategies. Larger scale studies should be carried out that allow replication of these data.

The association between prenatal endocrine-disrupting chemical exposure and altered resting-state brain fMRI in teenagers.

Many studies have reported that prenatal exposure to endocrine-disrupting chemicals (EDCs) can cause adverse behavioral effects or cognitive dysfunction in children. This study aimed to investigate a relationship of the concentration of prenatal EDCs and brain function in teenagers. We recruited 59 mother-child pairs during the third trimester of pregnancy, and collected and examined the concentration of EDCs, such as heavy metals, phthalates and perfluoroalkyl substances (PFASs), in maternal urine and serum. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected in teenagers 13-16years of age, and fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) were performed to find the association between maternal EDC concentrations and the functional development of the teenage brain. We found a correlation between MBP concentration and activity in the superior frontal gyrus, middle frontal gyrus, middle temporal gyrus and inferior temporal gyrus in the combined group of boys and girls. We also observed a correlation between MBzP concentration and activity in the anterior cingulum gyrus and insula in girls. We found a correlation between lead concentration and activity in the cuneus in the combined group. We also observed a correlation between MeHg concentration and activity in the superior temporal gyrus, caudate nucleus and putamen in the combined group. The PFOS results revealed a negative relationship between activity in the right putamen in boys, girls and the combined group after phthalate or heavy metals were applied as covariates. The PFNA results showed a negative correlation between activity in the left/right putamen and left caudate nucleus in boys, girls and the combined group after phthalate, heavy metals or PFOS were applied as covariates. We examined the correlations between maternal EDC concentrations and brain development and found that the associations with resting-state teenage brains in some circumstances are sex-related.

Extrastriatal 123I-FP-CIT SPECT impairment in Parkinson\u2019s disease \u2013 the PPMI cohort

BackgroundNeuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson’s disease (PD). We undertook a case-controlled analysis of 123I-FP-CIT SPECT images to measure extrastriatal serotonergic transporters (SERT) in PD using the Parkinson’s Progression Markers Initiative (PPMI) cohort.MethodsWe included all PD (n = 154) and Control subjects (n = 62) with available 123I-FP-CIT SPECT imaging and high-resolution T1-weighted MRI for coregistration (PD: mean age 61.6 years, 62% male, disease duration 26 months, MDS-UPDRS III score 22). 123I-FP-CIT SPECT images were processed with PETPVE12 using an exploratory voxel-wise analysis including partial-volume effect correction. Linear regressions were performed in the PD group to assess correlations between region of interest 123I-FP-CIT uptake and clinical motor and non-motor impairment.ResultsCompared to Controls, PD exhibited an uptake reduction in bilateral caudate nucleus, putamen, insula, amygdala and right pallidum (family-wise error (FWE)-corrected p < 0.05). While lower putaminal uptake on the contralateral side to clinically more affected side was associated with higher MDS-UPDRS III score (p = 0.022), we found a trend association between higher geriatric depression scale and lower pallidum uptake (p = 0.09). Higher SCOPA-AUT gastrointestinal subscore was associated with lower uptake in mean putamen and caudate nucleus (p = 0.01 to 0.03), whereas urological subscore was inversely correlated with mean caudate nucleus, putamen, and pallidum uptake (p = 0.002 to 0.03). REM sleep behaviour disorder screening questionnaire was associated with lower 123I-FP-CIT binding in caudate nucleus, putamen and pallidum (all p < 0.05). No significant association was found for Montreal Cognitive Assessment (all p > 0.45) or excessive daytime sleepiness (all p > 0.29).ConclusionsIn addition to the well-established striatal deficit, this study provides evidence of a major extrastriatal 123I-FP-CIT impairment, and therefore of an altered serotonergic transmission in early PD.

Factors associated with development and distribution of granular/fuzzy astrocytes in neurodegenerative diseases.

Granular/fuzzy astrocytes (GFAs), a subtype of “aging‐related tau astrogliopathy,” are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N = 26), and progressive supranuclear palsy (PSP, N = 10), Alzheimer’s disease (AD, N = 20) and primary age‐related tauopathy cases (PART, N = 18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation and (iii) immunohistochemical features useful to understand the formation process of GFAs. In AGD cases, GFAs consistently occurred in the amygdala (100%), followed by the putamen (69.2%) and caudate nucleus and frontal cortex (57.7%, respectively). In PSP cases without AGD, GFAs were almost consistently noted in all regions examined (90–100%). In AD cases without AGD, GFAs were less frequent, developing preferably in the putamen (35.0%) and caudate nucleus (30.0%). PART cases without AGD had GFAs most frequently in the amygdala (35.3%), being more similar to AGD than to AD cases. Ordered logistic regression analyses using all cases demonstrated that the strongest independent factor of GFA formation in the frontal cortex and striatum was the diagnosis of PSP, while that in the amygdala was AGD. The age was not significantly associated with GFA formation in any region. In GFAs in AGD cases, phosphorylation and conformational change of tau, Gallyas‐positive glial threads indistinguishable from those in tufted astrocytes, and the activation of autophagy occurred sequentially. Given these findings, AGD, PSP, AD and PART cases may show distinct distributions of GFAs, which may provide clues to predict the underlying processes of primary tauopathies.

Late-onset oro-facial dyskinesia in Spinocerebellar Ataxia type 2: a case report

BackgroundGenetic familiar causes of oro-facial dyskinesia are usually restricted to Huntington’s disease, whereas other causes are often missed or underestimated. Here, we report the case of late-onset oro-facial dyskinesia in an elderly patient with a genetic diagnosis of Spinocerebellar Ataxia type 2 (SCA2).Case presentationA 75-year-old man complained of progressive balance difficulty since the age of 60 years, associated with involuntary movements of the mouth and tongue over the last 3 months. No exposure to anti-dopaminergic agents, other neuroleptics, antidepressants, or other drugs was reported. Family history was positive for SCA2 (brother and the son of the brother). At rest, involuntary movements of the mouth and tongue were noted; they appeared partially suppressible and became more evident during stress and voluntary movements. Cognitive examination revealed frontal-executive dysfunction, memory impairment, and attention deficit. Brain magnetic resonance imaging (MRI) disclosed signs of posterior periventricular chronic cerebrovascular disease and a marked ponto-cerebellar atrophy, as confirmed by volumetric MRI analysis. A dopamine transporter imaging scan demonstrated a bilaterally reduced putamen and caudate nucleus uptake. Ataxin-2 (ATXN2) gene analysis revealed a 36 cytosine-adenine-guanine (CAG) repeat expansion, confirming the diagnosis of SCA2.ConclusionsSCA2 should be considered among the possible causes of adult-onset oro-facial dyskinesia, especially when the family history suggests an inherited cerebellar disorder. Additional clinical features, including parkinsonism and motor neuron disease, may represent relevant cues for an early diagnosis and adequate management.

Left-hemispheric predominance of nigrostriatal deficit in isolated REM sleep behavior disorder.

Unilateral onset of parkinsonism due to nigrostriatal damage of the contralateral hemisphere is frequent in Parkinson disease (PD). There is evidence for a left-hemispheric bias of motor asymmetry in right-handed patients with PD indicating a hemispheric dominance. Isolated REM sleep behavior disorder (IRBD) constitutes the prodromal stage of PD and other synucleinopathies. To test the hypothesis that right-handed patients with IRBD exhibit left-hemispheric predominance of subclinical nigrostriatal dysfunction, we evaluated this aspect using neuroimaging instruments. In 167 right-handed patients with IRBD without parkinsonism, we evaluated in each hemisphere the integrity of the striatal dopaminergic terminals by dopamine transporter (DAT)-SPECT and the substantia nigra echogenicity by transcranial sonography. DAT-SPECT showed lower specific binding ratio (SBR) in the left striatum and left caudate nucleus than in the right striatum and right caudate nucleus. The percentage of patients with lower SBR was greater in the left striatum and left caudate nucleus than in the right striatum and right caudate nucleus. In those who developed a synucleinopathy in <5 years from DAT-SPECT, there was a lower SBR in the left putamen and left caudate nucleus than in the right putamen and right caudate nucleus. Substantia nigra echogenic size was greater in the left than in the right side in patients with hyperechogenicity and among individuals who phenoconverted in <5 years from transcranial sonography. Right-handed patients with IRBD exhibit left-hemispheric predominance of subclinical nigrostriatal dysfunction. In premotor PD, the neurodegenerative process begins asymmetrically, initially impairing the nigrostriatal system of the dominant hemisphere.

Lack of Asymmetry of Nigrostriatal Dopaminergic Function in Healthy Subjects.

In right-handed patients with Parkinson's disease (PD) or isolated rapid eye movement sleep behavior disorder, dopamine transporter (DAT) [(123)I]β-carboxymethyoxy-3-β-(4-iodophenyl) tropane single photon emission computed tomography (SPECT) shows predominant nigrostriatal deficit in the left striatum. This suggests that in PD patients, the nigrostriatal system of the dominant hemisphere is more susceptible to disease-related dysfunction. To confirm this hypothesis, we investigated whether the nigrostriatal function is symmetric in healthy controls and in patients with PD. In 113 right-handed healthy controls and 279 right-handed early-PD patients, we examined the striatal dopaminergic terminals function in each hemisphere using DAT-SPECT. In the controls, DAT-SPECT showed symmetric specific binding ratios in the putamen and caudate nucleus of each hemisphere. In patients with PD, the specific binding ratio was lower in the left than in the right putamen. Right-handed healthy controls have symmetric nigrostriatal dopaminergic function. The left hemispheric predominance of nigrostriatal deficit seen in right-handed premotor and manifest PD represents an early pathological feature of the disease. © 2020 International Parkinson and Movement Disorder Society.

Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank

BackgroundX-linked ichthyosis (XLI) is an uncommon dermatological condition resulting from a deficiency of the enzyme steroid sulfatase (STS), often caused by X-linked deletions spanning STS. Some medical comorbidities have been...

\u201cDiabetic striatopathy\u201d: clinical presentations, controversy, pathogenesis, treatments, and outcomes

Diabetic striatopathy (DS) is a rare medical condition with ambiguous nomenclature. We searched PubMed database from 1992 to 2018 for articles describing hyperglycemia associated with chorea/ballism and/or neuroimages of striatal abnormalities. Descriptive analysis was performed on demographic/clinical characteristics, locations of striatal abnormalities on neuroimages, pathology findings, treatment strategies, and outcomes. In total, 176 patients (male:female = 1:1.7) were identified from 72 articles with mean age 67.6 ± 15.9 (range, 8–92). Among them, 96.6% had type 2 DM with 17% being newly diagnosed. Average blood glucose and glycated hemoglobin concentrations were 414 mg/dL and 13.1%, respectively. Most patients (88.1%) presented with hemichorea/hemiballism. Isolated putamen and combined putamen-caudate nucleus involvements were most common on neuroimaging studies with discrepancies between CT and MRI findings in about one-sixth of patients. Unilateral arm-leg combination was the most frequent with bilateral chorea in 9.7% of patients. Chorea and imaging anomalies did not appear concomitantly in one-tenth of patients. Successful treatment rates of chorea with glucose-control-only and additional anti-chorea medications were 25.7% and 76.2%, respectively, with an overall recurrence rate being 18.2%. The most commonly used anti-chorea drug was haloperidol. To date, four out of six pathological studies revealed evidence of hemorrhage as a probable pathogenesis.