Changes In Basal Ganglia Research Articles

Associations between elevated uric acid and brain imaging abnormalities in pediatric patients with methylmalonic acidemia under 5 years of age

Methylmalonic acidemia (MMA) is the most common inborn organic acidemia, presenting multisystemic complications. Uric acid may have neurotoxic or neuroprotective effects due to its antioxidant or pro-inflammatory properties; however, its role in MMA brain injury remains unclear. We examined the correlation between the serum uric acid levels and brain imaging features of MMA. Data were collected from a cross-sectional study of 216 patients with MMA and 216 healthy matched controls aged 0–5 years in China. Serum uric acid levels were measured, and magnetic resonance imaging and computed tomography findings were retrieved from hospital records. Overall, 74.1% patients had brain abnormalities. Patients in the MMA group with abnormal brain imaging had higher serum uric acid levels than those in the MMA normal brain imaging and control groups. The area under the curve of serum uric acid was 0.74, 0.91, and 0.93 for MMA diagnosis with abnormal brain images, basal ganglia changes, and globus pallidus changes, respectively. Higher serum uric acid levels were independently associated with abnormal brain images. Children aged < 5 years with abnormal brain images in MMA exhibit elevated serum uric acid levels, serving as an effective auxiliary diagnostic indicator and independent risk factor for brain tissue injury.

Neurovascular coupling of striatal dopamine D2/3 receptor availability and perfusion using simultaneous PET/MR in humans

The midbrain dopamine system contributes to important neural functions in the basal ganglia, and is involved in aspects of pathological processes in schizophrenia. In preclinical and clinical studies, pharmacological blockade or stimulation of brain dopamine receptors alters cerebral perfusion, which is a surrogate marker of metabolic activity. However, there is scant documentation of this neurofunctional coupling in relation to individual differences in the dopamine system of healthy humans. We therefore tested the hypothesis that baseline dopamine D2/3 receptor availability predicts individual blood flow responses to challenge with a dopamine agonist.We used [18F]fallypride positron emission tomography (PET) imaging to quantify dopamine D2/3 receptor availability as binding potential (BPND) in nine healthy subjects. Using simultaneous perfusion-weighted functional magnetic resonance imaging (fMRI), we measured perfusion at baseline and after challenge with the dopamine agonist apomorphine.Results of this multimodal imaging study revealed a strong negative association between baseline D2/3 dopamine receptor availability and apomorphine-induced perfusion changes in the human basal ganglia. There was considerable intra-individual variation in the neurovascular response to the apomorphine challenge, which may call for further investigation of the dopaminergic regulation of cerebral perfusion in patients with schizophrenia.This study describes a novel paradigm for assessing dopamine sensitivity, facilitating an exploration of the dopamine supersensitivity hypothesis.

Study of Involuntary Limb Movements as a Presenting Feature in Nonketotic Hyperglycemia.

Background Hyperglycaemia can rarely manifest as hemichorea/hemiballismus, which subsides with adequate control of blood sugar. Our study accounted for patients with abnormal, involuntary limb movements with high blood sugar, excluding other conditions leading to or mimicking such a clinical appearance. It is very important to identify such patients as chorea secondary to an underlying etiology like hyperglycemia, whichcan be cured. Material & methods This study was done in IMS & SUM Hospital for a duration of one year, from March 2019 to February 2020, with a total of 11 cases with abnormal limb movements with a blood sugar of 250 mg% and above. Results In this study, 36.36%( n=4) of patients were female, and 63.63% (n=7) were males. The mean age of the patients at presentation was 66.5 years. Eighteen point one percent (18.1%; n=2) of the patients showed hemiballismus, 36.3% (n=4) showed hemichorea, 18.1% (n=2) showed hemiathetosis, 9.1% (n=1) showed myoclonus, and 18.1% (n=2) showed hemiballismus with hemichorea. The mean duration to correct hyperglycemia was found to be 34 hours and the mean duration to correct abnormal limb movements was 90.54 hours. Eighty-one point eight percent (81.8%; n=9) of patients showed basal ganglia changes on brain imaging.

Basal Ganglia Compensatory White Matter Changes on DTI in Alzheimer's Disease.

The volume reduction of the gray matter structures in patients with Alzheimer's disease is often accompanied by an asymmetric increase in the number of white matter fibers located close to these structures. The present study aims to investigate the white matter structure changes in the motor basal ganglia in Alzheimer's disease patients compared to healthy controls using diffusion tensor imaging. The amounts of tracts, tract length, tract volume, quantitative anisotropy, and general fractional anisotropy were measured in ten patients with Alzheimer's disease and ten healthy controls. A significant decrease in the number of tracts and general fractional anisotropy was found in patients with Alzheimer's disease compared to controls in the right caudate nucleus, while an increase was found in the left and the right putamen. Further, a significant decrease in the structural volume of the left and the right putamen was observed. An increase in the white matter diffusion tensor imaging parameters in patients with Alzheimer's disease was observed only in the putamen bilaterally. The right caudate showed a decrease in both the diffusion tensor imaging parameters and the volume in Alzheimer's disease patients. The right pallidum showed an increase in the diffusion tensor imaging parameters but a decrease in volume in Alzheimer's disease patients.

Naltrexone engages a brain reward network in the presence of reward-predictive distractor stimuli in males

The non-selective opioid receptor antagonist, naltrexone is one of the most prescribed medications for treating alcohol and opioid addiction. Despite decades of clinical use, the mechanism(s) by which naltrexone reduces addictive behavior remains unclear. Pharmaco-fMRI studies to date have largely focused on naltrexone's impact on brain and behavioral responses to drug or alcohol cues or on decision-making circuitry. We hypothesized that naltrexone's effects on reward-associated brain regions would associate with reduced attentional bias (AB) to non-drug, reward-conditioned cues. Twenty-three adult males, including heavy and light drinkers, completed a two-session, placebo-controlled, double-blind study testing the effects of acute naltrexone (50 mg) on AB to reward-conditioned cues and neural correlates of such bias measured via fMRI during a reward-driven AB task. While we detected significant AB to reward-conditioned cues, naltrexone did not reduce this bias in all participants. A whole-brain analysis found that naltrexone significantly altered activity in regions associated with visuomotor control regardless of whether a reward-conditioned distractor was present. A region-of-interest analysis of reward-associated areas found that acute naltrexone increased BOLD signal in the striatum and pallidum. Moreover, naltrexone effects in the pallidum and putamen predicted individual reduction in AB to reward-conditioned distractors. These findings suggest that naltrexone's effects on AB primarily reflect not reward processing per se, but rather top-down control of attention. Our results suggest that the therapeutic actions of endogenous opioid blockade may reflect changes in basal ganglia function enabling resistance to distraction by attractive environmental cues, which could explain some variance in naltrexone's therapeutic efficacy.

ODP261 Non-Ketotic Hyperosmolar Hyperglycemia Induced Hemichorea-Dystonia Syndrome, Without Radiologic Striatopathy

Abstract Background Movement disorder is an uncommon complication of Hyperglycemic crisis. It is often associated with diabetic striatopathy which is a clinico-radiologic entity that is associated with acute changes of the contralateral basal ganglia. Isolated dyskinetic-dystonic disorder without obvious radiologic lesion is a rare clinical entity. Case Report A 42-years-old woman with a history of type 2 diabetes mellitus was admitted with a 1-week history of involuntary right arm and face movements and 3 weeks of polyuria. She had recurrent choreiform right arm movements without athetosis or hemiballismus lasting about 2. Additionally, she experiences right cervicofacial dystonia. There was no involvement of the lower extremities, no loss of consciousness and no other neurologic deficit between attacks. Physical examination was essentially unveiling with no focal neurologic deficits or tremors. Initial work up showed elevated; blood glucose to 620mg/dl (65–110), serum sodium of 148mEq/L (135–145) and serum osmolality of 330mmol/kg (275–295). Work up was negative for acidosis, with pH of 7.39 (7.32–7.42), bicarbonate of 23mEq/L (23–31) and no ketones on urinalysis. Other relevant test including serum bilirubin, transaminases, ammonia level, calcium, ceruloplasmin and cupper were normal. An initial non-contrast CT scan of the brain was negative for acute pathology and MRI did not show any lesions in basal ganglia. E. E. G was also normal. Movements recurred twice in hospital, and she received IV lorazepam without much response. She was diagnosed with non-Ketotic hyperosmolar hyperglycemic chorea- dystonia syndrome. She received IV normal saline and started on insulin therapy resulting in improvement in serum glucose to 255 by the next morning. She was discharge after 72 hours with no recurrence at 2 weeks follow up visit. Discussion Hyperglycemic crisis may rarely be associated with dyskinetic syndromes, often due to the development of diabetic striatopathy and about 80% are without ketosis. The mechanism is believed to be due to impaired GABA synthesis in the basal ganglia. Prevalence of hyperglycemia induced striatopathy stands at 1 per 100,000. The commonest manifestation is that of hemiballismus and chorea. Very few cases of dystonia have been reported. It is a clinico-radiologic diagnosis with basal ganglia abnormalities on imaging stemming from edema, microhemorrhages or calcific changes. There are very few case reports of hyperglycemic dyskinetic syndromes without CNS changes on MRI. The average time for resolution of MRI changes is 60 days thus we believe our patient had no radiologic striatopathy. In majority of cases, resolution of hyperglycemia leads to clinical resolution of dyskinetic spells. Occasionally, some patients may require medications such as antipsychotics including haloperidol, or benzodiazepines such as clonazepam to control movements. In conclusion, movement disorder related to hyperglycemia though rare, can be disabling. Prognosis is excellent if a timely clinical diagnosis is made. Presentation: No date and time listed

Pallidal Activity Related to Posture and Movement during Reaching in the Cat.

We tested the hypothesis that the pallidum contributes to the control of both posture and movement. We recorded neuronal activity from the pallidum in a task in which male cats reached forward from a standing posture to depress a lever. In agreement with previous studies, we found that a majority of pallidal cells (91/116, 78%), including neurons in both the entopeduncular nucleus and the globus pallidus, showed significant modulation of their activity during reaching with the contralateral limb. Mostly different populations of cells were active during the transport (flexion) and lever press (extension) phase of the task. Most cells showed dynamic patterns of activity related to the movement. However, a modest proportion of modulated cells (18/91, 20%) showed properties consistent with a contribution to the control of anticipatory postural responses, whereas a further 10% showed activity consistent with a contribution to postural support during the movement. Although some cells that showed modified activity only during reaches with the contralateral forelimb, many cells (65/91, 71%) were also activated during reaches with the ipsilateral forelimb. This was particularly true for cells related to the lever press, many of which discharged similarly during reaches of either limb. This suggests a context-dependent control of movement and posture in which the same muscles are used for different functions during contralateral and ipsilateral reach. Comparison with the results from recordings made previously from the motor cortex and the pontomedullary reticular formation in the same task show more similarities with the former than the latter.SIGNIFICANCE STATEMENT Pathologic changes in basal ganglia function frequently lead to problems with postural stability and gait initiation. Here, we show that some neurons in one of the output regions of the basal ganglia, the pallidum, show discharge activity compatible with a contribution to postural control. At the same time, we note that such cells are a minority in this region with most cells being related to movement rather than posture. We also show that many neurons are active during movements of both the contralateral and ipsilateral limbs, sometimes with identical discharge patterns. We suggest that this indicates a context-dependent regulation of movement and posture in the pallidum.

Changes in Volume of Subregions Within Basal Ganglia in Obsessive-Compulsive Disorder: A Study With Atlas-Based and VBM Methods.

BackgroundThe role of basal ganglia in the pathogenesis of obsessive–compulsive disorder (OCD) remains unclear. The studies on volume changes of basal ganglia in OCD commonly use the VBM method; however, the Atlas-based method used in such research has not been reported. Atlas-based method has a lower false positive rate compared with VBM method, thus having advantages partly.ObjectivesThe current study aimed to detect the volume changes of subregions within basal ganglia in OCD using Atlas-based method to further delineate the precise neural circuitry of OCD. What is more, we explored the influence of software used in Atlas-based method on the volumetric analysis of basal ganglia and compared the results of Atlas-based method and regularly used VBM method.MethodsWe analyzed the brain structure images of 37 patients with OCD and 41 healthy controls (HCs) using the VBM method, Atlas-based method based on SPM software, or Freesurfer software to find the areas with significant volumetric variation between the two groups, and calculated the effects size of these areas.ResultsVBM analysis revealed a significantly increased volume of bilateral lenticular nucleus in patients compared to HCs. In contrast, Atlas-based method based on Freesurfer revealed significantly increased volume of left globus pallidus in patients, and the largest effect size of volumetric variation was revealed by Freesurfer analysis.ConclusionsThis study showed that the volume of bilateral lenticular nucleus significantly increased in patients compared to HCs, especially left globus pallidus, which was in accordance with the previous findings. In addition, Freesurfer is better than SPM and a good choice for Atlas-based volumetric analysis of basal ganglia.

Microstructural changes of basal ganglia in migraine with restless legs syndrome: findings from a neuroimaging study.

In this study, it is planned to investigate the integrity of the basal ganglia structures in migraineurs with restless legs syndrome (RLS) to explore this relationship. In this study, 58 patients who were diagnosed migraine and 51 healthy controls (HCs) were included. Patients diagnosed with migraine were divided into two groups: Group I (migraine without RLS) and Group II (migraine with RLS). The integrity of basal ganglia was evaluated with region of interest diffusion tensor imaging method which allows us to assess microstructural changes of the tissue. The mean age of thepatients was 35.98 ± 7.92years, and the mean age of the HCs was 33.84 ± 11.06. 84.5% (n = 49) of the patients were female and 15.5% (n = 9) were male. 82.4% (n = 42) of the HCs were female, 17.6% (n = 9) were male. The number of thepatients without RLS was 41 (Group I), and the number of thepatients with RLS was 17 (Group II). When basal ganglia structures were compared between groups of thepatients with and without RLS, the fractional anisotropy (FA) value of the left putamen differed (Group I: 0.30 ± 0.06 vs. Group II: 0.25 ± 0.7, p = 0.01). The significant relationship was found attack frequency and presence of RLS with left putamen FA values according to multiple regression analysis. It was determined in this study that the changes in the microstructure of putamen, one of the basal ganglia structures, may be associated with the presence of RLS in migraineurs.

Transient Response of Basal Ganglia Network in Healthy and Low-Dopamine State.

The basal ganglia (BG) are crucial for a variety of motor and cognitive functions. Changes induced by persistent low-dopamine (e.g., in Parkinson’s disease; PD) result in aberrant changes in steady-state population activity (β band oscillations) and the transient response of the BG. Typically, a brief cortical stimulation results in a triphasic response in the substantia nigra pars reticulata (SNr; an output of the BG). The properties of the triphasic responses are shaped by dopamine levels. While mechanisms underlying aberrant steady state activity are well studied, it is still unclear which BG interactions are crucial for the aberrant transient responses in the BG. Moreover, it is also unclear whether mechanisms underlying the aberrant changes in steady-state activity and transient response are the same. Here, we used numerical simulations of a network model of BG to identify the key factors that determine the shape of the transient responses. We show that an aberrant transient response of the SNr in the low-dopamine state involves changes in the direct pathway and the recurrent interactions within the globus pallidus externa (GPe) and between GPe and subthalamic nucleus (STN). However, the connections from D2-type spiny projection neurons (D2-SPN) to GPe are most crucial in shaping the transient response and by restoring them to their healthy level, we could restore the shape of transient response even in low-dopamine state. Finally, we show that the changes in BG that result in aberrant transient response are also sufficient to generate pathologic oscillatory activity in the steady state.

A Perplexing Case of Pituitary Apoplexy Masquerading as Meningoencephalitis

Pituitary apoplexy (PA) is extremely rare in children and adolescents. It is a life-threatening condition usually results from sudden hemorrhage or infarction induced swelling in a pituitary adenoma. The clinical manifestations of PA include severe headaches, impaired consciousness, fever, visual disturbance, and variable ocular paresis. Therefore, the presence of meningeal irritation may lead to misdiagnosis as a case of meningoencephalitis or spontaneous subarachnoid hemorrhage, and delay in the proper management of the disease. We report a case of 17-year-old pubertal boy who developed sudden severe headache, vomiting, slurring of speech and abnormal behaviour followed by impaired sensorium with fever. The patient who was initially diagnosed with meningoencephalitis (ME) based on clinical presentation and cerebrospinal fluid (CSF) analysis, which was consistent with bacterial meningitis. MRI of brain was performed, confirming a pituitary macroadenoma with hemorrhage and ischemic changes in both basal ganglia and pons. A complete analysis of the pituitary hormones revealed decreased cortisol and thyroid hormone level and hyperprolactinemia and he was subsequently started on placement corticosteroid and L-thyroxine therapy and cabergoline. After 14/ days of antimicrobial therapy with ceftriaxone and ampicillin, the patient improved and was discharged on hormone replacement therapy and surgical advised. Hereby, we report our case with a review of literatures. Bangladesh J Medicine July 2022; 33(1) : 85-88

Basal ganglia correlates of wellbeing in early adolescence

It has been suggested that biological markers that define mental health are different to those that define mental illness. The basal ganglia changes dramatically over adolescence and has been linked to wellbeing and mental health disorders in young people. However, there remains a paucity of research on wellbeing and brain structure in early adolescence. This cross-sectional study examined relationships between grey matter volume (GMV) of basal ganglia regions (caudate, putamen, pallidum and nucleus accumbens) and self-reported wellbeing (COMPAS-W), in a sample of Australian adolescents aged 12 years (N = 49, M = 12.6, 46.9% female). Significant negative associations were found between left hemisphere caudate GMV and scores on ‘total wellbeing’, ‘composure’ and ‘positivity’. The results of this study indicate that smaller caudate GMV at age 12 is linked to increased subjective wellbeing. While seemingly counter-intuitive, our finding is consistent with previous research of decreased GMV in the pons and increased COMPAS-W scores in adults. Our results suggest that protective neurobiological factors may be identifiable early in adolescence and be linked to specific types of wellbeing (such as positive affect and optimism). This has implications for interventions targeted at building resilience against mental health disorders in young people.

S1552 A Rare Care of Pancreatic Neuroendocrine Tumor and Hyperammonemic Encephalopathy

Introduction: Hyperammonemic encephalopathy infrequently occurs as the presenting manifestation of a pancreatic neuroendocrine tumor (PNET) without associated hepatic failure. We present a rare case of a patient with neurologic decline requiring hospitalization who was diagnosed with a PNET and hyperammonemic encephalopathy without liver failure. Case Description/Methods: A 59-year-old male attorney with hypertension presented to his primary care physician with a bilateral intention tremor and 2 weeks later developed progressively worsening cognition. His medical history was otherwise unremarkable. Upon hospitalization, vital signs were normal. A neurologic exam showed 1/4 recall and impaired attention. Labs revealed an elevated ammonia (219 mg/dL) and total bilirubin of 5.9 mg/dL (indirect 4.1 mg/dL). His CBC, CMP, AST/ALT/Alkaline phosphatase, coagulation panel, heavy metal screen, B1, B6, B12, folate, HIV, TSH, RPR, Lyme, infectious evaluation (including COVID), and lumbar puncture were normal. A brain MRI showed nonspecific bilateral basal ganglia changes. A RUQ ultrasound showed a pancreatic mass. His mental status improved after 2 days of lactulose titrated to 3-4 soft bowel movements daily. A chest / abdominal / pelvic CT scan revealed an 11.3 cm heterogeneous pancreatic mass encasing the splenic artery and abutting greater than 50% of the superior mesenteric vein, without evidence of pulmonary or hepatic metastases. CA 19-9 was 13 U/mL. Ultrasound-guided biopsy revealed a well-differentiated neuroendocrine tumor (WHO Grade 2) positive for synaptophysin, Cam 5.2, Chromogranin A, Ki67 5%, and mitotic count < 2/5 mm 2. The patient underwent an open distal pancreatectomy and splenectomy;a liver nodule, positive for well-differentiated neuroendocrine cells, was found. 5/65 lymph nodes were positive for metastatic disease. Pathologic stage was T3N1M1a. A PET scan, done approximately a month after surgery, showed mild metabolic activity in the pancreatic body and multiple liver metastases not seen on CT scan. Currently, the patient is being followed by oncology and is receiving Lanreotide. Discussion: This case is unusual because the patient presented with encephalopathy without evidence of hepatic failure. It is postulated that the encephalopathy was the result of microvascular portosystemic shunting due to unrecognized hepatic metastases. This case study emphasizes the potential need for advanced imaging in patients with PNET and encephalopathy when initial studies suggest no evidence of hepatic failure.

Normal-sized basal ganglia perivascular space related to motor phenotype in Parkinson freezers.

Changes in basal ganglia (BG) perivascular spaces (PVSs) are related to motor and cognitive behaviors in Parkinson’s disease (PD). However, the correlation between the initial motor phenotype and PVSs distribution/burden in PD freezing of gait (FOG) remains unclear. In addition, the normal-sized PVSs (nPVSs) have not been well-studied. With high-resolution 7T-MRI, we studied nPVSs burden in BG, thalamus, midbrain and centrum semiovale. The numbers and volume of nPVSs were assessed in 10 healthy controls, 10 PD patients without FOG, 20 with FOG [10 tremor dominant (TD), 10 non-TD subtype]. Correlation analyses were further performed in relation to clinical parameters. In this proof of concept study, we found that the nPVS burden of bilateral and right BG were significantly higher in freezers. A negative correlation existed between the tremor score and BG-nPVSs count. A positive correlation existed between the levodopa equivalent daily dose and BG-nPVSs count. The nPVS burden correlated with the progression to FOG in PD, but the distribution and burden of nPVS differ in TD vs. non-TD subtypes. High resolution 7T-MRI is a sensitive and reliable tool to evaluate BG-nPVS, and may be a useful imaging marker for predicting gait impairment that may evolve into FOG in PD.

Basal ganglia-orbitofrontal circuits are associated with prospective memory deficits in Wilson's disease.

Degenerative changes in the basal ganglia (BG) are thought to contribute to neurological symptoms in Wilson's disease (WD). However, very little is known about whether and how the BG have an influence on prospective memory (PM) by interacting with the cerebral cortex. Here, we employed structural magnetic resonance imaging to systematically examine the effect of volume atrophy of BG on cortical thickness and to evaluate the relationships between cortical thickness of regions associated with BG atrophy and PM performance in WD. Cortical thickness atrophy in the left temporal pole and medial frontal gyrus are not related to degenerative changes in BG. Cortical thickness in the left superior frontal gyrus and right orbitofrontal gyrus (ORB) have stronger correlations with volume atrophy of the left accumbens, pallidum, and putamen in WD when compared with healthy controls. Furthermore, the cortical thickness of the right ORB is not only significantly correlated with PM performance but can also distinguish the severity of PM impairment in WD. Additionally, the middle cingulate cortex was related to volume atrophy of the accumbens, and its cortical thickness has a significant positive correlation with event-based PM. Together, these findings highlight that BG-orbitofrontal circuits may serve as neural biomarkers of PM and provide implications for the neural mechanisms underlying cognitive impairment in WD.

Clinical heterogeneity in patients with m.4412G > A MT-TM mutation and different heteroplasmy levels

The identification of the m.4412G > A MT-TM (mt-tRNAMet) mutation was first reported in 2019. The affected individual presented with childhood-onset seizures and myopathy and bilateral basal ganglia changes, with heteroplasmy levels in muscle as high as 90%. Here, we describe another adult-onset patient with the same mutation and additional phenotypes, including hearing impairment, cerebellar ataxia, progressive dementia, and myopathy. The 10% heteroplasmy level observed in skin fibroblasts from this patient are lower than those in the previously reported patient. Our report suggests possible clinical heterogeneity in patients with mitochondrial tRNA mutations based on heteroplasmy levels.

The Relationship Between Brain Metabolites Alterations and Neuropsychological Deficits in Patients with Methamphetamine Use Disorder: A Proton Magnetic Resonance Spectroscopy Study.

Chronic use of methamphetamine induces neuropsychological deficits and neurochemical changes in frontostriatal regions. This study aimed to examine the relationship between brain metabolites alterations in frontostriatal regions and neuropsychological deficits in patients with methamphetamine use disorder. A total of 30 methamphetamine users and 20 control participants were selected and a battery of standardized executive function, attention, and memory tasks, including the Wisconsin Card Sorting Test, Stroop Test, and Wechsler Memory Scale, was administered to them. Proton-Magnetic resonance spectroscopy (H-MRS) of N-Acetylaspartate/Creatine (NAA/Cr), Choline/Creatine (Cho/Cr), and glutamate + glutamine/creatine (Glx/Cr) in dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and basal ganglia (BG) were also undertaken. Current findings indicated that there were significant differences between two groups in metabolite ratios including NAA/Cr, Cho/Cr, and Glx/Cr in three areas, except for Glx/Cr in BG. Moreover, compared to healthy controls, methamphetamine users showed poorer performance in all neuropsychological tests. Finally, a significant relationship was found between regional metabolites alterations, particularly in the ACC, and neuropsychological deficits in methamphetamine users. In addition to neurochemical changes and neuropsychological deficits in patients with methamphetamine use disorder, current results highlighted the relationship between these changes in DLPFC, ACC, and BG with cognitive deficits in methamphetamine users.

Organothiophosphate Induced Acute and Reversible Parkinsonism: Case Report and Literature Review

Introduction: Organophosphate compound poisoning is one of the most common causes for admission to the Medical Intensive Care Unit. Parkinsonism is a primary neurotoxic manifestation of organophosphate intoxication. In this case report, we present the case of a 26 year old man who had the experience of organothiophosphate poisoning. Case presentation: A 26 year old man was admitted with tremors in upper and lower limbs together with the rigidity of all 4 limbs as well as difficulty in swallowing and in daily activities like walking, rising from chair, and turning on bed. He had consumed organophosphorus compound quinalphos, 15 days before. The basal ganglia changes were documented radiologically by Magnetic Resonance Imaging (MRI). Gradual recovery was observed by treatment with dopaminergic agents and central anticholinergics over few weeks. Only 0.5% of organophosphate poisoning patients develop neurotoxic manifestations in the form of extrapyramidal syndromes such as Parkinsonism. Discussion: The occurrence of Parkinsonism as a complication of organophosphate poisoning raises safety concerns, especially in developing countries. Yet, this study is the first case report on Organothiophospahate induced Parkinsonism. Conclusion: Clinicians should be aware of the possibility of extrapyramidal manifestations following organophosphate poisoning and the patients should be asked for regular follow-ups as the symptoms may appear even 1 month after the poisoning.

Maintained Visual-, Auditory-, and Multisensory-Guided Associative Learning Functions in Children With Obsessive-Compulsive Disorder.

Sensory-guided acquired equivalence learning, a specific kind of non-verbal associative learning, is associated with the frontal cortex–basal ganglia loops and hippocampi, which seem to be involved in the pathogenesis of obsessive–compulsive disorder (OCD). In this study, we asked whether visual-, auditory-, and multisensory-guided associative acquired equivalence learning is affected in children with OCD. The first part of the applied learning paradigm investigated association building between two different sensory stimuli (where feedback was given about the correctness of the choices), a task that critically depends upon the basal ganglia. During the test phases, which primarily depended upon the hippocampi, the earlier learned and hitherto not shown but predictable associations were asked about without feedback. This study involved 31 children diagnosed with OCD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria and 31 matched healthy control participants. The children suffering from OCD had the same performance as the control children in all phases of the applied visual-, auditory-, and multisensory-guided associative learning paradigms. Thus, both the acquisition and test phases were not negatively affected by OCD. The reaction times did not differ between the two groups, and the applied medication had no effect on the performances of the OCD patients. Our results support the findings that the structural changes of basal ganglia and hippocampi detected in adult OCD patients are not as pronounced in children, which could be the explanation of the maintained associative equivalence learning functions in children suffering from OCD.

Ischemic injury precipitates neuronal vulnerability in Parkinson's disease: Insights from PINK1 mouse model study and clinical retrospective data

IntroductionIncreasing evidence demonstrates the relevant association between Parkinson's disease (PD) and vascular diseases/risk factors, as well as a worse clinico-pathological progression in those patients with vascular comorbidity. The mechanisms underlying this relationship have not been clarified yet, although their comprehension is critical in a perspective of disease-modifying treatments development or prevention. MethodsWe performed an experimental protocol of ischemic injury (glucose-oxygen deprivation, OGD) on PTEN-induced kinase 1 knockout (PINK1−/−) mice, a well-established PD model, looking at both electrophysiological and morphological changes in basal ganglia. In addition, 253 PD patients were retrospectively analysed, to estimate the prevalence of vascular risk factors. ResultsIn PINK1−/− mice, the OGD protocol induced electrophysiological (prolonged depolarization) and morphological alterations (picnotic cells, cellular loss and swelling, thickening of nuclear chromatin) in striatal medium spiny neurons and nigral dopaminergic neurons. Vascular comorbidity occurred in 75% of PD patients. ConclusionsThe ischemic injury precipitates neuronal vulnerability in basal ganglia of PINK1−/− mice, probably through an impairment of mitochondrial metabolism and higher oxidative stress. These experimental data may provide a potential mechanistic explanation for both the association between vascular diseases and PD and their reciprocal interactions in determining the clinico-pathological burden of PD patients.