Basal Ganglia Research Articles

A patient with heterochronous double primary tumor of basal ganglia germ cell tumors followed by diffuse hemispheric glioma: a case report.

Basal ganglia germ cell tumor (BGGCT) is a rare central nervous system (CNS) tumor. Diffuse hemispheric gliomas, H3 G34-mutant (DHGs) is an invasive glioma involving the cerebral hemispheres. The diagnosis of DHGs depends on the integration of histopathology and molecular pathology. We reported a patient with an initial diagnosis of BGGCT that was sensitive to subsequent chemoradiotherapy. Unfortunately, a second high-grade glioma was found on magnetic resonance imaging (MRI) six years later. Subsequently, the tumor was completely removed after surgery and the following histopathology plus next generation sequencing (NGS) testing confirmed the diagnosis of DHGs. Interestingly, we found a germline likely pathogenic variant in FANCA. After surgery, the patient received Stupp regimen. The patient had a relapse 13months after the Stupp regimen and was doing well after surgery. This is the first report of a patient with heterochronous double primary tumor of BGGCT followed by DHGs.

Neonatal Brain MRI: Periventricular Germinal Matrix Mimicking Hypoxic-ischemic White Matter Injuries.

As pregnancy progresses, the germinal matrix volume decreases. Residual periventricular germinal matrix may be mistaken for hypoxic-ischemic white matter injury. This study aims to determine the prevalence and imaging characteristics of these findings. This retrospective study analyzed brain MRIs of newborns from 2012-2023, performed within the first week of life. MRIs were done for suspected hypoxic-ischemic injuries, post-natal neurological symptoms, and evaluation of prenatally diagnosed structural anomalies. Image analysis targeted the remnants of the frontal periventricular germinal matrix, assessing its imaging characteristics, including diffusion, T1, and T2 signal characteristics, and laterality. Frontal migrating cell bands were also assessed. Seventy newborns were included (mean gestational age at delivery was 38.3 ± 2.1 weeks, mean scan age 5.1 ± 1.9 days). Frontal periventricular gray matter was detected in 39 newborns (90% bilateral) on T2-weighted images, negatively correlated with gestational age (r = -0.31, p = 0.013); none showed decreased ADC or shortened T1 signal compared with the basal ganglia. Frontal periventricular bands were found in 37 newborns (97.3% bilateral), strongly correlating with periventricular gray matter (r = 0.71, p < 0.001). No correlation was found between clinical hypoxic-ischemic injuries and these features. The presence of frontal periventricular gray matter observed in early neonatal MRIs, without decreased ADC values or shortened T1 signal, is developmental, reflecting a late maturation phase. Careful interpretation of MRI characteristics, including diffusion, T1, and T2 signal intensities, is necessary before attributing these findings to hypoxic-ischemic white matter injury.

From Sound to Movement: Mapping the Neural Mechanisms of Auditory–Motor Entrainment and Synchronization

Background: Humans exhibit a remarkable ability to synchronize their actions with external auditory stimuli through a process called auditory–motor or rhythmic entrainment. Positive effects of rhythmic entrainment have been demonstrated in adults with neurological movement disorders, yet the neural substrates supporting the transformation of auditory input into timed rhythmic motor outputs are not fully understood. We aimed to systematically map and synthesize the research on the neural correlates of auditory–motor entrainment and synchronization. Methods: Following the PRISMA-ScR guidelines for scoping reviews, a systematic search was conducted across four databases (MEDLINE, Embase, PsycInfo, and Scopus) for articles published between 2013 and 2023. Results: From an initial return of 1430 records, 22 studies met the inclusion criteria and were synthesized based on the neuroimaging modality. There is converging evidence that auditory–motor synchronization engages bilateral cortical and subcortical networks, including the supplementary motor area, premotor cortex, ventrolateral prefrontal cortex, basal ganglia, and cerebellum. Specifically, the supplementary motor area and the basal ganglia are essential for beat-based timing and internally guided rhythmic movements, while the cerebellum plays an important role in tracking and processing complex rhythmic patterns and synchronizing to the external beat. Self-paced tapping is associated with additional activations in the prefrontal cortex and the basal ganglia, suggesting that tapping in the absence of auditory cues requires more neural resources. Lastly, existing studies indicate that movement rate and the type of music further modulate the EEG power in the alpha and beta frequency bands. Conclusions: These findings are discussed in the context of clinical implications and rhythm-based therapies.

Syntax and the brain: language evolution as the missing link(ing theory)?

This paper provides proof of concept that neurolinguistic research on human language syntax would benefit greatly by expanding its scope to include evolutionary considerations, as well as non-propositional functions of language, including naming/nicknaming and verbal aggression. In particular, an evolutionary approach can help circumvent the so-called granularity problem in studying the processing of syntax in the brain, that is, the apparent mismatch between the abstract postulates of syntax (e.g. Tense Phrase (TP), Determiner Phrase (DP), etc.) and the concrete units of neurobiology (neurons, axons, etc.). First, we decompose syntax into its evolutionary primitives, identifying one of the earliest stages as a simple, flat combination of just one verb and one noun. Next, we identify proxies ("living fossils") of such a stage in present-day languages, including compounds and small clauses, lacking at least some layers of structure, e.g. TPs and DPs. These proxies of ancestral language have been subjected to fMRI neuroimaging experiments. We discuss the finding that less hierarchical small clauses, in contrast to full sentences with TPs and DPs, show reduced activation in the left Broca's area (BA) 44 and the right basal ganglia, consistent with the hypothesis that more recent, more elaborate syntax requires more connectivity in the Broca's-basal ganglia network, whose neuronal density has been significantly enhanced in recent evolution, implicating mutations in FOXP2 and other genes. We also discuss the finding that the processing of ancestral verb-noun compounds, which are typically used for (derogatory) naming and nicknaming, shows enhanced activation in the right fusiform gyrus area (BA 37), the area that is implicated in the processing of metaphoricity and imageability, but also in naming and face recognition, opening up an intriguing possibility that the enhanced face recognition in humans was facilitated by the early emergence of a simple syntactic strategy for naming. The considerations in this paper are consistent with the hypothesis of a gradual gene-culture co-evolution of syntax and the brain, targeting cortico-striatal brain networks. It is also of note that a sound grounding in neurobiology of language should in turn inform syntactic theories themselves.

Magnetic resonance imaging quantitative assessment of corticospinal tract damage in basal ganglia infarction.

To retrospectively explore the role of magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) in analyzing the corticospinal tract injury in acute cerebral anterior circulation infarction in the basal ganglia region and the correlation between DTI parameters and neurological function scores, patients with acute cerebral infarction and stroke had undergone plain MRI and DTI sequence scanning were enrolled. Diffusion tensor tractography was used to perform 3-dimensional reconstruction of bilateral corticospinal tracts (CST). The image data were processed to obtain fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values, and the correlation between the DTI parameters and neurological function scores of National Institutes of Health Stroke Scale (NIHSS) was evaluated. A total of thirty-two patients with acute ischemic cerebral infarction were retrospectively enrolled, including 19 males and 13 females with a mean age 63.22 ± 7.78 years. The CST score was 0 in 2 (6.25%) patients, 1 in 9 (28.13%), 2 in 9 (28.13%), 3 in 7 (21.88%), and 4 in 5 (15.63%). The FA value significantly (P = .01) decreased (0.52 ± 0.03 vs 0.62 ± 0.04) on the ischemic side compared with that on the normal side. A significant (P < .05) difference was detected in the number of nerve fibers (223.3 ± 110.0 vs 246.7 ± 104.4) rather than in the ADC values (0.86 ± 0.06 vs 0.84 ± 0.06) between the ischemic and healthy sides. The FA and ADC values were not significantly (P > .05) different according to the CST scores 0, 1, 2, 3, or 4 between the ischemic and healthy sides. There was a significant (P < .05) negative correlation between the FA value on the infarcted side and the NIHSS score. In conclusion, with the DTI technology, varying degrees of damage to the corticospinal tract at the infarcted side can be detected and important clinical information can be provided for the diagnosis and prognosis of acute cerebral infarction by evaluating the degree of corticospinal tract injury.

Time to Treatment and Outcomes of Hemorrhagic Stroke, Comparing Patients Entering Surgery before and after 120 Minutes Upon Arrival at the Emergency Department Pattani Hospital

Background: The duration between a patient’s hospital arrival and the point at which they enter surgery for hemorrhagic stroke affects survival, length of stay, health care costs, and outcome (Glasgow Outcome Scale). Therefore, a study to explore the effects of time on these outcomes is warranted. Objective: To compare treatment outcomes of patients with hemorrhagic stroke having entered surgery before and after 120 minutes upon arrival at the emergency department. Materials and Methods: A therapeutic and interventional study with a retrospective observational cohort design at Pattani Hospital in patients with hemorrhagic stroke who received treatment between October 2018 and April 2023. A retrospective review of medical records, which collected clinical characteristics and the time to treatment. Glasgow Outcome Scale was evaluated at 72 hours, two weeks, one month, and date of hospital discharge. Length of stay, health care costs, and survival status at date of hospital discharge were analyzed. Comparative analysis was performed by Fisher’s exact probability test and t-test, and prognostic analysis was performed by risk ratio. Results: Of all the patients in the present study, 49 and 182 received treatment before and after 120 minutes, respectively, upon arrival at the emergency department. Clinical characteristics of gender, age, underlying conditions, regular medications, and level of consciousness were not significantly different between the two groups. Patients who entered surgery within 120 minutes of arrival had more occurrences of basal ganglia hemorrhage compared with those who received surgery thereafter. Furthermore, patients who received surgery within 120 minutes had a 11.4% increased chance of survival. The number needed to treat (NNT) hemorrhagic stroke patients with a time to treatment of under 120 minutes is 9. However, there was an associated increase in complications, health care cost, and length of stay. The Glasgow Outcome Scale improvement was greater only in the two-week follow-up period. These results were similar when subarachnoid hemorrhage and anticoagulating medication used were excluded. Conclusion: Patients with hemorrhagic stroke who receive early surgical treatment have lower mortality rates. Adequate provision of personnel and facilities for delivering prompt care should be made available. Measures should be taken to reduce the complications of patients who receive surgical treatment after 120 minutes upon arrival at the emergency department.

MELAS Presenting as Bilateral Symmetric Occipital and Temporal Cortices Lesions: A Case Report and Literature Review.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) is one of the most common maternally inherited mitochondrial diseases. The stroke-like episode affecting the cortical cortex is the hallmark of MELAS; however, it rarely presents as simultaneously bilateral symmetric cortices lesions. We reported a case of MELAS in a 46-year-old female patient with bilateral symmetric occipital and internal temporal cortices involvements on brain magnetic resonance imaging (MRI). A literature review of MELAS patients and a retrospective analysis were performed. She had a family history of diabetes. Although she denied a history of diabetes, elevated blood glucose was noted after admission, and diabetes was diagnosed. Laboratory examination revealed elevated lactate acid and creatine kinase levels in blood. Cranial computed tomography (CT) image demonstrated basal ganglia calcification, as well as subtle decreased attenuation in bilateral symmetric occipital and internal temporal cortices. Brain magnetic resonance imaging (MRI) demonstrated symmetric gyriform hyperintensity in bilateral occipital lobes and internal temporal lobes in both grey and white matter on fluid-attenuated inversion recovery (FLAIR) images with restricted diffusion on diffusion weighted images (DWI). A genetic test revealed a point mutation in the mtDNA(3243A > G) by blood examination. Literature review showed that there were 231 eligible patients with MELAS identified from 212 published papers. Symmetric cortical involvements were seen in 15 (6.5%) patients on brain MRI. MELAS should be considered as a potential diagnosis in the patients with bilateral symmetric stroke-like cortices lesions.

“Efficacy of Rehabilitation Exercises in Patients with Parkinson's Disease”

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease caused by a deficiency in the neurotransmitter dopamine in the basal ganglia. The gradual debilitating nature of PD makes it extremely difficult to function daily and interact with others. Rehabilitation has recently been suggested as an efficient and supplemental treatment for Parkinson's disease. Therefore, this study aimed to evaluate the efficacy of rehabilitation exercises for PD patients. Methods: This prospective study was conducted in the Department of Physical Medicine &amp; Rehabilitation, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from July'2022 to June'2023. In our study, we included 60 patients diagnosed with Parkinson’s disease based on clinical indication and proper investigation. Patients were divided into two groups – Group A (Patients who received rehabilitation therapy) &amp; Group B (Patients who received no intervention). Result: The MDS-UPDRS III scores were significantly lower in the rehabilitation group compared to the no -intervention group (P-value &lt;0.001). The rehabilitation group also performed significantly better in the M-PAS (p&lt;0.001). In terms of gait speed, the rehabilitation group showed higher comfort and faster gait speeds than the no-intervention group. The current study revealed that the majority of patients in the rehabilitation group (43%) mildly improved, with the maximum number (57%) of patients in the group experiencing an efficacy duration of three months. Conclusion: Our findings show that MS, walking problems, balance, and postural control dysfunction can all be improved in PD patients with 4 weeks of rehabilitation treatment therapy, compared to patients who did not undergo rehabilitation treatment.

Molecular Modeling and In Vitro Functional Analysis of the RGS12 PDZ Domain Variant Associated with High-Penetrance Familial Bipolar Disorder.

Bipolar disorder's etiology involves genetics, environmental factors, and gene-environment interactions, underlying its heterogeneous nature and treatment complexity. In 2020, Forstner and colleagues catalogued 378 sequence variants co-segregating with familial bipolar disorder. A notable candidate was an R59Q missense mutation in the PDZ (PSD-95/Dlg1/ZO-1) domain of RGS12. We previously demonstrated that RGS12 loss removes negative regulation on the kappa opioid receptor, disrupting basal ganglia dopamine homeostasis and dampening responses to dopamine-eliciting psychostimulants. Here, we investigated the R59Q variation in the context of potential PDZ domain functional alterations. We first validated a new target for the wildtype RGS12 PDZ domain-the SAPAP3 C-terminus-by molecular docking, surface plasmon resonance (SPR), and co-immunoprecipitation. While initial molecular dynamics (MD) studies predicted negligible effects of the R59Q variation on ligand binding, SPR showed a significant reduction in binding affinity for the three peptide targets tested. AlphaFold2-generated models predicted a modest reduction in protein-peptide interactions, which is consistent with the reduced binding affinity observed by SPR, suggesting that the substituted glutamine side chain may weaken the affinity of RGS12 for its in vivo binding targets, likely through allosteric changes. This difference may adversely affect the CNS signaling related to dynorphin and dopamine in individuals with this R59Q variation, potentially impacting bipolar disorder pathophysiology.

Surgical Management of large Basal Ganglia Hemorrhage: A Bi-institutional Experience

Background and Aim: Numerous prognostic factors for spontaneous intracerebral hemorrhage have been advocated; however, only a few studies have specifically addressed basal ganglia bleed prognosis and management. Regarding basal ganglia bleeding, this study determines the predictors of functional outcomes and predictors of severe disability or death in surgically treated cases. Methods and Materials/Patients: This was a one-time follow-up study of 271 spontaneous basal ganglia bleed patients undergoing surgical intervention over 3 years. An electronic hospital database was used to collect data regarding clinical and radiological parameters and functional outcomes according to the glasgow outcome scale (GOS) three months after the hemorrhage. Results: We analyzed 271 cases, with a mean age of 50.8±13.57 years. At the end of 3 months, 53.87% of patients had favorable outcomes (GOS=4, 5), 9.59% had poor outcomes (GOS=2, 3) and mortality was 37.75% (GOS=1) at the end of 3 months. Independent predictors of poor outcome were age (odd ratio [OR]=1.81, 95% CI, 1.09%, 3.02%, GCS OR=6.93, 95% CI, 1.52%, 31.51%), hematoma volume more than 60 mL (OR=12.73, 95% CI, 3.29%, 49.23%, midline shift (OR=2.78, 95% CI, 1.64%, 4.73%), the left side of bleed (OR=1.81, 95% CI, 1.11%, 2.94%), intraventricular hemorrhage (OR=2.94, 95% CI, 1.72%, 5.02%) and intraventricular hemorrhage associated with hydrocephalus (OR=22.30, 95% CI, 6.35%, 78.27%). There was a significant association between these factors and poor outcomes (P&lt;0.05). Conclusion: Almost half of the patients with large basal ganglia hemorrhage survivors were severely disabled or died within three months after the event. Basal ganglia hemorrhage was associated with severe disability or death among patients aged over 60 years with left-side bleeding, low GCS on admission, preoperative computed tomography scan showing midline shift of more than 5mm with the presence of intraventricular hemorrhage or associated hydrocephalus and a large hematoma volume.

Impairment of Neuronal Activity in the Dorsolateral Prefrontal Cortex Occurs Early in Parkinsonism.

Parkinson's disease (PD) is often characterized by altered rates and patterns of neuronal activity in the sensorimotor regions of the basal ganglia thalamocortical network. Little is known, however, regarding how neuronal activity in the executive control network of the brain changes in the parkinsonian condition. Investigate the impact of parkinsonism on neuronal activity in the dorsolateral prefrontal cortex (DLPFC), a key region in executive control, during a go/nogo reaching task. Using a within-subject design, single and multi-unit neuronal activity was recorded in the DLPFC of a nonhuman primate before and after the induction of mild parkinsonism using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coincident with development of mild parkinsonian motor signs, there was a marked reduction in the percentage of DLPFC cells with significant task-related firing rate modulation during go and nogo conditions. These results suggest that DLPFC dysfunction may occur early in parkinsonism and contribute to cognitive impairments and disrupted executive function often observed in PD patients.

Basal ganglia theta power indexes trait anxiety in people with Parkinson's disease.

Neuropsychiatric symptoms are common and disabling in Parkinson's disease (PD), with troublesome anxiety occurring in one-third of patients. Management of anxiety in PD is challenging, hampered by insufficient insight into underlying mechanisms, lack of objective anxiety measurements, and largely ineffective treatments. In this study, we assessed the intracranial neurophysiological correlates of anxiety in PD patients treated with deep brain stimulation (DBS) in the laboratory and at home. We hypothesized that low-frequency (theta-alpha) activity would be associated with anxiety. We recorded local field potentials (LFP) from the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi) DBS implants in three PD cohorts: 1) patients with recordings (STN) performed in hospital at rest via perioperatively externalized leads, without active stimulation, both ON or OFF dopaminergic medication; 2) patients with recordings (STN or GPi) performed at home while resting, via a chronically implanted commercially available sensing-enabled neurostimulator (Medtronic PerceptTM device), ON dopaminergic medication, with stimulation both on or off; 3) patients with recordings performed at home while engaging in a behavioral task via STN and GPi leads and electrocorticography paddles over premotor cortex connected to an investigational sensing-enabled neurostimulator, ON dopaminergic medication, with stimulation both on or off. Trait anxiety was measured with validated clinical scales in all participants, and state anxiety was measured with momentary assessment scales at multiple time points in the two at-home cohorts. Power in theta (4-8 Hz) and alpha (8-12 Hz) ranges were extracted from the LFP recordings, and their relation with anxiety ratings was assessed using linear mixed-effects models. In total, 33 PD patients (59 hemispheres) were included. Across three independent cohorts, with stimulation off, basal ganglia theta power was positively related to trait anxiety (all p<0.05). Also in a naturalistic setting, with individuals at home at rest with stimulation and medication ON, basal ganglia theta power was positively related to trait anxiety (p<0.05). This relationship held regardless of the hemisphere and DBS target. There was no correlation between trait anxiety and premotor cortical theta-alpha power. There was no within-patient association between basal ganglia theta-alpha power and state anxiety. We showed that basal ganglia theta activity indexes trait anxiety in PD. Our data suggest that theta could be a possible physiomarker of neuropsychiatric symptoms and specifically of anxiety in PD, potentially suitable for guiding advanced DBS treatment tailored to the individual patient's needs, including non-motor symptoms.

Decoding reveals the neural representation of perceived and imagined musical sounds.

Vividly imagining a song or a melody is a skill that many people accomplish with relatively little effort. However, we are only beginning to understand how the brain represents, holds, and manipulates these musical "thoughts." Here, we decoded perceived and imagined melodies from magnetoencephalography (MEG) brain data (N = 71) to characterize their neural representation. We found that, during perception, auditory regions represent the sensory properties of individual sounds. In contrast, a widespread network including fronto-parietal cortex, hippocampus, basal nuclei, and sensorimotor regions hold the melody as an abstract unit during both perception and imagination. Furthermore, the mental manipulation of a melody systematically changes its neural representation, reflecting volitional control of auditory images. Our work sheds light on the nature and dynamics of auditory representations, informing future research on neural decoding of auditory imagination.

Clinical characteristics of children with MT-TK gene m.8344A>G variation

Objective: To summarize the clinical characteristics of children carrying the m.8344A>G variant of MT-TK gene. Methods: A case series study was conducted to retrospectively collect data of 22 children with mitochondrial disease caused by MT-TK gene m.8344A>G variation who were treated at the Department of Neurology of Beijing Children's Hospital of Capital Medical University from January 2012 to January 2024. Their clinical data, laboratory tests, muscle pathology, genetic testing, and the follow-up results were analyzed. Pearson correlation analysis was used for correlation analysis. Results: Among the 22 children, there were 13 boys and 9 girls. The age of onset was 5.00 (2.75, 9.00) years. Fifteen children had myoclonic epilepsy with ragged-red fibers (MERRF), 3 had Leigh syndrome (LS), and 4 had LS-MERRF overlap syndrome (LS-MERRF). Myoclonus presented and worsened progressively in all 15 MERRF children, with 10 as the initial symptom and 5 developing progressively during the disease course. Myoclonus was predominantly focal, worsening with fine motor tasks or stress. Electroencephalogram monitoring in the 15 MERRF children revealed myoclonic seizures in 10 children, with 6 classified as myoclonic epilepsy, and 4 as subcortical myoclonus. Two children had generalized myoclonic seizures, and 1 each had absence seizures and generalized seizures. Twelve children had cerebellar ataxia, 10 children exhibited exercise intolerance, and 8 children had muscle weakness. Magnetic resonance imaging (MRI) revealed periventricular white matter involvement in 1 child and bilateral hippocampal involvement in 1 child, likely due to frequent seizures. All 3 children with LS exhibited developmental regressions, accompanied with 2 symptoms include cerebellar ataxia, muscle weakness, and dysphagia. The clinical manifestations of 4 LS-MERRF overlap children presented with combined features of MERRF and LS. Cranial MRI in the 7 LS and LS-MERRF children showed brainstem involvement (all affecting the midbrain) in 6 children and basal ganglia involvement in 4 children. Among the 22 children, 12 had m.8344A>G variant levels >90%, 3 had >80%-90%, 4 had >70%-80%, and 3 had >60%-70%. Higher variant level correlated with the LS phenotype and earlier onset age (r=0.47, -0.50; P=0.018 and 0.029, respectively). Sanger sequencing in 19 mothers revealed m.8344A>G variations in 18, with 4 showing exercise intolerance. Follow-up of 13 children on antimyoclonic treatment showed>75% reduction in seizures with levetiracetam monotherapy in 2 children, with combination therapy required in others. Most achieved >50% seizures reduction within 2 years, but the effectiveness declined with disease progression. Conclusions: The m.8344A>G variant is rare, with MERRF being the most common phenotype, while LS and LS-MERRF are less common. Children with higher ratio of the m.8344A>G variant are more likely to present LS phenotype. Myoclonus, primarily focal, is a key feature, with levetiracetam as the first-line treatment and benzodiazepines recommended for refractory cases.

Phenotype of patients with late diagnosis of 22q11 deletion: a review and retrospective study.

Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, typically presenting in neonates with congenital cardiac anomalies, hypocalcaemia and thymic hypoplasia. Some patients are diagnosed later in adolescence and adulthood, with less known about the clinical phenotype of these patients. To summarise key clinical features in cases of 22q11DS diagnosed during adolescence and adulthood. This is a retrospective cohort study of 22q11DS patients diagnosed after 13 years of age over 2010-2021, with a literature review of published cases highlighting other late diagnoses. The study was performed in a large multicentre tertiary health network in Melbourne, Australia. Patients diagnosed with 22q11DS after the age of 13 years were included in the study. Main outcome measures were key clinical features in cases of late diagnosis of 22q11DS. A literature search yielded 53 published case reports and one cohort study for review (62 subjects). Additionally, 10 cases of late diagnosis of 22q11DS were identified through a retrospective electronic medical chart review. Findings suggest that intellectual disability and learning difficulties, hypocalcaemia with hypoparathyroidism and facial dysmorphism remain key features in patients with a late diagnosis of 22q11DS, with hypocalcaemia being the most common presentation leading to diagnosis. Patients diagnosed in adulthood may lack classical clinical features of congenital cardiac anomalies and thymic hypoplasia. Immunological consequences of 22q11DS are also an important late-onset consideration. Atypical features may include basal ganglia calcification. Chromosome 22q11DS has diverse clinical features and a highly variable phenotype, likely contributing to underdiagnosis and later diagnoses.

Biophysical contrast sources for magnetic susceptibility and R2* mapping: A combined 7 Tesla, mass spectrometry and electron paramagnetic resonance study

Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R2* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26–91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R2* and QSM were calculated. We found that R2* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R2*. This study demonstrated the quantitative correlations between R2*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation.

Choroid Plexus Volume in Rural Chinese Older Adults: Distribution and Association With Cardiovascular Risk Factors and Cerebral Small Vessel Disease.

The choroid plexus (CP) is involved in neurodegenerative diseases. However, the association of CP with cardiovascular risk factors and cerebral small vessel disease in older adults remains unclear. This population-based study included 1263 participants (60 years and older) from the MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China) substudy (2018-2020), of which 111 individuals completed diffusion tensor imaging examination. CP volume was automatically segmented. White matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds, and lacunes were assessed following the Standards for Reporting Vascular Changes on Neuroimaging 1. Peak width of skeletonized mean diffusivity and free water were derived from diffusion tensor imaging images. We used linear regression models to evaluate the association between CP volume and cardiovascular risk factors, WMH volumes, and diffusion tensor imaging metrics, and logistic regression models to examine the association between CP volume and EPVS, cerebral microbleeds, and lacunes. The CP volume increased with age (P<0.001). Men (β coefficient=0.47 [95% CI, 0.29-0.64]) and participants with diabetes (β coefficient=0.16 [95% CI, 0.01-0.31]) had larger CP volumes than women and individuals without diabetes, respectively (P<0.05). Greater CP volume was significantly associated with larger total and periventricular WMH volumes and moderate to severe EPVS in basal ganglia (P<0.05) but not with deep WMHs, EPVS in centrum semiovale, lacunes, or cerebral microbleeds. In the diffusion tensor imaging subsample, enlarged CP was significantly associated with higher peak width of skeletonized mean diffusivity and free water of periventricular and deep white matter (P<0.05). An enlarged CP is associated with larger global and periventricular WMH volume and higher likelihoods of EPVS in basal ganglia and impaired white matter integrity, suggesting that an enlarged CP may represent a precursor of cerebral small vessel disease.

Multimodal gradients of basal forebrain connectivity across the neocortex

Cortical cholinergic projections originate from subregions of the basal forebrain (BF). To examine its organization in humans, we computed multimodal gradients of BF connectivity by combining 7 T diffusion and resting state functional MRI. Moving from anteromedial to posterolateral BF, we observe reduced tethering between structural and functional connectivity gradients, with the lowest tethering in the nucleus basalis of Meynert. In the neocortex, this gradient is expressed by progressively reduced tethering from unimodal sensory to transmodal cortex, with the lowest tethering in the midcingulo-insular network, and is also spatially correlated with the molecular concentration of VAChT, measured by [18F]fluoroethoxy-benzovesamicol (FEOBV) PET. In mice, viral tracing of BF cholinergic projections and [18F]FEOBV PET confirm a gradient of axonal arborization. Altogether, our findings reveal that BF cholinergic neurons vary in their branch complexity, with certain subpopulations exhibiting greater modularity and others greater diffusivity in the functional integration with their cortical targets.

Anti-dopamine receptor 2 antibody encephalitis in adults: a case report

BackgroundAnti-dopamine receptor 2 (D2R) antibody encephalitis (D2R encephalitis) is a subtype of autoimmune encephalitis (AE). Lesions in affected patients primarily involve the basal ganglia, resulting in a range of psychiatric and movement disorders. A majority of cases reported to date have impacted children or adolescents, whereas we here describe a case of adult-onset D2R encephalitis.Case presentationA 30-year-old female patient affected by insomnia, recent memory impairment, bradykinesia, decreased responsivity, increased muscular tone of the extremities, and involuntary shaking of the right limb. Magnetic resonance imaging (MRI) of the basal ganglia did not reveal any notable findings, and both serum and cerebrospinal fluid were positive for antibodies specific for D2R. D2R encephalitis was diagnosed following the exclusion of other diseases. The patient’s symptoms improved significantly with immunotherapeutic treatment, and she recovered fully over a 6-month follow-up period.ConclusionsD2R is a new form of AE that can develop in adults and can be effectively treated via immunotherapy.

Reaching and stepping respond differently to medication and cueing in Parkinson’s disease

The basal ganglia contribute to internal timekeeping, and dopaminergic medication has been observed to moderate timing deficits associated with Parkinson’s Disease (PD) during single joint movements. However, it is unclear whether similar effects can be observed in multi-joint movements. Twenty-five people with PD and twelve healthy peers performed repetitive reaching and stepping-in-place tasks with and without auditory cues at their self-selected maximal cadence. The PD group was measured ON and OFF medication. Reduced cadence error was found for both groups and tasks when cued, and ON PD exhibited decreased cadence compared to OFF PD. Overall timing variability was no different from controls, but differences were found in estimates of clock and motor variance using the Wing-Kristofferson model of interval timing. A medication and cueing interaction during the reaching task produced increased clock variance in uncued, ON PD. During the stepping task, clock and motor variance of the PD group were unaffected by cues, in contrast to the control group. Serial lag-one correlation was reduced in both groups for cued reaching, but was unaffected by cueing or medication in the PD group when stepping-in-place. These findings suggest that overall timing variability may not capture timing deficits in PD.