Differentiating Parkinson's disease (PD) from multiple system atrophy (MSA), especially the parkinsonian variant (MSA-P), remains challenging. Diagnostic inaccuracy contributes to suboptimal clinical outcomes. Therefore, clinically accessible biomarkers are warranted to support differential diagnosis in routine practice. The aim was to develop a multimodal imaging model combining T1-weighted (T1W) volumetry, quantitative susceptibility mapping, and neuromelanin (NM) magnetic resonance imaging (MRI) for distinguishing PD from MSA subtypes. A total of 387 participants were analyzed, comprising 141 with PD, 86 with MSA (51 cerebellar variant [MSA-C], 35 MSA-P), and 160 age- and sex-matched healthy controls. Group comparisons were performed for brain volumetry, susceptibility in deep gray matter, spatial heterogeneity of putaminal iron, NM content in the substantia nigra pars compacta (SNpc), and locus coeruleus (LC). Classification was conducted using a Gaussian Naïve Bayes classifier with fivefold cross-validation. Compared with PD and controls, (1) corrected volumes of the brainstem, bilateral cerebellar white matter, and gray matter were significantly reduced in MSA-C and MSA-P, (2) susceptibility was increased in the bilateral putamen in MSA-P and in the bilateral dentate nucleus in MSA-C, and (3) NM contrast was reduced in the bilateral SNpc in MSA-P and in the bilateral LC in MSA-C. The multimodal models yielded area under the curve values of 0.967 (PD vs. MSA-C), 0.884 (PD vs. MSA-P), and 0.879 (PD vs. MSA-P vs. MSA-C). Integration of volumetric, susceptibility, and NM measures with machine learning enables accurate differentiation of PD from MSA subtypes, which provides a potential means to differentiate parkinsonism in clinical practice. © 2025 International Parkinson and Movement Disorder Society.

ABSTRACTFahr's disease is a rare idiopathic neurodegenerative disorder characterized by symmetrical calcifications in the basal ganglia and cerebellar dentate nuclei. Although it may present with diverse neuropsychiatric symptoms, a significant number of cases remain asymptomatic and are only identified incidentally through neuroimaging performed for unrelated medical issues. We present a case of a 43‐year‐old woman who was brought to the emergency department following a high‐impact motor vehicle accident. Brain CT, performed as part of trauma assessment, revealed extensive findings consistent with severe traumatic brain injury, including cerebral edema, contusions, cisternal compression, and skull base fractures. Incidentally, bilateral symmetrical calcifications were noted in the basal ganglia and dentate nuclei—findings unrelated to acute trauma. Subsequent metabolic and endocrine evaluation ruled out secondary causes, confirming a diagnosis of Fahr's disease. This case highlights the diagnostic importance of incidental neuroimaging findings in the acute trauma setting. Although often overshadowed by life‐threatening injuries, such calcifications warrant further evaluation to distinguish Fahr's disease from secondary calcification due to metabolic or infectious etiologies. Recognizing Fahr's disease is essential, as it carries implications for long‐term neurological surveillance, genetic counseling, and family screening. It is worth mentioning that there is ongoing controversy regarding the most appropriate terminology for this condition, including terms such as Primary Familial Brain Calcification (PFBC) and Primary Bilateral Brain Calcification (PBBC), each of which has its own advantages and limitations. In conclusion, incidental detection of Fahr's disease during emergency neuroimaging emphasizes the need for clinical vigilance and a thorough diagnostic approach, even in critical care settings.

Congenital defects of the central nervous system (CNS) are one of the most common causes of death and disability in newborns. Therefore, it is extremely important to assess the development of the fetal CNS in the intrauterine period in time to identify any changes in its development and give appropriate advice to parents on pregnancy support, offer options for fetal therapy and type of delivery, as well as postpartum treatment and prognosis. The aim of our research was to determine the morphological features of the neural complexes of the human fetal hindbrain at 17-18 weeks of fetal development, the size and area of the cranial nerve nuclei in the region of the pons and the cerebellar nuclei. In a research study we used biological material obtained from the Vinnytsia Maternity Hospital after a termination of pregnancy in a healthy women for medical reasons, due to fetal chromosomal abnormalities not related to CNS developmental defects. The material for anatomical and histological examination were human fetuses with a gestation period of 17-18 weeks. The fetus`s weighed 250.8±14.5 g, and the parieto-coccygeal length were 163.3±8.4 mm. The researched tissue samples of hindbrain were fixed in a 10 % solution of neutral formalin, and then sections of 8-9 μm thick celluloid blocks were prepared for further histological examination. The preparations were stained with hematoxylin-eosin, toluidine blue according to the Nissl modification. For the statistical analysis of digital data Microsoft Excel 2016 and Statistica 6.1 were used. The normality of the distribution was assessed using the Shapiro-Wilk test, histograms were constructed for data visualization, and the standard deviation and variance of the samples were calculated. Histograms were constructed to visualize the data, the standard deviation and sample variance were calculated. The microscopic examination of the cerebellum revealed the outer granular, molecular, inner granular, intermediate, and ventricular layers. The presence of cerebellar nuclei, which were located in the intermediate layer, was also established. On the cerebellar section, the dentate nucleus was visualized as a thin curved line with its convex side directed laterally and dorsally. The abducens nucleus is located ventrally to the dorsal surface of the pons, laterally to the medial longitudinal fascicle. The facial motor nucleus is located medially to the abducens nucleus and has an elongated shape with indistinct borders. The trigeminal motor nucleus is laterally to the facial nucleus, has indistinct borders, a rounded shape, and consists of neurons at different maturation stages. In the lateral part of the pons is the vestibular nucleus, which has an irregular oval shape; the borders of the nucleus are indistinct. Also, below the vestibular nucleus, laterally, there is a cochlear nucleus, without clear contours, oval elongated shape. Thus, іn the posterior part of the brain at 17-18 weeks of fetal development, the nuclei of the abducens, trigeminal, facial, and vestibulocochlear nerves located in the pons. Dentate, globose, emboliform and fastigial nuclei also were found in the cerebellum.

Bilateral Dentate Nucleus Involvement in a Case of Enteric Fever-Triggered Minor Encephalopathy with Reversible Splenial Lesions.

Deep learning-based 3D reconstruction of dentate nuclei in Friedreich’s ataxia from T2*weighted MR images

A number of studies have suggested that the cerebellum has cognitive functions; however, the underlying neuronal mechanisms remain unclear. In this study, we demonstrated that sustained visual signals in the cerebellar dentate nucleus represent the visuomotor associative information. We recorded neuronal activity from the dentate nucleus when monkeys performed a learning task involving the association between visual objects and saccade directions. We found that sustained visual activity was greater during learning than during memory retrieval. This enhancement disappeared under the uncertain reward condition, in which the monkeys did not engage in learning behavior. Furthermore, sustained visual signals changed the response to visual objects depending on the associated saccade direction. This direction selectivity was positively correlated with modulation during learning. These results suggest that sustained visual signals in the dentate nucleus reflect learning related motivation and drive learning by increasing the strength of discrimination among visual objects.

Introduction: Post-traumatic cerebellar syndromes and memory disorders are highly disabling and refractory to conventional therapy. Deep brain stimulation (DBS) has shown therapeutic benefit in movement disorders, but its application in cerebellar and limbic circuits remains experimental. We report a pioneering case combining bilateral ventral intermediate nucleus (VIM) and Dentate nucleus (DN) stimulation for severe cerebellar ataxia and fornix stimulation for anterograde amnesia secondary to traumatic brain injury (TBI), supported by intraoperative electrophysiology.Clinical description: A 32-year-old male with severe TBI developed refractory pancerebellar syndrome (intention tremor, dysmetria, gait ataxia) and profound anterograde amnesia. MRI showed cerebellar and brainstem atrophy, hippocampal shrinkage, and thalamic involvement. DBS was proposed targeting the dentate nucleus bilaterally and the fornix. Microelectrode recordings in the VIM revealed multiple tremor cells with rhythmic bursting and low-frequency local field potentials (LFPs), confirming pathological oscillatory activity. Postoperative programming achieved marked reduction in tremor amplitude and improved motor coordination. Memory deficits persisted but showed mild improvement in short-term recall.Discussion: VIM trajectory was deliberately planned at a deeper level to engage the dendrorubrothalamic tract (DRETT) 3, a major cerebellothalamic pathway implicated in tremor generation. This approach aimed to modulate pathological oscillatory activity transmitted from the dentate nucleus through the red nucleus to the thalamus, optimizing tremor control. Dentate stimulation has shown variable success in ataxia, while fornix stimulation is primarily described in Alzheimer’s disease. Our findings suggest potential synergy, though cognitive recovery remains limited. Literature on combined approaches is scarce, underscoring the need for controlled trials.Conclusions: This case demonstrates the feasibility of combining cerebellar and limbic DBS targets for complex post-traumatic syndromes. DBS targeting DN, DRETT and fornix may offer benefit in refractory cerebellar ataxia with coexisting memory impairment after TBI. Intraoperative microrecording and LFP analysis provide valuable biomarkers for optimizing targeting and programming.

Spinocerebellar ataxia (SCA) is a genetically heterogeneous neurodegenerative disorder with no effective treatments. Although noninvasive cerebellar neuromodulation has shown positive outcomes, invasive approaches such as deep brain stimulation (DBS) remain inadequately evaluated in SCA. This study assessed the treatment outcomes of DBS targeting the cerebellar dentate nucleus (DN) in SCA patients over a 6-month follow-up. Six patients with heterogeneous SCA underwent bilateral DN-DBS. The stimulation parameters were programmed iteratively, and ataxia symptoms were evaluated at predefined intervals using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Individualized appropriate stimulation parameters (current, frequency, and pulse width) were established. At the 6-month follow-up, the SARA scores decreased by 43% (P = 0.014) and the ICARS scores by 51% (P = 0.013) compared with baseline. These findings provide evidence for the potential therapeutic efficacy of DN-DBS in SCA and offer preliminary insights for stimulation parameter programming. © 2025 International Parkinson and Movement Disorder Society.

The cerebellum contributes to associative learning, yet how cortical and nuclear populations interact during memory formation remains unclear. We recorded single neurons from Purkinje cells (PCs) in Crus I/II and from the dentate nucleus (DN) in monkeys learning a visuomotor association. Both populations encoded the association in a temporally distributed manner spanning stimulus onset to movement. Once learning was consolidated, DN population activity preceded that of PCs, suggesting a progressive transfer of information from the cerebellar cortex to the nuclei, where long-term memory traces are stabilized. Spike-time analyses revealed that temporal regularity and bursts provide coding dimensions independent of firing rate and dynamically modulated across learning. These temporal features likely facilitate plasticity during acquisition and stabilize network dynamics after consolidation. Together, the results identify the dentate nucleus as an active site of memory consolidation and highlight distributed, ensemble-level mechanisms underlying cerebellar learning and predictive control.

The cerebellum is crucial for predictive motor control and learning, but growing evidence suggests that it also generates forward models for nonmotor functions. Previous studies have reported periodic neuronal activity in the cerebellar dentate nucleus when animals predicted the timing of regularly presented visual stimuli. Since the dentate nucleus is an output structure, this activity likely reflects computations in the cerebellar cortex. Considering that Purkinje cells (PCs), the sole output of the cerebellar cortex, are more numerous than cerebellar nuclear neurons and that nuclear neurons also receive input from mossy and climbing fibers, information integration likely occurs within the cerebellar nuclei. To explore this, we recorded PC activity in the cerebellar crus lobules of three male monkeys trained to detect the omission of periodically flashing visual stimuli and compared it with dentate nucleus data. PCs showed gradually increasing periodic simple spike activity, with amplitudes proportional to the interstimulus intervals. As a population, PC signals slightly preceded those of dentate nucleus neurons and were more temporally variable. However, the individual dentate neuron activity was 84% explained by a linear sum of signals from a small subset of PCs. These results suggest that the main components of cerebellar output signals for temporal prediction may originate from the cerebellar cortex and are integrated within the deep nuclei before being sent to other brain regions. Furthermore, changes in complex spike activity were observed in more than half of the PCs, suggesting that synaptic plasticity in the cerebellar cortex may contribute to modulating these signals.

Introduction: Friedreich’s ataxia (FA) is an autosomal recessive neurodegenerative disorder caused by variants in the frataxin ( FXN) gene, leading to mitochondrial dysfunction and impaired energy metabolism. Cardiomyopathy is the leading cause of death in FA and represents a critical therapeutic target alongside progressive neurological decline. Hypothesis: AAV-mediated gene replacement therapy can safely restore FXN expression in disease-relevant tissues and modify the course of FA. Approach: A gene therapy candidate (SGT-212) utilizing an AAVhu68 capsid and a ubiquitous promoter to express human FXN was developed. SGT-212 was administered using a dual route of administration via intravenous (IV) and intraparenchymal dentate nucleus (IDN) infusions. Cardiac and neurologic efficacy was evaluated in conditional Fxn knockout mouse models (cKO and nKO, respectively). Long-term safety and biodistribution were assessed in non-human primates (NHPs). Results: In Fxn cKO mice, a single IV dose led to dose-dependent improvements in cardiac function (assessed by echocardiography), histopathology, and survival. FXN protein levels and the number of FXN+ cardiomyocytes increased in a dose-dependent manner. In Fxn nKO mice, a single IV administration improved sensorimotor function (Neuroscore, RotaRod), extended lifespan, and restored FXN expression in dorsal root ganglia. In NHPs, the gene therapy was administered via dual IV/IDN routes and monitored for 12 months. SGT-212 treatment was well tolerated across dose levels with no adverse findings. Robust expression of FXN was observed in key target tissues, including myocardium, DRG, and dentate nuclei. Conclusions: These nonclinical studies demonstrate that a one-time administration of SGT-212 can restore FXN expression in disease-relevant tissues, improve cardiac and neurologic phenotypes in mouse models, and is well tolerated in NHPs. These findings support advancement to a Phase 1b clinical trial using combined IV/IDN administration.

PET is the modality of choice for studying the biochemistry and physiology of the human brain invivo, although its low spatial resolution, attributable to inherent physical and technical constraints, has limited its ability to resolve small cerebral structures. Here, we report PET images of the human brain obtained at a volumetric resolution of nearly 2 µL. Methods: A dedicated ultra-high-resolution (UHR) PET scanner featuring 1.2-mm true pixelated detectors was developed to achieve microvolumetric spatial resolution. A partially assembled UHR PET scanner with an axial field of view of 143 mm was used to obtain 18F-FDG PET images of the human brain. Patients who had a clinical PET/CT scan subsequently underwent UHR PET on completion of their medical examination. UHR PET images were reconstructed using a 3-dimensional ordered-subset expectation maximization iterative algorithm with analytic coincidence function modeling. Reconstructed images were normalized to the Montreal Neurological Institute 152 brain template and analyzed using atlases for region identification. Relative SUVs to the cerebellum were extracted for selected small brain structures. Results: All major brain regions were easily identifiable in UHR PET images, including details of the primary motor and somatosensory cortices, caudate nucleus, putamen, thalamus, inferior colliculi, and dentate nuclei. Notably, regions rarely seen so distinctly with 18F-FDG PET, such as the subthalamic areas and brainstem nuclei, were successfully resolved, suggesting that UHR PET has the potential to provide enhanced quantification of these tiny cerebral structures. This was further confirmed by higher SUV ratios in the UHR PET images compared with the PET/CT images. The UHR PET image of 1 patient revealed hypermetabolic foci in the cerebellum that were not discernible on the PET/CT and MR images. Conclusion: UHR PET images of the human brain at nearly 2-µL volumetric spatial resolution were obtained. Previously indistinguishable, small, highly relevant regions of the brain were resolved, paving the way for more accurate and detailed studies with the potential for greater insight in neuropsychiatry, neurooncology, and neurodegenerative diseases.

The atypical Parkinsonian disorder progressive supranuclear palsy (PSP) forms a diagnostic challenge, resulting in frequent misdiagnosis and delay in treatment. Although structural MRI can detect PSP signs at more advanced stages, emerging diagnostic tools such as tau-PET and quantitative susceptibility mapping (QSM) may allow for earlier detection. This exploratory study aimed to investigate differences in QSM data of patients with PSP and healthy controls (HCs) and for the first time assess possible correlations between QSM and tau-PET data in patients with PSP to explore the relationship between tau aggregation and iron susceptibility. We retrospectively investigated differences in susceptibility values of brain structures, as assessed by QSM, between 11 HCs and 31 patients with PSP [Richardson's syndrome (PSP-RS): n = 14; other subtypes (PSP-nonRS): n = 17]. Additionally, we examined co-registered [18F]PI-2620PET and QSM data in the 31 patients with PSP to explore the relationship between tau accumulation and susceptibility changes. Compared to HCs, patients with PSP showed higher QSM values in left nucleus caudate (p = 0.04) and bilateral dentate nucleus (p = 0.04, p = 0.01). Patients with the subtype PSP-RS showed higher QSM values than HCs in left dentate nucleus (p = 0.02). The association between the patients' QSM and tau-PET data showed a significant positive correlation. These results suggest distinct patterns of regional iron accumulation in patients with PSP and its subtypes and support an association between iron and tau pathology. The data encourage further investigation in longitudinal studies and validation in larger cohorts to examine the value of QSM as a possible diagnostic biomarker.

Abstract Disclosure: L.N. Dhana: None. T.A. Nguyen: None. S. Badour: None. Introduction:Pseudohypoparathyroidism (PHP)is a rare, inherited disorder characterized by resistance toparathyroid hormone (PTH)at its target organs. Although it shares features withhypoparathyroidism, including hypocalcemia and hyperphosphatemia, a key distinction is thatserum PTH levels are elevated rather than suppressed, as seen in true hypoparathyroidism. PHPis divided into two main types: type 1 and type 2, with type 1 further subclassified into 1a, 1b,and 1c based on genetic and clinical factors.Case Presentation:The patient is a 28-year-old male with a known diagnosis of PHP1a. His medical history includeshypothyroidism due to TSH resistance, Albright hereditary osteodystrophy, and Fahr syndrome.On physical examination, he exhibits obesity, a round face, short stature, poor dentition, andbrachydactyly of the fourth digits bilaterally. Imaging reveals long-standing foreshortening of theright fourth metacarpal and a small sessile osteochondroma in the medial metaphyseal cortex ofthe left proximal tibia. A CT head scan shows symmetric calcification in the bilateral basalganglia and dentate nuclei, as well as early calcification in the subcortical white matter of theright frontal lobe. Additionally, there is diffuse thickening of the calvarium and skull base,consistent with Fahr syndrome.The patient was admitted to the Medical Intensive Care Unit for hypoxia and respiratory failure.During his hospitalization, the team inadvertently omitted his outpatient regimen of calciumcarbonate 500 mg daily. Upon admission, his calcium level was normal (8.6mg/dL, referencerange (RR)8.4–10.2 mg/dL),albumin was 3.7 g/dL, and ionized calcium was 1.06 mmol/L (RR1.05-1.30 mmol/L).Magnesium was normal at 2.0 mg/dL (RR1.5–2.8 mg/dL),but phosphoruswas elevated at 5.4 mg/dL (RR2.7–4.5 mg/dL).Vitamin D levels were insufficient at 23 ng/mL(RR20–120 ng/mL).Over the next several days, off calcium supplementation, his calcium levels gradually declined,reaching a nadir of 7.5 mg/dL with an elevated PTH level of 230 pg/mL (normalrange 12–88pg/mL).Calcium supplementation was initiated at 1000 mg twice daily on day six of hishospitalization. However, his calcium levels continued to drop, reaching 6.8 mg/dL (ionizedcalcium 0.81 mmol/L, RR 1.01–1.50 mmol/L)the following day, before gradually returning tonormal. The patient was ultimately discharged on his regular calcium regimen of 500 mg daily. Conclusion: This case highlights that, unlike patients with classic hypoparathyroidism, those withpseudohypoparathyroidism can tolerate a period without calcium supplementation. However, itunderscores the importance of timely recognition and supplementation, particularly inindividuals with altered mentation or additional comorbidities. Delays in starting calciumsupplementation can lead to serious, potentially life-threatening complications in these patients. Presentation: Sunday, July 13, 2025

Abstract We describe a patient who presented with spastic ataxic syndrome without cataract or xanthomas, and a diagnosis of cerebrotendinous xanthomatosis was made based on imaging and genetic tests. Magnetic resonance imaging of the brain revealed hyperintensities and mineralization of the bilateral dentate nuclei, and clinical exome sequencing showed a homozygous 5’ splice site variation in intron 6 of the CYP27A1 gene (chr2:219678911; G > A). The patient was treated with simvastatin 10 mg/day and ursodeoxycholic acid 300 mg/day. There was objective improvement in the clinical as well as the electrophysiological parameters following treatment. The report highlights the importance of a high index of suspicion, early diagnosis and timely treatment of this potentially reversible condition.

BackgroundA clear understanding of the alterations in iron deposition and their underlying mechanisms in patients with cerebral ischemia remains elusive. This cross-sectional study aimed to multidimensionally analyze cerebral iron deposition variations in patients with chronic unilateral middle cerebral artery (MCA) stenosis using quantitative susceptibility mapping (QSM), arterial spin labeling (ASL), and high-resolution vessel wall imaging (HR-VWI).MethodsQSM, ASL, and HR-VWI were performed on 26 patients with unilateral MCA stenosis <70%, 22 patients with stenosis ≥70%, and 24 healthy controls. Seventy-two brain subregions were automatically segmented on QSM and ASL images after registration with HR-VWI images. Susceptibility and cerebral blood flow (CBF) were compared across the three groups, and relationships between stenosis degree, vessel wall enhancement, susceptibility, and CBF were assessed.ResultsCompared to healthy controls or the unaffected sides within the stenosis groups, the affected sides exhibited abnormal iron deposition and alterations in CBF in specific brain regions, particularly those supplied by the MCA. These changes exhibited distinct patterns between the two stenosis groups. Increased susceptibility in key regions was generally associated with decreased CBF (Putamen: Psusceptibility =0.001, PCBF =0.013; globus pallidus: Psusceptibility =0.018, PCBF <0.001; insula: Psusceptibility =0.003, PCBF =0.012; middle frontal gyrus: Psusceptibility =0.041, PCBF =0.042; paracentral lobule: Psusceptibility =0.026, PCBF =0.001; inferior temporal gyrus: Psusceptibility =0.021, PCBF =0.048). Moderate-to-strong positive correlations were found between stenosis degree and susceptibility in regions such as the putamen, globus pallidus, substantia nigra, dentate nucleus, and Heschl’s gyrus (correlation coefficients: 0.627, 0.453, 0.345, 0.474, and 0.355, respectively). Additionally, moderate correlations were observed between ipsilateral susceptibility in the putamen, ipsilateral CBF in the globus pallidus, stenosis degree, and vessel wall enhancement (correlation coefficients: 0.302, −0.342, and 0.345, respectively).ConclusionsAbnormal iron deposition and CBF alterations in MCA stenosis patients displayed distinct patterns across varying stenosis severity. The observed correlations between stenosis degree, vessel wall enhancement, CBF, and susceptibility demonstrated these factors may contribute to variations in cerebral iron deposition.

The dysmetria of thought theory holds that the cerebellum is an integral node in the distributed neural circuits subserving cognition. We tested this theory in four rhesus monkeys with bilateral lesions in cerebellar dentate nuclei (DN), targeting ventral sectors linked with cerebral association cortices engaged in cognitive processing. Lesion localization was confirmed by MRI and histology. DN animals and controls were assessed for motor dexterity (Kuypers’ Task), attention, three-choice discrimination, recognition memory (Delayed Non-Matching to Sample task [DNMS]), working memory (Delayed Recognition Span Task [DRST]) and executive function (Conceptual Set Shifting Task [CSST]). Performance by the DN animals was not significantly different than controls on the Kuypers’ task and DNMS, but as a group they were impaired on DRST and CSST. DN monkeys achieved shorter spans on DRST. Their responses on CSST were more perseverative, and larger lesions produced greater deficits. This study provides the first empirical support for anatomical and functional MRI evidence of a motor-cognitive dichotomy in the cerebellar dentate nucleus. It highlights a within-cognition dichotomy in which cerebellum modulates dorsal stream cognitive functions (spatial awareness; dynamic actions of where and how) characterized by executive functions including working memory but is not engaged in ventral stream cognitive processes (static actions of object identification) exemplified by recognition memory.

Our group recently completed a trial of deep brain stimulation targeting the dentate nucleus in patients with poststroke hemiparesis. Although accurate, we found significant limitations to the Leksell G frame (Elekta) for posterior fossa stereotaxis. In this study, we assess the feasibility and accuracy of a commercially available custom-built stereotactic platform for posterior fossa targeting. The smaller profile of these devices, compared with conventional stereotactic headframe make it a promising alternative when surgical access is limited. Three anthropomorphic phantom models with posterior fossa targets marked by nylon screws were used. Each skull had a unique 4-legged microplatform designed from their fiducial location, target, and trajectory plans. We simulated posterior fossa stereotactic cannulation in the neurosurgical OR using standard equipment. Accuracy was evaluated by the deviation of the final cannula placement from the planned target and entry. The Euclidean distance between planned target and final cannula tip position ranged between 0.4 mm (skull 3) and 1.29 mm (skull 1). The mean target deviation from plan was 0.93 mm (SD ± 0.4 mm). The mean entry deviation from plan was 0.9 mm (SD ± 0.6 mm). The mean sagittal and coronal trajectory angulation error were 0.73° (SD ± 0.4°) and 0.04° (SD ± 0.02°), respectively. In this in vitro study, our data show that 3-dimensional printed, custom-made, single-use platforms may be feasible and accurate for posterior fossa stereotactic surgery. Further investigation with in vivo studies will be necessary to assess clinical practicality and accuracy in vivo.

Spinocerebellar degeneration (SCD) is a clinically and genetically diverse group, and the dominant form of SCD (AD-SCD) is generally referred to as spinocerebellar ataxia (SCA) that primarily affects the cerebellum. Some patients do not have a definitive genetic diagnosis but may carry unknown variants of known causative genes. Here, we screened for known SCA-associated genes in patients with suspected SCA. We examined 174 patients with SCA lacking abnormal repeat expansion of known causative genes. Whole-exome sequencing (WES) was performed to screen for variants in SCA-associated genes. The identified variants were confirmed by Sanger sequencing, and their pathogenicity was determined using five web-based algorithms. WES revealed novel single-nucleotide variants (SNVs) in three genes, ELOVL4, ELOVL5, and GRM1. Patients presented with symptoms other than cerebellar symptoms. One patient with an ELOVL4 variant exhibited skin changes, a typical symptom of ELOVL4 SCA, whereas the other ELOVL4 SCA patient had no skin changes and exhibited mild parkinsonism and calcification in the globus pallidus and dentate nucleus. The patient with an ELOVL5 variant exhibited bladder and rectal disturbances. Finally, patients with GRM1 variants showed few common features beyond the cerebellar symptoms. One patient showed white matter lesions, cognitive decline, and no-no head tremors, whereas the other showed spasticity. The identification of novel SNVs in these known SCA-associated genes will expand our understanding of the genetic landscape of SCA and facilitate the diagnosis of previously undiagnosed patients.

Abstract To establish anatomical and functional criteria, based on stereotactic imaging and electrophysiological recordings, which enable the precise implantation of electrodes in the dentate nucleus and its projections for the treatment of movement disorders.Ten patients with movement disorders or cerebellar abnormalities underwent bilateral deep brain stimulation (DBS) of the dentate nucleus (DN). The initial targets were defined using coordinates based on the fastigial point (FP); then, the target was refined through direct visualization of the DN using susceptibility weighted imaging (SWI) and T2-weighted magnetic resonance imaging (MRI) sequences and further adjusted based on reconstruction of the dentato-rubro-thalamic tract (DRTT).The ventral portion of the DN and the estimated vicinity of the DRTT were established as the target region, with the distal electrode contact positioned in the white matter and the proximal contacts within the DN. The coordinates were refined using direct imaging of the DN on SWI and T2 sequences, fused with stereotomography and contrast-enhanced volumetric T1 MRI. The electrode trajectory was adjusted to remain within the DN, as parallel and close as possible to the DRTT fibers. Surgical planning also defined the entry points and intracranial trajectories of the instruments, ensuring a safe path from the suboccipital bone to the targets, while avoiding venous sinuses and vessels visualized on contrast-enhanced images.Precise localization of the DN based on DRTT tractography proved feasible using currently available stereotactic and imaging processing resources. The technique described enables coregistration of computed tomography (CT), MRI, and tractography images, representing a simple, safe, and effective methodology for performing DBS of the DN.