Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

BACKGROUND: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated. OBJECTIVE: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group. METHODS: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated. RESULTS: Overall, people with PD had a regionally smaller posterior lobe (dmax = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (dmax = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (dmax = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17). CONCLUSIONS: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Microglial activation persists beyond clinical recovery following sport concussion in collegiate athletes.

Introduction: In concussion, clinical and physiological recovery are increasingly recognized as diverging definitions. This study investigated whether central microglial activation persisted in participants with concussion after receiving an unrestricted return-to-play (uRTP) designation using [18F]DPA-714 PET, an in vivo marker of microglia activation. Methods: Eight (5 M, 3 F) current athletes with concussion (Group 1) and 10 (5 M, 5 F) healthy collegiate students (Group 2) were enrolled. Group 1 completed a pre-injury (Visit1) screen, follow-up Visit2 within 24 h of a concussion diagnosis, and Visit3 at the time of uRTP. Healthy participants only completed assessments at Visit2 and Visit3. At Visit2, all participants completed a multidimensional battery of tests followed by a blood draw to determine genotype and study inclusion. At Visit3, participants completed a clinical battery of tests, brain MRI, and brain PET; no imaging tests were performed outside of Visit3. Results: For Group 1, significant differences were observed between Visits 1 and 2 (p < 0.05) in ImPACT, SCAT5 and SOT performance, but not between Visit1 and Visit3 for standard clinical measures (all p > 0.05), reflecting clinical recovery. Despite achieving clinical recovery, PET imaging at Visit3 revealed consistently higher [18F]DPA-714 tracer distribution volume (VT) of Group 1 compared to Group 2 in 10 brain regions (p < 0.001) analyzed from 164 regions of the whole brain, most notably within the limbic system, dorsal striatum, and medial temporal lobe. No notable differences were observed between clinical measures and VT between Group 1 and Group 2 at Visit3. Discussion: Our study is the first to demonstrate persisting microglial activation in active collegiate athletes who were diagnosed with a sport concussion and cleared for uRTP based on a clinical recovery.

Cholinergic nucleus 4 grey matter density is associated with apathy in Parkinson's disease.

Objective: The generation and maintenance of goal-directed behavior is subserved by multiple brain regions that receive cholinergic inputs from the cholinergic nucleus 4 (Ch4). It is unknown if Ch4 degeneration contributes to apathy in Parkinson's disease (PD). Method: We analyzed data from 106 pre-surgical patients with PD who had brain MRIs and completed the Frontal Systems Behavior Scales (FrSBe). Eighty-eight patients also completed the Beck Depression Inventory-2nd Edition. Cholinergic basal forebrain grey matter densities (GMD) were measured by applying probabilistic maps to T1 MPRAGE sequences processed using voxel-based morphometry methods. We used linear and hierarchical regression modelling to examine the association between Ch4 GMD and the FrSBe Apathy subscale scores. We used similar methods to assess the specificity of this association and potential associations between Ch4 target regions and apathy. Results: Ch4 GMD (p = .021) and Ch123 GMD (p = .032) were significantly associated with Apathy subscale scores on univariate analysis. Ch4 GMD, but not Ch123 GMD, remained significantly associated with apathy when adjusting for age, sex, levodopa equivalent doses, and disease duration. Centromedial amygdala GMD, which receives cholinergic inputs from Ch4, was also associated with apathy. Ch4 GMD was not associated with depression or disinhibition, nor was it associated with executive dysfunction when adjusting for clinical and demographic variables. Conclusions: Ch4 GMD is specifically associated with apathy in PD. Ch4 degeneration results in cholinergic denervation of multiple cortical and limbic regions, which may contribute to the cognitive and emotional-affective processing deficits that underlie the behavioral symptoms of apathy.

International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease.

BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax  = -0.20, dmin  = -0.09). The bilateral putamen (dleft  = -0.14, dright  = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Gamma Knife radiosurgery associated worsening of superficial siderosis due to a foramen magnum tumor - A case report.

Superficial siderosis (SS) of the brain results from a chronic iron toxicity due to repeated microscopic leakage of blood products into the subarachnoid space. We report on Gamma Knife Radiosurgery (GKRS) associated worsening of superficial siderosis in a patient with skull-base tumor. A 73 year-old male patient presented with clumsiness and gait ataxia and was diagnosed with foramen magnum meningioma. He was also noted to have superficial siderosis involving the mainly the infratentorial compartment. After a thorough evaluation of craniospinal axis, no other cause of bleeding was identified. Patient was treated with the GKRS. After GKRS, there was an initial radiological and clinical worsening of SS starting at 6 months and peaking at 2 years. The disease stabilized and showed mild reduction at 3 years. GKRS lead to an initial progression of superficial siderosis. However, over a longer period, tumor control and improvement of the siderosis was observed.

Increased intratumoral infiltration in IDH wild-type lower-grade gliomas observed with diffusion tensor imaging.

PURPOSE: Diffuse lower grade gliomas (LGG) with isocitrate dehydrogenase (IDH) gene mutations (IDHMUT) have a distinct survival advantage compared with IDH wild-type (IDHWT) cases but the mechanism underlying this disparity is not well understood. Diffusion Tensor Imaging (DTI) has identified infiltrated non-enhancing tumor regions that are characterized by low isotropic (p) and high anisotropic (q) diffusion tensor components that associate with poor survival in glioblastoma. We hypothesized that similar regions are more prevalent in IDHWT (vs. IDHMUT) LGG. METHODS: p and q maps were reconstructed from preoperative DTI scans in N = 41 LGG patients with known IDH mutation and 1p/19q codeletion status. Enhancing and non-enhancing tumor volumes were autosegmented from standard (non-DTI) MRI scans. Percentage non-enhancing tumor volumes exhibiting low p and high q (Vinf) were then determined using threshold values (p = 2 × 10-3mm2/s, q = 3 × 10-4 mm2/s) and compared between IDHWT and IDHMUT LGG, and between IDHMUT LGG with and without 1p/19q codeletion. RESULTS: Vinf volumes were significantly larger in IDHWT LGG than in IDHMUT LGG (35.4 ± 18.3% vs. 15.9 ± 7.6%, P < 0.001). Vinf volumes did not significantly differ between IDHMUT LGG with and without 1p/19q codeletion (17.1 ± 9.5% vs. 14.8 ± 5.8%, P = 1.0). CONCLUSION: IDHWT LGG exhibited larger volumes with suppressed isotropic diffusion (p) and high anisotropic diffusion (q) which reflects regions with increased cell density but non-disrupted neuronal structures. This may indicate a greater prevalence of infiltrative tumor in IDHWT LGG.

Agenesis of Anterior Falx Cerebri in Patient with Planned Interhemispheric Approach to Third Ventricle Mass.

BACKGROUND: Complete or partial agenesis of the falx cerebri may occur in pediatric patients with developmental anomalies. However, isolated agenesis of the falx in a developmentally normal adult is exceptionally rare. We describe the first reported case of a patient with a third ventricular mass associated with partial agenesis of the anterior falx cerebri, a circumstance that influenced surgical access to a third ventricular epidermoid cyst. CASE DESCRIPTION: A 60-year-old developmentally normal woman presented with progressively worsening aphasia and altered mental status. Brain magnetic resonance imaging showed obstructive hydrocephalus from a third ventricular mass. An anterior interhemispheric transcallosal approach was planned to remove the tumor. However, upon dural opening there was no evidence of a falx cerebri, an anomaly visible but not reported on the prior imaging studies. An interhemispheric fissure was present, but the medial frontal lobes were densely adherent, with multiple traversing veins within the superficial arachnoid of the fissure. Therefore, a left frontal transcortical approach was performed for microsurgical resection of the tumor. Histopathologic analysis identified the lesion to be an epidermoid cyst. CONCLUSIONS: Partial agenesis of the falx cerebri is exceedingly rare in a developmentally normal adult, particularly in the presence of an anatomically normal superior sagittal sinus. If present, however, it is important to note this association preoperatively because partial agenesis of the falx cerebri precludes an interhemispheric transcallosal approach to the lateral and third ventricles.

Imaging characteristics of cervical spine extra-arachnoid fluid collections managed conservatively.

OBJECTIVE: Determine the MRI characteristics of large post-traumatic cervical spine extra-arachnoid collections managed conservatively in clinically stable patients and whether evidence of clinical or imaging deterioration materialized. MATERIALS AND METHODS: Following IRB approval, we conducted a retrospective search for all patients (>16 years old) over a 17-months period who had an extra-arachnoid fluid collection reported on a post-traumatic cervical spine MRI. Patients were excluded if they had surgery for an unstable fracture (n = 21), emergent decompression (n = 1) or lacked a follow-up MRI within 15 days (n = 1). Two MSK radiologists recorded the size, morphology and MRI signal characteristics of the collections. RESULTS: Eight patients (5 male, 3 female) met the inclusion criteria (mean age 40 years; range 19-78 years). Seven of the eight patients had fluid collections that demonstrated thin, tapered margins, extended >7 vertebral bodies and involved >180 degrees of the spinal canal. The signal characteristics of these collections varied: hyper-T1/iso-T2 (n = 1), iso-T1/T2 (n = 3), hyper-T1/hypo-T2 (n = 3) and mixed-T1/T2 (n = 1). Six of seven collections were ventral. Follow-up MRI demonstrated resolution/significant decrease in size (n = 4 between 1 and 12 days) or no change/slight decrease in size (n = 3; between 2 and 11 days). None of the seven fluid collections enlarged, no patient had abnormal cord signal, and no patient's neurologic symptoms worsened. One of eight patients had a dorsal "mass-like" collection that was slightly smaller 9 days later. CONCLUSION: In stable patients with large, tapered post-traumatic cervical spine extra-arachnoid collections managed non-surgically, none developed (1) clinical worsening, (2) abnormal cord signal or (3) collection enlargement, regardless of the collection's signal characteristics.

A pilot study of focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor. METHODS: From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor. We recorded all safety data and measured the effectiveness of tremor suppression using the Clinical Rating Scale for Tremor to calculate the total score (ranging from 0 to 160), hand subscore (primary outcome, ranging from 0 to 32), and disability subscore (ranging from 0 to 32), with higher scores indicating worse tremor. We assessed the patients' perceptions of treatment efficacy with the Quality of Life in Essential Tremor Questionnaire (ranging from 0 to 100%, with higher scores indicating greater perceived disability). RESULTS: Thermal ablation of the thalamic target occurred in all patients. Adverse effects of the procedure included transient sensory, cerebellar, motor, and speech abnormalities, with persistent paresthesias in four patients. Scores for hand tremor improved from 20.4 at baseline to 5.2 at 12 months (P=0.001). Total tremor scores improved from 54.9 to 24.3 (P=0.001). Disability scores improved from 18.2 to 2.8 (P=0.001). Quality-of-life scores improved from 37% to 11% (P=0.001). CONCLUSIONS: In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized, controlled trials will be required to assess the procedure's efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.).