Imaging of Dentate Nucleus Pathologies: A Case Series

The dentate nucleus is the largest cerebellar nucleus, and it controls cognition and voluntary movement. It is found in each cerebellar hemisphere medially and posterolateral to the lateral ventricle. Pathologies of the dentate nucleus can be detected using computed tomography and magnetic resonance imaging of the brain. Here, we present a case series of seven different dentate nucleus diseases and their neuroimaging findings recovered from archives of our institution.

Region-specific alterations of perineuronal net expression in postmortem autism brain tissue

Genetic variance in ASD is often associated with mechanisms that broadly fall into the category of neuroplasticity. Parvalbumin positive neurons and their surrounding perineuronal nets (PNNs) are important factors in critical period plasticity and have both been implicated in ASD. PNNs are found in high density within output structures of the cerebellum and basal ganglia, two regions that are densely connected to many other brain areas and have the potential to participate in the diverse array of symptoms present in an ASD diagnosis. The dentate nucleus and globus pallidus were therefore assessed for differences in PNN expression in human postmortem ASD brain tissue. While Purkinje cell loss is a consistent neuropathological finding in ASD, in this cohort, the Purkinje cell targets within the dentate nucleus did not show differences in number of cells with or without a PNN. However, the density of parvalbumin positive neurons with a PNN were significantly reduced in the globus pallidus internus and externus of ASD cases, which was not dependent on seizure status. It is unclear whether these alterations manifest during development or are a consequence of activity-dependent mechanisms that lead to altered network dynamics later in life.

Apoptosis in the Dentate Nucleus Following Kindling-induced Seizures in Rats

Background: Epilepsy is a common neurological disorder characterized by abnormal and recurrent neuronal discharges that result in epileptic seizures. The dentate nuclei of the cerebellum receive excitatory input from different brain regions. Purkinje cell loss due to chronic seizures could lead to decreased inhibition of these excitatory neurons, resulting in the activation of apoptotic cascades in the dentate nucleus. Objective: The present study was designed to determine whether there is a presence of apoptosis (either intrinsic or extrinsic) in the dentate nucleus, the final relay of the cerebellar circuit, following kindling-induced seizures. Methods: In order to determine this, seizures were triggered via the amygdaloid kindling model. Following 0, 15, or 45 stimuli, rats were sacrificed, and the cerebellum was extracted. It was posteriorly prepared for the immunohistochemical analysis with cell death biomarkers: TUNEL, Bcl-2, truncated Bid (tBid), Bax, cytochrome C, and cleaved caspase 3 (active form). Our findings reproduce results obtained in other parts of the cerebellum. Results: We found a decrease of Bcl-2 expression, an anti-apoptotic protein, in the dentate nucleus of kindled rats. We also determined the presence of TUNEL-positive neurons, which confirms the presence of apoptosis in the dentate nucleus. We observed the expression of tBid, Bax, as well as cytochrome C and cleaved caspase-3, the main executor caspase of apoptosis. Conclusion: There is a clear activation of both the intrinsic and extrinsic apoptotic pathways in the cells of the dentate nucleus of the cerebellum of rats subjected to amygdaloid kindling.

Evaluation of the Effect of Multiple Linear Gadolinium-Based Contrast Agent Exposures on the Signal Intensity of the Dentate Nucleus in Multiple Sclerosis Patients

Background: Magnetic resonance imaging (MRI) with gadolinium (GAD)-based contrast agents has been the imaging modality of choice for early detection and monitoring of multiple sclerosis (MS) patients. Objectives: This study aimed to assess the effect of multiple injections of linear GAD-based contrast agents on the signal intensity of the dentate nucleus (DN) in MS patients. Patients and Methods: A cohort of 122 MS patients with GAD-enhanced MRI scans and 61 healthy controls were enrolled in this study. The final standard GAD-enhanced MRI scans were acquired using 1.5T MRI systems. Non-enhanced T1-weighted MRI was performed to assess the DN hyperintensity. The signal intensity ratio (SIR) was also calculated by setting the regions of interest (ROIs) on the DN and pons and dividing the signal intensity of DN to that of pons. The patients were also divided into two subgroups, based on the total number of MRI exposures (> 4 times vs. others), and the subgroups were compared in terms of the mean SIR and hyperintensity. Results: Overall, 68% (n = 83) of the patients were exposed to a contrast agent more than four times. Of these patients, 31.3% (n = 26) showed DN hyperintensity, while no hyperintensity was found in other patients or healthy controls (P < 0.02 for both). The mean SIRs were 1.10 ± 0.07 and 1.04 ± 0.02 in the patients and healthy controls, respectively (P < 0.001). Besides, the mean SIR was 1.14 ± 0.04 in patients with DN hyperintensity and 1.09 ± 0.07 in other patients (P < 0.001). Based on the results, the mean SIR was 1.12 ± 0.7 in patients with > 4 contrast injections, while it was 1.06 ± 0.04 in patients with < 4 contrast injections (P < 0.001). Conclusion: The SIR and visible DN hyperintensity increased by increasing the number of GAD injections, which could be due to the tissue deposition of GAD.

Aberrant Cerebello-Cerebral Connectivity in Remitted Bipolar Patients 1 and 2: New Insight into Understanding the Cerebellar Role in Mania and Hypomania

Bipolar disorder (BD) is a major mental illness characterized by periods of (hypo) mania and depression with inter-episode remission periods. Functional studies in BD have consistently implicated a set of linked cortical and subcortical limbic regions in the pathophysiology of the disorder, also including the cerebellum. However, the cerebellar role in the neurobiology of BD still needs to be clarified. Seventeen euthymic patients with BD type1 (BD1) (mean age/SD, 38.64/13.48; M/F, 9/8) and 13 euthymic patients with BD type 2 (BD2) (mean age/SD, 41.42/14.38; M/F, 6/7) were compared with 37 sex- and age-matched healthy subjects (HS) (mean age/SD, 45.65/14.15; M/F, 15/22). T1 weighted and resting-state functional connectivity (FC) scans were acquired. The left and right dentate nucleus were used as seed regions for the seed based analysis. FC between each seed and the rest of the brain was compared between patients and HS. Correlations between altered cerebello-cerebral connectivity and clinical scores were then investigated. Different patterns of altered dentate-cerebral connectivity were found in BD1 and BD2. Overall, impaired dentate-cerebral connectivity involved regions of the anterior limbic network specifically related to the (hypo)manic states of BD. Cerebello-cerebral connectivity is altered in BD1 and BD2. Interestingly, the fact that these altered FC patterns persist during euthymia, supports the hypothesis that cerebello-cerebral FC changes reflect the neural correlate of subthreshold symptoms, as trait-based pathophysiology and/or compensatory mechanism to maintain a state of euthymia.

Is Fahr’s disease a saviour for intracranial hypertensive bleeds? - A review

Fahr’s disease (FD) is a rare disorder characterised by abnormal deposition of calcium in different parts of brain especially in basal ganglia, thalamus and dentate nucleus. Association of FD with ischemic stroke has been described in past but very less literature available showing association of FD with haemorrhagic stroke. We present here a case of 70 years old hypertensive male patient suffering from FD with left thalamic acute haemorrhage. Although basal ganglia is a common site for hypertensive bleed, but in this hypertensive patient, basal ganglia was spared. We assume that this could be due to presence of calcification within vessel walls of basal ganglia that strengthen the walls and hence act as a saviour for basal ganglia bleed in this case.