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Movement Disorders Clinical Practice Sep 2023
Topics: Humans; Nystagmus, Pathologic; Olivary Nucleus; Eyelids
PubMed: 37772289
DOI: 10.1002/mdc3.13743 -
Cureus Jan 2024Hypertrophic olivary degeneration (HOD) is a rare form of trans-synaptic degeneration affecting the inferior olivary nucleus (ION). Its classical description involves a...
Hypertrophic olivary degeneration (HOD) is a rare form of trans-synaptic degeneration affecting the inferior olivary nucleus (ION). Its classical description involves a lesion in the Guillain-Mollaret triangle (GMT), characteristic imaging findings, and associated oculopalatal tremor. However, understanding of this disease entity is incomplete, as its overall rarity has limited strong classification. Case reports and small studies indicate that a variety of presentations can occur, including non-existent or non-classical lesions as well as variations in physical symptoms. Here we report the exceedingly rare case of idiopathic, nonlesional, unilateral HOD in a female patient.
PubMed: 38352106
DOI: 10.7759/cureus.52251 -
Tuberculosis (Edinburgh, Scotland) May 2024In about 1% of tuberculosis (TB) patients, Mycobacterium tuberculosis (M. tuberculosis) can disseminate to the meninges, causing tuberculous meningitis (TBM) with...
In about 1% of tuberculosis (TB) patients, Mycobacterium tuberculosis (M. tuberculosis) can disseminate to the meninges, causing tuberculous meningitis (TBM) with mortality rate up to 60%. Chronic granulomatous inflammation (non-necrotizing and necrotizing) in the brain is the histological hallmark of TBM. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) and the generated kynurenine metabolites exert major effector functions relevant to TB granuloma functioning. Here we have assessed immunohistochemically IDO1 expression and activity and its effector function and that of its isoform, IDO2, in post-mortem brain tissue of patients that demised with neurotuberculosis. We also related these findings to brain tissue of fatal/severe COVID-19. In this study, IDO1 and IDO2 were abundantly expressed and active in tuberculoid granulomas and were associated with the presence of M. tuberculosis as well as markers of autophagy and apoptosis. Like in fatal/severe COVID-19, IDO2 was also prominent in specific brain regions, such as the inferior olivary nucleus of medulla oblongata and cerebellum, but not associated with granulomas or with M. tuberculosis. Spatially associated apoptosis was observed in TBM, whereas in fatal COVID-19 autophagy dominated. Together, our findings highlight IDO2 as a potentially relevant effector enzyme in TBM, which may relate to the symptomology of TBM.
Topics: Humans; COVID-19; Granuloma; Indoleamine-Pyrrole 2,3,-Dioxygenase; Inflammation; Mycobacterium tuberculosis; Tryptophan; Tuberculosis, Meningeal
PubMed: 38460493
DOI: 10.1016/j.tube.2024.102495 -
ENeuro Feb 2024The olivocerebellar system, which is critical for sensorimotor performance and learning, functions through modules with feedback loops. The main feedback to the inferior...
The olivocerebellar system, which is critical for sensorimotor performance and learning, functions through modules with feedback loops. The main feedback to the inferior olive comes from the cerebellar nuclei (CN), which are predominantly GABAergic and contralateral. However, for the subnucleus d of the caudomedial accessory olive (cdMAO), a crucial region for oculomotor and upper body movements, the source of GABAergic input has yet to be identified. Here, we demonstrate the existence of a disynaptic inhibitory projection from the medial CN (MCN) to the cdMAO via the superior colliculus (SC) by exploiting retrograde, anterograde, and transsynaptic viral tracing at the light microscopic level as well as anterograde classical and viral tracing combined with immunocytochemistry at the electron microscopic level. Retrograde tracing in Gad2-Cre mice reveals that the cdMAO receives GABAergic input from the contralateral SC. Anterograde transsynaptic tracing uncovered that the SC neurons receiving input from the contralateral MCN provide predominantly inhibitory projections to contralateral cdMAO, ipsilateral to the MCN. Following ultrastructural analysis of the monosynaptic projection about half of the SC terminals within the contralateral cdMAO are GABAergic. The disynaptic GABAergic projection from the MCN to the ipsilateral cdMAO mirrors that of the monosynaptic excitatory projection from the MCN to the contralateral cdMAO. Thus, while completing the map of inhibitory inputs to the olivary subnuclei, we established that the MCN inhibits the cdMAO via the contralateral SC, highlighting a potential push-pull mechanism in directional gaze control that appears unique in terms of laterality and polarity among olivocerebellar modules.
Topics: Mice; Animals; Inferior Olivary Complex; Cerebellum; Olivary Nucleus; Synaptic Transmission; Cerebellar Nuclei
PubMed: 38242692
DOI: 10.1523/ENEURO.0262-23.2023 -
The Journal of International Advanced... Jul 2023We aimed to investigate the changes that may occur in the auditory neural network in pediatric congenital hearing loss cases.
BACKGROUND
We aimed to investigate the changes that may occur in the auditory neural network in pediatric congenital hearing loss cases.
METHODS
Fifty-four cochlear implant candidates and 47 normal-hearing controls were included in this retrospective study. Fractional anisotropy, radial diffusivity, and apparent diffusion coefficient maps were generated. We placed region of interest on the cochlear nucleus, superior olivary nucleus, lateral lemniscus, medial geniculate body, auditory radiation, Heschl's gyrus, inferior fronto-occipital fasciculus, superior longitudinal fascicle, and corpus callosum splenium. The area of the cochlear nerve was measured. Diffusion tensor imaging metrics, children's ages, and cochlear nerve area were compared.
RESULTS
Apparent diffusion coefficient and radial diffusivity values of patients were higher than the control group in all places except the radial diffusivity values of medial geniculate body. The fractional anisotropy values of the patients in lateral lemniscus, auditory radiation, Heschl's gyrus, inferior fronto-occipital fasciculus, superior longitudinal fascicle, and corpus callosum splenium were lower than the control group. There is a positive correlation between fractional anisotropy and age in both patient and control groups for all locations. The cochlear nerve area is lower in patients (0.88 ± 0.29) than in the control group (1.18 ± 0.14) (P = .000). The cochlear nerve area has a positive correlation with age in the patient group (P = .000) but has not in the control group. The cochlear nerve area positively correlates with fractional anisotropy values of all locations except fractional anisotropy values of medial geniculate body.
CONCLUSION
The alterations of diffusion tensor imaging metrics on the auditory pathway reflect the microstructural changes of white matter tracts.
Topics: Humans; Child; Diffusion Tensor Imaging; Auditory Pathways; Cochlear Implants; Retrospective Studies; Diffusion Magnetic Resonance Imaging
PubMed: 37528599
DOI: 10.5152/iao.2023.22998 -
Neurologia Jun 2024Ataxias are characterized by aberrant movement patterns closely related to cerebellar dysfunction. Purkinje cell axons are the sole outputs from the cerebellar cortex,...
Ataxias are characterized by aberrant movement patterns closely related to cerebellar dysfunction. Purkinje cell axons are the sole outputs from the cerebellar cortex, and dysfunctional activity of Purkinje cells has been associated with ataxic movements. However, the synaptic characteristics of Purkinje cells in cases of ataxia are not yet well understood. The nicotinamide antagonist 3-acethylpyridine (3-AP) selectively destroys inferior olivary nucleus neurons so it is widely used to induce cerebellar ataxia. Five days after 3-AP treatment (65mg/kg) in adult male Sprague-Dawley rats, motor incoordination was revealed through BBB and Rotarod testing. In addition, in Purkinje cells from lobules V-VII of the cerebellar vermis studied by the Golgi method, the density of dendritic spines decreased, especially the thin and mushroom types. Western blot analysis showed a decrease in AMPA and PSD-95 content with an increase of the α-catenin protein, while GAD-67 and synaptophysin were unchanged. Findings suggest a limited capacity of Purkinje cells to acquire and consolidate afferent excitatory inputs and an aberrant, rigid profile in the movement-related output patterns of Purkinje neurons that likely contributes to the motor-related impairments characteristic of cerebellar ataxias.
Topics: Animals; Purkinje Cells; Male; Rats, Sprague-Dawley; Rats; Cerebellum; Cerebellar Ataxia; Pyridines; Neuronal Plasticity
PubMed: 38830720
DOI: 10.1016/j.nrleng.2021.09.015 -
BioRxiv : the Preprint Server For... Oct 2023One of the characteristic areas of brainstem degeneration across multiple spinocerebellar ataxias (SCAs) is the inferior olive (IO), a medullary nucleus that plays a key...
One of the characteristic areas of brainstem degeneration across multiple spinocerebellar ataxias (SCAs) is the inferior olive (IO), a medullary nucleus that plays a key role in motor learning. In addition to its vulnerability in SCAs, the IO is also susceptible to a distinct pathology known as hypertrophic olivary degeneration (HOD). Clinically, HOD has been exclusively observed after lesions in the brainstem disrupt inhibitory afferents to the IO. Here, for the first time, we describe HOD in another context: spinocerebellar ataxia type 1 (SCA1). Using the genetically-precise SCA1 knock-in mouse model (SCA1-KI; both sexes used), we assessed SCA1-associated changes in IO neuron structure and function. Concurrent with degeneration, we found that SCA1-KI IO neurons are hypertrophic, exhibiting early dendrite lengthening and later somatic expansion. Unlike in previous descriptions of HOD, we observed no clear loss of IO inhibitory innervation; nevertheless, patch-clamp recordings from brainstem slices reveal that SCA1-KI IO neurons are hyperexcitable. Rather than synaptic disinhibition, we identify increases in membrane excitability as the more likely mechanism underlying this novel SCA1 phenotype. Specifically, transcriptome analysis indicates that SCA1-KI IO hyperexcitability is associated with a reduced medullary expression of ion channels responsible for spike afterhyperpolarization (AHP) in IO neurons - a result that has a functional consequence, as SCA1-KI IO neuron spikes exhibit a diminished AHP. These results reveal membrane excitability as a potential link between disparate causes of IO degeneration, suggesting that HOD can result from any cause, intrinsic or extrinsic, that increases excitability of the IO neuron membrane.
PubMed: 37961407
DOI: 10.1101/2023.10.23.563657 -
Clinical Neurology and Neurosurgery Sep 2023Hypertrophic olivary degeneration (HOD) is a rare condition caused by lesions of the dentato-rubro-olivary pathway, usually bilateral. We presented a case of a 64-year...
Hypertrophic olivary degeneration (HOD) is a rare condition caused by lesions of the dentato-rubro-olivary pathway, usually bilateral. We presented a case of a 64-year old male with HOD caused by a unilateral, posterior pontine cavernoma. The patient has not developed the typical palate myoclonus until recently. Isolated hand myoclonus with coexisting asterixis was present for years. This case shows unique HOD symptomatology and emphasizes the important role of MRI in the differential diagnosis of monomelic myoclonus.
Topics: Male; Humans; Middle Aged; Olivary Nucleus; Nerve Degeneration; Myoclonus; Tremor; Pons; Hypertrophy; Magnetic Resonance Imaging
PubMed: 37413873
DOI: 10.1016/j.clineuro.2023.107871 -
PLoS Biology Apr 2024Having two ears enables us to localize sound sources by exploiting interaural time differences (ITDs) in sound arrival. Principal neurons of the medial superior olive...
Having two ears enables us to localize sound sources by exploiting interaural time differences (ITDs) in sound arrival. Principal neurons of the medial superior olive (MSO) are sensitive to ITD, and each MSO neuron responds optimally to a best ITD (bITD). In many cells, especially those tuned to low sound frequencies, these bITDs correspond to ITDs for which the contralateral ear leads, and are often larger than the ecologically relevant range, defined by the ratio of the interaural distance and the speed of sound. Using in vivo recordings in gerbils, we found that shortly after hearing onset the bITDs were even more contralaterally leading than found in adult gerbils, and travel latencies for contralateral sound-evoked activity clearly exceeded those for ipsilateral sounds. During the following weeks, both these latencies and their interaural difference decreased. A computational model indicated that spike timing-dependent plasticity can underlie this fine-tuning. Our results suggest that MSO neurons start out with a strong predisposition toward contralateral sounds due to their longer neural travel latencies, but that, especially in high-frequency neurons, this predisposition is subsequently mitigated by differential developmental fine-tuning of the travel latencies.
Topics: Animals; Gerbillinae; Neurons; Acoustic Stimulation; Superior Olivary Complex; Sound Localization; Male; Olivary Nucleus; Sound; Female
PubMed: 38683852
DOI: 10.1371/journal.pbio.3002586 -
The Journal of Neuroscience : the... Feb 2024The olivo-cerebellar system plays an important role in vertebrate sensorimotor control. Here, we investigate sensory representations in the inferior olive (IO) of larval...
The olivo-cerebellar system plays an important role in vertebrate sensorimotor control. Here, we investigate sensory representations in the inferior olive (IO) of larval zebrafish and their spatial organization. Using single-cell labeling of genetically identified IO neurons, we find that they can be divided into at least two distinct groups based on their spatial location, dendritic morphology, and axonal projection patterns. In the same genetically targeted population, we recorded calcium activity in response to a set of visual stimuli using two-photon imaging. We found that most IO neurons showed direction-selective and binocular responses to visual stimuli and that the functional properties were spatially organized within the IO. Light-sheet functional imaging that allowed for simultaneous activity recordings at the soma and axonal level revealed tight coupling between functional properties, soma location, and axonal projection patterns of IO neurons. Taken together, our results suggest that anatomically defined classes of IO neurons correspond to distinct functional types, and that topographic connections between IO and cerebellum contribute to organization of the cerebellum into distinct functional zones.
Topics: Animals; Zebrafish; Larva; Olivary Nucleus; Neurons; Cerebellum
PubMed: 38195508
DOI: 10.1523/JNEUROSCI.2352-21.2023