Positioning Head Tilt in Canine Lysosomal Storage Disease: A Retrospective Observational Descriptive Study

Positioning head tilt is a neurological sign that has recently been described in dogs with congenital cerebellar malformations. This head tilt is triggered in response to head movement and is believed to be caused by a lack of inhibition of the vestibular nuclei by the cerebellar nodulus and ventral uvula (NU), as originally reported cases were dogs with NU hypoplasia. We hypothesized that other diseases, such as lysosomal storage diseases that cause degeneration in the whole brain, including NU, may cause NU dysfunction and positioning head tilt. Videos of the clinical signs of canine lysosomal storage disease were retrospectively evaluated. In addition, post-mortem NU specimens from each dog were histopathologically evaluated. Nine dogs were included, five with lysosomal storage disease, two Chihuahuas with neuronal ceroid lipofuscinosis (NCL), two Border Collies with NCL, one Shikoku Inu with NCL, two Toy Poodles with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Twenty-eight videos recorded the clinical signs of the dogs. In these videos, positioning head tilt was observed in seven of nine dogs, two Chihuahuas with NCL, one Border Collie with NCL, one Shikoku Inu with NCL, one Toy Poodle with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Neuronal degeneration and loss of NU were histopathologically confirmed in all diseases. As positioning head tilt had not been described until 2016, it may have been overlooked and may be a common clinical sign and pathophysiology in dogs with NU dysfunction.

Sensorimotor Rehabilitation Promotes Vestibular Compensation in a Rodent Model of Acute Peripheral Vestibulopathy by Promoting Microgliogenesis in the Deafferented Vestibular Nuclei

Acute peripheral vestibulopathy leads to a cascade of symptoms involving balance and gait disorders that are particularly disabling for vestibular patients. Vestibular rehabilitation protocols have proven to be effective in improving vestibular compensation in clinical practice. Yet, the underlying neurobiological correlates remain unknown. The aim of this study was to highlight the behavioural and cellular consequences of a vestibular rehabilitation protocol adapted to a rat model of unilateral vestibular neurectomy. We developed a progressive sensory-motor rehabilitation task, and the behavioural consequences were quantified using a weight-distribution device. This analysis method provides a precise and ecological analysis of posturolocomotor vestibular deficits. At the cellular level, we focused on the analysis of plasticity mechanisms expressed in the vestibular nuclei. The results obtained show that vestibular rehabilitation induces a faster recovery of posturolocomotor deficits during vestibular compensation associated with a decrease in neurogenesis and an increase in microgliogenesis in the deafferented medial vestibular nucleus. This study reveals for the first time a part of the underlying adaptative neuroplasticity mechanisms of vestibular rehabilitation. These original data incite further investigation of the impact of rehabilitation on animal models of vestibulopathy. This new line of research should improve the management of vestibular patients.

SK Channels Modulation Accelerates Equilibrium Recovery in Unilateral Vestibular Neurectomized Rats

We have previously reported in a feline model of acute peripheral vestibulopathy (APV) that the sudden, unilateral, and irreversible loss of vestibular inputs induces selective overexpression of small conductance calcium-activated potassium (SK) channels in the brain stem vestibular nuclei. Pharmacological blockade of these ion channels by the selective antagonist apamin significantly alleviated the evoked vestibular syndrome and accelerated vestibular compensation. In this follow-up study, we aimed at testing, using a behavioral approach, whether the antivertigo (AV) effect resulting from the antagonization of SK channels was species-dependent or whether it could be reproduced in a rodent APV model, whether other SK channel antagonists reproduced similar functional effects on the vestibular syndrome expression, and whether administration of SK agonist could also alter the vestibular syndrome. We also compared the AV effects of apamin and acetyl-DL-leucine, a reference AV compound used in human clinic. We demonstrate that the AV effect of apamin is also found in a rodent model of APV. Other SK antagonists also produce a trend of AV effect when administrated during the acute phase of the vertigo syndrome. Conversely, the vertigo syndrome is worsened upon administration of SK channel agonist. It is noteworthy that the AV effect of apamin is superior to that of acetyl-DL-leucine. Taken together, these data reinforce SK channels as a pharmacological target for modulating the manifestation of the vertigo syndrome during APV.

Primary Graviceptive System and Astasia: Case Report and Literature Review

Purpose of ReviewAstasia refers to the inability to maintain upright posture during standing, despite having full motor strength. However, the pathophysiology and neural pathways of astasia remains unclear.Recent FindingsWe analyzed 26, including ours, non-psychogenic astasia patients in English literature. Seventy-three percent of them were man, 73% were associated with other neurologic symptoms and 62% of reported lesions were at right side. Contralateral lateropulsion was very common followed by retropulsion while describing astasia. Infarction (54%) was the most commonly reported cause. Thalamus (65%) was the most commonly reported location. Infarction being the mostly likely to recover (mean:10.6 days), while lesions at brainstem had longer time to recover (mean: 61.6 days).SummaryThe underlying interrupted pathway may be the primary graviceptive system, which composed of at least five unilateral and contralateral projection fibers from vestibular nuclei to thalamic nuclei, and thalamo-cortical projections including subcortical white matter tracts and cortical areas.

The brainstem in multiple sclerosis: MR identification of tracts and nuclei damage

Objective To evaluate the 3D Fast Gray Acquisition T1 Inversion Recovery (FGATIR) sequence for MRI identification of brainstem tracts and nuclei damage in multiple sclerosis (MS) patients. Methods From april to december 2020, 10 healthy volunteers and 50 patients with remitted-relapsing MS (58% female, mean age 36) underwent MR imaging in the Neuro-imaging department of the C.H.N.O. des Quinze-Vingts, Paris, France. MRI was achieved on a 3 T system (MAGNETOM Skyra) using a 64-channel coil. 3D FGATIR sequence was first performed on healthy volunteers to classify macroscopically identifiable brainstem structures. Then, FGATIR was assessed in MS patients to locate brainstem lesions detected with Proton Density/T2w (PD/T2w) sequence. Results In healthy volunteers, FGATIR allowed a precise visualization of tracts and nuclei according to their myelin density. Including FGATIR in MR follow-up of MS patients helped to identify structures frequently involved in the inflammatory process. Most damaged tracts were the superior cerebellar peduncle and the transverse fibers of the pons. Most frequently affected nuclei were the vestibular nuclei, the trigeminal tract, the facial nerve and the solitary tract. Conclusion Combination of FGATIR and PD/T2w sequences opened prospects to define MS elective injury in brainstem tracts and nuclei, with particular lesion features suggesting variations of the inflammatory process within brainstem structures. In a further study, hypersignal quantification and microstructure information should be evaluated using relaxometry and diffusion tractography. Technical improvements would bring novel parameters to train an artificial neural network for accurate automated labeling of MS lesions within the brainstem.

Vestibular CCK neurons drive motion-induced malaise

ABSTRACTPassive motion can induce kinetosis (motion sickness, MS) in susceptible individuals. MS is an evolutionary conserved mechanism caused by mismatches between motion-related sensory information and past visual and motion memory, triggering a malaise accompanied by hypolocomotion, hypothermia, hypophagia and aversion to novel foods presented coincidentally. Vestibular nuclei (VN) are critical for the processing of movement input, and motion-induced activation of VN neurons recapitulates MS-related signs. However, the genetic identity of VN neurons mediating MS-related autonomic and aversive responses remains unknown. Here, we identify a glutamatergic vestibular circuitry necessary to elicit MS-related behavioral responses, defining a central role of cholecystokinin (CCK)- expressing glutamatergic VN neurons in vestibular-induced malaise. Moreover, we show that CCK VN inputs onto the parabrachial nucleus activate Calca-expressing neurons and are sufficient to establish hypothermia and aversion to novel food. Together, we provide novel insight into the neurobiological regulation of MS, unravelling key genetically defined neural substrates for kinetosis.

CENTRAL VERTIGO

Central vertigo is a symptom characterized by a feeling of changes in body position or environment as a result of diseases originating from the central nervous system. Central vertigo is caused by a disease that extend from vestibular nuclei in medulla oblongata to ocular motor nuclei and integration system in mesencephalon to vestibulocerebellum, thalamus and vestibular cortex in temporoparietal and the neuronal pathway which mediate VOR (vestibulo-ocular reflex). The diseases can be vestibular migrain, TIA (Transient Ischemic Attack), Vertebrobasilar ischemic stroke, multiple sclerosis, tumor in cerebelopontine angle and congenital malformation like Dandy Walker Syndrome. Central vertigo can be diagnosed by performing several special tests. This examination can also distinguish central vertigo from its differential diagnosis, namely peripheral vertigo. Management of central vertigo can be in the form of acute attack management and specific management according to the cause.

An Integrated Perspective of Evolution and Development: From Genes to Function to Ear, Lateral Line and Electroreception

Four sensory systems (vestibular, lateral line, electroreception, auditory) are unique and project exclusively to the brainstem of vertebrates. All sensory neurons depend on a common set of genes (Eya1, Sox2, Neurog1, Neurod1) that project to a dorsal nucleus and an intermediate nucleus, which differentiate into the vestibular ear, lateral line and electroreception in vertebrates. In tetrapods, a loss of two sensory systems (lateral line, electroreception) leads to the development of a unique ear and auditory system in amniotes. Lmx1a/b, Gdf7, Wnt1/3a, BMP4/7 and Atoh1 define the lateral line, electroreception and auditory nuclei. In contrast, vestibular nuclei depend on Neurog1/2, Ascl1, Ptf1a and Olig3, among others, to develop an independent origin of the vestibular nuclei. A common origin of hair cells depends on Eya1, Sox2 and Atoh1, which generate the mechanosensory cells. Several proteins define the polarity of hair cells in the ear and lateral line. A unique connection of stereocilia requires CDH23 and PCDH15 for connections and TMC1/2 proteins to perceive mechanosensory input. Electroreception has no polarity, and a different system is used to drive electroreceptors. All hair cells function by excitation via ribbons to activate neurons that innervate the distinct target areas. An integrated perspective is presented to understand the gain and loss of different sensory systems.

Differences in the Structure and Function of the Vestibular Efferent System Among Vertebrates

The role of the mammalian vestibular efferent system in everyday life has been a long-standing mystery. In contrast to what has been reported in lower vertebrate classes, the mammalian vestibular efferent system does not appear to relay inputs from other sensory modalities to the vestibular periphery. Furthermore, to date, the available evidence indicates that the mammalian vestibular efferent system does not relay motor-related signals to the vestibular periphery to modulate sensory coding of the voluntary self-motion generated during natural behaviors. Indeed, our recent neurophysiological studies have provided insight into how the peripheral vestibular system transmits head movement-related information to the brain in a context independent manner. The integration of vestibular and extra-vestibular information instead only occurs at next stage of the mammalian vestibular system, at the level of the vestibular nuclei. The question thus arises: what is the physiological role of the vestibular efferent system in mammals? We suggest that the mammalian vestibular efferent system does not play a significant role in short-term modulation of afferent coding, but instead plays a vital role over a longer time course, for example in calibrating and protecting the functional efficacy of vestibular circuits during development and aging in a role analogous the auditory efferent system.

Parasitic encephalitis caused by Stephanurus dentatus in a pig in Brazil

A pig was in left lateral recumbency with limb spasticity, accentuated prostration, and strabismus, and was euthanized. During autopsy, yellowing of the leptomeninges at the ventral pons to medulla oblongata was noted. In the cerebellar peduncles, there was a focally extensive black-to-yellow area at the level of the vestibular nuclei. Histologic examination revealed a cross-section of a nematode larva, consistent with Stephanurus dentatus, bordered by edema and marked infiltration of mononuclear cells, plasma cells, and a few eosinophils. Vacuolation of the neuropil, with rare gitter cells and axonal spheroids, was also observed. We diagnosed parasitic encephalitis caused by S. dentatus migration based on the pathology findings and characterization of the parasite.