Schwannomas of the trochlear nerve are relatively rare, and most patients present with preoperative diplopia because of trochlear nerve palsy. We describe the case of a 61-year-old male patient with a trochlear nerve schwannoma and no pre- and postoperative diplopia, despite his trochlear nerve being cut during the operation. We aimed to investigate the frequency of postoperative diplopia associated with intraoperative trochlear nerve disturbance by reviewing previous case reports, wherein postoperative diplopia did not occur after the trochlear nerve was cut intraoperatively. We recorded the frequency of diplopia because of intraoperative trochlear nerve disturbance, such as the trochlear nerve being cut, in cases without pre- and postoperative diplopia. We searched the PubMed, Medline, and Google Scholar databases for works published from 1976 to 2020 and followed the preferred reporting items for systematic reviews and meta-analyses guidelines. We reviewed 36 publications and found 92 cases of trochlear nerve schwannoma. Surgical resection was performed for 43 patients, of whom 40 were kept under observation and 9 were treated with radiation therapy. Of the 43 cases, 9 without preoperative diplopia underwent gross total resection. We analyzed ten cases (including ours) without preoperative diplopia to check for postoperative diplopia. In total, four cases, including ours, did not display postoperative diplopia despite the trochlear nerve being cut. This may be attributed to the preoperatively acquired motor and sensory fusion in the patient's vision because of tumor progression. Our findings may benefit neurosurgeons who treat patients with schwannomas and help them predict patients' outcomes.

During spaceflight and immediately after it, adaptive neuroplastic changes occur in the sensorimotor structures of the central nervous system, which are associated with changes of mainly vestibular and visual signals. It is known that the movement of the eyeball in the vertical direction is carried out by muscles that are innervated by the trochlear nerve (CN IV) and the oculomotor nerve (CN III). To elucidate the cellular processes underlying the atypical vertical nystagmus that occurs under microgravity conditions, it seems necessary to study the state of these nuclei in animals in more detail after prolonged space flights. We carried out a qualitative and quantitative light-optical and ultrastructural analysis of the nuclei of the trochlear nerve in mice after a 30-day flight on the Bion-M1 biosatellite. As a result, it was shown that the dendrites of motoneurons in the nucleus of the trochlear nerve significantly reorganized their geometry and orientation under microgravity conditions. The number of dendritic branches was increased, possibly in order to amplify the reduced signal flow. To ensure such plastic changes, the number and size of mitochondria in the soma of motoneurons and in axons coming from the vestibular structures increased. Thus, the main role in the adaptation of the trochlear nucleus to microgravity conditions, apparently, belongs to the dendrites of motoneurons, which rearrange their structure and function to enhance the flow of sensory information. These results complement our knowledge of the causes of atypical nystagmus in microgravity.

The involvement of cranial nerves is being increasingly recognised in COVID-19. This review aims to summarize and discuss the recent advances concerning the clinical presentation, pathophysiology, diagnosis, treatment, and outcomes of SARS-CoV-2 associated cranial nerve mononeuropathies or polyneuropathies. Therefore, a systematic review of articles from PubMed and Google Scholar was conducted. Altogether 36 articles regarding SARS-CoV-2 associated neuropathy of cranial nerves describing 56 patients were retrieved. Out of these 56 patients, cranial nerves were compromised without the involvement of peripheral nerves in 32 of the patients, while Guillain-Barre syndrome (GBS) with cranial nerve involvement was described in 24 patients. A single cranial nerve was involved either unilaterally or bilaterally in 36 patients, while in 19 patients multiple cranial nerves were involved. Bilateral involvement was more prevalent in the GBS group (n=11) as compared to the cohort with isolated cranial nerve involvement (n=5). Treatment of cranial nerve neuropathy included steroids (n=18), intravenous immunoglobulins (IVIG) (n=18), acyclovir/valacyclovir (n=3), and plasma exchange (n=1). The outcome was classified as "complete recovery" in 21 patients and as "partial recovery" in 30 patients. One patient had a lethal outcome. In conclusion, any cranial nerve can be involved in COVID-19, but cranial nerves VII, VI, and III are the most frequently affected. The involvement of cranial nerves in COVID-19 may or may not be associated with GBS. In patients with cranial nerve involvement, COVID-19 infections are usually mild. Isolated cranial nerve palsy without GBS usually responds favorably to steroids. Cranial nerve involvement with GBS benefits from IVIG.

To spatially and temporally define ocular motor nerve development in the presence and absence of extraocular muscles (EOMs).

There is increasing evidence of both central and peripheral nervous system (PNS) involvement in COVID-19. We conducted this systematic literature review to investigate the characteristics, management and outcomes of patients with PNS, including the types and severity of cranial nerves (CN) involvement. We systematically searched on PubMed for studies reporting adult patients diagnosed with COVID-19 and PNS involvement until July 2021. From 1670 records, 225 articles matched the inclusion criteria, with a total of 1320 neurological events, in 1004 patients. There were 805 (61%) CN, 350 (26.5%) PNS, and 165 (12.5%) PNS plus CN events. The most frequently involved CN were the facial, vestibulo-cochlear and olfactory nerve in 27.3%, 25.4% and 16.1%, respectively. Guillain-Barre syndrome spectrum was identified in 84.2% of PNS events. We analysed 328 patients reported in 225 articles with CN, PNS, and PNS plus CN involvement. The patients with CN involvement were younger (mean age 46.2±17.1, p = .003), and were more frequently treated as outpatients (p < .001), mostly with glucocorticoids (p < .001). Patients that had PNS with or without CN involvement were more likely to be hospitalized (p < .001), and to receive intravenous immunoglobulins (p = .002) or plasma exchange (p = .002). Patients with CN, PNS, and PNS plus CN had severe COVID -19 disease in 24.8%, 37.3%, 34.9% respectively. The most common neurological outcome was mild/moderate sequelae in patients with CN, PNS, and PNS plus CN in 54.7%, 67.5% and 67.8% respectively (p = .1) and no significant difference was found between the three categories regarding death, disease severity, time from disease onset to neurological symptoms, lack of improvement and complete recovery. CN involvement was the most frequent PNS finding. All three categories of PNS involvement were rather associated to non-severe COVID-19 but it may be an important cause of hospitalization and post COVID-19 sequelae.

Dynein, the retrograde motor protein, is essential for the transport of cargo along axons and proximal dendrites in neurons. The dynein heavy chain mutation Loa has been reported to cause degeneration of spinal motor neurons, as well as defects of spinal sensory proprioceptive neurons, but cranial nerve nuclei have received little attention. Here, we examined the number and morphology of neurons in cranial nerve nuclei of young, adult, and aged heterozygous Loa mice, with a focus on the trigeminal, facial, and trochlear motor nuclei, as well as the proprioceptive mesencephalic trigeminal nucleus. By using stereological counting techniques, we report a slowly progressive and significant reduction, to 75% of wild-type controls, in the number of large trigeminal motoneurons, whereas normal numbers were found for sensory mesencephalic trigeminal, facial, and trochlear motoneurons. The morphology of many surviving large trigeminal motoneurons was substantially altered, in particular the size and length of perpendicularly extending primary dendrites, but not those of facial or trochlear motoneurons. At the ultrastructural level, proximal dendrites of large trigeminal motoneurons, but not other neurons, were significantly depleted in organelle content such as polyribosomes and showed abnormal (vesiculated) mitochondria. These data indicate primary defects in trigeminal α-motoneurons more than γ-motoneurons. Our findings expand the Loa heterozygote phenotype in two important ways: we reveal dendritic in addition to axonal defects or abnormalities, and we identify the Loa mutation as a mouse model for mixed motor-sensory loss when the entire neuraxis is considered, rather than a model primarily for sensory loss.

Different somatic motor neuron subpopulations show a differential vulnerability to degeneration in diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy and spinobulbar muscular atrophy. Studies in mutant superoxide dismutase 1 over-expressing amyotrophic lateral sclerosis model mice indicate that initiation of disease is intrinsic to motor neurons, while progression is promoted by astrocytes and microglia. Therefore, analysis of the normal transcriptional profile of motor neurons displaying differential vulnerability to degeneration in motor neuron disease could give important clues to the mechanisms of relative vulnerability. Global gene expression profiling of motor neurons isolated by laser capture microdissection from three anatomical nuclei of the normal rat, oculomotor/trochlear (cranial nerve 3/4), hypoglossal (cranial nerve 12) and lateral motor column of the cervical spinal cord, displaying differential vulnerability to degeneration in motor neuron disorders, identified enriched transcripts for each neuronal subpopulation. There were striking differences in the regulation of genes involved in endoplasmatic reticulum and mitochondrial function, ubiquitination, apoptosis regulation, nitrogen metabolism, calcium regulation, transport, growth and RNA processing; cellular pathways that have been implicated in motor neuron diseases. Confirmation of genes of immediate biological interest identified differential localization of insulin-like growth factor II, guanine deaminase, peripherin, early growth response 1, soluble guanylate cyclase 1A3 and placental growth factor protein. Furthermore, the cranial nerve 3/4-restricted genes insulin-like growth factor II and guanine deaminase protected spinal motor neurons from glutamate-induced toxicity (P < 0.001, ANOVA), indicating that our approach can identify factors that protect or make neurons more susceptible to degeneration.

COVID-19 is caused by the coronavirus SARS-CoV-2 that has an affinity for neural tissue. There are reports of encephalitis, encephalopathy, cranial neuropathy, Guillain-Barrè syndrome, and myositis/rhabdomyolysis in patients with COVID-19. In this review, we focused on the neuromuscular manifestations of SARS-CoV-2 infection. We analyzed all published reports on SARS-CoV-2-related peripheral nerve, neuromuscular junction, muscle, and cranial nerve disorders. Olfactory and gustatory dysfunction is now accepted as an early manifestation of COVID-19 infection. Inflammation, edema, and axonal damage of olfactory bulb have been shown in autopsy of patients who died of COVID-19. Olfactory pathway is suggested as a portal of entry of SARS-CoV-2 in the brain. Similar to involvement of olfactory bulb, isolated oculomotor, trochlear and facial nerve has been described. Increasing reports Guillain-Barrè syndrome secondary to COVID-19 are being published. Unlike typical GBS, most of COVID-19-related GBS were elderly, had concomitant pneumonia or ARDS, more prevalent demyelinating neuropathy, and relatively poor outcome. Myalgia is described among the common symptoms of COVID-19 after fever, cough, and sore throat. Duration of myalgia may be related to the severity of COVID-19 disease. Few patients had muscle weakness and elevated creatine kinase along with elevated levels of acute-phase reactants. All these patients with myositis/rhabdomyolysis had severe respiratory complications related to COVID-19. A handful of patients with myasthenia gravis showed exacerbation of their disease after acquiring COVID-19 disease. Most of these patients recovered with either intravenous immunoglobulins or steroids.

Protocadherin 9 (Pcdh9) is a member of the protocadherin family, which includes many members involved in various phenomena, such as cell-cell adhesion, neural projection, and synapse formation. Here, we identified Pcdh9 protein in the mouse brain and examined its distribution during neural development. Pcdh9, with a molecular weight of approximately 180 kDa, was localized at cell-cell contact sites in COS-1 cells transfected with Pcdh9 cDNA. In cultured neurons, it was detected at the growth cone and at adhesion sites along neurites. In the E13.5 brain, prominent Pcdh9 immunoreactivity was detected in the dorsal thalamus along with other regions including the vestibulocochlear nerve. As development proceeded (E15.5-P1), Pcdh9 immunoreactivity became observable in various brain regions but was restricted to certain fiber tracts and brain nuclei. Interestingly, many Pcdh9-positive brain nuclei and fascicles belonged to the vestibular (e.g. vestibulocochlear nerve, vestibular nuclei, and the vestibulocerebellum) and oculomotor systems (medial longitudinal fascicles, oculomotor nucleus, trochlear nucleus, and interstitial nucleus of Cajal). In addition, we examined the distribution of Pcdh9 protein in the olfactory bulb, retina, spinal cord, and dorsal root ganglion. In these regions, Pcdh9 and OL-protocadherin proteins were differentially distributed, with the difference highlighted in the olfactory bulb, where they were enriched in different subsets of glomeruli. In the mature retina, Pcdh9 immunoreactivity was detected in distinct sublaminae of the inner and outer plexiform layers. In the dorsal root ganglion, only certain subsets of neurons showed Pcdh9 immunoreactivity. These results suggest that Pcdh9 might be involved in formation of specific neural circuits during neural development.

Extraocular motoneurons resist degeneration in diseases such as amyotrophic lateral sclerosis. The main objective of the present work was to characterize the presence of neurotrophins in extraocular motoneurons and muscles of the adult rat. We also compared these results with those obtained from other cranial motor systems, such as facial and hypoglossal, which indeed suffer neurodegeneration. Immunocytochemical analysis was used to describe the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in oculomotor, trochlear, abducens, facial, and hypoglossal nuclei of adult rats, and Western blots were used to describe the presence of neurotrophins in extraocular, facial (buccinator), and tongue muscles, which are innervated by the above-mentioned motoneurons. In brainstem samples, brain-derived neurotrophic factor was present both in extraocular and facial motoneuron somata, and to a lesser degree, in hypoglossal motoneurons. Neurotrophin-3 was present in extraocular motor nuclei, while facial and hypoglossal motoneurons were almost devoid of this protein. Finally, nerve growth factor was not present in the soma of any group of motoneurons, although it was present in dendrites of motoneurons located in the neuropil. Neuropil optical density levels were higher in extraocular motoneuron nuclei when compared with facial and hypoglossal nuclei. Neurotrophins could be originated in target muscles, since Western blot analyses revealed the presence of the three molecules in all sampled muscles, to a larger extent in extraocular muscles when compared with facial and tongue muscles. We suggest that the different neurotrophin availability could be related to the particular resistance of extraocular motoneurons to neurodegeneration.

The variegated pelage and social complexity of the African wild dog (Lycaon pictus) hint at the possibility of specializations of the visual system. Here, using a range of architectural and immunohistochemical stains, we describe the systems-level organization of the image-forming, nonimage forming, oculomotor, and accessory optic, vision-associated systems in the brain of one representative individual of the African wild dog. For all of these systems, the organization, in terms of location, parcellation and topology (internal and external), is very similar to that reported in other carnivores. The image-forming visual system consists of the superior colliculus, visual dorsal thalamus (dorsal lateral geniculate nucleus, pulvinar and lateral posterior nucleus) and visual cortex (occipital, parietal, suprasylvian, temporal and splenial visual regions). The nonimage forming visual system comprises the suprachiasmatic nucleus, ventral lateral geniculate nucleus, pretectal nuclear complex and the Edinger-Westphal nucleus. The oculomotor system incorporates the oculomotor, trochlear and abducens cranial nerve nuclei as well as the parabigeminal nucleus, while the accessory optic system includes the dorsal, lateral and medial terminal nuclei. The extent of similarity to other carnivores in the systems-level organization of these systems indicates that the manner in which these systems process visual information is likely to be consistent with that found, for example, in the well-studied domestic cat. It would appear that the sociality of the African wild dog is dependent upon the processing of information extracted from the visual system in the higher-order cognitive and affective neural systems.

Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system and transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP, it is critical to identify the regions within the brainstem that process CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3)H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe nucleus, gracile nucleus, spinal trigeminal nucleus, and spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear nucleus, dorsal raphe nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens nucleus, and motor trigeminal nucleus; protein coexpression of CLR and RAMP1 was observed in these areas via immunofluorescence. [(3)H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that drugs inhibiting CGRP signaling may not be able to penetrate the central nervous system to antagonize receptors in these brain regions.