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Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.

Many COVID-19 patients are presenting with atypical clinical features. Happy hypoxemia with almost normal breathing, anosmia in the absence of rhinitis or nasal obstruction, and ageusia are some of the reported atypical clinical findings. Based on the clinical manifestations of the disease, we are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of the nucleus tractus solitarius may be the reason for happy hypoxemia in COVID-19 patients.

Herpes zoster oticus (Ramsay Hunt Syndrome) is characterized by facial nerve paralysis, ear pain and auricular skin rash. It occurs as a result of reactivation oflatent varicella zoster virus infection in the geniculate ganglion of the facial nerve. Major clinical symptoms include 7th nerve paralysis or cranial nerve paralysis and vesicles along the nerve with cocomitant ear pain. Other cranial nerve involvement although uncommon, can be found in some cases. In this study, a 74-year-old female patient had ipsilateral 8th, 9th and 10th cranial nerves injury. Cranial nerve paralysis accompanied with injury has been repor ted in R amsay Hunt Syndrome.

We carried out a clinical and epidemiological study of adult patients with varicella-zoster virus central nervous system infection diagnosed by PCR in cerebrospinal fluid. Twenty-six patients were included. Twelve (46.2 %) patients were diagnosed with meningitis and fourteen (53.8 %) with meningoencephalitis. Twelve (46.2 %) had cranial nerves involvement (mainly the facial (VII) and vestibulocochlear (VIII) nerves), six (23.1 %) had cerebellar involvement, fourteen (53.8 %) had rash, and four (15.4 %) developed Ramsay Hunt syndrome. Three (11.5 %) patients had sequelae. Length of stay was significantly lower in patients diagnosed with meningitis and treatment with acyclovir was more frequent in patients diagnosed with meningoencephalitis. We believe routine detection of varicella-zoster virus, regardless of the presence of rash, is important because the patient may benefit from a different clinical management.

Enterovirus 71 (EV71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, motor trigeminal nucleus, reticular formation, and facial nucleus; viral titers were significantly higher in the brainstem than in the spinal cord samples. Mice given preinfection hyperimmune serum showed a marked reduction of ipsilateral viral antigen/RNA and viral titers in the brainstem in a dose-dependent manner. With optimum hyperimmune serum given after infection, brainstem infection was significantly reduced in a time-dependent manner. A delay in disease onset and a reduction of disease severity and mortality were also observed. Thus, EV71 can directly infect the brainstem, including the medulla, via cranial nerves, most likely by retrograde axonal transport. This may explain the sudden cardiorespiratory collapse in human patients with fatal encephalomyelitis. Moreover, our results suggest that passive immunization may still benefit EV71-infected patients who have neurologic complications.

Neurodegenerative diseases are associated with neuronal inclusions, comprised of protein aggregates. In Alzheimer's Disease (AD) and Lewy Body Disease (LBD) such lesions are distributed in a hierarchical retrograde transynaptic spatial pattern. This implies a retrograde transynaptic temporal propagation as well. There can be few explanations for this other than infectious agents (prions and viruses). This suggests that AD and LBD (at least) may have infectious origins. Transynaptic infiltration of the CNS along cranial nerve or other major projections, by one or more infectious agents has important implications. The clinical syndrome and natural history of each neurodegenerative disorder will reflect its portal of entry. There may be a different neurodegenerative syndrome for each cranial nerve or other portal of entry, and not all may manifest as "dementia". Each syndrome may be associated with more than one pathological lesion. Each pathology may be associated with several clinical syndromes. Host-parasite interactions are species specific. This may explain the rarity of AD-like pathology in most other older mammals. Over evolutionary timescales, the human brain should be adapted to predation by neurotropic agents. Viewed from this perspective, the prion-like pro-inflammatory and pro-apoptotic properties of β-amyloid and other proteins may be adaptive, and anti-microbial. Reductions in synaptic density may slow the progress of invading pathogens, while perineuronal nets and other structures may guard the gates. This suggests a defense in depth of a structure, the brain, that is inherently vulnerable to invasion along its neural networks., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Reactivation of the varicella-zoster virus (VZV) along the sensory nerves innervating the ear, including the geniculate ganglion, is responsible for herpes zoster oticus (HZO). In some cases, HZO is associated with polyneuropathy of the cranial nerves, although the mechanism of this involvement is not known. To explain this phenomenon and based on some clinical considerations, the present authors hypothesize an intersynaptic spread of VZV along the reflex pathways of the brainstem., (Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Despite vaccination, varicella-zoster virus (VZV) remains an important pathogen. We investigated VZV latency in autopsy specimens from vaccinees, in gastrointestinal tissue removed surgically, and in a guinea pig model. We propose that retrograde transport from infected skin and viremia deliver VZV to neurons in which it becomes latent. Wild type (WT) VZV was found to be latent in many ganglia of vaccinated children with no history of varicella, suggesting that subclinical infection with WT-VZV occurs with subsequent viremic dissemination. The 30% to 40% rate of WT-VZV zoster reported in vaccinees and occasional trigeminal zoster due to vaccine type VZV (vOka) are consistent with viremic delivery of VZV to multiple ganglia. Most human intestinal specimens contained latent VZV within neurons of the enteric nervous system (ENS). Induction of viremia in guinea pigs led to VZV latency throughout the ENS. The possibility VZV reactivation in the ENS is an unsuspected cause of gastrointestinal disease requires future investigation.

Background: Infection with human herpesvirus 7 (HHV-7) generally results in a febrile illness with accompanying exanthema subitum., Objectives: To ascertain and describe the role of HHV-7 in a case of acute myeloradiculoneuropathy., Patient: A previously healthy young man with complaints of motor weakness, dysphasia, and nasal voice., Methods: Serological examinations were performed with the patient's serum. We also examined virus genome DNA in cerebrospinal fluid by regular and real-time polymerase chain reaction. Moreover, we checked the antiganglioside antibody level in the patient's serum samples by the immunoblot analysis., Results: Serological studies revealed significant change in titers of antibodies against cytomegalovirus, Epstein-Barr virus, and HHV-7, but only HHV-7 genome was detected in the cerebrospinal fluid, with its disappearance after therapy. No antiganglioside antibody was detected in the patient's serum., Conclusion: The unique clinical picture of the present patient might be closely related to the reactivation of HHV-7 in the nervous system.

Nipah virus, a newly emerged zoonotic paramyxovirus, infects a number of species. Human infections were linked to direct contact with pigs, specifically with their body fluids. Clinical signs in human cases indicated primarily involvement of the central nervous system, while in pigs the respiratory system was considered the primary virus target, with only rare involvement of the central nervous system. Eleven 5-week-old piglets were infected intranasally, orally, and ocularly with 2.5 x 10(5) PFU of Nipah virus per animal and euthanized between 3 and 8 days postinoculation. Nipah virus caused neurological signs in two out of eleven inoculated pigs. The rest of the pigs remained clinically healthy. Virus was detected in the respiratory system (turbinates, nasopharynx, trachea, bronchus, and lung in titers up to 10(5.3) PFU/g) and in the lymphoreticular system (endothelial cells of blood and lymphatic vessels, submandibular and bronchiolar lymph nodes, tonsil, and spleen with titers up to 10(6) PFU/g). Virus presence was confirmed in the nervous system of both sick and apparently healthy animals (cranial nerves, trigeminal ganglion, brain, and cerebrospinal fluid, with titers up to 10(7.7) PFU/g of tissue). Nipah virus distribution was confirmed by immunohistochemistry. The study presents novel findings indicating that Nipah virus invaded the central nervous system of the porcine host via cranial nerves as well as by crossing the blood-brain barrier after initial virus replication in the upper respiratory tract.

The etiology of idiopathic cranial nerve palsies often remains unresolved. It has been hypothesised that viral reactivation of herpesviruses in the corresponding nuclei in the brainstem is the cause. We investigated the distribution of herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) in nuclei that are associated with peripheral sensory ganglia [oculomotor (nIII), facial (nVII) nuclei] and in nuclei that are not associated with peripheral sensory ganglia [trochlear (nIV), abducens (nVI), and hypoglossal (nXII) nuclei] of five human brainstems. Samples of the cranial nerve nuclei and adjacent control tissue were taken from histological sections after precise identification of every single nucleus and control tissue. DNA and RNA amplification methods were used to determine the prevalence and distribution of HSV-1 and VZV. The distribution of human herpes virus type 6 (HHV-6) was also determined and served as a control, since HHV-6 infection has never been associated with idiopathic cranial nerve palsies. HSV-1 was distributed at random in all cranial nerve nuclei and control tissue, whereas VZV DNA was not detected in any of the samples examined. Surprisingly, HHV-6 was present in almost all samples where HSV-1 was also present, however, the latency associated transcript (LAT) of HSV-1 was not found in any of the samples positive for HSV-1 DNA. The absence of LAT in the samples positive for HSV-1 and the distribution of HSV-1 and HHV-6 do not support the hypothesis that idiopathic cranial nerve palsies result from viral reactivation in the brainstem nuclei.

A susceptible individual exposed to herpes simplex virus (HSV) will develop latent infection in multiple cranial nerve ganglia. There are a few quantitative studies of the viral load within the trigeminal ganglion, but none that investigate other cranial nerve ganglia. In this study, human trigeminal, geniculate, vestibular (Scarpa's) and cochlear (spiral) ganglia were obtained from willed body donors. Real time quantitative polymerase chain reaction (PCR) analysis of the HSV DNA polymerase gene was performed on ipsilateral ganglion sets from the same individual. Viral load, expressed as HSV genomes per 105 cells, was significantly greater in the vestibular ganglion (mean +/- SD, 176705 +/- 255916) than in the geniculate (9948 +/- 22066), cochlear (3527 +/- 9360), or trigeminal (2017 +/- 5578) ganglia. There was not a significant correlation among ganglia from the same individual. The results support the hypothesis that neuronal subpopulations have variable susceptibility to HSV infection.

An experimental transmission study aimed at fulfilling Koch's postulates for a herpesvirus-associated stomatitis-rhinitis in Mediterranean tortoises is presented. Clinical, pathologic, serologic, and molecular studies were performed linking tortoise herpesvirus with the pathogenesis of stomatitis-rhinitis. Four adult Greek tortoises received either intranasally or intramuscularly two tortoise herpesvirus isolates by primary experimental infection and secondary challenge 11 months later. After the primary experimental infection and the secondary challenge, clinical signs of illness developed, which included conjunctivitis, diphtheritic oral plaques, and oral discharge. At 4 weeks after the secondary challenge, all tortoises were humanely euthanatized and evaluated. Although neutralizing antibodies developed after the primary experimental infection, they apparently did not prevent the later development of recurrent clinical signs. Polymerase chain reaction (PCR) and reverse transcription-PCR analyses allowed sensitive characterization of the systemic distribution of the herpesvirus DNA sequences and their presence in the cranial nerves and brains of the infected tortoises. Despite the failure to recover the herpesviruses used in the transmission study, the findings support the premise that tortoise herpes-virus is a primary pathogen of Greek tortoises.

Ramsay Hunt syndrome is characterized by facial nerve paralysis, herpetic vesicles in or around the ear and pain often associated with vestibulocochlear nerve involvement. It is thought to be a cranial polyneuropathy caused by the herpes zoster virus. We present an extreme and unusual variant of this disease with involvement of VIIth, VIIIth, Xth, XIth and XIIth cranial nerves as well as C2-4 sensory dermatomes and profound systemic upset which caused some diagnostic uncertainty.

A detailed history and the results of the physical examination of seven patients with unusual and not typical Guillain-Barré syndrome were described. The patients presented various levels of lesions and some signs and symptoms were not typical of classic clinical features. The variety of the clinical picture suggests the damage of nervous system in many places and at various levels, not only in the peripheral nerves, but also in the central nervous system. The heterogeneity of aetiology and aetiopathogenesis and immunological individual patient's reaction probably is the cause of the involvement of different structures.

Varicella-zoster virus has been associated with a variety of neurological manifestations. We describe a patient with the Ramsay Hunt Syndrome who developed a contralateral cerebral infarction.