Clinical neurophysiology and cerebrospinal liquor analysis to detect Guillain-Barré syndrome and polyneuritis cranialis in COVID-19 patients: A case series.

We report a case series of five patients affected by SARS-CoV-2 who developed neurological symptoms, mainly expressing as polyradiculoneuritis and cranial polyneuritis in the 2 months of COVID-19 pandemic in a city in the northeast of Italy. A diagnosis of Guillain-Barré syndrome was made on the basis of clinical presentation, cerebrospinal fluid analysis, and electroneurography. In four of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 g/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases a significant decrease in amplitude of compound motor action potential compound muscle action potential (cMAP). Four patients presented a mild facial nerve involvement limited to the muscles of the lower face, with sparing of the forehead muscles associated to ageusia. In one patient, taste assessment showed right-sided ageusia of the tongue, ipsilateral to the mild facial palsy. In three patients we observed albuminocytological dissociation in the cerebrospinal fluid, and notably, we found an increase of inflammatory mediators such as the interleukin-8. Peripheral nervous system involvement after infection with COVID-19 is possible and may include several signs that may be successfully treated with immunoglobulin therapy.

Assay for improved detection of antigen-specific immune cells from extrasanguinous fluids.

In this approach, pre-stained cells from extrasanguinous fluids (ESFs) are stimulated in the presence of blood from the same individual. Thus, blood-derived antigen-presenting cells enable stimulation of both ESF- and blood T cells. Pre-staining allows distinction of T cells from ESF and blood, and simultaneous analysis of antigen-specific T cells in both compartments.

Alarmins and central nervous system inflammation in HIV-associated neurological disorders.

In the era of highly active antiretroviral therapy (HAART), HIV-1-associated neurocognitive disorders (HAND) persist in infected individuals with adequate immunological and virological status. Risk factors for cognitive impairment include hepatitis C virus co-infection, host genetic factors predisposing to HAND, the early establishment of the virus in the CNS and its persistence under HAART; thus, the CNS is an important reservoir for HIV. Microglial cells are permissive to HIV-1, and NLRP3 inflammasome-associated genes were found expressed in brains of HIV-1-infected persons, contributing to brain disease. Inflammasomes can be triggered by alarmins or danger-associated molecular patterns (DAMPs), which directly stimulate the production of proinflammatory mediators by glial cells, contribute to blood-brain barrier injury through induction of release of various proteases and allow the passage of infected macrophages, and trigger IL-1ß release from primed cells. Amongst alarmins involved in HIV-1-induced neuropathogenesis, IL-33 and high-mobility group box 1 (HMGB1) are of particular interest. Neurocognitive alterations were recently associated with dysregulation of the IL-33/ST2 axis in the CNS, leading to the induction of neuronal apoptosis, decrease in synaptic function and neuroinflammation. Specific biomarkers, including HMGB1 and anti-HMGB1 antibodies, have been identified in cerebrospinal fluid from patients with HAND, correlated with immune activation and identifying a very early stage of neurocognitive impairment that precedes changes in metabolites detected by magnetic resonance spectroscopy. Moreover, HMGB1 plays a crucial role in HIV-1 persistence in dendritic cells and in the constitution of viral reservoirs. In this review, the mechanisms whereby alarmins contribute to HIV-1-induced CNS inflammation and neuropathogenesis will be discussed.

Novel avian bornavirus in a nonpsittacine species (Canary; Serinus canaria) with enteric ganglioneuritis and encephalitis.

A canary bird (Serinus canaria) died with nonsuppurative ganglioneuritis of the proventriculus and gizzard and encephalitis, lesions comparable to proventricular dilatation disease (PDD) of psittacine birds. Recently, several genotypes of a novel avian bornavirus have been linked to PDD. In the canary, bornaviral antigen was detected by immunohistochemistry in both neural and extraneural tissues. The widespread viral dissemination was confirmed by reverse transcription-PCR. Sequence analysis revealed a unique genotype of avian bornavirus. This observation suggests that bornaviruses are natural pathogens of several avian species and that the family Bornaviridae comprises more viral genotypes (or viral species) than previously assumed.

Polyneuritis cranialis and vasculopathy caused by varicella zoster virus without rash.

The neurological disorders caused by Varicella Zoster Virus (VZV) in the absence of skin rash are a challenge to the clinician. The presentation varies from acute to subacute to chronic. Reactivation of VZV usually produces zoster (shingles), meningitis or meningoencephalitis, cerebellitis, isolated or multiple cranial nerve palsies (polyneuritis cranialis), myelitis, and vasculopathy. In our case, we report a 41-year-old female presented with right oculomotor, vestibulocochlear and facial neuropathies occurred 1 year before admission and making the diagnosis. There were no skin or mucosa lesions. Magnetic Resonance Imaging revealed multiple subcortical infractions in the right temporal and occipital lobes which consist with silent vasculopathy. The diagnosis was confirmed by the existence of anti-VZV IgG in cerebrospinal fluid (CSF).

Purification of a herpes-like virus from abalone (Haliotis spp.) with ganglioneuritis and detection by transmission electron microscopy.

A herpes-like virus was for the first time purified from abalone diagnosed with ganglioneuritis. Pleuropedal ganglia, pedal nerve cords, head and epipodial tissue was collected and homogenized from abalone populations exhibiting high mortality and clinical signs consistent with herpes-virus like ganglioneuritis. Following ultracentrifugation by sucrose gradient prepared in sea-water, the purified virus was negatively stained and examined under a transmission electron microscope. Virus particles were observed to have an icosahedral capsid appearance surrounded by an envelope with numerous spikes on the external surface. The capsid ranged 92-109 nm in diameter and the enveloped virus was approximately 150 nm in diameter. Virus particles were found mainly at the interface of 40-50% sucrose gradients, and a few presented at the interface of 50-60% sucrose gradients. Isopycnic gradient centrifugation was performed in a potassium tartrate gradient and caesium chloride gradient, where the buoyant density of the herpes-like virus was determined to be 1.17-1.18 g/mL. The use of sea-water as the buffer in preparation of the gradient was critical in the preliminary purification of the herpes-like virus, and more efficient harvesting of the virus was achieved by sucrose and potassium tartrate gradients than caesium chloride gradient. The described method, whilst proving successful for purifying a herpes-like virus from abalone, may also be applicable to other viruses from marine animals.

Avian Ganglioneuritis in Clinical Practice.

Avian ganglioneuritis (AG) comprises one of the most intricate pathologies in avian medicine and is researched worldwide. Avian bornavirus (ABV) has been shown to be a causative agent of proventricular dilatation disease in birds. The avian Bornaviridae represent a genetically diverse group of viruses that are widely distributed in captive and wild populations around the world. ABV and other infective agents are implicated as a cause of the autoimmune pathology that leads to AG, similar to human Guillain Barrè syndrome. Management of affected birds is beneficial and currently centered at reducing neurologic inflammation, managing secondary complications, and providing nutritional support.

A case study of Ramsay Hunt Syndrome in conjunction with cranial polyneuritis.

RATIONALE: Ramsay Hunt syndrome in conjunction with cranial polyneuritis is not extensively documented, and is very easily misdiagnosed. PATIENT CONCERNS: A case of a 53-year-old male with Ramsay Hunt syndrome in conjunction with cranial polyneuritis is presented with early symptoms of vertigo, cephalalgia, and facial palsy, followed by zoster oticus 10 days later. DIAGNOSES: Diagnosis was challenging as this condition presents with multiple neuropathies, and attempting to diagnose based on clinical symptoms was often misleading. Polymerase chain reaction can be used to test for presence of the virus in the cerebrospinal fluid, followed by targeted drug therapy. INTERVENTIONS: Acupuncture, in conjunction with fire cupping, bloodletting around the afflicted region on the face, as well as oral consumption of herbal medicine and vitamins for nerve nourishment was given to treat this disease. OUTCOMES: Due to misdiagnosis resulting in delayed treatment, peripheral facial paralysis was left as the main sequelae, while other symptoms responded quickly to treatment. After a 6-month follow-up, facial palsy was still present. LESSONS: Considering that targeted antiviral therapy can be used to increase the effectiveness of treatment, early diagnosis, and timely use of medication is critical.

Neurological Manifestations of Dengue Infection.

Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS), peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

HIV-related neurological syndromes reduce health-related quality of life.

BACKGROUND: Human immunodeficiency virus (HIV) infection frequently results in neurological complications but the impact of different neurological syndromes on patients' quality of life remains unknown. METHODS: We investigated health-related quality of life (HRQoL) parameters among HIV/Acquired Immune Deficiency Syndrome (AIDS) patients with and without neurological disease, including 11 dimensions of HRQoL within the Medical Outcomes Short-form Health Survey-HIV. RESULTS: Comparisons of sociodemographic and systemic clinical variables did not differ between HIV/AIDS patients with (n=94) and without (n=75) neurological disease. However, patients with neurological diseases exhibited significantly lower HRQoL scores compared to matched controls, which was most evident among HIV/AIDS patients with cognitive impairment and sensory neuropathy. Prospective analysis revealed diminishing HRQoL scores prior to neurological diagnosis followed by a progressive and sustained improvement in HRQoL scores after intervention over a 96-week period. CONCLUSIONS: These studies indicate that while HIV-related neurological diseases are associated with reduced HRQoL scores, enhanced neurological care has a positive impact on HIV/AIDS patients' overall well-being.

A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team.

BACKGROUND: Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. METHOD: A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. RESULTS: The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated. CONCLUSIONS: Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.

A phase I/II trial of nimodipine for HIV-related neurologic complications.

BACKGROUND: Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders. METHODS: To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg p.o., five times daily; 30 mg p.o., three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy. RESULTS: Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo. CONCLUSIONS: Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.

Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link.

There is substantial epidemiological evidence supporting the concept that respiratory syncytial virus (RSV) lower respiratory tract infection in infancy may be linked to the development of reactive airway disease (RAD) in childhood. However, much less is known concerning the mechanisms by which this self-limiting infection leads to airway dysfunction that persists long after the virus is cleared from the lungs. A better understanding of the RSV-RAD link may have important clinical implications, particularly because prevention of RSV lower respiratory tract infection may reduce the occurrence of RAD later in life. Among the mechanisms proposed to explain the chronic sequelae of RSV infection is the interaction between the subepithelial neural network of the airway mucosa and the cellular effectors of inflammatory and immune responses to the virus. The body of clinical literature linking RSV and RAD is reviewed herein, as are the cellular and molecular mechanisms of neuroimmune interactions and neural remodeling that may underlie this link, and the possibility that preventing the infection may result in a decreased incidence of its chronic sequelae.

Painful and non-painful neuropathy in HIV-infected patients: an analysis of somatosensory nerve function.

Fifteen to 50% of AIDS-patients suffer from distal predominantly sensory neuropathy (DSP), which is commonly associated with painful symptoms. In the present study, we have focused on the function of fine calibre nerve channels, in 36 consecutive HIV-1-infected patients with painful (PPN) (n=20; 54%) and non-painful (PN) (n=16) sensory neuropathy, assessed by clinical, quantitative thermal testing (QTT) (31/36), and peripheral nerve conduction examination (32/36). Control QTT data were obtained from 49 healthy subjects with a corresponding age- and sex distribution. Demographics, antiviral treatment, immunological status, and nerve conduction examination did not differ between patients with and without painful symptoms. Hypoaesthesia to warmth, cold, and heat pain was observed in both neuropathy groups when compared to healthy controls. However, the perception threshold to warmth was more often impaired (p<0.01) and the level of impairment was more pronounced (p<0.001) in patients with painful neuropathy. Furthermore, increased pain sensitivity to cold was found only in patients with painful symptoms (p<0.05). An abnormal outcome of any QTT parameter was found in all patients with pain, but only among 62% of patients without pain, p<0.01, and the cumulative frequency of abnormalities in any of the four thermal percepts (warmth, cold, heat pain, and cold pain) was higher in patients with painful symptoms, p<0.0001. This study demonstrates a more pronounced impairment of C-fibre-mediated innocuous warm perception in patients with painful neuropathy, which in the setting of impaired or absent heat pain perception suggests a more generalised loss of function in somatosensory C-fibre channels.

Highly variable distribution of HSV-1-specific DNA in human geniculate, vestibular and spiral ganglia.

Viral reactivation in temporal ganglia is the suspected cause of Bell's palsy, vestibular neuritis and sudden hearing loss. Since the distribution of latent herpes simplex type 1 (HSV-1) in geniculate, vestibular and spiral ganglia of individual human temporal bones could have implications for the explanation of isolated as well as combined disorders of these three cranial nerves, we examined these ganglia in 18 human temporal bones of adults by nested polymerase chain reaction. In all of the temporal bones HSV-1 specific DNA was detected: 10/18 (56%) of the geniculate, 11/18 (61%) of the vestibular and 9/18 (50%) of the spiral ganglia samples were positive. All combinations of positive and negative ganglia were found in individual temporal bones at roughly equal frequencies. These data support a viral etiology of all three conditions, especially their occasional combinations.

Horner's syndrome associated with mononeuritis multiplex due to cytomegalovirus as the initial manifestation in a patient with AIDS.

We report on a 60-year-old male with AIDS who presented Horner's syndrome that was associated with mononeuritis multiplex due to cytomegalovirus (CMV) infection. This is the first case who presented Homer's syndrome in the course of AIDS. Horner's syndrome associated with mononeuritis multiplex in this patient was the initial manifestation without any opportunistic infections. Since Horner's syndrome and mononeuritis multiplex in the present case were both improved by ganciclovir, it is important to consider CMV infection when Horner's syndrome or mononeuritis multiplex is observed in immunocompromised patients, such as those with HIV-1 infection or AIDS, even if they do not show any other opportunistic infections.

Unusual causes of trigeminal neuralgia treated by gamma knife radiosurgery. Report of two cases.

The purpose of this paper was to present two cases of secondary trigeminal neuralgia (TN) with an unusual origin and lesion location. In two cases TN was caused by lesions along the course of the trigeminal nerve within the pons and adjacent to the fourth ventricle. Both cases presented with typical TN. Brain magnetic resonance imaging revealed linear or wedge-shaped lesions adjacent to the fourth ventricle, extending anterolaterally and lying along the pathway of the intraaxial trigeminal fibers. The involvement of the nucleus of the spinal trigeminal tract and of the principal sensory trigeminal nucleus with segmental demyelination are suggested as possible causes for trigeminal pain in these cases. It is postulated that these lesions are the result of an old viral neuritis. The patients underwent gamma knife radiosurgery and their clinical responses have been encouraging to date.

Herpes zoster brachial plexus neuritis.

This is the first report of brachial plexus inflammation associated with clinical herpes zoster paresis. A 78-year-old female with a 3-week history of herpes zoster of the C4, C5, and C6 dermatomes developed left upper arm monoplegia. She died from an acute myocardial infarction. Post-mortem provided a rare opportunity to study the neuropathology of herpes zoster motor involvement. Histology of the brachial plexus showed extensive lymphocytic infiltration, myelin breakdown, and preservation of axons without vasculitis. The cervical spinal cord showed perivascular lymphocytic cuffing and no anterior horn necrosis. We suggest, the brachial plexus inflammation was a distal extension of a dorsal ganglionitis. Brachial plexus neuritis may be a direct cause of reversible upper limb paresis in herpes zoster. We demonstrate the motor neuropathy is an inflammatory demyelinative process consistent with the recovery observed in a number of patients. We postulate post-herpetic neuralgia may be related to an ongoing inflammatory process.

Herpetic tracheitis and brachial plexus neuropathy in a child with burns.

Herpetic tracheobronchitis is a well-recognized clinical entity that most commonly occurs in immunocompromised patients, including patients with burns. Although the diagnosis of herpetic tracheobronchitis is usually not made until postmortem examination, the presence of the condition can be established when histologic specimens of a patient with upper airway obstruction are studied. In this article, a case is described in which a child developed herpetic tracheitis after undergoing elective intubation after the grafting of burns of the face, neck, and upper extremity. The tracheitis resulted in severe upper airway obstruction that required tracheal dilatation and sequential bronchoscopic excisions of granulation tissue. The patient also developed a brachial plexus neuropathy that was most likely related to herpetic infection.