The Diversity of Neurological Complications Associated with Herpes Zoster: A Retrospective Case Series of 26 Patients.

Objects This study clarified a variety of neurological phenotypes associated with varicella-zoster virus (VZV) reactivation. Methods This retrospective single-center study included consecutive patients with herpes zoster accompanied by neurological disturbances from April 2016 to September 2022. A comparative analysis was performed to examine whether or not the neurological phenotype and severity were associated with the distribution of herpes zoster, clinical and laboratory findings, and treatments. Results Twenty-six patients with a median age of 74 years old were enrolled. None of the patients had been vaccinated against herpes zoster. Of the 26 patients, 14 (54%) developed monoparesis, 5 (19%) developed meningitis, 5 (19%) developed encephalitis, 1 (4%) developed paraplegia, and 1 (4%) developed bladder and rectal problems. Monoparesis of the upper limb is associated with herpes zoster involving the cervical and thoracic dermatomes, whereas meningitis and encephalitis often occur in patients with herpes zoster in the trigeminal and thoracic dermatomes. Neurological disability was generally severe [modified Rankin Scale (mRS) score ≥3] on admission [17 of 26 (65%) patients]. Good recovery after admission was associated with a lower mRS value before the onset of neurological disability, clinical meningitis, and elevated cell counts and protein levels in the cerebrospinal fluid. Good recoveries were observed in patients with herpes zoster in the trigeminal or thoracic dermatomes more frequently than in other dermatomes. Conclusion This study revealed that VZV-related neurological complications are heterogeneous, commonly leading to severe disability and poor outcomes, and that neurological phenotypes and outcomes are related to the distribution of herpes zoster.

Lead Encephalopathy in a 73-year-old Man Manifesting as Acute Disturbance of Consciousness with a Unique Magnetic Resonance Imaging Appearance.

A 73-year-old man was admitted with Cheyne-Stokes respiration and progressive disturbance of consciousness over the course of a month. Cranial magnetic resonance imaging revealed signs suggestive of angioedema in the posterior limb of the internal capsule, external capsule, and subcortical white matter. Acute lead encephalopathy was diagnosed based on abnormally high plasma lead levels. After methylprednisolone pulse therapy followed by chelation therapy, the patient fully recovered. In this case, the angioedema with a distinctive magnetic resonance imaging appearance was attributed to the cytotoxic effects of lead on the nervous system, which responded well to methylprednisolone pulse therapy.

Antineutrophil cytoplasmic antibody-associated vasculitis with predominant truncal muscle weakness: a retrospective case series.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently leads to mononeuritis multiplex, which are characterized by distal weakness associated with sensory disturbances. Although AAV has also been reported to be associated with myopathy, the pathogenesis and characteristics remain unclear. We aimed to show the clinical and laboratory findings in AAV-associated myopathy. Methods: This retrospective single-center study included patients with the diagnosis of AAV who had been admitted to the neurology department and had biopsy specimens of muscle and/or nerve tissue. Results: We identified four patients with a distinct clinical presentation of muscle weakness in the trunk and proximal limbs. The weakness resembled that of inflammatory muscle disease. These patients denied symptoms associated with neuropathy, and had normal serum creatine kinase (CK) levels. Needle electromyography (needle EMG) showed spontaneous electrical activity at rest, and results of magnetic resonance imaging (MRI) suggested inflammatory myopathy. Muscle biopsy specimens from all four patients revealed vasculitis and inflammation in proximity to the affected vessels, without any discernible characteristics of other myopathies. The patients also complained of symptoms affecting other organs, such as the ears and kidneys, which is typical of AAV cases. Remission induction therapy, such as cyclophosphamide pulse therapy in addition to oral prednisolone, were effective for all four patients. However, relapses occurred in two patients during maintenance therapy and two patients died of aspiration pneumonia. Discussion: The clinical course of our patients might represent a subtype of AAV that is characterized by muscle weakness of the trunk and proximal extremities and arises from vasculitis within the muscles. The clinical manifestations of our patients were similar to those of patients with inflammatory myopathy with regard to the distribution of muscle weakness, MRI and needle EMG findings. However, there are notable differences between AAV associated myopathy vs. inflammatory myositis like dermatomyositis; (1) the absence of elevated CK levels, (2) the presence of complications in other organs, (3) distinct pathological findings, and (4) severe outcomes. Awareness that AAV patients with muscle involvement could have a subtype of AAV that seriously affects various organs is critical for an accurate diagnosis and effective therapeutic management.

[Clinical features of 8 patients with multifocal motor neuropathy in the long-term follow-up].

OBJECTIVE: To clarify the clinical and long-term characteristics of multifocal motor neuropathy (MMN). METHODS: We retrospectively evaluated data from 8 consecutive MMN patients in Yamaguchi University Hospital from 2005 to 2020. Clinical information including dominant hand, occupations, hobbies, nerve conduction data, protein level in cerebrospinal fluid (CSF), responsiveness to intravenous immunoglobulin (IVIg) therapy as initial therapy as well as maintenance therapy were collected. RESULTS: Unilateral upper limb was initially affected in all patients and a dominant upper extremity was affected in six of them. Seven patients had occupations or hobbies which were associated with overuse of their dominant upper extremity. CSF protein level was normal or slightly elevated. Nerve conduction studies showed conduction blocks in 4 cases. Effectiveness of IVIg treatment as initial therapy was observed in all patients. Maintenance therapy was not needed in 2 patients because of mild symptoms with stable clinical course. Long-term maintenance therapy with immunoglobulin was effective in 5 patients during the follow-up period. CONCLUSION: Dominant upper extremity was frequently affected and most patients had job or habit associated with its overuse, suggesting that physical overload induces inflammation or demyelination in MMN. IVIg was commonly effective as both introduction and long-term maintenance therapies. Complete remission was achieved after several IVIg treatments in some patients.

[Varicella-Zoster Virus Infection in the Central Nervous System].

Varicella-zoster virus (VZV) is known to causes various inflammatory disorders of the central nervous system (CNS) such as encephalitis, meningitis, and myelitis. Similar to the varicella rashes, these conditions are associated with the reactivation of VZV. Ganglionitis and vasculitis, in particular, may be linked to the pathogenesis of VZV infection in the CNS. This review provides an overview of the clinical presentation, diagnosis, treatment, and prognosis of VZV infection in the CNS based on its distinct pathophysiology.

New BBB Model Reveals That IL-6 Blockade Suppressed the BBB Disorder, Preventing Onset of NMOSD.

BACKGROUND AND OBJECTIVES: To evaluate the pathophysiology of neuromyelitis optica spectrum disorder (NMOSD) and the therapeutic mechanism and levels of interleukin-6 (IL-6) blockade (satralizumab), especially with respect to blood-brain barrier (BBB) disruption with the new in vitro and ex vivo human BBB models and in vivo model. METHODS: We constructed new static in vitro and flow-based ex vivo models for evaluating continued barrier function, leukocyte transmigration, and intracerebral transferability of neuromyelitis optica-immunoglobulin G (NMO-IgG) and satralizumab across the BBB using the newly established triple coculture system that are specialized to closely mimic endothelial cell contact of pericytes and endfeet of astrocytes. In the in vivo study, we assessed the effects of an anti-IL-6 receptor antibody for mice (MR16-1) on in vivo BBB disruption in mice with experimental autoimmune encephalomyelitis in which IL-6 concentration in the spinal cord dramatically increases. RESULTS: In vitro and ex vivo experiments demonstrated that NMO-IgG increased intracerebral transferability of satralizumab and NMO-IgG and that satralizumab suppressed the NMO-IgG-induced transmigration of T cells and barrier dysfunction. In the in vivo study, the blockade of IL-6 signaling suppressed the migration of T cells into the spinal cord and prevented the increased BBB permeability. DISCUSSION: These results suggest that (1) our triple-cultured in vitro and in ex vivo BBB models are ideal for evaluating barrier function, leukocyte transmigration, and intracerebral transferability; (2) NMO-IgG increased the intracerebral transferability of NMO-IgG via decreasing barrier function and induced secretion of IL-6 from astrocytes causing more dysfunction of the barrier and disrupting controlled cellular infiltration; and (3) satralizumab, which can pass through the BBB in the presence of NMO-IgG, suppresses the BBB dysfunction and the infiltration of inflammatory cells, leading to prevention of onset of NMOSD.

Immunohistochemical analysis of huntingtin-associated protein 1 in adult rat spinal cord and its regional relationship with androgen receptor.

Huntingtin-associated protein 1 (HAP1) is a neuronal interactor with causatively polyglutamine (polyQ)-expanded huntingtin in Huntington's disease and also associated with pathologically polyQ-expanded androgen receptor (AR) in spinobulbar muscular atrophy (SBMA), being considered as a protective factor against neurodegenerative apoptosis. In normal brains, it is abundantly expressed particularly in the limbic-hypothalamic regions that tend to be spared from neurodegeneration, whereas the areas with little HAP1 expression, including the striatum, thalamus, cerebral neocortex and cerebellum, are targets in several neurodegenerative diseases. While the spinal cord is another major neurodegenerative target, HAP1-immunoreactive (ir) structures have yet to be determined there. In the current study, HAP1 expression was immunohistochemically evaluated in light and electron microscopy through the cervical, thoracic, lumbar, and sacral spinal cords of the adult male rat. Our results showed that HAP1 is specifically expressed in neurons through the spinal segments and that more than 90% of neurons expressed HAP1 in lamina I-II, lamina X, and autonomic preganglionic regions. Double-immunostaining for HAP1 and AR demonstrated that more than 80% of neurons expressed both in laminae I-II and X. In contrast, HAP1 was specifically lacking in the lamina IX motoneurons with or without AR expression. The present study first demonstrated that HAP1 is abundantly expressed in spinal neurons of the somatosensory, viscerosensory, and autonomic regions but absent in somatomotor neurons, suggesting that the spinal motoneurons are, due to lack of putative HAP1 protectivity, more vulnerable to stresses in neurodegenerative diseases than other HAP1-expressing neurons probably involved in spinal sensory and autonomic functions.