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A patient with reactivated varicella zoster virus (VZV) manifesting in the left-sided dermatome L3 and S2-S4 developed tonic spasms which morphed into myoclonic jerks, paresis, rigidity and hypoesthesia of the left leg. Later, stimuli-sensitive myoclonus progressed to affect the upper body and was accompanied by fever surges with high-frequency myoclonus, hypertensive derailment, dysphagia and other features of the brainstem with autonomic dysfunction. Cerebrospinal fluid tested positive for VZV, MRI showed no signs of myelitis and EEG was negative for epilepsy. However, on clinical presentation, progressive encephalomyelitis with rigidity and myoclonus, a variant of the more well-known stiff person syndrome, was suspected and later supported by positive serum testing for associated anti-glycine receptor antibodies. Initially established antiviral, anti-epileptic and symptomatic treatment was then extended with intravenous immunoglobulin therapy. Only additional corticosteroid treatment led to a reduction in myoclonus, and uptitration of benzodiazepines decreased rigidity., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Human brucellosis, one of the most common zoonoses worldwide, is rare in Japan. Brucella canis is the specific pathogen of human brucellosis carried by dogs. According to an epidemiological study of B. canis infection in Japan, B. canis is the specific pathogen of human brucellosis in dogs. We herein report a rare case of meningoencephalomyelitis caused by B. canis in a 68-year-old Japanese man. Neurobrucellosis was diagnosed based on a serum tube agglutination test and abnormal cerebrospinal fluid findings. The patient was started on targeted treatment with a combination of doxycycline and streptomycin. Although extremely rare, neurobrucellosis should be considered in patients with a fever of unknown origin and unexplained neurological symptoms.

A new outbreak of monkeypox has been reported worldwide with CNS complications like encephalitis or myelitis being extremely rare. We present a case of a 30-year-old man with PCR-confirmed diagnosis of monkeypox who developed rapid neurological deterioration with extensive inflammatory involvement of the brain and spinal cord on MRI. Because of the clinical and radiological resemblance to acute disseminated encephalomyelitis (ADEM), it was decided to indicate treatment with high-dose corticosteroids for 5 days (without concomitant antiviral management due to lack of availability in our country). Given the poor clinical and radiological response, 5 days of immunoglobulin G were administered. During follow-up the patient's clinical condition improved, physiotherapy was started and all associated medical complications were controlled. To our knowledge, this is the first reported monkeypox case with severe CNS complications treated with steroids and immunoglobulin in the absence of specific antiviral treatment., (© 2023. The Author(s).)

Background: Glatiramer acetate (GA) is a well-established treatment option for patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis (MS) with few side effects. The double transgenic mouse model spontaneous opticospinal encephalomyelitis (OSE), based on recombinant myelin oligodendrocyte glycoprotein 35-55 reactive T and B cells, mimicks features of chronic inflammation and degeneration in MS and related disorders. Here, we investigated the effects of prophylactic GA treatment on the clinical course, histological alterations and peripheral immune cells in OSE. Objective: To investigate the effects of prophylactic glatiramer acetate (GA) treatment in a mouse model of spontaneous opticospinal encephalomyelitis (OSE). Methods: OSE mice with a postnatal age of 21 to 28 days without signs of encephalomyelitis were treated once daily either with 150 µg GA or vehicle intraperitoneally (i. p.). The animals were scored daily regarding clinical signs and weight. The animals were sacrificed after 30 days of treatment or after having reached a score of 7.0 due to animal care guidelines. We performed immunohistochemistry of spinal cord sections and flow cytometry analysis of immune cells. Results: Preventive treatment with 150 µg GA i. p. once daily significantly reduced clinical disease progression with a mean score of 3.9 ± 1.0 compared to 6.2 ± 0.7 in control animals ( p < 0.01) after 30 d in accordance with positive effects on weight ( p < 0.001). The immunohistochemistry showed that general inflammation, demyelination or CD11c + dendritic cell infiltration did not differ. There was, however, a modest reduction of the Iba1 + area ( p < 0.05) and F4/80 + area upon GA treatment ( p < 0.05). The immune cell composition of secondary lymphoid organs showed a trend towards an upregulation of regulatory T cells, which lacked significance. Conclusions: Preventive treatment with GA reduces disease progression in OSE in line with modest effects on microglia/macrophages. Due to the lack of established prophylactic treatment options for chronic autoimmune diseases with a high risk of disability, our study could provide valuable indications for translational medicine.

Background: The role of thymus in the immune cascade of the body is still under active clinical scrutiny. Meanwhile, there is an unravelling of myriad presentations of thymoma with effects on various organ systems. These effects arise both due to autoimmunity or a paraneoplastic process secondary to thymoma. However, an occasional patient can be a conundrum and may give no clue regarding the pathogenesis and etiology of its clinical profile., Material and Methods: We present an enigmatic case of a 30-year-old male presenting with superficial fungal infections followed by multiaxial neurological involvement against a background of thymoma. Extensive workup for bacterial, viral, autoimmune and paraneoplastic etiologies were negative. Thymectomy confirmed thymoma (Type AB) but failed to ameliorate the progression of symptoms. He developed recurrent episodes of severe sepsis which remitted with sensitive antibiotics only to reappear again. Immunological profile showed complete absence of peripheral circulating B-cells with reversal of CD4/CD8 ratio, findings compatible with Good's syndrome. Radiological findings showed only progressive brain atrophy without any hyperintensity. He was also treated with intravenous immunoglobulins but failed to respond with the same., Results: Autopsy revealed features of panencephalitis (neuronophagia, neuronal loss, perivascular lymphocytic cuffing and microglial nodules) with virus particles detected ultrastructurally. Although the distinction between seronegative autoimmune encephalitis versus a viral encephalomyelitis often blurs histologically, we speculated viral encephalomyelitis to have happened toward the latter part of his long illness. To our knowledge, this is a case of Good's syndrome presenting with seronegative autoimmune panencephalitis superimposed with a viral infection.

Multiple sclerosis (MS) is an immunopathological disease that causes demyelination and recurrent episodes of T cell-mediated immune attack in the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is a well-established mouse model of MS. The roles of T cells in MS/EAE have been well investigated, but little is known about the role of CCR5 + cells. In the present study, we investigated whether treatment with DAPTA, a selective CCR5 antagonist, could modulate the progression of EAE in the SJL/J mice. EAE mice were treated with DAPTA (0.01 mg/kg) intraperitoneally daily from day 14 to day 42, and the clinical scores were evaluated. We further investigated the effects of DAPTA on IFN-γ-, TGF-β-, IL-10-, IL-17A-, IL-22-, T-bet, STAT4-, RORγT-, AhR-, Smad3-, and Foxp3-expressing CCR5 + spleen cells using flow cytometry analysis. We further explored the effects of DAPTA on mRNA/protein expression of IFN-γ, IL-10, IL-17A, IL-22, TGF-β, T-bet, STAT4, RORγT, AhR, Foxp3, and NF-H in the brain tissue. The severity of clinical scores decreased in DAPTA-treated EAE mice as compared to that in the EAE control mice. Moreover, the percentage of CCR5 + IFN-γ + , CCR5 + T-bet + , CCR5 + STAT4 + , CCR5 + IL-17A + , CCR5 + RORγt + , CCR5 + IL-22 + , and CCR5 + AhR + cells decreased while CCR5 + TGF-β + , CCR5 + IL-10 + , CCR5 + Smad3 + , and CCR5 + Foxp3 + increased in DAPTA-treated EAE mice. Furthermore, DAPTA treatment significantly mitigated the EAE-induced expression of T-bet, STAT4, IL-17A, RORγT, IL-22, and AhR but upregulated Foxp3, IL-10, and NF-H expression in the brain tissue. Taken together, our data demonstrated that DAPTA could ameliorate EAE progression through the downregulation of the inflammation-related cytokines and transcription factors signaling, which may be useful for the clinical therapy of MS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Advances in the understanding of equine protozoal myeloencephalitis (EPM) are reviewed. It is now apparent that EPM can be caused by either of 2 related protozoan parasites, Sarcocystis neurona and Neospora hughesi, although S neurona is the most common etiologic pathogen. Horses are commonly infected, but clinical disease occurs only infrequently; the factors influencing disease occurrence are not well understood. Epidemiologic studies have identified risk factors for the development of EPM, including the presence of opossums and prior stressful health-related events. Attempts to reproduce EPM experimentally have reliably induced antibody responses in challenged horses, but have not consistently produced neurologic disease. Diagnosis of EPM has improved by detecting intrathecal antibody production against the parasite. Sulfadiazine/pyrimethamine (ReBalance) and the triazine compounds diclazuril (Protazil) and ponazuril (Marquis) are effective anticoccidial drugs that are now available as FDA-approved treatments for EPM., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder. We report a 59-year-old man who presented with progressive encephalomyelitis causing diplopia, bulbar palsy, severe dysautonomia, followed by stiffness and myoclonic cluster. Laboratory tests showed mild pleocytosis, with markedly elevated plasma levels of norepinephrine, epinephrine, and arginine vasopressin. Glycine-receptor antibodies were identified in both serum and CSF. Despite a poor response to methylprednisolone, immunoglobulins, and plasma exchange, α-blocker stabilized dysautonomia. Dysautonomia is presumed to be due to antibody-mediated disinhibited sympathetic hyperactivity; however, this case suggests that concomitant use of α-blocker with immunotherapy may ameliorate dysautonomia., (Copyright © 2021 Elsevier B.V. All rights reserved.)