The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity.

Herpes simplex virus encephalitis (HSE) is the leading cause of non-epidemic encephalitis in the developed world and, despite antiviral therapy, mortality and morbidity is high. The emergence of post-HSE autoimmune encephalitis reveals a new immunological paradigm in autoantibody-mediated disease. A reductionist evaluation of the immunobiological mechanisms in HSE is crucial to dissect the origins of post-viral autoimmunity and supply rational approaches to the selection of immunotherapeutics. Herein, we review the latest evidence behind the phenotypic progression and underlying immunobiology of HSE including the cytokine/chemokine environment, the role of pathogen-recognition receptors, T- and B-cell immunity and relevant inborn errors of immunity. Second, we provide a contemporary review of published patients with post-HSE autoimmune encephalitis from a combined cohort of 110 patients. Third, we integrate novel mechanisms of autoimmunization in deep cervical lymph nodes to explore hypotheses around post-HSE autoimmune encephalitis and challenge these against mechanisms of molecular mimicry and others. Finally, we explore translational concepts where neuroglial surface autoantibodies have been observed with other neuroinfectious diseases and those that generate brain damage including traumatic brain injury, ischaemic stroke and neurodegenerative disease. Overall, the clinical and immunological landscape of HSE is an important and evolving field, from which precision immunotherapeutics could soon emerge.

Endovascular treatment for vaccine-induced cerebral venous sinus thrombosis and thrombocytopenia following ChAdOx1 nCoV-19 vaccination: a report of three cases.

BACKGROUND: Vaccine-induced thrombosis and thrombocytopenia (VITT) is a rare complication following ChAdOx1 nCoV-19 vaccination. Cerebral venous sinus thrombosis (CVST) is overrepresented in VITT and is often associated with multifocal venous thromboses, concomitant hemorrhage and poor outcomes. Hitherto, endovascular treatments have not been reviewed in VITT-related CVST. METHODS: Patient records from a tertiary neurosciences center were reviewed to identify patients who had endovascular treatment for CVST in VITT. RESULTS: Patient records from 1 January 2021 to 20 July 2021 identified three patients who underwent endovascular treatment for CVST in the context of VITT. All were female and the median age was 52 years. The location of the CVST was highly variable. Two-thirds of the patients had multifocal dural sinus thromboses (sigmoid, transverse, straight and superior sagittal) as well as internal jugular vein thromboses. Intracerebral hemorrhage occurred in all patients; subarachnoid blood was noted in two of them, and intraparenchymal hemorrhage occurred in all. There was one periprocedural parenchymal extravasation which abated on temporary cessation of anticoagulation. Outcome data revealed a 90-day modified Rankin Scale (mRS) score of 2 in all cases. CONCLUSIONS: We demonstrate that endovascular treatment for VITT-associated CVST is feasible and can be safe in cases that deteriorate despite medical therapy. Extensive clot burden, concomitant hemorrhage, rapid clinical progression and persistent rises in intracranial pressure should initiate multidisciplinary team discussion for endovascular treatment in appropriate cases.

Isolated abducens nerve palsy in a patient with asymptomatic SARS-CoV-2 infection.

The neuro-ophthalmological complications of SARS-CoV-2 infection are emerging but the spectrum of presentations and pathophysiological mechanism underpinning the association remains to be fully determined. We describe the case of a 44-year-old female who presented with a 12-hour history of diplopia preceded by a mild headache and found to have an isolated right abducens nerve palsy. Initial vital signs were normal but she developed a fever and nasopharyngeal swab confirmed SARS-CoV-2 infection by RT-PCR. All other investigations returned normal including blood tests, chest X-ray, MRI brain and cerebrospinal fluid analysis. She remained systemically well, and there was complete resolution of the abducens palsy and diplopia at two week follow up. In the absence of an alternative underlying cause or risk factors identified, the aetiology was presumed to be microvascular and potentially related to the viral infection. We add to the evolving literature of neuro-ophthalmological associations of SARS-CoV-2, discuss possible causal mechanisms and suggest considering asymptomatic SARS-CoV-2 infection in cases of isolated abducens palsy without clear risk factors.

Late-onset Leber's hereditary optic neuropathy presenting with longitudinally extensive myelitis harbouring the m.14484T>C mutation: Extending the genotype-phenotype spectrum.

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease leading to visual loss, typically in young men, and rarely displays extra-ocular manifestations including spinal cord disease. We report the case of a 57-year-old man who presented with a longitudinally extensive dorsal column lesion as the first manifestation of LHON, with the onset of bilateral progressive optic neuropathy 11 months later, harbouring the m.14484T>C mutation. To our knowledge this is the most extensive cord lesion preceding optic neuropathy traversing the cervical and thoracic cord. We review the literature of all published cases of LHON in which spinal cord involvement was the presenting feature of the disease, summarising the clinical phenotype, demographics, radiological characteristics and genotype. We highlight the importance for diagnostic vigilance in patients with either longitudinally extensive dorsal column myelopathy, optic neuropathy or both.

Rhomboencephalitis.

Rhomboencephalitis-inflammation of the brainstem and cerebellum-has myriad clinical presentations including encephalopathy, cranial neuropathies, long tract signs and cerebellar dysfunction and is associated with significant morbidity and mortality. There are a variety of potential underlying causes that respond variably to treatment, including infections, parainfective syndromes, inflammatory disorders including autoimmune encephalitis and paraneoplastic syndromes. Here, we review its clinical presentation and outline a practical approach to its investigation, aiming to facilitate prompt diagnosis and confirmation of the underlying cause, to start appropriate management early and optimise the clinical outcome.

Bickerstaff's brainstem encephalitis associated with anti-GM1 and anti-GD1a antibodies.

Bickerstaff's brainstem encephalitis (BBE) is a Guillain-Barré syndrome (GBS) spectrum disorder associated with predominantly central nervous system predilection. Patients exhibit a variable constellation of depressed consciousness, bilateral external ophthalmoplegia, ataxia and long tract signs. Although the pathophysiology is not fully understood, it has been associated with anti-GQ1b antibodies in two-thirds of patients. We present a patient with clinical features consistent with BBE and positive anti-GM1 and anti-GD1a antibodies. A diagnostic approach to the acutely unwell patient with brainstem encephalitis is explored in this clinical context with a literature review of the aforementioned ganglioside antibody significance. Intravenous immunoglobulin therapy is highlighted in BBE using up-to-date evidence-based extrapolation from GBS.

Sneddon Syndrome: A Case Report Exploring the Current Challenges Faced with Diagnosis and Management.

Sneddon syndrome (SS) is a rare medium-vessel vasculopathy which characteristically presents with livedo racemosa (LR) and complications such as strokes. This case report describes a female presenting acutely with a stroke and, initially, no evidence of LR. Her antiphospholipid antibodies were negative, and her neuroimaging revealed multiple territory strokes with extensive vasculopathy and fragile neo-formed vessel collateralisation. She had progressive memory loss and multiple transient ischaemic attacks on a background of established infarctions. SS should be considered in any idiopathic medium-vessel vasculopathy despite the absence of LR. Medical therapy can be challenging and the importance of antiphospholipid status in risk stratifying anticoagulation against antiplatelet therapy is discussed with a proposed rheumatology management strategy. The medical option of hydroxychloroquine should be considered in all patients in view of its anti-thrombotic properties and efficacy in diseases such as systemic lupus erythematosus and antiphospholipid syndrome with the suggestion that SS may be a forme fruste of these diseases. Neurosurgical options should be considered for recurrent transient neurological symptoms. For our patient, this included an extracranial to intracranial bypass via a radial artery graft for haemodynamic stroke management confirmed on SPECT imaging. The traditional hallmark of SS has previously been LR. This case highlights an atypical presentation stressing the importance of diagnostic vigilance in a patient with an idiopathic medium-vessel vasculopathy, together with balancing the medical risk of antiplatelet therapy, anticoagulation and thrombolysis whilst revealing possible neurosurgical options in select SS patients.

Regression of Nevi After Candida Injection for the Treatment of Verruca Vulgaris.

The most common treatment methods for verruca vulgaris are destructive methods that are often painful and treat individual verruca. Thus immune modulators, including Candida immunotherapy, are used to treat persistent recalcitrant and multiple verrucas simultaneously. Very few side effects are reported with Candida immunotherapy; they include vitiligo and now halo nevi. Physicians need to be aware of and discuss side effects with patients undergoing Candida immunotherapy.

Targetoid hemosiderotic hemangioma: a case report of multiple asymptomatic lesions.

Targetoid hemosiderotic hemangioma (THH) is a benign vascular tumor characterized by a central violaceous papule with a clear periphery bordered by an ecchymotic ring. Originally coined by its characteristic halo appearance with hemosiderin deposits, not all THHs have this classic halo or hemosiderin composition. We report a unique case of THH in which the patient presented with multiple lesions with no prior trauma. Multiple THH lesions have been linked to minor trauma; however, the presence of 4 concurrent lesions with the absence of trauma makes this THH presentation atypical and unique.