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Background: 22q11.2 microdeletion is the most common microdeletion syndrome in humans with a prevalence of 13 per 100 000 live births, and it is a multisystem condition with variable phenotypic presentations. Methods: We present a case of an adult patient with Dandy-Walker syndrome who presented to our epilepsy clinic with 2 years of new-onset seizures and cognitive decline and 1 year of psychotic symptoms. Results: Patient had a non-revealing autoimmune and malignancy work-up. Continuous scalp vEEG study showed bursts of 1-2 Hz generalized fronto-centrally predominant spike or polyspike and slow wave discharges. Several myoclonic jerks were time-locked with the generalized discharges indicative of cortical myoclonus. MRI brain revealed periventricular nodular heterotopia in addition to findings suggestive of Dandy-Walker syndrome. Array-based comparative genomic hybridization demonstrated a 22q11.2 microdeletion seen in 22q11.2 deletion syndrome. Conclusion: Our case illustrates the challenges of diagnosing genetic disorders in adults especially when the initial diagnosis is dependent on a number of factors, including the patient's age, the severity of the phenotypic features, and the awareness of the physician.
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Symptoms of autonomic dysfunction, particularly those of orthostatic intolerance, continue to represent a major component of the currently recognized post-acute sequelae of SARS-CoV-2 infections. Different pathophysiologic mechanisms can be involved in the development of orthostatic intolerance including hypovolemia due to gastrointestinal dysfunction, fatigue-associated deconditioning, and hyperadrenergic state due to pandemic-related anxiety. Additionally, there has been a well-established association of a common primary autonomic disorder like postural orthostatic tachycardia syndrome, a subtype of orthostatic intolerance, with antecedent viral infections. Here we report a case of neuropathic type postural orthostatic tachycardia syndrome as a form of autonomic neuropathy that developed following COVID-19 infection.
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COVID-19 , Intolerância Ortostática , Síndrome da Taquicardia Postural Ortostática , COVID-19/complicações , Progressão da Doença , Fadiga/complicações , Humanos , Intolerância Ortostática/complicações , Intolerância Ortostática/diagnóstico , Síndrome da Taquicardia Postural Ortostática/complicações , Síndrome da Taquicardia Postural Ortostática/diagnóstico , SARS-CoV-2RESUMO
As the novel coronavirus, SARS-CoV-2, has enveloped the world in a pandemic, it has become clear that the symptoms extend far beyond the respiratory system and have particularly caused a wide range of neurologic CNS complications, including diffuse leukoencephalopathy. Here, we describe a case of a 59-year-old male with severe COVID-19 infection who developed severe encephalopathy, which persisted well after his acute infection had subsided and had begun to improve from his respiratory dysfunction. He was found to have diffuse leukoencephalopathy with concomitant diffusion restriction on MR imaging. This case represents a delayed onset of leukoencephalopathy secondary to hypoxia in a small but growing cohort of COVID-related leukoencephalopathy due to similarities in imaging features and lack of superior alternate diagnosis. Patient's clinical improvement suggests reversibility with likely pathology being demyelination rather than infarction.
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COVID-19/complicações , Hipóxia Encefálica/virologia , Leucoencefalopatias/virologia , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
The virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current pandemic known as coronavirus disease 2019 (COVID-19) with severe respiratory illness as the predominant manifestation. Neurologic complications from COVID-19 were reported in the early stages of the pandemic and are now increasingly recognized. These include various symptoms like headache and anosmia as well as neurologic complications of severe COVID-19 like encephalopathy, seizures, and stroke. There are few reports of direct involvement of the central nervous system with SARS-CoV-2 causing meningoencephalitis. There is concern for higher incidence and severity of COVID-19 in patients with chronic neurologic conditions. Here, we review the emerging literature along with our anecdotal experience in regard to these neurologic manifestations in patients with COVID-19 and detail the putative pathophysiologic mechanisms for the same.
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Opportunistic infections of the central nervous system are classically associated with immunosuppression arising from infection with human immunodeficiency virus and with various hematologic malignancies. However, over the past few years, they are increasingly associated with transplantation and various immunosuppressive treatments used to treat autoimmune diseases. They cause significant morbidity and mortality and remain a diagnostic challenge due to the absence of typical signs and symptoms of infection and mimicry by various noninfectious causes. The pathogens associated with these infections are often commonly found pathogens of low virulence in immunocompetent hosts and include various bacteria, parasites, fungi, or viruses. These infections can present as various clinical syndromes, including meningitis, encephalitis, space-occupying lesions, stroke-like presentations, or even neoplastic manifestations. Progressive multifocal leukoencephalopathy can be seen in patients with multiple sclerosis on various new immunomodulatory drugs in addition to patients with human immunodeficiency virus, transplantation, or hematologic malignancies, and is characterized by multifocal white matter lesions. Human herpesvirus-6 causes severe encephalitis in transplant recipients, known as posttransplantation acute limbic encephalitis. Neoplastic manifestations like Epstein-Barr virus-associated primary central nervous system lymphoma and posttransplantation lymphoproliferative disorders are particularly challenging to diagnose and manage. Modern diagnostic techniques, including advanced imaging techniques like magnetic resonance spectroscopy, use of polymerase chain reaction, and metagenomic sequencing, can be helpful in early recognition of pathogens. Treatment of most of these involves lowering of immunosuppression when possible and use of specific antimicrobial agents when available. Improved outcomes can be seen when early diagnosis is made.
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Infecções do Sistema Nervoso Central/diagnóstico , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Infecções Oportunistas/diagnóstico , Infecções por Roseolovirus/diagnóstico , Anti-Infecciosos/uso terapêutico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Herpesvirus Humano 6/isolamento & purificação , Humanos , Infecções Oportunistas/tratamento farmacológicoRESUMO
BACKGROUND: A number of cerebral manifestations are associated with JC polyomavirus (JCPyV) which are diagnosed by detection of JCPyV in cerebrospinal fluid (CSF), often with the support of cerebral imaging. Here we present an unusual case of a kidney transplant patient presenting with progressive neurological deterioration attributed to JCPyV encephalopathy. METHODS: Quantitative polymerase chain reaction JCPyV was used prospectively and retrospectively to track the viral load within the patient blood, urine, CSF, and kidney sections. A JCPyV VP1 enzyme-linked immunosorbent assay was used to measure patient and donor antibody titers. Immunohistochemical staining was used to identify active JCPyV infection within the kidney allograft. RESULTS: JC polyomavirus was detected in the CSF at the time of presentation. JC polyomavirus was not detected in pretransplant serum, however viral loads increased with time, peaking during the height of the neurological symptoms (1.5E copies/mL). No parenchymal brain lesions were evident on imaging, but transient cerebral venous sinus thrombosis was present. Progressive decline in neurological function necessitated immunotherapy cessation and allograft removal, which led to decreasing serum viral loads and resolution of neurological symptoms. JC polyomavirus was detected within the graft's collecting duct cells using quantitative polymerase chain reaction and immunohistochemical staining. The patient was JCPyV naive pretransplant, but showed high antibody titers during the neurological symptoms, with the IgM decrease paralleling the viral load after graft removal. CONCLUSIONS: We report a case of atypical JCPyV encephalopathy associated with cerebral venous sinus thrombosis and disseminated primary JCPyV infection originating from the kidney allograft. Clinical improvement followed removal of the allograft and cessation of immunosuppression.
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Vírus JC/isolamento & purificação , Transplante de Rim/efeitos adversos , Rim/virologia , Leucoencefalopatia Multifocal Progressiva/virologia , Infecções por Polyomavirus/virologia , Adulto , Anticorpos Antivirais/sangue , Biópsia , Angiografia Cerebral/métodos , Esquema de Medicação , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Vírus JC/genética , Vírus JC/imunologia , Rim/cirurgia , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/imunologia , Leucoencefalopatia Multifocal Progressiva/terapia , Angiografia por Ressonância Magnética , Masculino , Nefrectomia , Flebografia/métodos , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/terapia , Reoperação , Resultado do Tratamento , Carga ViralRESUMO
Sarcoidosis is an idiopathic multisystem granulomatous disorder. Neurologic manifestations in sarcoidosis are varied and making a diagnosis of neurosarcoidosis can be difficult as it mimics various other neurologic diseases. Knowledge of the syndromes associated with neurosarcoidosis can help guide the diagnostic evaluation. Definitive diagnosis requires neurologic tissue evidence of noncaseating granuloma, but in practice probable diagnosis is often made through nonneurologic biopsy and a characteristic syndrome and imaging. Treatment remains empiric, but new advances in immunologic therapy hold promise for effective and less-toxic regimens.
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Encéfalo/patologia , Doenças do Sistema Nervoso Central/diagnóstico , Sarcoidose/diagnóstico , Medula Espinal/patologia , Corticosteroides/uso terapêutico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/patologia , Humanos , Imageamento por Ressonância Magnética , Sarcoidose/tratamento farmacológico , Sarcoidose/patologiaRESUMO
OBJECTIVE: To describe the clinical, neuroimaging, immunologic, and virologic characteristics of JC virus-associated granule cell neuronopathy (JCV GCN) in a natalizumab-treated patient with multiple sclerosis (MS) who developed immune reconstitution inflammatory syndrome (IRIS) after natalizumab withdrawal. METHODS: We obtained longitudinal clinical data as well as MRI and proton magnetic resonance spectroscopy from this patient with MS. We measured JCV-specific cellular immune response in his peripheral blood by intracellular cytokine staining and sequenced a fragment of JCV VP1 capsid gene detected in his CSF. We contrast our findings with the first recently reported case. RESULTS: This patient presented with worsening cerebellar symptoms and progressive cerebellar atrophy without new MS lesions on MRI after 63 months of natalizumab monotherapy. JCV DNA was detected in his CSF by PCR and harbored novel GCN-type mutations in the VP1 gene. He developed IRIS upon discontinuation of natalizumab and plasma exchange, which manifested itself by a worsening of clinical symptoms and contrast enhancement in the cerebellum on MRI. Treatment with corticosteroids resulted in resolution of IRIS, as demonstrated by proton magnetic resonance spectroscopy. The patient had a strong JCV-specific T-cell response in his peripheral blood and remains alive after 15 months from onset of symptoms, although with significant disability. He did not have MS relapse on glatiramer acetate. CONCLUSIONS: JCV GCN should be considered in patients on natalizumab presenting with progressive cerebellar symptoms and cerebellar atrophy, and is associated with mutations in the JCV VP1 gene. Natalizumab withdrawal may be complicated by JCV GCN IRIS, and require treatment with corticosteroids.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Capsídeo/efeitos dos fármacos , Vírus JC/efeitos dos fármacos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Adulto , Humanos , Síndrome Inflamatória da Reconstituição Imune/induzido quimicamente , Síndrome Inflamatória da Reconstituição Imune/genética , Vírus JC/imunologia , Masculino , Esclerose Múltipla/diagnóstico , Mutação/genética , NatalizumabRESUMO
JC virus (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy, JCV granule cell neuronopathy, and JCV encephalopathy. Whether JCV can also cause meningitis has not yet been demonstrated. We report a case of aseptic meningitis resulting in symptomatic hydrocephalus in a human immunodeficiency virus-seronegative patient. Brain imaging showed enlargement of ventricles but no parenchymal lesion. She had a very high JC viral load in the cerebrospinal fluid (CSF) and developed progressive cognitive dysfunction despite ventricular drainage. She was diagnosed with pancytopenia and passed away after 5.5 months. Postmortem examination revealed productive JCV infection of leptomeningeal and choroid plexus cells, and limited parenchymal involvement. Sequencing of JCV CSF strain showed an archetype-like regulatory region. Further studies of the role of JCV in aseptic meningitis and in idiopathic hydrocephalus are warranted.
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Soronegatividade para HIV , Hidrocefalia/etiologia , Vírus JC/patogenicidade , Meningite Asséptica/complicações , Idoso , Transtornos Cognitivos/etiologia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Soronegatividade para HIV/imunologia , Humanos , Vírus JC/isolamento & purificação , Meningite Asséptica/virologia , Pancitopenia/etiologiaRESUMO
OBJECTIVE: To determine the frequency of hyperintense cortical signal (HCS) on T1-weighted precontrast magnetic resonance (MR) images in progressive multifocal leukoencephalopathy (PML) patients, its association with seizure risk and immune reconstitution inflammatory syndrome (IRIS), and its pathologic correlate. METHODS: We reviewed clinical data including seizure history, presence of IRIS, and MR imaging scans from PML patients evaluated at our institution between 2003 and 2012. Cases that were diagnosed either using cerebrospinal fluid JC virus (JCV) polymerase chain reaction, brain biopsy, or autopsy, and who had MR images available were included in the analysis (n=49). We characterized pathologic findings in areas of the brain that displayed HCS in 2 patients and compared them with isointense cortex in the same individuals. RESULTS: Of 49 patients, 17 (34.7%) had seizures and 30 (61.2%) had HCS adjacent to subcortical PML lesions on MR images. Of the 17 PML patients with seizures, 15 (88.2%) had HCS compared with 15 of 32 (46.9%) patients without seizures (p=0.006). HCS was associated with seizure development with a relative risk of 4.75 (95% confidence interval=1.2-18.5, p=0.006). Of the 20 patients with IRIS, 16 (80.0%) had HCS compared with 14 of 29 (49.3%) patients without IRIS (p=0.04). On histological examination, HCS areas were associated with striking JCV-associated demyelination of cortical and subcortical U fibers, significant macrophage infiltration, and a pronounced reactive gliosis in the deep cortical layers. INTERPRETATION: Seizures are a frequent complication in PML. HCS is associated with seizures and IRIS, and correlates histologically with JCV focal leukocortical encephalitis.