RESUMEN
INTRODUCTION: Listeria monocytogenes infection is a severe disease affecting mainly aged people and patients with immune depression. The incidence of listeriosis seems to be increasing. In the present study cases of listeriosis from two hospitals are analyzed with the aims of studying changes in its incidence, clinical forms of presentation and possible factors associated with mortality. METHODS: Retrospective multicentric study of patients with culture-proven listeriosis in two university hospitals in Madrid between 1977 and 2021. Epidemiological and clinical variables, as well as factors for immune depression, complementary studies and treatments were registered. Factors associated with mortality were analyzed. RESULTS: A total of 194 cases of listeriosis were analyzed. The incidence of listeriosis among in-patients increased through the study period, with a significant drop in the number of cases in 2020. The most common clinical presentations were isolated bacteriemia (37.1%) and central nervous system involvement (CNS) (36.6%). Symptoms of gastroenteritis occurred in 21% of cases. Other focal infections were present in 16.5% of patients, the most frequent were spontaneous bacterial peritonitis (8.2%), cholecystitis (2.1%), respiratory infection (1.5%) and vascular prothesis infection (1.5%). In-hospital mortality was 24.7%. Independent factors associated with mortality at admission were age (Odds Ratio [OR] 1.027, 95% confidence interval [IC95%] 1.003-1.056) and a diagnosis of a solid tumor (OR 3.525, IC95% 1.652-7.524). CONCLUSIONS: This study confirms an increasing incidence of listeriosis in our millieu. The most common clinical presentations were isolated bacteriemia and central nervous system involvement. In-hospital mortality was associated with age and the diagnosis of a solid tumor.
Asunto(s)
Bacteriemia , Listeria monocytogenes , Listeriosis , Neoplasias , Humanos , Anciano , Estudios Retrospectivos , Pronóstico , Listeriosis/diagnóstico , Listeriosis/epidemiología , Bacteriemia/complicaciones , Neoplasias/complicaciones , Neoplasias/epidemiologíaRESUMEN
Patients with herpes simplex virus (HSV) encephalitis (HSE) often develop neuronal autoantibody-associated encephalitis (AE) post-infection. Risk factors of AE are unknown. We tested the hypotheses that predisposition for AE post-HSE may be involved, including genetic variants at specific loci, human leucocyte (HLA) haplotypes, or the blood innate immune response against HSV, including type I interferon (IFN) immunity. Patients of all ages with HSE diagnosed between 1 January 2014 and 31 December 2021 were included in one of two cohorts depending on whether the recruitment was at HSE onset (Spanish Cohort A) or by the time of new neurological manifestations (international Cohort B). Patients were assessed for the type of neurological syndromes; HLA haplotypes; blood type I-IFN signature [RNA quantification of 6 or 28 IFN-response genes (IRG)] and toll-like receptor (TLR3)-type I IFN-related gene mutations. Overall, 190 patients (52% male) were recruited, 93 in Cohort A and 97 in Cohort B. Thirty-nine (42%) patients from Cohort A developed neuronal autoantibodies, and 21 (54%) of them developed AE. Three syndromes (choreoathetosis, anti-NMDAR-like encephalitis and behavioural-psychiatric) showed a high (≥95% cases) association with neuronal autoantibodies. Patients who developed AE post-HSE were less likely to carry the allele HLA-A*02 (4/21, 19%) than those who did not develop AE (42/65, 65%, P = 0.0003) or the Spanish general population (2005/4335, 46%, P = 0.0145). Blood IFN signatures using 6 or 28 IRG were positive in 19/21 (91%) and 18/21 (86%) patients at HSE onset, and rapidly decreased during follow-up. At Day 21 after HSE onset, patients who later developed AE had higher median IFN signature compared with those who did not develop AE [median Zs-6-IRG 1.4 (0.6; 2.0) versus 0.2 (-0.4; 0.8), P = 0.03]. However, a very high median Zs-6-IRG (>4) or persistently increased IFN signature associated with uncontrolled viral infection. Whole exome sequencing showed that the percentage of TLR3-IFN-related mutations in patients who developed AE was not different from those who did not develop AE [3/37 (8%) versus 2/57 (4%), P = 0.379]. Multivariate logistic regression showed that a moderate increase of the blood IFN signature at Day 21 (median Zs-6-IRG >1.5 but <4) was the most important predictor of AE post-HSE [odds ratio 34.8, interquartile ratio (1.7-691.9)]. Altogether, these findings show that most AE post-HSE manifest with three distinct syndromes, and HLA-A*02, but not TLR3-IFN-related mutations, confer protection from developing AE. In addition to neuronal autoantibodies, the blood IFN signature in the context of HSE may be potentially useful for the diagnosis and monitoring of HSE complications.
Asunto(s)
Encefalitis por Herpes Simple , Interferón Tipo I , Enfermedades del Sistema Nervioso , Humanos , Masculino , Femenino , Encefalitis por Herpes Simple/complicaciones , Encefalitis por Herpes Simple/genética , Receptor Toll-Like 3/genética , Autoanticuerpos , Antígenos HLA-ARESUMEN
Progressive multifocal leukoencephalopathy (PML) is a demyelinating central nervous system disease infection by JC virus (JCV) in patients with a significant decline in cellular immunity. No specific treatment has demonstrated efficacy, and the disease progresses to death in most patients. Recent findings have shown stabilization or improvement of PML lesions after treatment with checkpoint inhibitors (CPI) based on immune reconstitution. Nevertheless, immunotherapy may specifically cause autoimmune diseases or may deteriorate pre-existing ones. We report a case of a patient under treatment for advanced ductal breast carcinoma and systemic sclerosis, who developed PML. The therapeutic approach included withdrawal of drugs with possible immunosuppressive effect and treatment with pembrolizumab. In the absence of reliable markers to predict CPIs response and a concern for an autoimmune worsening, immunotherapy was administered late in the course of the disease. Finally, she did not experience an autoimmune disease flare-up; however, pembrolizumab could not prevent disease progression. We believe that potential autoimmune complications should not delay treatment initiation with CPIs in PML.
Asunto(s)
Neoplasias de la Mama , Virus JC , Leucoencefalopatía Multifocal Progresiva , Esclerodermia Sistémica , Femenino , Humanos , Progresión de la Enfermedad , Esclerodermia Sistémica/complicaciones , Neoplasias de la Mama/complicacionesRESUMEN
The field of Autoimmune Neurology is expanding rapidly, with new neural antibodies being identified each year. However, these disorders remain rare. Deciding when to test for these antibodies, when and what samples are to be obtained, how to handle and study them correctly, and how to interpret test results, is complex. In this article we review current diagnostic techniques and provide a comprehensive explanation on the study of these patients, in an effort to help with correct diagnosis minimizing false positive and false negative results. We also propose routine storage of samples and referral of certain cases to specialized research laboratories.
Asunto(s)
Anticuerpos , Neurología , HumanosRESUMEN
Paraneoplastic cerebellar degeneration (PCD) is one of the most prevalent neurological paraneoplastic syndromes, typically associated with small cell lung cancer (SCLC). PCD is thought to be caused by proteins expressed by tumor cells which trigger an antibody-mediated immune response. Despite PCD being commonly associated with anti-Yo, anti-Hu and anti-Tr/DNER antibodies, PCD is the most prevalent paraneoplastic syndrome in patients harboring anti-Zic4 antibodies. We report what, to our knowledge, is the first known case of anti-Zic4 mediated PCD in a patient with EGFR-mutated metastatic non-small cell lung cancer (NSCLC). Our patient was in complete response (CR) to targeted therapy and presented to the emergency room with drowsiness, unsteady gait and memory lapses. The diagnostic work-up revealed a diffuse cerebellar atrophy in the MRI, ruling out brain metastasis and leptomeningeal carcinomatosis. A body-CT scan showed no signs of recurrent disease. The cerebrospinal fluid (CSF) was within normal parameters. An onconeural antibody panel was conducted in a peripheral blood sample, detecting high levels of anti-Zic4 antibody by indirect immunofluorescence (IFI), results later confirmed by immunoblot testing. With the suspected diagnosis of an anti-Zic4 PCD, the case was discussed with the neurology department and treatment with high dose methylprednisolone was initiated. Considering the lack of substantial clinical benefit, the patient was then treated with intravenous immunoglobulins (IVIG) for 5 days, showing modest improvement. At this time, the patient presented minor disease relapse in the form of a sub-centimetric pulmonary nodule. Despite one cycle of chemotherapy, the patient's neurological condition deteriorated leading to fatal pneumonia secondary to progressive dysphagia. There is scarce evidence of paraneoplastic syndromes in EGFR-mutated NSCLC. Further research is warranted to stablish a possible association between anti-Zic4 and the EGFR molecular pathway.
RESUMEN
Severe cases of Coronavirus Disease 2019 (COVID-19) can present with multiple neurological symptoms. The available neuropathological studies have described different lesions; the most frequent was the presence of neuroinflammation and vascular-related lesions. The objective of this study was to report the neuropathological studies performed in a medical institution, with abundant long intensive care unit stays, and their associated clinical manifestations. This is a retrospective monocentric case series study based on the neuropathological reports of 13 autopsies with a wide range of illness duration (13-108 days). A neuroinflammatory score was calculated based on the quantification of CD8- and CD68-positive cells in representative areas of the central nervous system. This score was correlated afterwards with illness duration and parameters related to systemic inflammation. Widespread microglial and cytotoxic T-cell activation was found in all patients. There was no correlation between the neuroinflammatory score and the duration of the illness; nor with parameters of systemic inflammation such as the peak of IL-6 or the HScore (a parameter of systemic macrophage activation syndrome). Two patients had global hypoxic ischaemic damage and five patients had subacute infarcts. One patient had many more brain vascular microthrombi compared to the others and multiple subacute pituitary infarcts. SARS-CoV-2 RNA was not detected with qRT-PCR. The proportion of brain lesions in severe COVID-19 patients could be related to illness duration. In our series, with abundant long hospitalisation stays, neuroinflammation was present in all patients and was more prominent between day 34 and day 45 after onset of symptoms. Clinical correlation showed that two patients with the highest neuroinflammatory scores had severe encephalopathies that were not attributable to any other cause. The second most frequent lesions were related to vascular pathology.
Asunto(s)
COVID-19 , Enfermedades del Sistema Nervioso , COVID-19/complicaciones , Humanos , Infarto , Inflamación , Interleucina-6 , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/patología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
The role of immunosuppression among coronavirus disease 2019 (COVID-19) patients has not been elucidated and management may be challenging. This observational study included confirmed COVID-19 patients. The primary endpoint was the development of moderate-severe acute respiratory distress syndrome (ARDS). Time to moderate-severe ARDS, the need for mechanical or noninvasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints. Of 138 patients included, 27 (19.6%) were immunosuppressed (IS) and 95 (68.8%) were male, with a median (IQR) age of 68 (54-78) years. A significantly lower proportion of IS patients (25.9%) compared to non-IS patients (52.3%) developed moderate-severe ARDS, in both unadjusted (0.32; 95% CI, 0.13-0.83; p = .017) and adjusted (aOR, 0.25; 95% CI, 0.08-0.80; p = .019) analyses. After stratifying by pathologies, only IS patients with autoimmune diseases remained significant (aOR 0.25; 95% CI, 0.07-0.98; p = .046). Nonsignificant trends toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected among IS. In our cohort of COVID-19 patients, nonsevere immunosuppression was associated with a lower risk of moderate-severe ARDS, especially among AD. This suggests a potential protective effect from a hypothesized hyper-inflammatory response.
Asunto(s)
COVID-19/inmunología , Síndrome de Dificultad Respiratoria/inmunología , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/virología , Estudios de Cohortes , Coinfección , Femenino , Hospitalización , Humanos , Terapia de Inmunosupresión , Masculino , Persona de Mediana Edad , Proyectos Piloto , Síndrome de Dificultad Respiratoria/epidemiología , Síndrome de Dificultad Respiratoria/virología , Estudios Retrospectivos , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , España/epidemiologíaRESUMEN
Immunosuppressed patients are at higher risk for developing herpes zoster (HZ), and neurological complications are frequent in them. However, the influence of immunosuppression (IS) on the severity and prognosis of neurological complications of varicella-zoster virus (VZV) reactivation is unknown. We studied retrospectively patients with neurological complications due to VZV reactivation who attended our hospital between 2004 and 2019. We aimed to assess the clinical spectrum, potential prognostic factors, and the influence of the immune status on the severity of neurological symptoms. A total of 98 patients were included (40% had IS). Fifty-five patients (56%) had cranial neuropathies which included Ramsay-Hunt syndrome (36 patients) and cranial multineuritis (23 patients). Twenty-one patients developed encephalitis (21%). Other diagnosis included radiculopathies, meningitis, vasculitis, or myelitis (15, 10, 6, and 4 patients, respectively). Mortality was low (3%). At follow-up, 24% of patients had persistent symptoms although these were usually mild. IS was associated with severity (defined as a modified Rankin scale greater than 2) (odds ratio, 4.23; 95% confidence interval, 1.74-10.27), but not with prognosis. Shorter latency between HZ and neurologic symptoms was the only factor associated with an unfavorable course (death or sequelae) (odds ratio, 0.82; 95% confidence interval, 0.71-0.95). In conclusion, the clinical spectrum of neurological complications in VZV reactivation is wide. Mortality was low and sequelae were mild. The presence of IS may play a role on the severity of neurological symptoms, and a shorter time between HZ and the onset of neurological symptoms appears to be a negative prognostic factor.
Asunto(s)
Encefalitis por Varicela Zóster/inmunología , Herpes Zóster Ótico/inmunología , Herpes Zóster/inmunología , Herpesvirus Humano 3/patogenicidad , Inmunosupresores/efectos adversos , Neuritis/inmunología , Radiculopatía/inmunología , Anciano , Anciano de 80 o más Años , Encefalitis por Varicela Zóster/complicaciones , Encefalitis por Varicela Zóster/diagnóstico , Encefalitis por Varicela Zóster/mortalidad , Femenino , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Herpes Zóster/mortalidad , Herpes Zóster Ótico/diagnóstico , Herpes Zóster Ótico/etiología , Herpes Zóster Ótico/mortalidad , Humanos , Terapia de Inmunosupresión , Masculino , Meningitis Viral/diagnóstico , Meningitis Viral/etiología , Meningitis Viral/inmunología , Meningitis Viral/mortalidad , Persona de Mediana Edad , Mielitis/diagnóstico , Mielitis/etiología , Mielitis/inmunología , Mielitis/mortalidad , Neuritis/diagnóstico , Neuritis/etiología , Neuritis/mortalidad , Pronóstico , Radiculopatía/diagnóstico , Radiculopatía/etiología , Radiculopatía/mortalidad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Vasculitis/diagnóstico , Vasculitis/etiología , Vasculitis/inmunología , Vasculitis/mortalidad , Activación Viral/efectos de los fármacos , Latencia del Virus/efectos de los fármacosRESUMEN
INTRODUCTION: An increased incidence of stroke in HIV-infected patients has already been reported, suggesting that HIV infection may be a cerebrovascular risk factor. The objective of this study was to assess temporal trends in the proportion of HIV infection among patients with stroke in Spain. METHODS: Data were obtained from the minimum basic dataset (MBDS) of all patients hospitalized in Spain between 1997 and 2012 with a primary or secondary diagnosis of stroke. The annual proportion of HIV infection and time trends (stratifying by type of stroke and HIV stage) were calculated, and predictors of HIV infection and the social and economic impact of HIV-infected (HIV+) and non-infected (HIV-) patients were analyzed. RESULTS: Of 857,371 patients hospitalized with an incident stroke, 2134 (0.25%) had HIV infection. A 2.5% year-on-year increase (OR 1.025, 95% CI 1.015-1.036, p<0.0001) of the proportion of HIV-infected patients was observed due to an increase in the asymptomatic stage of the infection (per year OR 1.077, 95% CI 1.057-1.097, p<0.0001), as the proportion of patients with AIDS remained stable. Factors independently associated with HIV infection and stroke were active smoking, stimulating drugs and hepatitis C virus (HCV) infection. A higher mortality rate, longer hospital stay and a higher cost per hospitalized patient was observed among HIV+ patients. CONCLUSIONS: From 1997 to 2012, there was an increase in the proportion of HIV infection among patients hospitalized with stroke irrespective of the classical vascular risk factors, reinforcing the role of HIV infection as a cerebrovascular risk factor.
Asunto(s)
Infecciones por VIH , Accidente Cerebrovascular , Infecciones por VIH/epidemiología , Humanos , Estudios Retrospectivos , España/epidemiología , Accidente Cerebrovascular/epidemiologíaAsunto(s)
Corea/complicaciones , Degeneración Combinada Subaguda/complicaciones , Deficiencia de Vitamina B 12/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Corea/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Médula Espinal/diagnóstico por imagen , Degeneración Combinada Subaguda/diagnóstico por imagen , Deficiencia de Vitamina B 12/diagnóstico por imagenRESUMEN
OBJECTIVES: To describe the neurological manifestations of invasive aspergillosis presenting with a focal neurological deficit compatible with an acute stroke. MATERIALS AND METHODS: Retrospective analysis of a clinical series of patients between 2011 and 2017 with invasive aspergillosis and neurological symptoms compatible with an acute brain stroke. Clinical and epidemiological data, microbiological results, radiological findings, treatment, and course were recorded. RESULTS: Five patients were selected with a mean age of 55.4years. All patients were immunosuppressed. In 4, systemic infection was unknown. In every case, neurology on call was alerted because of acute focal neurological symptoms. None of the patients received revascularization procedures. Galactomannan antigen was positive in all of the patients and culture was positive in 3. Mortality was 100% despite specific antifungal treatment. CONCLUSIONS: Acute stroke can be the first manifestation of disseminated aspergillosis. This form of presentation was frequent in our series and should be suspected in immunocompromised patients with acute neurological deficits.
Asunto(s)
Neuroaspergilosis/microbiología , Infecciones Oportunistas/microbiología , Accidente Cerebrovascular/microbiología , Antifúngicos/uso terapéutico , Autopsia , Femenino , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroaspergilosis/diagnóstico , Neuroaspergilosis/inmunología , Neuroaspergilosis/mortalidad , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/mortalidad , Estudios Retrospectivos , Factores de Riesgo , España , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/mortalidad , Resultado del TratamientoRESUMEN
OBJECTIVES: Substantia nigra hyperechogenicity (SN+) detected by transcranial ultrasound (TUS) is useful for Parkinson's disease (PD) diagnosis. Approximately 15% false negative results of unknown significance are reported. However, most TUS studies are transversal, and diagnosis of PD may change during follow-up. METHODS: Analysis of our prospective registry of TUS in clinical practice, selecting patients with sufficient bone window, to whom TUS was performed because of suspected PD, and a minimum of 3-year follow-up. Subjects were classified regarding SN echogenicity (SN+/SN-). RESULTS: 172 patients (122 SN+, 50 SN-), mean age 71 years (25-90), were included. At the end of follow-up, PD diagnosis was retained by 91% SN+ vs. 54% SN- subjects (p < 0.0001), while final diagnosis of atypical parkinsonism (3%SN+ vs. 16%SN-, p:0.0059) was more frequent in SN-. Dopaminergic therapy response was associated with SN+ (88% SN+ vs. 50% SN-, p < 0.0001), as were abnormal DaTSCANs (90%SN+ vs. 56%SN-, p 0.0027). SN echogenicity had 80% sensitivity and 68% specificity for PD diagnosis, while SPECT had 91% and 73%, respectively. SN+ was the only baseline predictor of keeping PD diagnosis at the end of follow-up, with an odds ratio of 12 (95% CI 3-42) (p < 0.001). CONCLUSIONS: In our sample of patients with suspected PD, SN hyperechogenicity predicted PD diagnosis in the long term with a high odds ratio. Conversely, a baseline normal SN echogenicity was associated with a poorer response to PD therapy and change to a different diagnosis from PD. Normal SN appears to be a caveat for clinicians to check for atypical parkinsonism features during follow-up.
Asunto(s)
Ecoencefalografía , Enfermedad de Parkinson/diagnóstico por imagen , Sustancia Negra/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Estudios Prospectivos , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND: Herpes simplex encephalitis can trigger autoimmune encephalitis that leads to neurological worsening. We aimed to assess the frequency, symptoms, risk factors, and outcomes of this complication. METHODS: We did a prospective observational study and retrospective analysis. In the prospective observational part of this study, we included patients with herpes simplex encephalitis diagnosed by neurologists, paediatricians, or infectious disease specialists in 19 secondary and tertiary Spanish centres (Cohort A). Outpatient follow-up was at 2, 6, and 12 months from onset of herpes simplex encephalitis. We studied another group of patients retrospectively, when they developed autoimmune encephalitis after herpes simplex encephalitis (Cohort B). We compared demographics and clinical features of patients who developed autoimmune encephalitis with those who did not, and in patients who developed autoimmune encephalitis we compared these features by age group (patients ≤4 years compared with patients >4 years). We also used multivariable binary logistic regression models to assess risk factors for autoimmune encephalitis after herpes simplex encephalitis. FINDINGS: Between Jan 1, 2014, and Oct 31, 2017, 54 patients with herpes simplex encephalitis were recruited to Cohort A, and 51 were included in the analysis (median age 50 years [IQR 5-68]). At onset of herpes simplex encephalitis, none of the 51 patients had antibodies to neuronal antigens; during follow-up, 14 (27%) patients developed autoimmune encephalitis and all 14 (100%) had neuronal antibodies (nine [64%] had NMDA receptor [NMDAR] antibodies and five [36%] had other antibodies) at or before onset of symptoms. The other 37 patients did not develop autoimmune encephalitis, although 11 (30%) developed antibodies (n=3 to NMDAR, n=8 to unknown antigens; p<0·001). Antibody detection within 3 weeks of herpes simplex encephalitis was a risk factor for autoimmune encephalitis (odds ratio [OR] 11·5, 95% CI 2·7-48·8; p<0·001). Between Oct 7, 2011, and Oct 31, 2017, there were 48 patients in Cohort B with new-onset or worsening neurological symptoms not caused by herpes simplex virus reactivation (median age 8·8 years [IQR 1·1-44·2]; n=27 male); 44 (92%) patients had antibody-confirmed autoimmune encephalitis (34 had NMDAR antibodies and ten had other antibodies). In both cohorts (n=58 patients with antibody-confirmed autoimmune encephalitis), patients older than 4 years frequently presented with psychosis (18 [58%] of 31; younger children not assessable). Compared with patients older than 4 years, patients aged 4 years or younger (n=27) were more likely to have shorter intervals between onset of herpes simplex encephalitis and onset of autoimmune encephalitis (median 26 days [IQR 24-32] vs 43 days [25-54]; p=0·0073), choreoathetosis (27 [100%] of 27 vs 0 of 31; p<0·001), decreased level of consciousness (26 [96%] of 27 vs seven [23%] of 31; p<0·001), NMDAR antibodies (24 [89%] of 27 vs 19 [61%] of 31; p=0·033), and worse outcome at 1 year (median modified Rankin Scale 4 [IQR 4-4] vs 2 [2-3]; p<0·0010; seizures 12 [63%] of 19 vs three [13%] of 23; p=0·001). INTERPRETATION: The results of our prospective study show that autoimmune encephalitis occurred in 27% of patients with herpes simplex encephalitis. It was associated with development of neuronal antibodies and usually presented within 2 months after treatment of herpes simplex encephalitis; the symptoms were age-dependent, and the neurological outcome was worse in young children. Prompt diagnosis is important because patients, primarily those older than 4 years, can respond to immunotherapy. FUNDING: Mutua Madrileña Foundation, Fondation de l'Université de Lausanne et Centre Hospitalier Universitaire Vaudois, Instituto Carlos III, CIBERER, National Institutes of Health, Generalitat de Catalunya, Fundació CELLEX.
Asunto(s)
Encefalitis por Herpes Simple/complicaciones , Encefalitis por Herpes Simple/epidemiología , Encefalitis/epidemiología , Encefalitis/etiología , Enfermedad de Hashimoto/epidemiología , Enfermedad de Hashimoto/etiología , Adolescente , Adulto , Anciano , Animales , Autoanticuerpos/metabolismo , Niño , Preescolar , Estudios de Cohortes , Encefalitis/líquido cefalorraquídeo , Encefalitis/diagnóstico por imagen , Encefalitis por Herpes Simple/líquido cefalorraquídeo , Encefalitis por Herpes Simple/diagnóstico por imagen , Femenino , Glutamato Descarboxilasa/metabolismo , Enfermedad de Hashimoto/líquido cefalorraquídeo , Enfermedad de Hashimoto/diagnóstico por imagen , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Ratas , Receptores de N-Metil-D-Aspartato/inmunología , Factores de Riesgo , Estadísticas no Paramétricas , Adulto JovenRESUMEN
Neurological manifestations associated with HHV-7 have been described in primary infection in children, and very occasionally in immunocompromised adult patients. However, the role of HHV-7 reactivation as a cause of central nervous system (CNS) diseases in immunocompetent adults has not yet been defined. We retrospectively analyzed clinical and microbiological features of adults with neurological symptoms who underwent lumbar puncture and a multiplex polymerase chain reaction (PCR) for herpesviruses (HHV-1-8) and enteroviruses performed in cerebrospinal fluid (CSF), during a 4-year period. A total of 251 subjects were included. Mean age was 55 years, ranging 15-89. Globally, HHV-7 DNA was detected in CSF in 14 patients (5.6%). It was detected in 1 of 36 patients with microbiologically confirmed CNS infections, and in 7 of 172 patients with diagnoses of non-infectious neurological disorders (Specificity 0.96, 95% confidence interval 0.93-0.99). Additionally, HHV-7 DNA was detected in 6 of 21 patients (28.6%) with probable CNS infections (compatible clinical syndrome and CSF changes) in the absence of other causative agent: four meningitis, one myelitis, and one encephalitis. Treatment with foscarnet was effective in achieving improvement of symptoms and clearance of HHV-7 DNA in CSF in the cases of encephalitis and myelitis, while ganciclovir was ineffective in the case of encephalitis. Our results show that HHV-7 reactivation may cause CNS disease in immunocompetent adults and that detection of HHV-7 DNA in CSF as a false-positive result or as asymptomatic reactivation in adult patients with neurological diseases is uncommon. Foscarnet seems the first-line treatment for HHV-7 CNS disease.
Asunto(s)
ADN Viral/genética , Encefalitis Viral/diagnóstico , Herpesvirus Humano 7/genética , Meningitis Viral/diagnóstico , Mielitis/diagnóstico , Infecciones por Roseolovirus/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , ADN Viral/líquido cefalorraquídeo , ADN Viral/aislamiento & purificación , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/tratamiento farmacológico , Encefalitis Viral/virología , Femenino , Foscarnet/uso terapéutico , Ganciclovir/uso terapéutico , Herpesvirus Humano 7/aislamiento & purificación , Humanos , Masculino , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/tratamiento farmacológico , Meningitis Viral/virología , Persona de Mediana Edad , Mielitis/líquido cefalorraquídeo , Mielitis/tratamiento farmacológico , Mielitis/virología , Estudios Retrospectivos , Infecciones por Roseolovirus/líquido cefalorraquídeo , Infecciones por Roseolovirus/tratamiento farmacológico , Infecciones por Roseolovirus/virología , Punción Espinal/métodosRESUMEN
We report a new transthyretin (ATTR) gene c.272C>G mutation and variant protein, p.Leu32Val, in a kindred of Bolivian origin with a rapid progressive peripheral neuropathy and cardiomyopathy. Three individuals from a kindred with peripheral nerve and cardiac amyloidosis were examined. Analysis of the TTR gene was performed by Sanger direct sequencing. Neuropathologic examination was obtained on the index patient with mass spectrometry study of the ATTR deposition. Direct DNA sequence analysis of exons 2, 3, and 4 of the TTR gene demonstrated a c.272 C>G mutation in exon 2 (p.L32V). Sural nerve biopsy revealed massive amyloid deposition in the perineurium, endoneurium and vasa nervorum. Mass spectrometric analyses of ATTR immunoprecipitated from nerve biopsy showed the presence of both wild-type and variant proteins. The observed mass results for the wild-type and variant proteins were consistent with the predicted values calculated from the genetic analysis data. The ATTR L32V is associated with a severe course. This has implications for treatment of affected individuals and counseling of family members.
Asunto(s)
Neuropatías Amiloides Familiares/genética , Salud de la Familia , Leucina/genética , Mutación/genética , Prealbúmina/genética , Valina/genética , Neuropatías Amiloides Familiares/fisiopatología , Bolivia , Análisis Mutacional de ADN , Femenino , Humanos , Persona de Mediana Edad , Conducción Nerviosa/genética , Prealbúmina/metabolismoRESUMEN
BACKGROUND: HHV7 reactivation has been occasionally reported as a cause of encephalitis or myelitis in transplant recipients, but to our knowledge it has never been associated with neurological disease in HIV-infected patients. We report a case of acute myelitis in an HIV-infected patient, with sustained HHV-7 DNA amplification in cerebrospinal fluid (CSF) and a favourable response to foscarnet. CASE REPORT: A 40 year-old man with HIV infection was admitted with asymmetric hypoesthesia in legs and paraparesis. He was receiving treatment with efavirenz, emtricitabine and tenofovir, his CD4 count was 580/mm3 and HIV viral load was undetectable. Magnetic resonance imaging showed a focal central hyperintensity on T2 and STIR sequences, on the torathic spinal cord, with slight enhancement after intravenous gadolinium. All microbiological studies were negative except for HHV-7 DNA amplification in CSF. With a diagnosis of idiopathic transverse myelitis, treatment with high-dose intravenous methylprednisolone was initiated. However, paraparesis continued worsening, and a second CSF obtained 12 days after the first one resulted again in HHV-7 amplification. RESULTS: The patient was treated with a 2 week course of foscarnet, and a rapid neurological improvement was noted. After treatment, PCR for HHV-7 in CSF was negative. Neurological exam was normal one month after treatment initiation. CONCLUSION: HHV-7 reactivation may cause neurological disease in patients with HIV infection. Foscarnet is an effective treatment in HHV-7 associated myelitis.
Asunto(s)
Coinfección , Infecciones por VIH/diagnóstico , Herpesvirus Humano 7 , Mielitis/diagnóstico , Mielitis/virología , Infecciones por Roseolovirus/diagnóstico , Adulto , Antivirales/uso terapéutico , Recuento de Linfocito CD4 , ADN Viral , Foscarnet/uso terapéutico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Herpesvirus Humano 7/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Mielitis/tratamiento farmacológico , Infecciones por Roseolovirus/tratamiento farmacológico , Infecciones por Roseolovirus/virología , Médula Espinal/patología , Resultado del Tratamiento , Carga Viral , Activación ViralRESUMEN
BACKGROUND AND PURPOSE: Stroke on board aircraft has been reported in retrospective case series, mainly focusing on economy class stroke syndrome. Data on the actual incidence, pathogenesis, and prognosis of stroke in commercial flights are lacking. METHODS: A prospective registry was designed to include all consecutive patients referred from an international airport (40 million passengers a year) to our hospital with a diagnosis of ischemic stroke or transient ischemic attack and onset of symptoms during a flight or immediately after landing. RESULTS: Forty-four patients (32 ischemic strokes and 12 transient ischemic attacks) were included over a 76-month period (January 2008 to April 2014). The estimated incidence of stroke was 1 stroke in 35 000 flights. Pathogeneses of stroke or transient ischemic attack were atherothrombotic in 16 (36%), economy class stroke syndrome in 8 (18%), cardioembolic in 7 (16%), arterial dissection in 4 (9%), lacunar stroke in 4 (9%), and undetermined in 5 (12%) patients. Carotid stenosis >70% was found in 12 (27%) of the patients. Overall prognosis was good, and thrombolysis was applied in 44% of the cases. The most common reason for not treating patients who had experienced stroke onset midflight was the delay in reaching the hospital. Only 1 patient with symptom onset during the flight prompted a flight diversion. CONCLUSIONS: We found a low incidence of stroke in the setting of air travel. Economy class stroke syndrome and arterial dissection were well represented in our sample. However, the main pathogenesis was atherothrombosis with a high proportion of patients with high carotid stenosis.