RESUMEN
The complement system is an important component of innate and adaptive immunity that consists of three activation pathways. The classic complement pathway plays a role in humoral immunity, whereas the alternative and lectin pathways augment the innate response. Impairment, deficiency, or overactivation of any of the known 50 complement proteins may lead to increased susceptibility to infection with encapsulated organisms, autoimmunity, hereditary angioedema, or thrombosis, depending on the affected protein. Classic pathway defects result from deficiencies of complement proteins C1q, C1r, C1s, C2, and C4, and typically manifest with features of systemic lupus erythematosus and infections with encapsulated organisms. Alternative pathway defects due to deficiencies of factor B, factor D, and properdin may present with increased susceptibility to Neisseria infections. Lectin pathway defects, including Mannose-binding protein-associated serine protease 2 (MASP2) and ficolin 3, may be asymptomatic or lead to pyogenic infections and autoimmunity. Complement protein C3 is common to all pathways, deficiency of which predisposes patients to severe frequent infections and glomerulonephritis. Deficiencies in factor H and factor I, which regulate the alternative pathway, may lead to hemolytic uremic syndrome. Disseminated Neisseria infections result from terminal pathway defects (i.e., C5, C6, C7, C8, and C9). Diagnosis of complement deficiencies involves screening with functional assays (i.e., total complement activity [CH50], alternative complement pathway activity [AH50], enzyme-linked immunosorbent assay [ELISA]) followed by measurement of individual complement factors by immunoassay. Management of complement deficiencies requires a comprehensive and individualized approach with special attention to vaccination against encapsulated bacteria, consideration of prophylactic antibiotics, treatment of comorbid autoimmunity, and close surveillance.
Asunto(s)
Proteínas del Sistema Complemento , Síndromes de Inmunodeficiencia , Humanos , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/inmunología , Activación de ComplementoRESUMEN
OBJECTIVE: No biomarkers reliably predict risk for sudden unexpected death in epilepsy (SUDEP). Postictal generalized electroencephalography (EEG) suppression (PGES) is a possible biomarker for SUDEP risk. However, its utility in predicting SUDEP remains uncertain. We had observed that postictal tonic electromyography (PTEMG) activity follows some generalized convulsive seizures (GCS). PTEMG activity and PGES may have a common pathophysiologic basis. PGES is associated with periictal respiratory distress. There is evidence that tonic EMG occurs with brain hypoxia. Thus PTEMG activity may be related to seizure-associated hypoxemia. Pronounced variation occurs among expert clinicians in identifying PGES, thereby limiting its utility as a biomarker. Characteristics of PTEMG activity and its relationship to preceding GCS have not been explored. We studied PTEMG activity characteristics, its relationship to the preceding seizure and associated respiratory dysfunction. METHODS: We reviewed 145 GCS in 66 patients undergoing video-EEG telemetry (VET). The presence of PTEMG activity was defined when tonic EMG occurred for at least 3 seconds following seizure termination and was identified with filter settings at 5-200 Hz. Duration of PTEMG activity, the seizure, PGES, seizure-associated peripheral capillary oxygen saturation (SpO2 ) change, and end-tidal CO2 were analyzed. We compared data from GCS with and without PTEMG activity. RESULTS: Ninety of 145 seizures with GCS had PTEMG activity. The remainder had postictal slowing without PTEMG activity, and cessation of activity was followed by EEG slowing. Duration of the initial PTEMG discharge was 39.1 (mean) ± (standard deviation) 17.9 seconds. SpO2 nadir was lower (P = 0.005) in seizures with PTEMG activity than in those without (72% vs 77%). End-tidal CO2 was higher (P = 0.05) in seizures with PTEMG activity than in those without (63 vs 56 mm Hg). PGES duration was 35.6 ± 22.2 seconds and associated with duration of PTEMG activity (P < 0.001). SIGNIFICANCE: The novel finding is that PTEMG activity occurs following 62% of GCS and that seizures with PTEMG activity have greater severity of respiratory dysfunction than seizures without. PTEMG activity is readily discerned by visual analysis of VET at appropriate filter settings and has the potential of being a complementary or surrogate biomarker of PGES for assessing SUDEP risk.
Asunto(s)
Electroencefalografía , Epilepsia Generalizada/fisiopatología , Trastornos Respiratorios/fisiopatología , Convulsiones/fisiopatología , Adolescente , Adulto , Anciano , Ondas Encefálicas/fisiología , Muerte Súbita , Electroencefalografía/métodos , Femenino , Humanos , Hipoxia/fisiopatología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To investigate potentially high-risk cardiac arrhythmias (PHAs) following focal to bilateral tonic-clonic seizures (FBTCSs) and generalized tonic-clonic seizures (GTCSs) and to study the association of PHAs with seizure characteristics and the severity of associated ictal respiratory dysfunction. METHODS: Electrocardiographic (EKG) and pulse oximetry (SpO2 ) data were recorded concurrently with video-electroencephalographic telemetry in the epilepsy monitoring unit (EMU). One minute of preictal EKG, the ictal EKG, and 2 min of ictal/postictal data were reviewed for each seizure. Nonsustained ventricular tachycardia, bradyarrhythmia, and/or sinus pauses were considered as PHAs. FBTCSs/GTCSs with PHAs were compared to those that had only ictal sinus tachycardia. RESULTS: Data from 69 patients with 182 FBTCSs/GTCSs with usable SpO2 and EKG recordings were available. There were 10 FBTCSs/GTCSs in 10 patients with a PHA. The presence of PHAs was not associated with seizure duration or SpO2 nadir. FBTCSs/GTCSs with a PHA were significantly associated with the duration of oxygen desaturation < 90% when compared with FBTCSs/GTCSs with only sinus tachycardia (Mann-Whitney, p = 0.042). Desaturation duration of <100 s was not significantly associated with occurrence of PHAs (p = 0.110) when compared with seizures that had only sinus tachycardia. The odds ratio for occurrence of PHA was 7.86 for desaturation durations ≥ 125 s versus desaturations < 125 s (p = 0.005). The odds ratio increased to 13.09 for desaturation durations ≥ 150 s (p < 0.001). Preictal and ictal/postictal arrhythmias occurred with focal seizures that did not progress to FBTCSs. Four patients with focal seizures had ictal/postictal PHAs without preictal PHAs. Two of these patients had evidence for prior cardiac disturbance. SIGNIFICANCE: PHAs following a single FBTCS/GTCS in the EMU are significantly associated with the duration of ictal/postictal hypoxemia. It is possible that FBTCS/GTCS-associated hypoxemia may trigger fatal cardiac arrhythmias in a subset of susceptible patients dying of sudden unexpected death in epilepsy.