Hemorrhagic Shock And Encephalopathy Syndrome Research Articles

Hemorrhagic shock and encephalopathy syndrome: A call for new clinical criteria for early intervention

Background: Current epidemiological diagnostic criteria for hemorrhagic shock and encephalopathy syndrome (HSES) may not be optimal for early identification in clinical settings. We analyzed the specific timing at which Bacon's criteria were met after encephalopathy onset.Methods: This retrospective observational study was conducted at the National Center for Child Health and Development, a quaternary-care facility that receives critically ill patients from a wide geographic area, between January 2014 and December 2023. Cases of HSES were identified using Bacon's criteria. Data on detailed time courses after seizure onset were extracted from medical records. The primary outcome was the time at which Bacon's criteria were met, measured using median values.Results: Of the 206 patients with acute encephalopathy, 13 had HSES. Four were excluded due to insufficient data. Only one patient met Bacon's criteria based on initial examinations, while eight met them after presentation. The median time from seizure onset to meeting Bacon's criteria was 4 h. Early diagnostic markers included abnormal blood coagulation, renal dysfunction, and elevated enzyme levels. The median time to initiation of steroid pulse therapy was 11.5 h; it was 9 h for plasma exchange. Irreversible brain damage, indicated by cerebral edema, occurred at a median of 7 h post-seizure.Conclusions: The existing criteria fail in the context of early diagnosis. Routine practice should include early blood tests, including those for coagulation abnormalities, for patients with febrile status epilepticus to identify HSES at an early stage. Future research should validate new diagnostic criteria and explore additional interventions.

Clinical characteristics of SARS-CoV-2-associated encephalopathy in children: Nationwide epidemiological study

ObjectiveSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sometimes triggers acute encephalopathy as a serious neurological complication in children. We previously reported the clinico-radiological findings of SARS-CoV-2-associated encephalopathy. The advent of the SARS-CoV-2 omicron variant led to a marked increase in pediatric patients with coronavirus disease 2019 (COVID-19); however, epidemiological changes with acute encephalopathy according to the emergence of SARS-CoV-2 have not yet been documented. Therefore, the present study investigated epidemiological differences in SARS-CoV-2-associated encephalopathy during the BA.1/BA.2 and BA.5 predominant periods and also between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. MethodsWe conducted a nationwide survey of SARS-CoV-2-associated encephalopathy in Japanese children between June and November 2022. We compared the present results during the BA.5 predominant period and previous findings during the BA.1/BA.2 predominant period. We also compared the clinico-radiological syndromes of encephalopathy between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. ResultsAlthough many patients with SARS-CoV-2-associated encephalopathy in the BA.5 predominant period had seizures as their initial symptoms, no significant differences were observed in the clinical features. Patients with SARS-CoV-2-associated encephalopathy had worse outcomes than those with non-SARS-CoV-2-associated encephalopathy (p-value = 0.003). Among 103 patients with SARS-CoV-2-associated encephalopathy, 14 (13.6%) had severe types of acute encephalopathy, namely, encephalopathy with acute fulminant cerebral edema (AFCE) and hemorrhagic shock and encephalopathy syndrome (HSES). Also, 28 (27.2%) patients with SARS-CoV-2-associated encephalopathy had poor outcome: severe neurological sequelae or death. Ninety-five patients (92.2%) were not vaccinated against SARS-CoV-2. ConclusionsIn SARS-CoV-2-associated encephalopathy, high percentages of AFCE and HSES can result in poor outcomes.

Successful mild brain hypothermia therapy followed by targeted temperature management for pediatric hemorrhagic shock and encephalopathy syndrome.

Hemorrhagic shock and encephalopathy syndrome (HSES) is the most severe form of acute encephalopathy that progresses rapidly, often resulting in death or severe neurological sequelae. We report the case of a 4-year-old girl with HSES with shock and impaired consciousness. Blood test results showed hypercytokinemia, and the 4-year-old patient was immediately admitted to the intensive care unit. Within 4 h of symptom onset, she received mild brain hypothermia therapy with a target body temperature of 35°C. Methylprednisolone pulse, high dose immunoglobulin, and large doses of circulatory drugs were administered. After 72 h of brain hypothermia therapy, targeted temperature management with a target body temperature between 36°C and 37°C was continued for 96 h. The patient was diagnosed with HSES based on acute encephalopathy with shock, hypercytokinemia, low platelet count, coagulation disorder, renal damage, and intestinal bleeding. Magnetic resonance imaging results revealed no signs of any specific acute encephalopathy. She was discharged without neurological sequelae 28 days after symptom onset. Mild brain hypothermia therapy initiated in the early stages followed by targeted temperature management may be an effective way to improve neurological outcomes in children suffering from HSES.

Super-refractory status epilepticus and pharmacoresistant epilepsy in an infant with hemorrhagic shock and encephalopathy syndrome

Introduction. Hemorrhagic shock and encephalopathy syndrome (HSES) is a rare disorder with prevalence at an early age. The main features of HSES are acute diarrhea, shock, disseminated intravascular coagulation, multisystem impairment, and encephalopathy. The prognosis is very poor, with high mortality, especially in cases with status epilepticus. Case outline. The presented infant had typical features of HSES associated with super-refractory status epilepticus as de novo epileptic event, followed by pharmacoresistant epilepsy. Clinical course of the disease was very severe and required urgent circulatory and respiratory support, and simultaneous management of super-refractory status epilepticus by continuous intravenous infusion of midazolam, barbiturate, and levetiracetam. The outcome was very poor with serious neurological consequence and resistant epileptic seizures. Conclusion. The treatment of the presented patient with HSES was very challenging due to a lifethreatening condition associated with super-refractory status epilepticus, and further pharmacoresistant epilepsy. Additionally, the choice of antiepileptic drugs is limited due to multisystem impairment and adverse effects which might worsen the already severe course of the disease.

Elevated cytokine, chemokine, and growth and differentiation factor-15 levels in hemorrhagic shock and encephalopathy syndrome: A retrospective observational study

Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a ‘cytokine storm’. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1β (IL-1β), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.

Diagnosis and treatment of hemorrhagic shock and encephalopathy syndrome

Hemorrhagic shock and encephalopathy syndrome(HSES) is an acute-onset disease whose clinical manifestations are fever, shock, diarrhea, severe disseminated intravascular coagulation and liver and kidney dysfunction, with rapid progression, poor prognosis and high mortality rate.At present, the etiology of HSES is unknown, and it is widely believed that the pathogenesis of HSES is related to infection, high fever, cytokine storm and genetics.There is lack of specific diagnostic markers for the diagnosis of HSES, which mainly depends on some specific clinical features and the exclusion of other diseases.All patients are provided given fluid therapy, intracranial pressure reduction and supportive treatments.It is essential to improve the recognition of HSES, and early diagnosis and early intervention may improve efficacy, and reduce mortality rate and disability rate. Key words: Hemorrhagic shock; Encephalopathy syndrome; Diagnosis; Treatment

Research progress of hemorrhagic shock and encephalopathy syndrome

Hemorrhagic shock and encephalopathy syndrome (HSES)is a devastating disease in infants which was first proposed by Levin in 1983.The main clinical manifestations of HSES are associated with acute onset of high fever, diarrhea, rapidly followed by convulsions, unconsciousness, bleeding tendency, shock and multiorgan dysfunction.The pathological manifestations include punctate bleeding, necrosis or inflammatory changes in multiple organs.The etiology of this syndrome is unknown, and the prognosis is poor.Despite intensive treatment, the fatality rate is still high and the survival is often associated with severe neurological sequelae.At present, there is no effective treatment for this disease, and mainly early symptomatic and supportive treatment can be obtained. Key words: Hemorrhagic shock and encephalopathy syndrome; Research progress; Child

“Symptomatic” infection-associated acute encephalopathy in children with underlying neurological disorders

BackgroundDevelopment of infection-associated acute encephalopathy (AE) is precipitated by several factors, including viral agents, age, and genetic polymorphisms. In addition, children with prior underlying neurological disorders can also present with AE. MethodWe reviewed 55 children with AE who were referred to hospitals participating in the Status Epilepticus Study Group from 1988 to 2013. AE was classified into eight subtypes: acute encephalopathy with biphasic seizures and late reduced diffusion (AESD); hemiconvulsion–hemiplegia syndrome (HH); acute necrotizing encephalopathy; hemorrhagic shock and encephalopathy syndrome (HSES); clinically mild encephalitis/encephalopathy with a reversible splenial lesion; acute encephalitis with refractory, repetitive partial seizures; Reye-like syndrome; and unclassified. ResultOf the 55 AE cases, 14 (25.4%) had underlying neurological disorders, including perinatal insults (n=6) and genetic syndrome and/or brain malformations (n=8). These preceding morbidities were relatively common in AESD (6/18, 33.3%), HH (3/9, 33.3%), and HSES (3/6, 50.0%). History of epilepsy or febrile seizures were frequent in HH cases (4/9, 44.4%), whereas they were rare in other AE subtypes. ConclusionAmong the AE subgroups, HH, HSES, and AESD frequently emerged in preceding etiologies with augmented neuronal excitability. These subgroups may have distinct pathomechanism from the “cytokine storm” mediated AEs during childhood.

Serum biomarker kinetics with three different courses of HHV-6B encephalitis

Human herpesvirus-6B (HHV-6B) encephalitis can clinically manifest as hemorrhagic shock and encephalopathy syndrome (HSES), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and acute necrotizing encephalopathy (ANE). To compare the underlying pathophysiology, we measured several biomarkers of interest in patients with these three different courses. Based on their clinical course and neuroimaging analysis, Cases 1, 2 and 3 were diagnosed as HSES, AESD, and ANE, respectively. HHV-6B was isolated from peripheral blood obtained during the acute phase in all three patients, and was detected in the cerebrospinal fluid of Cases 2 and 3. In Case 1, a marked increase in levels of several serum cytokines (IL-1β, IL-6, and IL-10) and chemokines (IL-8, MIG, MCP-1, and IP-10) was observed at disease onset. Subsequently, serum cytokine levels gradually became undetectable and chemokine levels stabilized by day 11 of illness. In Case 2, only two cytokines (IL-6 and IL-10) were slightly elevated at disease onset. In Case 3, the kinetics appeared to follow an up-and-down pattern. Additionally, in all three patients, TIMP-1 concentrations remained high during the observation period, and MMP-9 decreased quickly a few days after disease onset, and then returned to normal level.

Epidemiology of acute encephalopathy in Japan, with emphasis on the association of viruses and syndromes

A research committee supported by the Japanese government conducted a nationwide survey on the epidemiology of acute encephalopathy in Japan using a questionnaire. A total of 983 cases reportedly had acute encephalopathy during the past 3years, 2007–2010. Among the pathogens of the preceding infection, influenza virus was the most common, followed by human herpesvirus-6 (HHV-6) and rotavirus. Among syndromes of acute encephalopathy, acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was the most frequent, followed by clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), acute necrotizing encephalopathy (ANE) and hemorrhagic shock and encephalopathy syndrome (HSES). Influenza virus was strongly associated with ANE and MERS, HHV-6 with AESD, and rotavirus with MERS. Mortality was high in ANE and HSES, but was low in AESD, MERS and HHV-6-associated encephalopathy. Neurologic sequelae were common in AESD and ANE, but were absent in MERS.

Central nervous system pathology in fatal swine-origin influenza A H1N1 virus infection in patients with and without neurological symptoms: an autopsy study of 15 cases

The first influenza pandemic of the twenty-first century was caused by a swine-origin, influenza A (H1N1) virus that contained genes from human, swine, and avian influenza A viruses [4]. It has long been recognized that a small subset of influenza patients develops neurologic complications [1]. Central nervous system (CNS) pathology in influenza virus infection is thought to be indirect and multifactorial [15] and whether H1N1 infects the brain or cerebrospinal fluid (CSF) remains controversial [2]. The current model is that H1N1 triggers a cytokine storm that disrupts the blood–brain barrier and activates glial cells. Subsequent disseminated intravascular coagulation (DIC) and liver and renal dysfunction triggered by hypercytokinemia may also contribute to CNS damage [15]. A number of clinical syndromes affecting the CNS have been described in the context of influenza infection. Although these syndromes have overlapping features and can be caused by other viruses and toxic agents, they have specific clinical, radiological, and laboratory criteria for their diagnosis and the pathogenesis and predisposing factors differ. Classical Reye’s syndrome is a non-inflammatory encephalopathy with associated hepatic microvesicular fatty change and hyperammonemia, and is usually precipitated by the use of salicylates [5]. Reye’slike syndrome occurs at a younger age and does not have the microvesicular fatty change and mitochondrial abnormality of classical Reye’s syndrome [13] and it is not associated with salicylate use. Hemorrhagic shock and encephalopathy syndrome (HSES) occurs in infants, and there is associated fever, shock, DIC, hepatic and renal dysfunction, and the brain shows edema with occasional intracranial hemorrhage [3]. Acute necrotizing encephalopathy (ANE) was first described in Japan in 1995 [8], and then subsequently in other countries [7, 16]. MRI and autopsy studies show bilateral symmetrical infarcts in the thalamus, basal ganglia, cerebellar and cerebral white matter, and brainstem tegmentum. CSF protein is typically elevated and the mortality rate is high. Some infants have complex febrile seizures at the onset, followed by delayed involvement of bilateral frontal lobes or the entire cerebral hemisphere [12]. Recently, familial and recurrent ANE has been described and is associated with mutation in the Ranbinding protein gene (RANBP2) [10]. Like earlier influenza pandemics, the recent pandemic of novel influenza A (H1N1) infection has resulted in a number of cases with neurological complications [2, 7, 16]. The purpose of the present study was to document the changes present in the brains of fatal H1N1 virus patients to determine if cases without documented neurologic A. Mukherjee and J.E.G. Peterson contributed equally to this work.

Hemorrhagic Shock and Encephalopathy Syndrome in a Quadriplegic Child

A case presentation of hemorrhagic shock and encephalopathy syndrome (HSES). To describe an unusual complication of uncontrolled fever in a tetraplegic child and to discuss possible pathophysiological mechanisms in these circumstances. HSES is a rare and dramatic disorder of unknown origin occurring mainly in infants and young children. Clinical features of HSES associate hyperpyrexia, acute diarrhea, circulatory collapse, coma, convulsions, and multiple organ failure (MOF). Altered physiologic thermoregulatory response in infants exposed to abruptly increased core temperature or altered thermal environment, and links with heat stroke, have been mentioned in previous publications. We report a case of HSES occurring in a 6-year-old girl with post-traumatic C4 quadriplegia. She eventually experienced hyperpyrexia, deep shock, watery diarrhea, and severe MOF developed rapidly. Despite rapidly resolving MOF, severe brain lesions consistent with HSES were observed and resulted in permanent neurologic impairment. Negative bacterial and viral screening eliminated a septic origin. In this child, impaired thermoregulatory response to acute hyperpyrexia resulting from complete quadriplegia could be the necessary condition for the development of HSES in the presence of acute hyperpyrexia of unknown origin. Quadriplegic patients, especially young children, could be considered at increased risk of developing severe MOF and acute central nervous system impairment consistent with HSES, when exposed to heat stress and should be treated promptly.

Hemorrhagic shock and encephalopathy syndrome – the markers for an early HSES diagnosis

BackgroundThe hemorrhagic shock and encephalopathy syndrome (HSES) is a devastating disease that affects young children. The outcomes of HSES patients are often fatal or manifesting severe neurological sequelae. We reviewed the markers for an early diagnosis of HSES.MethodsWe examined the clinical, biological and radiological findings of 8 patients (4 months to 9 years old) who met the HSES criteria.ResultsAlthough cerebral edema, disseminated intravascular coagulopathy (DIC), and multiple organ failure were seen in all 8 cases during their clinical courses, brain computed tomography (CT) scans showed normal or only slight edema in 5 patients upon admission. All 8 patients had normal platelet counts, and none were in shock. However, they all had severe metabolic acidosis, which persisted even after 3 hours (median base excess (BE), -7.6 mmol/L). And at 6 hours after admission (BE, -5.7 mmol/L) they required mechanical ventilation. Within 12 hours after admission, fluid resuscitation and vasopressor infusion for hypotension was required. Seven of the patients had elevated liver enzymes and creatine kinase (CK) upon admission. Twenty-four hours after admission, all 8 patients needed vasopressor infusion to maintain blood pressure.ConclusionCT scan, platelet count, hemoglobin level and renal function upon admission are not useful for an early diagnosis of HSES. However, the elevated liver enzymes and CK upon admission, hypotension in the early stage after admission with refractory acid-base disturbance to fluid resuscitation and vasopressor infusion are useful markers for an early HSES diagnosis and helpful to indicate starting intensive neurological treatment.

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Two girls--Case 1 aged 4 and Case 2 aged 5--were admitted due to sudden onset of fever, disturbed consciousness, and convulsions. On admission, laboratory and hematological data in both cases was normal, although AST, ALT, LDH and CPK were markedly increased with conspicuously depressed platelet counts within 36hr of admission. Both had common symptoms of high fever(>40°C), bleeding, and hemorrhagic shock. Plasma exchange was conducted on days 2 and 3 for Case 1, but she died on day 9 after admission due to brain edema. Case 2 died on day 2 after admission due to hemorrhagic shock. Both had inflammation of the upper respiratory tract and influenza virus detected from pharyngeal swabs. Clinical and laboratory findings are compatible with hemorrhagic shock and encephalopathy syndrome (HSES). Its etiology in unknown and the outcome is often fatal or associated with severe neurological sequelae despite intensive treatment. The relationship between influenza virus infection and HSES is currently unknown and should be examined in future studies.

Hemorrhagic Shock and Encephalopathy Syndrome: A Case Report

Hemorrhagic shock and encephalopathy syndrome (HSES) is a sudden-onset symptom complex that in-volves multisystem failure and includes encephalopathy, shock, coma, convulsions, prerenal azotemia, hepatic dysfunction, and bleeding coagulopathy and progressive thrombocytopenia in previously healthy infants and children. Its radiologic findings have rarely been reported, and it has not been described in Korea. We present a case of clinically diagnosed HSES, and include the CT and MRI findings.

CT scan abnormalities in a series of patients with hemorrhagic shock and encephalopathy syndrome.

Hemorrhagic shock and encephalopathy syndrome (HSES) affects children under 1 year of age and is characterized by seizures, shock and certain laboratory abnormalities, including coagulation abnormalities. It has a high mortality and many of the survivors are neurologically abnormal. To describe abnormalities observed on initial and follow-up CT scans in a group of patients suffering from HSES. Retrospective review of records and CT scans of ten patients with HSES who were admitted to the intensive care unit of the Children's Hospital and Medical Center, Seattle. Cerebral edema was seen in all cases when the CT scan was obtained between 1 and 7 days after onset of HSES. The basal ganglia and cerebellum were relatively spared, and no hemorrhage was seen. Patients with moderate or marked cerebral edema usually had a poor prognosis. All survivors had significant neurologic sequelae. CT scans obtained after 7 days often showed encephalomalacia with ex vacuo ventricular enlargement. CT scans obtained between 24 h and 4 days after onset will show the acute changes of HSES. CT scans during the initial and convalescent stages of HSES can provide useful information about cerebral edema and encephalomalacia, which occur frequently with this illness.

Cerebral Infarction Complicating Hemorrhagic Shock and Encephalopathy Syndrome

Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe, life-threatening illness affecting infants and young children. Patients stricken with this illness suffer high rates of neurological injury and mortality. We describe a child with HSES whose course was complicated by global cerebral infarction. This injury, although extensive and severe, was not appreciated during the initial examination of the child. Cerebral infarction during HSES may not be detected reliably unless imaging studies of the central nervous system are preformed after cerebral edema has resolved. CASE REPORT The patient was a 7-week-old girl born to a healthy 20-year-old woman. The infant had been healthy until 1 week prior to admission when she developed an upper respiratory tract infection.

Hemorrhagic shock and encephalopathy syndrome

Hemorrhagic shock and encephalopathy syndrome (HSES) is a devastating symptom complex that affects previously healthy infants and is associated with significant mortality and neurologic morbidity. The syndrome was first reported less than ten years ago, and there continues to be debate regarding whether HSES actually represents a distinct clinical entity or instead is a manifestation of heat illness, occult sepsis or endotoxic shock, or perhaps toxic ingestion. Nevertheless, the signs and symptoms described as HSES present in a typical fashion in the emergency department with sudden onset of shock, encephalopathy, seizures, and coagulopathy. Even with the initiation of intensive support in the ED, the outcome is probably dismal. We describe a case of HSES and review the presentation, proposed etiologies, and management of this catastrophic illness.

MLA reliability assurance—A continuing program : Thomas H. Poyer and Thomas D. Schoonmaker. Proc. IEEE A. Reliab. Maintainab. Symp., Los Angeles, 17–19 January 1978, p. 428

Development of infection-associated acute encephalopathy (AE) is precipitated by several factors, including viral agents, age, and genetic polymorphisms. In addition, children with prior underlying neurological disorders can also present with AE.We reviewed 55 children with AE who were referred to hospitals participating in the Status Epilepticus Study Group from 1988 to 2013. AE was classified into eight subtypes: acute encephalopathy with biphasic seizures and late reduced diffusion (AESD); hemiconvulsion–hemiplegia syndrome (HH); acute necrotizing encephalopathy; hemorrhagic shock and encephalopathy syndrome (HSES); clinically mild encephalitis/encephalopathy with a reversible splenial lesion; acute encephalitis with refractory, repetitive partial seizures; Reye-like syndrome; and unclassified.Of the 55 AE cases, 14 (25.4%) had underlying neurological disorders, including perinatal insults (n = 6) and genetic syndrome and/or brain malformations (n = 8). These preceding morbidities were relatively common in AESD (6/18, 33.3%), HH (3/9, 33.3%), and HSES (3/6, 50.0%). History of epilepsy or febrile seizures were frequent in HH cases (4/9, 44.4%), whereas they were rare in other AE subtypes.Among the AE subgroups, HH, HSES, and AESD frequently emerged in preceding etiologies with augmented neuronal excitability. These subgroups may have distinct pathomechanism from the “cytokine storm” mediated AEs during childhood.