Effects of mild hypothermia and steroid pulse combination therapy on acute encephalopathy associated with influenza virus infection: report of two cases

We treated two children with influenza-associated acute encephalopathy by a combination of mild hypothermia and steroid pulse therapy. Case 1, a 2-year-and-3-month-old boy, admitted to our hospital 7 days after the onset of central nervous symptoms. The brain MRI-CT revealed laminar cortical necrosis and severe brain edema. EEG showed very low voltage. Brain edema improved by the combination therapy. He had sequelae, but was able to eat. Case 2, a 1-year-and-10-month-old boy, admitted to our hospital 5 days after the onset of central nervous symptoms. Brain MRI showed frontal dominant cortical edema. EEG showed high voltage delta bursts. The combination therapy was effective, but he remained mental handicapped. The outcome was better compared to our previous cases of acute encephalopathy. The combination therapy is intended to counteract cytokines, and was considered to be an effective treatment against acute encephalopathy associated with an influenza virus infection.     

Changes of brain edema after initiation of mild hypothermia therapy in children

To determine the effects of mild hypothermia therapy (34 degrees C) for brain edema caused by hypoxic ischemic encephalopathy (HIE) or acute encephalitis/encephalopathy, we reviewed the charts and serial brain CT images in six children (males 3, average age 1.6 years) treated with mild hypothermia therapy between November 2006 and April 2009. Both of the two children with HIE after cardiopulmonary arrest did not show any deterioration of brain edema after the initiation of hypothermia therapy. However, two of four non-HIE patients (acute encephalitis/encephalopathy 3 cases and metabolic encephalopathy plus HIE 1 case) showed progressive brain edema during the cooling phase and re-warming phase, respectively. There were no differences between patients with and those without progressive brain edema with regard to the interval until initiation of mild hypothermia therapy, duration of cooling phase, duration of re-warming phase, or peak serum NSE (neuron-specific enolase) levels. However, two children with progressive brain edema showed a delayed NSE peak time (15 and 13 days after onset, respectively), compared with those without progressive brain edema (2-6 days after onset). Our study suggests that serial measurement of serum NSE might be useful marker for adjusting the methods of hypothermia therapy according to neuropathology. Further study is necessary to establish optimal hypothermia therapy especially in children with acute encephalitis/ encephalopathy.     

Clinical diversity in acute necrotizing encephalopathy.

Acute necrotizing encephalopathy is a novel disease entity, proposed by Mizuguchi et al in 1995, that shows a characteristic selective and symmetric involvement of the thalamus, brain stem, and cerebellum. It usually leaves sequelae. The etiology of acute necrotizing encephalopathy is unknown. We describe here six patients aged 6 months to 5 years (four boys and two girls). Four cases were typical, and the patients' cranial computed tomographic scans and magnetic resonance imaging showed irreversible symmetric involvement of the thalamus, brain stem, and cerebellum. Three of the patients died, and one was left with severe sequelae. In the other two patients, who had selective reversible thalamic involvement, the disease was mild; one also showed transient unilateral thalamic involvement. These patients recovered completely. We consider the illness in these two patients to fit the criteria of the mild form of acute necrotizing encephalopathy. We believe that acute necrotizing encephalopathy has some clinical diversity, as is seen in other neurologic disorders, and that a mild form could exist.     

Combined therapy with hypothermia and anticytokine agents in influenza A encephalopathy

Two children with influenza A-related encephalopathy were treated with a combination of mild hypothermia (deep body temperature of the forehead: 35 degrees C) and anticytokine agents (high-dose methylprednisolone and ulinastatin), while receiving amantadine. One of the cases exhibited acute necrotizing encephalopathy on computed tomography (CT). Although no severe complications occurred, correctable hypokalemia and hyperglycemia occurred in both cases. Both patients recovered without any neurological sequelae. Our therapeutic protocol appears to be effective for managing influenza A-related encephalopathy.     

Clinical characteristics of acute encephalopathies associated with influenza H1N1-2009 in children

We report 12 cases of acute encephalopathy associated with influenza H1N1-2009 treated according to Japanese guideline (2009). In all 12 cases, electroencephalogram presented diffuse or localized high-amplitude slow waves. Brain CT and MRI showed abnormalities in 4 and 6 cases, respectively. We used hypothermia therapy for 5 patients. One patient showed impairment in short term memory, while the rest of the patients showed no sequelae. These 12 cases presented here suggest the early recognition and therapy according to the newly proposed guideline may reduce severe sequelae and mortality by acute encephalopathy associated with influenza H1N1-2009.     

Efficacy of Dextromethorphan and Cyclosporine A for Acute Encephalopathy

Acute encephalopathy with biphasic seizures and late reduced diffusion was recently established clinicoradiologically as an encephalopathy syndrome. The outcome of this encephalopathy is characterized by a low mortality rate and high incidence of neurologic sequelae. Although the exact pathogenesis of this encephalopathy is uncertain, excitotoxic injury with delayed neuronal death is proposed. On the basis of this hypothesis, we tried a combination therapy of N-methyl-D-aspartate receptor antagonist, dextromethorphan, and apoptosis inhibitor, cyclosporine A, in four patients with acute encephalopathy with biphasic seizures and late reduced diffusion. All patients recovered except for hyperactivity in one patient. Furthermore, an additional four patients with near-miss encephalopathy, who showed mild disturbance of consciousness at 24 hours after prolonged febrile seizures associated with exanthem subitum, recovered without secondary seizures by the early administration of dextromethorphan. The combination regimen of dextromethorphan and cyclosporine A could be effective for the treatment and prevention of acute encephalopathy with biphasic seizures and late reduced diffusion.     

A case of acute encephalitis with refractory, repetitive partial seizures, presenting autoantibody to glutamate receptor Gluepsilon2

An 11-year-old male was admitted to our hospital because of high-grade fever, repetitive seizures, and prolonged impairment of consciousness (Glasgow coma scale E1, M5, V1). His seizures were repetitive complex partial seizures that expanded from the unilateral face to the corresponding side of the body. He sometimes developed secondary generalized seizures. While most seizures lasted 1 or 2 min, intractable seizures also frequently (about 5 times/h) occurred. We diagnosed him as encephalitis/encephalopathy, and treated him with artificial respiration, thiamylal sodium, mild hypothermia therapy, steroid pulse therapy, massive gamma-globulin therapy, etc. Afterwards, he had sequelae, such as post-encephalitic epilepsy (same seizures continued to recur), hyperkinesia, impairment of immediate memory, change in character (he became sunny and obstinate), dysgraphia, and mild atrophy of the hippocampus, amygdala, and cerebrum. However, he could still attend a general junior high school. He was diagnosed as acute encephalitis with refractory, repetitive partial seizures (AERRPS). In this case, he was positive for autoantibody to glutamate receptor Gluepsilon2 IgG or IgM in an examination of blood and spinal fluid, and we presumed that this may have influenced his sequelae. In this case, a combination of mild hypothermia therapy, steroid pulse therapy, and massive gamma-globulin therapy was effective.     

Acute encephalopathy of Bacillus cereus mimicking Reye syndrome

We present an 11-year-old boy diagnosed as having acute encephalopathy and liver failure with the underlying condition of a metabolic dysfunction. He developed convulsions and severe consciousness disturbance following gastroenteritis after the ingestion of some fried rice. He showed excessive elevation of transaminases, non-ketotic hypoglycemia and hyperammonemia, which were presumed to reflect a metabolic dysfunction of the mitochondrial beta-oxidation, and he exhibited severe brain edema throughout the 5th hospital day. He was subjected to mild hypothermia therapy for encephalopathy, and treated with high-dose methylprednisolone, cyclosporine and continuous hemodiafiltration for liver failure, systemic organ damage and hyperammonemia. The patient recovered with the sequela of just mild intelligence impairment. In this case, Bacillus cereus, producing emetic toxin cereulide, was detected in a gastric fluid specimen, a stool specimen and the fried rice. It was suggested that the cereulide had toxicity to mitochondria and induced a dysfunction of the beta-oxidation process. The patient was considered as having an acute encephalopathy mimicking Reye syndrome due to food poisoning caused by cereulide produced by B. cereus.     

Effect of long-term mild hypothermia or short-term mild hypothermia on outcome of patients with severe traumatic brain injury.

To compare the effect of long-term mild hypothermia versus short-term mild hypothermia on the outcome of 215 severe traumatic brain injured patients with cerebral contusion and intracranial hypertension. At three medical centers, 215 patients aged 18 to 45 years old with an admission Glasgow Coma Scale < or =8 within 4 h after injury were randomly divided into two groups: long-term mild hypothermia group (n = 108) for 5+/-1.3 days mild hypothermia therapy and short-term mild hypothermia group (n = 107) for 2+/-0.6 days mild hypothermia therapy. All patients had intracranial hypertension and frontotemporoparietal contusion with midline shift >1 cm confirmed on computed tomographic scan. Glasgow Outcome Scale at 6-month follow-up, 47 cases had favorable outcome (43.5%), and other 61 cases had unfavorable outcome (56.5%) in the long-term mild hypothermia group. However, only 31 cases had favorable outcome (29.0%), and other 76 cases had unfavorable outcome (71.0%) in the short-term mild hypothermia group (P < 0.05). The intracranial pressure significantly rebounded after rewarming in the short-term mild hypothermia group, but not in the long-term mild hypothermia (P < 0.05). Furthermore, the incidence of stress ulcer, epilepsy, pulmonary infection, intracranial infection did not significantly differ between the two groups (P > 0.05). Compared with short-term mild hypothermia, long-term mild hypothermia significantly improves the outcome of severe traumatic brain injured patients with cerebral contusion and intracranial hypertension without significant complications. Our data suggest that 5 days of long-term cooling is more efficacious than 2 days of short-term cooling when mild hypothermia is used to control refractory intracranial hypertension in patients with severe traumatic brain injury.     

β-七叶皂苷钠联合亚低温疗法对重型颅脑损伤患者脑组织氧分压影响的临床研究

目的观察β-七叶皂苷钠联合亚低温疗法对重型颅脑损伤患者脑组织氧分压(PbrO2)的影响。方法 60例急性重型颅脑损伤患者,随机分为常规治疗组(对照组)及β-七叶皂苷钠联合亚低温治疗组(观察组)。对两组患者的预后情况进行比较,同时分别测定和比较治疗前及治疗后24 h、48 h、72 h及7 d的PbrO2的变化。结果两组患者的预后及不同时间PbrO2水平的差异有统计学意义。结论β-七叶皂苷钠联合亚低温疗法能够提高重型颅脑损伤患者的PbrO2、改善脑组织代谢。     

亚低温联合丁苯酞治疗重度急性一氧化碳中毒脑损害的疗效分析

目的 探讨亚低温联合丁苯酞治疗重度急性一氧化碳中毒脑损害的临床疗效。方法 将符合标准的患者122例随机分为研究组和对照组各61例,研究组在高压氧等常规治疗基础上加用亚低温及丁苯酞,对照组给予高压氧等常规治疗,观察并比较2组GCS评分、昏迷时间、病死率及迟发性脑病发生率、治疗效果。结果 研究组治疗1、2、3 d后GCS评分均高于对照组(P<0.05); 研究组昏迷时间(16.74±6.57 h)低于对照组(22.19±7.03 h)(P<0.05); 研究组病死率为1.64%,低于对照组6.56%(P>0.05); 研究组迟发脑病发生率为18.03%,低于对照组40.98%(P<0.05); 研究组痊愈率45.90%、总有效率85.24%,均优于对照组痊愈率26.23%、总有效率65.57%(P<0.05)。结论 亚低温联合丁苯酞治疗重度急性一氧化碳中毒脑损害能提高GCS评分,缩短患者的昏迷时间,降低迟发脑病的发生率,可以提高患者的治疗效果和生存质量。     

Tuberculous encephalopathy with and without meningitis clinical features and pathological correlations

Thirty cases of tuberculous encephalopathy with and without meningitis are described with delineation of the different clinical types.

The following were the main clinical categories in this series: (1) tuberculous meningitis with encephalopathy in 15 cases (1 fulminating, 2 acute, 6 subacute and 6 chronic); (2) serous tuberculous meningitis with encephalopathy in 8 cases (4 subacute and 4 chronic); (3) tuberculous encephalopathy without meningitis in 6 cases (3 fulminating, 1 acute, 1 subacute and 1 chronic); and (4) acute haemorrhagic encephalopathy in 1 case.

The main clinical features of diffuse brain involvement were impaired consciousness, convulsions, involuntary movements, decerebrate and decorticate postures, paralysis, pyramidal, extrapyramidal and cerebellar signs.

In all cases there was evidence of tuberculosis. There was pathological evidence of miliary tuberculosis in 7, intracranial tuberculosis in 15, intrathoracic in 11, and abdominal in 8. Acid-fast bacilli were detected in the cerebrospinal fluid in 1 case and in the meningeal exudate in another. Radiological evidence of the disease was present in 15 cases. A family history of tuberculosis was obtained in 6 cases.

All the 4 cases with a fulminating illness and 3 acute cases died; 6 of the 7 with a subacute illness died; and 4 of the 14 with a chronic illness died. Of the 13 who survived, 4 recovered fully, while 9 showed mild or severe sequelae, in 2 of whom the illness ran a very prolonged course.

The neuropathological changes were those of an oedematous encephalopathy with diffuse or patchy myelin loss in the white matter, commensurate glial reactions, occasional haemorrhagic and glial nodules, and with moderate to severe diffuse changes in the grey matter, especially the cortex.

Pathogenetic mechanisms are discussed and the role of inflammatory, vascular and allergic factors are considered. The latter appear more significant and sensitivity to tuberculoprotein or to brain itself may be responsible.     

A case of rhabdomyolysis associated with Salmonella encephalopathy

We report a case of severe rhabdomyolysis associated with Salmonella encephalopathy. A 3-year-old girl was admitted to our hospital because of status convulsives and unconsciousness. She was diagnosed as having Salmonella encephalopathy with rhabdmyolysis, and was treated by mild hypothermia and mechanical ventilation. Five days later she developed anuria with increased serum levels of myoglobin, CK and creatinine. And the diagnosis of acute renal failure was made. Peritoneal dialysis was begun from 6 days after admission. Hyperinfusion, the usual therapy of rhabdomyolysis, was not performed. She survived showing gradual improvement of renal function and consciousness. In a case of rhabdomyolysis complicating a neurologic disorder, a well-known poor prognostic factor, priority should be given to brain protection rather than to symptomatic treatment of rhabdomyolysis.     

Infection-related acute encephalopathy: CT scan/MRI finding, laboratory examination and prognosis

CT/MRI findings, laboratory examinations and prognoses of 42 patients with acute encephalopathy (AE) (Japan Coma Scale > or = 200) were reported. 1. Findings on CT/MRI were divided into the following 7 categories: Group 1 (normal), Group 2 (CT/MRI looked normal in acute phase, but brain atrophy developed and progressed slowly by weeks or months), Group 3 (CT/MRI looked normal within a few days after the onset of AE, but cortical laminar necrosis developed at 4-5 days after the onset), Group 4 (marked brain edema developed within 2 days after the onset of AE), Group 5 (AE with symmetric thalamic lesions), Group 6 (symmetric pallidum, lesions on MRI which appeared after brain edema disappeared), and Group 7 (the brain shrinked during acute phase, which normalized on the follow up CT/MRI). 2. Serum AST elevated in approximately 50% of the patients with AE. Sixty percent of them exhibited DIC, whose prognoses were poor. Cerebrospinal fluids (CSF) neopterin (NP) and/or interleukin (IL)-6 were elevated in all the 8 patients examined. In the two cases whose serum NP and IL-6 were measured at the same time, their values in the CSF were higher than those in the serum in one case, and almost the same in the other. In a patient with a condition mimicking hemorrhagic shock and encephalopathy, serum IL-6 concentration was very high (94,000 pg/ml). 3. Mild hypothermia (around 34 degrees C) combined with methylprednisolone pulse therapy was excellently effective on AE. A 6-year-old boy exhibited tonsillar herniation at admission recovered well to be able to run. 4. Differentiation between Reye syndrome and HSE, and the pathogenesis of AE were also discussed.     

A severely brain-damaged case of 3-hydroxyisobutyric aciduria

We report a male case of 3-hydroxyisobutyric aciduria (3HiB-uria) with severe brain damage. He had mild asphyxia at birth. He needed tube feeding for a month. He showed mild dysmorphic features, including low set ears, a long philtrum and micrognathia. At 4 months of age he had acute encephalopathy. Thereafter, severe brain damage remained and mechanical ventilation care was needed all day. After he had been admitted to our hospital at 3 years of age, repeated organic acid analysis of urine confirmed the diagnosis of 3HiB-uria. This patient had been previously diagnosed as having cerebral palsy and sequelae of acute encephalopathy.     

亚低温治疗对重型颅脑损伤患者血浆内皮素的影响

目的探讨亚低温治疗重型颅脑损伤的临床疗效及其对血浆内皮素(ET)分泌的调控作用。 方法选取50例重型颅脑损伤患者,分为观察组(n=25)和对照组(n=25)。对照组给予常规治疗,观察组给予常规治疗联合亚低温治疗。比较两组血浆ET表达、颅内压(ICP)及临床预后。 结果治疗后第1~5天,观察组患者血浆ET均显著低于对照组,组间比较差异显著(P<0.05)。治疗后第1~5天,观察组患者ICP均显著低于对照组,组间比较差异显著(P<0.05)。观察组中预后良好7例、轻残8例、重残6例、植物生存2例、死亡2例;对照组预后良好3例、轻残4例、重残10例、植物生存3例、死亡5例,观察组预后情况明显优于对照组,组间比较差异显著(P<0.05)。 结论亚低温治疗的脑保护作用可能与抑制ET分泌,降低ICP有关。     

重型颅脑损伤患者亚低温治疗的临床研究

目的 通过比较重型颅脑损伤患者亚低温治疗组与常温治疗组的预后来证实亚低温治疗的脑保护作用. 方法 选取重型颅脑损伤患者76例(GCS≤8分),分为亚低温治疗组(36例)和常温治疗组(40例).常温治疗组患者应用脱水降颅压、营养神经、止血、抑制胃酸分泌、营养支持等常规治疗.亚低温治疗组患者除常规治疗外,合并应用冰毯实行亚低温治疗(患者躺在冰毯垫上,通过体表散热使中心体温和脑温降至所需温度,通常为32～34℃,并根据病情需要维持3～14 d).结果亚低温治疗组患者预后优于常温组,差异有统计学意义(P<0.05). 结论 亚低温治疗对重型颅脑损伤患者具有脑保护作用,能提高临床疗效,值得推广应用.     

亚低温治疗重型颅脑损伤的临床分析

目的 探讨亚低温对重型颅脑损伤的脑保护作用及临床疗效.方法 回顾性分析我院收治的251例特重型颅脑损伤患者,常规治疗组182例和亚低温治疗组69例.亚低温治疗组均在受伤后24 h内行亚低温治疗,比较两组的手术疗效及对患者预后的影响.结果 与常温治疗组比较,亚低温治疗组恢复良好率显著提高,病死率显著降低,预后改善显著,且并发症无明显增加.结论 在常规治疗的基础上加用亚低温治疗特重型颅脑外伤,可以明显改善患者的预后;能显著降低特重型颅脑损伤的死残率.     

Successful use of mild hypothermia therapy in an adult patient of non-herpetic acute encephalitis with severe intracranial hypertension]

A 41-year-old man was admitted to our hospital suffering from generalized convulsion with a high fever and disturbed consciousness one week after exhibiting flu-like symptoms. We made a diagnosis of acute viral encephalitis, based on the clinical features and the evidence of pleocytosis with an increase in protein in the CSF. On admission, MRI was normal and CRP was negative. The levels of transaminase, ammonia, and blood sugar were normal, so that an adult Reye's syndrome could be ruled out. Herpes simplex encephalitis and influenza encephalopathy were also ruled out because of viral examinations, and specific agents could not be determined. Clinical symptoms subsided once after he was treated with dexamethasone, acyclovir, and anti-convulsants, until generalized convulsion accompanied by a high fever again occurred on the 9th day. On the 18th day, the patient showed anisocoria and ataxic respiration due to severe brain edema. Mild hypothermia therapy to rectal temperature 35 degrees C was induced under mechanical ventilation. Cranial CT taken 3 days after the therapy began to show the improvement of the brain edema. After 7 days of the therapy, his clinical symptoms began to recover dramatically. On the 46th day, he was discharged from hospital without showing almost any neurological symptoms. Mild hypothermia therapy should be considered for adult patients as well as non-adult patients suffering from acute encephalitis with severe intracranial hypertension.     

Case of adult influenza type A virus-associated encephalopathy successfully treated with primary multidisciplinary treatments]

The patient in this study was a 43-year-old woman who had become unconscious after contracting influenza virus type A infection. Brain CT showed severe brain swelling. Brain MRI also showed brain edema with no specific abnormality on T2-weighted images. We diagnosed her as having influenza type A virus-associated encephalopahty and treated her with Oseltamivir, methylprednisolone pulse therapy, and a high dose of intravenous immunoglobulins. In addition, we treated her with hypothermia and a high dose of intravenous ATIII because of the severe brain swelling and possibility of DIC. After the treatments, brain swelling had improved, and she regained consciousness without any sequelae. Adult influenza virus-associated encephalopathy is rare. We were able to successfully treat our patient with primary multidisciplinary treatments without causing sequelae.