Acute Encephalitis With Refractory, Repetitive Partial Seizures Research Articles

Vagus nerve stimulation therapy improved refractory epilepsy secondary to acute encephalitis with refractory, repetitive partial seizures (AERRPS)

Abstract Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is a rare condition. The seizure control of this encephalopathy is poor. The purpose of this report is to evaluate the utility of vagus nerve stimulation (VNS) in a patient with AERRPS. A 14-year-old boy presented with fever and headache. He developed epileptic facial twitching and eyelid fluttering. Various types of antiepileptic drugs did not control his seizures. He underwent VNS at the age of 21. After 5 years of VNS therapy, his seizure frequency decreased from daily to monthly. For patients with AERRPS, VNS may be a treatment option.

Acute encephalitis with refractory, repetitive partial seizures: A case report and literature review.

A male 46 year-old patient was admitted to the Emergency Intensive Care Unit of Qinghai Provincial People's Hospital (Xining, China) in December 2008 with complaints of a headache and fever that had lasted for three days. In addition, the patient had experienced two general convulsions accompanied with consciousness disorders for 7 h. Although the patient's clinical manifestations, laboratory tests and cerebrospinal fluid examinations were consistent with numerous features associated with acute encephalitis, the patient's clinical course was different to that of acute encephalitis, and the prognosis was poor. The clinical course of the patient fully complied with the diagnostic criteria of acute encephalitis with refractory, repetitive partial seizures (AERRPS), as follows: i) The acute phase of encephalitis lasted >2 weeks; ii) partial seizures accompanied with general seizures occurred throughout the acute and convalescent course; iii) frequent seizures, a number of which resulted in a sustained state, were more prominent in the acute phase; iv) seizures were difficult to control; and v) known viral encephalitis and systemic metabolic disorders were excluded from the diagnosis. Based on previous reports and the present study, it can be concluded that AERRPS does not respond to the majority of anti-epileptic drugs, and while high-dose phenobarbital was effective in the current study, it was not able to fully control the focal and general seizures. Despite this, phenobarbital is required for maintenance in the recovery phase.

Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS

Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B, IL6, IL10, TNFA, IL1RN, SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN, the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls (p=0.0067), and A allele at rs4251981 in 5′ upstream of IL1RN with borderline significance (p=0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40–10.8, p=0.0057). For SCN1A, no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A, the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance (p=0.011).We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases.

High‐dose phenobarbital with intermittent short‐acting barbiturates for acute encephalitis with refractory, repetitive partial seizures

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by repetitive seizures during the acute and chronic phases and has a poor neurological outcome. Burst-suppression coma via continuous i.v. infusion of a short-acting barbiturate is used to terminate refractory seizures, but the severe side-effects of short-acting barbiturates are problematic. We report on a 9-year-old boy with AERRPS who was effectively treated with very-high-dose phenobarbital (VHDPB) combined with intermittent short-acting barbiturates. VHDPB side-effects were mild, especially compared with those associated with continuous i.v. infusion of short-acting barbiturates (dosage, 40-75 mg/kg/day; maximum blood level, 290 μg/mL). Using VHDPB as the main treatment, short-acting barbiturates were used intermittently and in small amounts. This is the first report to show that VHDPB, combined with intermittent short-acting barbiturates, can effectively treat AERRPS. After treatment, convulsions were suppressed and daily life continued, but intellectual impairment and high-level dysfunction remained.

Autopsy findings of a patient with acute encephalitis and refractory, repetitive partial seizures

Chikako Ogawa *, Jun Natsume , Hiroyuki Yamamoto , Naoko Ishihara , Atsushi Tashiro , Hiroyuki Kidokoro , Tamiko Negoro , Mari Yoshida , Kazuyoshi Watanabe a Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Pediatrics, Social Insurance Chukyo Hospital, Nagoya, Japan Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan

Effect of levetiracetam in acute encephalitis with refractory, repetitive partial seizures during acute and chronic phase.

To clarify the effect of levetiracetam (LEV) for acute and chronic seizure control in acute encephalitis with refractory, repetitive partial seizures (AERRPS). We retrospectively reviewed the clinical course of six AERRPS cases treated with LEV, and explored the acute phase termination by withdrawal from barbiturate-induced coma under artificial ventilation, and the reduction in seizure frequency during the chronic phase. LEV was administrated orally or via nasogastric tubes as an add-on agent during acute (n=3; age 8-10 years) and chronic (n=3; age 19-30 years) AERRPS. In the acute phase, administration of LEV (50-60 mg/kg/d) in combination with phenobarbital (n=3; peak 57.9-76.1 μg/ml) and potassium bromide (n=2; 30-36 mg/kg/d)) resulted in successful reduction of intravenous barbiturate dosage and withdrawal from artificial ventilation. In the chronic phase, seizure frequency reduced by >75% for 5-18 months with LEV 750-1500 mg/d. LEV may affect seizure control in AERRPS, particularly during the chronic phase, through its unique action of inhibition of excitatory neurotransmitter release. The regimen of oral barbiturate, potassium bromide and LEV would be worth for trial during the acute phase of AERRPS.

Ketogenic diet therapy is effective in encephalitis with refractory seizures

Objective and importance:Although ketogenic diet therapy is effective in refractory seizures in childhood, its effect on adult encephalitis with similar refractory seizures and prolonged encephalopathy has not been well reported.Clinical presentation:We report here a case of a 22-year-old man with acute encephalitis with refractory repetitive partial seizures (AERRPS).Intervention:Partial seizures of the face developed to repeated generalized convulsions, which were refractory against anti-epileptic drugs and a high dose of propofol. After struggling for 9 months, he dramatically recovered after ketogenic diet therapy.Conclusion:Ketogenic diet therapy may be an important tool to help cure AERRPS.

The expanding spectrum of febrile infection-related epilepsy syndrome (FIRES)

In recent years, a number of phenomena included in the group of probable epileptic encephalopathies of autoimmune origin have been described. Their common denominator is abrupt onset, usually after a self-limited febrile illness, and a clinical picture of repetitive seizures or difficult-to-control status epilepticus. These symptoms occur mostly in children and have received a wide range of names, despite their highly similar presentations with minor distinctive aspects. Such denominations include acute encephalitis with refractory repetitive partial seizures (AERRPS), febrile infection-related epilepsy syndrome (FIRES) or new-onset refractory status epilepticus (NORSE). Recently, several authors have advocated a simplification of this heterogeneous range of diagnoses, with Ismail and Kossoff suggesting the definition of a single post-infectious syndrome with common characteristics. We report a case of acute encephalopathy after a febrile illness with complete remission of symptoms following antiepileptic and steroid treatment. We conducted an extensive workup including Video-EEG monitoring and speculate on the nature and classification of these syndromes and their growing clinical spectrum.

Acute encephalopathy with a novel point mutation in the SCN2A gene

Mutations of the neuronal voltage-gated sodium channel alpha subunit type II (SCN2A) cause various epileptic syndromes, but have never been reported in association with acute encephalopathy. To validate the involvement of SCN2A mutations in acute encephalopathy, we screened 25 patients and found a novel missense mutation (Met1128Thr) in a patient with acute encephalitis with refractory, repetitive partial seizures (AERRPS). This finding suggests that SCN2A mutation is a predisposing factor for acute encephalopathy.

An immunologic case study of acute encephalitis with refractory, repetitive partial seizures

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is a neurologic syndrome characterized by extraordinarily frequent and refractory partial seizures, which immediately evolve into refractory epilepsy. To elucidate the pathophysiology of AERRPS, we performed an immunologic study of an affected boy, revealing decreased natural killer (NK) cell activity in the peripheral blood mononuclear cells. IgG antibodies against the glutamate receptor (GluR)ε2, ζ1, and δ2 subunits were all positive in both the serum and cerebrospinal fluid (CSF). There were raised plasma concentrations of interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ as well as an extremely elevated CSF level of IL-6. These findings suggest that AERRPS is immune-mediated encephalitis, in which both autoimmunity and exaggerated cytokine production are involved. NK cell dysfunction may be the underlying abnormality in this AERRPS case, which might have contributed to the production of GluR autoantibodies.

小児非ヘルペス性急性辺縁系脳炎の1例 : acute encephalitis with refractory, repetitive partial seizures (AERRPS) との比較

小児非ヘルペス性急性辺縁系脳炎の1例 : acute encephalitis with refractory, repetitive partial seizures (AERRPS) との比較

English

To investigate the safety and side effects of prolonged treatment with high-dose phenobarbital in patients suffering from acute encephalitis with refractory, repetitive partial seizures (AERRPS), 5 AERRPS patients meeting the Sakuma’s criteria were recruited from July 2003 to September 2008. During the treatment with high-dose phenobarbital, the blood pressure, heart rate, cardiac rhythm, respiratory rate, blood gas, skin conditions, state of consciousness, pupil size, seizures and long-range electroencephalogram were monitored. After intravenous bolus injection of phenobarbital (200 mg) or intramuscular infection of phenobarbital for induction, and then phenobarbital was intravenously administrated at 1 to 1.5 mg/kg/h or intramuscularly given (200 mg) (or intravenous bolus injection) q 2 to 4 h to maintain plasma concentrations. The daily overall dose of phenobarbital was 1.2 to 2.4 g. The serum level of phenobarbital reached 100 μg/ml within 24 h and remained for 24 d to 100 d. Follow up was carried out for at least 6 months. During the treatment of high dose phenobarbital, these 5 patients were in coma and the scores of Glasgow coma scale were 3 to 5. The brainstem reflex was mostly preserved and the spontaneous breathing was absent. The side effects in the circulation system included arrhythmia and hypotension. Sinus tachycardia (n = 3) and ventricular/supraventricular tachycardia (n = 2) were controlled by amiodarone, and the blood pressure was decreased by 40 to 55/64 to 86 mmHg (n = 2) which resolved after dopamine treatment (5 to 10 μg/kg/min). Liver injury was evident and observed in all 5 patients. The serum levels of alanine aminotransferase, aspartate aminotransferase and γ glutamyl transferase was 57 to 385 IU/L, 38 to 365 IU/L and 54 to 542 IU/L, respectively. The maximal level of serum ammonia was 187 μg/dl. No yellow skin was observed, and the serum levels of direct and indirect bilirubin were normal. Skin reaction was mild and kidney function almost intact. When the serum level of phenobarbital was decreased to 50 μg/ml, the consciousness and spontaneous breathing recovered and side effects were nearly absent. It is indicated that severe side effects may occur during prolonged treatment with high-dose phenobarbital. When this strategy is necessary, assisted ventilation is recommended and side effects should be closely monitored.   Key words: Encephalitis, status epilepticus, phenobarbital, side effect. safety.

Genetic seizure susceptibility underlying acute encephalopathies in childhood

We herein investigated risk factors of pediatric acute encephalopathy (AE) regarding the hitherto uncharacterized genetic background of seizure susceptibility underlying the pathogenesis of AE. The study included 15 patients with a history of various types of AE in childhood. We undertook the mutational analysis of the neuronal sodium channel alpha 1 subunit (SCN1A) gene which is the most representative gene for hyperthermia-induced seizure susceptibility. Six patients (40%) had a positive family history of seizures or AE, especially febrile seizures, in first- or second-degree relatives. The SCN1A-R1575C mutation was detected in a patient with a history of acute encephalitis with refractory, repetitive partial seizures (AERRPS) and also in the patient's apparently healthy father. In the present study, dense familial seizure predisposition was present in the patients with AE. Although the presence of seizure susceptibility alone is insufficient to cause AE, it can exacerbate seizures and the subsequent development of inflammatory reactions in the brain when environmental factors are included. Genetic seizure susceptibility may contribute to some types of AE in childhood.

Acute Encephalitis with Refractory, Repetitive Partial Seizures

Clinical characteristics and outcome of 29 children (19 male; 10 female) with acute encephalitis with refractory, repetitive partial seizures (AERRPS) were analyzed in a retrospective, multicenter nationwide questionnaire-based study in Japan.

Acute encephalitis with refractory, repetitive partial seizures (AERRPS): a peculiar form of childhood encephalitis

We conducted a nationwide multicenter study in Japan to elucidate the clinical and laboratory characteristics of acute encephalitis with refractory, repetitive partial seizures (AERRPS). Clinical and laboratory features, treatment, and outcome were assessed using a structured questionnaire. Twenty-nine children were enrolled in the study. Refractory and repetitive partial seizures accompanied by fever were the cardinal clinical features. Partial seizures consisted principally of eye deviation or facial twitching, being periodically repeated during the acute phase. These seizures were refractory to conventional anticonvulsants and were only suppressed by high-dose intravenous barbiturate administration. Rhythmic activities on electroencephalography and non-specific cerebral atrophy on neuroimaging were common. Serum or cerebrospinal antibodies against GluRepsilon2 were positive in six patients. General prognosis was unfavorable due to intractable epilepsy and cognitive deficits. Based on the peculiar and homogenous features, AERRPS can be regarded as a distinct clinical entity.

Acute encephalitis with refractory, repetitive partial seizures

Background: Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is a new epileptic syndrome described by Sakuma in Japan in 2001. The clinical manifestations, neuroimaging findings and outcome of AERRPS in Taiwan have not been reported. Methods: From 2000 to 2006, we collected cases that fulfilled the diagnostic criteria of AERRPS and analyzed the clinical course, virology, medication, electroencephalographic findings, neuroimaging characters and prognosis retrospectively. Results: Fourteen children aged from 1 year and 2 months to 15 years and 6 months were enrolled. They presented with prodromic symptoms including fever ( n = 13, 92.9%), upper respiratory tract infection symptoms ( n = 12, 85.7%) and gastrointestinal tract discomfort ( n = 6, 42.9%). Seizures occurred 3–14 days after antecedent symptoms with patterns of generalized tonic–clonic seizures, focal seizures or myoclonic seizures. The seizures were refractory to combinations of antiepileptic drugs (AEDs). Prolonged fever ( n = 14, 100.0%), hypersensitivity to AEDs ( n = 11, 78.6%) and liver function impairment ( n = 8, 57.1%) were noted during the period of hospitalization. The follow-up EEG findings were similar to those of initial findings including epileptiform discharges and/or generalized background slow waves. Initial brain MRI scans were normal but later showed focal or multifocal abnormal signal intensity followed by generalized brain atrophy in more than 50% of cases. The general prognosis was poor with variable psychomotor retardation and persistence of refractory epileptic seizures. Conclusions: The similarities of the clinical features support AERRPS as a new epileptic syndrome. More study is needed to specify the etiology of the syndrome as the first step for more effective treatment.

Clinical Characteristics of Acute Encephalopathy of Obscure Origin: A Biphasic Clinical Course Is a Common Feature

To evaluate the clinical characteristics of acute encephalopathy of obscure origin (AE). We examined clinical, imaging, and laboratory findings in children with AE. Specific subtypes of AE such as Reye's syndrome (RS), acute necrotizing encephalopathy (ANE), hemorrhagic shock and encephalopathy (HSE), acute encephalitis with refractory, repetitive partial seizures (AERRPS), and hemiconvulsion-hemiplegia syndrome (HH) were diagnosed. Other AE patients were regarded as non-specific subtype. Nineteen patients were identified; specific AEs in 14 and non-specific AE in 5. Patients with RS, ANE, HSE frequently showed neuroimaging abnormalities (9/9) and significant elevation of liver enzymes (7/9) within 2 days after onset. Prognoses were extremely poor; early death in 6 and severe neurological sequelae in 3. Two of the 3 HH patients and 4 of the 5 non-specific AE patients showed biphasic clinical courses (AEBC); consciousness levels transiently improved following initial seizures and were exacerbated at the fourth to sixth days. In AEBC, neuroimaging abnormalities were rarely observed during the acute phase (1/5) but were detectable at clinical exacerbation. They rarely showed severely abnormal elevation in liver enzymes (1/6) and resulted in mild to moderate neurological sequelae (6/6). A biphasic clinical course is a common feature in HH and non-specific AE.

A case of acute encephalitis with refractory, repetitive partial seizures, presenting autoantibody to glutamate receptor Gluε2

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 γ-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 Gluε2 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 γ-globulin therapy was effective.

不随意運動出現とともに一時的ながら発作消退をみたacute encephalitis with refractory, repetitive partial seizuresの1例

不随意運動出現とともに一時的ながら発作消退をみたacute encephalitis with refractory, repetitive partial seizuresの1例