In the present study, we described the clinical and laboratory characteristics of CFS that required hospitalization. Although large studies on clinical features of febrile seizures have recently been published [15, 16], to the best of our knowledge, this is the first report to describe the detailed characteristics of acute-phase CFS.
Our study showed that the median duration of convulsive seizures was 30.5 min and the median time from seizure onset to full recovery of consciousness was 175 min in patients with CFS. This differs from the findings of previous reports on seizure duration and recovery time. Okumura et al. [17] examined the clinical features of prolonged unconsciousness and delirious behavior in children with FS and showed that the duration of seizures was < 5 min in 90.2% and the duration of unconsciousness was < 30 min in 93% of the seizures, leading to the conclusion that prolonged unconsciousness is rare in children with FS. In prior studies of epileptic seizures conducted by Allen et al. [18] and McKenny-Fick et al. [19], the median duration and recovery time of FS were 2.5 and 18 min, respectively. The discrepancy between our study and previous studies can be explained by the difference in the study participants. Patients with SFS were not included in our study, while the previous studies included patients with SFS. In addition, the hospital setting may have influenced this difference. While the previous reports mentioned above were conducted in hospitals providing secondary-level pediatric care, our hospital is a tertiary referral hospital for children. Therefore, there may be a tendency for more severe cases to be referred to our hospital instead of to other institutes.
In a previous study on febrile status epilepticus (FSE), which was defined as FS without full recovery lasting ≥ 30 min, Shinnar et al. [20] reported the consequences of 119 cases of FSE, showing that seizures lasted for a median of 68 min, 24% of the seizures lasted > 2 h, and 87% of the seizures did not stop spontaneously and were treated with benzodiazepines. Our study demonstrated that convulsive seizures of CFS lasted a median of 30.5 min and 6.8% of the convulsive seizures lasted > 2 h, and two-thirds of the seizures required anticonvulsants. In addition, half of the participants had FSE. In our study, the severity of seizures was milder than that reported by Shinnar et al. [20] because our study also included patients who had seizures lasting < 30 min. However, it is particularly worth noting that half of the patients with CFS had FSE. Berg et al. [9] reported that CFS and FSE accounted for approximately 35% and 5% of all FS, respectively. Therefore, our patients with CFS had more FSE than previously reported. We may have encountered only some of the more severe cases of CFS.
The most notable aspect of our study is its detailed focus on the duration of impaired consciousness and the distribution of blood test results. Prolonged impaired consciousness and abnormal laboratory values are expected to be more common in patients with CFS and FSE than in those with SFS. However, almost all previous reports on CFS and/or FSE, including that of Shinnar et al. [20], did not mention the details of the duration of impaired consciousness or blood test values. Therefore, these points could be considered the greatest novelty of this study.
The definitive diagnosis of CFS in the acute phase is sometimes challenging because patients with both CFS and acute encephalitis/encephalopathy (AEE) exhibit impaired consciousness with or without seizures as an initial manifestation. There is a well-established consensus on the clinical case definition and diagnostic methods for encephalitis [21]. However, in some cases of AEE, there may be no significant cerebrospinal fluid pleocytosis or no demonstrable neuroimaging abnormalities [21]. Therefore, complete differentiation between CFS and AEE at an early stage can sometimes be impossible in practice and often confounds clinicians, especially when symptoms during the acute phase are severe. Our previous report on the risk factors related to poor outcomes in patients with fever and seizures showed that refractory status epilepticus, consciousness disturbance or hemiplegia at 6 h from onset, or AST > 90 IU/L within 6 h of onset were associated with poor outcomes, leading to the final diagnosis of AEE [22, 23]. In addition, several reports have suggested that prolonged impaired consciousness and abnormal laboratory findings such as elevation of AST, LDH, Glu, and/or Cr might predict poor outcomes or AEE in children with seizures [24,25,26,27,28,29,30]. These abnormalities are sometimes observed in CFS, but their details in CFS have remained unclear. Our study is the first report to describe this information of acute-phase CFS, showing that impaired consciousness lasting > 6, 8, and 12 h was observed in 13.9%, 7.6%, and 1.9% of CFS cases, and 97 percentile values of AST, LDH, Cre, and Glu were 74 IU/L, 468 IU/L, 0.40 mg/dL, and 266 mg/dL, respectively. This information may be useful in that data outside of these ranges should alert an alternative diagnosis other than CFS at an early stage. Therefore, our findings may provide important information for appropriate acute management of CFS.
The present study has several limitations. First, this study was based on data from a single tertiary care institution; hence, our hospital is more likely to encounter more severe cases than other institutions. Second, since severe cases requiring intensive care were excluded, only mild cases may have been extracted, resulting in some selection bias. Third, even though we presented detailed data on the recovery time of consciousness, we did not identify independent factors that affected it. Previous reports have shown that the use of antiepileptic drugs significantly increased recovery time [18, 19]. In our report, two-thirds of patients were treated with one or more anticonvulsants. Therefore, drug administration may have resulted in a longer time to complete recovery of consciousness. However, factors other than drug type that affect recovery time need to be considered, such as the actual drug dose administered and the time taken from onset to the start of treatment. The present study design did not provide sufficient information on the drug dose and time from onset to treatment initiation, and thus it was not possible to examine factors that independently affected recovery time. Finally, this study only described the detailed characteristics of acute-phase CFS and did not compare the findings with those of patients with related disorders such as SFS or AEE. Therefore, the findings of this study do not allow us to differentiate CFS from these conditions. To confirm the clinical validity of the findings of this study as reliable information for the differential diagnosis of CFS, comparative studies with SFS and AEE are needed.
