Acta neurologica Scandinavica. Supplementum最新文献

Theophylline-associated seizures (TAS) are considered a neurologic emergency, as they can sometimes be intractable and difficult to stop with standard treatments such as intravenous administration of diazepam. As a consequence, a proportion of patients who experience status epilepticus while receiving theophylline will require endotracheal intubation. The optimal first-line therapy for TAS has not yet been fully investigated. We compared 54 cases of TAS with 779 cases of non-TAS, that had presented at a single institution between 1991 and 2002. Among the 54 cases of TAS, 36 experienced generalized tonic-clonic seizures, with the remainder experiencing partial seizures. TAS occurred mainly in children under 3 years of age, and serum theophylline levels were within the therapeutic range in 78% of the cases. The duration of TAS tended to be longer than for non-TAS, and intravenous administration of diazepam was less effective in controlling TAS (45%), compared with non-TAS (68%). Many cases required repeated injections of diazepam, and 15 cases (27%) eventually required endotracheal intubation. Reports concerning the therapy for TAS were also reviewed. Theophylline is known to antagonize the effects of benzodiazepines, and this may explain why drugs such as diazepam are relatively ineffective in treating TAS. In TAS, the prompt use of barbiturates is recommended when diazepam is not effective, to avoid potential brain injury secondary to status epilepticus.

Background: Hypsarrhythmia is generally associated with infantile spasms, a combination referred to as West syndrome. It is debatable whether hypsarrhythmia is usefully regarded as a form of non-convulsive status epilepticus (NCSE).

Summary points: The earliest English language description of hypsarrhythmia reported an almost continuous EEG pattern, although later studies showed a degree of state dependence. Its principal features are very high amplitude and irregular slow waves with superimposed multifocal epileptiform discharges. Paroxysms of spasms are clearly overt seizure events, and there are variable EEG patterns associated with this ictus. There remains a debate about the definitional boundaries of hypsarrhythmia, and about the defining characteristics of NCSE. There is evidence that hypsarrhythmia is an age-dependent EEG pattern that evolves, sometimes independently of clinical features. Frequently, hypsarrhythmia is associated with delay in or regression of neuro-developmental skills, and recent studies have reported that a longer lead time to diagnosis and effective treatment is associated with poorer long-term neuro-developmental outcomes. Recent consensus definitions and classifications of NCSE have suggested boundaries that permit inclusion of hypsarrhythmia as an EEG pattern of NCSE. In practice, adopting the idea that hypsarrhythmia is a form of NCSE might lead to earlier appropriate investigation of infants with subtle developmental delay or regression, hence avoiding treatment delays and potentially preserving developmental potential.

Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthem subitum. It occurs worldwide, but is most prevalent in East Asia, and every year several hundreds of Japanese children are affected by influenza-associated encephalopathy. Mortality has recently declined, but is still high. Many survivors are left with motor and intellectual disabilities, and some with epilepsy. This article reviews various syndromes of acute encephalopathy by classifying them into three major categories. The first group caused by metabolic derangement consists of various inherited metabolic disorders and the classical Reye syndrome. Salicylate is a risk factor of the latter condition. The second group, characterized by a systemic cytokine storm and vasogenic brain edema, includes Reye-like syndrome, hemorrhagic shock and encephalopathy syndrome, and acute necrotizing encephalopathy. Non-steroidal anti-inflammatory drugs, such as diclofenac sodium and mephenamic acid, may aggravate these syndromes. Severe cases are complicated by multiple organ failure and disseminated intravascular coagulation. Mortality is high, although methylprednisolone pulse therapy may be beneficial in some cases. The third group, characterized by localized edema of the cerebral cortex, has recently been termed acute encephalopathy with febrile convulsive status epilepticus, and includes hemiconvulsion-hemiplegia syndrome and acute infantile encephalopathy predominantly affecting the frontal lobes. Theophylline is a risk factor of these syndromes. The pathogenesis is yet to be clarified, but an increasing body of evidence points to excitotoxicity and delayed neuronal death.

Convulsive status epilepticus (CSE) in childhood is a medical emergency and its aetiology and outcome mean that it should be studied separately from adult CSE. The incidence in developed countries is between 17 and 23/100,000 with a higher incidence in younger children. Febrile CSE is the commonest single group with a good prognosis in sharp distinction to CSE related to central nervous system infections which have a high mortality. The aim of treatment is to intervene at 5 min and studies indicate that intravenous (i.v.) lorazepam may be a better first-line treatment than rectal diazepam and i.v. phenytoin a better second-line treatment than rectal paraldehyde. An epidemiological study strongly supports the development of prehospital treatment with buccal midazolam becoming a widely used but unlicensed option in the community. More than two doses of benzodiazepines increase the rate of respiratory depression without obvious benefit. The 1 year recurrence rate is 17% and the hospital mortality is about 3%.

Objectives: To assess hippocampal volumes (HV) and signal changes on diffusion-weighted imaging (DWI) within 5 days of prolonged febrile seizures (PFS) and compare them with the PFS duration and EEG.

Methods: We studied 12 children (mean age: 32 +/- 21 months, range 10 months-5 years) within 5 days of a first episode of PFS (a seizure or series of seizures lasting for 30 min or longer, without return of consciousness between the seizures). The HV measurements were carried out using high-resolution magnetic resonance imaging and signal intensity abnormalities were evaluated visually on DWI. HV in patients were compared with those of 13 neurologically normal controls (mean age 31 +/- 16 months, range 15 months-5 years). HV abnormalities correlated with PFS duration. HV and DWI abnormalities were compared with EEG abnormalities.

Results: Seizure duration ranged from 40 to 95 min. In seven out of twelve patients, seizures were refractory and lasted for 60 min or longer despite intravenous infusion of diazepam. In the patients with PFS for 60 min or longer, HV were significantly larger than that of controls. In all patients, there was a positive correlation between HV and seizure duration. DWI showed hyperintensity in unilateral hippocampus in three patients with intractable seizures, ipsilateral thalamus in two, and cingulate in one. EEG showed abnormalities in temporal areas ipsilateral to the DWI abnormalities in these patients.

Conclusions: Large HV and hippocampal hyperintensity on DWI were seen in patients with refractory PFS. Our results suggest that medically refractory PFS lasting for 60 min or longer may cause structural changes in limbic structures that could promote later epileptogenesis.

Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABAA (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABAA receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, 'spare' subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed.