Human herpesvirus 6-associated encephalopathy in a child with Dravet syndrome.

Dravet syndrome presents with generalized and unilateral clonic or clonic-tonic seizures that occur during the first year of life, followed by severe epilepsy. Prolonged seizures are often provoked by fever and usually followed by recovery of the previous condition. We describe the case of a 13-month-old girl with Dravet syndrome who experienced severe neurological sequelae as a result of human herpesvirus 6-associated encephalopathy. Biphasic clinical course was observed, with fever and prolonged seizures at onset and late seizures refractory against antiepileptic agents. Serum concentrations of proinflammatory cytokines and matrix metalloproteinase-9, which have been associated with development of acute encephalopathy, were not markedly increased in this patient, suggesting that these molecules were not the main causes of neuronal damage in this patient. Instead, seizure susceptibility due to SCN1A mutation may have contributed to acute encephalopathy in our patient.

Pertussis-associated encephalitis/encephalopathy with marked demyelination in an unimmunized child.

Encephalitis/encephalopathy is a rare, but severe, complication of pertussis. Here, we report a case of an unimmunized 7-year-old boy with confirmed pertussis complicated by acute encephalitis/encephalopathy. Eighteen days after the onset of pertussis, generalized seizures began. Magnetic resonance imaging (MRI) indicated that marked demyelination without cytotoxic edema may have occurred to the patient. Notably, this is the first report to show precise MRI findings of pertussis-associated encephalitis/encephalopathy. Markedly increased myelin basic protein levels in the cerebrospinal fluid were consistent with the MRI findings. There was no evidence of direct invasion of the causative bacterium or its products into the central nervous system. The levels of interleukin-6 and -10 in the cerebrospinal fluid were higher than those in serum. Taken together, we conclude that indirect immune-mediated mechanisms may have contributed to the pathogenesis of the encephalitis/encephalopathy.

Acute encephalopathy in children with Dravet syndrome.

PURPOSE: The occurrence of acute encephalopathy in children with Dravet syndrome has been reported sporadically. This study clarified the features of acute encephalopathy in children with Dravet syndrome. METHODS: Through the mailing list of the Annual Zao Conference on Pediatric Neurology, we collected 15 patients with clinically diagnosed Dravet syndrome, who had acute encephalopathy, defined as a condition with decreased consciousness with or without other neurologic symptoms, such as seizures, lasting for >24 h in association with infectious symptoms. KEY FINDINGS: There were seven boys and eight girls. A mutation of the SCN1A gene was present in nine (truncation in six and missense in three). The frequency of seizures during the 3 months before the onset of acute encephalopathy was monthly in seven children and none in three. The median age at the onset of acute encephalopathy was 44 months (range 8-184 months). All children had status epilepticus followed by coma as the initial manifestation. Two different distributions of brain lesions were observed on diffusion-weighted images during the acute phase: cerebral cortex-dominant lesions with or without deep gray matter involvement and subcortical-dominant lesions. Four children died; nine survived with severe sequelae, and two had moderate sequelae. SIGNIFICANCE: We must be aware that acute encephalopathy is an important complication in children with Dravet syndrome, and associated with fulminant clinical manifestations and a poor outcome.

Comparison of the levels of human herpesvirus 6 (HHV-6) DNA and cytokines in the cerebrospinal fluid and serum of children with HHV-6 encephalopathy.

Primary human herpesvirus-6 (HHV-6) infection is a common cause of acute sporadic encephalopathy in Japanese children. Occasionally, HHV-6 is not detected in the cerebrospinal fluid (CSF) of patients with encephalopathy, for example, in those with focal viral encephalitis, such as herpes simplex viral encephalitis. This indicates that HHV-6 encephalopathy is caused by an indirect mechanism, although this is not fully understood. HHV-6 DNA, cytokines (interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12 p70, tumor necrosis factor-alpha, interferon-gamma), and matrix metalloproteinase-9 were quantitated in both the CSF and serum of 13 patients with HHV-6 encephalopathy during the acute phase of the disease. HHV-6 DNA was detected in the CSF of seven patients with HHV-6 encephalopathy. The viral DNA concentration was significantly higher in serum than in CSF (mean 1.64 x 10(4) vs. 5.70 x 10(1) copies/ml; P = 0.003). The lack or low level of viral DNA in the CSF samples suggests that direct invasion of the central nervous system by HHV-6 is not the main cause of encephalopathy. Additionally, the IL-10 concentration was significantly higher in serum than in CSF (P < 0.001), whereas there was no significant difference in IL-6 levels between the CSF and serum samples. Interestingly, the IL-8 concentration was significantly higher in CSF than in serum (P = 0.038). The distribution of these cytokines differed between CSF and serum. The high CSF concentration of IL-8 could play an important role in the pathogenesis of encephalopathy.

[Acute encephalitis/encephalopathy associated with transient involuntary movement and limbic dysfunction in the recovery phase].

We report 3 patients aged 3 - 4 years who presented with impaired consciousness and status epilepticus or a cluster of seizures, followed by transient involuntary movements and limbic dysfunction in the recovery phase. In all the patients, the involuntary movements were observed mainly on the left side and consisted of dystonia, athetosis, chorea, facial myoclonus, and oral dyskinesia. The patients also showed stereotypic movement, oral tendency, visual agnosia, and emotional disturbance, which suggested limbic dysfunction resembling Klüver-Bucy syndrome. Single-photon emission computed tomography (SPECT) revealed hypoperfusion of the unilateral basal ganglia and the adjacent frontal and temporal lobes. No obvious lesions were observed on brain MRI in the acute phase in 2 patients, who recovered completely during the follow-up period. However, the last patient, who had abnormalities with regard to the limbic system and subcortical white matter on diffusion-weighted image in the acute phase, exhibited mental retardation, epilepsy, and persistent oral tendency during the follow-up period.

Effect of corticosteroids in a twin child with idiopathic localization-related epilepsy.

Corticosteroids have been used only in the treatment of special epileptic syndromes or epileptic encephalopathies, such as infantile spasms. We report an antiepileptic effect of corticosteroids that were used for treatment of nephropathy in a monozygotic twin child with idiopathic localization-related epilepsy (I-LRE). The patient and her monozygotic twin sister exhibited repeated partial seizures at two years of age and electroencephalogram (EEG) showed focal spikes in the occipital area and, on other occasions, the centro-parietal areas. After oral antiepileptic drugs were started, the twins still exhibited occasional seizures. The patient had IgA nephropathy at four years of age and intravenous methylprednisolone and oral prednisolone were administered. Her seizures and epileptiform discharges on EEG disappeared, while her sister continued to have seizures and EEG abnormalities. When the dose of oral predonisone was reduced, the seizures relapsed and EEG again revealed focal spikes. We conclude that corticosteroids exhibit efficacy towards seizures and epileptiform discharges on EEG in patients with I-LRE without epileptic encephalopathies.

Transient splenial lesions in children with "benign convulsions with gastroenteritis".

"Benign convulsions with mild gastroenteritis (CwG)" is recognized as a benign situation-related seizure. Neuroimaging studies usually do not reveal any abnormalities. We report MRI diffusion-weighted image (DWI) findings of two patients who were clinically diagnosed with CwG. DWI demonstrated a transient abnormality in the splenium of the corpus callosum. Although viral encephalitis or encephalopathy should be carefully differentiated in patients clinically diagnosed with CwG, frequent seizures might cause transient splenial abnormality in patients with CwG.

Ictal EEG in patients with convulsions with mild gastroenteritis.

The aim of this study is to reveal detailed clinical manifestations and an evolution of ictal EEG discharges of convulsions with mild gastroenteritis (CwG). We recorded ictal EEGs of six patients with CwG. Clinical manifestations included loss of responsiveness, motion arrest, cyanosis, lateral eye deviation, and hemifacial convulsion. Automatism was not observed in any patients. A generalized tonic-clonic convulsion was observed in five of six patients. Ictal EEGs demonstrated that all seizures were of focal onset that evolved into a secondarily generalized seizure. The region of the onset of ictal discharge was the occipital area in three patients, parietal in one, central in one, and frontal in one, respectively. The seizure of patients with CwG is likely to be a partial seizure with secondary generalization.

Electroencephalographic (EEG) findings in posterior reversible encephalopathy associated with immunosuppressants.

Posterior reversible encephalopathy has been reported in patients who receive immunosuppressants. Compared with radiologic studies, electroencephalographic (EEG) findings are not well described. We performed EEG serially in three children who suffered from posterior reversible encephalopathy associated with tacrolimus or cyclosporine. EEG showed continuous focal rhythmic activities in the acute period. EEG findings normalized after the clinical manifestations had disappeared. We conclude that EEG is useful for the diagnosis and follow-up of posterior reversible encephalopathy.

Treatment and outcome in patients with febrile convulsion associated with epileptiform discharges on electroencephalography.

The aim of this study is to determine the efficacy of prophylactic treatment for patients with febrile convulsions (FCs) in whom electroencephalograms (EEGs) revealed epileptiform discharges. We retrospectively investigated 43 patients who met the following criteria: (a) at least one FC during the study period; (b) epileptiform discharges were first recognized; (c) no unevoked seizures before epileptiform discharges were first seen; (d) normal psychomotor development and no neurological abnormality; and (e) follow-up >3 years. The clinical characteristics, treatment, and a later occurrence of FCs or unevoked seizures were studied. EEGs revealed focal epileptiform discharges in 25 patients and generalized ones in 18. There was no significant difference in the rate of recurrence of FC or occurrence of unevoked seizures between those with focal and generalized epileptiform discharges. No prophylaxis was performed in ten patients, 14 patients being treated with intermittent diazepam and 19 with a daily anticonvulsant. The rate of recurrence of FC was not significantly different between patients with and without prophylaxis. Unevoked seizures were only observed in two patients undergoing daily treatment. Intermittent or daily anticonvulsant therapy will not reduce the risk of recurrence of FCs or later development of unevoked seizures in patients with FC with epileptiform discharges.

Sharp waves in preterm infants with periventricular leukomalacia.

We studied the incidence of positive and negative sharp waves in two pairs of twin infants with periventricular leukomalacia and compared it with that of normal cotwins by using remontage and refiltering functions of digital electroencephalography. Three electroencephalograms were serially performed in each infant. After the usual visual inspection with bipolar montage and low-cut filter of 0.5 Hz, the electroencephalogram montage was changed into monopolar derivation, and the low-cut filter into 5 Hz. The number of positive or negative sharp waves per minute, with an amplitude of more than 50 microV, was independently calculated. The number of negative sharp waves was large in the occipital and Pz areas in both infants with periventricular leukomalacia. The number of positive ones was large in the Cz area in both infants with periventricular leukomalacia. Disorganized patterns were observed in all electroencephalograms in the infants with periventricular leukomalacia on visual inspection. In conclusion, digital electroencephalography analysis using remontage and refiltering demonstrated an increased number of sharp transients in preterm infants with periventricular leukomalacia. The application of a higher low-cut filter will be useful for the assessment of sharp transients in neonatal electroencephalography.

Physiological evidence of interaction of first- and second-order motion processes in the human visual system: a magnetoencephalographic study.

Humans have several mechanisms for the visual perception of motion, including one that is luminance-based (first-order) and another that is luminance-independent (second-order). Recent psychophysical studies have suggested that significant interaction occurs between these two neural processes. We investigated whether such interactions are represented as neural activity measured by magnetoencephalography (MEG). The second-order motion of a drifting sinusoidal grating, which is defined by the speed of the dot motion, did not generate a response. Apparent motion (AM) of the square area, defined by the speed of randomly moving dots, evoked a magnetic response whose latency and amplitude changed with the distance that the area moved (a second-order characteristic), though the response properties were significantly different from those for the first-order AM. AM, defined by both first- and second-order attributes, evoked an MEG response and the latencies and the amplitudes were distributed between those for the first- and second-order motions. The cortical source of the response was estimated to be around MT+. The results show a distinct difference in the neural processing of the second-order motion that cannot be explained by the difference in visibility, and they indicate that the interaction of the neural processes underlying first- and second-order motion detection occurs before the MEG response. Our study provides the first physiological evidence of a neural interaction between the two types of early motion detection.

Absence seizures in patients with localization-related epilepsy.

We studied the clinical features of 12 patients with localization-related epilepsy (LRE) associated with absence seizures (AS). AS did not appear in any patients before partial seizures (PS) were first observed. The interval between the onset of PS and AS ranged from 1 month to 7.2 years (mean 2.11 years). The duration of AS (mean 5 months) was short compared with that of PS (mean 3.8 years). Carbamazepine (CBZ) was used in seven patients at the onset of AS. It was discontinued in five but continued in the other two. AS was initially treated with valproate in ten patients. Three of them needed additional antiepileptic drugs: clonazepam in two patients and ethosuximide in one. All patients became free from AS after treatment for AS was started, whereas PS was relatively intractable. Generalized spike-and-waves were often observed before the onset of AS. The interval between the first appearance of generalized spike-and-waves and the onset of AS ranged from 1 to 53 months (mean 20 months). AS in patients with LRE will be relatively benign and transient, and will respond well to antiepileptic drugs.

[A case of infantile epileptic encephalopathy with frequent focal motor status convulsivus: successful treatment with zonisamide].

We reported a 41-day-old girl starting with partial status convulsivus. She had suffered from infantile epileptic encephalopathy manifesting with recurrent focal motor status convulsivus, eventually requiring general anesthesia for the treatment. She had had never myoclonic seizures nor tonic spasms. The examinations including brain MRI scan and metabolic screening tests were all negative. The ictal EEGs showed the onset of the seizures from the left frontal region. Interictal EEG demonstrated multifocal spike discharges as well as discontinuous abnormal EEG pattern resembling suppression-burst during sleep. The seizures were resistant to the multiple antiepileptic drugs, but zonisamide achieved full seizure control as well as improvement of the EEG. Her psychomotor development was severely retarded at 3 years of age.