Case Report: Chronic inflammatory demyelinating polyradiculoneuropathy rather than hemophagocytic lymphohistiocytosis-the initial phenotype of PRF1 gene mutation.

Perforin is essentially involved in the granule-dependent killing activities of cytotoxic T lymphocytes and NK cells. Monoallelic PRF1 mutation increases the risk of autoimmune diseases, and biallelic PRF1 mutation causes familial hemophagocytic lymphohistiocytosis-2. Here, we report a case of a 12-year-old girl with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), followed by a rapidly progressive onset of hemophagocytic lymphohistiocytosis (HLH) 9 months later, alongside manifestations of demyelinating encephalopathy. Genetic sequencing revealed a heterozygous nonsense mutation in the PRF1 gene (c.984G>A; p.W328*) and a heterozygous missense mutation in the PRF1 gene (c.1349C>T; p.T450M). Eventually, she died because of no suitable allogeneic hematopoietic stem cell available in time. Our observations suggest that CIPD might represent the initial phenotype of biallelic PRF1 mutation and could serve as an early sign of subsequent HLH. A comprehensive understanding of this condition is paramount for timely diagnosis, treatment, and ultimately improved patient outcomes.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

Vigabatrin-associated brain abnormalities on MRI in tuberous sclerosis complex patients with infantile spasms: are they preventable?

Background: Vigabatrin (VGB) is currently the most widely prescribed first-line medication for individuals with infantile spasms (IS) and especially for those with tuberous sclerosis complex (TSC), with demonstrated efficacy. Meanwhile, its adverse events, such as vigabatrin-associated brain abnormalities on magnetic resonance imaging (MRI; VABAM), have also been widely reported. Objectives: The objectives of this study were to observe the occurrences of VABAM in patients with IS caused by TSC (IST) and further explore the associated risk factors. Methods: Children with IS receiving VGB were recruited from our institution; clinical, imaging, and medication data were collected. Cerebral MRI was reviewed to determine the occurrence of VABAM. Group comparisons (IS caused by TSC and other etiologies) were performed; subgroup analyses on IST were also performed. Next, a retrospective cohort study of children taking VGB was conducted to explore risk/protective factors associated with VABAM. Results: The study enrolled 172 children with IS who received VGB. VABAM was observed in 38 patients (22.1%) with a peak dosage of 103.5 ± 26.7 mg/kg/day. Subsequent analysis found the incidence of VABAM was significantly lower in the 80 patients with IST than in the 92 patients with IS caused by other etiologies (10% versus 32.6%, p-value < 0.001). In subgroup analyses within the IST cohort, VABAM was significantly lower in children who received concomitant rapamycin therapy. Univariate and multivariate logistic regression analysis of the 172 IS children showed that treatment with rapamycin was the independent factor associated with a lower risk of VABAM; similar results were observed in the survival analysis. Conclusion: The incidence of VABAM was significantly lower in IST patients. Further research is needed to examine the mechanisms that underlie this phenomenon and to determine if treatment with rapamycin may reduce the risk of VABAM.

The Instigation of the Associations Between Melatonin, Circadian Genes, and Epileptic Spasms in Infant Rats.

Background: Infantile spasm (IS) is one of the most common catastrophic epilepsy syndromes in infancy characterized by epileptic spasm. While adrenocorticotropic hormone (ACTH) is the first-line treatment for IS, it is evident that the seizures associated with IS exhibit a clear circadian rhythm; however, the precise mechanisms underlying such seizures remain unclear. Melatonin is an important amine hormone and is regulated by circadian rhythm. Circadian proteins, especially Aryl Hydrocarbon Receptor Nuclear Trasnslocator-like Protein (ARNTL or BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), and their target proteins Period Circadian Regulator 1 (PER1), Period Circadian Regulator 2 (PER2), Cryptochrome 1 (CRY1), and Cryptochrome 2 (CRY2), play key roles in circadian rhythm. This study explored the relationships between melatonin, genes associated with circadian rhythm, and epileptic spasm. Materials and Methods: Eighteen female rats were mated with nine male rats and 16 became pregnant. Twelve pregnant rats were subjected to prenatal stress by forced swimming in cold water from the day of conception. Rat pups produced by stressed mothers received an intraperitoneal injection of N-methyl-D-aspartate (NMDA) on the 13th day after birth and were divided into four groups: NMDA (15 mg/kg), NMDA+ACTH (20 IU/kg), NMDA+melatonin (55 mg/kg), and NMDA+ACTH+melatonin (n = 36/group). Offspring from four dams that were not subjected to prenatal stress were used as controls. We then recorded latency and the frequency of flexion seizures. All offspring were sacrificed on the 14th day after birth and CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was analyzed by western blotting, immunohistochemistry, and immunofluorescence. Results: NMDA induced spasm-like symptoms in rats. ACTH and melatonin significantly increased seizure latency and significantly reduced the frequency of seizures (P < 0.05). CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was significantly lower in the NMDA group than the controls (P < 0.05). ACTH significantly increased the expression of CLOCK, BAML1, PER1, and CRY1 (P < 0.05) and melatonin significantly increased the expression of CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 (P < 0.05) compared with those of the NMDA group. There were no significant differences in the expression of BMAL1, CRY2, PER1, and PER2 when compared between the NMDA+ACTH+melatonin and control groups (P > 0.05). Conclusion: ACTH and melatonin significantly increased the expression of circadian genes and improved NMDA-induced seizures. The anticonvulsant effects of ACTH and melatonin are likely to involve regulation of the expression of these genes.

The Efficacy of Fecal Microbiota Transplantation for Children With Tourette Syndrome: A Preliminary Study.

Therapies for Tourette syndrome (TS) are insufficient, and novel therapies are needed. Fecal microbiota transplantation (FMT) has been a potential therapy for several neurological diseases. Here, we report a preliminary study to investigate the effects of FMT on patients with TS. Five patients with TS received a single administration of FMT via endoscopy. Tic symptoms were assessed by Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) and adverse effects were recorded at week 8 following FMT. Lipopolysaccharide (LPS) levels and 14 cytokines levels were measured. The microbiota profile in feces were analyzed by shotgun metagenomics. Four patients (4/5) responded positively to FMT (YGTSS-TTS reduction rate >25%) at week 8 with high safety. The levels of LPS and cytokines varied after FMT. FMT shifted the composition of the gut microbiota in patients close to that of the donor and continuously changed the abundance of Bacteroides coprocola, Dialister succinatiphilus and Bacteroides vulgatus. The restoration of B.coprocola was correlated with the improvement in tic symptoms (Spearman R = -0.900, P = 0.037). In conclusion, FMT was indicated a potential effective and safe alternative for patients with TS. However, larger clinical trials are needed to confirm the influence of microbiota in TS. Trial Registration: chictr.org.cn Identifier: ChiCTR-IIR-17011871, URL: http://www.chictr.org.cn/showproj.aspx?proj=19941.

Cobb Syndrome Manifesting as Repetitive Seizures in a 10-Year-Old Girl: A Case Report and Literature Review.

Cutaneous vertebral medullary angiomatosis, also known as Cobb syndrome, is a rare segmental neurocutaneous syndrome. This syndrome is considered to be a non-hereditary congenital disease that is usually associated with arteriovenous malformations in the skin and spine. The clinical manifestations are complex because the lesions can involve the spine, spinal cord, skin, and even the viscera. Here, we present the case of a 10-year-old girl who was admitted to hospital due to headache with two episodes of convulsions. Previous examination at another hospital found no evidence of any abnormalities on either cranial or intracranial vascular magnetic resonance imaging (MRI). However, the patient had a history of subcutaneous hemangioma. Following exhaustive tests at our hospital, she was diagnosed with Cobb syndrome. She received surgery, treatment for decreasing intracranial pressure, and hormonal and nutritional support. She subsequently remained stable, with no recurrence of convulsions over a 9-year follow-up period. Here, we expand upon the clinical manifestations of Cobb syndrome and propose mechanisms for the underlying pathogenesis. We hope that our experience can help avoid missed diagnoses and misdiagnosis and provide more clinical evidence for early diagnosis.

Establishment and utility assessment of posterior reversible encephalopathy syndrome early warning scoring (PEWS) scale establishment and utility assessment of PEWS scale.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a complication that occurs during various diseases' treatment. Imaging examination is the gold standard for diagnosis. PRES frequently occurrence in patients with hematological malignancies results in poorer prognosis and higher mortality. We aim to establish a practical and operable scale for early prediction, assessment of the severity of the Posterior Reversible Encephalopathy Syndrome, and timely intervention for better prognosis. METHODS: The scale designed by reviewing the literature and by referring to clinical practice. We assessed the reliability and validity of the scale. Scale-based assessment of children undergoing chemotherapy for acute lymphoblastic leukemia conducted as early warning and intervention for those who may have PRES. RESULTS: Establishment of Posterior Reversible Encephalopathy Syndrome early warning scoring (PEWS) scale included three parts, as follows: (1) risk factors, including underlying disease, hypertension, Infection, and drug toxicity; (2) clinical features, including high cranial pressure, visual symptoms, seizure, and disturbance of consciousness; and (3) EEG features, including slow wave and epileptiform discharges. Utility assessment of PEWS scale showed that in 57 patients with acute lymphoblastic leukemia, 54 scored less than 10 and none of them detected as PRES. The other two had scores of 12 and 13 both diagnosed with PRES by brain MRI scan. CONCLUSIONS: PEWS scale can predict PRES early. PRES was highly suspected when the score was 10 points and more. Thus, prophylactic intervention can give to improve the prognosis of PRES.

Intermittent oral levetiracetam reduced recurrence of febrile seizure accompanied with epileptiform discharge: a pilot study.

BACKGROUND: In previous study, we have found intermittent oral levetiracetam (LEV) can effectively prevent recurrence of febrile seizure (FS). This study aimed to analyze the effects of the preventive on the patients with frequent FS accompanied with epileptiform discharge. METHODS: Patients with frequent FS were assigned to undergo Electroencephalogram (EEG). At the onset of fever, the patients who presented epileptiform discharge were orally administered with LEV with a dose of 15-30 mg/kg per day twice daily for 1 week, thereafter, the dosage was gradually reduced until totally discontinued in the second week. The seizure frequency associated with febrile events and FS recurrence rate during a 48-week follow-up were analyzed. RESULTS: among the 19 patients presented epileptiform discharge on EEG, 31.58% (6 of 19) had complex FS, 68.42% (13 of 19) had simple FS. Up to 57.89% (11 of 19) had a family history of seizure disorder and 36.84% (7 of 19) had a family history of FS in first-degree relatives. 42.11% (8 of 19) happened the first FS episode at the age < 18 months. 36.84% (7/19) presented generalized spikes, 63.16% (12/19) showed focal spikes. During the 48-week follow-up period, the patients experienced 26 febrile episodes, none of them presented seizure recurrence. CONCLUSION: Intermittent oral LEV can prevent the seizure recurrence of FS accompanied with epileptiform discharge in 48-week. However, further randomized controlled trials should be conducted. TRIAL REGISTRATION: ChiCTR-IPR-15007241 ; Registered 1 January 2014 - Retrospectively registered.

Sirolimus alternative to blood transfusion as a life saver in blue rubber bleb nevus syndrome: A case report.

RATIONALE: Blue rubber bleb nevus syndrome (BRBNS) is a rare disease characterized by multiple venous malformations. The gastrointestinal bleeding and secondary iron deficiency anemia are the most common complications. There are currently no effective treatments for BRBNS. Here, we report a case of successful treatment with a small dose of sirolimus of a BRBN patient with a de novo gene mutation. PATIENT CONCERNS: A 12-year-old female was admitted to our hospital with multiple hemangiomas for 12 years. The patient often displayed melena; she recently received transfusion of 2 units of red blood cells once every 2 weeks. Multiple fist-sized hemangiomas were piled up on both sides and back of the neck, and were also noted on the arms, legs, chest, back, and on the tip of the tongue. The laboratory findings demonstrated severe anemia. Blood sample sequencing detected a heterozygous de novo mutation c.2545C > Tin the TEK gene. DIAGNOSES: Based on these findings, final diagnosis of Blue rubber bleb nevus syndrome (BRBNS) was made. INTERVENTIONS: After the diagnosis, low-dose sirolimus was orally administered. OUTCOMES: The patient's hemoglobin was increased after treatment with sirolimus for 1 month. Since the initial treatment with sirolimus, she had not received any blood transfusions. The skin and mucosal hemangioma decreased significantly, and new digestive tract hemorrhage, muscle hematoma, or adverse drug reactions were not observed. LESSONS: we report a case of a mutation in exon 15 of the TEK gene leading to BRBN. It was successfully treated with a small dose of sirolimus as an alternative to blood transfusion in order to save the of BRBN patient's life.

Hypercapnia-induced brain acidosis: Effects and putative mechanisms on acute kainate induced seizures.

AIMS: This study investigated the mechanism of the anticonvulsant effects of carbogen containing 5% CO2 in a kainic acid (KA) rat model. MAIN METHODS: Four-week-old Sprague-Dawley rats were divided into four groups: control, carbogen, KA+air, and KA+carbogen. Carbogen containing 5% CO2 was applied immediately after KA injection, and cortical pH was recorded. High-performance liquid chromatography was used to detect the release of γ-aminobutyric acid (GABA) and glutamate. We used electrophysiology to measure cortical and hippocampal activities. KEY FINDINGS: Carbogen increased the onset latency of seizure (KA+air group, 26.12±2.11min; KA+carbogen group 43.65±2.78min, P<0.001) and reduced the frequency of seizures (KA+air group, 12.50±1.77; KA+carbogen group, 5.63±1.59, P<0.001). Carbogen inhalation could reduce cortical pH (KA+air group, 7.04±0.04; KA+carbogen group, 6.82±0.03, P<0.001). After carbogen inhalation, the levels of excitatory amino acid glutamate decreased (595.90±7.51 in KA+air group vs. 467.95±4.82 in KA+carbogen s group, P<0.001), whereas GABA increased significantly (158.30±5.05 in KA+air group vs. 216.62±5.59 in KA+carbogen, P<0.05). Carbogen reduced both electrohippocampalogram (119.57±2.83 in KA+air group vs. 107.48±2.95 in KA+carbogen group, P<0.01) and electrocorticogram (130.74±2.48 in KA+air group vs. 115.35±2.11 in KA+carbogen group, P<0.01). SIGNIFICANCE: Carbogen containing 5% CO2 decreased seizures by reducing cortical pH, by increasing GABA release, and by affecting electrical activity of the brain.

Epileptic seizure, as the first symptom of hypoparathyroidism in children, does not require antiepileptic drugs.

OBJECTIVE: Patients with hypoparathyroidism exhibit metabolic disorders (hypocalcemia) and brain structural abnormalities (brain calcifications). Currently, studies have determined whether antiepileptic drug (AED) treatment is required for epileptic seizures in children with hypoparathyroidism. METHOD: This study aims to evaluate the data of two medical centers in Beijing based on the diagnosis of epileptic seizures as the first symptom of hypoparathyroidism in children. RESULT: A total of 42 patients were included and assigned into AED and non-AED treatment groups in a 1:2 matched case-control study. Results show that the seizure outcome after 1 year of AED treatment is not significantly different from that of the control. In the subgroup analysis of patients with subcortical calcifications, the seizure outcome is still not significantly different from that of the control. CONCLUSION: Thus, AED treatment cannot improve the seizure outcomes in children with parathyroid disorder, even in such cases as suspected structural seizure caused by subcortical calcifications. Clinicians must take adequate considerations on the use of AEDs in these patients. Epileptic seizures, as the first symptom of hypoparathyroidism in children, do not require epilepsy drugs.

Treatment with Oral ATP decreases alternating hemiplegia of childhood with de novo ATP1A3 Mutation.

BACKGROUND: Alternating hemiplegia of childhood is an intractable neurological disorder characterized by recurrent episodes of alternating hemiplegia accompanied by other paroxysmal symptoms. Recent research has identified mutations in the ATP1A3 gene as the underlying cause. Adenosine-5'-triphosphate has a vasodilatory effect, can enhance muscle strength and physical performance, and was hypothesized to improve the symptoms of paroxysmal hemiplegia. METHODS: A 7-year-old boy with alternating hemiplegia of childhood who was positive for a de novo ATP1A3 mutation was treated with adenosine- 5'- triphosphate supplementation orally as an innovative therapy for 2 years. Outcome was evaluated through the follow-up of improvement of hemiplegic episodes and psychomotor development. Side effects and safety were monitored in regularity. RESULTS: With the dosage of adenosine-5'-triphosphate administration increased, the patient showed significantly less frequency and shorter duration of hemiplegic episodes. Treatment with adenosine-5'-triphosphate was correlated with a marked amelioration of alternating hemiplegia of childhood episodes, and psychomotor development has improved. The maximum dose of oral administration of adenosine-5'-triphosphate reached 25 mg/kg per day. Adenosine-5'-triphosphate therapy was well tolerated without complaint of discomfort and side effects. CONCLUSIONS: The 2-year follow-up outcome of adenosine-5'-triphosphate therapy for alternating hemiplegia of childhood was successful.

Levetiracetam: Probably Associated Diurnal Frequent Urination.

Diurnal frequent urination is a common condition in elementary school children who are especially at risk for associated somatic and behavioral problems. Levetiracetam (LEV) is a broad-spectrum antiepileptic drug that has been used in both partial and generalized seizures and less commonly adverse effects including psychiatric and behavioral problems. Diurnal frequent urination is not a well-known adverse effect of LEV. Here, we reported 2 pediatric cases with epilepsy that developed diurnal frequent urination after LEV administration. Case 1 was a 6-year-old male patient who presented urinary frequency and urgency in the daytime since the third day after LEV was given as adjunctive therapy. Symptoms increased accompanied by the raised dosage of LEV. Laboratory tests and auxiliary examinations did not found evidence of organic disease. Diurnal frequent urination due to LEV was suspected, and then the drug was discontinued. As expected, his frequency of urination returned to normal levels. Another 13-year-old female patient got similar clinical manifestations after oral LEV monotherapy and the symptoms became aggravated while in stress state. Since the most common causes of frequent micturition had been ruled out, the patient was considered to be diagnosed with LEV-associated psychogenic frequent urination. The dosage of LEV was reduced to one-third, and the frequency of urination was reduced by 60%. Both patients got the Naranjo score of 6, which indicated that LEV was a "probable" cause of diurnal frequent urination. Although a definite causal link between LEV and diurnal urinary frequency in the 2 cases remains to be established, we argue that diurnal frequent urination associated with LEV deserves clinician's attention.

Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development.

BACKGROUND: Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. METHODS: The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. RESULTS: The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P < 0.05). Age at onset of epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups. CONCLUSIONS: Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence.

Development of a mouse model of infantile spasms induced by N-methyl-D-aspartate.

Using N-methyl-D-aspartate (NMDA) injection, we attempt to develop a mouse model for infantile spasms (IS). Experiments were performed in postnatal 11- to 13-day-old C57 and Balbc mice. In the pilot experiment, mice were injected with different doses of NMDA (7, 15, and 30 mg/kg) to determine the optimal age and convulsant doses of NMDA. In further experiment optimal age mice were divided into five groups: group A, control group that received intraperitoneal injection of physiological saline; group B, convulsion group that was given intraperitoneal NMDA; group C, pretreatment group that received adrenocorticotropin (ACTH) injection (100 IU/kg) 30 min before NMDA administration; group D, electroencephalogram (EEG) group that received EEG recording, group E, performance group that received motor and learning test at different time point after NMDA administration. The behaviors of each group were observed continuously for 3h, the latency and the total numbers of spasms were recorded. Pilot experiments showed that a 15 mg/kg dose of NMDA could induce typical spasm-like seizures in P13 C57 mice, NMDA administration caused anxiety and deficits in motor and cognitive functions at early time and that large doses of ACTH reduced the number of seizures and rating scale (P<0.05). The NMDA mouse model has the following characteristics: age dependency, spasm-like seizures, cognitive impairment and response to ACTH, which fulfills the criteria of an IS model.

An 8-year old boy with continuous spikes and waves during slow sleep presenting with positive onconeuronal antibodies.

OBJECTIVE: To determine the etiology of epilepsy with continuous spikes and waves during slow sleep (CSWS)/electrical status epilepticus during sleep (ESES) in an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus. MATERIAL & METHODS: A combination of clinical characterization and follow-up, video EEG and laboratory investigations. RESULTS: We report the case of an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus, who presented with intellectual disability, pharmacotherapy-resistant epilepsy and CSWS/ESES. Although the patient's neuroblastoma had been successfully treated 8 years prior to presentation and an extensive workup did not show a tumor reoccurrence, testing for onconeuronal antibodies was positive for anti-Ma2 and anti-CV2/CRMP5 antibodies. High-dose intravenous methylprednisolone and a taper of oral methylprednisolone were given, leading to a significant clinical improvement. During the taper the patient's condition and EEG manifestations deteriorated again necessitating another cycle of steroid therapy, which lead to a stable improvement. During a 6-month follow-up no CSWS/ESES was seen on EEG and anti-Ma2 and anti-CV2/CRMP5 antibodies remained undetectable. CONCLUSION: This case suggests that onconeuronal antibodies may be involved in the pathogenesis of CSWS/ESES.

Febrile seizure recurrence reduced by intermittent oral levetiracetam.

OBJECTIVE: Febrile seizure (FS) is the most common form of childhood seizure disorders. FS is perhaps one of the most frequent causes of admittance to pediatric emergency wards worldwide. We aimed to identify a new, safe, and effective therapy for preventing FS recurrence. METHODS: A total of 115 children with a history of two or more episodes of FS were randomly assigned to levetiracetam (LEV) and control (LEV/control ratio = 2:1) groups. At the onset of fever, LEV group was orally administered with a dose of 15-30 mg/kg per day twice daily for 1 week. Thereafter, the dosage was gradually reduced until totally discontinued in the second week. The primary efficacy variable was seizure frequency associated with febrile events and FS recurrence rate (RR) during 48-week follow-up. The second outcome was the cost effectiveness of the two groups. RESULTS: The intention-to-treat analysis showed that 78 children in LEV group experienced 148 febrile episodes. Among these 78 children, 11 experienced 15 FS recurrences. In control group, 37 children experienced 64 febrile episodes; among these 37 children, 19 experienced 32 FS recurrences. A significant difference was observed between two groups in FS RR and FS recurrence/fever episode. The cost of LEV group for the prevention of FS recurrence is lower than control group. During 48-week follow-up period, one patient in LEV group exhibited severe drowsiness. No other side effects were observed in the same patient and in other children. INTERPRETATION: Intermittent oral LEV can effectively prevent FS recurrence and reduce wastage of medical resources.

Genetic and biochemical findings in Chinese children with Leigh syndrome.

This study investigated the genetic and enzymological features of Leigh syndrome due to respiratory chain complex deficiency in Chinese patients. The clinical features of 75 patients were recorded. Mitochondrial respiratory chain enzyme activities were determined via spectrophotometry. Mitochondrial gene sequence analysis was performed in 23 patients. Five core pedigrees were investigated via restriction fragment length polymorphism and gene sequencing. Psychomotor retardation (55%), motor regression (20%), weakness (29%), and epilepsy (25%) were the most frequent manifestations. Sixty-four patients (85.3%) had isolated respiratory complex deficiencies: complex I was seen in 28 patients (37.3%); complex II, seven (9.3%); complex III, six (8%); complex IV, ten (13.3%); and complex V, 13 patients (17.3%). Eleven patients (14.7%) had combined complex deficiencies. Mitochondrial DNA mutations were detected in 10 patients. Eight point mutations were found in mitochondrial structural genes: m.4833A>G in ND2, m.10191T>C in ND3, m.12338T>C and m.13513G>A in ND5, m.14502T>C and m.14487T>C in ND6, m.8108A>G in COXII, and m.8993T>G in ATPase6. Three mutations were found in tRNA genes: m.4395A>G in tRNA-Gln, m.10454T>C in tRNA-Arg, and m.5587T>C in tRNA-Ala. One patient and their mother both had the m.12338T>C and m.8993T>C mutations. In conclusion, mitochondrial respiratory chain complex I deficiency and structural gene mutations frequently occur in Chinese Leigh syndrome patients.

[Electron microscopic analysis of biofilm on tracheal tubes removed from intubated neonates and the relationship between bilofilm and lower respiratory infection].

OBJECTIVE: Mechanical ventilation support is a very important method for the salvage of serious patients. However, it can result in the formation of an adherent matrix of bacteria on the surfaces of implanted materials which is termed "biofilm". Biofilm is dense bacterial communities attached to a solid surface and surrounded by an exopolysaccharide matrix. One of the most important features of bacterial biofilm is their resistance to antimicrobial agents and host immune system components. As a consequence, diseases involving biofilm are generally chronic and difficult to treat. The present study was conducted to explore the relationship between ETT-biofilm and the lower respiratory infection by observing microbial colonization and associated biofilm accumulation on the surface of endotracheal tubes (ETTs) removed from neonates treated with intubated mechanical ventilation. METHODS: Twenty neonates undergoing mechanical ventilation (from January to June in 2005) were recruited into this study. Clinical data about lower respiratory infection for each case were collected. ETTs were collected at the first time of extubation. A sterile control tube was also processed. For each ETT, a 1-cm-long cross-sectional segment was divided into two portions for both scanning electron microscopy (SEM) and aerobic/anaerobic cultures. The presence of biofilm on the surface of ETTs were examined by SEM, meanwhile, bacteria harvested from the surface of ETTs and the secretions of lower respiratory tract were isolated, identified and assessed on antimicrobial susceptibility, respectively. RESULTS: The diagnosis on admission of the twenty cases included: neonatal respiratory distress syndrome (10), meconium aspirate syndrome (2), severe asphyxia (2), pneumatothorax (2), severe pneumonia (1), scleredema neonatorum (1), inborn pulmonary hypoplasia (1) and recurrent apnea (1). Thirteen cases did not present symptoms and signs of lower respiratory infection before mechanical ventilation. However, during the mechanical ventilation process, symptoms and signs of lower respiratory infection presented and lasted until extubation. Nine of the above mentioned thirteen cases (70%) had the same duration of tube use as mechanical ventilation duration (mean: 3.6 days). Observation by SEM showed that colonization was time dependent and the incidence of microbial colonization increased when the duration of tube use exceeded one days (12/20). There were no obvious bacterial colonies except that some amorphous material was noted in 5 of 20 ETTs as early as one day of tube use. Up to 2 days of tube use (4/20), attached bacterial colonization was seen embedded in amorphous material (3/4). Up to 3 days (7/20), a layer of biofilm formation presented on ETTs (5/7). Furthermore, biofilm architecture became more mature and complex if the duration exceeded 3 days. Neither bacteria nor biofilm formation was seen on the control ETT. The results of aerobic/anaerobic cultures showed that there were 14 cultures from ETTs (normal flora grew in 4) and 7 pathogens were isolated; 13 cultures from the secretions of lower respiratory tract (normal flora grew in 1) and 10 pathogens were isolated. Seven samples had the same pathogen both on the surface of ETTs and in the secretions of lower respiratory tract, which accounted for 50% of the positive cultures from ETTs, including Xanthomonas maltophilia (2), Klebsiella pneumoniae (2), Acinetobacter lwoffii (1), Acinetobacter baumannii (1) and normal flora (1). The gram-negative bacteria isolated from the surface of ETTs and the secretions of lower respiratory tract presented multi-resistance to antibiotics. CONCLUSIONS: The ETT-biofilm develops into mature and complex form with the duration of tube use increase. This study provides evidence that there is correlation between microbial colonization, biofilm formation on the surface of ETTs and the lower respiratory infection in neonates who were intubated and ventilated for a prolonged period. ETT-Biofilm could also be a possible source of the recurrent infection. Increased attention must be paid to modification of the ETT to prevent or substantially reduce biofilm formation.