Efficacy analysis of oral dexamethasone in the treatment of infantile spasms and infantile spasms related Lennox-Gastaut syndrome.

OBJECTIVE: Treatment with adrenocorticotropic hormone (ACTH) or a corticosteroid is the first choice for infantile spasms (IS), and vigabatrin is the first choice for children with tuberous sclerosis. Although corticosteroids may be also effective against IS and IS-related Lennox-Gastaut syndrome (LGS), the use of dexamethasone (DEX), a kind of corticosteroid, for these diseases has been rarely reported. This retrospective study aimed to evaluate the efficacy and tolerability of DEX for the treatment of IS and IS-related LGS. METHODS: Patients diagnosed as having IS (including patients whose condition evolved to LGS after the failure of early treatment) in our hospital between May 2009 and June 2019 were treated with dexamethasone after failure of prednisone treatment. The oral dose of DEX was 0.15-0.3 mg/kg/d. Thereafter, the clinical efficacy, electroencephalogram (EEG) findings, and adverse effects were observed every 4-12 weeks depending on the individual patient's response. Then, the efficacy and safety of DEX in the treatment of IS and IS-related LGS were retrospectively evaluated. RESULTS: Among 51 patients (35 cases of IS; 16 cases of IS-related LGS), 35 cases (68.63%) were identified as responders to DEX treatment, comprising 20 cases (39.22%) and 15 cases (29.41%) with complete control and obvious control, respectively. To discuss the syndromes individually, complete control and obvious control were achieved in 14/35 and 9/35 IS cases and in 6/16 and 6/16 IS-related LGS cases, respectively. During DEX withdrawal, 11 of the 20 patients with complete control relapsed (9/14 IS; 2/6 LGS). The duration of dexamethasone treatment (including weaning) in most of the 35 responders was less than 1 year. However, 5 patients were treated with prolonged, low-dose maintenance therapy, which continued for more than 1.5 years. These 5 patients showed complete control, and 3 patients had no recurrence. Except for one child who died of recurrent asthma and epileptic status 3 months after stopping DEX, there were no serious or life-threatening adverse effects during DEX treatment. CONCLUSION: Oral DEX is effective and tolerable for IS and IS-related LGS. all LGS patients were evolved from IS in this study. The conclusion may not apply to patients with other etiology and courses of LGS. Even when prednisone or ACTH is failed, DEX may still be considered as a treatment option. For children who respond to DEX but do not show complete control after 6 months of treatment, prolonged treatment with low-dose DEX administered in the morning might be considered.

Current Status, Diagnosis, and Treatment Recommendation for Tic Disorders in China.

Tic disorders (TD) are a group neuropsychiatric disorders with childhood onset characterized by tics, i.e. repetitive, sudden, and involuntary movements or vocalizations; and Tourette syndrome (TS) is the most severe form of TD. Their clinical manifestations are diverse; and are often associated with various psychopathological and/or behavioral comorbidities, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and sleep disorders. Individual severity and response to treatment are highly variable, and there are some refractory cases, which are less responsive to conventional TD treatment. TD/TS are also common in the Chinese pediatric population. To help improve the understanding of TD for pediatricians and other health professionals, and to improve its diagnosis and treatment in China, the Chinese Child Neurology Society (CCNS) has developed an Expert Consensus on Diagnosis and Treatment of TD in China, which is based on our clinical experience and the availability therapeutic avenues. It is focused on clinical diagnosis and evaluation of TD and its comorbidities, psychological and educational intervention, nonpharmacological therapy, pharmacological treatment, including traditional Chinese medicine and acupuncture, as well as prognosis in children with TD in China. A summary of the current status of TD and up-to-date diagnosis and treatment recommendations for TD in China is presented here.

Asymmetric Slow-Spike-Wave Patterns with Maximal Discharges Contralateral to MRI Lesions Predict Better Surgical Prognosis in Symptomatic Lennox-Gastaut Syndrome or Lennox-Gastaut Phenotypes.

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe subtype of childhood-onset epileptic encephalopathy with drug-resistant and poor surgical prognosis. However, electroencephalogram (EEG) patterns of symptomatic LGS or LG phenotypes with structural brain lesions including focal abnormalities or asymmetric slow-spike-wave (SSW) patterns remain largely unknown. Due to the contradictory lateralization difference between MRI lesions and EEG pattern in symptomatic LGS or LG phenotypes, it is difficult to determine the precise lateralization of epileptic lesions, which is crucial to better surgical prognosis. This study is aim to ascertain the clinical characteristics of the EEG patterns, and its relationship with MRI lesions and to evaluate its prognostic value of surgical treatment in symptomatic LGS or LG phenotypes. METHODS: Twenty-four symptomatic LGS cases with asymmetric EEG SSW patterns and contralaterally independent or contralaterally dominant MRI lesions were collected, and their clinical features were analyzed retrospectively. RESULTS: In this cohort, most of lesions were perinatal or acquired during the first 6 months of life. The most common etiology was intracerebral hemorrhage. The LGS patients with both asymmetric SSW and focal sporadic epileptic waves (SEW) patterns showed the best surgical outcome with Engel class I level. Asymmetric SSW patterns with maximal discharges contralateral to MRI lesions were frequently observed in most of symptomatic LGS or LG phenotypes. Predominantly diffuse destructive lesions led to an attenuated voltage of ipsilateral scalp EEG producing an asymmetric SSW pattern in those patients with symptomatic LGS or LG phenotypes. CONCLUSIONS: Our study reveals a special SEW EEG pattern in symptomatic LG patients with asymmetric SSW and MRI lesions contralateral to the dominant EEG patterns. Contradictory lateralization difference between MRI and EEG probably arises from the relative voltage attenuation presenting in EEG ipsilateral to huge destructive lesions from early life. Our study suggests that the independent focal SEW activity remaining ipsilateral to the MRI lesion can potentially predict better surgical prognosis in symptomatic LGS or LG phenotypes.

A prospective study of dexamethasone therapy in refractory epileptic encephalopathy with continuous spike-and-wave during sleep.

PURPOSE: Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) is an intractable form of epilepsy that has no consensus protocol for corticosteroid therapy. This prospective study aimed to evaluate the efficacy and tolerability of dexamethasone for the treatment of CSWS. METHODS: Patients (age: 4 years to 12 years and 5 months) with CSWS that failed to respond to several antiepileptic drugs and prednisolone at our pediatric neurology outpatient clinic between 2007 and 2015 were treated with dexamethasone and prospectively analyzed. An initial 4-week dexamethasone (0.15 mg/kg/day p.o.) scheme was employed, and response was assessed. If effective, dexamethasone was maintained for 2-3 months and then slowly weaned over several months, depending on individual patient response at each follow-up. Systemic evaluations (clinical evaluations, electroencephalography recordings, and analysis of side effects) were performed regularly thereafter. RESULTS: Among 15 patients, 7 were defined as initial responders after 4-week dexamethasone treatment based on comprehensive clinical and electroencephalogram evaluations. The duration of dexamethasone treatment (including weaning) in these 7 patients was 6 to 10 months, and the follow-up duration was 6 months to 7 years. Three patients had no relapse after dexamethasone withdrawal at last follow-up. Among the other 4 patients, relapse was observed during dexamethasone withdrawal (n=1) or at 2-6 months after discontinuation of dexamethasone therapy (n=3). There were no serious or life-threatening side effects, and all observed side effects were reversible after discontinuation of dexamethasone. CONCLUSIONS: Continuous oral dexamethasone treatment is an effective and tolerable therapy and should be an option for the treatment of CSWS.

Levetiracetam efficacy in children with epilepsy with electrical status epilepticus in sleep.

PURPOSE: Epilepsy with electrical status epilepticus in sleep (ESES) is a devastating disease, and we sought to evaluate the efficacy of levetiracetam (LEV) for the treatment of patients with this epileptic encephalopathy in China. METHODS: Clinical data from all patients with ESES who received LEV therapy at our pediatric neurology outpatient clinic between 2007 and 2014 (n=71) were retrospectively analyzed. The LEV dosage was 30-50mg/kg/day. Electroencephalography recordings and neuropsychological evaluations were performed repeatedly for 3-75months after the start of LEV therapy. RESULTS: Thirty-five (70%) of 50 patients who had seizures at the start of LEV therapy had a >50% reduction in seizure frequency. Positive response on EEG was found during the first 3-4months of LEV therapy in 32 (45%) of 71 patients, with normalization of EEG in 5 patients. Relapse occurred in 8 (25%) of the initial electrical responders. Hence, 47 patients (66%) still suffered from ESES and only 13 patients regained their baseline level of function at the last follow-up. The response to LEV was significantly associated with ESES duration, age at onset of ESES, and etiology of epilepsy. Although fatigue and anorexia were the primary adverse events, LEV was well-tolerated by all patients. CONCLUSIONS: Levetiracetam is safe and may be efficient when used to treat ESES syndrome; however, the efficacy EEG neuropsychological outcomes is limited on the whole.

Efficacy of levetiracetam in electrical status epilepticus during sleep of children: a multicenter experience.

BACKGROUND: Electrical status epilepticus during sleep is characterized by epilepsy, a specific electroencephalographic pattern, and neuropsychological impairment. This study aims to evaluate the efficacy and safety of levetiracetam in treating children with electrical status epilepticus during sleep. METHODS: A multicenter, retrospective, open-label study enrolled 73 children (mean age: 8 years) affected by electrical status epilepticus during sleep. The efficacy was rated according to the seizure frequency and electroencephalography response. RESULTS: After a mean treatment period of 19 months (range: 6 to 24 months), 33 (63.5%) of 52 patients became seizure-free or had experienced remarkable reduction in seizures. The electrical status epilepticus of 41 (56.2%) of 73 patients disappeared off their electroencephalography. The electroencephalography efficacy of levetiracetam treatment was noted in the monotherapy (61.9%) and add-on (53.9%) groups. The clinical (67.7%) and electroencephalography (64.3%) response rates of the idiopathic group were better than those of the symptomatic group (57.1% and 45.2%, respectively). No patient discontinued the trial because of intolerability of side effects. CONCLUSIONS: Levetiracetam is effective in individuals with electrical status epilepticus during sleep with tolerable side effects.

Surgical treatment for epilepsy in 17 children with tuberous sclerosis-related West syndrome.

The efficacy of surgery for the treatment of epilepsy in patients with West syndrome secondary to tuberous sclerosis is unclear. The charts of 17 patients with tuberous sclerosis and secondary West syndrome who underwent a one-stage surgical resection with a combined palliative operative procedure were reviewed. Engel classification was used to classify the patients with regard to seizure status following surgery. After surgery, 11 patients were in Engel class I, 4 in class II, and 2 in class III. The EEG after surgery was normal in 8 patients, significantly improved in 8, and without significant improvement in 1 patient. Six patients had a recurrence of seizures after surgery, which included 3 patients with continuing spasms and 3 patients where the spasms had resolved but had developed either partial seizures or generalized tonic-clonic seizures. There were significant improvements in the Gesell Developmental Schedules for motor field (P=0.003), adaptive field (P=0.003), language field (P=0.033), and personal-social field (P=0.007). Thus, a one-stage surgical approach can be used to produce satisfactory outcomes in young children with tuberous sclerosis who have secondary West syndrome and seizures that do not respond to conventional antiepileptic therapy, even in when there are multiple epileptogenic foci.

Guillain-Barré syndrome in Chinese children: a retrospective analysis.

We reviewed the clinical and electrophysiologic features of 293 children with Guillain-Barré syndrome admitted to the Children's Hospital of Chongqing Medical University between 2000 and 2009. The male/female ratio was 2.02, and the syndrome occurred most frequently in those between 1 and 4 years of age. There was no seasonal variation. A total of 46.1% patients had experienced an infection 1 to 4 weeks before the onset of the syndrome. The main subtype was acute motor axonal neuropathy (50.0%), with acute inflammatory demyelinating polyradiculoneuropathy (38.1%) ranked as second in frequency. The mean motor disability score at nadir was 3.36 ± 1.00 for all patients, with mild variations among the different subgroups. No significant difference was found in age, seasonal occurrence, cerebrospinal fluid abnormality, and functional status at nadir between the acute motor axonal neuropathy and the acute inflammatory demyelinating polyradiculoneuropathy groups. A total of 36.5% patients had sensory symptoms at admission. Approximately 9.5% of patients required mechanical ventilation. Typical cytoalbuminologic dissociation at cerebrospinal fluid examination was demonstrated in 88.0% of those who underwent lumbar puncture.

[Experimental study on the damage of immature brain induced by chronic treatment with exogenous glucocorticosteroid].

OBJECTIVE: To explore the possibility of brain damage induced by exogenous glucocorticosteroid (GC) at therapeutic level during early life. METHOD: Totally 192 healthy Sprague-Dawley (SD) rats were selected and divided into three groups including PD7, PD15 and PD60 corresponding to three age-groups in human, i.e., the full-term newborn, one-year-old infant and adult, respectively. According to the therapeutic regime for infantile spasms, the dose of prednisone and ACTH was designed as 6 mg/(kg.d) and 150 U/(m(2).d) respectively. SD rats of different age-groups were treated with prednisone or ACTH and normal saline as the control for 4 days. The specimens were collected on Day 4 or 3 weeks after treatment. Body and brain weights were measured when the rats were sacrificed. Histological studies on the tissues of frontal lobe and hippocampus were performed by Nissl staining. Ultrastructural changes of brain were observed by the transmission electron microscopy. Expression of apoptosis-related proteins Bcl-2 and Bax in neurons was detected by immunohistochemistry. Neuronal apoptosis was detected by TUNEL. Mitochondria membrane potential of neurons in frontal lobe and hippocampus were detected by flow cytometry, and the Caspase-3 activity was detected by spectrophotometric assay. RESULT: (1) Significant reduction of brain weight [prednisone group of PD7: (0.78 +/- 0.08) g, control group: (0.89 +/- 0.08) g] and decrease of neurons numbers [(77.7 +/- 4.7) neurons per VF, control group: (102.3 +/- 5.9) neurons per VF] with cellular ultrastructural abnormalities in the frontal cortex were observed in infantile rats, including PD7 and PD15 groups. However none of the differences in brain weight and frontal cerebral cortex neurons were detected 3 weeks after drug discontinuation in PD7 group. (2) Compared with NS control, the numbers of TUNEL-positive cell (prednisone group of PD7: (114.8 +/- 8.1) cells per VF, control group: (56.3 +/- 5.6) cells per VF], Caspase-3 activity (345.3 +/- 13.0, control group: 166.3 +/- 6.4) and Bax protein expression (0.27 +/- 0.02, control group: 0.15 +/- 0.06) in neurons of the infant rats increased significantly but their potentials of mitochondrial membrane (112.9 +/- 8.6, control group: 140.5 +/- 5.6) were reduced remarkably, especially in PD7 group. CONCLUSION: (1) Long-term use of ACTH or prednisone could induce brain damage. The younger the rats were, the more liable they were to the damage and more severe the damages were, and the less possibly to recover completely from the damage. (2) The pathogenesis of the brain injury induced by GC is primarily due to up-regulated Bax protein expression resulted from the enhanced ratio of Bax to Bcl-2 and increased mitochondria membrane potential, followed by Caspase enzymes activation and irreversible excessive apoptosis.

[Activated factor of immature neurons for excessive apoptosis induced by exogenous glucocorticosteroid].

OBJECTIVE: To confirm the key inducing factor of excessive apoptosis in immature brain under the exposure of exogenous glucocorticosteroid and observe the characteristics of mitochondrial oxidative stress and intracellular [Ca(2+)]i overload as compared to healthy adult rats. METHODS: A total of 192 healthy Sprague-Dawley (SD) rats selected for the study were divided into three groups including PD7, PD15 and PD60 corresponding human age stages including full-term newborn, one-year infant and adult respectively. To mimic the therapeutic regime for infantile spasms, 8 rats in each group was treated with prednisone (6 mg x kg(-1) x d(-1)), ACTH (150 U x m(-2) x d(-1)), normal saline for 4 days and drug withdrawal for 3 weeks. Rats were deeply anesthetized and sacrificed by decapitation. The mitochondrial concentrations of GSH, SOD, MDA, Na(+)-K(+)-ATPase and intracellular [Ca2+i] were all determined by spectrophotometer. The cellular NMDA-R1 expression was measured by immunohistochemistry. RESULTS: Both prednisone and ACTH caused neuron reduced and TUNEL-positive cell increased in the frontal lobe, specially in PD7 group of prednisone, that were 77.7 +/- 4.7 neurons per VF (control group: 102.3 +/- 5.9) (P = 0.002), 114.8 +/- 8.14 (control group: 56.3 +/- 5.6) (P = 0.029) respectively. The mitochondrial levels of GSH, SOD and Na+-K+-ATPase decreased after prednisone and ACTH administration at different level in different age groups whereas the concentration of MDA increased. These changes were significant in PD7 group after prednisone administration, that were 158.3 +/- 6.1 mg/g prot of GSH (control group: 225.1 +/- 9.5 mg/g prot) (P = 0.006), 155.8 +/- 4.3 U/mg prot of SOD (control group: 228.1 +/- 9.2 U/mg prot) (P = 0.006), 14.6 +/- 3.5 U/mg prot of Na+-K+-ATPase (control group: 20.8 +/- 5.5 U/mg prot) and 10.4 +/- 0.9 nmol/mg prot of MDA (control group: 4.8 +/- 1.9 nmol/mg prot) (all P < 0.01). [Ca(2+)]i level in neuron increased, specially in PD7 group after prednisone administration, that was 164.6 +/- 11.9 nmol/L (control group: 125.8 +/- 6.03 nmol/L) (P = 0.003). Similar to [Ca(2+)]i changes, the density of NMDA-R1 also increased mostly in PD7 group after prednisone administration, that was 0.36 +/- 0.03 (control group: 0.21 +/- 0.05) while that was only 0.18 +/- 0.05 in PD60 group (control group: 0.15 +/- 0.02). At 3 weeks post-dosing, all of them returned to normal level. CONCLUSION: Dysfunctions of oxidation and antioxidation in mitochondria of immature neurocytes are induced by prednisone or ACTH within the therapeutic levels. Enhanced expressions of NMDA-R1, Bax and superoxide contribute to excessive apoptosis of immature neurocytes induced by exogenous glucocorticosteroid. The possible determining factors for immature brain is more vulnerable to exogenous glucocorticosteroid damage. It may be associated with the physiologically high intracellular level of calcium concentration and NMDA-R1 expression.

Efficacy and safety of levetiracetam as an add-on therapy in children aged less than 4 years with refractory epilepsy.

In the past decade, most studies on levetiracetam were conducted on patients aged > or = 4 years of age. The authors sought to assess the efficacy and safety of levetiracetam as an adjunctive treatment of children <4 years of age with refractory epilepsy. The mean levetiracetam dosage used on the 24 patients in this study was 38.85 mg/kg per day, and the mean duration of treatment was 40 weeks. During the study, levetiracetam was tapered off in 2 patients due to seizure worsening and was discontinued in other 2 patients due to unacceptable adverse effects. Levetiracetam therapy was effective in 58.3% of patients, with 20.8% achieving seizure freedom. Eight patients showed no obvious response and the remaining 2 patients showed divergent responses. Although adverse effects were seen in 37.5% of patients, all adverse effects were tolerable or resolved with time or discontinuation. Therefore, the authors conclude that levetiracetam treatment is effective and safe in young children with refractory epilepsy.

[Polyneuro-electrophysiological studies of myoclonus in children].

OBJECTIVE: To explore the clinical and neuroelectrophysiological characteristics of myoclonus of different origins in children. METHOD: Thirty-two children with myoclonic seizure were analyzed by video electroencephalogram-electromyogram (VEEG-EMG) polygraphic recordings, jerk-locked back averaging (JLA) and short latency somatosensory evoked potential (SSEP). They were classified into cortical myoclonus (CM), subcortical myoclonus (SCM), and unidentified group according to their generating locations, and also were classified into epileptic and non-epileptic myoclonus based on their different properties. RESULT: The 32 patients included 14 with CM, 14 with SCM and 4 with unidentified origin. (1) CM group: the myoclonic patients presented as focal and/or multifocal seizures in 11 cases and as generalized in another 3 patients besides focal myoclonus. Arrhythmic jerks were shown completely in 11 cases and rhythmic seizures were concomitant in another 3 patients. Myoclonus sensitivity to sensory stimulus was observed in 10 patients. The durations of EMG burst were 10-52 ms. Background EEGs were presented normal in 4 patients and slowing in 10 patients. The epileptiform discharges in interictal EEG were variable. The ictal EEG showed epileptic discharges with each clinical jerk in 9 cases but only with some jerks in 4 patients. Another one had no any EEG abnormality in each jerk. The myoclonus-related spikes were disclosed in 13 cases by JLA. Of the 10 cases who underwent SSEP, giant SSEPs were seen in 3 cases including the one with normal EEG and JLA analyses. (2) SCM group: myoclonus was presented as generalized in 8 cases and as focal in 6 cases. All the patients showed arrhythmic jerks and 14 cases were not sensitive to stimulus. The durations of EMG burst were from 60 ms to 400 ms. Normal background EEGs were presented in 6 patients and slowing in 8 patients. The interictal EEG showed no consistent abnormality. Epileptic discharges associated with myoclonus seizures were not found in any of 9 patients but were observed with some seizure changes in 5 cases. There was no myoclonus-related spike by JLA in this group. SSEPs were normal in all patients. (3) The group with unidentified origin: the durations of EMG were from 60 ms to 400 ms, and their EEG and SSEP recordings were normal. In addition, 32 patients could be classified as epileptic myoclonus in 14 cases and nonepileptic myoclonus in 18 cases by the polyneurophysiological tests. CONCLUSION: (1) It is not reliable to identify myoclonus seizures and their clinical properties depending on their interictal and ictal EEGs only. (2) Polyneuroelectrophysiological tests, including EEG-EMG, JLA, and SSEP, seem to be valuable and useful to identify the generating locations and properties for different myoclonus in children.

Long-term antiepileptic drug administration during early life inhibits hippocampal neurogenesis in the developing brain.

Certain antiepileptic drugs (AEDs) that are commonly used to treat seizures in children also affect cognition, and these effects can persist into adulthood, long after drug withdrawal. Widespread enhancement of apoptosis may be one mechanism underlying these lasting cognitive changes. Whether AEDs affect other processes in brain development during early postnatal life has not, however, been systematically analyzed. Here we determined whether chronic administration of common AEDs during early life alters cell proliferation and neurogenesis in the hippocampus. Postnatal day 7 (P7) rats received phenobarbital, clonazepam, carbamazepine, valproate, topiramate, or vehicle for 28 days. Bromodeoxyuridine was administered on P34 to label dividing cells. Cell proliferation was assessed 24 hr later, and cell survival and differentiation were assessed 28 days later. Phenobarbital and clonazepam significantly inhibited cell proliferation by 63% and 59%, respectively, and doublecortin immunoreactivity (indicator of neurogenesis) in the dorsal hippocampus was also significantly decreased by 26% and 24%, respectively. Survival of new cells steadily decreased in phenobarbital and clonazepam groups over 28 days. Reduced cell proliferation and survival resulted in fewer new neurons in the dentate gyrus, as confirmed by neuronal counting on P62. There were, however, no differences in cell distribution pattern or differentiation toward neuron and glial cells when phenobarbital and clonazepam groups were compared with controls. There were no changes in rats exposed to carbamazepine, valproate, or topiramate. Thus, inhibiting cell proliferation, survival, and neurogenesis in the developing hippocampus may be another potential mechanism underlying brain impairment associated with certain AED therapies in early life.

[Establishment of animal model of myoclonus originating from axis of cortex-thalamus].

OBJECTIVE: To develop a series of experimental animal models of myoclonus with different origins consistent with myoclonus seizure in clinic setting. METHODS: GABA(A) antagonist SR95531 was microinjected into the primary motor cortex (PMC), corpus striatum, nucleus reticular of the thalamus (NRT) to induce myoclonus (EMG burst of myoclonus

[Peripheral nerve damage and its pathogenesis induced by antiepileptic drugs in rats].

OBJECTIVE: To explore the possibility of peripheral nerve damage induced by antiepileptic drugs (AEDs) in different age rats and its pathogenesis. METHODS: Adult (2-month-old) and infant (7-day-old) rats were divided into 8 groups (n = 16 in each) and treated with the following 7 AEDs respectively: phenytoin [PHT, 62.5 mg/(kgxd)], phenobarbital [PB, 30.0 mg/(kgxd)], sodium valproate [VPA, 312.5 mg/(kgxd)], clonazepam [CZP, 1.25 mg /(kgxd)], carbamazepine [CBZ, 187.5 mg/(kgxd)], topiramate [TPM, 40 mg/(kgxd)], oxcarbazepine [OXC, 312.5 mg/(kgxd)], remaining one group was used as control. Four weeks later, 8 rats were sacrificed randomly from each group and serum, sciatic nerves and spinal cord samples were collected. The rest half rats were sacrificed 4 week after AEDs withdrawal. Histological observations were performed on the sciatic nerves samples, including teased fibers, semi-thin sections and electron microscopy. The activity of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in serum and sciatic nerves were detected respectively. Expression of apoptosis-related proteins Bcl-2 and Bax was detected by immunohistochemistry. Neurons apoptosis in the anterior horns of spinal cord were detected by TUNEL. RESULTS: (1) Except for TPM group, various incidence (7.2% - 20.2%) of teased fibers abnormalities were observed in all the other different age groups. PHT group showed the most serious changes followed by PB (adult) or VPA (infant), CBZ, CZP and OXC groups. The predominant abnormality of teased fibers was demyelination. (2) There was no significant difference in the incidence of pathologic changes in teased fibers between adult and infant groups. Four weeks after AEDs withdrawal, recovery of pathologic changes in teased fibers in infant groups was much better than adult. (3) Significantly increased expression of Bax protein and ratio of Bax/Bcl-2 was only found in infant rats treated with PB, CNP or VPA compared with control (P < 0.05), the results of TUNEL was in accordance with immunohistochemistry. (4) Compared with control, the activity of T-AOC and SOD decreased in both infant and adult rats treated with PHT, CZP, CBZ and OXC, and the reduction of SOD activity in serum and sciatic nerves samples was also found in PB groups. Serum activity of GSH-PX was decreased in both age groups treated with PHT, PB, VPA, CZP, CBZ and OXC. The reduction of GSH-PX activity in sciatic nerves samples was remarkably in both adult and infant rats treated with PHT, PB, CBZ, OXC as well as the infant rats treated with CZP. CONCLUSIONS: Six AEDs (PHT, PB, CBZ, VPA, CZP, OXC) showed the potential to cause peripheral nerves damage. Demyelination was the predominant pathologic change. Both adult and infant rats had the same susceptibility. Recovery of pathologic changes in teased fibers in both age groups was slow, but infant rats were prone to revive more quickly. There was no significant correlation between spinal cord neuron apoptosis and peripheral nerves damages in rats treated with AEDs. Breakdown of oxidation-antioxidation balance was closely related to development of peripheral nerves damages caused by most AEDs.

Evaluation of open-label topiramate as primary or adjunctive therapy in infantile spasms.

OBJECTIVE: A multicenter open-label clinical trial was conducted to evaluate the clinical usefulness of topiramate (TPM) as primary or adjunctive therapy for infantile spasms in the postmarketing period in China. METHODS: Thirty-four centers participated in the trial. Patients included in the study had 1 or more seizures per day before treatment. One hundred twenty (22.1%) very young patients with an age younger than 6 month and 64.2% of patients were younger than 1 year at start of treatment. All patients received a starting dose of 0.5 to 1 mg kg d TPM twice daily. The dosage was increased by 0.5 to 1 mg kg d every 5 to 7 days up to 3 to 5 mg kg d. The resulting range of the total TPM dosage was 25 to 200 mg d (3.57-20 mg kg d), with a median value of 73.9 mg d. Seizure outcomes were measured by intention-to-treat analysis. Patients were seen by a neurologist, and their data were evaluated at the day of inclusion and after 4, 8, 12, 16, and 20 weeks (from visit 1 to visit 5) of treatment. RESULTS: Five hundred forty-four patients entered the study. After 20 weeks of TPM treatment, 239 patients (43.9%) were seizure-free. A higher proportion of patients in the monotherapy group than in the add-on therapy group showed a seizure rate reduction. An increase in seizure frequency was observed in 8 patients (1.5%) during the 20-week treatment period. Nineteen patients were withdrawn before completing the study, and in 46 cases, some data of the structured data files and questionnaires were missing. No efficacy of TPM treatment was recorded in these cases. Adverse effects occurred in 211 patients (38.8%). Most frequent side effects were anorexia and somnolence. CONCLUSIONS: Topiramate proved to be an effective and safe monotherapy and add-on therapy in patients with infantile spasms younger than 1 year.

[Clinical and polyneuroelectrophysiological characteristics of infantile spasm].

OBJECTIVE: To explore the characteristics of various seizure types in infantile spasm (IS) and to recognize the clinical and electrophysiological differences among spasm, myoclonic and tonic seizures. METHODS: Totally 681 seizures of 8 infants with IS were analyzed, including 20 episodes of non-cortical myoclonus which were finally ruled out by video-electroencephalogram-electromyogram polygraphic recordings (VEEG-EMG) and off-line analysis of jerk-locked back averaging (JLA). As a control, the data of 58 myoclonic seizures collected from an infant with Aicardi syndrome within two months before his typical clinical presentations of IS were also analyzed. RESULTS: Three types of seizures were recorded from the 8 infants, including spasm, myoclonic and tonic seizures with the incidence of 94.4%, 4.5%, and 1.1%, respectively. Spasms were mostly presented as body muscle contraction axially, which often occurred in clusters and evolved in a crescendo-decrescendo manner; 85.7% of them lasted for 0.4 - 3.0 s and 14.3% for 3 - 7 s. In addition, there were 273 seizures which were identified as subtle spasms according to their ictal EEG with high voltage slow wave (HVS) and fast wave bursts in most. There was no constantly time-locked EEG correlating to spasms even when JLA was applied for analysis. Myoclonic seizures were shock-like muscle constraction lasting for less than 400 ms with or without visible epileptic discharges in its ictal EEG. However, there was a time-locked cortical discharge discerned by JLA in epileptic myoclonus. Tonic seizures were consisted of sustained muscle contractions involving limbs and trunk, lasting for more than 3 s. Its ictal EEGs were more likely low amplitude fast waves and medium amplitude theta activities. Some spasms, named as tonic spasm, could be distinguished from tonic seizure according to the seizure duration which was always less than 2 s in tonic spasms and their different EEG patterns. CONCLUSIONS: There were various seizure types in IS but spasm was the predominant one. With polyneuroelectrophysiological tests including EEG-EMG and JLA, it would be much helpful to precisely recognize the different common seizure types including spasm, tonic spasm, myoclonic and tonic seizure during infancy which is important for the diagnosis, classification and treatment of infantile epilepsy.