After the first description of infantile spasms (IS) in 1841, extensive clinical and laboratory investigations have been done to find the pathophysiology and the optimal treatments. The concept of the “infantile spasms” has been evolved to the “epileptic spasms”, which includes the spasms outside the infancy the pathophysiology of IS, however, is still unknown. There have been a few randomized trials that proved the efficacy of the anecdotally used drugs in IS including hormonal therapy and vigabatrin. Due to its relative low incidence (1/2000) and the variable etiologies, clinical studies have difficulties in making a clear conclusion. Thus, animal models were eagerly sought to find the pathophysiology based treatments with definite efficacy and several models are now available. In this paper, the current understandings of the epileptic spasms as well as the translational researches using the animal models of IS are reviewed. The latest evidences of therapeutics in IS are discussed shortly.
Incidence ; Infant ; Infant, Newborn ; Models, Animal ; Spasm* ; Spasms, Infantile ; Translational Medical Research ; Vigabatrin

Psychopharmacology has developed over approximately the past five decades. The remarkable proliferation of information in this area has made it difficult for clinicians to understand the characteristics of various psychotropic agents. Atypical antipsychotics including amisulpride, asenapine, aripiprazole, blonanserin, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and zotepine cause fewer extrapyramidal problems and have many clinical applications, but they can cause metabolic disturbances. Mood stabilizers and lamotrigine are widely used for bipolar disorder. Other novel anticonvulsants such as topiramate, oxcarbazepine, gabapentin, tiagabine, pregabalin, vigabatrin, levetiracetam, and riulzole have also been tested with diverging or inconclusive results. Antidepressants are commonly used in the clinical treatment of depression and anxiety disorder. However, the mechanism of action of medications used in the treatment of psychiatric disorders remains unclear. Understanding the mechanisms of action and clarifying the diagnosis may enhance the treatment outcome in psychiatry. In this review, we analyzed clinical pharmacology data for each drug within a class and discussed clinical strategies for administering currently available antipsychotics, mood stabilizer/anticonvulsants, and antidepressants widely used for various psychiatric indications.
Aripiprazole ; Amines ; Anticonvulsants ; Antidepressive Agents ; Antipsychotic Agents ; Anxiety Disorders ; Benzodiazepines ; Bipolar Disorder ; Carbamazepine ; Clozapine ; Cyclohexanecarboxylic Acids ; Depression ; Dibenzothiazepines ; Dibenzothiepins ; Fructose ; gamma-Aminobutyric Acid ; Heterocyclic Compounds with 4 or More Rings ; Lurasidone Hydrochloride ; Isoindoles ; Isoxazoles ; Nipecotic Acids ; Quetiapine Fumarate ; Pharmacology, Clinical ; Pregabalin ; Piperazines ; Piperidines ; Piracetam ; Psychopharmacology ; Pyrimidines ; Quinolones ; Risperidone ; Sulpiride ; Thiazoles ; Treatment Outcome ; Triazines ; Vigabatrin

PURPOSE: The aim of this study is to investigate the incidence, clinical features and outcome in pediatric tuberous sclerosis complex(TSC) patients with epilepsy. METHODS: Fifty seven of 74 patients (77.0%) were included in the study, who were diagnosed with epilepsy associated with TSC from 1991 to 2008. Clinical data were obtained from medical records retrospectively. RESULTS: Of the 57 patients, initial seizure types were infantile spasms (n=25, 43.8%), complex partial seizure (n=24, 42.1%), generalized tonic seizure (n=5, 8.7%), simple partial seizure (n=2, 3.4%), and atonic seizure (n=1, 1.7%), respectively. Seventeen patients (29.8%) had changes of their seizure types during the clinical course. Excluding the five patients with insufficient data, 52 patients were treated with antiepileptic drugs and four of them underwent epilepsy surgery. Twenty-six of 52 patients (50.0%) with medical treatment and two patients (50.0%) with epilepsy surgery became seizure free. Among the patients with infantile spasms, vigabatrin induced seizure freedom in 13 of 14 patients (92.8%) within four weeks, and five of them maintained seizure remission with vigabatrin monotherapy. CONCLUSIONS: Half of epileptic patients showed good responses to medical treatment, especially vigabatrin for infantile spasms. Epilepsy surgery can be treatment option for selected patients.
Anticonvulsants ; Child ; Epilepsy ; Freedom ; Humans ; Incidence ; Infant ; Infant, Newborn ; Medical Records ; Retrospective Studies ; Seizures ; Spasms, Infantile ; Tuberous Sclerosis ; Vigabatrin

OBJECTIVETo investigate the protective effects of vigabatrin and atropine against the acute toxicity of dimethoate in male Kun-min mice.

METHODSThe therapeutic schedules of vigabatrin (50 or 100 mg/kg) and (or) atropine (2.5 or 5.0 mg/kg) were performed according to the L(9) (3(4)) orthogonal test table. The survival time, the righting reflex and the onset of muscle fasciculations were observed after the administration of dimethoate.

RESULTSFirst, the main effects of vigabatrin, atropine and the interaction between them were statistically significant in the Univariate analysis of the survival time at the alpha level of 0.05 (F(V)= 4.73, P(V)= 0.015, F(A)= 50.88, P(A)= 0.000, F(VxA)= 4.17, P(VxA)= 0.007). The range of atropine was more than double of that of vigabatrin or their interaction (R(A)> 2RV or 2R(VxA)). So not only atropine and vigabatrin but also their combination interaction protected mice against dimethoate lethality. The atropine played the major role in diminishing the lethality induced by dimethoate. Second, only vigabatrin, while not atropine, delayed the mice from dimethoate-induced muscle fasciculation according its statistical results (F(V)= 6.87, P(V)= 0.003, F(A)= 0.03, P(A)= 0.968, F(VxA)= 1.134, P(VxA)= 0.356). It should be noted that vigabatrin could not completely prevent dimethoate induced-muscle fasciculation in the test. At last, both atropine and vigabatrin could maintain the righting reflex in the intoxication, however there was no interaction between them (F(V)= 5.81, P(V)= 0.006, F(A)= 9.05, P(A)= 0.001, F(VxA)= 1.34, P(VxA)= 0.257).

CONCLUSIONCombined treatment with atropine and vigabatrin in the organophosphates intoxication seems reasonable and acceptable.

Acute Disease ; Animals ; Atropine ; therapeutic use ; Dimethoate ; poisoning ; Disease Models, Animal ; Insecticides ; poisoning ; Male ; Mice ; Vigabatrin ; therapeutic use

Menkes disease, so called kinky-hair syndrome, is a rare, genetic and progressive neurodegenerative disorder. It is caused by a mutation in the ATP7A gene, which codes for the copper transporting ATPase in the cell organelles. The dysfunction of many copper-dependent enzymes results in low concentration of copper in some tissues and accumulation of copper in others. We report a boy presented with kinky hairs, developmental delay, hypotonia and connective tissue abnormalities at the age of 4 months. Despite the treatment with various antiepileptic drugs, atonic seizures still persisted. At the age of 7 months, his atonic seizures was changed into extensor spasms with modified hypsarrhythmia for some years. The seizure were controlled by topiramate and vigabatrin. At the age of 22 months, serum copper and ceruloplasmin rechecked as 17 ug/dL(80-150 ug/dL) and 7.3 mg/dL(20-46 mg/ dL) respectively. The gene study showed ATP7A mutation and the patient was diagnosed as Menkes disease so that copper-histidine was daily injected. We experienced a case of a 4-month-old boy with Menkes disease and infantile spasm, confirmed by ATP7A mutation.
Adenosine Triphosphatases ; Anticonvulsants ; Ceruloplasmin ; Connective Tissue ; Copper ; Hair ; Humans ; Infant ; Infant, Newborn ; Male ; Menkes Kinky Hair Syndrome* ; Muscle Hypotonia ; Neurodegenerative Diseases ; Organelles ; Seizures ; Spasm ; Spasms, Infantile* ; Vigabatrin

PURPOSE: To investigate perimetric changes in pediatric and adolescent patients treated with vigabatrin and to assess the relationship between the visual field defect and the cumulative dose, the duration of treatment, or the age when vigabatrin was first taken. METHODS: Pediatric and adolescent patients treated with vigabatrin for seizure for at least 6 months were examined with Goldmann perimetry. The cumulative dose, the duration of treatment, the age when vigabatrin was first taken, and whether a combination of anticonvulsants and vigabatrin was taken were recorded. Mean radial degree (MRD) determination from the right eye was used to compare the amount of constriction. RESULTS: Visual field constriction developed in 19 (27.1%) out of 70 patients and MRD decreased by 22.7% a mean duration of 86.7+/-27.4 months of treatment. The visual field significantly decreased in the superior, nasal, and inferior field with temporal and central sparing (p<0.001). There was a statistically significant correlation between the average MRD and the cumulative dose (r2=0.1772, p<0.001), and the duration of treatment (r2=0.1713, p<0.001), but no correlation between the average MRD and either the age when vigabatrin was first taken, or the combination of anticonvulsants with vigabatrin. CONCLUSIONS: Visual field constriction developed in one quarter of pediatric and adolescent patients treated with vigabatrin, which significantly correlated with the cumulative dose and the duration of treatment. Therefore, a regular examination of the visual field is warranted for pediatric and adolescent patients treated with vigabatrin.
Adolescent* ; Anticonvulsants ; Constriction ; Humans ; Seizures ; Vigabatrin* ; Visual Field Tests ; Visual Fields*

We studied the prevalence, type and severity of vigabatrin (VGB)-attributed visual field defects (VFDs), and used these data to assess the associated risk factors in pediatric patients. Medical records were retrospectively reviewed for 67 pediatric patients who received VGB alone or in combination with other antiepileptic drugs, and who had undergone visual field examinations using a Humphrey visual field analyzer. Of the 67 patients, 15 had VGB-attributed VFDs: 13 had nasal arcuate type, 1 had nasal and temporal constricted type and 1 had nasal constricted type. In terms of severity, 7 patients had Grade I VGB-attributed VFDs, 5 had Grade II, 2 had Grade III, and 1 had Grade IV. Although there were no significant differences between the VFD and non-VFD groups with regards to all tested parameters, there were no cases of VGB-attributed VFDs in patients with total treatment durations <2 yr and cumulative doses <10 g/kg. In conclusion, the prevalence of VGB-attributed VFDs in VGB-treated pediatric epilepsy patients was 22%. The high frequency of VGB-attributed VFDs indicates that physicians should inform all patients of this risk prior to VGB treatment and perform periodic visual field examinations.
Visual Fields/drug effects ; Vision Disorders/*chemically induced ; Vigabatrin/adverse effects/*therapeutic use ; Time Factors ; Risk Factors ; Retrospective Studies ; Male ; Humans ; Female ; Epilepsy/*drug therapy ; Drug Therapy, Combination ; Drug Monitoring/statistics & numerical data ; Child ; Anticonvulsants/adverse effects/*therapeutic use ; Adult

People with epilepsy are at increased risk of cognitive impairment as a result of multiple factors:the underlying etiology of epilepsy, the effects of seizures themselves, and the central nervous system effects of antiepileptic drugs (AEDs). Cognitive effects of AEDs are of special concern because AEDs are the major therapeutic modality for seizures. All commonly used AEDs have some effect on cognitive function. The risk of AEDs cognitive adverse effects is increased with polypharmacy and at higher dosages and higher AED blood levels. Also children and the elderly are especially vulnerable to adverse effects on cognition. The most common AED cognitive effects include psychomotor slowing, reduced vigilance, and impairments in memory. This review focuses on studies of the cognitive effects of the new AEDs, and in particular on studies that compare cognitive effects of the old and new drugs. The available evidence is insufficient to support definite conclusions about the cognitive effects of the new AEDs. Neuropsychological testing has been the major method of objectively examining cognitive function related to the use of AEDs but a number of methodological problems blur the results. However, some of the new AEDs appear to produce fewer adverse cognitive effects than the old AEDs. Lamotrigine, for which a relatively large number of studies are available, has demonstrated a favorable cognitive profile overall, both in volunteers and in patients with epilepsy. Oxcarbazepine appears not to affect cognitive function in healthy volunteers or adults with newly diagnosed epilepsy. Gabapentin, tiagabine, and vigabatrin also have shown few cognitive effects compared with placebo. Although dose and titration speed may be confounding factors in some of the studies of topiramate, there is clear evidence that this agent does affect cognitive function, with specific effects on attention and verbal function. Additional studies are needed to delineate fully the relative effects of all the new AEDs to each other and to the older AEDs.
Adult ; Aged ; Anticonvulsants* ; Central Nervous System ; Child ; Cognition ; Epilepsy ; Healthy Volunteers ; Humans ; Memory ; Neuropsychological Tests ; Polypharmacy ; Seizures ; Vigabatrin ; Volunteers

PURPOSE: Recently, several reports have documented persistent visual field changes associated with long-term use of Vigabatrin, an antiepileptic drug. Epilepsy is a common disease in children, therefore we investigated perimetric changes in children who were on Vigabatrin treatment. METHODS: Total 36 eyes of 18 patients who had been treated with Vigabatrin were tested with Humphrey Field Analyzer. The visual fields were assessed using central 30-2 threshold test and peripheral 60-4 threshold test. RESULTS: In central 30-2 threshold tests, 13 eyes(40.6%) showed mild visual field constrictions and 4 eyes(12.5%) showed severe visual field constrictions. In peripheral 60-4 threshold tests, 23 eyes(71.8%) showed visual field changes. CONCLUSIONS: Asymptomatic visual field loss may develop in Vigabatrin-treated children. Regular examinations of the visual field is warranted for Vigabatrin-teated children.
Child* ; Constriction ; Epilepsy ; Humans ; Vigabatrin* ; Visual Fields*

PURPOSE: The authors carried out this study to determine the relationship between vigabatrin (VGB) and visual field defect. METHODS: Seventy eight patients older than 8 years who had epilepsy which had developed and been diagnosed, and were receiving add-on therapy, were the subjects of this study. If suspicious results were obtained from the initial test with the Humphrey automatic perimeter, the patient was tested again with the Goldman perimeter. Follow-up examinations were performed on these patients after 6 months. RESULTS: In this study, five of the 78 patients had suspicious primary test results, but upon the second examination they were all found to be normal. Thus there were no patients with visual field defects. CONCLUSIONS: VGB is a drug which may cause visual field defects, but in this study no patients presented with this symptom. Instead of limiting the use of VGB due to the adverse effect of visual field defect in the initial treatment of partial seizure and infantile spasm untreatable with other medication, if used with care it may not cause serious problems. Screening for visual defect is recommended, and in patients taking VGB regular examination is necessary.
Child* ; Epilepsy ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Mass Screening ; Seizures ; Spasms, Infantile ; Vigabatrin* ; Visual Fields*