Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. Autophagy is a process in which cytoplasmic components such as organelles and proteins are delivered to the lysosomal compartment for degradation, and plays an essential role in the maintenance of cellular homeostasis. The activity of autophagy is enhanced during oxidative stress. The objectives of this work were first to study the inhibitory action of antioxidant ascorbic acid on behavioral changes and brain damage induced by high doses of pilocarpine, then to study the effect of ascorbic acid on oxidative stress (MDA and SOD were used to estimate oxidative stress) and activated autophagy (beclin 1 was used to estimate autophagy) induced by seizures, aiming to further clarify the mechanism of action of this antioxidant compound. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (500 mg/kg, i.p.) on the behavior and brain lesions observed after seizures induced by pilocarpine (340 mg/kg, i.p., P340 model) in rats. Ascorbic acid injections prior to pilocarpine suppressed behavioral seizure episodes by increasing the latency to the first myoclonic, clonic and tonic seizure and decreasing the percentage of incidence of clonic and tonic seizures as well as the mortality rate. These findings suggested that oxidative stress can be produced and autophagy is increased during brain damage induced by seizures. In the P340 model, ascorbic acid significantly decreased cerebral damage, reduced oxidative stress and inhibited autophagy by reducing de novo synthesis of beclin 1. Antioxidant compound can exert neuroprotective effects associated with inhibition of free radical production and autophagy. These results highlighted the promising therapeutic potential of ascorbic acid in treatment for seizures.

Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.

The ketogenic diet was developed in the 1920s as a treatment for intractable childhood seizures when few antiepileptic drugs (AEDs) were available. There are still children whose seizures are refractory even to modern therapy, but use of the ketogenic diet appears to be waning. At Johns Hopkins, we continue to believe that the diet is very effective and well accepted by patients and families. To reevaluate our opinion of the efficacy and acceptability of this form of therapy in patients cared for in the 1980s with the newer AEDs, we analyzed the records of 58 consecutive patients who had been started on the diet. Before using the diet, 80% of the patients had multiple seizure types and 88% were treated with multiple AEDs; these children were among our most intractable patients. Despite this, seizure control improved in 67% of patients with the ketogenic diet, and actuarial analysis indicated that 75% of these improved patients continued the diet for at least 18 months. Sixty-four percent had AEDs reduced, 36% became more alert, and 23% had improved behavior. The improvement in these patients with intractable seizures and the length of time that families maintained the regimen indicate that the ketogenic diet continues to have a very useful therapeutic role in selected patients and their families.

Celiac disease (CD) is Gluten sensitive enteropathy with a wide spectrum of severity and protean clinical manifestations. Patients with atypical (non-diarrhoeal) presentations are missed as the diagnosis of Celiac Disease is not considered. We present three young girls (ages 18, 19, 23 at presentation) who were admitted to our hospital as intractable seizures. All had low serum calcium, features of rickets/osteomalacia and anaemia. This prompted us to consider malabsorption due to CD. The diagnosis of CD was confirmed by serologic tests (IgA transglutaminase and IgG antigliadin antibodies) and biopsy of the duodenum. In all patients gluten free diet not only provided drug free control of seizures but also helped correct other features of malabsorption like hypocalcaemia and anaemia as the primary pathology behind these symptoms was corrected. We wish to highlight that hypocalcaemia of CD which may present as intractable seizures can be treated only by treating CD with gluten free diet and not by oral vitamin D and Calcium alone.

BACKGROUND:Congenital hyperinsulinism (CHI) is the most frequent cause of hypoglycemia in children. In addition to increased peripheral glucose utilization, dysregulated insulin secretion induces profound hypoglycemia and neuroglycopenia by inhibiting glycogenolysis, gluconeogenesis and lipolysis. This results in the shortage of all cerebral energy substrates (glucose, lactate and ketones), and can lead to severe neurological sequelae. Patients with CHI unresponsive to medical treatment can be subjected to near-total pancreatectomy with increased risk of secondary diabetes. Ketogenic diet (KD), by reproducing a fasting-like condition in which body fuel mainly derives from beta-oxidation, is intended to provide alternative cerebral substrates such ketone bodies. We took advantage of known protective effect of KD on neuronal damage associated with GLUT1 deficiency, a disorder of impaired glucose transport across the blood-brain barrier, and administered KD in a patient with drug-unresponsive CHI, with the aim of providing to neurons an energy source alternative to glucose.

METHODS:A child with drug-resistant, long-standing CHI caused by a spontaneous GCK activating mutation (p.Val455Met) suffered from epilepsy and showed neurodevelopmental abnormalities. After attempting various therapeutic regimes without success, near-total pancreatectomy was suggested to parents, who asked for other options. Therefore, we proposed KD in combination with insulin-suppressing drugs.

RESULTS:We administered KD for 2 years. Soon after the first six months, the patient was free of epileptic crises, presented normalization of EEG, and showed a marked recover in psychological development and quality of life.

CONCLUSIONS:KD could represent an effective treatment to support brain function in selected cases of CHI.

We report the case of a child presenting with nonfebrile seizures 6 and 13 days after the first vaccination with a measles, mumps, rubella, and varicella (MMRV) combination vaccine. Measles virus RNA was detected in the patient's serum, throat, and urine. Genotyping revealed the Schwarz vaccine virus strain.

Abstract Since the introduction of the H1N1 influenza vaccine in the wake of the 2009 H1N1 influenza pandemic, many serious and nonserious adverse events related to the vaccine have been reported. We describe a 59-year-old African-American man with severe chronic heart failure and chronic obstructive pulmonary disease who experienced a new-onset, generalized tonic-clonic seizure less than 1 hour after receiving the H1N1 vaccine. He had never experienced any reactions to previous seasonal influenza vaccines. His medical history, physical examination, and targeted investigations revealed no evidence of other potential etiologies for his seizure. After this event, the patient, who was discharged without anticonvulsant therapy, remained seizure free for the next 10 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship (score of 4) between the patient's seizure and the receipt of the H1N1 vaccine. This is the first case report, to our knowledge, to suggest a possible association between the H1N1 influenza vaccine and seizure. The mechanism of the association is unclear. Further case series may clarify the nature of the association.

The aim of the present study was to evaluate serum selenium levels in children receiving olive oil-based ketogenic diet (KD) for intractable seizures for at least 1 year. Out of 320 patients who were initiated on KD, patients who continued receiving KD for at least 12 months were enrolled. Sixteen patients who had selenium deficiency at the time of starting KD were excluded. Finally, a total of 110 patients (mean age 7.3 ± 4.2 years) were included. Serumselenium levels were measured at baseline and at 3, 6, and 12 months after treatment initiation by using atomic absorption spectroscopy. Selenium deficiency was defined as a serum selenium level<48 μg/L at each visit. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. Mean duration of KD was 15.3 ± 4.3 months. Mean serum selenium levels were significantly lower at 6 and 12 months of KD treatment (66.2 ± 23.3 and 57.2 ± 16.2 μg/L, respectively) compared to pre-treatment levels (79.3 ± 25.7 μg/L) (p = 0.001). On the other hand, selenium levels did not show any significant difference at 3 months of KD treatment (70.0 ± 21.2 μg/L) compared to baseline levels (p = 0.076). A total of 54 patients (49.1%) were diagnosed with selenium deficiency, and oral selenium medication was initiated for these patients. No relevant clinical findings were detected, and echocardiographic findings were normal in all patients. The decline of the serum selenium concentrations after 6 and 12 months of ketogenic diet suggests that patients onthis highly prescriptive dietary treatment need close monitoring of this trace element.

Objectives The purpose of this study was to characterize patients who were diagnosed with glucose transporter protein 1 deficiency syndrome (Glut1D), and also to assess the efficacy of ketogenic diet (KD) therapy on seizure control, cognitive functions, and other neurological disorders. Patients and Methods We studied six unrelated patients with the classical phenotype of Glut1D, focusing on clinical and laboratory features, the KD therapy and outcome over the 25-month follow-up period. Results Five patients became seizure-free with the onset of ketosis, and anticonvulsants were discontinued. Other neurological features such as ataxia, spasticity, and dystonia showed a less striking improvement than seizure control. There was no significant change in the intelligence quotient (IQ) level or microcephaly. In all patients, alertness, concentration, motivation, and activity resulted in a moderate improvement of variable degree. The early-onset adverse effects of KD were observed in five patients. The KD regimen failed in one patient, therefore, his diet was changed with an alternative to KD. Conclusions Treatment with KD resulted in a marked improvement in seizures and cognitive functions but its effect appeared to be less striking on the other neurological disorders of the patients. When the classic KD is not tolerated, an alternative to KD may be helpful.

The Emotional Freedom Technique (EFT) is defined and described as a clinical procedure for the relief of psychological and physical distress that patients often bring to the attention of nurses. Frequently referred to as"tapping,"this technique combines the cognitive reprocessing benefits of exposure and acceptance therapy with the energetic disturbance releases associated with acupuncture and other energy therapies. More than 60 research articles in peer-reviewed journals report a staggering 98% efficacy rate with the use of this procedure from psychological distress (posttraumatic stress disorder, phobias, anxiety, depression, etc.) to physical conditions (asthma, fibromyalgia, pain, seizure disorders, etc.) to performance issues (athletic, academic). Perhaps because of this, this technique has encountered a fair degree of skepticism within the health care community. Easily taught as a self-help aid that patients can administer to themselves, EFT becomes an efficacious tool in the hands of nurses who are seeking whole person approaches for the healing of a wide variety of psychological and physical conditions. A conceptual framework, mechanisms of action, evidence of safety, literature review, and case studies are also included.

The brain aspartate-glutamate carrier (AGC1) is specifically expressed in neurons, where it transports aspartate from the mitochondria to the cytosol, and plays a role in transfer of nicotinamide adenine dinucleotide (NADH)-reducing equivalents into the mitochondria as a part of the malate-aspartate shuttle. Deficient function of AGC1 underlies an inborn error of metabolism that presents with severe hypotonia, arrested psychomotor development, and seizures from a few months of age. In AGC1 deficiency, there is secondary hypomyelination due to lack of N-acetylaspartate (NAA), which is normally generated by acetylation of aspartate in the neuron and required for fatty acid synthesis by the adjacent oligodendrocyte. Based on experiences from AGC2 deficiency, we predicted that reduced glycolysis should compensate for the metabolic defect and allow resumed myelination in AGC1 deficiency. Carbohydrate restriction was therefore initiated in a patient with AGC1 deficiency at 6 years of age by introducing a ketogenic diet. The response was dramatic, clinically as well as radiologically. Psychomotor development showed clear improvement, and magnetic resonance imaging (MRI) indicated resumed myelination. This is the first successful treatment of secondary hypomyelination reported. Because AGC1 is driven by the proton gradient generated by the neuronal mitochondrial respiratory chain, the results have potential relevance for secondary hypomyelination in general.

:Myoclonic status in non-progressive encephalopathy (MSNPE) is characterized by the recurrence of long-lasting atypical status epilepticus associated with attention impairment and continuous polymorphous jerks, mixed with other complex abnormal movements, in infants suffering from a non-progressive encephalopathy. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies.

PURPOSE:In this study we assess the efficacy and tolerability of the KD in patients with MSNPE.

METHODS:Between March 1, 1980 and August 31, 2013, 99 patients who met the diagnostic criteria of MSNPE were seen (58 patients in Verona and 41 patients in Buenos Aires). Six of these 99 patients were placed on the KD using the Hopkins protocol and followed for a minimum period of 24 months.

RESULTS:Twelve months after initiating the diet, three patients had a 75%-99% decrease in seizures, two had a 50%-74% decrease in seizures, and the remaining child had a less than 50% seizure reduction. In five patients with a seizure reduction of more than 50%, the myoclonic status epilepticus disappeared within 6 months after starting the diet. All patients had very good tolerability and no adverse events were identified. In most of the patients AEDs were reduced.

CONCLUSION:The KD is a promising therapy for MSNPE, with most of our patients showing a more than 50% seizure reduction. In patients that responded well to the diet cognitive performance and quality of life also improved.

OBJECTIVE:To document the long-term outcome of the 83 children with difficult-to-control seizures who were enrolled prospectively in a study of the efficacy of the ketogenic diet and who had remained on the diet for 1 year.

METHODS:A total of 150 consecutive children were entered prospectively into a study of the ketogenic diet's efficacy and tolerability. Three to 6 years after diet initiation, all 150 families were sent a survey inquiring about their child's current health status, seizure frequency, and current anticonvulsant medications. They were asked about their experience with the diet and reasons for discontinuation. Several telephone attempts were made to contact those who did not respond to the written questionnaire. Responses were entered in an Access database and analyzed.

RESULTS:In 1999, 3 to 6 years after initiating the diet, 107 of 150 families responded to a questionnaire. Thirty-five additional families were interviewed by telephone, 4 were lost to follow-up, and 4 children had died, unrelated to the diet. Of the original 150 patient cohort, 20 (13%) were seizure-free and an additional 21 (14%) had a 90% to 99% decrease in their seizures. Twenty-nine were free of medications, and 28 were on only 1 medication; 15 remained on the diet. There were no known cardiac complications.

CONCLUSION:Three to 6 years after initiation, the ketogenic diet had proven to be effective in the control of difficult-to-control seizures in children. The diet often allows decrease or discontinuation of medication. It is more effective than many of the newer anticonvulsants and is well-tolerated when it is effective.

OBJECTIVE:The purpose of this case report is to describe the chiropractic management using upper cervical techniques of a 25-year-old woman diagnosed with juvenile myoclonic epilepsy (JME).

CLINICAL FEATURES:A 25-year-old woman had a history of JME, which was diagnosed at the age of 14 years. Her seizure episodes began shortly after trauma to her cervical spine and the onset of menarche.

INTERVENTION AND OUTCOME:After case history and physical examination, the patient received high-velocity, low-amplitude chiropractic spinal manipulation to her upper cervical spine using the Blair upper cervical chiropractic technique protocol. There was improvement in her seizure episodes and menstrual cycles following 12 weeks of chiropractic care.

CONCLUSION:This case study demonstrated improvement in a young woman with a seizure disorder after she received upper cervical chiropractic manipulation. This case suggests the need for more rigorous research to examine how upper cervical chiropractic techniques may provide therapeutic benefit to patients with seizure disorders.