Ketogenic diet effects on 52 children with pharmacoresistant epileptic encephalopathy: A clinical prospective study.

Objective: To evaluate the clinical impact of ketogenic diet (KD) on children with pharmacoresistant epileptic encephalopathy. Methods: In all, 52 children with pharmacoresistant epileptic encephalopathy that diagnosed in our hospital from July 2012 to June 2015 were selected, including West syndrome 38 cases, Lennox-Gastaut Syndrome 7 cases, Doose Syndrome 1 case, and Dravet syndrome 6 cases, and the effect, compliance, adverse reactions, electroencephalogram (EEG), and cognitive function were analyzed. Modified Johns Hopkins protocol was used to initiate KD, and Engel scale was used to evaluate the effect, and evaluated the effect of KD on the cognition, language, and motor function. Results: At 12 weeks of KD treatment, the patients achieved I, II, III, and IV grade effect were accounted for 26.9% (14/52 cases), 17.3% (9/52 cases), 11.5% (6/52 cases), and 44.2% (23/52 cases), respectively, according to Engel scale. KD has different effect on different epileptic syndromes, best effect on Doose syndromes of 100%, and better effect on West syndrome with the effect rate of 57.9%, and the total effect number was 22 cases. The reduction of epileptiform discharges in the awake state before KD treatment was correlated with the seizure time after 3 months of KD treatment (r = .330, p = .017). The cognitive function of 23 patients was improved, 12 patients had language improvement, and the motor function was improved in 10 patients. In all, 23 patients had adverse reactions, and all patients were tolerated and improved. Conclusion: KD has certain effect on children with pharmacoresistant epileptic encephalopathy, and it can reduce interictal epileptic discharge frequency, and improve the background rhythm of EEG. The reduction of epileptiform discharges in awake state is in favor of the reduction of seizures frequency, thus increasing the efficacy, and improve the cognitive function, language, and motor function to varying degrees, combined with less adverse reaction, which is worthy of clinical application.

Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia's encephalopathy.

Celia's encephalopathy (progressive encephalopathy with/without lipodystrophy, PELD) is a recessive neurodegenerative disease that is fatal in childhood. It is caused by a c.985C>T variant in the BSCL2/seipin gene that results in an aberrant seipin protein. We evaluated neurological development before and during treatment with human recombinant leptin (metreleptin) plus a dietary intervention rich in polyunsaturated fatty acids (PUFA) in the only living patient. A 7 years and 10 months old girl affected by PELD was treated at age 3 years with metreleptin, adding at age 6 omega-3 fatty acid supplementation. Her mental age was evaluated using the Battelle Developmental Inventory Screening Test (BDI), and brain PET/MRI was performed before treatment and at age 5, 6.5, and 7.5 years. At age 7.5 years, the girl remains alive and leads a normal life for her mental age of 30 months, which increased by 4 months over the last 18 months according to BDI. PET images showed improved glucose uptake in the thalami, cerebellum, and brainstem. This patient showed a clear slowdown in neurological regression during leptin replacement plus a high PUFA diet. The aberrant BSCL2 transcript was overexpressed in SH-SY5Y cells and was treated with docosahexaenoic acid (200 µM) plus leptin (0.001 mg/ml) for 24 h. The relative expression of aberrant BSCL2 transcript was measured by qPCR. In vitro studies showed significant reduction (32%) in aberrant transcript expression. This therapeutic approach should be further studied in this devastating disease.

Hyperammonaemic encephalopathy following an uncomplicated surgery.

A 59-year-old woman who underwent an uncomplicated exploratory laparotomy, adhesiolysis, small bowel resection and anterolateral thigh flap had a complicated postoperative period characterised by wound dehiscence and poor nutritional intake. 29 days postoperatively, a tremor developed in her upper limbs associated with weakness. Her Glasgow Coma Scale (GCS) fell to 4 and she was transferred to the intensive care unit. The patient was reviewed by multiple specialists and multiple differentials were considered and eliminated. Eventually, investigations revealed hyperammonaemic encephalopathy, being a result of low arginine and potentially small intestinal bacterial overgrowth. Following treatment with sodium benzoate, sodium phenylbutyrate and arginine along with haemodialysis and rifaximin, GCS and hyperammonaemia rapidly improved. She was stepped down to surgical high-dependency unit, continued arginine therapy with total parenteral nutrition and percutaneous endoscopic gastrostomy feeds. She was discharged with regular follow-up from surgeons and biochemistry and continues oral arginine therapy.

Encefalopatía hiperamoniémica tras cistectomía radical y derivación urinaria. Tratamiento nutricional / Hyperammonemic encephalopathy after urinary diversion. Diet therapy

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Modulation of Gut Microbiota-Brain Axis by Probiotics, Prebiotics, and Diet.

There exists a bidirectional communication system between the gastrointestinal tract and the brain. Increasing evidence shows that gut microbiota can play a critical role in this communication; thus, the concept of a gut microbiota and brain axis is emerging. Here, we review recent findings in the relationship between intestinal microbes and brain function, such as anxiety, depression, stress, autism, learning, and memory. We highlight the advances in modulating brain development and behavior by probiotics, prebiotics, and diet through the gut microbiota-brain axis. A variety of mechanisms including immune, neural, and metabolic pathways may be involved in modulation of the gut microbiota-brain axis. We also discuss some future challenges. A deeper understanding of the relationship between the gut bacteria and their hosts is implicated in developing microbial-based therapeutic strategies for brain disorders.

Enfermedades neurodegenerativas; aspectos nutricionales / Neurodegenerative diseases; nutritional aspects

Introducción: las enfermedades neurodegenerativas producen alteraciones en el nivel de conciencia o en los mecanismos de la deglución que con frecuencia hacen necesario un soporte nutricional especializado. Objetivo: revisar el riesgo de desnutrición, así como su tratamiento, en pacientes con enfermedad cerebral vascular, enfermedad de Parkinson, demencia y esclerosis lateral amiotrófica. Desarrollo: las enfermedades neurológicas degenerativas son una de las principales indicaciones de soporte nutricional en nuestro país. En los procesos agudos (enfermedad vascular cerebral), el correcto manejo nutricional se relaciona con una mejor evolución y con una disminución de las complicaciones. En los procesos neurodegenerativos crónicos (esclerosis lateral amiatrófica y demencia), la malnutrición es un problema importante que empeora el pronóstico de estos pacientes siendo, necesario un correcto manejo de la disfagia y sus complicaciones, así como la utilización de diferentes etapas de soporte nutricional. Una correcta valoración nutricional de estos pacientes, así como un claro esquema de intervención nutricional, es imprescindible en el seguimiento de su enfermedad. Por último, en la enfermedad de Parkinson avanzada, el soporte nutricional, como en las enfermedades neurodegenerativas anteriores, es de vital importancia, sin olvidarnos de la carga proteica y su distribución en la dieta de estos pacientes. Las sociedades científicas internacionales (American Society for Parenteral and Enteral Nutrition ASPEN) recomiendan, con un grado de evidencia B, realizar un cribaje de malnutrición a los pacientes con enfermedades neurológicas. Conclusiones: una correcta valoración nutricional, así como un adecuado soporte nutricional deben formar parte del proceso diagnóstico y terapéutico de estas enfermedades (AU)

Introduction: neurodegenerative diseases cause changes in the level of consciousness or swallowing mechanisms that often necessitate a specialized nutritional support. Objective: review the risk of malnutrition and its treatment in patients with cerebral vascular disease, Parkinson’s disease, dementia and amyotrophic lateral sclerosis. Development: degenerative neurological diseases are one of the main indications for nutritional support in our country. In acute processes (cerebral vascular disease), proper nutritional management is related to better outcomes and reduced complications. In chronic neurodegenerative processes (amyotrophic lateral sclerosis and dementia), malnutrition is a major problem that worsens the prognosis of these patients, the proper management of dysphagia and its complications, as well as the use of different stages of support being necessary nutritional. A correct nutritional evaluation of these patients and a right nutrition intervention is essential in monitoring their disease. Finally, in advanced Parkinson’s disease, nutritional support, as in previous neurodegenerative diseases, is of huge importance. Protein dietary load and its distribution in the diet of these patients are important, too. Finally, American Society for Parenteral and Enteral Nutrition ASPEN recommend, with a degree of evidence B, performing a screening of malnutrition in patients with neurological diseases. Conclusions: a correct nutritional evaluation and adequate nutritional support should be part of diagnostic and therapeutic process of these diseases (AU)

Role of walnuts in maintaining brain health with age.

Because of the combination of population growth and population aging, increases in the incidence of chronic neurodegenerative disorders have become a societal concern, both in terms of decreased quality of life and increased financial burden. Clinical manifestation of many of these disorders takes years, with the initiation of mild cognitive symptoms leading to behavioral problems, dementia and loss of motor functions, the need for assisted living, and eventual death. Lifestyle factors greatly affect the progression of cognitive decline, with high-risk behaviors including unhealthy diet, lack of exercise, smoking, and exposure to environmental toxins leading to enhanced oxidative stress and inflammation. Although there exists an urgent need to develop effective treatments for age-related cognitive decline and neurodegenerative disease, prevention strategies have been underdeveloped. Primary prevention in many of these neurodegenerative diseases could be achieved earlier in life by consuming a healthy diet, rich in antioxidant and anti-inflammatory phytochemicals, which offers one of the most effective and least expensive ways to address the crisis. English walnuts (Juglans regia L.) are rich in numerous phytochemicals, including high amounts of polyunsaturated fatty acids, and offer potential benefits to brain health. Polyphenolic compounds found in walnuts not only reduce the oxidant and inflammatory load on brain cells but also improve interneuronal signaling, increase neurogenesis, and enhance sequestration of insoluble toxic protein aggregates. Evidence for the beneficial effects of consuming a walnut-rich diet is reviewed in this article.

Diagnostic tools of early brain disturbances in an asymptomatic neonate with maple syrup urine disease.

Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder resulting from the defective activity of branched-chain 2-ketoacid dehydrogenase complex. Routine screening of newborn with tandem mass spectroscopy on the third day of life may detect elevated branched-chain amino acids in blood before the appearance of encephalopathic symptoms in MSUD cases. If undiagnosed by such a routine screening test, patients often present with encephalopathy and seizures. Clinical neurologic examination is supplemented by electroencephalography and imaging. Here, we report abnormal amplitude-integrated electroencephalography, electroencephalography, magnetic resonance imaging, and magnetic resonance imaging spectroscopy findings in a neurologically asymptomatic male newborn who was diagnosed with MSUD at the third week of life. These neurologic disturbances disappeared at the fourth month of life with appropriate special diet. Therefore, even in already asymptomatic cases, early neurologic deterioration of brain metabolism and structure can be detected with these early laboratory findings, indicating the importance of early diagnosis and management. Patients may also benefit from these investigations during the follow-up period.

Adult-onset cerebral folate deficiency.

OBJECTIVE: To report new manifestations of cerebral folate deficiency, a rare metabolic autoimmune syndrome,in an adult. DESIGN: Case report. SETTING: University teaching hospital. PATIENT: A 58-year-old woman with progressive memory loss and myoclonus presented for medical attention. Results of cerebral spinal fluid analysis showed low levels of tetrahydrobiopterin and 5-methyltetrahydrofolate. The patient's serum folate level was normal. Serum contained folate receptor 1 blocking and binding antibodies. RESULTS: The patient was treated successfully with folinic acid supplementation, and after 6 months of treatment,clinical symptoms had resolved. CONCLUSIONS: To our knowledge, we report the first case of adult-onset cerebral folate deficiency. Furthermore, this condition could represent a treatable form of early-onset dementia.

[Glucose transporter protein type 1 (GLUT-1) deficiency syndrome]. / Glukosetransportprotein type 1-mangel.

BACKGROUND: Glucose is the brain's main source of energy. To pass the blood-brain barrier, glucose transporter protein type 1 (GLUT-1) is essential. Mutations in the SLC2A1 gene which codes for GLUT-1 may therefore compromise the supply of glucose to the brain. The aim of this review is to describe the clinical consequences of such mutations, with special emphasis on GLUT-1 encephalopathy. MATERIAL AND METHODS: This review is based on a non-systematic literature search in PubMed and the authors' experience within the field. RESULTS: Epileptic or epilepsy-like are usually the first symptom in children with the GLUT-1 deficiency syndrome. Later on these children suffer delayed psychomotor development, microcephaly, ataxia, spasticity or movement disorders. EEG abnormalities may develop. GLUT-1 deficiency syndrome should be suspected in children with epilepsy-like seizures and delayed development combined with a low content of glucose in spinal fluid. The diagnosis is confirmed by genetic testing. Treatment is a ketogenic diet, as ketone bodies pass the blood-brain barrier using other transport proteins than GLUT-1. INTERPRETATION: GLUT-1-deficiency syndrome is a rare metabolic encephalopathy which is not well known and probably underdiagnosed. An early diagnosis and early start of a ketogenic diet may give these children a normal or nearly normal life.

Gluten sensitivity: from gut to brain.

Gluten sensitivity is a systemic autoimmune disease with diverse manifestations. This disorder is characterised by abnormal immunological responsiveness to ingested gluten in genetically susceptible individuals. Coeliac disease, or gluten-sensitive enteropathy, is only one aspect of a range of possible manifestations of gluten sensitivity. Although neurological manifestations in patients with established coeliac disease have been reported since 1966, it was not until 30 years later that, in some individuals, gluten sensitivity was shown to manifest solely with neurological dysfunction. Furthermore, the concept of extraintestinal presentations without enteropathy has only recently become accepted. In this Personal View, we review the range of neurological manifestations of gluten sensitivity and discuss recent advances in the diagnosis and understanding of the pathophysiological mechanisms underlying neurological dysfunction related to gluten sensitivity.

The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies.

Both calorie restriction and the ketogenic diet possess broad therapeutic potential in various clinical settings and in various animal models of neurological disease. Following calorie restriction or consumption of a ketogenic diet, there is notable improvement in mitochondrial function, a decrease in the expression of apoptotic and inflammatory mediators and an increase in the activity of neurotrophic factors. However, despite these intriguing observations, it is not yet clear which of these mechanisms account for the observed neuroprotective effects. Furthermore, limited compliance and concern for adverse effects hamper efforts at broader clinical application. Recent research aimed at identifying compounds that can reproduce, at least partially, the neuroprotective effects of the diets with less demanding changes to food intake suggests that ketone bodies might represent an appropriate candidate. Ketone bodies protect neurons against multiple types of neuronal injury and are associated with mitochondrial effects similar to those described during calorie restriction or ketogenic diet treatment. The present review summarizes the neuroprotective effects of calorie restriction, of the ketogenic diet and of ketone bodies, and compares their putative mechanisms of action.

Fígado e nutrição / Liver and nutrition

A desnutrição calórico-proteica é comum em todas as formas de cirrose e diminui o prognóstico naqueles pacientes na lista de espera ao transplante hepático. O racional na utilização de terapia nutricional naqueles pacientes na lista de espera ao transplante hepático. O racional na utilização de terapia nutricinal nesses pacientes baseia-se na grande melhora, oumesmo na estabilização do quadro metabólico, dando tempo para a regeneração do hepatócito. O autor revisa a terapêutica nutricional na abordagem das doenças hepáticas.

As primarily a metabolic organ, the liver orchestrates a complex away of biochemical process. The regulation of protein and energy metabolism is concentrated in the liver. Consequently the patients with liver disease have abnormal protein calorie malnutrition. The present work makes a revision of as the malnutrition it can alter the prognostic of cirrhotic patients.

Neuroprotective and neurorestorative signal transduction mechanisms in brain aging: modification by genes, diet and behavior.

Cells in the brain deploy multiple mechanisms to maintain the integrity of nerve cell circuits, and to facilitate responses to environmental demands and promote recovery of function after injury. The mechanisms include production of neurotrophic factors and cytokines, expression of various cell survival-promoting proteins (e.g. protein chaperones, antioxidant enzymes, Bcl-2 and inhibitor of apoptosis proteins), protection of the genome by telomerase and DNA repair proteins, and mobilization of neural stem cells to replace damaged neurons and glia. The aging process challenges such neuroprotective and neurorestorative mechanisms, often with devastating consequences as in Alzheimer's disease (AD), Parkinson's and Huntington's diseases and stroke. Genetic and environmental factors superimposed upon the aging process can determine whether brain aging is successful or unsuccessful. Mutations in genes that cause inherited forms of AD (amyloid precursor protein (APP) and presenilins), Parkinson's disease (alpha-synuclein and parkin) and trinucleotide repeat disorders (e.g. huntingtin and the androgen receptor) overwhelm endogenous neuroprotective mechanisms. On the other hand, neuroprotective mechanisms can be bolstered by dietary (caloric restriction, and folate and antioxidant supplementation) and behavioral (cognitive and physical activities) modifications. At the cellular and molecular levels, successful brain aging can be facilitated by activating a hormesis response to which neurons respond by upregulating the expression of neurotrophic factors and stress proteins. Neural stem cells that reside in the adult brain are also responsive to environmental demands, and appear capable of replacing lost or dysfunctional neurons and glial cells, perhaps even in the aging brain. The recent application of modem methods of molecular and cellular biology to the problem of brain aging is revealing a remarkable capacity within brain cells for adaptation to aging and resistance to disease.

Epilepsy, occipital calcifications, and oligosymptomatic celiac disease in childhood.

The association of epilepsy, occipital calcifications, and celiac disease has been recognized as a distinct syndrome. The objective of this study was to present the clinical, electrophysiologic, and neuroradiologic features in a series of patients with this syndrome. Thirty-two patients with the constellation of epilepsy, occipital calcifications, and celiac disease were identified in our epilepsy clinic. The mean age was 11 years and the mean length of follow-up was 7.4 years. The 1990 criteria of the European Society of Pediatric Gastroenterology and Nutrition were used to diagnose celiac disease. The Kruskal-Wallis statistics test was employed with a signficance of P < .05. Thirty-one patients had partial seizures, 21 of them with symptoms related to the occipital lobe. In most patients, the epilepsy was controlled or the seizures were sporadic. Three developed severe epilepsy. Occipital calcifications were present in all cases. Computed tomography in 7 patients showed hypodense areas in the white matter around calcifications, which decreased or disappeared after a period of gluten-free diet in 3 patients. A favorable outcome of epilepsy was detected in patients with the earliest dietary therapy. This study presents the largest series of children with this syndrome outside Italy. White-matter hypodensities surrounding calcifications are rarely reported. A prompt diagnosis of celiac disease might improve the evolution of the epilepsy and may improve cognitive status.