Adam L. Hartman

Neuroprotective and disease-modifying effects of the ketogenic diet.

The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimers disease and Parkinsons disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially &bgr;-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury. This review summarizes the experimental, epidemiological and clinical evidence indicating that the ketogenic diet could have beneficial effects in a broad range of brain disorders characterized by the death of neurons. Although the mechanisms are not yet well defined, it is plausible that neuroprotection results from enhanced neuronal energy reserves, which improve the ability of neurons to resist metabolic challenges, and possibly through other actions including antioxidant and anti-inflammatory effects. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet.

The Ketogenic Diet: One Decade Later

The ketogenic diet, a high fat, adequate protein, low carbohydrate diet, has, during the past decade, had a resurgence of interest for the treatment of difficult-to-control seizures in children. This review traces its history, reviews its uses and side effects, and discusses possible alternatives and the diet’s possible mechanisms of action. Finally, this review looks toward possible future uses of the ketogenic diet for conditions other than epilepsy.

Clinical Aspects of the Ketogenic Diet

Summary:  The ketogenic diet remains a valuable therapeutic option for patients with intractable epilepsy. Clinical aspects of the diets success may provide insights into epileptogenesis and anticonvulsant action. The diets efficacy has been established primarily through large case series. The diet has been used successfully in patients with many different epilepsy syndromes in countries around the world. Potential adverse effects can be avoided with careful attention during the diets initiation and maintenance phases. In the last decade, variations to the classical ketogenic diet have been utilized. Ketogenic diets now are being used for diseases other than epilepsy. This critical analysis of the diet should provide the impetus for further clinical and basic research into the diets application and mechanisms of action.

How do you improve compliance

Compliance, or adherence, as it relates to health care is the extent to which a persons behavior coincides with medical or health advice. Medication compliance is critical for all aspects of pediatrics, specifically in successful treatment, disease prevention, and health promotion. Compliance depends on the patients and physicians committing to the same objectives. It is unfortunate that numerous studies and physician accounts reveal difficulties in achieving compliance with pediatric medication therapy. Medication compliance in pediatric patients ranges from 11% to 93%. At least one third of all patients fail to complete relatively short-term treatment regimens. Poor compliance places children at risk for problems such as continued disease, complicates the physician-patient relationship, and prevents accurate assessment of the quality of care provided. This article presents the issue in the context of its incidence of and barriers to compliance and provides general principles to improve compliance in pediatrics by improving communication and characteristics of the practice setting. A one-on-one relationship between physician and patient is needed for communication and improved compliance.

Ketone bodies in epilepsy

J. Neurochem. (2012) 121, 28–35.

Ketogenic diet for adults in super-refractory status epilepticus

Objective: To describe a case series of adult patients in the intensive care unit in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours or more despite appropriate anesthetic treatment) who received treatment with the ketogenic diet (KD). Methods: We performed a retrospective case review at 4 medical centers of adult patients with SRSE treated with the KD. Data collected included demographic features, clinical presentation, diagnosis, EEG data, anticonvulsant treatment, and timing and duration of the KD. Primary outcome measures were resolution of status epilepticus (SE) after initiation of KD and ability to wean from anesthetic agents. Results: Ten adult patients at 4 medical centers were started on the KD for SRSE. The median age was 33 years (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had encephalitis. The median duration of SE before initiation of KD was 21.5 days (IQR 28) and the median number of antiepileptic medications used before initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three patients had minor complications of the KD including transient acidosis and hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the KD. Conclusion: We describe treatment of critically ill adult patients with SRSE with the KD, with 90% of patients achieving resolution of SE. Prospective trials are warranted to examine the efficacy of the KD in adults with refractory SE. Classification of evidence: This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE.

Ketogenic diets: new advances for metabolism-based therapies.

PURPOSE OF REVIEW Despite myriad anticonvulsants available and in various stages of development, there are thousands of children and adults with epilepsy worldwide still refractory to treatment and not candidates for epilepsy surgery. Many of these patients will now turn to dietary therapies such as the ketogenic diet, medium-chain triglyceride diet, modified Atkins diet, and low glycemic index treatment. RECENT FINDINGS In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first-line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome). Adults are also one of the most rapidly growing populations being treated nowadays; this group of patients previously was not typically offered these treatments. In 2009, two controlled trials of the ketogenic diet were published, as well as an International Expert Consensus Statement on dietary treatment of epilepsy. Ketogenic diets are also now being increasingly studied for neurological conditions other than epilepsy, including Alzheimers disease and cancer. Insights from basic science research have helped elucidate the mechanisms by which metabolism-based therapy may be helpful, in terms of both an anticonvulsant and possibly a neuroprotective effect. SUMMARY Dietary therapy for epilepsy continues to grow in popularity worldwide, with expanding use for adults and conditions other than epilepsy.

How Does the Ketogenic Diet Work? Four Potential Mechanisms

The ketogenic diet and its newer variants are clinically useful in treating epilepsy. They can also have antiepileptogenic properties and can eventually have a role in treating other neurologic and nonneurologic conditions. Despite being nearly a century old, identifying the molecular underpinnings of the ketogenic diet has been challenging. However, recent studies provide experimental evidence for 4 distinct mechanisms that could contribute to the antiseizure and other beneficial effects of these diets. These mechanisms include carbohydrate reduction, activation of adenosine triphosphate (ATP)–sensitive potassium channels by mitochondrial metabolism, inhibition of the mammalian target of rapamycin pathway, and inhibition of glutamatergic excitatory synaptic transmission.

High-dose oral prednisolone for infantile spasms: An effective and less expensive alternative to ACTH

The ideal treatment of infantile spasms is unclear, but many studies advocate hormonal treatment. In the United States, intramuscular ACTH is most widely used, despite the problematic financial cost and side effect profile. Since September 2007, we have replaced ACTH with high-dose oral prednisolone (40-60 mg/day) according to the 2004 United Kingdom Infantile Spasms Study (UKISS). Ten of 15 (67%) infants with new-onset and previously treated infantile spasms became spasm free within 2 weeks; 4 later recurred. More children with an idiopathic etiology for infantile spasms were spasm free than were symptomatic cases (88% vs 43%, P=0.10). Spasm freedom was equivalent to our most recent 15 infants receiving ACTH, with 13 (87%) responding, P=0.16. Oral prednisolone had fewer adverse effects (53% vs 80%, P=0.10) and was less expensive (

The anticonvulsant activity of acetone, the major ketone body in the ketogenic diet, is not dependent on its metabolites acetol, 1,2-propanediol, methylglyoxal, or pyruvic acid.

200 vs approximately