Ketogenic diet in the treatment of pharmacoresistent epilepsy. Domestic experience and perspectives

The article concentrates on the experience of using the ketogenic diet (KD) in neurological practice in children with epilepsy resistant to anticonvulsant treatment. Prescription of KD in combination with drug therapy or without it allowed to achieve 100% control over seizures (confirmed by electroencephalographic study), significant progress in psycho-speech, cognitive, motor development in 21% of cases, which increased the chances of socialization of children and improved family life quality.

Posterior Reversible Leukoencephalopathy Syndrome in a Patient after Acute COVID-19 Infection

The SARS-CoV-2 infection affects numerous organs, including the central nervous system. The neuroinvasive abilities and neuroinflammation may lead to short- and long-term neurological manifestations. Among neurological disorders associated with SARS-CoV-2 infection, posterior reversible encephalopathy syndrome (PRES) has been described in a few case-based observational studies during the acute phase of COVID-19 hospitalization. We present a case of a patient who developed seizures and PRES after recovering from an acute severe COVID-19 infection.A 90-year-old African American female with multiple comorbidities and a severe COVID-19 infection was discharged home in stable condition after two weeks of hospitalization. A week later, she developed new-onset generalized tonic-clonic seizures requiring readmission to the hospital. The patient’s clinical course and brain imaging supported PRES. Her mentation returned to baseline with supportive care and anticonvulsant treatment. Follow-up brain MRI four months later demonstrated resolution of FLAIR signal abnormalities confirming PRES. SARS-CoV-2 insult on the cerebrovascular endothelial cells likely continued and despite the clinical recovery eventually resulted in PRES. We believe that this is the first case describing the presentation of PRES after recovery from severe acute COVID-19 infection.

The syndrome of transient epileptic amnesia: a combined series of 115 cases and literature review

The term Transient Epileptic Amnesia was coined in 1990 to describe a form of epilepsy causing predominantly amnestic seizures which could be confused with episodes of Transient Global Amnesia. Subsequent descriptions have highlighted its association with ‘atypical’ forms of memory disturbance including accelerated long-term forgetting, disproportionate autobiographical amnesia and topographical amnesia. However, this highly treatment responsive condition remains under-recognised and undertreated. We describe the clinical and neuropsychological features in 65 consecutive cases of transient epileptic amnesia referred to our study, comparing these to our previous cohort of 50 patients and to those reported in 102 literature cases described since our 2008 review. Findings in our two cohorts are substantially consistent: the onset of transient epileptic amnesia occurs at an average age of 62 years, giving rise to amnestic episodes at a frequency of around 1/month, typically lasting 15-30 minutes and often occurring on waking. Amnesia is the only manifestation of epilepsy in 24% of patients; olfactory hallucinations occur in 43%, motor automatisms in 41%, brief unresponsiveness in 39%. The majority of patients describe at least one of the atypical forms of memory disturbance mentioned above; easily provoked tearfulness is a common accompanying feature. There is a male predominance (85:30). Epileptiform changes were present in 35% of cases, while suspected causative MRI abnormalities were detected in only 5%. Seizures ceased with anticonvulsant treatment in 93% of cases. Some clinical features were detected more commonly in the second series than the first, probably as a result of heightened awareness. Neuropsychological testing and comparison to two age and IQ-matched control groups (n = 24 and 22) revealed consistent findings across the two cohorts, namely elevated mean IQ, preserved executive function, mild impairment at the group level on standard measures of memory, with additional evidence for accelerated long-term forgetting and autobiographical amnesia, particularly affecting episodic recollection. Review of the literature cases revealed broadly consistent features except that topographical amnesia, olfactory hallucinations and emotionality have been reported rarely to date by other researchers. We conclude that transient epileptic amnesia is a distinctive syndrome of late-onset limbic epilepsy of unknown cause, typically occurring in late middle age. It is an important, treatable cause of memory loss in older people, often mistaken for dementia, cerebrovascular disease and functional amnesia. Its aetiology, the monthly occurrence of seizures in some patients and the mechanisms and interrelationships of the interictal features – amnestic and affective – all warrant further study.

Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study

Background The low carbohydrate, high fat ketogenic diet can be an effective anticonvulsant treatment in some pediatric patients with pharmacoresistant epilepsy. Its mechanism(s) of action, however, remain uncertain. Direct sampling of cerebrospinal fluid before and during metabolic therapy may reveal key changes associated with differential clinical outcomes. We characterized the relationship between seizure responsiveness and changes in lipid and carbohydrate metabolites. Methods We performed metabolomic analysis of cerebrospinal fluid samples taken before and during ketogenic diet treatment in patients with optimal response (100% seizure remission) and patients with no response (no seizure improvement) to search for differential diet effects in hallmark metabolic compounds in these two groups. Optimal responders and non-responders were similar in age range and included males and females. Seizure types and the etiologies or syndromes of epilepsy varied but did not appear to differ systematically between responders and non-responders. Results Analysis showed a strong effect of ketogenic diet treatment on the cerebrospinal fluid metabolome. Longitudinal and between-subjects analyses revealed that many lipids and carbohydrates were changed significantly by ketogenic diet, with changes typically being of larger magnitude in responders. Notably, responders had more robust changes in glucose and the ketone bodies β-hydroxybutyrate and acetoacetate than non-responders; conversely, non-responders had significant increases in fructose and sorbose, which did not occur in responders. Conclusions The data suggest that a differential and stronger metabolic response to the ketogenic diet may predict a better anticonvulsant response, and such variability is likely due to inherent biological factors of individual patients. Strategies to boost the metabolic response may be beneficial.

Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study

Background: The low carbohydrate, high fat ketogenic diet can be an effective anticonvulsant treatment in some pediatric patients with pharmacoresistant epilepsy. Its mechanism(s) of action, however, remain uncertain. Direct sampling of cerebrospinal fluid before and during metabolic therapy may reveal key changes associated with differential clinical outcomes. We characterized the relationship between seizure responsiveness and changes in lipid and carbohydrate metabolites. Methods: We performed metabolomic analysis of cerebrospinal fluid samples taken before and during ketogenic diet treatment in patients with optimal response (100% seizure remission) and patients with no response (no seizure improvement) to search for differential diet effects in hallmark metabolic compounds in these two groups. Optimal responders and non-responders were similar in age range and included males and females. Seizure types and the etiologies or syndromes of epilepsy varied but did not appear to differ systematically between responders and non-responders. Results: Analysis showed a strong effect of ketogenic diet treatment on the cerebrospinal fluid metabolome. Longitudinal and between-subjects analyses revealed that many lipids and carbohydrates were changed significantly by ketogenic diet, with changes typically being of larger magnitude in responders. Notably, responders had more robust changes in glucose and the ketone bodies b-hydroxybutyrate and acetoacetate than non-responders; conversely, non-responders had significant increases in fructose and sorbose, which did not occur in responders. Conclusions: The data suggest that a differential and stronger metabolic response to the ketogenic diet may predict a better anticonvulsant response, and such variability is likely due to inherent biological factors of individual patients. Strategies to boost the metabolic response may be beneficial.

Older Patients May Have More Frequent Seizures among Children Diagnosed as Benign Convulsions with Mild Gastroenteritis

Purpose Benign convulsions with mild gastroenteritis (CwG) is a condition that does not usually require treatment. However, when the patient experiences multiple seizures or prolonged seizures, anticonvulsant treatment may be required. We investigated this study to identify the factors that may influence on the number or duration of seizures at CwG. Methods We retrospectively analyzed the medical records of CwG patients who were admitted to the Department of Pediatrics at Sanggye Paik Hospital. Results A total of 105 children with CwG were enrolled. The mean age was 19.59 ± 7.09 months. The mean duration of seizure was 2.79 ± 5.51 minutes and mean number of seizure was 2.33 ± 1.70. Sixty-nine children had seizures less than twice, whereas 36 experienced three times or more. These groups differed significantly according to age in CwG (18.16 ± 7.08, vs. 22.33 ± 6.34 months, p < 0.05). When patients were divided into two groups based on age in CwG using a cut-off of 20 months, we found significant differences in seizure number (1.91 ± 1.27 vs. 3.11 ± 2.10, p < 0.05). There was also a positive correlation between patient age and frequency of seizures (R = 0.316, p = 0.001). Patients who received anticonvulsants were older (17.60 ± 6.87 vs. 22.04 ± 6.63 months, p < 0.05) and had more frequent (1.59 ± 1.37 vs. 3.26 ± 1.63, p < 0.05) and longer seizures (1.76 ± 2.75 vs. 4.07 ± 7.49 minutes, p < 0.05). Conclusion As the number of seizure in CwG was associated with age, treatment in older children may be required in acute stage.

Mental disorders in children with intractable epilepsy as a manifestation of forced normalization of the electroencephalogram (Landolt syndrome)

The forced normalization of the electroencephalogram (Landolt syndrome) is a rapid normalization of the electroencephalogram (decrease in or disappearance of paroxysmal activity) under the influence of anticonvulsant treatment of epilepsy patients, corresponding to a decrease in frequency or complete disappearance of seizures with the appearance of neuropsychiatric disorders (dysphorias, the syndrome of hyperactivity and attention deficit, mysophobia etc). The authors present a review of the literature on the Landolt syndrome, and own data.

Notfallversorgung und Erstbehandlung epileptischer Anfälle im Erwachsenenalter

Suspected epileptic seizures are a frequent cause of emergency hospital care. After single seizures, the emergency management includes safety measures and diagnostic efforts to distinguish epileptic seizures from its manifold mimics and to possibly detect acute causes of epileptic seizures. Convulsive status epilepticus requires rapid anticonvulsant treatment according to established protocols and diagnostics to rule out underlying acute brain diseases. After a first seizure, typical EEG- and MRI findings may indicate an elevated recurrence risk, thereby justifying the ultimate diagnosis of epilepsy and initiation of anticonvulsant therapy. This article reviews the recent definition of epilepsy, summarizes clinical characteristics of epileptic seizures and its mimics and provides an overview of established therapies of single convulsive seizures, convulsive status epilepticus and early care of adults after first unprovoked seizures.

Diadenosine-Polyphosphate Analogue AppCH2ppA Suppresses Seizures by Enhancing Adenosine Signaling in the Cortex

Epilepsy is a multifactorial disorder associated with neuronal hyperexcitability that affects more than 1% of the human population. It has long been known that adenosine can reduce seizure generation in animal models of epilepsies. However, in addition to various side effects, the instability of adenosine has precluded its use as an anticonvulsant treatment. Here we report that a stable analogue of diadenosine-tetraphosphate: AppCH2ppA effectively suppresses spontaneous epileptiform activity in vitro and in vivo in a Tuberous Sclerosis Complex (TSC) mouse model (Tsc1+/−), and in postsurgery cortical samples from TSC human patients. These effects are mediated by enhanced adenosine signaling in the cortex post local neuronal adenosine release. The released adenosine induces A1 receptor-dependent activation of potassium channels thereby reducing neuronal excitability, temporal summation, and hypersynchronicity. AppCH2ppA does not cause any disturbances of the main vital autonomous functions of Tsc1+/− mice in vivo. Therefore, we propose this compound to be a potent new candidate for adenosine-related treatment strategies to suppress intractable epilepsies.