There is considerable evidence that the hippocampal system contributes both to (1) the temporary maintenance of memories and to (2) the processing of a particular type of memory representation. The findings on amnesia suggest that these two distinguishing features of hippocampal memory processing are orthogonal. Together with anatomical and physiological data, the neuropsychological findings support a model of cortico-hippocampal interactions in which the temporal and representational properties of hippocampal memory processing are mediated separately. We propose that neocortical association areas maintain shortterm memories for specific items and events prior to hippocampal processing as well as providing the final repositories of long-term memory. The parahippocampal region supports intermediate-term storage of individual items, and the hippocampal formation itself mediates an organization of memories according to relevant relationships among items. Hippocampal-cortical interactions produce (i) strong and persistent memories for events, including their constituent elements and the relationships among them, and (ii) a capacity to express memories flexibly across a wide range of circumstances.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0140525X00035391

Two functional components of the hippocampal memory system

We have tested a simple and reliable measure of visuospatial ability in Alzheimer patients--the Clock Drawing Test. To determine the usefulness of this measure, we asked 67 Alzheimer patients and 83 normal controls to draw the face of a clock reading the time of 2:45. Six independent observers blindly evaluated the results with ratings from 10 (best) to 1 (worst). The mean performance score of Alzheimer subjects was 4.9 +/- 2.7 compared to 8.7 +/- 1.1 for normal controls (P less than .001). Inter-rater reliability for the clocks drawn by Alzheimer patients was highly significant (r = 0.86; P less than .001), and there was relatively little overlap between ratings for Alzheimer patients and normal controls. Furthermore, correlations were highly significant (P less than .001) between the mean score of clock drawings and three independent global measures of dementia severity. Although the Clock Drawing Test is certainly not a definitive indicator of Alzheimer's disease, the test is easy to administer and provides a useful measure of dementia severity for both research and office settings where sophisticated neuropsychological testing is not available.

Clock drawing in Alzheimer's disease. A novel measure of dementia severity.

Kindling and status epilepticus models of epilepsy: rewiring the brain.

Summary: Purpose: To assess which antiepileptic medications (AEDs) have the best evidence for long-term efficacy or effectiveness as initial monotherapy for patients with newly diagnosed or untreated epilepsy.

Methods: A 10-member subcommission of the Commission on Therapeutic Strategies of The International League Against Epilepsy (ILAE), including adult and pediatric epileptologists, clinical pharmacologists, clinical trialists, and a statistician evaluated available evidence found through a structured literature review including MEDLINE, Current Contents and the Cochrane Library for all applicable articles from 1940 until July 2005. Articles dealing with different seizure types (for different age groups) and two epilepsy syndromes were assessed for quality of evidence (four classes) based on predefined criteria. Criteria for class I classification were a double-blind randomized controlled trial (RCT) design, ≥48-week treatment duration without forced exit criteria, information on ≥24-week seizure freedom data (efficacy) or ≥48-week retention data (effectiveness), demonstration of superiority or 80% power to detect a ≤20% relative difference in efficacy/effectiveness versus an adequate comparator, and appropriate statistical analysis. Class II studies met all class I criteria except for having either treatment duration of 24 to 47 weeks or, for noninferiority analysis, a power to only exclude a 21–30% relative difference. Class III studies included other randomized double-blind and open-label trials, and class IV included other forms of evidence (e.g., expert opinion, case reports). Quality of clinical trial evidence was used to determine the strength of the level of recommendation.

Results: A total of 50 RCTs and seven meta-analyses contributed to the analysis. Only four RCTs had class I evidence, whereas two had class II evidence; the remainder were evaluated as class III evidence. Three seizure types had AEDs with level A or level B efficacy and effectiveness evidence as initial monotherapy: adults with partial-onset seizures (level A, carbamazepine and phenytoin; level B, valproic acid), children with partial-onset seizures (level A, oxcarbazepine; level B, None), and elderly adults with partial-onset seizures (level A, gabapentin and lamotrigine; level B, None). One adult seizure type [adults with generalized-onset tonic–clonic (GTC) seizures], two pediatric seizure types (GTC seizures and absence seizures), and two epilepsy syndromes (benign epilepsy with centrotemporal spikes and juvenile myoclonic epilepsy) had no AEDs with level A or level B efficacy and effectiveness evidence as initial monotherapy.

Conclusions: This evidence-based guideline focused on AED efficacy or effectiveness as initial monotherapy for patients with newly diagnosed or untreated epilepsy. The absence of rigorous comprehensive adverse effects data makes it impossible to develop an evidence-based guideline aimed at identifying the overall optimal recommended initial-monotherapy AED. There is an especially alarming lack of well-designed, properly conducted RCTs for patients with generalized seizures/epilepsies and for children in general. The majority of relevant existing RCTs have significant methodologic problems that limit their applicability to this guideline's clinically relevant main question. Multicenter, multinational efforts are needed to design, conduct and analyze future clinically relevant RCTs that can answer the many outstanding questions identified in this guideline. The ultimate choice of an AED for any individual patient with newly diagnosed or untreated epilepsy should include consideration of the strength of the efficacy and effectiveness evidence for each AED along with other variables such as the AED safety and tolerability profile, pharmacokinetic properties, formulations, and expense. When selecting a patient's AED, physicians and patients should consider all relevant variables and not just efficacy and effectiveness.

/pdf/ilae-treatment-guidelines-evidence-based-analysis-of-52n1wiaqh8.pdf

ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes.

Since the finding by [Johnson and Ascher (1987)][1] demonstrating that glycine enhances electrophysiological responses mediated by N-methyl-d-aspartate (NMDA)b-sensitive glutamatergic receptors, considerable interest has been devoted to this topic (for reviews, see [Dingledine et al. , 1990][2]; [

Glycine and N-Methyl-d-Aspartate Receptors: Physiological Significance and Possible Therapeutic Applications

A new model of chronic temporal lobe epilepsy induced by electrical stimulation of the amygdala in rat.

Comparison of oxcarbazepine and carbamazepine: a double-blind study

INTRODUCTION. The main action of paracetamol (acetaminophen) is presumed to be in the central nervous system. The central nervous system penetration of paracetamol has been described in children with intracranial pathologies but not in children with an intact blood-brain barrier. OBJECTIVE. We investigated the cerebrospinal fluid penetration of paracetamol in 32 healthy children, aged 3 months to 12 years, who were undergoing surgery in the lower body using spinal anesthesia. MATERIALS AND METHODS. In this open-label prospective study, children were given a single intravenous injection of paracetamol (15 mg/kg). Cerebrospinal fluid and venous blood samples were obtained between 5 minutes and 5 hours after injection. Paracetamol concentrations were determined from the cerebrospinal fluid and plasma by using a fluorescence polarization immunoassay. RESULTS. Paracetamol was detected in cerebrospinal fluid from the earliest sample at 5 minutes, although in this sample paracetamol concentration was below the limit of quantification of 1.0 mg/L. Subsequent paracetamol concentrations in cerebrospinal fluid ranged between 1.3 and 18 mg/L (median: 7.2 mg/L), plasma concentrations ranged between 2.4 and 33 mg/L, and cerebrospinal fluid/plasma ratios ranged between 0.06 and 2.0. The highest CSF paracetamol concentration was detected at 57 minutes. CONCLUSIONS. Paracetamol permeates readily into the cerebrospinal fluid of children. This fast and extensive transfer enables the rapid central analgesic and antipyretic action of intravenous paracetamol.

Toivo Halonen

Papers

A new model of chronic temporal lobe epilepsy induced by electrical stimulation of the amygdala in rat.

Comparison of oxcarbazepine and carbamazepine: a double-blind study

Paracetamol (acetaminophen) penetrates readily into the cerebrospinal fluid of children after intravenous administration

Dopaminergic system and monoamine oxidase-B activity in Alzheimer's disease.

Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy: one year follow-up.