bluuebunny/crossref_metadata_2025 huggingface dataset:
Memory Risks for Epilepsy Surgery Differ across Age
Authors: Meador Kimford J.
Published: December 2022

Interaction of Cognitive Aging and Memory Deficits Related to Epilepsy Surgery

Helmstaedter C, Reuber M, Elger CC

Ann Neurol 2002;52(1):89–94

Temporal lobe epilepsy surgery can cause significant memory impairment. This study was intended to examine whether surgery also could affect prognosis of memory loss in older age. Age regression of verbal memory was examined in 187 patients (before and 1 year after left temporal lobe surgery) and 264 healthy controls. Eighty patients underwent selective amygdalohippocampectomy, and 107 patients underwent anterior two-thirds temporal lobectomy. Amygdalohippocampectomy patients had mesiotemporal epilepsy; anterior two-thirds temporal lobectomy patients had more extramesial or diffuse seizure-onset zones. Memory was assessed by word-list learning for its more mesial (consolidation/retrieval) and more neocortical (learning) aspects. Patients showed significant preoperative memory impairment. Independent of seizure outcome and surgical approach, surgery had significant negative effects on learning and consolidation/retrieval. In the amygdalohippocampectomy group, preoperative and postoperative age regressions of learning and consolidation/retrieval were not different from those of controls. In the anterior two-thirds temporal lobectomy group, age regression of verbal learning became steeper after surgery, and consolidation/retrieval was negatively correlated with older age and later onset of epilepsy even before surgery. The data confirm that age regression of verbal memory in left temporal lobe epilepsy is similar to that in healthy controls. Both left anterior two-thirds temporal lobectomy and amygdalohippocampectomy worsen verbal learning and memory and bring patients closer to cognitive disability. Particularly in anterior two-thirds temporal lobectomy patients, surgery and reduced capacities for compensation cause acceleration of lifetime memory decline. The results support earlier and tailored epilepsy surgery and suggest that memory prognosis in older age should be considered if more extensive temporal resections would be inevitable.
Pregnancy Effects on Lamotrigine Levels
Authors: Harden Cynthia L.
Published: December 2022

Lamotrigine Clearance during Pregnancy

Tran TA, Leppik IE, Blesi K, Sathanandan ST, Remmel R

Neurology 2002;59(2):251–255

Objective

To evaluate changes in lamotrigine (LTG) clearance before, during, and after pregnancy.

Methods

Twelve pregnancies that had complete steady-state data before, during, and after pregnancy were evaluated. Data included weight, LTG dose, and LTG blood levels at preconception, during pregnancy, and postpartum, and concomitant use of other antiepileptic drugs (AEDs) and their dosages. Apparent clearance (L/[kg.day]) of LTG was calculated by dose/level/weight for time points at preconception; during the first trimester, second trimester, and third trimester; and postpartum. Apparent clearance was compared between preconception and each of the three trimesters. Statistical analysis was performed by using one-way analysis of variance, the Student-Newman-Keuls test, and the paired Student's t test.

Results

An increase in apparent clearance (>65%) was observed between preconception and the second and third trimesters (p < 0.05). Eleven pregnancies required higher doses of LTG to maintain therapeutic levels during pregnancy. There was no significant change in apparent clearance between the trimesters. A decrease in apparent clearance was observed between the last two trimesters and postpartum (p < 0.05). In the postpartum period, apparent clearances returned to the preconception baseline, and LTG doses were reduced.

Conclusion

Pregnancy increases LTG clearance by >50%. This effect occurs early in pregnancy and reverts quickly after delivery. LTG levels should be monitored before, during, and after pregnancy.
Do antiepileptic Drugs Make Seizures Worse? a Meta-Analysis
Authors: French Jaqueline A.
Published: December 2022

Aggravation of Partial Seizures by Antiepileptic Drugs: Is There Evidence from Clinical Trials?

Neurology 2002;59:79–83

Somerville ER

Objectives

To assess clinical trials for evidence that antiepileptic drugs (AEDs) aggravate partial seizures. To determine if the method used to examine drug efficacy can also be used to examine seizure aggravation.

Background

It is widely accepted that AEDs aggravate epilepsy in some patients. However, there is little published objective or quantitative evidence. Most reports concern generalized epilepsies.

Methods

Pharmaceutical companies responsible for the development of five of the new AEDs were asked to provide data concerning seizure increases during randomized placebo-controlled, add-on clinical trials in patients with uncontrolled partial seizures. Seizure frequency in individual patients taking drug or placebo was compared with the baseline pretreatment seizure frequency. The counterpart of the 50% reduction used in efficacy analyses is a 100% increase, because both represent a twofold change. A dose–response relation also was explored.

Results

More than 40% of subjects in clinical trials of tiagabine (TGB), topiramate (TPM), and levetiracetam (LEV) experienced an increase in seizures while taking a placebo. Seizure increases were no more likely to occur when taking any of the three drugs than when taking placebo. A doubling or more of seizure frequency was less likely to occur with TPM or LEV than with placebo but more likely with TGB. However, for TGB, this did not reach significance. There was some evidence for a dose–response effect with TGB but a negative effect with TPM (aggravation less likely with increasing dose). Data on gabapentin and lamotrigine were not provided.

Conclusions

Many patients with partial seizures have an increase in seizures when a new AED is added to their therapy. However, it occurs no more frequently when taking drug than placebo. It probably represents the spontaneous fluctuation of seizure frequency. When a patient who has started a new AED deteriorates, this is not necessarily a drug effect.
Implication of Status Epilepticus in Childhood Epilepsy
Authors: Vining Eileen P.G.
Published: December 2022

Status Epilepticus in a Population-based Cohort with Childhood-onset Epilepsy in Finland

Sillanpaa M, Shinnar S

Ann Neurol 2002;5:303–310

Little is known about the time course over which status epilepticus occurs in childhood-onset epilepsy and its impact on long-term prognosis. A population-based cohort of 150 children younger than 16 years with new-onset epilepsy between 1961 and 1964 residing in the catchment area of Turku University Hospital was observed prospectively until 1997. The occurrence of status epilepticus and recurrent status epilepticus, risk factors for status epilepticus, and the impact of status epilepticus on prognosis were examined. Of the 150 cases, 41 (27%) patients had an episode of status epilepticus, of whom 22 (56%) patients had two or more episodes. The risk of status epilepticus was highest at the onset of the disorder with 30 (73%) cases occurring before (n = 12) or at (n = 18) onset and 37 (90%) cases within 2 years of onset. On multivariable analysis, risk factors for status epilepticus included remote symptomatic cause, age at onset 6 years or younger, and partial seizures. Specific epilepsy syndromes also were associated with a differential risk of status epilepticus. The occurrence of status epilepticus did not alter the mortality rates and had only a modest impact on the probability of attaining remission. In subjects with no other neurologic handicap, social and educational outcomes were similar in those with status epilepticus and in those with no history of status epilepticus. We conclude that status epilepticus is a common occurrence in childhood-onset epilepsy. When it does occur, it occurs early in the course of the disorder. The occurrence of status epilepticus does not appear to have significant adverse impact on long-term prognosis of childhood-onset epilepsy.
Temporal Lobe Epilepsy in Patients Older than 50 Years
Authors: Marks William J.
Published: December 2022

Surgery for Temporal Lobe Epilepsy in Older Patients

Boling W, Andermann F, Reutens D, Dubeau F, Caporicci L, Olivier A

J Neurosurg 2001;95:242–248

Objective

The goal of this study was to evaluate the efficacy of surgery for temporal lobe epilepsy (TLE) in older (older than 50 years) patients.

Methods

The authors conducted a review of all patients aged 50 years or older with TLE surgically treated at the Montreal Neurological Institute and Hospital since 1981 by one surgeon (A.O.). Only patients without a mass lesion were included. Outcome parameters were compared with those of younger individuals with TLE, who were stratified by age at operation.

Results

In patients aged 50 years and older, the onset of complex partial seizures occurred 5 to 53 years (mean, 35 years) before the time of surgery. Postoperatively, over a mean follow-up period of 64 months, 15 (83%) patients obtained a meaningful improvement, becoming either free from seizures or experiencing only a rare seizure. Most surgery outcomes were similar in both older and younger individuals, except for a trend to more freedom from seizures and increased likelihood of returning to work or usual activities in the younger patients. Note that a patient's long-standing seizure disorder did not negatively affect the ability to achieve freedom from seizures after surgery.

Conclusions

Surgery for TLE appears to be effective for older individuals, comparing favorably with results in younger age groups, and carries a small risk of postoperative complications.
Does BDNF Contribute to Temporal Lobe Epilepsy?
Authors: Helen Scharfman
Published: December 2022

Brain-Derived Neurotrophic Factor Enhances Fast Excitatory Synaptic Transmission in Human Epileptic Dentate Gyrus

Zhu WJ, Roper SN

Ann Neurol 2001;50:188–194

Purpose

Brain-derived neurotrophic factor (BDNF) has trophic effects and modulates synaptic transmission in the hippocampal formation in animal studies. It also is upregulated in acute and chronic epilepsy models and in human temporal lobe epilepsy. This study was undertaken to examine the effects of BDNF on fast synaptic transmission in the human epileptic dentate gyrus.

Methods

Hippocampal specimens were acquired from patients with temporal lobe epilepsy during surgical removal of the anterior temporal lobe, intended to treat the epileptic condition. Whole-cell patch-clamp recordings were obtained from dentate granule cells in transverse hippocampal slices in vitro.

Results

Application of BDNF increased the amplitude and frequency of spontaneous excitatory postsynaptic currents and increased the amplitude of evoked excitatory postsynaptic currents. BDNF had no effect on spontaneous inhibitory postsynaptic currents but produced a decrease in amplitude of evoked inhibitory postsynaptic currents. The effects of BDNF were abolished by coapplication of the tyrosine kinase inhibitor K252a; therefore, BDNF enhances fast excitatory transmission in the epileptic human dentate gyrus and may play an important role in epileptogenesis in temporal lobe epilepsy.

Conclusions

This raises the possibility of designing therapies for this disorder that may be both anticonvulsant and antiepileptogenic.
Human Epilepsy Can be Linked to a Defective Calcium Channel
Authors: Noebels Jeffrey L.
Published: December 2022

Human Epilepsy Associated with Dysfunction of the Brain P/Q-type Calcium Channel

Jouvenceau A, Eunson LH, Spauschus A, Ramesh V, Zuberi SM, Kullmann DM, Hanna MG

Lancet 2001;358:801–807

Background

The genetic basis of most common forms of human paroxysmal disorders of the central nervous system, such as epilepsy, remains unidentified. Several animal models of absence epilepsy, commonly accompanied by ataxia, are caused by mutations in the brain P/Q-type voltage-gated calcium (Ca2+) channel. We aimed to determine whether the P/Q-type Ca2+ channel is associated with both epilepsy and episodic ataxia type 2 in human beings.

Methods

We identified an 11-year-old boy with a complex phenotype comprising primary generalised epilepsy, episodic and progressive ataxia, and mild learning difficulties. We sequenced the entire coding region of the gene encoding the voltage-gated P/Q-type Ca2+ channel (CACNA1A) on chromosome 19. We then introduced the newly identified heterozygous mutation into the full-length rabbit cDNA and did detailed electrophysiologic expression studies of mutant and wild-type Ca2+ channels.

Results

We identified a previously undescribed heterozygous point mutation (C5733T) in CACNA1A. This mutation introduces a premature stop codon (R1820stop), resulting in complete loss of the C terminal region of the pore-forming subunit of this Ca2+ channel. Expression studies provided direct evidence that this mutation impairs Ca2+ channel function. Mutant/wild-type coexpression studies indicated a dominant negative effect.

Conclusions

Human absence epilepsy can be associated with dysfunction of the brain P/Q-type voltage-gated Ca2+ channel. The phenotype in this patient has striking parallels with the mouse absence epilepsy models.
Epilepsy Research Takes Flight
Authors: Baraban Scott C.
Published: December 2022

Genetic Suppression of Seizure Susceptibility in Drosophila

Kuebler D, Zhang H, Ren X, Tanouye MA

J Neurophysiol 2001;86:1211–1225

Purpose

Despite the frequency of seizure disorders in the human population, the genetic and physiologic basis for these defects has been difficult to resolve. Although many genetic defects that cause seizure susceptibility have been identified, the defects involve disparate biologic processes, many of which are not neural specific. The large number and heterogeneous nature of the genes involved make it difficult to understand the complex factors underlying the etiology of seizure disorders. Examining the effect known genetic mutations have on seizure susceptibility is one approach that may prove fruitful. This approach may be helpful both in understanding how different physiologic processes affect seizure susceptibility and in identifying novel therapeutic treatments.

Methods

In this study, we have taken advantage of Drosophila, a genetically tractable system, to identify factors that suppress seizure susceptibility. Of particular interest has been a group of Drosophila mutants, the bang-sensitive (BS) mutants, which are much more susceptible to seizures than are wild type. The BS phenotypic class includes at least eight genes, including three examined in this study, bss, eas, and sda. Through the generation of double-mutant combinations with other well-characterized Drosophila mutants, the BS mutants are particularly useful for identifying genetic factors that suppress susceptibility to seizures.

Results

We found that mutants affecting Na+ channels, mlenapts and para, K+ channels, Sh, and electrical synapses, shak-B2, can suppress seizures in the BS mutants. This is the first demonstration that these types of mutations can suppress the development of seizures in any organism. Reduced neuronal excitability may contribute to seizure suppression. The best suppressor, mlenapts, causes an increased stimulation threshold for the giant fiber (GF), consistent with a reduction in single-neuron excitability that could underlie suppression of seizures. For some other double mutants with para and ShKS133, there are no GF threshold changes, but reduced excitability also may be indicated by a reduction in GF following frequency.

Conclusions

These results demonstrate the utility of Drosophila as a model system for studying seizure susceptibility and identify physiologic processes that modify seizure susceptibility.
Midline Spikes Associated with Focal Epilepsy
Authors: Cascino Gregory
Published: December 2022

Seizure Semiology and Neuroimaging Findings in Patients with Midline Spikes

Kutluay E, Passaro EA, Gomez-Hassan D, Beydoun A

Epilepsia 2001;42:1563–1568

Purpose

Midline epileptiform discharges are rare compared with discharges at other scalp locations. Neuroimaging results and semiologic seizure characteristics of patients with midline spikes are not adequately described. The aim of this study was to describe the neuroimaging findings and detailed seizure semiologies in patients with midline spikes.

Methods

We reviewed the EEG database of the University of Michigan Medical Center and identified 35 patients with midline spikes. Information about seizure types and neuroimaging results was obtained from a review of medical records. The seizures were classified according to the International League Against Epilepsy (ILAE) criteria and semiologic classification.

Results

Twenty-nine (83%) patients had a history of seizures. Complex partial seizures and simple partial seizures were the most common seizure types, experienced by 66% of patients. The age at seizure onset was within the first 10 years in 90% of patients. According to the semiologic seizure classification, automotor seizures and tonic seizures were the most common seizure types. Neuroimaging studies were abnormal in 45% of patients. When focal abnormalities were detected, they were lateralized to one of the frontal lobes in all cases.

Conclusions

Our results indicate that in the majority of patients, midline spikes represent focal epileptiform activity rather than fragments of generalized discharges, and are most commonly associated with seizures of partial onset. Automotor seizures and tonic seizures are the most common semiologies. Focal radiologic abnormalities tend to be lateralized to one of the frontal lobes.
A Gene for JME at Last: The α1 GABA Receptor Subunit
Authors: Noebels Jeffrey L.
Published: December 2022

Mutation of GABRA1 in an Autosomal Dominant Form of Juvenile Myoclonic Epilepsy

Cossette P, Liu L, Brisebois K, Dong H, Lortie A, Vanasse M, Saint-Hilaire JM, Carmant L, Verner A, Lu WY, Tian Wang Y, Rouleau GA

Nat Genet 2002;31:184–189

Although many genes that predispose for epilepsy in humans have been determined, those that underlie the classical syndromes of idiopathic generalized epilepsy (IGE) have yet to be identified. We report that an Ala322Asp mutation in GABRA1, encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A (GABA(A)), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABA(A) receptors that contain the mutant subunit show a lesser amplitude of GABA-activated currents in vitro, indicating that seizures may result from loss of function of this inhibitory ligand-gated channel. Our results confirm that mutation of GABRA1 predisposes towards a common idiopathic generalized epilepsy syndrome in humans.
Intrinsic Bursting Alone Does Not Beget Seizures
Authors: Benardo Larry S.
Published: December 2022

Long-Lasting Modification of Intrinsic Discharge Properties in Subicular Neurons Following Status Epilepticus

Wellmer J, Su H, Beck H, Yaari Y

Eur J Neurosci 2002;16:259–266

A single episode of status epilepticus (SE) induces neuropathologic changes in the brain that may lead to the development of a permanent epileptic condition. Most studies of this plasticity have focused on the hippocampus, where both synaptic function and intrinsic neuronal excitability have been shown to be persistently modified by SE. However, many other brain structures are activated during SE and also may be involved in the subsequent epileptogenic process. Here we investigated whether SE, induced in rats with pilocarpine and terminated after 40 minutes with diazepam (DZP), persistently modifies the intrinsic excitability of pyramidal neurons in the subiculum. Subicular slices were prepared from control and SE-experienced rats (2 to 5 weeks after SE). In the control group, only 4% of the neurons fired bursts in response to intrasomatic, threshold-straddling depolarizing current pulses (low-threshold bursters). The remaining neurons either fired bursts in response to strong (3 times threshold) depolarizations (35%; high-threshold bursters) or fired in a completely regular mode (61%; nonbursters). In the SE-experienced group, the fractions of low- and high-threshold bursters markedly increased to 29% and 53%, respectively. This change in firing behavior was associated with a marked increase in the size of the spike afterdepolarization, particularly in low-threshold bursters. Experimental suppression of Ca2+ currents selectively blocked low-threshold bursting but did not affect high-threshold bursting, suggesting that a dual Ca2+-dependent and Ca2+-independent mechanism controls bursting in these neurons. The persistent upregulation of intrinsic bursting in the subiculum, in concert with similar changes in the hippocampus, undoubtedly contributes to epileptogenesis after pilocarpine-induced SE.
Chronic Epilepsy Does Not Cause Measurable Structural Changes on MRI
Authors: Kanner Andres M.
Published: December 2022

The Structural Consequences of Newly Diagnosed Seizures

Liu RSN, Lemieux L, Bell GS, Sisodiya SM, Bartlett PA, Shorvon SD, Sander JWAS, Duncan JS

Ann Neurol 2002;52:573–580

Intractable epilepsy may be associated with widespread structural cerebral damage. We determined whether structural damage occurs to the hippocampus, cerebellum, and neocortex in the first few years after a diagnosis of seizures. Sixty-eight patients older than 14 years with newly diagnosed seizures and 90 matched controls underwent serial magnetic resonance imaging (MRI) brain scans 3.5 years apart. Using quantitative analysis of serial scans, we determined changes in hippocampal volume, hippocampal T2 relaxometry, and total and regional brain volumes. Thirty-four (50%) patients had recurrent unprovoked seizures between baseline and follow-up scans. One patient with preexisting hippocampal sclerosis (HS) did not develop progressive hippocampal damage. Group analyses found no difference in change in cerebral measures between patients and controls or between patients with and without recurrent seizures. Significant quantitative changes in individuals were largely attributable to preexisting cerebral lesions or alcohol abuse. Subtle changes detected in individuals over a 3.5-year period but were not related to a history of overt seizures. Our results show patients with newly diagnosed seizures are not generally at increased risk of seizure-induced structural cerebral damage as detected with MRI. Cerebral damage may occur before the onset of seizures or develop insidiously over a more prolonged period
Measurement and Significance of Changes in Benzodiazepine Receptors in Temporal Lobe Epilepsy
Authors: Cascino Gregory D.
Published: December 2022

Quantitative Analysis of Benzodiazepine Receptor in Temporal Lobe Epilepsy: [125I]Iomazenil Autoradiographic Study of Surgically Resected Specimens

Sata Y, Matsuda K, Mihara T, Aihara M, Yagi K, Yonekura Y

Epilepsia 2002;43(9):1039–1048

Purpose

To evaluate the changes of the inhibitory neurotransmitter receptor system related to epileptogenesis by measuring central benzodiazepine receptors (BZDRs) in surgically resected specimens of temporal lobe epilepsy by using [125I]iomazenil autoradiography.

Methods

Surgically resected specimens were obtained from 66 temporal lobe epilepsy patients [51 with mesial temporal lobe epilepsy (MTLE) and 15 with non-MTLE] receiving no BZDs and seven MTLE patients receiving BZDs. BZDR densities in brain sections were measured by using [125I]iomazenil autoradiography. Cell densities were measured from cresyl violet–stained sections.

Results

Compared with non-MTLE patients, non–BZD-treated MTLE patients showed remarkable reduction of BZDR density in the pyramidal cell region of cornu ammonis (CA) 1, CA3, and CA4, and a smaller but significant reduction in CA2 and the molecular and granule cell layers of dentate gyrus (mDG). In the MTLE group, the BZDR density in the mDG correlated with that in lateral cortex. Significant correlations between BZDR density and cell density were found in all hippocampal regions. A significant difference in BZDR density/cell-density ratio was observed in CA1 region between MTLE and non-MTLE. BZD-treated patients tended to have lower BZDR densities than did non–BZD-treated patients, although the differences did not reach significance. In all MTLE cases, [123I]iomazenil single-photon emission computed tomography (SPECT) showed decreased BZDR binding in MTL.

Conclusions

In MTLE, BZDR densities decreased parallel to reduction in cell density in most hippocampal subfields, but BZDR density appeared to decrease in excess of neuron loss in CA1. [125I]Iomazenil SPECT might be useful for detecting in vivo changes of BZDR density.
Verbal Memory Loss after ATL Based on Degree of Hippocampal Sclerosis
Authors: Harden Cynthia L.
Published: December 2022

Risk to Verbal Memory After Anterior Temporal Lobectomy in Patients with Severe Left-Sided Hippocampal Sclerosis

Martin RC, Kretzmer T, Palmer C, Sawrie S, Knowlton R, Faught E, Morawetz R, Kuzniecky R

Arch Neurol 2002;59:1895–1901

Background

Previous investigations indicate low risk for memory loss after anterior temporal lobectomy (ATL) in patients with severe hippocampal sclerosis (HS) compared with patients with mild HS. However, these conclusions have been established primarily with group-level analyses.

Purpose

To investigate individual base rate risk for verbal memory loss after ATL in patients who have pathologically verified mild, moderate, or severe HS.

Methods

One hundred fifteen patients with unilateral temporal lobe epilepsy (68 with left-sided and 47 with right-sided epilepsy) were included. Acquisition, retrieval, and recognition components of verbal memory, as measured by the California Verbal Learning Test, were assessed before and after ATL. Postoperatively, the degree of neuronal loss and reactive gliosis of the hippocampus was assessed with a three-tiered rating system establishing mild, moderate, and severe pathologic features. Patients with preoperative magnetic resonance imaging-based evidence of lesions outside the mesial temporal area (side of surgical resection) were excluded.

Results

Neither seizure laterality nor severity of HS was associated with preoperative verbal memory performance. Postoperatively, the left-sided ATL group demonstrated significant decline across the acquisition ( P < 0.01), retrieval ( P < 0.001), and recognition ( P < 0.001) verbal memory components compared with the right-sided ATL group. Patients who underwent left-sided ATL and had mild HS displayed the largest magnitude and percentage proportion of postoperative decline across all verbal memory components. However, 28 (48%) of the 58 patients who underwent left-sided ATL and who had moderate and severe HS displayed statistically reliable declines on retrieval aspects of verbal memory. Most patients undergoing right-sided ATL, regardless of the extent of hippocampal pathologic features, displayed no postoperative memory change.

Conclusions

Substantial individual heterogeneity of memory outcome exists across groups of patients undergoing ATL, with various degrees of pathologically verified HS. Patients undergoing left-sided ATL who have mild HS seem at greatest risk for broad-spectrum verbal memory decline. However, in examining outcome on a patient-by-patient basis, many patients undergoing left-sided ATL who have moderate to severe HS were also vulnerable to verbal memory loss. This risk seems selective to a retrieval-based aspect of verbal memory.
Sleep and Epilepsy: Something Else We Did Not Know
Authors: Bazil Carl
Published: December 2022

Sleep Deprivation Does Not Affect Seizure Frequency During Inpatient Video-EEG Monitoring

Malow BA, Passaro E, Milling C, Minecan DN, Levy K

Neurology 2002;59:1371–137

Purpose

To determine whether acute sleep deprivation facilitates seizures during inpatient monitoring in a controlled protocol.

Methods

Eighty-four patients with medically refractory partial epilepsy undergoing inpatient monitoring were assigned in consecutive blocks to either sleep deprivation every other night or to normal sleep. In both groups, subjects were requested to stay awake during the day, from 6 am to 10 pm. In the sleep-deprivation group, patients also stayed awake between 10 pm and 6 am every other night beginning with day 2. Patients were removed from sleep deprivation if they had two or more secondarily generalized seizures within 24 hours. Patients were removed from the normal sleep group and were sleep deprived if they did not have a complex partial or secondarily generalized seizure by day 6 of monitoring. In these patients removed from sleep deprivation or from normal sleep, data were analyzed up to and including the day of removal from the protocol.

Results

The sleep deprivation and normal sleep subjects did not differ in age, sex, seizure localization, or percentage dosage reduction in antiepileptic drugs from baseline at days 1 to 3 of monitoring. Protocol duration was 6.5 ± 2.4 days (mean ± SD) for the sleep-deprivation group and 5.8 ± 2.0 days for the normal sleep group. Seizures per day for complex partial, secondarily generalized, and combined complex partial and secondarily generalized, calculated from admission until end of protocol, did not differ significantly between the two groups.

Conclusions

Acute sleep deprivation did not affect seizure frequency during inpatient monitoring in our patients with intractable complex partial seizures with secondary generalization.
Neurotransmitter Supply and Demand in Epilepsy
Authors: Huguenard John
Published: December 2022

Block of Glutamate-Glutamine Cycle Between Astrocytes and Neurons Inhibits Epileptiform Activity in Hippocampus

Bacci A, Sancini G, Verderio C, Armano C, Pravettoni E, Fesce R, Franceschetti S, Matteoli M

J Neurophysiol 2002;88:2302–2310

Recurrent epileptiform activity occurs spontaneously in cultured CNS neurons and in brain slices in which γ-aminobutyric acid (GABA) inhibition has been blocked. We demonstrate here that pharmacologic treatments, resulting in either the block of glutamine production by astrocytes or the inhibition of glutamine uptake by neurons, suppress or markedly decrease the frequency of spontaneous epileptiform discharges both in primary hippocampal cultures and in disinhibited hippocampal slices. These data point to an important role for the neuron-astrocyte metabolic interaction in sustaining episodes of intense rhythmic activity in the CNS, and thereby reveal a new potential target for antiepileptic treatments.

A Neuronal Glutamate Transporter Contributes to Neurotransmitter GABA Synthesis and Epilepsy

Sepkuty JP, Cohen AS, Eccles C, Rafiq A, Behar K, Ganel R, Coulter DA, Rothstein JD

J Neuroscience 2002;22:6372–6379.

The predominant neuronal glutamate transporter, EAAC1 (excitatory amino acid carrier-1), is localized to the dendrites and somata of many neurons. Rare presynaptic localization is restricted to γ-aminobutyric acid (GABA) terminals. Because glutamate is a precursor for GABA synthesis, we hypothesized that EAAC1 may play a role in regulating GABA synthesis and thus could cause epilepsy in rats when inactivated. Reduced expression of EAAC1 by antisense treatment led to behavioral abnormalities, including staring-freezing episodes and electrographic (EEG) seizures. Extracellular hippocampal and thalamocortical slice recordings showed excessive excitability in antisense-treated rats. Patch-clamp recordings of miniature inhibitory postsynaptic potentials (mIPSCs) conducted in CA1 pyramidal neurons in slices from EAAC1 antisense-treated animals demonstrated a significant decrease in mIPSC amplitude, indicating decreased tonic inhibition. A 50% loss of hippocampal GABA levels was associated with knockdown of EAAC1, and newly synthesized GABA from extracellular glutamate was significantly impaired by reduction of EAAC1 expression. EAAC1 may participate in normal GABA neurosynthesis and limbic hyperexcitability, whereas epilepsy can result from a disruption of the interaction between EAAC1 and GABA metabolism
Neuroimaging Markers of Epileptogenesis
Authors: White H. Steve
Published: December 2022

Predictive Value of Cortical Injury for the Development of Temporal Lobe Epilepsy in 21-Day-Old Rats: An MRI Approach Using the Lithium-Pilocarpine Model

Roch C, Leroy C, Nehlig A, Namer IJ

Epilepsia 2002;43(10):1129

Purpose

Patients with temporal lobe epilepsy (TLE) usually had an initial precipitating injury in early childhood. However, epilepsy does not develop in all children who have undergone an early insult. As in patients, the consequences of the lithium-pilocarpine–induced status epilepticus (SE) are age dependent, and only a subset of 21-day-old rats will develop epilepsy. Thus with magnetic resonance imaging (MRI), we explored the differences in the evolution of lesions in these two populations of rats.

Methods

SE was induced in 21-day-old rats by the injection of lithium and pilocarpine. T2-weighted images and T2 relaxation-time measurements were used for detection of lesions from 6 hours to 4 months after SE.

Results

Three populations of rats could be distinguished. The first one had neither MRI anomalies nor modification of the T2 relaxation time, and these rats did not develop epilepsy. In the second one, a hypersignal appeared at the level of the piriform and entorhinal cortices 24 hours after SE (increase of 49% of the T2 relaxation time in the piriform cortex) that began to disappear 48 to 72 hours after SE; epilepsy developed in all these animals. The third population of rats showed a more moderate increase of the T2 relaxation time in cortices (14% in the piriform cortex) that could not be seen on T2-weighted images. Epilepsy developed in all these rats. Only in a subpopulation of the 21-day-old rats with epilepsy did hippocampal sclerosis develop.

Conclusions

These results suggest that the injury of the piriform and entorhinal cortices during SE plays a critical role for the installation of the epileptic networks and the development of epilepsy.
Epileptogenesis beyond the Hippocampus
Authors: Stafstrom Carl E.
Published: December 2022

On the Origin of Interictal Activity in Human Temporal Lobe Epilepsy In Vitro

Cohen I, Navarro V, Clemenceau S, Baulac M, Miles R

Science 2002;298(5597):1418–1421

The origin and mechanisms of human interictal epileptic discharges remain unclear. Here we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppressed by antagonists of either glutamatergic or γ-aminobutyric acid (GABA)ergic signaling. The network of neurons discharging during population events comprises both subicular interneurons and a subgroup of pyramidal cells. In these pyramidal cells, GABAergic synaptic events reversed at depolarized potentials. Depolarizing GABAergic responses in neurons downstream to the sclerotic CA1 region contribute to human interictal activity.
How a Sodium Channel Mutation Causes Epilepsy
Authors: Noebels Jeffrey L.
Published: December 2022

Functional and Biochemical Analysis of a Sodium Channel β1-Subunit Mutation Responsible for Generalized Epilepsy with Febrile Seizures Plus Type 1

Meadows LS, Malhotra J, Loukas A, Thyagarajan V, Kazen-Gillespie KA, Koopman MC, Kriegler S, Isom LL, Ragsdale DS

J Neurosci 2002;22(24):10699–10709

Generalized epilepsy with febrile seizures plus type 1 is an inherited human epileptic syndrome, associated with a cysteine-to-tryptophan (C121W) mutation in the extracellular immunoglobulin domain of the auxiliary β1 subunit of the voltage-gated sodium channel. The mutation disrupts β1 function, but how this leads to epilepsy is not understood. In this study, we make several observations that may be relevant for understanding why this β1 mutation results in seizures. First, with electrophysiological recordings from mammalian cell lines, coexpressing sodium channel asubunits and either wild-type β1 or C121Wβ1, we show that loss of β1 functional modulation, caused by the C121W mutation, leads to increased sodium channel availability at hyperpolarized membrane potentials and reduced sodium channel rundown during high-frequency channel activity, compared with channels coexpressed with wild-type β1. In contrast, neither wild-type β1 nor C121Wβ1 significantly affected sodium current time course or the voltage dependence of channel activation. We also show, by using a Drosophila S2 cell adhesion assay, that the C121W mutation disrupts β1-β1 homophilic cell adhesion, suggesting that the mutation may alter the ability of β1 to mediate protein-protein interactions critical for sodium channel localization. Finally, we demonstrate that neither functional modulation nor cell adhesion mediated by wild-type β1 is occluded by coexpression of C121Wβ1, arguing against the idea that the mutant β1 acts as a dominant-negative subunit. Together, these data suggest that C121Wβ1 causes subtle effects on channel function and subcellular distribution that bias neurons toward hyperexcitability and epileptogenesis.
Systematic headwater sampling of white‐spotted charr reveals stream capture events across dynamic topography
Authors: Masuda Taro , Shimono Yoshiko , Kishi Daisuke , Koizumi Itsuro
Published: December 2022

Aim

River system rearrangements such as stream capture play a crucial role in determining range expansion and gene flow of stream organisms between different watersheds. However, it is challenging to clarify the role of stream capture in dynamic landscapes where frequent connections and disconnections occur in stream networks. We hypothesized that fine‐scale sampling with genome‐wide analysis could reveal the effect of stream capture on the range expansion of stream fish and detect unidentified river rearrangement of headwater streams in a highly heterogeneous landscape.

Location

Honshu Island, Japan.

Taxon

Salvelinus leucomaenis.

Methods

To identify stream capture events from biological evidence, a sampling strategy was designed with fish collected from multiple pairs of adjacent headwater streams. This included a ‘typical site’ where the occurrence of a stream capture event has been confirmed with geological evidence. The genetic population structure was analysed using genome‐wide single nucleotide polymorphism (SNP) data using MIG‐seq, followed by a Bayesian clustering approach.

Results

Evidence was found for historical dispersal across watersheds, including a typical stream capture site. This cross‐drainage dispersal promoted gene flow among the three genetic groups of focal fish inhabiting western Honshu Island. The likelihood of past stream capture increased substantially when the inter‐headwater distance was less than 2000 m, or the altitudinal difference was less than 200 m in the current topography.

Main Conclusions

In highly dynamic areas, such as the study site, which is surrounded by active faults, stream capture may be frequent, and aids inter‐drainage dispersal of freshwater organisms, where large‐scale range expansions would otherwise be impossible. Systematic pairwise headwater sampling, together with genome‐wide SNP analysis, provides biological evidence for the history of water system rearrangements and enables the identification of geological events.
Process optimization of a cereal‐based fermented beverage (Boza) powder and investigating upscaling conditions
Authors: Gül Osman , Atalar İlyas , Törnük Fatih , Akgün Abdullah
Published: December 2022

Boza is a traditional fermented cereal‐based beverage, which should be consumed within 3–5 days after production due to its short shelf‐life. Spray drying process is an excellent option to overcome this problem to make the product least perishable. The optimal spray drying conditions for boza powder production in a laboratory‐scale spray dryer were investigated using, Response Surface Methodology. Air inlet temperature and feed flow rate were the main parameters that affected the responses such as powder yield, moisture content, cell viability, particle size, and solubility. The optimum spray drying conditions were 148°C air inlet temperature, 9°C feed temperature, and 10 ml/min feed flow rate. At these optimum conditions, deviations between predictive and experimental values were found very low. A 1.5 log cfu/g reduction in lactic acid bacteria (LAB) viability was achieved, however instant properties of boza powder should be improved by agglomeration processes. Laboratory and pilot scales were also compared at the determined optimum drying conditions. Approximately 0.4 log cfu/g difference in LAB viability was observed between the two scales.

Practical Applications

Boza is one of the most valuable fermented cereal products due to its high nutritional value. The short shelf life of Boza limits its consumption and makes it a seasonal product. Spray drying technology could provide overcome these challenges and improve the usability and durability of boza beverages. However, the quality of a spray‐dried product highly depends on process conditions. Therefore the effects of the spray drying process conditions on the physicochemical properties of boza powder and the scale‐up conditions were investigated for the first time in this study.
Exploring starches from varied sorghum genotypes compared to commercial maize starch
Authors: dos Santos Thaís Barbosa , da Silva Freire Neto Raimundo , Collantes Nathalia Ferreira , Chávez Davy William Hidalgo , Queiroz Valéria Aparecida Vieira , de Carvalho Carlos Wanderlei Piler
Published: December 2022

Sorghum has been lately attracted the attention for human consumption as a gluten‐free cereal rich in bioactive compounds. Sorghum starches isolated from brown (BRS305), red (BRS308), and white (CMSXS180) genotypes were compared to commercial maize starch, based on proximate composition, particle size distribution, microstructure, X‐ray diffraction, amylose and total starch content, solubility index, swelling power, pasting, and thermal properties. The carbohydrate content of sorghum starch samples ranged from 98.24 to 99.23 g/100 g (dry basis). The particle size distribution of the CMSXS180 sorghum genotype was very similar to commercial maize starch. The relative crystallinity values varied from 29.83% to 30.39%. The water solubility index and swelling power of sorghum starches were lower than those of maize starch. Sorghum genotypes paste profiles were similar, but greatly differed from maize showing the highest final viscosity (4042.0–4444.5 cP) compared to maize starch (3767.5 cP) and lower gelatinization enthalpy (∆H = 9–10.5 J/g) than maize starch (11.8 J/g). The results showed some distinct properties of sorghum starches when compared to maize starch, which may contribute to provide alternative uses, particularly in food products requiring very high viscosity and retrogradation.

Practical Applications

Sorghum pericarp is rich in bioactive compounds, which can be used as a main source of ingredients, for example, to the nutraceutical industry. The sorghum grain without pericarp (decorticated), used to produce purified starch (without chemical treatment), may contribute to the total use of this cereal by limiting chemical residues. In addition, sorghum starch has shown particular technological properties different from commercial maize starch, providing alternative uses in the food industry, for example, in products that require high viscosity from hot to cold processes.
Medical management of pediatric inflammatory bowel disease in the Asia‐Pacific region: A position paper by the Asian Pan‐Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group
Authors: Lee Way Seah , Arai Katsuhiro , Alex George , Treepongkaruna Suporn , Kim Kyung Mo , Choong Chee Liang , Mercado Karen S. C. , Darma Andy , Srivastava Anshu , Aw Marion M. ,   APPSPGHAN PIBD Working Group
Published: December 2022

Pediatric inflammatory bowel disease (PIBD) is rising rapidly in many industrialized and affluent areas in the Asia‐Pacific region. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in this region due to differences in disease characteristics and regional resources constraints. This position paper is an initiative from the Asian Pan‐Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) with the aim of providing an up‐to‐date, evidence‐based approach to PIBD in the Asia‐Pacific region, taking into consideration the unique disease characteristics and financial resources available in this region. A group of pediatric gastroenterologists with special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Gastrointestinal infections, including tuberculosis, need to be excluded before diagnosing IBD. In some populations in Asia, the Nudix Hydrolase 15 (NUD15) gene is a better predictor of leukopenia induced by azathioprine than thiopurine‐S‐methyltransferase (TPMT). The main considerations in the use of biologics in the Asia‐Pacific region are high cost, ease of access, and potential infectious risk, especially tuberculosis. This position paper provides a useful guide to clinicians in the medical management of children with PIBD in the Asia‐Pacific region.
Use of provider‐sponsored patient portals among older adults and their family caregivers
Authors: Burgdorf Julia G. , Fabius Chanee D. , Wolff Jennifer L.
Published: December 2022

Background

Millions of older adults co‐manage or delegate health responsibilities to one or more family caregivers. Patient portals facilitate health care management tasks, but little is known about portal use arrangements (i.e., individual or joint use) among older adults and their caregivers.

Methods

We sought to characterize individual and joint use of the patient portal and to identify how using arrangements varies by individual‐, interpersonal‐, and community‐level factors. We used linked 2017 National Health and Aging Trends Study, National Study on Caregiving, and American Community Survey data for a nationally representative sample of older adults (n = 1417; weighted n = 7.4 million) and their caregivers (n = 2232; weighted n = 20.6 million). Patient portals used by older adults and caregiver(s) were assessed via self‐reports. We described portal use arrangements and tested for between‐group differences using weighted Wald tests. Caregiver's likelihood of accessing the portal was modeled using weighted, multivariable logistic regression.

Results

One in ten (10%) community‐living older adults were sole portal users, 3% were joint users with one or more caregivers, 14% solely relied on one or more caregivers as portal users, and 74% reported no portal use. Older adults whose portal was only used by caregiver(s) were more likely to be Medicaid‐enrolled (20% vs. 1%; p < 0.001), have dementia (43% vs. 5%; p < 0.001), and be homebound (65% vs. 27%; p < 0.001). Caregivers were more likely to use the portal if they were college‐educated adjusted odds ratio (aOR): 1.68; p < 0.01) and reported caregiving‐related emotional difficulty (aOR: 1.92; p < 0.001) and doing more than their “fair share” (aOR: 1.48; p = 0.03), and were less likely if Black (versus White) (aOR: 0.61; p = 0.01).

Conclusions

Patient portals could be a valuable platform for identifying and supporting caregivers of high‐need older adults, but existing disparities in portal access must be closed to ensure equitable support.