Attentional control influence habituation through modulation of connectivity patterns within the prefrontal cortex: Insights from stereo-EEG.

Attentional control, guided by top-down processes, enables selective focus on pertinent information, while habituation, influenced by bottom-up factors and prior experiences, shapes cognitive responses by emphasizing stimulus relevance. These two fundamental processes collaborate to regulate cognitive behavior, with the prefrontal cortex and its subregions playing a pivotal role. Nevertheless, the intricate neural mechanisms underlying the interaction between attentional control and habituation are still a subject of ongoing exploration. To our knowledge, there is a dearth of comprehensive studies on the functional connectivity between subsystems within the prefrontal cortex during attentional control processes in both primates and humans. Utilizing stereo-electroencephalogram (SEEG) recordings during the Stroop task, we observed top-down dominance effects and corresponding connectivity patterns among the orbitofrontal cortex (OFC), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG) during heightened attentional control. These findings highlighting the involvement of OFC in habituation through top-down attention. Our study unveils unique connectivity profiles, shedding light on the neural interplay between top-down and bottom-up attentional control processes, shaping goal-directed attention.

Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults.

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7-11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8-0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.

Multi-conformers caused by conformational change of A-ring in the C18- and C19-N-dealkyl diterpenoid alkaloids.

This paper describes a rare phenomenon of multi-conformers caused by conformational change of A-ring in the C18- and C19- N-dealkyl diterpenoid alkaloids. The possible reasons for the generation of multiple conformational isomers are complex, which could be affected by the substituents at C-1, C-3, C-13, C-14, and C-15, pH, solvents, the intramolecular hydrogen bond between 1α-OCH3/1α-OH and N-H groups, acid-base treatment, preparation methods, and work-up procedures.

Synthesis of Three-Dimensionally Fascinating Diterpenoid Alkaloids and Related Diterpenes.

Three-dimensional cage-like natural products represent astounding and long-term challenges in the research endeavors of total synthesis. A central issue that synthetic chemists need to address lies in how to efficiently construct the polycyclic frameworks as well as to install the requisite substituent groups. The diterpenoid alkaloids that biogenetically originate from amination of diterpenes and diversify through late-stage skeletal reorganization belong to such a natural product category. As the characteristic components of the Aconitum and Delphinium species, these molecules display a rich array of biological activities, some of which are used as clinical drugs. More strikingly, their intricate and beautiful architectures have rendered the diterpenoid alkaloids elusive targets in the synthetic community. The successful preparation of these intriguing compounds relies on the development of innovative synthetic strategies.Our laboratory has explored the total synthesis of a variety of diterpenoid alkaloids and their biogenetically related diterpenes over the past decade. In doing so, we have accessed 6 different types of skeletons (atisine-, denudatine-, arcutane-, arcutine-, napelline-, and hetidine-type) and achieved the total synthesis of 6 natural products (isoazitine, dihydroajaconine, gymnandine, atropurpuran, arcutinine, and liangshanone). Strategically, an oxidative dearomatization/Diels-Alder (OD/DA) cycloaddition sequence was widely employed in our synthesis to form the ubiquitous [2.2.2]-bicyclic ring unit and its related ring-distorted derivatives in these complex target molecules. This protocol, in combination with additional bond-forming key steps, allowed us to prepare the corresponding polycyclic alkaloids and a biogenetically associated diterpene. For example, bioinspired C-H activation, aza-pinacol, and aza-Prins cyclizations were used toward a unified approach to the atisine-, denudatine-, and hetidine-type alkaloids via ajaconine intermediates in our first work. To pursue the synthesis of atropurpuran and related arcutine alkaloids, we harnessed a ketyl-olefin radical cyclization to assemble the carbocycle and an aza-Wacker cyclization to construct the unusual pyrrolidine ring. Furthermore, a one-pot alkene cleavage/Mannich cyclization tactic, sequential Robinson annulation, and intramolecular aldol addition were developed, which facilitated the formation of the napelline alkaloid scaffold and the first total synthesis of liangshanone. Finally, the utility of the Mannich cyclization and enyne cycloisomerization reactions allowed for access to the highly functionalized A/E and C/D ring fragments of aconitine (regarded as the "Holy Grail" of diterpenoid alkaloids). This Account provides insight into our synthetic designs and approaches used toward the synthesis of diterpenoid alkaloids and relevant diterpenes. These endeavors lay a foundation for uncovering the biological profiles of associated molecules and also serve as a reference for preparing other three-dimensionally fascinating natural products.

Comparison of the real-world effectiveness of vertical versus lateral functional hemispherotomy techniques for pediatric drug-resistant epilepsy: A post hoc analysis of the HOPS study.

OBJECTIVE: This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom. METHODS: We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-event method and calculated using the Kaplan-Meier survival method. RESULTS: Data for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri-insular/peri-Sylvian or trans-Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI] = 53.5%-70.2%) of the entire cohort at 10-year follow-up. Seizure freedom was 88.8% (95% CI = 78.9%-94.3%) at 1-year follow-up and persisted at 85.5% (95% CI = 74.7%-92.0%) across 5- and 10-year follow-up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%-91.5%) at 1-year to 72.1% (95% CI = 66.9%-76.7%) at 5-year to 57.2% (95% CI = 46.6%-66.4%) at 10-year follow-up for the lateral subgroup. Log-rank test found that vertical hemispherotomy was associated with durable seizure-free progression compared to the lateral approach (p = .01). Patients undergoing the lateral hemispherotomy technique had a shorter time-to-seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08-6.04, p = .03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05-12.86, p = .04) compared to those undergoing the vertical hemispherotomy technique. SIGNIFICANCE: This pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise-based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long-term seizure outcomes.

Hemispherectomy Outcome Prediction Scale: Development and validation of a seizure freedom prediction tool.

OBJECTIVE: To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug-resistant epilepsy. METHODS: We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques. RESULTS: Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow-up = 24 months), and 1050 of 1237 (85%) were seizure-free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18-fluoro-2-deoxyglucose-positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom. SIGNIFICANCE: Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision-making.

Total Synthesis of Liangshanone.

The first total synthesis of liangshanone, a hexacyclic ent-kaurane diterpenoid alkaloid, has been completed. Its intricate cagelike framework was assembled through several key transformations, including an oxidative dearomatization/Diels-Alder (OD/DA) cycloaddition sequence, a tandem alkene cleavage/Mannich cyclization, a Robinson-type annulation, and an intramolecular aldol reaction. Notably, an organocatalytic enantioselective α-hydroxymethylation process allowed the preparation of an enantiomerically enriched tricyclic intermediate that should enable asymmetric access to the target natural product.

A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report.

BACKGROUND: Epilepsy is a complex disorder caused by various factors, including genetic aberrance. Recent studies have identified an essential role of the sodium channel Nav1.6, encoded by the gene SCN8A, in epileptic encephalopathy. CASE PRESENTATION: Using parent-offspring trio targeted-exome sequencing, we identified a de novo heterozygous missense mutation c.3953A > G (p.N1318S) in SCN8A in a 3-year-and-9-month Chinese female patient with early infantile epileptic encephalopathy and a normal magnetic resonance imaging of the brain. CONCLUSIONS: This de novo mutation was only detected in the patient but not in her parents. Bioinformatic analysis indicates the pathogenicity of this mutation. Administration of the sodium channel blocker well controlled seizures in the patient. Therefore, we recommend trio targeted-exome sequencing as a routine method for pathogenic variant screening in patients with intractable epilepsy and a normal MRI.

Degradation of high-concentration simulated organic wastewater by DBD plasma.

In this study, a high-concentration simulated organic wastewater, made by dissolving methyl violet in water, was degraded using dielectric barrier discharge (DBD) plasma generated in air and O2 respectively. The decoloration rate and chemical oxygen demand (COD) of wastewater were evaluated during plasma treatments with the initial concentration of methyl violet of 300 mg L-1. Results showed that the highest decoloration rate of around 100% within 10 min and the highest COD decrease of 33% within 60 min could be achieved with the O2 plasma treatment at the discharge voltage of 10 kV, while air plasma treatment showed lower efficiency in decolorizing the methyl violet solution and lower COD decrease (24%) after 60 min treatment. UV-Vis spectroscopy and chemical analysis of generated by-products during the plasma-enabled degradation process revealed that the methyl violet molecules could be completely decomposed into some refractory organics in the solution. Based on the experimental results and literature review, a pathway of methyl violet degradation attributed to energetic electrons and highly reactive species generated by DBD was proposed.

Stochastic dual-plane on-axis digital holographic imaging on irregular surfaces.

An imaging method based on dual-plane on-axis digital holography is proposed for the situation in which an object is on the irregular surface of a transparent medium. Light propagation of the object on the uneven surface of the medium is analyzed and simulated. The diffracted pattern of the object is deformed or destroyed by the refracted light of the medium. Dual-plane on-axis digital holography is used to eliminate the twin image. In order to retrieve the information lost in the reconstructed image due to destructive interference, the object is illuminated by a stochastic beam that is a speckle wave produced by a ground glass. Simulated and experimental results are presented, to demonstrate that the proposed method can be used for imaging on the irregular surface of a transparent medium.

New C20-diterpenoid alkaloids from Aconitum vilmorrianum and structural revision of 2-O-acetylorochrine and orochrine.

Three new C20-diterpenoid alkaloids vilmorrianines E (1), F (2), and G (3) were isolated from the whole plants of Aconitum vilmorrianum, along with one artifact N-chloromethyl vilmorrianine E hydrochloride (4), as well as two known alkaloids hemsleyaconitines F (5) and G (6). The structures of 1-4 were established by HR-ESI-MS, 1D-, 2D-NMR (HMQC, HMBC, and NOESY), and single-crystal X-ray diffraction analysis. In addition, the structures of naturally occurring 2-O-acetylorochrine (7) and orochrine (8) were revised to be the known alkaloids heterophylloidine (9) and deacetyl heterophylloidine (10), respectively, on the basis of consideration of transannular effect and chemical correlations.

Collective Total Syntheses of Atisane-Type Diterpenes and Atisine-Type Diterpenoid Alkaloids: (±)-Spiramilactone†B, (±)-Spiraminol, (±)-Dihydroajaconine, and (±)-Spiramines†C and†D.

The first total syntheses of the architecturally complex atisane-type diterpenes and biogenetically related atisine-type diterpenoid alkaloids (±)-spiramilactone B, (±)-spiraminol, (±)-dihydroajaconine, and (±)-spiramines C and D are reported. Highlights of the synthesis include a late-stage biomimetic transformation of spiramilactone B, a facile formal lactone migration from the pentacyclic skeleton of spiramilactone E, a highly efficient and diastereoselective 1,7-enyne cycloisomerization to construct the functionalized tetracyclic atisane skeleton, and a tandem retro-Diels-Alder/intramolecular Diels-Alder sequence to achieve the tricyclo[6.2.2.0] ring system.

Synthesis of Atisine, Ajaconine, Denudatine, and Hetidine Diterpenoid Alkaloids by a Bioinspired Approach.

A unified approach to four different (atisine, ajaconine, denudatine, and hetidine) diterpenoid alkaloid skeletons was developed and applied to the total synthesis of the natural products dihydroajaconine (2, atisine type) and gymnandine (4, denudatine type). The synthesis features a biogenetically inspired strategy that relies on C-H oxidation, aza-pinacol coupling, and aza-Prins cyclization as key steps.

Generating skeletal diversity from the C19 -diterpenoid alkaloid deltaline: a ring-distortion approach.

The development of new drugs calls for large collections of diverse molecules with considerable complexity. Ring distortion of natural products provides an efficient and facile approach to access new architectures with intriguing biological activities, by harnessing their inherent complexity. In this study, such a strategy has been explored on an abundant C19 -diterpenoid alkaloid, deltaline, enabling the synthesis of 32 new derivatives bearing a broad spectrum of unique scaffolds. Extensive spectroscopic studies including X-ray crystallographic analyses strongly supported the structures of the obtained novel skeletons, which present comparable opportunities with the great contributions made by nature for discovery of new lead compounds.

Reversal of P-glycoprotein-mediated multidrug resistance by the novel tetrandrine derivative W6.

Overexpression of ATP-dependent efflux pump P-glycoprotein (P-gp) is the main cause of multidrug resistance (MDR) and chemotherapy failure in cancer treatment. Inhibition of P-gp-mediated drug efflux is an effective way to overcome cancer drug resistance. The present study investigated the reversal effect of the novel tetrandrine derivative W6 on P-gp-mediated MDR. KBv200, MCF-7/adr and their parental sensitive cell lines KB, MCF-7 were used for reversal study. The intracellular accumulation with P-gp substrates of doxorubicin was determined by flow cytometry. The expression of P-gp and ERK1/2 was investigated by western blot and real-time-PCR (RT-PCR) analysis. ATPase activity of P-gp was performed by P-gp-Glo(TM) assay systems. In comparison with P-gp-negative parental cells, W6 produced a favorable reversal effect in the MDR cells, as determined using the MTT assay. W6 significantly and dose-dependently increased intracellular accumulation of P-gp substrate doxorubicin (DOX) in P-gp overexpressing KBv200 cells, and also inhibited the ATPase activity of P-gp. W6 inhibited P-gp expression in KBv200 cells in a time-dependent manner, but it had no effect on MDR1 expression. In addition, W6 significantly decreased the ERK1/2 activation in KBv200 cells. Our results showed that W6 effectively reversed P-gp-mediated MDR by inhibiting the transport function and expression of P-gp, demonstrating the potential clinical utility of W6.

[Identification of aminoalcohol-diterpenoid alkaloids in Aconiti Lateralis Radix Praeparata and study of their cardiac effects].

In order to affirm the cardioactive components in Fuzi, we identified a group of aminoalcohol- diterpenoid alkaloids in Fuzi using ultra high-performance liquid chromatography coupled with electrospray ionization mass spectrometer (UPLC-ESI-MS) method. Among a total of forty-one isolated ingredients, thirteen major aminoalcohol-diterpenoid alkaloids were identified by comparing their retention times and MS spectra with those of the reference substances. Moreover, Fuzi samples from different places of origin and with different processing methods were examined and their components displayed a pattern of high similarity, though the relative abundance varies probably due to their different processing methods. Furthermore, the cardiac effect of each identified alkaloid was individually evaluated using the isolated bullfrog heart perfusion experiment. Among the thirteen aminoalcohol diterpenoid alkaloids tested, six of them significantly enhanced the amplitude rates. Taken together, we affirm that the cardioactive components in Fuzi are aminoalcohol-diterpenoid alkaloids, shedding light on future studies of the mechanisms and development of these cardioactive compounds.

Identification of hub genes significantly linked to temporal lobe epilepsy and apoptosis via bioinformatics analysis.

Background: Epilepsy stands as an intricate disorder of the central nervous system, subject to the influence of diverse risk factors and a significant genetic predisposition. Within the pathogenesis of temporal lobe epilepsy (TLE), the apoptosis of neurons and glial cells in the brain assumes pivotal importance. The identification of differentially expressed apoptosis-related genes (DEARGs) emerges as a critical imperative, providing essential guidance for informed treatment decisions. Methods: We obtained datasets related to epilepsy, specifically GSE168375 and GSE186334. Utilizing differential expression analysis, we identified a set of 249 genes exhibiting significant variations. Subsequently, through an intersection with apoptosis-related genes, we pinpointed 16 genes designated as differentially expressed apoptosis-related genes (DEARGs). These DEARGs underwent a comprehensive array of analyses, including enrichment analyses, biomarker selection, disease classification modeling, immune infiltration analysis, prediction of miRNA and transcription factors, and molecular docking analysis. Results: In the epilepsy datasets examined, we successfully identified 16 differentially expressed apoptosis-related genes (DEARGs). Subsequent validation in the external dataset GSE140393 revealed the diagnostic potential of five biomarkers (CD38, FAIM2, IL1B, PAWR, S100A8) with remarkable accuracy, exhibiting an impressive area under curve (AUC) (The overall AUC of the model constructed by the five key genes was 0.916, and the validation set was 0.722). Furthermore, a statistically significant variance (p < 0.05) was observed in T cell CD4 naive and eosinophil cells across different diagnostic groups. Exploring interaction networks uncovered intricate connections, including gene-miRNA interactions (164 interactions involving 148 miRNAs), gene-transcription factor (TF) interactions (22 interactions with 20 TFs), and gene-drug small molecule interactions (15 interactions involving 15 drugs). Notably, IL1B and S100A8 demonstrated interactions with specific drugs. Conclusion: In the realm of TLE, we have successfully pinpointed noteworthy differentially expressed apoptosis-related genes (DEARGs), including CD38, FAIM2, IL1B, PAWR, and S100A8. A comprehensive understanding of the implications associated with these identified genes not only opens avenues for advancing our comprehension of the underlying pathophysiology but also bears considerable potential in guiding the development of innovative diagnostic methodologies and therapeutic interventions for the effective management of epilepsy in the future.

MXene V2C-coated runway-type microfiber knot resonator for an all-optical temperature sensor.

We present an all-optical temperature sensor device made of an MXene V2C integrated runway-type microfiber knot resonator (MKR) for the first time. MXene V2C is coated on the surface of the microfiber by optical deposition. The experimental results show that the normalized temperature sensing efficiency is ∼1.65 dB °C-1 mm-1. The high sensing efficiency of the temperature sensor we proposed benefits from the efficient coupling of the highly photothermal material MXene and the runway-type resonator structure, which provides a better idea for the preparation of all-fiber sensor devices.

Epileptic seizures worsen the gait and motor abnormalities in adult patients with Dravet syndrome (with a case report and literature review).

Dravet syndrome (DS), previously known as severe myoclonic epilepsy in infancy (SMEI), is considered the most serious "epileptic encephalopathy." Here, we present a man with a de novo SCN1A mutation who was diagnosed with DS at the age of 29. In addition to pharmaco-resistant seizures and cognitive delay, he also developed moderate to severe motor and gait problems, such as crouching gait and Pisa syndrome. Moreover, it deteriorated significantly following an epileptic seizure. The patient presented with severe flexion of the head and trunk in the sagittal plane and fulfilled the diagnostic criteria for camptocormia and antecollis. After a week, it spontaneously alleviated partially. We applied levodopa to the patient and had a good response. Functional Gait Assessment (FGA) was assessed at three different times: 4 days after the seizure, 1 week after the seizure, and after taking levodopa for 2 years. The results were 4, 12, and 19 points, respectively. We postulated that: (1) gait and motor deficits are somehow influenced by recurrent epileptic episodes;(2) the nigrostriatal dopamine system is involved. To our knowledge, we were the ones who first reported this phenomenon.