We report a 39-year-old male who had generalized tonic-clonic seizure with loss of awareness. Investigations led to a diagnosis of a left temporal lobe tumor. He underwent resection of the mass with consequent loss of brain tissue in the temporal lobe and was found to have a complete right homonymous hemianopia in the immediate postoperative period. Macular ganglion cell analysis on optical coherence tomography (OCT) showed homonymous thinning affecting the inferonasal sector in the right eye and inferotemporal sector in the left eye. This case demonstrates transsynaptic retrograde degeneration through the interruption of the inferior optic radiation, and its corresponding effect on the structure and function of the affected retinal field. Temporal lobe lesions may cause not only a homonymous visual f ield defect contralateral to the side of the lesion but also result to homonymous sectoral thinning of the macular ganglion cell complexes in both eyes located ipsilateral to the side of the lesion.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

The dorsal and ventral visual streams have been considered to play distinct roles in visual processing for action: the dorsal stream is assumed to support real-time actions, while the ventral stream facilitates memory-guided actions. However, recent evidence suggests a more integrated function of these streams. We investigated the neural dynamics and functional connectivity between them during memory-guided actions using intracranial EEG. We tracked neural activity in the inferior parietal lobule in the dorsal stream, and the ventral temporal cortex in the ventral stream as well as the hippocampus during a delayed action task involving object identity and location memory. We found increased alpha power in both streams during the delay, indicating their role in maintaining spatial visual information. In addition, we recorded increased alpha power in the hippocampus during the delay, but only when both object identity and location needed to be remembered. We also recorded an increase in theta band phase synchronization between the inferior parietal lobule and ventral temporal cortex and between the inferior parietal lobule and hippocampus during the encoding and delay. Granger causality analysis indicated dynamic and frequency-specific directional interactions among the inferior parietal lobule, ventral temporal cortex, and hippocampus that varied across task phases. Our study provides unique electrophysiological evidence for close interactions between dorsal and ventral streams, supporting an integrated processing model in which both streams contribute to memory-guided actions.
Humans ; Male ; Female ; Adult ; Young Adult ; Hippocampus/physiology* ; Memory/physiology* ; Parietal Lobe/physiology* ; Temporal Lobe/physiology* ; Visual Perception/physiology* ; Electrocorticography ; Visual Pathways/physiology* ; Electroencephalography

We report a 39-year-old male who had generalized tonic-clonic seizure with loss of awareness. Investigations led to a diagnosis of a left temporal lobe tumor. He underwent resection of the mass with consequent loss of brain tissue in the temporal lobe and was found to have a complete right homonymous hemianopia in the immediate postoperative period. Macular ganglion cell analysis on optical coherence tomography (OCT) showed homonymous thinning affecting the inferonasal sector in the right eye and inferotemporal sector in the left eye. This case demonstrates transsynaptic retrograde degeneration through the interruption of the inferior optic radiation, and its corresponding effect on the structure and function of the affected retinal field. Temporal lobe lesions may cause not only a homonymous visual f ield defect contralateral to the side of the lesion but also result to homonymous sectoral thinning of the macular ganglion cell complexes in both eyes located ipsilateral to the side of the lesion.
Human ; retinal ganglion cells ; hemianopsia ; temporal lobe

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

Humans ; Epilepsy, Temporal Lobe/surgery* ; Mossy Fibers, Hippocampal ; Brain-Derived Neurotrophic Factor ; Dentate Gyrus

Objective: To investigate clinicopathological features of multinodular and vacuolar neurodegenerative tumor (MVNT) of the cerebrum, and to investigate its immunophenotype, molecular characteristics and prognosis. Methods: Four cases were collected at the General Hospital of Southern Theater Command, Guangzhou, China and one case was collected at the First People's Hospital of Huizhou, China from 2013 to 2021. Clinical, histological, immunohistochemical and molecular characteristics of these five cases were analyzed. Follow-up was carried out to evaluate their prognoses. Results: There were four females and one male, with an average age of 42 years (range, 17 to 51 years). Four patients presented with seizures, while one presented with discomfort on the head. Pre-operative imaging demonstrated non-enhancing, T2-hyperintense multinodular lesions in the deep cortex and superficial white matter of the frontal (n=1) or temporal lobes (n=4). Microscopically, the tumor cells were mostly arranged in discrete and coalescent nodules primarily within the deep cortical ribbon and superficial subcortical white matter. The tumors were composed of large cells with ganglionic morphology, vesicular nuclei, prominent nucleoli and amphophilic or lightly basophilic cytoplasm. They exhibited varying degrees of matrix vacuolization. Vacuolated tumor cells did not show overt cellular atypia or any mitotic activities. Immunohistochemically, tumor cells exhibited widespread nuclear staining for the HuC/HuD neuronal antigens, SOX10 and Olig2. Expression of other neuronal markers, including synaptophysin, neurofilament and MAP2, was patchy to absent. The tumor cells were negative for NeuN, GFAP, p53, H3K27M, IDH1 R132H, ATRX, BRG1, INI1 and BRAF V600E. No aberrant molecular changes were identified in case 3 and case 5 using next-generation sequencing (including 131 genes related to diagnosis and prognosis of central nervous system tumors). All patients underwent complete or substantial tumor excision without adjuvant chemoradiotherapy. Post-operative follow-up information over intervals of 6 months to 8 years was available for five patients. All patients were free of recurrence. Conclusions: MVNT is an indolent tumor, mostly affecting adults, which supports classifying MVNT as WHO grade 1. There is no tumor recurrence even in the patients treated with subtotal surgical excision. MVNTs may be considered for observation or non-surgical treatments if they are asymptomatic.
Adult ; Female ; Humans ; Male ; Brain Neoplasms/pathology* ; Cerebrum/pathology* ; Neurons/metabolism* ; Seizures ; Temporal Lobe/pathology* ; Biomarkers, Tumor/metabolism*

Temporal lobe epilepsy, with a variety of etiological, symptomatic, electrophysiological characteristics, has the highest incidence among all focal epilepsy, and a high rate of progression to refractory epilepsy. Surgery is an effective treatment, but traditional methods are usually difficult to accurately locate the epileptogenic zone, which may be resolved by stereotactic-electroencephalogram(SEEG) technique. Radiofrequency thermocoagulation and MRI-guided laser interstitial thermal therapy based on SEEG provide a new accurate and minimally invasive choice for refractory epilepsy patients with high surgical risk and difficulty.
Drug Resistant Epilepsy/surgery* ; Electrocoagulation/methods* ; Electroencephalography ; Epilepsy, Temporal Lobe/surgery* ; Humans ; Stereotaxic Techniques

BACKGROUND: Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model. METHODS: Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups. RESULTS: ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001). CONCLUSION ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.
Adenosine Monophosphate ; Anterior Thalamic Nuclei ; Cyclic AMP-Dependent Protein Kinases ; Deep Brain Stimulation ; Epilepsy/therapy* ; Epilepsy, Temporal Lobe/therapy* ; Hippocampus ; Humans ; Mossy Fibers, Hippocampal ; Signal Transduction

BACKGROUND: Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level. METHODS: We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses. RESULTS: The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance. CONCLUSION Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.
Animals ; Deep Brain Stimulation ; Epilepsy, Temporal Lobe/therapy* ; Hippocampus ; Humans ; Macaca ; Seizures