Altered cortical excitability in tuberous sclerosis and the effect of mTOR inhibitors: An intracranial electrical stimulation study

IF 3.7 3区医学 Q1 CLINICAL NEUROLOGY Clinical Neurophysiology Pub Date : 2025-02-04 DOI:10.1016/j.clinph.2025.02.001

Kishore Vedala , Gewalin Aungaroon , David Ritter , Hansel M. Greiner , Jeffrey R. Tenney , Jesse Skoch , Paul S. Horn , James L. Leach , Francesco T. Mangano , Darcy Krueger , Ravindra Arya

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引用次数: 0

Abstract

Objective

We used electrical stimulation mapping (ESM) of functional responses, after-discharges (ADs), and unwanted electrical stimulation-induced seizures (EIS) to explore differences in cortical excitability in tuberous sclerosis complex (TSC) patients on mTOR inhibitors, TSC patients not on mTOR inhibitors, and drug-resistant epilepsy (DRE) of unknown etiology.

Methods

In 20 patients with TSC and 10 patients with DRE of unknown etiology, incidence and current thresholds of physiologic (language and motor) and pathologic (ADs, EIS) responses were analyzed using mixed effects models against disease phenotype (TSC vs unknown) and use of mTOR inhibitors.

Results

Patients with TSC showed a higher incidence and required a lower threshold current to elicit motor responses and ADs compared to those with DRE of unknown etiology. In TSC patients, mTOR inhibitors increased the threshold for motor responses and ADs, and decreased the incidence of face motor responses, language responses, and ADs.

Conclusions

TSC patients exhibit higher physiologic and pathologic cortical excitability evidenced by a higher incidence and lower current thresholds of ESM responses, which appears to be mitigated by mTOR inhibitors.

Significance

To our knowledge, this is the first study providing direct intracranial evidence for altered cortical excitability in TSC and the corrective effect of mTOR inhibitors.

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来源期刊

Clinical Neurophysiology 医学-临床神经学

CiteScore

8.70

自引率

6.40%

发文量

932

审稿时长

59 days

期刊介绍： As of January 1999, The journal Electroencephalography and Clinical Neurophysiology, and its two sections Electromyography and Motor Control and Evoked Potentials have amalgamated to become this journal - Clinical Neurophysiology. Clinical Neurophysiology is the official journal of the International Federation of Clinical Neurophysiology, the Brazilian Society of Clinical Neurophysiology, the Czech Society of Clinical Neurophysiology, the Italian Clinical Neurophysiology Society and the International Society of Intraoperative Neurophysiology.The journal is dedicated to fostering research and disseminating information on all aspects of both normal and abnormal functioning of the nervous system. The key aim of the publication is to disseminate scholarly reports on the pathophysiology underlying diseases of the central and peripheral nervous system of human patients. Clinical trials that use neurophysiological measures to document change are encouraged, as are manuscripts reporting data on integrated neuroimaging of central nervous function including, but not limited to, functional MRI, MEG, EEG, PET and other neuroimaging modalities.