Aberrant Sensory Gating of the Primary Somatosensory Cortex Contributes to the Motor Circuit Dysfunction in Paroxysmal Kinesigenic Dyskinesia

Paroxysmal kinesigenic dyskinesia (PKD) is conventionally regarded as a movement disorder (MD) and characterized by episodic hyperkinesia by sudden movements. However, patients of PKD often have sensory aura and respond excellently to antiepileptic agents. PRRT2 mutations, the most common genetic etiology of PKD, could cause epilepsy syndromes as well. Standing in the twilight zone between MDs and epilepsy, the pathogenesis of PKD is unclear. Gamma oscillations arise from the inhibitory interneurons which are crucial in the thalamocortical circuits. The role of synchronized gamma oscillations in sensory gating is an important mechanism of automatic cortical inhibition. The patterns of gamma oscillations have been used to characterize neurophysiological features of many neurological diseases, including epilepsy and MDs. This study was aimed to investigate the features of gamma synchronizations in PKD. In the paired-pulse electrical-stimulation task, we recorded the magnetoencephalographic data with distributed source modeling and time-frequency analysis in 19 patients of newly-diagnosed PKD without receiving pharmacotherapy and 18 healthy controls. In combination with the magnetic resonance imaging, the source of gamma oscillations was localized in the primary somatosensory cortex. Somatosensory evoked fields of PKD patients had a reduced peak frequency (p < 0.001 for the first and the second response) and a prolonged peak latency (the first response p = 0.02, the second response p = 0.002), indicating the synchronization of gamma oscillation is significantly attenuated. The power ratio between two responses was much higher in the PKD group (p = 0.013), indicating the incompetence of activity suppression. Aberrant gamma synchronizations revealed the defective sensory gating of the somatosensory area contributes the pathogenesis of PKD. Our findings documented disinhibited cortical function is a pathomechanism common to PKD and epilepsy, thus rationalized the clinical overlaps of these two diseases and the therapeutic effect of antiepileptic agents for PKD. There is a greater reduction of the peak gamma frequency in PRRT2-related PKD than the non-PRRT PKD group (p = 0.028 for the first response, p = 0.004 for the second response). Loss-of-function PRRT2 mutations could lead to synaptic dysfunction. The disinhibiton change on neurophysiology reflected the impacts of PRRT2 mutations on human neurophysiology

Postictal Aphasia with Transient Sulcal Hyperintensity on MRI

A 38-year-old man had postictal global aphasia after generalized tonic-clonic seizure, but recovered within 1 day. There was a focal increase in the signal intensity of the left frontoparietal sulci on fluid-attenuated inversion recovery magnetic resonance (MR) sequence 6 hours after the seizure, which disappeared 1 month later. The transient seizure-induced MR hyperintensity was possibly caused by ictal or postictal hyperemia and breakdown of the blood-brain barrier. This report aims to increase awareness of this condition and avoid unnecessary management

Isolated Acute Hearing Loss as the Presenting Symptom of Leptomeningeal Carcinomatosis

Leptomeningeal carcinomatosis is characterized by diffuse infiltration of the meninges by metastatic cancer. We report a rare case of leptomeningeal carcinomatosis with an initial presentation of isolated acute hearing loss. Progressive unsteady gait and multiple cranial nerve palsies ensued. Computed tomography of the chest with contrast revealed a 2 cm nodule over the right upper lung. Cytology of cerebrospinal fluid confirmed the diagnosis of adenocarcinoma. The patient was discharged after diagnosis. Isolated acute hearing loss is a rare initial presentation in leptomeningeal carci-nomatosis, not necessarily with a known history of malignancy. A high index of suspicion is mandatory for accurate diagnosis

Short-term Results of Vagus Nerve Stimulation in Pediatric Patients with Refractory Epilepsy

Vagus nerve stimulation (VNS), an alternative method to manage patients with medically intractable epilepsy, has shown favorable results in reducing seizure relapse and improvements in quality of life. In 1997, the U.S. Food and Drug Administration approved the use of this device as an adjunctive therapy for intractable seizure in adults and adolescents older than 12 years of age. Methods: We present a preliminary study of pediatric patients, who suffered from medically intractable seizure and underwent VNS implantation after observation of the baseline seizure frequency. Classification of epileptic syndrome, seizure patterns, age of onset, seizure frequency reduction and adverse effects were recorded. Results: Patients who underwent VNS implantation included four adolescents and four children. The follow-up duration ranged from 9–33 months. All the patients were responders after the beginning of the stimulation. Five of the eight patients responded to VNS with a seizure frequency reduction rate > 50%, and four of the eight patients experienced a ≥ 90% seizure reduction. No significant adverse effects were noted in all patients during the observation period. Conclusion: The effective management of medically intractable seizure remains challenging to most clinical physicians. In addition to ketogenic diet and epilepsy surgery, VNS provides an alternative way to manage this issue. Our results suggest that VNS is well tolerated in pediatric patients, and is a favorable and safe method of treating intractable seizure in common clinical practice

Increased Intrinsic Connectivity of the Default Mode Network in Temporal Lobe Epilepsy: Evidence from Resting-State MEG Recordings

<div><p>The electrophysiological signature of resting state oscillatory functional connectivity within the default mode network (DMN) during spike-free periods in temporal lobe epilepsy (TLE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in TLE, and we examined the effect of lateralized TLE on functional connectivity. Sixteen medically intractable TLE patients and 22 controls participated in this study. Whole-scalp 306-channel MEG epochs without interictal spikes generated from both MEG and EEG data were analyzed using a minimum norm estimate (MNE) and source-based imaginary coherence analysis. With this processing, we obtained the cortical activation and functional connectivity within the DMN. The functional connectivity was increased between DMN and the right medial temporal (MT) region at the delta band and between DMN and the bilateral anterior cingulate cortex (ACC) regions at the theta band. The functional change was associated with the lateralization of TLE. The right TLE showed enhanced DMN connectivity with the right MT while the left TLE demonstrated increased DMN connectivity with the bilateral MT. There was no lateralization effect of TLE upon the DMN connectivity with ACC. These findings suggest that the resting-state functional connectivity within the DMN is reinforced in temporal lobe epilepsy during spike-free periods. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction and prognosis in patients with TLE.</p></div

Clinical characteristic of TLE patients.

<p>R, right; L, left; T, temporal lobe; CPS, complex partial seizure</p><p>SPS, simple partial seizure; SGTCS, secondary generalized tonic-clonic seizure</p><p>MTS, mesial temporal sclerosis; VM, vascular malformation</p><p>Encephalom, encephalomalacia; F, frontal; AEDs, anti-epileptic drugs</p><p>Clinical characteristic of TLE patients.</p