Taken together, these data suggest that most GJB1 mutations cause neuropathy by a loss of normal connexin 32 function. Therefore, treatment of male patients with Charcot-Marie-Tooth disease type 1X may prove amenable to gene replacement strategies.

Charcot-Marie-Tooth disease type 1A (CMT1A), the most frequent form of CMT, is caused by a 1.5 Mb duplication on the short arm of chromosome 17. Patients with CMT1A typically have slowed nerve conduction velocities (NCVs), reduced compound motor and sensory nerve action potentials (CMAPs and SNAPs), distal weakness, sensory loss and decreased reflexes. In order to understand further the molecular pathogenesis of CMT1A, as well as to determine which features correlate with neurological dysfunction and might thus be amenable to treatment, we evaluated the clinical and electrophysiological phenotype in 42 patients with CMT1A. In these patients, muscle weakness, CMAP amplitudes and motor unit number estimates correlated with clinical disability, while motor NCV did not. In addition, loss of joint position sense and reduction in SNAP amplitudes also correlated with clinical disability, while sensory NCV did not. Taken together, these data strongly support the hypothesis that neurological dysfunction and clinical disability in CMT1A are caused by loss or damage to large calibre motor and sensory axons. Therapeutic approaches to ameliorate disability in CMT1A, as in amyotrophic lateral sclerosis and other neurodegenerative diseases, should thus be directed towards preventing axonal degeneration and/or promoting axonal regeneration.

Twelve patients with refractory temporal lobe epilepsy and unilateral hippocampal sclerosis had repeat volumetric magnetic resonance imaging scans after a mean of 3.4 years to determine whether progressive hippocampal volume loss occurred. Seizure-free patients showed no change in hippocampal volume. Patients with continuing seizures had a decline in ipsilateral hippocampal volume that correlated with seizure frequency. Patients with medically refractory temporal lobe epilepsy and unilateral hippocampal sclerosis have progressive hippocampal atrophy.

OBJECTIVE We determined the clinical impact and developmental changes of auditory-language-related augmentation of gamma activity at 50–120 Hz recorded on electrocorticography (ECoG). METHODS We analyzed data from 77 epileptic patients ranging 4 – 56 years in age. We determined the effects of seizure-onset zone, electrode location, and patient-age upon gamma-augmentation elicited by an auditory-naming task. RESULTS Gamma-augmentation was less frequently elicited within seizure-onset sites compared to other sites. Regardless of age, gamma-augmentation most often involved the 80–100 Hz frequency band. Gamma-augmentation initially involved bilateral superior-temporal regions, followed by left-side dominant involvement in the middle-temporal, medial-temporal, inferior-frontal, dorsolateral-premotor, and medial-frontal regions and concluded with bilateral inferior-Rolandic involvement. Compared to younger patients, those older than 10 years had a larger proportion of left dorsolateral-premotor and right inferior-frontal sites showing gamma-augmentation. The incidence of a post-operative language deficit requiring speech therapy was predicted by the number of resected sites with gamma-augmentation in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions of the left hemisphere assumed to contain essential language function (r2=0.59; p=0.001; odds ratio=6.04 [95% confidence-interval: 2.26 to 16.15]). CONCLUSIONS Auditory-language-related gamma-augmentation can provide additional information useful to localize the primary language areas. SIGNIFICANCE These results derived from a large sample of patients support the utility of auditory-language-related gamma-augmentation in presurgical evaluation.

Objective We measured cortical gamma-oscillations in response to visual-language tasks consisting of picture naming and word reading in an effort to better understand human visual-language pathways. Methods We studied six patients with focal epilepsy who underwent extraoperative electrocorticography (ECoG) recording. Patients were asked to overtly name images presented sequentially in the picture naming task and to overtly read written words in the reading task. Results Both tasks commonly elicited gamma-augmentation (maximally at 80–100 Hz) on ECoG in the occipital, inferior-occipital-temporal and inferior-Rolandic areas, bilaterally. Picture naming, compared to reading task, elicited greater gamma-augmentation in portions of pre-motor areas as well as occipital and inferior-occipital-temporal areas, bilaterally. In contrast, word reading elicited greater gamma-augmentation in portions of bilateral occipital, left occipital-temporal and left superior-posterior-parietal areas. Gamma-attenuation was elicited by both tasks in portions of posterior cingulate and ventral premotor-prefrontal areas bilaterally. The number of letters in a presented word was positively correlated to the degree of gamma-augmentation in the medial occipital areas. Conclusions Gamma-augmentation measured on ECoG identified cortical areas commonly and differentially involved in picture naming and reading tasks. Longer words may activate the primary visual cortex for the more peripheral field. Significance The present study increases our understanding of the visual-language pathways.

Objective We determined the utility of electrocorticography (ECoG) and stimulation for detecting language-related sites in patients with left-hemispheric language-dominance on Wada test. Methods We studied 13 epileptic patients who underwent language mapping using event-related gamma-oscillations on ECoG and stimulation via subdural electrodes. Sites showing significant gamma-augmentation during an auditory-naming task were defined as language-related ECoG sites. Sites at which stimulation resulted in auditory perceptual changes, failure to verbalize a correct answer, or sensorimotor symptoms involving the mouth were defined as language-related stimulation sites. We determined how frequently these methods revealed language-related sites in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions. Results Language-related sites in the superior-temporal and inferior-frontal gyri were detected by ECoG more frequently than stimulation (p < 0.05), while those in the dorsolateral-premotor and inferior-Rolandic regions were detected by both methods equally. Stimulation of language-related ECoG sites, compared to the others, more frequently elicited language symptoms (p < 0.00001). One patient developed dysphasia requiring in-patient speech therapy following resection of the dorsolateral-premotor and inferior-Rolandic regions containing language-related ECoG sites not otherwise detected by stimulation. Conclusions Language-related gamma-oscillations may serve as an alternative biomarker of underlying language function in patients with left-hemispheric language-dominance. Significance Measurement of language-related gamma-oscillations is warranted in presurgical evaluation of epileptic patients.

Objectives The goal of this study was to determine the consistency of human reviewer spike detection and then develop a computer algorithm to make the intracranial spike detection process more objective and reliable. Methods Three human reviewers marked interictal spikes on samples of intracranial EEGs from 10 patients. The sensitivity, precision and agreement in channel ranking by activity were calculated between reviewers. A computer algorithm was developed to parallel the way human reviewers detect spikes by first identifying all potential spikes on each channel using frequency filtering and then block scaling all channels at the same time in order to exclude potential spikes that fall below an amplitude and slope threshold. Its performance was compared to the human reviewers on the same set of patients. Results Human reviewers showed surprisingly poor inter-reviewer agreement, but did broadly agree on the ranking of channels for spike activity. The computer algorithm performed as well as the human reviewers and did especially well at ranking channels from highest to lowest spike frequency. Conclusions Our algorithm showed good agreement with the different human reviewers, even though they demonstrated different criteria for what constitutes a ‘spike’ and performed especially well at the clinically important task of ranking channels by spike activity. Significance An automated, objective method to detect interictal spikes on intracranial recordings will improve both research and the surgical management of epilepsy patients.

This article characterizes gating in normal subjects using P50, N100, and P200 components in a paired-click paradigm and compares the test-retest reliabilities of the three components. Sixty-seven normal subjects had gating data from a standard paired-click paradigm; 30 had test-retest data. The test-retest reliability of the amplitudes, latencies, and sensory gating indices derived from the P50, N100, and P200 responses were compared. Measured gating ratios showed either normal or positively skewed distributions. Test-retest reliability of the P50 gating ratio did not reach significance, but N100 and P200 ratios showed better reliability (.50 and .64). The P50 difference score was more reliable (.61), and the N100 and P200 test-retest reliabilities of difference scores were high (.83 and .81, respectively). N100 and P200 attenuation is reliable; further work is needed to develop more reliable P50 gating measures.