Faculty Bibliography

Mutations of the TRIM8 gene coding for a tripartite motif protein have been reported in a patient with epileptic encephalopathy by Sakai and colleagues. We present here two additional patients with TRIM8 mutations: an eight year old girl with pharmacoresistant epileptic encephalo-pathy associated with stereotypies and glomerular protei-nuria, and further clinical details of a patient reported by the Epi4K consortium. Exome sequencing revealed de novo truncating mutations of TRIM8 in our patient as well as the patient from the trio sequenced by the Epi4K consortium. The de novo mutations were confirmed by Sanger sequencing. Our case presented nephrotic syndrome not reported in the patient of Sakai and colleagues and the Epi4K consortium case. The clinical presentation of these patients overlaps with Galloway-Mowat syndrome, but mutations in the WDR73 gene were absent suggesting a Galloway-Mowat-like phenotype in our cases. Moreover, Galloway-Mowat syndrome seems to result in earlier death than in our cases. These observations suggest that phenotypic variability is observed in patients with TRIM8 mutations and genetic testing of TRIM8 should be expanded to patients with EE associated with dysmorphic features or nephrotic syndrome

Over the last decades, psychophysical and electrophysiological studies in patients and animal models of Parkinson's disease (PD), have consistently revealed a number of visual abnormalities. In particular, specific alterations of contrast sensitivity curves, electroretinogram (ERG), and visual-evoked potentials (VEP), have been attributed to dopaminergic retinal depletion. However, fundamental mechanisms of cortical visual processing, such as normalization or "gain control" computations, have not yet been examined in PD patients. Here, we measured electrophysiological indices of gain control in both space (surround suppression) and time (sensory adaptation) in PD patients based on steady-state VEP (ssVEP). Compared with controls, patients exhibited a significantly higher initial ssVEP amplitude that quickly decayed over time, and greater relative suppression of ssVEP amplitude as a function of surrounding stimulus contrast. Meanwhile, EEG frequency spectra were broadly elevated in patients relative to controls. Thus, contrary to what might be expected given the reduced contrast sensitivity often reported in PD, visual neural responses are not weaker; rather, they are initially larger but undergo an exaggerated degree of spatial and temporal gain control and are embedded within a greater background noise level. These differences may reflect cortical mechanisms that compensate for dysfunctional center-surround interactions at the retinal level.

Cingulate epilepsy manifests with a broad range of semiologic features and seizure types. Key clinical features may elucidate ictal involvement of certain subregions of the cingulate gyrus. Ictal and interictal electroencephalogram findings in cingulate epilepsy vary and are often poorly localized, adding to the diagnostic challenge of identifying the seizure onset zone for presurgical cases, particularly in the absence of a lesion on imaging. Recent advances in multimodal imaging techniques may contribute to ictal localization and further our understanding of neural and epileptic pathways involving the cingulate gyrus. Beyond medication and surgical resection, new techniques including stereotactic laser ablation, responsive neurostimulation, and deep brain stimulation offer additional approaches for the treatment of cingulate epilepsy.

Objective: To explore the applicability of an ambulatory inertial sensor (G-walk) to characterize gait function during the Timed Up and Go (TUG) Test under three different conditions.
Background(s): In Parkinson's disease (PD), the current lack of both reliable and feasible biomarkers of gait function and mobility limits the objective characterization of motor ability, clinical progression, and responsiveness to treatments. Current assessments of motor function rely on a clinicians' subjective judgement and/or the patient's self-reported questionnaires, which are not sensitive in capturing subtle changes over time and restrict comparability across raters. Ambulatory inertial sensors allow for non-invasive, wireless transmission of accurate quantitative data and therefore, may represent a useful tool in ambulatory settings. Design/Methods: Nineteen (19) PD patients (H&Y <4) and 10 agematched controls (CTRL) were consecutively enrolled to undergo inertial TUG (iTUG) testing under three experimental conditions: normal walking (iTUGnorm), dual task walking (iTUGcog), and at maximum speed (iTUGfast). The time needed to complete each test was sub-divided into six distinct phases quantified by the sensor: sitto- stand (1), forward gait (2), mid-turn (3), return gait (4), end-turn (5) and stand-to-sit (6). Other assessments included UDPRS Part III, MoCA, depression, fatigue, Benton and Rey-Osterrieth visual tests.
Result(s): A total of nineteen PD patients and ten CTRLs completed all assessments. PD patients were divided into mild (H&Y=2, n=12) and moderate (H&Y=3, n=7) disease severity. One-way-ANOVA and correlation analysis were performed. Different patterns of kinematic performance were observed (figure 1.A and 1.B). In PD, iTUG correlations were found with cognitive function, visual performance and motor severity, while in CTRLs there was only a correlation with motor performance only. iTUGfast performance seemed more sensitive experimental condition when PD was stratify by severity (figure 1.B).
Conclusion(s): iTUG assessed by an ambulatory inertial sensor is a quick, sensitive and feasible tool for objective measurements of functional mobility in PD. Utilizing validate tests for mobility and gait under different stress conditions can provide distinct information of gait function and mobility. Future longitudinal studies are warranted to better characterize the sensitivity to disease progression and the potential for monitoring and optimizing therapeutic interventions in this patient population. (Figure Presented)

Background/UNASSIGNED:There are multiple complications reported for anterior cervical diskectomy and fusion (ACDF), one of the most common cervical spine operations performed in the US (e.g. estimated at 137,000 ACDF/year). Methods/UNASSIGNED:Multiple studies analyzed the risks and complications rates attributed to ACDF. Results/UNASSIGNED:In multiple studies, overall morbidity rates for ACDF varied from 13.2% to 19.3%. These included in descending order; dysphagia (1.7%-9.5%), postoperative hematoma (0.4%-5.6% (surgery required in 2.4% of 5.6%), with epidural hematoma 0.9%), exacerbation of myelopathy (0.2%-3.3%), symptomatic recurrent laryngeal nerve palsy (0.9%-3.1%), cerebrospinal fluid (CSF) leak (0.5%-1.7%), wound infection (0.1-0.9%-1.6%), increased radiculopathy (1.3%), Horner's syndrome (0.06%-1.1%), respiratory insufficiency (1.1%), esophageal perforation (0.3%-0.9%, with a mortality rate of 0.1%), and instrument failure (0.1%-0.9%). There were just single case reports of an internal jugular veing occlusion and a phrenic nerve injury. Pseudarthrosis occurred in ACDF and was dependant on the number of levels fused; 0-4.3% (1-level), 24% (2-level), 42% (3 level) to 56% (4 levels). The reoperation rate for symptomatic pseudarthrosis was 11.1%. Readmission rates for ACDF ranged from 5.1% (30 days) to 7.7% (90 days postoperatively). Conclusions/UNASSIGNED:Complications attributed to ACDF included; dysphagia, hematoma, worsening myelopathy, recurrent laryngeal nerve palsy, CSF leaks, wound infection, radiculopathy, Horner's Syndrome, respiratory insufficiency, esophageal perforation, and instrument failure. There were just single case reports of an internal jugular vein thrombosis, and a phrenic nerve injury. As anticipated, pseudarthrosis rates increased with the number of ACDF levels, ranging from 0-4.3% for 1 level up to 56% for 4 level fusions.