Faculty Bibliography

OBJECTIVE/UNASSIGNED:Since motor nerve conduction slowing can occur due to loss of large axons, we investigate the conduction slowing profile in amyotrophic lateral sclerosis (ALS) and identify the limits beyond which the diagnosis of exclusive axonal loss is unlikely. METHODS/UNASSIGNED:First, using linear regression analysis, we established the range of motor conduction slowing in 76 chronic inflammatory demyelinating polyneuropathy (CIDP) patients. Demyelinating range confidence intervals were defined by assessing conduction velocity (CV), distal latency (DML), and F-wave latency (F) in relation to distal compound muscle action potential (CMAP) amplitude of median, ulnar, fibular, and tibial nerves. Results were subsequently validated in 38 additional CIDP patients. Then, the newly established demyelination confidence intervals were used to investigate the profile of conduction slowing in 95 ALS patients. RESULTS/UNASSIGNED:CV slowing, prolonged DML, and abnormal F were observed in 22.2%, 19.6%, and 47.1% of the studied nerves respectively in ALS patients. When slowing occurred, it affected more than one segment of the motor nerve, suggesting that CMAP amplitude dependent conduction slowing caused by an exclusive loss of large axons is the main mechanism of slowing. No ALS patient had more than 2 nerves with CV slowing in the confidence interval defined by the regression equations or the American Academy of Neurology (AAN) research criteria for CIDP diagnosis. CONCLUSIONS/UNASSIGNED:The presence of more than two motor nerves with CV slowing in the demyelinating range defined by the regression analysis or AAN criteria in ALS patients suggests the contribution of acquired demyelination or other additional mechanisms exist in the electrodiagnostic profile of ALS.

INTRODUCTION/UNASSIGNED:Extracting regularities from ongoing stimulus streams to form predictions is crucial for adaptive behavior. Such regularities exist in terms of the content of the stimuli and their timing, both of which are known to interactively modulate sensory processing. In real-world stimulus streams such as music, regularities can occur at multiple levels, both in terms of contents (e.g., predictions relating to individual notes vs. their more complex groups) and timing (e.g., pertaining to timing between intervals vs. the overall beat of a musical phrase). However, it is unknown whether the brain integrates predictions in a manner that is mutually congruent (e.g., if "beat" timing predictions selectively interact with "what" predictions falling on pulses which define the beat), and whether integrating predictions in different timing conditions relies on dissociable neural correlates. METHODS/UNASSIGNED:= 20) performing a repetition detection task. RESULTS/UNASSIGNED:Our results reveal that temporal predictions based on beat or interval timing modulated mismatch responses to violations of "what" predictions happening at the predicted time points, and that these modulations were shared between types of temporal predictions in terms of the spatiotemporal distribution of EEG signals. Effective connectivity analysis using dynamic causal modeling showed that the integration of "what" and "when" predictions selectively increased connectivity at relatively late cortical processing stages, between the superior temporal gyrus and the fronto-parietal network. DISCUSSION/UNASSIGNED:Taken together, these results suggest that the brain integrates different predictions with a high degree of mutual congruence, but in a shared and distributed cortical network. This finding contrasts with recent studies indicating separable mechanisms for beat-based and memory-based predictive processing.

INTRODUCTION/UNASSIGNED:Alzheimer's disease (AD) and epilepsy are reciprocally related. Among sporadic AD patients, clinical seizures occur in 10-22% and subclinical epileptiform abnormalities occur in 22-54%. Cognitive deficits, especially short-term memory impairments, occur in most epilepsy patients. Common neurophysiological and molecular mechanisms occur in AD and epilepsy. The choroid plexus undergoes pathological changes in aging, AD, and epilepsy, including decreased CSF turnover, amyloid beta (Aβ), and tau accumulation due to impaired clearance and disrupted CSF amino acid homeostasis. This pathology may contribute to synaptic dysfunction in AD and epilepsy. METHODS/UNASSIGNED:= 12) using laser capture microdissection (LCM) followed by label-free quantitative mass spectrometry on the choroid plexus adjacent to the hippocampus at the lateral geniculate nucleus level. RESULTS/UNASSIGNED: DISCUSSION/UNASSIGNED:We found altered signaling pathways in the choroid plexus of severe AD cases and many correlated changes in the protein expression of cell metabolism pathways in AD and epilepsy cases. The shared molecular mechanisms should be investigated further to distinguish primary pathogenic changes from the secondary ones. These mechanisms could inform novel therapeutic strategies to prevent disease progression or restore normal function. A focus on dual-diagnosed AD/epilepsy cases, specific epilepsy syndromes, such as temporal lobe epilepsy, and changes across different severity levels in AD and epilepsy would add to our understanding.

BACKGROUND/UNASSIGNED:Anterior transthoracic, posterolateral (i.e., costotransversectomy/lateral extracavitary), and transpedicular approaches are now utilized to address anterior, anterolateral, or lateral thoracic disk herniations (TDH). Notably, laminectomy has not been a viable option for treating TDH for decades due to the much lower rate of acceptable outcomes (i.e., 57% for decompressive laminectomy vs. over 80% for the posterolateral, lateral, and transthoracic procedures), and a higher risk of neurological morbidity/paralysis. METHODS/UNASSIGNED:Patients with TDH averaged 48-56.3 years of age, and presented with pain (76%), myelopathy (61%-99%), radiculopathy (30%-33%), and/or sphincter loss (16.7%-24%). Those with anterior/anterolateral TDH (30-74%) were usually myelopathic while those with more lateral disease (50-70%) exhibited radiculopathy. Magnetic resonance (MR) studies best defined soft-tissue/disk/cord pathology, CAT scan (CT)/Myelo-CT studies identified attendant discal calcification (i.e. fully calcified 38.9% -65% vs. partial calcification 27.8%), while both exams documented giant TDH filling > 30 to 40% of the canal (i.e., in 43% to 77% of cases). RESULTS/UNASSIGNED:Surgical options for anterior/anterolateral TDH largely included transthoracic or posterolateral approaches (i.e. costotransversectomy, lateral extracavitary procedures) with the occasional use of transfacet/transpedicular procedures mostly applied to lateral disks. Notably, patients undergoing transthoracic, lateral extracavitary/costotransversectomy/ transpedicular approaches may additionally warrant fusions. Good/excellent outcomes were quoted in from 45.5% to 87% of different series, with early postoperative adverse events reported in from 14 to 14.6% of patients. CONCLUSION/UNASSIGNED:Anterior/anterolateral TDH are largely addressed with transthoracic or posterolateral procedures (i.e. costotransversectomy/extracavitary), with a subset also utilizing transfacet/transpedicular approaches typically adopted for lateral TDH. Laminectomy is essentially no longer considered a viable option for treating TDH.

INTRODUCTION:For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy. METHODS:This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and > 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed. RESULTS:Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at >2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale. DISCUSSION:Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores.

OBJECTIVE:To comprehensively examine the associations between changes in carbohydrate intake and weight change at four year intervals. DESIGN:Prospective cohort study. SETTING:Nurses' Health Study (1986-2010), Nurses' Health Study II (1991-2015), and Health Professionals Follow-Up Study (1986-2014). PARTICIPANTS:136 432 men and women aged 65 years or younger and free of diabetes, cancer, cardiovascular disease, respiratory disease, neurodegenerative disorders, gastric conditions, chronic kidney disease, and systemic lupus erythematosus before baseline. MAIN OUTCOME MEASURE:Weight change within a four year period. RESULTS:The final analyses included 46 722 women in the Nurses' Health Study, 67 186 women in the Nurses' Health Study II, and 22 524 men in the Health Professionals Follow-up Study. On average, participants gained 1.5 kg (5th to 95th centile -6.8 to 10.0) every four years, amounting to 8.8 kg on average over 24 years. Among men and women, increases in glycemic index and glycemic load were positively associated with weight gain. For example, a 100 g/day increase in starch or added sugar was associated with 1.5 kg and 0.9 kg greater weight gain over four years, respectively, whereas a 10 g/day increase in fiber was associated with 0.8 kg less weight gain. Increased carbohydrate intake from whole grains (0.4 kg less weight gain per 100 g/day increase), fruit (1.6 kg less weight gain per 100 g/day increase), and non-starchy vegetables (3.0 kg less weight gain per 100 g/day increase) was inversely associated with weight gain, whereas increased intake from refined grains (0.8 kg more weight gain per 100 g/day increase) and starchy vegetables (peas, corn, and potatoes) (2.6 kg more weight gain per 100 g/day increase) was positively associated with weight gain. In substitution analyses, replacing refined grains, starchy vegetables, and sugar sweetened beverages with equal servings of whole grains, fruit, and non-starchy vegetables was associated with less weight gain. The magnitude of these associations was stronger among participants with overweight or obesity compared with those with normal weight (P<0.001 for interaction). Most of these associations were also stronger among women. CONCLUSIONS:The findings of this study highlight the potential importance of carbohydrate quality and source for long term weight management, especially for people with excessive body weight. Limiting added sugar, sugar sweetened beverages, refined grains, and starchy vegetables in favor of whole grains, fruit, and non-starchy vegetables may support efforts to control weight.