Faculty Bibliography

The term "startle" describes a sudden involuntary movement of the body in response to an unexpected stimulus. The startle reflex in humans is a normal physiologic symmetric flexor response present starting around 6 weeks of age and remaining for life. Conditions with an abnormal or exaggerated startle are collectively referred to as startle syndromes, and are a rare, heterogeneous group of disorders. The startle syndromes are categorized into three broad groups: (1) hyperekplexia, (2) stimulus-induced disorders, and (3) neuropsychiatric startle disorders. While startle syndromes are often relatively benign, medical emergencies can arise as complications from the abnormal startle. Most concerning is the increased morbidity and mortality from apneic episodes in patients with hyperekplexia, which can unfortunately lead to sudden death. Therefore, prompt recognition and treatment of this disorder is imperative. In this chapter, we review the normal human startle reflex and then provide an overview of the startle syndromes, with a particular focus on hyperekplexia given the movement disorder emergencies seen in this syndrome.
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BACKGROUND:Alzheimer's disease, the most common cause of dementia, causes a progressive and irreversible deterioration of cognition that can sometimes be difficult to diagnose, leading to suboptimal patient care. METHODS:We developed a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted MRI scans, with or without cognitive scores. For each patient, a biomarker called "Alzheimer's Predictive Vector" (ApV) was derived using a two-stage least absolute shrinkage and selection operator (LASSO). RESULTS:is significantly altered in patients with ADrp-like phenotype. CONCLUSIONS:This new data analytic method demonstrates potential for increasing accuracy of Alzheimer diagnosis.

Background and objectives/UNASSIGNED:) in a group of cognitively normal middle-aged and older adults. Methods/UNASSIGNED:Our study was a retrospective analysis of prospectively collected data. Subjects were enrolled for studies assessing the role of hippocampal hemodynamics as a biomarker for AD among cognitively healthy elderly individuals (age > 50). Participants without cognitive impairment, stroke, and active substance abuse were recruited between January 2008 and November 2017 at the NYU Grossman School of Medicine, former Center for Brain Health. All subjects underwent medical, psychiatric, and neurological assessments, blood tests, and MRI examinations. To estimate CVR, we increased their carbon dioxide levels using a rebreathing protocol. Relationships between BMI and brain measures were tested using linear regression. Results/UNASSIGNED:in women (β = -0.20, unstandardized B = -0.08, 95% CI -0.13, -0.02). Discussion/UNASSIGNED:These findings lend support to the notion that obesity is a risk factor for hippocampal hemodynamic impairment and suggest targeting obesity as an important prevention strategy. Prospective studies assessing the effects of weight loss on brain hemodynamic measures and inflammation are warranted.

BACKGROUND:Tuberous sclerosis complex (TSC) and some focal cortical dysplasias (FCDs) are associated with dysfunctional mTOR signaling, resulting in increased cell growth and ribosomal S6 protein phosphorylation (phospho-S6). mTOR inhibitors can reduce TSC tumor growth and seizure frequency, and preclinical FCD studies indicate seizure suppression. This pilot study evaluated safety of mTOR inhibitor everolimus in treatment resistant (failure of >2 anti-seizure medications) TSC and FCD patients undergoing surgical resection and to assess mTOR signaling and molecular pathways. METHODS AND FINDINGS/RESULTS:We evaluated everolimus in 14 treatment resistant epilepsy patients undergoing surgical resection (4.5 mg/m2 daily for 7 days; n = 4 Active, mean age 18.3 years, range 4-26; n = 10, Control, mean age 13.1, range 3-45). Everolimus was well tolerated. Mean plasma everolimus in Active participants were in target range (12.4 ng/ml). Brain phospho-S6 was similar in Active and Control participants with a lower trend in Active participants, with Ser235/236 1.19-fold (p = 0.67) and Ser240/244 1.15-fold lower (p = 0.66). Histologically, Ser235/236 was 1.56-fold (p = 0.37) and Ser240/244 was 5.55-fold lower (p = 0.22). Brain proteomics identified 11 proteins at <15% false discovery rate associated with coagulation system (p = 1.45x10-9) and acute phase response (p = 1.23x10-6) activation. A weighted gene correlation network analysis (WGCNA) of brain proteomics and phospho-S6 identified 5 significant modules. Higher phospho-S6 correlated negatively with cellular respiration and synaptic transmission and positively with organophosphate metabolic process, nuclear mRNA catabolic process, and neuron ensheathment. Brain metabolomics identified 14 increased features in Active participants, including N-acetylaspartylglutamic acid. Plasma proteomics and cytokine analyses revealed no differences. CONCLUSIONS:Short-term everolimus before epilepsy surgery in TSC and FCD resulted in no adverse events and trending lower mTOR signaling (phospho-S6). Future studies should evaluate implications of our findings, including coagulation system activation and everolimus efficacy in FCD, in larger studies with long-term treatment to better understand molecular and clinical effects. CLINICAL TRIALS REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT02451696.

The utility of the Victoria Symptom Validity Test (VSVT) as a performance validity test (PVT) has been primarily established using response accuracy scores. However, the degree to which response latency may contribute to accurate classification of performance invalidity over and above accuracy scores remains understudied. Therefore, this study investigated whether combining VSVT accuracy and response latency scores would increase predictive utility beyond use of accuracy scores alone. Data from a mixed clinical sample of 163 patients, who were administered the VSVT as part of a larger neuropsychological battery, were analyzed. At least four independent criterion PVTs were used to establish validity groups (121 valid/42 invalid). Logistic regression models examining each difficulty level revealed that all VSVT measures were useful in classifying validity groups, both independently and when combined. Individual predictor classification accuracy ranged from 77.9 to 81.6%, indicating acceptable to excellent discriminability across the validity indices. The results of this study support the value of both accuracy and latency scores on the VSVT to identify performance invalidity, although the accuracy scores had superior classification statistics compared to response latency, and mean latency indices provided no unique benefit for classification accuracy beyond dimensional accuracy scores alone.

It is now well-established that essential tremor (ET) can manifest with different clinical presentations and progressions (i.e., upper limb tremor, head tremor, voice tremor, lower limb tremor, task- or position-specific tremor, or a combination of those). Common traits and overlaps are identifiable across these different subtypes of ET, including a slow rate of progression, a response to alcohol and a positive family history. At the same time, each of these manifestations are associated with specific demographic, clinical and treatment-response characteristics suggesting a family of diseases rather than a spectrum of a syndrome. Here we summarize the most important clinical, demographic, neuropathological and imagingfeatures of ET and of its subtypes to support ET as a family of identifiable conditions. This classification has relevance for counseling of patients with regard to disease progression and treatment response, as well as for the design of therapeutic clinical trials.