Toward a Precision Medicine Approach to the Outpatient Assessment and Treatment of Functional Neurological Disorder.

Functional neurological disorder (FND) is a neuropsychiatric condition. In this field, prospective psychotherapy trials and consensus recommendations for physiotherapy, occupational therapy, and speech language therapy have been published. However, significant clinical complexities remain. "Rule in" signs - while critical for making a positive diagnosis - do not equate to a personalized treatment plan in many instances. Here, we propose that the neuropsychiatric assessment and real-time development of a work-in-progress biopsychosocial clinical formulation aids the development of a patient-centered outpatient treatment plan. This precision medicine approach is based on the literature, expert opinions and our clinical experience working in an interdisciplinary FND service.

A machine learning eye movement detection algorithm using electrooculography.

STUDY OBJECTIVES: Eye movement quantification in polysomnograms (PSG) is difficult and resource intensive. Automated eye movement detection would enable further study of eye movement patterns in normal and abnormal sleep, which could be clinically diagnostic of neurologic disorders, or used to monitor potential treatments. We trained a long short-term memory (LSTM) algorithm that can identify eye movement occurrence with high sensitivity and specificity. METHODS: We conducted a retrospective, single-center study using one-hour PSG samples from 47 patients 18-90 years of age. Team members manually identified and trained an LSTM algorithm to detect eye movement presence, direction, and speed. We performed a 5-fold cross validation and implemented a "fuzzy" evaluation method to account for misclassification in the preceding and subsequent 1-second of gold standard manually labeled eye movements. We assessed G-means, discrimination, sensitivity, and specificity. RESULTS: Overall, eye movements occurred in 9.4% of the analyzed EOG recording time from 47 patients. Eye movements were present 3.2% of N2 (lighter stages of sleep) time, 2.9% of N3 (deep sleep), and 19.8% of REM sleep. Our LSTM model had average sensitivity of 0.88 and specificity of 0.89 in 5-fold cross validation, which improved to 0.93 and 0.92 respectively using the fuzzy evaluation scheme. CONCLUSION: An automated algorithm can detect eye movements from EOG with excellent sensitivity and specificity. Noninvasive, automated eye movement detection has several potential clinical implications in improving sleep study stage classification and establishing normal eye movement distributions in healthy and unhealthy sleep, and in patients with and without brain injury.

Multimodal deep learning for Alzheimer's disease dementia assessment.

Worldwide, there are nearly 10 million new cases of dementia annually, of which Alzheimer's disease (AD) is the most common. New measures are needed to improve the diagnosis of individuals with cognitive impairment due to various etiologies. Here, we report a deep learning framework that accomplishes multiple diagnostic steps in successive fashion to identify persons with normal cognition (NC), mild cognitive impairment (MCI), AD, and non-AD dementias (nADD). We demonstrate a range of models capable of accepting flexible combinations of routinely collected clinical information, including demographics, medical history, neuropsychological testing, neuroimaging, and functional assessments. We then show that these frameworks compare favorably with the diagnostic accuracy of practicing neurologists and neuroradiologists. Lastly, we apply interpretability methods in computer vision to show that disease-specific patterns detected by our models track distinct patterns of degenerative changes throughout the brain and correspond closely with the presence of neuropathological lesions on autopsy. Our work demonstrates methodologies for validating computational predictions with established standards of medical diagnosis.

Using the Biopsychosocial Model to Guide Patient-Centered Neurological Treatments.

The biopsychosocial model was defined by George L. Engel to propose a holistic approach to patient care. Through this model, physicians can understand patients in their context to aid the development of tailored, individualized treatment plans that consider relevant biological, psychological, and social-cultural-spiritual factors impacting health and longitudinal care. In this article, we advocate for the use of the biopsychosocial model in neurology practice across outpatient and inpatient clinical settings. To do so, we first present the history of the biopsychosocial model, and its relationships to precision medicine and deep phenotyping. Then, we bring the neurologist up-to-date information on the components of the biopsychosocial clinical formulation, including predisposing, precipitating, perpetuating, and protective factors. We conclude by detailing illustrative neurological case examples using the biopsychosocial model, emphasizing the importance of considering relevant psychological and social factors to aid the delivery of patient-centered clinical care in neurology.

Neuropsychiatric Treatment Approaches for Functional Neurological Disorder: A How to Guide.

There is a growing body of knowledge regarding management of functional neurological disorder (FND). The aim of this article is to guide the clinician through FND clinical management, from delivery of the diagnosis, to creation of a biopsychosocially-informed treatment plan, to troubleshooting common issues that arise throughout longitudinal care. We review the evidence and core principles of both rehabilitative therapies (physical therapy, occupational therapy, and speech and language therapy) and psychological therapies for the treatment of FND, and discuss the benefits of engaging a multidisciplinary and interdisciplinary team. The optimal timing of specific therapeutic interventions is also discussed, emphasizing a patient-centered perspective. Resources for further reading, for both patients and clinicians, are provided throughout. Additional research is needed to further optimize the therapeutic approach to patients with FND, including the need to develop novel treatments for those that do not positively respond to currently available interventions.

Evaluation and Management of First-Time Seizure in Adults.

First seizures are often perceived as devastating events by patients and their families due to the fear of having a life-long disease. One in 10 people experiences one or more seizures during their lifetime, while 1 in 26 people develops epilepsy. Acute symptomatic seizures are often related to a provoking factor or an acute brain insult and typically do not recur. Careful history and clinical examination should guide clinicians' management plans. Electroencephalography and brain imaging, preferably with epilepsy-specific magnetic resonance imaging, may help characterize both etiology and risk of seizure recurrence. Antiepileptic drugs should be initiated in patients with newly diagnosed epilepsy. In patients without an epilepsy diagnosis, the decision to prescribe drugs depends on individual risk factors for seizure recurrence and possible complications from seizures, which should be discussed with the patient. Counseling about driving and lifestyle modifications should be provided early, often at the first seizure encounter.

A journey into the unknown: An ethnographic examination of drug-resistant epilepsy treatment and management in the United States.

Patients often recognize unmet needs that can improve patient-provider experiences in disease treatment management. These needs are rarely captured and may be hard to quantify in difficult-to-treat disease states such as drug-resistant epilepsy (DRE). To further understand challenges living with and managing DRE, a team of medical anthropologists conducted ethnographic field assessments with patients to qualitatively understand their experience with DRE across the United States. In addition, healthcare provider assessments were conducted in community clinics and Comprehensive Epilepsy Centers to further uncover patient-provider treatment gaps. We identified four distinct stages of the treatment and management journey defined by patients' perceived control over their epilepsy: Gripped in the Panic Zone, Diligently Tracking to Plan, Riding a Rollercoaster in the Dark, and Reframing Priorities to Redefine Treatment Success. We found that patients sought resources to streamline communication with their care team, enhanced education on treatment options beyond medications, and long-term resources to protect against a decline in control over managing their epilepsy once drug-resistant. Likewise, treatment management optimization strategies are provided to improve current DRE standard of care with respect to identified patient-provider gaps. These include the use of digital disease management tools, standardizing neuropsychiatrists into patients' initial care team, and introducing surgical and non-pharmacological treatment options upon epilepsy and DRE diagnoses, respectively. This ethnographic study uncovers numerous patient-provider gaps, thereby presenting a conceptual framework to advance DRE treatment. Further Incentivization from professional societies and healthcare systems to support standardization of the treatment optimization strategies provided herein into clinical practice is needed.

Social aspects of life in patients with functional seizures: Closing the gap in the biopsychosocial formulation.

The human, as a biological system, is an open system embedded within larger systems -including the family, culture, and socio-political environment. In this context, a patient with functional seizures (FS) is embedded in relationships, educational/professional institutions, culture, and society. Both connection to these broader systems and the quality of these connections, as well as the soundness of each system in and of itself, influence the health and well-being of patients in positive or negative ways. The social aspects of life are important determinants of health and quality of life across the lifespan. The current narrative review brings out several overarching themes in patients with FS. Sections on attachment, marriage, social networking, and stigma highlight the central roles of supportive and affirmative relationships across the lifespan. The section on education underscores the importance of keeping children and youth with FS connected within their school environments, as well as managing any barriers - learning difficulties, school response to FS events, stigma, etc.-that can diminish this connection. Finally, the sections on employment and driving highlight the value of being an active participant in one's society. In summary, FS impacts patients across most social aspects of life domains regardless of age - factors that are important when developing biopsychosocial formulations. This review concludes that the multidisciplinary management of FS requires careful assessment of social aspects of life in patients which can then be targeted for treatment, to improve their quality of life, facilitating recovery, and reducing the risk of relapse.

Predicting problematic pornography use among male returning US veterans.

Problematic Pornography Use (PPU) is the most common problem behavior among individuals with compulsive sexual behavior (CSB). Previous research suggests US veterans are at a greater risk of engaging in PPU. The present study sought to investigate further PPU among male military veterans. Data from 172 male veterans who endorsed ever watching pornography and completed the Problematic Pornography Use Scale (PPUS) were included in the study. Participants completed self-report questionnaires, including demographic information, psychiatric co-morbidities, impulsivity, as measured by the UPPS-P, pornography-related behaviors, and pornography craving as measured by Pornography Craving Questionnaire (PCQ). Younger age and lower educational attainment were associated with higher PPUS scores. Depression, anxiety, post-traumatic stress disorder (PTSD), insomnia, and impulsivity were positively associated with higher PPUS scores. There was no statistically significant association between PPU with suicidal ideation or alcohol use disorder. In the multivariable hierarchical regression, depression, frequency of use, and higher PCQ scores were associated with higher PPUS scores, although only the latter two remained significant in the final model. Understanding the risk factors via more frequent screening for PPU will help with the development of treatment protocols for this problematic behavior.

Towards an Outpatient Model of Care for Motor Functional Neurological Disorders: A Neuropsychiatric Perspective.

Functional neurological disorder (FND), a condition at the intersection of neurology and psychiatry, is a common and disabling outpatient referral to neurology and neuropsychiatry clinics. In this perspective article, we focus on the motor spectrum of FND (mFND), including individuals with functional movement disorders (FND-movt), functional limb weakness/paresis (FND-par) and functional [psychogenic non-epileptic/dissociative] seizures (FND-seiz). Over the past several decades, there have been dedicated efforts within the neurologic and psychiatric communities to create "rule-in" diagnostic criteria, as well as thoughtful approaches to the clinical interview, delivery of the diagnosis and the development of a patient-centered treatment plan. These advances allow the promotion of good clinical practices in the outpatient assessment and management of mFND. Informed by the literature and our prior clinical experiences, we provide suggestions on how to evaluate individuals with suspected functional motor symptoms - including conducting sensitive psychiatric and psychosocial screenings. Additional sections discuss common "rule-in" neurological examination and semiologic signs of motor FND, as well as approaches to deliver the diagnosis and formulate a treatment plan based on individual patient needs. To aid the development of shared (partially overlapping) expertise that catalyzes an interdisciplinary approach to mFND, the use of physiotherapy for therapeutic motor retraining and cognitive behavioral therapy to examine relationships between symptoms, thoughts, behaviors and emotions are also discussed. Additional clinical research is needed to further refine and operationalize the assessment and management of mFND, across clinics, healthcare settings and countries.