Functional neurological disorder (FND) is a prevalent neurologic condition, yet existing treatment approaches yield inconsistent outcomes. We propose a unifying framework that conceptualizes FND as a disorder triggered and perpetuated by individuals lacking targeted tools to reconcile the cumulative impact of intolerance of uncertainty (IU) and multidimensional allostatic overload. Expanding upon predictive coding and IU theories from neuroscience and psychology research, we argue that during times of uncertainty, individuals with FND exhibit a higher rate of prediction error but lack the energy, resources, and adaptive capacity to respond. This sustained hyperactivation of the brain and body trigger and perpetuate FND. We propose that FND treatment requires a strategic and progressively tiered behavioral approach. First, the individual with FND must be taught behavioral skills to gain immediate symptom control and shift automatic, hyperactive processes into conscious awareness. Only then, can practices from Acceptance and Commitment Therapy, Dialectical Behavioral Therapy, and Mindfulness Therapy be leveraged. These practices help explicitly identify sources of uncertainty and teach how to effectively respond to hyperactive processes with skills that optimize function, commitment to values, and well-being. This framework offers testable hypotheses and a pathway to more effective, individualized care for FND.

Background Difficulty tolerating the uncertainty of ambiguous or unpredictable situations may influence how patients with functional motor disorder (FMD) respond to treatment. However, only one study has examined the role of intolerance of uncertainty (IU) in FMD treatment.Objectives This study sought to expand on prior findings in a larger sample of patients with FMD who completed an intensive motor-retraining programme.Methods A consecutive cohort of 109 patients with FMD completed a 1-week intensive outpatient motor-retraining programme. Patients rated their IU using the Intolerance of Uncertainty Scale-12 and functional motor outcomes using three empirical measures before and after treatment. Univariate and multivariable analyses were conducted to (1) characterise the rate of elevated IU, (2) evaluate potential changes in IU across the programme, (3) examine whether changes in IU predict improvements in motor functioning and (4) determine if IU incrementally predicts functional improvements in patients with clinically elevated IU.Results Findings revealed that clinically elevated IU was common (yielding a base rate of 44%) and that the ‘prospective’ subtype of IU significantly decreased with 1 week of FMD treatment. Change in IU was not significantly associated with improved functional outcomes across the sample. However, change in prospective IU did predict patient-specific functional outcomes among those with clinically elevated IU (R2=11%).Conclusions Findings support prior work suggesting that certain subtypes of IU are common, modifiable and related to treatment outcomes in FMD. The ‘prospective’ subtype of IU may represent an operative factor that can enhance the efficacy of existing FMD rehabilitation programmes.

Background Intolerance of Uncertainty (IU) has never been explored in functional motor disorder (FMD) or any functional neurological disorder but perceptions of control are theoretically relevant. Objective To evaluate if IU changes in people with FMD completing intensive 1-week motor retraining treatment, and if IU change associates with outcome. Methods A consecutive cohort of 45 FMD patients completed a 1-week intensive outpatient motor retraining treatment. At program beginning and end, patients self-rated IU using the Intolerance of Uncertainty Scale-12 (IUS-12) and four functional impairment measures. Paired t-tests analyzed program changes in IU and functional outcomes. Linear regressions analyzed association strength between IU change and outcome. Results IU improved with FMD treatment (p < 0.001). Pre- to post-treatment IU was improved in 32/45 (71%), stable in 5/45 (11%), and worsened in 8/45 (18%). Age, symptom duration, and FMD phenotype did not predict IU improvement. Self-rated function improved across measures with treatment (p < 0.001). Program change in IU positively predicted outcome on 3 of 4 measures. Conclusions IU improves with FMD rehabilitation, even without explicit psychological focus of treatment, regardless of age or FMD phenotype. Improving IU associates with positive FMD treatment outcomes suggesting an important treatment target in FMD.

Psychologists have been applying neurorehabilitation models of care for many years. These practitioners come from different training backgrounds and use a variety of titles to refer to themselves despite considerable overlap in practice patterns, professional identification, and salary. Titles like 'neurorehabilitation psychologist' and 'rehabilitation neuropsychologist' are sometimes used by practitioners in the field to indicate their specialty area, but are not formally recognized by the American Psychological Association, the American Board of Professional Psychology, or by training councils in clinical neuropsychology (CN) or rehabilitation psychology (RP). Neither the CN or RP specialties alone fully address or define the competencies, skill sets, and clinical experiences required to provide high quality, comprehensive neurorehabilitation psychology services across settings. Therefore, irrespective of practice setting, we believe that both clinical neuropsychologists and rehabilitation psychologists should ideally have mastery of specific, overlapping competencies and a philosophical approach to care that we call neurorehabilitation psychology in this paper. Trainees and early career professionals who aspire to practice in this arena are often pressured to prioritize either CN or RP pathways over the other, with anxiety about perceived and real potential for falling short in their training goals. In the absence of an explicit training path or formal guidelines, these professionals emerge only after the opportunity, privilege, or frank luck of working with specific mentors or in exceptional patient care settings that lend themselves to obtaining integrated competencies in neurorehabilitation psychology. This paper reflects the efforts of 7 practitioners to preliminarily define the practice and philosophies of neurorehabilitation psychology, the skill sets and competencies deemed essential for best practice, and essential training pathway elements. We propose competencies designed to maximize the integrity of training and provide clear guideposts for professional development.

Objective: To critically review contemporary theoretical models, diagnostic approaches, clinical features, and assessment findings in Functional Cognitive Disorder (FCD), and make recommendations for neuropsychological evaluation of this condition. Method: Narrative review. Results: FCD is common in neuropsychological practice. It is characterized by cognitive symptoms that are not better explained by another medical or psychiatric disorder. The cognitive symptoms are associated with distress and/or limitations in daily functioning, but are potentially reversible with appropriate identification and treatment. Historically, a variety of diagnostic frameworks have attempted to capture this condition. A contemporary conceptualization of FCD positions it as a subtype of Functional Neurological Disorder, with shared and unique etiological factors. Patients with FCD tend to perform normally on neuropsychological testing or demonstrate relatively weak memory acquisition (e.g. list learning trials) in comparison to strong attention and delayed recall performance. Careful history-taking and behavioral observations are essential to support the diagnosis of FCD. Areas of ongoing controversy include operationalizing "internal inconsistencies" and the role of performance validity testing. Evidence for targeted interventions remains scarce. Conclusions: Neuropsychologists familiar with FCD can uniquely contribute to the care of patients with this condition by improving diagnostic clarity, richening case formulation, communicating effectively with referrers, and leading clinical management. Further research is needed to refine diagnosis, prognosis, and treatment.

Treatment trials for functional seizure (FS) help improve functioning and reduce disability in affected individuals. Clinical trials have prioritized clinician-defined outcomes, but no studies have directly asked adults with FS what they hope to accomplish. This study examined patient-defined goals for treatment in a consecutive cohort of 826 adults with FS referred for outpatient treatment. Goals were reviewed and sorted into 6 categories with 32.5% of goals related to seizure management, 21.8% to abstract functional improvement, 20.3% to concrete functional improvement, 14.8% to seizure education, 10.1% to psychiatry tools, and 0.5% to Other. Although treatment trials have prioritized reduced event frequency as a primary outcome, people with FS most frequently prioritize goals for functional improvement. Data suggests that rehabilitation metrics of FS treatment outcome may be just as, or more important to adults with FS than what medical providers prioritize for outcome success. Study findings have implications for how to define FS treatment success and suggest equal prioritization of patient-centered goals to medically-defined goals in trial design.

Aim: To identify and raise awareness of healthcare service gaps for individuals with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Materials & methods: An ALSP patient journey map from symptom onset throughout disease course was developed using existing literature, patient and clinician feedback from a structured workshop and community survey data regarding attitudes toward genetic testing. Results: ALSP diagnosis is frequently delayed due to low awareness of this rare condition and symptom overlap with more common neurological conditions. Multiple factors impact patients' decision-making regarding genetic testing for ALSP, symptom management and participation in research studies. Conclusion: These results highlight the challenges faced by individuals with ALSP and should support program development to improve patient care. PLAIN LANGUAGE SUMMARY Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare and fatal neurological disease. Symptoms generally appear between the ages of 40 and 50 years and worsen rapidly. Many patients have changes in memory, personality, behavior, and movement.A patient journey map shows important events that patients experience over the course of a disease. The map can be used to identify challenges that patients face and where the quality of medical care can be improved. This patient journey map for ALSP is based on published scientific articles, a workshop where patients and others who have experience with ALSP talked about their challenges, and answers to questions from a survey on genetic testing for ALSP.The map shows that diagnosis of ALSP is often delayed. Because ALSP is a rare disease, few medical providers have experience managing it. Medical providers may not suspect it because many ALSP symptoms overlap with symptoms of other common neurologic diseases. Genetic testing is needed to be sure that a person has ALSP, but it can be hard for patients to get tested since it is expensive and there may not be a testing center nearby. Finally, some people might not want to get tested if they are fearful of getting a diagnosis.This patient journey map should be used to raise awareness of ALSP and the challenges faced by patients and those who care for them. It may also help researchers and medical providers know how to better support patients who have ALSP. TWEETABLE ABSTRACT This patient journey map, developed to identify gaps in the care of patients with ALSP, highlights diagnostic challenges and barriers to genetic testing. It should be used to guide future research and advocacy to address challenges and better meet the needs of the ALSP community.

Coronavirus disease 2019 (COVID-19) infection is associated with risk of persistent neurocognitive and neuropsychiatric complications. It is unclear whether the neuropsychological manifestations of COVID-19 present as a uniform syndrome or as distinct neurophenotypes with differing risk factors and recovery outcomes. We examined post-acute neuropsychological profiles following SARS-CoV-2 infection in 205 patients recruited from inpatient and outpatient populations, using an unsupervised machine learning cluster analysis, with objective and subjective measures as input features. This resulted in three distinct post-COVID clusters. In the largest cluster (69%), cognitive functions were within normal limits, although mild subjective attention and memory complaints were reported. Vaccination was associated with membership in this “normal cognition” phenotype. Cognitive impairment was present in the remaining 31% of the sample but clustered into two differentially impaired groups. In 16% of participants, memory deficits, slowed processing speed, and fatigue were predominant. Risk factors for membership in the “memory-speed impaired” neurophenotype included anosmia and more severe COVID-19 infection. In the remaining 15% of participants, executive dysfunction was predominant. Risk factors for membership in this milder “dysexecutive” neurophenotype included disease-nonspecific factors such as neighborhood deprivation and obesity. Recovery outcomes at 6-month follow-up differed across neurophenotypes, with the normal cognition group showing improvement in verbal memory and psychomotor speed, the dysexecutive group showing improvement in cognitive flexibility, and the memory-speed impaired group showing no objective improvement and relatively worse functional outcomes compared to the other two clusters. These results indicate that there are multiple post-acute neurophenotypes of COVID-19, with different etiological pathways and recovery outcomes. This information may inform phenotype-specific approaches to treatment.

Patients with psychogenic nonepileptic seizure (PNES) who fail performance validity testing (PVT) may appear to produce non-valid cognitive profiles. Consequently, they may not get referred to treatment and events persist, with worsening disability and high resource utilization. As a result, we report pre- and post-treatment neuropsychological evaluation findings in a 59-year-old woman with a confirmed diagnosis of PNES established using video-EEG monitoring. At pre-treatment baseline neuropsychological evaluation, PNES events occurred weekly to daily. Performance was impaired across PVTs and across multiple cognitive domains. After behavioral intervention specific to PNES, these events substantially reduced in frequency to rare stress-induced flares. Post-treatment neuropsychological evaluation revealed marked improvement of most cognitive and behavioral scores from baseline, and valid PVT scores. We review predisposing, precipitating, and perpetuating factors for PNES and cognitive impairment in this case and discuss the patient's outcome from treatment. Effectively managing PNES events and dissociative tendencies while reducing unnecessary pharmacological interventions appears to have allowed this patient to function closer to her optimal state. This case illustrates the complexity of Functional Neurologic Disorder (FND) clinical presentation and challenges the assumption that suboptimal neuropsychological performance predicts poor treatment engagement and outcome. We showcase the reversibility of PNES and cognitive manifestations of FND using targeted psychotherapeutic interventions, which resulted in reduced disability and associated healthcare costs, as well as re-engagement in life.

Introduction:The neuropsychological profile of CSF1R-related leukoencephalopathy (CRL) is undefined. This study defines the profile, contrasts it with that of other dementia syndromes, and highlights measures sensitive to cognitive impairment.Methods:We administered a standardized battery of neuropsychological tests to five consecutive CRL cases.Results:The neuropsychological profile of CRL reflects impaired general cognitive function, processing speed, executive function, speeded visual problem solving, verbal fluency, and self-reported depression and anxiety. Confrontation naming and memory are preserved. Within cognitive domains, certain measures more frequently identified impairment than others.Discussion:CRL impairs general cognitive function, processing speed, executive function. Language and visual problem solving may be impaired if processing speed is required. Confrontation naming and memory are uniquely preserved, contrasting CRL to other dementia syndromes. Cognitive screens excluding processing speed and executive function may not detect CRL cognitive manifestations. Findings sharply define cognitive impairment of CRL and inform cognitive test selection.

discuss prophylactic with presymptomatic CSF1R pathogenic variant carriers.

The objective of this study is to determine the effect of hematopoietic stem cell transplantation (HSCT) on disease progression in patients with CSF1R-related leukoencephalopathy.

BACKGROUND:Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease-modifying treatment. OBJECTIVE:The objective of this study was to determine the effect of HSCT on disease progression. METHODS:We collected all available clinical data from a cohort of 7 patients with CSF1R-related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board-certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI). RESULTS:Our patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow-up time (median, 11; range, 2-27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden. CONCLUSIONS:This is the largest series of patients with CSF1R-related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to be considered when evaluating a patient's candidacy for transplant. HSCT appears to be the first disease-modifying therapy for CSF1R-related leukoencephalopathy. This milestone may serve as a foothold toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease-specific therapies. © 2021 International Parkinson and Movement Disorder Society.

Objectives: Patients with aneurysmal subarachnoid hemorrhage (aSAH) often sustain substantial cognitive and functional impairment. Traditional outcome measures have emphasized radiographic and gross clinical outcomes, but cognitive and functional outcomes are less frequently documented. This pilot study assessed the feasibility of administering longitudinal cognitive and neuropsychological testing and tracked patterns of functional improvement in aSAH patients. Patients and methods: Standardized cognitive and neuropsychological testing were administered to a prospective cohort of aSAH patients admitted for treatment to our tertiary care center. Thirty consecutive aSAH patients (Hunt and Hess score 1-3) were enrolled over 23-months and baseline evaluations were completed within 24-h after admission. Patients were followed prospectively after treatment (coiling or clipping) at 1-, 3-, 6-, and 12-months. Functional outcome measures included the Montreal Cognitive Assessment, the Neuropsychiatric Inventory-Questionnaire, and the Functional Activities Questionnaire. Results: Of the 30 patients, 23 (77%) followed-up at 3-months, 21 (70%) at 6-months, and 19 (63%) at 12-months. Improvement from baseline to follow-up at 12-months was noted for general cognitive function (p = .004), memory (p = .025), and executive function (p = .039), with the greatest improvement occurring within 6-months. Daily function also improved mostly within 6-months (p = .022) while changes in neuropsychological disturbances were insignificant from baseline to follow-up at 12-months (p = .216). Conclusion: Standardized cognitive and neuropsychological testing provides metrics for evaluating functional outcomes following treatment of aSAH. The addition of a brief battery of tests to routine clinical and radiographic evaluations is feasible. The main limitations are related to practice and referral patterns, and future studies are needed to evaluate the impact of treatment modalities on functional outcomes.

Tuesday, April 28April 14, 2020Free AccessMultivariate Analysis of Survival in an Amyotrophic Lateral Sclerosis Clinic Population (5268)Jaimin Shah, Marka Van Blitterswijk, Rosa Rademakers, Otto Pedraza, Beth Rush, Jany Paulett, Janay Caradonna, Leonard Petrucelli, and Bjorn OskarssonAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.5268 Letters to the Editor

ObjectiveThe objective of this study was to describe clinical features, [18F]‐fluorodeoxyglucose (FDG)‐positron emission tomography (PET) metabolism and digital pathology in patients with logopenic progressive aphasia (LPA) and pathologic diagnosis of diffuse Lewy body disease (DLBD) and compare to patients with LPA with other pathologies, as well as patients with classical features of probable dementia with Lewy bodies (pDLB).MethodsThis is a clinicopathologic case‐control study of 45 patients, including 20 prospectively recruited patients with LPA among whom 6 were diagnosed with LPA‐DLBD. We analyzed clinical features and compared FDG‐PET metabolism in LPA‐DLBD to an independent group of patients with clinical pDLB and regional α‐synuclein burden on digital pathology to a second independent group of autopsied patients with DLBD pathology and antemortem pDLB (DLB‐DLBD).ResultsAll patients with LPA‐DLBD were men. Neurological, speech, and neuropsychological characteristics were similar across LPA‐DLBD, LPA‐Alzheimer's disease (LPA‐AD), and LPA‐frontotemporal lobar degeneration (LPA‐FTLD). Genetic screening of AD, DLBD, and FTLD linked genes were negative with the exception of APOE ε4 allele present in 83% of LPA‐DLBD patients. Seventy‐five percent of the patients with LPA‐DLBD showed a parietal‐dominant pattern of hy pometabolism; LPA‐FTLD – temporal‐dominant pattern, whereas LPA‐AD showed heterogeneous patterns of hypometabolism. LPA‐DLBD had more asymmetrical hypometabolism affecting frontal lobes, with relatively spared occipital lobe in the nondominantly affected hemisphere, compared to pDLB. LPA‐DLBD had minimal atrophy on gross brain examination, higher cortical Lewy body counts, and higher α‐synuclein burden in the middle frontal and inferior parietal cortices compared to DLB‐DLBD.InterpretationWhereas AD is the most frequent underlying pathology of LPA, DLBD can also be present and may contribute to the LPA phenotype possibly due to α‐synuclein‐associated functional impairment of the dominant parietal lobe. ANN NEUROL 2021;89:520–533