Materiały źródłowe

• #1 Functional Neurologic Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551567/

  Functional neurologic disorder, formally conversion disorder, is a psychiatric disorder characterized by signs and symptoms affecting sensory or motor function inconsistent with patterns of known neurologic diseases or other medical conditions and significantly impacting the patients ability to function. […] Conversion disorder, also known as functional neurological symptom disorder (FND), is a psychiatric disorder characterized by symptoms affecting sensory or motor function. These signs and symptoms are inconsistent with patterns of known neurologic diseases or other medical conditions. Although functional neurologic disorder has no organic basis, the symptoms significantly impact a patients ability to function. […] Psychological, social, and biological factors can all contribute to, precipitate, or perpetuate functional neurologic disorder. Often, there is a trauma, adverse life event, or acute/chronic stressor preceding symptoms of functional neurologic disorder.

• #2 Mayo Clinic Health Library – Functional neurologic disorder/conversion disorder | Swiss Medical Network

  https://www.swissmedical.net/fr/healtcare-library/con-20228115

  Functional neurologic disorder a newer and broader term that includes what some people call conversion disorder features nervous system (neurological) symptoms that can’t be explained by a neurological disease or other medical condition. […] The cause of functional neurologic disorder is unknown. The condition may be triggered by a neurological disorder or by a reaction to stress or psychological or physical trauma, but that’s not always the case. Functional neurologic disorder is related to how the brain functions, rather than damage to the brain’s structure (such as from a stroke, multiple sclerosis, infection or injury). […] The exact cause of functional neurologic disorder is unknown. Theories regarding what happens in the brain to result in symptoms are complex and involve multiple mechanisms that may differ, depending on the type of functional neurological symptoms.

• #2 Functional Neurologic Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551567/

  The hypotheses formulated to explain the etiology and the pathogenetic mechanisms of FND are manifold. For example, the role of microglia and neuroimmunity and, in turn, the altered control of synaptic plasticity have theoretical explanations. These processes could explain the FND-associated motor dysfunctions. […] Neurobiological models suggest that functional neurologic disorder results from changes in higher-order cortical processing. The general, broad hypothesis is that frontal and subcortical areas of the brain may be activated by emotional stress, which then leads to input to inhibitory basal ganglia-thalamocortical circuits, which then reduce conscious sensory or motor processing. […] One study conducted by Spence et al. compared three patients with weakness secondary to functional neurologic disorder with both normal controls and controls that researchers asked to feign weakness. The patients were asked to move a joystick while undergoing PET comparison. The patients with functional neurologic disorder demonstrated decreased left dorsolateral prefrontal cortical activity when they attempted to move the affected limb. This study suggests that patients with functional neurologic disorder are distinct from those who are feigning symptoms.

• #3 Functional Neurologic Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551567/

  Another study by Voon et al. examined the relationship between emotion and symptom production in patients with functional neurologic disorder. Researchers asked the patients to perform an emotional task, and functional MRI showed an abnormal correlation between activation of the amygdala and the supplementary motor area.

• #4 A Framework for Understanding the Pathophysiology of Functional Neurological Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7930164/

  The symptoms of functional neurological disorder (FND) are a product of its pathophysiology. The pathophysiology of FND is reflective of dysfunction within and across different brain circuits that, in turn, affects specific constructs. […] While we have gained a considerable understanding of FND, there is more work to be done, including determining how pathophysiological abnormalities arise as a consequence of etiologic biopsychosocial factors of FND. […] The different symptoms of FND arise from one or a combination of specific abnormal constructs. […] Abnormal constructs can be mapped onto specific brain circuits. […] A diminished sense of agency, for example, is mediated by dysfunction involving a multimodal integration network, including the right temporoparietal junction (TPJ).

• #5 A Framework for Understanding the Pathophysiology of Functional Neurological Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7930164/

  Conceptually, it is important to highlight that the salience network overlaps with the central pain matrix and the multimodal integration network, underscoring the importance of these overlapping circuits not only in emotion processing but also in other interrelated constructs. […] Patients with FND have movements which lack self-agency and are experienced as involuntary. […] A number of studies have shown right TPJ dysfunction in patients with hyperkinetic movement disorders, as was first demonstrated in functional tremor. […] While more work is needed to clarify this process, there are at least two possibilities: either the TPJ agency circuit is impaired or the feedforward signal is abnormal due to abnormal influences on the motor apparatus. […] Impairments in attention have been characterized in FND.

• #6 A Framework for Understanding the Pathophysiology of Functional Neurological Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7930164/

  The salience circuit, used as the primary example here, comprises the dorsal anterior cingulate cortex, anterior insula, dorsal amygdala, periaqueductal gray (PAG), and hypothalamus, and is implicated in detecting and responding to homeostatic demands. […] Heightened emotional reactivity, arousal and defensive responses occur from increased bottom-up amygdala and PAG activations. […] This under-regulation of emotional response is relevant to deficits in fear extinction, while over-regulation is linked to dissociative responses. […] Task and resting-state neuroimaging studies in FND show increased functional connectivity between salience/limbic/paralimbic and motor control circuits. […] Increased limbic-motor circuit connectivity is theorized to represent heightened limbic influence over motor behavior in patients with FND.

• #7 Conversion disorder/functional neurological disorder – a narrative review on current research into its pathological mechanism | European Journal of Psychiatry

  https://www.elsevier.es/en-revista-european-journal-psychiatry-431-articulo-conversion-disorder-functional-neurological-disorder–S0213616320300367

  This study only showed two thirds of participants have an elevated CRP reading. This emphasises the complexity of the condition as if it was a simple pathology where inflammation was the one and only cause, you would expect a much higher majority of the patients with FND to have an elevated CRP reading. However, since only two thirds of patients had elevated CRP levels, it indicates a more complicated process is the underlying cause. […] Upregulation of sympathetic nervous system and downregulation of parasympathetic nervous system would cause an inflammatory state in the body. […] The aforementioned theories hypothesised from Kozlowska indicated that there was a possible pathology of CD/FND that involved changes in activity on the brain’s glial cells. […] This dysregulation of autonomic nervous system has been well recorded in this population.

• #8 Conversion disorder/functional neurological disorder – a narrative review on current research into its pathological mechanism | European Journal of Psychiatry

  https://www.elsevier.es/es-revista-european-journal-psychiatry-431-articulo-conversion-disorder-functional-neurological-disorder–S0213616320300367

  The neuroendocrine system is intrinsic in controlling inflammation in both the CNS and further-a-field, and with the glial cells being highly sensitive to changes in the hypothalamic-pituitary adrenal axis (HPA), the main producer of glucocorticoids, this could mean that glial cells are involved in the pathophysiology of CD/FND. […] The current level of research suggests a correlation between inflammation and adverse childhood events, with links between inflammation and CD/FND. However, interestingly there seems to be trends in CD/FND symptoms where only certain symptoms are caused by certain inflammatory factors. […] Finally, there seems to be a collection of proteins and structures that seem to be involved in the overall pathogenesis of FND, including BDNF, inflammatory factors, and the limbic system. Currently, there is no direct relationship between all these different factors with no explanation how they are involved in the pathophysiology, or even if they are directly involved or merely a change that occurs because of different processes having knock-on effects.

• #9 Understanding Functional Neurological Disorder: Recent Insights and Diagnostic Challenges

  https://www.mdpi.com/1422-0067/25/8/4470

  Functional neurological disorder (FND), formerly called conversion disorder, is a condition characterized by neurological symptoms that lack an identifiable organic purpose. […] Recent advances in neuroimaging and a deeper exploration of its epidemiology, pathophysiology, and clinical presentation have shed new light on this disorder. […] The etiology of Functional Neurological Symptom Disorder, formerly known as conversion disorder, is multifaceted, involving various biological, psychological, and social factors. […] Several neurobiological factors contribute to functional neurological disorder (FND). In patients with FND, abnormalities have been reported in neurotransmitters such as dopamine, serotonin, and gamma-aminobutyric acid (GABA). […] Moreover, the presence of inflammatory markers and microglial activation in FND patients suggests a possible immune-mediated mechanism of symptom generation.

• #10 Understanding Functional Neurological Disorder: Recent Insights and Diagnostic Challenges

  https://www.mdpi.com/1422-0067/25/8/4470

  FND may also be caused by abnormalities in neuroplasticity, including synaptic plasticity and cortical reorganization, which affect the brain’s ability to adapt to environmental stressors and maintain normal neuronal function. […] Neuroimaging studies have started to unveil the complex neural circuitry involved in FND, pointing towards a multi-network brain disorder implicating limbic, salience, self-agency, multimodal integration, and attentional and sensorimotor circuits. […] The pathophysiology of functional neurological disorder (FND) is multifaceted, involving complex interactions across various neural networks. […] Recent advancements in neuroimaging have been pivotal in elucidating these mechanisms, revealing alterations in limbic, salience, self-agency, multimodal integration, attentional, and sensorimotor circuits.

• #11 Glutamatergic dysfunction, neuroplasticity, and redox status in the peripheral blood of patients with motor conversion disorders (functional movement disorders): a first step towards potential biomarkers discovery | Translational Psychiatry

  https://www.nature.com/articles/s41398-023-02500-8

  Functional movement disorders (FMD) are characterized by the presence of neurological symptoms that cannot be explained by typical neurological diseases or other medical conditions. […] First evidence showed that, compared to healthy controls (CTR), FMD patients presented increased levels of glutamate+glutamine in the anterior cingulate cortex/medial prefrontal cortex, and decreased levels of glutamate in the cerebrospinal fluid, suggesting that a glutamatergic dysfunction might play a role in FMD pathophysiology. […] Our findings give further evidence that glutamatergic dysfunction might be involved in the pathophysiology of FMD, possibly representing a biomarker of disease; moreover, since glutamatergic and dopaminergic systems are closely interconnected, our results might have a relevance in terms of treatment options for FMD patients.

• #12 Glutamatergic dysfunction, neuroplasticity, and redox status in the peripheral blood of patients with motor conversion disorders (functional movement disorders): a first step towards potential biomarkers discovery | Translational Psychiatry

  https://www.nature.com/articles/s41398-023-02500-8

  Recent evidence highlighted the presence of alterations in levels of glutamate, the major excitatory neurotransmitter, in patients with FMD: in a recent case-control study conducted with magnetic resonance spectroscopy (MRS), our group detected an increase of glutamate + glutamine (Glx) levels in the limbic system of patients suffering from FMD, with respect to healthy controls (CTR). […] In a subsequent study, we found significantly lower glutamate levels in the cerebrospinal fluid (CSF) of FMD patients, compared to CTR, again arguing in favor of a glutamatergic dysfunction in patients with FMD. […] Our results lead us to hypothesize, first, that a dysregulation of the glutamatergic pathway would be present in patients with FMD, possibly representing a biomarker of disease. […] These findings are in line with our previous studies arguing in favor of a glutamatergic dysfunction in FMD: compared to CTR, FMD patients showed increased levels of Glx in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and lower cerebrospinal fluid CSF levels of glutamate.

• #13 Conversion Disorders: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/287464-overview

  Conversion symptoms suggest a physical disorder but are the result of psychological factors. According to the psychodynamic model, the symptoms are a consequence of emotional conflict, with the repression of conflict into the unconscious. In the late 1880s, Freud and Breuer suggested that hysterical symptoms resulted from the intrusion of „memories connected to psychical trauma” into the somatic innervation. This mind-to-body process was referred to as conversion. Others have introduced attachment theory as a means to understanding conversion disorder in terms of the freeze response and the appeasement defense behavior seen in animal subjects. […] The patient has been postulated to derive primary and secondary gain. With primary gain, the symptoms allow the patient to express the conflict that has been suppressed unconsciously. With secondary gain, symptoms allow the patient to avoid unpleasant situations or garner support from friends, family, and the medical system that would otherwise be unobtainable. According to sociocultural theories, the direct expression of emotions is impermissible and somatization takes its place. In behavioral models, conversion symptoms are viewed as a learned maladaptive behavior that is reinforced by the environment.

• #14 Understanding Functional Neurological Disorder: Recent Insights and Diagnostic Challenges

  https://www.mdpi.com/1422-0067/25/8/4470

  Cognitive-behavioral models suggest that its functional neurologic symptoms may result from cognitive, emotional, and behavioral influences at the subconscious levels of processing. […] Neurobiologic models suggest that FND is posited to involve intricate abnormalities in the neural networks, rather than being linked to a singular brain structure anomaly. […] The Bayesian model offers a theoretical framework that is increasingly used to conceptualize the pathophysiology of functional neurological disorder (FND). […] Understanding FND through the lens of the Bayesian model has significant implications for treatment.

• #15 Mechanism of Functional Neurological Symptoms | ACNR Journal

  https://acnr.co.uk/articles/mechanism-of-functional-neurological-symptoms/

  The crucial first step in the production of functional symptoms is therefore proposed to be the instigation of an abnormal belief/expectancy relating to the symptom(s). […] The second step required for symptom generation is simply the activation of this ‘rogue representation’ / ‘previously mapped conversion motor representation’ / ‘abnormal intermediate level prior’. […] The last step in the model is that activation of the ‘rogue representation’ is not accompanied by the normal neural ‘baggage’ that accompanies voluntary movement or normal sensory experience, and hence it is misattributed by the patient as being a symptom and out of their control.

• #16 Mayo Clinic Health Library – Functional neurologic disorder/conversion disorder | Swiss Medical Network

  https://www.swissmedical.net/fr/healtcare-library/con-20228115

  Basically, parts of the brain that control the functioning of your muscles and senses may be involved, even though no disease or abnormality exists. […] Symptoms of functional neurologic disorder may appear suddenly after a stressful event, or with emotional or physical trauma. Other triggers may include changes or disruptions in how the brain functions at the structural, cellular or metabolic level. But the trigger for symptoms can’t always be identified.

• #17 Conversion Disorder: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17975-conversion-disorder

  Functional neurological symptom disorder better known as conversion disorder is a mental health condition that causes physical symptoms. The symptoms happen because your brain converts the effects of a mental health issue into disruptions of your brain or nervous system. The symptoms are real but dont match up with recognized brain-related conditions. […] Conversion disorder creates disruptions in your brain that cause physical symptoms. Functional MRI which lets experts see your brain activity can see the effects of conversion disorder. People who have conversion disorder usually have less activity or unusual activity in parts of their brain related to their symptoms. Those changes in brain activity arent something a person can fake. […] Experts dont know exactly why conversion disorder happens. However, they do know that its more likely to happen along with certain circumstances and some medical conditions. […] Common circumstances seen in people with conversion disorder include: A history of childhood abuse. Having other mental health conditions, especially depression or anxiety. A recent stressful or traumatic event. A recent health condition or event acting as a trigger for conversion disorder.

• #18 Functional Movement Disorders: Updates and Clinical Overview

  https://www.e-jmd.org/journal/view.php?doi=10.14802/jmd.24126

  Functional movement disorder (FMD) is a type of functional neurological disorder that is common but often difficult to diagnose or manage. […] Recent neuroimaging studies that aid in understanding the pathophysiology are also discussed. […] While functional disorders have been most commonly referred to as psychogenic or conversion disorder in the past few decades, they have historically been termed hysteria. […] Much progress has been made in research on FMD, and recent work in the past 20 years has improved the understanding and management of this disorder. […] Recent fMRI studies have shown that there is decreased functional connectivity between the right temporoparietal junction (TPJ) and bilateral sensorimotor regions and impaired hemodynamic responsiveness of the dorsolateral prefrontal cortex and presupplementary cortex to changes in the loss of movement control in patients with FMD.

• #19 Functional Movement Disorders: Updates and Clinical Overview

  https://www.e-jmd.org/journal/view.php?doi=10.14802/jmd.24126

  Dysfunction of these areas, which play a role in self-agency, is thought to contribute to patients subjective sense of involuntariness in abnormal movements. […] More recent studies have continued to examine the neurobiological importance of early-life maltreatment (ELM) in the development of FND or FMD. […] These findings highlight the effects of early-life physical or sexual abuse in the development of FMD, as well as gene-environment interactions that may be relevant. […] Studies conducted on FMD thus far support the relationship between emotional processing and this disorder on the basis of altered activation of brain regions relevant to emotional processing and increased functional connectivity between these areas and movement-related brain regions. […] It is encouraging to see renewed interest in this disorder and active measures being taken, such as use of the proposed terminology of FMD, as well as progress in research leading to increased understanding of the pathophysiology.

• #20 Decade of progress in motor functional neurological disorder: continuing the momentum | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/92/6/668

  Functional neurological disorder (FND) is a prevalent, disabling and costly condition at the neurologypsychiatry intersection. […] Mechanistically, greater importance has been given to determining how functional neurological symptoms develop, highlighting roles for misdirected attention, expectation and self-agency, as well as abnormal influences of emotion/threat processing brain areas on motor control circuits. […] Recent work, using neuroimaging and other experimental approaches, has also begun to contextualise the role of emotion/threat processing in the pathophysiology of mFND. […] An important implication of this work has been to support mFND as a brain-based condition. […] The path forward is one that continues building an integrated, mechanistic framework for mFND that is neither exclusively psychological nor neurological.

• #21 Functional Neurological Disorder: Historical Trends and Urgent Directions | Velazquez-Rodriquez | Journal of Neurology Research

  https://www.neurores.org/index.php/neurores/article/view/754/722

  Common pathophysiological processes across various FND subtypes have been demonstrated in clinical trials, and the need for a transdiagnostic approach capable of therapeutically targeting shared dysfunctional cognitive, emotional, autonomic, behavioral, and social dynamics, has been proposed. […] The frequent dysfunction in these four networks: limbic, cognitive, autonomic, and sensorimotor (somatic), has not been systematically assembled into educational and management models. […] An integrative pathophysiological model could prompt physicians to investigate with patients, in a biographically and biopsychosocial-spiritual manner, how their risk factors, represented by the outer boxes, could have given origin to dysfunctional limbic, autonomic, sensorimotor (somatic), and cognitive processes.

• #22 Functional Neurological Disorder: Historical Trends and Urgent Directions | Velazquez-Rodriquez | Journal of Neurology Research

  https://www.neurores.org/index.php/neurores/article/view/754/722

  Functional neurological disorder (FND) is caused by dysfunctional structures, and networks within the nervous system, in the presence of normal anatomy and tissue structure, what experts convey as normal hardware but dysfunctional software. […] The pathophysiological mechanisms of FND may include the following: 1) Childhood trauma and epigenetics; 2) Psychological model and the limbic system; 3) Defense mechanisms; 4) Cognitive and learning theories; 5) Hypnosis model; and 6) Stress and neurobiological theories. […] Summarizing in a single model, all the pathophysiological evidence described in the above theories, can deepen our understanding of the dysfunctional processes taking place within the nervous system, and affecting the physical body, while avoiding mind-body dualism. […] The involvement of these four functional regions, limbic system, neo-cortex, ANS, sensorimotor processes, in the pathophysiology of FND has been demonstrated in the studies cited in the previous sections.

• #23 Functional Neurological Disorder: Historical Trends and Urgent Directions | Velazquez-Rodriquez | Journal of Neurology Research

  https://www.neurores.org/index.php/neurores/article/view/754/722

  A multi-network treatment algorithm is founded in an all-inclusive pathophysiological model and targets all the dysfunctional processes within the limbic, autonomic, sensorimotor (somatic) and cognitive networks, regardless of the patients identified etiology or lack of thereof, as some patients describe not having been exposed to the most common risk factors.

• #24 A Framework for Understanding the Pathophysiology of Functional Neurological Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7930164/

  Attentional abnormalities have been well characterized using neuropsychological testing, with disruptions in sustained and selective attention observed in some individuals with FND. […] Interoception refers to the process by which the nervous system senses, interprets, and integrates internal bodily signals, providing a moment-by-moment mapping of the body’s internal landscape across conscious and unconscious levels. […] Mechanistically, interoception is conceptualized as a bidirectional process between the brain and body, with feedback and feedforward loops leading to an internal representation of the body. […] Neural circuits of interoception include those mapping autonomic, chemosensory, endocrine, and immune systems. […] The pathophysiology of FND unfolds within the context of developmental trajectories, life experiences, sex differences, social-cultural norms and many other factors within a biopsychosocial model.

• #25 A Framework for Understanding the Pathophysiology of Functional Neurological Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7930164/

  Adverse early life events are one example. […] In FND, it is not only the occurrence of stressful events and elevation of biological stress markers, but also the addition of greater perceived stress and/or lack of awareness of this stress that appears to contribute to and result from the underlying pathophysiology. […] Overall, while there are other fruitful research directions not addressed by this article, we have detailed important constructs and circuits implicated in the pathophysiology of FND that would benefit from additional rigorous research inquiry to move the field forward.

• #26 A framework for understanding the pathophysiology of functional neurological disorder | CNS Spectrums | Cambridge Core

  https://www.cambridge.org/core/journals/cns-spectrums/article/framework-for-understanding-the-pathophysiology-of-functional-neurological-disorder/C37DBE94BB9BDD90CDEBF7640EAF7D0D

  The symptoms of functional neurological disorder (FND) are a product of its pathophysiology. The pathophysiology of FND is reflective of dysfunction within and across different brain circuits that, in turn, affects specific constructs. […] While we have gained a considerable understanding of FND, there is more work to be done, including determining how pathophysiological abnormalities arise as a consequence of etiologic biopsychosocial factors. […] To facilitate advances in this underserved and important area, we propose a pathophysiology-focused research agenda to engage government-sponsored funding agencies and foundations.

• #27 Functional Neurological Disorders: Exploring Unmet Needs – UT Southwestern Medical Center

  https://physicianresources.utswmed.org/news/functional-neurological-disorders-exploring-unmet-needs

  Neuropsychiatry, a field of medicine committed to understanding brain-behavior relationships, is well positioned to advance our understanding of contributing risk factors and the neural mechanisms underlying FNDs, says Chadrick Lane, M.D., Assistant Professor of Psychiatry and the inaugural Clinical Neuroscience Scholar within the Peter ODonnell Jr. Brain Institute at UT Southwestern Medical Center. […] Dr. Lane notes that neuroimaging studies have illustrated differences in those living with an FND compared to those without an FND. Networks in the brain responsible for emotional regulation, allocation of attention, and the perception of volitional control over movements may be working less effectively in those with an FND. […] The fundamental pathophysiology of all FNDs remains incomplete. Current understanding includes overactivity of the limbic system, symptom modeling as part of a predictive coding framework, and dysfunction of self-agency networks. Studies have demonstrated brain anatomical differences (gray matter volume and cortical thickness) and connectivity differences using fMRI between patients with an FND compared to those without.

• #28 Functional Neurological Disorders: Exploring Unmet Needs – UT Southwestern Medical Center

  https://physicianresources.utswmed.org/news/functional-neurological-disorders-exploring-unmet-needs

  These early studies, though in their infancy, note alterations in brain function that may provide clues to the neural underpinnings of FNDs however, longitudinal studies are still needed to address the question of causality, Dr. Lane says. […] FNDs are real conditions that arise from extraordinarily complex biological, psychological, and social interactions. Recovery is possible, he concludes.

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