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NEUROBIOLOGY OF PSYCHOGENIC NONE-EPILEPTIC EVENTS

Psychogenic non-epileptic events/eizure (PNES) are disabling and frequent. The diagnosis is based on clinical features and is reliable. However, misconception about the neurobiology of PNES prevents a good communication of the diagnosis and many patients and/or caregivers avoid clarifying or naming the diagnosis as there is a fear to address the issue of what “psychogenic” may mean and represent in terms of stigmatization. This talk will highlight what neurosciences has found over the last decades to better understand the neurobiology of PNES and how brain mechanisms may be involved in this disorder. It will address the question of misconception and myths surrounding the diagnosis of PNES. It will show that neural networks (motor control, multimodal integration, emotion regulation, attention) play a role in the disorder along with genetic and environmental (bio-psycho-social) factors

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Psychogenic nonepileptic seizures (PNES) represent a common diagnostic problem in routine neurologic practice and consist of paroxysmal, time-limited alterations in motor, sensory, autonomic, and/or cognitive signs and symptoms that are not accompanied by ictal epileptiform activity. Estimates vary but most published data suggest that about 20% patients referred to epilepsy centers for recurrent refractory seizures have PNES. Moreover, disease duration prior to establishing the diagnosis of PNES may be very long, which illustrates that PNES are usually not missed but are misclassified and inappropriately treated for a long time as epilepsy.

Most PNES patients fulfill the diagnostic criteria of conversion/dissociative disorders, addressing the diagnosis towards a psychiatric – rather than neurological - domain. Notably, advanced neuroimaging studies revealed abnormalities of the sensori-motor network and its connections in patients with psychogenic movement disorders, providing a unifying pathomechanism that may underlie both these conditions for an organic brain disorder. The clinical scenario of PNES is further complicated by the co-occurrence of several psychopathological diseases, frequently reactive to traumatic events. A large body of evidence suggests that experiences of trauma are closely linked to PNES and a significant proportion of patients report sexual abuse. Likewise, there is evidence that dissociative and depressive symptoms in PNES patients are linked to a positive history of sexual abuse. Overall, identifying these key risk factors highlight the importance of considering different psychotherapeutic approaches on the basis of the particular subgroup of patients with PNES.

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Psychogenic diseases are attributable to a variety of psychological and social factors that may trigger the onset of symptoms and influence the course of the disease. Whenever psychological factors are involved, both placebo effects and their evil twins, nocebo effects, play an important role. These involve a number of mechanisms, ranging from expectation, anxiety, reward to learning phenomena, such as Pavlovian conditioning, cognitive and social learning. There is also some evidence of different genetic variants in placebo responsiveness, and these give rise to high response variability. Overall, the concept that is emerging today is that placebos and drugs share common mechanisms of action. Therefore, the understanding of these mechanisms in placebo responders and nonresponders has important clinical implications and applications, such as reduction of drug intake and diagnosis and management of psychogenic diseases. Overall, exploring placebo responsiveness through a neuroscientific approach gives us insights into the biology of the human brain, better medical care, and better understanding of its impact on society, particularly in those conditions in which the psychogenic nature of the disease plays a key role.