Psychogenic non-epileptic seizures

Historical Perspective

Initially, the disease was observed in 1900 BCE by the Egyptians and the condition was named hysteria, at the rise of Christianity at that time it was considered a demon possession. Later a similar condition was observed and it was described as major hysteria by French neurologist Jean-Martin Charcot it was believed that the disease might be caused by the dynamic lesion that affects the motor pathway however according to Sigmund Freud, the founder of psychoanalysis, the condition may occur due to psychiatric conflict that converts into physical symptoms.https://doi.org/10.1007/978-3-030-44507-2_11

Classification(2)PMID: 27208925

Numerous classification systems have been proposed based on age, semiology and video EEG analysis to categorized PNES, classification for the disease was put forward in 2016 and it was better to understand and manage the diverse manifestation of the disease it was based on the concept that all the subtype of PNES resemble to the subtype of seizures it was categorized in to four categories including.

• Hypermotor
• Akinetic
• Focal motor
• PNES with “Subjective symptom

Pathophysiology

PNES also known as Pseudoseizures and functional neurological disorder (FND) ,it resembles like epileptic seizures but the etiology of the seizures vary. Two of these disease are different on the basis of abnormal epileptic form of discharged which is observed in seizures related to epilepsy but not in PNES, psychotic non epilepsy is associated with mental symptoms and psychological issue such as stress or trauma (3) PMID: 34339046 except those major difference the condition is also distinguished on the basis of various factors like duration of episodes, postictal phase, number of episodes ,patients history of mental health ,lactate level ,presence of brain structural pathology and other physical symptoms also help to differentiate between two conditions including tongue biting , vomit and incontinence(4)PMID: 34396517, PNES shows EEG normal and the treatment of this condition is not same as epilepsy. Traditional epileptic drugs(AEDs) is not good for the treatment of PNES (5) PMID: 34730239.

To advance the treatment and decrease the burden of the common disease understanding of the etiology is necessary but it is still unknown some recent Investigations suggest that the diseases may occur due to abnormal brain activity in limbic system and prefrontal cortex. The limbic system that involve in emotional and memory processes shows abnormalities (6) PMID: 28808618, and functional white matters such as uncinate fasciculus (UF) fibers increase connectivity in PNES (7)PMID: 25868002,decrease in gray matter and cotical thickness in prefrontal area observed including cingulate gyrus, middle frontal gyrus, and superior frontal gyrus (8) PMID: 29080235.Except above mansion brain regions abnormalities are also obsereved in insular cortex and supplementary motor area (SMA) this region of the brain is mostly report in the structural and functional imagine of the brain it is involve in the sensory emotion and cognitive processes of the brain and also control heart rate and blood pressure. And SMA is associated with coordination moment of the body (9) PMID: 30850473.

All above mansion studies suggest that development and maintenance of the disease occur due to abnormalities in the region that control cognition ,emotion ,heart rate and coordination muscle of the body.

Causes(10) PMID: 37092766

The underlying causes of disease are complex and can be understand through biopsychosocial model of PNES that highlight predisposing, precipitating, and perpetuating factors in the disorder.

Predisposing factors:

It makes a person susceptible to the condition it includes genetic, temperamental, other neurological problems that exist along with PNES, and childhood trauma

Precipitating factors:

It involves stressful events that trigger the onset of the diseases.

Perpetuating factors:

It can maintain or worsen the condition such as lack of social support and avoidance behaviors.

Psychiatric disorders other factors:

They also contribute to the diseases like anxiety, mood disorders, alcohol use disorder, post-traumatic stress disorder, trauma history, and family history of epilepsy are recognized as risk factors for PNES

Epidemiology and Demographics

Annually, reported incidence of PNES is ranging between 1.4 to 4.9 individual per 100,000 with the prevalence estimated to be between 2 and 33 per 100,000 individuals. These figures emphasize the significance of PNES as a relatively common condition within the spectrum of neurological disorders(11) PMID: 36577410

Age

The diseases is reported in the age of 30-40 years(12)

Gender

PNES is two to three times more common in teenagers, children, and women were in higher number as compare to male population(12)

Diagnosis

Diagnosis of the disease is difficult due to seizure in present or past therefore it is mostly misdiagnosed and treated as epilepsy, early correct diagnosis is necessary before treatment it can save patient quality of life and decrease disease burden and reduce the coast of the disease diagnosis of the condition involve gathering and analyzing data from multiple sources like Patients history, home video recording, direct seizures observation , Peri-ictal ECG changes, Video-EEG, Provocation techniques, Showing seizure videos to patients and witnesses, Biomarkers.

Home video recording:

The initial diagnosis by using home video recording when combine with clinical data these video can make the confident diagnosis(13) PMID: 27328162

Direct seizures observation:

The diagnosis can be made by direct observation of seizures but not always the sign that suggest the PNES are tightly closed eyes, respond to environmental stimuli like light touch , no sign of bluish skin, normal pupil reaction to light, self protective moment that are not observed in epileptic seizures(14) PMID: 30214985

Peri-ictal Ictal ECG changes:

ECG machine recording is synchronized with EEG recording it provide a valuable diagnostic information because the heart rate of Epileptic seizure and PNES vary, the heart rate is sudden in epileptic seizure where as it is not same in PNES

Video-EEG:

To confirm the diagnosis Vedio EEG play it important role it is important to take multiple recording on EEG to ensure that all seizures are recorded properly and analyzed, providing a comprehensive basis for an accurate diagnosis and effective treatment planning. (15)PMID: 27450307

Provocation techniques:

Technique include any method that focus patients attention on their seizures this technique is required to reduce the time of monitoring and it enhance the results of EEG recordings and this method is employed by the task force at the time when the seizures are not recorded, method that are employed for the technique are included detail history of the seizures, routine activation method like photic stimulation, nocebo technique can provoke seizure in patient having PNES. This technique do not differentiate the disease with epilepsy(14) PMID: 30214985

Showing seizure videos to patients and witnesses:

Inorder to correctly diagnose the disease it is necessary to take interview of the witness the perspective of the witness is also important and it help to diagnose the diseases presence of witness is necessary at the time of EEG recording (14) PMID: 30214985

Laboratory test:

Although blood test are not help to detect the disease but some time it provide hints like blood oxygen level is high in patient with PNES where as it it lower in tonic clonic seizures and creatine phosphokinase level (CPK) do not arie in PNES where as increaseafter tonic clonic seizures (16) PMID: 29204018

MRI

MRI is used to detect the abnormal neural activities at the area of prefrontal cortex (17) abnormal connectivity and neural activity are observed in structure of limbic system including hippocampus and amygdala(17) PMID: 33238045

Treatment

The delay in diagnosis of PNES has been estimated to be about 8 years. During this period patients are often treated with antiepileptic drugs being thereby exposed to potential adverse drug side-effects. Among the later adverse effects that is of remarkable clinical importance is the possible teratogenic risk for women of childbearing age. Moreover, patients with ES/PNES can mistakenly be classified as drug-resistant epilepsy and treated with complex combinations of antiepileptic compounds or even referred to epilepsy surgery In 2013, the International League against Epilepsy (ILAE) Neuropsychobiology Commission gave health professionals guidelines on how to treat patients with psychogenic non-epileptic seizures (PNES). They outlined three key stages in managing disease are PNES diagnosis, the communication of the diagnosis, and the treatment (18)PMID: 23458467.Treatment strategies for PNES include cognitive behavioral therapy (CBT) as an effective intervention (CBT), when combined with standard medical care, has shown promise in reducing dissociative seizure frequency(19) PMID: 34196269