Functional neurological seizure disorder

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Research question: Provide research on functional seizures, AKA non epileptic seizures: assessment criteria that should be met to confirm the diagnosis; functional implications of PNES e.g. How does it show up for an individual?; treatment recommendations with specific evidence on Cognitive Behavioural Therapy.

Date: 21/9/2022

Requestor: n/a review of previous TAB research

Endorsed by (EL1 or above):

Researcher: redacted: s22(1)(a)(ii) - irrelevant mater

Cleared by: redacted: s22(1)(a)(ii) - irrelevant mat

Functional neurological seizure disorder ………………………………………………………………………… 1

Contents ……………………………………………………………………………………………………….. 1
Summary ………………………………………………………………………………………………………. 2
Functional Neurological Seizure Disorder …………………………………………………………… 2
Diagnosis ………………………………………………………………………………………………………. 4

4.1  DSM-V clinical criteria ................................................................................................ 4

4.2  vEEG ......................................................................................................................... 5

4.3   Clinical assessment ................................................................................................... 6

5. Presentation …………………………………………………………………………………………………… 6

5.1   Functional Implications .............................................................................................. 6

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5.2 Risk and prognostic factors …………………………………………………………………………… 7

5.3 Presentation of functional neurological seizures vs epileptic seizures ………………….. 7

Treatment ……………………………………………………………………………………………………… 8

6.1 Cognitive behaviour therapy ………………………………………………………………………….. 8

6.2 Psychoeducation …………………………………………………………………………………………. 9

6.3 Allied health therapy …………………………………………………………………………………….. 9

6.4 Neuromodulation ……………………………………………………………………………………….. 10

6.5 Medication ………………………………………………………………………………………………… 10

References ………………………………………………………………………………………………….. 11

2. Summary

This research is a review of the ‘Functional Seizures’ research paper completed by TAB Tactical Research Team in 2019.

Functional neurological seizure disorder is listed under somatic symptom disorders in the Diagnostic and Statistical Manual of Mental Disorders, 5th Ed. While it has previously been considered a diagnosis of exclusion, advances in understanding of the disorder have enabled the development of diagnostic criteria to confirm the diagnosis. Importantly, functional neurological seizure disorder can co-occur with other neurological conditions such as epilepsy and multiple sclerosis.

Functional neurological seizure disorder predominantly affects women. Functional symptoms may result in motor deficits, sensory dysfunction and/or cognitive impairment. The prognosis for functional neurological seizure disorder largely depends on the time to diagnosis and adherence to the treatment plan. Cognitive behaviour therapy, psychoeducation, and allied health support may have a role in the treatment of the disorder.

3. Functional Neurological Seizure Disorder

Functional neurological seizure disorder (FND) is one of the most common causes of neurological disability (Medina et al, 2021). Functional neurological seizure disorder can present and feel similar to epileptic seizures, but they are a physical symptom to a psychological disturbance without any physiological connection to epilepsy and therefore sit alongside somatic symptom disorders in the Diagnostic and Statistical Manual of Mental

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Disorders, 5th Ed. (DSM V) (American Psychiatric Association (APA), 2013; Epilepsy Action Australia, 2020; Marcolini & Tolchin, 2021).

Historically, there have been multiple names for functional neurological seizure disorder in the literature, including (Epilepsy Action Australia, 2020):

Psychogenic non-epileptic seizure (PNES)
Pseudo seizures
Dissociative seizures
Non epileptic events
Non epileptic attack disorder (NEAD)
Functional seizures
Conversion disorder (psychiatric diagnosis)

The terms ‘functional neurological seizure disorder’ and ‘functional seizure’ are becoming more commonly used as they are considered more neutral than some of the earlier terms that had negative connotations for patients (Asadi-Pooya & Bazrafshan, 2020; Marcolini & Tolchin, 2021).

The true prevalence of functional neurological seizure disorder is not clear, however around 15% of presentations to general neurology clinics are attributed to functional neurological seizure disorder (Ahmad & Ahmad, 2016; Forejtova et al, 2022; Maggio et al, 2020). Patients are most commonly female, with initial presentation in their late teens to mid-twenties (Ahmad & Ahmad, 2016; Kerr et al, 2021; Marcolini & Tolchin, 2021), although motor symptoms tend to have their mean onset at ages 30-39 years (APA, 2013). Diagnosis prior to puberty is uncommon, with approximately only 1% of patients who undergo video-electroencephalography (vEEG) being diagnosed with the condition (Kerr et al, 2021).

People who experience functional neurological seizure disorder often have a history of trauma or psychological stressors such as physical or sexual abuse, neglect, and social or family conflict (Ahmad & Ahmad, 2016; APA, 2013; Marcolini & Tolchin, 2021). The condition is associated with comorbid psychiatric and psychological difficulties, poor quality of life, elevated mortality rates, and frequent use of the health system (Marcolini & Tolchin, 2021). Of note, there has been found to be a strong relationship between fibromyalgia and functional neurological seizure disorder, with one study in particular determining that out of 36 patients diagnosed chronic pain or fibromyalgia, 27 were also found to have functional neurological seizure disorder (Benbadis, 2005).

The prognosis for functional neurological seizure disorder can be poor, particularly when treatment begins more than 6-12 months after symptom onset (Gill, 2019; Gupta & Lang, 2009). Functional neurological seizure disorder can result in substantial physical disability (APA, 2013). The severity of long-term disability can be similar to that evident in people with other

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Diagnosis

Functional neurological seizure disorder is often misdiagnosed for several years (Medina et al, 2021), the average delay being 7 to 10 years (Kerr et al, 2021; Marcolini & Tolchin, 2021). Possibly due to the stigma of being a psychological condition, and a fear that doctors believe the symptoms are due to malingering or fictitious disorder, patients often do not adhere to treatment after diagnosis and remain high users of healthcare (Marcolini & Tolchin, 2021; Medina et al, 2021).

Diagnosis of functional neurological seizure disorders should be based on a combination of data, including: patient history and witness observations, clinical observations, and ictal (during a neurological episode) and interictal (between episodes) electroencephalography (Asadi-Pooya & Bazrafshan, 2020).

DSM-V clinical criteria

Functional neurological seizure disorder is classified as a conversion disorder in the chapter ‘Somatic Symptom and Related Disorders’ in the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5). This set of diagnostic criteria emphasises the importance of making a rule-in positive diagnosis rather than an exclusionary diagnosis that was common in the past (Aybek & Perez, 2022). Table 1 outlines the diagnostic criteria for functional neurological seizure disorder.

Table 1

DSM V diagnostic criteria for functional neurological disorder:

A. One or more symptoms of altered voluntary motor or sensory function
B. Clinical findings provide evidence of incompatibility between the symptom and recognised neurological or medical conditions.
C. The symptom or deficit is not better explained by another medical or mental disorder.
D. The symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning and warrants medical evaluation.

The ICD-10-CM code depends on the symptom type:

Specify symptom type:

(F44.4) With weakness or paralysis

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(F44.4) With abnormal movement (e.g., tremor, dystonia, myoclonus, gait disorder)

(F44.4) With swallowing symptoms

(F44.4) With speech symptom (e.g., dysphonia, slurred speech)

(F44.5) With attacks or seizures

(F44.6) With anaesthesia or sensory loss

(F44.6) With special sensory symptom (e.g., visual, olfactory, or hearing disturbance)

(F44.7) With mixed symptoms

Specify if:

Acute episode: Symptoms present for less than 6 months.

Persistent: Symptoms occurring for 6 months or more.

Specify if:

With psychological stressor (specify stressor)

Without psychological stressor

Diagnosis of functional neurological seizure disorder relies on clinical evidence that shows the symptoms of concern have not developed due to another recognised neurological disorder, such as epilepsy. Importantly, an individual can be diagnosed with both functional neurological seizure disorder and another neurological disease such as epilepsy or multiple sclerosis (APA, 2013).

Associated features that can support the diagnosis of functional neurological seizure disorder, although not specific to the disorder, include (APA, 2013):

a history of other functional somatic symptoms or disorders, particularly including pain and fatigue
onset that is associated with stress or trauma, either psychological or physical. Although this temporal relationship may only be true for up to 50% of individuals
‘la belle indifference’ (i.e., the lack of concern about the implications of the symptom) has been associated with functional neurological seizure disorder, but is not specific and should not be used to make the diagnosis

4.2 vEEG

Video electroencephalography (vEEG) is the gold standard method to diagnose functional neurological seizure disorder (Lopez & LaFrance, 2022; Marcolini & Tolchin, 2021). Extended vEEG evaluations enable greater diagnostic certainty to capture seizure events without epileptiform abnormalities immediately before, during or following seizures (Marcolini & Tolchin, 2021). Compared to epileptic seizure waveforms, functional neurological seizure

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disorder typically demonstrates normal awake brain electrical activity during impaired or lost consciousness events (Marcolini & Tolchin, 2021). Extended vEEG can be performed in an epilepsy monitoring unit; for individuals whose episodes are infrequent, single channel electromyography can be obtained at home over weeks or months to support the diagnosis (Marcolini & Tolchin, 2021).

4.3 Clinical assessment

An accurate diagnosis is best achieved using a combination of the patient history, information from observers, physical examination, evaluation of ictal semiology with a normal ictal vEEG, and psychiatric evaluation (Lopez & LaFrance, 2022; Marcolini & Tolchin, 2021).

There is no reliable laboratory test that is sensitive or specific to the diagnosis of functional neurological seizure disorder (Marcolini & Tolchin, 2021). Currently, research suggests there may be subtle differences in the structural and functional MRI of an individual with functional neurological seizure disorder compared to a healthy control, however these results are preliminary and cannot be used in clinical diagnosis or exclusion of functional neurological seizure disorder (Marcolini & Tolchin, 2021).

5. Presentation

5.1 Functional Implications

Patients may present with motor and/or sensory or cognitive neurological symptoms (Barnett et al, 2020) that can present acutely and resolve quickly or be long lasting (Nicholson et al, 2020). This results in a wide range of possible functional impairment, including (APA, 2013; Barnett et al, 2020; Gill, 2019; Nhan & Cheah, 2020; Nicholson et al, 2020):

Limb weakness or paralysis
Gait disorders
Balance problems
Movement disorders such as tremor, jerks and dystonia
Episodes of apparent unresponsiveness with or without limb movements, possibly resembling epileptic seizures, syncope or coma
Dysphagia
Communication difficulties
Speech disturbance, including reduced or absent speech volume, altered speech articulation, prosody or fluency
Fatigue
Chronic pain

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Risk and Prognostic Factors

Sensory symptoms such visual disturbances (e.g., double vision), cognitive symptoms (e.g., planning difficulties, mental slowness, black outs, memory difficulties), tactile disturbances (e.g., altered, reduced or absent skin sensation), or hearing disturbances.

• Bladder and bowel problems

The following are risk and prognostic factors associated with functional neurological seizures (APA, 2013):

• Maladaptive personality traits, especially emotional instability, are common.

• There may be a history of abuse and neglect.

• Stressful life events, including physical injury, are common but not universal.

• Other neurological diseases that cause similar symptoms, e.g., around 20% of individuals with functional neurological symptom disorder also have epilepsy.

• Individuals with functional neurological seizure disorder may show higher rates of suicidal thoughts and attempts than individuals with a recognised neurological disease.

• Short duration of symptoms and agreement with the diagnosis are positive prognostic factors, whereas maladaptive personality traits, comorbid physical disease and receipt of disability benefits appear to be negative prognostic factors.

Presentation of Functional Neurological Seizures vs Epileptic Seizures

People with functional neurological seizure disorder experience transient episodes of altered awareness (Marcolini & Tolchin, 2021). The seizures are believed to be an involuntary coping mechanism, and people who experience these types of seizure are more likely to use maladaptive coping mechanisms to handle stress (Epilepsy Action Australia, 2020).

Differentiating functional neurological seizures from epileptic seizures can be difficult as both show alterations in behaviour, consciousness, sensation and perception (Nhan & Cheah, 2020; Thimm & Belon, 2011). The table below highlights how a person may present during a functional neurological seizure compared to an epileptic seizure (Nhan & Cheah, 2020; Thimm & Belon, 2011):

Table 2

Functional neurological seizures versus epileptic seizures

| Behaviour | Functional neurological seizure | Epileptic seizure |

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Duration over 5 mins	common	rare
Gradual onset	common	rare
Eyes and mouth closed	common	rare
Resisting eye opening	common	very rare
Post ictal weeping/upset	occasional	rare
Post ictal nose rubbing/cough	rare	occasional
Side to side head movements	common	rare

Type of body movements

Pelvic thrusting; out-of-phase or side-to-side oscillatory movements;
chaotic and disorganized thrashing;
ictal stuttering; post-ictal whispering

Type of body movements (continued)

Pelvic thrusting; quick, tonic posturing; vocalization

Respiration	often fast	ceases
Grunting sound	occasional	common
Recall for period of unresponsiveness	common	very rare
Aura	common	common
Attacks rising from sleep	occasional	common
Self-injury	occasional	occasional
Tongue laceration	occasional	occasional
Incontinence	common	common

Treatment

In addition to treatment options, how the diagnosis is delivered and received influences adherence to the treatment plan and therefore prognosis (Aybek et al, 2022; Marcolini & Tolchin, 2021).

Cognitive behaviour therapy

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A number of randomised controlled trials support the efficacy of cognitive behaviour therapy to reduce seizure activity, improve psychosocial functioning, fewer somatic symptoms and improve quality of life (Aybek et al, 2022; Marcolini & Tolchin, 2021), however long-term follow- up generally indicated the effect did not remain significant (Aybek et al, 2022). A systematic review of 11 studies investigating the efficacy of cognitive behaviour therapy for functional neurological seizure disorder suggested moderate to large significant effects on measures of physical symptoms, and small to moderate effect sizes for mental health, function and quality of life (Gutkin et al, 2021). It was noted in this systematic review that the success of cognitive behaviour therapy depends on the patient accepting their symptoms may relate to psychological factors. Although Goldstein et al (2021) reported improvement in quality of life and psychosocial functioning at 12 months, this was not 12 months post-cessation of therapy but rather after the 12th month of therapy. Therefore, as reported by Aybek et al (2022), the effect of the therapy may decrease over time which might suggest that individuals need to have ongoing cognitive behaviour therapy for ongoing remission or decrease in symptoms.

6.2 Psychoeducation

While psychoeducation may not reduce seizure frequency, there is some evidence that it improves psychosocial functioning as they develop greater understanding of their diagnosis, acceptance and belief in the treatment plan (Aybek et al, 2022). An important consideration is this effect may not be evident for online education and self-help interventions (Aybek et al, 2022). Implementing psychoeducation to improve understanding of the diagnosis may encourage adherence to the treatment plan and increase the likelihood of better outcomes (Medina et al, 2021).

6.3 Allied health therapy

Physiotherapy is the first treatment option for patients with motor symptoms, with an emphasis on motor retraining (Aybek et al, 2022). Data from randomised controlled trials and observational studies have demonstrated efficacy of physiotherapy for functional neurological seizure disorder with improvements in gait, social functioning and quality of life reported (Aybek et al, 2022; Maggio et al, 2020). Maggio et al (2020) reports an average of 34% improvement in motor function was observed after adherence to weekly physiotherapy for an average of 7 weeks.

Support from a speech therapist may be necessary for individuals who demonstrate speech, language and swallowing impairments, however the efficacy and long-term outcomes after speech and language therapy for individuals with significant impairment does not appear well studied (Barnett et al, 2019).

A professional education paper by Nicholson et al (2020) has offered recommendations for the role of occupational therapy for patients with functional neurological disorder. Occupational therapy can provide practical support to overcome the effects of disability on activities of daily living. This may include education, vocational rehabilitation, assistive technology assessment,

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6.4 Neuromodulation

Research into the efficacy of neuromodulation for functional neurological seizure disorder is limited but emerging, therefore included in this research paper. As part of a systematic review, Oriuwa et al (2022) analysed data from one paper investigation the effects of TMS on functional seizures. All participants (N = 7) received high frequency repetitive stimulation of the right temporoparietal junction for 30 sessions over 30 weeks, and all experienced a significant decrease in weekly seizure frequency. At 3 months follow up, 4 participants had sustained remission in seizure activity.

6.5 Medication

Antiseizure medications have no role in the treatment of functional neurological seizure disorder, and may actually increase morbidity due to side effects (Lopez & LaFrance, 2022). While individuals with functional neurological seizure disorder may be prescribed medication for other psychological disorders, such as antidepressants, there is currently no medication to prescribe specifically for the symptoms of functional neurological seizure disorder.

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References

Aybek, S., & Perez, D. L. (2022). Diagnosis and management of functional neurological disorder. BMJ (Clinical research ed.), 376, o64. https://doi.org/10.1136/bmj.o64

Ahmad, O., & Ahmad, K. E. (2016). Functional neurological disorders in outpatient practice: An Australian cohort. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 28, 93–96. https://doi.org/10.1016/j.jocn.2015.11.020

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596

Asadi-Pooya, A. A., & Bazrafshan, M. (2020). Is patient acceptance of the diagnosis of functional (psychogenic nonepileptic) seizures linked to their clinical characteristics?. Journal of psychosomatic research, 136, 110193. https://doi.org/10.1016/j.jpsychores.2020.110193

Barnett, C., Armes, J., & Smith, C. (2019). Speech, language and swallowing impairments in functional neurological disorder: a scoping review. International journal of language & communication disorders, 54(3), 309–320. https://doi.org/10.1111/1460-6984.12448

Barnett, C., Davis, R., Mitchell, C., & Tyson, S. (2020). The vicious cycle of functional neurological disorders: a synthesis of healthcare professionals’ views on working with patients with functional neurological disorder. Disability and Rehabilitation. DOI:10.1080/09638288.2020.1822935

Benbadis S. R. (2005). A spell in the epilepsy clinic and a history of “chronic pain” or “fibromyalgia” independently predict a diagnosis of psychogenic seizures. Epilepsy & behavior, 6(2), 264–265. https://doi.org/10.1016/j.yebeh.2004.12.007

Epilepsy Action Australia. (2020). Epilepsy trainer news: feature – psychogenic non-epileptic seizures. Accessed from https://www.epilepsy.org.au/epilepsy-trainer-news-feature-psychogenic-non-epileptic-seizures/

Forejtová, Z., Serranová, T., Sieger, T., Slovák, M., Nováková, L., Věchetová, G., Růžička, E., & Edwards, M. J. (2022). The complex syndrome of functional neurological disorder. Psychological medicine, 1–11. Advance online publication. https://doi.org/10.1017/S0033291721005225

FND Australia. (2019). Discover options for FND treatment in Australia. Accessed from https://fndaus.org.au/fnd-treatment-australia/

Gill, K. (2019). Consumer and carer experiences of FND/CD in Australia: The silent crisis. Commissioned by the National Mental Health Commission, Sydney.

Goldstein, L. H., Robinson, E. J., Pilecka, I., Perdue, I., Mosweu, I., Read, H., et al. (2021). Cognitive behaviour therapy compared with standardised medical care for adults with dissociative non-epileptic seizures: the CODES RCT. Health Technol Assess, 25(43).

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Gupta, A., & Lang, A. E. (2009). Psychogenic movement disorders. Current Opinion in Neurology, 22(4), 430–436. doi:10.1097/WCO.0b013e32832dc169

Kerr, W. T., et al. (2021). Title: Functional seizures across the adult lifespan: female sex, delay to diagnosis and disability. Seizure, 91, 476–483.

Lopez, M. R., & LaFrance, W. C. (2022). Treatment of Psychogenic Nonepileptic Seizures. Current neurology and neuroscience reports, 22(8), 467–474. https://doi.org/10.1007/s11910-022-01209-3

Maggio, J. B., et al. (2020). Outpatient physical therapy for functional neurological disorder: A preliminary feasibility and naturalistic outcome study in a U.S. cohort. J Neuropsychiatry Clin Neurosci, 32, 85–89. doi:10.1176/appi.neuropsych.19030068

Marcolini, E., & Tolchin, B. (2021). Functional seizures. Emergency Medicine Clinics of North America, 39(1), 123–132. https://doi.org/10.1016/j.emc.2020.09.007

Medina, M., et al. (2021). Using patient centred clinical neuroscience to deliver the diagnosis of functional neurological disorder (FND): Results from an innovative educational workshop. Academic Psychiatry, 45, 185–189. https://doi.org/10.1007/s40596-020-01324-8

Nhan, P., & Cheah, V. (2020). Functional neurological disorder (FND) learning guide. Mater Centre for Neurosciences. Accessed from https://fndaustralia.com.au/resources/FND-Learning-guide-for-nurses.pdf

Nicholson, C., et al. (2020). Occupational therapy consensus recommendations for functional neurological disorder. J Neurol Neurosurg Psychiatry, 91, 1037–1045. doi:10.1136/jnnp-2019-322281

Oriuwa, C., et al. (2022). Neuromodulation for the treatment of functional neurological disorder and somatic symptom disorder: a systematic review. Journal of neurology, neurosurgery, and psychiatry, 93(3), 280–290. https://doi.org/10.1136/jnnp-2021-327025

Thimm, A., & Bellon, M. (2011). The psychosocial effects of psychogenic non-epileptic seizures (PNES). The Epilepsy Report, (2), 4–6.

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Functional neurological seizure disorder

Functional neurological seizure disorder

Contents

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2. Summary

3. Functional Neurological Seizure Disorder

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Diagnosis

DSM-V clinical criteria

Table 1

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4.2 vEEG

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4.3 Clinical assessment

5. Presentation

5.1 Functional Implications

Risk and Prognostic Factors

Presentation of Functional Neurological Seizures vs Epileptic Seizures

Table 2

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Type of body movements

Type of body movements (continued)

Treatment

Cognitive behaviour therapy

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6.2 Psychoeducation

6.3 Allied health therapy

6.4 Neuromodulation

6.5 Medication

References

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