Caring for Patients with Functional Neurological Disorders in the ED: Updates, Pearls, and Pitfalls

Conversion Disorder Functional Neurological Disorder is not a diagnosis of exclusion. It is a diagnosis based on positive clinical features.

Definitions:

1. Medically Unexplained Physical Symptoms (MUPS)
   • Patient complaints and symptoms for which no medical etiology is identified
2. Somatic Symptom Disorder
   • Somatic symptoms that are distressing to a patient for at least 6 months
   • Importantly, patients have disproportionate and excessive thoughts and behaviours towards these symptoms
3. Functional Symptom
   • Another term for MUPS commonly used in all specialties
   • Every specialty sees patients with functional symptoms, for example:
     1. Cardiology – non-cardiac chest pain
     2. Gastroenterology – IBS
     3. Rheumatology – fibromyalgia
4. Functional Neurological Disorder (FND)
   • Previously conversion disorder
   • Term for a constellation of functional symptoms that are neurologic in nature
   • DSM 5 updated criteria will be explained below

Epidemiology:

1. Carson, Handb Clin Neuro, 2016
   • 60-75% Women to men
   • Average age 35-50 years
2. Williams, J Psychosom Res, 2001
   • 1 in every 25 ED visits is somatization
3. Stone, Brain, 2009
   • 30% of patients had symptoms not fully explained by their diagnosed condition
   • 4% prevalence of functional neurological disorder
4. Kroenke, Am J Med, 1989
   • Retrospective review of 1,000 patients with new complaints
   • Etiology identified in only 16%
5. Carson, J Neuro Neurosurg Psych, 2011
   • Multi-centre prospective cohort study of 3781 patients showed that compared to patients with an etiology, patients with unexplained symptoms had:
     1. Worse physical health
     2. Higher anxiety
     3. Increased rates of unemployment for health reasons
     4. Increased rates of receiving disability
6. Reuber, Ann Neurol, 2003
   • Prognosis for psychogenic non-epileptic seizure (PNES) is worse than epilepsy
     1. Higher rates of spells
     2. More disability
     3. Longer duration of illness
7. Gelauff, J Neuro Neurosurg Psych, 2014
   • Systematic review of 9 studies
   • Time from symptom onset to receiving diagnosis was a prognostic factor for recovery
     1. Important to recognize FND early and as ED physicians we are well-positioned to do so given the high presentation rate

Pathophysiology:

1. Vuilleumier, Brain, 2001
   • 7 patients prospectively enrolled with functional sensorimotor loss
   • Vibrostimulatory stimulus applied and SPECT
   • Re-scanned 6 months after recovery
   • Findings:
     1. Decreased cerebral blood flow and hypoactivation of thalamus and basal gang.
        1. Hypoactivation of basal ganglia and thalamus in FND
2. Burke, Neuroimage, 2014
   • 10 patients with functional sensory loss
   • Vibrostimulatory stimulus to affected vs. unaffected limb with fMRI done
     1. Trend towards lower somatosensory cortex activation
     2. Higher activation in contralateral paralimbic structure (10 of them)
        • These are emotional centres that can regulate integration of neural impulses
   • Conclusions:
     1. Emotional suppression of sensory-integration stimuli in FND
3. Parees, Brain, 2014
   • 14 patients and 14 controls
   • Background:
     1. Sensory attenuation is a phenomenon of experiencing self-generated stimuli with less intensity than externally generated stimuli
        • Example: you can’t tickle yourself but someone else can tickle you easily
     2. Question: do patients with sensory FND have impaired sensory attenuation?
   • Force-matching experiment
     1. Classic experiment for this
     2. Robot puts pressure on participant’s finger. Immediately after patient needs to match the pressure that they felt, on their own finger (a thin pressure probe checks the pressure)
     3.  Expected:
        • Due to sensory attenuation, participants apply more force than the robot (they experience their own force as less)
   • Results:
     1. Functional sensory loss patients were more accurate
     2. Intriguing as it is easier to fake inaccuracy than it is to fake accuracy
   • Conclusions:
     1. Impaired sensory attenuation in patients with FND

1. Parees, Brain, 2012
   • 10 patients with functional tremor, 8 patients with Parkinsonian tremor
   • Wore actigraph (device that measures amount of time with tremor)
   • In spite of knowing that the objective was to see how they could estimate what proportion of time they had a tremor:
     1. Parkinson’s overestimated by 23%
     2. Functional overestimated by 80%
   • Conclusions:
     1. Impaired attention in FND
        • Whenever they attended or perceived their hand they thought it was tremorous, even if this was a small percentage of the time
2. Limitations of all studies
   • Small case-control studies
   • Heterogeneity in types of FND
   • Larger studies needed for validation and replication

Conclusions

• Pathophysiological basis of FND likely includes the following:
  1. Hypoactivation of basal ganglia
  2. Emotional suppression by paralimbic structures
  3. Loss of sensory attenuation
  4. Alterations of attention and perception

Differences with malingerers

• Prevalence of malingering in MUPS is around 1%
• Studies show different brain activation in FND vs. feigners
  1. FND: less activation of left dorso-lateral prefrontal cortex which is involved in the generation of action, choice or planning of movement
  2. Evidence that FND is different from malingerers:
     • Homogeneity of symptoms
     • Persistence over time
     • High frequency during video EEG even though told diagnosis is functional
     • Persistence after shown maneuvers
     • Historical consistency
• Red flags for malingering in the ED:
  1. Inconsistency in patient’s history
  2. Inconsistency from patient’s history to collateral history
  3. Inconsistency between patient’s history and medical records
  4. Inconsistency in patient throughout multiple encounters
•  Spectrum:
  1. Low intent of symptoms in FND
  2. Malingering = external gain
  3. Factitious = internal gain

Diagnosis in the ED:

• DSM 5 criteria:
  • One or more symptoms of altered motor or sensory function
  • Clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions
  • The symptom or deficit is not better explained by another medical or mental disorder
  • The symptom or deficit causes clinically significant distress or impairment
• Malingering is not a criterion
• No requirement to identify a psychosocial stressor
  • Key for us in the ED as in our brief encounters we might not identify a stressor

Clinical signs

1. Motor
   • Hoover
     1. Sens 63, Spec 100
     2. Applies only to proximal leg weakness

• Give way weakness
  1. Sens 69, Spec 98
  2. Caution in:
     • Pain
     • Language barrier
     • Cognitive barriers for patient not able to follow commands
     • Neglect (eg. Stroke)

• Motor inconsistencies
  2. Sens 13, Spec 98
  3. Example:
     • Weakness of plantar flexion at bedside, but able to ambulate on tip-toes
  4. Pathology that can rarely mimic it:
     • Apraxias

• Pronator drift
  1. Used by expert consensus (no sens/spec available for FND)
  2. Expected in upper motor weakness: drift of limb and pronation
  3. Observations in functional weakness: isolated drift with no pronation

• Tremor entrainment
  1. Used by expert consensus (no sens/spec available for FND)
  2. Historical clues for functional tremor:
     • Abrupt onset
     • Associated with psychosocial stressor
     • Onset after injury
  3. Sign:
     • Patient to copy movement generated by examiner with ONE hand (both arms extended)
       • Important for patient to copy movement rather than generate it on his/her own
     • Contralateral hand (ie. Hand that is NOT copying movement) shows one of:
       • Acquires frequency/movement of movement patient is copying and performing with other hand
       • Tremor stops
       • Unable to perform test

1.  Sensory
   • Non-anatomical sensory loss
     2. Sens 70, Spec 100
     3. Caution is required as this can be mimicked by multiple concurrent processes or MS

• Midline splitting = sensory defects that stop at midline
  1. Sense 20, Spec 93
  2. Caution as this can be mimicked by lacunar strokes

2. Gait

• Dragging monoplegic leg
  1. Sens 8.4, Spec 100
  2. Physiologic hemiplegic gait = circumduction of hip
  3. Functional monoplegic gait = dragging leg behind body
• Huffing and puffing sign
  1. Sens 8.4, Spec 100
  2. Patients seen “huffing and puffing” and over-exerting in attempt to generate movement. Rare in physiologic weakness as patients are just unable to move

3. La Belle Indifference – is it useful?

• Stone, Br J Psychiatry, 2006
  1. Systematic review of 11 studies (356 functional patients, 157 organic patients)
  2. Prevalence the same in both groups (21 vs. 29%)
  3. No discriminatory value

Limitations

• No high-quality studies
• Selection bias, non-consecutive sampling, high heterogeneity
• Lack of blinding
• Use of clinical sign as component of diagnosis

Summary for clinical signs used to raise suspicion of FND

1. Motor:
   • Hoover sign
   • Give-way weakness
   • Motor inconsistencies
   • Drift without pronation
   • Tremor entrainment
2. Sensory – caution if in isolation:
   • Non-anatomical sensory loss
3.  Gait:
   • Dragging monoplegic leg
   • “Huffing and Puffing”

Treatment and Management in the ED:

Summary

• Disclose the diagnosis
• Avoid investigations and admissions if possible
• Refer to outpatient neurology

Disclosure of diagnosis

• Elements of an evidence-based therapeutic disclosure:
  • Explain:
    • What they do have
      • “You have functional weakness,” or “this is functional sensory loss that you are experiencing”
    • The mechanism of the symptoms
      • Use analogies:
        • “Think of your brain like a computer. The hardware is intact and not damaged, the problem lies in its software”

• How you made the diagnosis
  1. Show them the signs (eg. Hoover sign, give-way weakness, etc.)
     • “Can you see how when you are not attending to your leg it’s working fine? This tells me that the your nervous system is intact and there’s no damage – but your body is having difficulty sending messages to your leg and improves with distraction”
     • “Can you see how when you are distracted your tremor disappears?”
  2. You believe them
  3. Reversibility
     • “Because your nervous system is not damaged, the problem is entirely reversible”

• Common pitfalls in disclosing the diagnosis:
  • Telling them what they don’t have and expecting them to be satisfied
    1. They will be wondering what they do have
    2. They came to the ED seeking a diagnosis because of the distress their problem is causing them
  • Preemptively attributing their symptoms to psychological problems
    1. While stress is a major contributor to most patients with FND, they might be unaware of stressors or psychological burden
    2. Without having the time and relationship to effectively tease this out, you risk losing their trust in your diagnosis
  • Using the “negative workup” as the evidence for their diagnosis
    1. As Dr. Stone put it in his interview from 2015:
       • “It’s much more persuasive for patients to know that they have a typical feature of a common condition, than to be told ‘well all the tests are normal’. That explanation usually is greeted with a sort of ‘well, perhaps they just haven’t done all the tests.”

• Resources after disclosing:
  • Provide patients with neurosymptoms.org
    1. Written by a functional specialist
    2. Patient-centered language
    3. Covers almost all functional disorders for more patient info

Avoiding investigations:

• Patients with FND are typically over investigated (Hatcher, BMJ, 2008)
  • Example:
    1. Wei, J, Epilepsy Behav, 2018:
       • Retrospective review of 224 patients with PNES
       • 66% received brain imaging before diagnosis
       • 1 in 5 received at least 4 CT or MRIs before receiving diagnosis

• Investigations are generally not anxiolytic
  • Example:
    1. Howard, J Neurol Neurosurg Psych, 2005:
       • 150 patients with chronic daily headache
       • Stratified by HADS + vs. –, ITT analysis
       • Minimal crossover (93% vs 4%)
       • No difference in anxiety at 1 year
       • Only difference at 1 year: fewer referrals if MRI offered

Referral to neurologist:

• Local opinion:
  • “Every [patient with FND] should be referred to a neurologist. However, the timing of the consult does not have to be in the ED and most often is best for it not to be in the ED.”  C. De Meulemeester, The Ottawa Hospital
• Goals of referral:
  • Confirm diagnosis
  • Arrange therapy
  • Refer to psychiatry
  • Identify concurrent neurological disorders
• Importance of referral:
  • High degree of organic disease in patients with FND
  • FND is a red flag for underlying neurologic disease
  • Conversely, organic neurologic disease is a risk factor for FND
    1. Stone, J, Neurol, 2012
       • Scottish study of 2467 outpatient neurology patients
       • Proven neurological disease
       • Concomitant functional symptom in 1 in 8 of these patients

• Examples of therapies supported by RCTs that neurologists can help arrange:
  • Physiotherapy
  • CBT

+/- Referral to ED psychiatry if:

• Multiple recurrent visits
• Need to establish care-plan
• Suspect factitious disorder or malingering

Psychogenic Non-Epileptic Seizures:

1. Last year 905 ED visits to TOH for seizures
   • More than 2/3 had diagnosis of “unspecified convulsions” – term used also when suspicion for PNES but no confirmation of diagnosis
   • Local experts suggest 30% of our outpatient elective epilepsy monitoring unit admissions have diagnosis of PNES
     • Consistent with literature

2. ED accuracy in recognizing epileptic vs. non-epileptic seizures
   • Wasserman, Epilepsy Behav, 2017
     • 44% accuracy
   • Important to be precise as disclosing PNES diagnosis carries benefits:
     • 40% cessation of seizures immediately after receiving diagnosis (Aboukasm, Epilepsia, 1998)
     • 39% fewer ED visits (Jorsch, Epilepsy & Behav, 2011)

3. Recognizing PNES
   • Most PNES mimic generalized tonic-clonic (GTC) seizures
   • Recognize PNES by understanding all features and nuances of prototypical GTC seizures and identifying deviations
     • Prototypical GTC seizure:
       1. Pre-ictal phase
          • Patient normal
       2. Tonic phase
          • Onset is abrupt
          • Epileptic cry
       3. Posturing – predominantly extensors over flexors
       4. Clonic phase
          • Gradual transition to clonic phase
          • Initially high frequency, low amplitude convulsions
          • Gradual transition to low frequency, high amplitude convulsions
       5. Post-ictal phase
          • Stertorous breathing
          • Confusion
       6. Amnesia
   • Findings (LaFrance, Epilepsia, 2013; Erba, Seizure, 2017):
     • Validated, favouring epileptic seizures:
       1. Stertorous breathing
          • Sens 61-91, Spec 100
       2. Post-ictal confusion
          • Sens 67, Spec 84
     • Validated, favouring PNES:
       1. Asynchronous movements
          • Sens 44-96, Spec 93-100
       2. Pelvic thrusting
          • Sens 1-44, Spec 92-100
       3. Side-to-side movements
          • Sens 15-63, Spec 92-100
       4. Closed eyes
          • Sens 34-96, Spec 74-100
       5. Ictal crying
          • Sens 13-37, Spec 100
   • Other findings used by expert consensus (Chen, Continuum, 2016):
     • Favouring epileptic seizures:
       1. Impaired corneal reflex
       2. Extensor plantar reflexes
       3. Gaze deviation
          • Away from epileptic focus during ictus
          • Towards epileptic focus during post-ictal phase (due to hypoactivation)
     • Favouring PNES:
       1. Self-protection or guarding with arm drop over face
       2. Visual fixation (can be tested with mirror)
       3. Increases or suppresses with suggestibility
       4. Fluctuating course (e.g. fluctuation in clonus frequency and amplitudes)
       5. Absence of tonic phase
       6. Responding to examiner
   • Caveats:
     • Large spectrum of how PNES and epileptic seizures can present
       1. Eg:
          • Frontal seizures can present with bizarre behaviour
          • Focal seizures can retain consciousness
          • PNES subtypes include focal mimickers
     • Gold-standard diagnosis and confirmation is with video EEG

4. Approach to patient with prolonged seizure:
   • If VS abnormal (i.e. hypoxia) or clearly epileptic, then treat as epileptic
   • If VS normal and clearly PNES: then reassure, disclose diagnosis, and refer for gold standard video EEG
   • If VS normal and unsure as to whether epileptic or PNES: then call neurology for opinion +/- ED EEG