STROKE/2020/029076-R2

Functional neurological disorder: a common and treatable stroke mimic

Topical review

Authors:Stoyan Popkirov, MD1,2* Jon Stone, PhD3

Alastair M. Buchan, DSc2,4

1 Department of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany2 Wissenschaftskolleg zu Berlin - Institute for Advanced Study, Berlin, Germany3 Centre for Clinical Brain Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK4 Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom

*Corresponding author:Dr. Stoyan PopkirovUniversitätsklinikum Knappschaftskrankenhaus BochumIn der Schornau 23-2544892 BochumGermany

popkirov@gmail.com+492342990

Cover title: Functional neurological disorder mimicking strokeTables: 3Figures: 1Word Count: 5292

Keywords: diagnosis; differentiation; imaging; stroke mimic; conversion disorder; functional neurological disorder; psychogenic

Twitter:@popkirov@jonstoneneuro

BACKGROUND

The hyperacute clinical diagnosis of stroke remains a major challenge, as one in four suspected

cases turns out to be a ‘stroke mimic’.1 In large registries, among patients that are treated with

intravenous thrombolysis, the upward-trending rate of misdiagnosis is 3.5-4.1%.2, 3 Considering

the safety of thrombolysis in stroke mimics (complication rate 1.5%),3 and its potential benefit

in acute ischemic stroke, it seems permissible to err on the side of over-treatment. As strategies

to reduce the door-to-needle time are being implemented, the rate of thrombolysis of stroke

mimics has increased noticeably.3-5 This problem will not be overcome by optimizing clinical

pathways or emerging technologies, but by focusing on clinical skills.

A common type of stroke mimic is functional neurological disorder presenting with limb

weakness, numbness or speech disturbances (previously known as psychogenic or conversion

disorder).1 Two recent studies from large centers in London, UK, and Doha, Qatar, demonstrate

rates of functional stroke mimics of 8%.6, 7 Functional stroke mimics are often considered

elusive, since they have traditionally been seen as diagnoses of exclusion, characterized by

psychiatric comorbidities such as anxiety, neuroticism or traumatization. However, the

diagnostic criteria for functional neurological disorder have fundamentally changed with the

last revision of the Diagnostic and Statistical Manual of Mental Disorders, replacing what was a

principle of exclusion with a phenotype-based diagnosis supported by specific clinical signs that

demonstrate inconsistency, reversibility and top-down modulation of symptoms.8 As the utility

of examination techniques and clinical signs to identify functional weakness, numbness and

speech disorders are increasingly established, it is now timely to provide a state-of-the-art

review, tailored to the needs of the clinician working in acute stroke care.

FUNCTIONAL LIMB WEAKNESS AND SENSORY DEFICITS

Presentations with limb weakness and sensory disturbances comprise about 70% of all

functional stroke mimics.1 Like stroke syndromes, functional motor and sensory deficits are

1

typically lateralized, often as hemiparesis.9-11 Between-group differences in demographic

characteristics can be found in large studies, but cannot differentiate between etiologies at the

individual patient level. On the contrary, stereotypical biases based on gender, age or social

background are typical pitfalls for misdiagnosis. Similarly, the medical history regarding the

acute problem or comorbidities is unlikely to help with ascertaining the diagnosis. For example,

although panic accompanies acute-onset functional paresis in 59% of cases and could be taken

as a red flag for a functional disorder,12 it is also reported at symptom onset by 64% of stroke

patients.13 Similarly, migraine or peripheral injury are common precipitants of acute-onset

functional limb weakness,12 but are also found in acute ischemic stroke.14, 15

Clinical features such as anxiety and age will inevitably alter pre-test probability of stroke, but

ultimately the diagnosis of functional motor or sensory symptoms relies primarily on

characteristic clinical signs. A large variety of examination techniques and signs that aim to

differentiate functional from pathophysiological weakness and numbness have been described

since early work on “hysteria”. Those signs are passed on through clinical mentoring, and are

dutifully collated in literature reviews, but only a few of them are sufficiently specific and

reliable in order to contribute to the differential diagnosis (table 1). Many signs are not proven

to be helpful (or are proven to be unhelpful), and should thus be explicitly discouraged for

emergency decision-making, as they lead to misdiagnosis (table 2).

In functional limb weakness the patient’s motor deficit is chiefly determined by an abnormal

(computational) prediction of weakness that can be encoded at various levels of the motor

control pathway.16 The presentation is thus determined by attention and expectation, with

voluntary movements affected more so than automatic ones. Most bedside tests aim to tease out

this difference and demonstrate the inconsistency between voluntary and involuntary

movements. However, in stroke-related paresis, movement can also be modulated by attention

or emotion, harboring the potential for false positives. It is thus advisable to seek confirmation

from several clearly positive signs before reaching a final diagnosis.

2

Table 1 Examination techniques for the diagnosis of functional stroke mimics with motor symptoms

Sign Description Comment PPV*

Hoover’s sign Hip flexion and extension testing

reveals inconsistency in attended vs.

unattended movement in affected leg

False positive in patients with

supplementary motor area or

parietal lobe strokes possible

67-

100%

Hip abductor sign Hip abduction testing reveals

inconsistency in attended vs.

unattended movement in affected and

unaffected leg

Limited evidence for utility in

clinical practice

100%

Drift without

pronation

The affected arm drifts downward

without pronation

Only testable in mild to moderate

upper limb weakness

93-

100%

Unilateral facial lip

pulling/platysma

contraction/jaw

deviation

Functional facial spasm or dystonia

typically presents with contraction of

platysma which may pull the lip down

or the jaw to one side

May be accompanied by

orbicularis oculis activity and

ipsilateral convergent spasm

which can mimic a 6th nerve palsy

n/a

Give-way weakness

(collapsing

weakness)

Sudden loss of tone or strength during

strength testing

False positive in patients with

joint/limb pain or when

instructions are unclear

60-

100%

Global or inverse

pyramidal pattern

of weakness

Weakness of upper limb with

extensors weaker than flexors and vice

versa in lower limbs

No formal studies but good

evidence that such a pattern is

not found in structural disorders

causing limb weakness

n/a

* PPV: positive predictive values – to be interpreted with caution; based on studies from various settings; taken from Stone & Aybek, 201617. N/a: not available.

Table 2 Examination techniques not suited for acute stroke workup due to insufficient specificity, reliability, evidence and/or practicability (see 17-19 for descriptions)

Abduction finger signArm drop testAtypical distribution of weakness

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Thigh trunk testBowlus-Currier TestCo-contraction signForced choice / systematic failureLa belle indifférenceMidline splitting of sensory lossMonrad-Krohn’s testNon digiti quinti signNon-anatomic distribution of sensory symptomsPseudo-waxy flexibilitySensitivity to suggestionSplitting of vibration senseSternocleidomastoid test

Give-way weakness describes the sudden loss of tone or strength during isometric muscle

strength testing. It has good inter-rater reliability, as well as excellent specificity and positive

predictive value for functional limb weakness.17, 19 In patients with leg weakness it can manifest

during gait assessment as “knee buckling”. An important caveat is that it can occur due to joint

or limb pain, especially in patients with pre-existing conditions. Moreover, patients might want

to “help out” during assessment, or demonstrate their symptom to the examiner.

A pattern of global or inverse pyramidal weakness is common in functional limb weakness

instead of the usual pattern of stronger flexors in the arms and extensors in the legs. In studies

of patients with a variety of upper and generalized lower motor neuron weakness (e.g. Guillain-

Barré syndrome), this pattern is consistently found. Achieving global or inverse pyramidal

weakness requires a process that preferentially affects the strongest voluntary muscles, in

keeping with a disorder of willed movement.

For functional leg weakness, Hoover’s sign has the best clinical utility.17 It can be conducted

when the patient is seated or lying down (figure), and reveals a normalization of hip extension

on the weak side during hip flexion of the non-paretic lower limb. In a prospective study of 124

patients with suspected stroke and leg weakness, Hoover’s sign was positive in 5/8 functional

stroke mimics and in none of the definite stroke cases, yielding a sensitivity of 63% (CI: 24-

4

91%) and specificity of 100% (CI: 97-100%).20 The positive predictive value was 100% (CI: 46-

100%), the negative predictive value was 99% (CI: 96-100%). This prospective study found no

false positives, but those definitely occur in acute stroke, particularly in supplementary motor

area lesions,21, 22 or in cases of ‘pseudoparesis’ due to parietal lobe lesions.23

The hip abductor sign is similar to Hoover’s sign and describes weakness of voluntary hip

abduction which returns, through automatic movements, to normal during contralateral hip

abduction against resistance.24 (figure). In a study of 33 patients with lateralized leg weakness

(16 functional and 17 organic, of whom 8 with stroke), this sign achieved 100% sensitivity and

specificity.24

Downward drift with pronation indicates cortical weakness. Drift without pronation is a typical

finding in patients with functional arm weakness (figure). In a study of 26 patients with

functional arm weakness and 28 controls with “organic” paresis (23 due to stroke), drift

without pronation identified functional arm weakness with a sensitivity of 100% (CI: 84-100%)

and a specificity of 93% (CI: 76-98%).25

Functional motor disorders of the face are generally easy to distinguish from facial symptoms of

stroke. The unilateral lip-pulling sign (figure) reveals a characteristic functional dystonic

movement disorder of the face that may give a superficial appearance of weakness but is

actually caused by overactivity, typically of platysma and or the muscles of jaw deviation. 26

Ipsilateral orbicularis oculis contraction may be an accompanying feature. Other facial or axial

signs include the trunk-thigh test,27 which has a low interrater reliability,19 and the “wrong-way”

tongue deviation away from paretic side28 (towards hemiparesis in most strokes29), which

remains to be evaluated systematically and can be “false positive” in medullary infarctions.30

The proposed sternocleidomastoid muscle test, in which head rotation is more likely to be weak

towards the side of hemiparesis in patients with functional paresis,31 is problematic as it is

documented as a common finding in stroke.32, 33

5

In most cases, functional limb weakness is accompanied by sensory deficits. However, sensory

testing in general has low interrater reliability,34, 35 and most diagnostic signs that have been

suggested for identifying functional sensory disturbance do not have the required specificity.

For example, non-anatomical distributions of acute sensory symptoms, such as a glove-like

distribution, are found in patients with distal arm paresis due to cortical stroke. 36 Another

proposed feature of functional hemisensory disturbance is so-called ‘midline-splitting’. Since

cutaneous nerves of the trunk typically overlap a couple of centimeters at the midline, an exact

splitting of deficits is often attributed to a functional disorder. However, midline splitting can be

found in patients with clear organic causes of sensory loss,37-39 particularly in pure sensory

stroke, which can remain MRI-negative.40 Other proposed signs for functional sensory

symptoms, such as ‘splitting of vibration sense’ (vibration is felt less on the numb side of the

forehead or sternum despite intact bone conduction), similarly lack specificity for use in stroke

workup.38, 39 It should be noted that these clinical signs may show better specificity when

combined with the above mentioned motor signs.17

In conclusion, clear positive signs of inconsistency of deficits should support the diagnosis of

functional neurological disorder. Diagnosis based solely on psychosocial factors, psychiatric

comorbidity or negative imaging is not clinically indicated and a common source of error in the

diagnosis of FND.41 Even minor symptoms that indicate acute cerebrovascular pathology, such

as clear upper motor neuron facial weakness,21 should discourage acute diagnosis of a

functional disorder.

FUNCTIONAL SPEECH AND LANGUAGE DISORDERS

An acute isolated voice (phonation) disorder would be a very rare stroke presentation, although

partial vocal cord paralysis can often accompany other deficits. Functional aphonia or

dysphonia can usually be diagnosed by demonstrating normal sound production on prompted

coughing or throat clearing or other signs of inconsistency of presentation.

6

One of the commonest kinds of functional speech disorder is stuttering.42 It can accompany

functional movement disorders43 and dissociative (nonepileptic) seizuires44 or occur in

isolation. The following features can help to distinguish it from (very rare45) acute stroke-

related neurogenic stuttering: excessive variability of presentation; excessive consistency

(stuttering on every syllable/word); struggling behaviors such as grimacing and neck extension

(though “articulatory groping” can accompany apraxia of speech); absence of accompanying

dysarthria, aphasia or apraxia of speech; agrammatic or telegraphic speech without aphasia. 42

One of the most reliable distinguishing features of functional stuttering is its quick and complete

response to therapy, though that will not be available in the emergency setting.

Dysarthria (difficulty with articulation) is a common symptom of stroke, but occurs in isolation

in only 1.3-2.8% of cases.46, 47 In cases of moderate to severe isolated dysarthria, the patient will

always report some degree of dysphagia as well, since the motor components of speaking and

swallowing overlap. In functional dysarthria patients might complain of a globus sensation, but

will rarely have any other swallowing difficulties. Functional dysarthria is only very rarely an

isolated presenting symptom, so diagnosis can usually be determined by its variability and by

close examination of accompanying symptoms.

An inability to produce language, aphasia, is another common presenting sign of stroke, usually

in the context of clearly identifiable anterior circulation stroke syndromes. When aphasia

presents without limb motor deficits, additional signs such as facial weakness, hemianopia or

sensory disturbance are usually found.48 Truly isolated aphasia accounts for only 3% of acute

stroke presentations, and has an 86% likelihood of being a stroke mimic.49 Functional aphasia is

also rare and usually presents as non-fluent aphasia with preserved comprehension and

naming.50 Its agrammatism can sound like broken English or baby talk (“me sleepy”), compared

to Broca’s telegraphic speech (“I sleepy”), and speech patterns are generally more inconsistent

than in stroke aphasia. There is some evidence that a proportion of patients with foreign accent

syndrome have a primary functional neurological disorder.51

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NEUROIMAGING

Although advanced structural and functional neuroimaging techniques can detect subtle

statistical alterations in groups of patients with functional neurological disorder compared to

controls,52 routine imaging cannot at present establish (or disprove) the diagnosis. When

clinical assessment strongly suggests a functional stroke mimic, the role of neuroimaging is to

detect concomitant (cerebrovascular) pathology. Normal scans can only serve as evidence

against acute ischemia when there is a clear incongruence between imaging features and

observed symptoms. Since lacunar strokes can remain undetected in all available imaging

modalities, incongruous findings can only relate to presentations that suggest non-lacunar (i.e.

territorial) infarcts. Examples of such findings would be lack of early ischemia signs in late

presentations, normal MRI in someone with a dense hemiparesis and lack of dense artery sign

or conjugated eye deviation on CT when large vessel occlusion is suggested clinically.53, 54

Perfusion CT imaging can visualize territorial ischemia in cases when nonenhanced CT is

normal, but false negative findings are not uncommon. Atypical perfusion changes can reveal

other stroke mimics such as focal epileptic seizures.55

If available, emergency MRI with diffusion weighted imaging (DWI) can be used to visualize

ischemic brain damage. However, according to a recent meta-analysis about 7% of acute

ischemic stroke cases have no detectable DWI lesions.56 In a study of 701 acute ischemic stroke

cases who had undergone acute MRI, 31 had no DWI lesion, and 6 (19%) of those were

retrospectively determined to have had functional symptoms.57 True DWI-negative stroke cases

all corresponded to lacunar or posterior circulation stroke syndromes such as ataxic

hemiparesis or isolated internuclear ophthalmoplegia.57 Thus, a DWI-negative stroke that does

not correspond to a known stroke syndrome58 should prompt specific reexamination regarding

functional neurological deficits.

8

In summary, neuroimaging can only support, but not prove the diagnosis of functional

neurological disorder; and it can detect an acute infarction, but cannot exclude it with absolute

certainty. Although it cannot thus establish the diagnosis of a functional stroke mimic on its

own, it can tip the scales sufficiently to guide treatment.

DECIDING ON A DIAGNOSIS

The diagnostic decision of acute-onset functional neurological disorder vs.

imaging-negative/atypical stroke has to be reached as quickly as possible. While the above

mentioned examination techniques can be incorporated into the neurological examination

without significant delay, further information from collateral history or short-term observation

might not be available acutely, leading to variable levels of diagnostic confidence at the end of

the emergency workup.11 Considering the proven safety of thrombolysis for stroke mimics, only

a high level of certainty regarding the phenotype-based diagnosis of a functional stroke mimic,

supported by positive clinical signs and normal neuroimaging, can justify withholding acute

stroke treatment, i.e. thrombolysis. In all other cases, the possibility of a functional disorder can

be communicated early on, but a competing suspicion of acute ischemia should prompt stroke

treatment algorithms in consideration of the short therapeutic windows. Follow-up

examinations will usually settle the final diagnosis. Studies of functional motor disorder

including stroke-like presentations suggest a very low rate of misdiagnosis (less than 1%) at

follow up,59-61 although more studies from a hyperacute setting are required.

MANAGEMENT

Treatment begins with an open and clear communication of the problem (table 3). 62 A simple

explanation of the disorder can be offered, making clear that the loss of motor control or

sensation results from abnormal brain functioning rather than structural damage (“software,

not hardware”); as such, it is potentially reversible through appropriate therapy. It is important

to keep in mind that a functional neurological disorder is just as real, worrisome, and disabling

as stroke can be. Terms such as “hysteria”, “psychogenic” and “conversion” imply an unproven

9

etiology and are likely to offend.63 Psychological risk factors, when present, should not be

ignored, but are best addressed later in treatment once patients have a secure understanding of

their condition. This is similar to addressing smoking or lifestyle issues in relation to ischemic

stroke later as part of rehabilitation. If patients have been managed under the working

diagnosis of ‘stroke’ so far, the distinction should be made clear, as well as the fact that the

diagnosis is based not just on normal imaging, but primarily on specific clinical signs. There may

be particular value in showing patients the positive clinical signs that establish the diagnosis: it

emphasizes that the diagnosis is not reached by exclusion and reveals the nature of the problem

(a deficit of voluntary but not automatic movement) as well as the potential for improvement.64

Provision of information, for example from websites such as www.neurosymptoms.org or

patient organizations such as www.fndhope.org, may be helpful, but should not be regarded as a

substitute for treatment.

As the patient achieves a degree of confidence in the diagnosis, treatment is more likely to be

helpful. Patients with functional limb weakness have been shown to benefit from specialized

physiotherapy that relies on retraining movement emphasizing the promotion of automatic

movements with diverted attention .65 A feasibility trial of this approach compared to a standard

neurophysiotherapy showed high rates of improvement66 and a multicenter randomized

controlled trial of specialized physiotherapy for functional motor disorder is currently

underway.67 Importantly, physiotherapy is different than that for stroke. Techniques that focus

attention on the impairment, such as strengthening or balancing exercises, are unlikely to help,

and walking aids should be avoided. Instead, normalization of movement is aimed for through

distraction techniques and task-oriented exercises.65 Functional dysarthria or aphasia respond

well to specialized speech therapy.42 Stroke clinicians are well suited to manage acute

multidisciplinary treatments and initiate appropriate long-term rehabilitation.

If acute psychiatric symptoms such as severe anxiety or suicidality are present

(neuro)psychiatric assessment is necessary. Some patients with functional disorders will

10

benefit from psychotherapy, exploring how risk factors may have contributed to vulnerability

and perpetuation of symptoms, but clinicians should avoid the idea that all patients need or

benefit from such treatment, and it is typically best delivered after some improvement in motor

function has occurred. As with stroke, successful treatment of functional neurological disorder

is a multidisciplinary endeavor which may include occupational68 and speech therapy42 in

addition to modalities already mentioned. It should be stressed that functional motor and

sensory symptoms have a prognosis comparable to that of “organic” cases, with about half of

patients showing no improvement in the long term.59 The associated disability should not be

underestimated, and the rate of spontaneous remissions should not be overestimated.

Table 3 Principles of treatment for functional neurological disorder presenting to the stroke

service

Positive Clinical Diagnosis and Communication

Make a diagnosis based on positive diagnostic features, not on normal investigations

Explain diagnosis clearly, preferably demonstrating positive features

Provide accessible material to allow the patient to understand the diagnosis

Physiotherapy

Link principles of physiotherapy to ideas of brain retraining: promotion of ‘normal’ automatic

movements and suppression of ‘abnormal’ voluntary movement

Emphasis on goal-directed task-specific movement, e.g. kick a football, rather than specific

limb movements

Use of full length mirror or video for visual feedback

Psychological therapy

Assessment/formulation of potential predisposing, precipitating and perpetuating factors

Treatment of comorbid anxiety, depression and other psychiatric disorders

‘Retraining’ of aberrant cognitions and behaviors in relation to movement

Occupational Therapy

Careful use of aids and appliances, only as short term solutions; requires planning to stop

using

Focus on goal-directed activities which may often involve overcoming fear-avoidance

Speech and Language Therapy

Identification and promotion of normal automatic sounds and identification of aberrant

involuntary speech sounds

11

ACKNOWLEDGEMENTS

We thank Dr. Natalie Zadrozny for assistance with the figure.

SOURCES OF FUNDING

None.

DISCLOSURES

S.P. received a speaker’s honorarium (Novartis).

J.S. is supported by an NHS National Research Scotland Career Fellowship and reports

independent expert testimony work for personal injury and medical negligence claims, royalties

from UpToDate for articles on functional neurological disorder and runs a free non-profit self-

help website, www.neurosymptoms.org.

A.M.B. is a co-founder of Brainomix which is developing eASPECTS.

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Figure.

Positive clinical signs of Functional Neurological Disorder: (A) Hoover’s sign: Right hip

extension is weak, but normalizes during contralateral flexion. (Gray and white arrows indicate

examiner’s and patient’s active movements respectively; striped arrows indicate patient’s

automatically/involuntarily generated movement in the affected limb.) (B) Hip abductor sign:

Right hip abduction is weak, but normalizes during contralateral abduction. (Arrows same as

above.) (C) Drift without pronation in functional arm weakness; with pronation in stroke. (D)

Unilateral lip pulling with ipsilateral platysma contraction in functional facial dystonia.

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