Mental health outcomes of encephalitis: An international web‐based study

Abstract

Background and purpose
Acute encephalitis is associated with psychiatric symptoms. Despite this, the extent of mental health problems following encephalitis has not been systematically reported.

Methods
We recruited adults who had been diagnosed with encephalitis of any aetiology to complete a web‐based questionnaire.

Results
In total, 445 respondents from 31 countries (55.1% UK, 23.1% USA) responded. Infectious encephalitis constituted 65.4% of cases, autoimmune 29.7%. Mean age was 50.1 years, 65.8% were female, and median time since encephalitis diagnosis was 7 years. The most common self‐reported psychiatric symptoms were anxiety (75.2%), sleep problems (64.4%), mood problems (62.2%), and unexpected crying (35.2%). Self‐reported psychiatric diagnoses were common: anxiety (44.0%), depression (38.6%), panic disorder (15.7%), and posttraumatic stress disorder (PTSD; 21.3%). Severe mental illnesses such as psychosis (3.3%) and bipolar affective disorder (3.1%) were reported. Self‐reported diagnosis rates were broadly consistent with results from the Psychiatric Diagnostic Screening Questionnaire. Many respondents also reported they had symptoms of anxiety (37.5%), depression (28.1%), PTSD (26.8%), or panic disorder (20.9%) that had not been diagnosed. Rates of psychiatric symptoms did not differ between autoimmune and infectious encephalitis. In total, 37.5% respondents had thought about suicide, and 4.4% had attempted suicide, since their encephalitis diagnosis. More than half of respondents (53.5%) reported they had no, or substandard, access to appropriate mental health care. High rates of sensory hypersensitivities (>75%) suggest a previously unreported association.

Conclusions
This large international survey indicates that psychiatric symptoms following encephalitis are common and that mental health care provision may be inadequate. We highlight a need for proactive psychiatric input.

Full text

Eur J Neurol. 2024;31:e16083.  
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https://doi.org/10.1111/ene.16083
wileyonlinelibrary.com/journal/ene
Received:28June2023
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Accepted :18Septemb er2023
DOI : 10.1111/ene.16083
ORIGINAL ARTICLE
Mental health outcomes of encephalitis: An international
web- based study
Matt Butler1 | Yasmin Abdat1 | Michael Zandi2 | Benedict D. Michael3 |
Ester Coutinho1,4 | Timothy R. Nicholson1 | Ava Easton3,5 | Thomas A. Pollak1
This is an op en access arti cle under the ter ms of the CreativeCommonsAttribution License, which permits use, distribution and reproduction in any medium,
provide d the original wor k is properly cited.
©2023TheAuthors .European Journal of Neurologypublishe dbyJohnWiley&SonsLtdonbeha lfofEurop eanAca demyofNeurolog y.
MattBu tleran dYasminAb datarejo intfir stauth ors.
1NeuropsychiatryResearchan dEducation
Group, King's College London, London, UK
2DepartmentofNeuroinflammation,
UniversityCollegeLondonQueenSquare
Instit uteofNeurology,London,U K
3Depar tment of Clinic al Infec tion,
Microbiology, and Immunology, University
of Liverpool, Liverpool, UK
4CenterforNeuros cienceandCell
Biolog y, University of Coimbra, Coimbr a,
Portugal
5Encepha litisSo ciety,Malton,UK
Correspondence
MattButler,Neuro psychiatryRe search
andEduc ationGroup,King'sCollege
London, London, UK.
Email:matthew.butler@kcl.ac.uk
Funding information
Wellcome Trust Docto ral Clinical
ResearchFellow,Gr ant/AwardN umber :
227515/Z/23/Z; UKRI/MRC, Grant/
AwardNumber:MR /V03605X /1;National
Instit ute for He alth Res earch, Grant /
AwardNumber:CO-CIN-01;Med ical
Research Council; MRC/UKRI, Grant/
AwardNumber:MR /V0 07181/1;Medical
ResearchCouncil,Gra nt/AwardNumber:
MR/T028750/1;Wellcome,Grant /Award
Number:ISSF201902/3
Abstract
Background and purpose: Acute encephalitis is ass ociated with psychi atric symptoms .
Despite this, the extent of mental health problems following encephalitis has not been
systematically reported.
Methods: We recruited adults who had been diagnosed with encephalitis of any aetiol-
ogytocompleteaweb-basedquestionnaire.
Results: Intotal,445respondentsfrom31countries(55.1%UK,23.1%USA)responded.
Infectious encephalitis constituted 65.4% of cases, autoimmune 29.7%.Mean age was
50.1 years,65.8%werefemale,andmediantimesinceencephalitisdiagnosiswas7 years.
Themostcommonself-reportedpsychiatricsymptomswereanxiety(75.2%),sleepprob-
lems (64.4%), mood problems (62.2%), and unexpected crying (35.2%). Self-reported
psychiatricdiagnoseswerecommon:anxiety(44.0%),depression(38.6%),panicdisorder
(15.7%),and posttraumatic stress disorder(PTSD; 21.3%). Severemental illnesses such
as psychosis (3. 3%) and bipolar affe ctive disorder (3.1%) were repo rted. Self-repor ted
diagnosis rates were broadly consistent with results from the Psychiatric Diagnostic
Screening Questionnaire.Manyrespondentsalsoreportedtheyhadsymptomsof anxi-
ety (37.5%),d epression (28.1%), PTSD (26.8%), or p anic disorder (20.9%) that ha d not
been diagnosed. Rates of psychiatric symptoms did not differ between autoimmune and
infectious encephalitis. In total, 37.5% respondents had thought about suicide, and 4.4%
had attempted suicide, since their encephalitis diagnosis. More than half of respond-
ents(53.5%)reportedtheyhadno,orsubstandard, accesstoappropriate mentalhealth
care. High rates of sensory hypersensitivities (>75%) suggest a pr eviously unrepor ted
association.
Conclusions: This large international survey indicates that psychiatric symptoms follow-
ingencephalitisarecommon and that mentalhealthcareprovision may be inadequate.
We highlight a need for proactive psychiatric input.
KEYWORDS
autoimmune encephalitis, hypersensitivities, infective encephalitis, mental health, psychiatric

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INTRODUCTION
Encephalitisisadevast atingdisorderwithaglobalincidenceof0.5–
16/100,000 per year [1]. It is defined by the presence of inflamma-
tion in the brain parenchyma associated with clinical evidence of
neurological dysfunction [2].Aetiologiesaregroupedintotwocate-
gories:infectiousandimmune-mediated[3]. In as many as 37%, the
cause is unknown, although improving diagnostics may be reducing
this figure [4].
The clinical presentations of acute encephalitis are dependent on
factors such as the causative agent and the brain regions af fected.
Common acute features include headache, seizures, focal neurolog-
ical signs, movement disorders, personality/behavioural changes,
and cognitive impairment/confusion [4].
Althoughdirectcomparisonsarelacking,itisprobablethatauto-
immune encephalitis is more likely to present with isolated or more
prominent psychiatric features in the context of subtle neurological
signs. In an earlyseries of N-methyl-D-aspartate(NMDA)receptor
(NMDAR) antibodyencephalitis, asmany as 80% of patients were
initially assessed by mental health services [5]. This figure has de-
creased as awareness of the condition has improved [6], but misdiag-
nosis encephalitis still occurs in a bidirectional manner [7, 8].
Mortality varies by geographical region but can be up to 30%
in infectious encephalitis, and in autoimmune encephalitis it ranges
between 12% and 40% [1].Many more survivorsare left withlife-
changing neurological injury and dysfunction. Common sequelae
include physical, cognitive, emotional, behavioural, and social diffi-
culties [9 – 1 1 ].
Whereascognitivesequelaehavebeenexploredinsomedetail,
studies have seldom directly addressed mental health outcomes [12,
13]. Of these, the majority have had small sample sizes or focus on
a relatively narrow range of symptoms [14–19], or on specific sub-
type s of encephalitis in sp ecific populati on groups (e.g., chil dren)
[20] and therefore may be unrepresent ative. Fur ther research is
thusrequiredtoassessmentalhealthoutcomesinencephalitisofall
aetiologies. Todate,there have beenno large-scale data exploring
thelong-termmentalhealthoutcomesofencephalitisfrompatients'
perspectives.
Furthermore, recent evidence has pointed toward sensory
(hyper)sensitivitiesbeingassociatedwithacquiredbraininjury,lead-
ing to the suggestion that these may also be a feature in patients
who have had encephalitis [21].
In this stu dy,we a imed to charac terize self-re ported ment al
health outcomes in the encephalitis population. We aimed to col-
lect dat a on self-repor ted symptoms a nd diagnoses, i n addition
to using a validated diagnostic screening tool for common men-
tal health disorders. We also wished to underst and patients'
experiences of their initial diagnosis, the management of their
postencephalitis symptoms, presence or absence of sensory hy-
persensitivities, and perceptions about the impact of their en-
cephalitis diagnosis. To achieve this, we created a web-based
questionnaire that was distributed to an international sample of
encephalitis patients.
METHODS
Design and materials
Thiswasacross-sectionalobservationalstudycodesignedwiththe
EncephalitisSociety.Aweb-basedsurvey(seeSupplementaryInfor-
mation)wascreatedusingtheplatformQualtrics.Respondentswere
recruitedover19 weeksthroughanopenaccesslinkviasocialmedia
platfo rms and mailing list s of the Encephali tis Society. Quest ions
werewritteninclearEnglish,andmedicalterminologywasavoided
where possible.
Respondentswereindividualswho self-reporteda diagnosisof
encephalitis, of any subtype, by a medical professional. Respondents
were asked to read the electronic participant information sheet,
which detailed the aims and scope of the study. Following this, they
wereaskedtoprovideconsent.Asingle£50voucherprizedrawwas
offered to respondents who agreed to provide their email address.
Question themes included basic demographics, encephalitis
diagnosis and characteristics, experience with and management
of postencephalitis symptoms/diagnoses, and illness perceptions.
Questions were in theformat of tick-boxes,visual analogue scales
(VAS), and free-text fields. Whererespondents wereasked to rate
the degree to which they agree to a statement, this was on a scale
from 0 representing "strongly disagree" to 50 representing "neither
agree nor disagree" to 100 representing "strongly agree".
Participants were asked whether they had experienced any sen-
sory hypersensitivities since their encephalitis diagnosis, and were
prompted to answer by sensory modalit y (light s, sounds, touch,
taste,temperature,smell,other).
QuestionsonmoodwereadaptedfromtheMaudsleythree-item
VAS(M3VAS),whichhasbeenvalidatedagainsttheQuickInventory
of Depressive Symptomatology 16-item scale [22]. Respondents
were, for example, asked to rate their current mood over the past
2 weeks onavisual scaleof 1–100,where 0represented "not atall
depressed" and 100 represented "extremely depressed".
Respond ents were asked qu estions fro m the Brief Illne ss Per-
ception Questionnaire (BIPQ), a validated scale usedto assessthe
cognitive and emotional representations of illness [23]. In this study,
questi ons were modif ied to change the wo rd "illness" to "po sten-
cephalitis symptoms", and respondents were asked to rank each an-
swer on a VAS ranging from, for example, 0 = "no control at all"to
100 = "fullcontrol".
Respondents completed the Psychiatric Diagnostic Screening
Ques ti on na ire(PDS Q),abr ief,self-re po rtscaledesignedtos cr ee nfor
13 of the most common mental health disorders as per the Diagnos-
ticand StatisticalManual of Mental Disorders,4thedition [24]. The
PDSQresponseswerescoredasperthePDSQscoringinstructions.
Data analysis
Data were an alysed usin g IBM SPSS Sta tistics 28 . Age was cal cu-
lated as year of birth to survey year; similarly, length of symptoms

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MENTAL HEALTH OUTCOMES OF ENCEPHALITIS
and time since diagnosis were calculated as year of occurrence to
survey year (2022).Unlessotherwise stated,data arepresentedas
mean (±SD) or median (interquartile range[IQR]). Whererespond-
ents were given the option to select more than one answer, mutually
incompatible answers were removed from analysis.
Descriptivestatistics(i.e.,frequencies,proportions/percentages,
measuresofcentraltendencyanddispersion)wereusedtosumma-
rizethedata.Chi-squaredtests,independentt-tests,andanalysisof
variance tests were used where appropriate.
Data visualizations were created in RStudio (version
2023.06.0-421).
Ethics
This study conforms with the World Medical Association Declara-
tion of Helsinki. The study was approved by King's College London
ResearchEthicsCommittee(Ref:17778).
RESULTS
Demographics
In total, 4 45 respondents from 31 countries completed the survey
(Table 1); 45 were completed by carersand 32with carerassistance.
All4 45respondentsreportedthattheyhadbeendiagnosedwithen-
cephalitisby amedicalprofessional:300(72.8%) byaneurologist,49
(11.9%)byaninfectio usd iseasesdoctor,n ine(2.2%)byapae diatrician,
two(0. 5%)byapsychiatrist,and52(12.6%)byanothert ypeofdoctor.
The mean age was 50.1 years (SD = 15.6, range = 18–85); 292
(65.8%)werefemale. Most respondentsresided in the UK(n = 245,
55.1%) or the USA (n = 103, 23.1%, ), but response s were received
from 29 add itional countrie s (2.2% from low- and middl e-income
countrie s). In total, 432 (98 .2%) had comp leted mand atory edu ca-
tion. More than half (n = 241, 54.3%,) were married; 182 (40.9%)
wereinsomeformofemployment,withmorethanaquarterunem-
ployed (n = 122,27.4%).
Acute encephalitis
Average time since encephalitis symptoms began was a median of
7.0 years (IQR = 3.0–15.0). Infectious encephalitis constituted 286
(65.4%)cases;themostcommoncaus at iveinfe cti ou sagentw as he rp es
simplex virus (n = 167,41.0%ofallrespondents).Autoimmuneenceph-
alitisconstituted130(29.7%),caseswiththemostcommontypebeing
anti-NMDARencephalitis(n = 38,9.3%ofallrespondents;Figure 1).
Nearly h alf (n = 209, 47.5%) re ported h aving received a n incor-
rect diagnosis before their final diagnosis. Incorrect diagnoses in-
cluded physical diagnoses (n = 131, 29.8%), psychiatric diagnoses
(n = 37,8.4%),bothpsychiatricandphysicaldiagnoses(n = 15,3.4%),
and unknown (n = 5,1.1%).Themostcommonmisdiagnoses(n = 200)
included upper respiratory tract infection (n = 24,12.0%),meningitis
(n = 17, 8 .5%), migraine (n = 13 , 6.5%), mixed psych iatric diagnos es
(n = 12,6.0%),mixedmedicaldiagnoses(n = 11,6.1%),andpsychiat-
ric diagnoses not otherwise specified (n = 11,6.1%).
Severityofacuteillness
Of valid responses (n = 442), 268 (60.6%) reported being admitted
to a general hospital ward when their encephalitis first star ted and
40 (9.0%)to intensive care (ITU) or high-dependency care, and 53
(12.0 % )rep o r t e dthe y wer e not a d mit te dto h o spi t a l .Thi r t y r e spon d -
ents (6.8 %) were admit ted to a psychiat ric hospit al. Overa ll, there
was no effect of severity based on admission type on likelihood of
developing a psychiatric outcome (z- s c o r e < 2.0onchi-squaredtests
forallmentalhealthdiagnosesforpatientsadmittedtoITU).
Psychiatric symptoms and diagnoses
Int ot al,402(9 0.4%)ind ic at ed th at th ey ha da tlea st on ec ur rentps yc hi-
atric symptom.Symptoms,bothphysical and ment al, were commonly
TAB LE 1 Demographicsofrespondentsfromthestudy.
Characteristic n%
Gendera444 —
Female 292 65.8%
Male 149 33.6%
Age 444 —
Meanyear s(SD) 50.1(15.6) —
Range, years 18–85 —
Employmentstatus 4 45 —
Full-time 97 21.8%
Part-time 55 12.4%
Self-employed 30 6.7%
Unemployed 122 27. 4%
Retired 95 21.3%
Student 20 4.5%
Other 26 5.8%
Country of residence 445 —
UKandNor thernIrelan d 245 55.1%
USA 103 23.1%
Australia 34 7. 6%
Canada 12 2.7%
Otherb51 11.5%
aTwopreferredtoself-describe,onepreferrednottosay.
b"Other"includesBelgium(1),Brazil(1),Croatia(2),Cyprus(1),
Dominic anRepublic(1),Finland(1),France(1),Germany(3),Greece
(1),India(4),Indonesia(3),Ireland(6),Isr ael(1),Italy(4),Lebanon(1),
Lesotho(1),Namibia(1),theNetherlands(1),NewZealand(5),Norway
(2),Philippines(1),Por tugal(2),Romania(1),Singapore(1),SouthAfrica
(1),Spain(2),andSwitzerland(2).

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co-occurring(Figure 2).Self-reportedpsychiatricdiagnosesmadebya
medical professional are presented in Table 2.N um bersof re sp ondents 
that felt they were suffering from a psychiatric diagnosis that had not
beenformallydiagnosedarereportedinSupplementaryTables S 1 – S 3 .
When asked to rate the degree to which they felt their enceph-
alitis wasthe cause of their mental health problems (0 = not at all,
100 = entirely),medianresponsewas80.0(IQR = 50.0–100.0).
Intotal,98of445(22.0%)ofrespondents werecurrentlyunder
acommunitymental healthteam(secondary care),and215 of 445
(48.3%)hadundergonesomeformoftalkingtherapy.
Of those who responded (n = 413), 24.2% felt they had not
hadaccesstoappropriatementalhealthcare,andafurther29.3%
thought the access to mental health care could have been bet-
ter; 28.8% felt they had access to appropriate mental health care,
and the remaining 17.7% had not looked; patients in the UK fared
the worst (for breakdown by countr y please see Supplementary
Information).
In total, 37.5% of respondents had thought about suicide, and
4.4% of all respondents had attempted suicide since their enceph-
alitis diagnosis.
Psychiatricdiagnosticscreeningquestionnaire
Usingthecutoff scoresprovidedin thePDSQmanual, participants
met screening criteria in the following frequencies: social phobia,
161 of 347 (46.4%); depression, 143 of 347 (41.2%); obsessive–
compulsivedisorder(OCD),136of346(39.3%);posttraumaticstress
disorder(PTSD), 118of 347 (34.0%);generalized anxiety disorder
(GAD),111of347(32.0%);agoraphobia,103of347(29.7%);psycho-
sis,88of347(25.4%);panicdisorder,84of3 47(24.2%);alcoholuse
disorder,57of347(16.4%);eatingdisorder,36of346 (10.4%);and
drugusedisorder,12of347(3.5%).
Concordance of PDSQ scores versus self-reported diagnoses
(formal diagnoses + s elf-repor ted missed diagn oses) was variab le:
depression,41.2%versus44.4%; OCD, 39.3%versus14.9%; PTSD,
34.0%versus30.8%;GAD,24.2%versus62.4%;psychoticdisorder,
25.4% versus 3 .9%; panic, 24.2% ve rsus 21.5%; alco hol use disor-
der, 16.4% versus 4.1%; substance use disorder, 3.5% versus 3.6%.
Overall,the PDSQ led to a higher rate of likely diagnoses than did
self-reportforOCD,psychoticdisorder,andalcoholusedisorder.
Infectious versus autoimmune
Overall, rates of major self-reported psychiatric diagnoses and
symptoms did not significantly differ between autoimmune and in-
fectiousencephalitisonchi-squaredtesting( Table 3).
Brief Illness Perception Questionnaire
Mean and median scores on the BIPQ are summarized in Figure 3.
MaudsleyVAS
Figure 4summarizestheresultsfromtheM3VAS.Mean(SD)val-
ues (of 100) were as follows: suicidality, 15.3 (26.6); mood, 41.8
(32.1); anhedon ia, 47.3 (32. 5). Median scores (ra nge) were as fol-
lows:suicidality,0.0(0.0–20.0);mood,40.0(10.0–70.0);anhedonia,
50.0(19.0–77.5). Notably,whereas most respondentsexperienced
relatively low levels of suicidal ideation (modal value = 0, 70.5%of
FIGURE 1 Encephalitissubtypes.Notallrespondentssubmitted
responses about the aetiological agent (n = 407included).AWhere
known, other aetiologies included mumps (n = 4),influenza(n = 2),
COVID-19(n = 1),equine(n = 1),measles(n = 1),mycoplasma(n = 1),
scarlet fever (n = 1),andWestNilevirus(n = 1).BWhere known,
other aetiologies included Bickerstaff (n = 1),acutenecrotizing
encephalopathy (n = 1),anti-dipeptidyl-peptidase-likeprotein-6
(n = 1),anti-GAD(n = 1),anti-glialfibrillar yacidicprotein(n = 1),
anti-Hu(n = 1),paraneoplastic(n = 1),andRasmussen(n = 1).
ADEM,acutedisseminatedencephalomyelitis;CASPR2,contactin-
associatedprotein-like2;EBV,epstein-barrvirus;HSV,herpes
simplexvirus;JEV,Japaneseencephalitisvirus;LGI1,leucine-rich,
glioma-inactivated1;NMDAR ,N-methyl-D-aspart atereceptor.
SREAT,steroid-responsiveencephalopathyassociatedwith
autoimmunethyroiditis;TBE,tick-borneencephalitis;VGKC,
voltagegatedpotassiumchannel;VZ V,varicella-zostervirus.
Total sample
(n=437)
Infecous
(n=229,65.4%)
HSV
(n =167,41.0%)
VZV
(n=19, 4.7%)
TBE
(n=8,2.0%)
EBV
(n=3,0.7%)
JEV
(n=2,0.5%)
OtherA
(n=30, 7.4%)
Autoimmune
(n=112,29,7%)
An-NMDAR
(n=38, 9.3%)
An-LGI1
(n=13, 3.2%)
An-VGKC
(n=6,1.5%)
An-CASPR2
(n=1,0.2%)
ADEM
(n=15, 3.4%)
SREAT
(n=6,1.5%)
OtherB
(n=33, 8.4%)
Other
(n=13, 0.9%)
Unknown
(n=53, 3.9%)
Missing
(n=30)

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respon dents in lowes t centile), a mino rity of patie nts exper ienced
highlevels(7.0%ofrespondentsinhighestthreecentiles).
Hypersensitivities
In total, 325 of 414 (78.5%) h ad experie nced at leas t one sensor y
hypersensitivity; 99 (23.9%) had two hypersensitivities, and 164
(39.6%) three or more hyp ersensitiv ities. By modal ity, there were
light hypersensitivitiesin 233 (56.3%),sound hypersensitivities in
250(60.4%),touchhypersensitivitiesin93(22.4%),tastehypersen-
sitivitiesin95(22.9%),temperaturehypersensitivitiesin170(41.1%),
andsmellhypersensitivitiesin23(5.6%).
Hypersensitivities were found to have a significant effect on
daily life of r esponden ts. On a sc ale of 0 = "not affe cting dail y life
at all" to 10 = "severelyaffecting daily life",mean (SD) hypersensi-
tivitieswereratedasfollows:light,5.3(2.6);sound,5.8(2.6);touch,
5.5(2.7);taste, 5.1(2.8);andtemperature,5.8(2.5). Therewere no
differences bet ween anxiety and depression scores in those with or
without hypersensitivities.
Management of symptoms
The most common treatment used among respondents at any
point following encephalitis was medication (64.5% of total sample,
n = 287);morespecifically,nonopiatepainkillers(31.5%oftotalsam-
ple, n = 140) antidepressants (33.3% oftotal sample, n = 148), ben-
zodiazepines (20.7% of total sample, n = 92),sleepingtablets(16.9%
of total sample, n = 75), opiates (16.2% of total sample, n = 72), an-
tipsychotics (11.0% of total sample, n = 49),andmedicinal cannabis
(6.3% of total sample, n = 28)hadbeen used.Bothanswersof "no"
andmissing responses to thesequestions were takenas indication
thatthe participanthadnotused the medication.Self-reportedef-
fectiveness of these treatments is summarized in Table 4.
Other forms of therapy included occupational therapy (n = 143,
40.4%), neuropsychological rehabilitation (n = 132, 37.3%), cogni-
tive behavioural therapy (n = 123,34.1%),andotherpsychotherapy
(n = 107,30.6%).
Legal nonprescribed substances had also been used to help
managesymptomsfollowingencephalitisin19.1%ofrespondents
and include energy drinks/caffeine (n = 27, 7.4%), cannabidiol
FIGURE 2 Conditionalprobabilitymatrixofsymptomco-occurrence.Numbersinthegridindic atetheproportion(prop)ofrespondents
withsymptom/featureAwhoalsohadsymptom/featureB.Thestrengthoftheproportionisrepresentedbythecolourofthesquare
betweensymptoms;darkercoloursindicatestrongerco-occurrenceofasymptom/featureAwithasymptom/featureB.Symptomswere
labeled as present if they had occurred at any time since the encephalitis diagnosis.

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(CBD; n = 27,7.4%),alcohol(n = 19,5.2%),tobacco (n = 10,2.7%),
and e-cigarettes/nicotine (n = 4, 1.1%). Mean (SD) effective-
ness of legal substances wereas follows(0 = not effectiveatall,
100 = completelyeffective):caffeine,53.6(32.0);CBD,67.3(29.9);
alcohol , 42.3 (23.8); tobac co, 49.7 (40 .9); and e-cigaret tes/nico-
tine,49.7(47.6).
In total, 6.5% had obtained medication without prescription to
treat their symptoms following encephalitis.
TAB LE 2 Formalmentalhealthorpsychiatricdiagnosesinrespondents.
Diagnosis nYes, currently
Yes, in the past, after my
encephalitis diagnosis
Yes, in the past, before my
encephalitis diagnosis No
Depression 409 101(24.7%) 57(13.9%) 34(8.3%) 217(53.1%)
Anxiety 402 127(31.6%) 50(12.4%) 35(8.7%) 190(47.3%)
Panic disorder 396 32(8.1%) 30(7.6%) 15(3.8%) 319(80.6%)
Posttraumatic stress disorder 396 43(10.9%) 41(10.4%) 14(3.5%) 298(75.3%)
Obsessive–compulsivedisorder 397 25(6.3%) 15(3.8%) 7(1.8%) 350(88.2%)
Psychotic disorders 400 7(1.8%) 6(1.5%) 9(2.3%) 378(94. 5%)
Bipolar disorder 398 9(2.3%) 3(0.8%) 6(1.5%) 380(95.4%)
Personality disorder 398 18(4.5%) 13(3.3%) 10(2.5%) 357(89.7%)
Impulse control disorder 397 8(2.0%) 13(3.3%) 1(0.3%) 375(94. 5%)
Alcoholdependence 398 7(1.8%) 7(1.8%) 5(1.3%) 379(95.2%)
Drug dependence 397 7(1.8%) 2(0.5%) 4(1.0%) 384(96.7%)
Other 301 3(1.0%) 3(1.0%) 4(1.3%) 291(96.7%)
TAB LE 3 Comparisonofpsychiatricsymptomsanddiagnosessplitbyautoimmuneandinfectioussubtypes.
Autoimmune Infectious
Yes Past No Ye s Past No
Symptoms Anxiety 91(72.8%) 16(12.8%) 18(14.4%) 209(76.0%) 34(12.4%) 32(11.6%)
Mood problems 66(52.4%) 36(28.6%) 24(19.0%) 181(66.6%) 47(17.3%) 44(16.2%)
Psychosis 9(7.5%) 39(32.5%) 72(60.0%) 25(9.6%) 46(17.8%) 188(72.6%)
Aggression 30(24.8%) 35(28.9%) 56(46.3%) 86(32.2%) 44(16.5%) 137(51.3%)
Diagnoses Anxiety 52(42.6%) 10(8. 2%) 60(49.2%) 111(43.7%) 23(9.1%) 120(47.2%)
Depression 38(31.4%) 12(9.9%) 71(58.7%) 108(40.5%) 20(7.6%) 136(51.9%)
Panic 11(9.2%) 5(4.2%) 104(86.7%) 43(17.2%) 8(3 .2%) 199(79.6%)
PTSD 21(17.5% ) 4(3.3%) 95(79.2%) 53(21.2%) 10(4.0%) 188(74.9%)
Psychosis 6(5.0%) 6(5.0%) 108(90.0%) 7(2.8%) 3(1.2%) 245(96.1%)
Bipolar 7(5.8%) 5(4.2%) 107(89.9%) 4(1.6%) 0(0.0%) 250(98.4%)
Pers. dis. 10(8.4%) 5(4.2%) 104(87.4%) 18(7.1%) 4(1.6%) 232(91.3%)
PDSQCaseness Depression 43(39.8%) 91(41.6%)
PTSD 36(33.3%) 74(33.8%)
Eatingdisorder 14(13.1%) 20(9.1%)
OCD 39(36.4%) 87(39.7%)
Panic 27(25.2%) 53(24.1%)
Psychosis 26(24.3%) 56(25.5%)
Agoraphobia 27(25.2%) 69(31.4%)
Socialphobia 45(42.1%) 104(47.3%)
Alcoholabuse 14(13 .1%) 39(17.7%)
Drug abuse 4(3.7%) 6(2.7%)
GAD 25(23.4%) 82(37.2%)
Abbreviations:GAD,generalizedanxiet ydisorder;OCD,obsessive–compulsivedisorder;PDSQ,PsychiatricDiagnosticScreeningQuestionnaire;
Pers.dis.,personalit ydisorder;PTSD,posttraumaticstressdisorder.

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FIGURE 3 Violinplotofkerneldensit y
estimates from the Brief Illness Perception
Questionnaire(BIPQ)withoverlaid
boxplots. There were no differences
in mean BIPQ subscores between
autoimmune and infectious groups.
FIGURE 4 Violinplotofkerneldensit y
estimatesfromtheMaudsleythree-
item visual analogue scale. Individual
participant scores are represented by
dots (the random vertical distribution of
thedotsisavisualaidonly).Respondents
wereaskedhowseverely/frequentlythey
have experienced thoughts or feelings
aboutsuicideoverthepast2 weeks.
Medication Unhelpful Somewhat helpful Helpful
Antidepressants,n = 126 33(26.2%) 47(37.3%) 46(36.5%)
Benzodiazepines, n = 81 15(18.5%) 28(34.6%) 38(46.9%)
Antipsychotics,n = 44 19(43.2%) 13(29.5%) 12(27.3%)
Sleepingtablets,n = 71 16(22.5%) 33(46.5%) 22(31.0%)
Opiates, n = 64 12(18.8%) 28(43. 8%) 24(37.5%)
Nonopioidpainkillers,n = 114 25(21.9%) 4 0(35.1%) 49(43.0%)
Medicinal cannabis, n = 77 13(16.9%) 14(18.4%) 50(64.9%)
TAB LE 4 Self-reportedeffectivenessof
treatments.

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In total, 7.5% (n = 29)had triedillegal street substancestohelp
manage symptoms following encephalitis, which included cannabis
(n = 21,5.4%),psilocybin(n = 4,1.0%),andcocaine(n = 3,0.8%).
DISCUSSION
This study represents the largest international survey on psychi-
atric symptoms following encephalitis, acquiring data on an un-
precedented breadth of psychiatric symptomatology in a markedly
underresearched patient group. Responses indicated high rates of
self-reported mental health symptoms and diagnoses, with many
reportingthat they had notreceivedadequate psychiatric care fol-
lowing encephalitis. The high rates of psychiatric disorders following
encephalitis likely have multiple overlapping causal factors, which
include pathogenic brain effects, medication response, residual
symptoms, psychological readjustment, and the repercussions of
change in functional status and/or resultant physical disability.
The psychiatric community has become increasingly aware of
encephaliti ssi ncethefi rs tde scriptionsofNMDARsubtypepresent-
ing with psychotic symptoms [25]. Auto immune encephal itis now
represents a differential diagnosis for acute, new onset severe psy-
chiatric presentations including psychosis [8, 26]. The current study
found that psychiatric symptoms are also very common in the years
following encephalitis, indicating that awareness of mental health
associations should not be solely restricted to acute presentations.
There are many data indicating that people with other neurolog-
ical disorders (select examples include epilepsy, Parkinson disease,
and migraine) have comorbid psychiatric disorders at rates much
higher than population averages [27]. Traumatic brain injury is as-
sociated with the development of both neurological and psychiatric
sequelae[28]. The relationship is complex and bidirectional; neuro-
logical patients with disorders including depression and anxiety re-
port a higher burden of somatic symptoms [29], and recovery from
depression in neurological patients is associated with improvement
in overall health status, including physical health [30].
Despite this, numerous studies have shown that physicians in
general, and neurologist s in particular, do not systematically ask
about patient's mental health in routine outpatient clinical encoun-
ters [29]. In a 2022 survey of 5500 adults with neurological disor-
ders, 61%were not asked abouttheir mentalwell-beingwithin the
preceding3 years[31].Assuch,considerablementalhealthdifficul-
ties may be missed.
In line with recent recommendations that liaison psychiatry
should adopt proactive models of working [32], we suggest that
mental health outcomes in encephalitis could be improved either by
ongoing involvement of psychiatry or neuropsychiatry in clinical fol-
low-up.In one studyoflong-termpsychosocialoutcomes in61pa-
tientswithanti-NMDARencephalitis,involvementofpsychiatrywas
associated with eightfold increased odds of returning to work or ed-
ucation [17].Nevertheless, systematic evaluationofthe efficacyof
mentalhealthinterventionsinpatientswithencephalitis-associated
mentalillnessisurgentlyrequired.
Ourdataregarding suicidality are deeply concerning. Although
suicidality and completed suicide have been observed as a feature
of anti-NMDAR encephalitis in one series [33], this represents a
relatively understudied area, given the contribution of suicide to
avoidable deaths. In an epidemiological study of >7 million Danish
citizens, patients who had had encephalitis were at an increased risk
ofdeathbysuicide(incidentrateratio = 1.7vs.noneurologicaldiag-
nosis);thisrateiscomparabletoindividualswithepilepsy,Parkinson
disease, and head injury, and is higher than stroke and dementia [34].
This is a concern of considerable urgency and mandates further re-
search as well as increased clinical awareness.
The high rates of sensory hypersensitivities seen in our survey
havenotpreviously been reported. Sensory processing issues are
common in traumatic brain injury [35], cerebral tumours [36], au-
tism spec trum disorders [37], and migraine [38]. The presence of
sensory hypersensitivity in these disorders correlates with depres-
sion [36], mental distress [35],and a poorerqualit y of life [39]. In
our study, there was no association between anxiety and depres-
sion and sensory hypersensitivities, potentially suggesting diverg-
ing pathophysiological mechanisms. Further work is required to
more fully elucidate the nature, extent, underlying mechanisms,
and impac ts of sensory hypersensitivities in people who have had
encephalitis.
Misdiagnosis was commonly reported by respondents. In this
study, a physical health misdiagnosis was more common than a
psychiatric misdiagnosis, likely because of the predominance of in-
fectious encephalitis diagnoses among respondent s. Increasing the
awareness and understanding of encephalitis among health care
professionals is therefore likely to be useful in the general hospital/
general practice as well as the mental health setting. Misdiagnosis
is bidirectional; a recent study indicated that misdiagnosis occurs in
approximatelyonequarterofpatientswithautoimmune encephali-
tis, albeit with significant variance between health care set tings. The
most common conditions incorrectly diagnosed as autoimmune en-
cephalitiswerefunctionalneurologicdisorder(FND),neurodegener-
ative disease, and primary psychiatric disease [7].FNDinparticular
is likely to be a common misdiagnosis in both directions and may be
seen as an additional diagnosis in some cases.
Strengths and limitations
Strengthsofthisstudyincludethelargeinternationaldataset,broad
focus, and emphasis on patient s' own perspectives. The use of an
onlineplatformtocompletethequestionnairemeantthatwecould
reach an international cohor t with limited financial or temporal
burdens.
The study has several potential limitations. The responses to
thequestionnairewere self-reported. Werecruited participants
through the social media and mailing lists of the Encephalitis
Society,which may not be representative of the entireenceph-
alitis population. The data are likely to be subject to response
and recall bias, insofar as more severely physically or cognitively

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9 of 10
MENTAL HEALTH OUTCOMES OF ENCEPHALITIS
challenged people may have been less able to complete the sur-
vey, despite our explicit signposting of the possibility of carers
completing it on their behalf. Conversely, however, some indi-
viduals who have made a full recover y may be less likely to en-
gage with t he Encephalitis S ociety or with e ncephalitis-related
content online, and therefore potentially less likely to access or
complete ourques tionnaire.We did not collectinformation on
length of time following encephalitis that respondents developed
symptoms. We also did not collect any information on cognition
or cognitive complaints.
There are attendant limitations to using screening tools such as
thePDSQ,whichbothmayoverestimatetheprevalenceofdisorders
andnotcaptureothers.Finally,thequestionnairewasonlyavailable
inEnglish.
CONCLUSIONS
Results from this large international survey indicate high rates of
self-reported mental health symptoms and diagnoses following
encephalitis. Despite the high rates, many respondents repor ted
that mental health care provision following their encephalitis was
inadequate. Overall, these results highlight a need for increased
provision of proactive psychiatric care and represent a call to ac-
tion for increased research on mental health outcomes of enceph-
alitis. Given the treatment responsiveness of many mental health
symptoms and diagnoses, this is likely to represent a global op-
portunity for reducing morbidity and mortality in this challenging
condition.
FUNDING INFORMATION
M.B. is a Wellcome Trust Doctoral Clinical Research Fellow
(227515/Z/23/Z).B.D.M. is supported to conduct COVID-19 Neu-
roscience Research by the UKRI/MRC (MR/V03605X/1). B.D.M.
is supported for additional neurological inflammation research due
to viral inf ection by gra nts from the Nat ional Instit ute for Health
Research (award CO-CIN-01), Medical Research Council (MC_
PC_19059),NIHRHealthProtectionResearchUnitinEmergingand
Zoonotic Infections at University of Liverpool, MRC/UKRI (MR/
V007181/1),MedicalResearchCouncil(MR/T028750/1),andWell-
come (ISSF201902/3).B.D.M. is further supported by the Medical
ResearchFoundation(MRF-CPP-R2-2022-100003).
CONFLICT OF INTEREST STATEMENT
A.E. is employed by the Encephalitis Society,which helped design
and disseminate the survey.
DATA AVAIL AB ILI T Y STAT EME N T
The data that support the findings of this study are available from
thecorrespondingauthoruponreasonablerequest.
ORCID
Matt Butler https://orcid.org/0000-0002-9734-6539
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SUPPORTING INFORMATION
Additional supporting information can be found online in the
Suppor tingInformationsectionattheendofthisarticle.
How to cite this article: ButlerM,AbdatY,ZandiM,etal.
Mentalhealthoutcomesofencephalitis:Aninternational
web-basedstudy.Eur J Neurol. 2024;31:e16083. doi:10.1111/
ene.16083