Criminality in patients with autoimmune encephalitis: A case series

Abstract Background and purpose Despite it being an immunotherapy‐responsive neurological syndrome, patients with autoimmune encephalitis (AE) frequently exhibit residual neurobehavioural features. Here, we report criminal behaviours as a serious and novel postencephalitic association. Methods This retrospective cohort study included 301 AE patients. Five of who committed crimes underwent direct assessments and records review alongside autoantibody studies. Results Five of 301 patients (1.7%) with AE exhibited criminal behaviours, which included viewing child pornography (n = 3), repeated shoplifting, and conspiracy to commit murder. All five were adult males, with LGI1 autoantibodies (n = 3), CASPR2 autoantibodies, or seronegative AE. None had evidence of premorbid antisocial personality traits or psychiatric disorders. Criminal behaviours began a median of 18 months (range = 15 months–12 years) after encephalitis onset. At the time of crimes, two patients were immunotherapy‐naïve, three had been administered late immunotherapies (at 5 weeks–4 months), many neurobehavioural features persisted, and new obsessive behaviours had appeared. However, cognition, seizure, and disability measures had improved, alongside reduced autoantibody levels. Conclusions Criminal behaviours are a rare, novel, and stigmatizing residual neurobehavioural phenotype in AE, with significant social and legal implications. With caution towards overattribution, we suggest they occur as part of a postencephalitis limbic neurobehavioural syndrome.

Here, we describe clinical features, focused on residual behavioural features, from a small but important group of AE patients who committed crimes.By reporting timing of administered immunotherapies, clinical features over time, and the marked social consequences, alongside autoantibody levels, we cautiously propose criminality may be a rare, residual, and markedly impactful feature of AE that relates to an established disturbance of limbic neurocircuitry without evidence of an immunological relapse.

ME THODS
A total of 301 patients were seen in the Oxford Autoimmune Neurology Clinic, UK, as clinical or research referrals between 2014 and 2021, with antibodies against LGI1 (n = 121), the NMDAR

RE SULTS
Five of 301 (1.7%) patients reported criminal behaviours, which included viewing online child pornography (n = 3, in one case also indecent public exposure), repeated shoplifting (n = 1), and conspiracy to commit murder (n = 1).The three patients viewing illegal materials were formally prosecuted, and the theft led to a ban from the relevant supermarket.
All were male, with onset of AE in their 40s-60s (Table 1).Acute features were typical for AE (Figure 1a): all with amnesia, behavioural disturbances, especially irritability and aggression, and insomnia; four showed affective features (low mood and anxiety); three exhibited apathy, emotionality, or seizures, and two displayed delusions and/or mania.Visual hallucinations or hypersexuality were only reported in one patient each.None showed obsessive-compulsive tendencies acutely, and none had premorbid antisocial behaviours, criminal convictions, or psychiatric disorders.
Criminal behaviours occurred at a median of 18 months (range = 15 months-12 years) after symptom onset.Two patients had not received immunotherapies before crimes were committed.
The remaining three had lags from symptom onset to immunotherapy administration of 5 weeks (n = 1) or 4 months (n = 2).At the time of criminal activities, no patient was on immunotherapies, and two were receiving neurotropic drugs (Table 1).
In two patients, the criminal behaviours occurred over several weeks alongside development of multiple psychiatric features, including grandiose delusions, euphoria, irritability, and obsessivecompulsive behaviours.The latter included the repeated use of a mobile phone with frequent screen tapping, obsessions over car parking orientations, and compulsive shoplifting.In the other three patients, no new behavioural features emerged around the times of crimes.In all patients, no changes in seizures or cognition were observed around the periods of criminal activity, and reinvestigation with magnetic resonance imaging and cerebrospinal fluid (CSF) studies in four patients was unremarkable.
Upon confessing the crimes, all felt marked guilt and three of five patients were rejected by their families, necessitating new accommodation and social networks.One was later reintegrated into their original family although with ongoing domestic consequences.
At last follow-up, LGI1-and CASPR2-autoantibody levels had fallen approximately 30-fold (Figure 1d) from first samples, with associated reductions in immunoglobulin G binding to limbic rodent brain regions (Figure 1e).

DISCUSS ION
We identify criminality in ~2% of a substantial AE cohort, occurring during the chronic phase in males in their fourth to sixth decades.
Around the time of offences, these five subjects showed obsessive-compulsive behaviours, absent at disease onset, and, in two, new onset disinhibitory psychopathology.In addition, all patients showed persistent deficits in several domains of behaviour, memory, sleep, emotionality, and apathy.This was despite considerable and sustained improvements in traditional disability, seizure, and cognitive outcomes, with substantial reductions in autoantibody levels.

TA B L E 1 Clinical characteristics of five autoimmune encephalitis patients who committed crimes.
a On imaging, a lung tumour was diagnosed, although no biopsy was performed.
Criminality occurred in two patients (one with LGI1 and one with CASPR2 antibodies) who were immunotherapy-naïve, and in three administered late immunotherapies (after 4 months in two).Such lags are increasingly unusual in clinical practice and exceed the ~30day threshold that predisposes to poor shorter term outcomes [2][3][4].
Therefore, we propose late and limited immunotherapies may be partly responsible for multiple residual neurocognitive syndromes, now including criminality.Given that two patients showed hypomania and disinhibition around the time of their criminality, it may be that vigilance for worsening neurobehavioural features can help identify future high-risk patients and mitigate crimes.
None of our patients showed premorbid antisocial behaviours or criminal convictions, and they took minimal medications when crimes were committed.Hence, no obvious confounding factors were identified in ascribing criminality to AE.Yet, we continue to urge significant caution in this association, as accessing online pornography is common in elderly men, can frequently include violent or unlawful material [7,8], and, overall, crimes are undertaken by ~0.2% of males older than 50 years [9,10].Hence, given our baseline demographic, this may represent a chance association, unrelated to AE.
Perhaps more likely, static postencephalitic lesions underlie the residual neurobehavioural features that manifested with criminality.This limbic-centric neurocircuitry is consistent with density of antigenic targets in the medial temporal lobe, and pattern of IgG reactivities (Figure 1e).Indeed, these regions are implicated in disinhibited behaviours, mania, and criminality in Parkinson disease, frontotemporal lobe dementias, and other neurological conditions [11,12].Hence, there is broad anatomical plausibility for these clinical observations.
As criminality led to formal prosecutions and major domestic, social, and legal consequences, this feature induced a markedly reduced QoL.Yet, mRS suggests "good" outcomes, indicating a need for more patient-focused measures in AE [5,6].Furthermore, a joined-up approach to multidisciplinary neurology and psychiatric care, alongside advice from societies experienced in AE, will greatly benefit these patients.
Study limitations include the referral bias of more immunotherapy-resistant patients, the limited data available from medical assessments immediately at the time of crimes when legal proceedings took precedence, the lack of formal access to Police (n = 54), or contactin-associated protein 2-like (CASPR2; n = 46), other rarer targets or seronegative AE (n = 25), or non-autoimmune diagnoses (n = 55).From five with criminal behaviours, detailed clinical phenotyping was performed using direct patient, partner, and carer interviews, case note review, and measures of cognition (Addenbrooke Cognitive Examination [ACE]), mood (Hospital Anxiety and Depression Scale [HADS]), and disability (modified Rankin Scale [mRS]).Mann-Whitney U-tests were used for statistics.All patients provided written informed consent (Research Ethics Committee approval 16/YH/0013).
Ages are intentionally approximated to preserve anonymity.

F I G U R E 1
Acute and chronic features associated with five patients with autoimmune encephalitis (AE) who committed crimes.(a-d) Number of patients (0-5) with each of 16 features (a) and their modified Rankin Scale (mRS) scores (b; **p = 0.0079, Mann-Whitney test), Addenbrooke Cognitive Examination (ACE) results (c; *p = 0.03, Mann-Whitney test), and autoantibody levels (d; measured by live cell-based assay end point dilutions; shown as a log scale) in both acute and chronic phases of AE.(e) Representative examples of acute and chronic serum IgG binding to rodent brain sections (from Patient #1).AutoAb, autoantibody; ns, not significant.