ABSTRACT
Objective: In patients with encephalitis, the development of acute symptomatic seizures is highly variable, but when present is associated with a worse outcome. We aimed to determine the factors associated with seizures in encephalitis and develop a clinical prediction model. Methods: We analysed 203 patients from 24 English hospitals (2005-2008) (Cohort 1). Outcome measures were seizures prior to and during admission, inpatient seizures and status epilepticus. A binary logistic regression risk model was converted to a clinical score and independently validated on an additional 233 patients from 31 UK hospitals (2013-2016) (Cohort 2). Results: In Cohort 1, 121 (60%) patients had a seizure including 103 (51%) with inpatient seizures. Admission Glasgow Coma Scale (GCS) ≤8/15 was predictive of subsequent inpatient seizures (OR (95% CI) 5.55 (2.10 to 14.64), p<0.001), including in those without a history of prior seizures at presentation (OR 6.57 (95% CI 1.37 to 31.5), p=0.025).A clinical model of overall seizure risk identified admission GCS along with aetiology (autoantibody-associated OR 11.99 (95% CI 2.09 to 68.86) and Herpes simplex virus 3.58 (95% CI 1.06 to 12.12)) (area under receiver operating characteristics curve (AUROC) =0.75 (95% CI 0.701 to 0.848), p<0.001). The same model was externally validated in Cohort 2 (AUROC=0.744 (95% CI 0.677 to 0.811), p<0.001). A clinical scoring system for stratifying inpatient seizure risk by decile demonstrated good discrimination using variables available on admission; age, GCS and fever (AUROC=0.716 (95% CI 0.634 to 0.798), p<0.001) and once probable aetiology established (AUROC=0.761 (95% CI 0.6840.839), p<0.001). Conclusion: Age, GCS, fever and aetiology can effectively stratify acute seizure risk in patients with encephalitis. These findings can support the development of targeted interventions and aid clinical trial design for antiseizure medication prophylaxis.
ABSTRACT
Herpes simplex virus (HSV) encephalitis affects 2-4 people per million/year. Immunocompomised patients can have atypical presentations of HSV encephalitis, including a lack of cerebrospinal fluid (CSF) pleocytosis. We present the case of a patient who was receiving ustekinumab therapy for psoriasis which inhibits interleukin (IL)-12 and IL-23 signalling pathways. The initial presentation was suggestive of encephalitis, but he was discharged prior to the reporting of HSV positivity due to the lack of CSF pleocytosis. On representation, he had worsening symptoms and imaging showed midline shift, indicating cerebral oedema despite the immunosupressant effects of ustekinumab. He required intensive care unit support and treatment with high dose aciclovir and dexamethasone; after a month of treatment he made a good recovery. This case is the first to report a link between ustekinumab and HSV encephalitis, and also emphasises that imunocompromised patients can lack CSF pleocytosis and develop significant cerebral oedema which responds to immune suppression.