An isolated insular stroke mimics a bout of overt hepatic encephalopathy in a patient with cirrhosis

The manifestations of hepatic encephalopathy (HE) vary from mild neuropsychiatric abnormalities to coma.[1]European Association for the Study of the LiverEASL Clinical Practice Guidelines on the management of hepatic encephalopathy.J Hepatol. 2022; 77: 807-824Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar,[2]Amodio P. Montagnese S. Lights and shadows in hepatic encephalopathy diagnosis.J Clin Med. 2021; 10: 341Crossref PubMed Scopus (4) Google Scholar Diagnosis and differential diagnosis can be challenging, especially in the hospital setting, where patients may suffer from other metabolic encephalopathies or neurological/psychiatric disorders.1European Association for the Study of the LiverEASL Clinical Practice Guidelines on the management of hepatic encephalopathy.J Hepatol. 2022; 77: 807-824Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 2Amodio P. Montagnese S. Lights and shadows in hepatic encephalopathy diagnosis.J Clin Med. 2021; 10: 341Crossref PubMed Scopus (4) Google Scholar, 3Amodio P. Hepatic encephalopathy: diagnosis and management.Liver Int. 2018; 38: 966-975Crossref PubMed Scopus (33) Google Scholar Moreover, HE might also occur on top of pre-existing disease, such as dementia.[1]European Association for the Study of the LiverEASL Clinical Practice Guidelines on the management of hepatic encephalopathy.J Hepatol. 2022; 77: 807-824Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Any potential HE precipitating factor should be identified and treated promptly.[1]European Association for the Study of the LiverEASL Clinical Practice Guidelines on the management of hepatic encephalopathy.J Hepatol. 2022; 77: 807-824Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar In patients with delirium and cirrhosis, even those with a working diagnosis of HE, a set of laboratory tests including a full blood count, glucose, electrolytes, blood gases, C-reactive protein, urinalysis, alcohol/other drugs, thyroid-stimulating hormone and ammonia should be performed. A normal blood ammonia level has a high negative predictive value.[1]European Association for the Study of the LiverEASL Clinical Practice Guidelines on the management of hepatic encephalopathy.J Hepatol. 2022; 77: 807-824Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar,[4]Nicolao F. Efrati C. Masini A. Merli M. Attili A.F. Riggio O. Role of determination of partial pressure of ammonia in cirrhotic patients with and without hepatic encephalopathy.J Hepatol. 2003; 38: 441-444Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar Herein, we present the case of a 52-year-old male with a history of mixed aetiology cirrhosis (HBV and alcohol) diagnosed in 2021 after a first episode of ascites. At the time, alcohol consumption was active and F1 oesophageal varices plus a gastric ulcer were detected on oesophagogastroduodenoscopy. No portal-systemic shunt was documented on abdominal imaging. He was discharged on treatment with a proton-pump inhibitor, carvedilol, tenofovir, and diazepam as needed. In December 2022, the patient was admitted to A&E because of confusion and slurred speech, and his wife also reported he was “capable of saying just a few words”. In A&E, he was normal on physical and neurological examination, except for spatial and temporal disorientation, slurred speech and lethargy. He was admitted to our ward with a working diagnosis of HE, despite normal ammonia levels (20 mmol/L) on no ammonia-lowering drugs. He had high potassium (5.8 mmol/L) and slightly low sodium (134 mmol/L); C-reactive protein, haemoglobin, creatinine, prothrombin time, bilirubin, blood alcohol levels, venous pH and thyroid-stimulating hormone were all normal; MELD (model for end-stage liver disease) and MELD-Na were 7.[5]Kamath P.S. Kim W.R. The model for end-stage liver disease (MELD).Hepatology. 2007; 45: 797-805Crossref PubMed Scopus (1183) Google Scholar A brain CT scan was negative for acute events but documented some degree of vasculopathy. In the ward, the patient was initially treated with nil by mouth, intravenous fluids and antibiotics; HE precipitating factors were not identified and ammonia remained normal on repeated testing. Symptoms started to improve at 36 hours. The patient was less confused and less sleepy and reported he had been taken to A&E because he “wanted to speak, but the words would not come out”. This was considered to suggest non-fluent aphasia, the CT scan was repeated and documented thickening of the left insular cortical ribbon (Fig. 1), which is compatible with an insular stroke. Treatment with aspirin (100 mg QD)[6]American Heart Association Stroke CouncilCouncil on cardiovascular and stroke nursing, council on clinical cardiology, and council on peripheral vascular disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American heart association/American stroke association.Stroke. 2014; 45: 2160-2236PubMed Google Scholar and intravenous proton-pump inhibitors was instituted, taking into consideration the low hemorrhagic risk (F1 varices) and the high risk of stroke; non-selective beta-blockers were re-started to minimize the risk of gastro-intestinal bleeding prior to repeating an oesophagogastroduodenoscopy, which was unchanged. An electroencephalogram performed after three days was near-normal, except for some slow activity over the temporal regions. For logistical reasons, it was not possible to perform a cerebral MRI; this was performed over a month after the event and was substantially negative. The insula is a small but anatomically and functionally complex part of the human cortex, located within the Sylvian fissure[7]Nieuwenhuys R. The myeloarchitectonic studies on the human cerebral cortex of the Vogt-Vogt school, and their significance for the interpretation of functional neuroimaging data.Brain Struct Funct. 2013; 218: 303-352Crossref PubMed Scopus (148) Google Scholar and implicated in motor, somato-sensory, vestibular, autonomic, speech and cognitive functions.[8]Lemieux F. Lanthier S. Chevrier M.C. Gioia L. Rouleau I. Cereda C. et al.Insular ischemic stroke: clinical presentation and outcome.Cerebrovasc Dis Extra. 2012; 2: 80-87Crossref PubMed Google Scholar The insula is supplied by a proximal branch of the middle cerebral artery, thus vascular occlusions often involve adjacent structures supplied by the same artery.[9]Giammello F. Cosenza D. Casella C. Granata F. Dell'Aera C. Fazio M.C. et al.Isolated insular stroke: clinical presentation.Cerebrovasc Dis. 2020; 49: 10-18Crossref PubMed Scopus (5) Google Scholar Such occlusions have poor functional outcomes when the insula is involved.[9]Giammello F. Cosenza D. Casella C. Granata F. Dell'Aera C. Fazio M.C. et al.Isolated insular stroke: clinical presentation.Cerebrovasc Dis. 2020; 49: 10-18Crossref PubMed Scopus (5) Google Scholar By contrast, isolated insular strokes (IIS) are rare, clinically heterogeneous and difficult to diagnose, but tend to have a good prognosis.[8]Lemieux F. Lanthier S. Chevrier M.C. Gioia L. Rouleau I. Cereda C. et al.Insular ischemic stroke: clinical presentation and outcome.Cerebrovasc Dis Extra. 2012; 2: 80-87Crossref PubMed Google Scholar,[9]Giammello F. Cosenza D. Casella C. Granata F. Dell'Aera C. Fazio M.C. et al.Isolated insular stroke: clinical presentation.Cerebrovasc Dis. 2020; 49: 10-18Crossref PubMed Scopus (5) Google Scholar Typical IIS symptoms are motor deficits, speech disorders and sensory impairment, whereas atypical ones include sleepiness, confusion, agitation, anxiety and spatial-temporal disorientation,[9]Giammello F. Cosenza D. Casella C. Granata F. Dell'Aera C. Fazio M.C. et al.Isolated insular stroke: clinical presentation.Cerebrovasc Dis. 2020; 49: 10-18Crossref PubMed Scopus (5) Google Scholar besides autonomic, auditory and vestibular disturbance.[9]Giammello F. Cosenza D. Casella C. Granata F. Dell'Aera C. Fazio M.C. et al.Isolated insular stroke: clinical presentation.Cerebrovasc Dis. 2020; 49: 10-18Crossref PubMed Scopus (5) Google Scholar Our patient presented with one typical (aphasia) and three atypical (spatial-temporal disorientation, mental confusion and sleepiness) IIS symptoms. The latter are, of course, also part of the HE syndrome.[2]Amodio P. Montagnese S. Lights and shadows in hepatic encephalopathy diagnosis.J Clin Med. 2021; 10: 341Crossref PubMed Scopus (4) Google Scholar In conclusion, the diagnosis of HE is challenging, even when the a priori probability is high. This case was further complicated by the significant overlap between IIS and HE symptoms. The authors received no financial support to produce this manuscript. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. CM: patient care and manuscript drafting; RG: patient care and manuscript drafting; FC: imaging interpretation and patient care; PA: revision of the manuscript for important intellectual content; SM: patient care, drafting and revision of the manuscript. The following are the supplementary data to this article: Download .pdf (2.42 MB) Help with pdf files Multimedia component 1