Despite the advances in neuroscience and medical therapy for epilepsy, status epilepticus, especially when refractory or super-refractory (defined as seizure that continues or recurs ≥24 hours after onset of anaesthetic therapy, including cases that recur on reduction or withdrawal of anaesthesia),1 remains an enormous challenge. Multiple and high-dose drug loading is usually prescribed but may be futile. New modalities of treatment including hypothermia and ketogenic diets have been tried with some success in reported case series.2 We report a case of new-onset super-refractory status epilepticus treated successfully with electroconvulsive therapy (ECT).

A 31-year-old male with a history of childhood asthma presented to Tuen Mun Hospital in November 2012 following onset of generalised tonic-clonic seizure at home. He had upper respiratory symptoms with fever, myalgia, and cough for a week previously. There was no history of recent travel or drug abuse.

Physical examination revealed no focal neurological abnormalities. Investigations showed a normal routine blood picture and renal function except mild liver impairment with alanine aminotransferase level of 72 U/L. General autoimmune (antinuclear antibodies, anti–early nuclear antigen antibodies, C3/C4 and antithyroid antibodies) and toxicology screening were negative. Dried blood spot test for neurometabolic screening was also negative. Examination of cerebrospinal fluid showed white blood cell count 9 per mm3, red blood cell 2 per mm3, protein 0.54 g/dL, and glucose 5.4 g/dL. Microbiological investigations (herpes simplex virus, human immunodeficiency virus, Japanese encephalitis virus, varicella zoster virus, and enteroviruses) were negative. Serology for neurosyphilis and leptospirosis was also negative. Serum anti-CASPR2 Ab, anti-LGI1 Ab, anti-VGKC Ab, and anti-NMDAR Ab (serum and cerebrospinal fluid) were all negative.

He was initially treated with intravenous acyclovir and ceftriaxone for presumed acute infectious meningoencephalitis. Routine electroencephalogram (EEG) showed a generalised slow background of 4 to 6 Hz without epileptiform discharges. He developed a clustering of generalised tonic-clonic seizures 2 days later and was admitted to the intensive care unit. He underwent mechanical ventilation and aggressive treatment with medication at the maximal tolerable dosage including intravenous phenytoin (300 mg/d), valproate (1200 mg/d), midazolam (~60 mg/h), propofol (up to 110 mg/h), phenobarbitone (300 mg/d), and levetiracetam (3000 mg/d). Despite treatment he remained convulsive with seizures evident on EEG. Intravenous immunoglobulin was first given 8 days following admission for possible autoimmune encephalitis but was unsuccessful. Electroencephalogram showed generalised epilepti-form discharges and runs of EEG seizure activity over the bitemporal and bifrontocentral regions. His condition was later complicated by rhabdomyolysis and renal failure (creatine phosphokinase up to 47 000 U/L) that was controlled by aggressive intravenous fluid administration.

Magnetic resonance imaging of the brain (Fig 1) showed multiple patchy areas of cortical T2 hyperintensity bilaterally that were more indicative of epileptic changes with the possibility of encephalitis. Electroencephalogram finally reached burst suppression and seizure suppression following infusion of thiopentone (300 mg/h) and ketamine (220 mg/h). The former was withdrawn because of sepsis that was treated with ticarcillin/sulbactam and meropenem/ertapenem. The generalised epileptiform discharges and seizures returned 8 days later despite such aggressive treatment.

Hypothermia by external cooling (18 days after admission) with body temperature reduced to 32°C with a ketogenic diet (81% lipid, 4.7% Chinese hamster ovary and 13.9% protein) and urine ketosis had no effect. Plasmapheresis was attempted on day 22 but also failed.

Finally, ECT was attempted using the spECTrum 5000Q (Techsan, Czech Republic) and followed the standard psychiatric protocol for treatment of refractory major depression. Ketamine and propofol continued throughout the procedure. The first course of ECT commenced 30 days after admission, and was administered 3 times per day for 3 days:

• Day 1: pulse width at 0.5 ms, frequency 40 Hz × 1 and 60 Hz × 2, duration of 8 seconds, current 800 mA, 200 J
• Day 2: pulse width at 0.5 ms, frequency 60 Hz × 2 and 80 Hz × 1, duration of 8 seconds, current 800 mA, 200 J (tonic seizure, EEG seizure, and R arm clonus-induced)
• Day 3: pulse width at 0.5 ms, frequency 80 Hz × 3, duration of 8 seconds, current 800 mA, 200 J (tonic seizure–induced and EEG showed spindle coma)

Attenuation and abolition of continuous lateralised epileptiform discharges and seizures were achieved with interictal focal epileptiform discharge over the right frontal region only. The EEG seizure induced by stimulation comprised generalised fast beta activities different to the patient’s own seizure activities.

The EEG from the first day of the first course stimulation is shown in FIgure 2.3 4 The second course was given 8 days later (again thrice per day for 3 days) as there was no sustainable improvement. In this course, all therapies were given with pulse width 0.5 ms, frequency 80 Hz, duration of 8 seconds, and current 800 mA, 200 J after referencing the EEG response of the last stimulation. Arm clonus, with one arm paralysed with muscle relaxants and the other for observing EEG-induced seizure and threshold titration, was observed in 10 of the 15 stimulations.

Electroencephalogram 1 week after completion of the second course showed a triphasic wave pattern rather than the previous generalised periodic discharges with EEG seizures over the right frontocentral and right hemisphere. The patient had hyperammonaemia, likely secondary to hepatotoxicity due to the prolonged use of multiple antiepileptics and anaesthetics, and was treated with sodium benzoate.

Oxcarbazepine and lacosamide were added for focal electrographic seizures. Electroencephalogram 10 days after ECT continued to show generalised continuous slow waves with intermittent rhythmic slowing of 1 Hz. There was some eye blinking but no ictal EEG changes.

Electroencephalogram 1 month after ECT showed an improved background of 6 to 8 Hz and occasional EEG seizures over the right frontocentral region, as well as clinically automotor seizures.

The patient was transferred back to the general ward 1 month later and commenced active rehabilitation. He was discharged home 3 months later, although he continued to require a frame for walking and experienced short duration of breakthrough seizures. His positron emission tomography scan later showed no evidence of malignancy. One year later, the patient remained ambulatory with aids but with cognitive decline and personality changes. He was able to self-care, but his seizures remained pharmacoresistant.

This is the first case of super-refractory status epilepticus, defined as status epilepticus that continues or recur ≥24 hours after the onset of anaesthetic therapy including those cases that recur on reduction or withdrawal of anaesthesia,1 that has been treated with ECT successfully in our locality.

There are only individual reports describing the use of ECT for status epilepticus over the last 30 years,5 6 although its use was first described in the 1940s. It was not until the introduction of super-refractory status epilepticus7 that the role of multiple exploratory therapies (those without support from systemic investigations or clinical trials including use of ketamine, hypothermia, ketogenic diet, and ECT) were added to the management protocol.8 The most promising news for this specific seizure status nonetheless comes from the recent discovery of the treatable autoimmune encephalitic nature of many such cases with specific identifiable antibodies such as anti-NMDAR Ab, anti-LGI1 Ab, and anti-VGKC Ab.

The term NORSE (new-onset refractory status epilepticus) was introduced in 20059 for patients with refractory status epilepticus and no history of seizures and no identifiable aetiology. Reviewing the limited literature, these cases reported usually have features suggestive of an infectious or inflammatory nature with febrile episodes or abnormal cerebrospinal fluid pleocytosis.10 These cases are most likely to be autoimmune encephalitis, but the antibodies are not available or have not yet been identified. Our patient was likely true NORSE, although the possibility of a postinfectious or autoimmune mechanism cannot be excluded as the panel of testing has not been exhausted.

Electroconvulsive therapy in status epilepticus was first described by Carrasco González et al in 1997 and Viparelli and Viparelli in 1992.5 11 Since then, there have been other case reports or series reporting success of this therapy, both in adult and paediatric patients.12 13 It is usually applied with the withdrawal of anticonvulsants or anaesthetics. Mechanisms suggested include enhanced gamma-aminobutyric acid inhibition, the effect of paradoxical stimulation of status epilepticus and electrical modulation.14 In our patient, anticonvulsants or anaesthetic agents were given without an end date and we applied ECT in addition to, not instead of, such drug therapy. The EEG epileptiform discharges showed immediate attenuation following electrical stimulation, and supports the possibility of enhancing the seizure threshold or an inhibitory mechanism. The later EEG changes were related to significant metabolic encephalopathy (hyperammonaemia) rather than previous runs of epileptiform discharges, also suggested the modulatory effect of ECT when a course was given rather than just a few shots. Of course, one would also argue that the improvement could be the late effect of previous intravenous immunoglobulin or plasmapheresis although these had no immediate effect on the EEG or clinical seizures or epileptiform discharges.

Despite the apparent successful outcome for our patient following the addition of ECT, we require more cases, both adult and paediatric, with such treatment applied as well as a clear definition of the status epilepticus stages (early, refractory or super-refractory) and specific categorisation of the syndrome and aetiology (autoimmune or cryptogenic to be NORSE) before we can confidently support the role and effectiveness of this physical therapy.

The authors have no conflicts of interest to disclose.

1. Shorvon S, Trinka E. The London-Innsbruck Status Epilepticus Colloquia 2007-2011, and the main advances in the topic of status epilepticus over this period. Epilepsia 2013;54(Suppl 6):11-3. Crossref

2. Cervenka MC, Hocker S, Koenig M, et al. Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus. Neurology 2017;88:938-43. Crossref

3. Hirsch LJ, LaRoche SM, Gaspard N, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2012 version. J Clin Neurophysiol 2013;30:1-27. Crossref

4. Beniczky S, Hirsch LJ, Kaplan PW, et al. Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia 2013;54(Suppl. 6):28-9. Crossref

5. Carrasco González MD, Palomar M, Rovira R. Electroconvulsive therapy for status epilepticus. Ann Intern Med 1997;127:247-8. Crossref

6. Griesemer DA, Kellner CH, Beale MD, Smith GM. Electroconvulsive therapy for treatment of intractable seizures. Initial findings in two children. Neurology 1997;49:1389-92. Crossref

7. Shorvon S. Super-refractory status epilepticus: an approach to therapy in this difficult clinical situation. Epilepsia 2011;52(Suppl 8):53-6. Crossref

8. Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 2011;134:2802-18. Crossref

9. Wilder-Smith EP, Lim EC, Teoh HL, et al. The NORSE (new-onset refractory status epilepticus) syndrome: defining a disease entity. Ann Acad Med Singapore 2005;34:417-20.

10. Gall CR, Jumma O, Mohanraj R. Five cases of new onset refractory status epilepticus (NORSE) syndrome: outcomes with early immunotherapy. Seizure 2013;22:217-20. Crossref

11. Viparelli U, Viparelli G. ECT and grand mal epilepsy. Convuls Ther 1992;8:39-42.

12. Kamel H, Cornes SB, Hegde M, Hall SE, Josephson SA. Electroconvulsive therapy for refractory status epilepticus: a case series. Neurocrit Care 2010;12:204-10. Crossref

13. Lambrecq V, Villéga F, Marchal C, et al. Refractory status epilepticus: electroconvulsive therapy as a possible therapeutic strategy. Seizure 2012;21:661-4. Crossref

14. Walker MC. The potential of brain stimulation in status epilepticus. Epilepsia 2011;52(Suppl 8):61-3. Crossref

A 56-year-old man underwent laparoscopic cholecystectomy for acute cholecystitis at another hospital in December 2013. The cholecystectomy was uneventful and the patient was discharged home 3 days later. However, after hospital discharge, the patient presented with recurring upper abdominal pain, tarry stool, and fever. He was admitted to another hospital 4 weeks after the cholecystectomy because of fever, right upper quadrant pain, and haematemesis. Emergency oesophagogastroduodenoscopy and colonoscopy were performed. No bleeding source was identified. Computed tomography (CT) revealed subhepatic fluid collection; old-blood–stained fluid was drained by image-guided catheter drainage. The patient was transferred to the Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, for further treatment.

When the patient arrived at hospital, his blood pressure was approximately 90/60 mm Hg and his pulse rate was 110 beats per minute. Laboratory studies revealed the following values: haemoglobin level, 72 g/L; white blood cell count, 20.3 × 10⁹ /L; platelet count, 388 × 10⁹ /L; total bilirubin, 164 μmol/L; alanine aminotransferase, 187 IU/L; and alkaline phosphatase, 337 IU/L. The patient was treated with intravenous fluid hydration and was transfused with three units of packed red blood cells. He was also given a course of antibiotics. Abdominal CT showed a cystic artery pseudoaneurysm of 1.22 × 1.96 × 1.38 cm (anterior-posterior × transverse × longitudinal dimensions). Two subhepatic collections with haematoma were also visible, over the gallbladder fossa and below hepatic segment 6. Selective right hepatic artery angiography revealed a pseudoaneurysm at the cystic artery. This aneurysm was embolised with stainless steel coils (Fig 1). The catheter for subhepatic collection drainage was then replaced with one with better positioning. Endoscopic retrograde cholangiopancreatography was performed the next day. The cholangiogram showed a dilated biliary tree with haemobilia; most of the blood clots were extracted using a balloon. A cystic duct stump leak was observed after blood clot removal, and a 10-cm-long 11.5-F biliary stent was inserted for biliary drainage (Fig 2). Liver function improved gradually. The patient was discharged from hospital 2 weeks after admission.

Follow-up CT no longer showed pseudoaneurysm and instead showed a resolving collection. Endoscopic retrograde cholangiopancreatography with stent removal was performed 3 months later. The cholangiogram showed a normal biliary tree. The patient recovered and liver function test results were normal.

Hepatic artery or cystic artery pseudoaneurysms are rare complications of laparoscopic cholecystectomy, with cystic artery involvement being reported much less frequently in the literature. Pseudoaneurysm formation is a consequence of vascular injury; important causes include arterial access procedures, accident trauma, and surgical trauma.1 Two-thirds of cases are iatrogenic.1 With the advent of laparoscopic cholecystectomy, iatrogenic hepatobiliary injury is now another cause. Concomitant formation of cystic artery pseudoaneurysm and cystic duct stump leak is a rare complication of laparoscopic cholecystectomy. The majority of pseudoaneurysms present within 6 weeks after the operation.2 3

We have reported a case of laparoscopic cholecystectomy that was complicated by a cystic artery pseudo-aneurysm and a cystic duct stump bile leak, which were managed with angiographic coil embolisation and endoscopic biliary drainage, respectively. The patient presented with the classic Quincke’s triad of haemobilia, namely upper gastrointestinal bleeding, right upper quadrant pain, and obstructive jaundice. The aetiology most likely originated from the infected fluid collection after cholecystectomy, which caused a series of events, including cystic duct stump leak, cystic artery pseudoaneurysm, and haemobilia, in that order. First, bile leakage is a potential complication of cholecystectomy and the cystic duct stump is the most common site of leakage.4 The contributing factor of cystic duct stump leak in the current case was likely cystic duct stump necrosis secondary to mechanical or thermal injury during cholecystectomy, as well as adjacent infection. Second, haemobilia can occur secondary to a cystic artery pseudoaneurysm, although extremely rarely. Artery pseudoaneurysm is a continuous inflammatory process that leads to erosion in the elastic and muscular components of the arterial wall, ultimately resulting in pseudoaneurysm formation. The likely precipitating factors in the current case include initial clip encroachment of the vasculature, mechanical or thermal injury, and continuous inflammation due to the adjacent infected bile or collection.

Pseudoaneurysm can present with bleeding in the form of haemobilia, haematemesis, or melaena. In the current case, upper gastrointestinal bleeding from haemobilia resulted from the cystic artery pseudoaneurysm’s communication with the cystic duct. The resulting symptoms were typical of Quincke’s triad of upper abdominal pain, upper gastrointestinal haemorrhage, and jaundice.5 However, these symptoms are present collectively only in a minority (32%-40%) of patients.5 Thus, detection relies heavily on both clinical reasoning and imaging techniques. If intra-abdominal collection or haemorrhage is suspected clinically, arterial-phase CT is appropriate to detect any pseudoaneurysm. Since gastrointestinal haemorrhage is one of the presentations, urgent oesophagogastroduodenoscopy may be arranged first to rule out any suspected upper gastrointestinal pathology. However, as in the current case, if that procedure fails to show any bleeding source, urgent CT should be considered. Close observation and timely arrangement of appropriate procedures are essential.

Prompt recognition with adequate management was very important in the current case. The treatment of our patient included five objectives: achieving haemostasis, controlling the cystic duct stump leak, relieving obstructive jaundice, controlling the infection with antibiotics, and draining the intra-abdominal collection. Untreated haemobilia poses an immediate threat to life. It can lead to acute haemodynamic instability, necessitating detection, access, and control of the pseudoaneurysm. Arterial-phase CT is a good initial non-invasive mode of detection of laparoscopic cholecystectomy complications. It can be used to evaluate intra-abdominal collection, biliary tree dilatation, and possible bile duct injury, and to visualise pseudoaneurysms or haemorrhage. Arterial-phase CT also allows a three-dimensional assessment of the bile duct and vasculature. Selective arterial angiography can provide a real-time evaluation of pseudoaneurysms and bleeding. At the same time, it can provide the chance of immediate therapeutic intervention. Transarterial embolisation is the treatment of choice for haemostasis, and a high success rate, of 75% to 100%, has been reported.2 3 5 When bleeding control by embolisation fails, repeated sessions of transarterial embolisation for haemostasis or surgical intervention to repair or ligate the artery is necessary. Endoscopic retrograde cholangiopancreatography with stent placement or sphincterotomy is highly effective in diagnosing haemobilia, controlling cystic duct stump leakage, and relieving obstructive jaundice. We favoured stenting over sphincterotomy because of a presumed lower risk of immediate complications.

The lessons to be learnt from this case include the importance of (1) meticulous surgical techniques (such as good haemostasis, careful use of powered devices, proper use of endoclips, and adequate drainage of the operative field), and (2) early recognition and prompt management.

In conclusion, cystic artery pseudoaneurysm is a rare, potentially life-threatening complication of laparoscopic cholecystectomy, and prompt recognition and treatment are essential. Haemobilia may be present many weeks after the initial injury.

The authors have no conflicts of interest to disclose.

1. Green MH, Duell RM, Johnson CD, et al. Haemobilia. Br J Surg 2001;88:773-86.

2. Senthilkumar MP, Battula N, Perera M, et al. Management of a pseudo-aneurysm in the hepatic artery after a laparoscopic cholecystectomy. Ann R Coll Surg Engl 2016;98:456-60. Crossref

3. Nicholson T, Travis S, Ettles D, et al. Hepatic artery angiography and embolization for hemobilia following laparoscopic cholecystectomy. Cardiovasc Intervent Radiol 1999;22:20-4. Crossref

4. Lau WY, Lai EC, Lau SH. Management of bile duct injury after laparoscopic cholecystectomy: a review. ANZ J Surg 2010;80:75-81. Crossref

5. Merrell SW, Schneider PD. Hemobilia—evolution of current diagnosis and treatment. West J Med 1991;155:621- 5.

A 78-year-old woman was diagnosed with atrial fibrillation in September 2015. An echocardiogram showed no evidence of valvular heart disease. She was prescribed dabigatran 110 mg twice a day. In December 2016, she was admitted to our hospital for acute ischaemic stroke, presenting with a sudden onset of decreased level of consciousness. Apart from atrial fibrillation, she also had hypertension, diabetes mellitus, hyperlipidaemia, and a history of hip fracture with bilateral hip implants, requiring a rollator for walking.

On the day of admission, she was reported by her carer to be poorly responsive, with no verbal response and no spontaneous limb movement. She was last seen well 30 minutes previously. Physical examination revealed bilateral pinpoint pupils and no verbal response. She had slight flexion of her four limbs to pain and her National Institutes of Health Stroke Scale (NIHSS) score was 34. The blood pressure was 142/64 mm Hg. There was no hypoglycaemia. Naloxone was given with no improvement. Cerebral computed tomography (CT) showed no early infarct changes but bilateral subcortical white matter hypodensities, compatible with small vessel disease (Fig a). A clinical diagnosis was made of acute ischaemic brainstem stroke. The family confirmed that the patient had been taking dabigatran regularly as prescribed, with the last dose taken about 2 hours before symptom onset. She had taken no sedative medications.

After obtaining informed consent, an intravenous bolus of 5 g idarucizumab was given. Blood for clotting profile, including thrombin time, was taken before treatment and 5 minutes afterwards. Intravenous recombinant tissue plasminogen activator (r-tPA) was then given at 0.6 mg/kg body weight 10 minutes after the start of idarucizumab injection, 2 hours from symptom onset. The prolonged activated partial thromboplastin time (APTT) and thrombin time (TT) normalised after administration of idarucizumab. The Table shows the clotting variables before and after idarucizumab. By the next morning, the patient had regained her speech although her response was slow with dysarthria and dysphagia. She could raise her four limbs against gravity, power being grade 3. Follow-up CT at 24 hours post r-tPA showed no significant infarct and no bleeding (Fig b). Transcranial Doppler ultrasonography showed no evidence of significant vertebrobasilar occlusive disease. By day 2, she had recovered further neurologically, with improvement in alertness, dysarthria and dysphagia, and could tolerate oral feeding. Limb power was grade 4+ over four limbs. Pupils were no longer pinpoint. She was recommenced on dabigatran 150 mg twice a day on day 2 based on her age and creatinine clearance. The patient was discharged on day 7 with her neurological function returned to baseline.

This is the first report in Hong Kong of the successful use of idarucizumab to reverse the anticoagulant effect of dabigatran, followed by intravenous thrombolysis with r-tPA for the treatment of ischaemic stroke. Novel oral anticoagulants (NOACs) are now increasingly used for the prevention of cardioembolic stroke in patients with non-valvular atrial fibrillation. Dabigatran, which acts as a thrombin inhibitor, is one such NOAC. Idarucizumab is a monoclonal antibody that has a high affinity for binding to the immunoglobulin G fragment of dabigatran. A 5-g dose was shown to be able to reverse the anticoagulant effect of dabigatran within minutes and had a good safety profile in the study of Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD trial).1

Patients who develop an acute ischaemic stroke while taking dabigatran are often excluded from treatment with intravenous thrombolysis owing to their bleeding risk. For patients who are not candidates for mechanical thrombectomy or who are in institutions where an endovascular thrombectomy service is not routinely available, giving intravenous thrombolysis after reversal of the anticoagulant effect is a treatment option. There is no pro-anticoagulant effect from idarucizumab itself, and an in-vitro study demonstrated no interaction between idarucizumab and r-tPA–induced thrombolysis.2 As far as we know, there have been five case reports at the time of writing of this article, all from German centres, that have reported the successful use of idarucizumab for this indication; none had any haemorrhagic complications.2 3 Four of these studies reported successful thrombolysis with good neurological recovery, whereas one study reported failed clinical improvement in a patient with infarcts in multiple territories.3 Diener et al4 have published an expert opinion on the management of these ischaemic strokes based on their experience in Germany. They proposed that for patients who have taken dabigatran in the preceding 24 hours from the time of assessment (or 96 hours if the creatinine clearance is <30 mL/min), or for patients in whom time of last dabigatran dose is unknown and who have a prolonged APTT or TT, idarucizumab should be given if the patient is not a candidate for mechanical thrombectomy. In our institution, we do not have point-of-care devices to test clotting function, the turnaround time for APTT and TT results may be hours, and dabigatran concentrations cannot be measured in our laboratory. We therefore propose that for patients in whom time of last dabigatran dose is unknown, idarucizumab can still be considered with the family’s consent to enable early intravenous thrombolysis. For the same reason, we did not wait for the results of APTT or TT to confirm reversal of dabigatran’s effect before initiating intravenous thrombolysis. Idarucizumab rapidly and completely reversed the anticoagulant activity of dabigatran in 88% to 98% of patients in the RE-VERSE AD trial.1

Safety (avoidance of symptomatic intracranial haemorrhages) was our top concern for this patient. As she had multiple risk factors for intracranial haemorrhage (old age, high NIHSS score, cerebral white matter disease and on anticoagulant therapy), we gave r-tPA at a dose of 0.6 mg/kg body weight. This dose was associated with significantly fewer symptomatic intracranial haemorrhages in the recent ENCHANTED trial.5

Following reversal of effect, dabigatran can be resumed as early as 24 hours afterwards. Although our patient had improved by the next day, she still had significant dysphagia and could not tolerate oral feeding. By the second day, she had improved further so dabigatran was resumed at a higher dose based on her age and renal function.

In conclusion, idarucizumab can be considered to reverse the anticoagulant effect of dabigatran in patients with ischaemic stroke within a therapeutic window, so that they may benefit from intravenous thrombolytic therapy.

All authors have disclosed no conflicts of interest.

1. Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015;373:511-20. Crossref

2. Berrouschot J, Stoll A, Hogh T, Eschenfelder CC. Intravenous thrombolysis with recombinant tissue-type plasminogen activator in a stroke patient receiving dabigatran anticoagulant after antagonization with idarucizumab. Stroke 2016;47:1936-8. Crossref

3. Kafke W, Kraft P. Intravenous thrombolysis after reversal of dabigatran by idarucizumab: a case report. Case Rep Neurol 2016;8:140-4. Crossref

4. Diener HC, Bernstein R, Butcher K, et al. Thrombolysis and thrombectomy in patients treated with dabigatran with acute ischemic stroke: Expert opinion. Int J Stroke 2017;12:9-12. Crossref

5. Anderson CS, Robinson T, Lindley RI, et al. Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. N Engl J Med 2016;374:2313-23. Crossref

Endoscopic retrograde cholangiopancreatography (ERCP) is a standard endoscopic technique for treating biliary obstruction and cholangitis. The presence of surgically altered gastrointestinal anatomy, however, poses a major technical difficulty to the procedure due to the long and tortuous access to the small bowel. We report a three-case series with successful attempts at short double-balloon enteroscopy (DBE)–assisted ERCP in patients with postoperative gastrointestinal anatomy. The enteroscope employed was EC-450BI5, Fujifilm endoscopy (Fig 1) and the sedation agents used in all procedures were dexmedetomidine and fentanyl continuous infusion combined with bolus midazolam.

A 76-year-old man was admitted to our hospital in December 2015 with acute cholangitis that presented as fever and deranged liver function tests (LFT) with predominant elevation of alkaline phosphatase (ALP). He had a history of stroke, hyperlipidaemia, and a Billroth II gastrectomy performed 30 years ago. Blood cultures grew Escherichia coli. Ultrasonography of the hepatobiliary system revealed a 5-mm stone in the common bile duct (CBD).

The first ERCP using a standard side-view duodenoscope and end-view gastroscope failed to identify the papilla. He continued to receive antibiotic treatment, with the fever reduced but liver biochemistry remained elevated. The DBE-assisted ERCP was performed 2 weeks later with an enteroscope of 152-cm working length. The papilla was reached over the afferent limb of the small bowel by manipulation of the overtube only (no balloon inflation), followed by successful cannulation of the CBD. Cholangiogram revealed a 1.2-cm dilated CBD with two intraductal filling defects (Fig 2a). Pre-cut papillotomy on-stent was performed with pre-insertion of a 7-French 7-cm plastic biliary stent. The plastic stent was removed after papillotomy and the papilla was dilated using a controlled radial expansion (CRE) balloon dilator of 12-mm size and subsequently stones were removed by a basket. The ERCP procedure was completed in 115 minutes and there were no complications. The patient’s LFT had normalised at a follow-up 3 weeks later.

An 80-year-old man presented in January 2016 with a history of hypertension, pulmonary fibrosis, and cerebral infarct. A Billroth II gastrectomy had been performed 10 years previously for gastrointestinal bleeding. He had an episode of acute cholangitis 4 months ago. Endoscopic retrograde cholangiopancreatography using a standard end-view gastroscope failed to reach the papilla and the infection resolved after a course of antibiotic. Follow-up magnetic resonance cholangiopancreatography 3 weeks earlier had revealed a 1.2-cm distal CBD stone with the CBD dilated to 1.7 cm. He then attended the hospital again for fever, E coli septicaemia, and an obstructive pattern of liver derangement; bilirubin level was 93 µmol/L and ALP level was 1224 U/L. Percutaneous transhepatic biliary drainage was established and antibiotics were continued until DBE-assisted ERCP was performed 2 weeks later. With the push-pull manoeuvre, the blind end of the afferent loop was reached. Initially, a nearby minor papilla was mistaken as the major papilla and repeated attempts failed to cannulate it.

The true major papilla was then identified 5 cm proximal to the minor papilla and pre-cut papillotomy was performed due to difficult cannulation. The impacted CBD stone was removed following papillotomy and balloon sphincteroplasty was performed with a 12-mm CRE balloon. Subsequent cholangiogram was clear with a 1.5-cm dilated CBD. The operating time was 163 minutes. The patient remained asymptomatic and LFT had normalised at a follow-up 1 month later.

A female patient aged 81 years with a history of mild Parkinson’s disease had undergone gastrectomy 30 years ago for peptic ulcer disease. She presented to our hospital in February 2016 for biliary pancreatitis with sudden onset of jaundice associated with epigastric pain. Amylase level was elevated to 698 U/L, bilirubin level to 35 µmol/L, and an ALP level of 1001 U/L. Ultrasonography of the hepatobiliary system detected grossly dilated intrahepatic ducts (IHD) and the CBD measured up to 2.4 cm in diameter with one obstructing CBD stone measuring 1.5 cm. The first gastroscopy confirmed a previous total gastrectomy with Roux-en-Y reconstruction. Percutaneous transhepatic biliary drainage was attempted but failed due to the resolution of the IHD dilatation. The patient was then managed conservatively with antibiotics and a DBE-assisted enteroscopy was scheduled 3 weeks later. The 152-cm DBE identified the blind end of the afferent limb while the endoscope advanced to 140 cm from the incisors after push-pull manoeuvre (Fig 2b to d). Successful guidewire cannulation was followed with a cholangiogram that showed a dilated CBD with no filling defect. In view of the recent history of biliary obstruction and the possibility of a passed stone, the papilla was dilated to 13.5 mm with the CRE balloon and good bile drainage was observed. The operating time was 130 minutes. The major difficulty encountered was that the tip of the enteroscope was very unstable making it difficult to maintain the distal blind end and it was easily slipped out proximally. As such, repeated endoscope manipulation was required to achieve optimal positioning. Postoperatively, the patient was well, bilirubin normalised, and ALP level had reduced to 266 U/L at 1-month follow-up.

Balloon enteroscopy–assisted ERCP using either single-balloon enteroscopy or DBE has been reported to be an effective modality for ERCP in these patients.1 2 3 Traditional DBE with 200-cm length and narrow (2.2-mm) accessory working channel limits the utilisation of conventional ERCP accessories. Recent attempts with a short 152-cm DBE have been highly successful.1 2 4 To date, there have been approximately 200 reports of patients who have undergone ERCP using this short DBE procedure. The success rate for reaching the blind end of the afferent limb was 86% to 100%; it is not inferior to that achieved using a long-type balloon enteroscope.4 The short-type enteroscope accommodates the use of most available accessories to perform ERCP-related procedures such as sphincterotomy, balloon dilatation, stone extraction, and deployment of plastic or metallic stents.

In our small series, all patients ran an uneventful course during the perioperative and postoperative period and none had any apparent complications. The overall procedural complication rate has been reported to be 8% to 10%, with the rate of major complications of perforation or emphysema being around 3.5%.4 The risk of complications, however, may vary according to different surgical approaches with consequent significant differences in the endoscopic techniques anticipated.3 4 5 Since it is a relatively new and evolving endoscopic technique, these rates are still experience-dependent and patients should be closely observed after the procedure.

The ERCP in the patient with Roux-en-Y reconstruction posed particular technical difficulties. The endoscopist should review previous surgical reports in detail to map and anticipate the endoscopic view at the anastomotic site. On reaching the Roux-en-Y anastomosis, identification of the pancreatobiliary limb is often difficult. After choosing either limb, the endoscopist could perform endoscopic marking by a clip or Indian ink tattoo at the entrance of the chosen limb (Fig 2c). If the chosen limb is confirmed wrong under fluoroscopy, the endoscopist can return the endoscope to the Roux-en-Y anastomosis and then insert the endoscope into the other limb. A marking at the entrance of a limb has been shown to be useful as it avoids repeated misidentification of the limb to be entered.6

Barotrauma is the major cause of intestinal perforations and may be a result of excessive air insufflation forming a closed loop between the blind end and the inflated overtube or enteroscope balloon.7 Use of carbon dioxide insufflation instead of air insufflation may reduce the chance of this closed-loop phenomenon. Additionally, use of a transparent hood at the tip of the enteroscope with instillation of water into the intestinal lumen has also been suggested to maintain the endoscopic view without gas insufflation and avoid consequent barotrauma.8

With regard to the cannulation techniques, the catheter exits from a 7 o’clock direction of the enteroscope during DBE-assisted ERCP. Endoscopists should attempt to locate the papilla at 6 o’clock of the endoscopic view to facilitate biliary cannulation (Fig 2b). In case of an unstable endoscopic manoeuvre, an inflated enteroscope balloon may help to grip the intestine and stabilise the manipulation. In cases where the papilla is located at 11 to 12 o’clock in the endoscopic view, the overtube balloon should remain inflated and the enteroscope rotated to solve difficult cannulation.6

In conclusion, short DBE-assisted ERCP is a safe and effective endoscopic method to treat patients with surgically altered anatomy and biliary conditions. Nonetheless local experience in enteroscopy-assisted ERCP, particularly using the short DBE, is scant because of the unavailability of the endoscopic devices. Further discussion and training opportunities are encouraged to consolidate experience and minimise procedural complications in future practice.

1. Moreels TG. Altered anatomy: enteroscopy and ERCP procedure. Best Pract Res Clin Gastroenterol 2012;26:347-57. Crossref

2. Cheng CL, Liu NJ, Tang JH, et al. Double-balloon enteroscopy for ERCP in patients with Billroth II anatomy: results of a large series of papillary large-balloon dilation for biliary stone removal. Endosc Int Open 2015;3:E216-22. Crossref

3. Mönkemüller K, Bellutti M, Neumann H, Malfertheiner P. Therapeutic ERCP with the double-balloon enteroscope in patients with Roux-en-Y anastomosis. Gastrointest Endosc 2008;67:992-6. Crossref

4. Kato H, Tsutsumi K, Harada R, Okada H, Yamamoto K. Short double-balloon enteroscopy is feasible and effective for endoscopic retrograde cholangiopancreatography in patients with surgically altered gastrointestinal anatomy. Dig Endosc 2014;26 Suppl 2:130-5. Crossref

5. Katanuma A, Yane K, Osanai M, Maguchi H. Endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy using balloon-assisted enteroscope. Clin J Gastroenterol 2014;7:283-9. Crossref

6. Hatanaka H, Yano T, Tamada K. Tips and tricks of double-balloon endoscopic retrograde cholangiopancreatography (with video). J Hepatobiliary Pancreat Sci 2015;22:E28-34. Crossref

7. De Koning M, Moreels TG. Comparison of double-balloon and single-balloon enteroscope for therapeutic endoscopic retrograde cholangiography after Roux-en-Y small bowel surgery. BMC Gastroenterol 2016;16:98. Crossref

8. Yamamoto H. Be aware of the fatal risk of air embolism. Dig Endosc 2014;26:23. Crossref

An 85-year-old man presented with a history of odynophagia since March 2015. He was a chronic smoker but did not drink alcohol. He had a medical history of hypertension, diabetes mellitus, and gout. He was first seen by us in April 2015. At the first presentation, physical examination revealed an irregular 3-cm ulcerative mass arising from the left tonsil (Fig 1). The rest of his oral cavity was otherwise normal and there was no cervical lymphadenopathy. Carcinoma of the left tonsil was suspected. Computed tomographic (CT) scan of the head and neck disclosed a non-specific soft tissue thickening and mucosal contrast enhancement at the left side of the oropharynx. Transoral punch biopsy of the left tonsillar mass was performed. Histopathology revealed no evidence of malignancy with heavy stromal infiltration by neutrophils, lymphocytes, and plasma cells plus focal microabscess formation. No granuloma or fungal elements were seen.

Subsequent upper gastrointestinal endoscopy was performed and disclosed the left tonsillar mass with no other abnormalities within the hypopharynx, oesophagus, or stomach. Because of the progressive odynophagia, a nasogastric feeding tube was inserted; as there was no improvement and the diagnosis was still elusive, left tonsillectomy was performed on the same day and was uneventful.

Histopathological examination of the left tonsil showed lymphoid tissue with preserved architecture present beneath the stratified squamous epithelium. Hyperplastic lymphoid follicles with germinal centre surrounded by mantle cells were present. Plasma cells were seen at the interfollicular area. There were no malignant cells. Immunostaining revealed more than 90% of plasma cells per high-power field with an immunoglobulin (Ig) G4:IgG ratio of more than 40% (Fig 2). The final diagnosis was IgG4-related disease of the left tonsil.

The patient refused workup with positron emission tomography–CT scan but clinically there was no feature of systemic IgG4-related disease so steroids were not prescribed. His odynophagia gradually improved and he could tolerate oral feeding with congee. The feeding nasogastric tube was removed. Unfortunately, the patient had a depressive mood and general debility. He eventually died of pneumonia in September 2015.

Immunoglobulin G4–related disease is a fibroinflammatory condition often associated with elevated serum IgG4 level.1 It is a multi-organ entity that encompasses various conditions formerly considered to be unrelated, single-organ diseases.2 It is notorious for its resemblance to malignant disease such as carcinoma of the pancreas. It is a source of undue anxiety for both patients and clinicians as the diagnosis may be difficult if the index of clinical suspicion for IgG4-related disease is low. Systemic symptoms (asthenia, weight loss, or fever) may occur in a minority of patients. The disease can affect the pancreas (autoimmune pancreatitis with abdominal pain), biliary tree (sclerosing cholangitis with jaundice), salivary glands or lacrimal gland (parotid, submandibular and lacrimal gland enlargement), lymph nodes, kidneys (tubulointerstitial nephritis with renal failure), and retroperitoneum (ureteric stricture).2

Measuring the serum IgG4 level is useful to establish the diagnosis of this uncommon disease3 and may avoid unnecessary diagnostic surgery. Although serum IgG4 level was initially thought to be a key diagnostic feature of IgG4-related disease, more recent evidence has devalued the significance of a raised level. The key to diagnosis is immunohistochemical demonstration of tissue infiltration by IgG4-bearing plasma cells and morphological evidence of lymphoplasmacytic infiltrates, storiform fibrosis, and obliterative phlebitis.2 Serum IgG4 assay was not done as this investigation was not available at our hospital. Nonetheless the diagnosis of IgG4-related disease of tonsil in this patient was obvious based on the histopathological examination with IgG4 immunostains.

Umehara et al4 proposed a set of criteria for the diagnosis of IgG4-related disease designed to be used irrespective of the specific organ involvement. The criteria are (1) serum IgG4 concentration of >135 mg/dL and (2) >10 IgG-positive plasma cells demonstrated per high-power field, of which >40% are IgG4-positive cells. Nevertheless the sensitivity is low for the diagnosis of autoimmune pancreatitis based on these criteria.

Of note, IgG4-related disease can manifest at the head and neck region. Kuttner’s tumour of the submandibular gland has been well reported and often masquerades as carcinoma.5 Nonetheless IgG4-related disease within the oral cavity is very rare. To the best of our knowledge, only one case of simultaneous IgG4-related lesions affecting the left border of the tongue and right tonsil has been reported in the literature.6 This patient presented with an elevated and nodular mass devoid of surface ulceration, associated with a generalised skin rash. The oral and cutaneous lesions gradually resolved after therapy with steroid.6 In contrast, our patient had an ulcerative mass without any skin rash. Both cases were initially suspected to be squamous cell carcinoma because of the alarming clinical features.

Steroid remains the mainstay of treatment for IgG4-related disease. It should be started early in order to prevent tissue fibrosis and thus irreversible organ damage, except in cases of asymptomatic disease of the submandibular gland or lymph node.7 Radiological abnormalities often vanish following the commencement of steroid therapy. Unfortunately, disease relapse is not uncommon after steroid therapy is tapered. There is no evidence to support the effectiveness of adding conventional steroid-sparing agents (eg azathioprine, methotrexate, or cyclophosphamide) to sustain remission for IgG4-related disease.7 Although remission can be achieved in more than 80% of patients with induction steroid therapy, some clinicians support the use of maintenance steroid at 5 mg or 2.5 mg daily for a durable response. However, disease may flare in a quarter of patients despite maintenance therapy. Moreover, the optimal duration for maintenance treatment is uncertain and the morbidity associated with steroid, although in low dose, is not negligible. Fortunately, repeated induction therapy with steroid for disease relapse is normally effective.7

In summary, IgG4-related disease can involve the tonsils and masquerade as tonsil carcinoma. Clinicians should consider IgG4-related disease as one of the differential diagnoses for a suspicious tonsillar mass. Early diagnosis of tonsillar mass with biopsy is essential to exclude tonsil carcinoma and to allow prompt steroid treatment for IgG4-related disease of tonsil which is curable.

1. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012;25:1181-92. Crossref

2. Stone JH, Brito-Zerón P, Bosch X, Ramos-Casals M. Diagnostic approach to the complexity of IgG4-related disease. Mayo Clin Proc 2015;90:927-39. Crossref

3. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001;344:732-8. Crossref

4. Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 2012;22:21-30. Crossref

5. Chow TL, Chan TT, Choi CY, Lam SH. Kuttner’s tumour (chronic sclerosing sialadenitis) of the submandibular gland: a clinical perspective. Hong Kong Med J 2008;14:46-9.

6. Khurram SA, Fernando M, Smith AT, Hunter KD. IgG4-related sclerosing disease clinically mimicking oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:e48-e51. Crossref

7. Khosroshahi A, Wallace ZS, Crowe JL, et al. International consensus guidance statement on the management and treatment of IgG4-related disease. Arthritis Rheumatol 2015;67:1688-99. Crossref