ACRT Journal

Introduction

GBS is one of the most common causes of acute, acquired weakness and is often provoked by a preceding infection. In some cases, it may be complicated by respiratory failure or autonomic dysfunction. The acute polyneuropathy of GBS is often triggered by an immune response to an antecedent infection or other event where cross-reacting epitopes on peripheral nerve are similar to those of the pathogen (molecular mimicry), and all myelinated nerves (motor, sensory, cranial, sympathetic) can be affected.

Bickerstaff brainstem encephalitis (BBE) is syndrome characterized by encephalopathy with ophthalmoplegia and ataxia [1], and is associated with the presence of antibodies to particular gangliosides that are present in neuronal tissue with homologues in some pathogens (anti-GQ1b antibodies).

The exact cause of Guillain-Barre syndrome is unknown; however, two-thirds of patients report symptoms of an infection in the six weeks preceding diagnosis and such infections include COVID-19, respiratory or a gastrointestinal infection, and Zika virus.

There is no known cure for Guillain-Barre syndrome, but several treatments appear to improve symptoms and reduce the duration of the illness. Although most people recover completely occasionally severe cases can be fatal. Whilst recovery may take several years, most people are able to walk six months after symptoms. Some people may have lasting effects from it, such as weakness, numbness or fatigue. Variant GBS can be associated with Bickerstaff brainstem encephalitis which may mimic brain death [1].

Diagnosis of brain death is established by criteria first established at a conference of the Royal Colleges and Faculties of the United Kingdom in 1976, namely that all brain stem reflexes are absent (the pupils are fixed in diameter with no response to light, no corneal reflex, oculovestibular reflexes are absent, no response to painful stimulation within the cranial nerve distribution, cough and gag reflexes are absent, and there is apnea). Electroencephalography (EEG) and cerebral angiography were not initially included although they may assist in difficult cases [2,3].

Sepsis and septic shock are the causes of AKI and are known as Sepsis-Associated AKI (SA-AKI) and accounted for more than 50% of cases of AKI in the ICU, and have a poor prognosis [4].

In our rare case series three cases of abdominal sepsis with AKI and GBS mimicking brain stem death are presented.

All patients presented to Madinat Zayed Hospital (MZH), SEHAAbu Dhabi-U.A.E., this is a secondary hospital with some tertiary subspecialties and 20 ICU beds between 2009 to 2023.

Case 1:

A 38-year-old male patient from Bangladesh was admitted in 2009 with an acute abdomen. Surgical exploration revealed a sealed peptic ulcer. The patient developed severe AKI (creat 930 μmol/l, urea 20 mmol/l bic 8 mmol/l) with anuria from admission and required renal replacement therapy in the form of intermittent hemodialysis. On the day three of admission, he developed unexplained respiratory failure and required intubation and mechanical ventilation. At day 7, he developed flaccid quadriplegia without sedation, and fixed dilated pupils, together with autonomic neuropathy in the form of low blood pressure and bradycardia. On day 15 he remained unwell with flaccid quadriplegia without sedation for 10 days, and no brainstem reflexes. An apnea test was performed and he was declared brain dead.

On day 33, he passed a large amount of urine and the dialysis was ceased. He started to move his lower jaw, and his pupils began reacting to light. The diagnosis was revised and the possibility of GBS (unexplained respiratory failure, autonomic neuropathy, a high CSF protein of 4.4 G/l) was entertained and he received IV immunoglobulin. Nerve conduction studies (NCS) confirmed diffuse symmetrical mixed sensory and motor axonal polyneuropathy.

On day 48 he started to respond to verbal stimuli, moving head right and left, but still had flaccid quadriplegia. By day 56 he was fully awake and communicating, but still had a flaccid quadriplegia, and he required continued mechanical ventilation because weak respiratory muscle until day 70. On day 78 he was transferred from ICU to the rehabilitation center with good outcome but with some residual neurological disability and moderate weakness mainly lower limbs.

Case 2:

A 28-year-old male African patient without any previous history of severe or chronic illness was admitted to the ICU in 2020 with an acute abdomen, ascites, high inflammatory markers (CRP 290 mg/l,WBC 34,000 cells/mm3), high liver enzymes (ALT309 IU/l ,AST306 IU/l), severe metabolic acidosis (pH 7.2, bic 14 mmol/l) and anuria with serum creatinine 872 μmol/l and urea 19 mmol/l. A CT abdomen with contrast revealed normal sized kidneys, but with irregular medullary enhancement and hypodense nonenhancing renal cortex (reverse rim sign) [5], Figure 1, consistent with renal cortical necrosis, requiring renal replacement therapy, initially with daily intermittent hemodialysis (IHD) from day 1 until day 5. However due to increasing hemodynamic instability he started continuous renal replacement therapy (CRRT) with regional citrate anticoagulation. On day 5 he required paracentesis of his tense ascites. On day 6 he developed unexplained type 2

respiratory failure, and was intubated and ventilated. On day 10 he was noted to have flaccid quadriplegia with no gag reflex, sluggish pupillary reactions, areflexia, ophthalmoplegia, and was not responding to painful stimuli and with absent doll’s eye, corneal and gag reflexes. Nevertheless, he had a high CSF protein (of 1.7 g/l) and normal EEG. His NCS showed features consistent with acute progressive demyelinating polyneuropathy. Anti-GQ1b antibodies were requested but were unavailable in our pathology department as we suspected a GBS, Miller-Fisher, Bickerstaff brainstem encephalitis overlap syndrome and he started therapeutic plasma exchange (TPE). After five sessions of TPE followed by intravenous immunoglobulin (IVIG), he started to obey commands with improvement of the power in all limbs.

Ascitic fluid analysis revealed high white cell count with 97% lymphocytes and a high protein (of 22 g/l) and tuberculous peritonitis was suspected, and so he started antituberculosis treatment on the day 18. Given the cortical necrosis we suspected irreversible renal disease and he started intermittent hemodialysis thrice weekly from day 37. After 64 days, he was transferred from the ICU to the rehabilitation center and required maintenance hemodialysis. On day 211, he had partial recovery of AKI with sufficient renal function to become dialysis independent, with serum creatinine about 140 μmol/l without renal replacement therapy (RRT).

Case 3:

 In 2023, a 44-year male patient from Bangladesh with history of hypertension, dyslipidemia was admitted with an acute abdomen, a serum creatinine of 444 µmol/l anuria, high inflammatory markers (CRP152 mg/l) and liver enzymes (AST1 50 IU/l ALT 142 IU/l) with a known previous baseline normal serum creatinine (81 µmol/l). A diagnosis of abdominal sepsis with secondary AKI was made and he required admission to ICU and started daily intermittent HD then CRRT. On day 9 the patient had an unexplained cardiac arrest, likely due to due to respiratory failure. He was successfully resuscitated but developed flaccid quadriplegia without sedation,

Motor Nerve Conduction Study:

with fixed dilated pupils, loss of deep reflexes, ophthalmoplegia, no response to light, no corneal reflex, absent cough and gag reflexes and brain death was considered. On day 18, the patient started to pass more urine suggesting some renal recovery. On day 22 NCS revealed severe axonal sensory and motor polyneuropathy affecting mainly lower limbs (Table 1) and he had a normal EEG. The CSF protein was high (1 g/l), again suggesting the diagnosis of GBS with overlap syndrome. He commenced TPE on day 24 and received 10 sessions with volume of 3 liters and replacement with albumin 5%, on alternate days, followed by IVIG 26 g/d for 5 days. We noted gradual improvement in his condition and he started to open his eyes, obey commands and power improved in all limbs (upper> lower). He was weaned from ventilator support on day 93 and transferred from ICU to a medical ward on day 96. He was discharged from the hospital after 171 days walking with assistance with mild weakness in the lower limbs and serum creatinine of 120µmol/l without renal replacement therapy.

Sensory Nerve Conduction Study

Table 1: NCS for case three-revealed severe axonal sensory and motor polyneuropathy affecting mainly lower limbs (RR = Reference range).