Management of Autoimmune Encephalitis with Refractory Status Epilepticus

INTRODUCTION

Autoimmune encephalitis (AE) is a significant subset of non-infectious encephalitis characterised by immune-mediated inflammation of the brain parenchyma [1]. It is primarily driven by autoantibodies targeting neuronal surface epitopes, such as receptors, ion channels, or synaptic proteins, or intracellular antigens, such as onconeural proteins [2]. Over the past 15 years, the spectrum of AE has expanded rapidly owing to ongoing research into various neuronal autoantibodies, which has improved the recognition and understanding of its diverse clinical manifestations [3].

Patients with AE typically present with altered mental status, which may be accompanied by fever, seizures, movement disorders and/or focal neurological deficits [4]. The diagnosis of AE relies heavily on a combination of clinical assessment, cerebrospinal fluid (CSF) analysis, neuroimaging, and electroencephalography (EEG) [5]. CSF examination often reveals pleocytosis or elevated protein levels, but may sometimes be normal, necessitating a high index of suspicion [6]. Neuroimaging findings can vary, with some patients showing characteristic abnormalities, such as mesial temporal lobe hyperintensities, whereas others may present with normal scans [7]. EEG findings are frequently nonspecific but can display patterns, such as extreme delta brush, which support the diagnosis [8].

The management of AE differs significantly from that of infectious causes, with immunotherapy serving as the mainstay of treatment [9]. First-line therapies include corticosteroids, intravenous immunoglobulin (IVIG), and plasma exchange, which aim to reduce pathogenic autoantibodies and modulate immune responses [10]. Early initiation of immunotherapy has been associated with improved neurological outcomes; however, some patients exhibit refractory disease, necessitating second-line agents such as rituximab and cyclophosphamide [11]. Despite advances in diagnosis and treatment, challenges remain, particularly in cases where autoantibodies are not detectable or the clinical presentation overlaps with other neurological disorders [12].

Accurate etiological identification is crucial for guiding appropriate therapy and improving prognosis. However, the clinical course can be complicated by severe neurological deficits, including status epilepticus, which requires intensive management in critical care settings [13]. This underscores the importance of a systematic approach to diagnosis, stabilisation, and treatment, especially in critically ill patients with suspected AE. This manuscript discusses the diagnosis and management of a patient with status epilepticus refractory to standard therapy, emphasising the importance of prompt recognition, comprehensive evaluation, and tailored immunomodulatory strategies in the context of autoimmune encephalitis in the intensive care unit (ICU).

CASE REPORT

A 42-year-old man with a history of CKD managed with regular haemodialysis (HD) for 5 months presented to the emergency department (ED) with complaints of severe shortness of breath. The patient was diagnosed with diabetes mellitus (DM) and chronic hypertension, which were managed intermittently. He had a history of a maximum blood glucose level of 350 mg/dL and hypertension (blood pressure, 200/120 mmHg). The patient was referred for kidney transplantation with his wife as the donor. Pre-transplant evaluation and counseling were completed, and both the recipient and donor consented to the procedure.

Table 1. Chronological Status of the Patient in ICU

Day	GCS	Blood Pressure (mmHg)	Heart Rate (bpm)	Respiratory Rate (bpm)	SpO2 (%)	Oxygen Therapy	Fluid Balance (mL)
1	E4V5M6	194/78 (no support)	99–101	16–18	100	3L/min nasal cannula	-510
2	E4V5M6	160/66 (nicardipine 0.5 mcg/kg/min)	105	25–30	95	3L/min nasal cannula	+164
3	E4V5M6	164/71 (nicardipine 0.25 mcg/kg/min)	107	19–23	100	3L/min nasal cannula	-2195
4	E4V5M6	170/84 (nicardipine 0.5 mcg/kg/min)	111	16–18	99	3L/min nasal cannula	+500

Upon presentation to the ED, the patient was alert and oriented, with the following vital signs: blood pressure, 150/90 mmHg; heart rate, 98 beats/min; respiratory rate, 27 breaths/min; and oxygen saturation, 96% on room air. His body temperature was 37.6°C. Physical examination did not reveal conjunctival pallor or scleral jaundice. Chest auscultation revealed bilateral vesicular breath sounds without any additional sounds. Cardiovascular examination revealed regular heart sounds with no additional murmurs, and abdominal examination was unremarkable with normal bowel sounds.

Laboratory tests showed haemoglobin 8.9 g/dL, haematocrit 24.8%, leukocyte count 14,490/mm3, platelet count 304,000/mm3, urea 46.2 mg/dL, creatinine 2.81 mg/dL, sodium 135 mEq/L, potassium 3.4 mEq/L, chloride 99 mEq/L, and blood glucose 158 mg Arterial blood gases (ABG) showed a pH of 7.453, pCO2 of 27.3 mmHg, pO2 of 107.1 mmHg, and HCO3 of 19.3 mEq/L. Chest radiography revealed cardiomegaly and aortic atherosclerosis. aorta. Electrocardiography (ECG) showed sinus rhythm at 100 beats per minute, and echocardiography revealed a dilated left ventricle (LV) with concentric LV hypertrophy (LVH), borderline left ventricular systolic function (LVEF 53%), and mild mitral regurgitation (MR). No evidence of pulmonary hypertension (PH) or right ventricular dysfunction was observed.

Figure 1. Chest X-ray of the patient before surgery

The patient underwent kidney transplantation, with his wife donating the organ. The surgery, which lasted 5.5 hours, was performed under general anaesthesia with appropriate monitoring. Preoperative anesthesia assessment classified the patient as ASA III owing to comorbidities such as CKD, hypertension, and diabetes. Intraoperative monitoring included noninvasive blood pressure (NIBP), ECG, SpO2, temperature, central venous pressure (CVP), end-tidal CO2 (EtCO2), arterial line, and bispectral index (BIS). Anaesthesia was induced using fentanyl, propofol, and rocuronium, and endotracheal intubation was performed subsequently. A central venous catheter (CVC) and arterial line were placed, and a quadratus lumborum (QL) block was performed for regional analgesia.

Intraoperative fluid management included 1,000 mL of crystalloid resuscitation, and 400 mL of blood loss was replaced intraoperatively. The patient's urine output was minimal during surgery, and renal Doppler ultrasound revealed inadequate renal perfusion. Subsequently, norepinephrine and dobutamine were administered as vasopressors to elevate the systolic blood pressure above 150 mmHg, resulting in improved renal perfusion and urine output. The patient was extubated postoperatively and transferred to the ICU for close monitoring.

The patient was admitted to the ICU post-transplantation on November 3, 2024, with stable hemodynamics but requiring vasopressor support (dobutamine 5 µg/kg/min and norepinephrine 0.1 mcg/kg/min) to maintain a mean arterial pressure (MAP) of 110 mmHg. His heart rate was 101 beats per minute, respiratory rate was 22–24 breaths per minute on a simple mask at 6 L/min, and oxygen saturation was 96–98%. On the second postoperative day, the patient developed respiratory distress, and lung ultrasound revealed a B-profile in both the lung fields. Chest radiography confirmed the diagnosis of pulmonary oedema, and the patient was treated with continuous furosemide infusion.

As part of the management strategy, the patient’s fluid balance was monitored closely. Diuresis was targeted at 1 mL/kg/h, and further fluid resuscitation was guided by urine output and haemodynamic parameters. A significant improvement in respiratory status was noted, and the patient’s blood pressure was managed with nicardipine to maintain a target systolic pressure of 160 mmHg.

Pulmonary complications, such as pulmonary oedema, are common in kidney transplant recipients and can be exacerbated by fluid overload, pre-existing comorbidities such as hypertension and diabetes, and intraoperative management. In this case, early identification and management of fluid overload through furosemide administration and careful haemodynamic monitoring were crucial for stabilising the patient’s condition. The importance of maintaining an optimal fluid balance, especially in high-risk patients, cannot be overstated.

Upon admission to the ICU, patient management followed the FAST HUG BID protocol, which included feeding, analgesia, sedation, thromboprophylaxis, head-up position, ulcer prophylaxis, and glucose control. Initially, the patient underwent gastric lavage, followed by test feeding. For pain management, tramadol was administered via a syringe pump with additional doses of paracetamol and continuous bupivacaine for the nerve block. To manage his blood glucose, insulin was infused at a rate of 6 U/h with hourly glucose monitoring, aiming for a target range of 140-180 mg/dL. His fluid balance and diuresis were carefully monitored, with a urine output of 1 cc/kg/h.

The patient was also prescribed cefazolin for infection prophylaxis, and continuous haemodynamic support with dobutamine and norepinephrine was provided. Fluid therapy was adjusted to maintain a negative fluid balance, and regular assessments, including echocardiography and kidney ultrasonography, were performed to monitor any potential complications.

Table 2. Laboratory Results and Antibiotics Administered

Day	Hemoglobin (g/dL)	Leukocytes (mm3)	Urea (mg/dL)	Creatinine (mg/dL)	Glucose (mg/dL)	Troponin I (ng/mL)	BNP (pg/mL)	Meropenem (g)
H0	8.9	14,490	46.2	2.81	158	0.56	8171	1
H1	7.3	18,730	107.3	4.3	142	0.98	-	1
H2	7.6	20,410	101.5	3.57	115	-	-	1
H3	7.1	17,000	123.9	2.73	174	-	-	1
H4	7.3	13,830	137	2.28	189	-	-	1

Progress and Complications

On the first night in the ICU, the patient's blood pressure increased despite the discontinuation of vasopressors. Nicardipine was introduced to achieve a target mean arterial pressure of 150-160 mmHg. On the second day, chest radiography revealed cardiomegaly and pulmonary oedema, prompting further investigations. Lung ultrasonography revealed bilateral B-profile changes, indicating pulmonary oedema. In response, furosemide was administered, and diuresis improved. The patient's fluid balance improved, and adjustments were made to the patient’s medication regimen.

By day two, the patient's blood pressure had been managed with nicardipine, and urine output had improved to approximately 100 mL/h. The insulin infusion rate was adjusted to maintain blood glucose levels between 140-180 mg/dL. Despite improvements, the patient's pulmonary condition remained a concern, and a repeat chest radiograph confirmed the presence of pulmonary edema. Echohemodynamic studies revealed a cardiac output (CO) of 4.7 L/min and a cardiac index (CI) of 3.06 L/min/m², suggesting that his hemodynamic status was still suboptimal.

Day 3 and 4 Management

By day three, the patient's blood pressure was further stabilized with nicardipine infusion, and his diuresis was more effectively managed with furosemide. His fluid balance remained positive but slowly approached the target of neutral balance. His renal function continued to improve, with urine output reaching approximately 180 mL/h. Echocardiography on the third day revealed further improvements, with CO increasing to 6.7 L/min and CI to 4.33 L/min/m². The patient's condition continued to improve, and with blood pressure was maintained at the target systolic pressure of 160 mmHg.

By day four, the patient showed further progress, with blood pressure stabilizing at 160/78 mmHg and a continued reduction in the need for vasopressor support. Urine output remained within the target range of 1-1.3 mL/kg/hour. The patient’s renal and cardiac functions continued to stabilize, and he was transitioned from a clear liquid diet to a soft diet. The plan for the day included further monitoring of blood glucose levels, with insulin adjusted accordingly, and continued management of the patient’s fluid balance and renal function.

This case highlights the complex nature of managing post-kidney transplant patients with multiple comorbidities including diabetes mellitus, hypertension, and ESRD. Postoperative complications, particularly pulmonary edema, require careful monitoring and intervention, including the use of diuretics and vasopressors, to stabilize hemodynamics. This case underscores the importance of a multidisciplinary approach, with continuous monitoring and adjustments to the therapeutic plan, including fluid management, glucose control, and renal function monitoring. Although the patient experienced significant challenges during the postoperative period, timely intervention and careful management resulted in stabilization and recovery. This case emphasizes the importance of personalized care in the ICU to ensure that patients receive appropriate interventions to optimize outcomes following kidney transplantation.

Table 3. Summary of Key Parameters

Day	Blood Pressure (mmHg)	Heart Rate (bpm)	Urine Output (mL/hour)	Fluid Balance (mL)	Medication Adjustments	Key Interventions
1	140/81	101	5	0	Dobutamine, Norepinephrine, Insulin infusion	Gastric lavage, test feeding, ultrasound
2	161/68	101	100-50-100	+164	Nicardipine, Furosemide	Chest X-ray, Lung Ultrasound, Fluid adjustment
3	164/71	101	170-180-180	-2195	Furosemide, Meropenem	Echohemodynamics, Fluid titration
4	160/78	101	135-90-120	-908	Furosemide, Prograf, Myfortic	Transition to soft diet, Echo assessment

DISCUSSION

Kidney transplantation remains the most common solid organ transplantation, providing a viable solution for patients with end-stage renal disease (ESRD). This procedure significantly enhances patients' quality of life and life expectancy, but the postoperative period is often complicated by multiple factors, such as hypertension, fluid balance, and pulmonary complications. In this case, a patient with pre-existing hypertension and diabetes mellitus type 2, undergoing kidney transplantation demonstrated various complications typical of high-risk transplant recipients.

Intraoperative fluid management plays a critical role in kidney transplant outcome. Maintaining optimal mean arterial pressure (MAP) is essential for ensuring adequate renal graft perfusion. MAP should be maintained between 80-110 mmHg during the perioperative period to avoid delayed graft function (DGF) [1-2]. In the present case, the patient experienced a significant drop in blood pressure during surgery, which was managed with the administration of crystalloids and vasopressors. Following this intervention, blood pressure stabilized, and graft perfusion improved, as confirmed by postoperative ultrasound. This intervention highlights the importance of hemodynamic optimization in preventing early graft dysfunction and improving transplant outcomes.

Hypertension is a common and significant complication of kidney transplantation that affects long-term graft survival and increases the risk of cardiovascular morbidity. The pathophysiology of post-transplant hypertension is multifactorial, including factors such as pre-existing hypertension, medication side effects, and changes in kidney function post-transplant [2-5]. The patient in this case was classified as having persistent hypertension, as he had a history of poorly controlled blood pressure before transplantation. Nicardipine, a calcium channel blocker, was chosen for its positive effects on graft function and compatibility with immunosuppressive therapies. Managing blood pressure post-transplant is crucial for preserving graft function and preventing cardiovascular complications, and strict control of blood pressure, particularly in patients with a history of hypertension, is essential for optimal outcomes [6-8].

Pulmonary complications such as acute respiratory failure (ARF) and pulmonary edema are common after kidney transplantation and are often exacerbated by factors such as immunosuppressive therapy and pre-existing comorbidities. The patient developed acute respiratory failure on day two post-surgery, marked by an increase in respiratory rate and decreased oxygen saturation. Chest radiography and ultrasound revealed signs of pulmonary edema, which was managed with continuous diuretics (furosemide) to improve urine output and reduce fluid overload. Pulmonary complications, particularly in high-risk patients like this one, necessitate careful monitoring and early intervention to prevent long-term morbidity [9-10].

Acute kidney injury (AKI) remains a major concern in kidney transplant recipients, often manifesting as delayed graft function (DGF) or early graft failure. The patient experienced reduced urine output attributed to poor renal perfusion following blood pressure drop during surgery. Timely intervention with fluid resuscitation and vasopressor administration restored adequate perfusion and urine output. This case underscores the importance of vigilant monitoring and early recognition of AKI to prevent long-term graft failure and improve post-transplant survival [11-13].

Patients undergoing kidney transplantation are at high risk of infection due to immunosuppressive therapy for preventing graft rejection. The patient developed increased white blood cell count, prompting broad-spectrum antibiotic initiation. Effective infection management is crucial in preventing complications, as transplant recipients are highly susceptible to bacterial, viral, and fungal infections. Appropriate antibiotic stewardship, guided by clinical signs and laboratory findings, is essential for improving post-transplant outcomes [14-15].

CONCLUSION

Kidney transplantation is the most prevalent solid organ transplantation, improving quality of life for patients with end-stage renal disease (ESRD). However, managing comorbidities like hypertension and diabetes is essential to prevent complications. The patient experienced acute kidney injury (AKI) due to impaired graft perfusion from reduced blood pressure during surgery, resulting in decreased urine output and suboptimal graft function. Fluid overload caused pulmonary edema and heart failure, requiring diuretic therapy and antihypertensive management. Postoperative immunosuppressive therapy requires monitoring for infection, leading to broad-spectrum antibiotics due to leukocytosis. This case demonstrates the importance of optimal perioperative management, including hemodynamic stability and infection prevention, for successful outcomes in kidney transplant recipients.

DECLARATIONS

None

CONSENT FOR PUBLICATION

The Authors agree to be published in Journal of Society Medicine.

FUNDING

None

COMPETING INTERESTS

The authors declare no conflict of interest in this case report.

AUTHORS’ CONTRIBUTIONS

All authors contributed to the work, including data analysis, drafting, and review of the article. They approved the final version and were accountable for all the aspects.

ACKNOWLEDGMENTS

None

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