
==== Front
J Clin Neurol
J Clin Neurol
JCN
Journal of Clinical Neurology (Seoul, Korea)
1738-6586
2005-5013
Korean Neurological Association

39227339
10.3988/jcn.2024.0059
Letter to the Editor
Refractory Status Epilepticus Associated With Dialysis Disequilibrium Syndrome
https://orcid.org/0000-0002-3957-7806
An Jaehyeong
https://orcid.org/0009-0007-8452-132X
Kang Ji Yun
https://orcid.org/0000-0002-2087-4851
Kim Hyun Kyung
Department of Neurology, National Medical Center, Seoul, Korea.
Correspondence: Hyun Kyung Kim, MD. Department of Neurology, National Medical Center, 245 Eulji-ro, Jung-gu, Seoul 04564, Korea. Tel +82-2-2260-7290, Fax +82-2-2268-0803, crespin97@gmail.com
9 2024
24 7 2024
20 5 542544
28 1 2024
01 5 2024
07 5 2024
Copyright © 2024 Korean Neurological Association
2024
Korean Neurological Association
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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pmcDear Editor,

Dialysis disequilibrium syndrome (DDS) is an uncommon neurological complication of hemodialysis that is attributed to rapid metabolic changes. The symptoms of DDS include headache, nausea, vomiting, fatigue, focal neurological deficits, disturbed consciousness, and seizure.123 The incidence of DDS-related seizures is low, and reports on DDS-associated status epilepticus (SE) are very scarce, with no reports of DDS-associated refractory SE.456 Here we report a case of severe headache and refractory SE related to DDS following hemodialysis.

A 67-year-old male presented to the emergency room with severe bilateral headache, nausea, and drowsiness that occurred immediately after receiving hemodialysis 1 hour previously. He had a history of hypertension and chronic kidney disease, and had started receiving hemodialysis 3 months before this presentation. He had no previous history of seizures or epilepsy. He initially underwent hemodialysis at a blood flow rate of 180 mL/min. Three days before he presented to the emergency room, the blood flow rate had been increased to 280 mL/min, after which he complained of severe headaches and fatigue.

On arrival, his blood pressure was 150/81 mm Hg, and his body temperature was 36.3℃. He was drowsy, but other neurological examinations were unremarkable. Initial brain computed tomography and diffusion-weighted imaging (DWI) revealed no acute or remote lesions. The results of blood tests were unremarkable except for a creatinine level of 3.77 mg/dL. After initial evaluations, and approximately 4 hours after the hemodialysis session, he exhibited two types of sudden recurrent seizures: 1) right head versive seizure to bilateral tonic–clonic seizure (BTCS) and 2) left arm clonic seizure to BTCS. He received intravenous (IV) lorazepam (4 mg) followed by IV valproate (2,000 mg) and fosphenytoin (1,800 mg), but the seizures recurred without recovering consciousness. The seizures persisted after additionally administering IV lacosamide (400 mg) and phenobarbital (500 mg). He was then intubated and administered continuous IV midazolam (5 mg/h), after which he did not experience any further breakthrough seizures. Electroencephalography showed generalized, low-voltage slow activity without epileptiform discharges or electrographic seizures. On the second day of admission, DWI revealed hyperintensities in the right high frontal and left lateral temporal areas with iso- to hypointensities in an apparent diffusion coefficient map (Fig. 1A-D). In the intensive care unit, continuous renal replacement therapy was initiated with a low blood flow rate of 90 mL/min. The IV midazolam was discontinued on the fourth day of admission, and he progressively recovered consciousness over the following 2 days.

A neurological examination performed 1 week later revealed only mild dysarthria. Fluid-attenuated inversion recovery (FLAIR) images revealed hyperintensities suggestive of vasogenic edema in the right frontal, parietal, and left temporal areas, including the areas previously showing restricted diffusion on DWI (Fig. 1E and F). Hemodialysis was restarted at a low blood flow rate of 180 mL/min, and the patient did not subsequently complain of headaches, seizures, or other neurological symptoms. Two months later, he had recovered fully without dysarthria. Follow-up FLAIR images revealed that the lesions had nearly disappeared (Fig. 1G and H).

This patient experienced headache soon after starting hemodialysis and then SE after increasing the blood flow rate during hemodialysis. Besides treatment for SE, neurological symptoms (including seizures) did not recur after slow-flow dialysis, and so the diagnosis was compatible with DDS.

The neurological manifestations of DDS are more common toward the end of hemodialysis, and are characterized by rapid urea clearance that accentuates the urea concentration gradient between the plasma and cerebrospinal fluid.2 Seizures commonly occur immediately after hemodialysis, but they may also occur up to several hours later.46 DDS is most often seen in patients at the initiation of hemodialysis, but it can also be observed chronically, especially if the dialysis regimen is changed.7 The incidence of DDS is poorly defined, but the overall incidence and severity have declined recently, primarily due to increased awareness of this complication and the implementation of preventive measures.1238

The incidence and common type of seizures in DDS have yet to be determined. An early study found seizures in 6% of patients with DDS,5 and a US study found that DDS accounted for 4.5% of seizure claims in the dialysis population.9 Primary BTCS was the predominant DDS-related seizure type in two case studies.24 Unlike previous reports, the present patient experienced two types of focal to BTCS and refractory SE. Brain magnetic resonance imaging (MRI) revealed reversible hyperintensity lesions, which may have been due to peri-ictal changes following SE. However, the lesions on MRI could also have been directly associated with DDS because they were more suggestive of vasogenic edema. It has been shown that DDS can cause reversible vasogenic edema or posterior reversible leukoencephalopathy syndrome.67

The pathogenesis of DDS is related to a reverse urea effect wherein there is a relatively slow removal of urea from the brain compared with a significant decrease in plasma urea concentration and organic osmolytes in the brain at the end of dialysis, leading to cerebral edema.23 Since DDS is primarily the result of osmotic fluid shifts into the brain, avoiding the generation of a significant osmotic gradient between the blood and brain is essential for preventing this complication.10 Slowing the dialysis rate and adding osmotically active substances (e.g., high-glucose dialysate or mannitol) are interventions that can prevent the development of DDS.123

DDS and related seizures are rare neurological complications associated with hemodialysis in patients with renal disease. However, DDS should also be considered in the differential diagnosis if seizures occur in patients with no definite etiology, especially after dialysis.

Availability of Data and Material

The datasets generated or analyzed during the study are not publicly available due to protection of personal health information, but are available from the corresponding author on reasonable request.

Fig. 1 Serial brain imaging of SE associated with dialysis disequilibrium syndrome. A–D: DWI performed 1 day after SE revealed high-signal-intensity lesions in the right high frontal and left lateral temporal areas (arrows) with iso- to hypointensities in an apparent diffusion coefficient map. E and F: FLAIR images performed 7 days after the initial DWI revealed high-signal-intensity lesions suggestive of vasogenic edema in the right frontal, parietal, and left temporal areas. A small amount of subdural hemorrhage owing to trauma related to SE was seen in the right occipital area. G and H: Follow-up FLAIR images obtained 2 months later showed that the lesions in the right frontal, parietal, and left temporal areas had nearly disappeared. DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; SE, status epilepticus.

Ethics Statement: The Institutional Review Board of the National Medical Center reviewed and approved the study protocol (Approval No. NMC-2024-01-010). The board waived the need to obtain informed consent.

Author Contributions: Conceptualization: Hyun Kyung Kim.

Data curation: Jaehyeong An, Ji Yun Kang.

Formal analysis: Hyun Kyung Kim.

Investigation: Jaehyeong An, Ji Yun Kang.

Methodology: Jaehyeong An, Ji Yun Kang.

Resources: Jaehyeong An.

Supervision: Hyun Kyung Kim.

Validation: Hyun Kyung Kim.

Visualization: Jaehyeong An.

Writing—original draft: Jaehyeong An, Hyun Kyung Kim.

Writing—review & editing: Hyun Kyung Kim.

Conflicts of Interest: The authors have no potential conflicts of interest to disclose.

Funding Statement: None
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