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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 41  |  Issue : 4  |  Page : 197-200

Reversible splenial lesion syndrome in hyponatremia


1 Clinic of Neurology, Yozgat City Hospital, Yozgat, Turkey
2 Infectious Disease Clinic, Yozgat City Hospital, Yozgat, Turkey

Date of Submission28-Aug-2020
Date of Decision05-Oct-2020
Date of Acceptance19-Nov-2020
Date of Web Publication03-Feb-2021

Correspondence Address:
Dr. Halil Onder
Clinic of Neurology, Yozgat City Hospital, Yozgat
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmedsci.jmedsci_240_20

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  Abstract 


Reversible splenial lesion syndrome (RESLES) is rare findings that are described in various etiological conditions. A few recent reports suggested hyponatremia as a potential etiological agent of RESLES. In this report, we illustrate a 46-year-old-male with RESLES who manifested with impairment of consciousness and recovered rapidly after normalization of hyponatremia. We discuss hyponatremia as a factor which might be playing a role either as a primary agent or a contributory one in this manifestation. Besides, we also discuss the possible significance of the other clinical factors including concurrent sinusitis and medication usage in association with RESLES. We think that the detailed illustration of this case may present substantial perspectives regarding the unknown aspects of the pathophysiology of RESLES. The clinical impact and underlying pathogenesis of this entity are warranted to be clarified in future large-scale studies.

Keywords: Hyponatremia, neuroimaging, pathogenesis, reversible splenial lesion syndrome


How to cite this article:
Onder H, Sade D. Reversible splenial lesion syndrome in hyponatremia. J Med Sci 2021;41:197-200

How to cite this URL:
Onder H, Sade D. Reversible splenial lesion syndrome in hyponatremia. J Med Sci [serial online] 2021 [cited 2021 Oct 25];41:197-200. Available from: https://www.jmedscindmc.com/text.asp?2021/41/4/197/308688




  Introduction Top


Reversible splenial lesion syndrome (RESLES) was first identified by Garcia-Monco et al. and the radiological feature of the disappearing or significantly improving lesion in follow-up studies was specifically emphasized.[1] Since then, many researchers have reported on the presence of RESLES, which is associated with a variety of disorders, including viral encephalitis, antiepileptic drug toxicity/withdrawal, hyponatremia, medication, and hypoglycemic encephalopathy.[2],[3],[4],[5] The diagnosis of RESLES is based on the magnetic resonance imaging (MRI) finding of a reversible isolated lesion with transiently reduced diffusion in the central portion of the splenium of the corpus callosum and clinically mild encephalitis/encephalopathy, which recovers with a resolution of the splenial lesion.[5] The exact pathogenesis of RESLES has not yet been elucidated; however, intramyelinic edema, interstitial edema in tightly packed fibers, and a transient inflammatory infiltrate constitute the main hypotheses underlying its pathogenesis. Remarkably, some authors have reported cases of RESLES in association with hyponatremia, and they have attempted to reveal the significance of hyponatremia as a risk factor for RESLES.[4],[6] In our opinion, a detailed investigation of patients with RESLES due to hyponatremia may also present perspectives regarding the specific physiological feature of the splenial corpus callosum and the unknown aspects of RESLES from other etiologies. In this report, we discuss the case of a patient with RESLES primarily associated with hyponatremia. We also discuss the contributory roles of other clinical features, including the use of immunomodulatory medication and prednisolone and concurrent sinusitis. In light of the evidence reported in the literature, we propose hypotheses regarding the underlying mechanisms of RESLES.


  Case Report Top


A 46-year-old-male patient was admitted to our emergency department with impairment of consciousness, and somnolence. It was learned that the patient had been suffering from a cough, nasal discharge, and sputum as well as anorexia and impairment in oral intake over the previous 2 days, and his consciousness had begun to deteriorate progressively 12 h before admission. The patient had a history of chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) over the past 3 years. Moreover, the diagnosis of myasthenia gravis (MG) was established 5 years before following investigations due to generalized weakness and bulbar symptoms. At that time, he was being treated with pyridostigmine 7 mg × 60 mg, prednisolone 1 mg × 10 mg, and azathioprine 3 mg × 50 mg. The vital signs at admission to the emergency service were as follows: Temperature of 38°C, a heart rate of 90 beats/min, and a respiratory rate of 12 breaths/min. The neurological examination revealed that the patient was nonoriented and mildly cooperative. He could not properly cooperate with the examination and he tended to sleep spontaneously without tactile stimulation. Other investigations were evaluated as normal, including motor, sensory, and cerebellar functioning. However, Kernig's and Brudzinski's signs were negative. The laboratory investigations revealed moderate hyponatremia (127 mM/L [136–146 mM/L]), neutrophilic leukocytosis (neutrophil: 89%), and the presence of c-reactive protein (27.9 mg/L [0–0.8 mg/L]). Further investigations for hyponatremia revealed serum osmolality of 270 mOsm/kg and a urinary sodium level of 25 mEq/L. The results of the other investigations, including liverkidney functions and thyroid functions, were within normal limits. Cranial diffusion-weighted imaging (DWI) revealed diffusion restriction in the splenial corpus callosum [Figure 1]. No other abnormalities in other locations were found in other MRI sequences (axial and coronal T2-fluid-attenuated inversion recovery, axial T1). With a prediagnosis of sinusitis and meningitis, the treatments of sulbactam 2 g, ceftriaxone 2 g × 2 g, and acyclovir 3 mg × 750 mg were started; 150 ml/h isotonic saline infusion was also initiated for acute hypovolemic hyponatremia, which was associated with impaired oral intake. The patient was hospitalized for further investigations.
Figure 1: The diffusion-weighted imaging (a and b) and apparent diffusion coefficient (c) images, recorded at admission to the emergency service, showing the diffusion-restricted lesion in the splenial corpus callosum

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The patient recovered rapidly in the following 1-day period, and he was evaluated as fully orientated and cooperative on the 2nd day of hospitalization. Concurrently performed laboratory investigations showed recovery of the hyponatremia (135 mM/L [136–146 mM/L]). Although the rapid clinical recovery was atypical for encephalitis, lumbar puncture (LP) investigation was also suggested at that time (on the 1st day of admission, the LP needle was unavailable). However, the patient declined the procedure. Routine electroencephalogram (EEG) investigation showed normal posteriorly dominant parietooccipital 8 Hz alpha activity. Based on the symptoms of coughing, fever, and massive nasal discharge, sinus computed tomography was performed, which confirmed massive ethmoidal sinusitis. Acyclovir was ceased, and the treatment was switched to moxifloxacin and meropenem. The cranial DWI performed 1 week later, showed almost complete resolution of the splenial lesion [Figure 2]. Taken together, the diagnosis of RESLES was established, and the etiology was associated primarily with hyponatremia extrapontine osmotic demyelination syndrome was also considered among differential diagnoses. However, no diffusion restriction was found in any locations other than splenial corpus callosum and correction of hyponatremia provided recovery of the clinical and radiological manifestations which were totally incompatible with the clinical course of osmotic demyelination syndrome. During the following 1-week period of antibiotherapy, no deterioration in this neurological condition occurred and he did not suffer from bulbar symptoms or weakness that would remind MG exacerbation. After completion of antibiotherapy, he was discharged with suggestions of previous therapies for MG, DM, and COPD.
Figure 2: The second diffusion-weighted imaging images (a; diffusion-weighted imaging image, b; apparent diffusion coefficient image, c; T-2 weighted image), performed 1 week after the first, showing nearly total resolution of the lesion. The arrow shows minimal hypointensity in the splenium on the apparent diffusion coefficient image

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  Discussion Top


The pathogenesis of RESLES is still not completely known. Various hypotheses have been suggested, such as axonal damage, intramyelinic edema, oxidative stress, and inflammatory mechanisms.[4],[5] Prominently, the pathogenesis of a reversible diffusion restricted lesion in this region has been attributed to excitotoxic mechanisms without brain ischemia.[7] Edema induced by glutamate in the excitotoxic mechanisms occurs predominantly in glial cells and myelinic sheaths. This involvement pattern protects axons from intracellular edema and irreversible neuronal damage.[7] Strikingly, this commissure is composed of axons and glial cells, while neuronal somata make up <1%.[8] This histopathological feature of the splenial corpus callosum may be important for the specific vulnerability of this region.

In our patient, the laboratory investigations revealed moderate hyponatremia and acute sinusitis. Another clinical feature of this patient was that he was taking immunomodulatory therapies for MG. We think that all these factors might have contributed in the occurrence of this condition. Takanashi et al. reported a large series of patients with RESLES, which they associated with hyponatremia.[4] They suggested that, from a clinical perspective, it is not possible to completely separate RESLES from hyponatremic encephalopathy or to rule out hyponatremia as a contributing factor of RESLES. However, they emphasized the probable mechanism of cerebral edema due to electrolyte/water imbalance as a common mechanism underlying RESLES. Sodium ions are the major cations of the extracellular fluid that play a role in the maintenance of internal fluid and electrolyte balance by constantly moving between both compartments, which is regulated by the sodiumpotassium pump.[9] The most important function of this pump is to prevent cells from swelling. If sodium is not “pumped” out, water accumulates within the cell, which causes swelling and ultimately bursting leading to cerebral edema in the brain.[9] Remarkably, the splenial corpus callosum contains the most compact area of callosal glia cells combined with a known largest density of axonal fibers.[8] It is demonstrated that the glial cells selectively swell in the presence of hyposmolar stress with sparing of neurons, suggesting that the presence of specific water channels localized in glial cells protect neurons from the water entry.[10] In light of this evidence, we think that hyponatremia might be functioning in this clinical output through a mechanism of catalyzing the occurrence of edema focally in the splenium. Supporting this view, the corpus callosum is known to be involved in functions of interhemispheric communication and many neuronal networks including awareness[11] which may explain the severe consciousness impairment in the affection of solely this location in RESLES.

On the other hand, the myelination pattern and dynamic of the splenial corpus callosum are shown to differ from remaining CC in studies on rats[12] that may be responsible for the specific vulnerability of this region from the intramyelinic edema. In light of these previous studies and hypothesized mechanisms,[1],[2],[3],[4],[5] we think that the particular involvement of the splenial corpus callosum in RESLES may be related to these specific histopathological features. Of note, the prednisolone use in this patient may also be considered as a contributory factor as reported in a few case reports previously.[2],[13] The long-and short-term regulatory effects of corticosteroids on the Na1-K1-ATPase may be suggested as a possible mechanism.[14] On the other hand, another hypothesis to explain the RESLES is the influx of inflammatory cells and macromolecules, combined with related cytotoxic edema.[5],[15] Knowing the therapies of azathioprine and prednisolone cause alterations on the immune system, the mechanism of the immune system response due to these medications may also be hypothesized to be a contributory factor. The newly onset sinusitis in our patient leading to the reactivation of this altered immune system might have functioned as an inducer mechanism at this point. However, these hypotheses are warranted to be clarified in future studies including large case series.

The major limitation of our study was that we did not perform a LP investigation to exclude underlying encephalitis. However, the clinical course of the patient who recovered extremely rapidly after correction of hyponatremia was atypical for encephalitis; and rather strongly supported hyponatremia as the etiological agent of RESLES.

In conclusion, we remark RESLES as a crucial and benign entity to be kept in mind among clinicians. Hyponatremia may be a substantial cause in this manifestation which may be playing role either as a primary agent or a contributory one. The clinical impact and underlying pathogenesis of this entity are warranted to be clarified in future large-scale studies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients has given his consent for his images and other clinical information to be reported in the journal. The patients understand that his names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Garcia-Monco JC, Cortina IE, Ferreira E, Martínez A, Ruiz L, Cabrera A, et al. Reversible splenial lesion syndrome (RESLES): What's in a name? J Neuroimaging 2011;21:e1-14.  Back to cited text no. 1
    
2.
Aksu B, Kurtcan S, Alkan A, Aralasmak A, Oktem F. Reversible corpus callosum splenial lesion due to steroid therapy. J Neuroimaging 2015;25:501-4.  Back to cited text no. 2
    
3.
Gallucci M, Limbucci N, Paonessa A, Caranci F. Reversible focal splenial lesions. Neuroradiology 2007;49:541-4.  Back to cited text no. 3
    
4.
Takanashi J, Tada H, Maeda M, Suzuki M, Terada H, Barkovich AJ. Encephalopathy with a reversible splenial lesion is associated with hyponatremia. Brain Dev 2009;31:217-20.  Back to cited text no. 4
    
5.
Tada H, Takanashi J, Barkovich AJ, Oba H, Maeda M, Tsukahara H, et al. Clinically mild encephalitis/encephalopathy with a reversible splenial lesion. Neurology 2004;63:1854-8.  Back to cited text no. 5
    
6.
Suzuki H, Kusaka T, Okada H. Clinically mild encephalitis/encephalopathy with a reversible splenial lesion caused by human parvovirus b19 infection: A case of two brothers with hereditary spherocytosis. Pediatr Neurol 2014;51:470-2.  Back to cited text no. 6
    
7.
Kang EG, Jeon SJ, Choi SS, Song CJ, Yu IK: Diffusion MR imaging of hypoglycemic encephalopathy. AJNR Am J Neuroradiol 2010;31:559-64.  Back to cited text no. 7
    
8.
Reyes-Haro D, Mora-Loyola E, Soria-Ortiz B, García-Colunga J. Regional density of glial cells in the rat corpus callosum. Biol Res 2013;46:27-32.  Back to cited text no. 8
    
9.
Pohl HR, Wheeler JS, Murray HE. Sodium and potassium in health and disease. Met Ions Life Sci 2013;13:29-47.  Back to cited text no. 9
    
10.
Kimelberg HK. Water homeostasis in the brain: Basic concepts. Neuroscience 2004;129:851-60.  Back to cited text no. 10
    
11.
Hofer S, Frahm J. Topography of the human corpus callosum revisited–comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. Neuroimage 2006;32:989-94.  Back to cited text no. 11
    
12.
Nuñez JL, Nelson J, Pych JC, Kim JH, Juraska JM. Myelination in the splenium of the corpus callosum in adult male and female rats. Brain Res Dev Brain Res 2000;120:87-90.  Back to cited text no. 12
    
13.
Renard D, Bonafe A, Heroum C. Transient lesion in the splenium of the corpus callosum after oral corticoid therapy. Eur J Neurol 2007;14:e19-20.  Back to cited text no. 13
    
14.
Therien AG, Blostein R. Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol 2000;279:C541-66.  Back to cited text no. 14
    
15.
Roychowdhury S, Maldjian JA, Grossman RI. Multiple sclerosis: Comparison of trace apparent diffusion coefficients with MR enhancement pattern of lesions. AJNR Am J Neuroradiol 2000;21:869-74.  Back to cited text no. 15
    


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