Reversible splenial lesion syndrome: A differential diagnosis of corpus callosum lesions.

Introduction

While the splenium of the corpus callosum (SCC) is an uncommon location in which transient lesions may be found, reversible splenial lesion syndrome (RESLES) has been reported (Doherty et al., 2005; Garcia-Monco et al., 2011; Garg et al., 2015; Pan et al., 2015; Zhu et al., 2016). RESLES is a clinico-radiological syndrome characterized by seizures, encephalopathy, headache and ataxia among others. It has been associated with several etiologies such as infections, metabolic, vascular, demyelinating diseases and sudden withdrawal of the antiepileptic drugs (AEDs) (Doherty et al., 2005; Garcia-Monco et al., 2011; Garg et al., 2015; Pan et al., 2015; Zhu et al., 2016). Classically, magnetic resonance imaging (MRI) shows reversible lesions on SCC with restricted diffusion-weighted imaging (DWI) and reduced apparent diffusion coefficient (ADC) value (Doherty et al., 2005; Garcia-Monco et al., 2011; Garg et al., 2015; Pan et al., 2015; Zhu et al., 2016). The aim of this report was to evaluate the clinico-radiological characteristics of a patient with RESLES in Argentina and to perform a brief review.

Case report

A previously healthy 36-year-old woman was admitted in June 2017 with a two days history of fever associated with headache, myalgia, asthenia and dry cough that improved with nonsteroidal anti-inflammatory drugs (NSADs). One day later, she had an episode of involuntary tonic movements in all four limbs, which lasted a few minutes, without loss of consciousness (LC). During hospitalization, she had two new episodes. During the first new episode, she had a left-gaze deviation and encephalopathy for a few minutes, without postictal state (PS). In the second episode, she presented tonic movements in all four limbs followed by dysarthria, but resolved within a few minutes, without LC or PS. Physical examination was normal. At disease onset, routine investigations on serum were all normal, except for the presence of leukopenia (3580 cells/microL) and a mild elevation in both aspartate transaminase (AST, 89 UI/L [normal = 5-35]) and alanine transaminase (ALT, 121 UI/L [normal = 6-35]). Laboratory test performed the day after revealed normal liver enzymes and gamma glutamyl transpeptidase. In this context, she denied alcohol or illicit drug abuse but a naproxen intake prior to the laboratory test was indicated during admission, which is described as a cause of transient increase in liver enzymes. However, her seizures did not improve at onset. Viral serologies were performed and results were negative for influenza A and B, adenovirus, coronavirus, parainfluenza virus, enterovirus, human immunodeficiency virus (HIV) and all types of herpes viruses (herpes virus simplex 1 and 2, Epstein-Barr, Varicela Zoster, cytomegalovirus and herpes 6). In addition, antibody results for lupus, Sjogren's syndrome, antiphospholipid syndrome, celiac disease, neuromyelielitis optica (aquaporin-4 antibody) as well as paraneoplastic syndrome (anti-Hu, anti-Yo and anti-Ri) were negative. Cerebrospinal fluid (CSF) examination revealed normal cell count, glucose concentration and total protein concentration as well as polymerase chain reaction (PCR) testing negative for all types of herpes viruses. Oligoclonal bands were also negative on CSF. Blood cultures were all negative including those for mycoplasma pneumoniae.

Electroencephalogram (EEG) examination was normal. As illustrated in Fig. 1 , brain MRI showed a central lesion in the SCC with restricted DWI. She was discharged without a specific treatment and had no further episodes at follow-up. Ten days later, brain MRI showed the lesion on SCC nearly disappeared in DWI and ADC, and RESLES associated with mild encephalitis/encephalopathy with a reversible isolated lesion of the splenium (MERS) was confirmed.

Fig. 1

Radiological characteristics of a RESLES.

A, B, C: MRI showed isolated central lesion in the SCC with restricted DWI and reduced ADC value. D: T1-weighted isointensity on SCC. E: Subtle T2-weighted/FLAIR hyperintensity MRI lesion on the SCC. F: Second MRI (follow-up imaging 10 days later) showed the lesion on SCC nearly disappeared in DWI and ADC.

Comment

We have presented a case of a 36-year-old woman with acute fever, confusion and 3 seizure episodes associated to a transient SCC lesion on brain MRI.

Encephalopathy has been defined as acute brain impairment such as fever, headache, behavior disorder, seizures and impairment of consciousness without evidence of inflammatory changes on serum or CSF (Zhu et al., 2016). If the patients present with febrile syndrome and inflammatory changes, they are called to have encephalitis (Zhu et al., 2016). Two classifications of acute encephalopathy were reported (Hoshino et al., 2012). The first was based on the microorganism that can cause the infectious process whereas the second was based on clinical, laboratory, MRI scan and pathological findings of encephalopathy (Hoshino et al., 2012; Zhu et al., 2016). In our patient, the diagnosis was RESLES associated with MERS related to self-limited respiratory illness. Thus, the infectious-related clinically MERS was reported as the most frequent cause of RESLES in childhood (Zhu et al., 2016). In addition, some cases of RESLES (13 patients) have been published in adults from Japan, India, Hong Kong, China, United States and Turkey (Hoshino et al., 2012; Zhu et al., 2016). In 2012, the diagnostic criteria for MERS were reported according to Hoshino et al (Hoshino et al., 2012). as follows: 1) Onset with neuropsychiatric symptoms, such as abnormal speech and/or behavior, and impaired consciousness and convulsion, within 1 week after fever onset; 2) Complete recovery without sequelae, mostly within 10 days after the onset of neuropsychiatric symptoms; 3) Hyperintensity lesion in the SCC, in the acute stage. T1 and T2 signal changes are mild; 4) Lesion may involve the entire corpus callosum and the cerebral white matter in a symmetric fashion; 5) Lesion disappears within 1 week, with no residual signal changes or atrophy.

RESLES associated with MERS has been described in a wide variety of inherited and acquired inflammatory and noninflammatory diseases (Doherty et al., 2005; Garcia-Monco et al., 2011; Garg et al., 2015; Pan et al., 2015; Zhu et al., 2016). The pathophysiological mechanism of RESLES is still unclear (Garg et al., 2015). Nevertheless, reversible intramyelinic edema was proposed as an important mechanism and this can occur by electrolyte and fluid imbalance leading to facilitation of oxidative stress and reversible SCC lesions (Doherty et al., 2005; Garg et al., 2015; Hoshino et al., 2012; Pan et al., 2015).

Neurological symptoms of MERS include altered consciousness, behavioral changes, motor deterioration and seizures in around half of the patients. Fever in MERS due to infectious process is described as prior to development of neurological and psychiatric symptoms. EEG abnormalities are found in approximately 50% of patients with MERS.

In clinical practice, establishing the correct diagnosis at disease onset can have an impact in terms of prognosis. Thus, brain MRI is the best tool available to differentiate lesions of the SCC. Transient SCC lesions with restricted DWI and ADC reduction on brain MRI can differentiate RESLES from ischemia. This pattern on brain MRI indicates the presence of cytotoxic edema in the SCC. Likewise, reduced ADC value might be explained by intramyelinic edema, transient inflammatory infiltrate and/or interstitial edema in tightly packed fibers. Usually, these lesions resolve completely on follow-up imaging (1-2 weeks) (Doherty et al., 2005; Garg et al., 2015; Pan et al., 2015).

Therefore, when we evaluate a patient with encephalopathy, to identify a reversible isolated SCC lesion on MRI at an early stage is very important due to the excellent prognosis most of these patients have. In this case, although the etiology was unknown (bacterial and viral cultures in both CSF and blood were all negative), the patient fulfilled diagnostic criteria for MERS and we think that MERS was caused by her previous self-limited respiratory illness (influenza-like syndrome). The laboratory findings did not detect any toxic, metabolic, vascular, autoimmune, AEDs and nonAEDs use, infectious or parainfectious process in this patient.

We were stimulated to communicate this case and add our data to the international data set. Previous data had come especially from Asia followed by Oceania (Australia) Europe and North America (Doherty et al., 2005; Garcia-Monco et al., 2011; Garg et al., 2015; Hoshino et al., 2012; Pan et al., 2015; Zhu et al., 2016), but there were no data from Latin America, which would be expected to present differences in comparison with patients in these other regions.

Conflicts of interest

None of the authors has any potential financial conflict of interest related to this manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or non-profit sectors.