In 2004, Tada et al[3] reported a series of 15 patients with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). In 2011, Garcia-Monco et al[5] reviewed the MEDLINE database from 1966 to 2007 and termed the presence of transient lesions involving SCC reversible splenial lesion syndrome (RESLES). Therefore, at times, RESLES associated with encephalitis/encephalopathy was interchangeably termed MERS [5, 13]. RESLES is characterized by reversible lesions in the central portion of the splenium of the corpus callosum (SCC)[3, 7]. RESLES is most often identified in patients with seizures and/or antiepileptic drug withdrawal[8, 9], and it is also associated with infections of various pathogens, such as influenza virus, rotavirus, measles, herpesvirus 6, adenovirus, mumps, Epstein-Barr virus, Escherischia coli, and others[10-12]. Typically, the clinical neurological symptoms of RESLES include mildly altered states of consciousness, delirium, and seizures after a range of previous viral infections but usually have complete recovery without neurological sequelae after a short disease course[13, 14].
There are few reports in the literature on MRI findings of porphyria cases with central nervous system (CNS) involvement [15, 16]. Many of studies suggested that MRI changes are related to posterior reversible encephalopathy syndrome (PRES)[17-19]. In this report, we have presented a new MRI finding of AIP that has not been previously reported.
According to Hoshino et al[20], the diagnostic criteria of RESLES (MERS) are as follows: (1) clinical onset associated with neuropsychiatric symptoms, such as impaired consciousness within 1 week after fever onset; (2) complete recovery without sequelae, mostly within 10 days after the onset of neuropsychiatric symptoms; (3) high-signal-intensity lesion in the SCC; (4) involvement of the entire corpus callosum and bilateral cerebral white matter with symmetrical pattern; (5) lesion disappearance within 1 week, with no residual signal changes or atrophy. Despite our proband undergoing the second MRI 15 days after the first one and without fever, she fulfils this diagnostic criterion. RESLES is classified as RESLES type I or RESLES type II, depending on the involvement of SCC alone or other white matter areas. Our patient was a RESLES type I case.
Acute intermittent porphyria (AIP) is one of four forms of acute porphyria that is caused by an inherited deficiency of PBGD, which catalyses the third enzymatic step in the biosynthesis of heme. Symptoms in AIP, which occur as intermittent attacks and may be life-threatening, are caused by excess production of porphyrin precursors on the visceral, peripheral, autonomic, and central nervous systems[1]. Clinical manifestations of CNS involvement include epileptic seizures, impaired consciousness, behavior changes and hyponatremia caused by inappropriate antidiuretic hormone syndrome[21, 22]. The symptoms of our proband included abdominal pain, nausea, vomiting, confusion, delirium, seizures and hyponatremia.
The reason for the transiently reduced diffusion within the lesions on MRI is still unknown, which has been suggested to be due to hypotonic hyponatremia or a myelin-specific neurotoxin released by a pathogen[6, 23]. The possible cause of hyponatremia of RESLES is SIADH, which is also considered a cause of hyponatremia in patients with AIP[22]. Since she had no evidence of infection, hyponatremia may be a contributing factor of RESLES in our proband. However, urine and blood osmolality of our proband were both lower than normal, perhaps because she had taken 0.25 mg tolvaptan 12 hours before. Tolvaptan could significantly decrease the urine osmolality[24, 25]. Tolvaptan did not exacerbate symptoms in the acute phase of AIP in our proband, and perhaps it is safe to use of tolvaptan in AIP with hyponatremia.
In mainland of China, laboratory investigations (erythrocytic PBG deaminase levels, urinary, fecal, and plasma porphyrin levels) are unavailable. Molecular genetic testing provides a precise diagnosis to differentiate AIP from other acute porphyrias and can then be used to identify AIP in relatives of the proband. In this study, we identified a novel HMBS gene mutation (W198*) in a Chinese family. Most cases of RESLES have occurred in children in East Asian populations, mostly Japan, and there has also been one case report of sisters with RESLES, which would support the genetic vulnerability hypothesis[26]. AIP is a hereditary disease, suggesting that a genetic factor might be involved in some RESLES patients. This is the first reported case of RESLES following AIP, and she had a novel HMBS nonsense mutation. Our case report widens the phenotype of the neurological manifestations associated with AIP. Since porphyria is a rare disease, the major limitation of our work was the small sample size. Further clinical, radiological and genetic studies of RESLES are necessary for a definite conclusion.