PC3086: Posterior Reversible Encephalopathy (PRES) with White Matter Lesions on MRI in a Leber Hereditary Optic Neuropathy patient- are Eyes the Window to the Diagnosis?

Introduction: Leber hereditary optic neuropathy (LHON) is associated with point mutations in mitochondrial DNA, characterized by bilateral optic neuropathy. There is sparse data describing neuropathological illustration of PRES and white matter lesions in LHON. Furthermore, Multiple sclerosis (MS) like symptoms with LHON known as Harding syndrome is reported in few case reports presenting diagnostic and treatment challenges. We present a case of 18-year-old male who presented with seizures, encephalopathy, found to have PRES and multiple white matter lesions in midbrain, pons, medulla, and upper cervical spine who was found to have DNAJC30 gene mutation confirming Leber Hereditary Optic Neuropathy. His encephalopathy and seizures resolved on pulse dose steroids.

Case Description: The proband is 18-year-old male with a history of progressive optic atrophy. He initially presented with steroid responsive vision loss and encephalopathy. He was found to have demyelinating lesions of the area postrema and brainstem. Following clinical improvement, he presented approximately one year later with dyspnea, headaches and loss of vision followed by a generalized tonic-clonic seizure.

The patient was in status epilepticus with seizures from the occipital lobe. He was treated with IV keppra, IV fosphenytoin and midazolam infusion. Neuroimaging revealed FLAIR hyperintensities in the bilateral frontal lobes, occipital lobes and areas of the mid brain, pons and medulla and upper cervical spine without restricted diffusion. His initial infectious labs and lumbar puncture returned negative. He was started on pulse dose steroids on 4th day of admission, repeat brain MRI after 4 days of pulse steroids was improved. Rapid genome sequencing revealed a homozygous likely pathogenic mutation c.24G>A (p.Trp8Ter) in the DNAJC30 gene. This is recently described autosomal recessive cause of LHON.

Discussion: The case presented is unique with several overlapping diagnostic challenges in a case of genetically proven LHON. The patient’s case differs from traditional LHON in that the patient has had multiple clinical attacks, white matter signal abnormalities without restricted diffusion, and an episode of PRES with status epilepticus. Although Harding’s syndrome has been reported as variant of LHON with demyelinating disease overlay, the patient’s subsequent presentation of PRES is atypical. The patient’s clinical and radiographic presentation is dissimilar from more diffuse mitochondrial disorders, such as Leigh’s disease. The etiology of PRES in this case remains unclear, he had only one documented high blood pressure and has had no other risk factors for PRES. His remarkable improvement in encephalopathy and improvement of hyperintensities on MRI post steroid treatment poses the question of this genetic disorder being associated with MS like symptoms (Harding syndrome).

Conclusion: The association between LHON and demyelinating disease is rare. The etiology of this symptom and radiographic cluster is unclear but a linkage with PRES may indicate a link between endothelial dysfunction, mitochondrial dysfunction, and demyelinating disease.