Co-Occurrence of Multiple Sclerosis and Amyotrophic Lateral Sclerosis in an FUS-Mutated Patient: A Case Report

Abstract

A concomitant presentation of relapsing remitting multiple sclerosis (RRMS) and amyotrophic lateral sclerosis (ALS) is quite rare. However, a review of the literature showed an increased co-occurrence of both diseases, including in genetically determined cases. We report the case of a 49-year-old woman with a history of RRMS who developed a progressive subacute loss of strength in her left arm. The patient’s father died from ALS, and her paternal uncle had Parkinson’s disease. Brain and cervical MRIs were performed, and new demyelinating lesions were excluded. Electromyography (EMG) of the upper limbs showed fibrillations and fasciculations in distal muscles of both arms. In the following months, the patient presented a progressive loss of strength in the proximal and distal muscles of the right arm and hyperreflexia in the lower limbs. EMG and central motor conduction were consistent with ALS. A genetic test was carried out, revealing a mutation in the FUS gene (exon 15; c. 1562 G>A). To our knowledge, the co-occurrence of MS and ALS in patients with FUS mutation is extremely rare. We hypothesize a common pathway for both diseases based on the possibility of a shared oligodendroglial dysfunction due to FUS mutation.

Keywords: FUS; amyotrophic lateral sclerosis; clinical neurophysiology; multiple sclerosis; oligodendroglial dysfunction.

Figure 1

Patient’s brain and spinal cord MRIs. 1.5 tesla brain and spinal cord MRI obtained before and after IV gadolinium injection. November 2006: axial fluid-attenuated inversion recovery (FLAIR) and t2 weighted sequences showed the presence of multiple demyelinating lesions located in the periventricular and hemispheric deep white matter (A) and cervical spinal cord (C), including one contrast enhancing lesion in the left fronto-parietal juxtacortical white matter (B). November 2011: FLAIR and t2 weighted sequences showed the presence of multiple demyelinating lesions within the periventricular and hemispheric deep white matter (D), left mesencephalic (E) and cervical spinal cord regions (F). February 2018: brain MRI FLAIR sequences showed the presence of multiple demyelinating lesions located in the periventricular and hemispheric deep white matter (G) and left mesencephalic region (H) (superimposable on previous MRI studies) without new contrast enhancing lesions. Cervical spinal cord t2 weighted sequences displayed the presence of multiple demyelinating lesions (unchanged with respect to the previous MRI study) together with cervical spondylosis with posterior osteophytosis without spinal cord and nerve roots compression (I).

Figure 2

Timeline of the patients history.