Abstract Details

Title Adult-onset Genetic Leukodystrophies Misdiagnosed as Multiple Sclerosis in Clinical Practice

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 052

Objective To describe the clinical and imaging features of patients with genetic leukodystrophies (gLD) initially misdiagnosed with multiple sclerosis (MS).

Background Misdiagnosis of MS remains relatively common. Adult-onset gLD are rare, difficult to diagnose, and can be overlooked in the diagnostic evaluation of potential MS mimics.

Design/Methods We identified patients referred to a single MS centerbetween 1/1/2000-8/1/2019 for white matter abnormalities (WMAs) on brain MRI, who initially had a suspected or established MS diagnosis, but ultimately had a confirmed diagnosis of gLD. Demographics, disease history, and laboratory and MRI data were retrospectively collected by chart review.

Results Nineteen patients were included: 13(68%) female, 17(89%) Caucasian, mean age at symptom onset: 40.3 (SD 12.2) years. The most common presenting symptoms were spastic paraplegia 7(37%) and headache 3(16%). Ultimately, 15(79%) developed spastic paraplegia, 12(63%) sensory, 9(47%) cognitive, 8(42%) urinary, and 7(37%) visual symptoms. Extra-neurological symptoms were present in 4(21%). gLD diagnoses included: Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy 4(21%), Hereditary Spastic Paraplegia 5(26%), Hereditary Diffuse Leukoencephalopathy with Spheroids 2(11%), Mitochondrial Encephalopathy Lactic Acidosis and Stroke-like Episodes 2(11%), and Autosomal Dominant Leukodystrophy with Autonomic Disease, Adult Onset Alexander Disease, Adult Polyglucosan Body Disease, Fragile X-associated Tremor/Ataxia Syndrome, Retinal Vasculopathy with Cerebral Leukoencephalopathy, and X-linked Adrenoleukodystrophy 1(5%) each. Genetic diagnoses were confirmed in all cases by single-gene analysis, gene panel, or whole genome sequencing. WMAs fulfilled the 2017 McDonald Criteria for dissemination in space in 7(37%) patients but were described as atypical in all but one case. Oligoclonal bands (OCBs) were present in 2(11%). Primary progressive MS was suspected in 13(68 %), and relapsing-remitting MS in 4(21%). 10(53%) were treated with steroids and 4(21%) were started on disease-modifying therapy.

Conclusions

Adult-onset gLD should be part of the differential diagnosis of MS and suspected in patients with progressive neurological symptoms, negative OCBs, and atypical WMAs.

Authors/Disclosures
Alise K. Carlson, MD (Cleveland Clinic) PRESENTER	Dr. Carlson has received research support from Biogen (fellowship grant 16696-P-FEL).
	No disclosure on file
Jeffrey A. Cohen, MD (Cleveland Clinic)	Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria. Dr. Cohen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSI. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celltrion.
Gabrielle Macaron, MD	Dr. Macaron has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD-Serono. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MedEdge. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Macaron has received research support from National MS Society/International Progressive Multiple Sclerosis Alliance .

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