1. Wolfram Syndrome: Classic Imaging Findings of an Uncommon Disease Eric Carolan, MD Jonathan M Morris, MD Control #1520 Poster EE-12

2. Relevant Disclosures None

3. Clinical Presentation 33 year-old female admitted with altered mental status in the setting of recurrent aspiration pneumonia.

4. Clinical Presentation Past Medical History Includes: Optic Nerve atrophy at age 5. Type I Diabetes Mellitus at age 8 Seizures at age 10. Urinary Incontinence at age 14. Ataxia and cognitive difficulties at age 30. Swallowing difficulties at age 30.

5. Imaging Findings Head CT without contrast was obtained for altered mental status

6. Imaging Findings (please scroll)

7. Imaging Findings Key imaging findings include: Marked atrophy of the pons Atrophy of the cerebellum and middle cerebellar peduncles.

8. Imaging Findings Pertinent negatives include: Minimal cerebral atrophy Minimal atrophy of the superior cerebellar peduncles

9. Wolfram Syndrome Originally described by Wolfram and Wagener in 1938 after following four siblings with early onset bilateral optic nerve atrophy and diabetes mellitus. Characterized by Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness These clinical features give rise to the alternate name, DIDMOAD.

10. Wolfram Syndrome Originally described by Wolfram and Wagener in 1938 after following four siblings with early onset bilateral optic nerve atrophy and diabetes mellitus. Characterized by Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness These clinical features give rise to the alternate name, DIDMOAD.

11. Wolfram Syndrome While the classic symptoms of optic nerve atrophy and diabetes mellitus can be seen early in life, diabetes insipidus, neurologic dysfunction, and sensorineural deafness can be seen in the teenage years 2. Inheritance pattern is autosomal recessive, associated with the WFS1 gene.

12. Wolfram Syndrome Although reports in the literature are rare, neuroimaging findings include atrophy of the brain stem, cerebellum, and middle cerebellar peduncles. Ito et al describe a case of Wolfram Syndrome demonstrating moderate atrophy of the brain stem and middle cerebellar peduncle with mild atrophy of the cerebellum, as well as atrophy of the infraorbital and intracranial optic nerves 3.

13. Wolfram Syndrome Although reports in the literature are rare, neuroimaging findings include atrophy of the brain stem, cerebellum, and middle cerebellar peduncles. Pakdemirli et al also describe a case with marked atrophy of brainstem and cerebellar vermis with atrophy of the optic nerves and moderate atrophy of the cerebral hemispheres 4.

14. Discussion While Wolfram Syndrome can have a similar appearance to other brain stem atrophic conditions such as Spinocerebellar Ataxia, Multiple System Atrophy, and Dentatorubral Pallidoluysian Atrophy, a few factors can be used to differentiate.

15. Discussion Age of onset can help distinguish from MSA from Wolfram, as MSA usually occurs after the fifth decade 3. Wolfram, Dentatorubral Pallidoluysian Atrophy, and Spinocerebellar Ataxia all demonstrate pontocerebellar atrophy. However, SCA and DRPLA will demonstrate atrophy of the superior cerebellar peduncles, which is not described in Wolfram 3.

16. Conclusion Wolfram syndrome is a rare autosomal recessive disorder with classic clinical findings and characteristic imaging findings including pontocerebellar atrophy and atrophy of the middle cerebellar peduncle with relative sparing of the cerebral hemispheres. Neuroradiologists should be aware of this condition when considering the differential of brain stem atrophic conditions.

17. Referrences 1. Wolfram DJ, Wagener HP. Diabetes mellitus and simple optic atrophy among siblings: report of four cases. Mayo Clin Proc 1938;9:715–18 2. Barrett T, Bundey S, Macleod A. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome Lancet 346(8988) 1458–1463 346(8988 3. Ito S, Sakakibara R, Hattori T. Wolfram Syndrome Presenting Marked Brain MR Imaging Abnormalities with Few Neurologic Abnormalities AJNR Am J Neuradiol 28:305– 06 Feb 2007 4. Pakdemirli E Karabulut N. Cranial Magnetic Resonance Imaging of Wolfram (DIDMOAD) Syndrome Australas Radiol 2005 49, 189- 191