Download Neuro Oncology: Neuroradiology

Wolfram Syndrome: Classic Imaging
Findings of an Uncommon Disease
Eric Carolan, MD
Jonathan M Morris, MD
Control #1520
Poster EE-12
Relevant Disclosures
• None
Clinical Presentation
• 33 year-old female admitted with altered mental
status in the setting of recurrent aspiration
pneumonia.
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.
Imaging Findings
• Head CT without contrast was obtained for
altered mental status
Imaging Findings (please scroll)
Imaging Findings
• Key imaging findings
include:
• Marked atrophy of
the pons
• Atrophy of the
cerebellum and
middle cerebellar
peduncles.
Imaging Findings
• Pertinent negatives
include:
• Minimal cerebral
atrophy
• Minimal atrophy of the
superior cerebellar
peduncles
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.
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.
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 years2.
• Inheritance pattern is autosomal recessive,
associated with the WFS1 gene.
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 nerves3.
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
hemispheres4.
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.
Discussion
• Age of onset can help distinguish from MSA
from Wolfram, as MSA usually occurs after the
fifth decade3.
• 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 Wolfram3.
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.
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
• 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, 189191