Hereditary Adult‐Onset Alexander Disease

1University of Minnesota, Minneapolis, MN

Meeting: Hospital Medicine 2011, May 10-13, Dallas, Texas.

Abstract number: 238

Case Presentation:

A 47‐year‐old white man with a history of alcohol abuse was transferred to our hospital with loss of consciousness and subsequently intubated en route for airway protection. His medical history was unremarkable. On initial presentation, the patient was sedated and comfortable on mechanical ventilation. Vital signs were normal. Physical exam, off sedation, was notable for bilateral conjugate gaze, intact corneal reflexes, minimal movements in extremities but not against gravity, deep tendon reflexes 21 in both upper and lower extremities, and bilateral positive Babinski's sign. Workup including a complete blood count, complete metabolic panel, drug screen, chest x‐ray, pan‐culture, echocardiography, and CT head/cervical spine were nonrevealing, except for elevated alcohol level on admission. MRI of the brain stem revealed severe generalized cerebral atrophy extending caudally to the proximal cervical spinal cord on T2 and T2 FLAIR images. Cerebrospinal fluid analysis included protein electrophoresis, acid‐fast bacilli smear, and culture, Herpes, West Nile virus, toxoplasmosis, syphilis, and Lyme titers were unremarkable. Electroencephalography showed no epileptiform activity. On further investigation, family history was notable for the presence of Alexander disease (AD). A pedigree of his family showed 10 of 20 family members were affected. The diagnosis of AD had been confirmed on autopsy in family members, and typical MRI findings were described in the affected family members. Based on the MRI and an inheritance pattern in the family, the diagnosis of adult‐onset Alexander disease was made, and likely progression of the disease was attributed to his chronic excessive alcohol intake. The patient remained ventilator dependent and subsequently underwent tracheostomy.

Discussion:

Adult‐onset Alexander disease (AOAD) is a subtype of Alexander disease, a rare and often fatal leuko‐dystrophy, characterized pathologically by the accumulation of eosinophilic inclusions in astrocyte cytoplasm (Rosenthal fibers), resulting from nonconservative mutations of chromosome 17q21, which encodes GFAP. It has an autosomal dominant mode of inheritance. Near 450 cases have been reported worldwide since Alexander's initial description in 1949. AOAD has variable features, including bulbar and pseudobulbar signs, spasticity, quadriparesis, and dysautonomia. Atrophy of the medulla and upper cervical spinal cord on MRI is a characteristic finding. Because of the rarity of the disease and the lack of controlled clinical trials, there are no clear recommendations about the diagnosis and treatment of AOAD. Its diagnosis does not require genetic testing and can be established based on clinical and MRI features.

Conclusions:

The purpose of reporting this case is to increase the general awareness of this rare condition and to provide an up‐to‐date literature review.

Disclosures:

N. Beliveau ‐ none

To cite this abstract:

Beliveau N. Hereditary Adult‐Onset Alexander Disease. Abstract published at Hospital Medicine 2011, May 10-13, Dallas, Texas. Abstract 238. Journal of Hospital Medicine. 2011; 6 (suppl 2). https://www.shmabstracts.com/abstract/hereditary-adultonset-alexander-disease/. Accessed September 18, 2019.

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