To elucidate a complex case of a young woman with weakness associated to atrophy in medulla and upper cervical cord.

Alexander disease results from an autosomal dominant toxic gain in function mutation in the glial fibrillary acidic protein gene. The adult-onset form of Alexander disease presents with bulbar signs, spastic paraplegia, ataxia, and other neurologic features. Very few cases of adult onset Alexander Disease have been described at Puerto Rico with positive GFAP mutation, characteristic imaging, and a lumbar puncture with CSF-specific oligoclonal bands without pleocytosis.

A 47 y/o woman started seven years prior with upper extremities paresthesias, gradually developing gait problems. A diagnosis of multiple sclerosis was done receiving treatment with various disease modifying therapies. Two days prior to hospitalization she developed a rapidly progressive worsening of weakness in the upper and lower limbs, dysphagia and complete inability to ambulate.

Physical examination demonstrated respiratory compromise requiring mechanical ventilation, quadriplegia, bilateral horizontal and vertical nystagmus with an oscillatory component on vertical eye movement, hyperreflexia and right foot sustained clonus.

MRI showed abnormal signal intensity involving portions of the paramedian thalami, hypothalamus, midbrain, pons, medulla, and central cervical cord. Significant atrophy of the medulla with some decrease in caliber of the cervical cord was noted down to the C6 level.

Laboratory results were negative for Lyme antibodies, HIV, RPR, HTLV I and II, dsDNA, ACE levels, Aquaporin-4 antibodies and Anti-Scleroderma 70. Lumbar puncture showed CSF-specific oligoclonal bands without pleocytosis. Due to the unusual progression and the imaging pattern subsequent genetic analysis of the GFAP gene was requested revealing a missense mutation in homozygous state (c.265T>C; p.Phe89Leu). 

The patient was diagnosed with adult-onset Alexander disease. This case stresses the importance of considering additional, though less common, potential etiologies in adult patients with a progressive demyelinating disease.