Brain Pathology Case of the Month - July 2008

Contributed by Michelle A. Stevens1, DO, Gabrielle A. Yeaney 2, MD and David Lacomis1,2, MD
1Department of Neurology, 2Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA


A 42-year-old man presented with three months of progressive proximal weakness, a thirty pound weight loss, and worsening dysphagia for solids. He had been hospitalized two months earlier for respiratory failure requiring intubation and five days of mechanical ventilation. Arterial blood gas on admission revealed a pH of 7.26; pCO2 58.8 torr; bicarbonate 26.2; and pO2 of 57.1 torr. A primary pulmonary etiology was not found, and he improved. During that hospitalization, an electromyogram of the upper extremities was normal. There were chronic neurogenic changes in the lower extremities. Low amplitude, short duration motor unit potentials suggestive of myopathy were noted in the cervical and thoracic paraspinal muscles.

His past medical history was significant for chronic low back pain, multiple lumbar surgeries, hypertension, glaucoma, and discoid lupus. He had been maintained on hydroxychloroquine 1000 mg/day for 15-20 years for discoid lupus. Neurologic examination revealed Medical Research Council grade 4/ 5 strength in neck flexor and proximal upper and lower extremity muscles. Distal muscles were strong. Tendon reflexes were diminished. There was mild distal loss of sensation from the toes to the ankles bilaterally. He was unable to rise from a chair without using his hands. Laboratory studies, including complete blood count, erythrocyte sedimentation rate, thyroid functions, and electrolytes were normal. Total creatine kinase was elevated at 509 IU/L (normal < 200). A repeat limited electromyogram immediately prior to deltoid needle muscle biopsy revealed mild fibrillation potential and positive wave activity along with short duration motor unit potentials in a proximal arm muscle.


Hematoxylin and eosin stained frozen sections of the left deltoid muscle revealed an abnormal variation in myofiber size with a mild increase in internalized nuclei. Rare degenerating and occasional regenerating fibers were noted. Inflammatory infiltrates were not seen. Most fibers showed multiple vacuoles containing granular amphophilic material (Figures 1, 2; size marker in figures 1-8 equals 40 microns). With the Gomori trichrome stain, purplish material was highlighted within the vacuoles and in the sarcoplasm (Figure 3). Oil red-O demonstrated lipid in some of vacuoles. The material in the vacuoles was strongly reactive for acid phosphatase (Figures 4, 5) and esterase (Figure 6). NADH- tetrazolium reductase reacted sections revealed a few small hyperreactive fibers and targetoid fibers. PAS stained sections contained no abnormal accumulations of glycogen. Examination of thioflavin-T and Congo red stains under fluorescence revealed no abnormal accumulations. ATPase reacted sections revealed loss of normal checkerboard pattern, mild myofiber atrophy of both type 1 and 2 fibers and vacuoles in both type 1 and 2 fibers (Figure 7; pH 9.4). Paraffin sections showed strong nonspecific immunoreactivity for ubiquitin in many vacuoles (Figure 8). Electron microscopy revealed curvilinear inclusions in vacuoles (Figures 9, 10) and myeloid bodies with lysosomal degradation products within membrane bound vacuoles (Figures 11, 12).


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