Contributed by Dianna Quan, MD1, B.K. Kleinschmidt-DeMasters, MD1, 2, 3
Departments of 1Neurology, 2Pathology, and 3Neurosurgery
University of Colorado Health Sciences Center, Denver, Colorado, U.S.A.
A 71-year-old man presented with slowly worsening numbness and weakness. Walking difficulties began when the patient was in his 30's. Over many years, he required progressively more assistance with ambulation, became wheelchair dependent, and finally bedridden. The diagnosis in life was unclear, but had over the years been variously considered to be Guillain-Barrč Syndrome (GBS), Friedreich's ataxia, or multiple sclerosis (MS).
GROSS AND MICROSCOPIC DESCRIPTIONS:
Autopsy examination was limited to the 1350 gram formalin-fixed brain, spinal cord, skeletal muscle, and a peripheral nerve segment submitted by the referring pathologist. Gross examination of cerebrum, brainstem, and cerebellum showed no meningeal opacification, hemorrhage, gyral atrophy, or infarction. On coronal sectioning, only inconspicuous, small, well-demarcated remote demyelinative plaques were identified in the cerebral and cerebellar white matter. With the exception of narrow bands of demyelination around the left occipital horn and a 5mm. periventricular plaque in the right parietal occipital lobe, the periventricular areas were devoid of plaques. Less than half a dozen very small, ovoid 2-4 mm. plaques were seen in toto at the cortical gray-white junctions of the bilateral temporal lobes and the right inferior parietal area. The largest plaque measured 11 mm. and was present in deep left occipital white matter. Cerebellum and brainstem were unaffected. Cranial nerves were not grossly enlarged.
The most striking gross findings were found in the spinal cord where a 1.8 cm long segment of mid-thoracic spinal cord was firm, atrophic, and discolored by plaque, without associated hydromyelia or syrinx cavity. Wedge shaped plaques typical for MS with the broad base on the pial surface of the cord could also be identified grossly in thoracic cord. Lumbar dorsal nerve roots were prominent. Fragments of submitted skeletal muscle and the 4.5 cm length peripheral nerve (not designated as to site) were grossly normal.
Microscopic examination demonstrated only rare perivascular mononuclear cells throughout cerebrum, cerebellum and brainstem. The few periventricular and cortical gray-white junction plaques that had been noted grossly were all identified as being remote areas of demyelination devoid of macrophage activity. Dorsal and ventral medulla showed bundles of Schwann cells surrounded by meningeal and parenchymal blood vessels (perivascular schwannosis) and rare mononuclear cells within cranial nerves. None of the cranial nerves showed onion bulb formation. The optic chiasm exhibited vague patches of myelin pallor on Luxol fast blue-periodic acid Schiff (LFB-PAS) stain for myelin.
In the 1.8 cm. segment of atrophic thoracic spinal cord, severe, near-total transverse demyelination was identified, with relative axonal preservation, intense chronic gliosis, and scattered axonal spheroids on H&E and Bielschowsky stains. No cavitation, vasculitis, vascular occlusions, or vasculitis was identified. Well-demarcated, wedge-shaped demyelinative lesions classic for multiple sclerosis were also observed in the cervical and thoracic cord (Figure 1A). Multiple dorsal sensory nerve roots of the lumbar cord were enlarged (Figure 1B) and showed reduced myelin content; increased numbers of Schwann cells separating individual nerve fibers (hypertrophic interstitial neuropathy) were easier to appreciate than full onion bulb formation at this level. Rare dorsal sensory spinal nerve roots at the cervical cord level also showed reduced myelin content and onion bulb formation, but were not enlarged (Figure 1C). The most intense lymphocytic inflammation was present focally in lumbar nerve roots (Figure 1D). Of interest, several small foci of apparent remyelination were found within the otherwise severely demyelinated areas of thoracic cord; these patches of myelin exhibited the darker blue color of peripheral myelin rather than the classic "robin's egg blue" of central myelin but did not extend to the surface of the cord (Figure 1E). Concentric whorling was difficult to appreciate in these CNS patches, but there was increased trichome and PAS staining in the patches, consistent with Schwann cell presence. Perivascular schwannosis was most prominent at the lumbar level and could be identified near the ventral fissure and the dorsal root entry zones (Figure 1F).
Peripheral nerve segments demonstrated moderately severe myelin and axonal loss but no ongoing myelin breakdown or vasculitis; scattered mononuclear cells were present. The most prominent onion bulb formation in the case was seen in peripheral nerve and best visualized by trichrome stain (Figure 1G). Onion bulbs showed strong immunostaining for S100 protein (Figure 1H) and negative immunostaining for CD34 (the opposite pattern to that seen in perineurioma). There was relatively better axonal preservation compared to the myelin loss. Skeletal muscle specimens revealed mild neurogenic atrophy but no primary myopathic changes.