A 34-year-old woman comes to the office due to a 2-day history of reduced sensation in her legs. Lately, the patient has also had significant fatigue, especially with exercise. Six months ago, she had an episode of visual blurring that resolved spontaneously after a few days. Medical history is significant for psoriasis, for which she uses a topical glucocorticoid ointment. The patient does not use tobacco or illicit drugs. Vital signs are normal. Examination indicates decreased pain and light touch perception in both legs below the level of the umbilicus. Mild bilateral spasticity is noted. Which of the following pathologic brain lesions is most specific for this patient's disease process?
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Reduced sensation and spasticity in the lower extremities suggest a lesion in the spinal cord. This, in conjunction with this patient's prior episode of blurred vision and her severe fatigue with exercise (Uhthoff's phenomenon), makes multiple sclerosis (MS) a likely diagnosis. MS is an immune-mediated disorder of the central nervous system (CNS), characterized by focal lesions of demyelination. Patients have various neurologic deficits that wax and wane (symptoms are disseminated across time and space).
Histologically, active MS plaques are characterized by perivenular inflammatory infiltrates made up primarily of autoreactive T lymphocytes and macrophages directed against myelin components. Extensive inflammation damages the blood-brain barrier, increasing inflammatory cell recruitment into the CNS (with the vessel wall remaining intact, unlike in CNS vasculitis). Infiltrating macrophages containing myelin debris are seen throughout the lesion, and recruitment of B lymphocytes to the perivascular spaces leads to the formation of myelin-specific antibodies. Patchy demyelination occurs, and while axons are typically spared, significant or prolonged disease may result in neuron death. Residual chronic findings include hypertrophy and hyperplasia of astrocytes (glial scarring).
(Choice A) Microglial nodules are nonspecific findings that can be seen in patients with MS, as well as in those with HIV encephalopathy and other viral infections. They are thought to be reactive lesions that occur in the setting of inflammation, rather than a specific pathologic finding.
(Choice B) Neuritic plaques and neurofibrillary tangles (tau protein) are characteristic findings in Alzheimer disease, which presents with memory impairment, not focal neurologic deficits, and is rare in young patients.
(Choice D) Spongiform encephalopathy is seen in prion diseases (eg, bovine spongiform encephalopathy, Creutzfeldt-Jakob disease). Patients present with rapid-onset dementia, myoclonus, and ataxia. Episodic or waxing and waning symptoms are more consistent with MS.
(Choice E) Negri bodies are viral inclusions in the cytoplasm of nerve cells in patients with rabies. Rabies occurs after a bite from an infected animal and presents with tingling or irritation at the inoculation site followed by hydrophobia, delirium, coma, and death. This disease is typically fatal within days of symptom presentation and would not be expected to cause focal abnormalities over a period of months.
Educational objective:
Multiple sclerosis is an immune-mediated disorder of the central nervous system characterized by focal demyelination (plaques). Histologically, plaques contain foci of perivenular inflammatory infiltrates made up primarily of autoreactive T lymphocytes and macrophages. Patchy demyelination occurs followed by astrocyte hyperplasia (glial scarring).