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Neuropathology Laboratories
Laboratory 3
Neurodegenerative and spinal cord diseases

Case 3-1
NP014 (Bielschowsky) [WebScope] [ImageScope]
NP014A (Tau) [WebScope] [ImageScope]
NP014B (Aβ amyloid)
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A 46-year-old woman was first evaluated for progressive memory loss and difficulty with everyday activities at home and at her work. The patient had a master’s degree and was a professor teaching primarily computer software technology. Her disease progressed over the next 11 years to where she could no longer dress herself, feed herself, nor recognize her children. She required full nursing care. The autopsy was limited to the brain, which weighed 900 gm. The cerebral convolutions were narrow with widened sulci, mainly seen in frontal and temporal lobes.

Microscopically, the characteristic findings in Alzheimer’s disease, neurofibrillary tangles and neuritic plaques, are seen. Tangles are basophilic, silver-staining, filamentous material in the cytoplasm of neurons. Electron-microscopically, they are composed of a pair of 10 mm-thick filaments in double helicals [paired helical filaments (PHF)]. (These are different from two normal cells: microtubules and neurofilaments.) Cells containing the abnormal tangles are thought to undergo disintegration and leave behind the tangles free in the tissue. (Tau – NP014A) “Plaques” are composed of swollen (“dystrophic”) neurites, containing material seen in the tangle, and also a core of amyloid fibrils. (Aβ – NP014B) Aβ is also seen as accumulation in the vessel walls (amyloid angiopathy). One might also find granulovacuolar degeneration: small basophilic granules surrounded by a halo, found most often in the pyramidal cells of the hippocampus. Hirano bodies – short, eosinophilic, rod-like structures – may be seen within the cell or extracellularly.

Diagnosis: Alzheimer's disease

Questions to consider:

  1. Which regions of the brain are progressively involved by Alzheimer's disease?
  2. Are the major microscopic abnormalities (neuritic or senile plaques, neurofibrillary tangles, amyloid angiopathy) specific for Alzheimer's disease?

Case 3-2
NP015 (Luxol ) [WebScope] [ImageScope]
NP015A (α synuclein)
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A 74-year-old man was diagnosed with Parkinson’s disease at the age of 62. He was later placed on Sinemet, to which he responded well. Some 6 years later he is still skiing, playing golf, and squash. Approximately a year before his death, he noticed some cognitive changes: forgetting things, difficulty adding, and sleep disturbances. These changes progressed rather rapidly. He was also having hallucinations. He died about a year and a half later. At autopsy his brain weighed 1610 gm. His cerebral convolutions showed little to no atrophy, as did his hippocampus. His substantia nigra showed marked pallor.

Microscopically, the cortex shows minimal gliosis with occasional neuritic plaques. However, widespread Lewy bodies (α synuclein – NP015A) are seen in cingulate cortex, entorhinal cortex, amygdala, and hypothalamus. Midbrain showed moderate neuronal loss in substantia nigra with gliosis. Some remaining neurons contain Lewy bodies.

Diagnosis: Lewy body dementia

Question to consider:

  1. What is the relationship between Lewy body dementia and Parkinson's disease with dementia?

Case 3-3
NP016 (Luxol) [WebScope] [ImageScope]
NP016A (Bielschowsky) [WebScope] [ImageScope]
NP016B (PTAH)
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A 57-year-old woman was hospitalized for chronic undifferentiated schizophrenia 4 years before death. She was uncommunicative and became virtually unresponsive. She developed bedsores and needed constant nursing care and feeding. At autopsy, the brain showed knife-edge atrophy of the gyri of the frontal and temporal lobes, especially at the poles, with relative sparing of the superior temporal gyri.

Microscopically, there is loss of neurons and gliosis of the cortex in the atrophic regions. Some remaining neurons are much enlarged. Occasionally, there is a large round “body” (inclusion) with indistinct margin occupying much of the cytoplasm. These argentophilic inclusions (Pick bodies: Bielschowsky – NP016A) are well seen in the pyramidal neurons of the hippocampus and fascia dentata. Pick cells (PTAH – NP016B), or ballooned neurons – pale, large cells – are also seen, especially in the cortex. These are thought to be evidence of axonal change distally.

Diagnosis: Pick disease

Question to consider:

  1. What are the ultrastructural features of the Pick body?

Case 3-4
NP017 (Luxol)
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A 49-year-old woman had progressive dementia and involuntary movements for some years (unstated). She was completely incapacitated for another five years, during which she was in a hospital. There, she developed primary disseminated tuberculosis. This was unrecognized in life, but, in addition to pneumonia and the severe brain disease, was a cause of death. The brain was small at autopsy (875 grams) predominately owing to the significant loss of volume of the basal ganglia and thalamus. Atrophy of the cerebral convolutions was less striking but real.

Microscopically, there are virtually no neurons (except for the larger neurons) remaining in the caudate and putamen nuclei; hypertrophied fibrillary astrocytes and other interstitial cells are about all that remain. Compare this section with the normal caudate nucleus, Slide NP002N.

Diagnosis: Huntington's disease

Questions to consider:

  1. What are some of the clinical features of Huntington's disease?
  2. What is the functional significance of the loss of the medium spiny striatal neurons?

Case 3-5
NP018 (PTAH)
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A 71-year-old man had longstanding Parkinson’s disease, manifested by tremor and paucity of movement. The Parkinson’s disease was treated and he lived with his family. He had an attack of syncope the day before he died, and another similar attack just prior to death. He could not be revived. At autopsy, the substantia nigra and locus coeruleus were not as dark as normal.

Microscopically, there is some loss of pigmented neurons in the substantia nigra with hypertrophied small astrocytes. Some pigmented neurons contain round bodies about 8 or 10 μ in diameter (erythrocytes in this tissue are about 5 μ) in the cytoplasm. H. H. Lewy, after whom they are named, described them first in the substantia innominata, not substantia nigra. Electron-microscopically, they are composed of filaments more densely packed at the center of the body. Lewy bodies occur in other pigmented neurons, and, as Lewy showed, in some non-pigmented ones. They may be found in neurons in the brain stem, spinal cord, and sympathetic ganglia.

Diagnosis: Parkinson's disease

Questions to consider:

  1. What are the ultrastructural features of Lewy bodies?
  2. How do the clinical features of Parkinson's disease relate to the loss of pigmented catecholaminergic neurons in the substantia nigra and locus ceruleus?

Case 3-6
NP019 (Luxol ) [WebScope] [ImageScope]
NP019A (H&E)
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A 39-year-old woman developed progressive mental deterioration a year and a half before death. She showed jerking movements of the extremities and some choreioform movements. She became bedridden, unresponsive, and incontinent followed by death. Her sister had died of the same disease 12 years earlier.

Microscopically, the characteristic findings consist of widespread microcystic appearance of gray matter in the neuropil between the cell bodies (status spongiosis), neuronal loss, and gliosis, often very marked. There is no inflammatory cellular response.

Diagnosis: Creutzfeldt-Jakob disease - Prion disease

Questions to consider:

  1. What distinguishes Creutzfeldt-Jakob disease, chronic wasting disease of deer and elk, and bovine spongiform encephalopathy from other neurodegenerative and infectious diseases?
  2. How is a definitive diagnosis of CJD made?

Case #3-7
NP020 (Luxol)
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A 33-year-old man had symptoms of amyotrophic lateral sclerosis for 4 years before death, beginning as weakness in one arm which then extended to the other limbs and progressed in severity. For some months before death, he was unable to talk. He had difficulty swallowing, using his tongue, and moving his eyes. There were fasciculations of muscles of the lower face, neck, and upper extremities. Oral pharyngeal secretions accumulated and he died. The ventral nerve roots of the spinal cord and the hypoglossal nerve roots were grossly atrophic, looking as thin as threads.

Microscopically, The spinal cord shows some loss of fibers in the lateral columns. There is loss of nerve cells and gliosis of the anterior horns, and corresponding loss of fibers from the anterior roots. It is hard to assess whether anterior horn cells are diminished in number, but there is usually no mistaking loss of anterior root fibers.

Diagnosis: Amyotrophic lateral sclerosis (ALS)

Questions to consider:

  1. What happens to muscle cells affected by neurogenic atrophy? (Robbins and Cotran, p. 1286)

Case 3-8
NP021 (Luxol)
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A 27-year-old man had weakness of the right arm, hoarseness, and diplopia for about 5 months before his first hospitalization. He was found to have two diseases, perhaps representing a single syndrome: syringomyelia (a tubular cavity in the spinal cord) and familial acro-osteolysis (a dissolution of some bony extremities). Deterioration of the base of his skull and upper spine let his skull sink downward onto his spine, compressing his brain stem. Both the brain stem compression and fluid pressure within the syrinx were temporarily relieved surgically, giving him some comfort, but he ultimately succumbed to pneumonia.

The syrinx cavity extended most of the length of the spinal cord and partially into the ventral medulla (“syringobulbia”). Syringomyelia seems to be a disorder originating in embryonic life, although other mechanisms have been suggested. The syrinx appears to be independent of the central spinal cord canal in most levels in this case, but occasionally encroaches upon it. The original central canal is normal and present in its usual place as a cluster of ependymal cells, although the cord in cross section is distorted by the syrinx. Cavities of syringomyelia are often quite eccentric, pressing on and damaging different parts of the cord. Syringobulbia, appearing as dorsolateral slits in the medulla, occurs frequently with syringomyelia. Rarely, the dorsal pons and midbrain are also affected.

Diagnosis: Syringomyelia

Questions to consider:

  1. What is a syrinx?
  2. What are the clinical signs and symptoms of a syrinx?

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Questions or comments? Dr. Killen: pkillen@umich.edu

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