Chapter 7, pp. 139-160

Ch 21, Peripheral Nerves, pp. 797-801
Ch 22, Central Nervous System, pp. 811-822; 824-830; 832-848

Click here for a review of the histology of the nervous system

UMich NP001 [DigitalScope]

This specimen is from a 70-year-old, right-handed woman who suffered from thromoboembolic occlusion of the left middle cerebral artery.

The affected hemisphere was pinker than normal and swollen at autopsy. The nervous tissue is undergoing necrosis: neurons show poor staining and often appear to be disintegrating. Similar to recently dead liver or myocardial cells, the cytoplasm of the neurons becomes eosinophilic and the nuclei disintegrate (karyorrhexis) (example). Neutrophils are emigrating from the capillaries and postcapillary venules (example) into the margins of the necrotic tissue and minute hemorrhages are sometimes present. Macrophages are not evident and there is not much astrocytic response. The neutrophils have exuded into the subarachnoid region, but there is little or no fibrin and no mononuclear cells accompanying the neutrophils as would occur in an infectious meningitis.

Questions to consider:

UMich NP001-1. How long ago did this stroke happen?

UMich NP001-2. What kind of deficits would you expect this patient to have had if she had survived?

UMich NP002 [DigitalScope]

A 71-year-old man had a cerebral vascular accident (CVA) involving a part of the right hemisphere in the domain of the middle cerebral artery.

The section of cortex and white matter contains myelinated fibers that have disintegrated to varying degrees. Phagocytes are engulfing fragments of these dead but still stained fibers (example). Capillaries and small vessels show adventitial connective tissue and endothelial cells that have proliferated. The dead cortex contains phagocytes and reactive vessels. Some parts of the white matter show phagocytes (some engulfing blue myelinated fiber fragments), and enlarged astrocytes with pink cytoplasm, side by side (example). By the third week, astrocytes begin the process of responding to ischemic and other injuries by hypertrophying, growing large fibers, and sometimes multiplying. This process, when it is fully developed, is termed gliosis.

Questions to consider:

UMich NP002-1. How long ago did this stroke happen?

UMich NP002-2. What kind of deficits would you expect this patient to have had if he had survived?

UMich NP003, Luxol stain [DigitalScope]

UMich NP004, PTAH stain [DigitalScope]


This specimen is from an individual that suffered from thromboembolic occlusion of the left and right anterior cerebral arterys.

There are regions of nearly complete destruction with amorphous residual dead brain tissue in which a loose mesh of vessels remains. Many of these vessels are no more than connective tissue strands, but some are patent functioning vessels. Contrast them with those of the infarction shown in the specimen above (Section UMich NP002). Phagocytes are mostly inactive. Within the cortical surface and the regions around the nearly completely destroyed zone, where some blood supply was retained, there are hypertrophied astrocytes. They have prominent fibers and the cells themselves have increased in numbers. These cells are shown best as dark purple in the PTAH (Section UMich NP004) stained section (example), but can also be seen well as pink with the Luxol stain (Section UMich NP003) (example).

Almost any process that destroys brain tissue sets in motion the same basic progression of morphologic changes that the infarct demonstrates: first, morphologic evidence of necrosis of the killed tissue elements, sometimes with neutrophils and hemorrhages in the initial stage; second, macrophage phagocytes and vascular proliferative activity; lastly, a cavity with surrounding gliosis in a zone of tissue that wasn’t completely destroyed.

Almost any process that destroys brain tissue sets in motion the same basic progression of morphologic changes that the infarct demonstrates: first, morphologic evidence of necrosis of the killed tissue elements, sometimes with neutrophils and hemorrhages in the initial stage; second, macrophage phagocytes and vascular proliferative activity; lastly, a cavity with surrounding gliosis in a zone of tissue that wasn’t completely destroyed.

There are swollen neurons in the partly damaged zone at the margin of the infarct. These are known as “chromatolytic neurons” (example). These neurons show an “axonal reaction” because their axons were essentially cut off some distance away in the actual infarct. Such cells may die, or remain chromatolytic for a long time, or they may slowly restored to normal appearance as they regenerate their axons. In such circumstances, the axons commonly go to the wrong places and make the wrong synapses. Abnormal electrical activity and clinical seizures may be the clinical manifestations of these abnormal connections.

Questions to consider:

UMich NP003-NP004-1. How long ago did this stroke happen?

UMich NP003-NP004-2. What kind of deficits would you expect this patient to have had in the period preceding his death?

DUKE CASE NUMBER 370 [DigitalScope]

Clinical History: The patient was a 87-year-old white female in an assisted care facility who was eating breakfast when she complained of a headache and became disoriented and confused shortly thereafter. She had a wide, ataxic gait and she exhibited loss of coordinated movement on the left side of the body along with hoarseness and difficuly swallowing. She had vertigo (sensation of the room spinning) and a leftward-beating nystagmus (eyes drifting slowly to her right and then quickly darting back to her left). Her left eyelid drooped (ptosis) and her left pupil was constricted (miosis). A sensory exam showed loss of pain sensation on the right side of her body (limbs and trunk) and the left side of her face. As a result of the nausea caused by the severe diziness, she vomited several times leading to an aspiration pneumonia which caused her death soon thereafter.

Image Gallery:

Questions to consider:

370-1. How long ago did this stroke happen? Which vessel was most likely occluded?

370-2. Why did this patient have a wide, ataxic gait and loss of coordinated movement?

370-3. Why did this patient have nystagmus and vertigo?

370-4. Why did this patient have the loss of pain and temperature sensation on the RIGHT side of her body but the LEFT side of her face?

370-5. Why did this patient have hoarseness and difficulty swallowing?

370-5. Why did this patient have left ptosis and miosis?

UMich NP006, H&E [DigitalScope]
UMich NP006A, GFAP stain (brown) [DigitalScope]

A 38-year-old man came to the hospital because his family said he was behaving peculiarly and had frequent seizures. Examination showed hemiparesis, a visual field defect, and mild papilledema. An arteriogram showed a large temporal lobe tumor, and it was partly removed surgically. He survived for several months, the course of his disease from the clinical onset being about 5 months.

The tumor showed homogenous tissue resembling gray matter in some places, regions of necrosis and hemorrhage in others, and still other regions that were firm, fibrous, and vascular. The tumor is truly multiform microscopically, with certain characteristics to look for. That it is a glioma is shown by parts of the tumor being composed of astrocytes (as shown in the H&E and immunohistochemically by GFAP – glial fibrillary acidic protein) of many sizes and shapes. Mitotic figures, often bizarre and polypoid, are common. Elongate and polygonal cells, sometimes differentiating as fibrillary astrocytes, form palisades at the margins of zones of necrosis. Vascular endothelial and adventitial connective tissue proliferation is extensive, making up a large proportion of the tumor

Questions to consider:

UMich NP006-1. The BEST diagnosis is:

1. Ependymoblastoma
2. Medulloblastoma
3. Glioblastoma
4. Astrocytoma

UMich NP006-2. The MOST LIKELY cell of origin of this neoplasm is:

1. Astrocyte
2. Oligodendrocyte
3. Ependymal cell
4. Microglial cell
5. Neuron

UMich NP006-3. From first symptom to death, the average untreated patient with this neoplasm lives:

1. 2 months
2. 6 - 12 months
3. 3 years
4. 5 years

UMich NP008 [DigitalScope]

A 50-year-old man had frontal headaches, weakness of the left hand, and difficulty remembering for about 9 months before he came to the hospital. Examination revealed right papilledema in addition to the other abnormalities. Carotid angiography showed a vascular tumor on the right sphenoid ridge. Although the tumor adhered to the right middle cerebral artery, it was surgically removed and the patient recovered. Six years after operation he reported himself in good health, active, and working. No further follow-up is available.

Microscopically, the tumor is composed of polygonal cells arranged in sheets and whorls of well-differentiated arachnoid cells. In the center of a few whorls the cells have degenerated, or died, and have formed or begun to form concentric rings of solid material – psammoma bodies (psammos = sand) (example). Miotic figures in meningiomas are usually rare, but this one shows a few.

Questions to consider:

UMich NP008-1. How would you classify this particular neoplasm (i.e. glioblastoma, oligodendroma, meningioma, etc.)?

UMich NP008-2. What is the presumed cell of origin of this type of neoplasm?

UMich NP008-3. What are some common sites of involvement by this type of neoplasm?

UMich NP008-4. What is the general prognosis for a patient with this type of neoplasm?

UMich NP012 [DigitalScope]

A 19-year-old student complains of chills, headache, nausea, and vomiting. Over the next day, the patient became confused and semicomatose. Physical examination revealed neck rigidity and a petechial skin rash. Although a diagnosis was promptly made, the patient succumbed to his illness.

Microscopically, there are a large number of inflammatory cells (predominantly neutrophils) in the leptomeninges. The brain itself is relatively spared by the inflammation. There is a mild degree of edema and a few of the blood vessels near the leptomeninges show minimal inflammation.

Questions to consider:

UMich NP012-1. What is the diagnosis?

UMich NP012-2. Given the age of the patient, what was the likely causative agent? What if the patient was a neonate? What if the patient were elderly?

UMich NP012-3. Which CSF abnormalities are usually found in patients with this particular condition?

UMich NP014, Bielschowsky silver stain [DigitalScope]
UMich NP0014A, Tau immunostain [DigitalScope]
UMich NP0014B, Aß immunostain [DigitalScope]

A 36-year-old woman was first evaluated for progressive memory loss and difficulty with everyday activities at home and at her work. Her disease progressed over the next 9 years to where she could no longer dress herself, nor feed herself. She required full nursing care.

At autopsy, the brain weighed 900 gm. The cerebral convolutions were narrow with widened sulci, mainly seen in frontal and temporal lobes. Other findings of interest included atrioventricular valve defects, outflow tract defects, simian palmar creases, and epicanthal folds.

Microscopically, neurofibrillary tangles and neuritic plaques are seen in the histological specimens (example --seen here in the hippocampus). The "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. Cells containing the abnormal tangles are thought to undergo disintegration and leave behind the tangles free in the tissue. (best seen in the Tau stain – UMich NP014A) (example)

The “plaques” are composed of swollen (“dystrophic”) neurites, containing material seen in the tangle, and also a core of amyloid fibrils. (best seen in the Aß stain – UMich NP014B) (example).

Questions to consider:

UMich NP014-1. What is the neurological disorder?

UMich NP014-2. The additional findings suggest congenital abnormalities as well. What is the most likely cause of these?

UMich NP014-3. Is the congenital abnormality at all related to the neurological disorder? If so, how?

UMich NP017 [DigitalScope]

A 49-year-old woman had progressive dementia and a movement disorder 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 was – along with pneumonia and the severe brain disease – a cause of death.

The brain was small at autopsy – 875 grams – owing very much to the great 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) left in the caudate (example) and putamen (example); hypertrophied fibrillary astrocytes and other interstitial cells are about all that remain.

Questions to consider:

UMich NP017-1. What is the diagnosis?

UMich NP017-2. The history states the presence of a 'movement disorder.' Would you expect the disorder to be HYPOkinetic or HYPERkinetic in nature?

UMich NP017-3. What is the cause of this disorder? Is it heritable? If so, is it recessive or dominant?

UMich NP018 [DigitalScope]

A 71-year-old man had a longstanding movement disorder that was being pretty well managed medically and he lived with his family. He had an attack of syncope the day before he died, and another similar attack in which he fell and hit his head leading to his death.

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 (example) with hypertrophied small astrocytes. Some pigmented neurons contain round bodies about 8 or 10 µm in diameter (erythrocytes in this tissue are about 5 µm) in the cytoplasm (example). Electron-microscopically, these bodies are composed of filaments more densely packed at the center of the body.

Questions to consider:

UMich NP018-1. What is the diagnosis?

UMich NP018-2. The history states the presence of a 'movement disorder.' Would you expect the disorder to be HYPOkinetic or HYPERkinetic in nature?

UMich NP018-3. What were some of the therapies that were likely being used to manage his disease?

UMich NP020 [DigitalScope]

A 33-year-old man had symptoms of progressive weakness 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.

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.

Questions to consider:

UMich NP020-1. What is the diagnosis?

UMich NP020-2. Would you expect to see any abnormalities in the cerebral cortex? If so, where (i.e. sensory cortex, motor cortex, visual cortex, etc.)?

UMich NP020-2. Would you expect to see HYPOreflexive signs or HYPERreflexive signs? (Or, maybe a little bit of both?)