Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com
Cyberfriends: The help you're looking for is probably here.
Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected.
DoctorGeorge.com is a larger, full-time service.
There is also a fee site at
www.afraidtoask.com.
|
|
 If you have a Second Life account, please visit my teammates and me at the Medical Examiner's office. |
|
 |
With one of four large boxes of "Pathguy" replies. |
I'm still doing my best to answer
everybody.
Sometimes I get backlogged,
sometimes my E-mail crashes, and sometimes my
literature search software crashes. If you've not heard
from me in a week, post me again. I send my most
challenging questions to the medical student pathology
interest group, minus the name, but with your E-mail
where you can receive a reply.
Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource. Someday you may be able to access these pictures directly from this page.
Also:
KCUMB Pathology Club
Freely have you received, freely give. -- Matthew 10:8. My
site receives an enormous amount of traffic, and I'm
handling about 200 requests for information weekly, all
as a public service.
Pathology's modern founder,
Rudolf
Virchow M.D., left a legacy
of realism and social conscience for the discipline. I am
a mainstream Christian, a man of science, and a proponent of
common sense and common kindness. I am an outspoken enemy
of all the make-believe and bunk that interfere with
peoples' health, reasonable freedom, and happiness. I
talk and write straight, and without apology.
Throughout these notes, I am speaking only
for myself, and not for any employer, organization,
or associate.
Special thanks to my friend and colleague,
Charles Wheeler M.D.,
pathologist and former Kansas City mayor. Thanks also
to the real Patch
Adams M.D., who wrote me encouragement when we were both
beginning our unusual medical careers.
If you're a private individual who's
enjoyed this site, and want to say, "Thank you, Ed!", then
what I'd like best is a contribution to the Episcopalian home for
abandoned, neglected, and abused kids in Nevada:
My home page
Especially if you're looking for
information on a disease with a name
that you know, here are a couple of
great places for you to go right now
and use Medline, which will
allow you to find every relevant
current scientific publication.
You owe it to yourself to learn to
use this invaluable internet resource.
Not only will you find some information
immediately, but you'll have references
to journal articles that you can obtain
by interlibrary loan, plus the names of
the world's foremost experts and their
institutions.
Alternative (complementary) medicine has made real progress since my
generally-unfavorable 1983 review linked below. If you are
interested in complementary medicine, then I would urge you
to visit my new
Alternative Medicine page.
If you are looking for something on complementary
medicine, please go first to
the American
Association of Naturopathic Physicians.
And for your enjoyment... here are some of my old pathology
exams
for medical school undergraduates.
I cannot examine every claim that my correspondents
share with me. Sometimes the independent thinkers
prove to be correct, and paradigms shift as a result.
You also know that extraordinary claims require
extraordinary evidence. When a discovery proves to
square with the observable world, scientists make
reputations by confirming it, and corporations
are soon making profits from it. When a
decades-old claim by a "persecuted genius"
finds no acceptance from mainstream science,
it probably failed some basic experimental tests designed
to eliminate self-deception. If you ask me about
something like this, I will simply invite you to
do some tests yourself, perhaps as a high-school
science project. Who knows? Perhaps
it'll be you who makes the next great discovery!
Our world is full of people who have found peace, fulfillment, and friendship
by suspending their own reasoning and
simply accepting a single authority that seems wise and good.
I've learned that they leave the movements when, and only when, they
discover they have been maliciously deceived.
In the meantime, nothing that I can say or do will
convince such people that I am a decent human being. I no longer
answer my crank mail.
This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.
This page was last updated February 9, 2008.
During the thirteen years my site has been online, it's proved to be
one of the most popular of all internet sites for undergraduate
physician and allied-health education. It is so well-known
that I'm not worried about borrowers.
I never refuse requests from colleagues for permission to
adapt or duplicate it for their own courses... and many do.
So, fellow-teachers,
help yourselves. Don't sell it for a profit, don't use it for a bad purpose,
and at some time in your course, mention me as author and KCUMB as my institution. Drop me a note about
your successes. And special
thanks to everyone who's helped and encouraged me, and especially the
people at KCUMB
for making it possible, and my teaching assistants over the years.
Whatever you're looking for on the web, I hope you find it,
here or elsewhere. Health and friendship!
y
BIBLIOGRAPHY / FURTHER READING
I urge anyone interested in learning more about
neuropathology
to consult these standard textbooks.
In my notes, the most helpful current
journal references are embedded in the text.
Students using these during lecture strongly prefer this.
And because the site is constantly being updated,
numbered endnotes would be unmanageable.
What's available online, and for whom, is always changing.
Most public libraries will be happy to help you get an article
that you need. Good luck on your own searches, and again,
if there is any way in which I can help you, please contact me at
scalpel_blade@yahoo.com.
Health and friendship!
Niels Bohr
I am presently adding clickable links to
images in these notes. Let me know about good online
sources in addition to these:
MedEdPORTAL -- American Association of Medical Colleges. Primarily for medical school faculty.
Pathology Education Instructional Resource -- U. of Alabama; includes a digital library
Pathopic -- Swiss site; great resource for the truly hard-core
Syracuse -- pathology cases
Alabama's Interactive Pathology Lab
"Companion to Big Robbins" -- very little here yet
Alberta
Pathology Images --hard-core!
Alberta Tumor Photos -- and lots more. Highly recommended.
Bristol Biomedical
Image Archive
EMBBS Clinical
Photo Library
Chilean Image Bank -- General Pathology -- en Español
Chilean Image Bank -- Systemic Pathology -- en Español
Connecticut
Virtual Pathology Museum
Australian
Interactive Pathology Museum
Semmelweis U.,
Budapest -- enormous pathology photo collection
Iowa Skin
Pathology
Loyola
Dermatology
History of Medicine -- National Library of Medicine
KU
Pathology Home
Page -- friends of mine
The Medical Algorithms Project -- not so much pathology, but worth a visit
National Museum of Health & Medicine -- Armed Forces Institute of Pathology
Telmeds -- brilliant site by the medical students of Panama (Spanish language)
U of
Iowa Dermatology Images
U Wash
Cytogenetics Image Gallery
Urbana
Atlas of Pathology -- great site
Visible
Human Project at NLM
Karolinska Institutet -- pathology links
Johns Hopkins CPC's
U. of Virginia Case Studies
Oklahoma Teaching Cases
Indiana U. Teaching Cases
SUNY Histopathology
West Virginia Case of the Month
Upstate NY Cases -- works only on some browsers
Society for Ultrastructural Pathologi -- electron microscope cases
WebPath:
Internet Pathology
Laboratory -- great site
My team:Ed Lulo's Pathology Gallery
Bryan Lee's Pathology Museum
Dino Laporte: Pathology Museum
Tom Demark: Pathology Museum
Dan Hammoudi's Site
Claude Roofian's Site
Medmark Pathology -- massive listing of pathology sites
Pathology Handout -- Korean student-generated site; I am pleased to permit their use of my cartoons
Estimating the Time of Death -- computer program right on a webpage
Pathology Field Guide -- recognizing anatomic lesions, no pictures
St.
Jude's Ranch for Children
I've spent time there and they are good. Write "Thanks
Ed" on your check.
PO Box 60100
Boulder City, NV 89006--0100
More of my notes
My medical students
Clinical
Queries -- PubMed from the National Institutes of Health.
Take your questions here first.
HealthWorld
Yahoo! Medline lists other sites that may work well for you
We comply with the
HONcode standard for trustworthy health
information:
verify
here.
Greenfield's Neuropathology
Robbins and Cotran Pathologic Basis of Disease
Rosai and Ackerman's Surgical Pathology
Rubin's Pathology: Clinicopathologic Foundations of Medicine
Silverberg's Surgical Pathology
The opposite of a correct statement is a
false statement. But the opposite of a profound
truth may well be another profound truth.
No one is born wise.
-- Ptahhotpe, c. 2350 B.C.
I do not understand my own behavior.
-- Paul of Tarsus, Romans 7
"It must be inconvenient to be made of flesh," said the Scarecrow, thoughtfully, "for you must sleep, and eat and drink. However, you have brains, and it is worth a lot of bother to be able to think properly."
-- Scarecrow, The Wizard of Oz
How many psychiatrists does it take to change a light bulb?
Only one, but it takes a long time, and the light bulb has to want to change.
-- Anonymous
A good person can be stupid and still be good. But a bad person must have brains.
-- Maxim Gorky
Ah, it is the fault of our science that it wants to explain all, and if it explain not, then it says there is nothing to explain.
-- Dr. Van Helsing, Dracula (Bram Stoker)
I'd rather have a free bottle in front of me than a prefrontal lobotomy.
-- Anonymous
For botulism
,
click here.
For tetanus, click here.
* Autopsy on brain and muscle: Arch. Path. Lab. Med. 119: 777, 1995.
* Jung accused Freud of "regarding the brain an appendage of the sexual organs." Be this as it may, our brains are what tells us "happy" or "not happy". Some people report themselves to be happier than others, and this tends to stay constant over time. Contrary to what you've been told (by "liberals" or "conservatives"), there's little-or-no correlation with age, race, economic class, or educational level. There's a strong correlation between being happy and (1) being basically in control of your own destiny; (2) being physically healthy; (3) being happily married; (4) living in a country where there's opportunity. See Sci. Am. 274(5): 79, May 1996.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
NEUROPATHOLOGY UNIT: LEARNING OBJECTIVES
Explain briefly what makes neuropathology more difficult than the pathology of other organ systems.
Describe the prevalence of CNS disease, and its impact.
Describe the behavioral correlates of "minimal brain damage", where there may be no demonstrable anatomic pathology.
Describe how brain lesions cause death, and what brain lesions will not in and of themselves cause death.
Describe the concept of selective vulnerability of neurons, giving examples.
Describe the common birth defects involving the brain, giving risk factors and clinical correlates insofar as they are known.
Give a full account of the etiology, anatomic pathology (brain and elsewhere), and clinical correlates of tuberous sclerosis.
Give the anatomic correlates of cerebral palsy, and what we know and don't know about its etiology.
Tell what leukodystrophies are, and what "sclerosis" means in the brain.
Describe how brain cells are injured and killed. Give a short account of excitotoxicity.
Recognize these developmental brain lesions:
Recognize these histopathologic features of brain cells:
Explain how cerebral edema occurs, and distinguish interstitial, intercellular and intracellular edema in terms of etiology and morphology.
Explain the causes of mass shifts in the brain, and the consequences of herniation.
Distinguish communicating and noncommunicating hydrocephalus, and hydrocephalus ex vacuo.
Tell about situation in which the brain is damaged from lack of oxygen, glucose, or blood flow. Describe factors determining the severity of the outcome. Give an account of the consequences of profound ischemia / hypoxia on the brain, and of hypoglycemia. Tell when damaged brain will liquefy, and when it will remain solid.
Describe the causes of cerebral infarction, and recognize them anatomically as applicable. Give a full account of the varying anatomic pathology of cerebral infarcts.
Describe the effect of blood in the ventricular system. Describe the causes, usual locations, and consequences of intracerebral hemorrhage.
Describe the causes and consequences of subarachnoid hemorrhage. Give a full account of berry aneurysms, including locations, histopathology, and known risk factors.
Explain the causes and consequences of germinal plate bleeds in babies. Describe the common neuropathology lesions in the premature nursery.
Describe the anatomic pathology and effects of hypertension on the brain.
Describe the impact of trauma directly on the brain. Distinguish concussion, contusion, and laceration. Give a full account of coup and contrecoup injuries, and of diffuse axonal injury. Describe the neuropathology of boxers.
Describe epidural and subdural hematomas, making sure to distinguish how they occur and how they impact on the patient.
Describe how the spinal cord is usually injured, and the anatomic pathology of acute and old spinal cord trauma.
Recognize these cerebrovascular problems grossly and/or microscopically as appropriate
Distinguish encephalitis, meningitis, and cerebritis.
Give a full account of common bacterial meningitis. Mention the most common bacteria producing meningitis in patients in various ages and situations. Describe the serious complications and how they occur.
Give the anatomic pathology, common agents, and clinical picture in viral meningitis. Mention non-infectious causes of meningeal inflammation.
Give full accounts of tuberculous and
cryptococcal
meningitis.
Describe the four different lesions of neurosyphilis. Briefly discuss the neuropathology
of Lyme disease.
Describe how brain abscesses occur, why they are so treacherous, and what they do.
Describe the anatomic pathology and clinical correlates of viral encephalitis
caused respectively by arbovirus, childhood exanthems, von Economo's,
herpes simplex I,
herpes simplex II,
CMV,
rabies,
and HIV. Name the virus that causes tropical spastic paresis.
Give a pathology account of
poliomyelitis.
Describe the agents, pathology and clinical correlates of the slow virus infections (subacute sclerosing panencephalitis, progressive multifocal leukoencephalopathy).
Give a full account of prion disease.
Briefly describe the effects on the nervous system of
Rocky Mountain spotted fever,
amoebas, toxoplasmosis,
cysticercosis, and trypanosomiasis.
Tell the common causes of headache, and the causes to rule out in the emergency room!
Recognize these CNS infections grossly and/or microscopically as appropriate:
encephalitis
Tell generally what we know about the neurodegenerative diseases, and why we are coming to refer to them today as the "proteinopathies".
Distinguish delirium, dementia, and mental retardation. Tell how patients with dementia may present. Give a full "differential diagnosis" for dementia in older people. Give the lab workup that screen for the common treatable causes.
Give a full account of what we know about the causes and the pathology of Alzheimer's disease. Describe likely future preventions and therapies for Alzheimer's. Describe Pick's disease and its relatives (the frontotemporal dementias).
Recognize Huntington's disease, and explain how the genetic lesions, with trinucleotide repeats, causes the cell injury and the genetic anticipation.
Tell what we know and don't know about the causes of Parkinsonism. Recognize depigmentation of the substantia nigra, and recognize idiopathic and postencephalitic Parkinsonism microscopically. Distinguish Parkinsonism from essential (benign familial) tremor.
Briefly describe the multiple systems atrophy diseases, including Shy-Drager. Give an account of progressive supranuclear palsy, Lewy body dementia, and the spinocerebellar ataxias.
Describe what we know about the causes of the motor neuron disease complex.
Describe what we know about the causes and anatomic pathology of schizophrenia. Give a short account of how society has made decisions about how to care for mentally-ill people.
Review the cellular lesions that are seen in the dementias. Recognize these neurodegenerative diseases grossly and/or microscopically as appropriate:
Give a full account of the anatomic pathology of multiple sclerosis, what we know of the etiology, and how these relate to the clinical progression. Briefly describe some other autoimmune demyelinating diseases.
Tell what we know about central pontine myelinolysis.
Describe the common leukodystrophies.
Describe the effects of alcoholism, carbon monoxide, Reye's, methanol, arsenic, manganese, Wilson's, the common storage diseases, and radiation.
Give accounts of Guillain-Barre, and of the common peripheral neuropathies.
Recognize these demyelinating, toxic, and peripheral nerve diseases grossly and/or microscopically as appropriate
Mention the common paraneoplastic CNS syndromes.
Recognize these tumors grossly and microscopically:
HOW IS NEUROPATHOLOGY DIFFERENT?
Facts about the brain:
The brain contains around 100 billion neurons. Even the best neuropathologist cannot appreciate loss of fewer than 30% of neurons on an H&E section.
We have all our neurons when we are babies, but they aren't yet connected as in an adult. Further, the brain is not fully myelinated until age 10-12 years. This probably explains most developmental milestones, including those of Piaget.
The brain has a great deal to do with our learning, thinking, mood, speech and behavior.
Brain disease is common.
"Stroke" (i.e., cerebrovascular disease) is "the third leading cause of death" in the developed world, and an extremely important cause of disability.
Alzheimer's disease, once considered either "rare" or "a normal part of growing old" and therefore ignored, is finally being recognized as a major public health problem.
There are about 17,000 cases of primary malignant brain tumors in the US yearly; the majority prove fatal.
There are about 500,000 people in the U.S. with severe sequelae of head injury.
In 1990, there were around 10,000 people in the U.S. in irreversible coma, at a cost of $130,000 per patient per year (Br. Med. J. 30: 1094, 1990). I have been unable to find more recent figures.
In prolonged coma, recovery with a return to a decent quality of life sometimes (though rarely) occurs if the coma is due to trauma, i.e., snapped fibers can grow back; NEJM 334: 24, 1996. It won't happen if the coma is due to ischemia / hypoxia, i.e., dead cells can't grow back; Acta Neurol. Belg. 97: 214, 1997. Obviously, in diabetic and renal coma and in poisoning, treating the underlying disease/poisoning is effective. But the very bad outlook of other non-traumatic coma lasting over three days is documented in Crit. Care Med. 30: 1382, 2002; the authors suggests Day 4 as the time to decide not to continue aggressive care. (* Make it Day 1 for me.* -- ERF.)
Many more are "locked in" ("Monte Cristo syndrome", only able to move their eyes; ethicists see Am. Acad. Neuro. statement Lancet 342: 130, 1993) or profoundly damaged so as to be unable to care for themselves. Different people will come to different conclusions about what this means.
At least some people who cannot move at all (even their eyes) are indeed conscious. In the 1990, there were reports suggesting that this may be common. One person who was considered to be "in persistent vegetative state" recognizes faces of people she knows as evidenced on PET scan: Lancet 352: 200, 1998. Similar studies of other unfortunates have given even more convincing results (Science 313: 1402, 2006). Today, PET scans reportedly distinguish the "minimally conscious state" with connections between the cortical association areas and the primary cortical areas preserved and recovery is sometimes possible (though the patients have some ability to communicate and appear unhappy), and the "persistent vegetative state", where they are disconnected and hope for recovery (especially after a year) is unrealistic (Arch. Phys. Med. Rehab. 87(12 S 2): S-67, 2006; Mayo Clin. Proc. 80: 1037, 2005.) In the persistent vegetative state, neuropathology is always widespread; in minimal conscious state and other cases of severe disability, there may be a single focl lesion (Neurology 56: 486, 2001). Don't confuse either with "akinetic mutism", a poorly-named syndrome in which the patient lies inert, follows with the eyes, says nothing or a single word, and seems emotionless. When you see this, think of damage to both cingulate gyri.
* Things are changing. In Canada, where the public pays for health care directly, they are now talking about ignoring families' wishes to do CPR on these patients (CMAJ 159: 18, 1998); not so long ago, this would have been unthinkable.
* For the facts on the Terri Schiavo case, see NEJM
Pretty much anything bad that happens to the brain can leave the person with minimal brain damage. Distinctive features are (1) poor judgement; (2) irritability; (3) poor impulse control; (4) lack of insight; (5) hyper- or hypo-sexuality; (6) inability to learn from experience.
As you might expect, we are coming to recognize the importance of past head injury in criminal misbehavior (for example, Am. J. Psychotherapy 44: 26, 1990, from Hopkins, past due; also J. Trauma 41: 972, 1996, army discharge followups). A kid hospitalized overnight after head injury is much more likely, years later, to have learning and/or behavioral problems (Pediatrics 94: 425, 1994).
Neurologic disease is seldom curable. Even more than other branches of medicine, neurology requires a special kind of physician. The focus is on rehabilitating, educating, finding resources, and helping people manage in spite of disabilities.
Neuropathology presents special difficulties for students at any level. "Big Robbins" lists several of the reasons. Brain disease is unlike disease in other organs because:
Function is localized in the brain, far more than in any other organ. Because of this, the site, rather than the nature of the pathologic process, typically determines symptoms.
A tiny lesion in an "eloquent" area may present striking clinical problems; a large infarct in a "silent" area is missed. Diverse lesions (infarcts, abscesses, tumors) in one site may produce similar problems, while similar pathologic processes at different sites will present different pictures.
A neuropathologist must be a good neuroanatomist, and it is essential to describe the location ("distribution") accurately in making clinico-pathologic correlations.
He or she will also describe diffuse processes (ischemic injury after shock, storage diseases), focal lesions (infarcts, abscesses, and tumors) and systematized lesions (i.e., Huntington's chorea, Parkinsonism, many others).
* By convention, a coronal section of brain will be displayed as if you are looking at the head from the back, and a horizontal section as if you are looking at the head from above.
Remember:
Cells of nervous tissue are selectively vulnerable to various diseases.
For example, Alzheimer's disease hits the hippocampus and cholinergic nucleus
of Maynert harder than the rest of the brain. Mercury
selectively damages the cerebellar granular neurons, methanol poisons the retina, and
poliomyelitis
destroys only the anterior horn cells.
Even short ischemia, severe hypoxia, or severe hypoglycemia will damage Sommer's sector (CA1) of the hippocampus (and other areas of the cortex), the Purkinje cells of the cerebellum, and the basal ganglia.
The brain cannot expand without becoming deformed, because the skull is solid. (It has to be, or brain injuries would be much more common.)
The interstitial space within the brain is quite small (gray matter 200 angstroms, white matter 800 angstroms).
The spinal fluid presents unique problems (high pressure hydrocephalus, dissemination of infections and cancer cells.)
The blood-brain barrier (when intact) alters brain tissue reactivity.
It is demonstrated by injecting the dye trypan blue (which is bound to albumin). It also explains why the lipid in the brain is not yellow (the yellow tryptophan metabolites do not cross the brain).
Ask a neurophysiologist about the exact nature of the blood-brain barrier. Both the endothelial cells
themselves and the astrocyte foot processes are probably important.
Of course, there is no blood-brain barrier in the choroid plexus or the area postrema (chemoreceptor trigger zone). Babies have less blood-brain barrier than we do. And don't expect there to be an effective blood-brain barrier in inflammation or neoplasia.
The brain has no lymphatics, making edema much more of a problem when it happens. (The absence of lymphatics does help prevent dissemination of infection to the brain.)
Neurons have limited ability to heal, and probably do not regenerate. This is probably a good thing, since regenerating neurons might lay down bogus memories (witness the adrenal medulla transplant patients, wait for the human stem cell experiments); it also prevents mature neurons (but not neuroblasts) from giving rise to tumors.
Brain lesions too subtle to see histologically or ultrastructurally can produce profound effects on behavior. (Many obviously organic brain diseases -- dyslexia, schizophrenia, attention-deficit disorder, manic-depression, idiopathic epilepsy, and so forth -- still are pathologically undefined.) This contrasts with all other organs of the body, in which considerable deviation from normal structure may be consistent with good health.
Certain nervous system disease processes (i.e., gliosis, spongiosis, demyelination, neuronal degeneration, the many curious inclusions) are not familiar from general pathology.
What makes all this even more difficult for beginners are the facts that...
* Future pathologists: The brain is fragile and decomposes rapidly
after death. Some hard-core pathologists deep-freeze the heads of
decomposed bodies and dissected them in sub-zero temperatures, just to
be able to see the anatomy.
* About half the human genome is supposed to be brain proteins.
This leave a lot of room for unrecognized syndromes and explanations
for personality and interest variables.
Tutorial on reading brain biopsies: Arch. Path. Lab. Med. 130:
1602 & 1639, 2006.
* One of the nut movements of the 1990's was
self-trepanation, i.e., drilling a hole in your own skull to
enable the brain to pulsate as it supposedly does before the sutures
are closed, enabling one to learn with a child's speed.
A few folks are stupid enough to try it.
This was presented on "ER" 11/12/98.
BRAIN DEVELOPMENT AND ITS PROBLEMS
Different patterns of malformation correlate with mishaps (known or unknown) at different times.
Known causes include maternal alcoholism, mercury poisoning, lead poisoning, radiation, and exposure to vincristine. Of course the links to folic acid deficiency and hypervitaminosis A in the case of neural tube defects are famous. But in the vast majority of cases, the etiology is never found.
Since the completion of the human genome project, dozens of genetic diseases have been found that cause malformations of the brain. Review: Neurology 65: 1873, 2005.
Week 3-4: The neural tube forms and fuses
Dysraphism: failure of the neural tube to close properly. A generic term for all the following.
Folic acid deficiency is now very well-known as a cause, and has resulted in the fortifying of foods in the US; incidence dropped by about a third (Teratology 66: 33, 2002; from the CDC). Parts of Canada had a 78% reduction: Br. Med. J. 324: 760, 2004; as you'd expect, it is greatest where the rate was highest (NEJM 357: 135, 2007).
Vitamin A (retinoids, but not carotenoids) toxicity also seems to be important, with an effect appearing above 10,000 U/day (NEJM 333: 1369, 1995).
* The VANGL1 locus has alleles that greatly increase risk: NEJM 356: 1432, 2007.
Anencephaly:
The most common congenital brain malformation (and among the most severe; * the ultimate is "anencephalus craniorachischisis").
In anencephaly, there is little or no forebrain, merely nubbins of abnormal nervous tissue (* area cerebrovasculosa). There is no top to the skull or orbits, and the eyes protrude. There is generally a scrambled brainstem. Of course, the pituitary and adrenals won't develop right, either.
{10331} anencephalic
{39138} anencephalic
{39140} omphalocele; child also had anencephaly
|
|
|
|
* Anencephaly is very common in Ireland and Wales (maybe 1 child in a few hundred, compared with maybe 1 in several thousand in the U.S. before fortification); there is a modest female preponderance.
This works even when you control for the fact that abortion of
an anencephalic fetus is illegal in Ireland. The anencephaly rates have also dropped in Ireland in the past
twenty years, probably due to
better diet (J. Epidem. Comm. Health 53: 782, 1999).
Currently, we screen for these problems by checking maternal serum for elevated alpha-fetoprotein, which oozes out of the defect in the fetus.
The most important known risk factor is lack of folic acid. The junk food diet is part of the problem, and some unborn children need much more folic acid than others do because of a mutant folic acid processing gene (Lancet 246: 1070, 1995). Mandatory fortification of cereal grains with folic acid went into effect in the US in 1998; this resulted in about a 25% drop in anencephalic births (MMWR 53: 362, 2004; I was hoping for a larger drop.)
Amniotic band syndrome can also cause anencephaly.
*Although your lecturer gives himself out to be pro-life, he is perplexed by the furor over using these kids as organ donors, a practice that the first Bush administration (acting on pressure) successfully got banned in the early 1990's (JAMA 273: 1614, 1995). In 1995, the AMA passed a resolution saying the practice was okay and should be reinstituted. They withdrew it after the "ethicists" went ballistic (Semin. Neuro. 17: 249, 1997). Letting these children serve as organ donors is still very illegal in the US (Medicine and Law 20: 417, 2001), and in addition to causing potential recipients to die, this prevents parents from finding meaning in the whole ordeal. The problem, of course, is that an anencephalic child cannot make an advance directive, and that the heart is only good if it's removed before the child dies of sepsis. For some people, that makes you a "murderer", "child abuser", etc., etc. Even conservative Christians are dissenting: see Christian Bioethics 6: 1, 2000 (talks about "soul"), and the Italians, not noted for radical social policies, use these children as donors (Ped. Trans. 3: 150, 1999). I'd like to know if there's any reader who would NOT sacrifice his or her last 24 unconscious-dying-hours on earth to save another person's entire life.... This is not how the US activists think, and thanks to them, children are dying that could be saved to live good-quality lives (NEJM 330: 387, 1994). Of course, the anencephalic baby has to die in the hospital, and the family would have to pay (maybe $7000 in 1983, the year of the "Baby Jane Doe" flap; J. For. Sci. 42: 1180, 1997). But that's politics. There's signs of change: The Kennedy Institute of Ethics (Journal 14: 249, 2004), not noted for indifference to the value of human life, accepted an article on anencephalic donors and other such situations, asking "Do donors really have to be dead, when they have nothing to lose?" and citing public opinion favorable to such organ procurement. More: Am. J. Bioethics 3: 1, 2003.
Encephalocele:
Deformed brain herniates out through a defect in the skull at birth, and bulges underneath the skin. This may be under the scalp, or in the neck; the latter may be a surprising cause of airway obstruction (J. Laryn. Ot. 113: 369, 1999).
{53752} encephalocele
{15843} encephalocele in amniotic band syndrome
{13397} encephalocele
Some of these children can survive and even lead useful lives.
Contrast "meningocele", in which only meninges (dura, arachnoid) herniate through skull or vertebral column.
Rachischisis ("the worst kind of spinal bifida"): Complete failure of dorsal closure of the spinal canal. The spinal cord lies at the bottom of a furrow, covered only by a thin membrane.
Cranioschisis: Skull defect analogous to rachischisis.
Cranium bifidum: Split skull. (* There are genetic syndromes.)
Myelocele ("meningomyelocele"; "bad spina bifida")
The spinal cord ("myelo-") herniates through a defect in the dorsal aspect of the vertebral column (much less often, the anterior aspect, for example, orbital and nasopharyngeal meningoceles).
Most are lumbar or sacral; in the cervical or thoracic areas, meningocele (i.e., the meninges herniate, but the cord does not) are more common.
With mandatory folic acid fortification, the "spina bifida" rates also dropped about 25% in the US (MMWR 51: 9, 2002).
{05224} myelocele
{12424} myelocele
{13396} myelocele
{13398} myelocele
Complications include distal weakness, incontinence, and meningitis.
80% have associated hydrocephalus.
Spina bifida occulta: A radiographic defect in a vertebral body, perhaps as trivial as lack of a spinous process. These are quite common and a non-problem unless there is an associated CNS defect. (Unanswered question: If "the cause of spina bifida is failure of closure of the neural tube", why does the mild version involve only the bone?)
Weeks 5-6: The rostral CNS cleaves into two hemispheres
Holoprosencephaly ("prosencephaly"; "holotelencephaly"): A single telencephalic hemisphere.
{10333} holoprosencephaly
{10336} holoprosencephaly
{25614} cyclops
There is likely to be absence of much of the limbic system ("arhinencephaly-plus"), and these brains
are generally small.
The worst cases are cyclops babies ("cyclopia"), with a single eye below the snout ("proboscis").
Cyclops or no, many of these kids have trisomy 13-15, and most will have some facial deformity
(especially cleft palates/lips).
Weeks 6-14: Neurons migrate to their proper positions
Agyria (lissencephaly): No gyri.
* Lis1, the gene for the common hereditary form cloned: Nature 364: 17, 1993. XLIS/DCX
Nature 370: 216,
1994; update Neurology 57: 416, 2001. Expect to learn lots about neuronal migration in the coming years due to these discoveries.
Macrogyria/pachygyria: A few big, abnormal gyri
Polymicrogyria: Too many gyri, each too small, with shallow sulci.
* Thanatophoric dwarves tend to have large, polymicrogyric temporal lobes.
* Some people who have polymicrogyria only around the sylvian fissure
have absent or poor language abilities without other obvious problems: Neurology 59: 245, 2002.
NOTE: In all three of the above conditions, the cortex will typically have only four
layers, if any
layering is recognizable. Check all these kids for trisomy 18.
{32949} polymicrogyria, gross
Agenesis of the corpus callosum:
Mild clinical syndrome, and in its partial variants quite common (maybe 1 person in 1000).
* Many of these patients supposedly have alexithymia (odd "Mr. Spock from Vulcan"
affect, no fantasy life, inability to answer "How do you feel?")
* Look for a lipoma, ependymal cyst, or meningioma here. Have a radiologist
show you the "bat wing" sign.
There is now a detailed classification scheme: Neurology 56: 220, 2001.
Arhinencephaly: No olfactory nerves or bulbs. Someimes there are other malformations as well.
Ectopias and heteroplasias: Neuron clumps in the white matter, where they don't belong.
Nobody knows why most of these happen.
Weeks 15-16: The brain is further modelled
Porencephaly: "A hole in the brain". "Defective closure of the telencephalon" and/or ischemic
injury, with destruction of nearby brain. There are cysts lined with ependyma, communicating with
the subarachnoid space.
{32139} porencephaly
Schizencephaly: A deep fissure in the brain, with a floor of brain substance.
Encephaloclastic porencephaly: The fissure is so deep that it reaches the ventricle.
{32943} encephaloclastic porencephaly
Most porencephaly cases are idiopathic. Known causes include TORCH and
infarcts (Arch. Dis. Child. 78: F121, 1998).
* Your lecturer has long taught that
many "idiopathic" cases are caused by trauma, i.e., somebody kicked or beat the pregnant
woman in the abdomen. The shape is exactly what you'd expect. And the classic
neuropathology literature describes this as being more common in children
born out of wedlock and in the underclass. A known example: Dev. Med. & Child Neuro
43: 52, 2001. Another J.A.Optom. 68: 519, 1997. After six months: The brain is already formed and the gyri are largely modelled, but it can
still be damaged (typically by ischemia, viruses, or some serious metabolic process).
Hydranencephaly: Replacement of the cerebral hemispheres by large cysts made of leptomeninges
and glia. There is no ependyma.
This results from ischemia / hypoxia or infection (i.e., TORCH). It may be diffuse or localized.
{10339} hydranencephaly (this happens to have been a case of
toxoplasmosis Ulegyria: An old term for gliosis in the depths of the sulci, and sparing of
the apices of the gyri.
Like hydranencephaly, it may be diffuse or localized. You can also see
ulegyria anytime
after localized cerebral ischemia insufficient to produce generalized
liquefaction * Granular atrophy: Probably ischemic; a mild form of ulegyria.
Etat marbre (* "status marmoratus"): "Marbling" of the corpus striatum from ischemic damage to
the basal ganglia around the time of birth, especially if there is also severe jaundice (i.e.,
kernicterus). Myelin grows irregularly on these masses of gray matter,
giving a marbled look. Some people with cerebral palsy have this lesion.
Periventricular leukomalacia: Loss of oligodendroglia around the ventricles, usually with some dystrophic
calcification.
The deep white matter is relatively poorly vascularized in newborns, and
perhaps this is the baby counterpart
to "watershed infarcts" in the adult.
Tough to place:
Arnold-Chiari: Small posterior fossa with...
(1) Elongated cerebellar tonsils that hang through the foramen magnum;
(2) A Z-shaped kink in the CNS at the cervical-medullary junction;
(3) A large foramen magnum and a small, shallow posterior fossa.
(4) A "beak-shaped" tectum (pressure from the tentorium)
Arnold-Chiari patients generally also have hydrocephalus with thickened, adherent leptomeninges, a
small cerebellum, and a lumber meningomyelocele. There are often other defects, especially
* polymicrogyria.
{32996} Arnold-Chiari (there is also pus in the ventricles)
There are a few syndromes with Arnold-Chiari, but usually it "just happens".
* Future neuro-pathologists: Arnold-Chiari is "Chiari malformation, type II".
(Chiari I is long-tonsils-only.)
Cerebellar hypoplasia may be seen in Down's or Arnold Chiari, or by itself.
Dandy Walker: Large posterior fossa.
No cerebellar vermis. Instead, the fourth ventricle is much dilated, and the roof (if
any) bulges out. {05236} Dandy Walker, no roof on vermis
There is generally hydrocephalus, and often a variety of associated malformations.
Physical diagnosticians: A tip-off is prominent occiput.
Craniosynostosis: Premature closure of one or more of the cranial sutures.
A common defect of unknown etiology.
Sometimes it's part of a syndrome; other times it "just happens". Today's
surgery usually gets good results.
Amyelia: No spinal cord.
Diastematomyelia: Double spinal cord, at least part of the way.
Microcephaly: Well-formed, but under 900 gm.
Megalencephaly: Well-formed, but too big (>1800 gm). * Causes
include tuberous sclerosis (often), neurofibromatosis (sometimes), Canavan's,
cerebral lipidoses, and Alexander's leukodystrophy as causes.
Tuberous sclerosis (* "hereditary multisystem hamartosis", * "Bourneville's disease", * "epiloia")
An autosomal dominant syndrome with extremely variable expressivity.
Identical twins are often highly discordant for severity (Neurology 62: 795, 2004).
* The genes are TSC1 (chromosome 9, hamartin) and TSC2 (chromosome 16, tuberin).
Review Neurology 53: 1384, 1999. There are some modifying genes too.
* The products of hamartin and tuberin interact, as you'd expect.
The whole subject of tubergenesis seems to be much more complex
than just a "second hit": Neurology 63: 1293, 2004.
Portions of the cortex lack the usual stratification of neurons into layers,
and these feel hard and are white, hence the "tubers" (potatoes).
There are likely to be
various odd hamartomas ("tubers"), calcifications, and tumors in the brain and elsewhere.
Everybody knows of the "candle gutterings", giant-cell astrocytomas on the
inner walls of the ventricles in tuberous sclerosis.
This is a very important cause of epilepsy and mental retardation. Look for adenoma sebaceum (fibrous
nodules on the muzzle area of the face) and "ash-leaf" spots (areas of hypo-pigmentation on the skin,
with the long axes parallel to the dermatomes; these are common in normals too).
{27928} tuberous sclerosis, face; adenoma sebaceum
Syringomyelia / syringobulbia: Probably acquired later in life, but discussed here.
There is a tubular cavity in the center of the cord (generally cervical) and/or brainstem (bad), with
surrounding gliosis and no ependyma. There is loss of pain and temperature (since the crossing spinothalamic tract is
damaged) over the corresponding levels. Eventually, other sensory and motor pathways may be
damaged.
{09022} syringomyelia; myelin stain; the tracts have been damaged by the syrinx above and below
Most often these conditions are idiopathic (and attributed to some mechanical problem involving
heartbeat); known causes include cord tumors and Arnold-Chiari.
* "Hydromyelia" is dilatation of the central canal, i.e., there is an
ependymal lining.
Neuroepithelial cysts probably arise from faulty migration during embryogenesis. They gradually
grow, and become symptomatic in adult life.
The best-known are the "colloid cysts" that occlude the foramen of Munro, often causing headache
only when the head remains in a particular position.
{15678} colloid cyst, foramen of Munro
Arachnoid cysts may be large and require surgical removal.
{01251} arachnoid cyst
Cerebral palsy: a lay person's umbrella term for a nonprogressive
brain defect present at (or presenting shortly after)
birth, with motor and often cognitive problems.
Around 100,000 kids in the U.S. have at least some degree of cerebral palsy. In around 0.2% of
kids, the problem is at least moderately severe. One quarter of kids diagnosed with cerebral palsy
cannot walk; one third are mentally retarded; one third are epileptic. Some kids outgrow the motor
problem.
Lay wisdom is that "cerebral palsy is the obstetrician's fault, the baby did not get enough oxygen to
the brain." (Ask a lawyer; this is probably true only of a minority of cases; the advances in
obstetrical and neonatal care in the last few decades have had no measurable impact on the rate of
cerebral palsy.) Other causes include almost everything on this list, or kernicterus.
Again, the most common anatomic correlate is periventricular leukomalacia
(quantitating it: Brain 128: 2562, 2005).
In the term infant with hemiplegia, the usual finding is ulegyria or some other ischemic brain injury
(sometimes just neuronal loss and gliosis), in the distribution of the middle cerebral artery. There is
often some other problem as well; in at least 15%, there's gross malformations of brain development.
In other term-born cerebral palsy patients, there are often a number of cystic lesions in the white
matter, sometimes communicating with the ventricles. These must be old infarcts.
Premature birth is a major risk factor for cerebral
palsy. For those weighing less than 1500 gm
at birth, the risk is 30x that for term babies. Those under 2500 gm are also at increased risk, though
less so. Again, in preemies who go on to develop cerebral palsy, the usual lesion is periventricular
leukomalacia (JAMA 296: 1602 & 1650, 2006).
In children of normal gestational age and birth weight, maternal infection
seems to be a common cause of cerebral palsy; nobody's looked at the anatomic
pathology yet (JAMA 278: 207, 1997).
* Children produced by in-vitro fertilization are at greater risk, but
mostly just because they are more likely to be born prematurely and/or with
low birth weight (Lancet 359: 461, 2002). Of course, meningitis in the
neonate is another cause (Clin. Ped. 40: 473, 2001).
* For a review of cerebral palsy, see NEJM 330: 188, 1994. The classic doctrine that it's the
obstetrician's fault goes back to the middle of the 19th century; the first serious challenge was by
neurologist Sigmund Freud, who thought it was a problem of fetal development.
{33069} cerebral palsy from birth hypoxia
Again, most developmental abnormalities of the brain are not inherited, and are of unknown
etiology.
CELLULAR REACTIONS IN THE NERVOUS SYSTEM
Histology terms:
Nissl substance is just rough endoplasmic reticulum in neurons. It's easy to see using special stains.
Neurofilaments are intermediate filaments typical of neurons.
Neuronal dropout (nerve cell depopulation) is important in many disorders.
{01278} red neurons
Atrophy and degeneration of neurons is common in many neuronal diseases, and (to a much lesser
degree) in simple aging.
Most of the time, loss of a single neuron provokes no reaction from adjacent glia, or any other
specific morphologic marker.
Sometimes, loss of a neuron produces trans-synaptic degeneration of the neurons with which it
communicates. The best example is atrophy of the lateral geniculate body in people who have
had an eye enuclated.
Intra-neuronal bodies (many of them
characteristic of the "proteinopathies", a
new fad name) include the following:
Neurofibrillary tangles are structures composed of twisted filaments, stainable with silver. They are
composed of tau protein, ubiquitin, and sometimes Aβ (Neurology 40: 975, 1990).
* Future pathologists: light up these (and the similar stuff in the neurites in Alzheimer senile
plaques, with Alz-50 stain!)
Neurofibrillary tangles are typical of Alzheimer's disease, progressive supranuclear palsy,
corticobasal degeneration, post-encephalitic
Parkinsonism,
amyotrophic lateral sclerosis of Guam, dementia of boxers, * Williams'
microdeletion (Arch. Neuro. 52: 209, 1995), and bad * Niemann-Pick storage disease (Brain
118(1): 119, 1995).
{01330} Lewy body
{01311} Pick body (the large black thing)
{01303} Hirano body (you need EM to appreciate the corduroy effect)
{01293} Granulovacuolar degeneration
{01314} Lafora body (PAS stain, "red sunflower")
* Neuroserpin forms bodies in a rare autosomal dominant illness (Am. J. Path. 170:
1305, 2007).
* Marinesco bodies are small inclusions in the nucleus, without a halo (i.e., "Cowdry type B"). Their
significance is unclear.
Melanin is normal in the substantia nigra, locus ceruleus, and dorsal motor nucleus of the vagus
nerve.
{01272} neuromelanin
Lipofuscin is common in older people (* "simple pigmentary atrophy").
{01270} lipofuscin; oil red O stain
Intra-neuronal storage is characteristic of certain inborn errors of metabolism (listed below). The
cytoplasm is distended, and the nucleus typically appears displaced.
* Ferrugination is hemosiderin-encrustation of
neurons near sites of past hemorrhage.
Axonal reaction is also known as central chromatolysis. If an axon is severed or otherwise injured,
the perikaryon (neuronal cell body) swells, rounds up and becomes pale-staining. The Nissl
substance disappears except just below the cell membrane, and the nucleus moves to the edge of the
cell. * "Peripheral chromatolysis": The neuron is recovering! * Healthy Clarke's column and some
other neuron groups can show central chromatolysis for some reason.)
{01275} axonal reaction, central chromatolysis; you
can just see the RER as purple at the rims of the affected neurons
Axonal degeneration is said to occur when a neuron cannot maintain the axon to which it is
attached.
Wallerian degeneration is the changes in an axon severed from its cell body.
{09602} Wallerian degeneration; corticospinal
tract is lost from a stroke higher up
Axonal spheroids are spherical or sausage-shaped knobs when axons have been damaged by
mechanical trauma ("diffuse axonal injury", the main lesion),
ischemia, radiation (famous), or in axonal diseases.
* Clinicians please note: The term "Betz cells", used as a synonym for cortical neurons ("You have
two Betz cells held together by an ethanol molecule / spirochete"), should be limited to the large
cortical neurons that supply axons to the descending pathways.
You remember that protoplasmic astrocytes occur mostly in gray matter, "fibrous astrocytes" occur
mostly in white matter, and that their "foot processes" / "end plates" have to do with the blood-brain
barrier.
The intermediate filaments in astrocytes are vimentin and glial fibrillary acid protein (GFAP, a
specific marker).
Gliosis is proliferation of astrocytes at sites of injury, the counterpart of "scarring" elsewhere in the
body.
Instead of laying down collagen or other extracellular material, the astrocyte cytoplasm itself
becomes the "scar", and there is no "scar contraction".
{01366} gliosis, special glial stain
The only fibroblasts in the CNS are in the blood vessels, and these typically only contribute to
healing when a hematoma must be organized or an abscess walled off.
* The clever pathologist distinguishes the wall of an abscess
from a glioblastoma by observing that fibroblasts do not stain with GFAP,
while spindle cell astrocytes do.
Gliotic scars, especially after penetrating injury, are considered to give rise to many cases of
epilepsy.
{1357} gemistocytes
Fibrillary astrocytes (not to be confused with fibrous astrocytes, a normal cell) result when
gemistocytes settle downward lose most of their cytoplasm, though not the complexity of their
processes.
Anisomorphic gliosis is a proliferation of neoplastic, slightly-atypical protoplasmic astrocytes, the
lowest-grade of astrocytoma.
Rosenthal fibers are pink-staining structures within the processes of large
astrocytes. They are shaped like slightly-crumpled hot-dogs. You can see them at any site of gliosis, and they help make the diagnosis of certain
astrocytomas. {01390} Rosenthal fibers
* Corpora amylacea ("polyglucosan bodies"; "fool's cryptococcus") are 10-50 spherical masses of
polysaccharide within astrocyte end-processes. They become common as the brain ages; look for them
in the subependymal and perivascular regions.
{00539} Alzheimer's type II glia (two of them)
NOTE: Neither type of "Alzheimer's glia" has anything to do with Alzheimer's disease.
* Decreased numbers of astrocytes is a maker for longstanding mild ischemia.
Oligodendroglia have small, lymphocyte-like nuclei with a halo (* formalin artifact).
They are primarily responsible for making myelin; unlike the Schwann cell, one oligodendrocyte
can wrap several axons. In the white matter, they are easy to spot. In the gray matter, look for them
around neurons ("satellite cells").
Diseases of oligodendroglia affect myelin. Leukodystrophies affect all myelin, and are usually
hereditary. Demyelinating diseases produce patchy myelin loss. You remember that
periventricular leukomalacia, the usual lesion in cerebral palsy,
features loss of oligodendroglia around the ventricles.
Sclerosis in CNS means loss of
myelin and its replacement by astrocytes.
Morphologically, the reactions of oligodendroglia are usually limited to dying and disappearing.
Herpes * Cytoplasmic inclusions in the oligodendroglia
are masses of scrambled microtubules,
specific for the multiple systems atrophy family
(Shy-Drager, striatonigral degeneration, olivopontocerebellar degeneration).
See Am. J. Path. 155: 1241, 1999. They are composed of synuclein,
alphaB-crystallin, and ubiquitin. You won't see Lewy bodies.
Ependyma seldom show much reaction, either. If ependymal cells die, gliosis between the cells
produces ependymal granulations.
Microglia is an ancient misnomer for macrophages in the brain. (* Philologists: Astrocytes and
oligodendroglia are "macroglia".)
Rod cells are reactive macrophages with elongated nuclei.
They are described in Rocky Mountain
spotted fever
Gitter cells are actively phagocytizing macrophages in the CNS). They are typically "gitting" rid of
dead myelin and other cell debris.
Microglial nodules are clusters of macrophages around damaged tissue. Think of viral or rickettsial
disease. (Don't expect to see good granulomas in diseases unique to the CNS.) You may actually
see the macrophages eating neurons (neuronophagia, naturally).
HIV giant cells are the familiar Langhans / foreign body type
resulting from macrophages that fuse in HIV infection.
They notice the HIV gp120 on each other's surfaces, and try to engulf each other.
{01461} neuronophagia
* Despite old teachings, there are always a few T-cells on patrol
in the brain, and even finding a group of B-cells doesn't necessarily
mean disease (Brain 126: 1058, 2003).
Worth noting: Neurons are very sensitive to ischemia (worst) and hypoxia (somewhat
better tolerated as long as there's blood flow, but still not good).
Oligodendroglia are less sensitive
than are neurons. Ependymal cells are even less sensitive, while astrocytes are the least sensitive,
capable of withstanding all but the most severe and prolonged hypoxia.
INCREASED INTRACRANIAL PRESSURE / HERNIATION
Increased intracranial pressure is said to be present when recumbent CSF pressure exceeds 200 mm
water (measure using the manometer during spinal tap!)
When brain volume (localized or generalized) increases for any reason (edema, trauma, hemorrhage,
tumor, inflammation, abscess, echinococcus, gumma, etc.), some blood is first pushed out of the
skull by venous compression, but this is minuscule. Any additional increase in brain volume will
increase intracranial pressure. Some CSF will be lost, and then the brain itself will be forced to
move within the skull.
Increased intracranial pressure first presents as headache, mental dullness, and nausea and vomiting
(the latter are important and are curiously omitted from "Big Robbins"). Clinicians of course look
for papilledema, pushing of the optic nerve forward into the eyeball.
The skull and even dural membranes are not going to budge for the expanding brain. Instead,
herniation will occur when brain volume is sufficiently increased. (The brain is being squeezed
through openings and around corners like toothpaste.)
Cingulate herniation (subfalcine herniation) results when one cingulate gyrus is pushed underneath
the falx. Occlusion of the callosal-marginal branch of the anterior cerebral artery can result.
{01465} cingulate herniation, view from above with falx removed
*Future angiographers: Detect these by finding displacement of the pericallosal arteries!
Uncal herniation (trans-tentorial herniation, hippocampal herniation) results when the medial
temporal lobe is pushed between the cerebral peduncles and the tentorium cerebelli.
{01471} tentorial herniation marks
Stretching of the third cranial nerve produces the famous "fixed dilated pupil" on the ipsilateral side. Crushing of the posterior cerebral artery against the edge of the tentorium results in occlusion, and
explains the cortical blindness (if unilateral, "homonymous hemianopsia") that often follows head
injury.
{01483} crushed posterior cerebral artery
Crushing of the cerebral peduncle on the same side
as the expanding lesion causes hemiparesis on the opposite side
of the body.
* You may also note paralysis of upward gaze (injury to the tectum) or sudden increase in
intracranial pressure (crushing shut of the aqueduct of Sylvius), and so forth.
* Expanding lesions in the posterior fossa can give reverse tentorial herniation. This causes many of
the signs above, and the tension on the fifth cranial nerves is painful.
{01477} reverse tentorial herniation marks
Tonsillar herniation (cerebellar herniation, brainstem herniation, "coning") results from
herniation of
the cerebellar tonsils out through the foramen magnum, compressing the medulla. The latter is the
mechanism of death in most cases of brain swelling.
{01474} tonsillar herniation damage
As the brainstem is pushed caudally, the penetrating vessels are affected, resulting in the centrally-located Dûret
hemorrhages ("Duret hemorrhages",
"secondary brainstem hemorrhages", "slit hemorrhages") in the pons
and midbrain. This is bad, and can leave a survivor locked-in.
{01485} Dûret hemorrhage
* "Big Robbins" states the vessels are avulsed, causing hemorrhage. Or maybe
they are occluded
by stretching, and then the ischemic regions become hemorrhagic when re-perfused during heroic
resuscitation attempts.
Trans-calvarial herniation is said to be present when brain herniates out through an open fracture in
the skull.
{01479} trans-calvarial herniation after-effect
Other causes of increased central venous pressure (cardiac septal defects,
congestive heart failure, AV malformations) or obstruction to the venous
outflow from the brain (i.e., little thrombi from hypercoagulable blood) also need to be
considered.
* You will learn on rotations about surgery (shunts, optic nerve
fenestration) for this relatively common clinical problem.
CEREBRAL EDEMA
Brain swelling is serious, since it leads to herniation (and maybe scrambles the neuropil, too.) Three
types are classically listed.
Vasogenic edema (the most common type) is fluid in the extracellular space. Either (1) the
capillaries have been damaged and are leaking protein (infarcts, infection, contusions, and
notoriously lead poisoning though no one knows how Pb damages the endothelium)
or (2) new, leaky capillaries are forming in an abnormal area (abscess,
primary or metastatic tumor).
Grossly, the white matter will be soft and wet, and more affected than gray (since the intercellular
space is larger in the white matter).
* Acute mountain sickness features cerebral edema, which now appears
to be due to the vessels in the white matter becoming leaky
(JAMA 280: 1920, 1998; update Lancet 361: 1967, 2003).
* Is high-altitude mountain climbing itself a risk factor for permanent brain
damage? First systematic survey indicates "Yes": Am. J. Med. 119:
168.e1, 2006.
{01464} edema after trauma
Microscopically, there are
Holoprosencephaly
WebPath Photo
{00141} polymicrogyria, gross
{01246} polymicrogyria, patient (severe disability)
)
{53696} hydranencephaly patient
.
Traditionally thought to be due to global hypoxia (i.e., apnea or
hypotension) around the time of birth, the idea that it is really
due to cytokine effect (Neurology 56: 1278, 2001) is
presently under consideration. It is common after neonatal cardiac surgery
(J. Thor. Card. Surg. 127: 692, 2004).
Whatever the cause, this is the most distinctive
lesion in the cerebral palsy that is so common in low-birth-weight
children (Am. J. Phys. Med. Rehab. 81: 297, 2002; Am. J. Ob. Gyn. 177: 19, 1997).
{17683} Arnold-Chiari, long cerebellar tonsils
* Again, usually the cause is obscure. There are a few rare syndromes.
{15466} Dandy Walker, no roof
{16600} Dandy Walker
{39058} Dandy Walker, thin roof
{27948} tuberous sclerosis, brain; note the white tubers
{01828} tuberous sclerosis, brain; the tubers appear as whiter areas of cortex
{01830} tuberous sclerosis, brain
{01252} arachnoid cyst
{01253} arachnoid cyst
{18763} kernicterus
{31972} kernicterus
{31989} kernicterus
{53734} kernicterus after-effects (small head)
Histopathology of neurons
Some nice pictures
Virginia Commonwealth University
Neurons are the principal units of nervous system circuitry, and the central characters in
neuropathology.
Acute necrosis of neurons shortly before bodily death results in "red neurons" with absent Nissl
substance and shrunken nuclei (i.e., the familiar coagulation necrosis ,
or ischemic cell change; they
dissolve after a few days). Fortunately for neuropathologists, you don't
see this unless the cell has been injured at few hours before total-body
death.
If the patient has survived 12 hours or more after an ischemic event, you'll usually
see red neurons. In physical trauma, the membranes are physically disrupted
and red neurons form even faster.
{01279} red neurons
{31969} red neurons (Purkinje cells are dead)
{01288} neurofibrillary tangles; the stringy stuff in the neuron
is stained poorly here
{01291} neurofibrillary tangles; the black, stringy stuff in the neurons
Neurofibrillary tangles
Several photos and essay
U. of Oklahoma
Lewy bodies are pink-staining spheroids made largely of ubiquitin,
parkin, and synuclein.
They are typical of idiopathic
Parkinson's disease (basal ganglia) and Lewy-body dementia (large numbers
in the cortex). You may
see some Lewy bodies in the cortex or basal ganglia in Alzheimer's.
* A variant is usual in the anterior horn cells in
amyotrophic lateral sclerosis (Neurology 48: 267, 1997; Neurology 49: 1612, 1997); it's composed
of superoxide dismutase, at least sometimes (Neurology 51: 871, 1998;
Am. J. Path. 163: 609, 2003).
Pick bodies are large, ovoid bodies that stain best with silver. They're made of tau protein.
On EM, they appear filamentous.
* Composition can vary; they may contain ubiquitin and/or light up for Alz-50 antigen (Arch. Neuro 51: 145, 1994.)
Balloon neurons, swollen for unknown reason, are typical
of Pick's and some of its variants, and * corticobasal degeneration.
Spongiform change (not to be confused with spongiosis)
consists of watery vacuoles in the perikaryons and processes of neurons. It's typical
of the prion
diseases. 
Hirano bodies are hyaline masses composed primarily of actin. They are typical of Alzheimer's
disease. Look in the hippocampus. 
Granulovacuolar degeneration appears as tiny vesicles with central, dense cores. It is typical of
Alzheimer's disease. 
Lafora bodies are masses of glucose polymer, mostly within neurons
(also liver and muscle; look especially in the dentate nucleus of the
brain). They are typical of the common hereditary form of
myoclonus
epilepsy (* gene "laforin"). 
Negri bodies in the cytoplasm in rabies
are actually masses of the virus.
{01337} Negri bodies in Purkinje cells
{01738} Negri body, sketch
Rabies
Yutaka Tsutsumi MD
Rabies
Negri body in a neuron
KU Collection
Neuronal storge diseases
Tay-Sachs plus essay
Virginia Commonwealth University
Sphingolipidosis
Brazil Pathology Cases
In Portuguese
{01276} axonal reaction, central chromatolysis
{09591} Wallerian degeneration, corticospinal tract
is lost from a stroke higher up (myelin stain)
Wallerian degeneration
WebPath Photo
Astrocytes show on H&E only as relatively large glial nuclei in the neuropil.
{01368} gliosis, special glial stain
Gemistocytes are astrocytes seen in reactive processes. They are large, pink cells.
Spongiosis
is
edema with lots of gemistocytes. (Don't confuse this with spongiform encephalopathy.)
{1360} gemistocytes
* Future neuropathologists: the fibers are made
up mostly of a crystallin plus GFAP.
{01393} Rosenthal fibers in * Alexander's disease (mutant GFAP;
worked out Nat. Genet. 27: 117, 2001)
The thankfully-rare "adult polyglucosan disease" features many of these in
the brain and heart.
The mutation is in the glycogen brancher enzyme (Muscle & Nerve 32: 672, 2005;
Neurology 61: 263, 2003).
Alzheimer's type I glia are monstrously enlarged astrocytes with huge, dark nuclei.
You seen them
in subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy.
Alzheimer's type II glia are astrocytes with edematous-looking, swollen nuclei. They
are seen in
liver failure and other states with high blood ammonia
(Reye's, urea cycle problems). Look in the gray matter. * Despite "Big Robbins",
only in one rare disease does the pale, swollen
nucleus contain glycogen.
{01383} Alzheimer's type II glia (one in the center)
and JC viruses produce typical inclusions in oligodendroglia; chronic measles (SSPE)
may do so as well.
,
typhus,
syphilis, and various viral infection.
Glia pathology
Best rod cells on the 'net
Virginia Commonwealth University
Neuropathology of HIV infection
Nice photos and article
Temple U.
Neuronophagia
WebPath Photo
{31975} Herniation marks
{01473} tentorial herniation marks
{01482} tentorial herniation marks
{00524} tentorial herniation, crushed cerebral peduncle
{00542} tentorial herniation, crushed cerebral peduncle
Beware: compression of the contralateral cerebral peduncle against the opposite tentorium --
Kernohan's notch ("crus syndrome") --
will produce "fixed dilated pupil" on the contralateral side.
{01476} tonsillar herniation damage
Tonsillar herniation
"Coning"
WebPath Photo
Certain drugs, notably some of the tetracyclines, and overdoing vitamin A,
can increase intracranial pressure, or it can be idiopathic ("pseudotumor cerebri";
"idiopathic intracranial hypertension").
Many patients with the idiopathic illness are overweight,
and the effect is perhaps due to the extra physical weight on the right
atrium and thus to the dural sinuses (J. Neurosurg. 101: 878, 2004).
Neuroanatomy
"Why I Support Amateur Boxing"
Anencephalic child
Open neural tube defect