NERVOUS SYSTEM DISEASE
Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com

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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. No texting or chat messages, please. Ordinary e-mails are welcome.

I am active in HealthTap, which provides free medical guidance from your cell phone. 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.

Freely have you received, give freely 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.

I am presently adding clickable links to images in these notes. Let me know about good online sources in addition to these:

Freely have you received, freely give. -- Matthew 10:8. My site receives an enormous amount of traffic, and I'm still handling dozens of 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:

I've spent time there and they are good. Write "Thanks Ed" on your check.

Help me help others

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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. 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.

During the eighteen 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!

BIBLIOGRAPHY / FURTHER READING

PicoSearch
  Help

More of Ed's Notes: Ed's Medical Terminology Page

Perspectives on Disease
Cell Injury and Death
Accumulations and Deposits
Inflammation
Fluids
Genes
What is Cancer?
Cancer: Causes and Effects
Immune Injury
Autoimmunity
Other Immune
HIV infections
The Anti-Immunization Activists
Infancy and Childhood
Aging
Infections
Nutrition
Environmental Lung Disease
Violence, Accidents, Poisoning
Heart
Vessels
Respiratory
Red Cells
White Cells
Coagulation
Oral Cavity
GI Tract
Liver
Pancreas (including Diabetes)
Kidney
Bladder
Men
Women
Breast
Pituitary
Thyroid
Adrenal and Thymus
Bones
Joints
Muscles
Skin
Nervous System
Eye
Ear
Autopsy
Lab Profiling
Blood Component Therapy
Serum Proteins
Renal Function Tests
Adrenal Testing
Arthritis Labs
Glucose Testing
Liver Testing
Porphyria
Urinalysis
Spinal Fluid
Lab Problem
Quackery
Alternative Medicine (current)
Preventing "F"'s: For Teachers!
Medical Dictionary

Courtesy of CancerWEB

Niels Bohr

Niels Bohr
The opposite of a correct statement is a
false statement. But the opposite of a profound
truth may well be another profound truth.

KCUMB Students
"Big Robbins" -- CNS
Lectures follow Textbook

KCUMB Students
"Big Robbins" -- Nerve / Muscle
Lectures follow Textbook

QUIZBANK -- Nervous system (all)

    Patterns of Nervous System Disease: 1, 20-21, 28-68, 385-386
    Stroke and Hemorrhage: 2-19, 22-27, 69-85, 162-230, 311-312
    CNS Infections: 85-161, 289
    Neurodegenerative disease: 232, 234-242, 244-248, 250-254, 256, 258, 262-266, 273, 276-282, 284-286, 291-294, 297-300, 302-304
    Demyelinating Disease, Poisons: 231, 233, 243, 249, 255, 257, 259-261, 267-272, 274-275, 283, 287, 290, 295-296, 301, 305-310, 313-333, 387
    Tumors: 334-384

INTRODUCTION

No one is born wise.

I do not understand my own behavior.

Be not angry that you cannot make others as you wish them to be, since you cannot make yourself as you wish to be.

"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."

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.

A good person can be stupid and still be good. But a bad person must have brains.

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. Abraham Van Helsing (pathologist), Dracula (Bram Stoker)

I'd rather have a free bottle in front of me than a prefrontal lobotomy.

Volumes are now written and spoken upon the effect of the mind upon the body. Much of it is true. But I wish a little more was thought of the effect of the body on the mind.

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 Blog
By a cyberfriend of mine
For those with a special interest

Brain, Nerve, Muscle
Photo Library of Pathology
U. of Tokushima

CNS
Taiwanese pathology site
Good place to go to practice

Neuropathology
Surgical Pathology Atlas
Nice photos, hard-core

Nervous System
Iowa Virtual Microscopy
Have fun

Neuropathology
Brown Digital Pathology
Some nice cases

"Why I Support Amateur Boxing"
Position paper by Ed
This is something about which
reasonable people can differ.

CNS
Photos, explanations, and quiz
Indiana U.

Neuropathology
Massive collection
In Portuguese

Neuroradiology
Radiology-Pathology
Uniformed Services

Inflammatory and Demyelinating Diseases
Great pictures in a clickable
handout, from Duke

Nancy Peress MD
Neuropathology
Good introduction

Dr. Fung
Oklahoma
Great stuff -- For advanced learners

Brain Exhibit
Virtual Pathology Museum
University of Connecticut

Dr. Fung
Neuropathology-web.org
Good easy introduction
Dimitri Agamanolis MD; thank you!

NEUROPATHOLOGY UNIT: LEARNING OBJECTIVES

HOW IS NEUROPATHOLOGY DIFFERENT?

BRAIN DEVELOPMENT AND ITS PROBLEMS

Week 3-4: The neural tube forms and fuses

{10331} anencephalic
{39138} anencephalic
{39140} omphalocele; child also had anencephaly

Anencephalic child

WebPath Photo

Anencephalic child

WebPath Photo

Anencephalic child
Poorly formed brain
WebPath Photo

Anencephaly
WebPath Photo

Anencephaly
WebPath Photo

Anencephaly
WebPath Photo

Rachischisis
WebPath Photo

Encephalocele
WebPath Photo

Encephalocele with exencephaly
WebPath Photo

{53752} encephalocele
{15843} encephalocele in amniotic band syndrome
{13397} encephalocele

{05224} myelocele
{12424} myelocele
{13396} myelocele
{13398} myelocele

Open neural tube defect

KU Collection

Lipomyelomeningocele
Pittsburgh Pathology Cases

Meningomyelocele

WebPath Photo

Meningomyelocele
WebPath Photo

Iniencephaly
WebPath Photo

Weeks 5-6: The rostral CNS cleaves into two hemispheres

{10333} holoprosencephaly
{10336} holoprosencephaly
{25614} cyclops

Holoprosencephaly

WebPath Photo

Holoprosencephaly

WebPath Photo

Holoprosencephaly

WebPath Photo

Holoprosencephaly

WebPath Photo

Holoprosencephaly
WebPath Photo

Holoprosencephaly
WebPath Photo

Holoprosencephaly
WebPath Photo

Weeks 6-14: Neurons migrate to their proper positions

{32949} polymicrogyria, gross
{00141} polymicrogyria, gross
{01246} polymicrogyria, patient (severe disability)

Weeks 15-16: The brain is further modelled

{32139} porencephaly

{32943} encephaloclastic porencephaly

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).

{10339} hydranencephaly (this happens to have been a case of toxoplasmosis)
{53696} hydranencephaly patient

Hydranencephaly

WebPath Photo

Hydranencephaly
WebPath Photo

Tough to place:

{32996} Arnold-Chiari (there is also pus in the ventricles)
{17683} Arnold-Chiari, long cerebellar tonsils

{05236} Dandy Walker, no roof on vermis
{15466} Dandy Walker, no roof
{16600} Dandy Walker
{39058} Dandy Walker, thin roof

{27928} tuberous sclerosis, face; adenoma sebaceum
{27948} tuberous sclerosis, brain; note the white tubers
{01828} tuberous sclerosis, brain; the tubers appear as whiter areas of cortex
{01830} tuberous sclerosis, brain

Tuberous sclerosis

WebPath Photo

Tuberous sclerosis

WebPath Photo

Tuberous sclerosis

WebPath Photo

{09022} syringomyelia; myelin stain; the tracts have been damaged by the syrinx above and below

{15678} colloid cyst, foramen of Munro

{01251} arachnoid cyst
{01252} arachnoid cyst
{01253} arachnoid cyst

{33069} cerebral palsy from birth hypoxia
{18763} kernicterus
{31972} kernicterus
{31989} kernicterus
{53734} kernicterus after-effects (small head)

Kernicterus
Brazil Pathology Cases
In Portuguese

Kernicterus
WebPath Photo

CELLULAR REACTIONS IN THE NERVOUS SYSTEM

Brain Cells I
From Chile
In Spanish

Brain Cells II
From Chile
In Spanish

Brain Cells III
From Chile
In Spanish

Histopathology of the brain
Several nice photos
Harvard

    NEURONS are the principal units of nervous system circuitry, and the central characters in neuropathology.

{01278} red neurons
{01279} red neurons
{31969} red neurons (Purkinje cells are dead)

Red neurons

WebPath Photo

Red neurons

WebPath Photo

{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

WebPath Photo

{01330} Lewy body

Lewy body
Tom Demark's Site

{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")


{01337} Negri bodies in Purkinje cells
{01738} Negri body, sketch

Rabies

Yutaka Tsutsumi MD

Rabies
Negri body in a neuron
KU Collection

Rabies
Negri bodies
Wikimedia Commons

{01272} neuromelanin

{01270} lipofuscin; oil red O stain

Intraneuronal storage
Tay-Sachs
WebPath Photo

Sphingolipidosis
Brazil Pathology Cases
In Portuguese

{01275} axonal reaction, central chromatolysis; you can just see the RER as purple at the rims of the affected neurons
{01276} axonal reaction, central chromatolysis

{09602} Wallerian degeneration; corticospinal tract is lost from a stroke higher up
{09591} Wallerian degeneration, corticospinal tract is lost from a stroke higher up (myelin stain)

Wallerian degeneration

WebPath Photo

{01366} gliosis, special glial stain
{01368} gliosis, special glial stain

Glial scar, outer cortical surface5
Gunshot wound
KCUMB Team

{01357} gemistocytes
{01360} gemistocytes

{01390} Rosenthal fibers
{01393} Rosenthal fibers in * Alexander's disease (mutant GFAP; worked out Nat. Genet. 27: 117, 2001)

{00539} Alzheimer's type II glia (two of them)
{01383} Alzheimer's type II glia (one in the center)

Neuropathology of HIV infection
Nice photos and article
Temple U.

{01461} neuronophagia

Neuronophagia

WebPath Photo

INCREASED INTRACRANIAL PRESSURE / HERNIATION

Edema and Herniation
From Chile
In Spanish

Brain Herniation
Radiology-Pathology
Uniformed Services

{01465} cingulate herniation, view from above with falx removed

{01471} tentorial herniation marks
{31975} Herniation marks
{01473} tentorial herniation marks
{01482} tentorial herniation marks
{00524} tentorial herniation, crushed cerebral peduncle
{00542} tentorial herniation, crushed cerebral peduncle

Brain that has herniated

WebPath Photo

Uncal herniation

WebPath Photo

{01483} crushed posterior cerebral artery

{01477} reverse tentorial herniation marks

{01474} tonsillar herniation damage
{01476} tonsillar herniation damage

Tonsillar herniation
"Coning"
WebPath Photo

{01485} Dûret hemorrhage

Duret hemorrhages

WebPath Photo

Duret hemorrhage

WebPath Photo

{01479} trans-calvarial herniation after-effect

CEREBRAL EDEMA

{01464} edema after trauma

Edema from micrometastases

WebPath Photo

Cerebral edema
Wide gyri, obliterated sulci
WebPath Photo

{01344} vasogenic edema, note bubbles
{01345} vasogenic edema, note bubbles
{01438} vasogenic edema, note bubbles

HYDROCEPHALUS ("water-heads")

Hydrocephalus
From Chile
In Spanish

{00191} hydrocephalic child

{32766} atrophy, attributed to alcoholism

Hydrocephalus ex vacuo

WebPath Photo

{00191} hydrocephalic child
{13394} hydrocephalus
{13395} hydrocephalus, transilluminated
{00194} hydrocephalic brain
{00197} hydrocephalic brain

VASCULAR DISEASE OF THE NERVOUS SYSTEM

HYPOXIA, ISCHEMIA, AND INFARCTION

{09443} atherosclerosis of major arteries
{53786} perinatal hypoxia case

Cerebral Infarcts
From Chile
In Spanish

Pathology of stroke
Good photos
Wash U.

{31968} widespread encephalomalacia, recent (purple / "lilac" cortex)

{00168} laminar necrosis; this is the slit running down the middle of the cortex, due to hypoxic damage long ago
{17731} laminar necrosis

{09604} watershed infarcts; you diagnose this by location
{09607} watershed infarcts

Watershed infarcts

WebPath Photo

{00165} diffuse hypoxic-ischemic injury, old; note the laminar necrosis
{33033} diffuse hypoxic-ischemic injury, old
{31970} diffuse hypoxic-ischemic injury, old

Diffuse hypoxic-ischemic injury
Old; patient kept alive on respirator
WebPath Photo

{15469} sponge brain

CEREBRAL INFARCTS

Pathology of Stroke
Some great photos
From Wash. U.

{00180} infarct with early softening
{17792} infarct with early softening

Brain infarct
Acute
WebPath Photo

Brain infarct
Acute
WebPath Photo

Fresh infarct

WebPath Photo

Intermediate age infarct

WebPath Photo

Intermediate age infarct

WebPath Photo

Fresh infarct

WebPath Photo

Intermediate age infarct

WebPath Photo

Intermediate age infarct
Lots of macrophages eating lipid
WebPath Photo

Intermediate age infarct

WebPath Photo

"Cystic" infarct

WebPath Photo

Cerebral Infarct
Australian Pathology Museum
High-tech gross photos

{00189} infarct, breaking apart
{06348} infarct, old; frontotemporal area
{10350} infarcts, old and recent
{10960} infarct, old, basal ganglia
{17694} infarct, old

Carotid thrombus

WebPath Photo

Organized thrombus

WebPath Photo

Fresh stroke
Some small hemorrhages
Wikimedia Commons

{18760} hemorrhagic infarct; note it consists of petechiae
{00145} hemorrhagic infarct

Hemorrhagic infarct

WebPath Photo

Infarct with petechiae

WebPath Photo

{15696} venous infarct
{15697} venous infarct

* Lenin's brain contained multiple, bilateral, old infarcts. See Neurology 42: 241, 1992. This disproves his friend Maxim Gorky's maxim that a bad person needs a good brain.

INTRACEREBRAL HEMORRHAGE

Brain Hemorrhages I
From Chile
In Spanish

Brain Hemorrhages II
From Chile
In Spanish

{00144} intracerebral hemorrhage
{01813} intracerebral hemorrhage
{01815} intracerebral hemorrhage
{09476} intracerebral hemorrhage

Hypertensive basal ganglia hemorrhage

WebPath Photo

Hypertensive basal ganglia hemorrhage

WebPath Photo

* Actor Richard Burton, just before he died of an intracerebral hemorrhage, scribbled these lines from Macbeth in his notebook: "The multitudinous seas incarnadine, making the green one, red" (i.e., Macbeth sees his victim's blood flowing so copiously as to turn the sea red)....


Macbeth

NON-TRAUMATIC SUBARACHNOID HEMORRHAGES (Lancet 369: 306, 2007)

{15656} berry aneurysm, ruptured
{15667} berry aneurysm,
{17699} berry aneurysm, PICA
{17712} berry aneurysm, ruptured
{18754} berry aneurysm, ruptured

Brain Aneurysms
From Chile
In Spanish

Berry aneurysm

WebPath Photo

Berry aneurysm

WebPath Photo

Subarachnoid bleed from berry aneurysm

WebPath Photo

Berry aneurysm
Incidental finding
KU Collection

{10848} AV malformation
{10849} AV malformation
{18759} AV malformation

AV malformation

WebPath Photo

Cryptic AV malformation
Pittsburgh Pathology Cases

AV malformation

WebPath Photo

AV malformation

WebPath Photo

{15661} cavernous hemangioma
{15662} cavernous hemangioma

{00521} germinal plate bleed, small
{09518} germinal plate bleed, large

Germinal plate, normal
WebPath Photo

Germinal plate hemorrhage
WebPath Photo

Germinal plate hemorrhage
WebPath Photo

Germinal plate hemorrhage

WebPath Photo

HYPERTENSIVE CEREBROVASCULAR DISEASE

{09446} "êtat criblé", French for multiple lacunes

Lacunar infarct
H&E
KCUMB Team

Lacunar infarct
Silver
KCUMB Team

Lacune

WebPath Photo

Lacune

WebPath Photo

NERVOUS SYSTEM TRAUMA

CNS TRAUMA

{18753} epidural hematoma

Epidural hematoma

WebPath Photo

{00533} acute subdural hematoma
{18758} acute subdural hematoma
{32107} acute subdural hematoma

Acute subdural
Bryan Lee

Acute subdural hematoma

WebPath Photo

{32110} chronic subdural hematoma
{32112} chronic subdural hematoma; despite the red, note the membrane

Subdural hematoma
Great x-ray
Pittsburgh Pathology Cases

Chronic subdural hematoma

WebPath Photo

Chronic subdural hematomas

WebPath Photo

{00155} cone-shaped coup contusion. He got hit bad on the left side of the head.
{17779} old contusion
{17780} coup contusion

{00545} contrecoup contusion (classic site, bottom of temporal lobe)
{25618} contrecoup contusion
{25617} contrecoup contusion

Contracoup injury

WebPath Photo

Contracoup injury

WebPath Photo

Contracoup injury, old

WebPath Photo

Contracoup injury, old

WebPath Photo

Axonal injury
Bryan Lee

Shaken baby
Axonal spheroids
WebPath Photo

Motor vehicle fatality

WebPath Photo

SPINAL CORD TRAUMA (review NEJM 330: 550, 1994)

A perennial licensure exam item: Lots of petechiae throughout the white matter? Fat embolus!

Fat embolus
Petechiae throughout white matter
KU Collection

Fat Embolus
Brain
WebPath Photo

Fat Embolus
Brain
WebPath Photo

Fat embolus

WebPath Photo

Fat embolus
Petechiae throughout white matter
KU Collection

CNS INFECTIONS

Pathology of nervous system infections
Great site
Yutaka Tsutsumi MD

Brain Inflammation I
From Chile
In Spanish

Brain Inflammation II
From Chile
In Spanish

INTRODUCTION

ACUTE PYOGENIC MENINGITIS

Purulent meningitis

WebPath Photo

Purulent meningitis

WebPath Photo

Purulent meningitis

WebPath Photo

Purulent meningitis

WebPath Photo

Purulent meningitis

WebPath Photo

Purulent meningitis

WebPath Photo

Meningococcal meningitis

Yutaka Tsutsumi MD

Meningococci
Gram stain
WebPath Photo

H.'flu meningitis
Pus around base of brain
Wikimedia Commons

Bacterial meningitis
Thick purulent exudate
KU Collection

Bacteria in the spinal fluid
Rogues' gallery
Yutaka Tsutsumi MD

Klebsiella meningitis

Yutaka Tsutsumi MD

Listeria meningitis

Yutaka Tsutsumi MD

Flavobacterium meningitis
Advanced students
Yutaka Tsutsumi MD

Acute Meningitis
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Pneumococcal meningitis
CDC
Wikimedia Commons

Purulent meningitis
Great labels
Romanian Pathology Atlas

{32838} acute pyogenic meningitis (this happens to have been E. coli)
{10857} acute pyogenic meningitis
{26174} acute pyogenic meningitis
{31992} acute pyogenic meningitis

ACUTE LYMPHOCYTIC MENINGITIS ("viral meningitis", benign "stiff neck", etc.)

CHRONIC MENINGITIS

Tuberculous meningitis

Yutaka Tsutsumi MD

Cryptococal meningitis

Yutaka Tsutsumi MD

Cryptococcal Meningitis
Pittsburgh Illustrated Case

Cryptococcosis
Infection in Virchow-Robin spaces
KU Collection

{06050} cryptococcus, PAS stain
{06055} cryptococcus, India ink preparation

BACTERIAL INFECTIONS OF THE BRAIN

{00162} brain abscesses
{15544} brain abscess (three in the prefrontal lobes)
{27590} brain abscesses

Brain Abscess
Great labels
Romanian Pathology Atlas

Peptostreptococcal brain abscess

Yutaka Tsutsumi MD

Brain abscesses
Pittsburgh Pathology Cases

Brain abscess

WebPath Photo

Brain abscess, organizing rim

WebPath Photo

MRI
Click on the brain abscess!

WebPath Photo

{09027} tabes dorsalis, spinal cord, myelin stain

Tabes dorsalis, myelin stain
Dorsal columns at bottom
Classic drawing, Adami & McCrae, 1914

Lyme disease of the brain
Pittsburgh Pathology Cases

CONVENTIONAL VIRUS INFECTIONS OF THE BRAIN

CMV of the nervous system
Pittsburgh Pathology Cases

Encephalitis japonicum
Viral encephalitis
Yutaka Tsutsumi MD

{01335} herpes; look closely, the thing really is in the nucleus (the dark structure adjacent to the inclusion is the nucleolus)
{15473} herpes encephalitis, residual

Herpes encephalitis

WebPath Photo

Herpes simplex encephalitis

Yutaka Tsutsumi MD

Poliomyelitis

Yutaka Tsutsumi MD

{01337} Negri body Old Yeller

CMV encephalitis in AIDS

Yutaka Tsutsumi MD

{37378} HIV giant-cell encephalitis

HIV-induced encephalopathy

Yutaka Tsutsumi MD

HTLV-1 myelopathy

Yutaka Tsutsumi MD

SLOW VIRUS INFECTIONS: Long incubation period (years), long relentless disease (months or years)

Subacute sclerosing panencephalitis
Measles
Yutaka Tsutsumi MD

{31956} progressive multifocal leukoencephalopathy; Alzheimer I bizarre large glial nucleus
{31957} progressive multifocal leukoencephalopathy; this shows the inclusion bodies better
{01744} PML inclusions, schematic diagram

JC virus
Progressive multifocal leukoencephalopathy
Yutaka Tsutsumi MD

PML
Great scans and photos
Pittsburgh Pathology Cases

Progressive Multifocal Leukoencephalopathy
Pittsburgh Illustrated Case

SPONGIFORM ENCEPHALOPATHIES ("unconventional agent encephalopathies"; a better name today would be "prion dementias"; some people call these "transmissible amyloidosis"; others group them with the proteinopathies as "diseases of protein misfolding"). Update Arch. Neuro. 62: 545, 2005; Lancet 363: 51, 2004.

Creuzfeldt-Jakob's disease

Yutaka Tsutsumi MD

Gerstmann-Straussler disease

Yutaka Tsutsumi MD

Prions
Pittsburgh Pathology Cases

Prion disease

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Prion disease

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Prion disease

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Prion disease

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Prion disease
Lots of amyloid ("kuru plaques")
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Knowledge makes you vain, education makes you humble.

OTHER BRAIN INFECTIONS

Aspergillus

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{08419} acanthamoeba, trust me
{08278} naegleria, trust me

Acanthamoeba
CDC
Wikimedia Commons

Naegleria meningoencephalitis

Yutaka Tsutsumi MD

Acanthamoeba of the brain
Great photos
Pittsburgh Pathology Cases

Acanthameba meningoencephalitis

Yutaka Tsutsumi MD

Amoebas in the brain
Fluorescence
Wikimedia Commons

Toxoplasma meningitis

Yutaka Tsutsumi MD

Toxoplasma encephalitis in AIDS

Yutaka Tsutsumi MD

{15472} toxoplasmosis of the brain in AIDS
{53733} brain damage from toxoplasmosis before birth
{32317} cat, trust me

Cysticercosis of the brain

Yutaka Tsutsumi MD

Cysticercosis
Pittsburgh Pathology Cases

Cerebral malaria

Yutaka Tsutsumi MD

HEADACHE

CNS DEGENERATIVE DISEASE

Neurodegenerative Disease
Click to see the images
Duke

Pathology of CNS Degenerative Disease
WebPath Tutorial

Neurodegenerative Diseases
Great pictures in a clickable handout
Duke

INTRODUCTION

ALZHEIMER'S DISEASE ("pre-senile dementia", "senile dementia", "old timer's disease", "brain failure", etc.; "a primer for practicing pathologists": Arch. Path. Lab. Med. 117: 132, 1993; for general physicians Lancet 377: 1019, 2011)

Alzheimer's with amyloid
Brazil Pathology Cases
In Portuguese

Alzheimer's disease
Photo essay
U. of Utah

{34478} brain atrophy

Brain atrophy

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Brain atrophy.
Alzheimer's.
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Alzheimer's disease
Silver stain
KU Collection

Brain atrophy

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Brain atrophy
Hydrocephalus ex vacuo
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{26762} neurofibrillary tangles

Neurofibrillary tangle

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Neurofibrillary tangles
Silver stain
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{01339} senile plaques
{01341} senile plaques, silver stain
{01342} senile plaques, immunoperoxidase stain for amyloid

Senile plaques
Silver stain
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Senile plaques
Silver stain
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Alzheimer's disease
Amyloid
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Alzheimer's disease
Senile plaque -- silver stain
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Alzheimer's
Senile plaques
Wikimedia Commons

FRONTOTEMPORAL DEMENTIAS ("lobar atrophy", "FTLD", formerly all lumped as "Pick's disease" and now sub-sub-classified Arch. Neuropath. 114: 5, 2007) is a pattern of cortical dementia, less common than Alzheimer's. Update of the frontotemporal lobe dementias for clinicians: Med. Clin. N.A. 86: 501, 2002; pathologists Brain 128: 1996, 2005 and Arch. Path. Lab. Med. 130: 1063, 2006 and (autopsy pathologists) Arch. Path. Lab. Med. 137: 314, 2013.

Pick's disease

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Pick's disease

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HUNTINGTON'S DISEASE ("Woody Guthrie's disease")

    This is an autosomal dominant disease (gene Htt, protein huntingtin, * chromosome 4, gene cloned Cell 72: 971, 1993, Nature 362: 408, 1993) with complete penetrance. Neurons disappear, most spectacularly in the head of the caudate nucleus.

      * The reason for the localization of the damage to the corpus striatum seems to be the mutant huntingtin's interaction with a protein called Rhes that is selectively localized there (Science 324: 1327, 2009).

      * There is also plenty of cell loss in the cortex, and its extent in the motor and cingulate cortex areas correlates with symptoms Brain 133: 1094, 2010.

    Between age 20 and age 50, mental function diminishes (* "subcortical dementia"), behavior, insight, and mood change for the worse (one group coins the phrase "beyond disgust" for the inability to recognize negative emotions and the things that should provoke them: Brain 130: 1715, 2007; more on the altered emotions that precede the movement disorder Brain 135: 1165, 2012). Then a movement disorder (chorea and athetosis, resembling a jerky dance) develops. Profound disability and death occur after 10-20 years.

Woody Guthrie
Woody
Guthrie

{32870} Huntington's brain, gross; not much caudate

Huntington's disease

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Huntington's disease

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Huntington's
Pittsburgh Pathology Cases

PARKINSON'S DISEASE ("paralysis agitans") and its relatives: Parkinsonism review: NEJM 339: 1130, 1998; Lancet 363: 1783, 2004; J. Clin. Inv. 116: 1744, 2006; Lancet 373: 2055, 2009; Nat. Med. 16: 653, 2010

Parkinson's

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Parkinson's

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Parkinson's disease
Lewy bodies
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Alpha synuclein staining
UK Tissue Bank
Good illustrations

{17754} Parkinson's vs. normal (midbrain sections)

CORTICOBASAL DEGENERATION (formerly "Pick's Type B") is a dementing disease with balloon cells, a distinctive tau-based pathologic lesion around astrocytes, and motor problems (notably alien limb, "My hand escaped and is doing its own thing.")

MULTIPLE SYSTEMS ATROPHY is now considered a single disease, because of its distinctive inclusions in the oligodendoglia.

PROGRESSIVE SUPRANUCLEAR PALSY ("PSP", Steele-Richardson) is an underdiagnosed, fairly-common (Neurology 44: 1015, 1994; Med. Clin. NA 83: 369, 1999; J. Clin. Path. 54: 427, 2001) dementing disorder of older adults with eye movement disorders (especially, problems with downward gaze), other movement disorders, and often dementia.

THE OTHER TAUPATHIES

ARGYROPHILIC GRAIN DISEASE, with silver-staining tau granules in limbic neurons (different from granulovacuolar degeneration, and without other Alzheimer features) is a common, newly-recognized entity seen in very old folks, with amnesia, delusions of persecution, and agitation (Acta Neuropath. 111: 320, 2006; now well-known Brain 131: 1416, 2008.) It's been under-recognized since special variants of the silver stains are required to see its lesions.

LEWY BODY DEMENTIA features neurons packed with synuclein-rich Lewy bodies throughout much of the brain. These patients have a rapid Alzheimer-like illness with some extrapyramidal symptoms (stiff and slow but usually no tremor), visual hallucinations (visual cortex lesions demonstrable on scan Brain 135: 569, 2012), and (often) exquisite sensitivity to the older neuroleptic drugs (chlorpromazine, etc. -- try one of the newer "atypical antipsychotics" instead.) It's not rare, but seldom diagnosed in life. See Br. Med. J. 305: 673, 1992; Neurology 42: 2131, 1992; clinico-pathologic correlation including tips on how to tell this from Alzheimer's in life Arch. Neuro. 59: 43, 2002.

TORSION DYSTONIA ("dystonia musculorum deformans") is a disease of children in which the muscle tone increases around the body, twisting it into curious positions. The one known gene is Torsin A (TOR1a / DYT1) which does not always express completely (Neurology 59: 445, 2002; Arch. Neuro. 57: 333, 2000.) The anatomic pathology in the brainstem includes inclusion bodies (not well-characterized; Ann. Neuro. 56: 540, 2004) and since the disease comes on over time, there's probably neurodegeneration involved. Neurosurgical procedures on the deep brain structures has resulted in spectacular recoveries (review Ped. Neuro. 14: 145, 1996).

* HEREDITARY SPASTIC PARAPLEGIA ("familial spastic paraparesis, etc.; Arch. Neuro. 60: 1045, 2003) is a family of thankfully-rare progressive genetic disorders (dominant and recessive) of varying expressivity. For some reason, the long axons in the corticospinal tracts that supply the legs undergo degeneration with the neurons themselves being preserved. At least eight loci are already known (J. Neuro. Neurosurg. Psych. 72: 43, 2002; pathology of the "spastin" mutant variant Neurology 55: 89, 2000).

ESSENTIAL TREMOR ("benign familial tremor") is a very common (1-2% of humankind), usually banal (sometimes severe) intention tremor. It is inherited as an autosomal dominant (possible loci Neurology 68: 790, 2007 and Brain 130: 1456, 2007), first manifests around age 20, and typically vanishes as soon as the "patient" drinks one beer (i.e., here's the three questions you need to ask to pretty-much clinch the diagnosis). If the patient really wants to be treated, or it's severe, try low-dose propranolol or gabapentin (Arch. Neuro. 56: 807, 1999) or mysoline or any of a variety of others (Am. Fam. Phys. 86: 292, 2012). More important, explain the nature of the process, and that it is NOT Parkinsonism or mental illness.

THE SPINOCEREBELLAR ATAXIAS (update Mayo Clin. Proc. 75: 475, 2000; the autosomal recessive group NEJM 366: 636, 2012.)

AMYOTROPHIC LATERAL SCLEROSIS ("Lou Gehrig's disease"; "creeping paralysis"; motor neuron disease complex; Am. Fam. Phys. 59: 1489, 1999; NEJM 344: 1688, 2001; BMJ 336: 658, 2008; Lancet 377: 942, 2011)

    "Motor neuron disease complex" is actually four diseases, featuring loss of the motor neurons

      1. Amyotrophic lateral sclerosis (loss of upper and lower motor neurons); this is the common one

      2. Progressive bulbar palsy (cranial nerves are most severely affected)

      3. Progressive muscular atrophy (lower motor neurons only)

      4. Primary lateral sclerosis (upper motor neurons only)

Lou Gehrig
Lou Gehrig

Amyotrphic lateral sclerosis

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Amyotrophic lateral sclerosis

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Amyotrphic lateral sclerosis

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MENTAL ILLNESS

    SCHIZOPHRENIA (Lancet 353: 1425, 1999; Mayo Clin. Proc. 77: 1068, 2002) is the most important of the "functional psychoses", supposedly affecting about 1% of humankind in every culture, every bit as devastating as Alzheimer's disease, but under-investigated (i.e., patients don't lobby, there's an awful stigma, and the rich are seldom affected). Schizophrenics consume 2.5% of health care expenditures, constitute 10% of the totally and permanently disabled, and represent around 14% of the homeless (Psych. Clin. N.A. 16: 413, 1993). Schizophrenia reviews: Lancet 346: 477, 1995; NEJM 330: 681, 1994. Schizophrenia as a cause of death (meds, agitated delirium, or the disease itself): J. For. Sci. Int. 48: 164, 2003. Being raised by a schizophrenic mother is one of the strongest predictors of growing up totally confused and being unable to cope as an adult.

      * There are rumors that schizophrenia is becoming less common among young people in the U.S. Perhaps this is because of 'flu shots, and/or perhaps this is due to fetal monitoring and more frequent cesarean sections (and perhaps this will prove to be the great benefit of fetal monitoring; stay tuned here.)

Mad Meg

Brugel's "Mad Meg"

Even in the DSM-IV era, I find Bleuler's "Four A's" helpful: Autism (apparent absorption in self and fantasy), Ambivalence (maintaining contradictory attitudes in logic-tight compartments, with striking lack of insight), loose Associations, and flat Affect. In schizophrenia, these are much more striking even than in us "normal folk".

Sensitive physicians know that the negativism, coldness, and lack of motivation of the schizophrenic can be as upsetting to family members as the delusions and hallucinations. Tell them it's nobody's fault and that it isn't that they are not loved.

Reasonably good models for schizophrenia (i.e., both being very crazy and being oriented in the three spheres) include acute intermittent porphyria, lupus, chronic mercury poisoning, ergotism, pellagra, neurosyphilis, frontal lobe meningioma, and some of the psychedelic experiences.

One Flew Over the Cuckoo's Nest
One Flew Over the
Cuckoo's Nest

Shakespeare's Ophelia

Until the mid-1990's, all public discussion of schizophrenia was dominated by ideology. In the 1960's ("B.F. Skinner says..."; "All people are born the same and if you aren't getting what you want, it is society's fault"; etc.), behaviorists wrote dogmatically about "the schizophrenogenic mother" ("She said to the child, 'I love you', but her body language said otherwise, and this prevented the child from distinguishing fantasy from reality"; "the double bind", etc., etc. Today's historians say a generation of mothers needs an apology: Lancet 379: 1292, 2012.) In the early 1970's, it was all the fault of "the schizophrenogenic father" instead; as with the "S-mother", evidence was "anecdotal" (i.e., the biological parents of crazy people act screwy themselves; stress sometimes precipitates symptoms) and "based on sound theory" (i.e., "all people are born the same", the left-wing/Skinnerian ideology of the day). Some 'sixties revolutionaries discussed schizophrenia as "a disease caused, more than any other, by our reactionary society", or denied its existence altogether (a Dr. Thomas Szasz, author of The Myth of Mental Illness, described witch-hunts and incarcerating people just for being different). 'Sixties rhetoric emphasized that traditional society was unreasonable and thus the people in the mental hospitals must be the sane ones. "The King of Hearts" put this on the silver screen. Ken Kesey (One Flew Over the Cuckoo's Nest) and Dr. R.D. Laing (The Politics of Experience) wrote their best-sellers. (Dr. Laing's own life-story was an ugly one.) The ACLU defended the rights of crazy people to refuse treatment (one 1970's study showed 99% were totally grateful after being brought back to earth). And some psychologists inveighed against the use of the obviously-effective phenothiazine drugs, which began cutting through hallucinations and delusions as soon as they were introduced in the 1950's. Confusing fantasy with reality always causes problems, and the beautiful 'sixties rhetoric resulted in disaster for the mentally-ill and their families. Today, only a few psychoanalysts still talk about curing schizophrenia through psychotherapy, and the rest of the world (even the other psychiatrists) just laughs at them (Nature 354: 693, 1991 was the last gasp). There are still occasional complaints from non-physicians about psychiatry being wicked because it is "authoritarian", or obsolete because it is "culture-bound" or "institutionalized" or "modernist rather than postmodernist" (Br. Med. J. 322: 724, 2001). These people ignore the fact that since the 1940's, free-world psychiatrists have only used coercion when a person cannot take care of himself/herself or a danger to others, and an examination of any psychiatry textbook will show that the discipline is characterized by a variety of perspectives and ways of understanding a particular person's problems.

The end result of all of the "enlightened thinking", of course, was de-institutionalization ("out of the back wards, into the back alleys"). This pleased the Left ("We're for every individual's freedom to be different"; "Even though the inmates got free food, clothing, shelter, medical care, and protection, and were otherwise unemployable, it violated their civil rights to have them work in the laundry and not get minimum wage and benefits"), the Right ("We're against able-bodied people living at public expense"), optimistic physicians ("The grateful patients will come regularly to their community mental health centers to get their medicines refilled"), and real humanitarians (there were, after all, serious abuses in the old "asylum" system). Well, everybody was pleased at first.... Today, the non-compliant mentally-ill whose families can no longer stand them are homeless, and this gets described as a "human rights problem" by the same people who got the asylums closed in the 1970's. Do you think Dr. Szasz ("Mental illness is a myth") has ever talked to his local "bag person"? By the way, schizophrenics ARE more likely to commit crimes, including violent crimes, including murder (Psych. Clin. N.A. 15: 575, 1994; a schizophrenic is 8 times as likely to commit murder as a non-psychotic counterpart: Arch. Gen. Psych. 53: 497, 1996), and only a fool believes that psychiatry can protect the public in today's political-economic "mental-health" environment. I hope that no one was surprised by an enormous study from Duke (Arch. Gen. Psych. 63: 490, 2006) that withdrawn schizophrenics rarely commit crimes but that people raging around and having delusions of persecution are very likely to hurt somebody. The best we're doing nowadays is "leveraging" -- the person doesn't get his/her welfare check if he/she does something violent (Am. J. Psych. 163: 1404, 2006; and the lawyers are all over this; it's emerged that during a six-month period, about 20% of those collecting welfare for mental illness will admit to hurting someone or at least threatening someone with a lethal weapon; same rate as the Duke study above.) The truth is that schizophrenics are more likely than non-schizophrenics to commit all categories of crime except sex crimes (Lancet 355: 614, 2000). In fact, people who stalk strangers (rather than previous sex partners) are usually psychotic (Lancet 355: 199, 2000). Even writers who seem to be advocates for "community mental health" and who emphasize that a majority of stranger-murders result from fights in bars or among druggies cannot hide the reality of senseless violence from schizophrenics (especially against family members and friends: Br. Med. J. 328: 754, 2004). As part of the illness, many schizophrenics do not believe they are sick, and do not want to take their medicine. Thanks mostly to "laws that protect the rights of the specially-challenged", it remains extremely difficult to keep a schizophrenic confined even after multiple episodes of dangerous behavior. The shooting of two guards in the US capitol by a chronically belligerent, chronically threatening, non-compliant schizophrenic named Russell Eugene Weston who had just been given "Greyhound therapy" (a one-way bus ticket out of the state) by the Montana mental-health system should have had an impact, but it didn't. Michael B. Laudor, a schizophrenic who successfully completed the curriculum at Yale Law School and who sold book and movie rights to his success story for $2 million, stopped taking his medicine and a few days later stabbed his pregnant girlfriend to death. In both of these high-profile cases, the families knew there was going to be trouble, but couldn't do anything. In 1982, the parents of Larry Robison did everything they could to have him forcibly treated, but were unable to prevent his committing mass murder. Anders Breivik, the 2011 Norwegian mass-killer, went unnoticed because he hung out with other political crazies. A mental patient is most likely to kill a family member when the family denies, misunderstands, or "spiritualizes" the illness (chilling reading: Crim. Behav. Mental Health 15: 154, 2005). The much-hyped "study" (Arch. Gen. Psych. 55: 393, 1998) finding that mentally-ill people in the community were no more likely to be violent than their underclass neighbors suffered from serious flaws, including omitting anybody who had been in jail, and not counting threats of violence, swinging-and-missing, fire-setting, or trashing rooms as being violent. The "study" also lumped in the burned-out schizophrenics, who are generally very passive and withdrawn, with the active and obviously troublesome ones. More recently, several studies have made it clear that schizophrenics are much more likely to commit violent crimes, especially violent sex crimes (Crim. Behav. Ment. Health 14: 108, 2004 -- note the conflict with some previous studies). A schizophrenic (compared with a non-schizophrenic) is over four times more likely to have been convicted of a crime (21.6% vs. 7.8%), and a violent crime (8.2% vs. 1.8%); the rate of substance abuse among schizophrenics is tremendously high but this doesn't explain all of this (Am. J. Psych. 161: 716, 2004; also JAMA 301: 2016, 2009). At present, there are maybe 300,000 or 400,000 chronically mentally ill Americans confined in jails and prisons. (Many are in jails for vagrancy.) There are only about 80,000 people in long-term mental health facilities. The truth is that this represents a conscious decision by society to turn care of these people over to law enforcement personnel (who are, for the most part, reality-oriented and respectful of the legitimate rights of all people) rather than non-physician (and non-scientifically-oriented) "mental health experts". But the damage has been done. In the past decade, the phenomenon of "mental health courts", judicial-system courts focused on managing these people, has become widespeard; expect continued growth (JAMA 297: 1641, 2007). The New England Journal is troubled by the "epidemic of incarceration", noting that a great number of these people are mentally ill (NEJM 364: 2081, 2011), but offers no better solution in a society where we cannot deal otherwise with the non-manageable, non-complaint mentally-ill. One of the major moral failures in my life was not speaking up when a group of mental health professionals called a nun a "self-righteous bitch" for no other reason than saying that she preferred -- just for herself -- a celibate lifestyle devoted to caring for the sick and needy. (My course evaluation would probably have been affected adversely, but I'm still ashamed I said nothing. This happened in 1974 or 1975.) It was at that moment that I realized who was really "caring for the mentally ill" in the community. Next year, on my "psych" rotation, the physicians talked to me again and again about how frustrating it was to have to work with such screwy "fellow-professionals" who wielded so much power. Perhaps things have changed since the mid-1970's. Among my favorite articles from the 1990's was "The Government-Sponsored Revolving Door" in NEJM 333: 777 & 794, 1995. Schizophrenics on welfare learn to act crazy and get admitted while they're broke and waiting for their checks, and recover when the check arrives; and in the study sample, the typical welfare-schizophrenic's largest single expenditure was for cocaine.

When psychotic symptoms are emerging, cognitive therapy of course does not reduce progression to psychosis or the distress that it causes, but seems to help these unfortunates cope somewhat better (BMJ 344: e2233, 2012). Not surprisingly, group art therapy does not help schizophrenics (BMJ 344: 846, 2012).

It is now perfectly clear that schizophrenia is a major organic nervous system disease. Before the disease fully manifests itself, brain cells die off and brain atrophy occurs (Am. J. Psych. 155: 1661, 1998); this is already well-underway during the first episode (Am. J. Psych. 157: 1829, 2000). Certain association areas in the cortex and thalamus are hit especially hard (Am. J. Psych. 159: 59, 2002; Arch. Gen. Psych. 60: 878, 2003; counting dendritic spines Am. J. Psych. 162: 1200, 2005); the more cortex lost, the worse the outcome (Am. J. Psych. 158: 1140, 2001); all patients have gray matter lesions and enlarged third ventricles, while the more impaired ones also have white matter lesions and enlarged lateral ventricles (Am. J. Psych. 166: 189, 2009). For a review of various studies at the light microscopic level, see Brain 122(4): 593, 1999; findings differ in different studies but generally agree that there is neuronal loss and cellular disarray in the cortex, without gliosis. The loss is selective, with the dorsolateral prefrontal cortex severely involved and nearby Broca's area completely spared (Arch. Gen. Psych. 60: 69, 2003; Am. J. Psych. 159: 1983, 2002); the more that's gone, the worse the outcome (Am. J. Psych. 158: 1140, 2001). The volume loss in the superior and middle temporal gyri is by now very well-known and there is talk about its being specific for schizophrenia (Am. J. Psych. 163: 2103, 2006). A rigorous study shows a distinctive pattern of loss in the basal ganglia (Brain 130: 678, 2007). There is more loss of cortex (and poorer outcome) over time if the patient gets classical antipsychotic agents, and LESS loss of cortex (and better outcome) than the untreated if the patient gets the newer agents (Arch. Gen. Psych. 68: 871, 2011). Counting dendrite intersections: Am. J. Psych. 161: 742, 2004. Further, schizophrenics have by-now-well-characterized volumetric loss of the white matter of the frontal, pareital, and fronto-parietal junctions at onset, and these get worse over time (Am. J. Psych. 164: 1082, 2007). Old studies of genetics are now giving way to the discovery of loci. Familial schizophrenia locus Science 288: 678, 2000. Neuregulin 1: Am. J. Hum. Genet. 71: 877, 2002; Am. J. Hum. Genet. 72: 83, 2003. More on the genetics: Lancet 361: 417, 2003. Update JAMA 299: 2017, 2008. "The schizophrenia susceptibility pathway": Nature Medicine 17: 470, 2011. Even in cases without simple inheritance, the genes obviously dominate family environment (old work on schizophrenia genetics: Lancet 1: 79, 1989; Nature 339: 305, 1989; Nature 340: 391, 1989; non-schizophrenic relatives tend to be a little-bit screwy and fill DSM criteria for schizophrenia-like illnesses Arch. Gen. Psych. 50: 527, 1993, J. Nerv. Ment. Dis. 182: 443, 1994; the adoption studies from Scandinavia, where they keep good records: Arch. Gen. Psych. 51: 442, 1994; and the neuroimaging studies show similar hippocampal changes Arch. Gen. Psych. 64: 297, 2007). The three best known loci (and all are clearly real) that confer susceptibility to schizophrenia are DYSBINDIN (DTNBP1), a protein expressed on the glutamine neurons (J. Clin. Invest. 113: 1353, 2004); altered forms run especially with schizophrenic negativism (Am. J. Psych. 162: 1824, 2005; Am. J. Psych. 163: 532, 2006). DISC1 ("disrupted in schizophrenia") and NEUREGULIN-1 (NRG1) are also major loci (update Nature 458: 976, 2009). There are conflicting results as to whether RGS4 is a schizophenia locus or not (Curr. Op. Psyc. 22: 154, 2009 -- reviews all the candidate genes and the postmortem brain chemistry.) Of course, the candidate genes are interconnected in the "schizophrenia susceptibility pathway" (Nat. Med. 17: 470, 2011). This is centered on the glutamine pathway, not the dopamine pathway. Watch for novel agents, but in a disease in which there are actually lost neurons, don't get your hopes up. Same or crazy, your DISC1 alleles seem to have to do with whether you're a socializer or a loner (Arch. Gen. Psych. 66: 134, 2009). KCNH2, a potassium channel: Nat. Med. 15: 448 & 509, 2009. Another locus called PCM1 runs with low orbitofrontal cortical volume and risk of psychosis (Arch. Gen. Psych. 63: 844, 2006). In twins discordant for the disease, magnetic imaging detects distinctive differences in the brains of the schizophrenic twin (NEJM 322: 789 & 842, 1990) which have been confirmed by neuropathologists (Schiz. Res. 3: 295, 1990; Br. Med. J. 305: 327, 1992; South. Med. J. 85: 907, 1992; more on twins J. Nerv. Ment. Dis. 181: 290, 1993). In monozygotic twins who are clearly discordant for schizophrenia, being the crazy twin correlates very strongly with obstetrical complications and/or problems during pregnancy or shortly after birth (Am. J. Psych. 151: 1194, 1994; there was no relation to trauma or to substance abuse; also Am. J. Psych. 157: 196, 2000; pre-eclampsia as a major risk Arch. Gen. Psych. 56: 234, 1999). In the poor nations, where obstetrical catastrophes and infantile brain trauma are more common, the rate of schizophrenia is supposedly no higher, but there's a strong link to these insults (Am. J. Psych. 151: 368, 1994). And prenatal exposure to famine and malnutrition is a strong risk factor: Am. J. Psych. 157: 1170, 2000; strong confirmation JAMA 294: 557, 2005. Currently, there's a lot of interest in obstetrical complications and/or a catastrophe during the second trimester of gestation as the added insult that makes the hereditary trait manifest itself: Br. Med. J. 305: 1256, 1992; Am. J. Psych. 149: 1355, 1992. And so forth. Schizophrenia's gotta be "multifactorial", with etiologies differing from patient to patient, and the psychiatrists had this settled by the early 1990's (Psych. Clin. N.A. 16: 269, 1993; Schiz. Bull. 19: 355, 1993). Also impressive is the finding of a striking increase in sporadic (not familial) schizophrenia following influenza A infection in the fifth month of pregnancy (Lancet 337: 1248, 1991; Arch. Gen. Psych. 47: 869, 1990; Am. J. Med. Genet. 48: 40, 1993). There is a huge excess of schizophrenics born in February and March, and in the city rather than in the country (NEJM 340: 603, 1999). An arcane statistical study of mental and behavioral illnesses that affect primarily the poor (Science 255: 946, 1992) concludes that (in contrast to depression, criminality, and illegal drug abuse), the tendency to schizophrenia causes downward social mobility, and is not the result of bad living conditions.

* Today's neuroleptic-antipsychotic drugs are potent dopamine antagonists, and dopamine-like drugs (notably amphetamine) can make a person act crazy and paranoid (but without the distinctive thought disorder of the schizophrenic). However, the old story about "high dopamine causes schizophrenia, low dopamine causes Parkinsonism, they are two ends of a continuum" just doesn't hold up to today's neuroscience; there are places in the schizophrenic's brain where dopamine is high, and other places where it is low (Am. J. Psych. 148: 1301 & 1474, 1991; striking decrease in D1 receptors in the prefrontal working-memory-processors that in turn correlates with the negative symptoms: Nature 385: 634, 1997). And the newer anti-schizophrenic drugs (clozapine, etc.) are "atypical neuroleptics" that selectively block the subset of dopamine receptors (D4) not involved in the extrapyramidal side effects of the more familiar anti-schizophrenic drugs, as well as 5HT2a receptors. Watch for more about D4 protein, which varies from person to person, and the origins of psychiatric illness: Nature 358: 109 & 149, 1992. D4 allele correlates with novelty-seeking / thrill-seeking (Nat. Genet. 12: 78, 1996). D2 claims flop: Science 264: 1696, 1994. A Beautiful Mind
A Beautiful Mind

* More plausible is the phencyclidine model for schizophrenia (ever see someone go crazy on "angel dust?"), and there's some new evidence that the N-methyl-D-aspartate receptor (blocked by phencyclidine and ketamine) is defective in schizophrenia (Am. J. Psych. 148: 1474, 1991; the ketamine model Arch. Gen. Psych. 51: 199, 1994). Not much more lately, but watch these.

The Caveman's Valentine
The Caveman's
Valentine
De-stigmatize and de-mystify this dread illness -- and explain the hallucinations not as "evidence of being crazy", but as exaggerations of perceptual errors that happen to anyone under stress (J. Nerv. Ment. Dis. 179: 207, 1991). The more the family misunderstands (and therefore criticizes) the patient, the worse the prognosis (Lancet 340: 1007, 1992); your role as educator is extremely important here. Tip: To control "the voices", try one ear plug, or a Walkman, or singing softly to oneself (Br. Med. J. 302: 327, 1991). There was a flap in the early 1990's about neuroleptic treatment causing earlier onset of Alzheimer's in schizophrenics. It's evidently not so (Am. J. Psych. 154: 861, 1997 autopsy studies.) Today there is talk about returning motivated schizophrenics to near-normal function (meaningful work, meaningful friendships) through cognitive-behavioral therapy, support for individuals and families, and other training (JAMA 312: 16, 2014).

CHILDHOOD AUTISM (formerly "childhood schizophrenia", semi-glamorized in the film "Rain Man"; reviews NEJM 347: 302, 2002; Lancet 374: 1627, 2009)

ASPERGER'S ("high functioning autism") is a relatively newly-described "disease", supposedly affecting mostly boys, running in families. Asperger's boys tend to be of normal or high intelligence, strongly focused on single topics (for example, math, chess, computers, a musical instrument, train schedules, pathology, skydiving, flattop haircuts, etc., etc.), are physically clumsy, find other people baffling, but don't commit crimes (well usually, the ones who do are refractory to treatment: Med. Sci. Law. 42: 237, 2002). Speech is rapid and lacks intonation. As kids, they are "little professors." After many social failures during adolescent and young adult life, they tend to withdraw and become odd loners. As teens and adults, they have to work hard to learn to use and read body language and to relate to others. Asperger's seems to be real, and I predict that its study will show something about the wiring of personality. Adults with Asperger's have greatly reduced 5-HT2A receptor density (Brain 125: 1594, 2002), and differences in brain anatomy especially in the frontostriatal connections (Brain 125: 1594, 2002). Properly managed, Asperger's offers a set of unique plusses both for the individual and -- if the interests are useful -- for society.

Of all the patient-care specialties, I am most intrigued by psychiatry. Many other pathologists share my fascination with the life of the mind.

* NOT TESTABLE, BUT WORTH YOUR ATTENTION: The never-ending series of old and new health-and-disease crazes are within the proper scope of any introductory study of pathology. Thankfully, the "repressed memories" business is now history, though thousands of lives were ruined. The craze began in 1985, and ended in 1999. I first mentioned the epidemic in class in 1987, and it proved to be as I described. Any doubts I had were dispelled by Psychoth. Psychosom. 57: 152, 1992 (among 100 kids who saw Dad kill Mom, every one of them remembered it in detail). For a history of this epidemic of iatrogenic disease, see J. Nerv. Ment. Dis. 192: 525, 2004.

* Probably the worst feature of this and the several other phony-child-abuse fiascoes was that they tended to discredit stories of child abuse that are really true, and to transform concern over child abuse into a preoccupation of the right-wing and left-wing lunatic fringes. As usual, the real losers are the children. Litigation (especially "Ramona v. Ramona" in California) has redefined a therapist's duty to third parties, and the "therapists" are being sued like they should be. Medilegal articles: Med. Sci. Law. 39: 112, 1999, Am. J. Psych. 156: 749, 1999; NZ Med. J. 111: 225, 1998; Comp. Psych. 39: 338, 1998; Psych. Serv. 52: 27, 2001. Perhaps the turning point came when Geraldo reversed himself on "enhanced memories" in 1995, declaring it to be "cr_p". In 1999 I was pleased to meet an attorney who told me that he "makes a good living" in a practice devoted almost entirely to suing these therapists, who he tells me in his part of the country are mostly "social conservatives."

      Our greatest foes, and whom we must chiefly combat, are within.

          -- Cervantes, "Don Quixote"

      The scars left from the child's defeat in the fight against irrational authority are to be found at the bottom of every neurosis.

          -- Erich Fromm

      Sexton: I think the whole world's gone mad.
      Death: Uh-uh. It's always been like this. You probably just don't get out enough.

          -- Neil Gaiman, "Death: The High Cost of Living"

      Madness may sound romantic to teenagers or comics readers, but in the end it is just a madness.

          -- Brenda Starr, Reporter

      Confusing fantasy and reality always leads to disaster.

          -- Goethe

      The best grapes do not grow from the best soil.

          -- French wine-maker's proverb

      The different sorts of madness are innumerable.

          -- Avicenna

      You deal with the madmen. All men are mad in some way or other; and inasmuch as you deal discreetly with your madmen, so deal with God's madmen, too -- the rest of the world.

          -- Dr. Abraham Van Helsing (pathologist) to Dr. John Seward (psychiatrist), in Dracula (Bram Stoker)

      MACBETH: Canst thou not minister to a mind diseased,
      Pluck from the memory a rooted sorrow,
      Raze out the written troubles of the brain,
      And with some sweet oblivious antidote
      Cleanse the stuffed bosom of that perilous stuff
      Which weighs upon the heart?

      DOCTOR: Therein the patient
      Must minister to himself.

SANE PSYCHIATRY FOR THE PRIMARY-CARE PHYSICIAN: A lot of the general practice of medicine is psychiatry. Here's how to be a good part-time psychiatrist most of the time. You get more information by asking open-ended questions and inviting the person to talk, but sooner or later you'll need to have things that are worthwhile to say, yourself. You'll need to know how to tell people things that they don't want to hear in a nice way that will not make them stop trying to change. If you actually want to help people with emotional and behavioral problems, focus on reminding them of what they can do, what's still intact (bad for any secondary gains, but good medicine), living in the present, and so forth. Today's psychiatrists give them "behavioral homework", which is simply common sense. Depression etc., both result from negative life events, and causes negative life events (J. Nerv. Ment. Dis. 185: 145, 1997). Cognative-behavior therapy actually changes the PET scan, but in complementary ways to what prozac does (Arch. Gen. Psych. 61: 34, 2003). Keep reminding people of how their screwy behavior and unrealistic attitudes ("faulty core beliefs") hurt them and those around them. Today, the scientifically-minded mental-health community seems to think that "adverse life events in childhood" are not by themselves the cause of mental illness or personality disorders (J. Pers. Disorder. 11: 34, 1997; lots more), though of course growing up in a home full of crazy people will teach behaviors that need to change in adult life. Keep watch on one's own thoughts and try to keep them from going in directions that aren't wholesome ("Zen", if you like -- though every great world-faith gives this good counsel.) Help them learn living and coping skills (i.e., explain to them how to do stuff that the rest of us may take for granted) rather than jabbering on about ("working through") their past traumas and present follies. Spending too much time figuring out exactly caused the problem can enable ongoing, harmful behaviors. Everybody resists adopting new behaviors, and troubled people even more so. Get them to confront their fears as boldly as they can. Know your issues and move forward, with guidance. And don't call this "empowerment", the 1990's grandiose-trendy word; troubled people already have the power to do plenty. To alter your feelings, alter your behavior first -- "fake it 'till you make it." Be strong. Don't do that any more. Don't run back to things that are childish. If you keep doing that, all you'll get is _____. Find pleasure and meaning in some other way.

People growing up in crazy environments acquire behaviors and attitudes that enable their emotional (and even physical) survival there, but that serve them badly in the larger world. Whatever the circumstances, one's emotional ties to one's origins are strong and these people resist changing their self-defeating behaviors. Honor their struggles to survive even as you help them leave this behind. You can help people realize why this is and that they don't need to be locked into it forever.

You may disagree with what a crazy person says, but don't argue; people who are not psychotic will come around as they realize that their thinking is no longer helpful and that they can change their behavior to deal with a world that's saner than their own childhood homes. Don't expect most people ever to understand all that may be obvious to you. But most people can learn new skills. Learn how to use a modest selection of the psychopharmaceutical agents, and use them sensibly; if a medication isn't working in two months, change it or just drop it. Remember the basics: Neurotics are troubled (lots of things upset them), personality-disorder folks are troublesome (they will upset you), and schizophrenia and most of the bad-affect states respond to medication but not to talking. Non-psychotic people with ideas that they recognize as not making sense can usually figure out, with your help, what the obsession stands for, and try to get what they really want by some more realistic route. Marriage counselling is largely the delicate art of getting the two people to listen to, and try to please, one another on a daily basis, and to extend basic human kindness across gender-differences (i.e., a man and a woman can learn to be nice to each other even though they cannot possibly understand each other; the other person isn't acting that way just to be hateful; guide and teach rather than criticize; "the relationship is more important than being right", and so forth). I'm told it's helpful to make an effort to have sex often even if neither partner is interested. When a relationship fails, remind the person of the ways in which the former beloved / the rival are doing the person a favor. There is no physician-patient confidentiality when a human life is in danger. Please remember how unreliable memory is. Especially in the ICU on medication, people may come out "remembering" nightmares that never happened (AJRCCM 177: 976, 2008).

In my lifetime as a student of medicine, I've never seen a disease that was considered "organic" in the 1950's prove to be "psychosomatic", but I've seen the opposite many times (hypertension, asthma, stomach ulcer, inflammatory bowel disease, atopic eczema, blepharospasm, and torticollis are only the beginning; there are even genetic animal models for folks like your instructor who strongly prefer to keep our fingernails super-short). And a good psychiatrist, seeing mental illness as arising from brain, appreciates both the cognitive-insight and the pharmacological therapies (Science 275: 1586, 1997).

INTERPERSONAL THERAPY, a common-sense "innovation", was the 1990's term for psychotherapy for the financially-responsible era, where things have to be cheap and have to work. The focus was on improving people's abilities to relate to others, no matter what the circumstances. (1) Deal with any grief and loss issues, emphasizing what's still intact; (2) Solve interpersonal role disparities (i.e., conflicts over who is supposed to do what); (3) Deal with role transitions (that was then, this is now, focus on the future rather than the past); (4) Teach them interpersonal skills and make them practice between sessions. You can't make somebody love you. Talk about the other person's interests, and be a diplomat. Relationships are more important than being right. If you want a relationship to be successful, try to figure out what the other person wants, and then try to provide it. They also (5) learn to watch for goofy "I can't because..." thinking, and other unhelpful thoughts, that prevent them from doing the things they need or want to do, and having them report each week. It turns out that simply letting your patients learn and practice these skills from an internet site is more effective than talking to them in a nurturing and supportive way: Br. Med. J. 328: 265, 2004. The sites were Blue Pages and Mood Gym. Here is another site I've found helpful (follow the links). Update for online CBT: BMJ 344: e2598, 2012.

COGNITIVE-BEHAVIORAL THERAPY is now the model for psychotherapy for people capable of insight. The focus is on education, facing fears, and learning skills.

NON-EVIDENCE-BASED PSYCHOTHERAPY (often not even physician-supervised) remains one of the great causes of ill-health in the Western world. Providers are usually well-intentioned and it's a good way of making a living -- essentially no knowledge or real education is required. The "repressed memories" fraud has ruined tens of thousands of families; it's still widespread. The "facilitated communication" fraud sent totally innocent persons to prison, as well as giving false hope to families of the extremely sick. Generally, the "therapists" focus on the past rather than the present, offer pity and ideology rather than the kick-in-the-butt we all need from time to time, and reinforce their victims' sense of helplessness, entitlement and/or victimhood -- which keeps them coming back. Call me unspiritual if you want -- you'll see the tremendous harm this does when you're in practice. Whenever anybody says, "Therapy taught me to blame...." or "After years of talking about my past with my therapist....", be aware you're dealing with someone who has been done a grave disservice.

* Physicians respect the religious beliefs of each patient, as long as nobody's getting hurt in a big way; these beliefs are a good topic for discussion. If "religion is what deals with matters of ultimate concern", one need not believe or even care about the "supernatural / paranormal" for "faith to be important." Totally sane people often report experiences with the paranormal (whatever that is). When I was an intern, a group of 15 housestaffers at lunch got into a discussion of out-of-body experience, who among us had experienced it personally, and what you told the patients who came in all worried after experiencing it; we decided it was "normal but something we don't understand". Unlike many "spontaneous" out-of-body experiences, the one's I've read about from the experimental lab (for example NEJM 357: 1829, 2007) do not involve autoscopy or the ability to move one's frame of perception. And crazy people often report experiences with the paranormal (whatever that is; the crazies' experiences are much more diverse and atypical than the "normals"). No matter what your faith background, if you're interested in this sort of thing you may enjoy "The Interior Castle", by Teresa of Avila. She was a spunky, brilliant, non-dogmatic and often-hilarious writer from a Jewish-Muslim-Christian background. Her book, written for both cloistered and in-the-world folks, deals with trying to tell "the real thing" from dreams, hallucinations, big egos, fakery, spiritual evil, and mental illness.

OTHER NON-NEOPLASTIC NERVOUS SYSTEM DISEASES

DEMYELINATING DISEASES

Inflammatory and Demyelinating Disease
Click to see the images
Duke

{01428} multiple sclerosis, myelin stain of white matter (note areas where the blue-staining myelin is lost)
{31776} multiple sclerosis
{31779} multiple sclerosis
{31797} multiple sclerosis
{31994} multiple sclerosis
{00527} demyelination in the spinal cord

Multiple Sclerosis
Pittsburgh Illustrated Case

Multiple sclerosis
Autopsy brain
KU Collection

Multiple sclerosis
Pittsburgh Pathology Cases

Multiple Sclerosis
Tom Demark's Site

DEVIC'S NEUROMYELITIS OPTICA is an aggressive demyelinating disease with retrobulbar neuritis and large lesions in the spinal cord (i.e., blindness and paralysis). The cause is an IgG antibody (NMO-Ig) directed against aquaporin-4, on the feet of astrocytes (Arch. Neuro. 63: 964 & 1398, 2006), and this is now defining for the disease (Neurology 66: 1485, 2006 -- well, now there's a paraneoplastic syndrome Arch. Neuro. 65: 629, 2008).

ACUTE DISSEMINATED ENCEPHALOMYELITIS ("post-infectious encephalomyelitis"; "post-vaccinial encephalomyelitis") is a rare disease that tends to follow (by a few days to 2 weeks) one of the "childhood diseases" (infamously measles and even worse the old smallpox and neural-based rabies vaccines) or one of the old-fashioned immunizations with lots of impurities (especially rabies). There is altered sensorium and/or movement, and both gray and white matter lesions and/or a very large lesion. Coma rapidly develops; many patients die, but most recover with little or no residual difficulty. In fatal cases, there is striking demyelinization around the blood vessels (much more than in common multiple sclerosis -- Brain 133: 333, 2010). See Ann. Neurol. 33: 18, 1993 (by Dr. Kepes at K.U.) Criteria for diagnosis are still under development: Neurology 68(16S2): S23, 2007.

Demyelination in multiple sclerosis

WebPath Photo

Demyelination in multiple sclerosis

WebPath Photo

Acute necrotizing encephalopathy of childhood

Yutaka Tsutsumi MD

{31988} central pontine myelinolysis

OTHER METABOLIC DISEASES OF THE CNS

{17659} superior vermal atrophy

Purkinje cell loss
Alcoholic
KCUMB Team

Superior (anterior) vermal atrophy

WebPath Photo

{31986} Marchiafava-Bignami

{31763} Wernicke's
{31985} Wernicke's
{31985} Wernicke's

Wernicke's
From Chile
In Spanish

Wernicke's

WebPath Photo

{31984} methyl alcohol poisoning. Not a pretty sight.

{31751} carbon monoxide after-effects
{18751} carbon monoxide after-effects
{31742} carbon monoxide after-effects

{00206} fatal arsenic poisoning
{00209} fatal arsenic poisoning

{31803} metachromatic leukodystrophy patient
{31807} metachromatic leukodystrophy, gross
{31981} metachromatic leukodystrophy, micro. The blue dye stains the metachromatic stuff pink.

{32004} Krabbe's globoid histiocytes

{01909} radiation necrosis

CNS TUMORS

Brain Tumors I
From Chile
In Spanish

Brain Tumors II
From Chile
In Spanish

Brain Tumors III
From Chile
In Spanish

INTRODUCTION

GLIOMAS

{01497} astrocytoma
{01501} astrocytoma
{01503} astrocytoma
{01518} astrocytoma
{01531} astrocytoma
{15706} astrocytoma
{01504} astrocytoma
{01506} astrocytoma
{01507} astrocytoma

Astrocytoma
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Astrocytoma
Pittsburgh Pathology Cases

Astrocytoma
"Cystic" / "Juvenile"
WebPath Photo

Glioma
Don't worry about what kind.
WebPath Photo

Brainstem glioma
Don't worry about what kind.
WebPath Photo

Brainstem glioma
Don't worry about what kind.
WebPath Photo

Glioma
Don't worry about what kind.
WebPath Photo

Well-differentiated astrocytoma

WebPath Photo

Astrocytoma

WebPath Photo

{01575} glioblastoma
{01576} glioblastoma, butterfly

Butterfly glioma

KU Collection

Glioblastoma
Australian Pathology Museum
High-tech gross photos

Glioblastoma
Coronal section
Wikimedia Commons

{01582} glioblastoma
{01584} glioblastoma, dead stuff
{01585} glioblastoma
{01587} glioblastoma, gemistocytes
{01596} glioblastoma, monster cells
{17721} glioblastoma

Glioblastoma

WebPath Photo

Glioblastoma

WebPath Photo

Glioblastoma

WebPath Photo

Glioblastoma
Pittsburgh Pathology Cases

Gliosarcoma
Pittsburgh Pathology Cases

{01542} juvenile pilocytic astrocytoma

Pilocytic astrocytoma
Pittsburgh Pathology Cases

Pilocytic astrocytoma
Pittsburgh Pathology Cases

Pilocytic astrocytoma
Lacking Rosenthal fibers
Pittsburgh Pathology Cases

Juvenile Pilocytic Astrocytoma
Pittsburgh Illustrated Case

{01618} oligodendroglioma
{01620} oligodendroglioma
{01624} oligodendroglioma with calcifications (shown reddish-purple here)
{01626} oligodendroglioma with calcifications

{01642} ependymoma (trust me)
{15699} ependymoma (trust me)

{01650} ependymoma
{01654} ependymoma
{01656} ependymoma, blepharoplasts

Anaplastic ependymoma
Pittsburgh Pathology Cases

Ependymoma

WebPath Photo

Ependymoma

WebPath Photo

Ependymoma

WebPath Photo

{01665} * myxopapillary ependymoma
{01666} * myxopapillary ependymoma

Myxopapillary ependymoma

WebPath Photo

Melanotic choroid plexus papilloma
Pittsburgh Pathology Cases

Choroid plexus carcinoma
Pittsburgh Pathology Cases

NEURONAL TUMORS


{31933} medulloblastoma, cord
{01677} medulloblastoma
{01686} medulloblastoma
{01687} medulloblastoma (cord and dura)
{18761} medulloblastoma

Medulloblastoma

KU Collection

PNET of brain
Pittsburgh Pathology Cases

Medulloblastoma

WebPath Photo

Medulloblastoma

WebPath Photo

Meningioma

WebPath Photo

Dysembryoplastic neuroepithelial tumor
Pittsburgh Pathology Cases

Polar spongioblastoma
Cordouroy tumor
Pittsburgh Pathology Cases

Neurocytoma
Pittsburgh Pathology Cases

MENINGIOMAS (Lancet 363: 1535, 2004)

Meningioma
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

{00221} meningioma, gross
{31996} meningioma
{00224} meningioma, micro
{09459} meningioma, with psammoma bodies
{09460} meningioma
{09462} meningioma

Meningioma
Pittsburgh Pathology Cases

Meningioma

WebPath Photo

Meningioma

WebPath Photo

Meningioma

WebPath Photo

Meningioma

WebPath Photo

Resected meningioma

WebPath Photo

Meningioma
Pittsburg Illustrated Case

Meningioma

WebPath Photo

Meningioma

WebPath Photo

Meningioangiomatosis
Pittsburgh Pathology Cases

Fibrous tumor of the meninges
Pittsburgh Pathology Cases

OTHER BRAIN TUMORS

Epstein-Barr brain lymphoma

Yutaka Tsutsumi MD

CNS Lymphoma
Biopsy
Wikimedia Commons

{01878} hemangioblastoma
{01882} hemangioblastoma
{01884} hemangioblastoma

{01897} chordoma (note the resemblance to primitive cartilage)
{01899} chordoma
{01906} chordoma ("bubble cells")

Coccygeal chordoma
Pittsburgh Pathology Cases

{01855} craniopharyngioma
{01858} craniopharyngioma
{01860} craniopharyngioma
{01861} craniopharyngioma
{10962} craniopharyngioma
{01857} craniopharyngioma cyst fluid

Hypothalamic hamartoma
Pittsburgh Pathology Cases

Craniopharyngioma

KU Collection

Craniopharyngioma
Notice the benign squamous pearl
KU Collection

{09442} melanoma
{29393} breast cancer metastasis

Metastatic lung cancer

WebPath Photo

Paraganglioma of the filum terminale
Pittsburgh Pathology Cases

PERIPHERAL NERVE

Peripheral Nerve Exhibit
Virtual Pathology Museum
University of Connecticut

Hydroxychloroquine neuropathy
Pittsburgh Pathology Cases

Acute motor axonal neuropathy
Pittsburgh Pathology Cases

Leprosy in the nerves

Yutaka Tsutsumi MD

{01846} schwannoma
{01849} schwannoma
{15694} eighth-nerve tumor

Peripheral Nerve Tumors
From Chile
In Spanish

Trigeminofacial malignant epithelioid schwannoma
Pittsburgh Pathology Cases

Schwannoma

WebPath Photo

Acoustic "neuroma"

WebPath Photo

Two phases of a schwannoma

WebPath Photo

Schwannoma
Looks like a generic benign spindle-cell tumor.
WebPath Photo

Acoustic neuroma
Pittsburgh Pathology Cases

Infarct with petechiae

WebPath Photo

Schwannoma
WebPath Photo

schwannoma
WebPath Photo

Click on the acoustic neuroma!
Gross specimen
WebPath Photo

Click on the acoustic neuromas
Scan.
WebPath Photo

Malignant Schwannoma
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Neurilemmoma (Schwannoma)
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

{11031} eighth-nerve tumor
{15693} eighth-nerve tumor

{01843} von Recklinghausen's of cauda equina
{01854} neurofibroma, trust me

Paraganglioma
Pittsburgh Pathology Cases

How many psychiatrists does it take to screw in a light bulb?
What do YOU think?

MIND AND BRAIN

{18601}

[Gilgamesh, the warrior-king, has left his kingdom to find an answer for death. On his journey, he meets a barmaid. She tells him:]

Gilgamesh, where are you hurrying to? You will never find the answer for which you are looking. When the gods created humankind, they allotted us to death, but life they retained in their own keeping. As for you, Gilgamesh, fill your belly with good things; day and night, night and day, dance and be merry, feast and rejoice. Let your clothes be fresh, bathe yourself in water, cherish the little child that holds your hand, and make your wife happy in your embrace; for this too is the lot of humankind.

                  -- 2600 B.C.

[Gilgamesh finally found his answer, though it was not the one he was looking for. The entire conversation between Gilgamesh and the barmaid has been repeated billions of times since.]

After sixty years on this planet, I have concluded (for now) that what we call "a person" is fundamentally a spiritual process. After reviewing what evidence I could find, it seems most reasonable to me to think that we inhabit our human bodies and human brains (the products of Darwin's world) only temporarily. This doesn't bother me as a man of science, since I'm impressed by anecdotal accounts of phenomena that do not fit the familiar scientific paradigms but that have resisted systematic study. Relativity and quantum theory have satisfied me that the universe is stranger than we think, or even than we can think, even before we consider the riddle of consciousness. Considering spirit and body to be distinct helps me deal (though not in full) with questions of religious faith in Darwin's world. Why spirit and body have been joined remains the great question, which I will pass along to you. Like Socrates, I've heard it whispered that the answer involves "Love" with a capital "L".

Humankind began performing ceremonial burials at least 50,000 years ago, and we may assume that we've been contemplating our own mortality at least since that time. While discovering the relationship of mind and brain would seem a key to determining the true nature of human beings, there seems to be no easy answer. Philosophers regard this as a key problem, and (to my knowledge) all the great world-faiths allow considerable room for discussion.

The mind and the body (brain) might be related in any of several ways. This is a short survey of the principal positions; my amateur effort made it past a philosophy professor when I first prepared it in 1984.

INTERACTIONISM describes the mind and brain are distinct and equally real; during life, the mind effects changes in the material brain (presumably by telekinesis). Philosopher Karl Popper and neurosurgeon Sir John Eccles currently (1984) maintain this view. Popper says "the mind plays on the brain as the pianist plays on the keyboard". Parapsychology has failed to demonstrate any such force to most people's satisfaction. Neuroscience hasn't found it, either (nor can I imagine how we could, at present). Physical causation is easily demonstrated in our world, but no case of non-physical causation been demonstrated. (But psychologists do continue to study mind as if it obeyed causal laws.) Of course, interactionism probably violates the laws of conservation of energy, momentum, and so forth. Niels Bohr (of the Bohr atom and much more) pointed out that the microprocesses of the brain are of an order of magnitude where quantum indeterminacy should make a difference. Anyway, the laws of physics have never really been tested for neurons. Most recently (late 1990's and after), a significant minority opinion in science is "quantum mind", the best-known of several proponents being major-league quantum physicist Roger Penrose. This is my position at least for now. An interactionist may believe (but does not have to believe) that all mental events are accompanied by physical change in the brain. NOTE: Some people (especially those interested in parapsychology) talk about "a different kind of matter", unknown to conventional science, which forms a second body for spirits, the dead, etc. (Popularized in Ghost.... and there are some interesting anecdotes.... but no convincing demonstrations have been forthcoming from the parapsychologists, despite decades of trying.) Dante (Purg. canto 25) describes how ontogeny recapitulates phylogeny (this will surprise those of you who believe that the medieval mindset was anti-science -- that's simply wrong) and follows this discussion with an account of interactionism (following Aquinas, Dante believed that God creates and infuses the soul when, and only when, the brain is prepared). After death, a new body is created from the matter of the spiritual realms. Philosophically, this is unrelated to interactionism (and not so interesting); the problems of how "mind" can be related to "subtle matter" are as difficult as defining how mind and brain interact.

PARALLELISM regards both mind and matter as closed systems, each with states determined by its own laws. However, they have been set in motion so that, in the course of time, every change in one corresponds to a change in the other. Leibnitz (co-discoverer of calculus) compared mind and brain to two clocks set in motion simultaneously. Though they always show the same hour, neither influences the other. I don't know anybody who believes this nowadays, or why anybody would.

EPIPHENOMENALISM sees mind as real and different from brain, but as dependent on brain and exerting no causality it. I suspect this is the practical view of most medical doctors.

MATERIALISM sees matter as possessing an ontological priority to mind. (Brain is ultimately "more real than" mind.) The assumption is that as neuroscience advances, it will become possible to explain all behavior without postulating mental causes. Interactionists assume the opposite, of course. RADICAL BEHAVIORISM, as explained by B.F. Skinner, defines behavior as the set of observable responses of an organism to stimuli. Skinner was unconcerned with non-observable mental states, denied that mental states are causes, are real, etc. Most of us, however, find being conscious interesting. For specialists: REDUCTIVE MATERIALISM describes the mental as no different from the physical. EMERGENTIST MATERIALISM views mental events as a special set, though a distinguished set, of brain states. ELIMINATIVE MATERIALISM denies the reality of mental states at all. LOGICAL BEHAVIORISM ddefined mental states in terms of dispositions to certain behaviors (although it might be hard to define these behaviors completely). It is hard for logical behaviorists to explain how one mental state causes another, or how a mental state can result in no behavior. CENTRAL-STATE IDENTITY THEORY views mental events as real and as causes, but they are identical with microstates of the brain. Some theorists claim (and I have no idea why) that all the mental events that could possibly exist must correspond to neuronal states. Others claim only that all known mental events correspond to neuronal states. The former theorists deny that a machine or a disembodied spirit or a Martian could think; the latter theorists consider this possible.

FUNCTIONALISM, based on information theory and work in artificial intelligence, seeks to avoid the difficulties of both interactionism and materialism. This view compares mind to computer software, brain to computer hardware. The "personal self" is the self-organizing portion of the program within the computer of the brain. Thus, it is meaningful to talk about mind affecting brain, whether or not we believe in the ultimate physical determinacy of the brain. The mind obeys its own set of laws. Exactly what "consciousness" has to do with all of this is unclear. Most of us do not think "consciousness" is the same as a computer program's ability to edit itself. Functionalists do not care whether all mental events are related to changes in neurons, or whether the same organization might be operative in other systems (machines, disembodied spirits, etc.) A personal after-life requires only that the same software be run on a different machine. David MacKay thinks this is quite possible; Roger Sperry is pessimistic....

Further reading for physicians on mind and body:

The grave is the first stage of the journey into eternity. -- Muhammad

NOTE: Studying for the licensure examination in basic sciences? Around this time, students often ask "What's the best way to review for 'National Boards' in Pathology"? The answer is, "Whatever book or set of notes you can read with comfort, comprehension, and interest." This might be anything from re-reading "Big Robbins" (generally favored by students who feel stronger), the "ERF handouts" or a review book, to various quiz books and quiz banks (generally favored by students who feel too weak to remain focused on a text; but be sure you look up why answers are right or wrong!). Only you can tell what feels right for you.

* ADVANCE DIRECTIVES

    Unless you are VERY confident that your family knows what you want, or that you will want whatever they decide for you, and that they are MORE comfortable making decisions than letting you be responsible for them... prepare your advance directive now.

    Mine has been essentially the same since 1973. Now that I've hit fifty years of age, make that percentage odds business equal to my chronolocial age.

    In case of serious disease or serious injury leaving me with less than a 50% chance of a return to meaningful life, institute no therapy except for hygiene and relief of pain and respiratory distress. If intravenous, endotracheal, or stomach lines are already in place, you must remove them. "Meaningful existence" means able to say, write, sign, or fingerspell the Lord's Prayer at the right time in a church service. This is a carefully considered definition that since the 1970s still meets every contingency of which I can think. Specifically, in case of an acute subarachnoid hemorrhage with coma, do not initiate any life-maintaining intervention. Administer analgesics and other comfort measures only. When there is less than a 50% chance of a return to meaningful life, allow me to die of dehydration if active euthanasia or death by organ donation is not feasible. I have experienced prerenal azotemia with BUN near 100 and it is not really so unpleasant. [I added this in 1977.] If I have less than a 50% chance of returning to work, or if I am fully retired, do not administer antibiotics. In an unwitnessed cardiac arrest or if I am fully retired, do not begin CPR or continue it if begun. In all circumstances, let the above serve as a guide to my thinking.

    On Annunciation Day 2010, after reading the American Heart Association statistics in Crit. Care Med. 38: 101, 2010, I had "No CPR" tattooed on my chest. This is something I had been wanting to do since medical school. The only exception would be open-chest surgery, as I am told is customary in "DNR" patients.

    I'm on record -- commenting on the very expensive chemotherapeutic agents that buy a few months -- that I'd decline any intervention at a cost more than $5k/month gained. I have previously remarked that as an invalid or inactive person not able to contribute further to those around me, it would be unconscionable for me to allow other living things to be killed to feed me. I have given myself out to be a mainstream Christian throughout my entire adult life. All spiritual values proceed from relationships among people -- in fact, I believe that even the Good Lord is a community of three Persons though this is a doctrine that I do not pretend to understand fully. Without the ability to act in relationships, my natural life has no value. My body goes for anatomic dissection and/or my organs are to go for transplantation as appropriate for my manner of death. You may consider me legally dead when I have no reflexes off medication. Although I am a gentle soul and have actually helped anti-death penalty activists, I have never opposed the death penalty itself. Let this be remembered in the unlikely event that I am murdered. My last will (2004) is in the possession of my house buddy, executor, and principal heir Lewis Burton. Memorial services follow the rite of the Episcopal Church, with white vestments please, as was the custom among the ancient Christians. Keep the tone light and humorous as I would have done, and remember that "All Creatures of our God and King" was my favorite hymn. There's a video of my reading Plato's "Phaedo" somewhere that people would enjoy on this occasion. After dissection (anatomy class, autopsy, or organ donation plus autopsy), my body is to be cremated and my ashes are to be scattered by other skydivers as per our custom. I expressly forbid burial under any circumstances, though keeping any interesting pathology specimens around for teaching is strongly encouraged. The atoms of which my body was composed never belonged to me and do not belong to my heirs, but to the Good Lord, and He deserves them returned to His creation. Have a nice day.

*SLICE OF LIFE REVIEW

{01152} brain, immature but normal
{01215} oligodendrocyte, normal
{01221} microglia, resting in normal cortex
{01222} dorsal root ganglion, normal
{01228} eye, normal
{01230} frontal lobe, normal cerebral cortex
{01231} occipital lobe, normal cerebral cortex
{01239} pineal gland, normal
{01273} neuron, normal
{01351} neuron, normal with glia
{01356} astrocytes, foot processes on capillaries
{01408} oligodendrocyte, normal nerve tracts
{01409} oligodendrocyte, normal
{01410} oligodendrocyte, normal
{01435} myelin, normal
{03695} transverse sinus ligament of marshall, normal
{04442} leptomeninges, normal over cortex
{04727} cerebellopontine angle, normal
{07194} trauma chemical injury, brain normal and carbon monoxide 7-4-112
{11369} pons, normal
{11402} vertebral basilar artery, normal
{11405} vertebral basilar artery, normal
{11408} vertebral basilar artery, normal
{12833} internal carotid artery, normal anatomy
{12836} internal carotid artery, normal anatomy
{12839} internal carotid artery, normal anatomy
{01209} neurons
{01224} {01226} {01228} cerebellum
{14597} microglia, normal
{10598} microglia, normal
{14599} microglia, normal
{14600} microglia, normal
{14601} peripheral nerve, normal
{14602} peripheral nerve, normal
{14603} peripheral nerve, normal
{14604} peripheral nerve, normal
{14605} schwann cells, normal
{14606} schwann cells, normal
{14608} nerve, normal
{15061} pineal gland, brain sand
{15062} pineal gland, brain sand
{15063} pineal gland, brain sand
{15064} pineal gland, brain sand
{15146} neuron, nissl substance (rer)
{15153} pyramidal cell, cerebral cortex
{15156} cerebellum, immature
{15157} neuron in a brain stem nucleus, #31 arrow on neuron cell body
{15158} choroid plexus, fetal brain of animal #31
{15159} dorsal root ganglion, #32
{15161} dorsal root ganglion, #32 arrow on bipolar cell
{15165} nerve, normal
{15314} pacinian corpuscle, finger tip
{17663} wernicke's encephalopathy, comparison with normal *mammillary bodies
{17859} brain, normal
{17860} brain, normal
{17861} brain, normal
{17862} brain, normal
{17863} brain, normal
{17864} brain, normal
{17865} brain, normal
{17866} brain, normal
{17872} infarct, brain frontal lobe looks normal
{19970} brain 32 weeks, normal
{19971} brain 32 weeks, normal
{19990} pineal gland with cyst, normal
{20155} brain, normal
{20713} pineal gland, brain sand
{20714} cochlea, normal
{20715} ciliary process, normal eye
{20716} optic nerve head and retina, normal
{20767} cerebral cortex of newborn, arrows in large cells layer v; note columnar arrangement
{20768} pyramidal cell in developing cortex, pial surface is toward bottom
{20769} choroid plexus, newborn
{20770} dorsal root ganglion, reduced silver
{20771} dorsal root ganglion, reduced silver
{20774} perineurium, transverse
{20775} nerve, longitudinal section
{25686} white matter, normal brain
{25687} cerebral cortex, normal
{30242} cranial nerves, normal
{30243} cranial nerves, normal
{30985} internal capsule and corona radiata, normal 1/10
{31018} cerebral cortex, normal
{31024} cerebral cortex, normal
{31027} skull, norm`l
{31030} skull, normal
{31045} posterior fossa, normal anatomy
{31048} vestibulocochlear nerve in cp angle, normal
{31051} cisterna magna and pons, normal brain
{31111} tentorial notch contents, normal
{31174} thalamus, normal
{31210} brain, normal
{31219} brain, normal
{31243} brain, normal
{31330} sella turcica, normal
{31339} brain, normal
{31354} brain, normal
{31358} skull, normal plain anatomy
{31361} skull, normal plain anatomy
{31364} frontal sinus, normal plain anatomy
{31370} lumbar spine anatomy, normal
{31373} lumbar spine anatomy, normal
{31376} lumbar spine anatomy, normal
{31385} lumbar spine anatomy, normal
{31388} lumbar spine anatomy, normal
{31418} internal carotid artery anatomy, normal
{31421} circle of willis anatomy, normal
{31433} venous drainage, brain normal anatomy
{31445} straight sinus joining torcula or * Conflnormal venous anatomy - with arrows
{31451} middle cerebral artery, normal anatomy
{31454} middle cerebral artery, normal anatomy
{31460} internal carotid artery anatomy, normal
{31463} vertebral basilar circulation, normal
{31466} basilar artery, normal
{31469} posterior cerebral artery, normal
{31475} vertebral basilar circulation, normal
{31490} vertebral basilar circulation, normal
{31511} spinal cord, normal
{31517} spinal cord, normal
{31575} down's syndrome, cerebral atrophy/normal
{31583} substantia nigra midbrain, normal
{31589} substantia nigra, normal confusing because melanin isn't black
{31631} caudate, normal histology
{31640} neuron and astrocytes in putamen, normal
{31642} cerebellum, normal & disrupted
{31760} wernicke's encephalopathy, normal mammillary body for comparison
{32912} cavum septum pellucidum, normal
{34331} dorsal root ganglion, normal
{34334} dorsal root ganglion, normal
{34337} dorsal root ganglion, normal
{35819} pineal, normal
{35822} pineal, normal
{35837} area postrema, normal
{35861} cerebral cortex, normal
{35870} neuron, normal cells in caudate
{35876} locus ceruleus, normal
{35915} purkinje cell, normal
{37284} Alzheimer's disease, normal neuron
{37335} caudate, normal for comparison
{37338} Huntington's disease, normal brain on top for comparison
{37500} germinal matrix, normal
{37513} germinal matrix, normal
{37515} germinal matrix, normal
{37609} brain, normal
{37665} brain, normal for comparison
{37678} aqueduct, normal midbrain
{37679} aqueduct, normal
{37680} aqueduct, normal
{40144} brain, normal
{49534} * Cerebellum, normal
{53716} EEG, normal

New visitors to www.pathguy.com
reset Jan. 30, 2005:

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Ed says, "This world would be a sorry place if people like me who call ourselves Christians didn't try to act as good as other good people ." Prayer Request

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Teaching Pathology

Pathological Chess


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