books book reviews

books on brain diseases

reviewed by T. Nelson


Infections of the Central Nervous System, 4e

by WM Scheld, RJ Whitley, CM Marra, eds
Wolters Kluwer Health, 2014, 907 pages

Reviewed by T. Nelson

Most people know that viruses, bacteria, and other pathogens cause some of the most dreaded diseases known to humanity: encephalitis, meningitis, poliomy­elitis, Creutzfeldt-Jakob / mad cow disease, tertiary syphilis, and many others. What they may not know is that even ordinary childhood diseases can also be deadly to the brain.

Take measles, for example. Measles isn't just a harmless rash. It attacks the body in three different places, one for each of the three proteins, called receptors, that bind to the measles virus: the epithelial cells in the lung, where the infection starts (nectin 4); the immune cells, which transport the virus throughout the body (SLAM protein); and the brain (CD46).

The rash in measles is caused by the body's immune cells infiltrating to sites of measles virus infection in the skin. Rashes are good; they indicate that the body is fighting the virus. In immuno­compromised patients, that rash never occurs, and a deadly brain infection called MIBE, or measles inclusion body encephalitis, results. Some children with normal immune systems get SSPE (subacute sclerosing panenceph­alitis), which only shows up 3–12 years after infection. Older ones get a more acute complication called ADEM (acute disseminated encephalo­myelitis), an autoimmune demyelinating disease (like MS) that starts two weeks after infection. So what we always thought was a simple rash is actually very complicated, and it can have lifelong, sometimes fatal, consequences.

Rubella, or German measles, is even nastier. Like regular measles, it can cause ADEM, but when a pregnant mother gets rubella, there is a 50:50 chance that the baby will have serious neurological disorders including microcephaly, mental retardation, and autism. This is called congenital rubella syndrome.

Vaccination is highly effective, but not without risks. One risk is Guillain-Barré syndrome (GBS), an ascending paralysis with paresthesia (prickling sensation), which can be caused by an immune reaction to a viral or bacterial infection, or by a vaccination. Some researchers now suspect that Franklin D Roosevelt had GBS and not polio as previously believed.

But how do virus particles, which are quite big, get past the blood-brain barrier and into the brain in the first place? Answer: they hitch a ride in immune cells, the very T cells that are supposed to protect us.

During an infection, T cells fill a small channel in the Virchow-Robin space, which is a small space that surrounds the blood vessels. This Virchow-Robin space acts as a staging area where the immune cells differentiate and gird themselves, like warriors before the battle, before entering the brain. The immune cells have the power to inflict lethal injury to any infected cell, but can also go wildly out of control. Often, the immune response does far more damage to the brain than the virus itself.

Many types of pathogens affect the brain, like herpes simplex virus (HSV-1 and HSV-2), varicella virus (which causes chickenpox and shingles), neuroborreliosis, a spirochete bacterium that causes the dreaded tick-borne Lyme disease, and parasitic amoebic infections, which have killed many unwary swimmers in the southern USA. Even viruses once thought to be relatively harmless, like HSV-1, HHV-6 and HHV-7, are deadly in the brain, and are now suspected of triggering Alzheimer's disease decades after the initial infection.

This textbook is more disease-oriented and more gripping than general textbooks like Fields Virology and White & Fenner's Medical Virology. If cost and bulk are issues, an eBook (also provided with the hardcover version) is available.

Later chapters on bacteria are a little repetitive,but it's clearly one of the most densely fact-filled books on brain diseases I've come across recently. It has color photos and many MRI images. If you've got some background in immunology and basic neurology, it really is a book that will keep you up at night, if not from scientific fascination. then from sheer hypo­chond­riacal anxiety. I think I'm getting Lyme disease already. And I can feel my polymorpho­nuclear leukocytes starting to get clogged up. Oh yes. There they go.

Fans in search of new longest words will be interested in reading about meningoen­cephalo­myelo­radiculopathy. I wanted to use that as the name of my computer, but it turns out Windows only allows fifteen characters. So now I am depressed.

nov 17, 2019. last edited dec 12, 2019


Neuroinflammation and Schizophrenia

by GM Khandaker, U Meyer, PB Jones, eds.
Springer, 2020, 244 pages

Reviewed by T. Nelson

Collection of 11 scientific articles on inflammation as a possible cause of schizophrenia. The emphasis is on the molecular biology, with little information on the disease agents that induce inflammation, or on the symptoms or treatment of schizophrenia itself. Some of the articles are full of interesting scientific ideas, and some are long lists of results from various papers, most of which contradict each other.

Schizophrenia is increasingly considered to be an autoimmune disease, but the evidence is not yet conclusive. See here for a discussion of the topic.

mar 08, 2020


Escourolle & Poirier's Manual of Basic Neuropathology, 6e

by F. Gray, C. Duyckaerts, U. de Girolami, eds
Oxford University Press, 2019, 443 pages

Reviewed by T. Nelson

This one covers brain infections in 1/25 as many pages as the book at left, and in correspondingly less detail. The same is true for the other chapters. Except for the chapter on hereditary metabolic diseases, it is purely descriptive: there's almost no molecular biology and little discussion of pathogenic mechanisms. And there are no citations to the medical literature at all.

So, why read it? Because (1) lots of of us have gaps in our knowledge; (2) you will get an up-to-date overview on diseases every person should know about; (3) it's very concise and accurate; and (4) Untold Stories of the ER is still in reruns. If nothing else, it will teach you what can happen to your brain in a car accident or if you get a subarachnoid hemorrhage or, heaven forbid, one of the hereditary mitochondrial encephalo­myelo­myopathies like Leigh disease, Kearns-Sayre syndrome, or Alpers syndrome.

Sample text:

Though often referred to as congenital, saccular aneurysms are almost never encountered in children or infants. . . . There is an increased incidence of intracerebral aneurysms in some systemic diseases, including autosomal dominant polycystic kidney disease, Ehlers-Danlos syndromes, pseudoxanthoma elasticum, fibromuscular dysplasia, sickle cell disease, and coarctation of the aorta. Their association with Marfan syndrome has been questioned by recent data. [p.86]

That said, this is a pure pathology book. Its sole purpose is to help the beginning neuropathologist figure out how the patient died. It assumes a knowledge of brain anatomy; a non-physician will want a real medical dictionary (the Android ones, even Stedman's, are convenient but mostly useless, even at this level). It won't help you diagnose anything: there are no MRIs or CT scans here, and almost no discussion of symptoms or treatment, only high resolution color photographs of clinical slides and spectacularly diseased brains. These are not for the squeamish. You will learn about such things as suppurative intracranial phlebitis, purulent necrosis, and pyocephalus. If you don't know what those terms mean, don't look them up.

Carbon monoxide poisoning doesn't just turn the entire brain bright red. Sometimes the patient seems to recover, but one to four weeks later gets personality changes, dementia, psychosis, and necrosis of the globus pallidus, known as Grinker's myelinopathy, which produces neuropsychiatric symptoms and parkinsonism.

Chapters include tumors, vascular pathology, infections, prions, demyelinating disorders, neurodegenerative diseases, acquired CNS diseases, hereditary metabolic disorders, and congenital malformations. There are also chapters on skeletal muscle, peripheral nerves, and the pituitary.

jan 18, 2020


Post-Traumatic Stress Disorder

by CB Nemeroff, CR Marmar, eds.
Oxford University Press, 2018, 816 pages

Reviewed by T. Nelson

There's only one book out there that discusses PTSD in terms of neuropathology and molecular biology, and this is it. It's a collection of 41 articles in five sections: history, epidemiology, pathophysiology, risk factors, and treatment.

The editors didn't do their job on this one. Many of the articles repeat each other. Half use numbered superscripts and half use long strings of APA-style references that make it a chore to read. The general idea is that PTSD and TBI are so strongly associated with each other and with other comorbidities like depression and drug use that it's hard to determine cause and effect. About half the authors are psychologists, so there are not just chapters on veterans but also on children, low-income countries, women, and LGBT populations. The treatment is the same for each: CBT (cognitive behavioral therapy) and SSRIs.

More emphasis is needed on women because twice as many women as men have PTSD, despite a lower incidence of trauma, so studying female populations could give us a big clue. The high incidence of PTSD in women is not due to sexual assault, but is due to greater vulnerability of the brain in women.

This could be significant, as there are also twice as many women as men with Alzheimer's disease, and PTSD is increasingly recognized as a risk factor for Alzheimer's. The same brain regions account for both disorders. But does PTSD really cause dementia, or do both disorders reflect differences in brain repair mechanisms? Or is the dementia caused by drug abuse, alcohol, social isolation, pain, brain injury, depression, or some other factor that is associated with PTSD?

These authors aren't the world's greatest writers, so reading this 800-page book is a slog. You'll get an overview of the field, but it's expensive. I had to read this one for my job. I only hope it's tax-deductible.

jan 26, 2020