The Neuropathology Of Zombies (19 page)

CHAPTER 25

The lab was calm. The microbiologist sat in the corner reading computer printouts, while the virologist stared anxiously at a digital timer. No one noticed me walk into the room.

“Why the glum faces?” I asked.

No one responded. Everyone just looked at me, annoyed. I could tell moral was slipping down the drain. I hoped something in the slides would give us all some hope.

“Have either of you had any luck?” I asked swiveling my head between the two bug doctors.
“No, no viruses have grown on the rapid cultures. Not that I would expect anything to show up, all the tests we have here are for the run of the mill things, like influenza. I’m not going to be able to grow anything exotic,” the virologist said.
“Same with me. All I am getting is normal flora. Nothing out of the ordinary,” replied the microbiologist.
I nodded my head and sat down at the microscope. A pile of cardboard slide trays were resting on the table. There must have been twenty of them.
“The problem with histology is that it’s all well and good to take the sections, but it’s another thing all together to have to look at them! What was I thinking taking this many slides!” I joked, opening the first tray.
“I put them in chronological order with Igor’s first, the biopsies from the Marine upstairs second, and then the two autopsies. I hope that’s ok,” stated the technician.
“That’s wonderful! Have you taken a peek yet?”
“Only to make sure the slides stained well. If I needed to do recuts, I wanted to do it as I was going along.”
“Alright, let’s see what’s gotten under Igor’s skin,” I said, slowly releasing a deep breath. The entire science team gathered around the microscope, there were enough eyepieces on the multi-headed beast for everyone to have a look.
The first slide landed on the stage of the microscope with a clink as the glass collided with the metal base. I moved the section swiftly under low magnification.
“Not much different than the frozen section, less artifact, but no real difference. There’s some decomp, here and here,” I said, moving the glowing arrow that projected onto the slide.
“But look over here, there’s a bit of inflammation in some of the spots where the epidermis is peeling off,” I continued.
I picked up the next slide, it was a tiny piece of nerve from Igor’s arm. I moved the tissue around for a minute before speaking.
“Now this is interesting. Look here, there is a near total loss of small myelinated fibers and a loss of the small unmyelinated fibers, too!”
I kept moving the slide around, hoping to suck as much information from it as I could. I had a clue and I was on the hunt.
“What is the significance of that, Doc?” the technician asked. His question was followed by the affirming grunts of the other men around the microscope.
“The small myelinated fibers carry pain information, without them, you can’t appreciate pain,” I answered while continuing to scan the slide.
“Hum, let’s go back to the skin section for a minute,” I said, switching slides.
I moved the glass around slowly and turned the objective to a higher power.
“I didn’t really notice it at first, but yeah, here it is. The biopsy isn’t too deep, but you can still see a couple of nerves twig and they’re also losing their small fibers. Interesting.”
I continued to look around the skin hoping to find something else. “I noticed that there were very few sweat glands while I was looking before, I didn’t think much of it because the biopsy was pretty superficial, but I think there are not enough sweat glands. I’m not sure.”
I placed the skin section back and began to pilfer through the trays.
“What are you looking for, Doc?” inquired the technician, with a helpful tone in his voice.
I fumbled with the slide trays, “I am looking for the skin sections I took from the Marine and from the two autopsy cases.”
“Here, I know where they are,” he said, and he sorted out the trays, handing me the slides I was looking for in a matter of seconds.
Without speaking I examined all the slides, switching back and forth, comparing them to one another. I was trying to decide if the findings I had noticed were real, or just my imagination.
After several minutes I spoke, “It’s real. The autopsy biopsies are deeper and show it better, but all of the skin sections show a loss of sweat glands; and the nerves in the dermis all show a loss of small fibers.”
“What could cause something like this?” the virologist questioned.
“Well,” I hesitated, “I have never actually seen it, but there are a certain family of inherited diseases called Hereditary Sensory Autonomic Neuropathy, or HSAN. There are five different types, each passed on genetically and involve the progressive loss of sensation, particularly the ability to feel pain. The age of onset varies from infants to adults. The various types have different manifestations, but many affected patients have multiple skin ulcers that can be very deep, down to the bone. Sometimes the ulcerations can be so severe that they can cause auto amputation, you know, the limb just falls off,” I explained, looking around the room.
“You’ve got it, Doc!” yelled the technician.
“I don’t think so. These diseases are passed on genetically, from mom and dad, here we have an illness that is acquired, meaning people are catching it. It would be very unlikely for everyone on the island to simultaneously start expressing the genes responsible for one of the HSAN diseases! No, this is something different.”
“I don’t know of any virus that could do something like this,” the virologist said.
“I have never seen these kinds of changes with a bacterium, fungus, or anything, I don’t think this is related to an infection,” the microbiologist added.
I stretched my arms and placed my hands on top of my head, and sighed. “I know. HSAN is essentially an autonomic neuropathy, there are some autonomic neuropathies that can be caused by metabolic diseases, maybe some heavy metal poisonings, but I have never seen anything like this. Where is the toxicologist?”
“We don’t have one, yet,” the technician answered.
“I think we need to get one, fast,” the microbiologist said.
I could feel their urgency turning into panic. Nerves were on edge, I expected an argument at any moment. These were brilliant men, stretched to their limits, grappling with a problem that was beyond their ability to understand. In my experience, such situations typically led to tantrums and rants, and occasionally fist fights.
“We have a lot more slides to look at, I suggest we stay focused and come to our conclusions after we have all the available data,” I warned.
We continued looking at the slides. The normal pink color of the lengthy, narrow strips of heart muscle was beginning to fade. The organ was autolyzed.
“The genetic control centers of the cells, the nuclei, that normally look like tiny purple dots in the middle of the muscle fiber are gone, and so is this tissue! Deco,” I pointed out under the scope.
I moved on to the next slide. “The liver normally shows chords of round cells radiating around a large centrally located vein. The ducts draining bile into the gall bladder, together with small arteries, are grouped together and lay on the outskirts, encircling the central vein and surrounding cells. This arrangement forms an octagon shape when viewed at low power. You can see that here, and here,” I said as I moved the illuminated arrow around the tissue.
“In these autopsy slides, the overall structure is preserved; however, notice how pale the pink staining is, that’s because the tissue is breaking down, just like the heart. There’s no inflammation, it looks pretty normal,” I said.
I looked at the autopsy cases together, first all the hearts, then the all the livers. This allowed me to make comparisons between the cases. I moved on to the kidneys.
“Same thing here. See these little balls lining up along the top of the kidney, those are the glomeruli, and they are essentially like little bags of cheesecloth. They strain the blood, acting as a filter. The stuff they separate from the blood becomes urine,” I said. The technician and a few of the Marines nodded with interest.
“They’re toast. All these little circles, these are the tubules, and they drain the fluid from the glomeruli and send it to the bladder. The kidney is one of the first organs to decay, so I am not surprised that it looks so bad,” I said, placing the slide back in tray. I reached for a section of lung.
The natural process by which the body breaks down was taking over and everything was beginning to dissolve in front of our eyes.
I was silent for a few moments.
“Doc, what is it?” asked the technician.
“Interesting. The lung is also decomposing, you can see that by the fading colors of the stain, but look at this, see all these little blue cells filling all the empty space?” I said, pointing to each blue dot individually. “These are chronic inflammatory cells called lymphocytes. It’s pneumonia. Lymphocytic infiltrates like this typically mean viral pneumonia. Bacterial infections usually cause an acute inflammatory response.
I lifted my head from the eyepieces.
“Can any toxins do this?” asked the virologist.
“They can, especially some of the heavy metals, but they have to be inhaled.”
“Maybe the toxin is an aerosol,” he said.
“Maybe, but it doesn’t explain the person to person transmission, especially via a bite.”
It was clear the virologist and I were not going to agree on etiology of this phenomenon. Our discord may cause problems down the road. He sat silently waiting for the next slide. I grabbed a section of spleen.
“The spleen plays a role in immunity. You can live without it, I am sure you all know someone who has had their spleen taken out. Without it, you become more susceptible to certain bacterial infections, so you have to have frequent vaccinations,” I said.
I glided the slide across the microscope stage. “This is interesting, too. See these circles of blue dots randomly located around the tissue. They’re called follicles, these are lymphocytes getting ready to battle. There are too many follicles, something called follicular hyperplasia. The most common cause of this change is a viral infection.”
I glanced at the virologist. He sat expressionless, his face buried in the eyepieces of the microscope.
I grabbed a section of intestine. It was rancid and putrefied during the autopsy, so I wasn’t expecting much from the histology. “Yeah, just as I suspected, the bowel is dead. The little fingers sticking up from the surface, those are the villi, they absorb the food you eat. They’re just ghosts, nothing left of them. The muscular wall of the intestine is degenerating, too, look how pale and blurry the staining is,” I said, moving the pointer arrow around the section.
We had sifted through all of the organ systems, all that remained were the neuropathology slides. I was anxious to see what was lurking inside the cerebrum. The decompositional process, combined with the injuries produced by the gunshot wounds, made my task more challenging, but the brains were salvageable at the autopsies and the anatomy easily identified. I was hopeful that the microscopic sections would reveal something.

CHAPTER 26

“Let’s go from the front of the brain to the back and see what we find. The frontal lobes were mostly decomposed at autopsy, but we’ll see,” I said, trying to hide my excitement as I placed the first slide under the lens.

“This part of inferior frontal lobe has segments of the orbital frontal gyri, which are the convolutions of the brain that sit in the skull just above the eye. Its job is to influence our ability to recognize the consequences of our actions. It allows us to choose between doing something bad, and doing something good. This area also overrides our reflexes to do socially unacceptable things. In this microscopic section it’s totally autolyzed. See how washed out the color of the slides is? It should be a nice bright pink, but it’s more of a dull gray. Also, the neurons are fading away, here and here,” I said, pointing the incandescent arrow at the large nerve cells that were dying.

“See all the holes in the tissue?” I directing their attention to the clear spaces in the slide, “This is decomposition. Look at the white matter under the cortex, it’s all bubbly, it’s decayed, too. Other than that there is nothing going on.” I was disappointed and my stomach sank. Maybe my expectations for the neuropathology were too high, what if I didn’t find anything? I needed a backup plan.

The next series of slides from the parietal lobe showed more of the same and I became depressed. I was confused and I felt that it was starting to show in my expressions and in the tone of my voice. Out of the corner of my eye I caught the virologist peering over his eyepieces, staring at me; I was almost certain I saw a sinister grin sneak across his face.

“Now let’s get down into the deep structures of the brain, the basal ganglia,” I said, reaching for the next slide.
“The basal ganglia help us with planning and initiating movement. It’s comprised of a few different collections of nerves, and I took sections of each region. This slide is thalamus; it’s kind of like the master control region of the brain. All the sensory and motor information coming into the from the spinal cord to the brain passes through here, and then goes on to the cortex. After spending some time in the cortex, the information passes back through the thalamus, and out to the rest of the body. It also plays a part in wake/sleep cycles, and is even involved in consciousness. Damage here can cause a host of issues, from coma to motor and sensory deficits,” I said, and stared down the eyepiece, the glass slide skirting around the stage.
“What have we here?” I asked, switching to a higher power. “See all these blue dots? They’re lymphocytes. See how they are surrounding the nerves and form these little clusters?” I moved the arrow from cluster to cluster as I spoke. “And out here, see these little clusters of blue dots away from the neurons? These are microglial nodules. The brain has its own inflammatory cells called ‘microglia’, and they transform into chronic inflammatory cells when the brain is stressed. Look at the big neurons, they’re surrounded by inflammation, but they are not dying. Usually when you see a pattern of inflammation like this, the neurons are being killed off, but here they’re not. Even stranger, they don’t seem to be decomposing, this area looks totally preserved.” I sat back in amazement, my mind was racing. I bent back over the microscope and switched the objective to the highest power.
“Microglial nodules are highly suggestive of a viral process, I’m going to take a closer look at the neurons; most viruses accumulate inside the cell and form structures called ‘inclusions’, which you can see, sometimes. The inclusions can be tiny spheres in the cytoplasm or nucleus, sometimes they cause the entire cell to look glassy.”
I skimmed the slide silently for a few minutes, “I don’t see any. Nope, no inclusions.” I placed the slide back in the tray.
“The next slide is the caudate and putamen, both are part of the basal ganglia, together they are called the striatum. The caudate has some interesting functions, you know that feeling you get that something isn’t right, ‘did I lock the door?’ ‘Did I turn of the stove?’ that’s caudate. The putamen helps us with our automatic behaviors, such as riding a bike, brushing your teeth,” I said, moving the section from side to side.
“Look at this, it’s the same process. Microglial nodules and inflammation around the neurons. There is also a considerable amount of inflammation around the small arteries passing through the tissue,” I said, and shifted the arrow to another visual field on the slide. “There is hemorrhage around some of the arteries, and look down here at the white matter, it’s also totally intact. There is no deco here at all. I just don’t know what to say, it shouldn’t be this well preserved.”
I was getting excited, I almost knocked over all the trays as I reached for the next slide.
I focused the low power objective. “This is the midbrain, I think it looks like a mouse’s head, with big ears and a tiny mouth. These black cells are the substantia nigra, they play a role in motor control. If they are diseased you end up with Parkinson’s disease. The substantia nigra is also involved in habituation, and it puts the breaks on some of the other basal ganglia structures. For example, if these neurons are injured, they are unable to act on the caudate and the putamen, and abnormal movements occur. If they fire too much, all motor function can stop. It’s a pretty important area. This looks very similar to the other sections. Lots of inflammation surrounding neurons, but the neurons are intact.
“Wait, look at this, in the pigmented neurons, these little inclusions. They’re not Lewy Bodies, which are small, round inclusions you see in Parkinson’s disease. No, they’re bigger, they look like neurofibrillary tangles. You see tangles in many neurodegenerative diseases, this is odd.” I looked thought all the mid brain slides and each one showed inclusions in the pigmented neurons. “Another piece of information, I have no idea what it means, though.”
“Just behind the substantia, these areas of pink-fluffy staining are called the cerebral peduncles, they are the collection of all the motor and sensory pathways that leave the cortex and travel to the entire body. They pass through the basal ganglia, which modifies the impulses they carry, before heading off to the rest of the body. They look a bit odd. There is no inflammation, but they are decomposing in some spots, while other regions are intact.”
I moved the slide around, and made a few soft humming sounds. “It’s not all decomposing, over here for example, on the opposite side of the substantia are the inferior colliculi, can you see these two humps right next to each other? This is the main auditory nucleus of the brain; it processes all the sound information. Look at these cells, not only do we have the inflammation like the other slides, the neurons are huge! They’ve doubled in size!” I said, switching to the highest power objective. “Maybe they’re so big because they are full of virus; let me see if I can find any inclusions.”
I looked around for several minutes and found no inclusions. “I’ve never seen anything like this. Nerve cells can get big when they degenerate, sometimes, but these cells are very much alive and kicking.”
I picked up the next midbrain section. “This piece was taken a bit higher up, here is the superior colliculus, and this is the major visual nucleus. It processes all the visual information. There’s the same inflammation here, too. It’s all around the neurons. The neurons are not nearly as big as the ones we just saw in the inferior colliculus and they’re not decomposed. Now, if you look down here, between the substantia nigra and the colliculus, this is the red nucleus. It’s called that because it has a reddish color in the brain. It helps control gait, mainly swinging arms when you walk, it manages the large muscles of the upper trunk. It’s a major player in babies when they crawl. There are a bunch of microglial nodules, and some of the neurons are being destroyed by inflammatory cells. Now that’s more like it, this is how a normal virus should behave!” I laughed.
“The rest of the midbrain looks alright. It’s not decomposing, anyway. Can you guys see the small hole in the middle? That hole is the cerebral aqueduct, and the groups of nerves off to the sides are nuclei that control some of the eye movements; they’re also surrounded by inflammation, but they look normal.
We had been sitting around the microscope for almost an hour. I was surprised the entire group was still with me. Everyone seemed interested and no one looked bored. “Anyone need a break?” I asked. “We’re almost done, just a few more slides.”
“No, I want to keep on going. I don’t understand a word you’re saying, Doc, but it sure is interesting!” one of the Marines chuckled.
“Alright then, on to the medulla.” I cheered.
I slipped the slide onto the stage of the microscope, “This part of the brain is where the heart and respiratory systems are controlled. Also, all the outgoing information coming from the cortex is placed in a particular order for its voyage down the spinal cord. As if that wasn’t enough, this is where all the incoming information arriving from the body via the spinal cord gets dispersed to the various parts of the basal ganglia and cortex. Also floating around here is a mesh of axons traveling between the medulla, the midbrain, and the basal ganglia called the reticular formation. This meshwork is where consciousness is said to originate. The reticular formation maintains our level of alertness by controlling our sleep/wake cycles. It plays a role in motor control by integrating muscle tone, balance and posture, too.
“Now, let’s take a look. In this section, we again have this diffuse inflammation around the neurons. The neurons appear to be pretty intact.” I switched to higher power, “But wait, here it is again, tangles. This is very odd. Why are there tangles in the medulla?” I asked, pointing the arrow at the affected cells. “See the tangles? They look like camp fires. I don’t get it.” I paused again as I scanned the slide, “The white matter tracts are ok, too, no decomposition.” Puzzled, I returned the slide to the tray.
“This is my favorite part of the brain,” I said holding a slide up to the light above our heads. “It’s called the hippocampus, it looks like a sea horse. This little guy takes all the stuff I am telling you now, which you’re holding in your short term memory, and stashes it in your long term memory, so next week when I quiz you all on this, you’ll remember it.”
There was a collective chuckle from the group. “It’s a very important part of the limbic system. The limbic system is a collection of structures that store emotional memory. Think of the emotional response you get from certain smells, or the sick feeling you get when you remember something bad that happened to you, that’s the limbic system.”
I lowered the slide and placed it on the microscope. “Wow. It’s gone! There is nothing left of it, totally autolysed. You can see the sea horse shape here, as it bends around, and look, all the neurons are fading away. And, there is no inflammation.”
“Huh, I wonder about the rest of the limbic system, let’s look at the amygdala,” I said reaching for the next set of slides. “The amygdala is very interesting. It’s where emotional responses are really set in stone. It also controls anger. There have been studies on monkeys where scientists have electrically stimulated the amygdala and found that the animals react with irritation, anger and rage; if the stimulus continues, the animal will attack. There have been cases where epileptic patients have attacked and severely injured nurses and doctors while having seizures that originated close to the amygdala. This region of the brain also controls the facial expressions of rage. In both animal and humans, electrical stimulation of the amygdala causes the nostrils to flair, the lips to retract in order to bare the teeth, and facial grimacing; they sort of look like rapid animals! Sexual feelings also come from the amygdala. In these same studies, people became preoccupied with sex, but they had a decrease in sexual activity. Tumors in this region can have a similar effect.”
“Sounds like the serial killer center,” one of the Marines joked.
“No, you’re right. Do you know who Charles Whitman was?” I asked.
My question was met with blank stares. “In 1966 he climbed to the top of the bell tower at the University of Texas and shot and killed 14 people and wounded 38 more. He was a quite a kid, good student, close to genius IQ, but as he grew older he began to become violent. He got into fights, beat his wife, stuff like that. His anger got so out of control he sought medical help, to no avail. Anyway, the day before he climbs the tower he beats, strangles and stabs his mother to death, and then does the same to his wife. What’s interesting is this: he had a malignant brain tumor that involved the amygdala. So, yeah, maybe it could be the serial killer center, though technically speaking Whitman was a mass murderer, or spree killer. Let’s see how our zombie amygdala looks.”
I moved the slide around. “Hopefully you can see there are several groups of neurons, each of these are called nuclei, as I said before, that just means collection of nerve cells. The amygdala has five. Now look at this higher power, there’s a ton of inflammation surrounding the nerve cells. And again, they are totally preserved.”
“Ok, let’s move on to the cerebellum. The cerebellum plays an important role in motor control. It’s doesn’t initiate movement, it smooth’s it out and really determines the accuracy and precision of movements; it’s our timing mechanism. Damage to the cerebellum doesn’t cause paralysis, it causes disturbances in posture and balance,” I spoke as I lifted the slide from the tray.
“I’ve always thought the cerebellum looked like cauliflower. It has millions of these little folds called folia that increase the surface area. Buy folding up onto itself it can cram a lot of tissue into a small space, and that increased volume means it can do more complicated things. The cerebellum was pretty soft at autopsy, let’s see if there’s anything going on here,” I said hopefully, placing the slide under the objective.
“Nothing, totally dead tissue. Deco city, dudes,” I said, giddy from all the work. My mind was starting to feel the effects of fatigue. At least I hoped it was fatigue, and not the result of my head injury. Thinking of it made my side hurt and I wondered if the pain medicine I had taken at the barracks was starting to wear off.
“Ok, we’re almost done just the spinal cord and eyes to go. I think we should look at the cord next. Anatomically, it’s divided into segments based on geography. There is the cervical cord, in your neck; the thoracic cord in your chest; and the lumbar cord in the abdomen. Motor information goes down and sensory information goes up. Now, over here on the sides are the motor neurons, and they’re also inflamed, just like in the brain. The nerve cells themselves look quite happy, no injury, no deco. But over here, just under the motor neurons, are the little pathways that carry pain information, they’re autolysed. No pain tracts left, at any level of the cord, or in the peripheral nerves we saw in the skin,” I said, switching from slide to slide comparing the different segments.
“Up here at the top of this slide are the tracts that carry sensory information regarding touch, not painful touch, but vibrations, and also the sense of where your body is located in space. There are two bundles on either side; they look like two big ‘M’s side-by-side. They are called the gracile fasciculus and the cuneate fasciculus; they carry this information about where the limbs are located in space to the cerebellum. Notice that the area is just light pink, there are no cells here, only axons; and notice how pale the staining is, and there are all these little holes, its autolyzing. It appears as though no sensory information what-so-ever is getting up to the brain; however, the motor tracts are perfectly fine. Very odd,” I finished.
“Now, finally, the eyes,” I said, grabbing for the last cardboard tray.
“The eye is really a bundle of nervous tissue. When light hits the retina, it causes the nerves to fire and send signals to the brain. The photoreceptors, or the nerves that detect the light, are called cones and rods. Cones are good for seeing color and rods are good for seeing in low light,” I said, shifting the slide.