The Despairing Librarian
|
The Royal Melbourne Hospital Melbourne, Australia June, 2011 |
|
The Tale
We begin our story with a 29 year old librarian working in one of the more reputable of Melbourne's many libraries. Normally an active person, she had felt generally tired and easily fatigued for several months, and noticed that she had developed a tendency to drop objects from her right hand if she was not paying attention. Moreover, she was experiencing headaches much more frequently than she was used to - she had never really suffered from them - lasting for days at a time.
All of this was a bit odd, but our librarian pushed through the fatigue and pain. After a while, things worsened. One day, out of the blue, her right hand and foot started to "twitch" - involuntarily, and uncontrollably. The twitching consisted of a brief flicker of motion of the hand or foot every few minutes. Our librarian became a bit more concerned at this point - who would not be, when two of their four limbs are taking on a life of their own - and she was thrown into tears periodically. Still, she continued on with work, as money was tight, and tried to ignore the twitches. They interfered with her walking; she had to be careful with the right foot, else it twitch right as she was about to step on it.
After a couple of weeks of constant fatigue, intermittent headaches, and incessant twitching of the right hand and foot, one more fateful event occurred: she developed naming and word-finding difficulties. The words were in her head, but she could not say them correctly, and she made naming errors - instead of calling a book a book, she would call it something else, even though in her mind, she knew that it was a book.
Enough was enough. Our despairing librarian finally allowed her concerned family to bring her to the emergency department of our hospital. The busy emergency doctors called us almost immediately.
She was despondent when I came upon her, and her tear-streaked eyes were a testament to fact that she had been crying. Our librarian was an attractive young lady of European ancestry, average height, and slim build. After teasing out her current problems, I inquired about medical issues in the past. She described a few problems that seemed unrelated - recurrent jaw abscesses in the past that had not plagued her for years; on and off depression; and mild asthma. Yes, she had smoked for the last 15 years, and no, she did not drink alcohol or use illicit drugs. Her family history was on the colourful side. An aunt had died suddenly in her fifties from what was discovered on autopsy to be a brain aneurysm. A grandmother and a great-grandfather had suffered from rheumatoid arthritis, and there was a great-aunt with systemic lupus erythematosus (a systemic autoimmune condition with the potential to harm not only the brain, but also the heart, joints, skin, lungs, blood vessels, liver, and kidneys). Our librarian was taking an antidepressant, sertraline, as management for her on and off depression, which of course lately had been more on than off. She was not aware of any allergies.
As I was speaking to her, I did notice the right hand intermittently writhing away every few seconds. Apparently by now, the movements - what our librarian called "twitches" - had worsened, increasing in frequency from every few minutes, to every few seconds. Even more disconcerting, they were no longer brief flickers of movement; they had evolved and were now athetoid (slow, writhing, and "snake-like") movements lasting several seconds at a time.
There was something else peculiar - her speech. It was certainly not normal. For starters, it was slow. Moreover, she did appear to have mild difficulties with finding certain words; she could find them mind you, but often she would pause for a few seconds, having to think about what she wanted to say. Apparently, this was a substantial improvement over what her speech had been the day before. Her word-finding difficulties, although subtle, were suggestive of a mild expressive aphasia (speech disorder marked by a reduction in the ability to produce language).
WIth the athetoid movements and mild expressive aphasia in mind, I began my examination, looking for further clues as to what might be going on. On the surface, her heart, lungs, and skin seemed fine, with a normal blood pressure and heart sounds, normal lung sounds, and no strange-looking rashes. Nothing to see here. I moved on to a neurological examination. Her cranial nerves - the nerves that control many of the sensations and movements in the face - were entirely normal. So far so good. However, things changed when I got to the upper and lower limbs (arms and legs). The right upper and lower limbs had increased tone (they were stiff), even when I asked our librarian to fully relax. There was also mildly reduced power on the right side, though I could not appreciate a particular pattern of weakness; all of the right-sided limb movements seemed a little on the weak side. Her upper and lower limb tendon reflexes were normal, as was her plantar reflex (also known as the Babinski response, elicited by rubbing the bottom of the foot with a blunt instrument). She had normal sensation in all limbs. Getting our librarian out of the stoic hospital bed to which she had been assigned, I observed her walking. The athetoid movements affecting her right leg forced her to walk slowly, and take care where she put her right foot, but otherwise there was no obvious gait abnormality.
I calmly reassured our poor librarian that while I was uncertain as to what was wrong with her, I had some clues, and that I would search for more until an answer was found. As our emergency department had ordered routine blood work and a computed tomography (CT) scan (a three dimensional x-ray) of her head, I walked over to a nearby computer to take a look. Her blood and electrolyte levels were within normal limits. The CT scan was also plum normal; her brain looked fine. I did not give too much thought to the normal-looking CT scan though, knowing that such scans are great at assessing bone and potential bleeds, but not so great at assessing abnormalities of the brain tissue itself. My next step was clear, and I ordered a magnetic resonance imaging (MRI) scan of her brain. An MRI scan is a radiological technique that uses strong magnetic fields and radiowaves to assess the movement of water molecules within body tissues, creating a nice anatomical image in the process. It can be done a few different ways. One way, diffusion weighted imaging (DWI), is great at picking up restricted water diffusion resulting from damage to a part of the brain. Damaged areas with restricted diffusion appear white on a DWI image. Processing DWI images further creates an apparent diffusion coefficient (ADC) map. A white area on a DWI image (called "DWI positive") with a corresponding dark area on ADC suggests cytotoxic edema (local swelling. such as that produced by a stroke) whereas a white area on DWI with a corresponding white area on ADC suggests vasogenic edema (local swelling usually from some other pathology, such as a tumour).
I compared the DWI and ADC images of our librarian's brain.
All of this was a bit odd, but our librarian pushed through the fatigue and pain. After a while, things worsened. One day, out of the blue, her right hand and foot started to "twitch" - involuntarily, and uncontrollably. The twitching consisted of a brief flicker of motion of the hand or foot every few minutes. Our librarian became a bit more concerned at this point - who would not be, when two of their four limbs are taking on a life of their own - and she was thrown into tears periodically. Still, she continued on with work, as money was tight, and tried to ignore the twitches. They interfered with her walking; she had to be careful with the right foot, else it twitch right as she was about to step on it.
After a couple of weeks of constant fatigue, intermittent headaches, and incessant twitching of the right hand and foot, one more fateful event occurred: she developed naming and word-finding difficulties. The words were in her head, but she could not say them correctly, and she made naming errors - instead of calling a book a book, she would call it something else, even though in her mind, she knew that it was a book.
Enough was enough. Our despairing librarian finally allowed her concerned family to bring her to the emergency department of our hospital. The busy emergency doctors called us almost immediately.
She was despondent when I came upon her, and her tear-streaked eyes were a testament to fact that she had been crying. Our librarian was an attractive young lady of European ancestry, average height, and slim build. After teasing out her current problems, I inquired about medical issues in the past. She described a few problems that seemed unrelated - recurrent jaw abscesses in the past that had not plagued her for years; on and off depression; and mild asthma. Yes, she had smoked for the last 15 years, and no, she did not drink alcohol or use illicit drugs. Her family history was on the colourful side. An aunt had died suddenly in her fifties from what was discovered on autopsy to be a brain aneurysm. A grandmother and a great-grandfather had suffered from rheumatoid arthritis, and there was a great-aunt with systemic lupus erythematosus (a systemic autoimmune condition with the potential to harm not only the brain, but also the heart, joints, skin, lungs, blood vessels, liver, and kidneys). Our librarian was taking an antidepressant, sertraline, as management for her on and off depression, which of course lately had been more on than off. She was not aware of any allergies.
As I was speaking to her, I did notice the right hand intermittently writhing away every few seconds. Apparently by now, the movements - what our librarian called "twitches" - had worsened, increasing in frequency from every few minutes, to every few seconds. Even more disconcerting, they were no longer brief flickers of movement; they had evolved and were now athetoid (slow, writhing, and "snake-like") movements lasting several seconds at a time.
There was something else peculiar - her speech. It was certainly not normal. For starters, it was slow. Moreover, she did appear to have mild difficulties with finding certain words; she could find them mind you, but often she would pause for a few seconds, having to think about what she wanted to say. Apparently, this was a substantial improvement over what her speech had been the day before. Her word-finding difficulties, although subtle, were suggestive of a mild expressive aphasia (speech disorder marked by a reduction in the ability to produce language).
WIth the athetoid movements and mild expressive aphasia in mind, I began my examination, looking for further clues as to what might be going on. On the surface, her heart, lungs, and skin seemed fine, with a normal blood pressure and heart sounds, normal lung sounds, and no strange-looking rashes. Nothing to see here. I moved on to a neurological examination. Her cranial nerves - the nerves that control many of the sensations and movements in the face - were entirely normal. So far so good. However, things changed when I got to the upper and lower limbs (arms and legs). The right upper and lower limbs had increased tone (they were stiff), even when I asked our librarian to fully relax. There was also mildly reduced power on the right side, though I could not appreciate a particular pattern of weakness; all of the right-sided limb movements seemed a little on the weak side. Her upper and lower limb tendon reflexes were normal, as was her plantar reflex (also known as the Babinski response, elicited by rubbing the bottom of the foot with a blunt instrument). She had normal sensation in all limbs. Getting our librarian out of the stoic hospital bed to which she had been assigned, I observed her walking. The athetoid movements affecting her right leg forced her to walk slowly, and take care where she put her right foot, but otherwise there was no obvious gait abnormality.
I calmly reassured our poor librarian that while I was uncertain as to what was wrong with her, I had some clues, and that I would search for more until an answer was found. As our emergency department had ordered routine blood work and a computed tomography (CT) scan (a three dimensional x-ray) of her head, I walked over to a nearby computer to take a look. Her blood and electrolyte levels were within normal limits. The CT scan was also plum normal; her brain looked fine. I did not give too much thought to the normal-looking CT scan though, knowing that such scans are great at assessing bone and potential bleeds, but not so great at assessing abnormalities of the brain tissue itself. My next step was clear, and I ordered a magnetic resonance imaging (MRI) scan of her brain. An MRI scan is a radiological technique that uses strong magnetic fields and radiowaves to assess the movement of water molecules within body tissues, creating a nice anatomical image in the process. It can be done a few different ways. One way, diffusion weighted imaging (DWI), is great at picking up restricted water diffusion resulting from damage to a part of the brain. Damaged areas with restricted diffusion appear white on a DWI image. Processing DWI images further creates an apparent diffusion coefficient (ADC) map. A white area on a DWI image (called "DWI positive") with a corresponding dark area on ADC suggests cytotoxic edema (local swelling. such as that produced by a stroke) whereas a white area on DWI with a corresponding white area on ADC suggests vasogenic edema (local swelling usually from some other pathology, such as a tumour).
I compared the DWI and ADC images of our librarian's brain.
|
DWI
|
ADC
|
This DWI image shows a large white area at the top left side of the brain (left on the scan equates to the right side of the brain and vice versa).
DWI positive in the left frontal area, and perhaps a little bit on the right.
As we move down, a few small DWI positive areas are seen in the left and right frontal cerebral cortex and deeper brain areas, some involving the basal ganglia on other images.
|
If you look carefully, you can see that this ADC image shows a corresponding darker area.
Corresponding dark area on the ADC seen in the left frontal area.
With tiny DWI lesions, any corresponding dark areas on the ADC image may not show up. Too small.
|
Clearly, there were multiple DWI positive areas within the cerebral cortex and basal ganglia with corresponding dark areas on the ADC images. This suggested that our librarian, only 29 years of age, was suffering from multiple ischemic strokes (in which the brain tissue has died from being deprived of oxygenated blood for too long) in these areas. However, I had to keep my mind open regarding other possibilities such as bacterial endocarditis (where bacteria infect the inner lining and valves of the heart and can be flung off to infect many areas of the brain), vasculitis (an infective or immune-mediated destructive condition that often affects multiple blood vessels), and lymphoma (cancer of the white blood cells resulting in numerous small tumours). These alternative had to be checked out. Importantly, all of the lesions found were involved in the anterior circulation (the part of the cerebral circulation that is fed by the internal carotid arteries) of the brain. Those internal carotid arteries also had to be looked at.
Our librarian was a couple of days into her admission by now, and putting on a brave face, but the finding of abnormalities within her brain was beginning to take its toll. She needed a diagnosis. My team and I ordered the next few tests with haste. To assess for bacterial endocarditis, we obtained a transesophageal echocardiogram (TOE) ultrasound of her heart (this involves putting a tube down the throat with a small ultrasound probe attachded at the tip). We saw no evidence of heart infection. To assess for vasculitis, we ordered a blood test for antinuclear antibodies (autoantibodies produced by one's own immune system that bind to cell nuclei) as well as a few other vasculitis blood tests, all of which came back normal. To assess for lymphoma, we performed a lumbar puncture (inserting a needle into the lower back to obtain cerebrospinal fluid) to look for cancerous cells, but her cerebrospinal fluid was immaculate.
With the alternative diagnoses excluded, a diagnosis of multiple strokes was looking likely. Now we had to find out where they were coming from. It was time to check out those internal carotid arteries, and we ordered a digital subtraction angiography (DSA) scan of the anterior circulation. Such a scan involves the introduction of a catheter into the femoral artery right up to the carotid arteries. A contrast agent is injected and x-rays are taken showing the contrast agent working its way through the cerebral blood vessels. Any abnormalities in the blood vessels are usually clearly identified.
Our librarian was a couple of days into her admission by now, and putting on a brave face, but the finding of abnormalities within her brain was beginning to take its toll. She needed a diagnosis. My team and I ordered the next few tests with haste. To assess for bacterial endocarditis, we obtained a transesophageal echocardiogram (TOE) ultrasound of her heart (this involves putting a tube down the throat with a small ultrasound probe attachded at the tip). We saw no evidence of heart infection. To assess for vasculitis, we ordered a blood test for antinuclear antibodies (autoantibodies produced by one's own immune system that bind to cell nuclei) as well as a few other vasculitis blood tests, all of which came back normal. To assess for lymphoma, we performed a lumbar puncture (inserting a needle into the lower back to obtain cerebrospinal fluid) to look for cancerous cells, but her cerebrospinal fluid was immaculate.
With the alternative diagnoses excluded, a diagnosis of multiple strokes was looking likely. Now we had to find out where they were coming from. It was time to check out those internal carotid arteries, and we ordered a digital subtraction angiography (DSA) scan of the anterior circulation. Such a scan involves the introduction of a catheter into the femoral artery right up to the carotid arteries. A contrast agent is injected and x-rays are taken showing the contrast agent working its way through the cerebral blood vessels. Any abnormalities in the blood vessels are usually clearly identified.
|
Right Internal Carotid Artery
|
Left Internal Carotid Artery
|
DSA of the right internal carotid artery (dark vessel) which is obstructed. Note the faint "puffs of smoke" at the top right. These collateral vessels are trying to bypass the obstruction.
|
This is a DSA of the left internal carotid artery, which also seems blocked.
|
Surprisingly, the internal carotid arteries were not only abnormal, they were almost completely obstructed. Moreover, numerous small collateral arteries had sprouted that were desperately attempting to bypass the obstruction.
There could be no doubt as to what this was, and our despairing librarian finally had a diagnosis - she had multiple ischemic strokes secondary to moyamoya disease.
There could be no doubt as to what this was, and our despairing librarian finally had a diagnosis - she had multiple ischemic strokes secondary to moyamoya disease.
The Condition
|
Moyamoya disease is a progressive and occlusive disease of the cerebral circulation characterized by (1) bilateral stenoses (narrowing) of cerebral blood vessels, particularly the distal internal and proximal middle cerebral arteries, and (2) fragile blood vessel collaterals appearing as "puffs of smoke" on angiography. Indeed, the term "moyamoya" means "puff of smoke" in Japanese; it has the highest prevalence in Japan.
Moyamoya disease starts with abnormal thickening of the intimal (innermost) layer of the affected arteries. The reason for this is not understood, the intima just thickens and starts growing inwards into the lumen. As it grows inwards, the artery narrows, and eventually may become occluded. This process cannot be stopped. However, the cerebral circulation does try to compensate by sprouting tiny blood vessel collaterals (the moyamoya vessels) to carry blood around the blockage. Unfortunately these vessels are fragile, and they often break, leaking blood out in the process and creating tiny bleeds within the brain. The bleeds create pressure, resulting in headaches, as well as tiny hemorrhagic strokes. That is not all - since the moyamoya vessels are so small and fragile they often do not adequately compensate for the loss of blood flow by the stenosed larger arteries, and so ischemic strokes and seizures can also occur as a result of the inadequate supply of oxygenated blood to various parts of the brain. Hemorrhagic and ischemic strokes result in focal neurological symptoms depending upon where they are located - in the case of our librarian, the basal nuclei (resulting in athetosis), the medial insular cortex (resulting in expressive aphasia), and the left primary motor cortex (resulting in right-sided weakness). Since the strokes are usually small, the brain can recover from them to some extent, and so the focal neurological symptoms may often be transient and improve within a short period of time, but unfortunately new strokes will continue to occur. Treatment starts with aspirin (a medication that inhibits thromboxane and in doing so prevents platelets from aggregating to form blood clots). This prevents clots from forming within the stenosed vessels, thus preventing some of the ischemic strokes from occurring. But aspirin alone is rarely enough - bypass surgery is usually required, which involves bypassing the obstructed internal carotid arteries with another blood vessel such as the superficial temporal artery. This artery normally supplies the temple and part of the eye, but can be diverted to the arteries beyond the obstruction through a small artificially created hole in the skull without incident. Without bypass surgery, one half to two-thirds of people with moyamoya disease will continue to suffer varying degrees of neurological decline and disability (Ezura et al, 1995; Kurokawa et al, 1985). With bypass surgery, around 90% of people with this condition will remain free of strokes and improve over the next five years (Fung et al, 2005; Scott and Smith, 2009). Long-term studies are lacking, but surgery probably helps quite a lot, and afterwards the moyamoya vessels regress and often disappear. |
Represented here is the Circle of Willis located at the bottom of the brain. The Circle of WIllis constitutes the heart and soul of the cerebral circulation. In moyamoya disease, the distal internal carotid and proximal middle cerebral arteries gradually narrow and may become occluded on both sides.
Normally, the internal carotid arteries supply the anterior and middle cerebral arteries (the big bright arteries at the top and sides).
In severe moyamoya disease, the internal carotid arteries are blocked and little if any blood can get through to the anterior and middle cerebral arteries.
|
Epilogue
Once we had a diagnosis for our despairing librarian, management was straightforward. We treated her with aspirin, and after a couple of days she started to feel better without any further decline. About a week after that our excellent neurosurgeons performed a left superficial temporal artery bypass, providing blood to the areas of brain beyond the compromised left internal carotid artery. A month after that, the same operation was performed on the right side. Our librarian returned to a normal life.
Months later, I received a message from her - she was doing great, and now appeared to be the polar opposite of despair. Moreover, her experience had stimulated her to make some important changes in her life, changes which will hopefully endure much longer than those few months of illness.
I will always remember that positive things may result from even the most awful of experiences.
Months later, I received a message from her - she was doing great, and now appeared to be the polar opposite of despair. Moreover, her experience had stimulated her to make some important changes in her life, changes which will hopefully endure much longer than those few months of illness.
I will always remember that positive things may result from even the most awful of experiences.
References
Ezura et al. 1995. Clinical and angiographic follow-up of childhood-onset moyamoya disease. Child's Nervous System 11(10), 591-594.
Fung et al. 2005. Revascularisation surgery for pediatric moyamoya: a review of the literature. Child's Nervous System 21(5), 358-364.
Kurokawa et al. 1985. Prognosis of occlusive disease of the circle of Willis (moyamoya disease) in children. Periatric Neurology 5, 274-277.
Scott and Smith. 2005. Moyamoya disease and moyamoya syndrome. New England Journal of Medicine 360, 1226-1237.
Ezura et al. 1995. Clinical and angiographic follow-up of childhood-onset moyamoya disease. Child's Nervous System 11(10), 591-594.
Fung et al. 2005. Revascularisation surgery for pediatric moyamoya: a review of the literature. Child's Nervous System 21(5), 358-364.
Kurokawa et al. 1985. Prognosis of occlusive disease of the circle of Willis (moyamoya disease) in children. Periatric Neurology 5, 274-277.
Scott and Smith. 2005. Moyamoya disease and moyamoya syndrome. New England Journal of Medicine 360, 1226-1237.
