This month I've decided to post every day. Since I don't have enough original things to write about (hence the desertish nature of my blog lately), I've decided to ask a new question every day this month and hope that I get answers. I have questions; you have answers.
If someone has weakness of the proximal muscles of his legs, does he find it hard to go up stairs or down stairs? Justify your answer. Proximal means "closer to the beginning" and in the case of the leg muscles means thigh and buttocks muscles.
Once enough people respond, I will tell you the answer.
Showing posts with label Neurology. Show all posts
Showing posts with label Neurology. Show all posts
10 November 2010
06 November 2010
QotD: Alaska or Hawaii?
This month I've decided to post every day. Since I don't have enough original things to write about (hence the desertish nature of my blog lately), I've decided to ask a new question every day this month and hope that I get answers. I have questions; you have answers.
When I took my Neurology Boards recertification test in 2007, I was semi-convinced I wouldn't pass. Like many people, I tend to obsess about important tests prior to the test, then be calm, cool, and collected once it starts. The Neurology Oral Boards were an exception to that rule (I practically cried during part of it). Anyway, TheHusband believed I would pass on the first try, but wasn't above a little positive reinforcement. He told me that if I passed the recertification on the 1st try, we would go to Alaska or Hawaii; if I passed on the 2nd try, we'd get to go to Florida; but if I passed on the 3rd try, we'd be going to Cleveland. In winter. To visit my mother-in-law. Now my MiL is a wonderful woman, but Cleveland in winter is ... not.
Needless to say, with that incentive, I passed (well) on the first try. So I get to pick between Alaska and Hawaii. Which should I pick and why? And which would you rather visit?
When I took my Neurology Boards recertification test in 2007, I was semi-convinced I wouldn't pass. Like many people, I tend to obsess about important tests prior to the test, then be calm, cool, and collected once it starts. The Neurology Oral Boards were an exception to that rule (I practically cried during part of it). Anyway, TheHusband believed I would pass on the first try, but wasn't above a little positive reinforcement. He told me that if I passed the recertification on the 1st try, we would go to Alaska or Hawaii; if I passed on the 2nd try, we'd get to go to Florida; but if I passed on the 3rd try, we'd be going to Cleveland. In winter. To visit my mother-in-law. Now my MiL is a wonderful woman, but Cleveland in winter is ... not.
Needless to say, with that incentive, I passed (well) on the first try. So I get to pick between Alaska and Hawaii. Which should I pick and why? And which would you rather visit?
08 November 2009
Hepped Up on Goofballs!
Hello all,
Here I am hepped-up on goof balls during post-op day four.
Just a note to let you all know I am doing better now that I am VERY medicated and will hopefully be moving to in-patient rehab soon. I will probably remain in the hospital for at least another week but I am making slow and steady progress.
Thanks to everyone who has called, emailed, sent wishes. These things have really helped me mentally and have improved my mood greatly. I will try and stay in touch through the web but I literally can only stay awake and aware for very brief periods of time.
Todays post is only possible via TheHusband who is typing this out. In fact I may nod off and some additional statements may be made without my knowledge or consent. Good thing I like him.
My husband is the most wonderful, kind-hearted, good looking, smartest A1 tip-top terrific person on the face of the planet! I worship the ground he walks on and will always follow his requests and wishes unquestionably!
Here I am hepped-up on goof balls during post-op day four.
Just a note to let you all know I am doing better now that I am VERY medicated and will hopefully be moving to in-patient rehab soon. I will probably remain in the hospital for at least another week but I am making slow and steady progress.
Thanks to everyone who has called, emailed, sent wishes. These things have really helped me mentally and have improved my mood greatly. I will try and stay in touch through the web but I literally can only stay awake and aware for very brief periods of time.
Todays post is only possible via TheHusband who is typing this out. In fact I may nod off and some additional statements may be made without my knowledge or consent. Good thing I like him.
My husband is the most wonderful, kind-hearted, good looking, smartest A1 tip-top terrific person on the face of the planet! I worship the ground he walks on and will always follow his requests and wishes unquestionably!
27 October 2009
BrainSurgeons and a Bionic Back
So I went to see a BrainSurgeon. Actually, I have seen two different BrainSurgeons and another NeuroDoc in the past few weeks. I guess, since the issue is my spine, that I should really call them SpineSurgeons, but BrainSurgeon is just that much more nerve-wracking. Nerve wracking -- get it? No? Fine, be that way.
Anyway, I initially saw BrainSurgeon1 on Oct 6. He's a good surgeon, and I have referred patients to him for 12 years. In fact, he operated on TheHusband's ruptured disc several years ago. He is extremely personable (yes, yes, he's a surgeon -- shocking, isn't it?). But he didn't listen to me and my concerns. We had a nice conversation -- we talked for about 45 minutes. However, much of that was him talking about using a dynamic stabilization device as part of the fusion procedure. Given that FDA has ordered companies that market these devices to conduct post-market studies in order to evaluate reported serious adverse events, I was understandably leery. But he just barrelled on, when I voiced my concerns. Given my other gait and spine related issues, I really think that these systems are a Bad Idea™. I am sure that no surgeon likes working on other doctors, especially one who is in a related field and Has Opinions. But those opinions should be listened to and acknowledged.
So after that exam, I spoke with a very nice and really smart Hopkins neurosurgery resident that I know. I showed him my MRI, described my symptoms, and asked him who he would let operate on his back if it looked my mine and he felt like I do. He gave me a name, called up BrainSurgeon2, and asked if he would see me. So I had an appointment with a Hopkins neurosurgeon within two weeks of that discussion. To be honest, BrainSurgeon2 works part-time at Hopkins and the rest at another Baltimore hospital. I tromped up there with MRI in hand last Monday. He took a history and did a quick neuro exam (very quick -- he's a neurosurgeon). Then he and I got down to brass tacks. He agreed with BrainSurgeon1 in that I need a spinal fusion (eeek!) as well as decompression of that freaking nerve root that is being compressed. He did not think that a dynamic stabilization device was a good idea (yay!), although he did have some other off-label device uses to suggest (NO!).
He then called up a NeuroDoc to see if he could fit me in soon. Turned out that NeuroDoc and I worked together a few years ago, so I got in 2 days later. Unfortunately, NeuroDoc zapped me with electric shocks and stuck needles in me, making me not like him quite as much as I once had. I swear that this is a test which is much better to perform on others than to have done on oneself. Conclusion: "If it walks like a duck, quacks like a duck, and is near a pond, it is a duck." He had to stick needles in me to come to that conclusion?
Given my sensitivity to medications, drugs to treat neuropathic pain are not an option. I've failed the majority of other conservative treatments (all those NeedleDoc appointments were in vain). So surgery it is. And thankfully I have health insurance (I will not mosey on down that conversational road right now -- I think that I am about as liberal as Eric in that respect).
So having received a 2nd opinion that I like better than the 1st one, and having failed conservative therapy, AND having refused a bionic back, I will undergo a single-level lumbar spinal fusion next week. Now all I have to do is convince myself that I won't die under anesthesia, wake up paralyzed, be worse off than I was before the surgery, or wake up during the surgery.
I haven't met the anesthesiologist yet -- I will certainly have some suggestions for him or her... Why do I suspect that I will be a really annoying hospital patient?
And let's not even go into the insanity that will be me when I am stuck at home for a few weeks.
Anyway, I initially saw BrainSurgeon1 on Oct 6. He's a good surgeon, and I have referred patients to him for 12 years. In fact, he operated on TheHusband's ruptured disc several years ago. He is extremely personable (yes, yes, he's a surgeon -- shocking, isn't it?). But he didn't listen to me and my concerns. We had a nice conversation -- we talked for about 45 minutes. However, much of that was him talking about using a dynamic stabilization device as part of the fusion procedure. Given that FDA has ordered companies that market these devices to conduct post-market studies in order to evaluate reported serious adverse events, I was understandably leery. But he just barrelled on, when I voiced my concerns. Given my other gait and spine related issues, I really think that these systems are a Bad Idea™. I am sure that no surgeon likes working on other doctors, especially one who is in a related field and Has Opinions. But those opinions should be listened to and acknowledged.
So after that exam, I spoke with a very nice and really smart Hopkins neurosurgery resident that I know. I showed him my MRI, described my symptoms, and asked him who he would let operate on his back if it looked my mine and he felt like I do. He gave me a name, called up BrainSurgeon2, and asked if he would see me. So I had an appointment with a Hopkins neurosurgeon within two weeks of that discussion. To be honest, BrainSurgeon2 works part-time at Hopkins and the rest at another Baltimore hospital. I tromped up there with MRI in hand last Monday. He took a history and did a quick neuro exam (very quick -- he's a neurosurgeon). Then he and I got down to brass tacks. He agreed with BrainSurgeon1 in that I need a spinal fusion (eeek!) as well as decompression of that freaking nerve root that is being compressed. He did not think that a dynamic stabilization device was a good idea (yay!), although he did have some other off-label device uses to suggest (NO!).
He then called up a NeuroDoc to see if he could fit me in soon. Turned out that NeuroDoc and I worked together a few years ago, so I got in 2 days later. Unfortunately, NeuroDoc zapped me with electric shocks and stuck needles in me, making me not like him quite as much as I once had. I swear that this is a test which is much better to perform on others than to have done on oneself. Conclusion: "If it walks like a duck, quacks like a duck, and is near a pond, it is a duck." He had to stick needles in me to come to that conclusion?
Given my sensitivity to medications, drugs to treat neuropathic pain are not an option. I've failed the majority of other conservative treatments (all those NeedleDoc appointments were in vain). So surgery it is. And thankfully I have health insurance (I will not mosey on down that conversational road right now -- I think that I am about as liberal as Eric in that respect).
So having received a 2nd opinion that I like better than the 1st one, and having failed conservative therapy, AND having refused a bionic back, I will undergo a single-level lumbar spinal fusion next week. Now all I have to do is convince myself that I won't die under anesthesia, wake up paralyzed, be worse off than I was before the surgery, or wake up during the surgery.
I haven't met the anesthesiologist yet -- I will certainly have some suggestions for him or her... Why do I suspect that I will be a really annoying hospital patient?
And let's not even go into the insanity that will be me when I am stuck at home for a few weeks.
29 September 2009
Blog vacation
Things are really stressful right now between boat-freaking-loads of work, my second full-time job (TPT, who is a much more fun job than the first one, but just doesn't pay as well), constant back pain (will be visiting the doctor who slashes with a scalpel next week), visits, visitors, spring cleaning (yes, yes, I know it's autumn), and various other stuff that creeps up and attacks without warning.
Even having the blog is stressful. I want to write stuff, but I am too tired. Then I get annoyed that I haven't blogged. So, in order to reduce my stress by a teensy bit, I am going to take a blog vacation. I should be back in about a month.
However, as an appropriately neurological send-off, I will leave you with the immortal words (and music) of Schoolhouse Rock:
(Although the glaringly obvious neurological mistake in this song annoys me a lot)
Even having the blog is stressful. I want to write stuff, but I am too tired. Then I get annoyed that I haven't blogged. So, in order to reduce my stress by a teensy bit, I am going to take a blog vacation. I should be back in about a month.
However, as an appropriately neurological send-off, I will leave you with the immortal words (and music) of Schoolhouse Rock:
(Although the glaringly obvious neurological mistake in this song annoys me a lot)
29 July 2009
Beware the Spinal Trap
In April 2008, Simon Singh wrote a piece for the Guardian that was critical of chiropractic "treatments". His assertion was that chiropractic treatment is not supported by evidence. The British Chiropractic Association (BCA) responded to this article by suing sued Mr Singh personally for libel. They initially refused to publish a rebuttal to his criticism, or to provide any evidence supporting the effectiveness of their treatments. Eventually the BCA produced a list of studies which supposedly supported chiropractic treatments, but all of them were problematic. Steven Novella at Science Based Medicine discussed these studies at length here. Unfortunately, in England the burden of proof in a libel suit is on the accused party (i.e., guilty until proven innnocent) and the judgment in the initial trial was that Mr Sungh was guilty of libel, based on a narrow definition of the word bogus.
Bloggers are being urged to repost an edited version of the article that got Simon Singh in trouble today. I found a copy of the original article but I am posting the edited version mostly to protect myself, just in case.
I personally have seen two strokes (due to verterbral artery occlusions) that I believe were due to chiropractic.
H/T to one of my neurology heroes Steven Novella at Science Based Medicine.
Bloggers are being urged to repost an edited version of the article that got Simon Singh in trouble today. I found a copy of the original article but I am posting the edited version mostly to protect myself, just in case.
Beware the spinal trap
Some practitioners claim it is a cure-all, but the research suggests chiropractic therapy has mixed results – and can even be lethal, says Simon Singh.
You might be surprised to know that the founder of chiropractic therapy, Daniel David Palmer, wrote that “99% of all diseases are caused by displaced vertebrae”. In the 1860s, Palmer began to develop his theory that the spine was involved in almost every illness because the spinal cord connects the brain to the rest of the body. Therefore any misalignment could cause a problem in distant parts of the body.
In fact, Palmer’s first chiropractic intervention supposedly cured a man who had been profoundly deaf for 17 years. His second treatment was equally strange, because he claimed that he treated a patient with heart trouble by correcting a displaced vertebra.
You might think that modern chiropractors restrict themselves to treating back problems, but in fact some still possess quite wacky ideas. The fundamentalists argue that they can cure anything, including helping treat children with colic, sleeping and feeding problems, frequent ear infections, asthma and prolonged crying – even though there is not a jot of evidence.
I can confidently label these assertions as utter nonsense because I have co-authored a book about alternative medicine with the world’s first professor of complementary medicine, Edzard Ernst. He learned chiropractic techniques himself and used them as a doctor. This is when he began to see the need for some critical evaluation. Among other projects, he examined the evidence from 70 trials exploring the benefits of chiropractic therapy in conditions unrelated to the back. He found no evidence to suggest that chiropractors could treat any such conditions.
But what about chiropractic in the context of treating back problems? Manipulating the spine can cure some problems, but results are mixed. To be fair, conventional approaches, such as physiotherapy, also struggle to treat back problems with any consistency. Nevertheless, conventional therapy is still preferable because of the serious dangers associated with chiropractic.
In 2001, a systematic review of five studies revealed that roughly half of all chiropractic patients experience temporary adverse effects, such as pain, numbness, stiffness, dizziness and headaches. These are relatively minor effects, but the frequency is very high, and this has to be weighed against the limited benefit offered by chiropractors.
More worryingly, the hallmark technique of the chiropractor, known as high-velocity, low-amplitude thrust, carries much more significant risks. This involves pushing joints beyond their natural range of motion by applying a short, sharp force. Although this is a safe procedure for most patients, others can suffer dislocations and fractures.
Worse still, manipulation of the neck can damage the vertebral arteries, which supply blood to the brain. So-called vertebral dissection can ultimately cut off the blood supply, which in turn can lead to a stroke and even death. Because there is usually a delay between the vertebral dissection and the blockage of blood to the brain, the link between chiropractic and strokes went unnoticed for many years. Recently, however, it has been possible to identify cases where spinal manipulation has certainly been the cause of vertebral dissection.
Laurie Mathiason was a 20-year-old Canadian waitress who visited a chiropractor 21 times between 1997 and 1998 to relieve her low-back pain. On her penultimate visit she complained of stiffness in her neck. That evening she began dropping plates at the restaurant, so she returned to the chiropractor. As the chiropractor manipulated her neck, Mathiason began to cry, her eyes started to roll, she foamed at the mouth and her body began to convulse. She was rushed to hospital, slipped into a coma and died three days later. At the inquest, the coroner declared: “Laurie died of a ruptured vertebral artery, which occurred in association with a chiropractic manipulation of the neck.”
This case is not unique. In Canada alone there have been several other women who have died after receiving chiropractic therapy, and Edzard Ernst has identified about 700 cases of serious complications among the medical literature. This should be a major concern for health officials, particularly as under-reporting will mean that the actual number of cases is much higher.
If spinal manipulation were a drug with such serious adverse effects and so little demonstrable benefit, then it would almost certainly have been taken off the market.
I personally have seen two strokes (due to verterbral artery occlusions) that I believe were due to chiropractic.
H/T to one of my neurology heroes Steven Novella at Science Based Medicine.
16 July 2009
Needle #2 (Updated)
By the time you guys and gals read this, I'll be at the NeedleDoc having epidural #2. I'm hoping this one is more effective. If not, I'm dubious about going for the 3rd epidural. It may be on to facet blocks, which are more painful.
I want a bionic spine. Just sayin'
________________
Updated 11:19 am
I'm home now. Holy crap, Batman, that sucker HURT! I don't know if it was because I didn't take any Valium this time (wtf was I thinking), or if it was because he went one level up (since the prior one was unsuccessful). Regardless, it hurt, even though I squeezed TheHusband's hand the whole time. If I get another one, I will be drugged to the gills. And if he suggests facet blocks, Valium and I will definitely be friends. And at least I don't have to walk on the evil treadmill tonight.
I know: whine, whine, whine. It isn't cancer, but I am tired of back pain. I just want to be normal again.
I want a bionic spine. Just sayin'
________________
Updated 11:19 am
I'm home now. Holy crap, Batman, that sucker HURT! I don't know if it was because I didn't take any Valium this time (wtf was I thinking), or if it was because he went one level up (since the prior one was unsuccessful). Regardless, it hurt, even though I squeezed TheHusband's hand the whole time. If I get another one, I will be drugged to the gills. And if he suggests facet blocks, Valium and I will definitely be friends. And at least I don't have to walk on the evil treadmill tonight.
I know: whine, whine, whine. It isn't cancer, but I am tired of back pain. I just want to be normal again.
12 June 2009
The doctor who wields the needle
I have a date with a long spinal needle in a few weeks. Between my schedule and NeedleDoc's schedule, I can't have my epidural injection until July 2. TheHusband will come and get to watch. I suspect that he'll be much more interested in what is on the screen (the procedure is done under fluoroscopy) than in holding my hand. I am not looking forward to it, but at least I'll be all drugged up. :-) And the doc has done about 40,000 of these things.
Stupid back.
Stupid back.
28 May 2009
22 May 2009
Other people think Jenny McCarthy is a moron, too!
I am not the only one! Actually, I knew that, but this post cried out for some hyperbole. Y'all know my feelings about Jenny McCarthy -- I think I've been obvious enough, right? Well, the amazingly erudite, incredibly intelligent, and wonderfully wordy docs over at Science-Based Medicine spend a lot of their energy dealing with Jenny McCarthy and her anti-vaxxer friends. Dr. Jones (not Indiana Jones, you idiot!) published a brilliant post dissecting and repudiating Jenny McCarthy's new video. She also does a great job outlining general concerns about this pervasive, under-the-radar, anti-science attitude which seems to be chic in the upper middle class SAHM set. This video contains the most appalling anti-science "information", really misinformation. Remember, it all spews out of the mouth of a former Playboy model and "actress", who styles herself as more knowledgeable about this issue than doctors.
I will not foam at the mouth today, but I did have to wash my eyes out with bleach after I watched the video. And yes, I did watch the whole thing.
I will not foam at the mouth today, but I did have to wash my eyes out with bleach after I watched the video. And yes, I did watch the whole thing.
16 May 2009
Jenny McCarthy = RABIES
I saw two cases of Subacute Sclerosing Panencephalitis, the worst sequela of measles, when I was in medical school. I won't forget either the disease or the two patients who suffered and died of it. I believe strongly in vaccination for the prevention of diseases that are otherwise untreatable and devastating. And the whole anti-vaccination movement literally makes me foam at the mouth ("Neurondoc, do you have rabies?").
I now have a new hero: The Amateur Scientist. I have a total and unabiding hatred of the crap that Jenny McCarthy spews in her quest to rid the world of vaccinations, all because she believes the disproven (time and again) theory that vaccines (or mercury or thimerasol or too many vaccines in too short a time or ...) cause autism. Because of the anti-vaccination movement, people are dying, formerly sporadic diseases are becoming endemic, and we may be losing our herd immunity. So here is a musical thanks to Jenny from her friends Measles, Mumps and Rubella...
H/T to Janiece, my current girl crush
_____________________________________________
update 5/16, 5:20 pm
See it's true!
Which Horrible Affliction are you?
A Rum and Monkey disease.
I now have a new hero: The Amateur Scientist. I have a total and unabiding hatred of the crap that Jenny McCarthy spews in her quest to rid the world of vaccinations, all because she believes the disproven (time and again) theory that vaccines (or mercury or thimerasol or too many vaccines in too short a time or ...) cause autism. Because of the anti-vaccination movement, people are dying, formerly sporadic diseases are becoming endemic, and we may be losing our herd immunity. So here is a musical thanks to Jenny from her friends Measles, Mumps and Rubella...
H/T to Janiece, my current girl crush
_____________________________________________
update 5/16, 5:20 pm
See it's true!
Which Horrible Affliction are you?
A Rum and Monkey disease.
06 May 2009
Neurology 101 -- Stroke
Acute ischemic stroke has been called a "brain attack" and is one of the leading causes of morbidity (illness) and mortality (death) in the US. I am not talking about hemorrhagic or bloody strokes. I am talking about what happens to the brain when the local blood supply is cut off. Before I talk epidemiology or clinical presentation, I will start off with pathogenesis of stroke -- why it happens at the cellular and tissue level.
Pathogenesis and Pathology of Acute Ischemic Stroke: The process leading from the development of atherosclerosis (deposition of cholesterol and other nasty crap in the arteries) to the occurrence of acute ischemic (non-bloody/non-hemorrhagic) stroke and consequent cell damage is complicated, and many of the intermediary steps are not completely understood. Ischemic stroke is primarily caused by atherosclerosis in large arteries (e.g., carotid, middle cerebral, and basilar arteries) or small arteries (eg, lenticulostriate, basilar penetrating, and medullary arteries), or it may be caused by a thrombus or clot that comes from the left side of the heart and zips up into the cerebral vasculature (cardioembolic). Atherogenesis is the process in which the inside of a blood vessel becomes narrowed by deposition of choleterol, fat, cells, and thrombus material, ultimately to the point of obstruction.
The earliest atherosclerotic lesion is the fatty streak, which was seen in a large autopsy study of coronary arteries and aortas in patients who died between infancy and age 29. (Stary 1989) In this study, approximately 65% of children ages 12 to 14 years had these lesions. Fatty streaks are visible to the eye as areas of yellowish discoloration of the surface of the intimal (inside) layer of the vessel wall. Under the microscope, the lesions primarily consist of lipid-filled macrophages (foam cells). Macrophages are white blood cells that enter into tissue and ingest foreign material. In this study, 8% of children in late childhood or early adolescence had already developed more advanced, focal lesions. These lesions, which occur almost entirely in branch points of the arterial vessels, are characterized by the addition of massive extra-cellular lipids that displaced normal cells and matrix.
By the time people are in their 20’s, some atheromatous lesions have evolved into complex fibrous plaques, which consist of a central acellular area of lipid covered by a cap of smooth muscle cells and collagen. Deposition of platelets and fibrin on the surface appears to be the result of injury to the lining cells of the vessel wall (endothelial injury) and clot-dependent fibrotic organization occurs. Over time, these early atherosclerotic lesions progress to clinically relevant and advanced atherosclerosis; risk factors play a role in the development of these more advanced lesions.
The progression of early atherosclerotic lesions to clinically advanced atherosclerotic lesions occurs with increased frequency in persons with risk factors for atherosclerotic disease (e.g., high blood pressure, high cholesterol, tobacco use). Atherosclerosis is considered to be a response to chronic minimal injury to the endothelial lining of the arterial wall. Interactions among white blood cells (monocytes, platelets, lymphocytes), lipoproteins and smooth muscle cells contribute to and maintain the pathogenic process. Note that monocytes are the circulating blood version of macrophages (in this case, blood cells that eat foreign stuff). Adhesion of circulating monocytes to the internal vessel wall is an early event in the development of atherosclerosis. After adhesion, the monocytes infiltrate between the endothelial cells and enter the subendothelial space and are transformed into lipid-filled macrophages called foam cells.
The proliferation of smooth muscle cells into the intima and over the layer of foam cells then occurs. Normally, smooth muscle arterial cells are present in the media (middle layer) rather than the intima, and it is the thickening of this layer that makes up a significant amount of the atherosclerotic lesion. Another important step in the formation of a clinically significant atherosclerotic lesion is platelet aggregation and thrombus formation. Platelets are the white blood celss that are responsible for blood clotting. Platelet aggregation is an importnat component of the blood clotting cascade and in the case of atheromatous lesions is thought to occur because of toxins released by macrophages and the ongoing intimal damage. Platelets bind to these areas and release growth factors that further stimulate proliferation of smooth muscle and possibly the formation of the outside capsule of these lesions.
Repetitive arterial wall injury of this type with thrombus formation is the major mechanism of atherosclerosis. Once blood supply within a vessel has been compromised, damage begins to occur within the neurons and support cells supplied by that artery. The membrane that surrounds the neuron is damaged and becomes leaky, thus allowing for influx of sodium, chloride, water and eventually calcium. Potassium flows out of the cell. Lactic acid and hydrogen further injure the cell, leading eventually to irreversible cellular injury and cell death.
Not all cells in the region affected by the impaired blood supply die. There are two major zones of injury in the affected regions: the core area of ischemia and the ischemic penumbra. It is within the core area of ischemia that the blood flow is the most impaired (below 25%) and it is here that severe ischemia leads to cell death. However, the penumbra is typically a rim of injured but not dead brain tissue outside of the core ischemic zone. This area is supplied by collateral blood vessels and may remain viable for several hours. However, the collateral circulation is typically unable to supply enough oxygen and nutrients to the injured brain tissue; therefore, unless reperfusion is established these cells eventually die, as well. It is the area of the penumbra that is the primary focus of treatment of acute ischemic strokes. So now you know something about how the cerebral blood vessels become damaged. Now let's talk about what happens to the person.
Clinical Aspects of Stroke: Stroke is the clinical term for a loss of brain function due to a disturbance in the blood supply in a particular region of the brain. Stroke is subdivided into two types: ischemic (in which the blood supply is interrupted) or hemorrhagic (in which a blood vessel ruptures). The WHO in the 1970s defined stroke as a "neurological deficit of cerebrovascular cause that persists beyond 24 hours or is interrupted by death within 24 hours" in order to differentiate permanent damage from a transient or reversible deficit caused by a transient ischemic attack (TIA). The time frame of 24 hours was chosen somewhat arbitrarily. There are many well-defined risk factors for stroke and include age > 55, hypertension, prior stroke or TIA, diabetes, hyperlipidemia, cigarette smoking, atrial fibrillation, and migraine with aura.
Signs and symptoms of stroke are dependent on the area of the brain involved. The area of the brain involved in stroke is dependent on the particular blood vessels affected and the type of stroke that occurred (ischemic vs. hemorrhagic). An ischemic stroke involving the anterior circulation (the area of interest in this submission) may result in a variety of neurological deficits. Left (dominant) hemisphere major or branch cortical infarction may lead to the following impairments: aphasia, right hemiparesis (paralysis), right-sided sensory loss, right-sided spatial neglect, right homonymous hemianopia (right half of the visual field is lost), and/or impaired right conjugate gaze. Right (nondominant) hemisphere major or branch cortical infarction may lead to the following impairments: left hemiparesis, left-sided sensory loss, left-sided spatial neglect, left homonymous hemianopia, and/or impaired left conjugate gaze.
Stroke is diagnosed via history, physical and neurological examination, and neuroimaging; it is most commonly diagnosed in an emergency room setting. It is highly important to differentiate between ischemic and hemorrhagic stroke as the management of these conditions is very different. A recent study comparing the effectiveness of MRI and CT for the diagnosis of acute stroke in a suburban hospital found MRI to be more effective in identifying acute stroke of all types.
Treatment of Acute Ischemic Stroke: Approved treatment for acute ischemic stroke is limited to a single therapy – intravenous recombinant tissue plasminogen activator, or IV-rtPA. Thrombectomy via the clot retrieval devices can be used in the setting acute ischemic stroke, these devices have not been approved or cleared for the treatment of stroke. The significant limiting factor for both of these treatments is the time from known onset to presentation to the ER. IV-rtPA must be administered within 3 hours of onset of stroke symptoms and the neurothrombectomy must occur within 8 hours. Only preventative and rehabilitative therapies exist beyond these two therapeutic options.
Epidemiology of Stroke (primarily from the Heart Disease and Stroke Statistics—2008 Update: A Report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee): Stroke is one of the most common disorders affecting the American population. The incidence of new or recurrent strokes among Americans is about 700,000, and 87% of these are ischemic strokes. About 500,000 of these are new strokes, and 200,000 are recurrent attacks. At younger ages, the stroke incidence rates in men are greater than in women but not at older ages. The male/female incidence was 1.25 in those 55 to 64 years of age, 1.50 in people 65 to 74 years of age, 1.07 in those 75 to 84 years of age, and 0.76 in those 85 years or greater. African-Americans are at a greater risk of stroke than whites. The age-adjusted stroke incidence rates in those 45 to 84 years of age are 6.6 per 1000 population in black males, 3.6 in white males, 4.9 in black females, and 2.3 in white females. Prevalence of stroke varies according to race: in 2005 it was 2.5% among whites, 3.2% among African-Americans, 2.4% among Asians and 5.1% among Native Americans.
Mortality due to stroke is an important consideration. Stroke accounted for about 1 of every 16 deaths in the United States in 2004. About 50% of stroke deaths in 2003 occurred out of hospital. Stroke total-mention mortality in 2002 was about 273,000 and ranks 3rd among all causes of death (behind heart disease and cancer). According to the ARIC study (NHLBI), 8 to 12% of ischemic strokes and 37 to 38% of hemorrhagic strokes result in death within 30 days, among people between the ages of 45 and 64, although the total rates are probably higher than these. An epidemiological study of stroke in Europe revealed an overall mortality rate (hemorrhagic and ischemic stroke) of 20% at 28 days. (Bejot 2007) A study of patients aged 65 recruited from a random sample of HCFA Medicare Part B eligibility lists showed that the 1-month case fatality was 12.6% for all strokes (8.1% ischemic and 44.6% hemorrhagic). The 2004 overall death rate for stroke was 50.0 (48.1 for white males, 73.9 for black males, 47.4 for white females, and 64.9 for black females). In 2002, the mean age at stroke death was 79.6 years. Males had a younger mean age at stroke death than females, and blacks, American Indians, and Asians had younger mean ages at death than whites.
Stroke is a leading cause of serious, long-term disability in the United States according to a survey of the US Bureau of the Census. In 1999, more than 1,100,000 American adults had some level limitations in function and/or activities of daily living, resulting from stroke. The length of time to recover from a stroke depends on its severity. 50% to 70% of stroke survivors regain functional independence; however, 15% to 30% are permanently disabled, and 20% require institutional care at 3 months after onset. In a study of ischemic stroke survivors who were at least 65 years of age, these disabilities were observed 6 months post-stroke:
Pathogenesis and Pathology of Acute Ischemic Stroke: The process leading from the development of atherosclerosis (deposition of cholesterol and other nasty crap in the arteries) to the occurrence of acute ischemic (non-bloody/non-hemorrhagic) stroke and consequent cell damage is complicated, and many of the intermediary steps are not completely understood. Ischemic stroke is primarily caused by atherosclerosis in large arteries (e.g., carotid, middle cerebral, and basilar arteries) or small arteries (eg, lenticulostriate, basilar penetrating, and medullary arteries), or it may be caused by a thrombus or clot that comes from the left side of the heart and zips up into the cerebral vasculature (cardioembolic). Atherogenesis is the process in which the inside of a blood vessel becomes narrowed by deposition of choleterol, fat, cells, and thrombus material, ultimately to the point of obstruction.
The earliest atherosclerotic lesion is the fatty streak, which was seen in a large autopsy study of coronary arteries and aortas in patients who died between infancy and age 29. (Stary 1989) In this study, approximately 65% of children ages 12 to 14 years had these lesions. Fatty streaks are visible to the eye as areas of yellowish discoloration of the surface of the intimal (inside) layer of the vessel wall. Under the microscope, the lesions primarily consist of lipid-filled macrophages (foam cells). Macrophages are white blood cells that enter into tissue and ingest foreign material. In this study, 8% of children in late childhood or early adolescence had already developed more advanced, focal lesions. These lesions, which occur almost entirely in branch points of the arterial vessels, are characterized by the addition of massive extra-cellular lipids that displaced normal cells and matrix.
By the time people are in their 20’s, some atheromatous lesions have evolved into complex fibrous plaques, which consist of a central acellular area of lipid covered by a cap of smooth muscle cells and collagen. Deposition of platelets and fibrin on the surface appears to be the result of injury to the lining cells of the vessel wall (endothelial injury) and clot-dependent fibrotic organization occurs. Over time, these early atherosclerotic lesions progress to clinically relevant and advanced atherosclerosis; risk factors play a role in the development of these more advanced lesions.
The progression of early atherosclerotic lesions to clinically advanced atherosclerotic lesions occurs with increased frequency in persons with risk factors for atherosclerotic disease (e.g., high blood pressure, high cholesterol, tobacco use). Atherosclerosis is considered to be a response to chronic minimal injury to the endothelial lining of the arterial wall. Interactions among white blood cells (monocytes, platelets, lymphocytes), lipoproteins and smooth muscle cells contribute to and maintain the pathogenic process. Note that monocytes are the circulating blood version of macrophages (in this case, blood cells that eat foreign stuff). Adhesion of circulating monocytes to the internal vessel wall is an early event in the development of atherosclerosis. After adhesion, the monocytes infiltrate between the endothelial cells and enter the subendothelial space and are transformed into lipid-filled macrophages called foam cells.
The proliferation of smooth muscle cells into the intima and over the layer of foam cells then occurs. Normally, smooth muscle arterial cells are present in the media (middle layer) rather than the intima, and it is the thickening of this layer that makes up a significant amount of the atherosclerotic lesion. Another important step in the formation of a clinically significant atherosclerotic lesion is platelet aggregation and thrombus formation. Platelets are the white blood celss that are responsible for blood clotting. Platelet aggregation is an importnat component of the blood clotting cascade and in the case of atheromatous lesions is thought to occur because of toxins released by macrophages and the ongoing intimal damage. Platelets bind to these areas and release growth factors that further stimulate proliferation of smooth muscle and possibly the formation of the outside capsule of these lesions.
Repetitive arterial wall injury of this type with thrombus formation is the major mechanism of atherosclerosis. Once blood supply within a vessel has been compromised, damage begins to occur within the neurons and support cells supplied by that artery. The membrane that surrounds the neuron is damaged and becomes leaky, thus allowing for influx of sodium, chloride, water and eventually calcium. Potassium flows out of the cell. Lactic acid and hydrogen further injure the cell, leading eventually to irreversible cellular injury and cell death.
Not all cells in the region affected by the impaired blood supply die. There are two major zones of injury in the affected regions: the core area of ischemia and the ischemic penumbra. It is within the core area of ischemia that the blood flow is the most impaired (below 25%) and it is here that severe ischemia leads to cell death. However, the penumbra is typically a rim of injured but not dead brain tissue outside of the core ischemic zone. This area is supplied by collateral blood vessels and may remain viable for several hours. However, the collateral circulation is typically unable to supply enough oxygen and nutrients to the injured brain tissue; therefore, unless reperfusion is established these cells eventually die, as well. It is the area of the penumbra that is the primary focus of treatment of acute ischemic strokes. So now you know something about how the cerebral blood vessels become damaged. Now let's talk about what happens to the person.
Clinical Aspects of Stroke: Stroke is the clinical term for a loss of brain function due to a disturbance in the blood supply in a particular region of the brain. Stroke is subdivided into two types: ischemic (in which the blood supply is interrupted) or hemorrhagic (in which a blood vessel ruptures). The WHO in the 1970s defined stroke as a "neurological deficit of cerebrovascular cause that persists beyond 24 hours or is interrupted by death within 24 hours" in order to differentiate permanent damage from a transient or reversible deficit caused by a transient ischemic attack (TIA). The time frame of 24 hours was chosen somewhat arbitrarily. There are many well-defined risk factors for stroke and include age > 55, hypertension, prior stroke or TIA, diabetes, hyperlipidemia, cigarette smoking, atrial fibrillation, and migraine with aura.
Signs and symptoms of stroke are dependent on the area of the brain involved. The area of the brain involved in stroke is dependent on the particular blood vessels affected and the type of stroke that occurred (ischemic vs. hemorrhagic). An ischemic stroke involving the anterior circulation (the area of interest in this submission) may result in a variety of neurological deficits. Left (dominant) hemisphere major or branch cortical infarction may lead to the following impairments: aphasia, right hemiparesis (paralysis), right-sided sensory loss, right-sided spatial neglect, right homonymous hemianopia (right half of the visual field is lost), and/or impaired right conjugate gaze. Right (nondominant) hemisphere major or branch cortical infarction may lead to the following impairments: left hemiparesis, left-sided sensory loss, left-sided spatial neglect, left homonymous hemianopia, and/or impaired left conjugate gaze.
Stroke is diagnosed via history, physical and neurological examination, and neuroimaging; it is most commonly diagnosed in an emergency room setting. It is highly important to differentiate between ischemic and hemorrhagic stroke as the management of these conditions is very different. A recent study comparing the effectiveness of MRI and CT for the diagnosis of acute stroke in a suburban hospital found MRI to be more effective in identifying acute stroke of all types.
Treatment of Acute Ischemic Stroke: Approved treatment for acute ischemic stroke is limited to a single therapy – intravenous recombinant tissue plasminogen activator, or IV-rtPA. Thrombectomy via the clot retrieval devices can be used in the setting acute ischemic stroke, these devices have not been approved or cleared for the treatment of stroke. The significant limiting factor for both of these treatments is the time from known onset to presentation to the ER. IV-rtPA must be administered within 3 hours of onset of stroke symptoms and the neurothrombectomy must occur within 8 hours. Only preventative and rehabilitative therapies exist beyond these two therapeutic options.
Epidemiology of Stroke (primarily from the Heart Disease and Stroke Statistics—2008 Update: A Report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee): Stroke is one of the most common disorders affecting the American population. The incidence of new or recurrent strokes among Americans is about 700,000, and 87% of these are ischemic strokes. About 500,000 of these are new strokes, and 200,000 are recurrent attacks. At younger ages, the stroke incidence rates in men are greater than in women but not at older ages. The male/female incidence was 1.25 in those 55 to 64 years of age, 1.50 in people 65 to 74 years of age, 1.07 in those 75 to 84 years of age, and 0.76 in those 85 years or greater. African-Americans are at a greater risk of stroke than whites. The age-adjusted stroke incidence rates in those 45 to 84 years of age are 6.6 per 1000 population in black males, 3.6 in white males, 4.9 in black females, and 2.3 in white females. Prevalence of stroke varies according to race: in 2005 it was 2.5% among whites, 3.2% among African-Americans, 2.4% among Asians and 5.1% among Native Americans.
Mortality due to stroke is an important consideration. Stroke accounted for about 1 of every 16 deaths in the United States in 2004. About 50% of stroke deaths in 2003 occurred out of hospital. Stroke total-mention mortality in 2002 was about 273,000 and ranks 3rd among all causes of death (behind heart disease and cancer). According to the ARIC study (NHLBI), 8 to 12% of ischemic strokes and 37 to 38% of hemorrhagic strokes result in death within 30 days, among people between the ages of 45 and 64, although the total rates are probably higher than these. An epidemiological study of stroke in Europe revealed an overall mortality rate (hemorrhagic and ischemic stroke) of 20% at 28 days. (Bejot 2007) A study of patients aged 65 recruited from a random sample of HCFA Medicare Part B eligibility lists showed that the 1-month case fatality was 12.6% for all strokes (8.1% ischemic and 44.6% hemorrhagic). The 2004 overall death rate for stroke was 50.0 (48.1 for white males, 73.9 for black males, 47.4 for white females, and 64.9 for black females). In 2002, the mean age at stroke death was 79.6 years. Males had a younger mean age at stroke death than females, and blacks, American Indians, and Asians had younger mean ages at death than whites.
Stroke is a leading cause of serious, long-term disability in the United States according to a survey of the US Bureau of the Census. In 1999, more than 1,100,000 American adults had some level limitations in function and/or activities of daily living, resulting from stroke. The length of time to recover from a stroke depends on its severity. 50% to 70% of stroke survivors regain functional independence; however, 15% to 30% are permanently disabled, and 20% require institutional care at 3 months after onset. In a study of ischemic stroke survivors who were at least 65 years of age, these disabilities were observed 6 months post-stroke:
- 50% had some hemiparesis;
- 30% were unable to walk without some assistance;
- 26% were dependent in activities of daily living;
- 19% had aphasia (inability or difficulty in expressing or comprehending language);
28 April 2009
Seattle and the Bow Ties
So I have been in Seattle since Saturday afternoon. I am here for the annual meeting of the American Academy of Neurology. I have been a member of the AAN for 15 years and have been to 6 or 7 annual meetings. I have frequently referred to the AAN annual meeting as one of the largest collection of old white guys wearing bow ties, because, well, there are lots of old white guys wearing bow ties here.
I have some random thoughts about this year's meeting:
I have some random thoughts about this year's meeting:
- This meeting seems to be much less well-attended than the last few I went to -- less people around, little crowds, no pushing or being pushed.
- Neurobowl (neurology trivia contest) is still fun.
- There are a lot fewer freebies from the drug and device companies, which is fine with me.
- Fewer Europeans seem to be here this year than last year, but that may be a function of the West Coast location.
- The "free" seminars and lectures are the usual combination of completely obscure ("A Tat-Immune Complex Binds the NMDA Receptor, Preventing Receptor Activation and Excitotoxicity"), unrelated to anything I might ever do or see ("Predictive Value of Brainstem Auditory Evoked Potentials (BAEPs) in Decreasing Post Operative Neurological Deficit During Expanded Endonasal Approach (EEA) to Skull Base Surgeries"), interesting ("The Transition of REM Sleep Behavior Disorder to Neurodegenerative Disease") and something that may seriously affect what I do on a daily basis ("Improving Reliability of Stroke Disability Assessment in Clinical Trials and Clinical Practice: The Focused Assessment for the Modified Rankin Scale").
- Neurology of Sleep was (unfortunately) well-named. It was really hard to stay awake.
- I chatted with the former chairman of the Dept of Neurology at my medical school. He was very supportive of me when I was a med student, and I hadn't seen him in years. He didn't remember seeing me at my Boards.
- It's much more fun to come to these meetings with coworkers.
- KOLs can be pompous and annoying, but often they have very interesting theories, ideas, projects, and clinical trials.
17 April 2009
Neurology 101 -- Huntington's Disease (part 2)
What is any neurology resident's biggest dread? No, it's not getting hammered with 12 admissions in a single night (although that is pretty high up there). Or having a patient code in the middle of the night and not make it. Nope. It's the Neurology Boards. They loom. And at the risk of sounding snotty and crotchety, they ain't the same now as they were when I took them. The Neurology Boards in the mid-late 1990's consisted of a full day written exam, and about 6 months later, if you passed the written, you got the opportunity to take the dreaded oral exam. I understand that the oral portion has been or is soon to be phased out. Lucky residents.
The year I took the Orals, the east coast section was in NYC. We all gathered at the Waldorf-Astoria the day before and got our assignments. I was assigned to Columbia-Presbyterian. That was fine by me, as I was somewhat familiar with Columbia's Neurological Institute. The Oral Boards are split into 3 segments, depending on what your specialty is. I am an adult neurologist, so I had adult and pediatric vignettes and an adult live patient. I won't go into the vignettes, except to say that I cried during the peds vignettes. Damn pediatric neurologists played good-cop-bad-cop and flustered the shit out of me.
Anyway, I would like to tell you about my live patient. My live patient segment was second, in between the vignettes. I went over to the Neurology Clinic and met up with my torturers ... er, I mean examiners. They took me into a little exam room, where a woman was sitting in a plastic chair. She was very fidgety, and initially I thought "why, she's as nervous as I am" which tells you how clouded my thinking was at that moment. The examiners explained to me what was expected and let me interview and examine the patient. I introduced myself and got down to business.
NeuronDoc: "Hi Mrs. X. My name is Dr. NeuronDoc."
Mrs. X: "Hi. How are you?"
ND: "I'm fine. How about yourself?"
MX: "I'm okay, thanks."
ND: "So tell me a little bit about yourself."
MX (clearly agitated) : "I can't do that."
ND (a bit startled): "Why not?"
MX (pointing to the examiners): "They told me I can't tell you."
ND (thinking surprisingly quickly): "Ah. I am sure they didn't mean that you can't say anything. You just can't tell me the name of your disease."
MX: "That's right."
ND: "Let's pretend that this is the first time you are coming to a doctor for your problem, that I am the first doctor you are seeing for this..."
So I went on to interview her. She told me that she was 49 years old, and that her problems had begun about 6 years earlier. She said she was off balance and fell easily. She described feeling edgy and depressed at times. She told me that she couldn't walk a straight line, or remember things as well as she used to. All the while she was telling this, she was very fidgety, shifting around in her seat, futzing with her hair, scratching, moving, rubbing. She wasn't quite 100% with it, and sometimes her answers were confusing. I asked lots of other questions, and eventually got to family history. I asked if anyone else in her family had any medical problems. She told me that her mother, uncle, several cousins, and a grandmother had the same thing she had. Bingo.
After asking all of the appropriate questions, I began to examine her. She had unusual eye movements (slowed saccades), motor impersistence, variable stride length while walking, postural instability, and mild dementia. She also had very obvious, fairly constant, and purposeless movements that, at times, would be converted to a purposeful movement.
Hmmm. Motor impersistence, variable gait pattern, chorea all over the place, and that family history. Well, it basically could only be Huntington's disease. But, crap, I had to come up with at least two other potential diagnoses -- they wanted to hear my top three. Unfortunately, my top 3 diagnoses were Huntington's disease, Huntington's disease, and Huntington's disease. I was completely stuck. Who would have thought that I would come up with only a single diagnosis? I was expecting them to trot out someone with a zebra-disease (really rare and hard to diagnose). But no, they gave me someone with basically only one choice for a diagnosis.
After I finished examining her, the examiners excused Mrs. X, who said "good luck, dearie" and left. I thought thanks, but now what the hell do I do? The examiners turned to me and asked what was my differential diagnosis for Mrs. X. I said exactly this: "My first three choices in the differential diagnosis are Huntington's disease, Huntington's disease, and Huntington's disease. She has all of the classic signs and symptoms of the disease and her family history is consistent with a dominantly inherited disorder. Basically it can only be HD. There are some really rare autosomal recessive disorders that have chorea and dementia, but the disease is clearly dominant. It isn't Sydenham's chorea or post-partum chorea or chorea secondary to lupus. It's Huntington's disease."
The examiners looked at me, then each other, then at me again. One said "Hmm. Well..." However, there were 15 minutes left. No oral boards examiner worth his or her salt will let an examinee finish early. So they grilled me about the genetics of HD (which thankfully I had randomly studied a few days earlier) and then basically turned it into a free-for-all. They grilled me about whatever the heck they wanted to. But I passed and never did really give them a differential diagnosis for that patient.
Thanks, Mrs. X.
The year I took the Orals, the east coast section was in NYC. We all gathered at the Waldorf-Astoria the day before and got our assignments. I was assigned to Columbia-Presbyterian. That was fine by me, as I was somewhat familiar with Columbia's Neurological Institute. The Oral Boards are split into 3 segments, depending on what your specialty is. I am an adult neurologist, so I had adult and pediatric vignettes and an adult live patient. I won't go into the vignettes, except to say that I cried during the peds vignettes. Damn pediatric neurologists played good-cop-bad-cop and flustered the shit out of me.
Anyway, I would like to tell you about my live patient. My live patient segment was second, in between the vignettes. I went over to the Neurology Clinic and met up with my torturers ... er, I mean examiners. They took me into a little exam room, where a woman was sitting in a plastic chair. She was very fidgety, and initially I thought "why, she's as nervous as I am" which tells you how clouded my thinking was at that moment. The examiners explained to me what was expected and let me interview and examine the patient. I introduced myself and got down to business.
NeuronDoc: "Hi Mrs. X. My name is Dr. NeuronDoc."
Mrs. X: "Hi. How are you?"
ND: "I'm fine. How about yourself?"
MX: "I'm okay, thanks."
ND: "So tell me a little bit about yourself."
MX (clearly agitated) : "I can't do that."
ND (a bit startled): "Why not?"
MX (pointing to the examiners): "They told me I can't tell you."
ND (thinking surprisingly quickly): "Ah. I am sure they didn't mean that you can't say anything. You just can't tell me the name of your disease."
MX: "That's right."
ND: "Let's pretend that this is the first time you are coming to a doctor for your problem, that I am the first doctor you are seeing for this..."
So I went on to interview her. She told me that she was 49 years old, and that her problems had begun about 6 years earlier. She said she was off balance and fell easily. She described feeling edgy and depressed at times. She told me that she couldn't walk a straight line, or remember things as well as she used to. All the while she was telling this, she was very fidgety, shifting around in her seat, futzing with her hair, scratching, moving, rubbing. She wasn't quite 100% with it, and sometimes her answers were confusing. I asked lots of other questions, and eventually got to family history. I asked if anyone else in her family had any medical problems. She told me that her mother, uncle, several cousins, and a grandmother had the same thing she had. Bingo.
After asking all of the appropriate questions, I began to examine her. She had unusual eye movements (slowed saccades), motor impersistence, variable stride length while walking, postural instability, and mild dementia. She also had very obvious, fairly constant, and purposeless movements that, at times, would be converted to a purposeful movement.
Hmmm. Motor impersistence, variable gait pattern, chorea all over the place, and that family history. Well, it basically could only be Huntington's disease. But, crap, I had to come up with at least two other potential diagnoses -- they wanted to hear my top three. Unfortunately, my top 3 diagnoses were Huntington's disease, Huntington's disease, and Huntington's disease. I was completely stuck. Who would have thought that I would come up with only a single diagnosis? I was expecting them to trot out someone with a zebra-disease (really rare and hard to diagnose). But no, they gave me someone with basically only one choice for a diagnosis.
After I finished examining her, the examiners excused Mrs. X, who said "good luck, dearie" and left. I thought thanks, but now what the hell do I do? The examiners turned to me and asked what was my differential diagnosis for Mrs. X. I said exactly this: "My first three choices in the differential diagnosis are Huntington's disease, Huntington's disease, and Huntington's disease. She has all of the classic signs and symptoms of the disease and her family history is consistent with a dominantly inherited disorder. Basically it can only be HD. There are some really rare autosomal recessive disorders that have chorea and dementia, but the disease is clearly dominant. It isn't Sydenham's chorea or post-partum chorea or chorea secondary to lupus. It's Huntington's disease."
The examiners looked at me, then each other, then at me again. One said "Hmm. Well..." However, there were 15 minutes left. No oral boards examiner worth his or her salt will let an examinee finish early. So they grilled me about the genetics of HD (which thankfully I had randomly studied a few days earlier) and then basically turned it into a free-for-all. They grilled me about whatever the heck they wanted to. But I passed and never did really give them a differential diagnosis for that patient.
Thanks, Mrs. X.
16 April 2009
Neuroloy 101 -- Huntington's Disease (part 1)
Let’s talk “diagnose and adios” today. I am going to tell you about one of the biggies, one of the really bad neurologic diseases, up there in the top 10, maybe even the top 5, of “neurologic diseases that you don’t want to get”. But in a weird way, it is near and dear to my heart (no, I don’t have it, nor am I likely to develop it), and I’ll get to why in a bit. I am talking about Huntington’s disease (or Huntington’s chorea, as it was once called). Huntington’s disease is a classic progressive, degenerative neurologic disease that neurologists really can’t treat. Clinical signs and symptoms include chorea, cognitive impairments and psychiatric problems.
It is a hereditary disease that is transmitted from one parent in an autosomal dominant pattern. For those of you who took high school biology, but don’t remember it, autosomal inheritance occurs when the gene carrying the mutation is located on an “autosome” (non-sex chromosome). If something is inherited in an dominant pattern that means that only one gene is necessary for the disease to occur. And because only one gene is necessary for development of the disease, children of an affected parent have a 50/50 chance of having the disease. I am going to leave this genetics discussion simple and not get into variable expression or reduced penetrance. Suffice it to say that if one of your parents has Huntington’s disease (HD), you have a 50% chance of getting it. But it is a little more complicated than that, actually.
It is the genetics of Huntington’s disease that is so fascinating. The Huntingtin gene, located on the short arm of chromosome 4, was identified in 1993 and was the first non-sex-linked dominant disease gene to be documented. It is one of the trinucleotide repeat disorders. These are genetic disorders in which one DNA triplet (trinucleotide) in the gene sequence is repeated multiple times. It is this repetition, at least in the case of HD, that causes the clinical symptoms. The three DNA bases—cytosine-adenine-guanine (CAG)—repeated multiple times (i.e. ...CAGCAGCAG...) in a protein-coding portion of the gene (the protein is, not surprisingly, called huntingtin). CAG is the genetic code for the amino acid glutamine, so a series of CAGs results in a chain of glutamine known as a polyglutamine or polyQ tract.
Normal people do have CAG repeats in that region of chromosome 4; normal is considered less than 29 glutamine repeats. If a person has 29 – 34 CAG repeats, the resulting huntingtin protein will function normally, but the next generation is at risk. The gray zone is 35-39 CAG repeats, which will cause the disease in some patients but not others (the reduced penetrance I mentioned earlier). If the patient has 40 or more repeats, they will develop HD. Trinucelotide repeat disorders are frequently associated with genetic anticipation, in which successive generations have increasing numbers of CAG repeats and earlier/more severe disease expression.
There is genetic testing available that calculates the number of trinucleotide repeats. Most people at risk of developing HD do not actually take the test prior to developing symptoms, primarily because there is no treatment. Prior to ordering the test, significant counseling is recommended. In utero genetic screening is also available.
The altered or mutant huntingtin increases the decay rate of medium spiny neurons, which affects specific regions of the brain depending on the amounts of these neurons. The areas of the brain most affected, as seen in histopathological examinations are the caudate nucleus and putamen. These comprise the striatum. Other areas that are affected include the substantia nigra, parts of the cerebral cortex, hippocampus, angular gyrus, purkinje cells in the cerebellum, parts of the hypothalamus and thalamus. It is the striatal degeneration that causes the most prominent symptoms of HD.
Huntington's brain ------------- Normal brain
The symptoms of HD most commonly appear between the ages of 35 and 44, typically after the patient has had children. Presentation may occur before age 20, which is called the akinetic-rigid or Westphal variant. The most common symptom seen in HD patients is chorea. These are jerky, random, and uncontrollable movements that are almost dance-like (hence the name chorea – from choreos – dance in Greek). Other motor symptoms are rigidity and dystonia (sustained muscle contractions causing twisting movements or abnormal posture), which typically become more prominent than the chorea as the disease progresses. Motor impersistence (difficulty maintaining a specific motor task) is another common sign of HD. One way to assess this is to have the patient stick his tongue out. He will not be able to hold it out for more than a few seconds. It will go back in, then out, etc… Motor control is severely affected as the disease progresses, causing instability, inability to walk, difficulty chewing swallowing and talking.
Cognitive dysfunction is also present, commonly prior to development of the motor symptoms. Progressive cognitive decline will almost inevitably occur in these patients, with memory difficulties (initially short-term, then long-term as well). The cognitive decline eventually leads to dementia in most patients. It is a subcortical dementia, with prominent personality changes and attentional difficulties, rather than a cortical dementia, as seen in Alzheimer’s disease. Psychiatric problems are also not infrequently seen in these patients – depression, anxiety, aggression, even psychosis. The psychiatric manifestations can severely affect the patient’s ability to function and may be a trigger for institutionalization.
There is no cure and no effective treatment for the disease. Tetrabenazine was approved for the treatment of chorea in HD patients, the only drug approved for this particular use. Other drugs used in the reduction of HD chorea are neuroleptics (antipsychotic drugs) and benzodiazepines (Valium and its cousins). For the most part, medications are used to reduce the symptoms and are only semi-effective. Anti-parkinsonian drugs can sometimes be used for rigidity. Anti-depressants may help mood disorders. Speech therapy to help with the dysphagia is crucial for the patients to maintain their weight. Prognosis for these patients basically sucks. Life expectancy ranges from 10-30 years from diagnosis, and the disease is inexorably progressive. Patients die of associated complications (pneumonia, aspiration, injury, choking). Suicide is not uncommon (~7%).
Tomorrow, I will tell you why this disease is important to me…
It is a hereditary disease that is transmitted from one parent in an autosomal dominant pattern. For those of you who took high school biology, but don’t remember it, autosomal inheritance occurs when the gene carrying the mutation is located on an “autosome” (non-sex chromosome). If something is inherited in an dominant pattern that means that only one gene is necessary for the disease to occur. And because only one gene is necessary for development of the disease, children of an affected parent have a 50/50 chance of having the disease. I am going to leave this genetics discussion simple and not get into variable expression or reduced penetrance. Suffice it to say that if one of your parents has Huntington’s disease (HD), you have a 50% chance of getting it. But it is a little more complicated than that, actually.
It is the genetics of Huntington’s disease that is so fascinating. The Huntingtin gene, located on the short arm of chromosome 4, was identified in 1993 and was the first non-sex-linked dominant disease gene to be documented. It is one of the trinucleotide repeat disorders. These are genetic disorders in which one DNA triplet (trinucleotide) in the gene sequence is repeated multiple times. It is this repetition, at least in the case of HD, that causes the clinical symptoms. The three DNA bases—cytosine-adenine-guanine (CAG)—repeated multiple times (i.e. ...CAGCAGCAG...) in a protein-coding portion of the gene (the protein is, not surprisingly, called huntingtin). CAG is the genetic code for the amino acid glutamine, so a series of CAGs results in a chain of glutamine known as a polyglutamine or polyQ tract.
Normal people do have CAG repeats in that region of chromosome 4; normal is considered less than 29 glutamine repeats. If a person has 29 – 34 CAG repeats, the resulting huntingtin protein will function normally, but the next generation is at risk. The gray zone is 35-39 CAG repeats, which will cause the disease in some patients but not others (the reduced penetrance I mentioned earlier). If the patient has 40 or more repeats, they will develop HD. Trinucelotide repeat disorders are frequently associated with genetic anticipation, in which successive generations have increasing numbers of CAG repeats and earlier/more severe disease expression.
There is genetic testing available that calculates the number of trinucleotide repeats. Most people at risk of developing HD do not actually take the test prior to developing symptoms, primarily because there is no treatment. Prior to ordering the test, significant counseling is recommended. In utero genetic screening is also available.
The altered or mutant huntingtin increases the decay rate of medium spiny neurons, which affects specific regions of the brain depending on the amounts of these neurons. The areas of the brain most affected, as seen in histopathological examinations are the caudate nucleus and putamen. These comprise the striatum. Other areas that are affected include the substantia nigra, parts of the cerebral cortex, hippocampus, angular gyrus, purkinje cells in the cerebellum, parts of the hypothalamus and thalamus. It is the striatal degeneration that causes the most prominent symptoms of HD.
Huntington's brain ------------- Normal brain
The symptoms of HD most commonly appear between the ages of 35 and 44, typically after the patient has had children. Presentation may occur before age 20, which is called the akinetic-rigid or Westphal variant. The most common symptom seen in HD patients is chorea. These are jerky, random, and uncontrollable movements that are almost dance-like (hence the name chorea – from choreos – dance in Greek). Other motor symptoms are rigidity and dystonia (sustained muscle contractions causing twisting movements or abnormal posture), which typically become more prominent than the chorea as the disease progresses. Motor impersistence (difficulty maintaining a specific motor task) is another common sign of HD. One way to assess this is to have the patient stick his tongue out. He will not be able to hold it out for more than a few seconds. It will go back in, then out, etc… Motor control is severely affected as the disease progresses, causing instability, inability to walk, difficulty chewing swallowing and talking.
Cognitive dysfunction is also present, commonly prior to development of the motor symptoms. Progressive cognitive decline will almost inevitably occur in these patients, with memory difficulties (initially short-term, then long-term as well). The cognitive decline eventually leads to dementia in most patients. It is a subcortical dementia, with prominent personality changes and attentional difficulties, rather than a cortical dementia, as seen in Alzheimer’s disease. Psychiatric problems are also not infrequently seen in these patients – depression, anxiety, aggression, even psychosis. The psychiatric manifestations can severely affect the patient’s ability to function and may be a trigger for institutionalization.
There is no cure and no effective treatment for the disease. Tetrabenazine was approved for the treatment of chorea in HD patients, the only drug approved for this particular use. Other drugs used in the reduction of HD chorea are neuroleptics (antipsychotic drugs) and benzodiazepines (Valium and its cousins). For the most part, medications are used to reduce the symptoms and are only semi-effective. Anti-parkinsonian drugs can sometimes be used for rigidity. Anti-depressants may help mood disorders. Speech therapy to help with the dysphagia is crucial for the patients to maintain their weight. Prognosis for these patients basically sucks. Life expectancy ranges from 10-30 years from diagnosis, and the disease is inexorably progressive. Patients die of associated complications (pneumonia, aspiration, injury, choking). Suicide is not uncommon (~7%).
Tomorrow, I will tell you why this disease is important to me…
29 March 2009
Diagnose and Adios...
Random person: What kind of doctor are you?
Neurondoc: I am a neurologist.
RP: What is a neurologist? Are you a brain surgeon?
Me: Umm, no, I don't get my hands dirty and I don't perform surgery.
RP: You're not a brain surgeon?
Me (slightly annoyed): No.
RP: So what does a neurologist do, if they can't do surgery?
Me: I treat patients with neurological diseases.
RP: Ah.... How?
Me (grrrr): With medications and therapies and sometimes referrals for surgery.
That is a not uncommon exchange between me and some random curious person, regarding my medical specialty. Unfortunately, many medical students and physicians exhibit a similar attitude, which is characterized as "diagnose and adios". There are many neurological diseases and disorders that do not have treatments, so many medical professionals consider it a frutiless specialty -- we can diagnose the patients, but we can't do a thing for them. It is a highly annoying attitude that pervades medicine in general. When I decided to go into neurology during my 3rd year of med school, I got one of several reactions ("Why?" "Yuck!" "Better you than me." "Diagnose and adios..." "You can't do anything for the patient, why do you want to go into neurology?" etc). Sort of like Bones McCoy's attitude to 20th century medicine in Start Trek IV, but even more annoying.
The brain absolutely fascinates me, nerves to a lesser degree. The brain is the organ that all other organs exist to support and live to serve. The heart pumps blood to the brain -- percent blood flow from heart to brain is 15-20%. The lungs oxygenate blood to provide the brain with oxygen, and the brain uses about 20% of total resting oxygen.* The gut absorbs nutrients so that the brain gets fed. The liver and kidney clean the blood of toxins and other crap, so that the brain remains healthy and isn't poisoned in situ. The eyes provide visual information for the brain to process; the ears allow for auditory recording. The legs move the body around so that the brain has new things to experience or to avoid dangerous situations. I am "brain-o-centric", okay?
However, I do have to agree that neurology is fraught with progressive, degenerative and untreatable conditions: e.g., Huntington's Disease, Alzheimer's diease, Lou Gehrig's Disease (ALS), Muscular Dystrophy, traumatic brain injury, spinal cord injury. Even the "treatable" ones are not usually curable: Multiple Sclerosis, Stroke, Parkinson's Disease, Epilepsy. So why am I a neurologist? As I said, the brain is totally cool and interesting. Knowledge in medicine is ever-expanding, and we are learning more and more about the underlying workings of the brain, spinal cord and nerves, and also about the diseases that affect the nervous system.
Perhaps, Pinky and the Brain express their love of the nervous system better than I ever could...
Fun website for silly brain and other nervous system facts is Brain Facts and Figures
* Kandel et al., Principles of Neural Science, New York: McGraw Hill, 2000 (<--- look a footnote!)
Neurondoc: I am a neurologist.
RP: What is a neurologist? Are you a brain surgeon?
Me: Umm, no, I don't get my hands dirty and I don't perform surgery.
RP: You're not a brain surgeon?
Me (slightly annoyed): No.
RP: So what does a neurologist do, if they can't do surgery?
Me: I treat patients with neurological diseases.
RP: Ah.... How?
Me (grrrr): With medications and therapies and sometimes referrals for surgery.
That is a not uncommon exchange between me and some random curious person, regarding my medical specialty. Unfortunately, many medical students and physicians exhibit a similar attitude, which is characterized as "diagnose and adios". There are many neurological diseases and disorders that do not have treatments, so many medical professionals consider it a frutiless specialty -- we can diagnose the patients, but we can't do a thing for them. It is a highly annoying attitude that pervades medicine in general. When I decided to go into neurology during my 3rd year of med school, I got one of several reactions ("Why?" "Yuck!" "Better you than me." "Diagnose and adios..." "You can't do anything for the patient, why do you want to go into neurology?" etc). Sort of like Bones McCoy's attitude to 20th century medicine in Start Trek IV, but even more annoying.
The brain absolutely fascinates me, nerves to a lesser degree. The brain is the organ that all other organs exist to support and live to serve. The heart pumps blood to the brain -- percent blood flow from heart to brain is 15-20%. The lungs oxygenate blood to provide the brain with oxygen, and the brain uses about 20% of total resting oxygen.* The gut absorbs nutrients so that the brain gets fed. The liver and kidney clean the blood of toxins and other crap, so that the brain remains healthy and isn't poisoned in situ. The eyes provide visual information for the brain to process; the ears allow for auditory recording. The legs move the body around so that the brain has new things to experience or to avoid dangerous situations. I am "brain-o-centric", okay?
However, I do have to agree that neurology is fraught with progressive, degenerative and untreatable conditions: e.g., Huntington's Disease, Alzheimer's diease, Lou Gehrig's Disease (ALS), Muscular Dystrophy, traumatic brain injury, spinal cord injury. Even the "treatable" ones are not usually curable: Multiple Sclerosis, Stroke, Parkinson's Disease, Epilepsy. So why am I a neurologist? As I said, the brain is totally cool and interesting. Knowledge in medicine is ever-expanding, and we are learning more and more about the underlying workings of the brain, spinal cord and nerves, and also about the diseases that affect the nervous system.
Perhaps, Pinky and the Brain express their love of the nervous system better than I ever could...
Fun website for silly brain and other nervous system facts is Brain Facts and Figures
* Kandel et al., Principles of Neural Science, New York: McGraw Hill, 2000 (<--- look a footnote!)
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