House MD Guide :: Blogs :: Differential Diagnosis:
A Medical Guide to House
Medical Trivia: Angioedema
In Episode 305, the patients' angioedema (swelling in their throats) was found to be due to C1 esterase inhibitor deficiency. Question: What medication mentioned by Chris Rock in Bigger and Blacker could you use to treat the most common side effect of a medication that is classically associated with causing angioedema? Answer: Robitussin. Angiotensin-converting enzyme inhibitors (used to lower blood pressure) are classically associated with causing angioedema and ... a cough. And nothing cures cough like Robitussin (see below). Chris Rock: When I was a kid, I had to be near-death to see a doctor, so my daddy got into the habit of putting Robitussin on everything, and I mean EVERYTHING!
[Impersonating his father and himself]
Chris Rock: Daddy, I got asthma! "Well here, take some Robitussin!" Daddy, I got cancer! "Here, take some Robitussin!" Daddy, I broke my leg! "Here, put some Robitussin on it... that's right, let the Robitussin sink in there."
Episode 102: Paternity
"What's the differential diagnosis for writing G's like a junior high school girl?" - Dr. House
Chief Complaint: Double vision, night terrors History of Present Illness: Dan is a 16-year-old man with no significant medical history who presents today with a recent episode of sudden-onset diplopia and a 3-week history of night terrors. He has been seen by 2 neurologists, who could not discern a cause. The patient's denies a history of post-traumatic stress disorder, though he does admit to a recent hit during a lacrosse game which occurred after the episode of diplopia. His family denies a history of sexual abuse. Past Medical History: None. Medications: None. Allergies: No known allergies. Social History: The patient lives with his parents at home. He plays lacrosse for his high school team. Use of alcohol, tobacco, and drugs is unknown. Family History: No significant history. Physical Exam: Nonfebrile. Gen: Observed a myoclonic jerk of the right leg. HEENT: Macular margins within normal limits and no lesions observed on retinal exam. "Color is good" [whatever that means]. Neuro: Left eye nonreactive to finger-flick [an approximation of the corneal reflex?]. Patient is only able to recite one animal that begins with "b" (baby elephant) [This does exist as a neuropsych test but by itself doesn't really tell you much]. Labs/Imaging:CBC, basic metabolic panel within normal limits. LFTs normal. Chest x-ray showed no abnormalities. CT head showed no abnormalities. MRI brain: No lesions in the white matter. No structural abnormalities. No space-occupying tumors. Medical Decision Making: Given the patient's history of night terrors prior to the recent onset of diplopia, a polysomnograph was performed, during which the patient experienced a night terror. A head CT scan and brain MRI were both reported as normal. A closer look at the MRI revealed meningeal enhancement and bowing of the corpus callosum, causing pressure on the cortex and brainstem, which may account for the patient's neurological symptoms. A radionucleotide cisternogram was ordered, which demonstrated blockage of CSF flow. Neurosurgery was consulted, who placed a shunt into the right lateral ventricle to relieve the blockage. CSF fluid analysis revealed oligoclonal bands and increased intrathecal IgG, consistent with a diagnosis of multiple sclerosis. A visual evoked potential was performed, which demonstrated slowing. The patient was found to be absent and was eventually located on the roof of the hospital, hallucinating that he was standing on the lacrosse field. Given the patient's age (and likelihood of sexual contact), a diagnosis of neurosyphilis was considered, which represents the final stage of syphilis. The patient was treated empirically with intrathecal penicillin. The patient began experiencing auditory hallucinations [while looking at Dr. Cameron's breasts] and became extremely agitated. The patient was given Ativan. The diagnosis was reconsidered. LFTs, BUN, and creatinine were normal. The patient had no history of diabetes, and examination of electrolytes demonstrated no anion gap. MRA showed no vasculitis. The patient's young age makes a degenerative cause very unlikely. No neoplasm was demonstrated on MRI. The WBC count was on the high end of normal, but the patient had experienced no fevers, making infection unlikely. A CT scan ruled out trauma as a cause of the symptoms. An EEG, left and right EOG were conducted, revealing no epileptiform activity. BP was 110/70. An EKG demonstrated normal QRS with T-wave inversions in multiple precordial leads [This finding suggests that the heart isn't getting enough oxygen. I'm surprised that this wasn't pursued further by checking troponin levels and maybe an echocardiogram given that a person this young shouldn't be having a heart attack.] LFTs at this point were 2 times the normal range. DNA testing was performed on the parent's saliva from their coffee cups. It was discovered that Dan's parents were not his biological parents. His adopted parents were confronted with the question of Dan's biological parents' family history. They revealed that the family history they had given had been that of the biological parents, though the immunization status of the patient's biological mother was unknown. If the parent's mother had not received the measles vaccine, the patient could potentially have subacute sclerosing pancencephalitis. A retinal biopsy was done to confirm the diagnosis, and an Omaya reservoir was placed for delivery of intraventricular interferon. The patient's condition improved. Differential Diagnoses:Dr. Cameron: Leukoencephalopathy Dr. Chase: Infection, liver process, kidney process, viral meningitis, neurosyphilis Dr. Foreman: None. Dr. House: Movement disorder, degenerative brain disease, multiple sclerosis, infection in his brain, subacute sclerosing pancencephalitisCommentary: This episode embodies why this show enthralls medical professionals. How many physicians have actually ever seen a case of subacute sclerosing panencephalitis? If you have, please comment (at the bottom) on how it presented. If there is power in numbers, I expect no responses, because any place with a high enough likelihood of this disease occurring also has a high likelihood of not having internet access. Subacute sclerosing panencephalitis (SSPE) is a sequelae of rubeola virus, also known as measles. This means that if a person had measles as a child, he or she would have a 8.5 out of a million chance of developing measles. In a country with a population of roughly 300 million (like the U.S.), about 2,550 people would develop this potentially fatal complication of measles. This is why some smart person invented the measles-mumps-rubella (MMR) vaccine. There is some controversy in the public about the possibility of MMR actually causing SSPE.  "I knew that MMR was a mistake from the start. Within 10 seconds I could see that it was a bad idea. All the vaccinations prior to MMR could occur in nature; they had never been combined before. Normally, viruses can't infect at the same time, so if you put more than one virus into a body at once you are making a grave error. Surely the point of vaccination is to make it safer for children, but with MMR a child could be overwhelmed, and might not recover. The deaths and severe reactions to MMR are just the tip of the iceberg. The Government should stop lying and recognise that MMR is one step too far. It's all nonsense. It's all about greed, and the gullibility of buyers at the Department of Health. These people are acting on behalf of the nation and they should be more sceptical."-- Dr. Peter Mansfield
With the MMR vaccine, about 0.7 people per million can develop SSPE, which would translate to 210 people in the U.S. (instead of 2,550). I guess I'm trying to make a few points. - Get your kids vaccinated.
- The number of people in the U.S. who have SSPE is slim to none.
- The number of doctors who have diagnosed SSPE is probably slim to none.
- The writers of the show can get away with a lot in this episode because there are very few doctors who could refute the disease presentation from their personal experience.
Anyways, let's get to business. A 16-year-old comes in with double-vision (diplopia) and night-terrors. Double-vision is actually a very telltale sign. In a young person, I personally would worry about multiple sclerosis and myesthenia gravis (2/3rds of myesthenia gravis cases present with diplopia as the first symptom). It would be nice if Dr. House had done an actual neurological exam, which might help tease these apart. Nonetheless, I found it interesting as to the things that he did test. By flicking his finger, he was maybe trying to approximate the corneal reflexes, which tests the the V1 branch of the trigeminal nerve and the facial nerve. If that's true, then Dan didn't blink when his left eye was flicked at, which would point towards a problem with the left trigeminal nerve, indicating a neurological problem. The other possibility is that Dr. House was just pretending to do a physical exam, and that this was entirely pointless. The other interesting thing is that Dr. House makes a big deal out of night terrors, which are generally considered a benign condition where a person wakes up at night out of deep sleep with a look of terror on their face and then goes back to bed with no memory of what happened (as opposed to a nightmare). The polysomnograph (sleep test) seemed completely unnecessary to me and certainly not something that needed to be done emergently as an inpatient. Since I'm thinking (based on the diplopia) that Dan might have myasthenia gravis or multiple sclerosis, I'd check the thymus gland on my physical exam, which if enlarged, would raise the possibility of myasthenia gravis. In terms of labs, I'd check for acetylcholine receptor antibodies (and MuSK antibody) and thyroid function tests. In terms of ruling out multiple sclerosis, I'd want to check the CSF for oligoclonal bands and increased IgG, though this could certainly wait until after the imaging. First up on the priority list for imaging would be an MRI of the brain. Because of the relative lack of MRI machines and the long times that MRI scans take, a head CT would probably be done first while the patient was in line to get their MRI. In this case, the head CT was normal, and an MRI read was normal (though House picked up on some "bowing" of the corpus callosum).  I have no idea what "bowing" exactly means, but I do know this. Radiologists are impulsive people. For anyone who's read a radiology report, "There are non-specific changes possibly consistent with the following 100 conditions " is a typical sentence. The only way a radiologist can get sued is if he or she doesn't see something that is there. The way that radiologists compensate for this is to comment on everything, including things that aren't even there. Basically, it's safer for a radiologist (from a medicolegal standpoint) to name every possibility in a given image than to miss something. I generally tend to go by the thinking that if a radiologist didn't see it, then it's not there.
If the labs were fine and everything looked normal on the CT and MRI, I'd probably discharge Dan from the hospital (maybe after a lumbar puncture to test the CSF for multiple sclerosis). I mean, come on! One episode of double-vision and a kick of the leg? That's not enough to get admitted at any hospital in the country! At most, I might offer him some Valium to suppress stage 3 and 4 sleep, during which night terrors are thought to occur (versus nightmares, which occur during REM sleep). Inevitably, Dan would get worse at home and would be back at the hospital in a few days feeling disoriented and hearing voices, and then he would probably be admitted.
At this point, I would certainly do a lumbar puncture to get cerebrospinal fluid (and consider a psychiatry consult). Dan's CSF showed oligoclonal bands and increased IgG. Ninety percent of people with multiple sclerosis have these in their CSF, but not everyone with this finding in the CSF has multiple sclerosis. At one point, Dr. Cameron references the McDonald criteria for the diagnosis of MS. Yeah, Dan has only had one attack and doesn't fit the criteria yet, but given his age where things like strokes are next to impossible, MS would still be at the top of the list. The assumption would be that given enough time, Dan would have a second attack and thus fit the criteria for MS diagnosis. I'd start Dan on Valium 5 mg 1-3 times a day to deal with the spasticity (and the night terrors too -- elegant, no?) and then I'd use intravenous methylprednisolone 1000 mg for 5 days followed by oral prednisode if Dan was having an acute attack of diplopia. Interestingly, a 1981 study published in Science magazine demonstrated that intrathecal interferon reduced exacerbations of multiple sclerosis. This is extremely similar to the final treatment that Dr. House offered Dan (interferon-beta in this 1981 study vs. interferon-alpha used for SSPE).
I would almost be willing to say that Dr. House was being dramatic in misdiagnosing MS as SSPE, but he decided to do a retinal biopsy to confirm, which I wouldn't necessarily have done. Actually, I received an e-mail from a reader of this site that the biopsy wouldn't be appropriate in this situation and that it was done with a needle going through the lens of the eye, which would have left Dan blind! From reading up on this online, I tend to agree that this was conducted improperly and that it wasn't even indicated in this case. I probably would have gone back and checked rubeola IgG titers in the CSF instead and acted based on those results (assuming that I was even vaguely considering SSPE as a possible diagnosis).
Taken from this Baylor case file, here are the diagnostic criteria for SSPE. Findings pertinent to Dan's case are in bold.
The diagnosis of SSPE can be made if three of the following five criteria are fulfilled: 1) typical clinical presentation with progressive cognitive decline and stereotypical myoclonus, 2) characteristic EEG changes, 3) elevated cerebrospinal fluid globulin levels without pleocytosis, 4) elevated CSF measles antibody titers [not checked by Dr. House], and 5) typical histopathologic findings in a brain biopsy or autopsy (Dyken 1985, Santoshkumar & Radhakrishnan 1998). The clinical course of SSPE is variable, but affected individuals generally progress through four loosely defined stages. The first stage is characterized primarily by behavioral and personality changes, and may be heralded by a change in school or work performance. The second stage involves continued cognitive decline as well as myoclonus, seizures, choreoathetosis, apraxia, and visual changes. Features of the third stage include the development of autonomic instability, rigidity, and decreasing levels of consciousness often with decorticate/decerebrate posturing. In the final stage, the patient demonstrates quadraparesis, akinetic mutism, active startle responses and coma. The myoclonus and rigidity is usually less prominent at this point. The overwhelming majority of cases follow a progressive downhill course leading to death; although there have been a few case reports of patients who have apparently gone into remission (Dyken 1985, Santoshkumar & Radhakrishnan 1998). Five percent of patients survive three months or less and 20% survive four or more years, with a mean survival of only 18 months (Singer et al. 1997). Singer et al. (1997) report that adult-onset patients are more likely than children to present with purely ophthalmologic complaints rather than the classical personality changes as their first symptom of disease. A wide variety of visual disorders have been associated with SSPE, including papilledema, retinitis, chorioretinitis, optic nerve pallor, homonymous visual field deficits, and cortical blindness. For this reason, and because of the presence of oligoclonal banding on CSF electrophoretic studies, a diagnosis of multiple sclerosis may sometimes be considered in the early stages of SSPE. The pathognomonic EEG findings in SSPE are periodic complexes with generalized bilateral, usually synchronous and symmetrical slow waves of high amplitude, classically occurring every 5-10 seconds (Dogulu et al. 1995, Gokcil et al. 1998). These periodic complexes are usually associated with clinically evident myoclonic or dystonic activity (Singer et al. 1997). Early in the course of SSPE, the EEG may show normal background activity, even in the presence of the periodic complexes. However, as the disease progresses, the background activity eventually becomes progressively slower, with the emergence of bifrontal slow activity. Magnetic resonance imaging may be relatively normal, or may show early changes of increased signal on T2-weighted sequences, frequently involving the periventricular or subcortical white matter. Later in the disease, MRI may show diffuse cerebral atrophy. Other findings, less commonly encountered, may include pial and parenchymal contrast enhancement, local mass effect of parenchymal lesions, and involvement of the splenium of the corpus callosum. Discrete basal ganglia and brainstem lesions have also been reported. The extent of MRI findings does not correlate well with the clinical neurologic status of the patients (Anlar et al. 1996, Brismar et al. 1996).  Histopathologic findings in SSPE consist of a pattern of gliosis, foamy macrophages in the white matter, perivascular and periventricular inflammatory changes, and Cowdry-A inclusion bodies. Usually, demyelination is symmetric, progressing from the occipital region and extending anteriorly, and involving the thalamus, putamen, and brainstem nuclei as well (Gascon 1996, Singer et al. 1997).
Conclusions: Overall, I think Dr. House did a pretty good job with this case. I think it's extremely odd that he didn't check a rubeola IgG titer in the CSF, as that would have satisfied the 3 (out of 5) criteria needed for the diagnosis of SSPE, which would mean that he wouldn't have needed to get a retinal biopsy.
Episode 101: Pilot
Chief Complaint: New-onset seizure. History of Present Illness: Ms. Rebecca Adler is a 29 year old woman who had her first seizure one month ago during which she became dysarthric followed by tonic-clonic motor activity. Protein markers for the 3 most prevalent brain cancers at an outside hospital were negative. The patient's symptoms have not responding to radiation. Past Medical History: None. Medications: None.
Allergies: No known allergies.
Social History: She is a schoolteacher at an elementary school in Trenton, New Jersey. She is Dr. Wilson's cousin.
Family History:1) Myocardial infarction: mother died of this 2) Cancer: none
Physical Exam: Not performed.
Labs/Imaging: Normal thiamine.
Medical Decision Making: A head CT with IV contrast (to rule out a mass lesion and/or hematoma) was performed, which revealed no abnormalities. Aneurysm, stroke, ischemic disease, Creutzfeld-Jacobs disease, and Wernicke's encephalopathy were considered as possible diagnoses. A normal thiamine level from an outside hospital record precludes a diagnosis of Wernicke's encephalopathy. Repeat thiamine level conducted here was also normal. A contrast MRI was scheduled to be performed but had to be stopped because of unauthorization by Dr. Cuddy. On repeat contrast MRI, patient had an anaphylactic reaction to the gadolinium contrast and had to be treated with epinephrine 0.5 mg s  ubcutaneously. Emergency tracheostomy performed, and an endotracheal tube was placed and promptly removed the next day. A diagnosis of cerebral vasculitis was considered, which would be consistent with the elevated erythrocyte sedimentation rate (despite the fact that the elevation was only mild). Steroids were given, to which the patient responded well. Environmental exposure to mold at the patient's school was considered, but none was found, The patient's elementary school students did reveal the presence of a parrot at the school, which led to the consideration of psittacosis. However, the fact that none of the schoolchildren were ill meant that this was likely not the cause of the patient's symptoms. The following day, the patient experienced temporary blindness followed by a generalized tonic-clonic seizure with supraventricular tachycardia up to 211 progressing to asystole, saturating 96% on room air. The patient was resuscitated with external defibrillation and experienced postictal confusion for 5 minutes, after which her mental status returned to baseline. Differential diagnoses under consideration included tumor, infectious processes, and vascular processes. In order to differen  tiate the 3 processes, all treatment was stopped to see how fast the patient declined. Decline over 1-2 months would point towards a tumor, decline over a few weeks would suggest an infection, and decline over a week would suggest a vascular process. The patient's home was also analyzed for environmental exposures. It was discovered that the patient's dog likely has fleas. Ham and eggs were discovered in the refrigerator. In terms of the patient's progress, she was unable to stand up at this point. It was found out that Ms. Adler was not in fact Dr. Wilson's cousin. Because ham is derived from pigs, a diagnosis of neurocystercosis was considered. The patient refused further treatment, and so an x-ray of her leg was performed to visualize worm larvae. A single lesion in the muscle was demonstrated, which confirmed the diagnosis. The patient was started on albendazole 400 mg bid x 4 weeks and discharged. Differential Diagnoses:
Dr. Cameron: Creutzfeldt-Jacobs disease Dr. Chase: Aneurysm, stroke, and ischemic disease Dr. Foreman: Wernicke's encephalopathy, psittacosis Dr. House: Cerebral vasculitis, neurocysticercosis
Commentary: Ms. Rebecca Adler is a 29-year-old woman with a new-onset seizure. Seizures aren't great things, and it makes sense to rule out dangerous causes of seizure before jumping to prescribing an anti-convulsant medication. In fact, one seizure doesn't generally even need to be treated with an anti-convulsant because approximately 50% of adults who have one seizure never have a second one. It is unclear whether Ms. Adler had more seizures, but given that she returned to this hospital after being ruled out for a tumor at an outside hospital, it is likely that Ms. Adler has had repeat episodes of seizure. Generally, a person needs to abstain from driving for 6 months following a seizure, so it's also curious as to how Ms. Adler was able to make it to the Princeton-Plainsboro Teaching Hospital (Maybe she got a ride from Dr. Wilson?). Anyways, here's the official work-up of a seizure as published in the American Family Physician journal in 1998 [1] (There's also a New England Journal of Medicine article in 2001 regarding diagnosis of seizures, but I'm going to try to stick to journals that are publicly available when possible). - Complete blood count, a basic metabolic panel, calcium, magnesium, and phosphorus.
- Toxicology screen and evaluating hepatic function with synthetic and enzyme studies
- Lumbar puncture is essential in patients in whom meningitis or encephalitis is suspected, as well as in immunocompromised patients, since occult meningitis is a common finding in this group.
- Magnetic resonance imaging (MRI) when a machine is available, which is more sensitive than computed tomography (CT) in identifying these lesions. If the patient presesents with new focal deficits, persistent altered mental status, fever, recent trauma, persistent headache, cancer, treatment with anticoagulation or immunocompromised state, an emergent CT scan is often performed, given its widespread availability and speed and its superior ability in the detection of acute hemorrhage, compared with MRI.
- Electroencephalography (EEG) for detection of epileptiform activity, strengthening the putative diagnosis; identification of focal electrocerebral abnormalities suggesting a focal structural brain lesion; and documentation of specific epileptiform patterns associated with particular epilepsy syndromes (for example, generalized spike-and-wave discharges associated with a generalized epilepsy, or focal discharges associated with a localization-related epilepsy).
During the course of Ms. Adler's evaluation, all of the above are presumably performed with the exception of a lumbar puncture, a tox screen, and an EEG. The CT shows no lesion, and an MRI (the best test for diagnosis of neurocystercercosis) couldn't be performed because of the patient's allergy to gadolinium contrast (which happens in 0.01% of patients [2]). Except for a case report here and there about diagnosing neurocystercosis with a lumbar puncture [3], the usual route of detection of neurocystercosis is via CT and MRI. At one point when Dr. Chase suggests using an x-ray to diagnose the disease, Dr. House remarks that it must be muscle that is x-rayed because the CSF (cerebrospinal fluid) has the same consistency as the cysticercosis (implying that this is the reason it wasn't seen on the CT scan of the head). This just seems to be entirely untrue. What you see in the brain (and muscle) is calcified cysts. A calcification has the same consistency as bone, so it should light up on a head CT, just like it did on the thigh muscle x-ray!  Conclusions: This is a ridiculous diagnosis. Yes, the thigh x-ray confirmed the presence of a lesion which is suggestive of cysticercosis, but there's no good reason that the same type of lesion should be completely absent from a head CT! Furthermore, why not check the stool for Taenia solium eggs (the organism responsible for cysticercosis)? If it's in the brain and in the muscle, it should be in the intestine where it all started, no? Ms. Adler admitted she was wearing a diaper at that point. I'm sure they could've just changed her diaper and taken the stool from the old one for sampling. The other thing that bothers me is that Dr. House dismisses the diagnosis of psittacosis (which comes from bird feces) on the basis of the kindergarten students not getting sick but was gung-ho about considering cysticercosis based on having ham in the fridge. It's not like each pig only goes into one packet of ham. If Ms. Adler got sick from a pig, then every other person who ate portions of that pig should be sick. This should've been picked up at a national level like episodes of mad cow disease from infected beef. Then again, Dr. Chase does tell Ms. Adler that this has been "in her system" for years, so maybe all her co-pig-eaters are dying while she's alive because of Dr. House. Just a thought. References:1) Marks WJ Jr, Garcia PA. Management of seizures and epilepsy. Am Fam Physician. 1998 Apr 1;57(7):1589-600, 1603-4.2) Murphy KJ, Brunberg JA, Cohan RH. Adverse reactions to gadolinium contrast media: a review of 36 cases. AJR Am J Roentgenol. 1996 Oct;167(4):847-9.3) Katz B. Central American mesencephalopathy. Surv Ophthalmol. 1994 Nov-Dec;39(3):253-9.
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