“Ah! To be in the Pink of Health!”
Case 4
Group Members: Sarah Glade, Nate Moore, Chau Nguyen, Phuong Pham, Muhammad Akhtar
Scribe: Kevin White
I. Problem Statement:
Pamela Hedgehog, a 76-year old female is brought to the clinic by her husband and her daughter. They are concerned because PH has been getting more and more confused over the past couple weeks and is reported to have gotten lost while on a walk and had to be brought home by a neighbor. PH is taking longer to do daily activities such as dressing herself and has fallen twice in the week leading up to the initial appointment. Her neurological exams reveal that she is alert but confabulatory, along with an unsteady gait and swaying excessively during the Romberg test. PH is admitted to the hospital after more tests and starts to get better, however just a month after being discharged she is re-admitted after suffering a seizure. It is determined that PH had been suffering from bismuth toxicity from using too much Pepto-Bismol after X-Ray revealed densities in the abdomen and bismuth levels were measured.
II. Hypotheses
• Dementia – PH’s family brought her into the clinic because they were worried about her cognitive function. She had been getting increasingly confused in the weeks leading up to the visit and getting lost on walks around the neighborhood. PH was unable to give reliable answers to basic questions and even gave different answers to questions regarding her family. A diagnosis of dementia seemed reasonable considering how she performed on the MMSE, SLUMS and MoCA tests, until PH was given Namzaric and her symptoms greatly improved within 10 days. This hypothesis was rejected after seeing that PH’s symptoms returned and resulted in a seizure after she was discharged from the hospital, as dementia patients do not usually see this sort of “up and down” with symptoms as she did.
• Alzheimer’s – Alzheimer’s is a form of dementia and PH was diagnosed with Alzheimer’s by the Doctor. The Namzaric therapy seemed to improve her symptoms. Her daughter described PH becoming more forgetful, and she scored below normal on all mental tests administered to her. This hypothesis was rejected after PH’s symptoms returned after being discharged from the hospital, and the discovery of non-specific densities in her bowel since this type of finding is not typical in Alzheimer’s patients.
• Stroke – Stroke patients can have many different challenges after suffering a stroke, including cognitive impairment and coordination issues. PH was reported to have fallen twice in the week leading up to the initial clinic visit, resulting in injury to her face and arms. PH also had observed gait ataxia, which can be a physical manifestation of coordination issues or other impairment. Additionally, both of her parents died due to cardiovascular complications with her mother dying due to heart failure and her father dying due to a stroke. PH also admits to smoking about ½ pack per week, which increases her risk for stroke. This hypothesis was rejected due to a lack of evidence such as atherosclerosis or mention of increased ASCVD risk.
• Adverse reaction to medications – PH takes many medications, some of which are over the counter items and herbal items to manage her symptoms of diminished cognitive function. PH was noted to have presented to the clinic with her tongue appearing to be black in color, which is a potential side effect of bismuth use. PH was discovered to have suspect densities in her abdomen upon X-Ray which could be explained by contrast used in imaging, but no such imaging had been ordered. Another potential explanation for the densities was a GI bleed, since PH was taking Advil (NSAID) with Pepto-Bismol which increases the risk for bleeding, but this was found not to be the case. This hypothesis was accepted due to the serum and urine bismuth levels being well above normal limits upon analysis, and presence of encephalopathy which was determined to be caused by the bismuth toxicity.
• Ataxia – Ataxia is a broad term for loss of coordination, which PH has been reported to demonstrate in the increased frequency of falls. She was also observed to have gait ataxia. This hypothesis was accepted as ataxia is a symptom of bismuth toxicity.
• Elder Abuse – Elder abuse is the intentional action or inaction of a caregiver that causes or creates harm for an older individual. The main evidence for this hypothesis was the unexplained increase in the number of falls PH suffered which resulted in cuts on her arms and face, but this hypothesis was ultimately rejected due to a lack of substantial evidence and more likely hypotheses being presented.
• Bismuth toxicity- PH’s bismuth concentrations were well above the normal limits, and she was diagnosed with encephalopathy. Bismuth has 3 different half-lives ranging from 1 hour to 72 days long which allows serum levels to build over time. A common indication of bismuth toxicity is a black coloring of the tongue, which PH presented with. PH’s initial symptoms of forgetfulness and declined cognitive function are likely attributed to the early stage and her later symptoms such as the seizure she suffered are likely attributed to the second phase of bismuth toxicity. This hypothesis was accepted because the abdominal X-Ray findings in addition to her symptoms lead the Doctor to measure her serum bismuth levels, which turned out to be well over the threshold for toxicity. Upon questioning her husband, it was discovered that PH consumes approximately 480 ml every other day for GI symptoms.
• Epilepsy- After PH returned to the clinic and reported that she had suffered from a seizure, epilepsy seemed like a possible explanation. Epilepsy is described as a group of related disorders characterized by a tendency for recurrent seizures, and the onset of epilepsy is most common in early childhood or after age 60 but can occur at any time. This hypothesis was rejected due to PH only suffering one isolated seizure and not having other symptoms commonly associated with seizures or epilepsy.
• Prion Disease- PH received a corneal transplant approximately 10 years prior, and the Doctor was concerned that she may have contracted a prion disease from the transplant. Prions are able to induce abnormal folding of proteins in the brain and are associated with neuronal loss. PH had symptoms consistent with certain types of prion diseases such as Kuru, including tremors, ataxia, postural instability, and dementia. PH had a CT scan done which revealed age related deterioration, which would have been much more pronounced if PH was positive for a prion disease, so this hypothesis was rejected.
• Metabolic Acidosis- Metabolic acidosis can be caused by several things and affects the body in many ways. PH had a bicarbonate concentration of 16 mEq/L and general altered mental status which are both indicative of metabolic acidosis. This hypothesis was accepted as PH’s bicarbonate concentration was below normal limits and her chloride ion concentration was above normal limits.
• Parkinson’s- PH was brought to the clinic and upon examination, swayed excessively during the Romberg test and hand a visible hand tremor, along with multifocal myoclonus observed. These symptoms lead us to believe Parkinson’s Disease was a possibility, especially since some Parkinson’s patients experience psychosis or dementia, and stage 3 Parkinson’s patients are described as losing their balance and falling more often to where daily activities are impaired. Additionally, PH’s CT scan came back normal, which is usually used to rule out other conditions like a stroke to keep Parkinson’s as a possible diagnosis. This hypothesis was ultimately rejected as more information regarding PH’s use of Pepto-Bismol became available.
III. Conclusions and Recommendations
Accepted Hypotheses
• Metabolic Acidosis- Metabolic acidosis can be caused by several things and affects the body in many ways. PH had a bicarbonate concentration of 16 mEq/L and general altered mental status which are both indicative of metabolic acidosis. This hypothesis was accepted as PH’s bicarbonate concentration was below normal limits and her chloride ion concentration was above normal limits.
• Bismuth toxicity- Bismuth subsalicylate is the active ingredient in Pepto-Bismol. 99% of the dug is not absorbed and is excreted, however the 1% of the drug is absorbed through the upper GI tract and distributes widely to the entire body and concentrates in the kidneys and the liver. The threshold for toxicity is 50 mcg/L and there is a correlation between serum concentration and the severity of symptoms. There are two phases to bismuth toxicity. The first phase starts with changes to mood and sleep and can last from weeks to months, and the second phase is a rapid escalation of symptoms. The second phase results in severe symptoms increasing over 1-2 days and presence of encephalopathy is noted. Not only were PH’s bismuth concentrations well above the normal limit, she was diagnosed with encephalopathy which is consistent with typical symptoms and progression of the toxicity. Bismuth has 3 different half-lives ranging from 1 hour to 72 days which allows serum levels to build over time. A common indication of bismuth toxicity is a black coloring of the tongue, which PH presented with. PH’s initial symptoms of forgetfulness and declined cognitive function are likely attributed to the early stage and her later symptoms such as the seizure she suffered are likely attributed to the second phase of bismuth toxicity. This hypothesis was accepted because the abdominal X-Ray findings in addition to her symptoms lead the Doctor to measure her serum bismuth levels, which turned out to be well over the threshold for toxicity. It was then discovered that PH consumes approximately 480 ml every other day for GI symptoms. PH’s overuse of Bismuth lead to encephalopathy, although it is not exactly known how this is caused. Encephalopathies are generally diseases involving degeneration of the brain, which would explain PH’s symptoms.
• Ataxia – Ataxia is a broad term for loss of coordination, which PH has been reported to demonstrate in the increased frequency of falls. She was also observed to have gait ataxia. This hypothesis was accepted as ataxia is a symptom of bismuth toxicity.
• Adverse reaction to medications – PH takes many medications, some of which are over the counter items and herbal items to manage her symptoms of diminished cognitive function. PH was noted to have presented to the clinic with her tongue appearing to be black in color, which is a potential side effect of bismuth use. PH was discovered to have suspect densities in her abdomen upon X-Ray which could be explained by contrast used in imaging, but no such imaging had been ordered. Another potential explanation for the densities was a GI bleed, since PH was taking Advil (NSAID) with Pepto-Bismol which increases the risk for bleeding, but this was found not to be the case. This hypothesis was accepted due to the serum and urine bismuth levels being well above normal limits upon analysis, and presence of encephalopathy which was determined to be caused by the bismuth toxicity.
Resolution and Rationale
Pamela Hedgehog, a 76-year-old woman was brought to the clinic by her husband and her daughter with concerns for her mental state. They report that PH has become increasingly confused over the last couple of weeks and that she has been more forgetful than usual. During the interview with the patient, we notice that while she is capable of answering questions, the information that she provides seems unreliable and gives different answers for questions regarding her family. PH is also noted to have cuts and bruises on her arms and face which she suffered from two falls in the week preceding the visit. PH also is observed to present with a hand tremor and gait ataxia. Her past medical history is positive for hypertension which is not controlled (BP 160/108), migraines, macular edema, glaucoma, corneal transplant at age 65, heartburn and indigestion, and celiac disease. Her medication list includes:
Enalapril
Inderal
Iluvien implant
Xalatan
Pepto-Bismol
Tums
Advil
Super Ginkgo
Cognitex
There a few drug-drug interactions in her medication list, one of which is an interaction with Advil and Pepto-Bismol which increases the risk for GI bleeds. This becomes relevant when an X-Ray reveals non specific densities in her abdomen, which we initially believed to be related to the drug-drug interaction. Cognitex is an over the counter supplement advertised to increase blood flow to the brain and provide crucial nutrients needed for improved cognitive function. Upon the Doctor’s initial diagnosis of Alzheimer’s, PH was directed to discontinue all herbal/OTC supplements and she was prescribed Namzaric which seemed to be an effective therapy. PH’s vitals are as follows:
BP: 160/108
Pulse/RR: Within normal limits
Temperature: 36.5 C
Height: 161 cm
Weight: 51 kg
PH is a retired teacher that lives at home with her husband and has two children and three grandchildren. PH smokes about half a pack per week. Her mother died at age 82 due to heart failure and her father died at 79 due to a stroke. This is significant because initially we believed PH to be suffering from the effects of a stroke or other cardiovascular event, due to her family history. The patient was alert but disoriented during the neurological exam, and her speech was fluent but confabulatory. PH swayed excessively during the Romberg exam and multifocal myoclonus was noted. Swaying and myoclonus led us to believe that Parkinson’s was a possible explanation for her symptoms.
The following day PH returns to the clinic for more tests. PH scored below normal on SLUMS, MMSE, and MoCA which lead us to believe she was suffering from some sort of dementia or brain injury due to stroke. The Doctor noted that she had a black color to her tongue after reporting to eat a standard breakfast, which made us question her use of the Pepto-Bismol. However this only seemed like a minor side effect and was not immediately considered the primary evidence for the cause to her symptoms, given the information from the cognitive function exams. Other test results came back and are as follows:
Potassium: 2.1 mEq/L
Cl: 108 mEq/L
Bicarbonate: 16 mEq/L
Serum Mg: 1.7 mEq/L
Urine pH: 7.0
These lab values pointed us in the direction of metabolic acidosis or possibly metabolic syndrome, but we still believed her to have a degenerative brain disease at this point. After the head CT showed signs of typical aging effects and stable sequela, we were able to rule out stroke as a diagnosis, as there would be a more obvious abnormality on the CT. PH is prescribed Namzaric and a potassium supplement and is admitted to the hospital.
PH seems to greatly improve while in the hospital, and the Namzaric appears to be a wonder drug to the daughter and a wonderful treatment for PH’s newly diagnosed Alzheimer’s. Upon discharge, PH is asked to continue all of her medications with the exception of the nutritional supplements. A month later PH returns to the clinic after suffering a seizure, and her symptoms have gotten worse. At this point we have ruled out dementia and Alzheimer’s due to the sporadic nature of her symptoms, which would be extremely atypical for a patient with those diseases. Her worsened symptoms include further decreased cognitive state, extreme confusion, postural instability, dysarthria and myoclonic jerks. She is readmitted to the hospital and treated with the anti-seizure medication valproate sodium. The Doctor questions PH’s husband regarding her home medications, and learns that she did as she was told and stopped taking the nutritional supplements. She only takes her maintenance medications, Advil and Pepto-Bismol since her stomach has been upset lately. The Doctor orders an X-Ray of the patient’s abdomen which revealed nonspecific densities in the bowel that resembled contrast, but no such contrast for imaging had been ordered. The Doctor is confused but has a suspicion of what may have been causing PH’s symptoms all along. It is at this point that we are confident the issue has been the usage of Pepto-Bismol, and this is confirmed when the next round of test results came back.
The Doctor asks the patient’s husband approximately how much Pepto-Bismol she takes and discovers that she drinks about 480 ml every other day. This leads the doctor to order one more lab test, and it returns as follows:
Serum Bismuth levels: 288 mcg/L
Urine Bismuth levels: 405.7 mcg/L
PH is diagnosed with encephalopathy due to overuse of Pepto-Bismol. The only treatment for this toxicity is simply to remove the offending agent and provide supportive therapy for PH’s other imbalances or conditions. As was seen when she was admitted to the hospital the first time, her symptoms improved tremendously when she was not taking any Pepto-Bismol. Our first hint towards bismuth toxicity was the black color of PH’s tongue but did not seem like a more likely diagnosis than any of the degenerative brain diseases at that point. The nonspecific densities in her abdomen upon X-Ray were a more direct hint and make a lot of sense looking back. Bismuth is absorbed through the GI tract, which is where the odd densities were discovered. Her serum and urine levels confirmed the toxicity, considering that bismuth is excreted in the urine and it was highly concentrated in the urine. Not much is known as to how bismuth toxicity causes encephalopathies, but it has been shown to typically be reversed upon removal of the agent, although it can potentially be permanent. Bismuth can be detected in the body for up to 5 months post use, so we expect most symptoms to resolve quickly, while some lingering effects last until the bismuth levels return to below the normal levels.
IIII. Top Five Learning Issues