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AMA Research Challenge 2023

Acute Liver Injury from High Dose Pulsed Steroid Therapy in a Patient with Multiple Sclerosis: A Case Report

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Learning Objective:
Identify Wernicke encephalopathy and copper deficiency as potential causes of neurologic abnormalities.
Case:
Wernicke encephalopathy is a potential consequence of heavy alcohol use. It classically presents with disorientation, ocular motor dysfunction, and ataxia. However, other medical complications may muddle this clinical picture. A 26-year-old previously healthy female presented with several months of worsening bilateral lower extremity weakness. She had multiple shots of hard liquor daily for several years and a low appetite for the past month following a friend’s death. Her last drink was three days before admission. On admission, vital signs were stable except for mild tachycardia. The patient was completely disoriented and unable to ambulate due to unsteadiness. She had an abnormal finger-to-nose test, bilateral vertical nystagmus, and stocking-glove pattern neuropathy. She also had leukopenia, normocytic anemia, and low serum thiamine, folate, and copper. HIV, RPR, vitamin B12 level, methylmalonic acid, urine drug screen, and lumbar puncture were all unremarkable. MRI brain was negative for mamillary body or thalamic changes. She was empirically treated for Wernicke encephalopathy using IV thiamine 500 mg TID for 2 days, then 200 mg daily for 5 days. After completing this, she was discharged with oral thiamine and folate supplementation for alcohol use disorder and gabapentin for neuropathy. She was instructed to purchase over-the-counter copper supplements for her copper deficiency. The patient made a full recovery other than she did not remember being hospitalized during a follow-up phone visit.
Discussion:
This patient’s neurological status was initially attributed to Wernicke encephalopathy given her disorientation, vertical nystagmus, and positive finger-to-nose test. However, she incidentally had low serum copper, which can be treated with oral supplements or cocoa. Copper deficiency is not classically associated with heavy alcohol use, though there has been literature hinting towards some association. Low copper can lead to leukopenia, normocytic anemia, and stocking-glove pattern neuropathy, all of which were present in this patient. She also lacked the contrast enhancement of the thalamus and mamillary bodies that is present in patients with Wernicke encephalopathy, which suggests that her clinical presentation was not solely from Wernicke encephalopathy. This case illustrates that although Wernicke encephalopathy is usually in the differential diagnosis of patients with neurologic abnormalities in the setting of heavy alcohol use, copper deficiency should also be included. Properly managing patients with such a complex clinical picture is essential to improve their neurologic status, avoid irreversible complications such as Korsakoff psychosis, and treat reversible vitamin and mineral deficiencies.

Mineral Mining: A Confounding Case of Wernicke Encephalopathy

Background:
Creutzfeldt-Jakob Disease (CJD) is a neurodegenerative process that manifests as a rapidly progressive dementia with a usual poor prognosis within 12 months. CJD can be further grouped into three main categories: sporadic (sCJD), genetic (gCJD), and acquired (aCJD). The worldwide incidence is around 1.5 to 2.0 per million person-years and about 85-95% of CJD can be attributed to sporadic CJD. The presentation of this disease can vary and therefore requires a criterion to make this consideration carefully. For sporadic CJD to meet the criteria for “probable,” it must have 3 main criteria: (1) Clinical findings of a neuropsychiatric disorder with a positive positive Real Time Quaking Induced Conversion (RT-QuiC) test or rapid dementia plus at least two of the following symptoms: myoclonus, visual or cerebellar abnormalities, pyramidal/extrapyramidal signs, and akinetic mutism, (2) a typical EEG findings of periodic sharp wave complexes, positive 14-3-3 CSF assay in disease duration of less than 2 years, or high signal in caudate/putamen regions on MRI brain scan or at least two cortical regions either on DWI or FLAIR, and (3) exclusion of other causes in diagnostic workup.

Case Presentation:
We report the case of a 61-year-old woman with a past medical history of hypothyroidism, psoriasis, and hypertension that presented for acute onset, rapidly progressive cognitive decline that was 1 month in duration. The patient’s clinical presentation of rapid cognitive decline, subtle cerebellar and upper motor neuron findings (e.g. pseudobulbar affect, slow speech), and MRI brain findings of cortical ribboning and restricted diffusion in the caudate nucleus was most consistent with probable sporadic CJD. Cerebral spinal fluid analysis revealed a positive Real Time Quaking Induced Conversion (RT-QuiC) test, t-tau protein of 18531 pg/mL (0-1149 pg/mL), and 14-3-3 gamma protein of 61440 Au/mL (<30-1999 Au/mL). An EEG revealed pseudo periodic triphasic sharp wave complexes over the left frontotemporal regions. Additional laboratory findings were obtained to rule out mimickers such as autoimmune encephalitis, Hashimoto’s encephalopathy, and CNS vasculitis. Upon receiving diagnosis, the patient’s condition rapidly worsened and died after 1 month possibly due to respiratory arrest.

Discussion:
This patient had an “atypical” presentation due to absence of hallmark symptoms such as myoclonus, however, the rapid course of the disease was consistent with the nature and course of sCJD. Definitive diagnosis of CJD requires neuropathological evaluation of brain tissue via immunohistochemistry or protease-resistant PrP/scrapie-associated proteins on Western blot via autopsy post-mortem. The patient presented in this report did not have an autopsy, however, with information gathered based on criteria from Center of Disease and Control, we have high clinical suspicion that this patient had probable sporadic CJD. There is no current FDA approved treatment that is available to treat this disease.

A Rare Case of Probable Sporadic Creutzfeldt-Jakob Disease

Background
Myasthenia gravis is classically described in the literature as an autoimmune disorder with antibodies directed at the acetylcholine receptor on the motor end plate. This autoimmune destruction of these key areas of the interface between the nervous system and the musculoskeletal system leads to weakness and fatigue in patients. Rarely in the literature has this been described as a molecular mimicry event secondary to viral illnesses like that of COVID-19. 

Case Report
Herein the authors describe the case of a 71-year-old right-handed female who presented with key symptoms of dyspnea, drooping eye lids, difficulty lifting her neck, dysphagia, slurring of speech, bilateral shoulder weakness, and needing to change eating positions due to discomfort of her shoulders and arms. The patient endorsed her eyelid drooping worsened in the later part of the day such that she had to tape her eyelids open in order to see. The patient underwent ice testing, trial of pyridostigmine, was discharged with a prescription for prednisone and pyridostigmine, set up with outpatient follow up, and was given a working diagnosis of COVID-19 induced myasthenia gravis.

Discussion
This case is important as it highlights three key lessons of importance within the literature on myasthenia gravis. First is the transient worsening of a patient when given corticosteroids. In high doses, steroids can worsen or send a person into myasthenic crisis which is the reason that they should not be utilized as primary treatment in crisis. Second is the etiology of myasthenia gravis, often there is not found an antecedent event in patients, however, the history of this case made it clear that this was likely a molecular mimicry event secondary to a COVID-19 infection. Thus, the authors desire to remind the readership of the importance of a thorough history and physical examination. Lastly, as a part of the diagnostic work up, the clinicians utilized an older physical examination maneuver known as the ice test. When utilized, this test has a high negative predictive value and therefore still has a place in bedside diagnostics when ruling out myasthenia gravis.

"It's been downhill since COVID": Myasthenia Gravis secondary to COVID Infection

Background:
Brainstem abscesses are collections of pus within the brainstem, which can cause inflammation, tissue damage, and compression of adjacent structures, leading to headache, fever, and focal neurological deficits. Brainstem abscesses are considered rare and potentially life-threatening, and pontine abscesses are even rarer. Both are often caused by the spread of infection from nearby structures like the middle ear, sinuses, and mastoid air cells but can also result from hematogenous spread. 

Case Presentation:
A 54-year-old male presented with numbness and clumsiness in his left hand and leg over a three-day period. These symptoms were preceded by a headache that awoke him the night before without accompanying fever. An initial brain magnetic resonance imaging (MRI) showed a 1.5 cm ring-enhancing lesion in the right pons. The patient’s blood cultures were negative as were screenings for tuberculosis, methicillin-resistant Staphylococcus aureus, human immunodeficiency virus, and hepatitis B virus; cysticercosis antibody testing was equivocal. The patient was started on ceftriaxone, vancomycin, and metronidazole.

Three days later, the patient showed worsening weakness in his left arm and leg. A repeat MRI showed thickening of the enhancing wall and formation of another lesion in the right dorsal paramedian pons. A lumbar puncture revealed 11 WBCs, two RBCs, a glucose level of 76 mg/dL, and a protein level of 62 mg/dL. Cerebrospinal fluid was clear, colorless, and negative for cultures, toxoplasma IgG, cryptococcal antigen, human simplex virus, and acid-fast bacteria. 

The patient underwent transfrontal stereotactic drainage of the lesion which revealed 1.3 cc of a purulent, foul-smelling material and the cultures of which grew Streptococcus pyogenes. A postoperative MRI showed a 0.85 cm abscess without hemorrhage. The patient stated improvements in strength and functionality but residual hemiparesis. After eight weeks, all antibiotics were stopped after verifying decreasing abscess size on an MRI.

Discussion:
The patient presented with a pontine abscess of both undetermined causal origins and unclear infections signs, namely the lack of fever and nausea which are commonly associated with brainstem abscess. Additionally, the stereotactic aspiration cultures grew Streptococcus pyogenes, which can exist in the oropharynx, yet our patient denied recent upper respiratory illness. 
This case reveals several learning points on cytogenic brainstem abscesses: the importance of early neuroimaging by MRI for a definitive diagnosis of brain abscesses and the value and utility of stereotactic aspiration, a minimally invasive procedure, which can treat nearly all brain abscesses measuring at least 1 cm, regardless of the location.


Cryptogenic Pontine Abscess Treated With Stereotactic Aspiration: A Case Report

Psychogenic Non-Epileptic seizures: Complex diagnosis and Interdisciplinary Management

Background: Vaginal Birth After Cesarean (VBAC) plays an essential role in current strategies to lower cesarean rates. Despite the American College of Obstetrics and Gynecology (ACOG) endorsement, Trial of Labor after Cesarean (TOLAC) attempt rates remain low. The Zavanelli maneuver is considered a last resort procedure used in the management of severe shoulder dystocia unable to be relieved by other techniques. It is the cephalic replacement of the fetal head back into the pelvis immediately followed by cesarean delivery. We discuss a case of a woman determined to have a vaginal birth after her prior birth required this heroic measure to facilitate delivery.

Case Presentation: A 34-year-old G4P1021 presented seeking care with a history of a complicated delivery requiring Zavanelli maneuver of a 4.4kg female infant. She was determined to avoid a repeat cesarean delivery and desired to pursue a trial of labor after cesarean section (TOLAC) this pregnancy. She addressed her modifiable risk factors and decreased her pre-pregnancy body mass index (BMI) to 26 from 39 kg/m2. She avoided excess weight gain during pregnancy (with a 25 pound gain versus 50 in her prior pregnancy). Her lifestyle changes influenced improvement in fetal growth with a current estimated fetal weight in the 50th percentile, compared to 95th percentile in her prior and her avoidance of gestational diabetes; whereas she was previously diagnosed. Consultation with three different perinatologists, all agreed her pursuit of TOLAC was reasonable. Nonetheless, she had to travel across state lines to find a provider willing to permit a trial of labor. She then presented in spontaneous active labor at 41 weeks gestation and went on to deliver a 3350g female infant in an uncomplicated vaginal delivery. She described this birth experience as euphoric.

Discussion: Practitioner fear was demonstrated as a barrier to this patient’s autonomy in delivery route decision. Risk factors for shoulder dystocia may vary in each pregnancy. Improvement in the overall risk profile should not be ignored when counseling patients and deciding on the best delivery route for that and future pregnancies. Decisions must be based on a thorough analysis of risk factors, past and present, and individualized to meet the goals of a woman's reproductive career.


Vaginal Birth After Cesarean after Zavanelli Maneuver: 
A Woman’s Right to Choose

Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) is a rare congenital anomaly that is characterized by the triad of uterus didelphys, obstructed hemivagina, and ipsilateral renal dysplasia. It is also known as Herlyn-Werner-Wunderlich syndrome. 

OHVIRA is typically diagnosed after menarche and is often associated with recurrent severe dysmenorrhea and vague lower abdominal pain, although the presentation can be variable. Due to the normal onset of menarche from the non-obstructed side, diagnosis of OHVIRA can easily be missed, which can lead to complications such as infection, pelvic inflammatory disease, and endometriosis. 

In this report, we present a case of OHVIRA syndrome in a 16-year-old girl who presented with lower abdominal pain and constipation. This case underscores the importance of maintaining a high index of suspicion for OHVIRA syndrome in adolescents with non-specific abdominal or pelvic symptoms.



When Constipation is More than Just Constipation: A Rare Case of OHVIRA Syndrome

Introduction : Glaucoma, a leading cause of irreversible blindness, presents a significant challenge in ophthalmology. While numerous treatment modalities exist, management becomes complex when patients exhibit intolerance to conventional treatments. This case highlights a patient with open angled glaucoma(AOG) who is unable to tolerate common glaucoma medications. 
Patient’s Main Concerns and Important Clinical Findings: A 79-year-old woman presents with a longstanding history of AOG, strongly influenced by her family history. The patient underwent significant obstacles due to intolerance to standard glaucoma eyedrops, including those that increase outflow (ie. Latanoprost) and aqueous suppressants for reduced inflow. 
Primary Diagnoses, Interventions, and Outcomes: The patient’s management involved multiple surgical interventions: two trabeculectomies were performed in the left eye (OS) in 1995 and 2006, with adjunctive 5-fluorouracil and mitomycin to inhibit fibroblast proliferation and increase the success rate of the surgery. Additionally, postoperative argon laser suture lysis was employed after both trabeculectomies to prevent hypotony. In the right eye (OD), the patient underwent argon laser trabeculoplasty in 2004, repeated as selective laser trabeculoplasty in 2007, and finally micropulse laser trabeculoplasty in 2009 and 2018. This series of procedures aimed to improve aqueous outflow through the trabecular meshwork. A trabeculectomy was also performed OD in 2018. As of the patient’s last examination on April 5, 2023, the patient’s vision was 20/80 OD and 20/500 OS, with intraocular pressures of 12 OD and 10 OS. Her visual fields showed stable superior and inferior loss, greater in OD than OS. 
Conclusion: This case illustrates the complexity of managing advanced glaucoma in patient’s intolerant to traditional medications. It highlights the necessity for personalized treatment strategies and the importance of building a supportive, ongoing relationship with patients dealing with lifelong diseases. Multiple surgeries may be required to control the disease, emphasizing the necessity for careful follow-up and dynamic treatment plans to preserve visual function. The case underscores the essence of ophthalmology - not just managing a disease, but guiding patients along a lifelong journey. 


Management Challenges in Advanced Open-Angle Glaucoma: A Case Report

Background
Guillotine amputations involve amputating an extremity with the wound left open, and are indicated in the setting of contamination. With lower extremity amputation, surgical options include below-knee amputation (BKA), through-knee amputation or knee disarticulation (KD), and above-knee amputation (AKA). BKAs preserve the knee joint and have been shown to have fewer complications and improved rehabilitation compared to KDs and AKAs. When BKAs are not feasible for a traumatic injury, an AKA is often chosen, due to difficulty or lack of understanding of KD surgery. While few RCTs have compared KDs to AKAs, they may be a viable alternative to AKAs.
Case Presentation
A 28-year-old male presented to the ED after being hit by a truck while on a motorcycle. Physical exam revealed severe injuries to the left lower extremity (LLE), including open tibia and fibula fractures, degloving of the associated soft tissue, obliteration of the anterior compartment of muscles, and a cool foot with no identifiable pulse. Radiographs revealed open, comminuted fractures of the left tibia and fibula. CTA of the LLE revealed abrupt cut-off of contrast at the level of the distal trifurcation of the popliteal artery, proximally in the tibia. 
The patient was urgently taken to the OR, where a guillotine amputation was performed through the knee joint (KD), due to the proximal nature of the fractures and level of vessel tear. KD was chosen over AKA in order to preserve the thigh musculature and therefore maximal function in this young, healthy patient. Three days later, he underwent irrigation and debridement of the LLE with wound closure. The patient was discharged home five days after wound closure, or eight days after admission. Three months out of surgery, the patient has done well with physical therapy and prosthetic usage; he will continue to be followed closely for rehabilitation and recovery. 
Discussion
Factors to be considered in the level of amputation include soft tissue viability for bone coverage, blood vessel viability, and wound contamination. When BKA is not possible, KD can offer an alternative to AKA. KDs present concerns of poor wound healing and stump breakdown, as well as increased risk of revision surgery. However, compared to ambulating on a normal leg, patients undergoing AKAs require 70% more energy expenditure. As compared to AKA, KD preserves the adductor muscles, leading to improved stability and reduced metabolic expenditure with ambulation. Therefore, KDs may result in improved rehabilitation and increased long-term functionality.


A Case of Traumatic Guillotine Knee Disarticulation

Background
Antiphospholipid syndrome (APS), a thrombo-inflammatory systemic autoimmune disease, refers to the presence of persistent procoagulatory antiphospholipid antibodies (APLA) in the setting of arterial/venous thrombosis and/or recurrent obstetric morbidity. Primary APS refers to disease manifestation in the absence of clinical or laboratory evidence of another disease. Secondary APS occurs in the presence of another autoimmune disorder, infection, drugs, or malignancy. APS is known to induce a hypercoagulable state which, in rare circumstances following surgical procedures, could present as acute upper limb ischemia. Successful limb salvage and revascularization requires a timely diagnosis and localization of the arterial occlusion.
Case Presentation
We present a case of a 40-year-old female, 10 days post breast implant surgery and reduction abdominoplasty, who developed arterial thrombosis of the right upper extremity and subsequently the right lower extremity. The patient has a 25-pack year smoking history. On her physical exam she had a cold, mottled, cyanotic right hand, thenar area, and thumb. The patient underwent multiple surgical procedures, including a thrombectomy with thrombolytic therapy for a right subclavian clot, subsequent arteriotomy for radial artery occlusion, a femoral and popliteal thrombectomy, and eventually multiple digital amputations, secondary to digital necrosis, with application of a groin flap. Following this procedure, she fell dehiscing the groin flap requiring three additional debridement procedures. Additional testing revealed positive ANA and lupus anticoagulants. She was subsequently diagnosed with antiphospholipid syndrome, explaining the cascade of thrombotic events.
Discussion
Taking into account patients' risk factors is essential in considering the diagnosis of APS. Timely recognition and diagnosis of APS is not only important to guide treatment and management, but also contributes to physicians’ understanding of the psychosocial impact of APS. The patient’s complications were not limited to physical manifestations, as there is a demonstrated psychosocial impact to the diagnosis of APS. This sequence of events contributed to her feelings of depression, which led to her pursuing psychiatric treatment. The large delay in finding the underlying cause of her symptoms certainly added to her anxiety and stress. Further demonstrating the need for consideration and further research investigating the psychiatric manifestations of APS, with an emphasis on depression. Additional considerations should be made regarding the timely diagnosis of APS in order to more aptly care for patients and limit the patients’ psychological toll.

Next from AMA Research Challenge 2023

Mineral Mining: A Confounding Case of Wernicke Encephalopathy