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AMA Research Challenge 2022

Uncommon Neuropsychiatric Manifestations in Thyrotoxicosis

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#### Event Details
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Ricardo Correa, MD, EdD
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Stuart M. Greenstein, MD
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Stephanie Strohbeen, MD
 
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Jessica Li, MD/PhD Candidate
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Charles Lopresto, DO

### Sponsor
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Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


poster

Background
Parkinson’s Disease and its treatments have been associated with affective changes, psychosis, and sensorial abnormalities given this pathology’s roots in dopaminergic neural circuitry. These effects are more commonly observed with high-dose dopaminergic agent administration or sharp dopamine agonist tapers, but they are relatively unique with levodopa withdrawal.

Case Presentation
A 70s-aged female Parkinson’s Disease patient was admitted for encephalopathy, affective changes, and hallucinations. She was anxious, but intermittently alert and oriented. She stopped her carbidopa-levodopa 25-100 mg, three tablets, thrice daily, one week prior due to abdominal pain. She subsequently experienced weakness, tremors, and hallucinations of people around her stove, then called emergency services. Her son verified her recent medication non-adherence. She lived alone and was recently unsupported. The possibility of accidentally taking excess levodopa was firmly denied.

The patient started levodopa five years ago, periodically complaining of stomach pain. Geriatric psychiatry outpatient managed her controlled depression. She had mild shadow hallucinations and cognitive decline in the past year, but the current episode was markedly worse. During inpatient neurology, confusion and agitation worsened. Infectious workup and head CT were unremarkable. Levodopa-carbidopa was restarted at home dose. Several drugs were added: Quetiapine 100 mg nightly plus a 25 and 75 mg tablet throughout the day, pimavanserin 34 mg daily, and a rivastigmine 4.6 mg daily patch. Psychiatry adjusted home lorazepam to 0.25 mg four times daily, continuing mirtazapine 15 mg nightly and desvenlafaxine 100 mg daily. Her mental status overall improved to an outpatient-manageable state over six weeks.

Discussion
Common high-dose side effects of dopaminergic agents include psychosis and hallucinations. Sharp medication tapers can also cause problems: E.g., Dopamine Agonist Withdrawal Syndrome with medications like pramipexole involves dysphoria and panic attacks. Exacerbated altered mental state and hallucinations from levodopa withdrawal is more unique; it has been observed, but mainly in rare, older reports. More common levodopa withdrawal complications include stiffness, rigidity, tremor, and thrombosis risk, versus hallucinations. Moreover, visual hallucinations, in general, have an inconsistent literature association with dopaminergic agents. This case presents an unusual levodopa withdrawal manifestation for clinical consideration when generating differential diagnoses and deciding treatment options.

Visual Hallucinations and Altered Mental Status Exacerbation Associated with Acute Levodopa Withdrawal

Background

Actinomyces species are gram-positive, anaerobic microorganisms found in the oral cavity and are often associated with dental abscesses or other oral-cervicofacial disease. Pulmonary actinomycosis is rare and its presentation may be confused with pulmonary tuberculosis or malignancy.

Case Presentation

A 66-year-old male with a PMH of psoriasis and tobacco use presented to the office with a several-week history of a productive cough with yellow sputum and malaise. He denied fevers, SOB, recent travel, weight loss and only drank alcohol socially. He was recently seen in an emergency department for similar symptoms, diagnosed with pneumonia, and completed an antibiotic course without clinical improvement. On physical examination, vital signs were within normal limits and lung auscultation
revealed scattered rhonchi bilaterally with bibasilar rales. HEENT exam revealed poor dentition. Laboratory studies were unremarkable. CT chest revealed a right lower lobe endobronchial soft tissue density with complete opacification of the basilar bronchi, along with scattered sub-centimeter nodules. He was referred for hospitalization where broad-spectrum antibiotics were initiated. A bronchoscopy
revealed a foreign body in the RLL, which was later confirmed to be a peanut; the patient subsequently reported eating peanuts in bulk. Cultures of endobronchial washings were positive for Actinomyces and Enterobacter. The remainder of his hospitalization was unremarkable; he was transitioned to Augmentin for a three-month course and discharged with outpatient follow-up. Repeat CT chest after completion of antibiotics revealed significant improvement in the RLL infiltrate.

Discussion

Pulmonary actinomycosis is a relatively rare disease; the exact incidence rate is unknown. Risk factors associated with the disease include underlying respiratory disorders, alcoholism, poor dental hygiene, and facial/dental trauma. Although it can occur at any age, it is usually seen in patients between 20-50 years of age. Symptoms can be nonspecific; patients may present with fever, SOB, productive cough, hemoptysis, chest pain, or malaise. Diagnostic imaging, such as chest x-ray and CT scan, may be helpful but definitive diagnosis requires cultures positive for Actinomyces species; this is often obtained via bronchoscopy. The treatment involves an extended course of antibiotics, usually a penicillin. The prognosis is excellent in patients with early detection and appropriate treatment.

A Nutty Finding: A Rare Case of Pulmonary Actinomycosis due to Peanut Aspiration

Introduction 
Propofol infusion syndrome (PRIS) is a rare and fatal complication of high dose administration of propofol. We introduce a case report of a critically-ill patient who received high-dose intravenous (IV) pushes of propofol that resulted in rhabdomyolysis, metabolic acidosis, shock, multi-organ failure, and death. 

Patient Course 
A 48-year-old male diagnosed with acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia was intubated and sedated with propofol and fentanyl. He initially improved on the ventilator, but began to suffer emesis. Ileus was suspected. Imaging was not consistent with aspiration. Patient began to require large propofol boluses for adequate sedation and ventilation, greater than 4mg/kg/hr for several hours. The patient declined with progressive renal failure and increasing creatine kinase (CK). Due to elevation of CK and concern for PRIS, sedative medication was changed to midazolam. Patient soon required continuous renal replacement therapy (CRRT) due to oliguria/hyperkalemia. Evidence of shock liver became apparent. Patient required progressive amounts of vasopressors. Family decided to pursue comfort measures due to poor prognosis. 

Discussion 
PRIS is related to impaired free fatty acid metabolism and mitochondrial activity disruption causing an imbalance between energy production and utilization leading to peripheral and cardiac muscle necrosis. Typically, doses greater than 4-5mg/kg/hr are used in PRIS cases. Other hallmarks of PRIS include metabolic acidosis, kidney and cardiac failure, and hypertriglyceridemia. Treatment is generally supportive. Immediate withdrawal of propofol is recommended on suspicion. Other risk factors for PRIS include mitochondrial disease, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake, or critical illness. 

Our patient’s history fits with PRIS, due to his treatment with steroids and vasopressors, along with large doses of propofol. Carbohydrate rich diet may slow the progression of PRIS. Our patient worsened after cessation of tube feeds, potentially contributing to this patient’s syndrome. After our presented patient’s clinical picture became more evident for PRIS, sedation was transitioned to a non-propofol regimen, utilizing midazolam. In retrospect, a cardiac workup may have benefited diagnosis, as the literature seems to demonstrate that cardiac involvement is common. Triglyceride surveillance may aid in detection of impending complications of propofol, due to correlation with iatrogenic pancreatitis. 

Conclusion 
PRIS is a rare, lethal syndrome that has the best prognosis with early detection; our case demonstrates need for high index of suspicion for PRIS, and utilization of early interventions such as recognition of laboratory excursions, withdrawal of propofol, utilization of fluids, and a carbohydrate rich diet.

A Rare Case of Propofol Related Infusion Syndrome

Background
Nontuberculous mycobacteria (NTM) are found ubiquitously in water supplies, dust and soil. Rarely they can cause pulmonary infections, although the true incidence is difficult to establish due to limitations in diagnosing the disease. Newer estimates project a higher incidence than previously thought, likely due to increased awareness of the pathogen and increased numbers of immunocompromised patients. NTM are difficult to diagnose because they do not grow in standard bacterial culture media. We present a case of a patient who required several encounters with the healthcare system before a pulmonary NTM could be established. 

Case Presentation
A patient with a history of COPD on home oxygen presented with acute hypoxic respiratory failure and unintentional 20% loss of body weight over 6 months. A cavitary lung lesion was discovered 6 months prior to this presentation. Biopsies at that time were inconclusive. The patient underwent sputum testing on this admission due to her failure to thrive and history of cavitary lesion. She had two positive acid fast bacilli sputum cultures, which further speciated to non-tuberculosis mycobacteria, Mycobacteria chimaera and Mycobacteria peregrinum. Susceptibilities were obtained and the patient was started on a multidrug regimen with good maintenance of her functional status. 

Discussion
NTM exist naturally in the environment and can be found anywhere from home shower heads to hospital dialysis machines. Diagnosis should not be considered until other causes have been ruled out. There are stringent guidelines for diagnosis, which pose an additional barrier to identifying and treating these patients. 
Guidelines for NTM pulmonary disease have the following criteria: both pulmonary and systemic symptoms must be present, there must be radiologic findings, and there must be appropriate exclusion of other diagnoses. There are microbiological criteria as well which requires at least two separate cultures. This further strains limited resources and jeopardizes the chance of making an appropriate diagnosis. NTM are difficult to diagnose because they do not grow in standard bacterial culture; few labs are capable of culturing these evasive bacteria. Despite this, clinicians should consider NTM in any patient who presents with signs of lung disease without a known cause.

Challenges in diagnosing non-tuberculosis mycobacterium lung infections

Diagnostic Challenge in a Rare Case of Pulmonary Veno-Occlusive Disease: Case Report

Balloon tamponade of bleeding varices is a temporizing measure as a bridge to treatment. The Minnesota tube has an esophageal and gastric balloon, with suction ports. No literature to date has explored the use of the suction ports as an alternative form of enteral access for medication and feeding administration in critically ill patients. We report a case of the novel use of a Minnesota Tube for enteral feeds in a critically ill patient awaiting liver transplantation after massive upper gastrointestinal bleed.

Novel Use of Minnesota Tube for Enteral Feeding In a Critically Ill Patient with Gastro-esophageal Bleeding

Propanol Ingestion Presenting as Severe Anion Gap Metabolic Acidosis and Osmolar Gap

Introduction:

Unilateral diaphragmatic paralysis is a condition in which either side of the diaphragm loses the ability to contract resulting in inadequate ventilation eventually leading to respiratory failure. Even though hypothermia-induced hemi diaphragmatic paralysis is a well-established complication of cardiac surgery, a unilateral diaphragmatic paralysis can also occur after automatic implantable cardioverter defibrillator placement.

CASE:

A 61-year-old female with a past medical history of hypertension, left bundle-branch block, Mobitz type 2 block, and chronic systolic heart failure presented to the emergency department with shortness of breath, fatigue, and orthopnea. A Multigated Acquisition (MUGA) scan at the time showed a left ventricle ejection fraction of 28% and a biventricular implantable cardioverter defibrillator placement was recommended. The left ventricular lead was unable to be placed percutaneously and the patient was referred for surgical implantation. The patient underwent left mini thoracotomy with epicardial left ventricle lead placement; the procedure was tolerated well.

Over the course of the next few months, the patient had repeated presentations of shortness of breath and was started on a beta adrenergic-glucocorticoid combination inhaler. This was followed by spirometry which failed to show a reactive airway and hence the inhaler was stopped. Interestingly however, the spirometry did show an extra thoracic restrictive volume flow loop. A chest Xray was obtained that showed left sided hemidiaphragm elevation which was progressively worsening. Since the surgery had been performed recently, this appeared to be a complication that was expected to resolve in around 6-8 months. A follow up Xray in 9 months post-surgery did not show resolution of the paralysis a thus a formal diagnosis of hemidiaphragm paralysis secondary to AICD placement was established. The patient was referred for a sniff test for confirmation.

Discussion:

This case illustrates that post procedure complications may present in unlikely ways even months after the intervention. The emphasis of having an all-rounded approach to presenting complaints cannot be underemphasized. Surgical history should be obtained at every instance as an anatomical cause of an apparent medical symptom can sometimes be the answer.

Unilateral diaphragmatic paralysis after Automatic Implantable Cardioverter Defibrillator placement

Background
Posterior fossa anomalies with prominent cerebrospinal fluid (CSF) spaces include entities such as Dandy-Walker spectrum, arachnoid cyst, mega cisterna magna, and Joubert Syndrome and Related Disorders (JSRD). Many of these have overlapping radiological findings. Several of the differentiating clinical markers only arise with development, making diagnosis difficult at a single point in time. Proper diagnosis requires longitudinal evaluation, careful consideration of diagnostic studies, at times genetic analysis. Continual re-assessment of the primary diagnosis is necessary to ensure proper diagnosis and treatment.

Case Presentation
A 15-year-old male was brought by his father to establish primary care. Father reported history of spastic quadriplegia and DWM and expressed concern about the patient’s episodic abnormal breathing patterns. Physical exam showed the patient was alert and interactive although speech was limited to “mom” and “dad”. The head was of normal circumference. There was bilateral exotropia, occasional nystagmus, and spastic muscle tone in all limbs. The lungs were clear to auscultation bilaterally. Referral was made to neurosurgery, who disputed the diagnosis of DWM given the clinical picture and prior imaging. A brain MRI showed severe vermis dysplasia with enlargement of the fourth ventricle, prominence of the posterior fossa CSF-spaces, diffusely abnormal foliation and fissuring of bilateral cerebellar hemispheres, and molar tooth sign (MTS) with deepening of the interpeduncular fissure and extension of the superior cerebellar peduncles. The patient received correction of diagnosis to JSRD.

Discussion
JSRD is a ciliopathy with autosomal and X-linked genetic variants. The primary diagnostic criteria are delayed developmental milestones, hypotonia evolving into truncal ataxia, and characteristic imaging. Secondary criteria include oculomotor apraxia and alternating episodes of tachypnea with apnea. “Pure” Joubert Syndrome expresses only primary and secondary criteria, while JSRD is considered when there are accompanying renal, hepatic, ophthalmic, and phalangeal abnormalities.

JSRD and DWM share several radiological criteria, including vermis hypoplasia and prominence of the posterior fossa CSF-space, leading to some diagnostic ambiguity. At a young age, patients with underlying JSRD or DWM may have similar clinical presentation. To ensure early differentiation clinicians should be aware of MTS as a pathognomonic radiologic finding for JSRD.


Joubert Syndrome and Related Disorders

Cranial empyema is a neurosurgical emergency. The body’s response attempts to wall off infection, resulting in a characteristic capsule that can be visualized through imaging. Organisms often correlate with patient age, medical history, and source of infection. In the setting of meningitis Streptococci, Staphylococci, Haemophilus, and other gram-negative bacilli predominate. In contrast, Escherichia and Salmonella species are often responsible for infections of existing subdural hematomas. According to prior studies, empyema of this etiology are typically less aggressive, in contrast to the refractory case seen in our patient. Neurologic prognosis is contingent on early diagnosis and management. We hope to discuss the importance of early radiologic follow-up and differentiating features between empyema and subacute subdural hematomas.


Next from AMA Research Challenge 2022

Visual Hallucinations and Altered Mental Status Exacerbation Associated with Acute Levodopa Withdrawal

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