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An acute dilated pupil signals dysfunction of the third cranial nerve or sympathetic/parasympathetic pupillary pathways. Life-threatening etiologies of third nerve cranial impairment include uncal herniation, cerebral aneurysm, or another space-occupying lesion. Consequently, the finding of an acute, unilateral, dilated pupil warrants immediate clinical evaluation and neuroimaging.
However, anisocoria without findings of oculomotor deficits is rare in compression-induced third cranial nerve palsies but is rather commonly associated with pharmacological etiologies or Adie’s pupil. Specifically, anticholinergics allow unopposed sympathetic stimulation of the dilator pupillae muscle, resulting in a dilated pupil. Administration of ipratropium through a face mask inhaler is common in intensive care respiratory management. However, masks are susceptible to leakage and displacement. Pupillary dilatation secondary to ipratropium has been described but is not widely known. We presented a case report where an unilateral anisocoria is secondary to contamination of ipratropium to the right eye.

AMA Research Challenge 2024 

Ipratropium-Induced Anisocoria due to an Ill-Fitting Face Mask Inhaler

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Abstract: 

Background: 

Myelitis is a debilitating neurological condition characterized by inflammation and demyelination of the spinal cord. It leaves two-thirds of patients with moderate to severe residual disability. Generally occurring independently, often as a complication of infection, it can also be a component of neuro-inflammatory spectrum disorders like multiple sclerosis, neuromyelitis Optica spectrum disorder (NMOSD), acute disseminated encephalomyelitis, and MOG antibody disease. NMOSD is distinct by the presence of aquaporin-4 IgG antibodies (AQP4-IgG) and has an estimated global prevalence of 1 in a million, predominantly affecting females. 

Case presentation: 

A 59-year-old female with a questionable history of Brown-Séquard syndrome in 2004, for which she avoided surgery due to concerns about losing mobility, presented with acute neck pain following a bug bite on the back of her neck, with pain and tingling sensation in both the hands. An MRI of the neck revealed T2-weighted hyperintense signals from the cervico medullary junction to the upper border of T1, indicating spinal cord edema(Figure 1). Blood work for paraneoplastic syndrome(s) was negative but the presence of AQP-4 antibodies confirmed the diagnosis of NMOSD. She was treated with a 5-day course of high-dose intravenous methylprednisolone and plasma-exchange, leading to significant symptom improvement. She was placed on rituximab monotherapy (1000 mg once every 6 months) for chronic treatment. 
case.png

Discussion: 

NMOSD is definitively diagnosed based on AQP-4 antibodies in serum and CSF with signs of area postrema syndrome and acute myelitis (2015 diagnostic criteria). Moreover, this patient's symptoms improved following immunotherapy, but not anti-infective medication. Intravenous methylprednisolone is typically used to treat acute NMOSD episodes. If unresponsive, plasma exchange can be added. Acute attack outcomes have improved in single case series by experimental therapies like IVIG, anti-CD20, and anti-complement therapy. 

Relapses have reduced with immunosuppressive maintenance therapy using rituximab, azathioprine, mycophenolate mofetil, and oral prednisone. Shi Z et al., with 281 Chinese NMOSD patients, showed azathioprine and mycophenolate mofetil lowered disability and relapse rates. Yaguchi H et al. found cyclophosphamide (monotherapy or in combination with methylprednisolone) effective in both acute and chronic phases. Approved immunotherapies, inebilizumab, eculizumab, and Satralizumab, reduce the relapses and the cumulative impairment. Newer biologics (theravulizumab, ublituximab, aquaporumab, and sedelestat) are undergoing review for use in NMOSD. 

Conclusion: 
For atypical presentation of NMOSD, a high index of suspicion is needed for early treatment and better patient outcomes. Although novel treatment modalities provide a hope for more effective treatment, more trials are required to estimate their safety and efficacy.

Neuromyelitis Optica Spectrum Disorder: A case report and a review of treatment modalities

Background 
Immediate reperfusion is vital to treating an acute ischemic stroke (AIS). Tenecteplase can be used for thrombolysis. However, there is a chance of early recurrence of ischemia which can affect the high cervical spinal cord (HCSC) which often gives a bad prognosis but with appropriate management, a good clinical outcome can still be expected. 

Case Presentation 
A 69-year-old female with no known comorbidities suffered an HCSC infarct after treatment with tenecteplase for an acute ischemic stroke. 

She presented with sudden pain in the right neck with nausea, diaphoresis, and dizziness. Neurologic examination was significant only for a left facial droop. CT angiogram showed an occlusion of the right vertebral artery at V3-V4 segment. She was given IV Tenecteplase within 4.5 hours of onset. 

Few hours later, she developed difficulty breathing. She had bilateral diaphragmatic paralysis resulting in respiratory acidosis requiring mechanical ventilation. Additionally, she developed quadriplegia. MRI brain showed an HCSC infarction. She was on ventilatory support for 2 months due to diaphragmatic compromise. She underwent a tracheostomy and percutaneous endoscopic gastrostomy. Multiple bronchoscopies were done to manage mucous plugs and retained secretions, and she received antibiotics for ventilator-associated pneumonia. 

Despite all complications, she was weaned to a speaking valve and eventually was able to communicate. Modified barium swallow showed tolerance to oral intake. Tracheostomy was successfully decannulated thereafter. 

She was eventually discharged with a motor exam of 2-3/5 in all extremities with no other focal neurologic deficits. 

Discussion 
The patient suffered from a mild ischemic stroke. Alteplase is the only approved thrombolytic drug by the Food and Drug Administration (FDA) for the treatment of AIS. If given within 3-4.5 hours of onset, it can prevent further disability. 

Coming in during the therapeutic window for thrombolysis, she was given tenecteplase, a modified variant of alteplase. Tenecteplase is FDA-approved for thrombolysis in acute myocardial infarction but has found off-label use for AIS. 

Early recurrence of ischemic stroke has been reported after alteplase. For tenecteplase, there are instances of expansion of the original infarct after thrombolysis but no documented report of an HCSC infarct as of this writing. Nevertheless, due to the similar pharmacokinetic properties of tenecteplase to alteplase, such a phenomenon of ischemic stroke recurrence may occur. 

Acute spinal cord infarct is a rare occurrence and usually involves non-cervical territory. It may be associated with episodes of hypotension and may present with quadriplegia and diaphragmatic paralysis which were all found in this patient. 


Risks of Thrombolytic Therapy: Uncommon Complications with A Good Outcome

Miller Fisher Syndrome (MFS) is an uncommon neurological disorder with an estimated yearly incidence of 1 in 1,000,000 in the United States. MFS is a variant of Guillain-Barre syndrome (GBS) characterized by ophthalmoplegia, ataxia, and areflexia, likely preceded by either a recent infection of the upper respiratory or gastrointestinal tracts, or vaccination. This syndrome most commonly affects adult males with a median age of 44 years. Here we want to draw attention to a rare case of MFS with atypical presentation in a 60-year-old female patient who presented to the Emergency Department (ED) with a medical history of hypertension and diabetes mellitus with complaints of blurred vision and walking difficulty for 2 days. She developed respiratory weakness requiring Intensive Care Unit (ICU) admission, and hyporeflexia, bilateral ptosis, and ophthalmoplegia subsequently. Provisional diagnosis of MFS was made upon cerebrospinal fluid (CSF) analysis which was later confirmed by the presence of Anti-GQ1b antibody. A single dose of Intravenous Immunoglobulin (IVIG) was sufficient to stabilize the patient’s condition, allowing her to be moved out of the ICU. Given the favorable prognosis of this disorder, early identification and effective drug treatment would minimize unnecessary medical interventions, curtail expenditures, and ease psychological distress.

Unusual Manifestation of Miller Fisher Syndrome as a Stroke-Mimic: A Case Report and Literature Review

Abstract Title
Unveiling the Unusual: Adrenoleukodystrophy and Paraphilia - A Rare Case Study
Background 
X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder affecting approximately 1 in 21,000 males, primarily impacting the white matter of the nervous system and the adrenal cortex. The cerebral forms of ALD, including childhood, adolescent, and adult variants, typically present initially with symptoms such as hyperactivity or inattention, followed by a progressive decline in cognitive, motor, visual, and auditory functions. Here, we present the case of a 22-
year-old male with ALD, who exhibits paraphilia along with neuropsychiatric manifestations of ALD, a unique presentation that has been scarcely documented.
Case Presentation 
A 22-year-old male with a medical history significant for adrenoleukodystrophy, seizure disorder, Asperger syndrome, Attention-Deficit/Hyperactivity Disorder, progressive hearing and visual loss was admitted due to altered mental status. His adoptive mother reported developmental delays and social cue difficulties since childhood, with a decline in functionality beginning in October 2023. Neuro-ophthalmological evaluation for progressive vision loss, led to a subsequent MRI which showed diffuse periventricular and subcortical white matter hyperintensities involving parietal, occipital, temporal, and frontal regions. Elevated very long chain fatty acids (VLCFA) confirmed ALD diagnosis. A month after admission, he developed compulsive rectal picking and digital manipulation leading to rectal bleeding. Psychiatry suggested that it could be due to either OCD-type skin picking or a gratifying sexual compulsion. The nursing staff reported frequent episodes of uncontrollable impulses for aggressive rectal digital manipulation ending in ejaculation, over the past three months, necessitating the use of restraints and mittens for his safety. Despite treatments including Paroxetine, risperidone, and 
anti-androgens, no improvement was noted. Guanfacine was later initiated to enhance frontal inhibition, yet efficacy remained limited. Upon discharge, transitioning to a group home was planned.
Discussion
ALD is a disorder in which defective beta-oxidation leads to the accumulation of very long-chain fatty acids in peroxisomes. It typically presents with neurobehavioral disturbances starting in childhood. The patient's behavioral symptoms began in childhood but were never formally evaluated. We believe an undiagnosed ALD might have contributed to his symptoms. ALD usually leads to hyposexuality due to adrenal insufficiency. However, our patient exhibited recurrent rectal digital stimulation suggesting impulsivity and disinhibition, which is a distinctive presentation. We hypothesize that the patient's paraphilia may be linked to his frontal lobe 
involvement. No evidence of adrenal insufficiency was observed in his labs. We emphasize the importance of considering ALD as a differential diagnosis when evaluating patients with neuropsychiatric disturbances, as it is a progressive and debilitating condition

Unveiling the Unusual: Adrenoleukodystrophy and Paraphilia - A Rare Case Study

Background: Cases of incarcerated gravid uterus (IGU) are quite rare at about 1 in 3000 pregnancies. IGU is defined as the entrapment of the gravid uterus between the pubic symphysis and the sacral promontory. Due to compression of adjacent structures, symptoms of IGU present non-specifically as urinary retention, dysuria, abdominal pain, and constipation, often causing this condition to be misdiagnosed. Reduction of an IGU proves to be crucial as serious complications such as urinary tract obstructions, urinary tract infections, renal failure, fetal growth restriction, fetal demise, and uterine wall rupture may occur. 

Case Presentation: A 34-year-old G2P1 woman at 12 3/7 weeks presented with difficulty urinating, difficulty stooling, and a feeling of incomplete emptying. At the patient’s first visit a week prior, it was thought that she had a urinary tract infection as it proved to be the most likely cause of her symptoms; however, cultures were negative and completion of the antibiotic treatment provided no relief. The patient was reevaluated the following week when an anterior displacement of the cervix on speculum exam was noted. This led to the diagnosis of an IGU, pivoting the management to passive and active reduction techniques. A catheter was placed to relieve the patient’s bladder. 2200 cc of urine were drained after which the patient reported significant relief of pelvic pressure. The patient was placed in the knee/chest position for two hours before a manual replacement was attempted. The uterus was lifted from the cul-de-sac, and the patient was sent home with the foley in case the incarceration recurred. She returned to the clinic 10 days later for a voiding trial after removal of the foley which proved to be successful. The patient is continuing with her pregnancy without any issues.

Discussion: IGU often presents with urinary symptoms and can be conservatively managed by draining of the bladder, non-invasive methods such as knee-chest, and manual reduction if none of these efforts are successful. Early identification and management of an IGU is crucial for a safe pregnancy. Due to its rarity, it is often not considered when patients present with non-specific or primarily urinary symptoms. Cases are often misdiagnosed, leading to a delay in treatment and resolution of symptoms for patients. In this case, we note that the presentation of an IGU can easily be attributed to other causes and that if identified properly, can be reduced earlier in the pregnancy to avoid serious complications.

A Case of an Initially Misdiagnosed Incarcerated Gravid Uterus (IGU)

Current research emphasizes that ectopic pregnancies (EPs) are quite rare, with roughly 1-2% incidence in typical pregnancies and 2-5% in pregnancies resulting from Assisted Reproductive Technology. Non-tubal EPs (NTEPs) are significantly less common with an incidence of <10% out of all ectopic pregnancies. This study includes seven patients evaluated for NTEP treatment from January 2017 to August 2023. The team assessed risk factors while conducting an in-depth analysis of lab values, ultrasounds, complications, demographics, and outcomes. Analysis shows that of the 7 NTEP patients, 1 patient had a low-implantation intrauterine pregnancy (IUP), 5 patients had cesarean ectopic pregnancies, and 1 patient had an upper cervical canal ectopic pregnancy. 5 of the NTEP patients required in-patient treatment due to complications. Treatment options included: Transvaginal US-guided MTX injection, dilatation and curettage (D&C), systemic methotrexate (MTX), uterine artery embolization (UAE), and manual vacuum aspiration (MVA). The limited data pool for this condition and lack of consensus on best treatment for NTEP indicates the need for further research, especially less invasive options for patients who desire fertility preservation. By demonstrating that this approach is applicable in a variety of treatment settings and NTEP patient scenarios, our study verifies consistency with prior research studies on transvaginal MTX injection for NTEP management.

A Case Series on Non-Tubal Ectopic Pregnancies with Emphasis on Transvaginal US-Guided Methotrexate Injection

Fitz-Hugh-Curtis syndrome is a rare but clinically significant complication of pelvic inflammatory disease. Patients characteristically present with pleuritic right upper quadrant pain secondary to the spread of pelvic inflammatory disease to the liver capsule. Additional clinical manifestations include cervicovaginal discharge, pelvic pain, cervical motion tenderness, and adnexal tenderness. This syndrome primarily affects women in their reproductive years and is classically linked to sexually transmitted infection with Chlamydia trachomatis and Neisseria gonorrhoeae. Long-standing disease may not manifest clinically; thus, diagnosis typically involves a combination of clinical evaluation and imaging modalities. When the diagnosis is not yet clear and complications of pelvic inflammatory disease are present (i.e., hydrosalpinx), diagnostic laparoscopy is indicated for direct visualization. The classic “violin-string” adhesions visualized on laparoscopy connecting the anterior hepatic surface to the abdominal wall are pathognomonic of the disease.

We present an atypical case of Fitz-Hugh-Curtis syndrome with a 26-year-old female who presented with long-standing dysmenorrhea, bilateral hydrosalpinx, and no prior history of sexually transmitted infection or pelvic inflammatory disease. She also lacked the characteristic right upper quadrant pain, which can sometimes be the only clinical manifestation of the disease. The diagnosis of Fitz-Hugh-Curtis syndrome was made based on laparoscopic visualization of extensive “violin-string” adhesions involving the liver, left fallopian tube, uterus, and peritoneum. Laparoscopic adhesiolysis and bilateral salpingectomy was performed, and the patient had an uncomplicated postoperative course.

Fitz-Hugh-Curtis syndrome can pose a diagnostic challenge as it has a spectrum of possible clinical manifestations. As seen in this case, laparoscopy revealed extensive adhesive disease and tubal inflammation yet, the patient did not meet the minimum criteria for pelvic inflammatory disease or complain of right upper quadrant pain at any time during the disease course. Obtaining imaging of the abdomen and pelvis via ultrasound and computed tomography can be particularly valuable in establishing the diagnosis and ruling out other pathology; however, laparoscopy is the gold-standard of diagnosis. Young, sexually active women presenting to the hospital with pelvic pain and bilateral hydrosalpinx should raise high clinical suspicion for Fitz-Hugh-Curtis syndrome, regardless of sexual history or clinical manifestation of perihepatitis. Early diagnosis and treatment with laparoscopy can help patients avoid the pain and suffering that can persist for years, as seen in this case. This case also stresses the importance of treating sexually transmitted infection and pelvic inflammatory disease early on before it progresses to chronic pelvic pain and infertility.

Fitz-Hugh-Curtis Syndrome and Bilateral Hydrosalpinx in the Absence of Sexually Transmitted Infection: A Case Report

Abstract Title:
The Hidden Threat: Understanding the Significance of Tubo-Ovarian Abscess in Women’s Health
Background:
A tubo-ovarian abscess (TOA) is a serious and potentially life-threatening inflammatory mass involving the fallopian tube, ovary, and other pelvic organs, often resulting from a pelvic inflammatory disease (PID). TOAs are more often caused by Escherichia coli, aerobic streptococci, Bacteroides fragilis, and Actinomyces israelii, while Neisseria gonorrhoeae and Chlamydia trachomatis are rarely found from within the abscess cavity. The signs and symptoms can present as an ectopic pregnancy, appendicitis, or ovarian torsion. Aggressive medical or surgical treatment is often required to prevent rupture and/or sepsis. This infection typically occurs in sexually active women, particularly those with a history of STIs, intrauterine device use, or PID.
Case Presentation:
A 37-year-old female patient, with a history of spontaneous abortions and dyspareunia, presented to the ED with right lower quadrant (RLQ) pain for three days and was diagnosed with COVID-19 on arrival. Her last menstrual period was one month ago, and she denies history of any STI or PID. The pain came on suddenly, was constant, stabbing in nature, rated as 10/10, mostly in the RLQ radiating to the back. She tried over-the-counter pain medications without any relief. Laying still makes the pain tolerable, but movement makes it worse. She also described having a mild burning sensation with urination for the past three days, but denied any blood in the urine, changes in frequency, urgency, vaginal discharge or odor.
A pelvic ultrasound showed bilateral hemorrhagic ovarian cysts with a recent rupture. Further imaging via CT showed concern for tubo-ovarian abscesses given associated hydrosalpinx. She was started on vancomycin, but she experienced a systemic reaction, prompting a switch to ceftriaxone and meropenem. She went into an emergent exploratory laparotomy with a right salpingo-oophorectomy and drainage of a left TOA.
Low molecular weight heparin was started for anticoagulation and antibiotics were continued. Neisseria gonorrhoeae was identified in the peritoneal pus as the causative organism. The patient was afebrile, hemodynamically stable, and discharged after five days with a prescription for levofloxacin and metronidazole for outpatient treatment. At the two-week follow-up, the surgical scar healed well, and the antibiotics were completed with no onset of new symptoms.
Conclusion: This case highlights the importance of thorough evaluation and multidisciplinary management involving hospitalists, ED physicians, and gynecologists in managing TOAs. Identifying the causative organism is crucial for targeted antibiotic coverage, preventing surgical site infections, and addressing potential bacterial growth. TOA cases can vary and considered in differential diagnoses.

The Hidden Threat: Understanding the Significance of Tubo-Ovarian Abscess

Small round blue cell tumors are rare, aggressive tumors that are uncommon in pediatric females and are uncommonly found outside the abdomen. A 9-year-old female with intracranial left frontal high grade small round blue cell sarcoma underwent left frontal craniotomy with gross total resection. The lesion was highly vascularized, continuously bled during surgery, and a large branch of the anterior cerebral artery had to be coagulated. A month later, the patient began proton beam radiation therapy; after 2 weeks of treatment, she noticed declining vision and memory. Exam showed a visual acuity of 20/200 in both eyes, moderate dyschromatopsia, bilateral central scotoma, and bilateral temporal optic nerve atrophy. Potential differential diagnoses for this case include vascular insult to the anterior cerebral arteries and their branches which supply the optic chiasm, elevated intracranial pressure prior to resection, side effects of radiation therapy, or malignancy recurrence and/or infiltration.

High Grade Small Round Blue Cell Sarcoma and Unexplained Bilateral Optic Atrophy

Title: Young and facing retinopathy: a warning sign of deeper health issues? 

Authors: Yasseen A. Amellal BA, Erik R. Rosas BA, Debby Song BA, Christopher B. Everett MD

Background: Severe diabetic retinopathy at a young age often reflects a broader challenge in the management of systemic diseases in socioeconomically disadvantaged populations. This case report aims to discuss the potential barriers through the challenges faced by a young patient with severe diabetic disease.

Case presentation: A 21-year-old woman reported to the emergency room with multiple severe systemic diabetic complications. On arrival, she endorsed severe diabetic retinopathy and other systemic complications such as diabetic gastroparesis, end stage renal dysfunction, and diabetic left foot ulcers complicated by osteomyelitis, requiring toe amputation. Funduscopic exam revealed right eye retinal neovascularization, macular edema, and tortuous venous bleeding. On chart review, an unfortunate pattern of inability to access adequate transportation, lack of insurance and inadequate follow up by providers was observed. These events resulted in multiple missed appointments. As such, the ocular injections for her diabetic retinopathy were often delayed several months beyond the recommended standard of care, leading to preventable deterioration in her vision. 

Discussion: This case underscores the interconnectedness of barriers to healthcare and the poor prognosis of systemic diseases that require regular management, like diabetic retinopathy. Early intervention and regular check-ups are crucial in mitigating severe complications of systemic disease such as diabetic retinopathy. Strategies must be developed to aid patients who frequently miss appointments. In the near future, new medication gene trial therapies could be a critical factor in addressing these challenges.

Next from AMA Research Challenge 2024

Neuromyelitis Optica Spectrum Disorder: A case report and a review of treatment modalities

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