A cold, a coma, and a Christmas miracle: How a young mother survived a rare brain disorder

Initially, brain scans showed a lesion on Cook’s brain, causing an immense amount of swelling. Physicians first suspected she had a large brain tumor that had spread to both sides of her brain.

“One of the last things I remember thinking was this doesn’t make sense—I just have a cold,” Cook recalled.

That night Cook arrived at Penn, Daniel Yoshor, MD, chair of the department of Neurosurgery, reviewed Cook’s scans. Experienced with identifying and removing brain tumors, Yoshor didn’t think the lesions on Cook’s scans were from a tumor. Instead, he made a risky recommendation to biopsy Cook’s brain.

The biopsy recommended by Yoshor revealed that Cook had an extremely rare and aggressive inflammatory disorder called acute hemorrhagic leukoencephalitis (AHLE), in which the immune system attacks the brain’s white matter. AHLE is so uncommon and fast-moving that it’s usually diagnosed after death—there is no standard treatment protocol, and mortality rates are extremely high.

A neurologist with a unique expertise in white matter disorders

At the same time, Jennifer Orthmann-Murphy, MD, PhD, an assistant professor of Neurology, was trying to reduce Cook’s brain swelling. Orthmann-Murphy is one of a few neurologists in the country specializing in rare white matter disorders, and leads an ‘Undiagnosed White Matter Disorders’ neurogenetics clinic at Penn.

Orthmann-Murphy sees patients with rare or unusual conditions that affect the white matter in the brain. White matter is the tissue that contains nerve fibers and myelin, the substance that insulates these fibers. A well-known disorder impacting white matter is multiple sclerosis (MS), where the body’s immune system mistakenly attacks the myelin and damages nerves, leading to pain and muscle weakness.

However, some people have genetic conditions, called leukodystrophies, that cause the white matter to deteriorate, leading to symptoms without an obvious cause, like loss of strength and balance, difficulty with learning new information or remembering old information, or changes to movement or coordination. Orthmann-Murphy’s clinic searches for genetic markers for dozens of different leukodystrophies to help make a diagnosis, and in some cases match an individual with a clinical trial of a treatment.

By a huge coincidence, weeks before Cook was admitted to the Neuro ICU, Orthmann-Murphy had attended a conference on leukodystrophies and other rare disorders, and so rare but fatal conditions like AHLE were fresh in her mind. She knew she had to act quickly.

A rare diagnosis with no clinical roadmap

While the exact cause of AHLE is unclear, limited evidence suggests that it can result from an autoimmune response triggered by an infection, resulting in the immune system mistakenly attacking the white matter.

AHLE onset is sudden and progresses quickly. As in Cook’s case, patients rapidly progress from mild symptoms, like headache and fever, to a coma within days. Analysis of the little data that exists shows that over half of individuals who get AHLE die, and those who survive have severe neurological deficits, like paralysis or impaired cognition, such as thinking, memory, learning, and problem-solving.

Coupled with the insights from the conference she had just attended, Orthmann-Murphy assembled a massive team of experts across Penn Medicine and the Children’s Hospital of Philadelphia (CHOP) to develop a treatment plan.

Each decision Orthmann-Murphy made to try to save Cook was based on advanced and specialized knowledge: from neuroinflammation specialists in the Multiple Sclerosis and related Neuroinflammatory Disorders Division at Penn and CHOP, to the neuropathologists Eddie Lee, MD, PhD, and Emily Pai, MD, PhD, who performed the biopsy, the MS Division pharmacists, the Immune Dysregulation Team at CHOP, Jose Pascual, MD, PhD, a Traumatologist on the NeuroICU and neurosurgery teams, to countless neurology and neurosurgery residents and fellows who provided care to Cook along throughout her stay.

“Usually when a patient has a neuroinflammatory disorder, we try one immune-targeted treatment at a time and evaluate how the patient responds and then adjust accordingly. We simply did not have time for that here; Shannon’s case was so severe and worsening so rapidly that we administered several treatments all at once to try and reduce the inflammation and brain swelling as quickly as possible,” said Orthmann-Murphy. “She required constant monitoring for two weeks straight.”

Cook was given multiple treatments, including antibiotics, steroids, and monoclonal antibodies. She also underwent several rounds of plasma exchange, a process where her plasma was filtered from her blood and replaced with fluids. When swelling in her brain persisted, she had surgery to remove a piece of her skull and relieve pressure on her brain. Yoshor also took a second brain biopsy to confirm her diagnosis and further guide treatment. Soon after this surgery and initiating the full course of immune-targeted medications, Cook’s condition began to stabilize. The pressure in her brain subsided, and her medications were slowly tapered off.

The team recently published Cook’s case study in the Journal of Neuropathology & Experimental Neurology, adding to the very limited literature on the condition.

“While rare, clinicians should know how to identify AHLE in a patient, which may hopefully result in rapid treatment and better outcomes,” said Orthmann-Murphy. “Although obtaining brain biopsies is associated with some risk, the information we learned from them may have saved Shannon’s life.”