Navigating difficult conversations in ALS

Patients may be in a state of shock, wondering how they have developed ALS and what it means for them. ALS experts, aren't always able to answer all of these questions as the causes and/or prognosis of ALS may not always be clear.^1,2

So how can healthcare providers offer an accurate explanation of the complexities behind ALS while maintaining a sense of compassion? More importantly, how can the physician and patient turn these conversations into ones of mutual understanding? Caroline Ingre, MD, PhD, who leads the ALS research program at Stockholm’s Karolinska Institute, shares some insights from her own experience.

Dr. Ingre listened as a patient explained her frustrations. A tightness that began in the patient’s shoulders years earlier had led to countless visits to different specialists, and eventually an ALS diagnosis. Finally, a blood test at Karolinska uncovered a genetic mutation that could be associated with the diagnosis: a repeat expansion mutation in C9orf72.²

So she explained that there are many factors believed to contribute to the causation and progression of ALS,² and it was risky to make guesses based on the general ALS population versus the facts behind each individual's personal data. The patient knew ALS meant a difficult journey ahead, but the inability to know what was going to happen next made it worse.

There were still too many unanswered questions for the patient. Dr. Ingre could only imagine what that felt like, and that was why she aimed to dig further.

Dr. Ingre observed the facts. The association of C9orf72 and ALS had been established just one year earlier. C9orf72-associated ALS had been traced back to hexanucleotide repeat expansions and was believed to be the most common form of genetic mutation associated with ALS among European patients.^4,5

Something was different about this patient. But what? Dr. Ingre believed that the insistence on using firm definitions of the disease and its presentation made it difficult to contextualize outlier cases like the current patient.

She believed the confusion lay in phenotypes: how a gene is expressed and what causes it to be expressed that way. There may be environmental factors, other genetic contributions, and even gender—all influencing how the disease progresses.^1,2 She explained this to her patient.

The patient listened to Dr. Ingre’s explanation but could not control herself anymore. “I can’t even rely on the supposed facts of ALS to tell me what I should expect?” she said, visibly shaken. “Can you tell me anything about what comes next?”

Dr. Ingre hoped a new project she was designing would reveal more answers to the patient’s many questions. She was building a patient registry and biobank for all patients with ALS in Sweden. By collecting samples of blood, hair, tissue, and spinal fluid every six months, researchers could chart the progression of ALS among different patients and compare data to identify biomarkers and trends. Over time, they might be able to generate more accurate expectations for patients—and potentially understand why this patient’s C9orf72-ALS was progressing so slowly.

Finally, drawing on her experience with the registry and biobank, Dr. Ingre informed the patient there were others out there like her. Some Stockholm-area women were diagnosed at a younger age relative to other ALS patients. Some had been with Dr. Ingre since before the identification of C9orf72 as a genetic cause of ALS. These relevant details sounded good to the patient. Nearly as important, she found out she wasn’t alone.

Several years later, the patient registry system is leading to meaningful results. Once as unsure as some of her former patients, Dr. Ingre now feels more comfortable in seeking to understand the differences between them. The individual stories of her patients—including the phenotypic presentation of specific gene mutations—led her to see ALS differently.

She now views ALS patients as subgroups, not members of one large collective. Their diseases are as unique as the patients themselves. “There are still a lot of things going on that we cannot understand that create a very personalized disease pattern for patients,” she says.

While the patient once did not know how long she could expect to live, now she has a better idea.⁶ And because she joined the patient registry, she knows the next patient who shares similar ALS characteristics could potentially have a more immediate idea of what to expect.

It pleased the patient to know she was potentially assisting future patients in finding clarity—and that her quest for knowledge had become part of a greater legacy.