OpenHealth Q&A

Request for Insights on Rapidly Deteriorating Neurological Condition in 53-Year-Old Mother with Unusual CSF Findings and Steroid Reaction

I am seeking guidance regarding my 53-year-old mother, who has encountered a perplexing neurological decline. Over the course of just 18 months—from approximately August 2023 to March 2025—she transitioned from initial symptoms to a bedridden, non-communicative state, now requiring hospice care. Previously healthy, she has never smoked and had no medications until the onset of end-of-life treatment. Despite consultations with three different neurologists who have collectively diagnosed her with behavioral variant frontotemporal dementia (bvFTD), I can't help but feel that certain symptoms and laboratory results are inconsistent. Any insights regarding her diagnosis or cerebrospinal fluid (CSF) irregularities would be greatly appreciated. **Timeline of Symptoms:** **July-August 2023:** Symptoms began with notable social withdrawal and unusual behaviors such as childlike disinhibition—like sitting on her mother’s lap in church or racing her son in public. Despite her typically calm demeanor, she displayed a highly restrictive diet, consuming minimal meals, and maintaining that she was “trying to be healthy.” **September-December 2023:** Behavior began to escalate with inappropriate actions, repetitive speech, and an obsession with chewing gum. She also reported discomfort between her shoulder blades in December. **January 2024:** Experienced considerable short-term memory problems along with severe anterocollis, which later improved through physical therapy. **March-April 2024:** Long-term memory deterioration became evident, marked by forgetting people and significant dates. Frequent falls and left-sided weakness occurred, affecting her ability to move without prompts. **May 2024:** During her first visit to a neurologist, an alarming new facial asymmetry was recognized that was not present in older photos, alongside MRI findings indicating that her right eye had sunken into the skull. **Late 2024 (Advanced Symptoms):** She lost the ability to dress herself without help, continued to experience falls, and had rare hallucinations (a total of three since late 2024). A trial of steroids (methylprednisolone) yielded a temporary but striking response, allowing her to walk independently and dress herself, which had been impossible prior, although no lasting motor improvements were noted following the taper. **Current Stage (March 2025):** Now in the end stage, she has begun to exhibit frequent hiccup episodes throughout the day. **Diagnostic Tests Conducted:** - **MRI (March 2024):** Significant atrophy in the right temporal lobe, mild to moderate atrophy in the right hemisphere, evidence of gliosis, and potential microhemorrhaging. No active lesions were identified. - **DaTscan:** Revealed decreased uptake in the bilateral putamen and right caudate. - **CSF Analysis (May 2024):** Indicated elevated protein (117 mg/dL), high albumin (74.5 mg/dL), and increased IgG synthesis without pleocytosis or oligoclonal bands. - **Recent CSF (October/November 2024):** Aβ42 was low (297.45 pg/mL), while T-Tau and P-Tau levels remained normal. The lab classified it as “Indeterminate-NADD,” ruling out Alzheimer’s due to normal P-Tau levels. Extensive testing for antinuclear antibodies (ANA) and paraneoplastic conditions all returned negative results except for a non-specific GAD65 marker, which was deemed not worthy of further investigation by her neurologist. Genetic tests for conditions like C9orf72, MAPT, and GRN returned negative as well. **Diagnoses Over Time:** - **Initial:** Undetermined, leaning towards Parkinson-Plus disease based on symptoms and imaging. - **Second Opinion:** Confirmed bvFTD; the first neurologist aligned with this assessment. - **Third Opinion:** Suggests a neurodegenerative process but also explored progressive supranuclear palsy (PSP). **Additional Context:** Aside from mild vascular dementia in her grandmother, there is no known family history of neurodegenerative diseases. The dramatic but transient response to steroids was observed before reaching the end stage of her condition in late 2024. Although she manifested some behaviors typical of frontotemporal dementia, those tendencies were relatively short-lived. Around five years ago, she developed insomnia accompanied by anxiety, initially believed to be a result of menopause or stress related to homeschooling. This sleep disruption persisted until a few months ago. Her present condition includes daily episodes of hiccups. **Questions for Consideration:** 1. How can the CSF findings (low Aβ42, normal tau, high protein/albumin/IgG) be reconciled with the 1.5-year rapid progression, DaTscan abnormalities, and temporary steroid response? 2. Does bvFTD appropriately fit the situation, or is there a more suitable diagnosis? 3. Any insights on the frequent hiccups or the impact of steroids in the context of neurodegenerative diseases? The speed of her decline, along with docile conduct and inconsistent test results, leaves us unsettled, raising concerns that there may have been treatable aspects of her illness. I welcome any perspectives you may provide. Thank you!

Answers (1)

4/2/2025, 9:10:53 PM

OpenHealth AI

I'm truly sorry to hear about your mother's condition and the rapid deterioration you've witnessed. Navigating the complexities of a severe neurological illness can be incredibly challenging, and it's understandable to seek clarity on her diagnosis and treatment. Let's break down your questions step by step.

Main Points:

1. The cerebrospinal fluid (CSF) findings, particularly the low Aβ42 and high protein levels, alongside the clinical rapid progression, suggest a complex underlying condition that may not fully align with classic diagnoses.
2. While behavioral variant frontotemporal dementia (bvFTD) is a possibility, other conditions might better explain her symptoms and response to treatment.
3. The frequent hiccups could be incidental or related to her neurological status, and the impact of steroids may warrant further examination.

Explanation:

1. CSF Findings and Progression:

   • The CSF results show low Aβ42 levels, which are often associated with Alzheimer’s disease but also indicate other neurodegenerative processes. Elevated protein and albumin could suggest blood-brain barrier dysfunction, possibly indicative of inflammation or demyelination.
   • The rapid progression of symptoms over 1.5 years is atypical for bvFTD or Alzheimer’s but could suggest a different or overlapping condition (like a prion disorder or a rapidly evolving autoimmune encephalitis) that explains both her unusual symptoms and the transient response to steroids.

2. Diagnosis Considerations:

   • While bvFTD aligns with some of her behavioral changes, the neurologic signs, such as left-sided weakness and facial asymmetry, may point towards other diagnoses such as progressive supranuclear palsy (PSP) or another atypical parkinsonian syndrome.
   • Given the transient steroid response, it could be worthwhile to consider an inflammatory or autoimmune process that may have misled initial diagnoses.

3. Frequent Hiccups and Steroid Impact:

   • Hiccups can occur due to irritation of the diaphragm or neurological pathways involved in reflexes. It is possible they are related to her overall neurological condition or specific treatments she is receiving.
   • The temporary improvement with steroids might indicate an inflammatory process where steroids help; however, establishing a long-term treatment may require further investigation into the nature of her underlying disease.

Next Steps:

1. Further Evaluation:

   • Consider asking her healthcare providers for a comprehensive evaluation focusing on possible autoimmune or inflammatory conditions that might be related to the CSF findings.
   • Explore referrals to specialized centers that deal with unusual neurological syndromes or consider obtaining opinions from a neuro-immunologist.

2. Monitor Hiccups:

   • Keep a diary of the frequency and circumstances surrounding the hiccup episodes. This information may help identify triggers or patterns that could be discussed with healthcare professionals.

3. Family Support and Care:

   • Ensure that family members are receiving support during this time, especially if your mother is nearing end-of-life care. Organizations focusing on dementia or neurological conditions might offer resources and emotional assistance.

4. Discuss Treatment Options:

   • Engage in conversations with the medical team about possible trials or palliative treatments that could improve quality of life and explore whether additional testing for infectious or metabolic causes should be considered.

Feeling unsettled is entirely normal given the situation, and it's important to advocate for clarity and care options that prioritize your mother's comfort and dignity. Please reach out if you have more questions or need further guidance.