Tuesday, May 16, 2023

GPT4 Analyzes a New England Journal Patient Case (65 y/o woman w neurologic signs)

I haven't tried giving GPT4 any dense clinical questions before.   

After reading a new book, The AI Revolution in Medicine, May 2023, co-authored by one of the top AI people at Microsoft (Lee), and at Harvard Med School (Kohane), and an excellent journalist (Goldberg), I realized GPT4 can already do pretty well at digesting clinical histories.

  • From the NEJM, here is a text of a recent complicated medical case study of a 65 year old woman.  
    • NEJM source here.  Text only, here.  
    • (The actual case results are here.  Not easy to figure out, it is lymphoma of CNS.  The NEJM poll didn't get this one, Cadasil was voted 44%, CJD 21%, lymphoma 10%.)
  • GPT4 can also summarize patient-doctor dialogs into clinical notes.




 GPT4 Assessment:

This 65-year-old woman presented with a complex set of symptoms including worsening neuropsychiatric symptoms (anhedonia, decreased energy, sadness, poor concentration, suicidal ideation), physical symptoms (weight loss, unsteady gait, recurrent falls, left-side weakness), and cognitive symptoms (impaired recall, mild inattention). While initially diagnosed with depression, her symptoms have progressively worsened over the past year, despite changes in her psychiatric medications. 

A number of neurological tests have been performed, which, while revealing some abnormalities (e.g., increased signal intensity in the pons and periventricular distribution on T2-weighted imaging, patchy hyperintensity involving the centrum semiovale, corona radiata, internal capsule, and corticospinal tract bilaterally on T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging), have not definitively diagnosed her condition. 

Furthermore, her physical and cognitive decline appears to have progressed despite psychiatric and physical therapy interventions.


Given the atypical presentation and progression of symptoms, it is necessary to consider additional diagnostic possibilities beyond a primary psychiatric disorder. The presence of unilateral weakness, along with neuroimaging abnormalities and cognitive symptoms, suggests a possible neurodegenerative or neurological condition.

The next steps should include:

Neurological Consultation: It is important to involve a neurologist in her care. A neurologist could perform a more detailed neurological examination and interpret the significance of her imaging findings in the context of her clinical presentation.

Further Imaging: Depending on the neurologist's assessment, further neuroimaging may be required. A PET scan, for example, could be useful in detecting metabolic changes in the brain associated with neurodegenerative diseases.

Lumbar Puncture (LP): An LP could be useful in looking for evidence of CNS inflammation or infection, or to assess biomarkers associated with neurodegenerative diseases (such as tau or beta-amyloid in Alzheimer's disease).

Neuropsychological Testing: This would provide a more comprehensive understanding of her cognitive deficits and could help differentiate between psychiatric and neurological causes of her cognitive symptoms.

Psychiatric Consultation: A detailed psychiatric evaluation could help determine the extent to which her psychiatric symptoms are contributing to her overall presentation.

Multidisciplinary Care Approach: A multidisciplinary team including neurologists, psychiatrists, physical therapists, occupational therapists, and social workers could work together to provide comprehensive care for this patient, addressing both her physical and mental health needs.

Consideration of atypical or rare causes: If standard tests do not provide a clear diagnosis, it may be necessary to consider rarer causes, such as prion diseases, mitochondrial diseases, or other rare neurodegenerative disorders. This may require more specialized testing and consultation with a specialist in these conditions.

Supportive Care: Regardless of the underlying diagnosis, this patient is clearly struggling with her daily activities and quality of life. Supportive care measures, such as physical therapy, occupational therapy, speech therapy, nutrition support, and mental health support, should be continued and optimized to help her manage her symptoms and maintain her quality of life.

This is a complex case, and it is important to keep an open mind and consider all possible causes of her symptoms. Her care should be patient-centered, and all decisions should be made in collaboration with the patient and her family.

Human physicians voted for a diagnosis of CADASIL, followed by CJD, followed by lymphoma.  The patient proved to have lymphoma (voted by only 10% of doctors).  

What is consistent with this final diagnosis, in retrospect?

 CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) and CJD (Creutzfeldt-Jakob Disease) are both neurological conditions, the first being a genetic disorder affecting the small blood vessels in the brain, and the second being a prion disease causing rapid neurodegeneration. While the patient's neurological symptoms and MRI findings could be suggestive of these conditions, they could also be consistent with central nervous system (CNS) lymphoma.

CNS lymphoma is a type of non-Hodgkin lymphoma where cancer cells form in the lymph tissue of the brain and/or spinal cord. Although this is a rare condition, it can present with a variety of neurological and psychiatric symptoms, depending on the areas of the brain affected.

In retrospect, the following findings are consistent with the diagnosis of CNS lymphoma:

Neuropsychiatric symptoms: Her depression, cognitive decline, and psychomotor retardation can be seen in CNS lymphoma due to the effect of the tumor on different parts of the brain.

Unilateral weakness and gait issues: Depending on the location of the tumor, CNS lymphoma can cause focal neurological symptoms, such as weakness on one side of the body.

Rapid progression of symptoms: CNS lymphoma can lead to a rapid decline in neurological function, consistent with this patient's history.

MRI findings: The presence of hyperintensities on T2-weighted and FLAIR imaging can be seen in CNS lymphoma. Although these findings are not specific and can be seen in a variety of neurological conditions, they can be suggestive of a brain tumor in the right clinical context.

Weight loss: Significant weight loss is a common symptom in lymphomas and could be an indirect sign of malignancy.

Increased white cell count: While not specific, an elevated white cell count can be seen in individuals with systemic malignancies, including lymphoma.

Failure to improve with psychiatric interventions: Despite aggressive treatment for depression, her condition worsened, which could suggest an underlying organic pathology like CNS lymphoma.

In summary, while this is a challenging case with symptoms that could be seen in a variety of psychiatric and neurological conditions, in retrospect, the above findings are consistent with the diagnosis of CNS lymphoma.

And on the other hand, from the data we had initially, are there any features of the case that would lead you AWAY from the diagnosis of Lymphoma?


Indeed, while certain features of this case are consistent with CNS lymphoma in retrospect, there are also features that might have initially led a clinician away from this diagnosis:

History of depression: The patient had a prior diagnosis of depression which seemed to correlate with her psychosocial stressors. This might have led clinicians to initially attribute her symptoms to a worsening of her depressive disorder, rather than considering an organic brain pathology like lymphoma.

Lack of typical CNS lymphoma symptoms: Although CNS lymphoma can present in many ways, some more common symptoms such as seizures, headaches, or changes in personality were not reported in this case.

Normal Contrast-enhanced MRI: CNS lymphoma often shows contrast enhancement on MRI due to disruption of the blood-brain barrier by the tumor. The absence of this finding in the case might have made CNS lymphoma less likely in the minds of the clinicians.

Absence of systemic symptoms: While the patient did have weight loss, she did not have other systemic symptoms often associated with lymphoma, such as night sweats or unexplained fevers.

Subacute presentation: While CNS lymphoma can cause rapidly progressive neurological symptoms, this patient's symptoms developed over several months. Depending on the clinician's experience and familiarity with CNS lymphoma, this may have been perceived as a more subacute presentation, potentially leading them away from a diagnosis of a rapidly growing malignancy like lymphoma.

This case underscores the diagnostic challenges that can arise in complex patients and the importance of maintaining a broad differential diagnosis, especially when patients do not respond as expected to initial treatments.

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