Puzzling Case

Be prepared, I don't have a diagnosis for this patient yet!


She is a 60-year-old with known past medical history of HLD and CKD. At her baseline before all symptoms started she had a normal cognitive function, no weakness no seizures, basically she was normal.

Symptoms started in October with nausea & vomiting for which she was admitted to a local hospital with negative workup. While there she developed DVT and was started on Eliquis. She was admitted walking and was discharged on a wheel chair. Family reported she started to have generalized weakness, mainly in her legs when these symptoms started. Couple weeks later with progressive weakness she presented to our ED.

Here, She was found to have areflexive weakness in both upper and lower extremity more in lower extremities with 2/5 muscle power. LP did show markedly elevated proteins (103 mg/dl) with normal cell count so a diagnosis of GBS was entertained and the patient was started on PLEX with minimal improvement.

At the end of PLEX course patient started to show gradual progressive cognitive decline and disorientation. MRI brain with contrast was normal. This was blamed on UTI that was treated with antibiotics and patient was discharged to inpatient rehab on 10/22.

While in rehab, patient continued to progress with increasing confusion, disorientation and abnormal movements (choreo-athetosis) involving both upper extremities. Neurology was called and asked to transfer patient back for further workup for encephalopathy. A repeat MRI brain with contrast was still unremarkable. LP was again negative for infections with normal cell count and elevated protein. IgG synthesis was normal but had only 2 oligoclonal bands unique to CSF.

Is it an encephalopathy related to Guillain Bare as in Bickerstaff encephalitis, or it is really not Guillain Bare and it may be all paraneoplastic neuropathy and encephalopathy or autoimmune disease with these elevated protein and 2 oligoclonal bands? She had significant GI symptoms prior to all of her symptoms, can this be part of DPPH VGKC?

Further tests were sent for Anti Gq1b, anti gangliosides, 14-3-3 and autoimmune encephalopathy panel (Mayo clinic ENC1). CT chest, abdomen and pelvis were negative. Patient was started on pulse steroids for empirical treatment of autoimmune encephalopathy without any improvement.



- Awake, alert, not attentive, not oriented to time, place or situation.

- Speech markedly slurred, incomprehensible in most part. Still able to follow simple commands though.

- No cranial nerve involvement. Normal EOM with no pursuit movement defect.

- Marked weakness 3/5 in both upper extremities and 0/5 in lower extremities with diffuse hypotonia and areflexia. Mute planter response.

- Abnormal movements, choreoathetotic movements in both upper extremities.

- Negative hyperekeplexia


Workup so far:

- MRI brain with contrast on 10/08 - 10/14 and 11/01 unremarkable. No restricted diffusion, no cortical ribboning and no white matter signal abnormality, no significant brain atrophy.

- CT chest, abdomen, pelvis unremarkable

- CSF: 10/09 with 1 WBC - 2 RBC - 60 glucose - 103 protein. 11/02 with 1 WBC - 44 RBC - 58 glucose - 125 protein - 2 OCB (7 CSF and 9 serum) - normal IgG index and synthesis rate - negative meningitis PCR panel

- TSH, ammonia, B12, B1 and electrolytes were all normal

- SPEP with IFA: unremarkable

- B1 53 (mildly decreased -> repleted) - Copper 1.59 (mildly elevated) -

- HIV, HTLV, crypto Ag and PCR negative


More advanced tests:

- Ganglioside panel negative for GQ1b but positive for GD1b (GD1b is associated with Guillain Bare, GQ1b is associated with Bickerstaff encephalitis) 

- Autoimmune encephalopathy panel in CSF and serum negative

- Paraneoplastic panel negative

- Anti MOG negative

- Anti MAG negative

- CSF tau elevated, 14-3-3 came back elevated but CSF RT-QuIC negative

- EEG x2 with one prolonged: negative apart from delta-theta slowing - no PSWC



My working differentials were:

  • Guillan Bare that developed Bickerstaff encephalitis: no pyramidal signs, no cranial nerve involvement, negative GQ1b.
  • Autoimmune encephalopathy: Still possible although ENC1 and ENS1 panels were negative. No response to steroids or PLEX. Normal MRI brain, no seizures.
  • Paraneoplastic encephalopathy: Still possible although CT chest/abdomen/pelvis are negative. Paraneoplastic and autoimmune encephalopathy panel in serum and CSF (which includes paraneoplastic causes as well) negative
  • CJD: that was the diagnosis I was waiting for. MRI and EEG findings are usually negative in the beginning of the disease so I ordered 14-3-3 which came back positive with elevated Tau, however RT-QuIC is negative !!

What do you think?

Any other differentials I should have looked at?

What should we make with the 14-3-3 result with negative Rt-QuIC, may be she needs olfactory mucosa RT-QuIC? but how it is going to change treatment?