new onset refractory epilepticus and chronic pachymeningite

Hello, I'm a resident un Neurology (in the epilepsy departement). I have a rather interesting case in my ward that i can't really wrap my head around, despite discussing it with with my collegues from general neurology and stroke and i would appreciate some input from the outside! I try to be not too specific because i dont want the patient to be easily identified.

Basically it's a 70ish female that was admitted after several focal secondarily generalised epileptic seizures last week. She had no history of seizures but she was known for having type 1 neurofibromatosis complicated by a voluminous T10 meningocele.

She also suffered from chronic vertigo and chronic headaches that led to the discovery of a pachymeningite at the beggining of 2022 as well as diffuse subarachnoidal bleeding with a predominantly posterior distribution. At the time a diagnosis of likely chronic cerebrospinal fluid hypotension was made, possibly linked to the meningocele but it was elected not to do surgery. No LP was done.

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Fast forward to today: she has refractory left temporal status epilepticus, with several lines of treatment initiated ( we used benzo levetiracetam, lacosamid, valproate, topiramate ..), we are doing our best to treat it symptomatically so it's not really my issue here.

My problem is for the etiology of this NORSE (new onset refractory status epilepticus): we've done 2 lumbar punctures with negative PCR for the most common bacterial agents ( listeria, e.coli, strepto pneumo / agalactiae, neisseria meningitis, haemophilis, cryptococus) as well as viral agents (HSV1-2 obivously, CMV enterovius, VZV.. ). Cultures are ongoing and we have no evidence of BK so far on the direct examination.

The most stricking thing we got was that the 2 LP that we did were clearly pinked colored, and contaminated by peripheric blood despite the LP being non traumatic. Cyto was no usable because of the blood contamination.

We were unable to obtain a cell count on the first LP because of the blood, but on the 2nd one we only had 8 WBC/mm3. First LP we have a 1,2 g/l protein count, 0,53g/l on the second one.

We've done 2 MRI that show a non specific left temporal hypersignal with a Pulvinar sign that is compatible with post ictal imaging or encephalitis. We see no sign of active subarachnoidal bleeding and there is not vascular abnormality but we still see the hemosiderosis with a posterior predominance

So if i have to summarize as far as our diagnosic hypothesis go we have:

- infectious causes: we can rule out HSV1-2 encepahlitis so we stopped acyclovir. PCR for other common virus was negative, we asked to search for tick born encephalitis, EBV and several other virus. Listeria was ruled out as well so we stopped amoxicilline. Meningeal tuberculosis is highly unlikely as the patient has never traveled outside of europe, the LP is normal and the specific assat (Quanttiferon) is neg so we can probably rule out tuberculousis.

- metabolic causes: we have no obvious metabolic abnormalities that would be pro epileptogenic

- iatrogenic causes: she has no medication prior to the hospitalisation

- paraneoplasic causes: TAP scanner wass normal apart from a segmentary distal PE (that is tricky to treat with the SHA...), small bilteral pleural effusion and peritoneal effusion. We asked for a PET scanner. Search for paraneoplasicc encephalitis is ongoing in the blood and LP is ongoing

- inflammatory causes: we have no history or clinical sign that would lead to an auto-inflammatory disorder. No white matter anomalies on the MRI. ANCA was negative, antiphospholipid antibodies as well. Search for Igg4 and MOG is on going given the pachymeningite, but it seems highly unlikely.

- neurodegenerative: creutzfeldt jakob seems unlikely with the very acute onset

I think thats pretty much it, i really dont understand why the LP is hemoragic, i've even done an MRI of the meningocele because i found a case report of an intra-meningocoele ruptured aneurysm in a NF1 patient, but it showved noting spectaular.

Do you see anything obvious that i might have missed?

My apopologies if i translated things incorrectly, i'mn not very familiar with some medical terms in english.