Provide supportive therapy, aspiration precautions, and IV hydration.

Withhold oral intake of food, medicine, and fluids during assessment of swallowing ability.

If swallowing is impaired, convert all oral medications and/or nutrition to IV.

Avoid medications that may cause CNS depression.

Under careful monitoring, low doses of lorazepam (0.25–0.5 mg IV q8h) or haloperidol (0.5 mg IV q6h) can be used in patients with agitation.

Obtain an expert consultation in neurology.

Perform funduscopic examination to evaluate papilloedema.

CNS MRI with or without contrast; diagnostic CSF puncture with measurement of the pressure in the CSF; spine MRI (if the patient has focal peripheral neuropathy); and CT scan of the brain (if a CNS MRI cannot be performed) are all options.

The patient should undergo 30 min of EEG examination every day until symptoms disappear if conditions permit; if no seizures are detected on EEG, the patient should be continually prescribed levetiracetam (p.o., 750 mg) q12 h.

If the EEG reveals nonconvulsive status epilepticus, consult a specialist or follow treatment recommendations (assess airway, breathing, and circulation; check blood glucose). The patient should be prescribed levetiracetam and lorazepam; levetiracetam 500 mg IV bolus, as well as maintenance doses of lorazepam 0.5 mg IV, with additional 0.5 mg IV every 5 min, as needed, up to a total of 2 mg to control electrographic seizures. If seizures persist, transfer the patient to the ICU and treat with a phenobarbital loading dose of 60 mg IV. Maintenance doses after resolution of nonconvulsive status epilepticus are as follows: lorazepam (0.5 mg IV q8h for 3 doses); levetiracetam (1,000 mg IV q12h); phenobarbital (30 mg IV q12h).

In the event of concurrent CRS, consider tocilizumab (8 mg/kg, IV) or siltuximab (11 mg/kg, IV).

Continue supportive therapy and neurological evaluation, as described for grade 1 CRES.

In cases of concurrent CRS, strengthen the management of CRS (see above).

Dexamethasone (10 mg, IV, q6h) or methylprednisolone (1 mg/kg, IV, q12h) should be administered if there is no response to anti-IL-6 therapy or no concurrent CRS.

Consider transferring the patient to the ICU if CRES is associated with grade ≥ 2 CRS.

Continue supportive therapy and neurological evaluation as described for grade 1 CRES.

Referral to the ICU is recommended.

Anti-IL-6 therapy is recommended in the case of concurrent CRS, if it has not been administered previously, as described for grade 2 CRS.

In the event that anti-IL-6 therapy does not produce a response, consider glucocorticoids. Corticosteroids are recommended until the CRES resolves to grade 1, and the dose can be gradually decreased in the absence of concurrent CRS.

For CSF pressure 20 mmHg with stage 1 or 2 papilloedema, manage in accordance with the recommendations [acetazolamide 1,000 mg IV, followed by 250–1,000 mg IV q12h (adjust dose on the basis of renal function and acid–base balance, monitored 1 or 2 times daily)].

Consider repeating neuroimaging (CT or MRI) every 2–3 days if the patient continues to experience grade ≥ 3 CRES.

Continue supportive therapy and neurological evaluation as described for grade 1 CRES.

Perform ICU monitoring, taking into account mechanical ventilation.

In the case of grade 3 CRES, provide anti-IL-6 therapy and repeat neuroimaging as described.

Administer high-dose corticosteroids until the CRES resolves to grade 1, then decrease the dose. For example, methylprednisolone (ivgtt, 1 g/day) can be administered for 3 consecutive days, followed by rapid tapering at 250 mg q12h for 2 days, 125 mg q12h for 2 days, and 60 mg q12h for 2 days.

Convulsive status epilepticus should be treated in the department of neurology or as recommended by the physician.

Papilloedema of stage ≥ 3 with CSF pressure ≥ 20 mmHg or brain edema should be treated by the department of neurology or as recommended.