25.2 Autoimmune Encephalitis and Acute Autonomic Hyperactivity (03.Q–R)

Why antibody disease and autonomic storms share an ICU bed

The ABPN content specifications split autoimmune encephalitis (03.Q) from acute autonomic hyperactivity (03.R). In the unit they collide: a young woman with anti–N-methyl-D-aspartate (NMDA) receptor encephalitis can hypoventilate and swing from tachycardia to asystole, and a trauma patient with paroxysmal sympathetic hyperactivity (PSH) can look like status epilepticus or septic shock. Treat the immune disease empirically when the syndrome is typical, and treat the autonomic syndrome only after you have excluded the mimics that kill.

Anti-NMDA receptor encephalitis

Anti-NMDA receptor encephalitis is the prototype surface-antibody encephalitis. It preferentially affects children and young women. An ovarian teratoma is the classic tumor in female adolescents and adults; extra-ovarian teratomas and other tumors are less common. HSV encephalitis can trigger later NMDA autoimmunity—do not stop the workup at a negative HSV PCR if a new movement disorder appears weeks later.

The course is stereotyped enough to recognize without the antibody result:

1. Viral-like prodrome
2. Psychiatric change, insomnia, memory loss, and seizures
3. Orofacial dyskinesias, dystonia, catatonia, and decreasing consciousness
4. Autonomic instability (labile blood pressure and heart rate, hypersalivation, hyperthermia) and central hypoventilation requiring ventilation

MRI is often normal or shows only subtle FLAIR change. EEG may show slowing; extreme delta brush is supportive but insensitive. CSF is more sensitive than serum for NMDA-receptor antibodies; send both. Do not wait two weeks for a send-out before treating a typical syndrome.

First-line therapy: high-dose corticosteroids plus IVIG or PLEX, and immediate tumor search. In women of reproductive age that search includes pelvic MRI or transvaginal ultrasound, not a chest radiograph alone. Resect the teratoma as soon as the patient is operable; leaving the tumor in place is associated with poorer and slower recovery. If there is no meaningful improvement, escalate to rituximab and/or cyclophosphamide. Recovery often takes months; autonomic storms and hypoventilation can persist after the movement disorder quiets. Titrate weans slowly and keep a low threshold to re-image the pelvis if the course stalls.

LGI1, CASPR2, and the rest of the panel

Leucine-rich glioma-inactivated 1 (LGI1) antibody disease typically affects older men. The pathognomonic clue is faciobrachial dystonic seizures (FBDS)—brief, frequent, ipsilateral face-and-arm jerks that often precede limbic encephalitis. Hyponatremia is common. Tumor association is low (thymoma is occasional). FBDS often respond to immunotherapy better than to ordinary antiseizure drugs; start immunotherapy rather than stacking three sodium-channel agents.

Contactin-associated protein-like 2 (CASPR2) antibody disease produces neuromyotonia, neuropathic pain, insomnia, and Morvan syndrome (encephalopathy plus peripheral nerve hyperexcitability). Thymoma is more relevant than in LGI1. Stop using voltage-gated potassium channel (VGKC) complex as a diagnosis; a double-negative VGKC radioimmunoassay without LGI1 or CASPR2 is not a reason to immunosuppress.

Other ICU-relevant antibodies:

Treat empirically if suspicion is high. Surface-antibody diseases respond; intracellular-antigen paraneoplastic syndromes respond less. That difference does not justify waiting for the panel in a ventilated, dyskinetic young woman.

Tumor search is age- and syndrome-directed: teratoma for NMDA, chest imaging for Hu and GABA-B, thymoma for CASPR2 and some AMPA, testicular ultrasound for Ma2. 18F-FDG PET is used when CT is unrevealing and the syndrome is paraneoplastic. Repeat the search if the patient plateaus.

Paroxysmal sympathetic hyperactivity after TBI

PSH is a syndrome of simultaneous, paroxysmal increases in sympathetic and motor activity after severe acquired brain injury, most often traumatic brain injury (TBI). A 2014 international consensus defined it as transient, concurrent rises in heart rate, blood pressure, respiratory rate, temperature, sweating, and motor posturing. Episodes are often triggered by suctioning, turning, or pain. Older names (sympathetic storm, diencephalic seizures, autonomic storm) still appear in stems.

Exclude seizure and sepsis first. The same patient can have both PSH and true seizures, ventriculitis, pulmonary embolism, alcohol withdrawal, neuroleptic malignant syndrome, or serotonin syndrome. A normal-appearing EEG during a stereotyped, stimulus-triggered run of tachycardia and diaphoresis supports PSH; a highly rhythmic EEG change supports seizure. Fever workup is still required. Do not start bromocriptine and close the case while an EVD is growing gram-negative rods.

Once mimics are addressed, treatment is conceptual rather than a single mandatory cocktail:

• Reduce triggers: premedicate for suction, treat pain, control fever, minimize unnecessary stimulation.
• Gabapentin (or pregabalin) for prevention of episodes, especially when dystonia is prominent.
• Propranolol as a nonselective beta blocker for tachycardia and hypertension (watch bronchospasm and cardiac failure).
• Morphine as an abortive for an acute storm.
• Bromocriptine as a dopamine agonist adjunct when episodes persist (confusion, nausea, and lowered seizure threshold are tradeoffs).
• Clonidine, dexmedetomidine, baclofen, and benzodiazepines appear in practice algorithms; none is proven in a large randomized trial, so the examination tests the idea of the class, not a secret milligram dose.

The PSH-Assessment Measure (PSH-AM) scores clinical features plus diagnosis likelihood. You do not need to memorize every point value; you do need to know that PSH is a diagnosis of pattern after exclusion.

Autonomic storms in Guillain-Barré syndrome and tetanus

Guillain-Barré syndrome (GBS) dysautonomia produces labile blood pressure, resting tachycardia, ileus, and suction-triggered bradycardia or asystole. Use short-acting vasoactive drugs, continuous telemetry, and avoid long-acting beta blockade you cannot reverse on the next hypotensive swing. This is not PSH; it is peripheral autonomic failure plus instability.

Tetanus produces muscle spasms, trismus, and true sympathetic storms. Management is airway protection, benzodiazepines or magnesium for spasms, metronidazole, human tetanus immunoglobulin, and short-acting control of blood pressure and heart rate. Do not treat tetanus storms as ordinary alcohol withdrawal.

Examination traps

• Waiting for serum-only NMDA antibodies while the patient hypoventilates; CSF is more sensitive.
• Calling LGI1 disease VGKC encephalitis and withholding immunotherapy because the radioimmunoassay is low-titer and double-negative.
• Treating every post-TBI tachycardia-fever cycle as pneumonia without examining for stimulus-triggered PSH—or the reverse, treating PSH while missing ventriculitis.
• Using a long-acting beta blocker as the only therapy for GBS autonomic swings.