How to manage neurologic emergencies

Strategies for treating status epilepticus, Guillain Barre, more

By Phyllis Maguire - April 2017

Published in the April 2017 issue of Today’s Hospitalist

See what our readers thought on how to treat neurologic emergencies here.

WHEN IT COMES TO neurologic emergencies, hospitalists can expect to find themselves smack
in the middle of them. “You may have to handle an emergency while you wait for the neurologist
to call back or show up,” said neurologist S. Andrew Josephson, MD, who directs the
neurohospitalist program at University of California, San Francisco. “Or you may be in a hospital
where a neurologist isn’t readily available, so you’ll have to manage these problems for an
extensive period.”

In either event, hospitalists need to know what to do in the first few minutes when emergencies
occur, Dr. Josephson told an audience of hospitalists at the UCSF’s management of the
hospitalized patient conference last fall. He spelled out what those initial strategies should be for
emergencies such as status epilepticus and suspected Guillain Barre, cerebellar stroke and
subarachnoid hemorrhage.

Status epilepticus
AN ARTICLE that appeared nearly 20 years ago in the April 2, 1998, issue of the New England
Journal of Medicine (NEJM) set a longstanding definition of status epilepticus. According to that
definition, patients should be considered as having status if they have seized 20 minutes.

“But we don’t go by that anymore, and the definition has

evolved for two reasons,” Dr. Josephson explained. One, the A seizure at one
average generalized convulsion lasts only about a minute and a minute that
half. “If someone is still seizing after two minutes, we now treat responds to 2 mg of
them quickly because we know neuronal damage can occur.” Ativan may be
completely resistant
And perhaps as important, it’s now well-established that the
to 10 mg of Ativan at
longer a seizure continues, the more resistant it is to
10 minutes.”
medication. “A seizure at one minute that responds to 2 mg of
Ativan may be completely resistant to 10 mg of Ativan at 10
minutes,” he pointed out. “We want to get on these patients
very quickly.”

First-line treatment is 2 mg of IV lorazepam every two minutes

for a total of 6 or 8 mg. If patients are still seizing, “we then
give fosphenytoin, not phenytoin.” The problem with phenytoin
through a peripheral IV is infiltrates, “and people can have bad
injuries. While fosphenytoin is more expensive, it’s still likely
cheaper than one phenytoin complication.” Other agents
~ S. Andrew Josephson,
commonly used at this stage are IV valproate and IV MD
levetiracetam, and a large trial is currently comparing these University of California,
San Francisco
agents head-to-head.

While Dr. Josephson doesn’t think doctors should have to

memorize medication doses, here’s one he suggested
physicians should know: The fosphenytoin dose they need to give is 20 mg per kilogram.

“Just about everyone, from the ED on up, gives just one gram, which is under-dosing most
patients,” he noted. “The first thing I usually do in the ED with these patients is give them the rest
of the fosphenytoin they should have gotten.”

First-time event?
But what do you do if the patient continues to seize after the fosphenytoin infusion has stopped?
“You can give more fosphenytoin, but very few of us do,” said Dr. Josephson. “Instead, we go
straight to general anesthesia and intubation.”

While patients are paralyzed, however, they may still be seizing. “They really need to be hooked
up to an EEG to make sure they don’t still have status,” he said. “This is an instance where you
really should consider transferring these patients to an institution that can perform continuous
EEG.”
As for work-up, the key question you need to answer is whether this is a first-time event or
someone with known epilepsy. For a first-time seizure, “we do a very extensive work-up, taking a
careful history of the spell and what was happening beforehand.” That work-up also includes
finding out what medications the patient is on and a careful neurologic exam.

“If a patient has any focal signs—weakness or numbness on one side, or if there is any focality to
the seizure such as it started on one side and then spread—then this is a focal seizure,” he noted.
That means the patient has a focal lesion in the brain, which indicates a mass or tumor until
proven otherwise. “Patients require a fair amount of neuro-imaging to work that up.”

For first-time seizures, Dr. Josephson also asks about head trauma, and he performs a utox
looking for cocaine and amphetamines, as well as an alcohol history, CBC, and lytes. The
electrolytes most likely to lead to seizures are low sodium, low magnesium, low calcium and low
glucose, as well as high calcium. “Make sure you send a Ca/Mg/Phos on all these folks,” he said.

Everyone also receives imaging, typically a CT with contrast. Plus, Dr. Josephson said he has “an
incredibly low threshold to lumbar puncture with someone with an unexplained first-time seizure,
given the incidence of meningitis and encephalitis.”

While patients also need an outpatient work-up including an EEG, MRI and neurologic consult, Dr.
Josephson said he rarely prescribes an anti-convulsive to patients after a single unprovoked first-
time seizure.

Known epilepsy
For patients with known epilepsy, the work-up is much simpler because these patients seize for
generally only one of two reasons, said Dr. Josephson.

One, something is going on with their medications: Patients may not be taking them, or they may
have started taking another drug, such as an antibiotic, that’s interacting with their anti-
epileptics. “We send levels, if possible.”

Or patients have a systemic infection such as a UTI, pneumonia or sepsis. “Even a mild viral
infection can lower the seizure threshold, so we spend a fair amount of time culturing these
people,” Dr. Josephson said. With these patients, it is important to speak with their primary
neurologist before changing any anti-epileptic drug regimen.

One new treatment option for status that may be on the horizon comes from the RAMPART
trial published in the Feb. 16, 2012, issue of NEJM. In that study, ambulances around the country
were randomized to treat seizing patients with either IV lorazepam or intramuscular midazolam
delivered in an auto-injector slapped in their thigh.

“That’s attractive if you’ve ever had to try getting an IV started in someone with status,” said Dr.
Josephson. “Plus, the IM midazolam was superior in terms of the absence of seizures when
patients arrived at the ED.”

One final pearl: Patients with an episode of status in the hospital should leave with status rescue
medications, typically a benzodiazepine, and their family members need to know how to
administer those.

Guillain Barre
GUILLAIN BARRE is now back in the news because of its strong association with the Zika virus.
“We’re not really sure what raises someone’s risk of Guilllain Barre as a response to Zika,” said Dr.
Josephson. “It may be more common in patients who are immunosuppressed.”

While Guillain Barre is still uncommon, hospitalists should consider it whenever patients show up
with numbness and weakness. And when patients have generalized weakness in all four limbs, it’s
imperative to order some cheap bedside pulmonary tests, including forced vital capacity (FVC)
(how much can they can blow out), as well as mean inspiratory force (MIF), or how much patients
can breathe in and expand their chest wall.

He presented the case of a patient who had an FVC of 1.2 liters and a MIF of minus 30. “This is
someone with pending ventilatory collapse who could die on you quickly,” he pointed out. And
because the patient is having a ventilatory problem, “you will not see it on the sat monitor.”

Another diagnostic clue: Protein is usually elevated in the cerebrospinal fluid after lumbar
puncture, “but early in the disease, it may not follow the rules,” he noted. Further, “the weakness
is not always ascending, like you read about in textbooks.”

While you always hear about areflexia with Guillain Barre, “hospitalists are seeing this early in the
course, so reflexes may still be present,” he added. “Then, patients quickly lose their reflexes.”
And only 30% of patients have some preceding illness such as campylobacter. “We can make the
diagnosis with electromyography, but usually it’s made clinically.”

What will kill the patient?

As for treatment, “You need to figure out what’s going to kill the patient,” Dr. Josephson said.
Because many could die of respiratory failure, patients need to be intubated early when their FVC
is less than 20 ccs per kilogram. If they aren’t intubated, patients need to be in the ICU or step-
down unit with serial MIFs and FVCs every six hours.

“If it’s getting worse,” he noted, “it’s time to intubate.”

Because a lot of these patients can die of thromboembolic disease, they receive subcutaneous
heparin. That affects not only the somatic nerves, but also the autonomic nerves.
“They can get ileus and cardiac arrhythmias, so we’re very careful to monitor these folks.”
Treatment is either IVIG, which is more convenient, or plasmapheresis, and “the earlier, the
better.” Treatment does not include corticosteroids.

Cerebellar stroke
IF YOU’RE CONDUCTING the finger-nose-finger portion of the neurologic exam and someone is
bad on both sides, “it is typically a metabolic or toxic issue,” said Dr. Josephson.

But if patients exhibit any asymmetry in the cerebellar exam, “that’s a real red flag. That’s a
cerebellar lesion until proven otherwise.” (When doing the exam, make sure you put the target far
enough out. “Dysmetria on finger-nose-finger is brought on only when patients extend completely
at the elbow.”)

As Dr. Josephson reminded the audience, the two types of vertigo are central and peripheral, and
95% of cases are peripheral. “It’s the 5% that worries us,” he said. Textbooks repeatedly list
factors—like severe vomiting, an inability to walk or sit without falling to one side, and nystagmus
—that the authors claim definitively indicate central vertigo. But all of those symptoms, he noted,
can be present in both central and peripheral forms of vertigo.

If you suspect a cerebellar ischemic stroke because of asymmetry on the cerebellar exam or
problems with cranial nerves, he said, “an MRI is probably required after a negative CT.”

When patients are having a cerebellar stroke or another process that raises their intracranial
pressure (ICP), how do you manage them? First, sit them up. “That helps venous return and it
lowers the ICP.”

You can also hyperventilate intubated patients, “but that works for only a very short time.” The
mainstay of treatment is quick osmotic agents, “and that’s generally mannitol,” Dr. Josephson
said. Neurosurgeons may want to place a ventriculostomy to drain the cerebrospinal fluid or
remove the back of the skull for decompression.

Medically, what really matters is managing the CPP, or cerebral perfusion pressure. “The CPP is
equal to the mean arterial pressure minus the ICP,” he noted. “In someone who’s herniating, it’s
typically very important to not drop their blood pressure.”

Subarachnoid hemorrhage
WHEN PATIENTS COME in with what they claim is the worst headache of their life, “the severity of
pain doesn’t really distinguish malignant from benign conditions,” said Dr. Josephson. What is
important is finding out how long it took the headache after onset to reach its most severe pain
level.
If it built over an hour or two, that could be a migraine or even meningitis. But “if the answer is
seconds or a few minutes, that’s a subarachnoid hemorrhage, no matter how severe or mild the
pain.” Patients with subarachnoid hemorrhages may have only modest pain, he pointed out, “but
they still have this incredibly characteristic sudden onset of headache.”

As for diagnosis, “CT is good early, LP is good late.” If the CT is negative but you suspect
subarachnoid hemorrhage, you must perform an LP. What you’re looking for depends on how
much time has passed since the headache began.

“Within the first six or eight hours, you will not see xanthochromia, so you’re looking for blood
that fails to clear,” Dr. Josephson said.

After eight or 12 hours, however, and lasting for up to two weeks, “you have to see
xanthochromia. If a patient in the ED complains of a sudden onset headache five days ago and
there’s no xantho when he gets tapped, it’s likely not a subarachnoid hemorrhage.”

As for treatment, “it’s very important to bring the blood pressure down quickly to less than 140,”
he said. Etiology is either an aneurysm, “which needs to be secured quickly,” or trauma.

Phyllis Maguire is Executive Editor of Today’s Hospitalist.