KISEP J Korean Neurosurg Soc 35 : 636-638, 2004

Persistent Autonomic Hyperfunction Following

Case Report Hypertensive Intracerebral Hemorrhage
Seung - Joon Lee, M.D.,1 Chun - Kee Chung, M.D. 1, 2
Department of Neurosurgery,1 Clinical Research Institute,2 Seoul National University
College of Medicine, Seoul, Korea

Persistent autonomic hyperfunction is not well-recognized disease entity. Recently the authors experienced one case
following hypertensive intracerebral hemorrhage in the basal ganglia. It was manifested as storms of hypertension,
tachycardia, hyperthermia, severe diaphoresis, hyperventilation and decerebrate posture. Extensive investigations on
infection, pheochromocytoma or status epilepticus revealed no abnormalities. Medications including antibiotics,
antipyretics and antiepileptic agents were administered, but in vain. However, intravenous morphine infusion managed
to stabilize his conditions. To our knowledge, the present case is the first one to be thermographed, and is the second
case next to Rossitch's report of autonomic dysfunction following intracerebral hemorrhage.

KEY WORDS : Autonomic hyperfunction Autonomic dysfunction Diencephalic epilepsy Diencephalic

seizure Hypertensive intracerebral hemorrhage Hypothalamic dysfunction.

Introduction minutes ago du-

ring telephone

S ince Penfield reported a patient having autonomic dysfu-

nction, and termed it as “diencephalic autonomic epilepsy”,
several case reports have discussed this phenomenon5). That
conversation.
He had arbitra-
rily quitted hy-
was not true hypothalamic lesion. However, various tumorous pertensive med-
conditions from thalamic and hypothalamic areas were repo- ications a year
rted3,9,12). In addition, cortical atrophy or diffuse axonal injury ago. He showed
associated with trauma1,2,5,11,14), brain abscess, infarctions, Glasgow Coma
hydrocephalus8,13) or neuroleptic malignant syndrome6) were Scales (GCS) 4,
reported to evoke the same phenomenon. Although modern fixed anisocoric
thermographies are developing, they have been effective in pupils with intact
some clinical situations of neuropathic conditions of complex corneal reflex, Fig. 1. Brain computed tomography showing
regional pain syndrome7) and nociceptive assessment4). negative doll's extensive intracerebral hemorrhage in the right
Therefore we decide to use the thermography for the patient eye phenomenon hemisphere, involving basal ganglia and
thalamus, with intraventricular hemorrhage.
with autonomic dysfunction. On addition, there has been no and decerebrate
case report of using thermography for this kind of syndrome posture with coarse, irregular respiration. Brain computed
except the presented case. Fortunately, the present case is the tomography(CT) revealed a huge intracerebral hemorrhage
second case next to Rossitch's report of autonomic dysfunction (ICH) in the right basal ganglia with subarachnoid hemorrhage
following intracerebral hemorrhage11). and intraventricular hemorrhage(Fig. 1). Transfemoral
cerebral angiography (TFCA) did not prove vascular abnor-
Case Report mality. Emergency craniotomy and hematoma evacuation
were performed.

A 30 year-old man was carried to our hospital emergency

room, because of a sudden loss of consciousness 30
Received：November 8, 2003 Accepted：March 25, 2004
Address for reprints：Chun-Kee Chung, M.D., Department of
Neurosurgery, Seoul National University College of Medicine, 28
Yeongeon-dong, Jongno-gu, Seoul 110-744 Korea
Tel : 02) 760-3701, Fax : 02)744-8459
E-mail : chungc@snu.ac.kr
Immediate postoperative GCS was 6. From postoperative
day 2, simultaneous developments of hypertension, tachypnea,
tachycardia, severe sweating and rigidity, occurred once or
twice per day. Blood pressure rose to 230mmHg, pulse rate to
132 beats per minute, respiration rate to 44 times per minute,
axillary temperature to more than 40 C. Severe diaphoresis
was also noticed. At the same time we observed the severe

636 J Korean Neurosurg Soc 35


signs of leadp-
ipe rigidity, Ch-
eyne-Stokes res-
piration and de-
cerebrate posture
to the extent of
opisthotonus.
Initially, we
tried ketoprofen,
labetalol, hydr-
alazine, for eme-
Fig. 2. Thermography during the autonomic rgent symptoma-
hyperfunction showing increased temperature tic relief, but only
on the left side of the face and the trunk.
individual con-
trols of hypertension or fever were achieved. Among those
symptomatic medications, only nalbuphine, partial morphine
agonist, showed the control of the storms dramatically for
several hours. Therefore, we had nothing but to infuse nalbu-
phine repeatedly for stabilization. Besides, we had to stop
valproate and the other drugs because the transaminases
serum levels rose to more than 700/500. In spite of hematoma
evacuation, with the intracranial pressure (ICP) sustaining
more than 30mmHg, GCS dropped to 3. Since brain CT reve-
aled brain swelling and hydrocephalus, external ventricular
drainage(EVD) was performed. But it was not enough to drop
the increased ICP. Thus we performed the second operation of
right frontal lobectomy on postoperative day 4. Postoperative
GCS was 5 and the increased ICP continued. On the second
postoperative days 2 and 3, as the ICP rose to as high as
43mmHg, the storms became so severe that only continuous
infusion of nalbuphine could relieve it incompletely at most.
Eventually, as the ICP dropped, the dose needed fell, the
serial storms also ameliorated, and his consciousness improved
to obey simple commands with his eyes and his right upper
extremity.
However, they reappeared on the second postoperative day
4 even though the ICP dropped below 20mmHg. At this stage,
we should consider other reasons for these unusual events.
We considered the possibility of coexisting pheochromocytoma,
because he had history of hypertension that had been hard to
control with multiple drugs management, and because he had
sweated excessively, especially whenever he had taken meals.
Thus, we tested for plasma cortisol, urinary catecholamines,
vanillyl mandelic acid, and metanephrine, which are specific
for pheochromocytoma, and performed abdominal CT, but
there was no abnormality. The second possibility was status
epilepticus because we had not given any antiepileptic drug
after the first operation because of elevated liver enzymes.
SJ Lee and CK Chung
The electroencephalography during an attack revealed features
of diffuse cortical dysfunction only, and video-electroence-
phalography resulted in no evidence. Also microbiological
culture studies from blood, sputum, urine and cerebrospinal
fluid and series of chest X-rays had been taken repeatedly, but
they failed to show evidence of infection.
Finally we considered the possibility of autonomic dys-
function four weeks after the second operation. For investi-
gation of abnormal thermoregulation, thermography was taken
during an attack, and it showed hyperthermia, contralateral to
the lesion of ICH (Fig. 2). Whenever every other means failed
to control, intramuscular injections of nalbuphine could expel
all the signs of the irritabilities dramatically. Intramuscular
injection showed more prolonged effect than intravenous
infusion.
Two months after the second operation, we started the more
specific replacement medication mentioned on the litera-
ture11,14), namely, bromocriptine by nasogastric tube and
morphine intravenously, instead of nalbuphine intramuscu-
larly. It took several days for morphine to come into effect. At
first, we gave him 5mg of morphine sulfate intravenously
every 6 hours, and a booster dose of 5mg for any attack
between the intervals. Bromocriptine was used simultaneously
for two weeks, but was stopped for suspected ineffectiveness.
Instead, baclofen was added to the medications for rigidity
control. Once the storms were under control, tapering of daily
dosage of morphine was tried. However, whenever the
taperings were attempted, relapses had occurred. At long last,
morphine was successfully tapered off in 3 months of
tapering, and necessarily with chlorpromazine, diazepam and
bromocriptine. Furthermore, he could take soft bread by
mouth and could express his opinions. His right side hemi-
paresis improved to grade III, but the left side hemiplegia
remained.
Discussion
P ersistent autonomic hyperfunction syndrome is clinical
diagnosis. The term “persistent” autonomic hyperfunction
is more appropriate for the present case, since it did not abort
spontaneously without opioid agonists, and there was no
epileptic abnormality in electroencephalogram in our case,
and there were many reports available without diencephalic
lesions. Because there was no consented diagnostic criteria
for this phenomenon, we arbitrarily defined at least three
findings of these spontaneous and sudden onset of systolic
blood pressure above 200mmHg, pulse rate above 120,
respiration rate over 30, and axillary temperature over 38.5 C
VOLUME 35 June, 2004 637
Persistent Autonomic Hyperfunction
simultaneously as autonomic hyperthermia. Therefore, differ-
ential diagnoses from status epilepticus, pheochromocytoma,
hyperthermia due to neuroleptic malignant syndrome, Cushing
response from increased ICP or hydrocephalus, are mandatory.
For exclusion diagnosis, we need electroencephalogram, abd-
ominal CT, plasma cortisol and valproate level, urinary cate-
cholamines, vanillyl mandelic acid, and metanephrine, which
are specific for pheochromocytoma, microbiological culture
studies from blood, sputum, urine and cerebrospinal fluid, and
series of chest X-rays for concomittent infection. Empirical
medications of antibiotics, antipyretics, and antiepileptic agents
had been administered, but in vain.
The role of imaging studies is complimentary; nevertheless
MRI usually reveals infarcted lesions around the diencephalon.
The authors used thermography to identify the abnormal
thermoregulation, caused by hypothalamic dysfunction.
Because it has been effective in clinical applications in complex
regional pain syndrome7) and nociceptive disorders4). Especially
on complex regional pain syndrome, thermography showed
93% of sensitivity and 89% of specificity7). The present case
showed left side hyperthermia, even though the regulation of
body temperature is known to express bilaterally. We expect
that autonomic dysfunction phenomenon occurs more frequ-
ently than the reported, but to our knowledge, our case is the
first one to be thermographed, and is the second case report of
autonomic dysfunction following intracerebral hemorrhage.
Though Penfield thought this as true diencephalic epilepsy10),
Bullard2) and Rossitch11) described it as autonomic dysfunction,
originating from cortical disinhibition by trauma1,5,14), or from
increased ICP by hydrocephalus8,10), accompanied by hypo-
thalamic fixed lesions.
At first, we use nalbuphine as pain control, not for autonomic
hyperfunction. But, without delay, we noticed the effect of
nalbuphine for those phenomenon. We changed nalbuphine
to morphine for the former was a partial opioid agonist and
could be used as intramuscularily, and the latter was a pure
opioid agonist and could be used as intravenously. Anatomically
wide overlaps of opioid receptor areas with the area of dopa-
minergic system exists, including the tuberoinfundibular, the
mesolimbic, and the nigrostriatal pathway systems throughout
the hypothalamus6).
638 J Korean Neurosurg Soc 35
Conclusion
T his case is the first reported case of persistent autonomic
hyperfuncion that showed contralateral hyperthermia by
thermography, and the second reported case following
intracerebral hemorrhage.
Acknowledgement
This work was supported in part by a grant from Seoul National
University Hospital.
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