Practical Pain Management - Traumatic Brain Injury Treatment of Post-Traumatic Headaches - 2013-06-17

Traumatic Brain Injury: Treatment of Post-traumatic Headaches
Published on Practical Pain Management (http://www.practicalpainmanagement.com)

Traumatic Brain Injury: Treatment of Post-traumatic
Headaches
Part 1 of this series described the biomechanics and pathophysiology of traumatic brain injuries, as
well as their symptoms: post-concussion syndrome, post-traumatic headache, and migraine. This
month, our author tackles treatment of TBI headaches.
By John Claude Krusz, PhD, MD [1]

Volume 13, Issue #5
Increased attention to traumatic brain injury (TBI) has raised renewed interest in one of its
consequencespost-traumatic headaches (PTH). Most often these have the characteristics of migraines,
migrainous headaches, and mixed tension-type headaches (TTH) and migraines, as was discussed in
Part 1 of this series.
1
There have been a number of recent articles in medical journals that have
renewed the debate about TBI, including an article by Robbins and Conidi on sports-related injuries.
According to Seifert, there are approximately 3.8 million sports-related concussions occurring each year,
providing unique treatment challenges for medical personnel.
3
The presence of new onset or persistent
headache following an injury often complicates return-to-play decisions.
The second part of this series specifically addresses the treatment of PTH and does not claim to be
comprehensive. It consists of three parts: Acute treatment of post-TBI headaches using migraine-
specific therapy, prophylactic therapy to suppress post-TBI headaches, and interventional treatments
used in our outpatient headache clinic.
Acute Therapy
Quite frankly, the "classic" migraine-specific abortive medications used for treatment of acute migraines
and migrainous headachesfor example, dihydroergotamine (DHE-45) and triptansare FDA indicated
for moderate to severe migraines. A reformulated diclofenac potassium preparation (Cambia), with very
rapid absorption kinetics, is also FDA indicated for mild to moderate migraine. The spectrum of abortive
medications is covered extremely well in some of the comprehensive textbooks about headaches and
migraines, including the role of opioids.
4-6
A selective list of FDA-approved agents are highlighted in
Table 1.
Page 1 of 18
[2]
Page 2 of 18
[3]
Migraine-specific abortive therapy centers on the triptan family of compounds. Theses agents primarily
decrease neural activity in trigeminovascular afferent nerves that are sending signals from dural nerve
endings to the trigeminal nucleus caudalis in the brainstem. They also have vasoconstrictive properties
on blood vessels in this system, but the main effect is on neural firing. Triptans act specifically on
serotonin (5HT)-1B and 1D receptors. They should be used for disabling migraines that are moderate to
severe in intensity. If migraines are present >2 to 3 times per week, it may be wise to consider a
suppressive or prophylactic medication (see next section).
Triptans can be used in conjunction with antiemetics (metoclopramide [Reglan], ondansetron [Zofran],
promethazine [Phenergan], etc), and perhaps anti-inflammatory compounds. They are indicated for
moderate to severe migraines, but early intervention in the migraine process is always desirable. Some
of the triptans are available in faster delivery systems like injectable and nasal spray.
Nausea should always be treated alongside the migraine. Our preference is for the prescription of the
more potent antiemetics, including ondansetron or metoclopramide. In the author's practice, we
successfully have used these, as well as droperidol intravenously (IV) in the clinic (in small doses).
Preventative Therapy
When TBI migraines become disabling to one's lifestyle and occur more frequently than 3 times per
Page 3 of 18
week despite successful treatment with triptans or other migraine-specific therapies, it may be time to
think about suppressive or prophylactic therapy. Only four medications are FDA approved for this
indication: topiramate (Topamax), valproate sodium, propranolol, and timolol (the last of which is
available as an optic solution primarily, and is very hard to find in tablet form). In addition, Botox is
currently the only medication approved for prophylactic treatment of chronic migraine (Table 2).
[4]
The first two medications were originally approved as anticonvulsants, but were found to be effective in
managing migraine, chronic daily headaches, and cluster headaches. Sedation and cognitive side
effects, such as confusion or memory problems, however, may limit the use of topiramate. Valproate
sodium has been a popular migraine preventive. The agent is usually well tolerated in the lower doses
used for headaches; however, the FDA recently issued a warning that valproate sodium can cause
decreased IQ scores in children whose mothers took the medication during pregnancy. The agency now
reports that these agents are contraindicated in pregnant women for the prevention of migraine
headaches.
7
The -blocker propranolol is often tried as initial prophylaxis therapy. Originally, it was
noted serendipitously to help migraine headaches when it was being used for management of blood
pressure and cardiac rhythm disorders.
When we think of preventative therapy, it is wise to think about co-morbid post-concussion symptoms.
This might include anxiety, depression, bipolar-like symptoms, seizures, high blood pressure, irritability,
poor sleep, and mood swings. Besides these FDA-approved medications, virtually all of the
anticonvulsants (we much prefer the phrase "neuronal stabilizing agents") have been tried in small
trials, which are usually open label in nature. For example, the author published the first data on
migraine and neuropathic pain management treated with oxcarbazepine, levetiracetam, and
zonisamide
8-10
soon after they were officially released as seizure medications. Other agents in this large
group were also studied for migraines, chronic daily headaches, and neuropathic pain by the same
Page 4 of 18
author.
11
Unfortunately, in the vast majority of these studies the industry chose not to study the
medication formally in a double-blind, placebo-controlled fashion.
Similarly, many agents that are approved for other uses have been used off-label for their abilities to
help migraine patterns. Post-TBI migraines, when accompanied by cognitive difficulties, have been
shown to respond to the treatment memantine (Namenda), officially on the market only for
management of dementia.
12,13
However, many studies, primarily from Europe, have used this agent for
various pain conditions off label, and we have used it as an agent to help with cognition after TBI.
14
Antidepressants, particularly the serotonin-norepinephrine reuptake inhibitors, can help depression and
anxiety, but they can also reduce pain and migraines post-TBI. The author has used venlafaxine
(Effexor), duloxetine (Cymbalta), and milnacipran (Savella) off-label in his clinical practice. Medication in
other categories (so-called antipsychotic agents) have also been used to suppress migraines (eg,
ziprasidone) and can be very useful in post-concussion headaches accompanied by irritability, mood
instability, and sleep disorders.
15
The bottom line on preventative therapy for post-TBI headaches and migraines is to look for
comorbidities that are present along with the headaches and to treat with an agent that can reduce the
migraine frequency and severity and the comorbid clinical state. Off-label use of medication is perfectly
legitimate as long as the clinician explains that to the patient. We always have a patient acknowledge
this for any treatment, oral or IV, and document this in their chart and on paper.
Interventions for Refractory Migraines
Headaches and migraines that occur after a TBI can be treated in any number of ways by healthcare
practitioners. This part of the article attempts to describe more aggressive and definitive treatments
available in the outpatient headache clinic setting.
The author's clinic compiled a track record in treating refractory headache and pain patients using IV
medication therapy. More than 95% of our clinic patients fared exceedingly well as far as their headache
and pain symptoms were concerned.
1
6 We arbitrarily defined success as a greater than 50% reduction
in the headache, based on a 0 out of 10 visual analog scale (VAS) from baseline. Very few of the
patients had to be retreated. This suggested that we were not only clinically efficient but, on a cost
basis, an aggressive clinic treatment of headache was less expensive than treatment in the emergency
department (ED) as well. It has been estimated that the direct medical costs and indirect costs, such as
lost productivity, of TBI totaled an estimated $76.5 billion in the United States in 2000.
17,18
In my opinion, the ideal headache clinic would offer a large number of IV services and be staffed by
nurses trained in IV therapy and monitoring with pulse oximetry. I strongly suggest that advanced
cardiovascular life supporttrained staff and a crash cart with oxygen and medications are in the clinic
treatment area.
I have listed all of the IV treatments to be described in the following sections in Table 3, which are based
on my clinical experience.
Page 5 of 18
[5]
[6]
Page 6 of 18
Suggested IV Interventions
MgSO
4
In many ways, IV magnesium sulfate (MgSO
4
) is sort of an "opening shot" for intractable headaches,
both TBI migraines and not. It can be given alone, or combined with either antiemetics or IV
corticosteroids. There is substantial literature on the use of IV magnesium for migraines and cluster
headaches.
19-22
The original studies by Mauskop and colleagues studied ion-sensitive Mg++ electrodes
to measure ionized magnesium, a technique not commonly available. Magnesium has primary effects as
a physiologic antagonist to calcium. It also blocks N-methyl-D-aspartic acid (NMDA)type glutamate
excitatory amino acid activity, and nitric oxide synthesis and releaseall of which are factors in
migraine pathophysiology or maintenance. In addition, magnesium augments serotonin, which may be a
direct means of blocking migraines. Multiple types of headaches, including migraines, migrainous
headaches, TTH, and cluster headaches responded to IV magnesium therapy.
19
The headache sufferers
with the best and longest response to this treatment also had the lowest ionized Mg++ levels, both for
migraines as well as for cluster headaches.
20
One study has summarized clinical data with IV MgSO
4
using doses of 0.5 to 1 g.
23
In general, the author uses higher doses than that, and typically uses 2.5 to
3 g.
21,22
Antiemetics
Antiemetics have been used along with acute opioid therapy for headaches and for pain treatment. This
is based on the notion that the use of both agents was somehow synergistic. Animal experiments
seemed to support this idea, but human studies are not at all conclusive on this point.
24
I've looked for
evidence of this, but it is almost non-existent; nausea is a prominent symptom accompanying
headache. Nevertheless, traditional ED treatment of headaches often uses a combination of opioids and
antiemetics. In the past, promethazine was the most frequently used antiemetic.
25
However, our
preference is to use either ondansetron or metoclopramide, both IV and intramuscular (IM), as a firstline
antiemetic in the clinic. This is based on a study of 202 migraine patients. The study found that IV
metoclopramide 20 mg was more effective than sumatriptan 6 mg subcutaneously at reducing pain
intensity scores (reduction of 7.2 vs 6.2, respectively) and pain-free rates (59% vs 35%, respectively).
26
There is a growing body of evidence that a blockade of central dopamine receptor systems can enhance
anti-nociception or the pain-relieving analgesic properties of opioids.
27-29
One study of neuropathic pain
suggested that bupropion might decrease neuropathic pain via an effect on presynaptic reuptake of
dopamine.
30
These properties might explain the ability of dopamine blockers, like metoclopramide or
droperidol, to reduce migraine headachesan effect we and others have noted in the clinic setting in
the treatment of migraines.
One of the initial studies using IV droperidol used quite high doses (mean 16.6 mg) and reported nearly
all of their patients being sedated and more than 50% having extrapyramidal symptoms 24 hours after
treatment.
31
We repeated the study in our clinic using from one fifth to one quarter of the dose of IV
droperidol with only 3% side effects and well over 50% success rate in reducing or eliminating refractory
migraines.
32
A double-blind trial of IM droperidol,
33
again using high doses of the medication, showed
efficacy; the placebo response rate was 57% vs 84% for droperidol. Once again, anxiety, akathisia, and
somnolence were rated as severe in 30% of patients, presumably due to the high doses employed.
Thus, keeping doses quite low (around 2 mg total) can be very effective and I have quite a number of
patients who use IM droperidol at home as rescue medication for their migraineseither with migraine-
specific therapy or to avoid a trip to the ED. The starting dose is 0.625 mg of IM droperidol, repeated
after 20 to 30 minutes, and once again if needed.
An older ED study using IM prochlorperazine compared with metoclopramide found the former to be
more reliable in reducing headache to the endpoint of the study (1 hour). Yet both groups required
additional rescue treatment with analgesics (57%-79%) after initial treatment with an antiemetic.
34
Another ED study compared the efficacy of IV MgSO
4
with prochlorperazine in acute headache patients.
Page 7 of 18
This small study (36 patients) found prochlorperazine to be statistically more effective at reducing pain
than magnesium (90% vs 56%, respectively) with fewer side effects.
35
One comment is that the dose of
the MgSO
4
was rather low at 1 g compared to our clinic IV doses of 2 g or greater.
Ondansetron, a 5-hydroxytriptamine type 3 receptor antagonist, is a very powerful antiemetic often
used in the management of chemotherapy-induced nausea and vomiting. The agent has been used
successfully in the clinical setting as an adjunctive medication for intractable vomiting associated with
prolonged migraines (dosage: 2-4 mg IV). A search of the literature surprisingly revealed very little data
to support its use in the treatment of acute or refractory migraines. Indeed, one small study involving 6
children described the development of severe daily migraine-like headaches during cancer treatment.
36
All patients had received daily doses of ondansetron and had a personal or family history of migraines,
which may have placed them at risk of developing ondansetron-associated migraine-type headaches.
The authors noted that all the children responded to stopping the medication and starting treatment
with standard anti-migraine therapy.
Corticosteroids
There is very little literature on the use of corticosteroids to treat migraines. More data are available for
the treatment of cluster headaches, status migrainosus, or analgesic rebound headaches.
37
We
frequently use dexamethasone (2-4 mg every 8-12 hours, as needed) for severe, refractory migraines
along with IV MgSO
4
. Both agents are compatible in the same IV bag (unpublished observations). Other
authors have published results from their own clinics, showing that dexamethasone was indeed
effective in their migraine and status migraine populations.
38,39
This is not necessarily followed by an
oral taper. Long-term use of steroids has its own side effect profile.
Dihydroergotamine
Before triptans, the gold standard for treating intractable migraines was DHE, a compound similar to,
but pharmacologically very different from, ergotamine. Many people forget that the pharmacologic
profile of DHE is predominantly that of a venoconstrictor, as well as a relatively mild arterial constrictor.
Ergotamine is a pure arterial vasoconstrictor. Also, ergotamine is fraught with the possibility of rebound
migraines and headaches (now termed "medication overuse headache"), whereas DHE does not have
this property. DHE can be given IV or IM and has a 10- to 14-hour half-life. The original IV DHE protocol
to treat refractory migraine headaches was introduced in 1986 by Professor Raskin and it became the
mainstay of inpatient and in-clinic treatments.
40
Typically, DHE (1 mg) is given every 8 hours with IV
metoclopramide 10 mg for 2 to 3 days. Comparisons of this protocol against "typical" treatment with
meperidine (75 mg) and promethazine (25 mg) showed similar efficacy with significantly fewer side
effects in the DHE/metoclopramide group,
41
making it very useful for office-based treatment of
migraines. Another small study evaluated the same protocol in a headache clinic against IV ketorolac
and found the DHE protocol to result in a greater degree of pain improvement (P=0.31) and better
function clinically (P=0.057).
42
Various IV protocols available for clinic use were subsequently
summarized by the same author.
43
Valproate
Divalproex sodium (Depakote), as an enteric-coated preparation, was approved in 1994 for oral use in
the prophylaxis of migraines in the United States. It was the first anticonvulsant molecule to be found
useful in treating migraines in a prophylactic manner.
44-46
An IV version of valproate sodium (Depacon)
was developed and was used for treatment of seizures. In our search for additional IV agents to use in
the clinic for intractable migraines, we turned to this compound and presented an initial open-label
study in poster form.
47
Our results showed an impressive reduction in migraine severity, both in this
initial trial and in subsequent studies. Soon thereafter, other open-label studies, including our own,
began to show up in the literature
48-50
documenting efficacy of valproate sodium IV in treating
migraines.
Page 8 of 18
Our study included 85 intractable migraineurs. We reported an 88% reduction in severity of migraine,
based on patient-rated VAS, in the IV valproate sodium group. The average dose of valproate was 720
mg, given IV over about 50 minutes (100-200 mg every 5-10 minutes).
47
Another study investigated the
use of valproate sodium (loading dose 15 mg/kg, followed by 5 mg/kg every 8 hours) in initial treatment
of chronic daily headache, transformed migraine, and analgesic overuse headaches.
51
The authors
stated that headache improvement was reported by 80% of the patients treated with IV valproate
sodium, especially if other agents were not effective.
A third study, however, found that valproate sodium was significantly less useful than prochlorperazine
(Compazine) in the ED for headache pain (9 mm vs 64.5 mm, respectively) and nausea symptoms (35.5
mm vs 2 mm, P<0.001).
52
A different study treated mostly chronic daily headaches, chronic TTH, and
unclassifiable chronic headaches (67%), with just over 30% episodic migraines. More than half of the
patients (57%) responded to valproate sodium treatment and the lower efficacy may be due to the
nature of the chronic headache population treated in this study.
53
We went over our initial study data and extracted 23 cases of bona fide status migrainosus from our
initial published study sample treated with IV valproate sodium in the headache clinic.
50
This very
difficult-to-treat migraine population responded similarly as the refractory migraineurs, but needed a
higher dose of valproate sodium (1,017 mg) and a longer treatment time (73 min vs 50 min). Thirteen of
the 23 patients (57%) rated their migraines as 0 out of 10 in severity after treatment.
54
Propofol
Sometimes, interesting results are stumbled upon serendipitously, as occurred in the case of the pre-
anesthetic agent propofol. We have used this agent routinely in the clinic as a mild sedative prior to
epidural steroid and facet nerve blocks in a conscious sedation manner. It was noted that some patients
who had migraines at the time of their blocks would comment on eradication of the migraine before the
block was performed, but after propofol was given. After researching the literature, we found no
mention of this agent in the treatment of migraines. We undertook a formal open-label study in the
headache clinic to treat refractory migraines unresponsive to usual abortive approaches. A cohort of 77
patients were treated and the results were dramatic.
55
Propofol was the most effective IV agent that we
had ever employed, with a 95% success rate in reducing ongoing migraine headaches. The total dose
(subanesthetic) was only 120 mg, given slowly by IV push 20 mg at a time. The specific pharmacologic
effect of propofol, with sole effects on subtypes of the gamma-aminobutyric acid type A (GABA-A)
receptor, is a unique mechanism of action. It caused speculation as to the role this receptor might play
in migraines. Since then, topiramate (Topamax) has been approved for migraine prophylaxis and one of
its mechanisms of action is on GABA-A receptors. We have also anecdotally looked at small numbers of
patients with painful disorders like trigeminal neuralgia, complex regional pain syndrome (CRPS), and
other pain flare-ups and they seem to also respond to propofol (unpublished data).
Lidocaine
Lidocaine is an indiscriminate blocker of sodium (Na+) channels. Blockade of this system has definite
implications for reducing neuropathic pain disorders. Many of the neuronal stabilizing agents include
this mechanism of action. All of the same agents have also been shown, at least in open-label trials, to
reduce migraines and other headaches.
56
I have used IV lidocaine, with pulse oximetry monitoring, in the clinic for many years for the treatment
of migraine, headache, and pain flare-ups. The paradigm is to treat very slowly, so as to saturate the
Na+ channels and obtain the best possible blockade. Often, the response is short-lived (12-48 h), which
buys time for other treatments to be put in place. Formal trials of IV lidocaine to treat acute migraine
headache were published some time ago. Two studies found poorer outcome in the lidocaine-treated
patients than with DHE, chlorpromazine treatment IV,
57
or against placebo.
58
The response to IV
lidocaine was better in chronic daily headache in two retrospective studies.
59,60
We have re-explored IV
Page 9 of 18
lidocaine for treatment of refractory migraines and have shown some promising data.
61,62
However, this
was an off-label use of lidocaine and, due to its ability to block neuropathic pain, it may play a roll in the
treatment of refractory migraine post TBI. More studies are in progress.
Ketamine
Some headache and pain physicians think that neuropathic pain, chronic daily headaches, and
migraines are, underneath it all, very similar in their biochemical underpinnings with respect to cellular
mechanisms. The fields of pain and headache management use common terminologies to describe
these processes. Nociceptive pain, peripheral and central sensitization, windup, long-term potentiation,
and neuroplasticity are concepts basic to the expression and maintenance of these disorders. Common
neurocellular and neurotransmitter pathways may explain the clinical expression of both neuropathic
pain and migraine and associated hyperalgesia and central sensitization.
63
On the treatment side of
things, why is it that medications with completely different structures but similar mechanisms of action
(propofol and topiramate, each of which act on GABA-A receptors) both reduce migraines, other
headaches, and pain?
Considering the evidence that excitatory amino acids like glutamate are the "bad guys" in promoting
nociception in generaland hyperalgesia and possibly allodyniait is not surprising that agents, which
antagonize this system might have utility in reducing pain and headache symptoms. Compounds that
block the NMDA sub-family of glutamate receptors either have low potency (dextromethorphan or
memantine) or they have higher potency and a narrow therapeutic index (ketamine).
64
Ketamine, an agent specifically active against NMDA-type glutamate receptors in subanesthetic doses,
has been little studied thus far, but may have theoretical implications for preventing chronic migraines.
One study administered ketamine intranasally to migraine patients who had pronounced and disabling
aura. Fewer than 50% had successful resolution with ketamine.
65
In this study the dose of ketamine was
low, but more work needs to be done with this specific blocker of NMDA glutamate receptor subtypes. A
poster described increased cerebrospinal fluid glutamate levels in chronic migraineurs compared to non-
migraine controls.
66
Patients with migraines and fibromyalgia had higher levels than patients without
chronic pain.
Glutamate, with its subtypes of receptor families, will be an active area of research and, hopefully,
treatment. As we have used IV ketamine in the clinic for more than 12 years, we have presented our
data for IV ketamine for treating refractory headaches and pain several times.
67,68
This is an ongoing
study, which includes post-TBI migraines and headaches (with and without pain) and may be the largest
database for migraine, cluster, chronic daily headache, and rare subtypes like paroxysmal hemicrania,
hemicrania continua, and trigeminal neuralgia with migraines.
69,70
Levetiracetam
Clinical data with the oral form of this neuronal stabilizing agent were the first available anywhere in the
treatment of refractory migraine headaches,
71
and this agent has a unique mechanism of action that
effectively blocks high-voltage calcium channelsanother major activity of many neuronal stabilizing
agents.
We developed an IV form of the same agent (with a compounding pharmacy) and evaluated
levetiracetam IV in the treatment of refractory migraines. Cluster headache flare-ups and pain flare-ups
like trigeminal neuralgia and CRPS have also been treated in the clinic.
72,73
This is a powerful, non-toxic
form of treatment for many difficult pain and headache flare-ups. The manufacturer subsequently
released an IV preparation for commercial use to treat only seizures, but our data preceded that
formulation by several years. It is important to note that the author uses this preparation only in
extremely refractory cases and very infrequently.
Page 10 of 18
Opioids: Tramadol
Tramadol has been available in the United States for a number of years and has been used in Europe for
more than 30 years. About 2 billion people worldwide have been treated for pain with this agent, which
is a opioid receptor agonist, as well as weak presynaptic reuptake inhibition of norepinephrine and
serotonin (like venlafaxine, duloxetine, or milnacipran).
I formulated a sterile IV preparation to treat headaches and pain. An IV form is available in Europe. I had
originally published data with the oral form of the medication in treating headaches
74
and was
impressed by its ability to treat chronic headaches and migraines. The IV preparation of tramadol turned
out to be very efficacious, very well tolerated, rapidly treated refractory migraines and mixed
headaches, and gave me another tool to use in the clinic when other agents failed.
75
Our most recent
accumulated data were presented this year. In our study, we treated 79 patients with IV tramadol. The
average dose was 423 mg (range: 250-1,100 mg), given over 95 minutes in our clinic. The results
showed an average reduction in pain severity after treatment from 7.46 on the visual analogue scale
(VAS) to 2.81 (P<.001).
76
Methocarbamol
Although methocarbamol is an older muscle relaxant preparation with uncertain pharmacologic
mechanism(s) of action, it is one of the very few available in an IV form and, for this reason, I sometimes
use it in the clinic to treat migraines and other headachesespecially if accompanied by a lot of neck
spasms. I know of no published studies looking at this medication in this setting. Therefore, all my
information is anecdotal and I rarely use it alone but, instead, often use it after other agents. I have had
about 200 patients over the last 15 years for whom the addition of methocarbamol (range: 300-500 mg)
was a positive element in their overall headache relief.
Baclofen
Baclofen is a GABA-B receptor agonist, a unique mechanism of action. I use it in an intrathecal sterile
form (Gablofen) for epidural and facet blocks, but a commercially available IV form is not available in
the United States. Therefore, we have a compounding pharmacy make up a sterile, neutral pH solution
for use in the headache and pain clinic. Our initial data with migraines
77
have since grown in numbers
and types of migraines treated
78,79
and these include post-TBI migraines with severe muscle spasms.
Our study examined 63 patients with migraine, and muscle spasm and pain who were given 5 to 10 mg
of IV baclofen at intervals of 10 to 15 minutes. Muscle spasm and pain as distinguished from migraines
were rated by patients using a VAS every 15 minutes. Results showed that headache severity
diminished from 7.9 on VAS to 3.2 (P<.001). At the end of treatment, migraines were absent in 24
patients.
79
Conclusion
The future of aggressive pain and headache treatment of TBI-related headaches will reside in the sphere
of the specialist's clinic. This is a cost- and time-effective mode of treating intractable pain and
headaches. Compared with the treatments commonly available in the ED, the outpatient clinic can offer
a wider variety of effective and definitive treatments and, thus, offer patients a maximum degree of
success for control of their intractable pain symptoms.
There are so many different combinations of pain presentations (eg, refractory post-TBI
migraines/headaches with pain and with nausea, or accompanying muscle spasms, burning). It seems
as if virtually every combination of IV medications at our disposal has been tried or given in our clinic at
one time or another. Of course, we make every effort to use one medication at a time and to carefully
document the percentage of pain reduction of that single agent. As you can imagine, agents that have
worked successfully, perhaps many times before, might not work in the next particular situation and so
Page 11 of 18
we always have a "game plan" for the next agent. The key is to have a wide and varied repertoire of
interventions to address each unique patient's pain presentation.
Post-traumatic headaches, often considered to be extremely difficult to treat, are actually easier to treat
than most people realize if you pay attention to the parameters outlined in this article. In the future, we
will undoubtedly have more unique pharmacologic agents to treat post-TBI migraines more effectively.
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13. Krusz JC. Memantine for migraine and tension-type headache prophylaxis. Pract Pain Manage.
2011;11(1):61-62.
14. Hopewell CA, Krusz JC, Thomson JA. Memantine for treatment of cognitive deficits after traumatic
brain injury. American Academy of Neurology Annual Meeting. Miami, Florida: April 2005.
15. Cammarata D, Krusz JC. Ziprasidone as prophylaxis for chronic daily headaches. 9th European
Federation of Neurological Societies Annual Meeting. Athens, Greece: September 2005.
16. Krusz JC, Belanger J. Cost effectiveness of clinic treatment of headaches and pain. 8th World
Congress. The Pain Clinic, Tenerife, Canary Islands. May 1998.
17. Finkelstein E, Corso P, Miller T, et al. The Incidence and Economic Burden of Injuries in the United
States. New York, NY: Oxford University Press; 2006.
18. Coronado, McGuire, Faul, Sugerman, Pearson. The Epidemiology and Prevention of TBI. 2012. (in
press).
19. Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulfate rapidly alleviates
headaches of various types. Headache. 1996;36(3):154-160.
20. Krusz JC, Belanger J. Intravenous magnesium sulfate in the treatment of headaches. American
Academy of Pain Management Annual Meeting. Atlanta, Georgia. September 1998.
21. Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clin
Neurosci. 1998;5(1):24-27.
22. Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulfate relieves cluster
headaches in patients with low serum ionized magnesium levels. Headache.
1995;35(10):597-600.
23. Unger J, Cady RK, Farmer-Cady K. Understanding migraine: treatment options. Emerg Med.
2003:50-55.
24. Richter PA, Burk MP. The potentiation of narcotic analgesics with phenothiazines. J Foot Surg.
Page 12 of 18
1992;31(4):378-380.
25. Vinson DR. Treatment patterns of isolated benign headache in US emergency departments. Ann
Emerg Med. 2002;39(3):215-222.
26. Friedman BW, Corbo J, Lipton RB, et al. A trial of metoclopramide vs sumatriptan for the
emergency department treatment of migraines. Neurology. 2005;64(3):463-468.
27. Taylor BK, Joshi C, Uppal H. Stimulation of dopamine D2 receptors in the nucleus accumbens
inhibits inflammatory pain. Brain Res. 2003;987(2):135-143.
28. Flores JA, El Banoua F, Galan-Rodriguez B, Fernandez-Espejo E. Opiate anti-nociception is
attenuated following lesion of large dopamine neurons of the periaqueductal grey: critical role
for D1 (not D2) dopamine receptors. Pain. 2004;110(1-2):205-214.
29. King MA, Bradshaw S, Chang AH, Pintar JE, Pasternak GW. Potentiation of opioid analgesia in
dopamine
2
receptor knock-out mice: evidence for a tonically active anti-opioid system. J
Neurosci. 2001;21(19):7788-7792.
30. Semenchuk MR, Davis B. Efficacy of sustained-release bupropion in neuropathic pain: an open-
label study. Clin J Pain. 2000;16(1):6-11.
31. Wang SJ, Silberstein SD, Young WB. Droperidol treatment of status migrainosus and refractory
migraine. Headache. 1997;37(6):377-382.
32. Krusz JC, Scott VB, Belanger J. IV Droperidol as a treatment for acute migraine headache.
Cephalalgia. 1999;19:356.
33. Silberstein SD, Young WB, Mendizabal JE, Rothrock JF, Alam AS. Acute migraine treatment with
droperidol: a randomized, double-blind, placebo-controlled trial. Neurology. 2003;60(2):315-321.
34. Jones J, Pack S, Chun E. Intramuscular prochlorperazine versus metoclopramide as single-agent
therapy for the treatment of acute migraine headache. Am J Emerg Med. 1996;14(3):262-264.
35. Ginder S, Oatman B, Pollack M, A prospective study of IV magnesium and IV prochlorperazine in
the treatment of headaches. J Emerg Med. 2000;18(3):311-315.
36. Khan RB. Migraine-type headaches in children receiving chemotherapy and ondansetron. J Child
Neurol. 2002;17(11):857-858.
37. Rozen TD. Migraine headache: immunosuppressant therapy. Curr Treat Options Neurol.
2002;4(5):395-401.
38. Saadah HA. Abortive migraine therapy in the office with dexamethasone and prochlorperazine.
Headache. 1994;34(6):366-370.
39. Gallagher RM. Emergency treatment of intractable migraine. Headache. 1986;28:74-75.
40. Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine.
Neurology. 1986;36(7):995-997.
41. Scherl ER, Wilson JF. Comparison of dihydroergotamine with metoclopramide versus meperidine
with promethazine in the treatment of acute migraine. Headache. 1995;35(5):256-259.
42. Klapper J. The pharmacologic treatment of acute migraine headaches. J Pain Symptom Manage.
1993;8(3):140-147.
43. Klapper JA, Stanton JS. Ketorolac versus DHE and metoclopramide in the treatment of migraine
headaches. Headache. 1991;31(8):523-524.
44. Hering Rand Kuritsky A. Sodium valproate has a prophylaxis effect in migraine: a double-blind
study vs placebo. Cephalalgia. 1992;12:81-84.
45. Jensen R, Brinck T, Olesen J. Sodium valproate has a prophylactic effect in migraine without
aura. Neurology. 1994;44(4):647-651.
46. Klapper JA. Divalproex sodium in migraine prophylaxis: a dose-controlled study. Cephalalgia.
1997;17(2):103-108.
47. Krusz JC, Scott VB, and Belanger J. Intravenous valproate sodium in the treatment of refractory
migraine headaches. Headache Update Annual Meeting. Orlando, Florida. July 1999.
48. Mathew NT, Kailasam J, Meadors L, Chernyschev 0, Gentry P. Intravenous valproate sodium
(Depacon) aborts migraine rapidly: a preliminary report. Headache. 2000;40(9):720-723.
49. Edwards KR, Norton J, Behnke M. Comparison of intravenous valproate versus intramuscular
dihydroergotamine and metoclopramide for acute treatment of migraine headache. Headache.
2001;41(10):976-980.
50. Krusz JC. Intravenous valproate sodium in the treatment of migraine headaches in the headache
clinic. Headache Quarterly. 2001;12:39-41.
Page 13 of 18
51. Schwartz TH, Karpitskiy VV, Sohn RS. Intravenous valproate sodium in the treatment of daily
headache. Headache. 2002;42(6):519-522.
52. Tanen DA, MillerS, French T, Riffenburgh RH. Intravenous sodium valproate versus
prochlorperazine for the emergency department treatment of acute migraine headaches: a
prospective, randomized, double-blind study. Ann Emerg Med. 2003;41(6):847-853.
53. Stillman MJ, Zajac D, Rybicki LA. Treatment of primary headache disorders with intravenous
valproate: initial outpatient experience. Headache. 2004;44(1):65-69.
54. Krusz JC, Cagle J, Scott V. IV valproate for status migrainosus in the headache clinic. Headache
and Pain. 2006;17:121-123.
55. Krusz JC, Scott V, Belanger J. Intravenous propofol: unique effectiveness in treating intractable
migraine headaches. Headache. 2000;40(3):41-46.
56. 56Krusz JC. Prophylaxis for chronic daily headache and chronic migraine with neuronal stabilizing
agents. Curr Pain Headache Rep. 2002;6(12):480-485.
57. Bell R, Montoya D, Shuaib A, Lee MA. A comparative trial of three agents in the treatment of
acute migraine headache. Ann Emerg Med. 1990;19(10):1079-1082.
58. Reutens DC, Fatovich DM, Stewart-Wynne EG, Prentice DA. Is intravenous lidocaine clinically
effective in acute migraine? Cephalalgia. 1991;11(6):245-247.
59. Hand PJ, Stark RJ. Intravenous lignocaine infusions for severe chronic daily headache. Med J Aust.
2000;172(4):157-159.
60. Williams DR, Stark RJ. Intravenous lignocaine (lidocaine) infusion for the treatment of chronic
daily headache with substantial medication overuse. Cephalalgia. 2003;23(10):963-971.
61. Krusz JC, Cagle J, Cammarata D. IV lidocaine: effective treatment for refractory migraines in the
clinic. American Headache Society 49th Annual Meeting. Chicago, Illinois. June 2007.
62. Krusz JC, Cagle J. Efficacy of IV lidocaine to treat pain and headache flareups in the outpatient
clinic. American Pain Society's 27th Annual Scientific Meeting. Tampa, Florida. April 2009:
Abstract 221.
63. Nicolodi M, Sicuteri F. Negative modulators of excitatory amino acids in episodic and chronic
migraine: preventing and reverting chronic migraine. Int J Clin Pharmacal Res.
1998;18(2):93-100.
64. Nicolodi M, Sicuteri F. Exploration of NMDA receptors in migraine: therapeutic and theoretic
implications. Int J Clin Pharmacal Res. 1995;15(5-6):181-189.
65. Kaube H, Herzog J, Kaufer T, Dichgans M, Diener HC. Aura in some patients with familial
hemiplegic migraine can be stopped by intranasal ketamine. Neurology. 2000;55(1):139-141.
66. Peres MFP, Zukerman E, Soares C, Augusto S, Alonso EO, Santos BFC, Faulhaber MHW. CSF
glutamate levels in chronic migraine. Cephalalgia. 2004;24:151-152.
67. Krusz JC, Cagle J, Cammarata D. IV ketamine: effective therapy in the clinic for refractory
migraines. 7th European Federation of Neurological Societies. Brussels, Belgium. August 2007.
68. Krusz JC, Cammarata D, Cagle S. IV ketamine for treatment of refractory pain disorders in the
clinic. 27th Annual Scientific Meeting, American Pain Society. Tampa, Florida. May 2008.
69. Krusz JC. Ketamine in an outpatient setting: effective treatment for neuropathic pain syndromes.
32nd Annual Scientific Meeting of the American Pain Society. New Orleans, Louisiana. May 2013:
Abstract 378.
70. Krusz JC. Ketamine IV - for CRPS, TN/TMD and other neuropathic pain in the outpatient pain
clinic. Fourth International Congress on Neuropathic Pain. Toronto, Canada. May 2013.
2000;12:54.
72. Krusz JC, Cagle J, Daniel D. Intravenous levetiracetam for acute intractable migraines.
73. Krusz JC, Daniel D, Cagle J. IV Levetiracetam efficacious for cluster headache. Cephalalgia.
2003;23:736.
74. Krusz JC, Longmire DR. Tramadol in the treatment of headaches. American Academy of Pain
Management Annual Meeting. Washington, DC. September 1996.
75. Krusz JC, Daniel D, Cagle J. IV tramadol for treating refractory migraines. 7th Congress European
Federation of Neurological Societies. Helsinki, Finland. August 2003.
76. Krusz JC. IV tramadol: very efficacious treatment for pain and headache in the outpatient clinic.
Page 14 of 18
Abstract 382.
77. JC Krusz, J Cagle, D Daniel, VB Scott-Krusz. IV baclofen: treatment for refractory migraines and
daily headaches C0-morbid with muscle spasm in the outpatient clinic. 15th Congress of the
International Headache Society. Berlin, Germany. June 2011: Abstract 15.
78. JC Krusz, J Cagle. IV baclofen for treating migraines accompanied by severe muscle spasm in an
outpatient setting. 64th Annual Meeting of the American Academy of Neurology. New Orleans,
Louisiana. April 2012: Abstract 3780.
79. Krusz, JC. Baclofen IV in the clinic: effective treatment for muscle spasm pain and migraines.
Abstract 381.

View Sources [7]
1. Krusz JC, Robbins L. Traumatic brain injury. Pract Pain Manage. 2013;13(4):22-31.
2. Robbins L, Conidi FX. Stop footballsave brains: a point counterpoint discussion. Headache.
2012;53(5):817-823.
3. Seifert TD. Sports concussion and associated post-traumatic headache. Headache.
2013;53(5):726-736.
4. Silberstein SD, Lipton RB, Goadsby PJ. Headache in Clinical Practice. 2nd edition. Oxford, UK:
Martin Dunitz Ltd; 2002.
5. Olesen J, Goadsby PJ, Ramadan NM, Tfelt-Hansen P, Welch KMA. The Headache. 3rd edition.
Philadelphia, PA: Lippincott, Williams & Wilkins; 2006.
6. Silberstein SD, Lipton RB, Dodick DW. Wolff's Headache and Other Head Pain. 8th edition.
Oxford, UK: Oxford University Press; 2008.
7. FDA. FDA warns pregnant women to not use certain migraine prevention medicines.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm350866.htm. Accessed
May 6, 2013.
8. Krusz JC, Nett RB. Oxcarbazepine as migraine prophylaxis. American Headache Society Annual
Meeting. Montreal, Canada: June 2000.
2000;12:54.
10. Krusz JC. Zonisamide in the treatment of headache disorders. Cephalalgia. 2001;21:374.
11. Krusz JC. Lamotrigine for chronic neuropathic pain. Eur J Neurol. 2002;9(suppl 2):185.
12. Cammarata D, Krusz JC. Memantine: novel mechanism for migraine and headache prophylaxis.
47th Annual Scientific Meeting of the American Headache Society. Philadelphia, Pennsylvania:
June 2005.
13. Krusz JC. Memantine for migraine and tension-type headache prophylaxis. Pract Pain Manage.
2011;11(1):61-62.
14. Hopewell CA, Krusz JC, Thomson JA. Memantine for treatment of cognitive deficits after traumatic
brain injury. American Academy of Neurology Annual Meeting. Miami, Florida: April 2005.
15. Cammarata D, Krusz JC. Ziprasidone as prophylaxis for chronic daily headaches. 9th European
Federation of Neurological Societies Annual Meeting. Athens, Greece: September 2005.
16. Krusz JC, Belanger J. Cost effectiveness of clinic treatment of headaches and pain. 8th World
Congress. The Pain Clinic, Tenerife, Canary Islands. May 1998.
17. Finkelstein E, Corso P, Miller T, et al. The Incidence and Economic Burden of Injuries in the United
States. New York, NY: Oxford University Press; 2006.
18. Coronado, McGuire, Faul, Sugerman, Pearson. The Epidemiology and Prevention of TBI. 2012. (in
press).
19. Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulfate rapidly alleviates
headaches of various types. Headache. 1996;36(3):154-160.
20. Krusz JC, Belanger J. Intravenous magnesium sulfate in the treatment of headaches. American
Academy of Pain Management Annual Meeting. Atlanta, Georgia. September 1998.
21. Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clin
Page 15 of 18
Neurosci. 1998;5(1):24-27.
22. Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulfate relieves cluster
headaches in patients with low serum ionized magnesium levels. Headache.
1995;35(10):597-600.
23. Unger J, Cady RK, Farmer-Cady K. Understanding migraine: treatment options. Emerg Med.
2003:50-55.
24. Richter PA, Burk MP. The potentiation of narcotic analgesics with phenothiazines. J Foot Surg.
1992;31(4):378-380.
25. Vinson DR. Treatment patterns of isolated benign headache in US emergency departments. Ann
Emerg Med. 2002;39(3):215-222.
26. Friedman BW, Corbo J, Lipton RB, et al. A trial of metoclopramide vs sumatriptan for the
emergency department treatment of migraines. Neurology. 2005;64(3):463-468.
27. Taylor BK, Joshi C, Uppal H. Stimulation of dopamine D2 receptors in the nucleus accumbens
inhibits inflammatory pain. Brain Res. 2003;987(2):135-143.
28. Flores JA, El Banoua F, Galan-Rodriguez B, Fernandez-Espejo E. Opiate anti-nociception is
attenuated following lesion of large dopamine neurons of the periaqueductal grey: critical role
for D1 (not D2) dopamine receptors. Pain. 2004;110(1-2):205-214.
29. King MA, Bradshaw S, Chang AH, Pintar JE, Pasternak GW. Potentiation of opioid analgesia in
dopamine
2
receptor knock-out mice: evidence for a tonically active anti-opioid system. J
Neurosci. 2001;21(19):7788-7792.
30. Semenchuk MR, Davis B. Efficacy of sustained-release bupropion in neuropathic pain: an open-
label study. Clin J Pain. 2000;16(1):6-11.
31. Wang SJ, Silberstein SD, Young WB. Droperidol treatment of status migrainosus and refractory
migraine. Headache. 1997;37(6):377-382.
32. Krusz JC, Scott VB, Belanger J. IV Droperidol as a treatment for acute migraine headache.
33. Silberstein SD, Young WB, Mendizabal JE, Rothrock JF, Alam AS. Acute migraine treatment with
droperidol: a randomized, double-blind, placebo-controlled trial. Neurology. 2003;60(2):315-321.
34. Jones J, Pack S, Chun E. Intramuscular prochlorperazine versus metoclopramide as single-agent
therapy for the treatment of acute migraine headache. Am J Emerg Med. 1996;14(3):262-264.
35. Ginder S, Oatman B, Pollack M, A prospective study of IV magnesium and IV prochlorperazine in
the treatment of headaches. J Emerg Med. 2000;18(3):311-315.
36. Khan RB. Migraine-type headaches in children receiving chemotherapy and ondansetron. J Child
Neurol. 2002;17(11):857-858.
37. Rozen TD. Migraine headache: immunosuppressant therapy. Curr Treat Options Neurol.
2002;4(5):395-401.
38. Saadah HA. Abortive migraine therapy in the office with dexamethasone and prochlorperazine.
Headache. 1994;34(6):366-370.
39. Gallagher RM. Emergency treatment of intractable migraine. Headache. 1986;28:74-75.
40. Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine.
Neurology. 1986;36(7):995-997.
41. Scherl ER, Wilson JF. Comparison of dihydroergotamine with metoclopramide versus meperidine
with promethazine in the treatment of acute migraine. Headache. 1995;35(5):256-259.
42. Klapper J. The pharmacologic treatment of acute migraine headaches. J Pain Symptom Manage.
1993;8(3):140-147.
43. Klapper JA, Stanton JS. Ketorolac versus DHE and metoclopramide in the treatment of migraine
headaches. Headache. 1991;31(8):523-524.
44. Hering Rand Kuritsky A. Sodium valproate has a prophylaxis effect in migraine: a double-blind
study vs placebo. Cephalalgia. 1992;12:81-84.
45. Jensen R, Brinck T, Olesen J. Sodium valproate has a prophylactic effect in migraine without
aura. Neurology. 1994;44(4):647-651.
46. Klapper JA. Divalproex sodium in migraine prophylaxis: a dose-controlled study. Cephalalgia.
1997;17(2):103-108.
47. Krusz JC, Scott VB, and Belanger J. Intravenous valproate sodium in the treatment of refractory
migraine headaches. Headache Update Annual Meeting. Orlando, Florida. July 1999.
Page 16 of 18
48. Mathew NT, Kailasam J, Meadors L, Chernyschev 0, Gentry P. Intravenous valproate sodium
(Depacon) aborts migraine rapidly: a preliminary report. Headache. 2000;40(9):720-723.
49. Edwards KR, Norton J, Behnke M. Comparison of intravenous valproate versus intramuscular
dihydroergotamine and metoclopramide for acute treatment of migraine headache. Headache.
2001;41(10):976-980.
50. Krusz JC. Intravenous valproate sodium in the treatment of migraine headaches in the headache
clinic. Headache Quarterly. 2001;12:39-41.
51. Schwartz TH, Karpitskiy VV, Sohn RS. Intravenous valproate sodium in the treatment of daily
headache. Headache. 2002;42(6):519-522.
52. Tanen DA, MillerS, French T, Riffenburgh RH. Intravenous sodium valproate versus
prochlorperazine for the emergency department treatment of acute migraine headaches: a
prospective, randomized, double-blind study. Ann Emerg Med. 2003;41(6):847-853.
53. Stillman MJ, Zajac D, Rybicki LA. Treatment of primary headache disorders with intravenous
valproate: initial outpatient experience. Headache. 2004;44(1):65-69.
54. Krusz JC, Cagle J, Scott V. IV valproate for status migrainosus in the headache clinic. Headache
and Pain. 2006;17:121-123.
55. Krusz JC, Scott V, Belanger J. Intravenous propofol: unique effectiveness in treating intractable
migraine headaches. Headache. 2000;40(3):41-46.
56. 56Krusz JC. Prophylaxis for chronic daily headache and chronic migraine with neuronal stabilizing
agents. Curr Pain Headache Rep. 2002;6(12):480-485.
57. Bell R, Montoya D, Shuaib A, Lee MA. A comparative trial of three agents in the treatment of
acute migraine headache. Ann Emerg Med. 1990;19(10):1079-1082.
58. Reutens DC, Fatovich DM, Stewart-Wynne EG, Prentice DA. Is intravenous lidocaine clinically
effective in acute migraine? Cephalalgia. 1991;11(6):245-247.
59. Hand PJ, Stark RJ. Intravenous lignocaine infusions for severe chronic daily headache. Med J Aust.
2000;172(4):157-159.
60. Williams DR, Stark RJ. Intravenous lignocaine (lidocaine) infusion for the treatment of chronic
daily headache with substantial medication overuse. Cephalalgia. 2003;23(10):963-971.
61. Krusz JC, Cagle J, Cammarata D. IV lidocaine: effective treatment for refractory migraines in the
clinic. American Headache Society 49th Annual Meeting. Chicago, Illinois. June 2007.
62. Krusz JC, Cagle J. Efficacy of IV lidocaine to treat pain and headache flareups in the outpatient
clinic. American Pain Society's 27th Annual Scientific Meeting. Tampa, Florida. April 2009:
Abstract 221.
63. Nicolodi M, Sicuteri F. Negative modulators of excitatory amino acids in episodic and chronic
migraine: preventing and reverting chronic migraine. Int J Clin Pharmacal Res.
1998;18(2):93-100.
64. Nicolodi M, Sicuteri F. Exploration of NMDA receptors in migraine: therapeutic and theoretic
implications. Int J Clin Pharmacal Res. 1995;15(5-6):181-189.
65. Kaube H, Herzog J, Kaufer T, Dichgans M, Diener HC. Aura in some patients with familial
hemiplegic migraine can be stopped by intranasal ketamine. Neurology. 2000;55(1):139-141.
66. Peres MFP, Zukerman E, Soares C, Augusto S, Alonso EO, Santos BFC, Faulhaber MHW. CSF
glutamate levels in chronic migraine. Cephalalgia. 2004;24:151-152.
67. Krusz JC, Cagle J, Cammarata D. IV ketamine: effective therapy in the clinic for refractory
migraines. 7th European Federation of Neurological Societies. Brussels, Belgium. August 2007.
68. Krusz JC, Cammarata D, Cagle S. IV ketamine for treatment of refractory pain disorders in the
clinic. 27th Annual Scientific Meeting, American Pain Society. Tampa, Florida. May 2008.
69. Krusz JC. Ketamine in an outpatient setting: effective treatment for neuropathic pain syndromes.
Abstract 378.
70. Krusz JC. Ketamine IV - for CRPS, TN/TMD and other neuropathic pain in the outpatient pain
clinic. Fourth International Congress on Neuropathic Pain. Toronto, Canada. May 2013.
2000;12:54.
72. Krusz JC, Cagle J, Daniel D. Intravenous levetiracetam for acute intractable migraines.
Page 17 of 18
73. Krusz JC, Daniel D, Cagle J. IV Levetiracetam efficacious for cluster headache. Cephalalgia.
2003;23:736.
74. Krusz JC, Longmire DR. Tramadol in the treatment of headaches. American Academy of Pain
Management Annual Meeting. Washington, DC. September 1996.
75. Krusz JC, Daniel D, Cagle J. IV tramadol for treating refractory migraines. 7th Congress European
Federation of Neurological Societies. Helsinki, Finland. August 2003.
76. Krusz JC. IV tramadol: very efficacious treatment for pain and headache in the outpatient clinic.
Abstract 382.
77. JC Krusz, J Cagle, D Daniel, VB Scott-Krusz. IV baclofen: treatment for refractory migraines and
daily headaches C0-morbid with muscle spasm in the outpatient clinic. 15th Congress of the
International Headache Society. Berlin, Germany. June 2011: Abstract 15.
78. JC Krusz, J Cagle. IV baclofen for treating migraines accompanied by severe muscle spasm in an
outpatient setting. 64th Annual Meeting of the American Academy of Neurology. New Orleans,
Louisiana. April 2012: Abstract 3780.
79. Krusz, JC. Baclofen IV in the clinic: effective treatment for muscle spasm pain and migraines.
Abstract 381.
First published on: June 1, 2013

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