Chicago Cluster Headache: Treatment and Prevention Trigeminal Autonomic Cephalgia Treatment and Prevention

Neuromuscular Dentist in Chicago, IL Accepting Patients Nationwide & Worldwide

Posted: January 2, 2019
Authored by:

This was originally published at WWW.ThinkBetterLife.com which is the website for my Highland Park, Illinois website serving the North Shore suburbs, Chicago, Lake County and Cook County.
There are several patient testimonials about SPG Blocks and neuromuscular dentistry being utilized for treatment of all types of headaches and migraines.

I have added a section at the end of some of the problems associated with medications utilized for treating these conditions.

Are Spenopalatine Ganglion Blocks Superior to standard drug regimens?
I believe you must look at both safety and effectiveness and possible side effects to evaluate any and all treatments.  Side effects, if any are rare with Sphenopalatine Ganglion Blocks.

Cluster Headache treatment can be divided into treatment of acute attacks and prevention and treatment should also be divided.

Cluster headaches common symptoms include:
Sudden onset of pain,Frequently behind the eye (retro-orbital) and around the eye (periorbital)
Pain rapidly builds to a peak intensity over 10 to 15 minutes
Restlessness or agitation
Nasal congestion or fullness
Eyelid drooping (ptosis) or swelling
Red, swollen or watery eyes
Sweating of the head and neck

They are more common in males and typically begin in late 20's to early thirties.

They are one of a group of disorders known as Trigeminal Autonomic Cephalgias. They have in common that they are autonomic in origin and are mediated by the Trigeminal Nervous System.

The Sphenopalatine Ganglion also known as Meckel's Ganglion or the PterygoPalatine Ganglion is the largest Parasympathetic ganglion of the head whick also includes sympathetic fibers and Trigeminal nerves that pass though it without synapse.

I have previously written on how SPG Blocks have successfully treated and prevented SUNCT (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing) in conjunction with a neuromuscular orthotic to eliminate noxious input to the Trigeminal nervous system.

Another Trigeminal Autonomic Cephalgia is the Paroxysmal Hemicrania that an article in Curr Pain Headache Rep. 2014 Apr;18(4):407. doi: 10.1007/s11916-014-0407-6. The article discusses how Greater Occipital Nerve blocks and Sphenopalatine Ganglion Blocks can treat these headaches.

The mainstay of treatment for Cluster Headaches for many years has been Oxygen administration that frequently stops acute attacks, it is safe and frequently effective. Triptans are also frequently utilized for both acute attacks and as a preventive measure.

Verampamil, a Calcium Channel Blocker and Lithium have been shown to be effective for many patients in preventing attacks.

A recent article in Curr Neuropharmacol. 2015;13(3):304-23 titled "The Neuropharmacology of Cluster Headache and other Trigeminal Autonomic Cephalalgias." does a review of most current treatments for acure attacks and prevention. (the entire PubMed abstract is copied below). It also discusses new methods of treatment such as neurostimulation.

Almost 100% of all headaches are mediated by the Trigeminal Nervous System. The TrigeminoCervical complex is primarily responsible for cervical and occipital headaches and the TrigeminoVascular System seem to be the primary for release of neurotransmitters and neuropeptides that cause vasodilation . CGRP or Calcitonin Gene Related Peptide is one of these that research is currently investigating.

Unfortunately some of the most effective treatments due not create windfall profits for drug companies and therefore do not receive significant funding for research.

The amazing results frequently seen by altering noxious neural input to the Trigeminal nerve with neuromuscular orthotics are left unfunded by both drug companies and the NIH.
The Sphenopalatine Ganglion Block has recently received more interest as companies investigate the viability onf implantable stimulators of the Sphenopalatine Ganglion.

New devices are also coming on the market to do SPG Blocks including the Sphenocath, the TX#^) and the MIRx Treatment Protocols and the Allevio device.

The injections continue to be highly effective but the self administration with cotton tipped applicators is, by far, the most cost effective method and more importantly it gives patients the ability to use SPG Blocks as preventives and for acute treatment.

I teach courses to physicians and dentists it giving SPG Blocks and I routinely teach my patients to self administer blocks intranasally.

Side Effects of drugs is always a major problem.  The following is a list of side effects from the Relpax website.  Relpax is an excellent drug but there are risks associated with its use that patients should be well aware of.

Following Relpax is information from the National Headache Foundation about Triptans and their side effects.

IMPORTANT SAFETY INFORMATION

Do not take RELPAX® (eletriptan HBr) if you:

  • Have heart disease or a history of heart disease
  • Have a history of stroke, transient ischemic attack
  • Have a history or current evidence of hemiplegic or basilar migraines (if you are not sure about this, ask your doctor)
  • Have peripheral vascular disease (e.g. narrowing of blood vessels to the legs, arms, stomach, intestines, or kidneys)
  • Have ischemic bowel disease (inadequate blood supply to the intestine)
  • Have uncontrolled blood pressure
  • Have taken other migraine medications in the last 24 hours, including other triptans, ergots, or ergot-type medications
  • Are allergic to RELPAX or any of its ingredients
  • RELPAX should not be used within at least 72 hours of treatment with the following medicines: Nizoral® (ketoconazole), Sporanox®(itraconazole), Serzone® (nefazodone), TAO® (troleandomycin), Biaxin® (clarithromycin), Norvir® (ritonavir), and Viracept® (nelfinavir)

All brands are trademarks of their owners.

Patients taking RELPAX may experience serious side effects, including:

Heart attacks and other heart problems. Heart problems may lead to death. Stop taking RELPAX and get emergency medical help right away if you have any symptoms of heart attack like discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back; chest pain or chest discomfort that feels like an uncomfortable heavy pressure; squeezing, fullness, or pain; pain or discomfort in your arms, back, neck, jaw, or stomach; shortness of breath with or without chest discomfort; breaking out in a cold sweat; nausea or vomiting; feeling lightheaded.

Medication overuse headaches. Some patients who take too many RELPAX may have worse headaches. If your headaches get worse your doctor may decide to stop your treatment with RELPAX.

Serotonin syndrome is a serious and life-threatening problem that can happen when taking RELPAX, especially when used with certain medications commonly used to treat depression such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). Tell your doctor right away if you experience mental changes such as hallucinations, fast heartbeat, high body temperature, trouble walking, or nausea, vomiting or diarrhea.

Changes in color or sensation in your fingers and toes (Raynaud’s syndrome).

Stomach and intestinal problems like sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever.

Problems with blood circulation to your legs and feet (cramping and pain in your legs or hips); like feeling of heaviness or tightness in your leg muscles, burning or aching in your feet or toes while resting, numbness, tingling, or weakness in your legs, cold feeling or color changes in 1 or both legs or feet.

Most common side effects are dizziness, nausea, weakness, tiredness and drowsiness. If you have these symptoms, do not drive a car or do anything where you need to be alert. Tell your doctor about any side effects you have.

RELPAX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

National Headache Foundation information on Triptans.  There are numerous side effects and many patients use more than recommended doses of these drugs.

Triptans are effective in reducing migraine symptoms and are generally well tolerated; however, migraine sufferers should discuss the following with their physician before taking triptans:

  • Triptans should not be used in combination with ergotamines for the treatment of migraine, and in some instances, should not be used in combination with monoamine oxidase inhibitors (MAOIs).
  • Triptans should not be used by those who have a past history of, or risk factors, for heart disease, high blood pressure, high cholesterol, angina, peripheral vascular disease, impaired liver function, stroke or diabetes.
  • Triptans should be taken only as prescribed by a physician.

Triptan medications There are currently seven triptan medications available in the United States.

Almotriptan — Axert® (Tablet)

Recommended dose

  • One 6.25 mg or 12.5 mg dose after the first sign of migraine
  • No more than two doses in 24 hours

Most common side effects

  • Tingling of the skin
  • Burning or prickly feeling
  • Numbness
  • Dizziness
  • Dry mouth
  • Headache
  • Nausea
  • Sleepiness

A more complete list of side effects from Axert  from www.rxlist.com include:

SIDE EFFECTS: Drowsiness, dizziness, nausea, sensations of tingling/numbness/prickling, or dry mouth may occur. If any of these effects persist or worsen, notify your doctor.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.

Chest/jaw/neck tightness can commonly occur shortly after using almotriptan. Only rarely are these signs of a serious condition. However, you may not be able to tell this apart from a serious reaction related to a lack of blood flow to the heart, brain or other parts of the body. Seek immediate medical attention if any of these unlikely but very serious (rarely fatal) side effects occur: chest pain, jaw/left arm pain, fainting, fast/irregular/pounding heartbeat, vision changes, weakness on one side of the body, confusion, slurred speech, sudden or severe stomach/abdominal pain, bloody diarrhea, change in the amount of urine.

Tell your doctor immediately if any of these unlikely but serious side effects occur: blue fingers/toes/nails, cold sensation of hands/feet, hearing changes, mental/mood changes.

This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.

In the unlikely event you have a serious allergic reaction to this drug, seek immediate medical attention. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Eletriptan — Relpax® (Tablet)

Recommended dose

  • One 20 mg or 40 mg dose at the start of a migraine
  • No more than two 20 mg or 40 mg doses may be taken in a 24-hour period

Most common side effects

  • Dizziness
  • Lack or loss of strength
  • Nausea
  • Sleepiness or unusual drowsiness
  • Pain or pressure sensation in the chest or throat

Frovatriptan — Frova® (Tablet)

Recommended dose

  • One 2.5 mg tablet after the start of a migraine
  • No more than three should be taken in a 24-hour period

Most common side effects

  • Dizziness
  • Fatigue
  • Headache other than migraine
  • Tingling of the skin
  • Dry mouth
  • Flushing (hot flashes)
  • Feeling hot or cold
  • Chest pain
  • Indigestion
  • Pain in the joints or bones

A more complete list of side effects of Frova from rxlist.com

What are the possible side effects of frovatriptan (Frova)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using frovatriptan and call your doctor at once if you have a serious side effect such as:

  • feeling of pain or tightness in your jaw, neck, or throat;
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
  • sudden numbness or weakness, especially on one side of the body;
  • sudden severe headache, confusion, problems with vision, speech, or balance;
  • sudden and severe stomach pain and bloody diarrhea;
  • numbness or tingling and a pale or blue-colored appearance in your fingers or toes; or
  • (if you are also taking an antidepressant) -- agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Less serious side effects may include:

  • mild headache (not a migraine);
  • feeling too warm or too cold;
  • dry mouth, upset stomach;
  • bone or joint pain;
  • pressure or heavy feeling in any part of your body;
  • dizziness, drowsiness, tired feeling; or
  • warmth, redness, or mild tingling under your skin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Naratriptan — Amerge® (Tablet)

Recommended dose

  • One 1 mg or 2.5 mg dose at the first sign of a migraine
  • No more than 5 mg in a 24-hour period

Most common side effects

  • Chest pain (severe)
  • Heaviness, tightness or pressure in the chest, throat and/or neck
  • Feeling of burning sensation
  • Sensation of warmth
  • Numbness
  • Sense of tightness around the chest and/or throat
  • Tingling of the skin
  • Dizziness
  • Drowsiness or increased tiredness
  • Nausea and/or vomiting

A more complete list of side effects from rxlist.com include

SIDE EFFECTS: Flushing, sensations of tingling/numbness/prickling/heat, weakness, drowsiness, or dizziness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.

Tell your doctor right away if you have any serious side effects, including: blue fingers/toes/nails, cold sensation of hands/feet, hearing changes, mental/mood changes.

Chest/jaw/neck tightness can commonly occur shortly after using naratriptan. Only rarely are these signs of a serious condition. However, you may not be able to tell this apart from a serious reaction related to a lack of blood flow to the heart, brain or other parts of the body. Get medical help right away if you have any very serious side effects, including: chest pain, jaw/left arm pain, fainting, fast/irregular/pounding heartbeat, vision changes, weakness on one side of the body, confusion, slurred speech, sudden or severe stomach/abdominal pain, bloody diarrhea, change in the amount of urine.

This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Amerge (naratriptan) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before taking naratriptan, tell your doctor or pharmacist if you are allergic to it; or to other triptan migraine drugs; or it you have other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart disease (e.g., chest pain, heart attack, irregular heartbeat), decreased blood flow in the brain (e.g., stroke, transient ischemic attack), blood circulation disease (e.g., ischemic bowel disease, Raynaud's disease), certain types of headaches (hemiplegic or basilar migraine), kidney disease, liver disease.

Tell your doctor if you have the following risk factors for heart disease: diabetes, family history of heart disease, high blood pressure, high cholesterol, overweight, smoker, female after menopause, male over age 40.

If you are at high risk for heart disease, your doctor may want to check your heart before prescribing naratriptan.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

The risk of heart disease and high blood pressure increases with age. Older adults may be more sensitive to the side effects of this drug, especially increased blood pressure and heart problems.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

Rizatriptan — Maxlt®, Maxlt- MLT® (Tablet, Orally Disintegrating Tablets)

Recommended dose

  • One 5 or 10 mg dose at the first sign of a migraine
  • No more than 30 mg in a 24-hour period

Most common side effects

  • Chest pain or heaviness, tightness/pressure in the chest
  • Pounding heartbeat
  • Feeling of burning sensation
  • Sensation of warmth
  • Numbness
  • Sense of tightness around the chest and/or throat
  • Tingling of the skin

A more complete list of side effects from rxlist.com include

Get emergency medical help if you have any of thesesigns of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using rizatriptan and call your doctor at once if you have a serious side effect such as:

  • feeling of pain or tightness in your jaw, neck, or throat;
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
  • sudden numbness or weakness, especially on one side of the body;
  • sudden severe headache, confusion, problems with vision, speech, or balance;
  • sudden and severe stomach pain and bloody diarrhea;
  • numbness or tingling and a pale or blue-colored appearance in your fingers or toes; or
  • (if you are also taking an antidepressant) -- agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Less serious side effects may include:

  • mild headache (not a migraine);
  • dry mouth, mild nausea;
  • pressure or heavy feeling in any part of your body;
  • dizziness, drowsiness, tired feeling; or
  • warmth, redness, or mild tingling under your skin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Sumatriptan — Imitrex® (Tablet, Nasal Spray Injection)

Recommended dose

  • Dosage varies depending on severity of migraines and type of delivery

Most common side effects

  • Flushing (hot flashes)
  • Tingling of the skin
  • Drowsiness
  • Dizziness
  • Weakness
  • Sensation of warmth or coldness
  • Burning at injection sites (if injection used)
  • Bitter taste at the back of throat (with nasal sprays)

A more complete list of side effects from rxlist.com include:

What are the possible side effects of sumatriptan (Imitrex)?

Get emergency medical help if you have any of thesesigns of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using sumatriptan and call your doctor if you have a serious side effect such as:

  • feeling of pain or tightness in your jaw, neck, or throat;
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
  • sudden numbness or weakness, especially on one side of the body;
  • sudden severe headache, confusion, problems with vision, speech, or balance;
  • sudden and severe stomach pain and bloody diarrhea;
  • seizure (convulsions);
  • numbness or tingling and a pale or blue-colored appearance in your fingers or toes; or
  • (if you are also taking an antidepressant) -- agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Less serious side effects may include:

  • mild headache (not a migraine);
  • pressure or heavy feeling in any part of your body;
  • feeling hot or cold;
  • dizziness, spinning sensation;
  • drowsiness;
  • nausea, vomiting, drooling;
  • unusual taste in your mouth after using the nasal spray;
  • burning, numbness, pain or other irritation in your nose or throat after using the nasal spray; or
  • warmth, redness, or mild tingling under your skin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Zolmitriptan — Zomig® (Tablet, Oral Ingesting Tablet, Nasal Spray)

  • Recommended dose
  • Dosage varies depending on severity of migraines and type delivery

Most common side effects

  • Chest pain (severe)
  • Heaviness, tightness, or pressure in chest
  • Feeling of burning sensation
  • Tingling of skin
  • Dizziness
  • Nausea
  • Sensation of warmth
  • Numbness
  • Sense of tightness around the chest and/or throat
  • Sleepiness or unusual tiredness
  • Muscle weakness
  • A more complete list of side effects from rxlist.com include:
  • Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

    Stop using zolmitriptan and call your doctor at once if you have a serious side effect such as:

    • feeling of pain or tightness in your jaw, neck, or throat;
    • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
    • sudden numbness or weakness, especially on one side of the body;
    • sudden severe headache, confusion, problems with vision, speech, or balance;
    • fast or pounding heartbeats, dizziness;
    • sudden and severe stomach pain and bloody diarrhea;
    • numbness or tingling and a pale or blue-colored appearance in your fingers or toes; or
    • (if you are also taking an antidepressant) -- agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

    Less serious side effects may include:

    • pressure or heavy feeling in any part of your body;
    • dry mouth, upset stomach;
    • feeling of pain or pressure in your neck or throat;
    • drowsiness, weakness; or
    • warmth, redness, or mild tingling under your skin.

    This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Curr Neuropharmacol. 2015;13(3):304-23.
The Neuropharmacology of Cluster Headache and other Trigeminal Autonomic Cephalalgias.


Costa A1, Antonaci F, Ramusino MC, Nappi G.
1National Institute of Neurology IRCCS C. Mondino Foundation, University of Pavia, via Mondino 2, 27100 Pavia, Italy. alfredo.costa@mondino.it.
Abstract
Trigeminal autonomic cephalalgias (TACs) are a group of primary headaches including cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). Another form, hemicrania continua (HC), is also included this group due to its clinical and pathophysiological similarities. CH is the most common of these syndromes, the others being infrequent in the general population. The pathophysiology of the TACs has been partly elucidated by a number of recent neuroimaging studies, which implicate brain regions associated with nociception (pain matrix). In addition, the hypothalamic activation observed in the course of TAC attacks and the observed efficacy of hypothalamic neurostimulation in CH patients suggest that the hypothalamus is another key structure. Hypothalamic activation may indeed be involved in attack initiation, but it may also lead to a condition of central facilitation underlying the recurrence of pain episodes. The TACs share many pathophysiological features, but are characterised by differences in attack duration and frequency, and to some extent treatment response. Although alternative strategies for the TACs, especially CH, are now emerging (such as neurostimulation techniques), this review focuses on the available pharmacological treatments complying with the most recent guidelines. We discuss the clinical efficacy and tolerability of the currently used drugs. Due to the low frequency of most TACs, few randomised controlled trials have been conducted. The therapies of choice in CH continue to be the triptans and oxygen for acute treatment, and verapamil and lithium for prevention, but promising results have recently been obtained with novel modes of administration of the triptans and other agents, and several other treatments are currently under study. Indomethacin is extremely effective in PH and HC, while antiepileptic drugs (especially lamotrigine) appear to be increasingly useful in SUNCT. We highlight the need for appropriate studies investigating treatments for these rare, but lifelong and disabling conditions.

Curr Pain Headache Rep. 2014 Apr;18(4):407. doi: 10.1007/s11916-014-0407-6.
Paroxysmal hemicrania: an update.
Prakash S1, Patell R.
Author information
Abstract
Paroxysmal hemicrania (PH) is an underreported and underdiagnosed primary headache disorder. It usually begins in the third or fourth decade of life. The recent observations indicate that it is equally prevalent in both males and females. PH is characterized by severe, strictly unilateral head pain attacks that occur in association with ipsilateral autonomic features. The attacks in PH are shorter and more frequent compared with cluster headache (CH) but otherwise PH and CH have similar clinical features. The hallmark of PH is the absolute cessation of the headache with indomethacin. However, a range of drugs may show partial to complete relief in certain groups of patients. Neuromodulatory procedures, such as greater occipital nerve blockade, blockade of sphenopalatine ganglion and neurostimulation of the posterior hypothalamus, are reserved for refractory PH.