​Kembara Xtra - Medicine - Cluster Headache

​Kembara Xtra - Medicine - Cluster Headache 
A primary headache condition marked by recurrent occurrences of intense, unilateral acute, searing, or piercing pain that is usually confined to the periorbital and/or temporal areas

Patients frequently pace the floor throughout an acute attack because lying down seems to make the pain worse. Autonomic symptoms include signs of parasympathetic hyperactivity (ipsilateral lacrimation, eye redness, and nasal congestion) and sympathetic hypoactivity (ipsilateral ptosis and miosis).
Individual attacks can range from once every other day to eight times per day and, if left untreated, can last anywhere from 15 to 180 minutes per day. Attacks typically occur in series (cluster periods), which are frequently seasonal and last for weeks or months, and are separated by remission periods, which typically last months to years. About 10-15% of patients have chronic symptoms without remissions (i.e., chronic cluster headache [cCH]).

Incidence of Epidemiology: 2 to 10/100,000
Prevalence
53 per 100,000 people.
Males outnumber females 4.3:1 overall.
Women frequently experience CH in their 20s.
Episodic/chronic ratio: 6:1 Mean age at onset: 30 years

Pathophysiology and etiology 
Complex and little understood The following are some potential mechanisms:
- Trigeminovascular system activation, which triggers the production of substance P, neurokinin, and calcitonin gene-related peptide (CGRP), among other vasodilatory peptides.
Trigeminal nociceptive pathways may be activated by posterior hypothalamic activation, leading to an attack, by increasing parasympathetic outflow. Alterations in the descending pain modulation network and disrupted pain modulation during cluster periods.

Genetics: Typically sporadic, autosomal dominant in 5% of cases, otherwise autosomal recessive or multifactorial
The evidence varies: First-degree relatives are 18 times more likely to get cluster headaches, and second-degree relatives are 1 to 3 times more probable.
More than 50% had migraines, and 18% had CH in their family history.

Risk factors include: being a man; being older (onset occurs before age 30 in 70% of cases); smoking during childhood; having a family history of CH; and having had head trauma personally.

Conditions in Common Depression (24%)
An increased risk of suicide due to the severity of the pain, a headache from overusing medications, and asthma (9%)
A history of migraines, which affects patients more often who are women Sleep apnea (30-80%)

Diagnoses are made in a clinical setting.
Criteria from the 2018 third edition of the International Classification of Headache Disorders
At least five episodes of extreme or very extreme unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes without treatment
- At least one ipsilateral symptom from the headache, such as:
Nasal congestion and/or rhinorrhea, conjunctival injection and/or lacrimation, and eyelid edema
Attack frequency: one every other day to eight per day for more than half the time during cluster periods; Forehead and facial sweating/flushing; Miosis and/or ptosis; Restlessness or agitation during acute attack
Episodic CH (eCH): In 80–90% of cases, at least two cluster periods spanning 7 days to 1 year, separated by a pain-free period of 3 months.

Chronic CH (cCH) is defined as continuing for at least one year without remission or for at least three months during remission.

An agonizing, unilateral, acute, scorching, or piercing pain that is usually localized to the periorbital and/or temporal region has been described as a headache's presenting history.
Tearing, nasal congestion, rhinorrhea, conjunctival injection, and sweating

The occurrence of headaches at the same time every day (typically at night) is known as circadian timing.
The presence of triggers like histamine, potent smells, or vasodilators like alcohol, nitroglycerin, and sildenafil.
A seasonal pattern of periods in clusters, which are frequently recurrent at the same time of the year.

clinical assessment 
Patients are typically seen in between bouts, therefore a physical checkup is frequently uneventful.
During an acute attack, distress, sobbing fits, agitation, and/or restlessness
During an acute attack, one may have ipsilateral lacrimation, conjunctival injection, ptosis, and miosis. One may also experience edematous nasal mucosa or rhinorrhea.

Differential diagnoses include hypnic headaches, trigeminal and other facial neuralgias, migraine, temporal arteritis, herpes zoster, and acute angle closure glaucoma. Paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and hemicrania continua are examples of these.
Additional CH:
- Pituitary tumors/meningiomas/carcinomas, brain arteriovenous malformations, carotid artery dissection, and intracranial artery aneurysms
- Cavernous hemangioma, also known as Tolosa-Hunt syndrome, or inflammation of the cavernous sinus

Laboratory Results 
The majority of diagnoses are clinical, and they are frequently delayed (more than 40% report a 5-year delay in diagnosis).
Initial examinations (lab, imaging)
For all trigeminal autonomic cephalgias, neuroimaging (MRI/CT head with comprehensive pituitary and cavernous sinus examination) is advised in order to rule out other intracranial disorders that might resemble TACs.

Management 
Many of the drugs covered in the section after that are employed off-label to treat CH.

Prevention Techniques 
Avoid significant changes in sleep patterns and give up smoking.
Refrain from drinking during the cluster period.
Avert abrupt elevation changes, which may affect oxygen levels.
Refrain from being exposed to chemicals, solvents, or other recognized triggers.

Medication 

Avoid using painkillers, particularly narcotic analgesics, during sudden episodes.
Acute attack abortion and transitional prophylaxis for the anticipated duration of the cluster period are the goals.
Long-term preventative measures for cCH
Before using vasoactive medications, such as triptans or ergot derivatives, evaluate your cardiovascular risk.

First Line - For immediate relief from acute attacks, use 100% oxygen at 12 to 15 L/min while sitting or standing with a demand valve oxygen mask. If you are resistant to lower-flow oxygen, use high flow; the side effect profile is favorable.

Caution 

The most effective treatment for acute attacks is sumatriptan - SubQ: 6 mg, up to 12 mg/24 h with at least 1 hour between injections; NNT = 2.4 and 3.3 for headache alleviation and pain free in 15 minutes, respectively.
- Intranasal: 20 mg once into a nostril on the side of the headache; repeat if necessary in two hours; maximum dose of 40 mg/24 hours; NNT = 3.2 for headache alleviation at 30 minutes.

Zolmitriptan-Intranasal: 5- and 10-mg dosages both effective; repeatable in 2 hours, maximum twice daily; NNT = 12 and 4.9 for headache alleviation in 15 minutes for 5 and 10 mg, respectively.
- NNT = 6.7 and 4.5 for headache alleviation in 30 minutes for 5 and 10 mg, respectively, when administered orally; repeat in 2 hours; maximum dose 10 mg/24 hr. (1),(2)[B]
ALERT
"Triptan sensations" include paresthesias, flushing, tingling, chest pain, and neck stiffness.
Triptans are not recommended for people with ischemic bowel disease, ischemic heart disease, stroke, uncontrolled hypertension, Prinzmetal angina, basilar migraine, hemiplegic migraine, or ischemic cardiac illness.
For prevention:
- To stop and cut down on additional attacks, use as soon as possible at the beginning of the cluster period.
Galcanezumab: 300 mg SC once a month until the cluster period is over. Only drugs that have been FDA-approved for eCH prevention. Nasopharyngitis, hepatic enzyme increase, local injection site reaction, and discomfort are the most frequent adverse effects; NNT = 5.2 (3).[B]
- Verapamil Start with 80 mg TID and increase by 80 mg/week to 480 mg, then if necessary, take 80 mg every two weeks. equivalent for either short- or long-acting. Although up to 960 mg/day may be required, most individuals react to daily doses of 200 to 480 mg; NNT = 1.2 (1)[A]
ALERT
Verapamil must be administered with a baseline ECG and repeated monitoring when dosage is increased because to the possibility of bradycardia, a prolonged PR interval, RBBB, or a total heart block.
Avoid grapefruit juice because it inhibits CYP3A4.

Next Line
In two double-blind, sham-controlled trials (ACT-1 and ACT-2), noninvasive vagus nerve stimulation (nVNS) showed modest benefit in short-term pain relief for eCH. FDA-approved for treating eCH.
Implantable devices, carotid atherosclerosis, cervical vagotomy, clinically severe hypertension, or arrhythmias are contraindications.
- Intranasal administration of 10 mg (1 mL) of lidocaine or 40 to 50 mg of 10% cocaine. No well-executed randomized controlled trials (RCTs) have been performed. Nasal congestion and foul tastes are the most typical adverse effects.
Octreotide: 100 g S. When triptans are not appropriate, patients may be given consideration. GI distress is the main side effect.
In a short RCT, a 10-mg regular-release tablet taken in the late evening reduced the incidence of headaches compared to a placebo. There were no side effects noted.
Start with 300 mg BID and increase it to a therapeutic range of 600-1500 mg per day for lithium. Lithium was shown to be equivalent to verapamil in a side-by-side comparison.
Monitoring of medication levels, liver, kidney, and thyroid function is necessary. Use caution when taking diuretics and nephrotoxic medications.
Keep an eye out for CNS consequences.
- In one small RCT, capsaicin 0.025% ipsilateral nostril for 7 days demonstrated efficacy.
- Topiramate: Several small, open-label trials using 100–200 mg/day demonstrated effectiveness.

Referral 

For individuals who are complex or refractory, think about referring them to a headache clinic or a neurology specialist.

Further Therapies 
Transitional prophylaxis: Used to drastically lower the incidence of attacks until a longer-term preventative medication is successful. Agents for longer-term maintenance are launched concurrently.
Prednisolone 1 mg/kg/day (maximum 60 mg) with a taper lasting no more than 18 days in order to prevent side effects. Numerous unreliable studies that did not involve rigorous testing only suggested benefits. Insomnia, psychosis, hyponatremia, edema, hyperglycemia, and peptic ulcer are side effects of short-term use.
Suboccipital nerve or greater occipital nerve steroid injections: 3.75 mg of cortivazol is injected into the suboccipital region on the ipsilateral side of the headache; one injection or a series of three injections, given 48 to 72 hours apart, reduces attack frequency during the cluster period when used as an add-on therapy to verapamil; NNT = 2.5.

pregnant women's issues
It is advised that breastfeeding specialists, obstetricians, pediatricians, and headache specialists work together.
Patient should be made aware of the scant research on therapy effectiveness and safety.
Oxygen is the most appropriate first-line therapy for acute treatment. Second-line treatments include subcutaneous sumatriptan (pregnancy Category C), intranasal triptans (pregnancy Category C), and intranasal lidocaine (pregnancy Category B).

Oral steroids (pregnancy Category C/D) or greater occipital nerve blockade can be used for transitional prophylaxis, but only at the lowest dose and for the shortest amount of time.
Verapamil (pregnancy Category C) is still the drug of choice for preventative therapy. Avoid if you can during the third trimester. Ergotamines and lithium are both classified as pregnancy categories X and D, respectively.

Surgery may be considered for people who are resistant to medicinal therapy or who have contraindications to it. There is no evidence for Botox or hyperbaric oxygen therapy.
Neurostimulation: A multicenter RCT demonstrated the effectiveness of bilateral occipital nerve stimulation (ONS) in reducing the severity and frequency of attacks in individuals with cCH. The CINTHA trial is still underway.
The hypothalamus has responded positively to deep brain stimulation (DBS), however there are also dangers of stroke, bleeding, and death.


Suicidal thoughts and intractable pain upon admission


Patient Follow-Up Monitoring
Predict cluster outbursts and start prophylactic early.
Keep an eye out for despair and suicidal thoughts, particularly in people with cCH.
When using drugs to treat CH, keep an eye out for negative drug reactions and side effects, such as the masking of an underlying cardiovascular condition.

Unpredictable but frequently chronic course is the prognosis
Attack frequency frequently declines with age. There is a chance that eCH can change into cCH.


Complications include depression and suicide as well as drug side effects that reveal coronary artery disease.