Headaches can be due to a variety of causes but are generally categorised into primary and secondary headaches (Box 17.1). The primary headaches, the main focus of this chapter, are headaches that are not caused by another disease or condition, unlike secondary headaches. The International Headache Society (IHS) maintains a list of conditions that can produce headache symptoms secondary to the disorder (International Headache Society 2004). This list is extensive and the clinician managing the headache patient needs to be familiar with these conditions and include or exclude them as appropriate. Such causes may include intracranial mass, vascular lesions, systemic disorders or infection. In particular, the clinician needs to be aware of the following danger signs that may indicate the need for aggressive investigation.

• Sudden onset of headache, severe in nature, that peaks quickly (minutes to a few hours) or that gets progressively worse. For example, subarachnoid haemorrhage may be of sudden onset, or headache due to infection such as abscess or meningitis may worsen over hours to days.

• Any patient that presents with the ‘worst headache of my life’.

• Focal neurological signs, particularly on the first occurrence of the headache, including changes in personality, mental status, and level of consciousness.

• Headache precipitated or made worse by bending, sneezing, coughing, or exertion. This may indicate raised intracranial pressure. Vomiting with headache may also be associated with raised intracranial pressure.

• Changes in the headache pattern of an existing headache sufferer.

• Association of headache with fever, rash, nucal rigidity, lymphadenopathy, and particularly if for the first time, photophobia.

• New headaches in patients under 5 or over 50 years of age.

Box 17.1

The primary and secondary headaches

Primary headaches	Secondary headaches (attributed to:)
Migraine Tension-type headaches Cluster headache and other trigeminal autonomic cephalalgias Other primary headaches

Head/neck trauma

Cranial/cervical vascular disorder

Non-vascular intracranial disorder

A substance or its withdrawal

Infections

Disorder of homeostasis

Disorder of the cranium, neck, ears, eyes, nose, sinuses, teeth, mouth or other cranial or facial structures

Psychiatric disorder

Adapted from IHS 2004, with permission.

Clinicians managing patients with headache should ensure they are familiar with these danger signs and the subsequent management needed.

The main body of this chapter, however, will focus mainly on the major primary headaches as defined by the IHS, and discuss their pathophysiology and management from a functional neurology perspective. The approach of functional neurology has much to offer the headache sufferer, as many of the headaches are due to physiological dysfunctions in discrete brain areas. These areas can then be targeted using either their presynaptic neuronal pools or embryological relationships to cause an improvement in the health or central integrative state of the area. The functional neurologist should also consider the overall homeostatic environment of the body, evaluating whether it is conducive to neuronal health and, if not, taking steps to improve it.

Migraine

Migraine is a common disabling condition that is ranked nineteenth by the World Health Organization amongst worldwide diseases causing disability (IHS 2004). Approximately 15–20% of the general population suffers from migraine headaches (Bolay et al. 2002). It has considerable social and economic impact; hence effective treatment strategies have the ability to make significant improvements in the quality of life of the sufferer, and have positive social benefit as well. In this chapter we will discuss the two most common forms of migraine, migraine with aura and migraine without aura, along with the childhood syndromes that are often the precursor of migraine.

Migraine without aura (MWOA)

Migraine without aura was previously known as common migraine.

The International Headache Society (2004) describes MWOA as: ‘Recurrent headache disorder manifesting in attacks lasting 4–72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity and association with nausea and/or photophobia and phonophobia’.

To be diagnosed with MWOA the individual must have had at least five attacks lasting 4–72 hours with at least two of the following characteristics: unilateral pain location, pulsating quality, moderate to severe pain intensity and/or aggravated by routine activity. It must also be accompanied by either nausea and/or vomiting or phono- and photophobia (Box 17.2) (IHS 2004).

Box 17.2

Diagnostic criteria for migraine without aura

Description

Recurrent headache disorder manifesting in attacks lasting 4–72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea and/or photophobia and phonophobia.

From IHS 2004, with permission.

Peripheral sensitisation in migraine

Migraine is a complex phenomenon that likely has multiple causes. However, current thought on the pathophysiology of migraine is that an initial activation of meningeal nociceptors causes a release of substance P and salcitonin gene related peptide (CRGP) from the nociceptive nerve endings, which in turn causes vasodilation and protein extravasation (Dalkara et al. 2006). This process is known as neurogenic inflammation and/or peripheral sensitisation. In peripheral sensitisation the increased sensitivity of the nociceptors to activation may develop to a degree that, in combination with central sensitisation, they are susceptible to activation by the arterial pulse and head movements (Dalkara et al. 2006). In this way, normal physiological activities may become sources of pain. The causes of the initial activation are still not fully described but several possible mechanisms are discussed below.

Central sensitisation

Accompanying peripheral sensitisation is the phenomenon of central sensitisation. Activation of trigeminovascular nociceptors leads to an increase in activity in the second-order neurons in the trigeminocervical nucleus (Bolay et al. 2002). Furthermore, activation in the trigeminocervical nucleus occurs with stimulation of both meningeal afferents and those from the greater occipital nerve (a branch of the C2 dorsal root), and that stimulation for just 5 minutes can lead to an increase in response in the nucleus for over an hour to other nociceptive stimuli, including if that stimulation is received from the C2 innervation (Goadsby 2005). This is particularly relevant for manual therapy practitioners with their focus on removal of pain generators from the cervical spine. It is likely that this sensitisation involves the activation of NMDA receptors in the nucleus as in vitro application of sumatriptan, an antimigraine drug, is effective in blocking NMDA receptor activation (Buzzi & Moskowitz 2005).

The cutaneous allodynia is often associated with migraine and is thought to be another symptom of this central sensitisation of the trigeminocervical nucleus. The allodynia usually occurs on the ipsilateral forehead to the headache, but has been documented to occur over the ipsi- and contralateral hands as well (Dalkara, Zervas et al. 2006).

Brainstem dysfunction and disinhibition

Brainstem dysfunction has also been implicated in migraine, both as a primary migraine generator, and through failure of brainstem pain inhibition mechanisms. Goadsby (2005) reports activation of the locus ceruleus and periaqueductal grey (PAG) in migraine without aura, and that these correspond to areas that have generated migraine-like symptoms in patients when stimulated electrically. Similarly, Goadsby reports excess iron has been found in the PAG of episodic and chronic migraineurs, and lesions in this area have been known to cause migraine. The notion of brainstem dysfunction is further supported by the presence of measured balance deficits, vestibular changes (Akdal et al. 2007; Akdal et al. 2009; Asai et al. 2009), and subclinical cerebellar deficits in migraineurs (Sandor et al. 2001).

The PAG is involved in descending pain control mechanisms, along with the locus ceruleus and raphae nuclei. In 2001, Knight and Goadsby (2001) published research that suggests that it is dysfunction in the PAG that leads to disinhibition of the trigeminocervical nucleus and hence pain.

The combination of brainstem dysfunction along with balance and cerebellar deficits presents many opportunities for intervention by the functional neurologist. This could also explain the anecdotal reports from clinicians who have found that cerebellar and vestibular rehabilitation programmes are useful in the treatment of migraine.

Mechanisms leading to initial trigeminovascular activation

The brain of the migraineur displays different neurophysiological behaviours to that of the normal individual. Evoked potential and transcranial magnetic stimulation (TMS) studies have shown that the cerebral cortex of the migraine sufferer shows an impaired ability to habituate to sensory stimulation across all sensory modalities (Schoenen 2006; Brighina et al. 2009). This is thought to be due to impaired functioning of inhibitory networks in the cortex, and it has been suggested that this dysfunction occurs in a manner similar to the GABA circuit down-regulation that occurs in sensory deafferentation (Brighina et al. 2009). Interestingly, Brighina et al. (2009) report that repeated trains of TMS have been shown to improve the functioning of the inhibitory networks that could have long-term effects. This is consistent with the functional neurology paradigm that it is possible to improve neuronal functioning by repeated stimulation within the tolerance of fatigue, thereby promoting gene expression, protein synthesis, and thus building plasticity.

It is logical to assume that this inability to habituate to sensory stimulation could predispose the cortex to excitotoxic events, and evidence suggests that this is the case (Dalkara et al. 2006). This is further supported by evidence that there is impaired energy metabolism in migraineurs (Lodi et al. 2006), which will predispose to anaerobic metabolism. Anaerobic metabolism is toxic to neurons and the metabolic by-products associated with it such as lactic acid are able to activate nociceptive fibres. Functional neurological interventions to promote aerobic metabolism and to protect from anaerobic metabolism should be considered by the clinician. Interventions that may be considered include:

• Supplementation with co-enzyme Q₁₀ due to its antioxidant capabilities and involvement in oxidative phosphorylation (Lodi et al. 2006);

• Supplementation with other antioxidants;

• Supplementation with magnesium to reduce the likelihood of activation of NMDA receptors on nociceptive fibres (Lodi et al. 2006);

• Reduction of circulating adrenaline levels as adrenaline reduces the threshold to activation of C fibres via the alpha 1 receptors. Examples may be stress reduction or the reduction of caffeine intake;

• Ensuring good respiratory mechanisms through preservation of the lumbar lordosis and normal rib mechanics;

• Management of autonomic function to ensure optimum vascular supply to the brain; and

• Lifestyle advice to ensure the patient only stimulates their nervous system within the tolerance of fatigue.

It is also thought that the migraineurs have immunological changes that predispose them to the activation of the inflammatory cascade, which in turn leads to the migraine attack. These triggers may be infections, foods, or other environmental factors (Longoni & Ferrarese 2006). Any management plan for the migraineur should include the identification and, as far as possible, the removal of the triggers. Headache diaries including diet and environmental exposures can be useful for identifying the triggers.

Migraine with aura (MWA)

Migraine with aura was previously known as classic migraine.

The International Headache Society (2004) describes MWA as: ‘Recurrent disorder manifesting in attacks of reversible focal neurological symptoms that usually develop gradually over 5–20 minutes and last for less than 60 minutes. Headache with the features of migraine without aura usually follows the aura symptoms. Less commonly, headache lacks migrainous features or is completely absent’ (Box 17.3).

Box 17.3

Diagnostic criteria for migraine with aura

Description

Recurrent disorder manifesting in attacks of reversible focal neurological symptoms that usually develop gradually over 5–20 minutes and last for less than 60 minutes. Headache with the features of migraine without aura usually follows the aura symptoms. Less commonly, headache lacks migrainous features or is completely absent.

Diagnostic criteria

C. Not attributed to another disorder

Adapted from IHS 2004, with permission.

In MWA, the individual suffers reversible focal neurological signs that are known as the aura. In the majority of cases this is followed by a headache consistent with that described in migraine without aura.

The signs and symptoms of the aura vary depending on the area of the brain involved. Almost all of individuals experience visual symptoms (99%), with sensory (31%), aphasic (18%), and motor (6%) symptoms being next most common (Russell & Olesen 1996). This is consistent with the discovery that the occipital cortex more excitable in migraineurs (Aurora et al. 1999). It is thought the aura corresponds to a phenomenon known as cortical spreading depression.

Cortical spreading depression

The aura of MWA is thought to be due to the phenomenon known as cortical spreading depression (CSD) (Hadjikhani et al. 2001). In CSD there is a slow travelling wave of neuronal and glial depolarisation in the cortex, which is followed by a long-lasting suppression of neural activity (Buzzi & Moskowitz 2005). It is accompanied by increases in extracellular ions, neurotransmitter such as glutamate, and a temporary increase in cortical blood flow, which is followed by a longer period of decreased flow. This is also associated with an increase in glucose utilisation in the cortex (Shinohara et al. 1979). This paradoxical finding of decreased neuronal activity in the presence of increased glucose utilisation could, in the author’s opinion, be explained by a shift to anaerobic metabolism in the affected neurons.

The blood flow changes can spread across multiple brain regions independent of vascular territories (Hoskins et al. 2006). These changes in blood flow are due to activation of the trigeminovascular system (the meningeal nociceptive system) by CSD, which is sufficient to cause headache and vasodilation (Bolay et al. 2002), triggering the sensitisation described above.

So what causes CSD to occur? Causes include high concentrations of excitatory amino acids and K⁺ ions, as well as energy failure (Somjen 2001). As mentioned earlier, there is impaired energy functioning in migraineurs, which under stress may fail, triggering CSD. In addition, the aforementioned failure to habituate to repeated sensory stimuli may cause sufficient elevation of excitatory amino acids and K⁺ to initiate CSD (Dalkara et al. 2006). In turn, the CSD causes the activation of the trigeminovascular system leading to the pain and other symptoms of the migraine headache (Fig. 17.1).

Figure 17.1 The factors and processes in migraine. Migraine has a complex pathophysiology where multiple causative factors can predispose the individual to activation of the trigeminovascular system and development of headache symptoms. In migraine with aura (MWA), these factors can trigger cortical spreading depression, which in turn activates the trigeminovascular system.

(from Bolay et al 2002, with permission)

Childhood periodic syndromes

The International Headache Society Classification lists three forms of childhood periodic syndromes that are often the precursor of migraine, namely cyclical vomiting, abdominal migraine and benign paroxysmal vertigo of childhood.

These conditions are more common than is expected, and are most likely underdiagnosed, as primary care providers do not recognise the conditions as being associated with migraine (Al-Twaijri & Shevell 2002). They are generally benign, self-limiting conditions, and hence recognition of the diagnosis can avoid unnecessary testing (Al-Twaijri & Shevell 2002). However they are a common precursor of migraine in adulthood (Cuvellier & Lepine 2010). Hence early identification and treatment of any causative brain dysfunction would be expected to reduce the likelihood of progression to adult migraine.

There is generally an easily uncovered family history of migraine and more classic migraine headaches may coexist, though this may be difficult to elicit in a young child (Al-Twaijri & Shevell 2002; Cuvellier & Lepine 2010). Important clinical features of these attacks are the fact that they are episodic, reversible and stereotypical. Between attacks, the child will be healthy, but will be quite unwell during the attack. There is a large number of possible differential diagnoses that must be excluded before a diagnosis of a periodic syndrome can be made (Cuvellier & Lepine 2010). Many diagnostic possibilities exist for most of the conditions, many of which are beyond the scope of a functional neurologist; therefore, appropriate co-management is required.

Cyclic vomiting

Cyclic vomiting is a syndrome of recurrent and discrete self-limiting episodes of severe nausea and vomiting (Box 17.4). In between episodes, the patient is sign free. There are four stages to the condition. The first is the interepisodic phase. The prodrome phase last on average 1.5 hours and is when the patient first feels the sense of nausea developing. This evolves into the emetic phase when the patient vomits on average 6 times an hour, with an average phase length of 41 hours. It is accompanied by marked autonomic signs. The recovery phase lasts around 6 hours and starts when the nausea ends and ends with the return to normal function. Girls are more affected than boys. The average age at diagnosis is 6; however, it can occur at any age (Cuvellier & Lepine 2010).

Box 17.4

From IHS 2004, with permission.

¹ In particular, history and physical examination do not show signs of gastrointestinal disease.

Current evidence suggests the condition is due to dysregulation of central neural pathways involved in nausea and vomiting. Other pathogenic factors with evidence are autonomic, gastrointestinal, mitochondrial, and central neuroendocrine conditions (Cuvellier & Lepine 2010).

Precipitating factors should be avoided; chocolate and cheese are often found to be triggers. Support of mitochondrial function may be helpful, in addition to a functional neurological assessment.

Abdominal migraine

Abdominal migraine has a childhood prevalence of 2.4–4.1%, and is more common in girls. The average age of onset is 7 years old, and it has peak prevalence at 10 years of age. There is usually a family history of migraine. The sufferer is healthy between attacks, but is very unwell during the attack. Weeks or months may separate the attacks (Cuvellier & Lepine 2010).

The symptoms are acute onset, recurring, midline abdominal pain, usually non-colicky, though 22% can be colicky. The attack may be preceded by an aura (Box 17.5). It usually lasts for hours and occurs with flushing, anorexia, pallor, dark shadows under the eyes, and possibly photophobia. Triggering events can include stress, exhaustion, some foods, and motion sickness (Cuvellier & Lepine 2010).

Box 17.5

From IHS 2004, with permission.

¹ In particular, history and physical examination do not show signs of gastrointestinal or renal disease or such disease has been ruled out by appropriate investigations.

The pathophysiology of abdominal migraine has not been well studied. Proposed hypotheses include autonomic instability, hypothalamo-pituitary-adrenal disturbances, mitochondrial and ion channel disorders (Cuvellier & Lepine 2010).

Non-pharmaceutical treatment options include avoidance of triggers, including foods that the family feels initiate attacks (Cuvellier & Lepine 2010). In the few cases the author has seen, saccadic eye movements, particularly in the planes of movement facilitated by the semicircular canals, have been effective in reducing attacks. This is probably due to the increased frontal cortex and brainstem activation that results, improving the central integrative state of autonomic centres.

Benign paroxysmal vertigo of childhood

Vertigo and dizziness are relatively rare in children, and many of the common adult conditions causing it are rare in children. Posterior fossa tumours are more common in children, and may present with vertigo. Benign paroxysmal vertigo of childhood is considered to be a common cause of vertigo in children (Box 17.6). It is more common in girls and the average age of onset is 2–4 years of age (Cuvellier & Lepine 2010). Forty-three per cent have a family history of migraine, and 13% go on to develop migraine (Ralli et al. 2009).

Box 17.6

Diagnostic criteria for benign paroxysmal vertigo of childhood

Description

This probably heterogeneous disorder is characterised by recurrent brief episodic attacks of vertigo occurring without warning and resolving spontaneously in otherwise healthy children.

Diagnostic criteria

A. At least five attacks fulfilling criterion B

B. Multiple episodes of severe vertigo ¹, occurring without warning and resolving spontaneously after minutes to hours

C. Normal neurological examination; audiometric and vestibular functions between attacks

D. Normal electroencephalogram

From IHS 2004, with permission.

¹ Often associated with nystagmus or vomiting; unilateral throbbing headache may occur in some attacks.

The vertigo lasts from a few seconds to several minutes, though rarely it may last hours, and has a sudden onset not related to position or movement. Nystagmus may be present during the attack. Audiology and EEG are normal (Ralli et al. 2009).

The pathogenesis is not known. Various authors have suggested peripheral and/or central vestibular dysfunction, but the findings of vestibular testing have not consistently borne this out (Cuvellier & Lepine 2010).

Cluster headache

Cluster headache (CH) is one of the trigeminal autonomic cephalgias, along with paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). CH is characterised by unilateral attacks of head pain with ipsilateral craniofacial autonomic disturbances (Box 17.7) (Leone & Bussone 2009).

Box 17.7

Diagnostic criteria for cluster headache

Description

Attacks of severe, strictly unilateral pain which is orbital, supraorbital, temporal, or in any combination of these sites, lasting 15–180 minutes and occurring from once every other day to eight times a day. The attacks are associated with one or more of the following, all of which are ipsilateral: conjunctival injection, lacrimation, nasal congestion, rhinorrhoea, forehead and facial sweating, miosis, ptosis, eyelid oedema. Most patients are restless or agitated during an attack.

From IHS 2004, with permission.

CH is relatively uncommon, with a lifetime incidence of 124 per 100 000 (Leone & Bussone 2009). CH can either be episodic or chronic. The episodic form is described as two or more periods lasting between 7 days and 1 year, with pain-free periods of at least 1 month. The chronic form is described as attacks that occur for more than 1 year or with pain-free periods of less than 1 month. Chronic CH may occur as a primary headache or can evolve from the episodic form (IHS 2004). CH has been found to have a genetic component, with the condition being more common in first- and second-degree relatives. DNA mutations in the mitochondria have also been suspected (Leone & Bussone 2009).

CH can be triggered by alcohol, though usually only during the cluster period, as well as by volatile substances like oil paints and solvents. Sleep and travelling across time zones can also trigger CH (Cohen et al. 2007).

Pathophysiology of cluster headache

There is debate around whether the source of CH is peripheral or central. Several features of the condition suggest a peripheral mechanism, with researchers finding raised venous level of calcitonin gene related peptide, thought to suggest peripheral inflammation. However, this is not unique to CH (Leone & Bussone 2009). Likewise, changes in blood flow due to trigeminovascular activation found in CH were found to be secondary to the pain, rather than the cause of it (Bussone 2008). CH can also be a secondary phenomenon due to intracranial lesions, and removal of the lesion usually removes the headache, and this lends support to the peripheral hypothesis (Leone & Bussone 2009).

Neuroimaging studies of CH patients have found that the ipsilateral posterior hypothalamus is activated in CH (Leone & Bussone 2009). The hypothalamus is primarily concerned with homeostasis and is involved in hormone synthesis, autonomic nervous system regulation, temperature control, behaviour, circadian rhythms, and arousal (Bussone 2008). The circadian nature of CH, the relationship with sleep, and the autonomic symptoms all point to the involvement of the hypothalamus in CH (Holland & Goadsby 2007). It is also involved in nociceptive regulation with pathways connecting both directly with the trigeminocervical nucleus (Leone & Bussone 2009) and indirectly via the periaqueductal grey, the raphae nuclei, and the locus ceruleus (Holland & Goadsby 2007).

It has been suggested that the hypothalamus is not the trigger of the attack but that it balances the various factors that allow for the development of the attack, and that dysfunction in it may allow for the factors to be out of balance (Holland & Goadsby 2007). Hypothalamic stimulation has been shown to be effective for CH. However, it takes weeks to months to have an effect, and it has no effect in the acute period. It has been suggested that its mechanism of action may not be through the activation of the hypothalamus itself, but through the activation of its connections, namely the pain matrix areas. The long-term stimulation may raise the levels of the metabolism in the hypometabolic areas described below (Leone & Bussone 2009). This is consistent with the functional neurology model.

Neuroimaging has also shown other parts of the pain matrix including the anterior cingulate, contralateral posterior thalamus, ipsilateral basal ganglia, bilateral insulae, and cerebellar hemispheres are activated in CH attacks (Leone & Bussone 2009). A PET study found decreased glucose utilisation (hypometabolism) in the prefrontal, orbitofrontal, and perigenual anterior cingulate cortices both during the headache period and out of it, and hypometabolism in the cerebellopontine area during the headache period. It has been suggested that there is a deficiency of top-down modulation of nociceptive circuits in CH sufferers, which leads to inadequate control of trigger mechanisms, thereby promoting the headache periods (Sprenger et al. 2007).

Thus it is likely that CH is a multifactorial condition with failure of cortical and brainstem pain control, as well as hypothalamic systems that leads to an imbalance of pro- and anti-nociceptive inputs regulating the trigeminovascular system.

Treatment of cluster headache

There are several pharmaceutical treatments for CH. Subcutaneous sumatriptan has a rapid effect and high success rate during an attack (Cohen et al. 2007).

For the functional neurologist, inhalation of 100% oxygen at 7–12 L/min via a nonrebreathing face mask is rapidly effective for most sufferers in the acute attack (Cohen et al. 2007). Oxygen has been shown to have a direct effect on the inhibitory projections from the brainstem to the central pain pathway (Bussone 2008).

Interestingly greater occipital nerve block has been shown to be effective in aborting a period of CH (Cohen et al. 2007). This presumably occurs due to decreased nociceptive drive into the trigeminocervical nucleus, which may suggest that manual cervical spine therapies may also be effective.

Tension-type headache

Tension-type headache (TTH) is one of the most common headache disorders, with an average lifetime prevalence of 46%. Children may be affected, but the peak incidence is 40–49 years of age. Females are slightly more affected than males, and become more so as chronicity increases (Loder & Rizzoli 2008).

The pain of TTH is usually mild to moderate, pressure or muscle type pain lasting hours to days with no neurological or constitutional symptoms. It is usually bilateral and may extend into the neck (Box 17.8). Patients often only begin to seek care as the severity and frequency of the headache increases (Loder & Rizzoli 2008).

Box 17.8

Diagnostic criteria for tension-type headache

Description

Infrequent episodes of headache lasting minutes to days. The pain is typically bilateral, pressing or tightening in quality and of mild to moderate intensity, and it does not worsen with routine physical activity. There is no nausea but photophobia or phonophobia may be present.

Diagnostic criteria

A. One of the following, and fulfilling criteria B–D

1. Infrequent TTH. At least 10 episodes occurring on <1 day per month on average (<12 days per year)

2. Frequent TTH. At least 10 episodes occurring on ≥1 but <15 days per month for at least 3 months (≥12 and <180 days per year)

3. Chronic TTH. Headache occurring on ≥15 days per month on average for >3 months (≥180 days per year)¹

B. Headache lasting from 30 minutes to 7 days

C. Headache has at least two of the following characteristics:

1. bilateral location

2. pressing/tightening (non-pulsating) quality

3. mild or moderate intensity

4. not aggravated by routine physical activity such as walking or climbing stairs

D. Both of the following:

1. no nausea or vomiting (anorexia may occur)

2. no more than one of photophobia or phonophobia

E. Not attributed to another disorder ¹

Adapted from IHS 2004, with permission.

¹ History and physical and neurological examinations do not suggest any of the disorders listed in groups 5–12 of the classification, or history and/or physical and/or neurological examinations do suggest such disorder but it is ruled out by appropriate investigations, or such disorder is present but headache does not occur for the first time in close temporal relation to the disorder.

Pathophysiology of tension-type headache

The pathophysiology of TTH has still not been fully described but the involvement of peripheral and central mechanisms has been recognised (Speciali et al. 2008). It is thought likely that the infrequent form of TTH is primarily due to peripheral mechanisms, with central mechanisms coming to bear in the frequent and chronic forms of the condition (Bendtsen & Jensen 2009).

The main model for TTH is that tender/trigger points in peripheral muscles produce nociceptive activation, which in time will cause central sensitisation. Trigger points are hyperirritable spots within a tight band of muscle that are painful to compression, and produce referred pain in a site distant from the spot (Simons et al. 1999). Trigger points can arise from a variety of causes including psychological stress and biomechanical dysfunction, and it has been shown that trigger points can cause peripheral sensitisation of muscle nociceptors (Fernandez-de-las-Penas et al. 2007). Furthermore, trigger points and postural changes are more common in headache sufferers (Marcus et al. 1999). Hence it is likely that, at least in infrequent TTH, myofascial factors are the likely cause of pain.

In chronic forms of TTH, three aspects may come into play. Sensitisation of second-order neurons in the trigeminocervical nucleus, sensitisation of suprasegmental neurons, and decreased activity in anti-nociceptive systems could all contribute to myofascial pain and tenderness (Bendtsen 2000). It is possible that the persistent peripheral sensitisation caused by trigger points could lead to central sensitisation occurring (Fernandez-de-las-Penas et al. 2007), as research has shown that persistent peripheral nociceptive input leads to input in the trigeminocervical ganglion (Goadsby 2005).

Studies of sensitivity to stimuli (pressure, thermal, and electrical) have found that chronic TTH sufferers have lowered thresholds, not only in the cranium, but in the periphery as well. The generalised nature of these changes indicate that the sensitisation is central rather than peripheral (Bendtsen 2000).

Prolonged activation of second-order nociceptive neurons can cause the activation of NMDA receptors. Once activated, the magnesium plug is removed from the receptor, and there is a calcium influx into the cell. This initiates a process of cellular events that can lead to long-term changes and lowered threshold to activation in the neuron. As the excitability of the neuron increases, it may become sensitive to mechanical stimuli, rather than simply nociceptive, which manifests clinically as allodynia (Bendtsen 2000).

Failure of descending pain inhibitory mechanisms will also contribute to central sensitisation. Structures such as the periaqueductal grey, the raphae nuclei, and the locus ceruleus act to regulate nociceptive transmission. Decreased output from these may in turn bring the lower-order neurons closer to threshold, making subsequent excitation and plasticity easier to achieve. Studies have shown cerebellar/brainstem dysfunction and changes in TTH sufferers including deviation of subjective visual vertical (a vestibular/otolithic sign) (Asai et al. 2009), increased sway in stabilometry (Ishizaki et al. 2002), and an increased reliance on vestibular inputs in posture control (So & Bent 2009).

In addition, TTH sufferers show the same volumetric brain changes seen in many chronic pain conditions. These changes are in the regions of the brain known to be involved in pain processing, namely the cingulate cortex, insula, and the orbitofrontal cortex and parahippocampus bilaterally. These changes are also seen in conditions such as irritable bowel syndrome, chronic back pain, and fibromyalgia. The changes correspond with the duration of chronic pain, so it is likely they are the consequence, rather than the cause of the chronic pain (May 2009).

Treatment of tension-type headache

Treatment of infrequent TTH should focus on removal of pain generators in the periphery and the removal of any triggering factors such as psychological stress, postural aberrancies, etc. Pain generators may include myofascial tenderness and trigger points. Ischaemic compression-type trigger point therapy has been found to be effective in treating trigger points (Simons et al. 1999). Some studies have found cervical spine manipulation to be effective in treating TTH, but this is yet to be replicated in a randomised, controlled trial. Other therapies such as acupuncture, ultrasound, and stretching may also be effective.

In the frequent and chronic forms of TTH, it is certainly reasonable to remove the peripheral pain generators, as they may be contributing to central sensitisation. Nutritional therapies such as magnesium supplementation to decrease NMDA receptor activation, and omega 3 fatty acids to minimise peripheral inflammation should also be considered.

Brainstem, cerebellar, and cortical influences should all be assessed. Dysfunction in any of these areas could have consequences for descending pain inhibition mechanisms. The author’s personal experience is that vestibulocerebellar and cortical stimulation can have a normalising impact on nociceptive sensation in the C2 and trigeminal distributions. Such stimulation can be applied according to the principles outlined in this text.

Conclusion

The primary headaches offer many therapeutic opportunities for functional neurologists and their patients. With a thorough understanding of the pathophysiology and the discrete brain areas involved, functional neurologists can develop therapeutic regimens to affect the oxygenation, fuel supply, and activation of the dysfunctional areas, leading to an improvement in the patient’s symptoms.

Clinical case answers

Case 17.1

17.1.1

The most likely form of headache in this case is Migraine without aura. The clinical features of more than five attacks lasting more than 4 hours, unilateral headache, severe pain intensity, and avoidance of usual activities, along with phono- and photophobia are consistent with the International Headache Society’s criteria. Clinical examination, and possibly neuroimaging, is required to exclude any other cause.

17.1.2

Allodynia is the sensation of pain from a stimulus that does not normally cause pain. Hyperalgesia is a greater than normal sensation of pain from a stimulus that is normally painful. This patient’s symptoms of tenderness to touch over the scalp are consistent with allodynia. Touch does not normally cause pain: therefore the scalp tenderness cannot be hyperalgesia.

17.1.3

Hyperalgesia can occur as a result of peripheral or central sensitisation or both. In peripheral sensitisation, neurogenic inflammation makes nociceptive nerve fibres easier to activate. In central sensitisation, second-order neurons in the trigeminocervical ganglion become easier to fire. This may occur due to loss of inhibition from GABA interneurons within the nucleus or decreased inhibition from higher structures like the periaqueductal grey, raphae nuclei, and the locus ceruleus. Also NMDA receptor activation on first- and second-order neurons in the nucleus can lead to plasticity (hence increased efficiency) in the neurons. Finally, convergent projections on second-order neurons can also build plasticity, i.e. greater occipital nerve (C2 nerve root) stimulation decreases the threshold to activation of second-order neurons to stimulation from trigeminal nociceptive afferents.

In allodynia, GABA interneuron inhibition of mechanoreceptor activation of second-order pain neurons is decreased or lost. In this situation, mechanical stimuli that are not normally painful (i.e. touch) can cause activation of second-order nociceptive neurons resulting in pain.

Case 17.2

17.2.1

Abdominal migraine.

17.2.2

It was felt likely that this boy was suffering from left cerebellar/pontomedullary and right cortical dysfunction. It was thought the abdominal symptoms were due to the pontomedullary dysfunction on the left. Abdominal neurological regulatory centres are located in this region.

17.2.3

Your treatment may vary but in this case treatment consisted of saccadic eye movements in the plane facilitated by the left anterior and posterior canals, with a pause for 3 seconds fixating at the end of each saccade performed five times, twice a day. The saccadic movements will utilise the frontal lobes bilaterally, but the addition of fixation (focused attention) further increases activity in the right frontal lobe. Using the left canal plane will increase activity in the brain areas facilitating these movements. After a few weeks, the same exercise in the plane facilitated by the right anterior and posterior canal was added. Spinal manipulation using an Activator™ adjusting instrument was performed on the lumbar and cervical spine. After five treatments he was symptom free and his optokinetic and pursuit eye movements were greatly improved.

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