Nummular Headache - a Case Report of a Rare Entity

The purpose of this manuscript is to shed light on systematic work-up of a diagnostic challenge such as nummular headache (NH), and to summarize the relevant literature on NH. The specific nature of the shape of the pain site is usually characteristic of NH. Multiple modalities of investigation including succinct imaging are necessary to successfully rule out other similar conditions. A 26-year-old female patient of Asian-Indian origin presented to the clinic with the chief complaint of chronic persistent left parietal headache for more than 10 years, which has been worsening over the past few days with no specific identifiable trigger. The diagnosis of nummular headache is challenging and confusing due to the rare occurrence and inadequate references in the literature. Appropriate imaging was done, which revealed no pathology that could explain the headache presentation. These findings are consistent with our diagnosis of nummular headache, and helped in the successful management of the case.

an intensity of 4 on a numerical pain scale (NPS) of 0-10. The episodic exacerbations were "pressure-like, sharp, and oppressive," the intensity of 8 on an NPS. There was no specific pattern to the paroxysmal exacerbations. The patient reported allodynia and dysesthesia in the same area. Symptoms occasionally switched to the opposite side. When it changed sides, the non-affected side was completely normal. When severe, which was often, the pain was nearly debilitating.
Temporal Pattern The temporal pattern was chronic progressive.
Aggravating Factors No aggravating factors were reported.
Relieving Factors Alleviating factors reportedly included rest and sleep. Over the counter, non-steroidal anti-inflammatory drugs (NSAIDs) had minimal effect.
Associated Features There were no associated features such as tearing, eye irritation, or edema with the exacerbation of pain.

Radiation/Referral
The pain was felt within the wellcircumscribed area and had no referral or radiation characteristics.
Sleep The patient reported that the pain neither woke her up, nor did she report routinely waking up with the pain.
Treatment History The past investigations included only a magnetic resonance imaging (MRI) scan of the brain without contrast, ordered 1 year earlier. There were no apparent abnormalities in the MRI report, and images were irretrievable. The patient had not been prescribed any medications thus far for this headache.
Medical History The medical history of the patient was noncontributory. The only positive history was that of migraine without aura since she was 12 years of age. The patient was able to distinctly differentiate between migraine pain and the current presenting pain symptoms. She also reported a fall from a flight of stairs approximately 10 years ago. No clinical or imaging evidence of concussion or brain injury were reported.
Clinical Examination Findings A comprehensive clinical evaluation was done with respect to the chief complaint. A cranial nerve screening elicited no obvious abnormalities. The patient's mandibular and cervical range of motions was within normal limits. Musculoskeletal examination of the head and neck revealed no discernible pathology. Testing at the site of pain (attempt to reproduce the pain locally) elicited allodynia and dysesthesia over a well-circumscribed 3-4 cm diameter area of the scalp over the left parietal bone. There were no other foci of pain; the contralateral side was completely normal. There were no changes in the color, texture, or quality of scalp tissue within the elliptical area of the pain. There were no trophic changes.

Discussion
Definition NH can be broadly defined as a primary headache disorder that affects a well-circumscribed, round, or oval area of the scalp, not attributed to any other disorders.
Classification IHS ICHD-3 4.8 and 4.8.1 Synonyms Circumscribed cephalalgia, circumscribed headache, coin-shaped headache, and epicranial headache Etiology and Pathophysiology In the latest classification, the International Headache Society (IHS) has included NH under primary headache and also describes a second related diagnosis of "probable NH" [3]. Similar to other primary headaches, the pathophysiology of NH is uncertain [4]. An interesting entity called secondary NH of varying etiologies [5•] ranging from head trauma [6, 7•], infection [8], post-surgery [7,9,10•], intracranial lesions [11,12], to insect sting [13••] has been suggested in the literature. There has been some suggestion that NH may be neuralgia of a terminal branch of the trigeminal nerve [14]. Others have postulated that NH might be a non-generalized disorder with sensitization restricted to the painful area [15]. There are some reported cases which indicate the presence of underlying aneurysms of the superficial arteries of the scalp causing secondary NH [16]. The presence of autoimmune biomarkers has been reported in primary NH cases [11] although no definitive association has been established. When other primary headaches occur comorbid with NH, the temporal and spatial characteristics have been reported to be independent of the NH pain [1••]. Both peripheral and central mechanisms have been proposed in the pathophysiology of NH [5•]. The peripheral mechanisms have been proposed to be responsible for such features of NH as topography, trophic changes, sensory changes, hyperalgesia, and response to locally injected medications such as botulinum toxin [5•]. Central mechanisms have been proposed to be responsible for such features as an extension of the painful area across the midline, multiple foci of headache, and ineffectiveness of local nerve block [5•].
One of the most comorbid conditions reported with NH is migraine [17•]. As alluded to earlier, autoimmunity and autoimmune disorders may be a comorbidity for NH. Lesions of the skull [12,18] or glands such as the pituitary [19] have been reported to co-exist in patients with NH. Literature suggests some association of NH with rare entities such as osteomyelitis of the cranium [1••, 20•] and complex regional pain syndrome (CRPS) of the scalp [2•, 20•]. Comorbidities of NH appearing in the literature also include bipolar disorder, anorexia, and depression [21••, 22, 23].
Epidemiology A very low incidence of NH has been reported in the literature [24]. The prevalence reported in the limited literature is 1.25% of all headache patients [25]. An overall prevalence of 5-6% has also been reported [20•, 26]. As of date, approximately 300 cases of NH have been reported [27]. The female to male predilection ratio has been variably reported as ranging from 2:1 to 1:1 [4,26,28]. There is a reported wide range of age of onset, with a mean of 45 years [27, 29•].

Clinical Presentation
Onset Although we could not find succinct references on the routine onset pattern of primary NH, it is usually described as slow as opposed to the secondary variant [30].
Location Location is classically described as the oval or round area of the scalp, approximately 0.5 to 4 in. in diameter, with well-delineated borders in most cases [31]. A site predilection of the parietal region of the scalp has been reported; it might also be present in the occipital, frontal, vertex, temporal region, or multiple sites [29•]. NH pain is mostly unilateral, with a right-side predilection, with a few left side cases and even fewer crossing the midline [27]. The location of the pain is usually single, and in much fewer cases at multiple foci [32]. The position of the foci of the pain may change, and when it does, the non-affected side(s) may or may not be normal [26,32,33].
Frequency The frequency of attacks has been described as intermittent (multiple attacks a day), variable, or continuous [21••, 27, 34].
Duration A continuous background pain with occasional exacerbations of severe pain has been reported [1••, 24, 26]. These exacerbations range from seconds to hours [3].
Intensity The intensity of the pain is usually described as mild to moderate. On occasions, it can be severe.
Quality The quality of the pain described by patients having NH is usually sharp, stabbing, and pressure-like [26,27]. One feature that is more commonly observed across the studies is that NH is "oppressive" in terms of quality [4, 21••].
Temporal Pattern The temporal pattern ratio for chronic to episodic is 2:1 [21••, 27]. Unlike migraine, the conversion of episodic to chronic is rare [17, 21••, 24]. A circadian occurrence of NH is also reported [27,31]. Spontaneous remissions up to 6 months or persistent remissions have been described in the literature [32].
Aggravating Factors NH does not have any aggravating factors. However, the exacerbations can be spontaneous or triggered by light tactile stimulus [21••].

Relieving Factors
No relieving factors except professional intervention have been mentioned in the literature.

Associated Features
The affected area commonly may show a variety of characteristics, including allodynia, hyperesthesia, dysesthesia, paresthesia, and/or tenderness [3]. There have also been reports of subtle temperature changes in the NH affected area compared with the unaffected areas [35]. Trophic changes have been reported in a few cases of NH [13]. Usually, with NH, there are no associated features like nausea, vomiting, light, or sound sensitivity. NH is typically not associated with autonomic features; however, rare cases of NH occurring with lacrimation and rhinorrhea have been reported [6]. There have been occasional reports of NH seemingly mimicking features of migraine, especially when the former occurs in relation to menstruation [36]. A specific but distinct entity called cephalalgia alopecia has been described in the literature as very similar to NH, but different in that the former shows different characteristics such as trophic changes (hair loss) pain quality (burning and stabbing) and pain in the associated areas (such as neck pain) [37].
Radiation or Referral Classic description of NH is that of an entity of well-circumscribed nature.
Lab Investigations and Imaging The diagnosis of NH is primarily by clinical features (well-circumscribed pain area) and the elimination of any underlying disease. It hence could be prolonged and challenging even for the seasoned clinician. A comprehensive search of the literature for guidelines and standards of care failed to reveal an absolute resolution to the question of what exact investigations should be conducted to "rule in" NH. We often found articles that were seemingly cross-quoting each other with no definitive standard of care, but suggestions and guidelines. Laboratory studies that are recommended include metabolic panel, complete blood picture, liver and thyroid function tests; alkaline phosphatase, autoimmune panel, and urinalysis [2•]. Several articles allude to how MRI is more sensitive than computed tomography (CT) and hence recommended to rule out secondary causes especially for evaluation of chronic headache presenting without neurologic symptoms [38•, 39-41]. Some cardinal articles have strongly recommended the use of MRI with gadolinium contrast as superior to any other technique or imaging due to the fact that MRI can pick up subtle tissue changes that might be missed in other forms of imaging [9]. Other investigative procedures such as Doppler ultrasound/angiography (to rule out superficial aneurysm) [16] and biopsy (when trophic changes are observed) [13] have also been suggested in the literature.

Management Options
Published clear guidelines/directions for managing NH patients were not found in the literature [2•]. The suggestions included varied modalities ranging from over the counter (OTC) NSAIDs to botulinum toxin and surgery. As for many primary headaches, modalities established include abortive, preventative, and adjunctive therapies.
Abortive Pharmacotherapy Although there are no medications that strictly fit the class of abortive medications, treatment by such medications as gabapentin could be considered abortive when used long term.
Preventive/Prophylactic Pharmacotherapy For preventive therapy, the first choice and the most robustly written up drug in terms of efficacy for NH is usually gabapentin with slow titration [2•, 7•, 14]. A recent narrative review suggests that out of the class of antiepileptic medications, gabapentin seems to be the most efficacious [48]. The moderate success has been reported with NSAIDs/indomethacin [2•, 6]. Moreover, other drugs such as amitriptyline, topiramate, carbamazepine, oxcarbazepine, lamotrigine, valproic acid, pregabalin, oral steroids, and opioids have also been reported with varying but much lesser effectiveness [4, 7•, 26, 27, 49]. Beta-blockers have been used by some clinicians with apparent good pain relief in a few cases [48]. Some articles have suggested a trial of triptans [16,34] followed by superficial angiography and ultrasonography of the superficial scalp blood vessels [16]. The effectiveness of local anesthetic nerve blocks such as auriculo-temporal and occipital nerve blocks [49] and local anesthetic subcutaneous injections has been deemed questionable [2•, 6, 7•, 27].
For patients who have insufficient benefit with orally administered drugs, or who are intolerant to such drugs, or who have refractory NH, botulinum toxin type A injection may be an effective alternative treatment [31,50,51].
Surgical There has been some mention in the literature of surgical removal of an artery that supplies the location of the pain [52]. However, we could not find an explanation of why arterectomies are performed in cases where local anesthetic blocks of the peripheral sensory nerve rendered "invariable success" in terms of complete pain relief.
Adjunctive Successful treatment with transcutaneous electrical nerve stimulation (TENS), in a case of NH without trophic changes has also been reported [21••, 22, 49]. In NH patients (otherwise healthy; without trophic changes), where conventional pharmacotherapies have been tried, and local nerve blocks and other therapies give only short-term or partial relief, a newer therapy-like subcutaneous peripheral nerve field stimulation may be considered [22]. Level A evidence has been reported for adjunctive therapies such as cognitive-behavioral therapy (CBT), biofeedback, and relaxation techniques in the management of primary headaches [53]. No published article was found relating to the use of these therapies in NH.

Lab Investigations/Imaging
Complete blood work including complete blood count (CBC) with differential, clotting factors, comprehensive metabolic panel, vitamin panel including vitamin A, B 3 , B 6 , B 12 , C, D 3 , folate, anti-Ro/SSA (SSA) and La/SSB (SSB) antibodies, anti-nuclear antibodies (ANA), rheumatoid factor (RF), and thyroid panel was ordered. All these results were normal. A thorough neurological examination was also performed, which failed to show any related abnormalities.
A new MRI of the brain and brainstem, with and without contrast, failed to reveal any pathology. However, there was an incidental finding of a well-circumscribed area in the left sphenoid sinus. A subsequent CT scan confirmed this finding. Upon consultation with an ear-nose-throat (ENT) surgeon, any association of a headache with the pathology was deemed questionable.
Nonetheless, surgical intervention in the sphenoid sinus was performed, resulting in the removal of a "fungal ball." There was no change in the headache pattern.

Working Diagnosis and Differential Diagnosis
Following the IHS, ICHD-3 criteria, the differential diagnosis included primary idiopathic stabbing headache, underlying epicranial anomalies, epicranial headaches, metastatic lesions of the cranial bones, infectious lesions of the cranial bones, and nummular headache. Considering the specific clinical features, the possible differential diagnoses of headache attributed to intracranial fungal or other parasitic infection in the cranium (ICHD-3: A 9.1.3), and persistent headache attributed to past intracranial fungal or other parasitic infection (ICHD-3: A 9.1.3.3) were ruled out. Thus, based on the patient's history, clinical findings, and diagnostic imaging, a final diagnosis of NH was made.

Clinical Presentation in the Context of Literature
Mode of onset, i.e., slow, in our patient's case, is consistent with the literature. There is an apparent association in this case with the pain initiation subsequent to a possible trauma (fall). The age of onset of our patient is 16 years, inconsistent with the mean age of onset of 45 years. Location of her pain is the left parietal region, whereas site predilection, according to the literature, is the right side. Her description of occasional switching of the sides of pain and elliptical shape of the painful area is also consistent with current literature. The patient's description of the quality of the headache is "oppressive/debilitating," goes along with the most published articles. The background nature of pain with occasional bursts of severe pain and association with migraines also are reported in the NH literature.
There are varying reports of sphenoid sinus pathologies, and the treatment for the same, being associated with NH. Our patient coincidentally had a fungal ball removed from her sphenoid sinus. It is worth noting that this surgical procedure did not change any characteristics of the pain.

Management
A trial of gabapentin starting from 300 mg twice daily, titrated up to 900 mg per day, did provide pain relief. However, the patient voluntarily stopped the medication due to significant reported side effects. Currently, the patient is reportedly tolerating the headache with pain intensity 2/10 on an NPS with NSAIDs and non-pharmacological approaches, including CBT, yoga, and meditation.

Conclusion
A comprehensive history is the first step in achieving an accurate diagnosis of NH. Successful diagnosis and management of this condition are challenging and confusing even for a seasoned clinician, due to the rare occurrence, scanty literature, and hence limited knowledge of this disorder. An examination must include imaging as it is essential in eliminating other underlying pathologies. The diagnosis is made from distinct clinical features after the exclusion of all other possible entities. Along with pharmacotherapy, adjunctive therapies should also be considered.
From a patient's perspective, it is truly frustrating to having to consult multiple providers and undergo multiple investigations. Our patient was glad to finally have a diagnosis, pain relief, and above all, relief from the stress of the possibility of having something ominous. The reassurance was given by us clinicians, with regard to the fact that this was not a psychogenic pain, also meant the improved quality of life for the patient.