Abstract
Idiopathic stabbing headache (ISH) is defined as the occurrence of short-lasting, painful jabs, restricted to the ophthalmic division of the trigeminal nerve. It is closely related to other forms of headache (such as migraine and tension-type headache) and has been reported among all age groups, including children and adolescents. As pathogenic mechanisms of the disease remain unclear, management decisions are empirical and limited to few options. Classically, indomethacin has been considered the first option, but therapeutic failure occurs in up to 35% of cases. In this setting, we report four patients with young-onset indomethacin-resistant ISH which had good responses to gabapentin and discuss the use of this drug in the presenting situation.
Introduction
Idiopathic stabbing headache (ISH) was first described by Lansche in 1964 as ‘ophthalmodynia periodica’ (1) and lately included as a separate entity in the classification of the International Headache Society (IHS) (2).
It is a paroxysmal disorder manifested by transient painful stabs, exclusively or predominantly felt in the distribution of the ophthalmic division of the trigeminal nerve. Epidemiological studies demonstrated that it occurs frequently and about 32.5% of an adult healthy population in Norway presented such paroxysms of pain (3). Previous reports have identified ISH in both normal and headache-prone adults (mainly affected by tension-type headache or migraine). However, recent papers have observed similar complaints in paediatric and adolescent populations (juvenile ISH) (4, 5).
Pathogenic mechanisms of this condition remain largely unknown, making therapeutic decisions empirical and sometimes challenging. Indomethacin has been traditionally seen as the first-line option, but failure occurs in up to 35% of cases so that novel treatment possibilities are clearly needed (6).
We report four patients with young-onset ISH attending the Headache Clinic at University Hospital, which were indomethacin-resistant but had remarkable responses to gabapentin (GBP).
Case reports
Case 1
A 21-year-old woman presented to the neurological unit complaining of intense stabbing headaches in the last 3 years. These attacks lasted fractions of a second and occurred two to three times every day, exclusively on frontal regions. Between episodes, the patient was completely free of pain. There was a previous history of migraine without aura since the age of 12 years and benign partial epilepsy with centro-temporal spikes already treated. Neurological examination and cranial magnetic resonance imaging with thin slices of skull base and angioresonance (complete MRI) revealed no abnormalities. She was then prescribed indomethacin 50 mg t.i.d. for 10 days but there was no relief. Rofecoxib 25 mg b.i.d. for 10 days led to a 50% decrease in pain frequency. Finally, GBP 400 mg b.i.d. was started, leading to complete pain relief in the first week, which remained during the following 6 months, when treatment was stopped and no recurrence was observed.
Case 2
A 31-year-old woman presented with daily attacks of disabling ice-pick-like pain over the last 6 years. These attacks recurred irregularly (once to 10 times every day) and were felt at different points of the scalp (vertex, frontal and temporal regions). They lasted about a second (according to the patient, ‘the time of an eye blink’), often being accompanied by local ‘shocks’. The patient did not suffer from any other type of primary headache but took hormonal replacement therapy for hypothyroidism. Her neurological examination was entirely normal and complete MRI showed only a small arachnoid cyst in quadrigeminal lamina (without signs of local compression). Indomethacin (50 mg three times per day for 10 days) and rofecoxib (25 mg twice per day for 10 days) were tried without improvement. Later, GBP 400 mg twice a day was introduced, and by the end of the second week pain was no longer noticed. This excellent response persisted for the next 6 months when GBP was suspended without return of symptoms.
Case 3
A 20-year-old woman developed severe headaches over the previous 2 years. The patient reported very brief episodes of pain (lasting about 1 s), resembling stabs, limited to periorbital regions and occurring mostly on the left side (70% of the time). She had around four pain attacks every day without accompanying symptoms. No association with other headaches was identified, and both neurological examination and complete MRI were normal. Indomethacin 50 mg t.i.d. for 10 days and later rofecoxib 25 mg b.i.d. for 10 days were prescribed without improvement. GBP 400 mg b.i.d. was then started and the attacks ceased entirely within 10 days. Six months later, treatment was interrupted and pain did not recur.
Case 4
A 18-year-old woman presented with a 6-year history of sharp ‘lightning’-like headaches, which occurred in paroxysms that lasted fractions of a second and were felt predominantly in the anterior regions of the scalp. These episodes occurred three to four times every day and were so intense that the patient would cry out. She had seen several neurologists and tried multiple medications (including serotonin reuptake inhibitors, flunarizine and propranolol) without success. Her past medical history was unremarkable except for early puberty hormonally treated between the ages of 4.5 and 11 years. Neurological examination and complete MRI were also normal. She was initially given indomethacin 50 mg t.i.d. for 10 days but no improvement was observed. Rofecoxib 25 mg b.i.d. for 10 days was then given, which reduced by 50% the frequency of pain attacks. GBP 400 mg b.i.d. was introduced and 3 days later the patient became asymptomatic. Treatment was not interrupted over the ensuing 2 months and relief persisted.
Discussion
ISH is a syndrome that includes typical headaches and occasionally other manifestations such as gastrointestinal discomfort and vertigo (7). However, definitive diagnosis depends basically on the characteristics of pain. According to the IHS, it must be: (i) confined to the head, exclusively or predominantly felt in the distribution of the first division of the trigeminal nerve (orbital, temporal and parietal regions); (ii) stabbing in nature and lasting fractions of a second; (iii) recurring at irregular intervals (hours to days); and (iv) occurring in the absence of organic disease.
This disorder is often characterized by a sudden onset, generally spontaneous but sometimes related to cerebrovascular disease, cranial trauma and herpes zoster. Its evolution is directly related to the frequency of the attacks, which is extremely variable (ranging from once a year to 50 attacks a day). Most of them present with unilateral episodes restricted to the temporal regions and lasting up to 3 s (6, 7). Unusual features have also been described such as predominantly posterior (8) or longer lasting (9) attacks of pain. Epidemiological data show a homogeneous distribution among age groups but a clear female preponderance (7).
Previous studies found a close relation between the occurrence of ISH and other headaches in adult patients. Piovesan et al. identified an association with migraine in 40.4% of cases (7) but a relation can also exist with tension-type headache and other trigemino-autonomic cephalalgias such as hemicrania continua or chronic paroxysmal hemicrania (10, 11). Particularly in migraineurs, the pain is usually localized and occurs preferentially on the side most frequently affected by migraine attacks (12).
Recent papers have described similar short-duration headaches in paediatric and adolescent populations (4, 5). These painful episodes shared some features with the adult form of ISH but were of different duration and related only loosely to other forms of primary headache (5). Our patients were all young women whose headaches began to be noticed between 12 and 25 years of age and whose presentation recalls this juvenile form of ISH.
Mechanisms involved in the pathogenesis of this condition remain unclear. Current theories attribute key roles to irritation of peripheral nerve roots (mainly trigeminal and greater occipital) and transitory deficits in central inhibitory pathways for pain control (13). Besides, the extremely short duration of the episodes and the stabbing quality of the pain closely resemble the pattern reported in trigeminal neuralgia and point to abnormal paroxysmal neuronal discharges.
Although available data on ISH treatment are scant, some drugs have been tried with conflicting results. Indomethacin has been classically considered the first option for such patients, but therapeutic failure occurs in at least 35% of cases (6, 14). The physiology underlying indomethacin responsivity and specificity is still unknown but experimental data suggest that possible reductions in cerebral and meningeal blood flow and antagonist effects in nitric oxide pathways may play key roles (15). In addition, there is an unfavourable side-effect profile, which limits its use under some circumstances. Therefore, refractory cases demand new possibilities for symptomatic relief. Jacome had one patient responsive to nifedipine (16) and Piovesan et al. reported three patients suffering from ISH that had good responses with specific inhibitors of cyclooxygenase 2 (COX-2) (13).
In our cases, therapeutic tests with both indomethacin and rofecoxib were performed leading to suboptimal improvement. Thereafter GBP was introduced, with favourable responses. All patients had complete relief of pain already in the first days of treatment. It is difficult to be certain that this full clinical response was related exclusively to GBP because the natural course of ISH may include spontaneous fluctuations. However, about 14% of ISH cases have persistent symptoms with almost daily attacks of pain following disease onset and without intercalated silent periods (6). Our group had such a chronic pattern of evolution, arguing against spontaneous improvement and supporting the efficacy of GBP. Besides, sustained pain relief after treatment withdrawal had also been reported earlier in chronic ISH patients taking indomethacin (6). This remarkable response may be related to improvement in peripheral neurogenic inflammation (13).
To our knowledge, this is the first report of the use of GBP in ISH patients. GBP was originally developed as a gamma-aminobutyric (GABA) mimetic compound with potent anticonvulsive effects. However, its efficacy in the treatment of chronic pain syndromes was soon recognized, including several types of head and cranial pains. It has been used for migraine prophylaxis (17), trigeminal neuralgia (18), SUNCT syndrome (19, 20), cluster headache (21, 22) and hemicrania continua (23) with promising results.
The precise mechanisms of action of GBP are still not completely defined but are probably related to both peripheral and central pathways of pain suppression (24). Pan et al. recently showed that GBP inhibits ectopic discharge activity from injured peripheral nerves (25). Similarly, there is clear evidence of an anti-allodynic effect of the drug related to antagonism of glutamate NMDA receptors and blockade of calcium channels in the central nervous system, particularly in the hippocampal area (26, 27). Other possible working mechanisms include enhancement of GABA-ergic pathways (28) modulating cortical responses to painful stimuli.
The good response obtained with GBP may help in the management of ISH patients. Especially for indomethacin-resistant or intolerant cases, this drug would be an effective and safe option. However, larger and better-designed trials are obviously needed to clarify this issue. The efficacy in other situations, such as late-onset ISH, remains to be defined.