A case of post-traumatic LASH syndrome responsive to indomethacin and melatonin (a man with a unique triad of indomethacin-responsive trigeminal autonomic cephalalgias)

Introduction

Long-lasting autonomic symptoms with hemicrania (LASH) syndrome is a newly recognized indomethacin-sensitive trigeminal autonomic cephalalgia (TAC) first reported by Rozen in 2000 (1). To date there are only three documented cases in the literature and no secondary cases reported (2,3). This headache disorder is unique in that it is dominated by its cranial autonomic features that must start before headache onset (usually by hours), then continue throughout the entire headache, which is normally of long duration (several days), and then persist on after headache resolution for a period of time, again usually hours (1). Like hemicrania continua (HC) and paroxysmal hemicrania (PH), LASH is exquisitely responsive to indomethacin, leading to complete syndrome resolution. A patient is presented who appeared to develop every form of indomethacin-sensitive TACs including LASH after a motor vehicle accident. His LASH syndrome showed complete alleviation to indomethacin and then to melatonin. This would be the first reported case of a secondary/post-traumatic LASH syndrome, the first reported case of a man with LASH, and the first LASH case to demonstrate complete response to melatonin. The ability of the patient to develop three distinct TACs after trauma is also a rare occurrence. The possibility that LASH, HC, and PH are a single disease state with variable clinical expression will be discussed.

Case presentation

A 44-year-old man had no prior headache history until after he was involved in a motor vehicle accident in September 2011. He was a military police officer in Kuwait when his vehicle collided with another vehicle going 90 miles per hour (mph). He was unsure if he struck his head, he had no loss of consciousness, but he did sustain a cervical whiplash injury. During that same month (he is not exactly sure of how long after the accident) he began to develop discrete short-lasting headaches of 15 minutes’ duration occurring in his left temple with associated left nasal rhinorrhea. The attacks could occur during the day or awaken him from sleep and they were always severe in intensity. He would experience two to three attacks every day but would be pain free in between attacks. This type of headache continued for 15 months then he began to develop a new type of headache. These headaches were also 100% left sided, but he now had head pain constantly without pain-free time involving the entire left side of his head from his occiput to his eye that was moderate in intensity and described as an ache. On top of this he would get exacerbations of head pain that were severe, mostly centering behind the left eye and that would last several hours in duration. During these exacerbations he would have flushing of his face and forehead but did not remember experiencing any other cranial autonomic symptoms. This type of headache lasted for 3.5 months in duration. He then developed a third type of headache, and this is the headache he presented to our headache clinic with three months after onset. This headache was episodic, lasting one to three days in duration, then he would have one to two days without any pain and the headaches would recur. Prior to each headache he would develop left eyelid swelling, left eye lacrimation, and left eyelid twitching and this would start several hours before his left hemicranial pain would begin. The headache would involve the entire left side of his head and during this time he would continue to experience the eyelid swelling, lacrimation, and eyelid twitching. In addition he would also get a sensation like a piece of wood was in his left eye. Once the headache resolved it would take another several hours before the cranial autonomic symptoms would stop. The only medications the patient had tried for his headaches were over-the-counter analgesics (ibuprofen) and a butalbital/acetaminophen/caffeine combination analgesic, and both were ineffective for all three headache types. On examination (not during an attack) there was greater occipital, temple, and trochlear notch tenderness on the left. Neurovascular examination was normal and there was no ptosis or miotic pupil present. The patient was given a diagnosis of LASH syndrome for his current headaches as his cranial autonomic symptoms preceded, continued with, and outlasted his hemicranial pain. However, his initial short-lasting headaches of 15 minutes’ duration would have met International Classification of Headache Disorders, third edition beta (ICHD-3 beta) criteria for chronic paroxysmal hemicrania (CPH) while the second headache he experienced would have met ICHD-3 beta criteria for HC; of course neither headache was treated with indomethacin to verify the diagnosis (4). To rule out secondary issues such as vessel dissection, neuroimaging was completed (magnetic resonance imaging (MRI) of the brain, magnetic resonance angiography (MRA) of the brain and neck) and these were normal studies. Indomethacin was started for LASH syndrome, and on 25 mg three times a day (TID) dosing he became pain free. Every time he tried to lower the dose or even if he was late taking a dose the pain returned. He remained on indomethacin for seven months, never being able to lower his daily dose below 75 mg without pain recurrence, so he was started on melatonin to see if either he could be switched entirely to this hormone for LASH prevention or at least be able to get on a lower dose of indomethacin with combination therapy. Melatonin has been used by the author (TDR) and others previously for indomethacin-sensitive headaches with success (5). When the patient reached 10 mg dosing of melatonin per night he was able to taper off all indomethacin and has been pain free through six months of follow-up with no side effects. He has also tried to stop melatonin on several occasions but had headache recurrence, thus indicating he was still experiencing his headache syndrome and not in remission.

Discussion

This is the fourth reported case of LASH syndrome to be introduced into the headache literature and the first secondary (post-traumatic) case of LASH to be published. We defined this patient’s headaches as post-traumatic as they occurred in succession after his trauma (motor vehicle accident) and as he had no prior headache history before the trauma. One could argue this could be a case of primary LASH syndrome as this particular headache began almost 18 months after his accident, and typically trauma-induced headaches develop within seven days after injury, but it seems unlikely the case patient would have developed any of his three successive TACs without the antecedent trauma (4). The generator of the headaches may have been head or cervical trauma but that is unknown. If he had head trauma it was mild with minimal if any concussive symptoms that he could remember. This case would be the first male to be documented with LASH syndrome. Prior to this patient all previously reported LASH cases have been female, but they had primary LASH syndrome. At present the true gender predominance of LASH is unknown secondary to the small number of cases reported (1–3). This is also the first patient with LASH syndrome to demonstrate melatonin responsiveness. With this case report melatonin now appears to be effective for almost all documented indomethacin-responsive headache disorders including HC, primary stabbing headache, and LASH syndrome (5–8). There is no report of melatonin being tried yet in PH. Melatonin with its similar chemical structure to indomethacin should definitely be used in all patients with indomethacin-responsive TACs if they do not have the rare indomethacin-cured form of their headache syndrome (9,10). Melatonin has none of the gastrointestinal or renal complications that beset chronic indomethacin usage, thus it is a safe long-term preventive treatment choice. Normally the authors will treat with indomethacin for six-plus months then try to taper off the medication. If headaches return then melatonin is started and tapered up to doses of 15 mg or higher in 3 mg–5 mg increments. The highest dose needed by one of the authors’ patients to achieve a pain-free state is 30 mg and this was accomplished without any sedation issues. The only recognized contraindication for melatonin is a history of significant asthma as this hormone can exacerbate this pulmonary condition.

LASH syndrome appears to be the rarest of the TACs. In actuality the authors have two other cases of primary LASH they are currently treating that would bring the LASH census to six total cases (five primary, one secondary). This does not seem like a significant number but early on when unique primary headache disorders such as HC, PH, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) were first introduced into the headache vernacular, individual cases were documented for years until a better understanding of clinical presentation, epidemiology, and pathogenesis was ascertained. This has yet to be achieved with LASH and that is why individual cases, especially those with unique findings (first secondary case and new treatment), need to be reported. At present there are no recognized ICHD (4) criteria for LASH syndrome and the disorder has not yet been recognized as a distinct entity by the ICHD. At some point LASH syndrome could be considered for future criteria, especially if more cases are added to the literature.

Finally, this patient provides another example of how multiple TACs can occur in a single individual. The transition from PH to HC to LASH is unique and has not been reported previously. Three separate TACs in a single patient have been reported prior but is quite rare, while two different TACs in a single patient are more widely documented but also uncommon (11,12). The diagnosis of PH and HC was a retrospective one for this patient as we did not actually meet him while he was experiencing these individual headaches; thus, how accurate these diagnoses are can come into question. Post-traumatic TACs have been reported as well in the literature but typically as a single type of TAC (13). This may be one of the first ever reported cases of three separate TACs developing after trauma. The question arises are PH, HC, and LASH a single disease entity with varying degrees of pain duration and cranial autonomic symptom duration or three distinct conditions? Totzeck et al. (12) discussed how HC is just the continuous form of PH in a recent documentation and discussion of dual TACs in individual patients. LASH could be just a more prolonged form of PH or an intermediate form of HC. Further reports and investigation of LASH cases (functional imaging, etc.) will help to determine if this is an epiphenomenon of other TACs or a distinct headache condition.

The patient has provided written consent for this case report.

Clinical implications

This is the first reported case of secondary long-lasting autonomic symptoms with hemicrania (LASH) syndrome.