Secondary chronic cluster headache treated by posterior hypothalamic deep brain stimulation: First reported case

Abstract

Introduction

Deep brain stimulation (DBS) of the posterior hypothalamus (pHyp) has been reported as an effective treatment for primary, drug-refractory and chronic cluster headache (CCH). We here describe the use of such a procedure for the treatment of secondary CCH due to a neoplasm affecting the soft tissues of the right hemiface.

Methods

A 27-year-old man affected by infiltrating angiomyolipoma of the right hemiface who subsequently developed drug refractory homolateral CCH underwent DBS of the right pHyp region at the Fondazione IRCCS Istituto Nazionale Neurologico Carlo Besta.

Results

After surgery, the patient presented a significant reduction in frequency of pain bouts. However, because of a subsequent infection, the entire system was removed. After re-implantation of the system, successful outcome was observed at 2 years follow-up.

Discussion

This brief report shows the feasibility of pHyp DBS in secondary drug-refractory CCH syndromes; future reports are needed in order to confirm our positive result.

Introduction

Chronic cluster headache (CCH) is a severe pain condition whose precise aetiology is unknown; treatment includes aborting therapies, such as triptans and oxygen inhalation, and preventing measures, such as verapamil, lithium and steroids. In rare cases CCH is refractory to medical treatment, and neuromodulation procedures have shown encouraging results.

Some literature reports describe CCH as secondary to various intracranial and extracranial conditions. Intracranial conditions include lesions causing trigeminal nerve root irritation. Secondary cases could derive from vascular lesions, malformation, neoplasms or other disturbances of the cranio-cervical region. These reports concluded that removal of the primary cause may result in cure of the affected patients or reduce the frequency of the attacks.

No reports have been made of the use of neurostimulation procedures for treatment of secondary CCH. We report on the first case in which neurostimulation was used for secondary CCH occurring as a result of a neoplasm affecting the soft tissues of the right hemiface (angiomyolipoma). Because of its infiltrative nature, it was not possible to remove the lesion.

Case report

At 24 years old the patient was discovered to have an infiltrating lesion of the soft tissues of the right hemiface, diagnosed as infiltrating angiomyolipoma 1 year later (2007). In the same period he began to suffer from severe right orbital and supraorbital pain attacks associated with conjunctival injection, lacrimation, nasal congestion, forehead and facial sweating, ptosis and oedema of the eyelid. Autonomic signs were paroxysmal and appeared only during painful attacks. Headache duration was about 30–60 minutes. A clinical evaluation performed at that time by a neurologist specializing in headache disorders found that the patient was suffering from multiple daily attacks of cluster headache (CH) with no remission, i.e. chronic CH. Subsequently, after sumatriptan injections were given, attacks were promptly aborted in 2–5 minutes, thus hampering further evaluation of attack duration. Occasionally, the patient suffered from continuous head pain on the same side between attacks.

Among others, the patient tried verapamil 720 mg/day, lithium carbonate 1500 mEq/day, methysergide 10 mg/day, topiramate 300 mg/day, valproate 1200 mg/day, pizotifen 6 mg/day, amytriptiline 60 mg/day, gabapentin 2400 mg/day, carbamazepine 1000 mg/day, oxacarbazepine 900 mg/day and prednisone 100 mg/day with no benefit; he also received both repeated greater occipital nerve (GON) and sphenopalatine ganglion (SPG) blockade on separate occasions, but none of these treatments was effective in controlling symptoms. He presented suicidal thoughts and was under observation by a psychiatrist, who prescribed various antidepressants.

Despite chemotherapeutic treatment (consisting of methotrexate, vinorelbine and taxole) and symptomatic treatment, the frequency and intensity of pain bouts worsened.

The patient was admitted to the Fondazione IRCCS Istituto Nazionale Neurologico Carlo Besta in February 2009. Before admission, he reported on few occasions up to 60 ‘attacks’ in 1day but we witnessed up to 12–14 attacks in 24 hours. Progressive reduction of time intervals between attacks in CH patients has been reported with up to 11 (66 mg) sumatriptan injections per day (1). It is possible that the same phenomenon, i.e. a progressive reduction of time intervals between attacks, occurred in our patient as a result of sumatriptan injection overuse, thus explaining the high number of reported attacks. In our patient, it is reasonable to hypothesize that the need to repeat sumatriptan injection in a short time can be attributed to pain recurrence rather then to a completely new CH attack. In fact in our patient CH attacks reduced to five to seven per day when sumatriptan injections were transiently stopped.

After neurological evaluation and extensive discussion with the patient and his relatives, we offered occipital nerve stimulation (ONS). Notwithstanding our indication to have ONS first, he refused ONS, instead asking for hypothalamic deep brain stimulation (hDBS). hDBS of the right posterior hypothalamus was performed. The procedure was done under stereotactic conditions and general anaesthesia (details about surgical technique are described in a previous paper (2)). Stereotactic coordinates of the target were: 2 mm lateral to the midline, 2 mm posterior to the interpeduncular point (IPP) and 5 mm below the anterior commissure-posterior commissure (AC-PC) plane (2). A post-operative brain computerized tomography (CT) scan demonstrated the correct positioning of the hypothalamic electrode and the absence of surgical complications (Figure 1).

Figure 1.

Post-operative brain computerized tomography scan slice at the level of the posterior hypothalamic electrode merged with pre-operative magnetic resonance imaging.

Stimulation parameters were: bipolar mode, 120 microseconds, 130 Hz, 2.2  V.

The patient reported a progressive and significant improvement of symptoms after surgery, and the frequency of CCH episodes dropped to one crisis every 2 months; he then reduced the dosage of sumatriptan accordingly. After another chemotherapeutic cycle, in November 2009, the patient suffered from sepsis due to a Klebsiella pneumoniae infection, with subsequent infection at the subcutaneous sites of the internal pulse generator (IPG) and the connection cable. We removed the stimulation system because of this complication and the patient gradually started to present the same frequency of pain bouts as in the pre-operative period. In December 2010 a new pHyp stimulation system was implanted, maintaining the same stimulation parameters used after the first implant; again the patient greatly benefited from the procedure, with subsequent reduction of pain bouts to one every 4 months for 19 months. At the last follow-up, in August 2012, attack frequency had gradually increased to four to five per day, promptly aborted by sumatriptan injection. The patient has been admitted to the Fondazione IRCCS Istituto Nazionale Neurologico Carlo Besta, amplitude has been increased up to 2.5 mA, intensity of pain attacks has begun to reduce and, in some cases attacks, ended without the need of sumatriptan. Unfortunately, the neoplasm is still slowly growing.

Discussion and conclusions

The exact pathophysiological mechanisms causing CH are still unknown, nevertheless several lines of evidence point to a role played by ‘peripheral’ and ‘central’ factors, including histaminergic and vascular dysregulation, variations in the cerebral concentration of different neuropeptides and trigemino-vascular reflexes (3,4). The efficacy of posterior hypothalamic DBS (2), coupled with the evidence of activation of this region (as revealed by positron emission tomography) during CH fits (5) raises the further question of whether the posterior hypothalamus is the primary generator of the painful attacks per se or is only a secondary element involved in this process.

Literature has ascribed secondary CH or cluster-like painful attacks to trigeminal root compression (6), cerebrovascular pathologies (7,8), neoplasms such as cervical meningioma (9), cavernous sinus metastasis (10), trigeminal neurinoma (11), Chiari malformation (12) and head injury (13). The fact that CH may result from so many different conditions makes the picture even more complex, although a major role for biochemical and hormonal factors is hypothesized.

Neurostimulation was proposed to our patient because the CH attacks were completely resistant to drugs. Because of the infiltrating nature of the neoplasm, surgical excision was not possible. In our patient, DBS could have exerted its therapeutic effects with at least three distinct mechanisms: 1. inhibition of posterior hypothalamic neurons; 2. increased pain threshold on affected trigeminal territory; 3. a more complex mechanism involving pain-matrix brain areas (14).

The good results observed in the reported patient, suggest that, in absence of significant surgical contraindications, this treatment can be considered in patients suffering from chronic drug-refractory secondary CH attributable to a secondary lesion, if primary surgery is non-amenable. In addition, a crucial role of the posterior hypothalamus in the pathophysiology of CH is confirmed also in secondary CH.