The trigeminal nerve complex is a very important and somewhat unique component of the nervous system. It is responsible for the sensory signals that arise from the most part of the face, mouth, nose, meninges, and facial muscles, and also for the motor commands carried to the masticatory muscles. These signals travel through a very complex set of structures: dermal receptors, trigeminal branches, Gasserian ganglion, central nuclei, and thalamus, finally reaching the cerebral cortex. Other neural structures participate, directly or indirectly, in the transmission and modulation of the signals, especially the nociceptive ones; these include vagus nerve, sphenopalatine ganglion, occipital nerves, cervical spinal cord, periaqueductal gray matter, hypothalamus, and motor cortex. But not all stimuli transmitted through the trigeminal system are perceivable. There is a constant selection and modulation of the signals, with either suppression or potentiation of the impulses. As a result, either normal sensory perceptions are elicited or erratic painful sensations are created. Electrical neuromodulation refers to adjustable manipulation of the central or peripheral pain pathways using electrical current for the purpose of reversible modification of the function of the nociceptive system through the use of implantable devices. Here, we discuss not only the distal components, the nerve itself, but also the sensory receptors and the main central connections of the brain, paying attention to the possible neuromodulation targets.
Trigeminal branch stimulation is a type of peripheral nerve stimulation ( PNS) used to treat a variety of craniofacial pain disorders. Common indications include trigeminal neuralgia, trigeminal neuropathic pain, trigeminal deafferentation pain, trigeminal postherpetic neuralgia, supraorbital neuralgia, and migraine headaches. Supraorbital and infraorbital arrays are the most common electrode configurations, although preauricular, mandibular branch, and subcutaneous peripheral nerve field stimulation arrays have also been described. Trigeminal branch stimulation may be used as a stand-alone neuromodulation therapy or it may be combined with occipital nerve, sphenopalatine ganglion, or Gasserian ganglion stimulation to treat more complex pain patterns. Consistent with other forms of PNS, trigeminal branch stimulation is a minimally invasive, safe, and straightforward method of treating medically refractory neuropathic pain.
Since its original introduction several decades ago, peripheral nerve stimulation (PNS) of the craniofacial region has been traditionally performed using devices intended for spinal cord stimulation applications with inevitably high rate of technical challenges and procedural complications. The lower invasiveness of recently developed wireless neurostimulation systems makes them much better suited for craniofacial applications. Here, we discuss the preliminary clinical data from several published reports and the ongoing multicenter prospective study of wireless PNS in the craniofacial region. Advances in wireless transmission of electrical signals may make wireless neurostimulation even more attractive in the future. Since most of the evidence supporting PNS for facial pain comes from small subsets of the population, case series and case reports, there will need to be larger, randomized controlled trials with cost efficacy analyses in order to validate the role of wireless PNS as the standard of care.
Electro-modulation of subcortical deep brain structures by surgically implanted electrodes is now standard evidence-based treatment for movement disorders such as Parkinson's disease and essential tremor and is approved for dystonia and obsessive-compulsive disorder under a humanitarian exemption. Historically, deep brain stimulation (DBS) for multiple indications has demonstrated acceptable complication rates, rare mortality, and reducing morbidity as the technology and the techniques of its application have advanced. DBS for the amelioration of pain has been performed since the early 1950s, and became widely used in the 1970s, when targeting the somatosensory thalamus was shown to be efficacious for intractable pain syndromes including facial pain. The technique fell out of favour in the late 1990s after 2 multicentre trials failed to meet end-point criteria. Since these trials, DBS for pain has remained for investigational or "off-label" use. Criticisms from previous literature have involved unsuitability of patient selection, as well as inconsistencies in neurosurgical technique. Clinical success with DBS for facial pain has been for the treatment of a variety of chronic neuropathic and nociceptive pain syndromes; including trigeminal neuropathy, post-herpetic neuralgia, deafferentation facial pain, "atypical" facial pain, cluster headaches and other trigeminal autonomic cephalalgias, as well as head and neck pathologies, most often which have been resistant to all other 1st- and 2nd-line medical and surgical treatments, when DBS has become a "last treatment option." An enhanced understanding of the mechanisms of action of DBS for pain will enhance outcome, and appropriately prescribe evolving novel nuclear brain targets.
Neuropathic facial pain can be exceedingly difficult to manage with conventional therapies. Since this pain may be excruciating and often debilitating and some patients do not respond or do not tolerate conventional treatments, the interest in neuromodulation therapies is increasing. One of the most commonly used neuromodulation therapies, spinal cord stimulation, has recently shown promise in treating facial pain. We reviewed the current literature to determine usefulness of spinal cord stimulation in management of refractory facial pain. Our review indicates that for some patients with intractable pain in portions of the face, cervical spinal cord stimulation may be effective at reducing pain.
Since the first successful use of high-frequency electrical stimulation of trigeminal branches for treatment of facial pain in 1962, neuromodulation techniques become well established but remain greatly underutilised. Most subsequent implantation techniques and commercial devices for peripheral nerve stimulation, available until the last decade, utilised frequencies in the range 1-100 Hz. With the commercial introduction of 10-kHz spinal cord stimulation, there has been renewed interest in peripheral applications of kHz frequency neuromodulation. High-frequency biphasic stimulation causes rapid onset, reversible conduction block in mammalian nerves which might be useful in human peripheral neuromodulation applications, but the conduction block induced at kilohertz frequencies may not be the only mechanism contributing to analgesia. We discuss likely mechanisms of action of high-frequency peripheral nerve stimulation and present several clinical examples of successful use of this modality in various facial pain conditions. A change to sub-threshold higher frequencies in the 10 kHz range adds a number of distinct advantages. The lack of paresthesias is welcomed by patients. The ability to place the stimulating electrode approximately 1 cm away from the targeted nerve has an anatomical and surgical advantage.
Neuropathic facial pain is notoriously difficult to treat, regardless of its origin and duration. Since the first reported sphenopalatine ganglion blockade by Sluder in 1908, this ganglion has assumed an important role among the structures targeted for the treatment of facial pain. Recent years have witnessed the rise of neuromodulation over ablative procedures, including the development of an implantable stimulation device specially designed for use in the pterygopalatine fossa. Sphenopalatine ganglion stimulation has been demonstrated as effective and safe for refractory cluster headache, today the major indication for this therapy, but increasing evidence shows that the effect on the autonomic system and cerebral circulation could justify an even wider use of sphenopalatine ganglion stimulation for other chronic headache syndromes and vascular diseases.
Non-invasive neuromodulation techniques such as transcranial direct current stimulation (tDCS) enable researchers and health care professionals to gain unique insight into brain functions and to treat a number of neurological and psychiatric conditions. Repeated applications of anodal tDCS over the primary motor cortex (M1) have been shown to produce long-lasting relief of neuropathic pain. tDCS is a technique that can induce and modulate brain plasticity and thus be suitable for treating diverse chronic pain conditions, disorders associated with substantial reorganization of central nervous system activity. The number of published basic research and clinical papers in this field is increasing exponentially, but the number of studies that include patients with facial pain is still limited, and there are no "gold standards" with regard to how to treat the various kinds of pain disorders. Pharmacoresistant facial pain is a substantial burden for the patient as manifested by its interference with daily functioning and reduced health status associated with pain severity. Without doubt, further trials are needed to optimize stimulation parameters and find effective protocols for this disorder. In addition, evaluation of the clinical effects of tDCS shows that low-intensity electrical stimulation techniques are exceptionally suitable for gaining further insight into the functional role of a given brain region, e.g. how brain processes emerge and can be altered in anatomically distributed, but functionally connected, brain networks.
Facial pain occurs in approximately 80% of patients with head and neck cancers. Pain in these settings may result directly from the tumor, or indirectly as a side effect of oncological treatment of the tumor. Optimizing treatment for cancer pain of the face, therefore, involves a variety of diagnostic and treatment considerations, with the development of a successful treatment algorithm dependent on accurate diagnosis of the anatomical location of the pain, its relationship to the facial pain pathway, the type of pain being treated and, finally, patient's prognosis and preference for treatment modality. Beyond direct treatments to reduce tumor burden, a wide variety of neuro-ablative and neuro-augmentative approaches are available that may be tailored to a patient's specific pain syndrome and individual clinical context, taking into account the patient's treatment goals, life expectancy, other cancer-related medical problems, and end-of-life issues.
Successful management of facial pain starts with making correct diagnosis. Diagnostic errors, particularly early on in evaluation of facial pain patients are not uncommon, and some of this may be related to the lack of uniform classification that would satisfy needs of different specialists. Here, we critically review several most common classification schemes and try to compare and contrast their strength and unique features. We also attempt to link multiple terminologies describing same clinical conditions and provide a rationale for developing a unified nosological approach. Based on our findings, we conclude that despite many previous attempts, much work needs to be done to create a universally accepted, comprehensive but at the same time simple and user-friendly, facial pain classification, with the ultimate goal of integrating such classification into a treatment-guiding algorithm(s).
Motor cortex stimulation (MCS) has been used in the treatment of intractable neuropathic facial pain for nearly 30 years. While efficacy rates have been noted as high as 88% in some studies, considerable variability in treatment response remains. Additionally, MCS is often cited as providing diminishing relief over time, and there are few long-term studies on efficacy. Complications are generally mild and include infection, hardware complication, seizure, and transient neurological deficit. Despite relatively minimal use, MCS remains a viable treatment option for the appropriately selected facial pain patients that have proved refractory to conservative management.
Despite the high incidence of facial pain, targeted drug delivery remains a rarely used technique for treatment of otherwise refractory pain. Two distinct paths have been described. The intraventricular route allows direct access to intracerebral opioid receptors. The more recently introduced upper cervical or cisternal intrathecal route, is based on the same theories as classical intrathecal route. Intraventricular route was first described by A.K. Ommaya; its use remains limited, mostly with morphine, despite a high clinical efficiency, probably because of the invasive nature of the procedure and the need for daily direct injections. The ability to connect the catheter to an implantable pump may help to facilitate the acceptance of this approach. The also rarely used high cervical intrathecal or cisternal route is very efficient, because facial pain signals are transmitted mainly via the trigeminal nerve roots and synapse on the second-order neurons in an area that extends from the lower brainstem to the C1 and C2 levels of the spinal cord. The risks of cervical puncture may explain the rarity of its use. However, new devices allowing a simpler lumbar approach and the ongoing opioid crisis are the factors that may facilitate the wider use of this effective technique for the treatment of facial pain.
The introduction of peripheral neuromodulation to treat headache and facial pain two decades ago opened up the field to non-neurosurgical practitioners, given the relatively low risk and technical ease of the procedure. These procedures, primarily occipital nerve stimulation (ONS) and trigeminal branch stimulation such as supra- and infraorbital nerve stimulation, are now established to be effective in a number of facial pain and headache syndromes, despite their lack of approval by regulatory agencies such as the US Food and Drug Administration (FDA). For that reason and others, dedicated hardware for these procedures has not yet been developed, thus relying on hardware designed for placement in the epidural space for spinal cord stimulation (SCS). This has led to a series of technical issues and device-related complications not traditionally seen with SCS. I will review the surgical technique of ONS and peripheral nerve stimulation of the head and face utilizing this equipment, and discuss methods learned by experienced practitioners over the years to minimize device-related complications.
Non-neuralgic trigeminal neuropathic pain can be challenging in terms of treatment as pharmacological interventions often tend to be ineffective. Within the pain-transmitting pathway, the Gasserian ganglion (GG) is a rather unique anatomical and physiological structure where the sensory (including pain) information from the entire half of the face undergoes primary processing in a very compact and clearly defined entity. Moreover, GG is positioned in a completely immobile intradural location (the Meckel's cave) and is insulated from the brain by a layer of dura. As a confluence of all three trigeminal branches, GG allows one to achieve clinical effect on the entire half of the face with a relatively small surgical intervention while maintaining an ability to select exact facial regions based on known somatotopic organization of nerve fibers. Therefore, when it comes to electrical neuromodulation, the GG stimulation (GGS) may be a unique solution for treatment of medically refractory facial pain. GGS was introduced in 1970s and continues to be a recognized surgical modality with multiple published clinical series describing multi-year experience in hundreds of facial pain patients. GGS is particularly useful in treatment of patients with chronic trigeminal neuropathic pain and persistent idiopathic facial pain who tried and failed or were not considered good candidates for the conventional surgical interventions. With advances in lead technology, intraoperative visualization and stereotactic navigation, percutaneous GGS became a minimally invasive surgical intervention that is recommended for consideration in complex facial pain. Here, we review the clinical data and summarize the current state of GGS in facial pain treatment.
Percutaneous electrical nerve stimulation (PENS) is a novel, minimally invasive and useful treatment modality. Its use in complex facial pain has been on the rise, and its utility will further increase with the advances in the technology and renewed interest in the field of peripheral neuromodulation. PENS therapy can be used both as diagnostic and therapeutic option. The precise mechanism of action is not known, although a combination of electrical neuromodulation and release of endogenous morphinelike substance in the central nervous system appears as plausible explanation. We analyse the various studies in the literature and discuss the Southampton data regarding facial pain treatment with PENS therapy. We believe that PENS therapy for facial pain and headache is currently underutilised. It is safe, economical and should certainly be part of the armamentarium in the treatment of complex facial pain and headache.
The main neuromodulatory methods using neurostimulation principles are described. It concerns peripheral nerve stimulation (PNS), spinal cord stimulation (SCS), deep brain stimulation (DBS), motor cortex stimulation (MSC), and repetitive transcranial magnetic stimulation (rTMS). For each method the history, pathophysiology, the principles for use and the associated diagnoses are mentioned. Special attention is focused on the most common neuromodulatory invasive methods like SCS and MCS and non-invasive methods such as rTMS. In addition to the positive effects, side effects and complications are described and discussed in detail. In conclusion, neuromodulatory (neurostimulatory) techniques are highly recommended for the treatment of different types of pharmacoresistant pain.
The most common primary cancers that metastasize to the brain are lung cancer, breast cancer, and melanoma. The established management approaches for brain metastasis include stereotactic radiosurgery, fractionated radiation therapy, and surgical resection. In the past the role of medical therapies in brain metastases was limited. In the last decade, our understanding of molecular drivers of brain metastases and CNS penetration of drugs across the blood-brain barrier has improved. The molecular targeted tyrosine kinase inhibitors have shown effectiveness in brain metastases with activating mutations from non-small cell lung cancer, breast cancer, and melanoma. More recently, immunotherapies have also shown efficacy in the management of these patients. These agents can be effective for both intracranial as well as extracranial disease and are being actively employed in this patient population.
Since its first reported use in 1976 in Sweden, Gamma Knife (GK) radiosurgery has become an accepted treatment option for intracranial meningioma, either upfront, in combination with planned subtotal resection, or as adjuvant/salvage treatment. Initially, GK was used in patients unfit for a major surgical procedure or for high-risk meningiomas adjacent to critical neurovascular structures. However, with the availability of larger and increasingly long-term follow-up studies, the proven durability of GK in the treatment of meningiomas means that it has become a treatment option for younger patients who want to avoid the risks of open surgery. Here we review the current indications, radiobiology, and patient outcomes following GK for intracranial meningioma 50 years on from its inception.
As a young neurosurgeon, Leksell trained with his mentor, Herbert Olivecrona, in the early 1930s. The experience set him off in search of a way to minimize neurosurgical trauma. Twenty years later, Leksell developed his own stereotactic instrument and published his seminal paper on how radiosurgery could potentially be done. This led to the first Gamma Knife installation in 1968. Over the subsequent 50 years Gamma Knife surgery has evolved to cover much of what is done in neurosurgery and there are more than 330 Gamma Knife centers all over the world. By the end of 2017 more than 1.2 million patients had undergone Gamma Knife surgery.
