Trigeminal Neuralgia

Trigeminal Neuralgia. Peter J Jannetta, ed. ISBN 9780-19-534283-3, Oxford University Press, USA; 254 pages.

Epileptiform neuralgia ... is accompanied by convulsive movements and I designate this form tic douloureux

-Armand Trousseau, 1853

Ernest Hemingway commented that all American literature begins with one book, Mark Twain's Huckleberry Finn. This reviewer suggests that all literature related to neuropathic pain (NP) should begin with a good book on trigeminal neuralgia (TN) (tic douloureux), not because it is similar but because of differences in its phenomenology and treatment from all other forms of NP. This is such a book, and it is edited by a master clinician, Peter Jannetta. If we can solve the mystery of this condition and its difference (or possible similarity at the inception of other NP), we may come a long way to arriving at a better understanding of the pathophysiology and natural history of other NP and improved treatments. TN challenges the suggested new NP definition, leaving a proportion of cases of this classical NP condition with most probably dysfunction as a cause, a term removed from the current suggested definition. TN is the most successfully treated NP, both medically (with carbamazepine) and surgically (various types). This is very different from other forms of NP, in which medical treatment is only moderately effective and surgical treatment has been largely abandoned except for rare exceptions. Jannetta applied Walter Dandy's observation (circa 1930s) of vascular loops compressing the trigeminal nerve root entry zone and James Gardner's early work (circa 1960) and used the operating microscope to cure this condition in many instances. This is unique in all of NP. Obviously, many questions arise because of these differences. This book is also useful to all specialists who use procedures to treat TN, but also should be of great interest to facial pain and NP pain researchers because of the clues that are scattered throughout it. It is also of value to all clinicians (pain doctors, neurologists, otolaryngologists, dentists and family doctors) who treat facial pain. I have in mind, particularly, dentists and otolaryngologists who may be on the forefront of contact because of the frequent misdiagnosis of TN and the fruitless use of dental and other procedures. This is an easily diagnosed condition and the typical form should not be treated by the dentist or ENT specialist.

The editor makes an apology for some redundancy in this multiauthored book, but this is not an issue because many chapters then become stand alone sections that can be read quickly if a reader has a particular subject of interest. High-quality books on TN in past years include the superb volumes by Barry Sessle and Gerhard Fromm (1991) and Joanna Zakrzewska (1995).

The foreword is a tribute to Peter Jannetta relating his ideas about microvascular decompression (MVD), its lack of acceptance and the subsequent gradual recognition that this was a curative operation for many patients. The preface by Jannetta is a good summary of the evolution of treatment, both medical and surgical, of this disorder. Here, Jannetta has raised the challenge to the new definition of NP that excludes the term dysfunction and requires a lesion. He considers TN to be dysfunction, and the success of MVD in rapidly alleviating the pain suggests that, indeed, dysfunction is a problem.

The chapter on the history of TN by the eminent neurologist Ken Casey and Jannetta is comprehensive and fascinating. It reviews the history of the clinical phenomenology, pathophysiology, and medical and surgical treatment of this condition. Of importance regarding drug treatment is Trousseau's 19th century concept of TN being similar to epilepsy ("epileptiform neuralgia" [sic]), which led to very successful treatment with carbamazepine. The second important point is that most of the information we have about this condition is observational. There have been few randomized controlled trials (RCTs), but nonetheless important ones demonstrating the effectiveness of carbamazepine by Blom in the 1960s. Things have not changed much medically since then. The conclusion about surgical treatment, which consists of choices between several modalities (intracavernous glycerol, radiofrequency, balloon compression, radiosurgery and MVD), is that MVD provides the highest rate of long-term patient satisfaction with the lowest rates of pain recurrence and better quality of life. Complication rates of MVD are listed as generally less than 1% but include death, stroke, hearing loss, cerebrospinal fluid leaks and infection. Nonetheless, these possible major but rare complications deter many patients from seeking this treatment, preferring either to struggle on with inadequate medical treatment or the more minor procedures of glycerol, balloon compression, radiofrequency or radiosurgery.

The chapter on anatomy and physiology is by Casey. It is a wonderfully succinct and lucid account of the complicated trigeminal system with its intricate organization. It does require some basic knowledge of neuroanatomy and the unsophisticated may require the use of anatomical drawings, but for those with the basic knowledge, the description is remarkable. Interesting information is included about the ultrastructural changes in the trigeminal ganglion and TN. Included is the work of Marshall Devor and colleagues on pathology at the site of vascular compression of the nerve root in a few cases, which, I believe, is probably not well known. This should be of great interest to both basic scientists and clinicians. The latter part of the chapter deals with surgical pathophysiology and would be of greatest interest to surgeons operating in this area. It contains extremely valuable information about the surgical anatomy when operating in this very small and complex area of the brain.

Typical and atypical symptoms are the subject of an important chapter by Jannetta, who has vast and highly respected experience with this condition. The chapter is brief and provides a clear description of the phenomenology of typical and atypical TN from the author's experience. Interestingly, it describes atypical TN as a constant burning pain starting out mildly and gradually worsening over time, but which may or may not evolve from typical TN (ie, shocklike triggered lancinating pain in the lower face). He describes a mixed form with elements of both so that it is a very simple classification but somewhat different from this reviewer's concept. This reviewer would more classify the constant steady burning pain, described as atypical TN, as non-TN neuropathic pain in the face if there is a lack of the typical unilateral, evoked (or nonevoked), shock-like component. However, if that were present, then I would consider it atypical TN. This is a small point because this is merely a matter of classification difference (although the sole presence of steady NP may raise concern about the lesser efficacy of surgery and risk of anaesthesia dolorosa). An essential point is very important, however, and that is to be clear that this pain should not be classified as atypical facial pain, which has a pejorative connotation of being emotional in origin or, as the author states, "neurotic" or "egodecompensation".

Following is a chapter aimed at the dentist, a succinct account in five pages, which can be read in a few minutes. When faced with a patient in whom a nondental facial pain is suspected, it quickly enables a rapid identification of the symptoms of TN and appropriate treatments, and to avoid dental procedures such as fillings, root canals and extractions, which have no role in most cases.

A comprehensive chapter on medical treatment is a must read for clinicians and divides drugs into anticonvulsants and nonanticonvulsants and rightly places carbamazepine as the first-line treatment based on RCTs performed in the 1960s, but also based on a large clinical experience since that time. It should be noted that TN is very difficult to study via RCTs because of its scarcity and also because of its variable natural history. It is pointed out in this chapter, generally, that the choice of drugs is based on clinical experience and there are relatively few recent RCTs, particularly of next-generation anticonvulsant drugs. Oxcarbazepine, a drug very similar to carbamazepine, but with less drug interactions, is reviewed as an alternative to carbamazepine, but based on quite small trials. The evidence regarding oxcarbazepine being superior to carbamazepine is based on uncontrolled data. RCTs have shown no difference and there is more concern about hyponatremia. The controlled release formulation of carbamazepine is not mentioned but is very useful to capture control at low doses when used every 8 h in place of the more short-acting carbamazepine, which lasts about 4 h and probably produces higher peaks and lower valleys, making it not as effective and less tolerated. The weak evidence for gabapentin and pregabalin is reviewed as well as for lamotrigine and topiramate. The remainder deals with nonanticonvulsant medications for TN and discusses a number of these documenting mainly uncontrolled open-label studies involving small numbers of patients with variable success with a variety of drugs. The chapter concludes by discussing special issues in current medical therapy including refractory TN, TN in the emergency room, with pregnancy and multiple sclerosis, sensitivity to medications, brand versus generic drugs, and mono- versus polytherapy as well as tapering medication. The chapter concludes that first-line therapy should be carbamazepine or oxcarbazepine but that a comparative trial has shown no advantage of oxcarbazepine, which is also a new drug and may have an increased incidence of hyponatremia and be more expensive. It discusses gabapentin as a second-line option, although stating it may be initially useful in some cases. It also mentions the use of combinations of drugs but points out that often this is not terribly useful. In essence, I think it corroborates this reviewer's experience that when carbamazepine or oxcarbazepine fail, usually one is going to have difficulty and often moves toward surgical procedures.

The section on the differential diagnosis, look-a-like diseases and atypical TN is one of the most important chapters in the book for clinicians. It is obviously written by authors with extensive experience and is practical. An important point is that there should be no problem mistaking typical TN. The chapter deals with myths about typical TN regarding sensory loss, unresponsiveness to carbamazepine and bilateral cases.

The various chapters on the evaluation of the preoperative patient and the more minor procedures with their risks and benefits such as radiofrequency lesioning, balloon compression, intracavernous glycerol and stereotactic radiosurgery (the gamma knife) will be primarily of interest to interventionalists who are not always neurosurgeons worldwide. However, there are many intriguing aspects of interest here to others and useful to the interested patient (and relative) facing a surgical procedure.

Surely, chapter 14 is the jewel in the crown of this book and is by Jannetta and colleagues. In the introduction of this chapter, Jannetta reviews the history underlying his thinking about the MVD operation. He reviews the work of Dandy and goes on to pay tribute to the contribution of Gardner. Jannetta then discusses, in detail, how he came to develop the MVD operation and the role of compression by arteries and veins, some quite occult, in producing TN, the cure by MVD and then the extrapolation to other conditions other than TN such as hemifacial spasm, glossopharyngeal neuralgia, vertigo, tinnitus, nervus intermedius neuralgia and Meniere's disease.

The final chapter on the future of medical therapy is by one of the foremost experts in the medical management of TN, Joanna Zakrzewska. This is a provocative chapter for clinical trialists. It begins with a section on genomics. One of the most important advances in recent years was the identification of a population of Asian patients who are at particular risk for carbamazepine-induced Stevens-Johnson syndrome, which is associated with the presence of HLA-B*1502. Of considerable interest would be the identification of genes associated with sodium channels because the drugs (predominantly anticonvulsants) that work are sodium channel blockers but with great variability in responsivity (overwhelmingly carbamazepine and oxcarbazepine in this category). There is a good discussion of the difficulties in conducting RCTs in TN which is, in this reviewer's opinion, the most difficult NP to study in this fashion. The reasons are that it is rare and difficult to generate patients, there are spontaneous remissions and it is very important to clearly diagnose typical TN rather than include atypical forms. There is also the ethical issue that this pain is excruciating and a placebo is probably not ethical, which means a head-to-head trial, which means larger numbers of patients. A discussion regarding the selection of patients for trials of TN ensues. It deals with the nature of the pain, its temporal profile, age, sex and rescue medication. The suggestions about clinical trial design are important such as N-of-1 and enrichment type studies, all particularly applicable to TN because of the problems discussed. There is then a further discussion of dosage, duration of trial, outcome measures, particularly the issue of disease-specific outcome measures, which should be assessed as occurs in TN such as pain triggered by brushing teeth, eating, washing, shaving and speaking, which are not rated in general function rating scales. The final discussion is of a variety of potential new drug treatment approaches. Obviously, new antiepileptic drugs are of prime importance because these are the ones that work best. Although the mainstay of current medical treatment is carbamazepine or oxcarbazepine, perhaps augmented by gabapentin in combination with other much less effective drugs, there is hope on the horizon for improved medical treatment. Although TN currently is the most successfully treated NP with pharmacotherapy, there do remain patients who do not respond and who lose responsivity over time, probably because of disease progression.

In conclusion, this is a superb book edited by one of the masters in this area with contributions by many experts but with the master's hand evident throughout. It should be of wide interest to clinicians, and clinical and basic researchers in facial pain but also to those interested in neuropathic pain generally, and to some patients and their relatives. It is practical but also stimulates thought regarding the singularity of this neuropathic condition with the particular efficacy of the specific sodium channel blocker carbamazepine and marked initial efficacy of a variety of surgical options. I highly recommend this small, reasonably priced volume.