Cervicogenic headache pain in the neck for some neurologists

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					                                                                                                                                               Reflection and Reaction

    Alter J, Lou F, RabinowitzA, etal. Systemic delivery of morpholino                Hoffman EP. Skipping toward personalized molecular medicine.
    oligonucleotide restores dystrophin expression bodywide and improves              N EnglJ A/led 2007; 357: 2719-22.
    dystrophic pathology. Nat A/led 2006; 12:175-77-                                  Aartsma-RusA, Fokkema IF, VerschuurenJJ, etal. Theoretic applicability of
    Mann CJ, Honeyman K, Cheng AJ, et al. Antisense-induced exon skipping             antisense-mediated exon skipping for Duchenne muscular dystrophy
    and synthesis of dystrophin in the mdx mouse. ProcNat/AcadSdUSA 2001;             mutations. Hum Mutat 2009; 30: 293-99.
    98: 42-47                                                                         Aartsma-Rus A, Janson AA, Kaman WE, et al. Antisense-induced multiexon
    van DeutekomJC, Bremmer-Bout MJanson AA, etal. Antisense-induced                  skipping for Duchenne muscular dystrophy makes more sense.
    exon skipping restores dystrophin expression in DMD patient derived               AmJ Hum Genet 2004; 74: 83-92.
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    357: 2677-86.                                                                     Assessment of the feasibility of exon 45-55 multiexon skipping for
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Cervicogenic headache: a pain in the neck for some
In this issue of The Lancet Neurology, Bogduk and Govind                         of the C3 afférents; this is certainly consistent with the see Review page 959
review the vexed topic of cervicogenic headache.1 As a                           laboratory anatomy.8 What would the convergence of
neurologist interested in headache, it seems self-evident                        these afférents predict? The data suggest that nociceptive
that this topic should be of interest. Much of what has                          activation in structures innervated by either trigeminal
passed for science in this field is rightly criticised by the                    or upper cervical afférents might result in a perception of
authors, and there seems no benefit in trawling over the                         pain that is not anatomically related to the structure with
arguments, for ifthere was no controversythere would be                          the pathology. Put simply, the anatomy predicts that the
no issue. As the authors say, the anatomy and physiology                         simple clinical localisation process of "pain marks the
are clear enough,2 so what is the problem? There are                             spot" is doomed to fail. Moreover, the data all suggest
several issues, again largely and capably discussed by                           that cervicogenic headache—headache from activation
Bogduk and Govind; I would like to highlight some of                             of nociceptors in the upper cervical spine—should exist.
these from the neurologist's perspective, as I think we                             An important aspect of the apparent controversy in this
need to get our house in order. The three particular topics                      field might relate substantially to referral bias. In the USA,
of note are: the clinical implications of the anatomy and                        more than 90% of patients who presentto a physician with
physiology, the problem of referral bias, and the issue of                       disabling headache lasting longer than 3 months have
primary versus secondary headache from a neurologist's                           migraine.9 This predominance of migraine is likely to feed
point of view. Finally, how should we proceed?                                   into neurology practice, which means that, whatever the
   Perhaps the most basic issue revolves around the                              prevalence of cervicogenic headache, neurological practice
anatomy and physiology of upper cervical segment                                 will be swamped with cases of migraine. If the above
nociceptive afférents and their projections to second-                           analysis of the anatomy and physiology is accepted, and
order neurons. In experimental animals, the cervical                             the data on neck symptoms in patients with premonitory
and ophthalmic division of trigeminal neurons clearly                            symptoms suggest that about 90% of these patients have
synapse on common second-order neurons34 in the                                  these symptoms,10 then most patients seen in neurology
trigeminocervical complex.5The basic data are supported                          or headache practice with neck discomfort have migraine.
by clinical observations, such as referred pain from                             This assumption does not mean cervicogenic headache
cervical muscles6 and the C2-3 zygapophysial joint.7                             does not exist, it does not demean it, nor imply anything
Interestingly, the clinical data reviewed1 suggest that the                      negative; this is just referral bias. In a recent retrospective
caudal limit of cranial referral in the neck is at the level                     study of patients who responded to occipital nerve Vol 8 October 2009                                                                                                                           875
      Reflection and Reaction

                   stimulation (importantly, done in collaboration with               even controlled blocks can only be part of the analysis—
                   a pain specialist), half the responders had headache of            without the detailed clinical picture, these blocks alone
                   cervical origin and about half had migraine;11 yet, in my          will not advance our understanding.
                   clinical practice, not one patient with headache of cervical          Finally, as most practitioners do not have facilities
                   origin has been implanted with an occipital stimulator out         for procedures such as diagnostic blocks under X-ray
                   of more than 50 patients. Why would this be? Is it that            control and, importantly, as the procedures do not in
                   patients with neck trauma that produces pain are just sent         isolation offer a definitive biological outcome, how do
                   to pain doctors, who do a very good job with them? When            we proceed? The term "cervicogenic headache" was
                   patients with migraine are sent to pain doctors, and local         introduced by Sjaastad and colleagues in 198313 with
                   measures fail, the patients find their way to neurology,           revised criteria proposed in 199014 and 1998.15The
                   thus giving neurologiststhetwo-prongedfalse impression             International Headache Society provides diagnostic
                   that true cervicogenic headache does not exist. It is almost       criteria that, unfortunately, overlaps in two places in
                   self-evident that cervicogenic headache exists: the neck           its classification: sections 11.2.1 and 13.12.16 It would
                   has the necessary structures and trauma is conceivable.            be ideal, indeed cost-effective, if we could diagnose
                   The problem is how common is this type of headache and             cervicogenic headache by history. Unfortunately, and key
                   how do we spot it? The fact that cervicogenic headache             to the hypothesis advanced by Bogduk and Govind (and
                   might not be common in neurology clinics should not                indeed consistent with the anatomy and physiology),
                   confound either its understanding or management, as                history-taking will most often not suffice. The only
                   this strategy will not help patients.                              way forward is collaboration to test clinical history and
                      An important issue, which is very complex to unravel,           examination, underpinned by local procedures. For
                   is the intersection of neck pathology with a primary               example, my impression is that caudad pressure on the
                   headache, typically migraine. If neck pathology in a               head with lateral rotation is a very sensitive marker of
                   genetically susceptible individual produces, triggers,             upper cervical pathology (the cervical grinding test),
                   or worsens the underlying predisposition to primary                but such clinical tests need the careful approach that
                   headache, what should we call it? If the previous                  Bogduk has pioneered. Moreover, unless neurology and
                   headache type is made worse in close temporal proximity            pain medicine can work together on prospective studies
                   to a neck injury than the International Headache Society           of diagnosis and treatment, this question will be as
                   classification says, judgment is required! If a patient            controversial in two decades from now as it has been in
                   has migraine that is normally triggered by red wine and            the past two decades. As this lack of consensus would not
                   drinks red wine 16 times a month, and has headache each            help our patients, non-collaboration is just unacceptable.
                   time 6 h later, they have migraine rather than chronic
                   daily headache of the red wine type. One could take the            Peter] Goadsby
                   same view of migraine triggered by skipping meals, say             Headache Group-Department of Neurology, University of
                                                                                      California, San Francisco, 1635 Divisadero Street, San Francisco,
                   17 days a month, or even, as I have seen, a daily afternoon
                                                                                      CA 94115, CA, USA
                   headache of 4-5 h duration triggered by a morning dose   
                   of glyceryl trinitrate. Each case is migraine, with a very         I have consulted for and done research funded by neuromodulation companies
                   distinct trigger. So, if a patient is migrainous (ie, has the      (Boston Scientific and Medtronic) interested in occipital nerve stimulation,
                                                                                      although this work has not been in the sphere of cervicogenic headache.
                   genetic predisposition), and has headache aggravated by
                                                                                      1    Bogduk N, Govind J. Cervicogenic headache: assessing the evidence for clinical
                   a neck injury, then it is migraine. This does not judge the             diagnosis, invasive tests, and treatment. Lancet Neural 2009; 8: 959-68.
                   treatment, nor does the treatment alter the underlying             2    Bartsch T, Goadsby PJ. Anatomy and physiology of pain referral in primary
                                                                                           and cervicogenic headache disorders. Headache Currents 2005; 2:42-48.
                   biology. The treatment of daily migraine induced by                3    Bartsch T, Goadsby PJ. Stimulation ofthe greater occipital nerve induces
                                                                                           increased central excitability of durai afferent input. Brain 2002;
                   glyceryl trinitrate is to stop glyceryl trinitrate, if possible;
                   the treatment of daily migraine triggered by neck                  4    BartschT, Goadsby PJ. Increased responses intrigeminocervical nociceptive
                                                                                           neurones to cervical input after stimulation ofthe dura mater.Brain 2003;
                   pathology is to alleviate that pathology. Greater occipital             126:18OI-I3.
                   nerve injections with lidocaine and methylprednisolone             5    Goadsby PJ, Bartsch T. On the functional neuroanatomyof neck pain.
                                                                                           Cephalalgia 2008; 28 (suppl 1): 1-7
                   can be useful in migraine,12 but in no way imply that              6    Feinstein B, LangtonJNK, Jameson RM, Schiller F. Experiments on pain
                   there is C2 branch pathology in these patients. Thus,                   referred from deep somatic tissues. J ßonejo/nt Surgery 1954; 36A: 981-97

876                                                                                                   Vol 8 October 2009
                                                                                                                                                 Reflection and Reaction

    Dwyer A, Aprill C, Bogduk N. Cervical zygapophysial joint pain patterns I:   12   Afridi SK, Shields KG, Bhola R, Goadsby PJ. Greater occipital nerve injection
    a study in normal volunteers. Spine 1990; 15: 453-57                              in primary headache syndromes—prolonged effects from a single injection.
    Goadsby PJ, Hoskin KL.The distribution oftrigeminovascular afférents in           Pain 2OO6; 122:126-29.
    the nonhuman primate brain Macaca nemestrina: a c-fos                        13   Sjaastad 0, Saunte C, Hovdal H, Breivik H, Greenback E. 'Cervicogenic'
    immunocytochemical study.J Anatomy 1997; 190: 367-75.                             headache, an hypothesis. Cephala/g/a 1983; 3: 249-56.
    Tepper SJ, Dahlof CG, Dowson A, etal. Prevalence and diagnosis of            14   Sjaastad 0, FredriksenT, PfaffenrathV. Cervicogenic headache: diagnostic
    migraine in patients consulting their physician with a complaint of               criteria. Headache 1990; 30:725-26.
    headache: data from the landmark study. Headache 2004; 44: 856-64.           15   Sjaastad 0, FredriksenT, PfaffenrathV; the Cervicogenic Headache
    Giffin NJ, Ruggiero L, Lipton RB, etal. Premonitory symptoms in migraine:         International Study Group. Cervicogenic headache: diagnostic criteria.
    an electronic diary study. Neurology 2003; 60: 935-40.                            Headache 1998; 38:442-45.
    Paemeleire K, Van BuytenJP, Van Buynder M, etal. Phenotype of patients       l6   Headache Classification Committee of the International Headache Society.
    responsive to suboccipital neurostimulation for refractory head pain.             The International Classification of Headache Disorders: 2nd edition.
    EurJ Neurol 2008; 15 (suppl 3): 10.                                               Cepfia/alg/a 2004; 24 (suppl 1): I-I60.

Can the WATCHMAN device truly PROTECT from stroke in
atrial fibrillation?
Atrial fibrillation causes 15-20% of ischaemic strokes                           device (via a catheter-based delivery system through
and the overall risk of stroke in patients with non-                             a trans-septal puncture) was compared with that of
valvular atrial fibrillation is about 5% per year globally.1                     long-term warfarin therapy. More than 700 patients
Warfarin has long been the cornerstone for decreasing                            fulfilled the inclusion criteria of having non-valvular
risk of stroke in patients with atrial fibrillation and its                      atrial fibrillation, being suitable for anticoagulation, and
efficacy has been well established.1 However, 14-44% of                          having a CHADS2 risk score of 1 or more. Most of the
patients with atrial fibrillation who are at risk of stroke                      patients who had the device implanted (349 of 408)
are ineligible for anticoagulation therapy, mostly owing                         stopped warfarin at 45 days (as predefined) once there
to the risks of major bleeding and falls.2 Even in patients                      was transoesophageal echocardiographic confirmation
who are eligible, the risk of bleeding, inconvenience                            of LAA closure, and then remained on aspirin and
of frequent monitoring and dose adjustments, drug                                clopidogrel for 6 months after randomisation, followed
Interactions, and restrictions on diet and alcohol intake                        by long-term aspirin monotherapy. The probability
perhaps explain why warfarin discontinuation rates are                           of non-inferiority of the device was greater than
estimated to be as high as 38% per year.2                                        99-9% with regard to the primary efficacy outcome
   More than 90% of atrial thrombi originate from the                            (occurrence of all types of stroke, cardiovascular or
left atrial appendage (LAA),3 and devices that can isolate                       unexplained death, or systemic emboli within up to
this structure from the systemic circulation and perhaps                         3 years), and patients who received the device had
obviate the need for long-term anticoagulation therapy                           fewer haemorrhagic strokes than the controls. However,
have been developed. Despite early interesting and                               the primary safety endpoint (which combined major
promising data from the PLAATO device (Percutaneous                              bleeding, serious pericardial effusion, and device
Left Atrial Appendage Transcatheter Occlusion; Appriva                           embolisation) was significantly greater in the device
Medical, CA, USA), this device was withdrawn by the                              group than in the control group (relative risk 1-69,
manufacturer in 2006.4                                                           95% Bayesian credible interval 101-319), mostly due
   Another device that has been developed for LAA                                to 22 (4-8%) of these patients undergoing either
occlusion is the WATCHMAN system (Aritech Inc, MN,                               percutaneous or surgical drainage of serious pericardial
USA), which is a self-expanding nitinol frame structure.                         effusions, none of which was fatal.
Early data on this system were reported in 2007,5 and this                          Several points arise in light of this study, some of
device is the focus of the recently published PROTECT-AF                         which might affect future work on atrial fibrillation. Not
(WATCHMAN Left Atrial Appendage System for Embolie                               all thrombi originate from the LAA, with up to a quarter
Protection in Patients with Atrial Fibrillation) study.6 In                      of strokes in patients with atrial fibrillation caused
this multicentre, non-inferiority trial, the efficacy and                        by cerebrovascular disease, complex atheromatous
safety of implantation of the percutaneous LAA closure                           plaques involving the aorta and carotid arteries, and Vol 8 October 2009                                                                                                                             877

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