Paroxysmal hemicrania and hemicrania continua: Review on pathophysiology, clinical features and treatment.

BACKGROUND: Paroxysmal hemicrania and hemicrania continua are indometacin-sensitive trigeminal autonomic cephalalgias, a terminology which reflects the predominant distribution of the pain, observable cranial autonomic features and shared pathophysiology. Understanding the latter is limited, both by low prevalence and the intricacies of studying brain function, requiring multimodal techniques to glean insights into such disorders. Similarly obscure is the curious response to indometacin. This review will address what is currently known about pathophysiology, the rationale for the current classification and, features which may confound the diagnosis, such as lack of cranial autonomic symptoms and those which are typically associated with migraine such as nausea, photophobia, phonophobia and aura. Despite these characteristics, a dramatic response to indometacin, which is not seen in migraine nor the other trigeminal autonomic cephalalgias , provides the hallmark of the diagnosis. The main clinical differential for paroxysmal hemicrania is based on temporal pattern and lies between cluster headache and short-lasting-neuralgiform headache attacks with tearing or additional cranial autonomic symptoms. For hemicrania continua it is more challenging as the main differential for which the disorder is often treated is migraine. A prior episodic pattern, often days at a time, and the tendency to exacerbation with analgesics will further deflect from the diagnosis. The relevance of this is that there is little overlap in therapeutics between paroxysmal hemicrania and hemicrania continua and other headache disorders and there are limited effective alternatives to indometacin. The most effective are other non-steroidal anti-inflammatory drugs including the newer COX-II inhibitors. Even though early reports suggest that a higher indometacin dose-requirement may herald a secondary precipitating pathology, this does not seem to be the case, with syndrome and response to treatment being similar with the primary disorder. In this context imaging of new onset paroxysmal hemicrania or hemicrania continua and implication of the results will be discussed as will alternative treatment options.

Guidelines for the management of trigeminal neuralgia.

Guidelines for the diagnosis and treatment of patients with trigeminal neuralgia (TN) advocate for a multidisciplinary team approach to improve the care of patients with acute and chronic TN. Evidence-based discussions and decisions are encouraged to establish care pathways for prompt diagnosis and treatment, and long-term outcomes data collection to improve care. The guidelines include summary materials for patients to inform them about their condition and available treatments.

Secondary cough headache: Independent course of headache and response to a COX-2 inhibitor.

We report on two patients with secondary cough headache who responded to the cyclo-oxygenase-2 (COX-2) inhibitor etoricoxib and showed an independent temporal course. This case report shows that secondary cough headache can also respond to medical treatment and can respond to a COX-2 inhibitor, not previously reported. As is seen in primary cough headache, the headache disorder can go into natural remission (case 1) while the secondary pathology progresses and conversely, persist once the secondary pathology has resolved (case 2). The course of the headache and that of the secondary pathology do not necessarily correlate. It is, therefore, proposed that any treatment of the secondary pathology is independent to that of the headache. In NSAID-intolerant cases a COX-2 inhibitor can be trialled first line.

Etoricoxib and celecoxib sensitive indomethacin-responsive headache disorders.

Indomethacin-responsive headaches encompass a group of disorders which include a subset of the trigeminal autonomic cephalalgias and other paroxysmal, often precipitated primary headaches. Many patients show a rapid therapeutic response to indomethacin, which is limited by intolerability. Etoricoxib and celecoxib, selective inhibitors of cyclo-oxygenase-2 (COX-2), spare gastroduodenal COX-1 activity and are less likely to cause gastrointestinal adverse effects than indomethacin. We report a case series of eight patients, seven who responded to etoricoxib and one patient who responded to celecoxib.

The efficacy of botulinum toxin type-A for intractable chronic migraine patients with no pain-free time.

AIM: This is a retrospective report of the efficacy of botulinum toxin-A, Botox® (Allergan), in intractable chronic migraine patients non-responsive to previous pharmacological management and with largely no pain-free time, including those with new onset daily persistent headache. METHODS: Thirty-three patients, all with severe Headache Impact Test (HIT)-6 scores at baseline, received 3-monthly injections of Botox® as per Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PRE-EMPT) protocol over a maximum 33-month period. Response criteria were a sustained reduction of HIT-6 scores below 60. RESULTS: Four patients had headache on at least 20 days a month; the remaining patients had daily headache with no pain-free time, including nine patients with new onset persistent migraine. There was a significant reduction in HIT-6 scores following Botox® therapy (x̅ = -5.45, p = 0.000920). Twenty-one percent of the cohort exhibited a sustained reduction in HIT-6 scores below 60. The number of headache days and pain-free time did not change in five of the six responders, but disability improved. There was no difference between patients with episodic migraine evolving to chronic as opposed to those with chronic migraine from onset. CONCLUSION: This report suggests that Botox® treatment is efficacious in intractable chronic migraine without pain-free time. The HIT-6 is a reliable and practical parameter to assess disability in this patient group. Use of such validated parameters should be considered with greater weight in future International Classification of Headache Disorders (ICHD) guidelines for controlled clinical trials.

Time to retire 'New daily persistent headache': Mode of onset of chronic migraine and tension-type headache.

New daily persistent headache is described as an enigmatic condition with daily headache from onset. It has posed challenges diagnostically and therapeutically.Methods: We conducted a study of patients referred to headache services based in Central and North-East London, United Kingdom, meeting the International Classificaiton of Headache Disorders - 3 criteria for New daily persistent headache. Information on demographics, phenotype and treatment responses were collected. The syndrome of the daily headache was also classified according any other ICHD-3-defined syndrome.Results: Of 162 patients, females comprised 68.5% with median age of onset 35 years. The daily headache experienced was chronic migraine in 89.7% and tension-type headache in 8.8%. Thunderclap-onset New daily persistent headache occurred in 14.8%. More than one headache syndrome was experienced in 15.4%, including cough, hypnic, sexual and stabbing headache. All aura types were experienced, most commonly brainstem aura in 39%. Prior headache was reported 53.7%. A persisting sub-form was present in 51.2%, relapsing remitting in 12.3% and 14.0% reported improvement; 19.8% were lost to follow-up. Only 11.1% reported an antecedent trigger. The most common premorbid disorders were psychiatric in 35.7%. A fifth improved on preventative medication, most commonly amitriptyline, propranolol and topiramate.Conclusion: Our cohort of New daily persistent headache is consistent with a mode of onset of migraine and tension-type headache which occurs in predisposed individuals.

Isolated headache is not a reliable indicator for brain cancer: the 2-week wait pathway for suspected CNS malignancies.

INTRODUCTION: The UK uses the 2-week-wait (2WW) pathway for rapid access to cancer services. It is unclear whether this is effective for brain cancer. METHODS: We retrospectively analysed all 2WW referrals for brain cancer between 2009 and 2016 in a district general neurology department. We compared clinical presentations to national guidelines and diagnoses of brain cancer. RESULTS: Of the 153 cases analysed, four brain cancers were identified: two glioblastomas and two metastases. Headaches were the most common referral. The end diagnosis was mostly migraine. The highest positive predictive value was for behavioural/personality change (5.3%) and sub-acute neurological deficit (3.2%). There was no significant association between any symptom(s) and brain cancer. CONCLUSION: The 2WW pathway is not effective in the diagnosis of brain cancer. Resources are better directed towards clinical research and treatment trials. Headache remains the most common reason for referral although it is not yet a reliable indicator of brain cancer.

Changes in peripheral and central sensitization in patients undergoing occipital nerve stimulation.

INTRODUCTION: Central sensitization and impaired conditioned pain modulation (CPM) response have been reported to contribute to migraine progression. Migraine patients can present with allodynia possibly attributed to increased sensitivity of peripheral ends of nociceptors with both peripheral and central sensitization. Occipital nerve stimulation (ONS) works by stimulating the distal branches of C1, C2 and C3 possibly altering the nociceptive traffic to the trigemino-cervical complex, brainstem and supranuclear connections. AIMS: This observational study explores peripheral and central sensitization in patients undergoing percutaneous ONS. METHODS: Following local regulatory approval, 13 patients undergoing ONS with dual Octrode 90 cm leads and rechargeable implantable pulse generator (IPG) (St Jude) were recruited to have quantitative sensory testing (QST) pre- and post-procedure 2 weeks, 1, 3, 6 and 12 months. RESULTS: Patients with intractable migraine demonstrated impaired CPM (mean baseline pressure pain thresholds (PPTs): 61.98 kPa vs 48.01 kPa cuff inflated) prior to ONS, reverting to an efficient CPM response within 2 weeks following ONS implant (68.9 kPa vs 104.5 kPa cuff inflated) and continuing positively over the next 12 months. In contrast, no statistical difference was observed in PPTs. CONCLUSION: This is the first reported observation highlighting the effects on central sensitization following ONS. A consistent and sustained improvement in CPM was observed in contrast to PPT's where there was no difference. Normalisation of the CPM response following ONS indicates that the treatment may reduce central sensitization in the migraine population.

Other primary headaches-thunderclap-, cough-, exertional-, and sexual headache.

This article reviews the disorders of thunderclap, cough, exertional and sexual headache. These are a group of paroxysmal and precipitated headaches, which often occur in bouts with prolonged remissions. Indometacin seems to be the most effective preventative. Each can occur in primary and secondary form. Thunderclap headache is the most frequently reported headache syndrome associated with a secondary pathology. Discussed are the complexities of whether all patients with thunderclap headache should have further investigation if timely computerised tomography is normal and, the relevance of abnormal imaging in these disorders, differentiating what is deemed to be secondary and managing the pain.

Paroxysmal Hemicrania.

Paroxysmal hemicrania (PH) is a primary headache disorder belonging to the group of trigeminal autonomic cephalalgias(TACs). Patients typically experience intense lateralzsed headaches with pain primarily in the ophthalmic trigeminal distribution (V1) associated with superimposed ipsilateral cranial autonomic features. PH is distinguished from other TACs by an exquisite responsiveness to therapeutic doses of indomethacin. Patients may need to be maintained on indomethacin for several months before trials of reduction can be attempted. The disorder does have a tendency toward chronicity. PH is uncommon, but early recognition will prompt initiation of effective treatment to avoid unsuccessful trials of drugs effective in other primary headaches. As with other TACs, hypothalamic and trigeminovascular mechanisms are implicated in the pathophysiologic mechanism of PH. Neuroimaging findings in PH demonstrate a posterior hypothalamic activation similar to that observed in the other TACs. This review will address the epidemiology, clinical presentation, pathophysiology, evaluation, and treatment of PH.

Other primary headaches.

The 'Other Primary Headaches' include eight recognised benign headache disorders. Primary stabbing headache is a generally benign disorder which often co-exists with other primary headache disorders such as migraine and cluster headache. Primary cough headache is headache precipitated by valsalva; secondary cough has been reported particularly in association with posterior fossa pathology. Primary exertional headache can occur with sudden or gradual onset during, or immediately after, exercise. Similarly headache associated with sexual activity can occur with gradual evolution or sudden onset. Secondary headache is more likely with both exertional and sexual headache of sudden onset. Sudden onset headache, with maximum intensity reached within a minute, is termed thunderclap headache. A benign form of thunderclap headache exists. However, isolated primary and secondary thunderclap headache cannot be clinically differentiated. Therefore all headache of thunderclap onset should be investigated. The primary forms of the aforementioned paroxysmal headaches appear to be Indomethacin sensitive disorders. Hypnic headache is a rare disorder which is termed 'alarm clock headache', exclusively waking patients from sleep. The disorder can be Indomethacin responsive, but can also respond to Lithium and caffeine. New daily persistent headache is a rare and often intractable headache which starts one day and persists daily thereafter for at least 3 months. The clinical syndrome more often has migrainous features or is otherwise has a chronic tension-type headache phenotype. Management is that of the clinical syndrome. Hemicrania continua straddles the disorders of migraine and the trigeminal autonomic cephalalgias and is not dealt with in this review.

Familial hemicrania continua.

There are now three known causative genes for familial hemiplegic migraine and increasing evidence to support a genetic predisposition to the more common types of migraine with and without aura, and for cluster headache. We present the first reported case of familial hemicrania continua. A mother and daughter developed hemicrania continua at the same time of life. Both showed an absolute response to indometacin and at similar doses. Both also suffered from migraine with aura. We discuss the increasing support for a genetic predisposition to dysfunction of the pain system within the brain manifesting as primary headache.

Primary Headache Disorders: Focus on Migraine.

Migraine is the most common disabling headache disorder.Most patients with disabling tension-type headache are likely to have migraine and accordingly respond to treatments efficacious in migraine.Individuals are genetically predisposed to experiencing recurrent migraine.Evidence supports migraine to be a primarily neural and not vascular mediated disorder.1-2% of the population have chronic daily headache associated with acute-relief medication overuse; the majority are migraineurs.The presence of acute-relief medication overuse renders preventative medication less adequately efficacious.

Imaging patients with suspected brain tumour: guidance for primary care.

The number of referrals by primary care practitioners to secondary care neurology services, particularly for headache, may be difficult to justify. Access to imaging by primary care practitioners could avoid referral without compromising patient outcomes, but the decision to refer is based on a number of complex factors. Due to the paucity of rigorous evidence in this area, available data are combined with expert opinion to offer support for GPs. The study suggests management for three levels of risk of tumour: red flags>1%; orange flags 0.1-1%; and yellow flags<0.1% but above the background population rate of 0.01%. Clinical presentations are stratified into these three groups. Important secondary causes of headache where imaging is normal should not be overlooked, and normal investigation does not eliminate the need for follow-up or appropriate management of headache.

Recurrent anterior chamber hemorrhage from an intraocular lens simulating amaurosis fugax.

Uveitis-glaucoma-hyphema syndrome is a rare late complication of anterior segment surgery. We present 2 unusual cases of this syndrome that were mistakenly diagnosed as amaurosis fugax, leading to contraindicated treatment. These cases illustrate the need for ophthalmologic examination during an episode of symptoms.

Headache and migraine.

Headache is the commonest neurological presentation. Most patients have a benign pain disorder. The majority manage themselves with over-the-counter medications. Unfortunately therapeutic strategies in primary and secondary health care remain suboptimal and thus the condition poorly managed.