LASH syndrome: New cases with a broadening clinical phenotype.

OBJECTIVE: To describe three new cases of the headache syndrome of long-lasting autonomic symptoms with hemicrania (LASH), and to establish a clinical phenotype utilizing all LASH cases noted in the medical literature. METHODS: A case series of patients was evaluated in an academic headache clinic over a two-year time period. LASH syndrome was defined by episodic headache attacks with associated cranial autonomic symptoms that start before headache onset, last the entire duration of the headache and continue on for a period of time after the headache ceases. RESULTS: Three patients were noted to have LASH syndrome in a two-year time period (2017-2018). One patient was diagnosed with primary LASH, while two others had probable secondary LASH from a secretory pituitary tumor. The primary LASH patient was female. She had on average one headache per week lasting 1-3 days in duration. She experienced migrainous associated symptoms along with their cranial autonomic symptoms. She also developed a fixed Horner's syndrome along with a typical headache attack, which was present for 6 months at the time of consultation. She had complete headache relief with indomethacin and her miosis and ptosis also resolved with treatment. Secondary LASH was diagnosed in two patients (one male, one female) both with prolactin secreting pituitary microadenomas. One of the patients had his headaches abolish with dopamine agonist therapy while the other patient did not respond to hormonal modulation but became pain free on indomethacin. Secondary LASH patients had less frequent headache episodes and lacked any migrainous associated features, but exhibited agitation with headache. CONCLUSION: LASH syndrome may be rare, but more reported cases are entering the headache literature. The temporal profile of onset and offset of cranial autonomic symptoms is key to making the diagnosis. Primary and secondary LASH may present differently based on gender predominance, the presence of migrainous associated features, and attack frequency. Secondary LASH appears to be indomethacin responsive, suggesting that medication effectiveness should not obviate the need to do testing for secondary etiologies.

Hints on Diagnosing and Treating Headache.

BACKGROUND: Headache, like dizziness, is one of the more common presenting complaints in outpatient care and in the emergency room. More than 200 varieties of headache have been described, and the false impression may arise that the diagnosis and treatment of these syndromes is a highly challenging task. METHODS: This review is based on pertinent articles retrieved by a selective search in PubMed. RESULTS: In primary headache, the headache is not a symptom but a disease in its own right. There are four types of primary headache: migraine, tension headache, trigeminal autonomic cephalalgia, and other primary headache disorders. By definition, the physical examination is normal, including the neurological examination. Secondary headache, in contrast, is a symptom of another disease (e.g., a tumor or cerebral hemorrhage). Triptans and nonsteroidal anti-inflammatory drugs (NSAID) are the drugs usually given for the acute treatment and prophylaxis of migraine. In tension headache, NSAID are given acutely, and tricyclic drugs for prophylaxis. There are various options for the treatment of trigeminal autonomic cephalalgia syndromes such as cluster headache and paroxysmal hemicrania. For group 4 headaches (other primary headache disorders), the treatment must be chosen on an individual basis; indomethacin is often effective. CONCLUSION: If the patient is clearly suffering from none of the four types of primary headache, the problem must be a headache of a secondary nature, potentially reflecting a dangerous underlying disease. The treatment of headache is usually successful and thus highly rewarding for physicians of all medical specialties.

Therapeutic Approaches for the Management of Trigeminal Autonomic Cephalalgias.

Trigeminal autonomic cephalalgia (TAC) encompasses 4 unique primary headache types: cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms. They are grouped on the basis of their shared clinical features of unilateral headache of varying durations and ipsilateral cranial autonomic symptoms. The shared clinical features reflect the underlying activation of the trigeminal-autonomic reflex. The treatment for TACs has been limited and not specific to the underlying pathogenesis. There is a proportion of patients who are refractory or intolerant to the current standard medical treatment. From instrumental bench work research and neuroimaging studies, there are new therapeutic targets identified in TACs. Treatment has become more targeted and aimed towards the pathogenesis of the conditions. The therapeutic targets range from the macroscopic and structural level down to the molecular and receptor level. The structural targets for surgical and noninvasive neuromodulation include central neuromodulation targets: posterior hypothalamus and, high cervical nerves, and peripheral neuromodulation targets: occipital nerves, sphenopalatine ganglion, and vagus nerve. In this review, we will also discuss the neuropeptide and molecular targets, in particular, calcitonin gene-related peptide, somatostatin, transient receptor potential vanilloid-1 receptor, nitric oxide, melatonin, orexin, pituitary adenylate cyclase-activating polypeptide, and glutamate.

Trigeminal autonomic cephalalgias: beyond the conventional treatments.

The trigeminal autonomic cephalalgias include cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, and hemicrania continua. While the majority responds to conventional pharmacological treatments, a small but significant proportion of patients are intractable to these treatments. In these cases, alternative choices for these patients include oral and injectable drugs, lesional or resectional surgery, and neurostimulation. The evidence base for conventional treatments is limited, and the evidence for those used beyond convention is more so. At present, the most evidence exists for nerve blocks, deep brain stimulation, occipital nerve stimulation, sphenopalatine ganglion stimulation in chronic cluster headache, and microvascular decompression of the trigeminal nerve in short-lasting unilateral neuralgiform headache attacks.

Sistema trigémino vascular y cefalea / Trigeminovascular System and Primary Headache

La fisiopatología de las cefaleas primarias es compleja e incluye un sinnúmerode interacciones que regulan el proceso nociceptivo. Dentro de los principalesresponsables de generar el dolor se encuentra el sistema trigémino vascular, que esun conjunto de estructuras que integran vías tanto centrales corticosubcorticales comoperiféricas, que desempeñan un papel activo no solo en la génesis del dolor, sino enlas manifestaciones autonómicas y visuales que acompañan la cefalea. Así mismo, estesistema es el responsable de los mecanismos de sensibilización central característicosdel dolor. En el artículo se desarrollan brevemente las principales estructuras queparticipan en la génesis de las cefaleas primarias y sus interacciones en las diferentespartes del sistema nervioso...

The pathophysiology of primary headache iscomplex and it includes several interactionsthat regulate the nociceptive process. The trigeminal-vascular system is perhaps one of theprincipal structures that generate pain due tothe integration of several pathways both centraland peripheral. In addition to this, the trigeminalvascular system also plays a central role inthe autonomic and visual symptoms that affectindividuals with headache and in the centralsensitization process. In this article we brieflydiscuss the main structures that participate in thepathophysiology of primary headaches and theirinteractions in the different levels of the centralnervous system...

Neuroimaging in cluster headache and other trigeminal autonomic cephalalgias.

The central nervous system mechanisms involved in trigeminal autonomic cephalalgias, a group of primary headaches characterized by strictly unilateral head pain that occurs in association with ipsilateral craniofacial autonomic features, are still not comprehensively understood. However, functional imaging methods have revolutionized our understanding of mechanisms involved in these primary headache syndromes. The present review provides a brief overview of the major modern functional neuroimaging techniques used to examine brain structure, biochemistry, metabolic state, and functional capacity. The available functional neuroimaging data in cluster headache and other TACs will thus be summarized. Although the precise brain structures responsible for these primary headache syndromes still remain to be determined, neuroimaging data suggest a major role for posterior hypothalamus activation in initiating and maintaining attacks. Furthermore, pathophysiological involvement of the pain neuromatrix and of the central descending opiatergic pain control system was observed. Given the rapid advances in functional and structural neuroimaging methodologies, it can be expected that these non-invasive techniques will continue to improve our understanding into the nature of the brain dysfunction in cluster headache and other trigeminal autonomic cephalalgias.

[Review of the target for the deep brain stimulation of chronic cluster headache]. / Revision de la diana para la estimulacion cerebral profunda de la cefalea en racimos cronica.

Cluster headache is included in the group of trigeminal autonomic cephalalgias. Although the pathophysiology of cluster headache has not yet been sufficiently established, the theory of a central origin tells us that this headache is produced by hypothalamic dysfunction. More than 50 patients have been treated with deep brain stimulation of the posterior nucleus of the hypothalamus from 2001. The results show clinical improvement in more than 60% of the cases, opening a promising issue for the treatment of the cluster headache persistent after medical treatment. The surgical target that have been used until now is based on the origin of the cluster headache in the hypothalamic dysfunction. Nevertheless, It has still some open questions as the lack of proving the posterior nucleus of the hypothalamus is the real origin of the cluster headache, the lack of consensus about the anatomy of the surgical target and the variability of the structures stimulated with the surgery. The aim of this article is a review of the target used and propose another surgical target based on physiopathological concepts to explain the improvement with the deep brain stimulation in these patients.

A history of cigarette smoking is associated with the development of cranial autonomic symptoms with migraine headaches.

OBJECTIVE: To look at the smoking history of migraine patients and to determine if a history of cigarette smoking is associated with the development of cranial autonomic symptoms with migraine headaches. BACKGROUND: It has recently been noted that a significant number of migraine patients may develop autonomic symptoms during their attacks of headache. Why some headache patients activate the trigeminal autonomic reflex and develop cranial autonomic symptoms while others do not is unknown. Cluster headache occurs more often in patients with a history of cigarette smoking, suggesting a link between tobacco exposure and cluster headache pathogenesis. Could cigarette smoking in some manner lead to activation of the trigeminal-autonomic reflex in headache patients? If cigarette smoking does lower the threshold for activation of the trigeminal autonomic reflex then do migraine patients who have a history of cigarette smoking more often develop cranial autonomic symptoms than migraineurs who have never smoked? METHODS: Consecutive patients diagnosed with migraine (episodic or chronic) who were seen over a 7-month time period at a newly established headache center were asked about the presence of cranial autonomic symptoms during an attack of head pain. Patients were deemed to have positive autonomic symptoms along with headache if they experienced at least one of the following symptoms: eyelid ptosis or droop, eyelid or orbital swelling, conjunctival injection, lacrimation, or nasal congestion/rhinorrhea. A smoking history was determined for each patient including was the patient a current smoker, past smoker, or had never smoked. Patients were deemed to have a positive history of cigarette smoking if they had smoked continuously during their lifetime for at least at 1 year. RESULTS: A total of 117 migraine patients were included in the analysis (96 female, 21 male). Forty-six patients had a positive smoking history, while 71 patients had no smoking history. Some 70% (32/46) of migraineurs with a positive history of cigarette smoking had cranial autonomic symptoms along with their headaches, while only 42% (30/71) of the nonsmoking patients experienced at least 1 autonomic symptom along with headaches and this was a statistically significant difference (P < .005). In total, 74% of current smokers had autonomic symptoms with their headaches compared with 61% of past smokers and this was not a statistically significant difference. There was a statistically significant difference between the number of current smokers who had autonomic symptoms with their headaches compared with the number of patients who never smoked and had autonomic symptoms (P < .05). Overall, 52% of the studied migraineurs had autonomic symptoms. There was a statistically significant difference between autonomic symptom occurrence in male and female smokers vs male and female nonsmokers. Each subtype of cranial autonomic symptoms was all more frequent in smokers. CONCLUSION: A history of cigarette smoking appears to be associated with the development of cranial autonomic symptoms with migraine headaches.

Patent foramen ovale in trigeminal autonomic cephalalgias and hemicrania continua: a non-specific pathophysiological occurrence?

Patent foramen ovale (PFO), a relatively common abnormality in adults, has been associated with migraine. Few studies also linked PFO with cluster headache (CH). To verify whether right-to-left shunt (RLS) is related to headaches other than migraine and CH, we used transcranial Doppler following microbubbles injection to detect shunts in 24 CH, 7 paroxysmal hemicrania (PH), one SUNCT, two hemicrania continua (HC) patients; and 34 matched controls. RLS was significantly more frequent in CH than in controls (54% vs. 25%, p=0.03), particularly above the age of 50. In the HC+PH+SUNCT group, RLS was found in 6 patients and in 2 controls (p=0.08). Smoking as well as the Epworth Sleepiness Scale correlated significantly with CH, smoking being more frequent in patients with RLS. PFO may be non-specifically related to trigeminal autonomic cephalalgias and HC. The headache phenotype in PFO patients probably depends on individual susceptibility to circulating trigger factors.

Patent foramen ovale in trigeminal autonomic cephalalgias and hemicrania continua: a non-specific pathophysiological occurrence? / Foramen oval patente em cefaleias trigêmino-autonômicas e hemicrania contínua: uma ocorrência fisiopatológica não específica?

Patent foramen ovale (PFO), a relatively common abnormality in adults, has been associated with migraine. Few studies also linked PFO with cluster headache (CH). To verify whether right-to-left shunt (RLS) is related to headaches other than migraine and CH, we used transcranial Doppler following microbubbles injection to detect shunts in 24 CH, 7 paroxysmal hemicrania (PH), one SUNCT, two hemicrania continua (HC) patients; and 34 matched controls. RLS was significantly more frequent in CH than in controls (54 percent vs. 25 percent, p=0.03), particularly above the age of 50. In the HC+PH+SUNCT group, RLS was found in 6 patients and in 2 controls (p=0.08). Smoking as well as the Epworth Sleepiness Scale correlated significantly with CH, smoking being more frequent in patients with RLS. PFO may be non-specifically related to trigeminal autonomic cephalalgias and HC. The headache phenotype in PFO patients probably depends on individual susceptibility to circulating trigger factors.

O forame oval patente (FOP), uma anormalidade cardíaca relativamente comum em adultos, tem sido associado à enxaqueca, mas raramente às cefaléias trigêmino-autonômicas (TACs). Utilizamos o Doppler transcraniano (DTC) para detecção de shunt direito-esquerdo (SDE) em 24 pacientes com cefaléia em salvas (CS), sete com hemicrania paroxística (HP), dois com hemicrania continua (HC) e um com SUNCT; alem de 34 controles. O SDE foi mais frequente nos pacientes com CS do que nos controles (54 por cento vs. 25 por cento p=0,03), particularmente acima de 50 anos. No grupo HP+HC+SUNCT, o SDE foi encontrado em seis pacientes e dois controles (p=0,08). O hábito de fumar, bem como sonolência excessiva diurna foram mais frequentes em paciente com CS. O FOP pode ter importância inespecífica na fisiopatologia das TACs e HC, na dependência da susceptibilidade individual a fatores desencadeantes.

Trigeminal autonomic cephalalgias: paroxysmal hemicrania, SUNCT/SUNA, and hemicrania continua.

The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders that include cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing/cranial autonomic features (SUNCT/SUNA). Hemicrania continua (HC) is often included with this group, although the second edition of The International Classification of Headache Disorders did not link the entities. Trigeminal autonomic cephalalgias are generally characterized by relatively short-lasting attacks of severe pain and lateralized associated features including the pain, cranial autonomic symptoms, and where present, migrainous symptoms, such as photophobia. Paroxysmal hemicrania has intermediate duration and intermediate attack frequency. Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing has the shortest attack duration and the highest attack frequency. Hemicrania continua has a continuous pain with exacerbations that can include cranial autonomic symptoms as part of the phenotype. The syndromes share much in their pathophysiology and investigation paths; however, their treatment is distinct, so that the accurate differentiation is important for optimal management.

Symptomatic trigeminal autonomic cephalalgias.

BACKGROUND: The trigeminal autonomic cephalalgias (TACs) are a group of primary headache syndromes characterized by strictly unilateral head pain that occurs in association with ipsilateral cranial autonomic features. The group includes cluster headache, paroxysmal hemicrania, and short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. These syndromes differ in attack duration and frequency as well as the response to therapy. Most of the cases of these syndromes are primary headaches, though numerous symptomatic cases have been described albeit that it is difficult to establish a causal relationship with the underlying pathology in most cases. REVIEW SUMMARY: We reviewed the literature to identify the cases of symptomatic TACs that were likely to be secondary to the reported underlying lesion. We also attempted to identify any clinical features that may be pointers for distinguishing these cases from primary cases and thereby inform the diagnostic workup of these disorders. CONCLUSION: Forty cases of symptomatic TACs were identified. These symptomatic headaches were associated with atypical phenotypes, abnormal examination, and poor treatment response though a significant minority had a typical presentation. A relatively high proportion of all TACs were secondary to pituitary tumors. It is difficult to draw up guidelines for the diagnostic workup required on the basis of this small retrospective case series. It remains unclear whether every TAC patient requires neuroimaging, though if it is considered then magnetic resonance imaging is the preferred modality. In addition, we suggest that all TAC patients should be carefully assessed for pituitary disease related symptoms but further investigations with magnetic resonance imaging of the pituitary gland and pituitary hormonal profile should only be undertaken in patients with atypical features, abnormal examination, or those resistant to the appropriate medical treatment.

Neuroimaging in trigeminal autonomic cephalgias: when, how, and of what?

PURPOSE OF REVIEW: Trigeminal autonomic cephalgias (TACs) are characterized by frequent, short-lasting headache attacks with ipsilateral facial autonomic features. They include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. The pathogenesis of TACs is largely unknown, but many case reports in the literature suggest that TACs are secondary to structural lesions. Thus, the question arises whether TAC patients should undergo neuroimaging. Here, we review the recent literature on secondary TACs and attempt to formulate guidelines for neuroimaging. RECENT FINDINGS: Recently, we published two reviews of, in total, 33 case reports of patients with a secondary TAC or TAC-like syndrome. Since then, 23 additional cases have been published. Here, we provide a summary of these 56 case reports. TACs were found to be associated with a wide range of both intracranial and extracranial neurovascular and structural lesions. We could not identify a 'typical' clinical warning profile for secondary TACs as these patients could present with clinical features that are entirely characteristic of a TAC, including alternating attack and attack-free periods, and excellent response to TAC-specific treatments. SUMMARY: Even clinically typical TACs can be caused by structural lesions. There are no 'typical' warning signs or symptoms. Neuroimaging should be considered in all patients with TAC or TAC-like syndromes, notably in those with atypical presentation. Depending on the degree of suspicion, additional imaging should be considered assessing intracranial and cervical vasculature, and the sellar and paranasal region.

[Cluster headache and other trigeminal-autonomic headaches]. / Algie vasculaire de la face et autres céphalées trigeminoautonomiques.

Cluster headache is a primary headache with a male predominance that presents in two forms: episodic and chronic, occurring at 45-to 60-day intervals with one to three headaches a day lasting 45 min to 2 h. An attack starts by a violent unilateral retro-ocular pain with sympathetic signs such as tearing and rhinorrhea. Diagnosis is made by questioning and therefore requires no complementary tests. Treatment for the attack consists of injectable sumatriptan or oxygen therapy, with long-term treatment with verapamil, lithium salts, or Topiramate; in certain cases in which the number of attacks is greater than two, injections of corticosteroids at the emergence of the Arnold nerve can be used, or in cases of attacks resistant to all treatments, hypothalamus stimulation surgery can be useful.

Deep brain stimulation in craniofacial pain: seven years' experience.

Cluster headache (CH) is a primary headache with excruciatingly painful attacks that are strictly unilateral. About 10% of cases experience no significant remission, and about 15% of these do not respond to medication, so surgery is considered. Neuroimaging studies show that the posterior inferior hypothalamus is activated during CH attacks and is plausibly the CH generator. We report on 16 chronic CH patients, with headaches refractory to all medication, who received long-term hypothalamic stimulation following electrode implant to the posterior inferior hypothalamus. After a mean follow-up of 23 months, a persistent pain-free to almost pain-free state was achieved in 13/16 patients (15/18 implants; 83.3%) a mean of 42 days (range 1-86 days) after monopolar stimulation initiation. Ten patients (11 implants) are completely pain-free. A common side effect was transient diplopia, which limited stimulation amplitude. In one patient, a small non-symptomatic haemorrhage into the 3rd ventricle occurred following implant, but regressed 24 h later. Persistent side effects are absent except in one patient with bilateral stimulation, in whom stimulation was stopped to resolve vertigo and worsened bradycardia, but was resumed later without further problems. Hypothalamic stimulation is an effective, safe and well tolerated treatment for chronic drug-refractory CH. It appears as a valid alternative to destructive surgical modalities, and has the additional advantage of being reversible.

Cefaleas primarias revisión de criterios diagnósticos y abordajes terapéuticos / Primary cephaleas: a revision of its diagnosis and therapeutic approach

Esta revisión aborda las cefaleas primarias, su diagnóstico y tratamiento. Para la IHS son: migraña, cefalea tensional, cluster y otros. Migraña: La segunda en prevalencia y la de mayor morbilidad, el aura diferencia la migraña con aura (Mca) de la sin aura (Msa). Epidemiología: prevalencia 10% con una relación 3: 1 mujer-hombre. Fisiopatología: es un trastorno nociceptivo central primario, con compromiso secundario vascular. Tratamiento: específico y no específico, tanto de las crisis como preventivo. Trastornos psiquiátricos y migraña: existe evidencia de correlación clínico patológica y farmacológica mayormente entre Mca y diversas patologías psiquiátricas. Migraña en el niño: se presenta con diferencias clínicas responde a otra farmacoterapia y es de gran importancia el enfoque familiar. Migraña y hormonas: el principal factor hormonal relacionado a la migraña es la caída hormonal. Migraña y epilepsia: comparte la hiperexcitabilidad cerebral y medicación. Migraña y enfermedad cerebrovascular: factores vasculares e isquémicos comunes. Medicina basada en la evidencia: supone un importante avance en la medición de la efectividad de los tratamientos. Cefalea tensional: la más frecuente de todas las cefaleas, subdiagnosticada. Diferencias entre episódica y crónica. Epidemiología: leve preponderancia femenina. Fisiopatología y factores influyentes: destaca el rol del sistema nociceptivo, el sedentarismo, el estrés y la tensión muscular. Tratamiento: farmacológico y no farmacológico. Cefalea en racimo: de menor prevalencia pero con clínica frondosa, muy invalidante pero con tratamiento efectivo. Otras cefaleas primarias: es importante desensibilizar de los factores desencadenantes. Conclusión: rescatamos conceptos sobre la tarea del médico de aliviar el sufrimiento del paciente, a través de un diagnóstico y un tratamiento adecuados.

This review focuses on primary headaches, its diagnosis and treatment. For the IHS specialists they are: migraine, tension-type headache (TTH), cluster and others. Migraine: the second in prevalence and the first in morbility, clinical features and differences between migraine with (Ma) and without aura (Mo). Epidemiology: 10% prevalence and 3: 1 women to men proportion. Patophysiology: primary central nociception disorder with secondary vascular involvement. Treatment: specific and non-specific, acute and preventive. Psychiatric disorders and migraine: there is evidence of clinical and pharmacologicallinks, mainly between Ma and several psychiatric disorders. Migraine in children’s: important clinical and therapeutic differences from adult, importance of family approach. Migraine and hormones: the importance of estrogens drops, as trigger factor, treatment. Migraine and epilepsy: both shares neuronal hyperexcitability pattern. Migraine and stroke: vascular and ischemic factors involved. Evidence-based medicine: improves treatment's results and studies outcome evaluation. TTH: first in prevalence, still highly sub diagnosed. Main clinical presentations: episodic and chronic. Epidemiology: slight female preponderance. Patophysiology and trigger factors: the role of limbic nociceptive system, sedentarism stress and muscular tension. Treatment: pharmacological and non-pharmacological. Cluster headache: low prevalence but high daily-living activities impact, effective treatment. Other primary headaches: variability of trigger factors and role of desensitization process. Conclusion: we remark the complexity of headache and the of physicians' role: to relief patients suffering, throughout a precise diagnosis and treatment.