Trigeminal neuralgia: a practical guide

Trigeminal neuralgia (TN) is a highly disabling disorder characterised by very severe, brief and electric shock like recurrent episodes of facial pain. New diagnostic criteria, which subclassify TN on the basis of presence of trigeminal neurovascular conflict or an underlying neurological disorder, should be used as they allow better characterisation of patients and help in decision-making regarding medical and surgical treatments. MR, including high-resolution trigeminal sequences, should be performed as part of the diagnostic work-up. Carbamazepine and oxcarbazepine are drugs of first choice. Lamotrigine, gabapentin, pregabalin, botulinum toxin type A and baclofen can be used either alone or as add-on therapy. Surgery should be considered if the pain is poorly controlled or the medical treatments are poorly tolerated. Trigeminal microvascular decompression is the first-line surgery in patients with trigeminal neurovascular conflict while neuroablative surgical treatments can be offered if MR does not show any neurovascular contact or where patients are considered too frail for microvascular decompression or do not wish to take the risk

The Clinical, Therapeutic and Radiological Spectrum of SUNCT, SUNA and Trigeminal Neuralgia

This thesis examines and compares the demographics, clinical phenotype, radiological findings and response to medical and surgical treatments of SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and SUNA (short-lasting unilateral neuralgiform headache attacks with autonomic symptoms). Given the similarities between SUNCT, SUNA and trigeminal neuralgia (TN), the demographics and clinical phenotype of these disorders were also compared. In the first study (Chapter 2) a cohort of 133 patients (SUNA=63 and SUNCT=70) was phenotyped and the clinical characteristics of SUNA compared to those of SUNCT. Statistically significant predictors for SUNCT rather than SUNA were only found for ipsilateral ptosis [OR: 3.37 (95% CI: 1.50, 7.66), p<0.0001] and rhinorrhoea [OR: 2.42 (95% CI: 1.09, 5.41), p=0.034]. Furthermore, a significantly higher proportion of SUNCT patients (n=56, 80.0%) reported marked lacrimation compared to SUNA patients (n=20, 46.5%) (P<0.001). In the second study (Chapter 3) 45 SUNCT and 34 SUNA patients had high-resolution cisternal imaging MRI scans to asses the presence of trigeminal neurovascular conflict. The prevalence of neurovascular contact on the symptomatic trigeminal nerves was higher (57.3%) than on the asymptomatic trigeminal nerves (25%) (P≤0.001). Severe neurovascular contacts were considerably more prevalent on the symptomatic side (47.6%), compared to the asymptomatic side (11.8%) (P≤0.001). There was no statistically significant difference in the proportion of neurovascular contacts on the symptomatic nerves between SUNCT (61.7%) and SUNA (57.1%) (P=0.67). The presence of a vascular contact and its location at the root entry zone were strong predictors for the nerve to be symptomatic rather than asymptomatic. In the third study (Chapter 4) the response to treatments of 161 SUNCT and SUNA patients was analysed. Our findings suggest that lamotrigine was the most effective treatment (responders: SUNCT= 53.5%, SUNA= 57.9%) followed by oxcarbazepine (responders: SUNCT= 44.8%, SUNA= 47.0%); duloxetine and topiramate were more effective in SUNCT rather than SUNA (duloxetine responders: SUNCT= 45.0%, SUNA: 11.8%; p= 0.027; topiramate responders: SUNCT= 33.3%, SUNA= 10.7%; p=0.028). Amongst transitional treatments intravenous lidocaine led to a significant headache improvement in 83.3% SUNCT (n=25) and in 76.5% SUNA (n=13) patients (p=0.73). A greater occipital nerve block was beneficial in 27.3% (n=21) of patients for a median of 21 days (IQR: 53 days; range: 1 to 150 days), without any significant difference between SUNCT (24.4%; n=11) and SUNA (37.0%; n=10) patients (p=0.42). We found intravenous dihidroergotamine able to worsen or even to precipitate a de novo SUNCT/SUNA when administered to manage a different primary headache disorder. In the fourth study (Chapter 5) occipital nerve stimulation (ONS) was tried in nine and trigeminal microvascular decompression was tried in ten refractory, chronic SUNCT and SUNA patients. At a median follow-up of 38 months (range 24-55 months) ONS led to a marked headache improvement in eight of the nine patients (89%). One patient did not report any benefit from the stimulator at 24 months’ follow-up and opted to have the ONS explanted. At a mean follow-up fo 19.6 months (range: 12-36 months) after trigeminal microvascular decompression surgery, seven patients (70%) became headache-free after the operation. Five of the seven patients (71.4%) remained headache-free at the last follow-up. The remaining two patients were headache-free respectively for 9 and 12 months before the headache relapsed. There were no major surgical and post-surgical complications. A comparison of the clinical phenotype of SUNA (n=133) and TN (n=79) was undertaken in the last study (Chapter 6). Several similarities between SUNA and TN were found. Furthermore, some clinical features, namely pain location in V1 (OR: 11.29 95%CI: 3.92, 35.50, p<0.001), spontaneous only attacks (OR: 44.40, 95%CI: 4.50, 437.83, p=0.001) and a chronic pain pattern (OR: 13.19, 95%CI: 4.04, 43.08, p<0.001) predicted the diagnosis of SUNA rather than TN. Similarly duration of the attacks <1 minute (OR: 7.95, 95%CI: 2.30, 27.57, p=0.001) and the presence of a refractory period in between triggered attacks (OR: 0.06; 95%CI: 0.02, 0.28, p-value <0.001) were predictors for TN rather than SUNA. In summary our novel findings advance the clinical understanding of SUNCT and SUNA and suggest that their relationship with TN may represent` a clinical continuum between disorders. This view will hopefully open novel research directions towards a better understanding of these complex clinical entities

A six year retrospective review of occipital nerve stimulation practice--controversies and challenges of an emerging technique for treating refractory headache syndromes

BACKGROUND: A retrospective review of patients treated with Occipital Nerve Stimulation (ONS) at two large tertiary referral centres has been audited in order to optimise future treatment pathways. METHODS: Patient's medical records were retrospectively reviewed, and each patient was contacted by a trained headache expert to confirm clinical diagnosis and system efficacy. Results were compared to reported outcomes in current literature on ONS for primary headaches. RESULTS: Twenty-five patients underwent a trial of ONS between January 2007 and December 2012, and 23 patients went on to have permanent implantation of ONS. All 23 patients reached one-year follow/up, and 14 of them (61%) exceeded two years of follow-up. Seventeen of the 23 had refractory chronic migraine (rCM), and 3 refractory occipital neuralgia (ON). 11 of the 19 rCM patients had been referred with an incorrect headache diagnosis. Nine of the rCM patients (53%) reported 50% or more reduction in headache pain intensity and or frequency at long term follow-up (11-77 months). All 3 ON patients reported more than 50% reduction in pain intensity and/or frequency at 28-31 months. Ten (43%) subjects underwent surgical revision after an average of 11 ± 7 months from permanent implantation - in 90% of cases due to lead problems. Seven patients attended a specifically designed, multi-disciplinary, two-week pre-implant programme and showed improved scores across all measured psychological and functional parameters independent of response to subsequent ONS. CONCLUSIONS: Our retrospective review: 1) confirms the long-term ONS success rate in refractory chronic headaches, consistent with previously published studies; 2) suggests that some headaches types may respond better to ONS than others (ON vs CM); 3) calls into question the role of trial stimulation in ONS; 4) confirms the high rate of complications related to the equipment not originally designed for ONS; 5) emphasises the need for specialist multidisciplinary care in these patients

Estudo comparativo de duas técnicas de análise baseadas em fluorescência de Raios-X para aplicação na caracterização de implantes

A implantodontia é uma área de extrema importância na atualidade. No Brasil são feitas 2,5 milhões de implantações por ano. Entretanto, a taxa de insucesso da osseointegração dos implantes dentários varia entre 1,5-3,5%, tendo sido reportado na literatura em até 10%. O insucesso pode estar relacionado com a composição química da superfície de implantes e por isso há um grande interesse na caracterização química dos mesmos. Uma revisão da literatura disponível sobre a caracterização química de implantes dentários evidenciou a falta de padronização com que as análises são realizadas. A fluorescência de raios-X é utilizada para análise química de amostras por ser um método direto, rápido, necessitando de pouco ou nenhum tratamento químico prévio. O objetivo deste estudo é investigar a influência de diversos parâmetros na análise química de duas técnicas que fazem uso de fluorescência de raios-X, uma por dispersão de energia (EDXRF) e outra por dispersão de comprimento de onda (WDXRF) utilizando-se latão na forma de 2 discos, limalha e 3 cilindros com dimensões similares ao de um implante dentário. Os parâmetros testados no WDXRF foram: dependência geométrica, posição da amostra no porta-amostras e limpeza de superfície. Já no EDXRF foram testados a região da análise, a dependência geométrica, limpeza da superfície, a variação do resultado de medidas em função do tempo e a adsorção de elementos na superfície. Os resultados mostraram que diversos fatores podem afetar os resultados obtidos nos equipamentos utilizados. Conclui-se que há necessidade de padronização dos procedimentos e equipamentos utilizados na caracterização química de implantes, associada a uma cuidadosa escolha do equipamento em função da informação desejada, permitindo assim a intercomparação entre os estudos

The development and validation of the Cluster Headache Quality of life scale (CHQ)

BACKGROUND: Cluster headache (CH) is a rare, excruciating and highly disabling primary headache disorder. Using non cluster headache specific measures, previous studies have shown that CH has a significant negative impact on patients’ quality of life (QoL), but a CH-specific QoL scale is currently unavailable. Thus, the objective of this study was to develop and validate a CH-specific QoL scale. METHODS: Based on a literature review, semi-structured patient interviews and expert panel consultation, we produced a 54-item questionnaire, which was pre-tested in a sample of CH patients and subsequently reduced to 47 items. The revised scale was then administered to CH sufferers attending a tertiary headache clinic and those registered with a patient group. A total of 406 completed questionnaires were received. To assess test-retest reliability, a subsample (N = 56) completed the scale on a second occasion, two weeks after the first. Standard statistical methods were used to analyse the data for validity and reliability. RESULTS: Item reduction and exploratory factor analysis led to 28-items, grouped into four subscales labelled “restriction of activities of daily living”, “impact on mood and interpersonal relationships”, “pain and anxiety”, and “lack of vitality”. The final CH-specific QoL scale, the CHQ, demonstrated satisfactory internal consistency (Cronbach’s alpha > 0.9) and test-retest reliability (intraclass correlation coefficient > 0.8), with good internal construct validity between subscales (range 0.52–0.75) and convergent validity with other QoL measures. CONCLUSIONS: We have developed and validated the first patient-reported outcome measure of QoL specifically for CH sufferers, which may be used to monitor QoL in clinical care and research

Medical treatment of SUNCT and SUNA: a prospective open-label study including single-arm meta-analysis

Introduction: The management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and shortlasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) remains challenging in view of the paucity of data and evidence-based treatment recommendations are missing. Methods: In this single-centre, non-randomised, prospective open-label study, we evaluated and compared the efficacy of oral and parenteral treatments for SUNCT and SUNA in a real-world setting. Additionally, single-arm meta-analyses of the available reports of SUNCT and SUNA treatments were conducted. Results: The study cohort comprised 161 patients. Most patients responded to lamotrigine (56%), followed by oxcarbazepine (46%), duloxetine (30%), carbamazepine (26%), topiramate (25%), pregabalin and gabapentin (10%). Mexiletine and lacosamide were effective in a meaningful proportion of patients but poorly tolerated. Intravenous lidocaine given for 7–10 days led to improvement in 90% of patients, whereas only 27% of patients responded to a greater occipital nerve block. No statistically significant differences in responders were observed between SUNCT and SUNA. In the meta-analysis of the pooled data, topiramate was found to be significantly more effective in SUNCT than SUNA patients. However, a higher proportion of SUNA than SUNCT was considered refractory to medications at the time of the topiramate trial, possibly explaining this isolated difference. Conclusions: We propose a treatment algorithm for SUNCT and SUNA for clinical practice. The response to sodium channel blockers indicates a therapeutic overlap with trigeminal neuralgia, suggesting that sodium channels dysfunction may be a key pathophysiological hallmark in these disorders. Furthermore, the therapeutic similarities between SUNCT and SUNA further support the hypothesis that these conditions are variants of the same disorder

Trigeminal microvascular decompression for short-lasting unilateral neuralgiform headache attacks

A significant proportion of patients with short-lasting unilateral neuralgiform headache attacks (SUNHA) are refractory to medical treatments. Neuroimaging studies have suggested a role for ipsilateral trigeminal neurovascular conflict with morphological changes in the pathophysiology of this disorder. We present the outcome of an uncontrolled open-label prospective single centre study conducted between 2012 and 2020, to evaluate the efficacy and safety of trigeminal microvascular decompression in refractory chronic SUNHA with magnetic resonance imaging evidence of trigeminal neurovascular conflict ipsilateral to the pain side. Primary endpoint was the proportion of patients who achieved an "excellent response", defined as 90-100% weekly reduction in attack frequency, or "good response", defined as a reduction in weekly headache attack frequency between 75% and 89% at final follow-up, compared to baseline. These patients were defined as responders. The study group consisted of 47 patients of whom 31 had SUNCT and 16 had SUNA (25 females, mean age ± SD 55.2 years ± 14.8). Participants failed to respond or tolerate a mean of 8.1 (±2.7) preventive treatments pre-surgery. Magnetic resonance imaging of the trigeminal nerves (n = 47 patients, n = 50 symptomatic trigeminal nerves) demonstrated ipsilateral neurovascular conflict with morphological changes in 39/50 (78.0%) symptomatic nerves and without morphological changes in 11/50 (22.0%) symptomatic nerves. Post-operatively, 37/47 (78.7%) patients obtained either an excellent or a good response. Ten patients (21.3%, SUNCT = 7 and SUNA = 3) reported no post-operative improvement. The mean post-surgery follow-up was 57.4 ± 24.3 months (range 11-96 months). At final follow-up, 31 patients (66.0%) were excellent/good responders. Six patients experienced a recurrence of headache symptoms. There was no statistically significant difference between SUNCT and SUNA in the response to surgery (p = 0.463). Responders at the last follow-up were however more likely not to have interictal pain (77.42% vs 22.58%, p = 0.021) and to show morphological changes on the magnetic resonance imaging (78.38% vs 21.62%, p = 0.001). The latter outcome was confirmed in the Kaplan Meyer analysis, where patients with no morphological changes were more likely to relapse overtime compared to those with morphological changes (p = 0.0001). All but one patient who obtained an excellent response without relapse, discontinued their preventive medications. Twenty-two post-surgery adverse events occurred in 18 patients (46.8%) but no mortality or severe neurological deficit was seen. Trigeminal microvascular decompression may be a safe and effective long-term treatment for short-lasting unilateral neuralgiform headache attacks patients with magnetic resonance evidence of neurovascular conflict with morphological changes

A single infusion of intravenous lidocaine for primary headaches and trigeminal neuralgia: a retrospective analysis

IntroductionIntravenous (IV) lidocaine has been used as a transitional treatment in headache and facial pain conditions, typically as an inpatient infusion over several days, which is costly and may increase the risk of adverse effects. Here we report on our experience using a single one-hour IV lidocaine infusion in an outpatient day-case setting for the management of refractory primary headache disorders with facial pain and trigeminal neuralgia.MethodsThis is a retrospective, single-center analysis on patients with medically refractory headache with facial pain and trigeminal neuralgia who were treated with IV lidocaine between March 2018 and July 2022. Lidocaine 5 mg.kg−1 in 60 mL saline was administered over 1 h, followed by an observation period of 30 min. Patients were considered responders if they reported reduction in pain intensity and/or headache frequency of 50% or greater. Duration of response was defined as short-term (&lt; 2 weeks), medium-term (2–4 weeks) and long-term (&gt; 4 weeks).ResultsForty infusions were administered to 15 patients with trigeminal autonomic cephalalgias (n = 9), chronic migraine (n = 3) and trigeminal neuralgia (n = 3). Twelve patients were considered responders (80%), eight of whom were complete responders (100% pain freedom). The average duration of the treatment effect for each participant was 9.5 weeks (range 1–22 weeks). Six out of 15 patients reported mild and self-limiting side effects (40%).ConclusionA single infusion of IV lidocaine might be an effective and safe transitional treatment in refractory headache conditions with facial pain and trigeminal neuralgia. The sustained effect of repeated treatment cycles in some patients may suggest a role as long-term preventive therapy in some patients

The neuropsychology of cluster headache: cognition, mood, disability, and quality of life of patients with chronic and episodic cluster headache.

Cluster headache (CH) is commonly regarded as one of the most disabling headache conditions, and referred to as one of the most painful conditions known to humankind. Although there has been some research indicating the severe impact of CH, there is little comprehensive evidence of its impact on quality of life, disability, mood, and cognitive function in both its episodic (ECH) and chronic (CCH) variants

The greater occipital nerve and its spinal and brainstem afferent projections. A stereological and tract-tracing study in the rat.

The neuromodulation of the greater occipital nerve (GON) has proved effective to treat chronic refractory neurovascular headaches, in particular migraine and cluster headache. Moreover, animal studies have shown convergence of cervical and trigeminal afferents on the same territories of the upper cervical and lower medullary dorsal horn (DH), the so-called trigeminocervical complex (TCC), and recent studies in rat models of migraine and craniofacial neuropathy have shown that GON block or stimulation alter nociceptive processing in TCC. The present study examines in detail the anatomy of GON and its central projections in the rat applying different tracers to the nerve and quantifying its ultrastructure, the ganglion neurons subserving GON, and their innervation territories in the spinal cord and brainstem. With considerable intersubject variability in size, GON contains on average 900 myelinated and 3,300 unmyelinated axons, more than 90% of which emerge from C2 ganglion neurons. Unmyelinated afferents from GON innervates exclusively laminae I-II of the lateral DH, mostly extending along segments C2-3 . Myelinated fibers distribute mainly in laminae I and III-V of the lateral DH between C1 and C6 and, with different terminal patterns, in medial parts of the DH at upper cervical segments, and ventrolateral rostral cuneate, paratrigeminal, and marginal part of the spinal caudal and interpolar nuclei. Sparse projections also appear in other locations nearby. These findings will help to better understand the bases of sensory convergence on spinomedullary systems, a critical pathophysiological factor for pain referral and spread in severe painful craniofacial disorders.pre-print659 K