A systematic review of screening diagnostic tools for trigeminal neuralgia.

Background and objective: Trigeminal neuralgia (TN) is a rare chronic neuropathic pain condition of sudden and severe pain, often described as an electric shock. Diagnosis is challenging for non-expert clinicians, particularly in primary care settings. We wanted to identify and assess the diagnostic accuracy of existing screening tools for TN and orofacial pain that could be used to support the diagnosis of TN in primary care. Databases and data treatment: We searched key databases (MEDLINE, ASSIA, Embase, and Web of Knowledge and PsycINFO) supplemented by citation tracking from January 1988 to 2021. We used an adapted version of the Quality of Diagnostic Accuracy Studies (QUADAS-2) to assess the methodological quality of each study. Results: Searches identified five studies, from the UK, USA and Canada; three validated self-report questionnaires; and two artificial neural networks. All screened for multiple orofacial pain diagnoses, including dentoalveolar pain, musculoskeletal pain (temporomandibular disorders) and neurological pain (trigeminal neuralgia, headache, atypical facial pain and postherpetic neuralgia). The overall quality assessment was low for one study. Conclusions: Diagnosis of TN can be challenging for non-expert clinicians. Our review found few existing screening tools to diagnose TN, and none is currently suitable to be used in primary care settings. This evidence supports the need to adapt an existing tools or to create a new tool for this purpose. The development of an appropriate screening questionnaire could assist non-expert dental and medical clinicians to identify TN more effectively and empower them to manage or refer patients for treatment more effectively.

The specialist management of non-temporomandibular orofacial pain: maxillofacial surgery's known unknown?

The management of orofacial pain is considered to be within the remit of oral and maxillofacial surgery (OMFS). In this study we aimed to provide an overview of the healthcare "journey" of a group of patients referred to a specialist unit with "complex" non-temporomandibular orofacial pain. We retrospectively reviewed all those who were referred over a six-month period and followed for up to three years. A total of 133 were included, 69% were female, and the mean (SD) duration of symptoms before assessment was 66.4 (88.8) months. Patients were treated for seven different conditions by a mean (SD) of 2.6 (1.2) specialties, and 3.2 (2.5) medications had been tried before assessment at the unit. A mean (SD) of 3.9 (3.3) appointments were attended over the three years, and 80% of patients were prescribed at least one medication. Patients were under the care of the unit for a mean (SD) of 11.9 (14.0) months, and 38% were still being seen at three years. Those with trigeminal neuralgia were most likely to remain in care at three years (p=<0.001), and those with burning mouth syndrome (p=<0.001) or persistent idiopathic facial pain (p=0.005) were most likely to be discharged. In the current NHS climate, the lack of resources to treat facial pain and the focus on a mix of skills, mean that OMF surgeons are likely to have an increasing role in the treatment of these patients. This paper provides an important insight into these conditions.

A systematic review of rescue analgesic strategies in acute exacerbations of primary trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) can have a significant impact on wellbeing and quality of life. Limited data exist for treatments that improve TN pain acutely, within 24 h of administration. This systematic review aims to identify effective treatments that acutely relieve TN exacerbations. METHODS: We searched Medline and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant English language publications. The reference list for all articles was searched for other relevant publications. All studies that satisfied the following PICO criteria were included: (i) Population-adults with acute exacerbation of primary TN symptoms; (ii) Intervention-any medication or intervention with the primary goal of pain relief within 24 h; (iii) Comparator-usual medical care, placebo, sham or active treatment; (iv) Outcome-more than 50% reduction in pain intensity within 24 h of administration. RESULTS: Of 431 studies, 17 studies were identified that reported immediate results of acute treatment in TN. The evidence suggests that the following interventions may be beneficial: local anaesthetic, mainly lidocaine (ophthalmic, nasal or oral mucosa, trigger point injection, i.v. infusion, nerve block); anticonvulsant, phenytoin or fosphenytoin (i.v. infusion); serotonin agonist, sumatriptan (s.c. injection, nasal). Other referenced interventions with very limited evidence include N-methyl-d-aspartate receptor antagonist (magnesium sulphate infusion) and botulinum toxin (trigger point injection). CONCLUSIONS: Several treatment options exist that may provide fast and safe relief of TN. Future studies should report on outcomes within 24 h to improve knowledge of the acute analgesic TN treatments.

European Academy of Neurology guideline on trigeminal neuralgia.

BACKGROUND AND PURPOSE: Trigeminal neuralgia (TN) is an extremely painful condition which can be difficult to diagnose and treat. In Europe, TN patients are managed by many different specialities. Therefore, there is a great need for comprehensive European guidelines for the management of TN. The European Academy of Neurology asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with TN. METHODS: A systematic review of the literature was performed and recommendations was developed based on GRADE, where feasible; if not, a good practice statement was given. RESULTS: The use of the most recent classification system is recommended, which diagnoses TN as primary TN, either classical or idiopathic depending on the degree of neurovascular contact, or as secondary TN caused by pathology other than neurovascular contact. Magnetic resonance imaging (MRI), using a combination of three high-resolution sequences, should be performed as part of the work-up in TN patients, because no clinical characteristics can exclude secondary TN. If MRI is not possible, trigeminal reflexes can be used. Neurovascular contact plays an important role in primary TN, but demonstration of a neurovascular contact should not be used to confirm the diagnosis of TN. Rather, it may help to decide if and when a patient should be referred for microvascular decompression. In acute exacerbations of pain, intravenous infusion of fosphenytoin or lidocaine can be used. For long-term treatment, carbamazepine or oxcarbazepine are recommended as drugs of first choice. Lamotrigine, gabapentin, botulinum toxin type A, pregabalin, baclofen and phenytoin may be used either alone or as add-on therapy. It is recommended that patients should be offered surgery if pain is not sufficiently controlled medically or if medical treatment is poorly tolerated. Microvascular decompression is recommended as first-line surgery in patients with classical TN. No recommendation can be given for choice between any neuroablative treatments or between them and microvascular decompression in patients with idiopathic TN. Neuroablative treatments should be the preferred choice if MRI does not demonstrate any neurovascular contact. Treatment for patients with secondary TN should in general follow the same principles as for primary TN. In addition to medical and surgical management, it is recommended that patients are offered psychological and nursing support. CONCLUSIONS: Compared with previous TN guidelines, there are important changes regarding diagnosis and imaging. These allow better characterization of patients and help in decision making regarding the planning of medical and surgical management. Recommendations on pharmacological and surgical management have been updated. There is a great need for future research on all aspects of TN, including pathophysiology and management.

Adverse effects of anti-epileptics in trigeminal neuralgiform pain.

BACKGROUND: Side effects of anti-epileptic drugs (AEDs) have not been adequately documented in trigeminal neuralgia and its variants. The aim of this observational cross-sectional study was to compare the A-B Neuropsychological Assessment Schedule (ABNAS), which measures cognitive side effects to the Adverse Events Profile (AEP), which looks at a broader range of side effects, and to investigate drug/dosage relationships with questionnaire scores to help determine a point at which a drug change would be indicated. METHODS: One hundred five patients were recruited from a facial pain clinic, over a 10-month period. Self-complete questionnaire scores were compared between patients using different AEDs. RESULTS: A-B Neuropsychological Assessment Schedule score correlated well with AEP indicating that cognitive side effects were a significant burden. Toxic range on the ABNAS was estimated to occur when scores were >43/72 (95% CI: 37.4-48.6). Polytherapy is weakly associated with the higher scores. Oxcarbazepine dosage was found to linearly correlate with AEP and ABNAS scores, better than carbamazepine dosage. Memory alteration was least common with lamotrigine and oxcarbazepine, and there was less association between fatigues with oxcarbazepine/pregabalin. CONCLUSION: Anti-epileptic drugs have significant side effects. The ABNAS questionnaire is a useful tool along with the AEP to recognize and monitor AEDs' side effects and to help to adjust medications to optimal dosage.

Referrals to a facial pain service.

AIM: To assess the quality of referral letters to a facial pain service and highlight the key requirements of such letters. METHOD: The source of all referral letters to the service for five years was established. For one year the information provided in 94 referrals was assessed. Using a predetermined checklist of essential information the referral letters were compared to these set criteria. RESULTS: The service received 7,001 referrals and, on average, general dental practitioners (GDPs) referred 303 more patients per year than general medical practitioners (GMPs). Seventy-one percent of all referrals were from primary care practitioners, the rest were from specialists. Over 70% of GMP and 52% of GDP letters included a past medical history, with GMPs more likely to suggest a possible diagnosis and include previous secondary care referrals. The mean score for GMP referrals compared to the standard proforma (maximum of 12) was 5.6 and for GDP referrals 5.0. A relevant drug history was included by 75.6% GMP compared to 38.7% of GDPs. GMPs were more likely to include any relevant mental health history. CONCLUSIONS: The overall quality of referral letters is low which makes it difficult for the specialists to provide robust treatment plans.

Comparison of tolerability and adverse symptoms in oxcarbazepine and carbamazepine in the treatment of trigeminal neuralgia and neuralgiform headaches using the Liverpool Adverse Events Profile (AEP).

BACKGROUND: Adverse effects of drugs are poorly reported in the literature . The aim of this study was to examine the frequency of the adverse events of antiepileptic drugs (AEDs), in particular carbamazepine (CBZ) and oxcarbazepine (OXC) in patients with neuralgiform pain using the psychometrically tested Liverpool Adverse Events Profile (AEP) and provide clinicians with guidance as to when to change management. METHODS: The study was conducted as a clinical prospective observational exploratory survey of 161 patients with idiopathic trigeminal neuralgia and its variants of whom 79 were on montherapy who attended a specialist clinic in a London teaching hospital over a period of 2 years. At each consultation they completed the AEP questionnaire which provides scores of 19-76 with toxic levels being considered as scores >45. RESULTS: The most common significant side effects were: tiredness 31.3 %, sleepiness 18.2 %, memory problems 22.7 %, disturbed sleep 14.1 %, difficulty concentrating and unsteadiness 11.6 %. Females reported significantly more side effects than males. Potential toxic dose for females is approximately 1200 mg of OXC and 800 mg of CBZ and1800mg of OXC and 1200 mg of CBZ for males. CONCLUSIONS: CBZ and OXC are associated with cognitive impairment. Pharmacokinetic and pharmacodynamic differences are likely to be the reason for gender differences in reporting side effects. Potentially, females need to be prescribed lower dosages in view of their tendency to reach toxic levels at lower dosages. Side effects associated with AED could be a major reason for changing drugs or to consider a referral for surgical management.

Differential diagnosis of facial pain and guidelines for management.

The diagnosis and management of facial pain below the eye can be very different dependant on whether the patient visits a dentist or medical practitioner. A structure for accurate diagnosis is proposed beginning with a very careful history. The commonest acute causes of pain are dental and these are well managed by dentists. Chronic facial pain can be unilateral or bilateral and continuous or episodic. The commonest non-dental pains are temporomandibular disorders (TMDs), especially musculoskeletal involving the muscles of mastication either unilaterally or bilaterally; they may be associated with other chronic pains. A very wide range of treatments are used but early diagnosis, reassurance and some simple physiotherapy is often effective in those with good coping strategies. Dentists will often make splints to wear at night. Neuropathic pain is usually unilateral and of the episodic type; the most easily recognized is trigeminal neuralgia. This severe electric shock like pain, provoked by light touch, responds best to carbamazepine, and neurosurgery in poorly controlled patients. Trauma, either major or because of dental procedures, results in neuropathic pain and these are then managed as for any other neuropathic pain. Red flags include giant cell arteritis which much be distinguished from temporomandibular disorders (TMD), especially in >50 yr olds, and cancer which can present as a progressive neuropathic pain. Burning mouth syndrome is rarely recognized as a neuropathic pain as it occurs principally in peri-menopausal women and is thought to be psychological. Chronic facial pain patients are best managed by a multidisciplinary team.

Classifying orofacial pains: a new proposal of taxonomy based on ontology.

We propose a new taxonomy model based on ontological principles for disorders that manifest themselves through the symptom of persistent orofacial pain and are commonly seen in clinical practice and difficult to manage. Consensus meeting of eight experts from various geographic areas representing different perspectives (orofacial pain, headache, oral medicine and ontology) as an initial step towards improving the taxonomy. Ontological principles were introduced, reviewed and applied during the consensus building process. Diagnostic criteria for persistent dento-alveolar pain disorder (PDAP) were formulated as an example to be used to model the taxonomical structure of all orofacial pain conditions. These criteria have the advantage of being (i) anatomically defined, (ii) in accordance with other classification systems for the provision of clinical care, (iii) descriptive and succinct, (iv) easy to adapt for applications in varying settings, (v) scalable and (vi) transferable for the description of pain disorders in other orofacial regions of interest. Limitations are that the criteria introduce new terminology, do not have widespread acceptance and have yet to be tested. These results were presented to the greater conference membership and were unanimously accepted. Consensus for the diagnostic criteria of PDAP was established within this working group. This is an initial first step towards developing a coherent taxonomy for orofacial pain disorders, which is needed to improve clinical research and care.

Patients' satisfaction after a comprehensive assessment for complex chronic facial pain at a specialised unit: results from a prospective audit.

OBJECTIVE: The aim of this audit was to investigate complex chronic facial pain patients' satisfaction after an initial, comprehensive, 45-60 minute consultation visit. DESIGN: Prospective audit using a post-visit satisfaction survey. SETTING: Specialised outpatient facial pain unit. METHODS: A convenience sample of 50 consecutive new patients were recruited. History, pain and psychosocial functioning were assessed through standard, validated pre-visit questionnaires. A post-visit satisfaction questionnaire was sent (twice if necessary) to patients by mail, and non-responders were contacted by telephone. MAIN OUTCOME MEASURES: Patients' satisfaction scores on pain management processes were evaluated. RESULTS: Response rate for the questionnaire was 63% (32/50) and 12 additional patients who did not respond to the questionnaire replied by telephone. Among questionnaire respondents, mean overall patient satisfaction was 8.1 ± 2.2 on an 11-point scale (best score 10), with no differences based on age, gender, diagnosis, length of symptoms and treatment. There was a trend of higher overall satisfaction among patients referred by dentists and specialists. Patients who had seen at least one specialist before their visit reported higher scores in understanding the reasons for their condition and what to do to treat their condition. CONCLUSIONS: A consultation with adequate time for history taking, addressing patients' goals and thorough explanation accompanied by written information, results in high satisfaction among patients with chronic facial pain.

Persistent orofacial muscle pain.

The pathophysiology of persistent orofacial myalgia has been the centre of much controversy. In this article we suggest a novel descriptive term; 'persistent orofacial muscle pain' (POMP) and review current evidence that supports the hypothesis that the induction of POMP involves the interplay between a peripheral nociceptive source in muscle, a faulty central nervous system component and decreased coping ability. In this context it is widely accepted that a complex interaction of variable intrinsic and extrinsic factors act to induce POMP and dysfunction.

Cranial neuralgias.

After a description of the anatomical-functional organization of the human trigeminal system, this chapter discusses the diagnostic and therapeutic options for trigeminal neuralgia (TN). In about 15% of patients who present with the clinical picture of typical TN, this is secondary to a major neurological disease, i.e., benign tumors of the cerebellopontine angle or multiple sclerosis. Some clinical criteria that were used to distinguish between classic and symptomatic TN, such as age at onset, involvement of the ophthalmic division, and responsiveness to medical treatment, are no longer considered reliable. It is recommended that all patients undergo magnetic resonance imaging (MRI) or trigeminal reflex recording. Carbamazepine (CBZ) and oxcarbazepine (OXC) are the first-choice medical treatments. Although other drugs may be effective, these are indicated when the patient cannot reach the therapeutic dosage of CBZ/OXC because of adverse events. Patients unresponsive to CBZ/OXC should be made aware of the available surgical interventions. Surgical procedures (including percutaneous lesions to the ganglion/root, microvascular decompression (MVD) in the posterior fossa, and gamma knife radiosurgery) are extremely efficacious with relatively few complications: each procedure has some advantage and disadvantage with respect to the other. Only MVD is a non-destructive procedure. This chapter also describes management of glossopharyngeal neuralgia, which is often misdiagnosed, and some other chronic pain conditions mediated by the trigeminal system, such as ophthalmic postherpetic neuralgia (PHN).

Bleeding complications after pacemaker or cardioverter-defibrillator implantation in patients receiving dual antiplatelet therapy: Results of a prospective, two-centre registry.

Introduction. The aim of the study was to define the prevalence of bleeding events in patients treated with dual antiplatelet therapy (DAT) in comparison with patients receiving only acetylsalicylic acid (ASA).Methods. Prospective two-centre registry of all first implantations of pacemakers, cardioverter-defibrillators and cardiac resynchronisation therapy units in patients receiving ASA (n=194) or DAT (n=53).Results. Bleeding complications were detected in 27 (16.2%) patients in the ASA group and in 13 (24.5%) in the DAT group. There was no significant difference in the overall number of complications between the patients receiving ASA or DAT, although there was a trend towards a higher incidence of overall complication rates in the DAT group (p=0.0637). The incidence of major complications (requiring blood transfusion or surgical intervention or prolonging hospital stay) was low (3.6%), and similar in both groups (3.6 and 3.8% respectively, ns). The rate of minor complications (subcutaneous haematomas) was greater in the DAT group (p=0.015).Conclusions. Treatment with DAT does not increase the risk of major bleeding complications as a result of device implantation; however, minor complications are significantly more frequent. Our results suggest that DAT could be continued in patients undergoing device implantation with a moderate risk of bleeding complications. (Neth Heart J 2010;18:230-5.).

Pilot study to evaluate the efficacy and tolerability of levetiracetam (Keppra) in treatment of patients with trigeminal neuralgia.

BACKGROUND AND PURPOSE: The objective of this study was to determine whether levetiracetam (LEV) is an effective drug for treatment of trigeminal neuralgia (TN). METHODS: Ten patients with TN were enrolled in a 10-week, prospective, open-label pilot study. The primary outcome measure was the visual analogue scale on daily pain diary and side effects. Serum levels of LEV were measured to assess correlation between drug levels and pain control. RESULTS: There was a significant tendency towards improvement in pain severity compared with baseline in four patients with higher doses of 4,000 mg/day. The four treatment responders had less pain compared with baseline (50-90% improvement) and three subjects continued the drug after study completion. All patients rated themselves on the global evaluation scale as much improved (n = 2), minimally improved (n = 3), no change (n = 1), minimally worse (n = 2), much worse (n = 1) and very much worse (n = 1). LEV was very well tolerated and there was no difference in side effects between the low and high doses of LEV evaluations. CONCLUSION: Given its established safety profile, a randomized, placebo-controlled, double-blind trial of LEV using enhancement enrollment design is needed to confirm these open-labelled findings using a wide variety of outcome measures.

Alternative respiration of fungus Phycomyces blakesleeanus.

Respiratory characteristics of germinating spores, developing mycelium and mitochondria of the fungus Phycomyces blakesleeanus were investigated by means of oxygen Clark-type electrode. The effects of respiratory inhibitors and metabolic compounds on oxygen consumption were tested. It was demonstrated that P. blakesleeanus apart of cyanide-sensitive respiration, CSR, possess alternative respiration, (cyanide-resistant respiration, CRR) which is constitutive and whose capacity decreases during development. Maximum is observed for activated spores where CRR capacity is significantly greater than CSR. After treatment with antimycin A, a third type of respiration insensitive to antimycin A and low concentration of SHAM (sufficient for inhibition of CRR), but sensitive to cyanide and high concentration of SHAM, has been expressed.

Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.

BACKGROUND: Trigeminal neuralgia (TN) is a common cause of facial pain. PURPOSE: To answer the following questions: 1) In patients with TN, how often does routine neuroimaging (CT, MRI) identify a cause? 2) Which features identify patients at increased risk for symptomatic TN (STN; i.e., a structural cause such as a tumor)? 3) Does high-resolution MRI accurately identify patients with neurovascular compression? 4) Which drugs effectively treat classic and symptomatic trigeminal neuralgia? 5) When should surgery be offered? 6) Which surgical technique gives the longest pain-free period with the fewest complications and good quality of life? METHODS: Systematic review of the literature by a panel of experts. CONCLUSIONS: In patients with trigeminal neuralgia (TN), routine head imaging identifies structural causes in up to 15% of patients and may be considered useful (Level C). Trigeminal sensory deficits, bilateral involvement of the trigeminal nerve, and abnormal trigeminal reflexes are associated with an increased risk of symptomatic TN (STN) and should be considered useful in distinguishing STN from classic trigeminal neuralgia (Level B). There is insufficient evidence to support or refute the usefulness of MRI to identify neurovascular compression of the trigeminal nerve (Level U). Carbamazepine (Level A) or oxcarbazepine (Level B) should be offered for pain control while baclofen and lamotrigine (Level C) may be considered useful. For patients with TN refractory to medical therapy, Gasserian ganglion percutaneous techniques, gamma knife, and microvascular decompression may be considered (Level C). The role of surgery vs pharmacotherapy in the management of TN in patients with MS remains uncertain.

AAN-EFNS guidelines on trigeminal neuralgia management.

Several issues regarding diagnosis, pharmacological treatment, and surgical treatment of trigeminal neuralgia (TN) are still unsettled. The American Academy of Neurology and the European Federation of Neurological Societies launched a joint Task Force to prepare general guidelines for the management of this condition. After systematic review of the literature the Task Force came to a series of evidence-based recommendations. In patients with TN MRI may be considered to identify patients with structural causes. The presence of trigeminal sensory deficits, bilateral involvement, and abnormal trigeminal reflexes should be considered useful to disclose symptomatic TN, whereas younger age of onset, involvement of the first division, unresponsiveness to treatment and abnormal trigeminal evoked potentials are not useful in distinguishing symptomatic from classic TN. Carbamazepine (stronger evidence) or oxcarbazepine (better tolerability) should be offered as first-line treatment for pain control. For patients with TN refractory to medical therapy early surgical therapy may be considered. Gasserian ganglion percutaneous techniques, gamma knife and microvascular decompression may be considered. Microvascular decompression may be considered over other surgical techniques to provide the longest duration of pain freedom. The role of surgery versus pharmacotherapy in the management of TN in patients with multiple sclerosis remains uncertain.