Demographic data
The study included 102 patients with CTN, 74 females and 28 males (F:M ratio 2.64:1). Of these, 1% were less than 30 years old, 23.5% were aged between 31 and 50 years, 50% between 51 and 70 years, and 25.5% were more than 70 years old. Most patients were retired (33.3%), the rest were employees (49%), unemployed (10.7%), and employers (7 %).
Consulted physicians
Most of patients (n = 88, 86.3%) had consulted a physician at the time of the first pain attacks. The remaining patients (n = 14, 13.7%) had not sought medical aid after the first episodes (so called “patient delay”). Figure 1 reports the distribution of the physicians consulted at the first visit: approximately half of patients had seen a primary care physician (n = 44, 43.1%), and nearly one third a dentist (n =31, 30.4%). The other consulted specialists were: neurosurgeons (n = 4; 3.9%,), otolaryngology (ENT) (n = 4; 3.9%), ophthalmologists (n = 1; 1%), rheumatologists (n = 1; 1%), emergency doctors (n = 1; 1%), physiotherapist (n = 1; 1%), while surprisingly only 15 patients (14.7%, 2 of which were headache specialists) had referred to a neurologist (Fig. 2). Only 18 patients (17.6%) received a correct diagnosis at the first consultation. It is worth noting that 84 patients (82.4%) consulted a second physician before a correct diagnosis was obtained, 38 patients (37.2%) a third specialist, and 12 patients (11.8%) even a fourth one. The specialists seen on a second consultation were: neurologists (n = 41; 48.7%) and headache specialists (n = 5; 6.0%), dentists (n = 18; 21.4%) ENT doctors (n = 12; 14.2%), primary care physicians (n = 3; 3.6%), neurosurgeons (n = 2, 2.4%), ophthalmologists (n = 2; 2.4%), others (n = 1; 1.2%). The third consultation was made by the following: neurologists (n = 20; 52.6%), headache specialists (n = 7; 18.4%), ENT doctors (n = 5; 13.2%), dentists (n = 2; 5.3%), ophthalmologists (n = 2; 5.3%), neurosurgeons (n = 1; 2.6%) and maxillo-facial surgeons (n = 1; 2.6%). When a fourth consultation had been necessary to reach a diagnosis, the consulted specialist were a neurologist (n = 11) and in only one case a general practitioner. One patient, in spite of having received the correct diagnosis of CTN by a neurologist at first consultation, had decided to ask a dentist for a second opinion.
Most of the patients consulted two physicians (n = 45; 44.1%) prior to obtain a correct diagnosis, while 26 patients (25.5%) consulted three physicians, 12 patients (11.7%) four physicians, and only 19 patients (18.7%) consulted one physician (Fig. 3). Eighty patients (78.4%) were already aware to suffer from CTN before submitting the questionnaire. Only few patients (n = 22, 21.6%) were diagnosed with CTN at the time of submission of the questionnaire.
We found that generally CTN diagnosis had been made by a neurologist (n = 72; 70.6%), or a headache specialist (n = 15; 14.7%). In a few cases, diagnosis was received by dentists (n =6; 5.9%), neurosurgeons (n = 6; 5.9%), and only in three cases by primary care physicians (n=3; 2.9%). Unfortunately, 49% of the patients interviewed were not aware of the existence of Headache Centers, or other specific structures dedicated to the treatment of headache and cranial neuralgias. Furthermore, 18.6% of the interviewed patients claimed to have self-diagnosed CTN on the basis of different sources of information (Internet n = 16, scientific books n = 1, or talk with other people suffering from CTN, n = 2), before seeking medical confirmation. Thirty-one patients (31.4%) in our study also suffered from another type of headache (migraine without aura n = 18, tension type-headache n = 12; cluster headache n = 1; Horton’ arteritis n = 1).
The mean interval between onset of the disease and specialist consultation (“Patient Delay”) in a Headache Center was 10.8±21.2 months (range 0-144 months). In Italy, delay was 8.02±14.2 months, whereas in other European Centers was up to 12.6±25.05 months. In our cohort, 2 outlier patients (Fig. 4) influenced significantly the average delay: one patient was indeed diagnosed after 72 months and another one after as long as 12 years. Three of the interviewed patients did not receive any headache specialist evaluation. The average time between disease onset and a correct diagnosis (“Diagnostic Delay”) was 7.2±12.5 months (in Italy 8.4±12.8 months, in the other European centers 7.13±13.01 months). Only in one patient no information was obtained. Misdiagnoses at first consultation were reported in 43 cases (42.1%), while 40 subjects (39.2%) did not receive a diagnosis during the visit; only 19 subjects (18.4%) received a correct one. Only one patient, despite obtaining the correct diagnosis, asked for a second specialist consultation. In the group of patients (n = 84) who underwent a second consultation, 28 patients (33.3%) were misdiagnosed, 11 patient (13.1%) did not receive a definite diagnosis, while 45 patients (53.6%) were not diagnosed correctly, although one received the indication for a nonspecific treatment with corticosteroids. In the group facing a third evaluation (n = 38), 6 subjects (15.8%) did not obtain a specific diagnosis, 6 patients received a misdiagnosis, while 26 patients (68.4%) received a correct diagnosis (15.8%) (Fig. 5).
The different diagnoses received before the correct one of CTN were also analyzed. The total number of misdiagnoses was 77 (mean number of diagnosis per patient: 0.75). Misdiagnoses on the first consultation were 43, on the second 28, and on the third 6. Overall, the reported misdiagnoses and related frequency were the following: dental problems (n = 37; 48%), including toothache, periodontal abscess, dental caries, dental granulomas; sinusitis (n = 11; 14.3%); unspecific facial pain (n = 7; 9.1%); unspecified headache (n = 6; 7.8%); migraine (n = 5; 6.5%); cluster headache (n = 4; 5.2%); temporomandibular joint dysfunction (n = 3; 3.9%); and tension-type headache (n = 1; 1.3%), glaucoma (n = 1; 1.3% ), otitis (n = 1; 1.3%) tonsillitis (n = 1; 1.3%).
Investigations
Instrumental and laboratory investigations prior to establish a CNT diagnosis had been carried out in almost all cases (95 patients; 93.1%). Most of patients (n = 70; 73.7%) had undergone a brain MRI in order to detect a possible neurovascular conflict or other causes of symptomatic TN; 40 patients (42.1%) had undergone a CT scan, 12 patients (12.6%) a skull X-rays, 8 patients (8.4%) an orthopantomography, 8 patients (8.4%) a blink reflex test, 2 patients (2.1%) a spine X-Ray, 2 patients (2.1%) a carotid ultrasound imaging, one patient (1%) an electroencephalogram (EEG). More than one instrumental examination had been performed in 37 patients (38.9%). In 25 patients (26.3%) some investigations (skull X-ray, orthopantomography, EEG, carotid ultrasound imaging, spine X-ray) appeared to be unnecessary [6-8].
Treatment
In our sample, 19 patients (18.6%) had not received any symptomatic treatment before diagnosis. The remaining patients had been prescribed symptomatic drugs, especially analgesics, such as NSAIDs (n = 69; 67.6%) and opiates (n = 19; 18.6%). In the latter group, 13 patients used opiates in association with NSAIDs. Then, 8 patients had been prescribed gabapentinoid drugs (gabapentin 100mg/day or pregabalin 150 mg/day), 3 patients had been treated with triptans as needed. Other treatments were: antibiotics (n = 1), benzodiazepines (n = 1), B vitamin supplements (n = 2), mannitol i.v. (n = 2), verapamil (n = 1), duloxetine (n = 1), topiramate (n = 1). Seven patients claimed to be on treatment with unspecified anti-epileptic drugs.
After that the correct diagnosis was established, the first-choice treatment was: carbamazepine in 80.3% (n = 82), gabapentinoid drugs in 11.7 % (n = 12), topiramate in 2% (n = 2), lamotrigine in 2% (n = 2); oxacarbazepine in 1% (n = 1), methylprednisolone in 1% (n = 1), opiates in 1% (n = 1), antidepressants not better specified in 1% (n = 1). In different phases of the disease, some patients switched to another pharmacological regimen, with the addition/substitution of a second drug. In 10 patients (9.8%) the drug introduced was lamotrigine, a choice due to partial/complete inefficacy of the first treatment, but the most frequent treatments chosen as second option were gabapentinoids 24.5% (n = 25), in addition/substitution to the first one. The other associated treatments were: unspecified antidepressants 6.8% (n = 7); carbamazepine 3.9% (n = 4), oxacarbazepine 1.9% (n = 2), venlafaxine 1.9% (n =2), duloxetine (n = 1). Five unresponsive patients had been treated with amitriptyline as a third choice. It is worth noting that 18 patients received a treatment not included in the dedicated guidelines for TN [6,8], i.e. topiramate (n = 2), methylprednisolone iv (n = 1), opiates (n = 1), amitriptyline (n = 5), duloxetine (n = 1), unspecified antidepressants (n = 8).
Before CTN diagnosis, 17.6% of the patients (n = 18) had already undergone some treatment procedures, such as tooth extraction (n = 10; 55.5%), in 2 cases even multiple, or treatments not recommended by guidelines, i.e acupuncture (n = 4; 22.2%); local injection of steroids (n = 2; 1.9%), anesthetics and botulinum toxin (n = 1), Thecar therapy (n = 1). Only 1 patient had undergone 3 subsequent microvascular decompression surgeries, and later a balloon compression and a percutaneous glycerol rhizolysis of Gasserian ganglion. Eighty-two patients (80.4%) had followed the therapy prescribed after the diagnosis, whereas 20 subjects (19.6%) had interrupted the treatment, due to the following reasons: side effects (in particular dizziness and asthenia) (n = 1), uneffectiveness (n = 17), leukopenia (n = 1), allergic reaction (n = 1).