Olfactory threshold increase in trigeminal neuralgia after balloon compression

Clinical Neurology and Neurosurgery 108 (2006) 721–725

Olfactory threshold increase in trigeminal neuralgia after balloon compression S.R.D.T. Siqueira a,∗ , J.C.M. N´obrega b , M.J. Teixeira c , J.T.T. Siqueira a a b

Dentistry Division, Hospital das Cl´ınicas, Medical School, University of S˜ao Paulo, SP, Brazil Neurology Division, Hospital das Cl´ınicas, Medical School, University of S˜ao Paulo, SP, Brazil c Neurology Department, Medical School, University of S˜ ao Paulo, SP, Brazil

Received 18 September 2005; received in revised form 17 December 2005; accepted 21 December 2005

Abstract Idiopathic trigeminal neuralgia (ITN) is a well-known disease often treated with neurosurgical procedures, which may produce sensorial abnormalities, such as numbness, dysesthesia and taste complaints. We studied 12 patients that underwent this technique, in order to verify pain, gustative and olfactory thresholds abnormalities, with a follow-up of 120 days. We compared the patients with a matched control group of 12 patients. Our results found a significant difference in the olfactory threshold at the immediate post-operative period (p = 0.048). We concluded that injured trigeminal fibers are probably associated with the increase in the olfactory threshold after the surgery, supporting the sensorial interaction theory. © 2006 Elsevier B.V. All rights reserved. Keywords: Trigeminal neuralgia; Compression of the trigeminal ganglion; Orofacial pain; Taste; Olfactory threshold

1. Introduction Idiopathic trigeminal neuralgia (ITN) is paroxysmal shock-like pain, respecting a trigeminal innervation territory, which is frequently treated with anticonvulsants [1]. It affects around 155:1,000,000 habitants in the USA [2], Italy [3] and France [4]. Although the initial relief with the clinical treatment, more than 75% of the patients need neurosurgery [5], due to less response along time to pharmacotherapy. Compression of the trigeminal ganglion with a balloon is a safe and efficient surgical option [6], but may cause complications like facial superficial sensitivity disturbances, eyes discomfort, corneal injuries, tropic abnormalities as skin and mucosa ulcers, masticatory problems, difficulties in using dental prosthesis, etc [7,8].

∗ Corresponding author at: Rua Maria Candida, 135 Vila Guilherme, S˜ ao Paulo, SP 02071-010, Brazil. Tel.: +55 11 6953 6082 (R)/6973 0642 (B); fax: +55 11 6973 0642. E-mail address: [email protected] (S.R.D.T. Siqueira).

0303-8467/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2005.12.007

Among this enormous variety of sensations recognized in the oral cavity, often patients’ complaints are associated to pain and taste. Therefore, pain and dysgeusia are usually disturbances that lead the patient to seek dental or medical care [9], and the interesting fact is that both may be caused by different oral stimuli, following different nervous pathways, although they are frequently treated as separate disorders, and also several considerations related to the patient’s interpretation may apply to them. Some painful neuropathic syndromes may present neurological abnormalities (sensitivity, reflexes, taste), as burning mouth syndrome (BMS): hypoalgesia, hyperalgesia, tactile hypoesthesia, thermal hypoesthesia, gustative disturbances, etc. [10,11], but they are rarely present in ITN [12], except after the compression of the ganglion with a balloon, tending to get to the normal state during the follow-up [13]. Gustative and olfactory abnormalities were verified after alcohol injection in the trigeminal ganglion, and after trigeminal rizothomy [14]. On the other hand, isolate cases and case series of ITN reported pain triggering by some gustative stimuli [15,16]. Besides, trigeminal fibers may be related to the taste sensa-

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tion and may transmit olfactory inputs by the nasal mucosa [9]. Pathological lesions affecting the V, VII and IX cranial nerves affect somatic sensory and special sensory afferents, and can result in mixed symptomatology. The “taste sensation” is modulated by gustative buds with a close relation with amyelinated fibres, that are stimulated by molecules or ions, and the chorda tympani nerve (from the VII cranial nerve) mediates it; there are also evidences that injuries in the maxillary trigeminal branch may affect the “taste sensation”, which is modulated by different cranial nerves, including the I, V, VII, IX and X [9]. Thus, the objective of this study was to investigate gustative and olfatory abnormalities in patients with ITN that underwent compression of the trigeminal ganglion as treatment.

2. Casuistic and methods Twelve patients with ITN, according to the International Association for the Study of Pain (IASP) criteria [17] were treated with compression of the trigeminal ganglion with a balloon at the Cranio-Facial Pain Clinic of the Neurology Department. A no. 4 Forgaty catheter was posicionated next to the trigeminal ganglion, through the ovale foramen; the balloon got a pear shape after its inflation when it was in the correct position. Compression duration varied from 0.5 to 1 min, and the mean volume was 0.7 mL. The patients were evaluated at the Orofacial Pain Clinic, of Dentistry Division of a large teaching hospital, at three distinct moments: (a) Before surgery, until 30 days; (b) Immediate post-operative period, 7 days (±2 days) after surgery; (c) Mediate post-operative period, 120 days (±14 days) after surgery. A control group of 12 subjects without orofacial pain was created to compare the gustative and olfactory thresholds with the ITN group. The protocol of evaluation was: (a) ITN sample characteristics The general characteristics of the ITN patients included: gender, age, side and branch affected, intensity of pain (VAS—visual analogical scale), habits like smoking and complications related to the surgery (numbness and other abnormalities). The sensitivity methods of ITN evaluation were (a) Superficial sensitivity in distinct areas of the face [13]: 1. Digital device for the pain threshold evaluation (IITC Woodland Hills CA, USA); 2. Digital device for the tactile threshold evaluation (von Frey filaments, IITC Woodland Hills CA, USA);

3. Thermal sensitivity (ThermoSensi TS2); 4. Corneal reflex evaluation with standard size von Frey filaments for the evaluation. (b) Gustative evaluation: 1. Gustative threshold Distinct substances applied with a dropcounter at the anterior, lateral, right and left tongue, and palate, beginning with the smaller molar concentration [18,19]: Sweet: glucose (0.01; 0.032; 0.1; 0.32; 1.0); Salty: sodium chlorate (0.01; 0.032; 0.1; 0.32; 1.0); Sour: citric acid (0.00032; 0.001; 0.0032; 0.01; 0.032); Bitter: urea (0.1; 0.32; 1.0; 3.2; 10.0). (c) Olfactory evaluation: 1. Olfactory threshold: 70% isopropanol solution in deionized pure water and in six dilutions, maintained in polyethylene bottles; the examination began with the smaller concentration, and a placebo bottle (distillated water) was also used for the patient’s comparison and definition about which bottle contains the isopropanol solution for four consecutive tries. The next concentration was offered to the patient in case of mistake [20]. This protocol was approved by the Ethics Committee of the hospital before the evaluations, and the patients had signed the consent form before the evaluations. Data were collected and analyzed with the nonparametric test of Friedman for the comparison between the patients and the control group, and the Spearman correlation was used for the comparison among the different sensitivity modalities at the ITN group.

3. Results From the initial 12 patients, one did not come for the immediate evaluation, and only nine completed the 120 days of follow-up. No patient presented pain recurrence during this period. 3.1. General characteristics of the sample Seven (55.5%) patients were female and 5 (45.5%) were male. The ages ranged from 39 to 86 years old (mean of 61.9 years old, S.D. = 15.3 years old). The right side was affected in 7 (55.5%) and the left side was affected in 5 (45.5%). The distribution of the trigeminal branch affected was: V1 (1), V2 (1), V3 (6), V2-3 (3), V1-2-3 (1). Two (18.2%) patients were smokers. The intensity of pain presented mean of 8.9 (S.D. = 1.2; ranging from 7 to 10) at the VAS scale. Immediate post-operative complications were: Herpes simplex in 5 (45.5%); skin ulcers in

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Table 1 Frequency of numbness, and intensity of numbness, numbness discomfort and dysesthesia in the group of ITN patients (mean, range and standard deviaton)

Constant Frequent Eventual Absent Range and mean of the intensity of numbness Range and mean of numbness discomfort Dysesthesia Range and mean of dysesthesia *

Pre-operative period (N = 12)

Immediate post-operative period (N = 11)

Mediate post-operative period (N = 9)

2 (16.7%) – 1 (8.3%) 9 (75.0%) 5.3 (3.0–8.0; S.D. = 2.5) 6.5 (6.0–7.0; S.D. = 0.7) 1 (8.3%) 8.0 (8.0–8.0; S.D. = 0.0)

7 (63.6%) – – 4 (36.4%) 7.4 (5.0–10.0; S.D. = 1.6) 5.8 (4.0–10.0; S.D. = 2.3) 2 (18.2%) 6.0 (6.0–6.0; S.D. = 0.0)

7 (77.8%)* – – 2 (22.2%) 6.4 (5.0–10.0; S.D. = 1.9) 5.8 (4.0–10.0; S.D. = 2.3) 3 (33.3%) 6.7 (4.0–10.0; S.D. = 3.1)

p = 0.576.

Table 2 Pain threshold evaluation of the trigeminal branches of the affected and the opposite side of the face of the patients Pain threshold evaluation

Pre-operative period (N = 12)

Immediate post-operative period (N = 11)

Mediate post-operative period (N = 9)

Affected V1 Opposite V1 Affected V2 Opposite V2 Affected V3 Opposite V3

38.5 (20–70; S.D. = 17.1) 38.7 (18–100; S.D. = 23.8) 33.5 (18–64; S.D. = 13.7) 32.5 (14–52; S.D. = 10.7) 45.8 (20–100; S.D. = 24.1) 35.1 (12–50; S.D. = 11.2)

39.8 (20–100; S.D. = 25.9) 23.6 (10–36; S.D. = 7.7) 37.3 (12–100; S.D. = 25.5) 28.2 (12–52; S.D. = 9.8) 43.3 (18–100; S.D. = 24.5) 30.6 (14–50; S.D. = 11.2)

38.3 (24–100; S.D. = 23.9) 26.1 (18–40; S.D. = 7.3) 43.7* (16–100; S.D. = 26.2) 24.3 (12–52; S.D. = 11.2) 39.3 (12–94; S.D. = 25.7) 28.2 (20–46; S.D. = 9.8)

Ranges, means and standard deviation. * p = 0.014.

2 (18.2%); Mucosa ulcers in 3 (27.2%); equimosis in 3 (27.2%). In the control group, 7 (55.5%) were female and 5 (45.5%) were male. The ages ranged from 42 to 66 years old (mean 58.0 years old, S.D. = 7.7 years old). Two patients were smokers (18.2%). No one complained about any taste abnormalities.

3.2. Numbness and other sensitivity complaints The number of patients with numbness and its intensity increased in the immediate post-operative period, maintaining in the mediate evaluation (p = 0.576) (Table 1). Numbness characteristics may be observed on Table 1. Before surgery, 4 (36.4%) patients had taste complaints. No other sensations disturbances were present.

3.3. Superficial sensitivity evaluation of the patients After 120 days, the pain threshold increased in the maxillary branch at the affected facial side (p = 0.014), and reduced in the ophthalmic and mandibular branches at the opposite facial side. No significant differences were observed in other trigeminal branches (Table 2). Subjective numbness were present in more patients than pinprick, cold, heat, tactile and corneal reflex abnormalities; all of them increased in the immediate post-operative evaluation, but tended to the beginning values after 120 days (Table 3). All sensitivity values are compatible to our anterior study [13]. 3.4. Gustative and olfactory thresholds Gustative threshold did not present differences between patients and the control group, or in the patients group, after

Table 3 Number of ITN patients with numbness complaints, pinprick, cold, heat, tactile and corneal reflex abnormalities Sensitivity

Pre-operative period (N = 12)

Immediate post-operative period (N = 11)

Mediate post-operative period (N = 9)

Subjective numbness Pinprick Cold Heat Tactile Corneal reflex

3 (25.0%) 2 (16.7%) 2 (16.7%) 3 (25.0%) 2 (16.7%) 1 (8.3%)

7 (63.6%) 9 (81.8%) 8 (72.7%) 8 (72.7%) 6 (54.5%) 3 (27.3%)

7 (77.8%)* 5 (55.5%) 6 (66.7%) 5 (55.5%) 3 (33.3%) 3 (33.3%)

There was an immediate increase in all modalities. * p = 0.576.

S.R.D.T. Siqueira et al. / Clinical Neurology and Neurosurgery 108 (2006) 721–725

the surgery. On the other hand, the olfactory threshold statistically increased in the immediate post-operative period (p = 0.048), but tended to the initial values after 120 days. The results are outlined on Table 4.

4. Discussion

There was a statistically significant difference in the olfactory threshold (p = 0.048). * p = 0.830. ** p = 0.185. *** p = 0.478. ****p = 0.976. *****p = 0.048.

0.388 (0.010–1.000; S.D. = 0.367) 0.18 (0.003–0.032; S.D. = 0.013) 0.209 (0.032–1.000; S.D. = 0.308) 0.918 (0.100–3.200; S.D. = 0.934) 1.42 (0.09–7.78; S.D. = 2.51) 0.296* (0.032–1.000; S.D. = 0.262) 0.013** (0.003–0.032; S.D. = 0.013) 0.163*** (0.010–1.000; S.D. = 0.291) 1.421**** (0.032–10.00; S.D. = 2.868) 4.37***** (0.29–23.33; S.D. = 6.87)

0.310 (0.032–1.000; S.D. = 0.248) 0.008 (0.001–0.010; S.D. = 0.004) 0.055 (0.032–0.100; S.D. = 0.033) 0.559 (0.003–1.000; S.D. = 0.402) 1.42 (0.09–7.78; S.D. = 2.18)

Mediate post-operative period (N = 9) Immediate post-operative period (N = 11) Pre-operative period (N = 12)

0.391 (0.032–1.000; S.D. = 0.3001) 0.0965 (0.010–1.000; S.D. = 0.285) 0.0152 (0.032–1.000; S.D. = 0.269) 1.256 (0.032–10.00; S.D. = 2.785) 1.17 (0.09–7.78; S.D. = 2.20) Sweet threshold Sour threshold Salty threshold Bitter threshold Olfactory threshold

Table 4 Means, ranges and standard deviation of the gustative and olfactory thresholds in the control group and in the patients group at all periods of evaluation

Controls (N = 12)

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Surprisingly, the data of this study showed ITN patients with a significant abnormality in the olfactory threshold at the immediate post-operative period (p = 0.048), although patients’ complaints were related to taste (36.4%). On the other hand, these patients did not present an increase in the pain threshold at the most of superficial facial regions except the maxillary branch (p = 0.014), and subjective numbness was more frequent than superficial pain, heat or cold abnormalities, which might suggest that deeper areas of the face were more affected by the procedure than the superficial region, specially the maxillary area. Our results suggest that there is a compromise in the “taste sensation” reported by the patients due to the trigeminal injury that occurred in the immediate post-operative period, which possibly affected the olfactory perception mediated by maxillary trigeminal afferents at the nasal mucosa [9], as we did not have any olfactory nerve damage, which is anatomically located distant to the area operated. There are already other studies with evidences of “taste sensation” abnormalities after trigeminal neurosurgical procedures, but no study has identified the exact afferents and pathways, which were involved in that findings [14]. This study, until the present moment, is the first one with evidence for the hypothesis that maxillary afferents may be related to olfaction, which was affected after the ganglion compression and injury of the trigeminal nerve. One possible mechanism for the reducement on the olfactory threshold after the surgery may be the interaction between the I and the V cranial nerves, which have both sensitive afferents on the same area (nasal mucosa), and the olfactory nerve function may depend on the trigeminal function, similar to the most accepted physiopathological theory for BMS, consisted on uncontrolled trigeminal inputs after inhibition of taste inputs of the chorda tympani nerve [10,11]. Anatomical studies in animals demonstrated that some lingual nerve fibres were ending at the nucleus Solitarius lateral, and its projections were in inctimal relation to second neurons of the chorda tympani nerve. Demyelization at this area would cause trigeminal pain and ageusia [14], and convergence of these two systems (sensitive and gustative) was observed in primates. Also, the “taste perception” depends on olfactory inputs, and there are neurons connecting central areas related to the I and VII nerves. Possibly, these trigeminal–chorda tympani-olfactory interactions could be responsible to our findings (trigeminal injury-taste complaints-reduced olfactory threshold). The observation that trigeminal fibers may be related to the “taste sensation” by transmiting olfactory inputs from the nasal mucosa [9] may explain why some

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case reports of trigeminal neuralgia were triggered by gustative stimuli [15]. In conclusion, this is an important evidence that supports the theory of sensorial interaction from Melzack and Wall [21], which occurs among sensorial modalities, such as pain, taste and smelling, and encourages new approaches that may confirm this theory among other sensorial modalities.

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