An Update on the Causes, Assessment and Management of Third Division

An update on the causes, IN BRIEF • Provides a history and examination of patients presenting with trigeminal PRACTICE assessment and management of neuropathy to facilitate clinicians in their assessment. • Reviews the literature demonstrating the differing causes of trigeminal neuropathy. third division sensory trigeminal • Presents a case series to outline the causes seen in our nerve injury clinic. • Highlights the importance of identifying neuropathies red flag symptoms for neoplasia. E. Carter,*1 Z. Yilmaz,2 M. Devine2 and T. Renton2 VERIFIABLE CPD PAPER

Introduction Sensory neuropathies of the mandibular division of the trigeminal (V3) nerve can be debilitating, causing difficulty with daily function. It has a variety of causes, including iatrogenic injury, usually caused by third molar removal, local anaesthetic administration, implant placement or endodontic treatment. Non-iatrogenic causes include infection, primary or secondary neoplasia and various medical conditions. Objective To review the aetiology, evaluation and management of V3 neuropathy in a retrospective case-series of patients referred to a specialist nerve injury clinic over an eight-year period, particularly focusing on the non-iatrogenic causes of this presentation. Methods A retrospective analysis of the case notes of 372 patients referred to the specialist nerve injury clinic between 2006 and 2014 was carried out to establish the cause of the neuropathy and subsequent management or referral. The assessment protocol of trigeminal neuropathy used in the clinic is also outlined. Results Most patients (89.5%) presented with neuropathy due to iatrogenic injury. Of the non-iatrogenic causes (10.5%), malignancy accounted for a fifth of presentations, and infection almost two- fifths, demonstrating the importance of prompt identification of a cause and management by the clinician, or referral to the appropriate specialty. Other, more rare causes are also presented, including multiple sclerosis, sickle-cell anaemia and Paget’s disease, highlighting the importance to the clinician of considering differential diagnoses. Conclusions This case series demonstrates the less frequent, but nevertheless important, non-iatrogenic causes which clinicians should consider when assessing patients with trigeminal neuropathy.

INTRODUCTION nerve) or a combination of these symptoms. area more difficult to tolerate compared with Sensory neuropathy of the mandibular divi- other parts of the body.4 Consequences include

The aims of this article are to review the pos- sion of the trigeminal nerve (V3) in particu- interference with daily social function, eating, sible causes of mandibular division trigeminal lar has been termed ‘numb chin syndrome,’1,2 drinking, speaking, kissing, applying makeup,

(V3) sensory neuropathies, present a retrospec- which is an umbrella term encompassing a tive case series of patients presenting with such range of aetiologies including iatrogenesis, neuropathy and describe recommended evalu- infection, metabolic, degenerative, inflam- ation and management of these patients. matory, trauma and neoplasia.3 Sensory neuropathy is altered sensory The trigeminal nerve is the 5th and larg- perception in the distribution of a nerve, est cranial nerve, and is a mixed motor and presenting as anaesthesia (complete loss of sensory nerve. It is the ‘protector’ sensory sensation), paraesthesia (altered sensation), system for the head and neck and the larger dysaesthesia (unpleasant sensation), neurosensory part forms the opthalmic, maxillary pathic pain (pain in the distribution of the and mandibular branches that carry affer- ents sensitive to external or internal stimuli from the skin, muscles, and joints of the face 1The Royal London Hospital, Oral and Maxillofacial Sur- gery Department, Turner Street, London, E1 1BB; 2King’s and mouth, and from the teeth (Fig. 1). The College London Dental Institute, Oral Surgery, Denmark mandibular branch is the only branch with a Opthalmic division Hill Campus, Bessemer Road, London, SE5 9RS motor component, which supplies the mus- *Correspondence to: E. Carter Maxillary division cles of mastication (Table1). Email: [email protected] Mandibular division The impact of trigeminal neuropathy must Refereed Paper not be underestimated. The face has one of Accepted 4 May 2016 the highest concentrations of sensory inner- Fig. 1 Lateral view of the head and neck DOI: 10.1038/sj.bdj.2016.444 depicting the areas innervated by V /V /V ©British Dental Journal 2016; 220: 627-635 vation, making sensory neuropathy in this 1 2 3

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5–7 shaving and sleeping; all functions that we Other traumatic iatrogenic causes of trigemi- V3 injury as a complication of implant take for granted and are the basis for socia- nal neuropathy include radiotherapy15 and treatment is becoming a major concern12,26,27 bility and life enhancement. Patients usually exposure to chemical agents such as trichlo- and incidence studies indicate a complica- expect and experience significant improve- roethylene, stilbamidine, and allopurinol.16 It tion rate not to be ignored.28,29 There are rare ments in jaw function, dental, facial, and has been shown that the use of whiteheads reports of resolution of implant related V3 overall body image following oral rehabili- varnish and surgicel have temporary effects neuropathies at over four years,30 but these 8 31 tation. V3 sensory neuropathy has a signifi- on peripheral neural function, and Carnoy’s are the exception rather than the norm. cant negative effect on the patient’s quality solution may have a permanent effect,17 this Many authors recommend referral of these of life and when the cause is iatrogenic, the has most relevance in surgery performed in injuries within four months,7,32 but this may psychological effects can be compounded.4 the region of the inferior dental nerve. be too late. We now understand that within

Causes of V3 sensory neuropathy include; Third molar surgery is a common cause of three months of injury, permanent central iatrogenic (surgical and medical), infections, iatrogenic injury to the mandibular division and peripheral neurological changes occur, neoplasia, systemic pathology and idiopathic of the trigeminal nerve10,18,19 although mod- rendering neurones unlikely to respond to causes. ern management strategies have been found surgical intervention.33

to successfully prevent injuries in high risk V3 sensory neuropathy has also been Iatrogenic - surgical cases.20,21 Following administration of an infe- reported in connection with mandibular A recent study reported that 63% of cases rior dental block injection, the prevalence of atrophy in the older population, particularly 11 of V3 sensory neuropathy were attributed to temporarily impaired lingual and inferior in edentulous individuals. Dentures which previous dental treatment.9 Iatrogenic injuries alveolar nerve function ranges from 0.15– cause compression of the mental nerve in to the mandibular division of the trigeminal 0.54%;6,22 permanent neuropathy is much less those with atrophic mandibles are a known nerve may be caused by a variety of differ- frequent (0.0001–0.01%).6,23 Inferior alveolar cause of paraesthesia in this group.34 ent treatment modalities such as maxillofacial nerve injury occurs in 1 in 14,000 inferior surgery (for example sagittal split osteoto- dental nerve block injections and is usually Iatrogenic medical mies, reduction and fixation of mandibular temporary (75%) but can persist and become Medication related osteonecrosis of the jaw fractures)4 and minor oral surgery (includ- permanent (at three months).24 Likewise, (MRONJ) has also been documented as a 10 3,35 ing third molar removal), implant place- extrusion of endodontic materials or instru- rare cause of V3 sensory neuropathy, with ment,11,12 inferior dental block and mental mentation beyond the apex in the region of removal of necrotic bone and antibiotic block anaesthesia,13 instrumentation beyond the mental foramen or inferior alveolar nerve administration resulting in resolution or the apex, extrusion of irrigation fluid and fill- may cause severe mechanical and chemical improvement of the associated symptoms.36 14 14,25 ing materials during endodontic treatment. injury resulting in V3 sensory neuropathy. In cases of suspected MRONJ related neuropathy it is important to rule out a primary

Table 1 The trigeminal nerve main divisions (V1, V2 and V3) or metastatic malignancy as many of these patients have been prescribed the medication Cornea for treatment of metastatic disease. Ciliary body Infection Conjunctiva Opthalmic branch V1 Local periapical infection of teeth has (Sensory) Nasal cavity been reported to cause V3 sensory neuropathy.9,37–42 Infection-related neuropathy Sinuses has been shown to resolve following non- Skin of eyebrows, forehead, and nose surgical endodontic therapy or extraction of the causative tooth,38,43 supporting the Side of nose theory that pressure caused by an expand- Lower eyelid ing infection and inflammation can cause Maxillary branch V2 (Sensory) paraesthesia. Upper lip Viral infections have also been implicated

Maxillary dentition in the development of V3 sensory neuropathy, with herpes zoster reactivation rarely Temporal causing neuropathy of the trigeminal nerve. Auricular The ophthalmic division is most commonly affected, however, the maxillary and man- Lower face dibular divisions can also be involved.43 Sensory Lower lip Acute and chronic osteomyelitis are poten-

tial causes of V3 sensory neuropathy, if there Oral mucosa – anterior two thirds of tongue is involvement of the mandibular canal.15,44 Mandibular branch V3 – gingivae and teeth Diffuse sclerosing osteomyelitis of the mandible has been reported as another cause of Muscles of mastication trigeminal neuropathy, with a small number of patients being successfully treated with bis- Temporalis Motor phosphonate infusions.45 Osteoradionecrosis Masseter and superinfection of osteoradionecrosed bone can also cause neuropathy,15,46 as can Pterygoids surgery to treat such cases.46

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Table 2 Important aspects to consider when taking the history of a patient presenting with Neoplasia trigeminal neuropathy Following exclusion of a dental cause, V3 Was the patient specifically warned of the possible sensory neuropathy is often considered as Preoperative consent complications (such as pain, numbness) after the a ‘red flag’ symptom because of its frequent and planning procedure? association with systemic malignancies.9 Was the procedure planned well before operating? When iatrogenic causes are excluded and if the neuropathy is only associated with the Severe pain on injection, during removal or endodontic treatment of a high risk tooth, or during mandibular division of the trigeminal nerve preparation of an implant bed it has been suggested that malignancy is the Iatrogenic cause Intraoperative most likely cause.44 Use of higher concentration LA agents Neoplasia local to the nerve, for example Multiple injections odontogenic or non-odontogenic tumours

Severe to extreme pain post-surgery may be indica- and cysts of the mandible can lead to V3 sen- tive of nerve injury sory neuropathies.44,47 These can occur as a result of peripheral nerve sheath neoplasia,48 Postoperative Persistent pain post-surgery that does not respond to anti-inflammatory drugs osteosarcoma of the mandible,1,15 multiple 1,49 Multiple postsurgical infections myeloma and direct extension of a squamous cell carcinoma of the lip.44 Spontaneous (nothing causes the pain) or elicited (for A wide variety of intracranial tumours example by tooth brushing or cold air) in various locations of the nervous system Ask whether the pain is: Constant or intermittent including the brainstem, meckles cave and Pulling (neuralgic), or burning (dysaesthetic) the cerebellar pontine angle cause clinical

symptoms which can mimic V3 sensory neu- Pain history Pain severity out of 10 (where 10 is worst pain ropathy.15 These include benign and malig- imaginable) nant neoplasms such as epidermoid cysts, Frequency of pain episodes 15,44 Enquire about: schwannomas and gliomas. Avoidance strategies Secondary neoplasms affecting the Use of medication nerve

Speaking Although any type of malignancy can metastasise, metastasis to the mandible Eating is a rare event. Charles Bell was probably the first to describe this V neuropathy in Drinking 3 1830 in an elderly woman with breast can- Kissing cer. Further cases of V3 sensory neuropathies Ask if they have any Functional history Brushing teeth/flossing teeth among women with breast cancer have been problems with: reported more recently.1,44,50 All histological Sleeping subtypes may be associated with this syn- Socialising drome, such as: • Adenoid cystic carcinoma3,44 Shaving • Colon, rectum cancer44,50 • Lung cancer (small cell and non-small Applying makeup cell carcinoma)1,3,44,50 Euroqol 5D (Quality of life) • Lymphoma (Hodgkin and non-Hodgkin), lymphosarcoma, Waldenstrom1,3,44 GAD-7 (Anxiety levels) • Myeloma1,49 PHQ-9 (Depression levels) • Prostate44,50 • Osteosarcoma1,15 MSPSS (Level of social support) • Squamous cell carcinoma of the lip44 OHIP-14 (Level of problems with teeth, mouth and • Thyroid carcinoma1 gums over the past 3 months) • Uterine carcinoma3 PCL – brief version (Screen for post-traumatic stress • Primary intra-osseous carcinoma.1 Patients complete these disorder) Psychological history questionnaires: CPAQ (Chronic pain acceptance) Lymphomas, breast and lung cancers Short-form McGill (Words used to describe their pain) are however, by far, the most frequently reported.15 No sex predominance is found, PainDetect Questionnaire (Screening tool for neu- the occurrence being due to the sex distri- ropathic pain; pain scores using the visual analogue bution of the underlining tumours. Brain scale, and other pain experiences) metastases can also result in symptoms mimicking V sensory neuropathy, with the PCS (Presence of catastrophising about their pain) 3 most commonly metastasising tumours to PSEQ (Level of confidence with carrying out various the brain being breast and lung cancer.15 tasks despite their pain)

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peripheral and or central neoplasias must be excluded. BACKGROUND TO THIS STUDY A dedicated orofacial pain and trigeminal nerve injury service has been running at King’s College Hospital for over seven years. Weekly multidisciplinary clinics run by an oral surgeon, neurologist, neurosur- geon, psychiatrist and psychologist assess and manage patients referred by general dental practitioners (GDPs), general medical practitioners (GMPs) and other hospital based dentists and doctors. Over one hun- dred new referrals are received each year. The clinic also has an online referral service for iatrogenic trigeminal nerve injuries (www.trigeminalnerve.org.uk). This article describes a retrospective case series of con- secutive patients referred for management of mandibular division trigeminal sensory neuropathy. Assessment and clinical history

All patients referred to the clinic with V3 sensory neuropathy were assessed by the same practitioner (TR). A full medical, social and dental history was taken. A detailed history of the probable causative event (for example, wisdom tooth removal) for the neuropathy (if iatrogenic cause suspected) was taken (Table 2). If a causative event was not linked to the onset of neuropathy, a detailed history was explored to exclude ‘red flag’ symptoms of neoplasia primarily, (Table 3) but also to consider other potential causes of neuropathy. Psychological assessment is important in the management of iatrogenic nerve injury as many patients are severely psychologi- cally affected.61 Several validated questionnaires are completed by the patient to establish their psychological state, anxiety or depression, pain intensity and effect on function and daily activity prior to con- sultation (Table 2). All patients who report changes to their psychological state or mental health issues are assessed by the liaison psychiatrist and may be referred on to the liaison psychologist for further treatment Fig. 2 Examination protocol for the mechanosensory evaluation of extra-oral dermatone of V3 Clinical examination Other medical causes connective tissue diseases,44 demyelinating It is important to recognise that a patient 3,44 A presenting symptom of isolated V3 sensory diseases such as multiple sclerosis, sar- may be anxious as those presenting with neuropathy can lead to the diagnosis of a coidosis,53 Sjögren’s syndrome,44,54 syphilis neuropathy are often concerned that they wide range of systemic medication condi- and diabetes mellitus.44,55–57 Among the more may have cancer or have had a previous tions.51 These can be grouped into degen- rare medical causes are sickle cell disease58,59 traumatic iatrogenic event. erative neurological disease, immunological, and Lyme disease.60 Initial extraoral examination routinely haematological, metabolic and endocrine. evaluates: Idiopathic trigeminal neuropathy V3 sensory neuropathy has been described • Cranial nerves excluding 1 and 8 (with both as an isolated symptom and as part of It has been proposed that V3 sensory neu- crude identification of any sensory a disease process such as vasculitis, which ropathy which cannot be attributed to any neuropathic area which is more closely can occur secondary to rheumatoid arthri- underlying cause could be secondary to investigated later [see text later in tis,50 cerebro-vascular accident (CVA),52 herpes simplex viral infections.16,51 However, methods]).

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• Temporomandibular joints Investigations pins and needles, itching, burning or • Facial and cervical lymph nodes The investigations for trigeminal neuropa- pain)

• Asymmetry, swellings or lesions thy depend upon the presentation, with • Change in subjective function in V3 • Facial scarring. iatrogenic injury focusing on the cause, dermatome (reduced or increased) and spontaneous neuropathy investigations • Abnormal clinical neurosensory tests Intraoral examination establishing if there is any neoplastic cause (reduced or increased sensation to light Initial examination should involve a thor- first and foremost, then focusing on the touch, sharp/blunt discrimination and ough assessment of dentition, oral hygiene, other possible medical causes. two point discrimination). mucosa, restorations and further testing of dental vitality, percussion, response to METHODS Outcome measures thermal stimuli and sensory changes to the The outcomes recorded included cause of V3 teeth and mucosa.3 Any signs of local dental Patient selection sensory neuropathy: infection, surgical trauma or local malignan- A retrospective analysis of the clinic letters • Iatrogenic (surgical) cies should also be noted. and patient records of all patients referred • Iatrogenic (medical) to the trigeminal nerve injury clinic between • Infection Vth nerve sensory examination January 2006 and January 2014 with V3 sen- • Systemic disease process

General sensory assessment of the skin and sory neuropathy was undertaken. V3 sensory • Neoplastic mucosa of all the divisions can be assessed neuropathy was defined as a patient present- • Idiopathic. using subjective function, light touch, mov- ing with subjective altered sensation in the ing point discrimination, sharp/blunt dis- mandibular division of the trigeminal nerve, Treatment required for symptomatic man- crimination and two point discrimination which was confirmed on clinical neurosen- agement of V3 sensory neuropathy: techniques. This is shown in Figure 2. sory examination (Fig. 2). • Reassurance and explanation Reflexes of the Vth cranial nerve include the • Surgical management of nerve injury jaw jerk reflex, which tests both sensory and Diagnostic criteria for V3 sensory • Removal of iatrogenic cause (for motor components of the trigeminal nerve, and neuropathy example, tooth extraction, implant the corneal reflex (cornea touched with cotton • Subjective altered sensation in removal) whisp) which tests both efferent sensory CN5 and mandibular division of trigeminal nerve • Pharmacological management (local or afferent motor CN7 resulting in bilateral blinking (patient report of numbness, tingling, systemic) due to the consensual reflex. This examination identifies the presence of a neuropathy and gives Table 3 Results information about the extent of involvement of the nerve. This should be mapped out to dem- Causes of mandibular trigeminal neuropathy Number of patients onstrate the area(s) affected for future reference. Iatrogenic causes: Vth nerve motor examination is only Mandibular Third Molar Removal 140 undertaken when patients present with obvi- ous motor symptoms or complaints of weak- Dental Local Anaesthetic – Inferior dental block 80 ness, trismus or spasms. This should identify Dental Implant 68 normality (no tremor, involuntary chewing or trismus) with symmetry on tightly clenched Endodontic Treatment 24 teeth. Abnormality of motor function (tremor, Bone Graft 6 trismus, involuntary movement and paralysis identified with deviation to the weak side on Excision of mucocele 6 mouth opening and/or vertical misalignment Apicectomy 5 of central medial incisors) can be detected. This provides information on the extent of the neu- Mandibular and maxillary osteotomies 4 ropathy, which gives further information about Non-iatrogenic causes: the likely location of a cause. Infection 12

• Previous history of malignant neoplasm Multiple Sclerosis 6 • >50 years of age Malignancy – Primary 4 • Previous history of immune suppression • Con rmed neurological abnormality Fractured mandible 3 • Sudden onset Malignancy – Metastases 3 • Associated with other symptoms, e.g. fever, weight loss Osteomyelitis 3 • Symptoms not corresponding to the presumed diagnosis Sickle Cell Anaemia 3 • Unexplained trismus Ameloblastoma 2 • Repeat attendances with the same symptoms, e.g. non-healing socket Brain stem tumour 1

Cranial Vascular malformation 1 Fig. 3 Red flags for neoplastic disease presenting as trigeminal Paget’s disease 1

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• Psychological management condition and all patients were referred on 8% and 4% of the patients. Confidence lev- • Resolution of neuropathy to neurology services for further investiga- els and ability to socialise at events were • Complete resolution tions, reviews and management. One 64-year affected among 4% and 6% of patients. • Partial resolution old lady, who had been referred to the oral Another problem reported by 6% of • No improvement. surgery department at KCH privately via a patients included interference with the pro- neurologist at Queen’s Square received a new nunciation of words, with one patient stating Data collection and analysis diagnosis of Paget’s disease of bone. that she slurred her words. Dribbling sen- Data collection was carried out retrospec- sations were reported by 12% of patients. tively from the clinic letters and patient Symptoms experienced Biting the lip was a problem for 8% of the records of all patients referred to the trigemi- Patients with non-iatrogenic V3 sensory neu- patients and one patient stated that they kept nal nerve injury clinic with V3 sensory neuropathy predominately experienced numb- biting their tongue. ropathy between January 2006 – January ness (56%) or tingling (30%) sensations. 2014 by two of the authors (EC and ZY). One patient described their symptoms as a Treatment required for Data was collected and entered into IBM ‘floppy swollen feeling’, another described symptomatic management of V3 Statistical Package for Social Sciences (SPSS) it as ‘itchiness’, whilst another stated it was sensory neuropathy: Version 22. Descriptive statistical analysis like ‘ants crawling across the area’ (or ‘for- Reassurance and explanation alone was suf- was carried out on the data using the above mication’). Paraesthesia was reported by 38% ficient in 12 patients without any dysaes- program to identify the aetiology of V3 sen- of patients, of whom 20% had evoked par- thesia or neuropathic pain. The remaining sory neuropathy in this series of patients. aesthesia and 18% experienced spontaneous patients had either a single type of treat- paraesthesia. One patient experienced both ment, or a mixture of treatments (for exam- RESULTS evoked and spontaneous paraesthesia. ple, systemic and/or topical medication with Equal numbers of patients experienced cognitive behavioural therapy (CBT). Nine Patient demographics evoked pain or spontaneous pain, at 28% patients were on more than one treatment 372 patients (73% females: 27% males) were of the cases. Three of these patients had method for their pain management. referred to the trigeminal nerve injury clinic both evoked pain and spontaneous pain. Surgical management of nerve injury with V3 sensory neuropathy between January The most frequent words used to describe was recommended for two patients. One of 2006 and January 2014. The average age their pain were sharp, shooting and tight- these patients was recommended debride- of patients was 45.6 (range 18–85 years ness. Other descriptors included pulling, dull, ment of the area, and it was suggested to [S.D. 13.5]). There was an average delay excruciating and radiating. 36% and 32% of the other patient that they potentially have between onset of symptoms and assess- patients reported allodynia and hyperalgesia, the retained roots removed and exploration ment on the clinic of 16.9 months (range respectively. of the inferior-dental nerve. Surgery was not 2.5 weeks – 3 years). Eighteen patients within the case series appropriate for the other patients either due experienced some form of allodynia, whereas to a significant delay in referral of greater Cause of V3 sensory neuropathy mechanical allodynia was experienced by than six months since the onset of symp-

The causes of V3 sensory neuropathy found 16 of these patients. Eight of these patients toms, they required other dental procedures, in 372 patients who presented to the clinic reported just mechanical allodynia; four of or because they were suffering from altered between January 2006 and January 2014 are these patients experienced both extraoral sensations, but not pain, and any surgery shown in Table 3. Results showed that 89.5% of (EO) and intraoral (IO) mechanical allodynia could have caused further damage. cases had an iatrogenic cause, and 39 (10.5%) and the other four only had EO mechanical Dental procedures were recommended for had other causes of neuropathy. Malignant allodynia. One patient experienced only EO all of the patients who had infection-related causes were rare at eight (2.2%) patients within heat allodynia. V3 sensory neuropathy. Such procedures the case series, accounting for 20.5% of the A mixture of mechanical, cold and/or heat included removal of the causative tooth to non-iatrogenic cases. Infection was the identi- allodynia was experienced by eight of the promote healing (five patients), removal of fied causative factor in 15 patients (4%) of the patients. EO and IO mechanical allodynia infected roots (one patient) and a proposed cases, and was the most common non-iatro- were experienced together with EO and IO removal of retained roots (one patient) but genic cause at 38.5%. This study focussed on cold allodynia in three patients. Three other this was very close to the inferior alveolar those patients who had non-iatrogenic causes patients only experienced EO mechanical nerve and therefore its extraction was high- of V3 sensory neuropathy. and cold allodynia. Two patients reported risk. A dentigerous cyst had to be removed Fifty-two percent of the 39 patients with a mixture of mechanical, cold and heat under general anaesthetic for one patient. non-iatrogenic V3 neuropathy were referred allodynia. Re-root canal treatment (RCT) was recom- from their GDP, 38% were referred from a mended for six patients, with slight possi- specialist in a tertiary care centre and 6% Functionality problems bility of extractions amongst two of these from their GMP. Owing to the nature of The most common functionality problem patients. One patient was recommended the notes available for the remaining two reported by 52% of the cases was speech. possible implant treatment for the ower patients, whom they were referred from was Eating was the second most common func- right second molar. Other dental treatments not known. The mean age of the patients tionality problem, reported by 40% of the included the placement of a bridge and one who had non-iatrogenic causes of neuropa- patients. Drinking was problematic for 28% patient was monitored over time to see any thy was 46.9 years (range 23 – 75), and 70% of patients and 26% stated that they had changes in radiolucency around the lower were female. problems with kissing. Brushing teeth was left 5 region with the possibility of taking Over half of the patients (58%) did not difficult for 24% of patients. Other function- antibiotics (clindamycin) for six weeks. have any other underlying medical condi- ality problems included interference with Pharmacological management of the tion. Of the six patients with multiple sclero- sleep (12%) and work (6%). Make-up appli- symptoms of V3 sensory neuropathy was sis, one had a pre-existing diagnosis of this cation and shaving were affected among required in 11 patients for ongoing pain. This

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included use of local and systemic medica- This case series also highlights six patients been previously reported.64–67 Other causes tion for pain management. Topical Versatis (15.4%) presenting with multiple sclerosis found in this case series highlight the impor-

(lidocaine 5%) patches were recommended to presenting with V3 neuropathy. Dentists may tance of understanding the principles of his- four patients. Two patients were taking tricy- not be familiar with non-iatrogenic trigemi- tory and examination in patients presenting clic antidepressant medication (amitriptyline nal neuropathic and should be aware of red with neuropathy affecting the trigeminal or nortriptyline) and anticonvulsant medica- flags indicating likely neoplasia (Table 3) nerve, and consideration of how the onset tion (gabapentin, pregabalin) was being used Spontaneous sensory neuropathy is always of symptoms may be related to the cause. by nine patients. Botox injections were not a clinical sign of concern, however the most Trigeminal sensory neuropathy may pre- recommended to any of the patients. common cause of non-iatrogenic cause of sent with hypofunction (partial or complete Eleven patients required referral to liai- third division trigeminal sensory neuropa- numbness) or hyperfunction with altered son psychiatry and psychology services for thy in this case series was dental periapical sensation (paraesthesia, dysaesthesia) and/or cognitive behavioural therapy to aid in pain infection. If a tooth root apex is close to neuropathic pain (allodynia – pain on touch management. Two of these patients were the inferior dental canal and the dental pulp or hyperalgesia- increased pain with painful also using Versatis patches and one patient becomes necrotic then leakage of necrotic stimuli).51 Examination often cannot differ- was taking Gabapentin in addition to CBT. tissue through the apex of the root will irri- entiate the iatrogenic from the spontaneous Two patients also had some dental treatment tate and inflame local nerve tissue. neuropathies. The history is therefore essen- (oral hygiene or RCT) in addition to CBT. Should a patient present with red flag tial to discern the cause of the symptoms. signs associated with trigeminal neuropa- General dental practitioners need to have Resolution of neuropathy thy, once local dental pathology is excluded, an understanding of the potential causes of Of those patients with a non-iatrogenic cause prompt referral to a neurologist is essential. trigeminal neuropathy, and therefore iden- of their V3 sensory neuropathy, patients who Red flags for neoplastic disease are shown in tify if there is a dental cause, which, (in the received a new diagnosis of a systemic con- Table 3. More difficult is establishing a medi- case of infection) they could potentially dition or neoplasia were referred on to the cal diagnosis for non-malignant spontane- treat, or refer to the appropriate clinician relevant specialty for further investigations ous neuropathy because, as discussed, there for other iatrogenic, neoplastic and medical and/or management. Complete resolution are a plethora of potential medical causes causes of these symptoms. Infections were of the neuropathy occurred amongst seven which will rarely present to dentists. Our implicated in 4% of cases. patients within the whole group of patients routine haematological investigations aim to A detailed history of any previous trau- with non-iatrogenic V3 sensory neuropathy. identify haematological causes (haematinic matic or medical event that may be related These patients who had complete resolu- deficiencies), diabetes, thyroid disease and to the neuropathy is paramount. Investigating tion had an infection-related neuropathy autoimmune diseases. More specific investi- certain risk factors may also reinforce your and their treatment predominately entailed gations may be required in many conditions diagnosis of iatrogenic neuropathy. For extraction of the affected tooth to manage presenting with trigeminal neuropathy such those patients with spontaneous neuropathy the infection. Five patients had partial reso- as multiple sclerosis (MS), lupus, orofacial a variety of causes have been reported and lution and 14 reported no change in their granulomatosis and infections including confirmed in this case series. Importantly, symptoms. The outcome for the remain- tuberculosis, oral and surgical infections. neoplasia must be suspected and excluded ing patients was unknown due to loss to MS most likely presents with ophthalmic where possible, should no iatrogenic cause be follow-up. signs before presenting with trigeminal implicated. Our case series demonstrates that neuropathy or neuralgic pain,63 therefore, although more uncommon, neoplasia can also DISCUSSION trigeminal neuropathy is unlikely to be the contribute towards the number of non-iatro- A case series of patients presenting with first presenting symptom of this condition; genic causes of neuropathy at approximately third division trigeminal (V3) sensory neu- however, this has been reported in some one fifth of cases. This highlights the impor- ropathy is discussed in this paper. V3 neu- patients. If a patient presents with trigeminal tance of differentiating iatrogenic from non- ropathy can be caused by a variety of causes, neuropathy and has known medical condi- iatrogenic causes early so that these cases are as illustrated in this patient case series, and tions, for example diabetes, then referral to not missed, and managed appropriately. spontaneous central or peripheral neopla- the patient’s GMP in the first instance for For patients presenting with iatrogenic sia must be excluded. Patients presented onward referral to a specialist physician or neuropathy, depending upon mechanism with underlying neoplasia in 2% of cases, neurologist is appropriate. and duration of the cause of the neuropa- thus clinicians must always be aware of Due to the specialism of the clinic, most of thy, various management strategies are this rare possibility and appropriately refer the trigeminal neuropathies seen in the oral recommended.64 As with other iatrogenic the patient for appropriate investigations. surgery clinic were iatrogenic in nature (Table neuropathies, acute medical management A recent review of trigeminal neuropathy, 3). This high proportion of patients with iat- may be appropriate. This can involve step ‘Numbness matters’ highlights the various rogenic neuropathy is also demonstrated in down steroids (prednisolone 50, 40, 30, causalities and diagnostic challenges and a previous report,9 which notes that due to 20 and 0 mg over five days) and non-steroi- suggests a possible assessment pathway.62 increasingly invasive dentistry many patients dal anti-inflammatories (NSAIDs) (ibuprofen Numb chin syndrome is a commonly used suffer from iatrogenic trigeminal neuropathy. 600 mg QDS), in addition vitamin B complex 3,68–70 term by neurologists referring to V3 neurop- Neurologists who are referred these patients injections. Treatment of post-surgical athy. This may be a misnomer, as highlighted may not be aware of the prevalence of this neuropathy does not have recommended in this paper, very few patients present- condition, and the range of potential dental evidence-based care and is usually managed ing with V3 neuropathy have anaesthesia causes of third molar removal, local anaes- symptomatically using systemic medications or numbness alone. As with most sensory thetic administration, implant placement, which can cause a plethora of complications neuropathies the characteristic presentation endodontics and dental infection. and are often poorly tolerated by the patient. includes anaesthesia, paraesthesia and elic- Iatrogenic trigeminal neuropathy risk fac- A topical approach to treating patients with ited or background neuropathic pain. tors, clinical profile and management have chronic neuropathic orofacial pain may be

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more useful for such cases, especially in the 9. Kalladka M, Proter N, Benoliel R, Czerninski R, Eliav 32. Hegedus F, Diecidue R J. Trigeminal nerve injuries avoidance of side effects. Such topical treat- E. Mental nerve neuropathy: patient characteristics after mandibular implant placement‑practical and neurosensory changes. Oral Surg Oral Med Oral knowledge for clinicians. Int J Oral Maxillo Implants ment may include the use of topical lidocaine Pathol Oral Radiol Endod 2008; 106: 364–370. 2006; 21: 111–116. patches,71 topical capsaicin,72,73 and topical 10. Bataineh A. Sensory nerve impairment following 33. Clark A K, Old E A, Malcangio M. Neuropathic pain local anaesthetic creams.74,75 Whilst there is mandibular third molar surgery. J Oral Maxillofac and cytokines: current perspectives. J Pain Res Surg 2001; 59: 1012–1017. 2013; 6: 803–814. some evidence that these topical methods 11. Wismeijer D, van Waas M A, Vermeeren J, Kalk W. 34. Szewka A J, Purdy H, Topel J, Jhaveri M D. Teaching provide pain relief, additional large con- Patients’ perception of sensory disturbances of the neuroimages: numb chin syndrome in an edentu- trolled clinical trials are required in order to mental nerve before and after implant surgery: a lous patient. Neurology 2011; 77: e38. prospective study of 110 patients. Br J Oral Maxil- 35. Zadik Y, Benoliel R, Fleissig Y, Casap N. Painful provide further clinical evidence for their use lofac Surg 1997; 35: 254–259. trigeminal neuropathy induced by oral bisphos- in pain management and to monitor any side 12. Kraut R, Chahal O. Management of patients with phonate-related osteonecrosis of the jaw: a new effects of using these topical methods.71,76,77 trigeminal nerve injuries after mandibular implant etiology for the numb-chin syndrome. Quintes- placement. J Am Dent Assoc 2002; 133: 1351–1354. sence Int 2012; 43: 97–104. This study did not endeavour to analyse 13. Hillerup S, Jensen R. Iatrogene nerveskader opstået 36. Otto S, Hafner S, Grotz K A. The role of inferior the differences between clinical presentation i almen tandlægepraksis. Hyppighed, årsager og alveolar nerve involvement in bisphosphonate-re- of iatrogenic versus other causes. Further symptomer. Tandlaegebladet 2001; 105: 614–622. lated osteonecrosis of the jaw. J Oral Maxillofac 14. Grotz K, Al-Nawas B, Aguiar Ed, Schulz A, Wagner Surg 2009; 67: 589–592. research would benefit clinicians in identi- W. Treatment of injuries to the inferior alveolar 37. Cavallito C DFF, Arduino P G, Broccoletti R, Carbone fying pain history, clinical, neurological and nerve after endodontic procedures. Clin Oral Inves- M. Numb chin syndrome. Annali di Stomatologia psychological differences between various tig 1998; 2: 73–76. 2013; 4: 1–48. 15. Becker M, Kohler R, Vargas M I, Viallon M, Delavelle 38. Di Lenarda R, Cadenaro M, Stacchi C. Paresthesia of causes of trigeminal neuropathy. J. Pathology of the trigeminal nerve. 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