Trigeminal neuralgia

TRIGEMINAL NEURALGIA: DEFINITION, DDx, MANAGEMENT, SURGERY, AND GKRS

1. Dr. Shahnawaz Alam Resident; MCh -Neurosurgery Moderated by: Dr. V. C. Jha HOD, Dept. of Neurosurgery TRIGEMINAL NEURALGIA DEFINITION, DDx, MANAGEMENT, SURGERY AND GKRS

2. INTRODUCTION Recurrent brief episodes of unilateral electric shock like pains, abrupt in onset and termination, in the distribution of one or more divisions of the trigeminal nerve that are typically triggered by innocuous stimuli. Incidence: 40-50 cases per million; Prevalence: 100-200 cases per million (1) Age group: 35-65 years (2); Right side more commonly affected; Gender: twice as common in females Hereditary forms of TGN rare (<5%); B/l TGN have higher hereditary predisposition {1} 1. Manzoni G, Torelli P. Epidemiology of typical and atypical craniofacial neuralgias. Neurological Sciences. 2005;26(S2):s65-s67. {2} Koopman J, Dieleman J, Huygen F, de Mos M, Martin C, Sturkenboom M. Incidence of facial pain in the general population. Pain. 2009;147(1):122-127.

3. D iagnosis of typical trigeminal neuralgia: five criteria paroxysmal sharp and shooting pain that is characterized by exacerbations and remissions, pain that follows the distribution of the trigeminal nerve, a normal neurologic examination that includes no significant loss of facial sensation, Magnetic resonance imaging (MRI) of the brain that demonstrates neither mass lesions nor demyelinating plaques, and pain that is induced by cutaneous stimulation.

4. BRIEF HISTORY First scientific account: Johannes Laurentius Bausch (1671) Synonyms: Suicide disease, Prosopalgia , Tic Douloureux, Fothergill’s Disease 1820  Charles Bell coined Trigeminal Neuralgia 1904  Percutaneous alcohol injection by Schloesser 1920  Spiller-Frazier technique of selective sectioning of Trigeminal nerve fibres, Walter Dandy: ‘arterial loop impingement’ 1940  Bergouinan used antiepileptic in TGN 1970 Leksell used stereotactic radiation 1996 Peter Janetta: MVD

5. DEFINITION (ICHD-3, 2018,IHS) Recurrent paroxysms of unilateral facial pain in the distribution(s) of one or more divisions of the trigeminal nerve, with no radiation beyond, and fulfilling criteria B and C A  All the p ain characteristics: lasting from a fraction of a second to 2 minutes severe intensity electric shock-like, shooting, stabbing or sharp in quality B  Precipitated by innocuous stimuli C  Not better accounted for by another ICHD-3 diagnosis.

6. Clinical features Pain may radiate to another division; Identification of Trigger Usually fail to show sensory abnormalities In severe cases can evoke contraction of the facial muscles of the affected side Mild autonomic symptoms like lacrimation or redness of eye may be present Refractory period TYPES: a) Classical Type b) Secondary Type c) Idiopathic Type

7. Classical TGN Classical TGN: Demonstration on MRI/Surgery of Neurovascular Compression and morphological changes Classical TGN: Purely Paroxysmal  pain free between attacks 2) Atypical TGN/Type II TGN: Concomitant continuous pain between attacks; Atypical- aching, throbbing, burning, >50% constant pain.

8. Morphological changes: Nerve root atrophy (demyelination, neuronal loss, microvasculature changes)/ displacement. Compression by artery more symptomatic than by compression of vein.

9. Secondary TGN Secondary TGN : An underlying disease known to cause neuralgia 1)TGN attributed to MS 2)TGN attributed to SOL 3)TGN attributed to other casues Idiopathic TGN Idiopathic TGN: MRI or electrophysiologic testing showing no abnormalities IASP definition: “ unilateral painful orofacial condition characterized by brief duration of electric shock-like sensation with an abrupt onset and termination, and limited to one or more sensory divisions of the trigeminal nerve”

10. Aetiology

11. Direct Compression Of Trigeminal Nerve Neurovascular Compression : (80-90% cases) Vascular Loop; SCA(85%)> AICA > PICA > VA Venous loop MC site: Dorsal Root Entry Zone near Pons Laminar Arrangement of fibres in Trigeminal nerve (Medial V2 ,Lateral/caudal V3 , rarely Cranial  V1 symptoms) Tumours(2%) : Meningioma/Vestibular Schwannoma/epidermoid/Tuberculoma/Arachnoid Cyst {Tumours at REZ cause neuralgia, peripheral compression causes more constant pain} AVM/Aneurysms

12. Systemic Diseases Multiple Sclerosis  I n 0.9-4.5% patients of MS; young, Bilateral presentation MR: demyelinating lesion at pontine REZ Vascular diseases, Rheumatism, Diabetes, HTN no proven role TGN association with atherosclerosis/Arterial hypertonia Following previous surgery; Allergic Hypothesis TM joint pathology, high position of petrous apex, acute bony angle of petrous ridge, short trigeminal nerve cisternal length .

13. Pathophysiology REZ/Redlich- Obersteiner’s Zone : boundary b/w CNS and PNS junction between myelin of Schwann and glial cells Visually identified as 1-2.5 mm Zone; Thin A delta nociceptive fibres are highly susceptible to pressure Long standing compression: membrane instability and demyelination interconnection between neurones Nerve deviation/distortion: groove formation nerve atrophy {Atrophic changes in proportion to severity of compression}

14. Pathogenesis Short Connection Theory: demyelination and cross talk (Pressure on highly susceptible A delta fibres; ectopic impulse generation; abnormal non synaptic transmission. Ignition Hypothesis: Trigeminal root ganglia neuronal abnormalities hyperexcitability of neurones and synchronous firing Pulsatile mechanical compression by vessel Cutaneous stimuli stimulate pain fibres which are in close proximity at REZ Focal demyelination not always present Central Pathogenetic Mechanism

15. Differential Diagnosis Deafferentation pain: post surgical injury/trauma {constant itching or burning pain , sensory loss} Dental causes : caries, abscess, periodontitits , cracked tooth unilateral and localised pain, usually constant, oral mucosal examination for causes. Temporo-Mandibular Joint Disorders  restricted mouth opening or cracking noises. on prolonged mouth opening, palpation of joint and local examination Salivary Gland Disorders  obstruction of flow of saliva :intermittent pain( tumors , stones) ; infection Maxillary sinusitis  Acute sinusitis, nasal discharge,tenderness , dull mild to moderate pain

16. Trigeminal Autonomic Cephalalgias Primary headache disorders with cranial autonomic symptoms and pain in Trigeminal nerve distribution. Cluster Headache, Paroxysmal Hemicranias, SUNCT, SUNA Cluster headache: temporal association with sleep (episodic, u/l typically periorbital, prolonged course of 15-180 mins, severe throbbing type, conjunctival injection). SUNCT/SUNA : paroxysmal ocular or periocular pain with ipsilateral autonomic symptoms intense: Conjunctival injection, lacrimation, nasal congestion, rhinorrhoea, sweating and flushing of forehead More common in V1 and least in V3

17. Difference between TGN and SUNCT/SUNA

18. Differential Diagnoses Post-Herpetic Neuralgia : Usually months after resolution of Herpes Zoster; Dermatomal Vesicopapular Rash; Allodynia, burning sharp pain; Sensory loss to pinprick, temperature in affected areas; Continuous pain with fluctuating severity Glossopharyngeal neuralgia: pain in throat- ear areas inferior to angle of mandible, precipitated by swallowing, chewing Nervus Intermedius neuralgia - brief paroxysmal pain in ear canal Hemifacial spasm/ Tolosa Hunt syndrome/ Migraine Perineural spread of head and neck malignancies

19. Red Flag Signs in clinical examination for Secondary Aetiologies Sensory or motor deficits in cranial nerve examination Abnormal oral, dental, or ear examination Age younger than 40 years Presence of bilateral symptoms Dizziness or vertigo Hearing loss or abnormality Pain episodes persisting longer than two minutes Pain outside of trigeminal nerve distribution Severe Autonomic symptoms

20. MRI Obersteiner Redlich zone: 1mm for motor root and 3 mm for sensory root Visual inspection: thinning of trigeminal myelin sheath Ventrolateral pons: two different roots Gasserian ganglion

21. MANAGEMENT

22. Treatment Modalities Available

23. Pharmacotherapy First line : CARBAMAZEPINE (Level A evidence) DOSE: 100 to 200 mg twice daily and increase in 200 mg daily dose as tolerated upto 600-800 mg daily and maximum of 1200 mg daily; Sodium channel blockade and membrane stabilisation ; Efficacy: 80% pain relief HLA-B 1502 individuals higher incidence of Steven Johnson syndrome and TEN, CBC , Sodium and LFT monitoring; CYP 450 system and failure of OCPs; 6 to 10% patients are unable to tolerate. Oxcarbamazepine : Similar efficacy to CBZ; Pro-drug ; Better Tolerability and fewer drug interactions; Weak enzyme inducer; Dose: 150 mg BD  increased 300 mg every 3 days to 300-600mg and maximum of 1800 mg. 2nd line Drugs :Lamotrigine, Baclofen, Pimozide

24. Second Line Drugs LAMOTRIGINE: Superior to placebo in CBZ refractory cases; starting dose at 25 mg/day to 200-400 mg/day gradually; slower titration gives slower occurance of side effects. BACLOFEN : GABAb receptor antagomist ; dose of 5-10mg TDS and increased slowly upto a maximum; dose of 90mg per day; Renal excreted drug Pimozide :Extrapyramidal side effects; Gabapentin, Pregabalin  moderate efficacy. Phenytoin(60% pain relief); Topiramate(75% pain relief); Levetiracetam(50% pain relief); TCA: No role in TGN; Quality of evidence poor. ACUTE EXACERBATION TREATMENT: initially used local anasthetic and iv lidocaine; Insufficient evidence and not recommended; Treatment duration: No definitive evidence of duration of treatment to conclude failure of first line drugs and indication for surgery

25. Surgical Modalities Percutaneous: Glycerol Retrogasserian Rhizolysis ; Radiofrequency Thermocoagulation; Percutaneous Microballon Compression. Invasive surgery: Microvascular Decompression; Partial sensory Rhizotomy; Internal Neurolysis; Cryotherapy Ablative vs Nonablative procedures.

26. When to refer for Surgery? No specific conclusion; 70% patients who failed primary therapy wished earlier surgery Failure of first line therapy; ? Second line therapy Age(old and young) and life expectancy(<20yrs) Anaesthetic fitness for Surgery; Severity of the Pain Which Surgical Procedure to choose ? MVD has higher and longer duration of pain control; MVD has 90 % pain control immediately and 73% at 5 years; Lower chance of hypoesthesia Peripheral Local anaesthetic techniques not effective. Gronseth G, Cruccu G, Alksne J, Argoff C, Brainin M, Burchiel K et al. 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. Neurology. 2008;71(15):1183-1190

27. Microvascular Decompression Long term success rate of 89-100%; More effective in classical TGN with only paroxysmal attacks Acute pain relief in 91% and recurrence of 18%; Initial outcome better than GKRS. Better at initial response and lower recurrence rate than partial sensory rhizotomy MVD and PBC has similar initial pain control but MVD has lower recurrence rate.

28. Microvascular Decompression Supine position, head rotated and fixed to opposite side, lateral decubitus position Linear retromastoid incision of approx. 3-5 cm with a fourth above the iniomeatal line Retromastoid Craniotomy made starting at inferior and posterior to the transverse -sigmoid junction Supralateral Cerebellar approach Dura opened in inverted L or C shaped fashion; CSF drained by gentle retraction of the cerebellum. Retraction of cerebellum in Inferomedial direction gently just below petro -tentorial junction (pure medial retraction = more injury to CN VIII). Exposure of Superior petrosal vein and arachnoid membrane just inferior to this vessel dissected; Superior petrosal venous bleed coagulated close to cerebellum.

29. Correct Identification of cranial nerves: 7th and 8th complex runs superficially, obliquely 5th nerve more medially and deeper; Careful arachnoid dissection with preservation of BS vessels Exposure of Trigeminal nerve REZ. Neurovascular Conflicts Most common by SCA or its branches along the superior shoulder f REZ Combined compression between SCA and AICA; Between Trigeminal and petrosal veins; By superior Petrosal vein.

30. Decompression requires elevating the SCA upward and away from the nerve; Arterial loops dissected along the length of the nerve; Multiple Vascular loops. Implant: Shredded Teflon; Placed at REZ and pushed ahead parallel to the nerve; Unshredded Teflon: more chance of displacement; Materials: Teflon(Polytetrafluoroethylene), Ivalon (Polyvinyl acetal). Partial sensory root sectioning is indicated in negative vessel explorations during surgery and large intraneural vein. Complications MC complication is aseptic meningitis(11%); Cranial nerve damage, Transient conductive hearing loss. SNHL  major long term complication (prevented by gentle retraction and prevention of AICA vasospasm) Prolonged post-operative vertigo /tinnitus; CSF rhinorrhoea(4%); Cerebellar contusions.

31. GKRS First used by Dr Leksell in 1971; Procedure: Leksell stereotactic head frame  MRI(T1w with or without contrast and T2 CISS sequences)Treatment planning GKRS. Single shot, 4 mm beam collimator diameter; Dose: 70-90 Gy .; Higher dose associated with higher post irradiation complications but better rates of improvement and lesser recurrence; Higher required doses placed isocentre anteriorly on TGN away from brainstem Target Selection: Options: REZ close to Brainstem(Pollock et al 90% pain control) Marseille point(distal most portion of cisternal CN V close to Meckels cave) (Regis et al. 87% pain control) Gasserian ganglion anteriorly(Messenger et al higher sensory complications) Pain relief better if isocentre located close to REZ; Less complications if target placed anteriorly; Anterior targets are likely to have same initial pain control.

32. A Gasserian gangliona ; B  Marseille point; C REZ; D Dual Centre

33. Gradual response Time to response after GKRS better in anterior retrogasserian target(median -4.1 weeks) vs REZ targets(median – 6.4 weeks). Median latency to symptom improvement- 2 months; Need some medications(although reduced dosage). Freedom from pain with medication(84.8%) vs without medication(53.1%); Long Term outcome: Good pain control of 45-65% by 5 years. Abnormal vessel: Doesn’t alter outcome. Redo GKRS: Can be done in patients with an earlier good response to GKRS; Primary GKRS > Secondary GKRS(in pain relief) Pain in V1: GKRS safest option as corneal hyposthesia never occur; No Radioprotectant role of CBZ/OXZ; Treatment failure if no symptomatic improvement by 180 days. Outcome: 75-90% patients had pain relief after 1 year of GKRS.

34. Predictors of good pain control: Type of Pain at presentation, post GK BNI score, Post GK facial numbness (major predictor of maintenance of pain relief). Patients with early response within 3 weeks had longer duration of complete free pain. Length of Cisternal segment of Trigeminal nerve; Target on Trigeminal nerve 5-8 mm away from brainstem Favourable outcomes: young patient, length of trigeminal nerve irradiated, higher dose of radiation, proximity of isocentre to Brainstem.

35. Stereotactic RS yields better response if done within 3 years of symptom onset. Poor prognosticator factors: atypical facial pain and presence of MS Recurrence rate of TGN post GKRS is 23% at approximately 8 to 20 months Side effects: facial numbness(more in anterior target or longer length of nerve irradiated or higher doses),parenchymal injuries, vascular injuries.

36. References: Youmans and Winn neurological surgery 8th edition Ramamurthi & Tandon's textbook of neurosurgery 3 rd edition Schmidek and Sweet: Operative Neurosurgical Techniques 6 th edition Internet THANK YOU