Trigeminal Neuralgia with nerve anatomy and recent advances

Detailed view on trigeminal neuralgia including course of the trigeminal nerve. The course is devided in several parts. The first line of non surgical medication along with First line of surgical management. The disease is also classified in various ways.

1. Trigeminal Neuralgia Dr. Madhan Prabhu

2. Trigeminal NeuralgIA Contents Introduction Classification Nerve Anatomy Pathophysiology Diagnosis Management Future Aspects Conclusion References

3. Trigeminal NeuralgIA Introduction A disorder characterised by recurrent unilateral brief electric shock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve and triggered by innocuous stimuli. - ICHD Paroxysmal, Intense, Sharp, Stabbing with or without Burning sensation No treatment is capable of reverting completely

4. Trigeminal NeuralgIA Other Names Tic Doulourex - Nicholaus Andre French - Painful Tic 1756 - Observations pratiques sur les maladies de l’urethre et sur plusiers faits convulsifs Fothergill’s Disease - John Fothergill English - First full and accurate description - 1773

5. Trigeminal NeuralgIA Classifications IHS / IASP Based on consensus of IHS and IASP for universal acceptance Most Recent Based Imaging/electrophysical finding Help guide further treatment modalities (Medical vs Surgical) QiLiang Chen , Dae Ik Yi, Josiah Nathan Joco Perez, Monica Liu, Steven D. Chang, Meredith J. Barad, Michael Lim and Xiang Qian - The Molecular Basis and Pathophysiology of Trigeminal Neuralgia - International Journal of Molecular Science - 25 March 2022

6. Trigeminal NeuralgIA IHS / IASP’s Classification Classical - Neurovascular Compression Secondary - Caused by underlying disease other than neurovascular compression eg. Multiple Sclerosis Idiopathic - Without obvious or visible Aetiology that are not fully understood QiLiang Chen , Dae Ik Yi, Josiah Nathan Joco Perez, Monica Liu, Steven D. Chang, Meredith J. Barad, Michael Lim and Xiang Qian - The Molecular Basis and Pathophysiology of Trigeminal Neuralgia - International Journal of Molecular Science - 25 March 2022

7. Trigeminal NeuralgIA Classification By Ramussen First classification (1990) Based on attack Characteristics Too broad to guide specific treatment based on symptoms alone QiLiang Chen , Dae Ik Yi, Josiah Nathan Joco Perez, Monica Liu, Steven D. Chang, Meredith J. Barad, Michael Lim and Xiang Qian - The Molecular Basis and Pathophysiology of Trigeminal Neuralgia - International Journal of Molecular Science - 25 March 2022

8. Trigeminal NeuralgIA Ramussen’s Classification Typical - Pain is Sharp, Electrical, Paroxysmal and mostly located in V2 and V3 Atypical - Pain is dull constant and located in all 3 division QiLiang Chen , Dae Ik Yi, Josiah Nathan Joco Perez, Monica Liu, Steven D. Chang, Meredith J. Barad, Michael Lim and Xiang Qian - The Molecular Basis and Pathophysiology of Trigeminal Neuralgia - International Journal of Molecular Science - 25 March 2022

9. Trigeminal NeuralgIA Classification By Burchiel’s - 7 types Based on Pain characteristics and eliciting event To provide a framework for better diagnose and treat different types of TN Attempts to guide differential diagnosis by using objective and reproduceble criteria Requires further studies to verify clinical utility QiLiang Chen , Dae Ik Yi, Josiah Nathan Joco Perez, Monica Liu, Steven D. Chang, Meredith J. Barad, Michael Lim and Xiang Qian - The Molecular Basis and Pathophysiology of Trigeminal Neuralgia - International Journal of Molecular Science - 25 March 2022

10. Trigeminal NeuralgIA Burchiel’s Classification Type I - Sharp, Electrical, Episodic due to Neurovascular compression Type II - aching, throbbing, burning constant pain >50% of the time TN due to Injury - Facial Trauma Trigeminal deafferentation Pain - Post Surgical TN Secondary to Multiple Sclerosis Infection - Post herpetic Atypical Somatoform facial pain QiLiang Chen , Dae Ik Yi, Josiah Nathan Joco Perez, Monica Liu, Steven D. Chang, Meredith J. Barad, Michael Lim and Xiang Qian - The Molecular Basis and Pathophysiology of Trigeminal Neuralgia - International Journal of Molecular Science - 25 March 2022

11. Trigeminal NeuralgIA Nerve Anatomy Largest Cranial Nerve Large Sensory and Smaller Motor Sensory - Ophthalmic, Maxillary, and sensory part of the mandibular Motor - Motor function to Muscles of mastication Fibers in the sensory root are axons of cells in trigeminal ganglion which occupies Meckel’s Cave Both roots exits the brain from pons at its junction with middle cerebral peduncle

12. Trigeminal NeuralgIA Nerve Anatomy The Large Sensory nucleus receives sensation from the 3 branches The lower part receives sensation from the ophthalmic branch and upper part from the Mandibular branch The tapered caudal part is the spinal tract and continues as substantia gelatinosa The spinal tract is the sensory nucleus, primarily for pain and temperature The motor nucleus is placed ventromedially to the sensory. It lies near the lateral angle of fourth ventricle of rostral part of the pons

13. Trigeminal NeuralgIA Course Brainstem Segment Cisternal Segment Cavernous Segment Peripheral Segment

14. Trigeminal NeuralgIA Brainstem Segment Houses both Sensory and Motor Nuclei Dominant Sensory subdivided into 3 types Major Sensory Mesencephalic Nucleus Spinal Trigeminal Nucleus Major Sensory nucleus is located in the lateral Pontine Nucleus Carrying Tactile sensation of touch and pressure

15. Trigeminal NeuralgIA Brainstem Segment Mesencephalic Nucleus - a superior extension of the major sensory nucleus Carries Proprioceptive Information of the Muscles of Mastication

16. Trigeminal NeuralgIA Brainstem Segment Spinal Trigeminal Nucleus - A caudal extension Major Sensory Nucleus Reaching the C2-C4 level of the Spinal Cord - merging Dorsal Grey Matter

17. Trigeminal NeuralgIA Brainstem Segment Single Smaller Motor Nucleus located in the MidPons - Anterior and Medial to Major Sensory Nucleus Motor innervation to MoM, Mylohyoid, Anterior Belly of Digastric, Tensor Velli Palatini, Tensor Tympani.

18. Trigeminal NeuralgIA Cisternal Segment Ventrolateral Midpons - 2 roots - Larger Sensory and Smaller Motor Larger Sensory is at the Posterolateral to Motor root Travels anterior and laterally through the pre pontine cistern, medially to the Petrous apex and enters the middle cranial fossa The nerve then penetrates a dural lined sinus - Meckel’s Cave

19. Trigeminal NeuralgIA Meckel’s Cave Posteriomedial Portion of the Middle Cranial Fossa Filled with CSF Containing Gaserion Ganglion Which lies on the trigeminal recess, a bony depression lies in the anterio-medial aspect of the petrous bone The sensory root enters the ganglion and gives V1,V2,V3 The motor root passes immediately beneath the ganglion, turns inferiorly to exit the skull base through foramen ovale together with the mandibular division of the sensory root, and enters the nasopharyngeal masticator space

20. Trigeminal NeuralgIA Cavernous Segment The ophthalmic and maxillary divisions of the sensory root continue further anteriorly within the lateral wall of the cavernous sinus Below cranial nerve IV and lateral to cranial nerve VI and cavernous-Internal carotid artery The nerves course from superomedial to inferolateral as they move anteriorly.

21. Trigeminal NeuralgIA Peripheral Segment - Ophthalmic Branch (V1) Leaves the anterior cavernous sinus Exits the intracranial compartment through the superior orbital fissure It gives off 3 major branches: lacrimal, frontal and nasocilliary nerves which provide sensory information from the forehead, nose and globe. Its terminal branch, the supra-orbital nerve, exits the orbit through the supra-orbital foramen and supplies sensory innervation to the upper third of the face

22. Trigeminal NeuralgIA Maxillary Branch (V2) Inferior aspect of the Cavernous sinus Exits the skull base through foramen Rotundum Enters Pterygopalatine fossa Gives of Meningeal, Zygomatic, pterygopalatine, Posterior superior alveolar Main trunk of the nerve continues anteriorly, enters the orbit through Infra orbital foramen and becomes infraorbital nerve and exits the infraorbital foramen Supplies sensory information to the midface, cheek, and maxillary teeth

23. Trigeminal neuralgia Maxillary Nerve

24. Trigeminal NeuralgIA Mandibular Branch (V3) Largest of 3, together with motor root exits the skull base through foramen Ovale Enters the nasopharyngeal masticatory space The root has 4 sensory branch: Buccal, Auriculotemporal, Lingual, and Inferior alveolar Nerve The terminal IAN enters the mandibular foramen at the lingual aspect of the mandibular ramus Travels along the body of the mandible in the Inferior alveolar canal Exits the Mandible at the parasymphyseal region through the Mental Foramen giving the terminal Mental Nerve The mandibular nerve supplies sensory information from lower third of the face, tongue, floor of the mouth and jaw

25. Trigeminal Neuralgia Mandibular Nerve

26. Trigeminal Neuralgia Motor Root Joins along the Mandibular division in Foramen Ovale Masticatory nerve supplying Temporal, Masseter, and pterygoid muscles Mylohyoid branch supplying Mylohyoid, Anterior belly of digastric Emerges from the pons, separately with Sensory root Bypasses the Trigeminal Ganglion After exiting Foramen Ovale, Divides into 2 major branches

27. Trigeminal NeuralgIA V1 - Ophthalmic Branch

28. Trigeminal NeuralgIA V2 - Maxillary Branch

29. Trigeminal NeuralgIA V3 - Mandibular Branch

30. Trigeminal NeuralgIA Aetiology Vascular Compression Multiple Sclerosis Tumors Cavernous Aneurysm Sensitization and Dysfunction of Central Pain-Related Circuits Diabetes Mellitus Herpes Simplex Infection

31. Trigeminal NeuralgIA Aetiology Alexandra Borges, Jan Casselman - Imaging the trigeminal nerve - European Journal Of Radiology - 03 feb 2010

32. Trigeminal NeuralgIA Pathophysiology Ignition Theory Demyelination Plaque Theory Bioresonance Theory Sensitization and Dysfunction of Central Pain-Related Circuits Diabetes Mellitus Herpes Simplex

33. Trigeminal NeuralgIA Pathophysiology - Ignition Theory The hypothesis focuses on three neurophysiological problems Neural triggering and afterdischarge - How does a trigger-stimulus event provoke a sensory response that outlasts itself, and indeed may continue to build after the stimulus has ended? Neural amplification - How does a localised, non-noxious trigger stimulus evoke a sensory response that spreads to cover a large contiguous tissue area and is intensely painful? Stop Mechanism - What prevents an attack from continuing indefinitely, and what causes the triggering mechanism to become temporarily refractory? Marshall Devour et al. “Pathophysiology of Trigeminal Neuralgia: The Ignition Hypothesis”, The Clinical Journal of Pain, 2002

34. Trigeminal NeuralgIA Neural Triggering - Afterdischarge The key to understand the persistence of sensation beyond the time of stimulus is that the sensory neurons innervating the face frequently become hyper-excitable when injured and generates impulse autonomously These ectopic pacemakers are plentiful in TN and include patches of demyelination, swollen end bulb, sprouts at the distal end of the axon These areas have “Hair Trigger” threshold, such that momentary stimulation induces a burst of spontaneous firing which lasts for tens of seconds, this is known as “Afterdischarge” Marshall Devour et al. “Pathophysiology of Trigeminal Neuralgia: The Ignition Hypothesis”, The Clinical Journal of Pain, 2002

35. Trigeminal Neuralgia Neural Triggering - Afterdischarge The autonomous firing of ectopic pacemaker sites may be augmented by positive feedback associated with neuron-to-neuron coupling. Each new neuron recruited to self-sustained afterdischarge activity after the initial trigger stimulus tends to recruit activity in additional neighbouring neurons. This Chain reaction induces paroxysmal explosion, the characteristic lightning attacks. This is known as “Ignition” “A spark ignites the inferno, but the sustained burning is fed by its own fuel” Marshall Devour et al. “Pathophysiology of Trigeminal Neuralgia: The Ignition Hypothesis”, The Clinical Journal of Pain, 2002

36. Trigeminal NeuralgIA Neural Amplification The intensity of TN attacks, and the finding that they are triggered by weak localised stimuli, indicate that something must be synchronising activity in large numbers of trigeminal ganglion neurons. Ephaptic cross-talk (i.e., electrical cross-talk) among neurons is a situation in which electrical currents in one neuron directly excite impulse activity in a neighbouring neuron. This type of communication is in contrast with Synaptic Communication, which is normal in brain. This does not occur in nerve fibers because they are insulated with glial derived cell - Myelin, mesaxon, satellite cell processes Marshall Devour et al. “Pathophysiology of Trigeminal Neuralgia: The Ignition Hypothesis”, The Clinical Journal of Pain, 2002

37. Trigeminal Neuralgia Neural Amplification In situations where this insulation is eroded or destroyed, nerve fibers can come into close contact with one another, permitting impulses to “jump” in either direction. Aδ Fibers are more affected than C fibers This explains why Mild touch triggers pain and, Nociceptive impulse does not trigger pain as much as Aδ Fibers Marshall Devour et al. “Pathophysiology of Trigeminal Neuralgia: The Ignition Hypothesis”, The Clinical Journal of Pain, 2002

38. Trigeminal NeuralgIA Stop Mechanism During the course of a burst, Calcium Channel Ions enters the neuron and activate calcium ion activated Potassium. Potassium ions flow out of the neuron through these channels, causing the neuron to hyperpolarize and the firing to stop. Long-term processes, such as partial remyelination and normalisation of membrane-channel deployment, may bring the triggering level below threshold for long periods. Marshall Devour et al. “Pathophysiology of Trigeminal Neuralgia: The Ignition Hypothesis”, The Clinical Journal of Pain, 2002

39. Trigeminal NeuralgIA Demyelination plaque Theory MS Due to inflammation Acute and Chronic Plaques Acute - Massively infiltrated with Macrophages - “Sea of Macrophages” Contains remnants of myelin sheaths Degradation of minor myelin proteins occurs within 1 to 3 days, denotes early active demyelination Larger, more abundant hydrophobic myelin protein are degraded upto 10 days, denotes late active demyelination Additional nerve compression accelerate Demyelination Bogdan F. Gh et al. “Pathology of Multiple Sclerosis: Where do we stand?”, American Academy of Neurology, August 2013

40. Trigeminal neuralgia Demyelination plaque Theory Chronic Plaque Myelin-laden macrophages are concentrated in the centrifugally expanding lesion and diminish in the hypo cellular inactive centre Chronic inactive plaques are completely demyelinated, sharply circumcised hypo cellular lesion characterised by substantial loss of axon and oligodendrocytes and minor infiltration by macrophages, microglia and lymphocytes Bogdan F. Gh et al. “Pathology of Multiple Sclerosis: Where do we stand?”, American Academy of Neurology, August 2013

41. Trigeminal NeuralgIA Bioresonance theory Physiological studies have shown that the organs of human body emit a fixed frequency called natural frequency Trigeminal Nerve when immersed in cerebrospinal fluid, vibrates at its own natural vibration frequency. The ends of nerve are fixed on the brain stem and the Meckel’s cave, while the middle part is immersed in the vibratory CSF When the surrounding parts of Trigeminal Nerve vibration alters or vibrates close to Trigeminal Nerve Frequency Bioresonance occurs This increase in amplitude damages the nerve fibers and affect the permeability of the membrane and affect the function of Ca+, K+ and Na+ De Ze Jia et al. “Bioresonance hypothesis: A new Mechanism on the pathogenesis of trigeminal neuralgia”Medical Hypotheses, 2010

42. Trigeminal NeuralgIA Sensitization and Dysfunction of Central Pain-Related Circuits Sensitization is a process in which the central Nociceptive system is hyper-excitable Obermann and colleagues demonstrated that pain-related evoked potentials are significantly augmented in all trigeminal divisions on both symptomatic and non-symptomatic sides Painful attacks in TN patients lead to increased activity in the trigeminal nuclei, thalamus, and somatosensory cortices - areas that are classically associated with pain-related sensory processing Multiple vital structures related to pain modulation, emotion, and memory are also activated during the attacks Sensitization in some of these structures has been implicated in other chronic pain conditions These pathological changes are often reversed after successful treatments, suggesting changes in these circuits not only link to the characteristic pain symptoms but also the psychocognitive aspect of the disease

43. Trigeminal NeuralgIA Diabetes Mellitus Diabetic Neuropathy is common in 3,4,6th cranial nerves than Trigeminal Nerve DM patients are more prone to neuropathic pain than neuralgic pain - Hot, burning, electric with pin and needle sensation especially in Peripheral areas Hyperglycaemia causes accelerated nerve damage, leading to TN Prolonged Hyper - causes Increased levels of AGE and PKC Certain Pro Inflammatory cytokines including IL-6 and TNF-𝞪 are thought to be involved in peripheral nerve damage Zheng Xu et al. “Diabetes Mellitus in Classical Trigeminal Neuralgia: A predisposing factor for its development” Clinical Neurology and Neurosurgery, 22 October 2016

44. Trigeminal NeuralgIA Herpes Simplex 80% in Ophthalmic branch After initial infection of the epithelium, gains access to termini of sensory neurons that innervate the skin and reaches the cell body of these cells by retrograde transport through the axons In case of facial infection it reaches the Trigeminal Ganglion and is in latent phase Herpes Simplex Encephalitis produced by active replication of HSV-1 causes neuronal cell death or apoptosis Luisa F. Duarte, Mónica A. Farías, Diana M. Álvarez, Susan M. Bueno, Claudia A. Riedel and Pablo A. González* , Herpes Simplex Virus Type 1 Infection of the Central Nervous System: Insights Into Proposed Interrelationships With Neurodegenerative Disorders, Frontiers in Cellular Neuroscience, 26 February 2019

45. Trigeminal NeuralgIA Trigger Zones A low threshold region for eliciting a response Research analysis shows virtually all patients have a trigger zone some of which are Gently touching the face Talking chewing Brushing Washing one’s face Giulia Di Stefano, Stine Maarbjerg, Turo Nurmikko, Andrea Truini and Giorgio Cruccu - Triggering trigeminal neuralgia - Cephalgia - 28 June 2017

46. Trigeminal NeuralgIA Pain Pathway Noxious Stimuli Myelinated Aδ and Non - myelinated C - fibers - First order neuron Transmitted through these afferent fibers to Sub-nucleus Caudalius synapse with second order neuron Subnucleus oralis, Subnucleus interpolaris and many reticular formation before synapsing into third order neuron The third-order neurons are thalamocorticobasal ganglia-limbic circuits Generate the descending motor and pain modulatory reactions to pain interpretation

47. Trigeminal NeuralgIA Diagnosis History Clinical Examination Diagnostic LA blocks CT Scan MRI Alexandra Borges, Jan Casselman - Imaging the trigeminal nerve - European Journal Of Radiology - 03 feb 2010

48. Trigeminal NeuralgIA PAIN HISTORY Chief Complaint HOPI Symptoms - Onset, Quality, Intensity, Frequency, Duration Aggravating and Alleviating Factors Past Treatments

49. Trigeminal NeuralgIA Diagnostic Criteria - Classical TN According IHS Paroxysmal attacks of facial or frontal pain that last a few seconds to less than 2 minutes, affecting one or more divisions of the trigeminal nerve and fulfilling criteria B and C The Pain has at-least one of the characters Intense, Sharp, Superficial or Stabbing Precipitated from Trigger Zones The patient is entirely asymptomatic between attacks

50. Trigeminal NeuralgIA Diagnostic Criteria - Classical TN Attacks are similar in individual patients There is no clinically evident neurological deficit Not attributed to another disease

51. Trigeminal NeuralgIA Diagnostic Criteria - Symptomatic Paroxysmal attacks pain lasting from few seconds to 2 mins, with or without persistence of aching between paroxysms affecting one or more division of the Trigeminal Nerve and full-filling criteria B Pain has at-least one of the following Intense, Sharp, Superficial or Stabbing Precipitated from Trigger Zones Attacks are similar in Individuals A causative lesion other than Vascular Compression, has been identified using special investigations

52. Trigeminal NeuralgIA Diagnostic Criteria - Idiopathic Same as Symptomatic Without a known cause

53. Trigeminal neuralgia Diagnosis Lars Bendtsen et al. “Advances in diagnosis, classification, pathophysiology, and management of trigeminal Neuralgia” Lancet Neurol, 2020

54. Trigeminal NeuralgIA Differential Diagnosis Though often considered a straightforward diagnosis to make, its differential diagnosis can be challenging, given the considerable overlap with other neuropathic and neuralgiform headache and oro-facial pain disorders Giorgio Lambru, Joanna Zakrzewska, Manjit Matharu - Trigeminal neuralgia: a practical guide - British Medical Journal - 09 June 2021

55. Trigeminal NeuralgIA Differential Diagnosis

56. Trigeminal NeuralgIA Management of TN Broadly classified into Pharmacological Surgical

57. Trigeminal neuralgia Pharmacological First Line Medication Carbamazepine Oxcarbazepine Alternative or Adjuvant Lamotrigine Baclofen Gabapentin Pregabalin Acute Adjuvant medication Lidocaine Sumatriptan Botulinum Toxin Type A Guidelines for the management of trigeminal neuralgia 2021 - Royal College of Surgeons of England

58. Trigeminal neuralgia Pharmacological Anticonvulsants - Carbamazepine - Blockade of voltage-sensitive sodium channels resulting in the stabilisation of hyper-excited neural membranes, inhibition of repetitive firing or reduction of propagation of synaptic impulses. Muscle Relaxant - Baclofen, a skeletal muscle relaxant, is a GABA analogue that activates GABAB receptors and thus depresses excitatory neurotransmission. Selective Serotonin Receptor Agonists - Sumatriptan - Causes inhibition of Calcitonin Gene Related Peptides (CGRP) and neurogenic inflammation. Botulinum toxin Type - A - Blocks the transmission of Nociceptive inputs.

59. Trigeminal neuralgia Medication for Trigeminal Neuralgia Giorgio Lambru, Joanna Zakrzewska, Manjit Matharu - Trigeminal neuralgia: a practical guide - British Medical Journal - 9 June 2021

60. Trigeminal neuralgia Surgical - Invasive Open Microvascular Decompression Percutaneous Radiofrequency Rhizotomy Retrogasserian glycerol Rhizotomy Balloon Compression of TN Stereotactic Surgery (Gamma Knife)

61. Trigeminal neuralgia Surgical - non invasive Peripheral Neurectomy Alcohol Injection Cryotherapy Selective Radiofrequency Thermocoagulation

62. Trigeminal neuralgia Microvascular Decompression First Line of Surgical intervention for patients with clear neurovascular compression The target point is Nerve - Pons Junction Approached from a sub-occipital craniotomy CSF aspirated - advancement to the nerve is done by gently retracting the superiolateral margin of the Cerebellum Most common finding is Superior cerebellar artery

63. Trigeminal neuralgia Microvascular Decompression Anterior inferior cerebellar artery or superior petrosal vein are the next most common findings After Arachnoid is dissected the vessel is freed Pieces of shredded teflon tape are placed between the nerve and the compressing vessel

64. Trigeminal neuralgia Radiofrequency Rhizotomy A 22 gauge - 10cm needle with a 5 mm active tip is used Entered into Foramen Ovale - with the help of lateral Fluoroscopy view the needle is assessed for the position in Meckel’s Cave It is then advanced 2 - 4 mm through the foramen such that it reaches the junction of petrous ridge of the temporal bone and clivus The stylet is then removed and aspirated to make sure no CSF or blood is present 50Hz, 1msec at 0.1 - 0.5V should cause Paresthesia in the Trigeminal distribution Patient is anaesthetised again for RF Rhizotomy - Performed in cycles of 45 - 90s at 60 - 90℃ Pulsed RF is non destructive method with long pauses which helps in heat dissipation which is usually seen in Conventional RF

65. Trigeminal neuralgia Retrogasserian Glycerol Rhizotomy Hakkansson Done under LA in awake patient Needle is inserted into the Trigeminal cistern using similar trajectories as Radiofrequency Rhizotomy Fluoroscopic Control is mandatory Once the needle is optimally placed small test dose of anhydrous sterile Glycerol is injected. This is followed by small increments upto a total of 0.1 - 0.4ml The patient is made to sit straight for 2 hours The glycerol causes selective chemical damage to small unmyelinated and myelinated nerve fibres from conducting pain

66. Trigeminal neuralgia Balloon Compression of TN Mullan and Lichtor published a 50 case report in 1983 Using a Fogatry type balloon compression Done under GA using a Fluoroscopic Control the fogatry needle is inserted into the Meckels Cave It is slowly inflated with 0.5 to 1ml Dye until it fills the cave ensuring adequate compression of the nerve Total Compression time varies from 1 - 6 mins This caused mild sensory loss with immediate pain relief The patient usually requires an overnight stay

67. Trigeminal neuralgia Stereotactic surgery (Gamma Knife) Primary alternative to invasive surgical technique SRS is a minimally invasive neuromodulative single session procedure, utilising focussed radiation which targets the trigeminal nerve with high precision. The pain-relieving effects of this treatment are not immediate the time to pain relief is typically between 1 and 3 months. Therefore not a suitable technique for acute TN crisis management. For Classical TN within 3 years of Onset

68. Trigeminal neuralgia Peripheral Neurectomy Peripheral neurectomies are a safe and cost-effective option for patients with medical co-morbidities, elderly and for population where there is lack of highly skilled neurosurgical centres Infraorbital Nerve Access to infraorbital nerve is gained through a maxillary vestibular approach Canal is identified and the nerve is retracted from the periosteum Nerve is dissected with a Diathermy and the canal is obturated with bone wax or chips of bone from the surrounding bone Pain relief is usually between 15 to 24 months

69. Trigeminal neuralgia Peripheral neurectomy Inferior alveolar Nerve Ginwala’s Access Inverted “Y” shaped incision is given over the anterior aspect of the Ramus Tendons of the medial pterygoid and Temporalis are raised and lingula is identified Once IANB is identified it is clamped and Cut using a Diathermy Following this a buccal incision is made I.r.t. premolars on the affected side The Mental foramen is identified, the mental nerve and End of the neurovascular bundle is clamped and dissected.

70. Trigeminal neuralgia Alcohol Injection Direct deposition of alcohol into the affected nerve peripheral branch causes chemical ablation of the nerve Alcohol causes destruction of nerve fibres. It can seep into the adjacent tissues and cause necrosis, resulting in pain and local oedema. High-risk recurrence of pain and with a moderate risk of developing dysesthesia Therefore restricted in patient only with comorbidities 0.5 - 1.0ml of absolute alcohol is injected directly into the nerve bundle under LA Needle has to be placed accurately to avoid dissipation

71. Trigeminal neuralgia Cryotherapy The nerve ending were exposed to extreme cold temperature 0f -50 to -70℃ Pain free effect lasted from 6 - 18 months Patients were well tolerated and willing to undergo repeated cryofreezing

72. Trigeminal neuralgia Selective radiotherapy thermocoagulation A neurosurgical procedure that uses a electrode to damage the Gasserian ganglion The procedure stops the conduction of pain signal to the brain by selectively damaging small myelinated and small unmyelinated pain fibers of the nerve, while sparring rest of the nerve

73. Trigeminal NeuralgIA Treatment Algorithm Giorgio Lambru, Joanna Zakrzewska, Manjit Matharu - Trigeminal neuralgia: a practical guide - British Medical Journal - 09 June 2021

74. Trigeminal neuralgia Recent advances Pharmacological Vixotrigine Eslicarbazepine Sumatriptan Intranasal CO2 Calcium Channel Blockers Miscellaneous Drugs Sourav Burman, Ankur Khandelwal, Arvind Chaturvedi - Recent Advances in Trigeminal Neuralgia and Its Management: A Narrative Review - Journal of Neuroanaesthesiology and Critical Care - 24 May 2021 Non - Pharmacological Pulsed RF Ozone Injection into the Gasserian Ganglion Cryotherapy Neuromodulation Low level Laser Therapy CO2 laser Neural Prolotherapy Nerve Combing Complimentary Medicine

75. Trigeminal neuralgia Prolotherapy Usually a 3 ml syringe with 0.5inch needle is used Injection of hypertonic dextrose saline with local anaesthetics at the trigger points and usually requires multiple sittings Targets neurogenic inflammation in subcutaneous nerves that potentially generates pain

76. Trigeminal neuralgia Focused ultrasound A team at the University of Maryland School of Medicine and the University of Maryland Medical Center have launched a new clinical trial investigating the use of focused ultrasound to address trigeminal neuralgia. Researchers are using focused ultrasound to ablate a small nucleus in the thalamus, located deep within the brain. This nucleus, called the central lateral nucleus is known to play a role in pain perception and transmission in patients with chronic pain conditions such as trigeminal neuralgia. MR scans conducted prior to treatment will help the team identify the target and plan the precise treatment.

77. Trigeminal neuralgia Platelet Lysate Platelet Lysate from PRP - concentrated healing growth factor

78. Trigeminal NeuralgIA Conclusion Trigeminal neuralgia is currently classified into three subgroups: idiopathic, classical and secondary, based on imaging findings; MR brain imaging with trigeminal sequences is therefore essential in the diagnostic work-up. An accurate diagnosis is crucial because the clinical management differs among the various forms of facial pain. Carbamazepine and oxcarbazepine remain the medications of choice. Lamotrigine, gabapentin, pregabalin, botulinum toxin type A and baclofen can be used as second-line treatments in mono-therapy or poly-therapy. In non - pharmacological cases, trigeminal microvascular decompression is the first-line surgery in patients with classical trigeminal neuralgia, whereas neuroablative surgical treatments and microvascular decompression can be considered in idiopathic trigeminal neuralgia. Pharmaco-resistant cases as well as cases where diagnosis is unclear should be referred to multidisciplinary facial pain teams led by neurologists specialising in headache disorders, where dedicated teams may confirm the diagnosis and offer advanced treatments.

79. Trigeminal Neuralgia References Giorgio Lambru et al. “Trigeminal Neuralgia: A Practical Guide”, British Medical Journal, 9 June 2021 QiLang Chen et al. “The Molecular Basis and Pathophysiology of Trigeminal Neuralgia”, International Journal of Molecular Science, 25 March 2022 Alexandra Borges et al. “Imaging the Trigeminal Nerve”, European Journal of Radiology”, 3 February 2010 Giulia Di Stefano et al. “Trigeminal Neuralgia secondary to multiple sclerosis: from the clinical picture to the treatment options”, The Journal of Headache and pain, 2019 Bogdan F. Gh et al. “Pathology of Multiple Sclerosis: Where do we stand?”, American Academy of Neurology, August 2013 T. J. Nuemikko et al. “ Trigeminal Neuralgia - pathophysiology, Diagnosis and current treatment”, British Journal of Anaesthesia, 2001 Mamta Agarwal, “Trigeminal Neuralgia secondary to Posterior Fossa Tumor”, National Journal of Maxillofacial Surgery, Vol 1- Issue 1-Jan-Jun 2010 - 71 - 73 De Ze Jia et al. “Bioresonance hypothesis: A new Mechanism on the pathogenesis of trigeminal neuralgia”Medical Hypotheses, 2010 Pawan Bista et al. “Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic pain” MDPI, 2019 Joanna Zakrzewska et al. “Trigeminal Neuralgia” British Medical Journal, September 2013 Marshall Devour et al. “Pathophysiology of Trigeminal Neuralgia: The Ignition Hypothesis”, The Clinical Journal of Pain, 2002 Zheng Xu et al. “Diabetes Mellitus in Classical Trigeminal Neuralgia: A predisposing factor for its development” Clinical Neurology and Neurosurgery, 22 October 2016 Mark Obermann, “Recent advances in understanding/management trigeminal neuralgia”, F 1000 Research, 2019

80. Trigeminal Neuralgia References Sourav Burman et al. “Recent advances in Trigeminal Neuralgia and its Management”, Journal or Neuroanaesthesiology and Critical care, 2021 Lars Bendtsen et al. “Advances in diagnosis, classification, pathophysiology, and management of trigeminal Neuralgia” Lancet Neurol, 2020 P.G.E. Kennedy et al. “Herpes simplex virus and the nervous system” Postgraduate Medical Journal, April 1984 Joseph R. Berger “Neurological Complication of Herpes Simplex Virus Type 2 Infection” Arch Neurol, May 2008 Luisa F. Duarte et al. “ Herpes Simplex virus type 1 infection of the central nervous system: Insights of the proposed interrelationships with neurodegenerative disorder”, Frontiers in cellular neuroscience, February 2019 Anne K Schreiber et al. “Diabetic Neuropathic pain: Physiopathology and treatment”, World Journal of Diabetes, April 2015 Mikel Sanchez et al. “Platelet rich plasma, a source of autologous growth factors and biomimetic scaffold for peripheral nerve regeneration” Expert Opinion in Biological therapy, 2016 Yoshihiro Sowa et al. “Involvement of PDFG-BB and IGF-1in activation of schwann cells platelet-rich plasma” Plastic and Reconstructive Surgery, December 2019 Florian Bernard et al. “Morphological and functional anatomy of trigeminal triangular plexus as an anatomical entity: a systematic review, Surgical and radiological anatomy, 9 march 2019 Dessy R Email et al. “Treatment of trigeminal neuralgia: role of radiofrequency ablation” Journal of Pain Research, 2010 Giulia Di Stefano et al. “Triggering Trigeminal Neuralgia” Cephalalgia 2017 Tumors of the Lateral Skull Base Oral and Maxillofacial Surgery for the Clinician - AOMSI