Diffusion tensor imaging for trigeminal neuralgia

Diffusion tensor imaging for trigeminal neuralgia

A total of 22 patients with classic trigeminal neuralgia and 22 healthy controls (HC) with matching age, gender, and education were selected. All subjects underwent 3.0 T magnetic resonance diffusion tensor imaging and high resolution T1-weighted imaging. The corpus callosum (CC) was reconstructed by DTI technology, which was divided into three substructure regions: genu, body, and splenium. Group differences in multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), were compared between CTN patients and HC, and correlations between the white matter change and disease duration and VAS in CTN patients were assessed.

Compared with HC group, CTN patients had extensive damage to the CC white matter. The FA of the genu (P = 0.04) and body (P = 001) parts decreased, while RD (P = 0.003; P = 0.02) and MD (P = 0.002; P = 0.04) increased. In addition, the authors observed that the disease duration and VAS of CTN patients were negatively correlated with FA.

The corpus callosum substructure region has extensive damage in chronic pain, and the selective microstructural integrity damage was particularly manifested by changes in axons and myelin sheath in the genu and body of corpus callosum 1).


Diffusion tensor imaging (DTI) has revealed microstructural changes in the symptomatic trigeminal root and root entry zone of patients with unilateral TN.

Noninvasive DTI analysis of patients with TN may lead to improved trigeminal neuralgia diagnosis of TN subtypes (e.g., TN1 and TN2) and improve patient selection for surgical intervention. DTI measurements may also provide insights into prognosis after intervention, as TN1 patients are known to have better surgical outcomes than TN2 patients 2).


As diffusion tensor imaging (DTI) is able to assess tissue integrity, Leal et al., used diffusion to detect abnormalities in trigeminal nerves (TGN) in patients with trigeminal neuralgia (TN) caused by neurovascular compression (NVC) who had undergone microvascular decompression (MVD).

Using DTI sequencing on a 3-T MRI scanner, we measured the fraction of anisotropy (FA) and apparent diffusion coefficient (ADC) of the TGN in 10 patients who had undergone MVD for TN and in 6 normal subjects. We compared data between affected and unaffected nerves in patients and both nerves in normal subjects (controls). We then correlated these data with CSA and V. Data from the affected side and the unaffected side before and 4 years after MVD were compared.

RESULTS: Before MVD, the FA of the affected side (0.37 ± 0.03) was significantly lower (p < 0.05) compared to the unaffected side in patients (0.48 ± 0.03) and controls (0.52 ± 0.02), and the ADC in the affected side (5.6 ± 0.34 mm2/s) was significantly higher (p < 0.05) compared to the unaffected side in patients (4.26 ± 0.25 mm2/s) and controls (3.84 ± 0.18 mm2/s). Affected nerves had smaller V and CSA compared to unaffected nerves and controls (p < 0.05). After MVD, the FA in the affected side (0.41 ± 0.02) remained significantly lower (p < 0.05) compared to the unaffected side (0.51 ± 0.02), but the ADC in the affected side (4.24 ± 0.34 mm2/s) had become similar (p > 0.05) to the unaffected side (4.01 ± 0.33 mm2/s).

CONCLUSIONS: DTI revealed a loss of anisotropy and an increase in diffusivity in affected nerves before surgery. Diffusion alterations correlated with atrophic changes in patients with TN caused by NVC. After removal of the compression, the loss of FA remained, but ADC normalized in the affected nerves, suggesting improvement in the diffusion of the trigeminal root 3).


Herveh et al. studied the trigeminal nerve in seven healthy volunteers and six patients with trigeminal neuralgia using the diffusion tensor imaging derived parameter fractional anisotropy (FA). While controls did not show a difference between both sides, there was a reduction of FA in the affected nerve in three of six patients with accompanying nerve-vessel conflict and atrophy. Reversibility of abnormally low FA values was demonstrated in one patient successfully treated with microvascular decompression 4).


3T MR diffusion weighted, T1, T2 and FLAIR sequences were acquired for Multiple sclerosis related trigeminal neuralgia MS-TN, TN, and controls. Multi-tensor tractography was used to delineate CN V across cisternal, root entry zone (REZ), pontine and peri-lesional segments. Diffusion metrics including fractional anisotropy (FA), and radial (RD), axial (AD), and mean diffusivities (MD) were measured from each segment.

CN V segments showed distinctive diffusivity patterns. The TN group showed higher FA in the cisternal segment ipsilateral to the side of pain, and lower FA in the ipsilateral REZ segment. The MS-TN group showed lower FA in the ipsilateral peri-lesional segments, suggesting differential microstructural changes along CN V in these conditions.

The study demonstrates objective differences in CN V microstrucuture in TN and MS-TN using non-invasive neuroimaging. This represents a significant improvement in the methods currently available to study pain in MS 5).


The aim of a study was to evaluate the microstructural tissue abnormalities in the trigeminal nerve in symptomatic trigeminal neuralgia not related to neurovascular compression using diffusion tensor imaging. Mean values of the quantitative diffusion parameters of trigeminal nerve, fractional anisotropy and apparent diffusion coefficient, were measured in a group of four symptomatic trigeminal neuralgia patients without neurovascular compression who showed focal non-enhancing T2-hyperintense lesions in the pontine trigeminal pathway. These diffusion parameters were compared between the affected and unaffected sides in the same patient and with four age-matched healthy controls. Cranial magnetic resonance imaging revealed hyperintense lesions in the dorsolateral part of the pons along the central trigeminal pathway on T2-fluid-attenuated inversion recovery sequences. The mean fractional anisotropy value on the affected side was significantly decreased (P = 0.001) compared to the unaffected side and healthy controls. Similarly, the mean apparent diffusion coefficient value was significantly higher (P = 0.001) on the affected side compared to the unaffected side and healthy controls. The cause of trigeminal neuralgia in our patients was abnormal pontine lesions affecting the central trigeminal pathway. The diffusion tensor imaging results suggest that microstructural tissue abnormalities of the trigeminal nerve also exist even in non-neurovascular compression-related trigeminal neuralgia 6).


DTI analysis allows the quantification of structural alterations, even in those patients without any discernible neurovascular contact on MRI. Moreover, our findings support the hypothesis that both the arteries and veins can cause structural alterations that lead to TN. These aspects can be useful for making treatment decisions 7).


The mean diameter of compression arteries (DCA) in NVC patients with TN (1.58 ± 0.34 mm) was larger than that without TN (0.89 ± 0.29 mm). Compared with NVC without TN and HC, the mean values of RD at the site of NVC with TN were significantly increased; however, no significant changes of AD were found between the groups. Correlation analysis showed that DCA positively correlated with radial diffusivity (RD) in NVC patients with and without TN (r = 0.830, p = 0.000). No significant correlation was found between DCA and axial diffusivity (AD) (r = 0.178, p = 0.077).

Larger-diameter compression arteries may increase the chances of TN, and may be a possible facilitating factor for TN 8).


Fractional anisotropy (FA) value quantitatively showed the alteration of trigeminal nerve (TGN) caused by Neurovascular compression (NVC). It provided direct evidence about the effect of NVC which facilitated the diagnosis and surgical decision of Type 2 trigeminal neuralgia (TN) . Besides, significant reduction of FA value may predict an optimistic outcome of microvascular decompression (MVD) 9).


Sophisticated structural MRI techniques including diffusion tensor imaging provide new opportunities to assess the trigeminal nerves and CNS to provide insight into TN etiology and pathogenesis. Specifically, studies have used high-resolution structural MRI methods to visualize patterns of trigeminal nerve-vessel relationships and to detect subtle pathological features at the trigeminal REZ. Structural MRI has also identified CNS abnormalities in cortical and subcortical gray matter and white matter and demonstrated that effective neurosurgical treatment for TN is associated with a reversal of specific nerve and brain abnormalities 10).


Forty-three patients with trigeminal neuralgia were recruited, and diffusion tensor imaging was performed before radiofrequency rhizotomy. By selecting the cisternal segment of the trigeminal nerve manually, they measured the volume of trigeminal nerve, fractional anisotropy, apparent diffusion coefficient, axial diffusivity, and radial diffusivity. The apparent diffusion coefficient and mean value of fractional anisotropy, axial diffusivity, and radial diffusivity were compared between the affected and normal side in the same patient, and were correlated with pre-rhizotomy and post-rhizotomy visual analogue scale pain scores. The results showed the affected side had significantly decreased fractional anisotropy, increased apparent diffusion coefficient and radial diffusivity, and no significant change of axial diffusivity. The volume of the trigeminal nerve on affected side was also significantly smaller. There was a trend of fractional anisotropy reduction and visual analogue scale pain score reduction (P = 0.072). The results suggest that demyelination without axonal injury, and decreased size of the trigeminal nerve, are the microstructural abnormalities of the trigeminal nerve in patients with trigeminal neuralgia caused by neurovascular compression. The application of diffusion tensor imaging in understanding the pathophysiology of trigeminal neuralgia, and predicting the treatment effect has potential and warrants further study 11).

References

1)

Li R, Chang N, Liu Y, Zhang Y, Luo Y, Zhang T, Zhao Q, Qi X. The Integrity of the Substructure of the Corpus Callosum in Patients with Right Classic Trigeminal Neuralgia-A Diffusion Tensor Imaging Study. J Craniofac Surg. 2020 Sep 22. doi: 10.1097/SCS.0000000000007082. Epub ahead of print. PMID: 32969923.
2)

Willsey MS, Collins KL, Conrad EC, Chubb HA, Patil PG. Diffusion tensor imaging reveals microstructural differences between subtypes of trigeminal neuralgia. J Neurosurg. 2019 Jul 19:1-7. doi: 10.3171/2019.4.JNS19299. [Epub ahead of print] PubMed PMID: 31323635.
3)

Leal PRL, Roch J, Hermier M, Berthezene Y, Sindou M. Diffusion tensor imaging abnormalities of the trigeminal nerve root in patients with classical trigeminal neuralgia: a pre- and postoperative comparative study 4 years after microvascular decompression. Acta Neurochir (Wien). 2019 May 2. doi: 10.1007/s00701-019-03913-5. [Epub ahead of print] PubMed PMID: 31049710.
4)

Herweh C, Kress B, Rasche D, Tronnier V, Tröger J, Sartor K, Stippich C. Loss of anisotropy in trigeminal neuralgia revealed by diffusion tensor imaging. Neurology. 2007 Mar 6;68(10):776-8. PubMed PMID: 17339587.
5)

Chen DQ, DeSouza DD, Hayes DJ, Davis KD, O’Connor P, Hodaie M. Diffusivity signatures characterize trigeminal neuralgia associated with multiple sclerosis. Mult Scler. 2016 Jan;22(1):51-63. doi: 10.1177/1352458515579440. PubMed PMID: 25921052.
6)

Neetu S, Sunil K, Ashish A, Jayantee K, Usha Kant M. Microstructural abnormalities of the trigeminal nerve by diffusion-tensor imaging in trigeminal neuralgia without neurovascular compression. Neuroradiol J. 2016 Feb;29(1):13-8. doi: 10.1177/1971400915620439. PubMed PMID: 26678753; PubMed Central PMCID: PMC4978338.
7)

Lutz J, Thon N, Stahl R, Lummel N, Tonn JC, Linn J, Mehrkens JH. Microstructural alterations in trigeminal neuralgia determined by diffusion tensor imaging are independent of symptom duration, severity, and type of neurovascular conflict. J Neurosurg. 2016 Mar;124(3):823-30. doi: 10.3171/2015.2.JNS142587. PubMed PMID: 26406792.
8)

Lin W, Zhu WP, Chen YL, Han GC, Rong Y, Zhou YR, Zhang QW. Large-diameter compression arteries as a possible facilitating factor for trigeminal neuralgia: analysis of axial and radial diffusivity. Acta Neurochir (Wien). 2016 Mar;158(3):521-6. doi: 10.1007/s00701-015-2673-4. PubMed PMID: 26733127; PubMed Central PMCID: PMC4752583.
9)

Chen F, Chen L, Li W, Li L, Xu X, Li W, Le W, Xie W, He H, Li P. Pre-operative declining proportion of fractional anisotropy of trigeminal nerve is correlated with the outcome of micro-vascular decompression surgery. BMC Neurol. 2016 Jul 16;16:106. doi: 10.1186/s12883-016-0620-5. PubMed PMID: 27422267; PubMed Central PMCID: PMC4947245.
10)

DeSouza DD, Hodaie M, Davis KD. Structural Magnetic Resonance Imaging Can Identify Trigeminal System Abnormalities in Classical Trigeminal Neuralgia. Front Neuroanat. 2016 Oct 19;10:95. Review. PubMed PMID: 27807409; PubMed Central PMCID: PMC5070392.
11)

Chen ST, Yang JT, Yeh MY, Weng HH, Chen CF, Tsai YH. Using Diffusion Tensor Imaging to Evaluate Microstructural Changes and Outcomes after Radiofrequency Rhizotomy of Trigeminal Nerves in Patients with Trigeminal Neuralgia. PLoS One. 2016 Dec 20;11(12):e0167584. doi: 10.1371/journal.pone.0167584. PubMed PMID: 27997548.

Occipital nerve stimulation for cluster headache

Occipital nerve stimulation for cluster headache

Occipital nerve stimulation (ONS) has been proposed chronic cluster headache treatment (rCCH) but its efficacy has only been showed in small short-term series.

Leplus et al. evaluated 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption.

At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%).

The results showed that longterm efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients 1).


33 patients, of whom 16 had chronic migraine (CM), nine had chronic cluster headache (CCH), and six had secondary headache disorders. PENS was given using Algotec® disposable 21 gauge PENS therapy probes (8 cm) to the occipital nerve ipsilateral to the pain (or bilaterally in cases of bilateral pain). Stimulation was delivered at 2 Hz/100 Hz, at 3 cycles/s, between 1.2 and 2.5 V depending on patient tolerability, for 25-28 min.

Six of nine patients with CCH improved significantly after the first session. In all patients with CCH, PENS therapy was well tolerated, with no significant adverse events reported. One patient with CCH reverted to an episodic cluster. Only four patients with CM experienced any benefit.

PENS therapy shows potential as a relatively non-invasive, low-risk, and inexpensive component of the treatment options for refractory primary headache disorders, particularly CCH 2).


Seventeen patients (12 CM and 5 CCH) were treated with bilateral burst pattern ONS, including 4 who had previously had tonic ONS. Results were assessed in terms of the frequency of headaches (number of headache days per month for CM, and number of attacks per day for CCH) and their intensity on the numeric pain rating scale.

Burst ONS produced a statistically significant mean reduction of 10.2 headache days per month in CM. In CCH, there were significant mean reductions in headache frequency (92%) and intensity (42%).

Paraesthesia is not necessary for good quality analgesia in ONS. Larger studies will be required to determine whether the efficacies of the two stimulation modes differ. Burst ONS is imperceptible and therefore potentially amenable to robustly blinded clinical trials 3).


Eight patients with medically intractable chronic cluster headache were implanted in the suboccipital region with electrodes for occipital nerve stimulation. Other than the first patient, who was initially stimulated unilaterally before being stimulated bilaterally, all patients were stimulated bilaterally during treatment.

At a median follow-up of 20 months (range 6-27 months for bilateral stimulation), six of eight patients reported responses that were sufficiently meaningful for them to recommend the treatment to similarly affected patients with chronic cluster headache. Two patients noticed a substantial improvement (90% and 95%) in their attacks; three patients noticed a moderate improvement (40%, 60%, and 20-80%) and one reported mild improvement (25%). Improvements occurred in both frequency and severity of attacks. These changes took place over weeks or months, although attacks returned in days when the device malfunctioned (eg, with battery depletion). Adverse events of concern were lead migrations in one patient and battery depletion requiring replacement in four.

Occipital nerve stimulation in cluster headache seems to offer a safe, effective treatment option that could begin a new era of neurostimulation therapy for primary headache syndromes 4).

References

1)

Leplus A, Fontaine D, Donnet A, Regis J, Lucas C, Buisset N, Blond S, Raoul S, Guegan-Massardier E, Derrey S, Jarraya B, Dang-Vu B, Bourdain F, Valade D, Roos C, Creach C, Chabardes S, Giraud P, Voirin J, Bloch J, Colnat-Coulbois S, Caire F, Rigoard P, Tran L, Cruzel C, Lantéri-Minet M; French ONS registry group. LongTerm Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache. Neurosurgery. 2020 Sep 28:nyaa373. doi: 10.1093/neuros/nyaa373. Epub ahead of print. PMID: 32985662.
2)

Weatherall MW, Nandi D. Percutaneous electrical nerve stimulation (PENS) therapy for refractory primary headache disorders: a pilot study. Br J Neurosurg. 2019 Oct 3:1-5. doi: 10.1080/02688697.2019.1671951. [Epub ahead of print] PubMed PMID: 31578882.
3)

Garcia-Ortega R, Edwards T, Moir L, Aziz TZ, Green AL, FitzGerald JJ. Burst Occipital Nerve Stimulation for Chronic Migraine and Chronic Cluster Headache. Neuromodulation. 2019 Jul;22(5):638-644. doi: 10.1111/ner.12977. Epub 2019 Jun 14. PubMed PMID: 31199547.
4)

Burns B, Watkins L, Goadsby PJ. Treatment of medically intractable cluster headache by occipital nerve stimulationlongterm follow-up of 8 patients. Lancet. 2007; 369:1099–1106

Postoperative pain

Postoperative pain

Perioperative pain assessment and management in neurosurgical patients varies widely across the globe. There is lack of data from developing world regarding practices of pain assessment and management in neurosurgical population.

A survey aimed to capture practices and perceptions regarding perioperative pain assessment and management in neurosurgical patients among anesthesiologists who are members of the Indian Society of Neuroanaesthesiology and Critical Care (ISNACC) and evaluated if hospital and pain characteristics predicted the use of structured pain assessment protocol and use of opioids for postoperative pain management.

A 26-item English language questionnaire was administered to members of ISNACC using Kwiksurveys platform after ethics committee approval. This outcome measures were adoption of structured protocol for pain assessment and opioid usage for postoperative pain management.

The response rate for this survey was 55.15% (289/524). One hundred eighteen (41%) responders informed that their hospital setup had a structured pain protocol while 43 (15%) responders reported using opioids for postoperative pain management. Predictors of the use of structured pain protocol were private setup (odds ratio [OR] 2.64; 95% confidence interval [CI] 1.52-4.59; p=0.001), higher pain intensity (OR 0.37; 95% CI 0.21-0.64; p<0.001) and use of pain scale (OR 7.94; 95% CI 3.99-15.81; p<0.001) while availability of structured pain protocol (OR 2.04; 95% CI 1.02-4.05; p=0.043) was the only significant variable for postoperative opioid use.

Less than half of the Indian neuroanesthesiologists who are members of ISNACC use structured protocol for pain assessment and very few use opioids for postoperative pain management in neurosurgical patients 1).


Studying the characteristics of postoperative pain at such an early stage allows for improved management. It helps to predict, according to the type of surgery and the anaesthesia used, those patients in which higher VAS values may be seen and to better adapt analgesic therapy 2).

Despite advances in surgical and anesthesiology techniques, many patients continue to experience postoperative pain after lumbar disc operations

The administration of tramadol with paracetamol was more effective than tramadol alone for early acute postoperative pain therapy following lumbar discectomy. Therefore while adding paracetamol in early pain management is recommended, continuing paracetamol for the late postoperative period is not advised 3).

Etiology

Epidural fibrosis and epidural adhesion after laminectomy are developed from adjacent dense scar tissue, which is a natural wound healing process 4) 5) 6) 7) , and ranked as the major contributor for postoperative pain recurrence after laminectomy or discectomy.

Treatment

The goal of postoperative pain management is to relieve pain while keeping side effects to a minimum. After hundreds of years of advances, the mainstay of pain therapy is still the opioids. While they are very effective analgesics, opioids also carry with them many undesirable side effects: sedation, respiratory depression, nausea and vomiting, hypotension and bradycardia, pruritus, and inhibition of bowel function. The treatment of complications such as nausea and pruritus may include the administration of antihistamines, which have an additive effect on sedation and respiratory depression.

References

1)

Sriganesh K, Bidkar PU, Krishnakumar M, Singh GP, Hrishi AP, Jangra K. Perioperative Analgesia In Neurosurgery (PAIN): A national survey of pain assessment and management among neuroanesthesiologists of India. Int J Clin Pract. 2020 Sep 23:e13718. doi: 10.1111/ijcp.13718. Epub ahead of print. PMID: 32966673.
2)

Cabedo N, Valero R, Alcón A, Gomar C. Prevalence and characterization of postoperative pain in the Postanaesthesia Care Unit. Rev Esp Anestesiol Reanim. 2017 Mar 28. pii: S0034-9356(16)30211-0. doi: 10.1016/j.redar.2016.11.006. [Epub ahead of print] English, Spanish. PubMed PMID: 28363327.
3)

Uztüre N, Türe H, Keskin Ö, Atalay B, Köner Ö. Comparison of Tramadol versus Tramadol with Paracetamol for efficacy of postoperative pain management in lumbar discectomy: a randomized controlled study. Int J Clin Pract. 2019 Sep 11. doi: 10.1111/ijcp.13414. [Epub ahead of print] PubMed PMID: 31508863.
4)

Alkalay RN, Kim DH, Urry DW, Xu J, Parker TM, Glazer PA. Prevention of postlaminectomy epidural fibrosis using bioelastic materials. Spine (Phila Pa 1976) 2003;28:1659–1665.
5)

Hsu CJ, Chou WY, Teng HP, Chang WN, Chou YJ. Coralline hydroxyapatite and laminectomy-derived bone as adjuvant graft material for lumbar posterolateral fusion. J Neurosurg Spine. 2005;3:271–275.
6)

Temel SG, Ozturk C, Temiz A, Ersozlu S, Aydinli U. A new material for prevention of epidural fibrosis after laminectomy: oxidized regenerated cellulose (interceed), an absorbable barrier. J Spinal Disord Tech. 2006;19:270–275.
7)

Yu CH, Lee JH, Baek HR, Nam H. The effectiveness of poloxamer 407-based new anti-adhesive material in a laminectomy model in rats. Eur Spine J. 2012;21:971–979.
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