Evaluation of the correlation of dorsal root ganglia and spinal nerves with clinical symptoms in patients with postherpetic neuralgia using magnetic resonance neurography.

Purpose: To assess changes of dorsal root ganglia (DRG) and spinal nerves in patients with postherpetic neuralgia (PHN), and investigate the correlation between DRG morphology and clinical symptoms in PHN patients using magnetic resonance neurography (MRN). Methods: In this case-control study, forty-nine lesioned DRG in 30 patients and 49 normal DRG in 30 well-matched (age, sex, height, weight) healthy controls were assessed. Clinical symptoms of patients (pain, allodynia, itching, and numbness) were assessed. MRN features (DRG volume (VDRG), the largest diameter (Dmax) of spinal nerves, signal intensity of DRG and spinal nerves (M-value)) were measured in all participants. Multilinear regression analysis was used to evaluate the relationship between the DRG morphology and clinical symptoms in patients. Results: The volume and relative M-value of lesioned DRG in patients were significantly higher than those on the same side of healthy controls (p = 0.013, p < 0.001, respectively). The mean Dmax and relative M-value of spinal nerves on the lesioned side were significantly higher than those on the contralateral and same side of healthy controls (p < 0.0001, p = 0.0001, p = 0.0011, p = 0.0053, respectively). No difference was found between the mean VDRG of the lesioned and contralateral sides. Multiple linear regression analysis revealed that disease duration was independent risk factor for the maximum rate of VDRG differences (p = 0.013). Conclusions: DRG and spinal nerves on the lesioned side are swollen during PHN. Disease duration is an independent risk factor for morphological differences in the lesioned DRG of PHN patients. This study provides important guidance for individualized treatments of PHN.

Aberrant functional and causal connectivity of the amygdala in herpes zoster and post-herpetic neuralgia patients.

OBJECTIVE: Resting-state functional magnetic resonance imaging (rs-fMRI) and Granger causality analysis (GCA) were used to observe the characteristics of amygdala and whole-brain effect connections in patients with herpes zoster (HZ) and post-herpetic neuralgia (PHN) and to determine their relationship with clinical features. METHODS: Rs-fMRI scans were performed on 50 HZ; 50 PHN; and 50 age-, sex- and education-year-matched healthy controls (HCs). Bilateral amygdala subregions were used as seeds for functional connectivity (FC). GCA was used to analyze the effective connection of brain regions that were significantly different among groups. Then, the correlation between FC, and GCA values and clinical indices was investigated. RESULTS: PHN had impaired FC between the amygdala subregion with the putamen, cortex, anterior cingulate cortex (ACC) to HCs and reduced FC of medial amygdala (MeA) with the parieto-occipital lobe and motor cortex to HZ; HZ had reduced FC of the lateral amygdala (LA) with the insula to HCs. GCA values from the bilateral LA to the bilateral ACC, left MeA to the bilateral ACC and left putamen, and right ACC to the bilateral MeA were reduced in PHN patients compared to HCs. Compared with HCs, the GCA values from the left MeA to the left ACC and right putamen were reduced in HZ. The GCA values from the amygdala subregion to the ACC were positively correlated with HAMA or HAMD scores in PHN. CONCLUSION: PHN showed reduced FC between the amygdala subregions and cortico-putamen and decreased effective connectivity from the amygdala subregion to the ACC and putamen. ADVANCES IN KNOWLEDGE: HZ and PHN patients had significant changes in effective connectivity in brain regions, including diverse functional areas emanating from and projecting to the amygdala. The current findings will provide a new perspective for understanding the neuropathophysiological mechanism HZ and PHN.

Greater functional connectivity between the ventral frontal cortex and occipital cortex in herpes zoster patients than post-herpetic neuralgia patients.

OBJECTIVE: This study aimed to compare whole brain network between herpes zoster (HZ) patients and post-herpetic neuralgia (PHN) patients, as well as to investigate the associations between whole brain network changes and pain intensity and the accuracy of classifying between different types of pain. METHODS: PHN patients (n = 50) and HZ patients (n = 50) and healthy controls (HCs) (n = 50) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Functional connectivity and global and local graph theory metrics were calculated by using Dosenbach-160 atlas. The relationship between neuroimaging indicators and clinical scales was evaluated using correlation analysis, and receiver operating characteristic (ROC) curves evaluated the feasibility of classifying PHN and HZ patients using specific neuroimaging indicators. RESULTS: (1) 10 greater average connectivities were found in HZ group among the default mode, frontoparietal, cingulo-opercular, sensorimotor, occipital networks (ONs), and cerebellum (p < 0.001). (2) HZ patients exhibited higher global efficiency than those in the PHN and HCs (t = 2.178, p = 0.038). (3) Multiple linear regression analyses indicated that functional connectivity between the ventral frontal cortex in the cingulo-opercular network and the occipital gyrus in the ON influenced the visual analog score pain scores (ß = 4.273; p = 0.004). CONCLUSION: The variation of functional connectivity between ventral frontal cortex in the cingulo-opercular network and occipital gyrus in the ON may be a robust neuroimaging marker of the transition from HZ to PHN patients. ADVANCES IN KNOWLEDGE: Whole-brain network analysis may be effective in distinguishing HZ and PHN patients and predicting pain intensity.

Elevated GABA level in the precuneus and its association with pain intensity in patients with postherpetic neuralgia: An initial proton magnetic resonance spectroscopy study.

PURPOSE: This study aimed to explore the changes in gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, and their correlations with clinical indicators in patients with postherpetic neuralgia (PHN). METHODS: A totally of 22 PHN patients and 21 sex-, age-, and education-matched healthy controls (HCs) underwent proton magnetic resonance spectroscopy scanning. The spectral data of GABA in the precuneus was obtained by Mescher-Garwood point-resolved spectroscopy, whereas the spectral data of Glu, total N-acetyl-l-aspartic acid (tNAA) and total choline (tCho) were obtained by point-resolved spectroscopy. The pain intensity of PHN was assessed by numeric rating scales (NRS). The edited GABA signal was displayed as GABA+ due to overlapping macromolecules and homocarnosine signals. Total creatine (tCr) level in individual was used as an endogenous reference. The neurometabolites levels of PHN patients were compared with those of healthy individuals and the correlations with clinical variables (pain duration and intensity) were analyzed. RESULTS: PHN patients had higher GABA+/tCr levels in the precuneus than HCs (P = 0.009), with no significant differences in the levels of Glu/ tCr, tNAA/ tCr and tCho/ tCr (all P > 0.05). The GABA+/ tCr levels were positively correlated with the NRS scores of the PHN patients (r = 0.473, P = 0.030). CONCLUSION: Increased GABA+/tCr levels in the precuneus and their association with pain intensity of PHN patients suggested a key role of the abnormalities of regional GABAergic neurons in the pathophysiological mechanisms of pain in PHN.

Pain-related reorganization in the primary somatosensory cortex of patients with postherpetic neuralgia.

Studies on functional and structural changes in the primary somatosensory cortex (S1) have provided important insights into neural mechanisms underlying several chronic pain conditions. However, the role of S1 plasticity in postherpetic neuralgia (PHN) remains elusive. Combining psychophysics and magnetic resonance imaging (MRI), we investigated whether pain in PHN patients is linked to S1 reorganization as compared with healthy controls. Results from voxel-based morphometry showed no structural differences between groups. To characterize functional plasticity, we compared S1 responses to noxious laser stimuli of a fixed intensity between both groups and assessed the relationship between S1 activation and spontaneous pain in PHN patients. Although the intensity of evoked pain was comparable in both groups, PHN patients exhibited greater activation in S1 ipsilateral to the stimulated hand. Pain-related activity was identified in contralateral superior S1 (SS1) in controls as expected, but in bilateral inferior S1 (IS1) in PHN patients with no overlap between SS1 and IS1. Contralateral SS1 engaged during evoked pain in controls encoded spontaneous pain in patients, suggesting functional S1 reorganization in PHN. Resting-state fMRI data showed decreased functional connectivity between left and right SS1 in PHN patients, which scaled with the intensity of spontaneous pain. Finally, multivariate pattern analyses (MVPA) demonstrated that BOLD activity and resting-state functional connectivity of S1 predicted within-subject variations of evoked and spontaneous pain intensities across groups. In summary, functional reorganization in S1 might play a key role in chronic pain related to PHN and could be a potential treatment target in this patient group.

The Curative Effect of Pregabalin in the Treatment of Postherpetic Neuralgia Analyzed by Deep Learning-Based Brain Resting-State Functional Magnetic Resonance Images.

This work aimed to investigate the brain resting-state functional magnetic resonance imaging (fMRI) technology based on the depth autoencoders algorithm and to evaluate the clinically curative effect of pregabalin in the treatment of postherpetic neuralgia (PHN). In this study, 40 patients with PHN were selected and rolled randomly into a treatment group and a control group (20 cases in each group). Then, a depth autoencoders algorithm was constructed and applied in the brain resting-state fMRI technology. The brains of 40 patients with PHN treated with pregabalin were scanned, and the time curve extracted from MRI images was convolved by linear drift removal bandpass filtering to reduce low-frequency drift and high-frequency noise, so the low-frequency amplitude was calculated. Based on the low-frequency amplitude method, the calculated low-frequency signal energy was eventually divided by the total power of the entire frequency band to obtain the low-frequency amplitude rate value. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (f-ALFF) before and after treatment were compared between the treatment group and the control group, and the visual analog scale (VAS) after treatment was also observed. After 4 weeks of taking the drug, the VAS scores of patients from the treatment group in the first week (6.5 ± 0.8 points), the second week (6.5 ± 0.8 points), the third week (3.1 ± 0.3 points), and the fourth week (2.3 ± 0.4 points) after treatment were lower steeply than the scores before treatment (8.3 ± 1.1 points) (P < 0.05). Resting-state fMRI images showed that the f-ALFF of the 4 brain areas in the treatment group was higher than that of the control group, mainly including the bilateral frontal lobes, bilateral parietal lobes, left parietal lobes, and right posterior cerebellar lobes. Besides, the f-ALFF of the 6 brain areas in the treatment group was lower than that of the control group, mainly including the right frontal lobe, right parietal lobe, right middle frontal gyrus, precuneus, left frontal lobe, and superior frontal gyrus. In conclusion, the resting-state fMRI technology based on the depth autoencoders algorithm could efficiently display the brain area characteristic changes of patients with PHN before and after treatment, thereby providing a reference for the diagnosis of the patient's condition.

Structural and functional brain abnormalities in postherpetic neuralgia: A systematic review of neuroimaging studies.

In recent decades, an increasing number of neuroimaging studies utilizing magnetic resonance imaging (MRI) have explored the differential effects of postherpetic neuralgia (PHN) on brain structure and function. We systematically reviewed and integrated the findings from relevant neuroimaging studies in PHN patients. A total of 15 studies with 16 datasets were ultimately included in the present study, which were categorized by the different neuroimaging modalities. The results revealed that PHN was closely associated with structural/microstructural and functional abnormalities of the brain mainly located in the 'pain matrix', including the thalamus, insula, parahippocampus, amygdala, dorsolateral prefrontal cortex, precentral gyrus and inferior parietal lobe, as well as other regions, such as the precuneus, lentiform nucleus and brainstem. Furthermore, a disruption of multiple networks, including the default-mode network, salience network and limbic system, may contribute to the neurophysiological mechanisms underlying PHN. The findings indicate that the cerebral abnormalities of PHN were not restricted to the pain matrix but extended to other regions, profoundly affecting the regulation and moderation of pain processing in PHN. Future prospective and longitudinal neuroimaging studies with larger samples will elucidate the progressive trajectory of neural changes in the pathophysiological process of PHN.

Deficits in ascending and descending pain modulation pathways in patients with postherpetic neuralgia.

Postherpetic Neuralgia (PHN), develops after the resolution of the herpes zoster mucocutaneous eruption, is a debilitating chronic pain. However, there is a lack of knowledge regarding the underlying mechanisms associated with ascending and descending pain modulations in PHN patients. Here, we combined psychophysics with structural and functional magnetic resonance imaging (MRI) techniques to investigate the brain alternations in PHN patients. Psychophysical tests showed that compared with healthy controls, PHN patients had increased state and trait anxiety and depression. Structural MRI data indicated that PHN patients had significantly smaller gray matter volumes of the thalamus and amygdala than healthy controls, and the thalamus volume was negatively correlated with pain intensity (assessed using the Short-form of the McGill pain questionnaire) in PHN patients. When the thalamus and periaqueductal gray matter (PAG) were used as the seeds, resting-state functional MRI data revealed abnormal patterns of functional connectivity within ascending and descending pain pathways in PHN patients, e.g., increased functional connectivity between the thalamus and somatosensory cortices and decreased functional connectivity between the PAG and frontal cortices. In addition, subjective ratings of both Present Pain Index (PPI) and Beck-Depression Inventory (BDI) were negatively correlated with the strength of functional connectivity between the PAG and primary somatosensory cortex (SI), and importantly, the effect of BDI on PPI was mediated by the PAG-SI functional connectivity. Overall, our results provided evidence suggesting deficits in ascending and descending pain modulation pathways, which were highly associated with the intensity of chronic pain and its emotional comorbidities in PHN patients. Therefore, our study deepened our understanding of the pathogenesis of PHN, which would be helpful in determining the optimized treatment for the patients.

Disrupted default mode network dynamics in recuperative patients of herpes zoster pain.

INTRODUCTION: Previous studies of herpes zoster (HZ) have focused on acute patient manifestations and the most common sequela, postherpetic neuralgia (PHN), both serving to disrupt brain dynamics. Although the majority of such patients gradually recover, without lingering severe pain, little is known about life situations of those who recuperate or the brain dynamics. Our goal was to determine whether default mode network (DMN) dynamics of the recuperative population normalize to the level of healthy individuals. METHODS: For this purpose, we conducted resting-state functional magnetic resonance imaging (fMRI) studies in 30 patients recuperating from HZ (RHZ group) and 30 healthy controls (HC group). Independent component analysis (ICA) was initially undertaken in both groups to extract DMN components. DMN spatial maps and within-DMN functional connectivity were then compared by group and then correlated with clinical variables. RESULTS: Relative to controls, DMN spatial maps of recuperating patients showed higher connectivity in middle frontal gyrus (MFG), right/left medial temporal regions of cortex (RMTC/LMTC), right parietal lobe, and parahippocampal gyrus. The RHZ (vs HC) group also demonstrated significant augmentation of within-DMN connectivity, including that of LMTC-MFG and LMTC-posterior cingulate cortex (PCC). Furthermore, the intensity of LMTC-MFG connectivity correlated significantly with scoring of pain-induced emotions and life quality. CONCLUSION: Findings of this preliminary study indicate that a disrupted dissociative pattern of DMN persists in patients recuperating from HZ, relative to healthy controls. We have thus provisionally established the brain mechanisms accounting for major outcomes of HZ, offering heuristic cues for future research on HZ transition states.

Early Treatment with Temporary Spinal Cord Stimulation Effectively Prevents Development of Postherpetic Neuralgia.

BACKGROUND: Some 7.7% of the Chinese population suffer from herpes zoster each year, with 29.8% proceeding on to develop postherpetic neuralgia (PHN). This amounts to over 32 million people per year. PHN is preceded by 2 phases of pain: acute herpetic neuralgia (AHN), and subacute herpetic neuralgia (SHN). Considering the large individual and economic burden, preventing the transition of AHN/SHN to PHN is crucial. However, to date this has been difficult. OBJECTIVES: To evaluate the efficacy of temporary spinal cord stimulation (tSCS) treatment and prevention of PHN. STUDY DESIGN: A retrospective, observational study. SETTING: Department of Pain Medicine. METHODS: From 2013 to 2017, 99 patients with AHN (n = 42), SHN (n = 34), and PHN (n = 23) underwent tSCS treatment (7-14 days) after failed pharmacologic and interventional therapies. Visual analog scale (VAS), Pittsburgh Sleep Quality Index (PSQI), and analgesic consumption were recorded at baseline, post-tSCS, and 1, 3, 6, and 12 months after tSCS treatment. RESULTS: Pooled results demonstrated statistically significant decreases in VAS scores and PSQI post-tSCS and at 1, 3, 6, and 12 months follow-up (P < 0.001). When compared with the PHN group, both AHN and SHN groups were clinically and statistically improved in VAS scores and PSQI (P < 0.001). Analgesic consumption decreased in all 3 groups after tSCS treatment, and downward linear gradient of medication in the AHN group was more significant than that in the SHN and PHN groups. At 12 months follow-up, 2.5% (1/40) patients in the AHN group, 16.0% (4/25) in the SHN group, and 62.5% (10/16) in the PHN group had ongoing pain >= 3/10 VAS score requiring analgesia. Expressed differently, at 12 months, 97.5% of the AHN group and 84% of the SHN group had pain of 2/10 VAS score or less versus only 37.5% of the PHN group. LIMITATIONS: This was a single-center, retrospective study, which made it difficult to collect complete data for all variables. The therapeutic effect of tSCS could not be studied independently. CONCLUSIONS: This retrospective analyses of 99 patients treated with tSCS (7-14 days) suggests that tSCS may be effective for treating and preventing PHN. Early treatment within 4 to 8 weeks was more likely to result in pain <= 2/10 VAS score, improvement in sleep, and no requirement for analgesia at 12 months. Early tSCS may be a promising prevention strategy against the development of chronic neuropathic pain following herpes zoster infection. Further research is justified. KEY WORDS: Herpes zoster, zoster-related pain, postherpetic neuralgia, temporary spinal cord stimulation.

A combined DTI and resting state functional MRI study in patients with postherpetic neuralgia.

PURPOSE: To explore the brain microstructural and functional changes in patients with postherpetic neuralgia (PHN). MATERIALS AND METHODS: 12 PHN patients and 12 healthy volunteers were enrolled. Diffusion tensor imaging (DTI) and resting-state functional MRI (rfMRI) sequences were scanned by a 3T MR scanner. Fractional anisotropy (FA) and mean diffusivity (MD) t-maps were obtained following DTI data processing. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were obtained following rfMRI data processing. A two sample t-test was performed to compare the FA, MD, ALFF and fALFF differences between the PHN patients and healthy controls. RESULTS: No significant differences were noted with regard to the parameters gender, age and education years between the two groups. FA, MD, ALFF and/or fALFF indicated significant alterations in specific pain or pain-related brain regions, such as brainstem, cerebellum, parietal lobe, precuneus, frontal lobe, temporal lobe, postcentral and precentral gyrus, corpus callosum, cingulate gyrus, putamen and insula. CONCLUSION: Multi-local alterations of spontaneous brain activity could form a network related to chronic pain, sensory discrimination, emotion and cognition, suggesting complicated central mechanisms of PHN. The combined-action of brain microstructure and function may play a critical role in comprehension of neurological mechanisms of PHN-induced pain.

Clinical Study of Ultrasound-Guided Methylene Blue Thoracic Paravertebral Nerve Block for the Treatment of Postherpetic Neuralgia.

AIM: To investigate the effect of ultrasound-guided methylene blue (MB) thoracic paravertebral nerve block (TPVB) on the treatment of postherpetic neuralgia (PHN). MATERIAL AND METHODS: A total of 27 patients with PHN were treated with ultrasound-guided TPVB. The blocking drug used was an MB compound preparation, and several indexes were recorded, including pain visual analogue scores (VAS), dosage of oral analgesic required, plasma interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and cortisol levels, basic viability, selfassessment, and satisfaction. RESULTS: The patients' VAS after TPVB were significantly reduced when compared to those before blocking. Furthermore, dosage of oral analgesic required, levels of plasma IL-6, TNF-α, and cortisol were reduced, and basic viability and self-assessments were significantly improved (p < 0.05). The treatment method was effective, did not cause any adverse effects, and patients reported higher degrees of satisfaction. CONCLUSION: Ultrasound-guided TPVB exerts significant effects on PHN. The patients' degree of pain and dosage of oral analgesic required were reduced, basic patient viability was improved, and patients reported higher degrees of satisfaction.

Neurosurgeons' Armamentarium for the Management of Refractory Postherpetic Neuralgia: A Systematic Literature Review.

BACKGROUND/AIMS: Postherpetic neuralgia (PHN) can be refractory to both medical and minimally invasive treatments. Its complex pathophysiology explains the numerous neurosurgical procedures that have been implemented through the years. Our objective was to summarize all available neurosurgical strategies for the management of resistant PHN and evaluate their respective safety and efficacy outcomes. METHODS: A comprehensive systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 38 studies comprising 811 patients with refractory PHN were included. The safety and efficacy of the following procedures were investigated: spinal cord stimulation (SCS), dorsal root entry zone (DREZ) lesioning, intrathecal drug delivery, caudalis DREZ lesioning, dorsal root ganglion (DRG) radiofrequency lesioning, peripheral nerve stimulation, gamma knife surgery, deep brain stimulation, cordotomy, percutaneous radiofrequency rhizotomy and Gasserian ganglion stimulation. CONCLUSIONS: There are several available neurosurgical approaches for recalcitrant PHN including neuromodulatory and ablative procedures. It is suggested that patients with resistant PHN undergo minimally invasive procedures first, including SCS, peripheral nerve stimulation or DRG radiofrequency lesioning. More invasive procedures should be reserved for refractory cases. Comparative studies are needed in order to construct a PHN neurosurgical management algorithm.

Herpes zoster ophthalmicus caught in the (Tr)act!

To emphasize the utility of contrast enhanced MRI for identifying the extent of disease in herpes zoster ophthalmicus with intracranial extension to help determine proper management. We present a rare case of herpes zoster ophthalmicus (HZ/HZO) with intracranial extension and MRI demonstration of involvement of the trigeminal nerve, the trigeminal nucleus, and the spinal trigeminal nucleus and tract. Herpes zoster is caused by reactivation of varicella zoster virus. Herpes zoster ophthalmicus with involvement of the ophthalmic division of the trigeminal nerve has been estimated to account for 10-20% of the cases (Yawn et al. in Mayo Clin Proc 88:562-570, 2013). While postherpetic neuralgia is the most common complication, HZ/HZO can rarely manifest in a more sinister manner resulting in multi-dermatomal involvement, disseminated disease, cranial arteritis (Walker in Radiology 107:109-110, 1973), cranial nerve paresis (O.d in Clinical Eye and Vision Care 11:75-80, 1999), hemiplegia (Cavaletti in The Italian Journal of Neurological Sciences 11:297-300, 1990), ocular/dysfunction (Kocaoglu in Türk Oftalmoloji Dergisi 48:42-46, 2018), and intracranial extension (Chen in BMC Infectious Diseases 17:213, 2017; Yawn in Mayo Clin Proc. 88:562-570, 2013). Contrast enhanced MRI (CE-MRI) can be of great benefit to elucidate the extent of disease and intracranial involvement for institution of more aggressive management to prevent further complications.

"From ear to trunk"-magnetic resonance imaging reveals referral of pain.

Referred and projecting pain can be observed in acute and chronic pain states. We present the case of a 69-year-old female patient with postherpetic neuralgia in dermatome Th2/3 who reported that touching the ipsilateral earlap (dermatome C2) would enhance pain and dynamic mechanical allodynia in the affected Th2/3-dermatome. The aim was to investigate possible underlying mechanisms of this phenomenon using the capsaicin experimental pain sensitization model, quantitative sensory testing, and functional spinal and supraspinal magnetic resonance imaging. The presented study provides evidence that a referral of pain from the ear to the trunk is possible. We discuss whether the observed phenomenon in combination with activation of pain-modulating areas on functional magnetic resonance imaging suggests either (1) a shift of descending pathways from inhibitory towards facilitating mode or (2) a deafferentation-induced reorganization of somatotopic maps, as the ear and the trunk are adjacent areas of the sensory homunculus. The results and a review about projection of pain in head-neck area are provided.

Local Brain Activity Differences Between Herpes Zoster and Postherpetic Neuralgia Patients: A Resting-State Functional MRI Study.

BACKGROUND: Herpes zoster (HZ) can develop into postherpetic neuralgia (PHN), both of which are painful diseases. PHN patients suffer chronic pain and emotional disorders. Previous studies showed that the PHN brain displayed abnormal activity and structural change, but the difference in brain activity between HZ and PHN is still not known. OBJECTIVES: To identify regional brain activity changes in HZ and PHN brains with resting-state functional magnetic resonance imaging (rs-fMRI) technique, and to observe the differences between HZ and PHN patients. STUDY DESIGN: Observational study. SETTING: University hospital. METHODS: Regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) methods were employed to analysis resting-state brain activity. Seventy-three age and gender matched patients (50 HZ, 23 PHN) and 55 healthy controls were enrolled. ReHo and fALFF changes were analyzed to detect the functional abnormality in HZ and PHN brains. RESULTS: Compared with healthy controls, HZ and PHN patients exhibited abnormal ReHo and fALFF values in classic pain-related brain regions (such as the frontal lobe, thalamus, insular, and cerebellum) as well as the brainstem, limbic lobe, and temporal lobe. When HZ developed to PHN, the activity in the vast area of the cerebellum significantly increased while that of some regions in the occipital lobe, temporal lobe, parietal lobe, and limbic lobe showed an apparent decrease. LIMITATIONS: (a) Relatively short pain duration (mean 12.2 months) and small sample size (n = 23) for PHN group. (b) Comparisons at different time points (with paired t-tests) for each patient may minimize individual differences. CONCLUSIONS: HZ and PHN induced local brain activity changed in the pain matrix, brainstem, and limbic system. HZ chronification induced functional change in the cerebellum, occipital lobe, temporal lobe, parietal lobe, and limbic lobe. These brain activity changes may be correlated with HZ-PHN transition. KEY WORDS: Herpes zoster, postherpetic neuralgia, resting-state fMRI (rs-fMRI), regional homogeneity (ReHo), fractional aptitude of low-frequency fluctuation (fALFF).

Abnormal Local Brain Activity Beyond the Pain Matrix in Postherpetic Neuralgia Patients: A Resting-State Functional MRI Study.

BACKGROUND: Postherpetic neuralgia (PHN) patients suffer debilitating chronic pain, hyperalgesia, and allodynia, as well as emotional disorders such as insomnia, anxiety, and depression. The brain structure and functional basis of PHN are still not fully understood. OBJECTIVES: To identify the changes of regional brain activity in resting-state PHN patients using regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) methods. Correlations between spontaneous pain intensity and ReHo or fALFF were analyzed. STUDY DESIGN: Observational study. SETTING: University hospital. METHODS: ReHo, fALFF change was analyzed in 19 PHN patients and 19 healthy controls to detect the functional abnormality in the brains of PHN patients. Correlations between ReHo, fALFF, and PHN pain intensity were assessed in the PHN group. RESULTS: PHN patients exhibited significantly abnormal ReHo and fALFF intensity in several brain regions, including the brainstem, thalamus, limbic system, temporal lobe, prefrontal lobe, and cerebellum compared with healthy controls. Correlation analysis showed that most of the ReHo values of the aforementioned brain regions positively correlated with visual analog scale (VAS) values. But much less correlation was found between fALFF and VAS. LIMITATIONS: (a) No specific emotional assessment was given for PHN patients before fMRI scans, therefore we cannot exclude whether the emotional disorders exist in these patients. (b) Relatively short pain duration (mean 5.4 months) and small sample size (n = 19) for the PHN group. CONCLUSIONS: For PHN patients, the local brain activity abnormality was not restricted to the pain matrix. Besides regions related to pain perception, areas in charge of affective processes, emotional activity, and pain modulation also showed abnormal local brain activity in a resting state, which may suggest complicated supraspinal function and plasticity change in PHN patients. ReHo was more closely correlated with pain intensity of PHN patients than fALFF. This work indicates that besides physical and emotional pain perception, mood disorder and pain modulation could be characteristic of PHN patients. This also supports the potential use of therapeutic interventions not only restricted to pain alleviation, but that also attempt to ameliorate the cognitive and emotional comorbidities. Key words: Postherpetic neuralgia, resting-state fMRI (rs-fMRI), mood disorder, limbic system, fractional aptitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo).

Gasserian Ganglion and Retrobulbar Nerve Block in the Treatment of Ophthalmic Postherpetic Neuralgia: A Case Report.

OBJECTIVES: Varicella zoster virus reactivation can cause permanent histological changes in the central and peripheral nervous system. Neural inflammatory changes or damage to the dorsal root ganglia sensory nerve fibers during reactivation can lead to postherpetic neuralgia (PHN). For PHN of the first division of the fifth cranial nerve (ophthalmic division of the trigeminal ganglion), there is evidence of inflammatory change in the ganglion and adjacent ocular neural structures. First division trigeminal nerve PHN can prove to be difficult and sometimes even impossible to manage despite the use of a wide range of conservative measures, including anticonvulsant and antidepressant medication. Steroids have been shown to play an important role by suppressing neural inflammatory processes. We therefore chose the trigeminal ganglion as an interventional target for an 88-year-old woman with severe ophthalmic division PHN after she failed to respond to conservative treatment. METHODS: Under fluoroscopic guidance, a trigeminal ganglion nerve block was performed with lidocaine combined with dexamethasone. A retrobulbar block with lidocaine and triamcinolone settled residual oculodynia. RESULTS: At 1-year follow-up, the patient remained pain free and did not require analgesic medication. CONCLUSION: To our knowledge, this is the first reported case of ophthalmic division PHN successfully treated with a combination of trigeminal ganglion and retrobulbar nerve block using a local anesthetic agent and steroid for central and peripheral neural inflammatory processes.

Microstructural Abnormalities in Gray Matter of Patients with Postherpetic Neuralgia: A Diffusional Kurtosis Imaging Study.

BACKGROUND: Changes in functional activity and connectivity have been shown in patients experiencing postherpetic neuralgia (PHN) pain. However, PHN-induced structural changes, particularly in the gray matter of which volume and density was widely reported to be altered by other chronic pain, have not been well characterized. OBJECTIVE: In this study, we aimed to detect the difference in the microstructure of gray matter of PHN patients as compared to the healthy controls, and to analyze the correlation between microstructural alterations and clinical features of PHN patients. STUDY DESIGN: Observational study. SETTING: University hospital. METHODS: Diffusional kurtosis imaging (DKI) was performed in 19 patients with PHN and in 19 age- and gender-matched healthy controls. Maps of axial kurtosis (K//), mean kurtosis (MK), radial kurtosis (K) in gray matter were calculated and compared between the 2 groups. Correlations between kurtosis metrics in the regions where between-group difference was detected and pain intensity as well as lesion duration were tested by Pearson's correlation. RESULTS: Compared with healthy controls, PHN patients exhibited significantly decreased DKI parameters in the bilateral insula and superior temporal gyrus, left middle frontal gyrus and occipital lobe, right cerebellum anterior lobe, right thalamus, caudate and parahippocampal gyrus. K// in the bilateral insula and MK in the right insula were negatively correlated with visual analogue scale (VAS) scores of PHN patients, whereas no correlation was found between DKI parameters and lesion duration of PHN pain. LIMITATION: Relatively small sample size. We still cannot determine the causal and effect relationship between the microstructural abnormalities in the gray matter and PHN. CONCLUSIONS: DKI can specifically reflect pathophysiological microstructural alterations in the cerebral gray matters of PHN patients. This feature enables magnetic resonance imaging (MRI) to be a potentially valuable technique for objectively estimating the severity of PHN pain, which would provide an opportunity for elucidating the central mechanisms underlying PHN as well. KEY WORDS: Postherpetic neuralgia, diffusional kurtosis imaging, insula cortex, gray matter, voxel-based analysis.

Treatment of postherpetic neuralgia using DREZotomy guided by spinal cord stimulation.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication following an episode of acute herpes zoster. The curative effect of current treatments is limited. OBJECTIVES: The purpose of this paper is to report a new treatment for PHN with a combination of dorsal root entry zone lesion (DREZotomy) and spinal cord stimulation (SCS). METHODS: Microsurgical DREZotomy assisted with SCS for target localization was performed in 6 patients with PHN. A visual analog scale (VAS) was used to evaluate the pain pre- and postoperatively. RESULTS: Except for 1 patient, in whom the test SCS was unsatisfactory, all patients finally underwent DREZotomy. These 5 patients experienced apparent symptom relief postoperatively, and the VAS score decreased from a baseline of 8.4 ± 1.14 to 2.4 ± 1.14 (p = 0.0020) and did not change significantly during the follow-up of up to 24 months. CONCLUSIONS: Microsurgical DREZotomy assisted with SCS for target localization is an effective remedy for PHN.