Toxina botulínica no tratamento da neuralgia pós herpética: um desafio terapêutico / Botulinum toxin in the treatment of postherpetic neuralgia: a therapeutic challenge

A neuralgia pós-herpética (NPH) é a principal complicação do herpes zoster. Caracteriza-se por dor que persiste por mais de três meses após o episódio de reativação do vírus varicela zoster, com impacto importante na qualidade de vida. A terapia de primeira linha da NPH consiste nos antidepressivos tricíclicos, inibidores de recaptação de serotonina e noradrenalina, além dos anticonvulsionantes pregabalina e gabapentina. Nos casos refratários, o uso subcutâneo da toxina botulínica A (TXB-A), é uma possibilidade terapêutica. A TXB-A, além de inibir a exocitose da acetilcolina na fenda sináptica da junção neuromuscular, também diminui a liberação de outros mediadores como glutamato, substância P e peptídeo relacionado à calcitonina, responsáveis pela ativação de nociceptores. Neste estudo, foram analisados os prontuários de seis pacientes com NPH, tratados com TXB-A concomitantemente à terapia padrão, no ambulatório de Dermatologia Geral do Hospital do Servidor Público Municipal de São Paulo, com o objetivo de avaliar se houve melhora da dor, através da comparação dos valores da escala visual de dor (EVA). Palavras-chave: Neuralgia pós herpética. Toxinas Botulínicas Tipo A. Herpes zoster.

The brain's structural differences between postherpetic neuralgia and lower back pain.

The purpose is to explore the brain's structural difference in local morphology and between-region networks between two types of peripheral neuropathic pain (PNP): postherpetic neuralgia (PHN) and lower back pain (LBP). A total of 54 participants including 38 LBP and 16 PHN patients were enrolled. The average pain scores were 7.6 and 7.5 for LBP and PHN. High-resolution structural T1 weighted images were obtained. Both grey matter volume (GMV) and morphological connectivity (MC) were extracted. An independent two-sample t-test with false discovery rate (FDR) correction was used to identify the brain regions where LBP and PHN patients showed significant GMV difference. Next, we explored the differences of MC network between LBP and PHN patients and detected the group differences in network properties by using the two-sample t-test and FDR correction. Compared with PHN, LBP patients had significantly larger GMV in temporal gyrus, insula and fusiform gyrus (p < 0.05). The LBP cohort had significantly stronger MC in the connection between right precuneus and left opercular part of inferior frontal gyrus (p < 0.05). LBP patients had significantly stronger degree in left anterior cingulate gyrus and left rectus gyrus (p < 0.05) while had significantly weaker degree than PHN patients in left orbital part of middle frontal gyrus, left supplementary motor area and left superior parietal lobule (p < 0.05). LBP and PHN patients had significant differences in the brain's GMV, MC, and network properties, which implies that different PNPs have different neural mechanisms concerning pain modulation.

Neurological Causes of Chest Pain.

PURPOSE OF REVIEW: Chest pain is a very common presenting complaint among patients in the hospital, a large proportion of whom have non-cardiac chest pain (NCCP). Neurological causes of NCCP have not been previously reviewed although several causes have been identified. RECENT FINDINGS: Chest pain has been reported as a symptom of multiple neurological conditions such as migraine, epilepsy, and multiple sclerosis, with varying clinical presentations. The affected patients are often not formally diagnosed for long periods of time due to difficulties in recognizing the symptoms as part of neurological disease processes. This paper will briefly summarize well-known etiologies of chest pain and, then, review neurological causes of NCCP, providing an overview of current literature and possible pathophysiologic mechanisms.

A novel method to simultaneously record spinal cord electrophysiology and electroencephalography signals.

The brain and the spinal cord together make up the central nervous system (CNS). The functions of the human brain have been the focus of neuroscience research for a long time. However, the spinal cord is largely ignored, and the functional interaction of these two parts of the CNS is only partly understood. This study developed a novel method to simultaneously record spinal cord electrophysiology (SCE) and electroencephalography (EEG) signals and validated its performance using a classical resting-state study design with two experimental conditions: eyes-closed (EC) and eyes-open (EO). We recruited nine postherpetic neuralgia patients implanted with a spinal cord stimulator, which was modified to record SCE signals simultaneously with EEG signals. For both EEG and SCE, similar differences were found in delta- and alpha-band oscillations between the EC and EO conditions, and the spectral power of these frequency bands was able to predict EC/EO behaviors. Moreover, causal connectivity analysis suggested a top-down regulation in delta-band oscillations from the brain to the spinal cord. Altogether, this study demonstrates the validity of simultaneous SCE-EEG recording and shows that the novel method is a valuable tool to investigate the brain-spinal interaction. With this method, we can better unite knowledge about the brain and the spinal cord for a deeper understanding of the functions of the whole CNS.

Efficacy of thermotherapy for herpes zoster and postherpetic neuralgia: A protocol for systemic review and meta-analysis.

BACKGROUND: Herpes zoster (HZ), is a painful skin rash disease with cutaneous symptoms and acute zoster-associated pain (ZAP). Postherpetic neuralgia (PHN), as the most frequent sequela of HZ, can persist a long time. Both HZ and PHN may significantly impact the quality of life and made great economical afford to affected patients. Its optimal treatment on HZ and PHN is still an urgent problem. In China, thermotherapy, including moxibustion and fire needle, is widely used because they can quickly promote the recovery of shingles and reduce the occurrence of PHN. Thermotherapy can also reduce pain intensity, relieve anxiety, and improve quality of life of PHN. Based on the current literatures, the effect and safety of thermotherapy will be systematically evaluated to provide appropriate complementary therapies for HZ and PHN. METHODS: Studies search for eligible randomized controlled trials (RCTs) that use thermotherapy including fire needle and moxibustion for HZ or PHN from the following databases: PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine Database (CBM), Technology Periodical database (VIP), and Wanfang database. Language restrictions for retrieving literature are English and Chinese. Their data extraction will be done by 2 researchers. Mean difference (MD) or relative risk (RR) with fixed or random effect model in terms of 95% confidence interval (CI) will be adopted for the data synthesis. To evaluate the risk of bias, the Cochrane's risk of bias assessment tool will be utilized. The sensitivity or subgroup analysis will also be conducted when meeting high heterogeneity (I2 > 50%). RESULTS: This meta-analysis will provide an authentic synthesis of the thermotherapy's effect on HZ and PHN, including incidence of postherpetic neuralgia and adverse events. DISCUSSION: The findings of the review offer updated evidence and identify whether thermotherapy can be an effective treatment for HZ and PHN for clinicians. REGISTRATION NUMBER: INPLASY2020110009.

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.

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.

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.

Efficacy of extracorporeal shockwave therapy in the treatment of postherpetic neuralgia: A pilot study.

Established conventional treatments for postherpetic neuralgia (PHN) and postherpetic itch (PHI) are difficult and often disappointing. In this study, the authors investigated the effect and mechanisms of extracorporeal shockwave therapy (ESWT) on pain and itch associated with PHN and PHI.Thirteen patients, 50 to 80 years of age, with symptoms associated with PHN or PHI (duration of persistent pain >3 months) and complaints of pain or itch rated >4 on a numerical rating scale (NRS), were included. ESWT was administered using a shockwave device (Piezo Shockwave, Richard Wolf GmbH, Knittlingen, Germany) to skin areas affected by pain or itch. An energy flux density of 0.09 to 0.16 mJ/mm at a frequency of 5 Hz and 2000 impulses was administered at 3-day intervals for 6 sessions. The NRS, 5D-Itch Scale, and Patients Global Impression of Change (PGIC) scale were used to evaluate the efficacy of ESWT.NRS scores of pain and itch and 5D-Itch Scale scores decreased significantly compared with before treatment and at the end of the treatment sessions (P < .0001, P = .001, P = .0002, respectively). There was a statistically significant difference between PGIC scores, which were checked every 2 sessions (P < .0001).ESWT is a noninvasive modality that significantly reduced PHN-associated pain and itch.

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.

Aggregate health and economic burden of herpes zoster in the United States: illustrative example of a pain condition.

Our objective was to develop comprehensive national estimates of the total burden of herpes zoster (HZ) among U.S. adults, including direct (ie, medical costs) and indirect (ie, productivity losses) costs, as well as its psychosocial impact (ie, quality of life losses). Using a patient-level microsimulation model, we projected health and economic outcomes among U.S. adults aged 18 years and older using a 10-year time horizon. We conducted a comprehensive systematic literature review to generate parameter values and conducted simulation modeling to generate our outcomes, including numbers of cases of uncomplicated HZ, postherpetic neuralgia (PHN), and ocular complications, productivity losses, and losses in quality-adjusted life years (QALYs). We used a societal perspective for outcomes; the costing year was 2015. Projected outcomes for an unvaccinated population included 1.1 million HZ cases, 114,000 PHN cases, and 43,000 ocular complications annually, resulting in approximately 67,000 QALYs lost. HZ and its complications would incur costs of $2.4 billion in direct medical costs and productivity losses annually. Projected QALY losses were most sensitive to HZ and PHN health utility values in the model. Cost estimates were most sensitive to the probability of HZ and to the costs per episode of PHN. The national burden of direct, indirect, and psychosocial HZ costs is substantial. Our results can inform economic analyses for HZ vaccines. Comprehensive, national assessments of the total burden of other painful conditions would be very informative.

Patient characteristics and analgesic efficacy of antiviral therapy in postherpetic neuralgia.

Postherpetic neuralgia (PHN) is the most common complication of shingles caused by reactivation of varicella zoster virus (VZV). Management of PHN is often suboptimal while using current conventional treatments. Antiviral therapy was used to reduce PHN-associated pain in two small trials which showed conflicting results. We hypothesize the analgesic efficacy of antiviral therapy on PHN is affected by patient characteristics including pathophysiology of the participants and serum vitamin D levels. Pathophysiology of PHN includes neuronal excitability and chronic VZV ganglionitis (persistent active VZV infection in ganglions). VZV-DNA positivity or a positive IgG coupled with a positive IgM indicates recent or current VZV infection. Positive VZV-DNA or IgG/IgM tests are used to confirm whether the patients experience chronic VZV ganglionitis. Antiviral therapy decreases pain in PHN patients with chronic VZV ganglionitis; whereas, antiviral therapy shows no effects in PHN patients with negative VZV-DNA or IgM. Vitamin D is a natural antiviral mediator. Studies show a high prevalence of vitamin D deficiency in hepatitis B/C virus-infected patients. Serum vitamin D levels and vitamin D supplementation are factors which affect the antiviral efficacy on hepatitis B/C virus infection. Serum 25-OHD levels of hospitalized patients with shingles were significantly lower compared to healthy controls. Accordingly, PHN patient may have a high prevalence of vitamin D deficiency which negatively affects the antiviral efficacy. Vitamin D supplementation may improve the antiviral efficacy on PHN. Future trials regarding antiviral therapy on PHN should consider patient characteristics and should be conducted among different subgroups of PHN patients.

The effects of repetitive transcranial magnetic stimulation on the whole-brain functional network of postherpetic neuralgia patients.

The effects of repetitive transcranial magnetic stimulation (rTMS), the clinical treatment for postherpetic neuralgia (PHN), on whole-brain functional network of PHN patients is not fully understood.To explore the effects of rTMS on the whole-brain functional network of PHN patients.10 PHN patients (male/female: 5/5 Age: 63-79 years old) who received rTMS treatment were recruited in this study. High-resolution T1-weighted and functional Magnetic Resonance Imaging (fMRI) were acquired before and after 10 consecutive rTMS sessions. The whole-brain functional connectivity networks were constructed by Pearson correlation. Global and node-level network parameters, which can reflect the topological organization of the brain network, were calculated to investigate the characteristics of whole-brain functional networks. Non-parametric paired signed rank tests were performed for the above network parameters with sex and age as covariates. P < .05 (with FDR correction for multi-comparison analysis) indicated a statistically significant difference. Correlation analysis was performed between the network parameters and clinical variables.The rTMS showed significant increase in characteristic path length and decrease of clustering coefficient, global, and local efficiency derived from the networks at some specific network sparsity, but it showed no significant difference for small-worldness. rTMS treatment showed significant differences in the brain regions related to sensory-motor, emotion, cognition, affection, and memory, as observed by changes in node degree, node betweenness, and node efficiency. Besides, node-level network parameters in some brain areas showed significant correlations with clinical variables including visual analog scales (VAS) and pain duration.rTMS has significant effects on the whole-brain functional network of PHN patients with a potential for suppression of sensory-motor function and improvement of emotion, cognition, affection, and memory functions.

Somatosensory profiles in acute herpes zoster and predictors of postherpetic neuralgia.

This prospective cohort study aimed to characterize the sensory profile during acute herpes zoster (AHZ) and to explore sensory signs as well as physical and psychosocial health as predictors for postherpetic neuralgia (PHN). Results of quantitative sensory testing of 74 patients with AHZ at the affected site and at the distant contralateral control site were compared to a healthy control group. Pain characteristics (Neuropathic Pain and Symptom Inventory and SES), physical functioning, and psychosocial health aspects (Pain Disability Index, SF-36, and STAI) were assessed by questionnaires. Patients with PHN (n = 13) at 6-month follow-up were compared to those without PHN (n = 45). Sensory signs at the affected site were thermal and vibratory hypesthesia, dynamic mechanical allodynia (DMA), pressure hyperalgesia, and high wind-up (18%-29%), as well as paradoxical heat sensations and pinprick hypalgesia (13.5%). The unaffected control site exhibited thermal and vibratory hypesthesia, DMA, and pressure hyperalgesia. Dynamic mechanical allodynia and pinprick hypalgesia were mutually exclusive. Postherpetic neuralgia was associated with DMA (38.5% vs 6.7%; P = 0.010) and vibratory hypesthesia (38.5% vs 11.1%; P = 0.036) at the control site, with mechanical gain and/or loss combined with normal thermal detection (affected site: 69.2% vs 31.1%; P = 0.023; control site: 53.8% vs 15.5%; P = 0.009). Pain Disability Index (P = 0.036) and SES affective pain perception scores (P = 0.031) were over 50% higher, and 6 of 8 SF-36 subscores were over 50% lower (P < 0.045) in PHN. Sensory profiles in AHZ indicate deafferentation and central but not peripheral sensitization. Sensory signs at distant body sites, strong affective pain perception, as well as reduced quality of life and physical functioning in the acute phase may reflect risk factors for the transition to PHN.

A post hoc analysis utilizing the FDA toxicity grading scale to assess injection site adverse events following immunization with the live attenuated Zoster Vaccine (ZVL).

BACKGROUND: ZOSTAVAX (ZVL; Zoster Virus Live), is a single dose, live, attenuated vaccine licensed for the prevention of herpes zoster (HZ) and post herpetic neuralgia (PHN) in adults ≥50 years of age. Injection site adverse events (AEs) of erythema, swelling and pain were solicited within 5 days post vaccination in the 2 pivotal studies of ZVL; ZEST (ZOSTAVAX Efficacy and Safety Trial) and SPS (Shingles Prevention Study). Protocol specified criteria were used to report the frequency and intensity of injection site AEs in ZEST and SPS studies. Subsequently, the FDA Toxicity Grading Scale provided guidance for uniform assessment of AEs across all adult vaccine clinical trials. The objective of this post-hoc analysis was to categorize the previously reported injection site AEs in two pivotal trials of ZVL according to the current FDA Toxicity Grading Scale. METHODS: The current FDA Toxicity Grading Scale provides a measure for classifying injection site AEs by four grades [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe) and Grade 4 (life threatening)]. Injection site erythema, swelling, and pain intensity gradings were assigned to the respective FDA Toxicity Grade based on this appropriation. A descriptive analysis of the proportion and risk difference (within 95% confidence intervals) of injection site AEs per the FDA Toxicity Grading Scale is provided. RESULTS: The frequency of injection site AEs (erythema, swelling, pain) after subcutaneous vaccination with ZVL were higher in recipients of ZVL compared with placebo. Majority of the injection site AEs observed were Grade 1 (mild) or Grade 2 (moderate) in intensity. Additionally, Grade 3 (severe) injection site AEs were observed infrequently. CONCLUSIONS: Application of the FDA Toxicity Grading Scale provides a uniform AE assessment tool across different adult vaccines. This post hoc summary of injection site AEs using FDA Toxicity Grading Scale provides further evidence of low frequency of severe injection site AEs post ZVL vaccination.

Electrophysiological characteristics of the frontal nerve in patients with herpetic ophthalmic neuralgia.

INTRODUCTION: The aim of this study was to explore a method for obtaining sensory nerve action potentials (SNAPs) of the supratrochlear (STN) and supraorbital (SON) nerves and evaluate the function of affected nerves in patients with herpetic ophthalmic neuralgia (HON). METHODS: Thirty healthy volunteers and 40 subjects with subacute HON participated in this study. RESULTS: The amplitudes and sensory conduction velocities (SCVs) that predicted HON were identified. The corresponding cutoff values for the amplitudes ranged from 11.10 µV to 12.45 µV. The corresponding cutoff values for the SCVs ranged from 43.14 m/s to 44.64 m/s. SCVs were markedly lower on the affected side compared with healthy volunteers (P < 0.05), and the amplitudes of SNAPs on the affected side were decreased by 36% compared with healthy volunteers (P < 0.05). DISCUSSION: SCVs of STN and SONs can be obtained with the 3-channel method and used to evaluate myelinated fibers in patients with HON. Muscle Nerve 57: 973-980, 2018.

Investigation of the Correlation between Postherpetic Itch and Neuropathic Pain over Time.

Postherpetic itch (PHI), or herpes zoster itch, is an intractable and poorly understood disease. We targeted 94 herpes zoster patients to investigate their pain and itch intensities at three separate stages of the condition (acute, subacute, and chronic). We used painDETECT questionnaire (PDQ) scores to investigate the correlation between PHI and neuropathic pain. Seventy-six patients were able to complete follow-up surveys. The prevalence of PHI was 47/76 (62%), 28/76 (37%), and 34/76 (45%) at the acute, subacute, and chronic stages, respectively. PHI manifestation times and patterns varied. We investigated the relationship of PHI with neuropathic pain using the visual analog scale (VAS), which is a measure of pain intensity, and the PDQ, which is a questionnaire used to evaluate the elements of neuropathic pain. The VAS and PDQ scores did not differ significantly between PHI-positive and PHI-negative patients. A large neuropathic component was not found for herpes zoster itch, suggesting that neuropathic pain treatments may not able to adequately control the itch. Accordingly, we suggest that a more PHI-focused therapy is required to address this condition.

A Rare Presentation of Cranial Polyneuropathy Without Rash Caused by Varicella Zoster Virus.

INTRODUCTION: Varicella Zoster Virus (VZV) is associated with many disorders of the central and peripheral nervous systems including neuralgia, meningitis, meningoencephalitis, cerebellitis, vasculopathy, myelopathy, Ramsay-Hunt syndrome, and polyneuritis cranialis. Cranial nerves V, VI, VII, VIII, IX, X, XI, and/or XII may be affected. The neurological disorders caused by VZV usually present with rash, but may rarely present without rash. CASE REPORT: We herein present a case of polyneuritis cranialis without rash caused by VZV affecting cranial nerves VII, VIII, IX, and X. After excluding other causes of the condition, we diagnosed VZV infection based on VZV DNA in the CSF and an elevated anti-VZV IgG level in serum. The patient responded well to antiviral therapy. CONCLUSION: VZV infection should be kept in mind during the differential diagnosis of polyneuritis cranialis; it is important to note that VZV re-activation may occur without rash.

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).