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1.  A comparison of three induction regimens using succinylcholine, vecuronium, or no muscle relaxant: impact on the intraoperative monitoring of the lateral spread response in hemifacial spasm surgery: study protocol for a randomised controlled trial 
Trials  2012;13:160.
Surgical microvascular decompression (MVD) is the curative treatment for hemifacial spasm (HFS). Monitoring MVD by recording the lateral spread response (LSR) intraoperatively can predict a successful clinical outcome. However, the rate of the LSR varies between trials, and the reason for this variation is unclear. The aim of our trial is to evaluate the rate of the LSR after intubation following treatment with succinylcholine, vecuronium, or no muscle relaxant.
Methods and design
This trial is a prospective randomised controlled trial of 96 patients with HFS (ASA status I or II) undergoing MVD under general anaesthesia. Patients are randomised to receive succinylcholine, vecuronium, or no muscle relaxant before intubation. Intraoperative LSR will be recorded until dural opening. The primary outcome of this study is the rate of the LSR, and the secondary outcomes are post-intubation pharyngolaryngeal symptoms, the rate of difficult intubations, the rate of adverse haemodynamic events and the relationship between the measurement of LSR or not, and clinical success rates at 30 days after surgery.
This study aims to evaluate the impact of muscle relaxants on the rate of the LSR, and the study may provide evidence supporting the use of muscle relaxants before intubation in patients with HFS undergoing MVD surgery.
Trials registration ChiCTR-TRC-11001504 Date of registration: 24 June, 2011.
The date the first patient was randomised: 30 September, 2011.
PMCID: PMC3502586  PMID: 22958580
Hemifacial spasm; Microvascular decompression; Muscle relaxant; Succinylcholine; Vecuronium; Intraoperative monitoring; Lateral spread response
2.  Intraoperative early change of latencies in Facial nerve function during Microvascular Decompression studied in patients with Hemifacial Spasm 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 89.
Primary hemifacial spasm (HFS) is reported mainly as a result of cross compression of blood vessel and facial nerve at its root exit zone (REZ). Generation of HFS could be due to hyperexcitability of facial nerve since microvascular decompression (MVD) has been an effective treatment in clinical experince of authors. Multimodal Intraoperative monitoring (MIOM) has been frequently used for care and constant evaluation of facial nerve during MVD. In HFS patients F waves of the facial muscle which is known to be induced from backfiring of facial motor nucleus, Blink reflexes and Lateral spread (abnormal muscle responses) before, during and after MVD have been used to evaluate the excitability of the facial motor nucleus and the treatment outcome after MVD procedure.
In 9 female HFS cases with abnormal lateral spread in their facial Electromyography (EMG), patients history, preoperative physical examination, electrodiagnosis and MIOM were perfored using a Moltimodal 40 channels electrophysiologic monitoring system (Nicolet Endeavor, VIASYS Healthcare, 2005, USA). Free run EMG, Stimulated EMG, bilateral blink reflexes and facial F waves were set for MIOM as indicators of MVD effectiveness.
Bilateral Orbicularis Oris/Oculi muscles were used for surface EMG recordings. Antidromic stimulatin of facial nerve branches and direct bipolar stimulation of the nerve in REZ, before and after its vascular contact at the site of operation applied by surgen. In all subjects, recordings were scheduled a week before, intaoperatively and every 2 weeks up to 3 months after operation.
In affected side of the face before MVD, threshold of F wave was reduced and excitability of blink reflex EMG responses were enhanced compared to the normal side. These responses remaind the same intraoperatively. In post operation recordings F waves and Blink reflex responses were as before in 7 subjects up to fourth week after the surgery, although with lower amplitude of the responses. These responses and Lateral spread of EMGs disappeared completely after 6 weeks. In 2 other subject these abnormal findings reduced slowly and subsequently disappeared after 12 weeks. In all cases, introperative recordings of F wave latencies and the latencies of R1 and R2 responses of blink reflexes were reduced significantly even before 20 minutes of decompression (P less than 0.03).
Propofol or Propofol/Ketamine mixture plus narcotic is suitable to obtain stable reproducible F waves and EMGs. Atracurium or other nondepolarizing muscle relaxant should be avoided. Muscle relaxants, mean arterial pressure (MAP) below 70 mmHg may cause bilateral reduction or loss of reflex responces and EMGs. In all cases, there was no postoperative clinically detectable complication.
MIOM could be useful technique in all patients undergoing any procedures around cranial nerves. Monitoring can practically reduce possibilities of neurologic deficit and reduce the potential risk of interventions around facial REZ. We conclude that in MVD for HFS, the use of stimulated EMGs for evaluating involved facial nerve is not sufficent because, practically, it could be limited to the efferent nerve fibers not the nucleuses.In these settings and similar procedures, if monitoring systems are avaiable, alternative multimodal methods with greater sensitivity and efficacy should be explored. MVD seems to be effective procedure for treatment of HFS and monitoring would help to optimise the MVD.
The study also supports the hypothesis that the hyperexcitability of the facial motor nucleus may be the main cause of hemifacial spasm. To aquire and maintain MIOM modalities, close collaboration of the anesthesioloist is nessesary.
Hemifacial spasm, Microvascular decompression, Multimodal intraoperative monitoring
PMCID: PMC3571615
3.  Monitoring of abnormal muscle response and facial motor evoked potential during microvascular decompression for hemifacial spasm 
To determine whether the monitoring of abnormal muscle response (AMR) and facial motor evoked potential (FMEP) during microvascular decompression (MVD) for hemifacial spasm (HFS) might be useful for predicting the postoperative clinical course and final outcomes.
We analyzed 45 HFS patients who underwent both AMR and FMEP monitoring during MVD. Patients were divided into two groups on the basis of post-MVD disappearance (group AMR-A) or persistence (group AMR-B) of AMR. With regard to FMEPs, patients were classified into one of the two groups according to the ratio of the final to baseline FMEP amplitudes recorded for the orbicularis oculi muscle: one group with a ratio of <50% (group FMEP-A), and the other with a ratio of ≥50% (group FMEP-B).
Twenty-one of the 26 (81%) patients in group AMR-A were assigned to group FMEP-A, whereas 9 of the 17 (53%) patients in group AMR-B were assigned to FMEP-B (P < 0.05). In 38 of the 40 (95%) patients in whom the AMRs disappeared or persisted at amplitudes <50% that at the baseline, HFS had subsided at the final follow-up. Forty of the 42 (95%) patients whose FMEP amplitude ratios indicated reduction in the amplitudes from the baseline, had complete relief of the symptoms. Nineteen of the 20 (95%) patients whose AMRs disappeared after MVD experienced immediate relief of their symptoms after the operation. With regard to 14 of the 20 (70%) patients whose AMRs persisted at the final recordings, the symptoms of HFS improved over time and eventually subsided (P < 0.001).
Intraoperative monitoring of both AMR and FMEP during MVD may be useful in predicting the postoperative outcomes in HFS patients. The AMR-related findings may help to predict whether HFS disappears immediately after surgery or some time later.
PMCID: PMC3512340  PMID: 23226604
Abnormal muscle response; facial-motor evoked potential; hemifacial spasm; microvascular decompression
4.  Repeat microvascular decompression for hemifacial spasm 
Objective: To report our experience with repeat microvascular decompression (MVD) for hemifacial spasm (HFS) in patients who have failed their first operation.
Methods: The authors describe 41 redo MVDs for HFS in 36 patients performed over a 3 year period. Seven patients underwent early re-operation after an aborted seventh nerve decompression. Eight patients underwent early re-operation for clinical failure. Eighteen patients underwent late re-operation for spasm recurrence long after their original MVD. Eight MVDs were performed on patients who had already undergone at least two prior operations.
Results: Twenty four patients experienced complete spasm resolution (70.6%), eight patients had near total resolution (23.5%), and two patients failed re-operation (5.9%). Two patients were lost to follow up (5.6%). A favourable outcome was reported by 82.4% of patients at a mean follow up interval of 18 months. A total of 91.7% of patients 50 years of age or younger were cured at follow up versus 59.1% of patients older than 50 (p = 0.04). Patients undergoing early re-operation were significantly more likely to be cured or improved than patients undergoing late re-operation (p = 0.03).
Conclusions: Repeat MVD for HFS is effective in experienced hands. Younger patients respond better to repeat MVD. Late repeat MVD for HFS is a reasonable treatment option, although results are less favourable than for early re-operation.
PMCID: PMC1739385  PMID: 16227555
5.  Time Course of Symptom Disappearance after Microvascular Decompression for Hemifacial Spasm 
This study is to investigate time course of symptom disappearance in patients whose spasm relieved completely after microvascular decompression (MVD).
Of 115 patients with hemifacial spasm (HFS) who underwent MVD from April 2003 to December 2006, 89 patients who had no facial paralysis after operation and showed no spasm at last follow-up more than 1.5 years after operation were selected. Symptom disappearance with time after MVD was classified into type 1 (symptom disappearance right after operation), type 2 (delayed symptom disappearance) and type 3 (unusual symptom disappearance). Type 2 was classified into type 2a (with postoperative silent period) and type 2b (without silent period).
Type 1, type 2a, type 2b and type 3 were 38.2%, 48.37%, 12.4% and 1.1%, respectively. Delayed disappearance group (type 2) was 60.7%. Post-operative symptom duration in all cases ranged from 0 to 900 days, average was 74.6 days and median was 14 days. In case of type 2, average post-operative symptom duration was 115.1 days and median was 42 days. Five and 3 patients required more than 1 year and 2 years, respectively, until complete disappearance of spasm. In type 2a, postoperative silent period ranged from 1 to 10 days, with an average of 2.4 days.
Surgeons should be aware that delayed symptom disappearance after MVD for HFS is more common than it has been reported, silent period can be as long as 10 days and time course of symptom disappearance is various as well as unpredictable.
PMCID: PMC2588317  PMID: 19096685
Hemifacial spasm; Microvascular decompression; Delayed resolution
6.  Effect of soluble P55 tumour-necrosis factor binding fusion protein on the local Shwartzman and Arthus reactions. 
British Journal of Pharmacology  1996;117(3):471-478.
1. In this study, the effects of a protein synthesis inhibitor, cycloheximide, and a soluble tumour necrosis factor (TNF) binding/IgG fusion protein, p55-sf2, on the priming and challenge stages of the local Shwartzman reaction (LSR) were assessed and compared with their effects on the acute inflammatory response induced by recombinant human tumour necrosis factor-alpha (rhTNF), lipopolysaccharide (LPS) and a reversed passive Arthus (RPA) reaction in rabbit skin. 2. The LSR was induced in skin by giving an intradermal (i.d.) priming injection of LPS followed by two i.v. challenge injections 20 h and 22 h later. Accumulation of 51-Cr-labelled red blood cells and [125I]-albumin were measured at 24 h as markers of haemorrhage and oedema formation, respectively. 3. The RPA reaction was induced in the rabbit by giving i.d. injections of Arthus anti-serum (anti-bovine-gamma-globulin, BGG) followed 5 min later by an i.v. injection of the antigen (BGG). Oedema formation and the accumulation of 111In-labelled neutrophils produced in the RPA reaction and in response to i.d. injection of rhTNF and LPS were measured over the 4 h period after inducing the responses. 4. A single local injection of cycloheximide (10 micrograms/site) did not inhibit neutrophil accumulation or oedema formation produced by 100% Arthus anti-sera. Although LPS injected i.d. induced a marked dose-dependent neutrophil accumulation, there was little associated plasma leakage. Cycloheximide (10 micrograms/site) did not significantly inhibit the neutrophil accumulation induced by LPS (0.1 microgram/site). In the LSR, priming i.d. injections of LPS caused a dose-dependent increase in haemorrhage and plasma leakage at skin sites after challenge with LPS (two injections of 100 micrograms, i.v.). Co-injection of a single dose of cycloheximide (10 micrograms/site) with LPS (30 micrograms/site) caused a marked reduction in the amount of haemorrhage. Local cycloheximide (10 micrograms/site) administered immediately before LSR challenge did not affect the responses produced in the LSR. 5. Neutrophil accumulation induced by TNF (0.17 micrograms/site) was abolished by co-administration of p55-sf2 (3 micrograms/site) whereas neutrophil accumulation induced by i.d. LPS and produced in the RPA reaction was not affected. In the LSR, haemorrhage and oedema formation were inhibited by p55-sf2 (3 micrograms/site) when it was administered i.d. with the LPS priming injection, but not when given i.d. immediately before LSR challenge. 6. These data suggest that the acute neutrophil accumulation produced in the RPA reaction and in response to i.d. LPS may not be dependent on local protein synthesis or TNF production. On the other hand, haemorrhage appears to be dependent on local protein synthesis during the priming phase but not during the challenge stage of the LSR. Importantly, haemorrhage and plasma leakage appear to be dependent on local TNF generation during the priming phase but not during the challenge stage of the LSR. Thus TNF appears to play a key role in the LSR in rabbit skin.
PMCID: PMC1909294  PMID: 8821536
7.  The Structure of the Oligomerization Domain of Lsr2 from Mycobacterium tuberculosis Reveals a Mechanism for Chromosome Organization and Protection 
PLoS ONE  2012;7(6):e38542.
Lsr2 is a small DNA-binding protein present in mycobacteria and related actinobacteria that regulates gene expression and influences the organization of bacterial chromatin. Lsr2 is a dimer that binds to AT-rich regions of chromosomal DNA and physically protects DNA from damage by reactive oxygen intermediates (ROI). A recent structure of the C-terminal DNA-binding domain of Lsr2 provides a rationale for its interaction with the minor groove of DNA, its preference for AT-rich tracts, and its similarity to other bacterial nucleoid-associated DNA-binding domains. In contrast, the details of Lsr2 dimerization (and oligomerization) via its N-terminal domain, and the mechanism of Lsr2-mediated chromosomal cross-linking and protection is unknown. We have solved the structure of the N-terminal domain of Lsr2 (N-Lsr2) at 1.73 Å resolution using crystallographic ab initio approaches. The structure shows an intimate dimer of two ß–ß–a motifs with no close homologues in the structural databases. The organization of individual N-Lsr2 dimers in the crystal also reveals a mechanism for oligomerization. Proteolytic removal of three N-terminal residues from Lsr2 results in the formation of an anti-parallel β-sheet between neighboring molecules and the formation of linear chains of N-Lsr2. Oligomerization can be artificially induced using low concentrations of trypsin and the arrangement of N-Lsr2 into long chains is observed in both monoclinic and hexagonal crystallographic space groups. In solution, oligomerization of N-Lsr2 is also observed following treatment with trypsin. A change in chromosomal topology after the addition of trypsin to full-length Lsr2-DNA complexes and protection of DNA towards DNAse digestion can be observed using electron microscopy and electrophoresis. These results suggest a mechanism for oligomerization of Lsr2 via protease-activation leading to chromosome compaction and protection, and concomitant down-regulation of large numbers of genes. This mechanism is likely to be relevant under conditions of stress where cellular proteases are known to be upregulated.
PMCID: PMC3374832  PMID: 22719899
8.  Predictors of lack of serological response to syphilis treatment in HIV-infected subjects 
Journal of the International AIDS Society  2014;17(4Suppl 3):19654.
The aim of this study was to determine factors associated with lack of serological response (LSR) to treatment of syphilis among HIV-infected subjects.
Materials and Methods
Retrospective, longitudinal study on HIV-infected subjects diagnosed and treated for syphilis and with an assessable serological response between 1 January 2004 and 15 September 2013. LSR was defined as a <4-fold decline of rapid plasma reagin (RPR) titer or a failed reversion to nonreactive (if RPR ≤1:4 at diagnosis) after one year since treatment. Diagnoses of syphilis were staged in early syphilis (primary, secondary and early latent) or late syphilis (tertiary and late latent) according to clinical examination and patient's history. Syphilis was classified in new infections [NI: positive RPR and TPHA (Treponema pallidum Haemagglutination assay) titers in subjects without previous history of syphilis] or re-infections [ReI: a ≥4-fold increase of RPR titer in subjects previously successfully treated for syphilis]. Syphilis treatment was prescribed according to CDC guidelines. The crude incidence rates (IRs) of LSR were calculated per 1000-person months of follow-up (PMFU) as the total number of LSR episodes divided by the cumulative time contributed by all subjects (interval time since each syphilis diagnosis and the date of ascertainment of response). Results are described as median (IQR) or frequency (%).
565 diagnoses of syphilis with an assessable serological response in 421 patients; 458 (81%) were early syphilis, 189 (33%) were NI, 376 (67%) were ReI. At first, diagnosis of syphilis median age was 41 (36–47) years, 419 (99.5%) males, 391 (93%) MSM, HIV-infected since 7.7 (3.5–12.9) years, 75 (18%) HCV or HBV co-infected, 56 (13%) with a previous AIDS diagnosis, 82 (19%) antiretroviral treatment naïve, 102 (24%) with HIV-RNA ≥50 cp/mL, CD4+=576 (437–749) cells/mm3, nadir CD4+=308 (194–406) cells/mm3. LSRs were observed in 70/565 (12.4%) treated syphilis. Incidence of LSR decreased over time [2004–2008 IR=25.1 (17.2–33.1)/1000 PMFU; 2009–2010 IR=21.1 (12.3–29.9)/1000 PMFU; 2011–2013 IR=10.6 (5.1–18.2)/1000 PMFU; Poisson regression: p=0.001]. Results of univariate and multivariate analysis on the risk of LSR are reported in Table 1.
In HIV-infected subjects we observed 12% of LSR to treatment of syphilis. LSR was associated with an older age, late syphilis, lower nadir CD4+ and detectable HIV viral load.
PMCID: PMC4224790  PMID: 25394158
9.  The Significance of Intraoperative Electromyographic “Lateral Spread” in Predicting Outcome of Microvascular Decompression for Hemifacial Spasm 
Objectives During microvascular decompression (MVD) of the facial nerve for hemifacial spasm (HFS), an abnormal muscle response can be recorded upon stimulation of the facial nerve, also known as the lateral spread response. This response may vanish after MVD and has been associated with a successful outcome. The purpose of this study was to determine if resolution of lateral spread correlated with the elimination of HFS in a single surgeon's experience.
Design and Setting (1) Retrospective analysis of 38 patients undergoing MVD with intraoperative electromyography for HFS. (2) Meta-analysis of studies from the literature.
Main Outcome Measure Presence or absence of HFS and any complications.
Results Lateral spread response was seen in 36 patients; 20 patients had full resolution. Of these, 15 patients became HFS free, and 5 five patients still had some degree of HFS. Sixteen patients had a persistent lateral spread response despite a technically successful MVD; 11 of these became spasm free, and 5 still suffered from some degree of facial twitching. Analyzing 16 studies reporting a total of 1301 patients, a significant correlation (p < 0.0001) between response cessation and resolution of HFS was found.
Conclusion The role of monitoring lateral spread response as a predictor for clinical outcome is limited.
PMCID: PMC4078166  PMID: 25072013
hemifacial spasm; intraoperative monitoring; microvascular decompression; lateral spread response
10.  Prognostic Factors of Hemifacial Spasm after Microvascular Decompression 
The factors that influence the prognosis of patients with hemifacial spasm (HFS) treated by microvascular decompression (MVD) have not been definitely established. We report a prospective study evaluating the prognostic factors in patients undergoing MVD for HFS.
From January 2004 to September 2006, the authors prospectively studied a series of 293 patients who underwent MVD for HFS. We prospectively analyzed a number of variables in order to evaluate the predictive value of independent variables for the prognosis of patients undergoing MVD. The patients were followed-up at regular intervals and divided into as cured and unsatisfactory groups based on symptom relief. Uni- and multivariate analyses were performed using logistic regression models.
A total 273 of 293 (94.2%) patients achieved symptom relief within one year after the operation. Intraoperatively, the indentation of the root exit zone was observed in 259 (88.5%) patients. Uni- and multivariate analyses revealed that the symptoms at postoperative 3 months (p<0.001) and indentation of the root exit zone (p=0.036) were associated with good outcomes.
The intraoperative finding of root exit zone indentation will help physicians determine the prognosis in patients with HFS. To predict the prognosis of HFS, a regular follow-up period of at least 3 months following MVD should be required.
PMCID: PMC2711230  PMID: 19609416
Hemifacial spasm; Microvascular decompression; Prognosis; Chronology
11.  Closed-Suction Drainage and Cerebrospinal Fluid Leakage Following Microvascular Decompression : A Retrospective Comparison Study 
We performed this study to investigate whether the use of closed-suction drainage following microvascular decompression (MVD) causes cerebrospinal fluid (CSF) leakage.
Between 2004 and 2011, a total of 157 patients with neurovascular compression were treated with MVD. MVD was performed for hemifacial spasm in 150 (95.5%) cases and for trigeminal neuralgia in 7 (4.5%) cases. The mean age of the patients was 49.8±9.6 years (range, 20-69). Dural substitutes were used in 44 (28.0%) patients. Ninety-two patients (58.6%) were underwent a 4-5 cm craniotomy using drainage (drainage group), and 65 (41.4%) did a small 2-2.5 cm retromastoid craniectomy without closed-suction drainage (no-drainage group).
Eleven (7.0%) patients experienced CSF leakage following MVD based on the criteria of this study; all of these patients were in the drainage group. In the unadjusted analyses, the incidence of CSF leakage was significantly related with the use of closed-suction drainage following MVD (12.0% in the drainage group vs. 0% in the no-drainage group, respectively; p=0.003; Fisher's exact test). Those who received dural substitutes and the elderly (cut-off value=60 years) exhibited a tendency to develop CSF leakage (p=0.075 and p=0.090, respectively; Fisher's exact test). In the multivariate analysis, only the use of closed-suction drainage was significantly and independently associated with the development of CSF leakage following MVD (odds ratio=9.900; 95% confidence interval, 1.418 to infinity; p=0.017).
The use of closed-suction drainage following MVD appears to be related to the development of CSF leakage.
PMCID: PMC3809436  PMID: 24175025
Microvascular decompression; Cerebrospinal fluid leakage; Closed-suction drainage; Hemifacial spasm; Trigeminal neuralgia
12.  Delayed Cranial Nerve Palsy after Microvascular Decompression for Hemifacial Spasm 
Microvascular decompression (MVD) for hemifacial spasm (HFS) is a safe and effective treatment with favorable outcomes. The purpose of this study was to evaluate the incidence of delayed cranirve ( VI, VII, and VIII ) palsy following MVD and its clinical courses.
Between January 1998 and December 2009, 1354 patients underwent MVD for HFS at our institution. Of them, 100 patients (7.4%) experienced delayed facial palsy (DFP), one developed sixth nerve palsy, and one patient had delayed hearing loss.
DFP occurred between postoperative day number 2 and 23 (average 11 days). Ninety-two patients (92%) completely recovered; however, House-Brackmann grade II facial weakness remained in eight other patients (8%). The time to recovery averaged 64 days (range, 16 days to 9 months). Delayed isolated sixth nerve palsy recovered spontaneously without any medical or surgical treatment after 8 weeks, while delayed hearing loss did not improve.
Delayed cranial nerve (VI, VII, and VIII) palsies can occur following uncomplicated MVD for HFS. DFP is not an unusual complication after MVD, and prognosis is fairly good. Delayed sixth nerve palsy and delayed hearing loss are extremely rare complications after MVD for HFS. We should consider the possibility of development of these complications during the follow up for MVD.
PMCID: PMC3488634  PMID: 23133714
Delayed facial palsy; Microvascular decompression; Delayed cranial palsy; Delayed hearing loss; Delayed abducens palsy
13.  The Efficacy and Safety of Microvascular Decompression for Hemifacial Spasm in Elderly Patients 
The purpose of this study was to examine the efficacy and safety of microvascular decompression (MVD) for hemifacial spasm (HFS) in elderly patients.
Between 1997 and June 2008, 1,174 patients had undergone MVD for HFS at our institute. Among these, 53 patients were older than 65 years. We retrospectively reviewed and compared the complication and the cure rates of these patients with those of younger patients.
There were 38 females and 15 males. The mean duration of symptoms of HFS of these patients was 94.6 months (range, 12-360 months), compared with 67.2 months (range, 3-360 months) in the younger group. The overall cure rate in elderly patients who underwent MVD for HFS during this period was 96.2%. Permanent cranial nerve dysfunctions, such as hearing loss and facial palsy, were seen in 2 patients (3.8%, 2/53) in the elderly group and 19 patients (1.7%, 19/1121) in the younger group. The difference in permanent cranial nerve dysfunction between the two groups was not statistically significant. There was no operative mortality in either group.
Microvascular decompression is the most effective surgical modality available for the treatment of HFS. Results of this study indicate that such technique can be performed in the elderly without higher rates of morbidity or mortality. Any patient with HFS, whose general health is acceptable for undergoing general anesthesia, should be considered as a candidate for MVD.
PMCID: PMC2899032  PMID: 20617090
Microvascular decompression; Hemifacial spasm; Elderly patients
14.  Mycobacterium tuberculosis Lsr2 Is a Global Transcriptional Regulator Required for Adaptation to Changing Oxygen Levels and Virulence 
mBio  2014;5(3):e01106-14.
To survive a dynamic host environment, Mycobacterium tuberculosis must endure a series of challenges, from reactive oxygen and nitrogen stress to drastic shifts in oxygen availability. The mycobacterial Lsr2 protein has been implicated in reactive oxygen defense via direct protection of DNA. To examine the role of Lsr2 in pathogenesis and physiology of M. tuberculosis, we generated a strain deleted for lsr2. Analysis of the M. tuberculosis Δlsr2 strain demonstrated that Lsr2 is not required for DNA protection, as this strain was equally susceptible as the wild type to DNA-damaging agents. The lsr2 mutant did display severe growth defects under normoxic and hyperoxic conditions, but it was not required for growth under low-oxygen conditions. However, it was also required for adaptation to anaerobiosis. The defect in anaerobic adaptation led to a marked decrease in viability during anaerobiosis, as well as a lag in recovery from it. Gene expression profiling of the Δlsr2 mutant under aerobic and anaerobic conditions in conjunction with published DNA binding-site data indicates that Lsr2 is a global transcriptional regulator controlling adaptation to changing oxygen levels. The Δlsr2 strain was capable of establishing an early infection in the BALB/c mouse model; however, it was severely defective in persisting in the lungs and caused no discernible lung pathology. These findings demonstrate M. tuberculosis Lsr2 is a global transcriptional regulator required for control of genes involved in adaptation to extremes in oxygen availability and is required for persistent infection.
M. tuberculosis causes nearly two million deaths per year and infects nearly one-third of the world population. The success of this aerobic pathogen is due in part to its ability to successfully adapt to constantly changing oxygen availability throughout the infectious cycle, from the high oxygen tension during aerosol transmission to anaerobiosis within necrotic lesions. An understanding of how M. tuberculosis copes with these changes in oxygen tension is critical for its eventual eradication. Using a mutation in lsr2, we demonstrate that the Lsr2 protein present in all mycobacteria is a global transcriptional regulator in control of genes required for adaptation to changes in oxygen levels. M. tuberculosis lacking lsr2 was unable to adapt to both high and very low levels of oxygen and was defective in long-term anaerobic survival. Lsr2 was also required for disease pathology and for chronic infection in a mouse model of TB.
PMCID: PMC4049101  PMID: 24895305
15.  Microvascular Decompression for Hemifacial Spasm Associated with Vertebrobasilar Artery 
Hemifacial spasm (HFS) is considered as a reversible pathophysiological condition mainly induced by continuous vascular compression of the facial nerve root exit zone (REZ) at the cerebellopontine angle. As an offending vessel, vertebrobasilar artery tends to compress much more heavily than others. The authors analyzed HFS caused by vertebrobasilar artery and described the relationships between microsurgical findings and clinical courses.
Out of 1,798 cases treated with microvascular decompression (MVD) from Jan. 1980 to Dec. 2004, the causative vessels were either vertebral artery or basilar artery in 87 patients. Seventy-nine patients were enrolled in this study. Preoperatively, computed tomography (CT) or brain magnetic resonance (MR) imaging with 3-dimentional short range MR technique was performed and CT was checked immediately or 2-3 days after anesthetic recovery. The authors retrospectively analyzed the clinical features, the compression patterns of the vessels at the time of surgery and treatment outcomes.
There were 47 were male and 32 female patients. HFS developed on the left side in 52 cases and on the right side in 27. The mean age of onset was 52.3 years (range 19-60) and the mean duration of symptoms was 10.7 years. Many patients (39 cases; 49.1%) had past history of hypertension. HFS caused only by the vertebral artery was 8 cases although most of the other cases were caused by vertebral artery (VA) in combination with its branching arteries. Most frequently, the VA and the posterior inferior cerebellar artery (PICA) were the simultaneous causative blood vessels comprising 32 cases (40.5%), and in 27 cases (34.2%) the VA and the anterior inferior cerebellar artery (AICA) were the offenders. Facial symptoms disappeared in 61 cases (77.2%) immediately after the operation and 68 cases (86.1%) showed good outcome after 6 months. Surgical outcome just after the operation was poor in whom the perforators arose from the offending vessels concurrently (p<0.05).
In case where the vertebral artery is a cause of HFS, commonly branching arteries associated with main arterial compression on facial REZ requires more definite treatment for proper decompression because of its relatively poor results compared to the condition caused by other vascular compressive origins.
PMCID: PMC2588300  PMID: 19096662
Hemifacial spasm; Vertebrobasilar artery
16.  Perioperative and long-term operative outcomes after surgery for trigeminal neuralgia: microvascular decompression vs percutaneous balloon ablation 
Head & Face Medicine  2008;4:11.
Numerous medical and surgical therapies have been utilized to treat the symptoms of trigeminal neuralgia (TN). This retrospective study compares patients undergoing either microvascular decompression or balloon ablation of the trigeminal ganglion and determines which produces the best long-term outcomes.
A 10-year retrospective chart review was performed on patients who underwent microvascular decompression (MVD) or percutaneous balloon ablation (BA) surgery for TN. Demographic data, intraoperative variables, length of hospitalization and symptom improvement were assessed along with complications and recurrences of symptoms after surgery. Appropriate statistical comparisons were utilized to assess differences between the two surgical techniques.
MVD patients were younger but were otherwise similar to BA patients. Intraoperatively, twice as many BA patients developed bradycardia compared to MVD patients. 75% of BA patients with bradycardia had an improvement of symptoms. Hospital stay was shorter in BA patients but overall improvement of symptoms was better with MVD. Postoperative complication rates were similar (21% vs 26%) between the BA and MVD groups.
MVD produced better overall outcomes compared to BA and may be the procedure of choice for surgery to treat TN.
PMCID: PMC2474589  PMID: 18597696
17.  Hemifacial Spasm and Neurovascular Compression 
The Scientific World Journal  2014;2014:349319.
Hemifacial spasm (HFS) is characterized by involuntary unilateral contractions of the muscles innervated by the ipsilateral facial nerve, usually starting around the eyes before progressing inferiorly to the cheek, mouth, and neck. Its prevalence is 9.8 per 100,000 persons with an average age of onset of 44 years. The accepted pathophysiology of HFS suggests that it is a disease process of the nerve root entry zone of the facial nerve. HFS can be divided into two types: primary and secondary. Primary HFS is triggered by vascular compression whereas secondary HFS comprises all other causes of facial nerve damage. Clinical examination and imaging modalities such as electromyography (EMG) and magnetic resonance imaging (MRI) are useful to differentiate HFS from other facial movement disorders and for intraoperative planning. The standard medical management for HFS is botulinum neurotoxin (BoNT) injections, which provides low-risk but limited symptomatic relief. The only curative treatment for HFS is microvascular decompression (MVD), a surgical intervention that provides lasting symptomatic relief by reducing compression of the facial nerve root. With a low rate of complications such as hearing loss, MVD remains the treatment of choice for HFS patients as intraoperative technique and monitoring continue to improve.
PMCID: PMC4227371  PMID: 25405219
18.  The Effect of Microvascular Decompression for Hemifacial Spasm Caused by Vertebrobasilar Dolichoectasia 
Hemifacial spasm (HFS) caused by vertebrobasilar dolichoectasia (VBD) is very rare, and in theses cases, it is difficult to decompress the nerve from its vascular compression. The objective of this study was to investigate the outcome of microvascular decompression (MVD) for HFS caused by VBD.
There were 10 patients of HFS caused by VBD at our hospital between September 1978 and September 2008. We evaluated magnetic resonance angiography (MRA) and time of flight magnetic resonance imaginge (TOF MRI) findings using the criteria for VBD. We compared the clinical outcomes of MVD for the 10 patients with VBD with the overall outcomes of the total 2058 MVDs performed for HFS.
The results of MVD for HFS caused by VBD were successful in 90.9% of cases. The postoperative complication rate in VBD was 45.5%. Offending vessels in patients with VBD were identified visually during surgery. Adverse effects after MVD were found in 4 patients. We found that the diameter of VBD was significantly greater in patients with complications than in those with no complications (p=0.028).
Our data shows that MVD may be a good treatment modality for HFS caused by VBD but care must be taken to avoid adverse effects from the procedure. It is important to detach the dolichoectatic artery from its surrounding structures sufficiently to allow it to be easily movable. In addition, attempts should be made to lessen the retraction of the cerebellum during release of the dolichoectatic artery.
PMCID: PMC3467381  PMID: 23091664
Microvascular decompression; Hemifacial spasm; Vertebrobasilar dolichoectasia
19.  Outcome of medical and surgical management in intractable idiopathic trigeminal neuralgia 
The neurovascular conflict in trigeminal neuralgia is an intractable condition; medical treatment is usually of long duration and can be annoying for both patients and clinicians.
This prospective study was designed to assess the outcome of microvascular decompression (MVD) in patients with more than 3 years' history of intractable idiopathic trigeminal neuralgia (TN) and poor response to drugs.
Materials and Methods:
Twenty-one patients (8 females and 13 males) with intractable idiopathic TN (group 1) underwent MVD and were followed up for 2 years. Group 2 (n = 15), which included 6 females and 9 males, received pharmacotherapy. The outcome responses of pain relief were evaluated using a 10-cm visual analog scale (VAS) and the Barrow Neurological Institute (BNI) scoring system. The patients' morbidity was recorded as well.
All patients fulfilling the inclusion criteria were offered MVD surgery. Freedom from pain was achieved immediately after surgery in 95.2% (n = 20) of patients in group 1, and 90.5% (n = 19) had sustained relief over the follow-up period. There were no statistical significance recurrences or surgical complications in group 1 (P>0.5), while 53.3% (n = 8) of the subjects in group 2 showed poor response with pharmacotherapy over the same period of time and many patients experienced drug intolerance that had statistical significance (P<0.01).
Early MVD in TN can help patients avoid the side effects of drugs and the adverse psychological effects of long-term pharmacotherapy and prolonged morbidity.
PMCID: PMC2824934  PMID: 20174498
Microvascular decompression; trigeminal neuralgia
20.  Hemifacial spasm: a prospective long-term follow up of 83 cases treated by microvascular decompression at two neurosurgical centres in the United Kingdom. 
OBJECTIVE--To evaluate the use of microvascular decompression (MVD) for the treatment of hemifacial spasm (HFS). METHODS--Eighty three patients with HFS who underwent MVD via a suboccipital craniectomy are presented. RESULTS--Seventy two out of seventy eight patients available for follow up remained free of any spasms at a mean follow up period of eight years. Two patients continued to have minor intermittent muscle twitches and three had recurrence of HFS. One patient's operation was not completed. Twenty had a transient complication and eight were left with permanent postoperative deficits, the commonest being unilateral sensorineural deafness. Seventy one patients declared themselves satisfied with the procedure. A causative vessel was found on the root exit zone of the seventh cranial nerve in 81 patients. CONCLUSION--The procedure seems to provide lasting relief for most patients. The correct operative technique is essential if complications are to be avoided.
PMCID: PMC486193  PMID: 8558156
21.  Long-Term Follow-Up of Microvascular Decompression for Trigeminal Neuralgia 
Skull Base  2011;21(5):313-322.
We conducted a study to evaluate the follow-up characteristics of patients with trigeminal neuralgia (TN) and to evaluate the factors affecting long-term outcome of microvascular decompression (MVD) in TN. Between 1983 and 2003, 156 patients with TN treated with MVD by 4 neurosurgeons at University Medical Centre Groningen/the Netherlands were evaluated. Baseline data from operative outcome were evaluated using univariate and multivariate analysis. The group consisted of 156 patients with TN: 90 females and 66 males with a median follow-up period of 9.7 years. The average age of initial symptoms was 51 years. The average duration of symptoms was 58 months. Postoperative 22 patients had a facial hyperpathia or hyperesthesia. Postoperatively, 137 patients had immediate relief. Postoperatively 1 year, 140 patients still had a good outcome of the operation. Twenty-seven patients with good immediate postoperative results had recurrent pain. From the group of patients with typical TN, 82% had good long-term results after operation. Patients with typical TN and immediate postoperative remission, in univariate analysis, had significantly more often an excellent/good postoperative outcome. Immediate postoperative remission is an independent predictive factor for a good long-term outcome. The long-term results of MVD in majority of patients were good with no mortalities and no major morbidities. Patients with typical TN had better long-term outcomes and less recurrence.
PMCID: PMC3312136  PMID: 22451832
Microvascular decompression; trigeminal neuralgia; typical trigeminal neuralgia; Jannetta; long-term follow-up
22.  Infranuchal Infrafloccular Approach to the More Vulnerable Segments of the Facial Nerve in Microvascular Decompressions for the Hemifacial Spasm 
We investigated the locations of compressing vessels in hemifacial spasm. To approach compression sites, we described and evaluated the efficacy of the infranuchal infrafloccular (INIF) approach.
A retrospective review of 31 consecutive patients who underwent microvascular decompression (MVD) through INIF with a minimum follow-up of 1 year was performed. Along the intracranial facial nerve, we classified the compression sites into the transitional zone (TRZ), the central nervous system (CNS) segment and the peripheral nervous system (PNS) segment. The INIF approach was used to inspect the CNS segment and the TRZ. Subdural patch graft technique was used in order to achieve watertight dural closure. The cranioplasty was performed using polymethylmethacrylate. The outcome and procedure-related morbidities were evaluated.
Twenty-nine patients (93%) showed complete disappearance of spasm. In two patients, the spasm was resolved gradually in 2 and 4 weeks, respectively. Late recurrence was noted in one patient (3%). The TRZ has been identified as the only compression site in 19 cases (61.3%), both the TRZ and CNS segment in 11 (35.5%) and the CNS segment only in 1 (3.2%). There was no patient having a compressing vessel in the PNS segment. Infection as a result of cerebrospinal fluid leak occurred in one patient (3%). Delayed transient facial weakness occurred in one patient.
The TRZ and the CNS segment were more vulnerable area to the compression of vessels. We suggest that surgical avenue with the INIF approach provides early identification of this area.c
PMCID: PMC2773391  PMID: 19893723
Hemifacial spasm; Microvascular decompression; Root exit zone
23.  Long‐term impact of multivessel disease on cause‐specific mortality after ST elevation myocardial infarction treated with reperfusion therapy 
Heart  2006;92(12):1760-1763.
To investigate the long‐term impact of multivessel coronary artery disease (MVD) on cause‐specific mortality in patients with ST elevation myocardial infarction (STEMI) treated with reperfusion therapy.
Methods and results
Patients with STEMI (n  =  395) treated with primary angioplasty or thrombolysis in the setting of a randomised clinical trial were enrolled in the study. Follow up was 8 (2) years. For patients who died all available records were reviewed to assess the specific cause of death. MVD was present in 57% of patients. Patients with MVD were older and more of them had diabetes and previous myocardial infarction. Compared with the non‐MVD group, residual left ventricular ejection fraction was lower (45.9% v 49.6%, p  =  0.001) and total mortality was higher in patients with MVD (32% v 19%, p  =  0.002). After adjustment for potential confounders this association was not significant (hazard ratio 1.4, 95% confidence interval (CI) 0.9 to 2.2). When the specific cause of death was considered, sudden death was comparable between patients with and without MVD (10% v 8%, p  =  0.49) but death caused by heart failure was significantly higher in patients with MVD (hazard ratio 7.4, 95% CI 1.7 to 32.2).
Patients with STEMI and MVD have a higher long‐term mortality than do patients with non‐MVD. MVD is not an independent predictor of long‐term total mortality or sudden death. However, MVD is a very strong and independent predictor of long‐term death caused by heart failure.
PMCID: PMC1861301  PMID: 16644856
24.  Value of Intraoperative Brainstem Auditory Evoked Potential Monitoring in Reducing the Auditory Morbidity Associated with Microvascular Decompression of Cranial Nerves 
Skull base surgery  1991;1(2):106-109.
The present study was performed to determine whether the intraoperative monitoring of brainstem auditory evoked potentials (BAEPs) during microvascular decompression operations is effective in preventing profound hearing loss or deafness in the ipsilateral ear. The authors retrospectively compared the auditory morbidity of posterior fossa microvascular decompression surgery for the treatment of tic douloureux and hemifacial spasm before and after the introduction of routine intraoperative BAEP monitoring in 1984. Each patient underwent a similar procedure performed by the same surgeon. The two patient groups were comparable with regard to age, sex, and indications for surgery, Auditory morbidity did not decline with the increasing experience of the surgeon prior to 1984; 10 (6.6%) of 152 primary operations (151 patients) in which monitoring was not performed were followed by a profound ipsilateral hearing loss or deafness. In the monitored group, none of 109 operations (104 patients) caused profound hearing loss or deafness. This significant decline in auditory morbidity is attributed by the authors to the use of intraoperative BAEP monitoring, which allows the surgeon to alter the operation in response to degradations in the wave patterns. Based on our experience and that of others, we believe that intraoperative BAEP monitoring is of value in reducing the auditory morbidity of posterior fossa microvascular decompression surgery.
PMCID: PMC1656316  PMID: 17170830
25.  The Treatment Outcome of Elderly Patients with Idiopathic Trigeminal Neuralgia : Micro-Vascular Decompression versus Gamma Knife Radiosurgery 
This study was designed to compare the efficacy of micro-vascular decompression (MVD) and Gamma knife radiosurgery (GKRS) for elderly idiopathic trigeminal neuralgia patients by analyzing the clinical outcome.
In the past 10 years, 27 elderly patients were treated with MVD while 18 patients were treated with GKRS (>65-years-old). We reviewed their clinical characteristics and clinical courses after treatment as well as the treatment outcomes. For patients who were treated with MVD, additional treatment methods such as rhizotomy were combined in some areas. In GKRS, we radiated the root entry zone (REZ) with the mean maximum dose of 77.8 (70-84.3) Gy and one 4 mm collimator.
The mean age was 68.1 years for MVD, and 71.1 years for GKS group. The average time interval between first presenting symptom and surgery was 84.1 (1-361) months, and 51.4 (1-120) months, respectively. The mean follow-up period after the surgery was 35.9 months for MVD, and 33.1 months for GKRS. According to Pain Intensity Scale, MVD group showed better prognosis with 17 (63%) cases in grade I-II versus 10 (55.6%) cases in GKRS group after the treatment. The pain recurrence rate during follow up did not show much difference with 3 (11.1%) in MVD, and 2 (11.1%) in GKRS. After the treatment, 2 cases of facial numbness, and 1 case each of herpes zoster, cerebrospinal fluid (CSF) leakage, hearing disturbance, and subdural hematoma occurred in MVD Group. In GKRS, there was 1 (5.6%) case of dysesthesia but was not permanent. Three cases were retreated by GKRS but the prognosis was not as good as when the surgery was used as primary treatment, with 1 case of grade I-II, and 1 case of recurrence. The maximal relieve of pain was seen just after surgery in MVD group, and 1 year after treatment in GKRS group.
For trigeminal neuralgia patients with advanced age, MVD showed advantages in immediately relieving the pain. However, in overall, GKRS was preferable, despite the delayed pain relief, due to the lower rate of surgical complications that arise owing to the old age.
PMCID: PMC2588323  PMID: 19096677
Elderly patient; Idiopathic trigeminal neuralgia; Micro-vascular decompression; Gamma knife radiosurgery

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