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ORIGINAL ARTICLE Microvascular Decompression for Hemifacial Spasm: Evaluating Outcome Prognosticators Including the Value of Intraoperative Lateral Spread Response Monitoring and Clinical Characteristics in 293 Patients Parthasarathy D. Thirumala,*† Aalap C. Shah,* Tara N. Nikonow,* Miguel E. Habeych,* Jeffrey R. Balzer,*‡ Donald J. Crammond,* Lois Burkhart,* Yue-Fang Chang,* Paul Gardner,* Amin B. Kassam,* and Michael B. Horowitz* Abstract: Hemifacial spasm is a socially disabling condition that manifests as intermittent involuntary twitching of the eyelid and progresses to muscle contractions of the entire hemiface. Patients receiving microvascular decompression of the facial nerve demonstrate an abnormal lateral spread response (LSR) in peripheral branches during facial electromyography. The authors retrospectively evaluate the prognostic value of preoperative clinical characteristics and the efficacy of intraoperative monitoring in predicting short- and long-term relief after microvascular decompression for hemifacial spasm. Microvascular decompression was performed in 293 patients with hemifacial spasm, and LSR was recorded during intraoperative facial electromyography monitoring. In 259 (87.7%) of the 293 patients, the LSR was attainable. Patient outcome was evaluated on the basis of whether the LSR disappeared or persisted after decompression. The mean follow-up period was 54.5 months (range, 9 –102 months). A total of 88.0% of patients experienced immediate postoperative relief of spasm; 90.8% had relief at discharge, and 92.3% had relief at follow-up. Preoperative facial weakness and platysmal spasm correlated with persistent postoperative spasm, with similar trends at follow-up. In 207 patients, the LSR disappeared intraoperatively after decompression (group I), and in the remaining 52 patients, the LSR persisted intraoperatively despite decompression (group II). There was a significant difference in spasm relief between both groups within 24 hours of surgery (94.7% vs. 67.3%) (P ⬍ 0.0001) and at discharge (94.2% vs. 76.9%) (P ⫽ 0.001), but not at follow-up (93.3% vs. 94.4%) (P ⫽ 1.000). Multivariate logistic regression analysis demonstrated independent predictability of residual LSR for present spasm within 24 hours of surgery and at discharge but not at follow-up. Facial electromyography monitoring of the LSR during microvascular decompression is an effective tool in ensuring a complete decompression with long-lasting effects. Although LSR results predict short-term outcomes, long-term outcomes are not as reliant on LSR activity. Key Words: HFS, Spasm, LSR, MVD, Decompression, BT, Facial nerve, CN VII, Monitoring. (J Clin Neurophysiol 2011;28: 56 –66) From the *Departments of Neurological Surgery, †Neurology, and ‡Neuroscience, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15213, U.S.A. Address correspondence and reprint requests to Parthasarathy D. Thirumala, M.D., Center for Clinical Neurophysiology, UPMC Department of Neurosurgery, UPMC Presbyterian, Suite B-400, 200 Lothrop Street, Pittsburgh, PA 15213, U.S.A.; e-mail: [email protected]. Copyright © 2011 by the American Clinical Neurophysiology Society ISSN: 0736-0258/11/2801-0056 56 H emifacial spasm (HFS) is a condition involving involuntary, repetitive, unilateral contraction of the muscles innervated by the facial nerve (cranial nerve [CN] VII). Typical HFS is caused by facial nerve irritation secondary to vascular compression at the root exit zone (RExZ), leading to involuntary, intermittent spasms beginning at the orbicularis oculi muscle and progressing down to the mentalis muscle. Neurophysiologic investigations have provided insight into the underlying mechanisms responsible for the abnormal muscle response, which appears as the lateral spread response (LSR) during routine intraoperative monitoring. Previous neurophysiologic studies (Nielsen, 1985) have demonstrated demyelination/ axonal injury and hyperexcitability of the facial motonucleus, as being responsible for the residual LSR. In a rat model, Kuroki and Moller (1994) showed that the facial motonucleus was involved in HFS, but previous injury causing demyelination (eg, pulsatile compression near the RExZ) was also required (Ruby and Jannetta, 1975). It is feasible that HFS is a total of the electrophysiologic phenomenon between the facial motonucleus, given the facilitated orthodromic activity in peripheral branches of CN VII, and demyelination. Nonsurgical treatments, such as medications and local intramuscular botulinum toxin (BT) injections, have been ineffective as long-term solutions for HFS. The only method for providing a long-term cure has been retromastoid craniotomy and facial nerve microvascular decompression (MVD), which has proved effective in curing ⬎90% of patients (Moller and Jannetta, 1984). During surgery, concurrent monitoring of brainstem auditory evoked responses is routinely used to detect eighth nerve dysfunction (Haines and Torres, 1991; Yamashita et al., 2002). The eighth cranial nerve (vestibulocochlear nerve) enables the patient to hear and is pertinent to maintaining balance and body position. Another important monitoring tool is intraoperative electromyography and recording of LSR, which can help surgeons to determine whether adequate decompression has been achieved. LSRs elicited by stimulation of the facial nerve branches denote the electrophysiologic perturbations consistent with HFS. When the offending vasculature is moved off the facial nerve, the LSR is known to disappear or become markedly attenuated. However, the practical value of LSR, as a predictor of surgical outcome and long-term prognosis, remains controversial. A retrospective study focusing on three time points (postoperative, discharge, and follow-up) was conducted on 293 patients who underwent MVD as a treatment for HFS. The study Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 Microvascular Decompression for Hemifacial Spasm FIGURE 1. A, Branches of the facial nerve (CN VII); cervical branch not depicted. B, Monitoring for the paradoxical lateral spread response (LSR). The zygomatic branch is stimulated (STIM), and an evoked EMG response can be recorded in the orbicularis oculi (REC 1). In patients with HFS, an abnormal evoked response, the LSR, can be seen in the mentalis muscle (REC 2). T, temporal; Z, zygomatic; B, buccal; M, marginal mandibular. investigated the efficacy of intraoperative monitoring in predicting spasm persistence or resolution and identified clinical characteristics that can potentially predict surgical outcome. METHODS Microvascular Decompression Between January 2000 and December 2007, our center performed 326 retromastoid MVD procedures for HFS. Preoperatively, all patients received a cranial MRI, audiometry, and facial EMG testing. Decompression was achieved by placing Teflon pledgets between the facial nerve as it exited the brainstem and the offending vessels, and/or by elevating and cauterizing compressive veins that could not be safely decompressed with Teflon. During surgery, facial EMG monitoring was performed from the initiation of general anesthesia until the time of dural closure. Stimulating needle electrodes were inserted intradermally over the zygomatic branches of the facial nerve at the middle point of a line between the ipsilateral tragus and external canthus of the eye. A 0.2- to 0.3-millisecond pulse wave with an intensity of 5 to 25 mV was applied. On stimulation of the zygomatic branch, which primarily innervated the orbicularis oculi muscle, the team recorded and reviewed the evoked LSR that appeared in the other facial muscles via peripheral branches, including the frontalis (temporal), orbicularis oris (buccal) and mentalis (marginal mandibular) muscles (Fig. 1). The eighth cranial nerve (CN VIII) function was concurrently monitored by looking for waveform shifts during the recording of brainstem auditory evoked responses. In some cases, use of neuromuscular blockade during anesthesia led to alterations in the LSR phenomenon due to muscular paralysis. Therefore, the anesthesiologist used a technique that maintained the train-of-four ratio at a level of at least 0.75. When complete decompression was achieved, the LSR was found to disappear in most patients. When the LSR persisted or simply decreased in amplitude, the surgeon looked again for persistent arterial or venous compression. Residual LSR was characterized as either an LSR that returned after initially disappearing during the procedure (after disappearing [AD]) or an LSR that persisted relatively unchanged throughout the decompression (never disappearing [ND]) (Fig. 2). After confirming that there were no further offending vessels, the surgeon terminated the procedure and closed the craniotomy in a routine fashion. from 322 operations performed on 293 patients with HFS; 29 operations were reexploration surgeries due to persistent or recurrent spasm. The patient population consisted of 103 men and 190 women ranging in age from 17 to 82 years (mean: 52.25 years). Clinical outcome data were obtained immediately after the operation, at discharge (mean: 3.91 ⫾ 1.98 days), and at a follow-up phone call during June 2008. Follow-up data were collected from 208 patients who had a minimum follow-up period of 9 months (mean: 54.5 ⫾ 27.8 months). We attempted to contact every patient identified during the record screening to obtain information regarding the patient’s present spasm status and operative complications and to confirm the accuracy of data collected from clinical notes and statements. Outcomes were divided into two categories: success (spasm relief) and failure (persistent spasm). Postoperative success was defined as complete spasm resolution with no residual twitching within 24 hours of operation and no more than two episodes of residual eye twitching before discharge. At follow-up, complete relief was defined as the reported absence of HFS, allowing for residual eye twitching at a frequency no more than one episode per month. Patients who experienced waxing and waning symptoms were asked to rate the frequency and severity of their current symptoms on a 1 to 10 scale. Patients were instructed to consider their preoperative symptoms as a 10 and rate their current symptoms in comparison to that value. Patients who reported spasm with frequency and severity ⬎3 on a 10 scale when compared with their preoperative spasm were considered to have persistent spasm. To minimize bias, an investigator other than the operating surgeons and neurophysiologists conducted all of the telephone interviews. Also, investigators responsible for collecting patient data at all three time points were blinded to LSR results. Statistical analyses were performed using SAS version 9.1.3 (SAS Institute, Cary, NC). Continuous variables were presented as mean ⫾ standard deviation and categorical variables as frequency (%). Group differences in demographic, clinical characteristics, and outcomes were assessed using t tests, 2 tests, and Fisher exact tests when appropriate. Logistic regression models were conducted to evaluate the association of LSR and outcome at each time point while adjusting for age, gender, prior BT use, platysmal spasm, preoperative facial weakness, and side of spasm. P ⬍ 0.05 was considered as statistically significant. RESULTS Data Collection and Analysis A retrospective study was conducted with Institutional Review Board approval from the University of Pittsburgh (IRB #: PR008120394). Of 326 MVD procedures, data were collected Copyright © 2011 by the American Clinical Neurophysiology Society Demographics Mean patient age was 52.25 ⫾ 12.05 years (range, 17– 82 years), with women to men ratio being 1.8:1. No patients exhibited 57 P. D. Thirumala et al. Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 FIGURE 2. Recording of the stimulus-evoked EMG responses from two different patients at the orbicularis oculi (A) and mentalis (B) muscles in response to stimulation of the zygomatic branch of the facial nerve. On decompression (arrow; A), the paradoxical LSR (mentalis) becomes variable in amplitude and morphology (after disappearing) and on complete decompression (B), the LSR eventually disappears with no significant change observed from the oculi muscle group. bilateral HFS (see Appendix, Table A2). The mean follow-up period was 54.5 ⫾ 27.8 months (range: 9 –102 months) (Table 1). Medical Hx Medical and surgical histories were obtained from each patient undergoing MVD. Twenty-two patients underwent a prior MVD at an outside institution. Two hundred seventeen patients (74.6%) received prior BT treatment, with the average time between the last injection and the most recent operation being 12 months (range: 1– 49 months). Patients who underwent BT treatment did so over a variable period (average: 4.23 years, range: 2 months–14 years). Common medications used to control HFS symptoms, including anticonvulsants and antipsychotics, are listed separately (see Appendix, Fig. A2). There was no gender bias regarding patients undergoing prior BT treatment (P ⫽ 0.561). 58 Preoperative Characteristics Seven patients had evidence of a Chiari I malformation on radiographic imaging. Nine patients had symptoms of atypical HFS (spasms began in the buccal-oral muscles and then progressed to involve the orbicularis oculi muscle). Sixty-seven (22.8%) patients exhibited moderate-to-severe preoperative facial weakness, as determined by the House-Brackmann score (House and Brackmann, 1985) (grade III and higher). Of note, patients with prior BT treatment were significantly more likely to demonstrate moderate-to-severe preoperative facial weakness (P ⫽ 0.01). One hundred thirty-seven (49.6%) patients had platysmal spasm, while 187 (85.8%) exhibited tonus (frequent eyelid locking), signs associated with an extended spasm history. One hundred twenty-six (43.0%) patients reported specific triggers that would initiate spasms. Thirty-six (12.3%) patients demonstrated functional hearing loss, as determined by the pure tone average during preoperative audiograms. Copyright © 2011 by the American Clinical Neurophysiology Society Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 TABLE 1. Summary of Demographic and Clinical Characteristics Variable No. cases Discharge data available Follow-up available Mean discharge time (days) Mean follow-up time (years) Mean age at operation (years) Gender Female Male Spasm presentation Left:right Preoperative Botox usage Tonus Platysmal spasm Specific triggers n (%) 293 (100.0) 292 (99.7) 208 (70.9) 3.91 ⫾ 1.98 4.54 ⫾ 2.32 52.25 ⫾ 12.25 190 (64.8) 103 (35.2) 164:129 217 (74.6) 187 (85.8) 137 (49.6) 126 (43.0) Microvascular Decompression for Hemifacial Spasm TABLE 3. Hemifacial Spasm Resolution Rates—Microvascular Decompression of the Facial Nerve (CN VII) All subjects Gender Male Female P Age ⬍50 ⱖ50 P Postoperative Discharge Follow-Up 88.0 (257) 90.8 (265) 92.3 (192) 90.3 (93) 86.8 (164) 0.376 95.2 (98) 88.4 (167) 0.056 98.7 (74) 88.7 (118) 0.010 90.4 (103) 86.5 (154) 0.325 91.2 (104) 90.5 (161) 0.823 93.2 (69) 91.8 (123) 0.707 Values are presented as % (n). Bold indicates statistical significance. TABLE 2. Compressing Vasculature Seen Near Facial Nerve Root Exit Zone During Operation Compressing Vessel AICA PICA VA Unnamed artery Vein Perforator n (%) 147 (50.2) 132 (45.1) 82 (28.0) 58 (19.8) 124 (42.3) 58 (19.8) AICA, anterior inferior cerebellar artery; PICA, posterior inferior cerebellar artery; VA, vertebral artery. Operative Findings Intraoperative Remarks The vessels compressing the RExZ, as identified by the surgeon, are summarized in Table 2. A majority (70.7%) of patients had multiple compressing vessels. Of 21 patients (7.2%) requiring a two-stage operation, 13 exhibited marked (ⱖ2 milliseconds) shifted brainstem auditory evoked responses during the first operation, which prompted the surgeon to terminate the procedure. Four patients had a planned staged procedure because of a preexisting Chiari I malformation (Chiari I decompressed during the first stage), while three other patients demonstrated dangerous cerebellar swelling during the first operation, which necessitated procedure termination and repeat surgery. During one operation, equipment malfunction necessitated procedure termination and a second-stage surgery. Operative Outcomes Facial spasm resolved in 257 patients (88.0%) within 24 hours of MVD (Table 3). Success rate increased to 90.8% at the time of discharge (3.91 ⫾ 1.98 days). Twenty-nine patients had persistent or recurrent spasm and underwent reexplorative surgery; results were similar to those of first-time patients undergoing MVD at each time point (see Appendix, Tables A4 and A5). It is noteworthy that 18 patients with immediate postoperative spasm experienced complete relief at discharge, and 10 patients with postoperative relief had Copyright © 2011 by the American Clinical Neurophysiology Society FIGURE 3. Outcome as a factor of demographics (age and gender). *P ⬍ 0.05. spasm recurrence by discharge. Among patients with follow-up data, only 16 patients (7.7%) had not experienced marked relief despite MVD. Of these 16 patients, 12 reported that their spasm had recurred during the follow-up time period, despite having complete postoperative relief. An additional 16 patients who were discharged with persistent spasm reported complete relief at follow-up (54.5 ⫾ 27.8 months). Although no significant gender differences were present when comparing outcomes within 24 hours of surgery (P ⫽ 0.376), a greater proportion of men had spasm resolution at discharge (95.2% vs. 88.4%) (P ⫽ 0.056). However, there was a significant gender difference in spasm relief at follow-up (98.7% vs. 88.7%) (P ⫽ 0.01) (Fig. 3). When dividing patients by age ⬍50 years and ⱖ50 years, younger patients had a slightly higher yet statistically insignificant relief rate (see Appendix, Table A1). Among patients with preoperative platysmal spasm, 22 (16.1%) experienced HFS 24 hours after the surgery. This rate was significantly greater than those without platysmal spasm (P ⫽ 0.022). There was a similar but statistically insignificant trend at discharge and at follow-up. Preoperative facial weakness also influenced operative outcome; patients with a H-B grade III or IV (moderate-to-severe) facial palsy were more likely to demonstrate persistent spasm than those with a grade I or II (mild) facial palsy within 24 hours of the surgery (P ⫽ 0.012) and at discharge (P ⫽ 0.016). Prior BT treatment did not predict a poor surgical outcome within 24 hours after the operation or at discharge. However, at the time of follow-up, 15 patients with a history of BT treatment reported persistent or recurrent spasm, whereas only one patient without prior BT continued to experience spasm (P ⫽ 0.076). There was no significant correlation between spasm laterality, preoperative 59 Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 P. D. Thirumala et al. tonus, or type of decompressed vasculature and outcome at any of the time points. Intraoperative Lateral Spread Monitoring Categorizing LSR at Termination of MVD Data regarding intraoperative monitoring of the LSR during MVD were available for 259 (87.4%) of the 293 patients. LSR on other 12.3% of patients was collected but could not be located for review at the time of this study. We divided these 259 patients into two groups, according to the disappearance (group I: LSR ⫽ 0) or persistence (group II: LSR ⬎0) of facial EMG activity immediately after decompression (see Appendix, Fig. A1). Demographic data were not significantly different between groups (Table 4). LSR disappearance (group I) was observed after facial nerve decompression in 207 of 259 patients (79.9%). Fifty-two patients (20.1%) had residual LSR postoperatively (group II). Five of these patients had an LSR amplitude increase when compared with baseline. There was no statistically significant difference between group I and II with regard to laterality, compressing vasculature, TABLE 4. Patients With Measured LSR: Demographics Parameter No. patients Gender (M:F) Age Mean age (years) No. patients aged ⬍50 years No. patients aged ⱖ50 years Operation First-time Reexploration Mean time to FUP (months) Residual LSR classification After disappearing Never disappearing Group I: LSR ⴝ 0 Group II: LSR >0 207 72:135 52 19:33 51.9 85 122 52.8 19 33 167 40 57.1 45 7 51.1 P — 0.813 0.638 0.327 — — LSR, lateral spread response; FUP, follow-up. 23 9 — — history of BT injections, or tonus/platysma involvement (Fig. 3). Although no statistical difference existed with regard to preoperative facial weakness, we observed an increasing proportion of patients with greater degrees of preoperative paresis having postoperative residual LSR (grade I, II: 15.5%; grade III: 17.0%; grade IV: 40.0%). More patients requiring venous decompression had residual postdecompression LSR (51.9%) than did those without venous involvement (42.0%) (P ⫽ 0.199). Reexploration patients (including operations at our institution) were more likely to have LSR resolution at MVD termination (85.1%) when compared with first-time operations (78.8%) (P ⫽ 0.327). Outcomes: Short-Term Prognostic Value Within group I, (patients in whom the LSR disappeared after decompression), spasms completely disappeared postoperatively in 195 of 207 patients; LSR monitoring therefore had a negative predictive value (NPV; proportion of patients without residual LSR that are spasm-free) of 94.7%. In contrast, only 67.3% of group II patients (patients in whom residual LSR was present after decompression) experienced immediate postoperative relief; the positive predictive value (proportion of patients with residual LSR that have persistent spasm) was 32.7% (Fig. 4). The specificity and sensitivity of intraoperative LSR monitoring for predicting postoperative surgical outcome were 60.7% and 84.8%, respectively (see Appendix, Table A3). There was a statistically significant difference in the postoperative spasm relief outcomes between the two groups (P ⬍ 0.0001), a trend which was also evident at discharge (94.2% vs. 76.9%) (P ⫽ 0.001). Five group II patients with postoperative spasm had complete relief by discharge. When 32 patients in group II were subdivided by whether the residual LSR was present throughout the entire operation (ND), or returned after initially disappearing during the operation (AD), no statistically significant difference in outcomes was identified. All group II patients with follow-up data whose LSR reappeared after initially resolving during the decompression (AD) described complete spasm relief at follow-up. Of six group II patients whose residual LSR was persistent during the entirety of the decompression (ND), one patient declared persistent spasm at follow-up. When separating patients in groups I and II by BT history or gender, we found no differences from the outcomes seen when FIGURE 4. Clinical characteristics of patients without residual lateral spreads (group I: lateral spread response [LSR] ⫽ 0) and with residual lateral spreads (group II: LSR ⬎0) during intraoperative electromyography. AICA, anterior inferior cerebellar artery; PICA, posterior inferior cerebellar artery; VA, vertebral artery. 60 Copyright © 2011 by the American Clinical Neurophysiology Society Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 Microvascular Decompression for Hemifacial Spasm FIGURE 5. MVD Outcomes at three major time points. A, Outcomes in patients without prior Botox treatment. B, Outcomes in patients with prior Botox treatment. C, Operative outcomes with respect to residual LSR status. ***P ⬍ 0.0005; **P ⬍ 0.005, when compared with patients without residual LSR. TABLE 5. Logistic Regression Analysis of the Association Between Perioperative Risk Factors and Spasm Persistence Postoperative Residual LSR Gender Age ⱖ50 years Prior BT use Platysmal spasm Weakness (H-B III, IV) Left-sided spasm Discharge Follow-Up OR (95% CI) P OR (95% CI) P OR (95% CI) P 9.59 (3.73–24.65) 0.75 (0.28–2.03) 1.93 (0.71–5.21) 0.42 (0.15–1.18) 5.46 (1.88–15.90) 1.86 (0.67–5.19) 0.74 (0.29–1.91) ⬍0.0001 0.572 0.197 0.098 0.002 0.238 0.537 5.50 (2.21–13.73) 0.43 (0.14–1.27) 1.04 (0.42–2.61) 0.41 (0.15–1.12) 2.74 (1.03–7.27) 1.65 (0.58–4.65) 0.95 (0.38–2.38) ⬍0.001 0.127 0.931 0.081 0.043 0.347 0.907 1.03 (0.19–5.43) 0.13 (0.02–1.07) 1.37 (0.36–5.15) 3.03 (0.34–26.92) 6.29 (1.25–31.55) 0.21 (0.02–1.77) 1.35 (0.38–4.79) 0.977 0.058 0.643 0.321 0.025 0.150 0.641 Reference group: gender (female), age ⬍50 years, no prior BT use, no platysmal spasm, H-B score 0/I/II (none or mild weakness), left-sided spasm. LSR, lateral spread response; BT, botulinum toxin; OR, odds ratio; CI, confidence interval. Bold indicates statistical significance. comparing groups I and II as a whole. In patients without previous BT use (n ⫽ 68), group I subjects (no postoperative LSR) were significantly more likely than those in group II (residual postoperative LSR) to have complete relief within 24 hours of the operation (96.3% vs. 50.0%) (P ⫽ 0.0001) and at discharge (94.4% vs. 57.1%) (P ⫽ 0.0002). This association was also true for patients with previous BT injections (n ⫽ 189) postoperatively, although with less statistical significance (94.1% vs. 75.7%) (P ⫽ 0.002). However, the outcomes of group I and II patients did not significantly differ at discharge (94.1% vs. 83.8%) (P ⫽ 0.081) when considering prior BT use (Fig. 5). Within the BT use subgroup, postoperative spasm disappeared in three patients with residual LSR by the time of discharge. When separating patients by gender, the association between residual LSR and persistent spasm was strongest within 24 hours of the operation (men: P ⫽ 0.0017; women: P ⬍ 0.0001) and remained significant for women at the time of discharge (P ⬍ 0.001). Outcomes: Long-Term Prognostic Value At the time of follow-up phone call with 208 patients, the outcomes between group I and II patients did not significantly differ (93.3% vs. 94.4%) (P ⫽ 1.000), although the NPV of LSR moniCopyright © 2011 by the American Clinical Neurophysiology Society toring for long-term outcomes was 93.3%. There was no significant statistical difference even when specifically considering patients without previous BT injections (P ⫽ 0.688), female patients (P ⫽ 1.000), and patients with recent follow-up (⬍2 years) (P ⫽ 0.402). Multivariate Logistic Regression Model The association between predisposing factors and spasm status at each time point was examined with a multivariate logistic regression model (Table 5). Predicting variables controlled for included residual LSR, gender, age (ⱖ50 years or ⬍50 years), prior BT treatment, platysmal spasm, preoperative facial weakness (H-B grade 0/I/II [absent/mild], or III/IV [moderate/severe]), and laterality (left or right). Postoperatively, persistent spasm was associated with residual LSR (odds ratio [OR]: 9.59; 95% confidence interval [CI]: 3.73–24.65; P ⬍ 0.0001) and preoperative platysmal spasm (OR: 5.46; 95% CI: 1.88 –15.90; P ⫽ 0.002). At discharge, residual LSR (OR: 5.50; 95% CI: 2.21–13.73; P ⬍ 0.001) and platysmal involvement (OR: 2.74; 95% CI: 1.03–7.27; P ⫽ 0.043) were also predictive of present spasm. However, at follow-up, only preoperative platysmal spasm was associated with persistent spasm (OR: 6.29; 95% CI: 1.25–31.55; P ⫽ 0.025). Men tended to report spasm 61 Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 P. D. Thirumala et al. less frequently than women (OR: 0.13; 95% CI: 0.02–1.07; P ⫽ 0.058). DISCUSSION CN VII MVD is an effective treatment for HFS. In our experience with 326 operations, postoperative outcomes, with respect to demographic variables, concurred with the results of previous studies (Barker et al., 1995; Ishikawa et al., 2001; Lovely et al., 1998) Men demonstrate a greater relief rate compared with women, a trend that was especially apparent at the time of followup, and patients aged 50 years and older at the time of operation have a similar resolution rate to that of younger patients (Shin et al., 1997). Although a majority of patients presented with left-sided spasm, laterality did not affect outcome. Outcome was not contingent on vessel type, although multiple vessels were frequently seen compressing the nerve. Excellent outcomes were achieved in the majority of patients within 24 hours of surgery (88.0% spasm-free). Eight additional patients achieved complete relief during their inpatient stay, increasing the resolution rate to 90.8% at discharge. Only 16 patients with follow-up (7.7%) had symptoms, demonstrating the long-lasting effects of MVD. The delayed spasm resolution may be attributed to the time required for remyelination of the damaged area, as well as the return of normal excitability of the facial motonucleus (Ishikawa, et al., 1997; Moller and Jannetta, 1985,a,b; Yamashita et al., 2001). Facial EMG monitoring aids in the perioperative diagnosis of HFS and has been considered by us to be a valuable intraoperative tool in ensuring a meticulous CN VII decompression. Pulsatile compression at the CN VII RExZ leads to the LSR (Ishikawa et al., 1996b; Jannetta et al., 1970; Moller and Jannetta, 1986). In line with recent studies (Isu et al., 1996; Kong et al., 2007; Sekula et al., 2009; Shin et al., 1997) demonstrating the usefulness of intraoperative LSR monitoring, we found that the disappearance of LSR at the end of MVD was predictive of spasm relief both immediately after the surgery (NPV ⫽ 94.7%) and at discharge. This finding was also true when focusing on individual genders and BT history, although the short-term correlation was weaker for those with prior BT injections. In light of the excellent surgical outcomes in ⬎90% of patients at discharge, we believe that intraoperative monitoring is an effective tool in identifying culprit vessels. Given the significant negative predictive value of LSR monitoring, the surgeon can be reassured that an adequate decompression has been achieved and avoid unnecessary operation time and resultant complications, especially when multiple vessels are involved. However, we did find that several patients with residual LSR were spasm-free after the surgery, reducing the positive predictive value of LSR monitoring for shortterm outcomes. This appeared to be more common when the nerve was found to be compressed by veins. In five patients with residual LSR and immediate postoperative spasm, symptoms disappeared by the time of discharge. Several more reported relief at follow-up, which detracted from the positive predictive value of LSR for long-term outcomes. All patients with follow-up data whose residual LSR reappeared after initially disappearing (AD) were spasm-free at follow-up, whereas only one patient with persistent intraoperative LSR (ND) had refractory spasm. A returning LSR (AD) may be the factor of additional minor vessel or dural involvement that resolves after hospital stay. Of note, when the LSR is found to reappear after initially disappearing, the surgeon will make the decision whether to continue surgery and look for additional compressing vasculature. Therefore, the proportion of patients with postoperative residual LSR at our center is comparatively less because several potential AD cases were resolved after further investigation into the compression. A persistent intraoperative LSR (ND), although not significantly predictive of spasm at 62 follow-up, could also be indicative of a different pathology for the patient’s spasm or an incomplete decompression. It is hypothesized that delayed LSR resolution is due to a variable duration for restoration of CN VII firing thresholds or remyelination in different patients (Goto et al., 2002; Huang et al., 1992; Ishikawa 2001; Li, 2005). In addition, BT-induced and postoperative facial weakness can make it difficult to ascertain spasm status in patients with subtle but persistent symptoms, detracting from the predictive value of the LSR in these subgroups. Some authors have described the significant predictive value of the LSR for outcomes at 1-year follow-up (Kong et al., 2007; Moller and Jannetta, 1987), whereas others question its value (Hatem et al., 2001; Joo et al., 2008; Kiya et al., 2001). We, too, investigated the predictive value of the LSR on long-term outcomes in our series. Our follow-up data were collected from patients with a mean follow-up period of 54.5 months, whereas prior studies document relatively short-term follow-up, with a mean period ⬍1 year (Sekula et al., 2009). Although we did not find a significant statistical correlation, LSR resolution was predictive of spasm relief at follow-up (NPV ⫽ 93.3%). However, residual LSR does not always correlate with a poor outcome because it may take several months for nerve excitability to normalize. Therefore, we recognize the importance of intraoperative LSR monitoring and agree with prior studies that recommend postoperative facial EMG testing. In addition to detecting when the LSR is fully normalized, postoperative testing can confirm that HFS-related complexes, synkinesis, and cross talk are eliminated and can thus be helpful in determining prognosis of persistent spasm, ascertaining recurrence, and planning for reexploration. Kim and Fukushima (1984) showed that synkinesis remains in the orbicularis oris and mentalis muscles on postoperative facial EMG monitoring 10 days after surgery. In evaluating outcomes after MVD for HFS, it is therefore important to continue observing patients with persistent spasm and discuss the likelihood of delayed resolution with the patient before considering reoperation. This can be difficult in practice because the refractory symptoms can be debilitating to the already anxious patient, and there is no guarantee of resolution even after 1 year. Also, early reoperation has been found to correlate with better outcomes compared with patients receiving late reoperations in one study (Engh et al., 2005), but complication rates for additional MVD operations need to be considered. Other institutions have advocated waiting 1 to 2 years before considering reoperation (Goto et al., 2002; Ishikawa et al., 2001; Li et al., 2005). Repeat EMGs may provide more insight into the neurophysiologic status of patients with persistent spasm and can be implemented before reoperation. The use of BT injections has long been advocated as a quick, noninvasive treatment for HFS, as well as blepharospasm (Laskawi, 2008), dystonias (Benecke and Dressler, 2007), and various other disorders involving muscle overactivity. However, BT frequently results in facial paresis (Yamashita et al., 2002). Patients also tend to become refractory to treatment, requiring larger and more frequent toxin doses over time, resulting in recurrent spasms. It is significant that almost three quarters of patients who underwent MVD have tried and been unsuccessful with BT in the past. This represents a larger proportion of patients who tried BT compared with that of previous series (Yamashita et al., 2002), pointing to increasing popularity. Although a statistically insignificant trend, the observation that 15 of 16 patients expressing persistent spasm at follow-up had received preoperative BT injections raises the issue that this drug may predispose a patient to recurrent spasm. We also found that severe preoperative facial weakness, which can occur after repeated BT treatment (House-Brackmann grade III or greater), is predictive of poor surgical outcome. To explain these findings, it Copyright © 2011 by the American Clinical Neurophysiology Society Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 is possible that paretic muscles (including those with weakness secondary to BT injections) have lower thresholds for firing during a period of spasmodic activity. A recent study suggests the HFS leads to mild facial nerve injury, which leads to greater vulnerability to BT injections (Misawa et al., 2008). In addition to preoperative paresis, involvement of the platysma muscle is another indicator of long-standing and severe spasm. Preoperative platysma muscle spasm was also found to correlate with poor outcome within 24 hours of surgery. In the univariate analyses, platysmal involvement did not correlate with spasm at discharge or follow-up, suggesting that the normal firing activity in different branches of CN VII is not immediately restored after decompression. However, we found a significant association between platysmal spasm and postsurgical spasm status when controlling for other perioperative characteristics in the multivariate analyses. Therefore, patients with these progressive symptoms are strongly encouraged to seek neurologic consultation and consider MVD to improve their prognosis after surgery. Study limitations include the inherent bias in evaluating LSR monitoring, which was actively being used to make intraoperative decisions, along with the absence of a control group. In addition, the “all-or-nothing” nature of the LSR categorization (LSR ⫽ 0 or LSR ⬎0) may account for some of the patients with persistent LSR but resolved spasm; even 95% disappearance of LSR was considered LSR persistence in this study. Finally, follow-up data may be problematic because some patients may not be objective about their clinical condition. Further investigations, which decrease the reliance on self-interpretation of surgical results, would be beneficial. CONCLUSIONS MVD for HFS is an effective treatment that can offer permanent symptom resolution. We identified preoperative clinical characteristics that affect outcome after MVD. Pertinent findings of this study include the following: Copyright © 2011 by the American Clinical Neurophysiology Society Microvascular Decompression for Hemifacial Spasm 1. Men expressed a greater relief rate compared with women at follow-up (P ⫽ 0.01). 2. A BT treatment history, which was positive in three quarters of patients, was associated with preoperative facial weakness (P ⫽ 0.01) and was also common in patients reporting spasm at follow-up (P ⫽ 0.076). 3. Preoperative facial weakness correlated with persistent spasm within 24 hours of operation (P ⫽ 0.012) and at discharge (P ⫽ 0.016), with a similar trend at the time of follow-up (P ⫽ 0.056). 4. Preoperative platysmal spasm correlated with persistent spasm within 24 hours of operation (P ⫽ 0.022) and exhibited a similar trend at the time of follow-up (P ⫽ 0.069). When controlling for other perioperative characteristics, we found a significant association of preoperative platysmal involvement with poor postoperative surgical outcome (OR: 5.46; 95% CI: 1.88 –15.90; P ⫽ 0.002), positive spasm status at discharge (OR: 2.74; 95% CI: 1.03–7.27; P ⫽ 0.043), and persistent or recurrent spasm at follow-up (OR: 6.29; 95% CI: 1.25–31.55; P ⫽ 0.025). It is recommended that patients with progressive symptoms (affecting multiple facial muscle groups) consider MVD and undergo surgery before muscles of the lower face and neck become involved. 5. LSR monitoring was predictive of surgical outcomes within 24 hours of operation (P ⬍ 0.0001) and at discharge (P ⫽ 0.001). When we adjusted for clinical and demographic variables, we found residual LSR to be significantly predictive of persistent postoperative spasm (OR: 9.59; 95% CI: 3.73–24.65; P ⬍ 0.0001) and spasm at discharge (OR: 5.50; 95% CI: 2.21– 13.73; P ⬍ 0.001). 6. Although LSR monitoring was not statistically associated with long-term reported outcomes (P ⫽ 1.00), postoperative LSR resolution was predictive of long-term spasm relief (NPV: 93.3%). 63 P. D. Thirumala et al. Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 APPENDIX FIGURE A1. LSR, lateral spread response; ND, never disappearing; AD, after disappearing. FIGURE A2. Common medications of patients referred for microvascular decompression. 64 Copyright © 2011 by the American Clinical Neurophysiology Society Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 TABLE A1. Microvascular Decompression Success Rate by Gender-Age Subgroups Age (Years) Postoperative ⬍50 ⱖ50 P Discharge ⬍50 ⱖ50 P Follow-up ⬍50 ⱖ50 P Male (%) Microvascular Decompression for Hemifacial Spasm TABLE A4. Reexploration Surgeries (University of Pittsburgh Medical Center) Female (%) 86.4 91.1 0.676 95.3 88.7 0.163 90.9 91.1 0.999 98.4 90.1 0.065 100.0 96.9 0.999 97.5 90.4 0.228 Time since previous MVD (n ⫽ 29) ⬍1 month ⬍1 year ⱖ1 year Time since recurrence (n ⫽ 17) ⱕ1 week ⬎1 week n No. Patients With Spasm 16 8 5 2 0 0 9 8 1 0 MVD, microvascular decompression. TABLE A5. Prognosis of First-Time vs. Reexploration Patients TABLE A2. Microvascular Decompression—Demographics Parameter Male Mean age (years) No. patients postoperative % patients with follow-up data (n) Mean time to follow-up (months) % with recorded (n) % with repeat operations (n) 53.2 75 68.0 (51) 66.1 84.0 (63) 12.0 (9) Female 50.9 148 66.2 (98) 70.7 89.2 (132) 18.2 (27) Outcome Postoperative Discharge Follow-up FirstTime Reexploration Patient Patient 87.6 91.6 93.6 90.2 86.3 85.7 P Redo: Redo: Other Within Institution UPMC P 0.597 86.4 (19) 93.1 (27) 0.641 0.283 90.9 (20) 82.8 (24) 0.684 0.155 78.6 (11) 90.5 (19) 0.369 Values are presented as % or % (n). UPMC, University of Pittsburgh Medical Center. TABLE A3. Predictive Value of Intraoperative Lateral Spread Monitoring on Spasm Relief During Microvascular Decompression, by Time Point Parameter test Sensitivity* Specificity† Positive predictive value‡ Negative predictive value§ 2 Postoperative Discharge Follow-Up P ⬍ 0.0001 60.7 84.8 32.7 94.7 P ⫽ 0.001 50.0 82.9 23.1 94.2 P ⫽ 1.00 16.7 80.5 5.6 93.3 Values are presented as %. *Proportion of patients with postoperative spasm that exhibit residual LSR at end of MVD. †Proportion of patients without postoperative spasm that exhibit disappearance of LSR at end of MVD. ‡Proportion of patients with residual LSR at end of MVD that exhibit postoperative persistent spasm. §Proportion of patients with disappearance of LSR at end of MVD that are without postoperative spasm. LSR, lateral spread response; MVD, microvascular decompression. Copyright © 2011 by the American Clinical Neurophysiology Society 65 Journal of Clinical Neurophysiology • Volume 28, Number 1, February 2011 P. D. Thirumala et al. 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