Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, which lasts for at least two months. Uncontrolled studies have suggested that intravenous immunoglobulin (IVIg) could help to reduce symptoms. This is an update of a review first published in 2002 and last updated in 2013. OBJECTIVES: To assess the efficacy and safety of intravenous immunoglobulin in people with chronic inflammatory demyelinating polyradiculoneuropathy. SEARCH METHODS: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers on 8 March 2023. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) and quasi-RCTs that tested any dose of IVIg versus placebo, plasma exchange, or corticosteroids in people with definite or probable CIDP. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome was significant improvement in disability within six weeks after the start of treatment, as determined and defined by the study authors. Our secondary outcomes were change in mean disability score within six weeks, change in muscle strength (Medical Research Council (MRC) sum score) within six weeks, change in mean disability score at 24 weeks or later, frequency of serious adverse events, and frequency of any adverse events. We used GRADE to assess the certainty of evidence for our main outcomes. MAIN RESULTS: We included nine RCTs with 372 participants (235 male) from Europe, North America, South America, and Israel. There was low statistical heterogeneity between the trial results, and the overall risk of bias was low for all trials that contributed data to the analysis. Five trials (235 participants) compared IVIg with placebo, one trial (20 participants) compared IVIg with plasma exchange, two trials (72 participants) compared IVIg with prednisolone, and one trial (45 participants) compared IVIg with intravenous methylprednisolone (IVMP). We included one new trial in this update, though it contributed no data to any meta-analyses. IVIg compared with placebo increases the probability of significant improvement in disability within six weeks of the start of treatment (risk ratio (RR) 2.40, 95% confidence interval (CI) 1.72 to 3.36; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 3 to 5; 5 trials, 269 participants; high-certainty evidence). Since each trial used a different disability scale and definition of significant improvement, we were unable to evaluate the clinical relevance of the pooled effect. IVIg compared with placebo improves disability measured on the Rankin scale (0 to 6, lower is better) two to six weeks after the start of treatment (mean difference (MD) -0.26 points, 95% CI -0.48 to -0.05; 3 trials, 90 participants; high-certainty evidence). IVIg compared with placebo probably improves disability measured on the Inflammatory Neuropathy Cause and Treatment (INCAT) scale (1 to 10, lower is better) after 24 weeks (MD 0.80 points, 95% CI 0.23 to 1.37; 1 trial, 117 participants; moderate-certainty evidence). There is probably little or no difference between IVIg and placebo in the frequency of serious adverse events (RR 0.82, 95% CI 0.36 to 1.87; 3 trials, 315 participants; moderate-certainty evidence). The trial comparing IVIg with plasma exchange reported none of our main outcomes. IVIg compared with prednisolone probably has little or no effect on the probability of significant improvement in disability four weeks after the start of treatment (RR 0.91, 95% CI 0.50 to 1.68; 1 trial, 29 participants; moderate-certainty evidence), and little or no effect on change in mean disability measured on the Rankin scale (MD 0.21 points, 95% CI -0.19 to 0.61; 1 trial, 24 participants; moderate-certainty evidence). There is probably little or no difference between IVIg and prednisolone in the frequency of serious adverse events (RR 0.45, 95% CI 0.04 to 4.69; 1 cross-over trial, 32 participants; moderate-certainty evidence). IVIg compared with IVMP probably increases the likelihood of significant improvement in disability two weeks after starting treatment (RR 1.46, 95% CI 0.40 to 5.38; 1 trial, 45 participants; moderate-certainty evidence). IVIg compared with IVMP probably has little or no effect on change in disability measured on the Rankin scale two weeks after the start of treatment (MD 0.24 points, 95% CI -0.15 to 0.63; 1 trial, 45 participants; moderate-certainty evidence) or on change in mean disability measured with the Overall Neuropathy Limitation Scale (ONLS, 1 to 12, lower is better) 24 weeks after the start of treatment (MD 0.03 points, 95% CI -0.91 to 0.97; 1 trial, 45 participants; moderate-certainty evidence). The frequency of serious adverse events may be higher with IVIg compared with IVMP (RR 4.40, 95% CI 0.22 to 86.78; 1 trial, 45 participants, moderate-certainty evidence). AUTHORS' CONCLUSIONS: Evidence from RCTs shows that IVIg improves disability for at least two to six weeks compared with placebo, with an NNTB of 4. During this period, IVIg probably has similar efficacy to oral prednisolone and IVMP. Further placebo-controlled trials are unlikely to change these conclusions. In one large trial, the benefit of IVIg compared with placebo in terms of improved disability score persisted for 24 weeks. Further research is needed to assess the long-term benefits and harms of IVIg relative to other treatments.

The Impact of Microelectrode Recording on Lead Location in Deep Brain Stimulation for the Treatment of Movement Disorders.

OBJECTIVE: During deep brain stimulation (DBS) surgery, microelectrode recording (MER) leads to target refinement from the initial plan in 30% to 47% of hemispheres; however, it is unclear whether the DBS lead ultimately resides within the MER-optimized target in relation to initial radiographic target coordinates in these hemispheres. This study aimed to determine the frequency of discordance between radiographic and neurophysiologic nucleus and whether target optimization with MER leads to a significant change in DBS lead location away from initial target. METHODS: Consecutive cases of DBS surgery with MER using intraoperative computed tomography were included. Coordinates of initial anatomic target (AT), MER-optimized target (MER-O) and DBS lead were obtained. Hemispheres were categorized as "discordant" (D) if there was a suboptimal neurophysiologic signal despite accurate targeting of AT. Hemispheres where the first MER pass was satisfactory were deemed "concordant" (C). Coordinates and radial distances between 1) AT/MER-O; 2) MER-O/DBS; and 3) AT/DBS were calculated and compared. RESULTS: Of the 273 hemispheres analyzed, 143 (52%) were D, and 130 (48%) were C. In C hemispheres, DBS lead placement error (mean ± standard error of the mean) was 0.88 ± 0.07 mm. In D hemispheres, MER resulted in significant migration of DBS lead (mean AT-DBS error 2.11 ± 0.07 mm), and this distance was significantly greater than the distance between MER-O and DBS (2.11 vs. 1.09 mm, P < 0.05). Directional assessment revealed that the DBS lead migrated in the intended direction as determined by MER-O in D hemispheres, except when the intended direction was anterolateral. CONCLUSIONS: Discordance between radiographic and neurophysiologic target was seen in 52% of hemispheres, and MER resulted in appropriate deviation of the DBS lead toward the appropriate target. The actual value of the deviation, when compared with DBS lead placement error in C hemispheres, was, on average, small.

Do older patients with acute or subacute subdural hematoma benefit from surgery?

PURPOSE: According to the international guidelines, acute subdural hematomas (aSDH) with a thickness of >10 mm, or causing a midline shift of >5 mm, should be surgically evacuated. However, high mortality rates in older patients resulted in ongoing controversy whether elderly patients benefit from surgery. We identified predictors of outcome in a single-centre cohort of elderly patients undergoing surgical evacuation of aSDH or subacute subdural hematoma (saSDH). MATERIALS AND METHODS: This retrospective study included all patients aged ≥65 years undergoing surgical evacuation of aSDH/saSDH from 2000 to 2015. One-year outcome was dichotomized into favourable (Glasgow Outcome Scale (GOS) 4-5) and unfavourable (GOS 1-3). Predictors of outcome were identified by analysing patient characteristics. RESULTS: Eighty-four patients aged ≥65 years underwent craniotomy for aSDH/saSDH during the 16 year time period. Twenty-five percent regained functional independence, 11% survived severely disabled, and 64% died. Most patients died of respiratory failure following withdrawal of artificial respiration or following restriction of treatment. Age of the SDH or Glasgow Coma Scores ≤8/intubation did not predict unfavourable outcome. All patients with bilaterally absent pupillary light reflexes died, also those who still exhibited one normal-sized pupil. CONCLUSION: The low number of operated patients per year probably suggests that this cohort represents a selection of patients who were judged to have good chances of favouring from surgery. Functional independence at one-year follow-up was reached in 25% of patients, 64% died. Patients with bilaterally absent pupillary light reflexes did not benefit from surgery. The tendency to restrict treatment because of presumed poor prognosis may have acted as a self-fulfilling prophecy.

Accuracy of Microelectrode Trajectory Adjustments during DBS Assessed by Intraoperative CT.

BACKGROUND/AIMS: Microelectrode recording (MER)-guided deep brain stimulation (DBS) aims to place the DBS lead in the optimal electrophysiological target. When single-track MER or test stimulation yields suboptimal results, trajectory adjustments are made. The accuracy of these trajectory adjustments is unknown. Intraoperative computed tomography can visualize the microelectrode (ME) and verify ME adjustments. We aimed to determine the accuracy of ME movements in patients undergoing MER-guided DBS. METHODS: Coordinates following three methods of adjustment were compared: (1) those within the default "+" configuration of the ME holder; (2) those involving rotation of the default "+" to the "x" configuration; and (3) those involving head stage adjustments. Radial error and absolute differences between coordinates were determined. RESULTS: 87 ME movements in 59 patients were analyzed. Median (IQR) radial error was 0.59 (0.64) mm. Median (IQR) absolute x and y coordinate errors were 0.29 (0.52) and 0.38 (0.44) mm, respectively. Errors were largest after rotating the multielectrode holder to its "x"-shaped setup. CONCLUSION: ME trajectory adjustments can be made accurately. In a considerable number of cases, errors exceeding 1 mm were found. Adjustments from the "+" setup to the "x" setup are most prone to inaccuracies.

Borders of STN determined by MRI versus the electrophysiological STN. A comparison using intraoperative CT.

BACKGROUND: It is unclear which magnetic resonance imaging (MRI) sequence most accurately corresponds with the electrophysiological subthalamic nucleus (STN) obtained during microelectrode recording (MER, MER-STN). CT/MRI fusion allows for comparison between MER-STN and the STN visualized on preoperative MRI (MRI-STN). OBJECTIVE: To compare dorsal and ventral STN borders as seen on 3-Tesla T2-weighted (T2) and susceptibility weighted images (SWI) with electrophysiological STN borders in deep brain stimulation (DBS) for Parkinson's disease (PD). METHODS: Intraoperative CT (iCT) was performed after each MER track. iCT images were merged with preoperative images using planning software. Dorsal and ventral borders of each track were determined and compared to MRI-STN borders. Differences between borders were calculated. RESULTS: A total of 125 tracks were evaluated in 45 patients. MER-STN started and ended more dorsally than respective dorsal and ventral MRI-STN borders. For dorsal borders, differences were 1.9 ± 1.4 mm (T2) and 2.5 ± 1.8 mm (SWI). For ventral borders, differences were 1.9 ± 1.6 mm (T2) and 2.1 ± 1.8 mm (SWI). CONCLUSIONS: Discrepancies were found comparing borders on T2 and SWI to the electrophysiological STN. The largest border differences were found using SWI. Border differences were considerably larger than errors associated with iCT and fusion techniques. A cautious approach should be taken when relying solely on MR imaging for delineation of both clinically relevant STN borders.

Optimization of Microelectrode Recording in Deep Brain Stimulation Surgery Using Intraoperative Computed Tomography.

BACKGROUND: Microelectrode recording (MER) is used to confirm targeting accuracy during deep brain stimulation (DBS) surgery. We describe a technique using intraoperative computed tomography (CT) extrapolation (iCTE) to predetermine and adjust the trajectory of the guide tube to improve microelectrode targeting accuracy. We hypothesized that this technique would decrease the number of MER tracks and operative time, while increasing the recorded length of the subthalamic nucleus (STN). METHODS: Thirty-nine patients with Parkinson's disease who underwent STN DBS before the iCTE method were compared with 33 patients undergoing STN DBS using iCTE. Before dural opening, a guide tube was inserted and rested on dura. Intraoperative computed tomography (iCT) was performed, and a trajectory was created along the guide tube and extrapolated to the target using targeting software. If necessary, headstage adjustments were made to correct for error. The guide tube was inserted, and MER was performed. iCT was performed with the microelectrode tip at the target. Coordinates were compared with planned/adjusted track coordinates. Radial error between the MER track and the planned/adjusted track was calculated. Cases before and after implementation of iCTE were compared to determine the impact of iCTE on operative time, number of MER tracks and recorded STN length. RESULTS: The use of iCTE reduced the average radial MER track error from 1.90 ± 0.12 mm (n = 54) to 0.84 ± 0.09 mm (n = 49) (P < 0.001) while reducing the operative time for bilateral lead placement from 272 ± 9 minutes (n = 30) to 233 ± 10 minutes (n = 24) (P < 0.001). The average MER tracks per hemisphere was reduced from 2.24 ± 0.13 mm (n = 66) to 1.75 ± 0.09 mm (n = 63) (P < 0.001), whereas the percentage of hemispheres requiring a single MER track for localization increased from 29% (n = 66) to 43% (n = 63). The average length of recorded STN increased from 4.01 ± 0.3 mm (n = 64) to 4.75 ± 0.28 mm (n = 56) (P < 0.05). CONCLUSION: iCTE improves microelectrode accuracy and increases the first-pass recorded length of STN, while reducing operative time. Further studies are needed to determine whether this technique leads to less morbidity and improved clinical outcomes.

Improving the accuracy of microelectrode recording in deep brain stimulation surgery with intraoperative CT.

Microelectrode recording (MER) is used to confirm electrophysiological signals within intended anatomic targets during deep brain stimulation (DBS) surgery. We describe a novel technique called intraoperative CT-guided extrapolation (iCTE) to predict the intended microelectrode trajectory and, if necessary, make corrections in real-time before dural opening. Prior to dural opening, a guide tube was inserted through the headstage and rested on dura. Intraoperative CT (iCT) was obtained, and a trajectory was extrapolated along the path of the guide tube to target depth using targeting software. The coordinates were recorded and compared to initial plan coordinates. If needed, adjustments were made using the headstage to correct for error. The guide tube was then inserted and MER ensued. At target, iCT was performed and microelectrode tip coordinates were compared with planned/adjusted track coordinates. Radial error between MER track and planned/adjusted track was calculated. For comparison, MER track error prior to the iCTE technique was assessed retrospectively in patients who underwent MER using iCT, whereby iCT was performed following completion of the first MER track. Forty-seven MER tracks were analyzed prior to iCTE (pre-iCTE), and 90 tracks were performed using the iCTE technique. There was no difference between radial error of pre-iCTE MER track and planned trajectory (2.1±0.12mm) compared to iCTE predicted trajectory and planned trajectory (1.76±0.13mm, p>0.05). iCTE was used to make trajectory adjustments which reduced radial error between the newly corrected and final microelectrode tip coordinates to 0.84±0.08mm (p<0.001). Inter-rater reliability was also tested using a second blinded measurement reviewer which showed no difference between predicted and planned MER track error (p=0.53). iCTE can predict and reduce trajectory error for microelectrode placement compared with the traditional use of iCT post MER.