Article Figures & Data
Figures
- FIGURE 1.
Diagram overview of study design. Maximally, 4 SPECT scans were acquired: 2 at initial VNS onset and 2 during chronic follow-up. Effect of acute stimulation was investigated in initial situation (A) and in chronic situation (B). Chronic changes were evaluated between baseline, prestimulus SPECT scan and chronic situation (C). This pre-VNS study was also compared with studies of age- and sex-matched healthy individuals (D). Below timeline, t, stimulus intensity, I, is schematically shown for different conditions.
- FIGURE 2.
Relationship between 99mTc-ECD uptake in right amygdala at initial, acute VNS stimulation and long-term seizure reduction in group of 10 patients for whom long-term perfusion measurements were assessed.
- FIGURE 3.
99mTc-ECD uptake difference caused by acute, initial VNS in thalamus (right [□] and left [▴]) in relation to prestimulus z score and to age- and sex-matched template of 20 healthy volunteers.
- FIGURE 4.
Chronic 99mTc-ECD uptake changes in thalamus and mesial temporal cortex (95% confidence interval for mean). Significant decreases are indicated with asterisk. LAM = left amygdala; LHI = left hippocampus; LPH = left gyrus parahippocampus (+ fusiform gyrus); LTH = left thalamus; RAM = right amygdala; RHI = right hippocampus; RPH = right gyrus parahippocampus (+ fusiform gyrus); RTH = right thalamus.
Tables
Patient no. Age at VNS (y) Sex Handed-ness (R/L) Disease duration (y) History Preoperative findings Baseline SPECT vs. reference data Clinical Neuropsychological Ictal EEG MRI 18F-FDG PET 1 26.7 M R 15 Meningitis CPS Normal R temp occ recr Normal Normal ↓ B prefrontal, ↑ L thal 2 47.4 M R 43 Lennox-Gastaut syndrome CPS + SG (atonic) MR Electro Discrete B atrophy Normal ↓ B severe frontal & occ, ↑ R amygdala 3 24.6 F R 24 Lennox-Gastaut syndrome, corpus callosotomy CPS ± SG MR R frontal spikes Normal NA ↓ Cing post, striatum, ↑ L thal, frontal 4 39.5 F R 27 None CPS B temp dys (L more) L temp recr B hip & amygdala ↓ L hemi ↓ L frontal temp par & subcortical 5 25.5 F R 23 Lennox-Gastaut syndrome CPS ± SG B memory dys Electro, B frontal rhythmic Normal ↓ B frontal temp cerebral & L thal ↑ R occ 6 9.8 M R 8 Febrile seizures CPS ± SG NA L & R recr L hip scler, R ant temp atrophy ↓ L post frontal ↓ R > L temp 7 12.4 M R 5 None CPS ± SG NA R central recr Normal ↓ L hemi ↓ L sup temp, ↑ R frontal 8 44.5 F R 23 Meningitis, febrile seizures CPS ± SG R temp occ dys R temp recr R hip scler Normal ↓ L prefrontal & R par, ↑ L amygdala 9 36.0 M R 22 Traumatic birth CPS NA R occ recr B occ gliosis NA ↑ L thal, pons 10 44.3 F R 44 None CPS/SPS Auras L hemi recr L hip SA ↓ L temp ↑ B thal & L temp 11 40.0 M R 3 Commotio cerebri, encephalitis CPS ± SG NA B recr B small hip ↓ global ↓ L > R frontal, ↑ L temp 12 38.4 F R 30 Forceps birth CPS ± SG NA L recr Normal ↓ L > R frontal ↑ L frontal, ↓ B occ 13 41.5 F R 40 Febrile seizures CPS Normal L and R delta waves Normal ↓ L temp ↓ B frontal 14 37.0 F R 14 Meningitis CPS ± SG B mesial temp dys L temp recr B hip sclerosis ↓ L ant temp ↓ L frontal, ↑ L thal B amygdala 15 30.9 F R 9 Febrile seizures CPS ± SG R post temp focus R temp recr R mesial temp atrophy ↓ R hemi Normal 16 16.3 F R 11 None CPS ± SG/SPS B frontal dys R > L ant recr Normal ↓ B temp ↓ occ, ↑ L frontal 17 31.4 M R 11 Head trauma CPS Frontal temp par dys L frontal temp recr Scar tissue R temp neocortical ↓ R temp ↓ R temp 18 36.5 M L 30 Encephalitis CPS R frontal & midtemp dys Muscle artifact R hip scler, cerebral atrophy ↓ L mesial temp & L cerebral ↓ R temp 19 47.6 M R 34 Febrile seizures CPS B frontal dys Normal B frontal schizencephaly, cerebral atrophy Normal ↓ frontal hypo, ↑ B temp & L amygdala 20 26.8 M R 14 Premature birth, trauma capitis CPS Normal Indep B temp theta waves R hip cyst ↓ L temp frontal ↑ B occ, ↓ L frontal 21 30.9 F R 17 Febrile seizures, ALL with total cranial irradiation CPS ± SG R temp par focus, diffuse dys R post temp par recr B par atrophy ↓ R post temp ↑ B occ 22 21.4 F R 15 None CPS Memory and verbal dys R temp recr Low-grade astr L visual cortex & hip & parahip & amygdala atrophy ↓ L frontal temp Normal 23 36.0 M R 20 None CPS B mesial temp dys NA Normal ↓ L lateral temp ↓ B frontal EEG = electroencephalography; temp = temporal; occ = occipital; recr = recruitment; B = bilateral; thal = thalamus; MR = mental retardation; elect = electrodecrement; NA = not available; cing = cingulum; post = posterior; dys = dysfunction; hip = hippocampus; hemi = hemisphere; par = parietal; scler = sclerosis; ant = anterior; sup = superior; SPS = simple partial seizures; SA = structure abnormality; hypo = hypoperfusion; indep = independent; ALL = acute lymphocytic leukemia.
- TABLE 2
VNS Characteristics and Clinical Efficacy at Time of Chronic Study and at Maximum Follow-Up
Patient no. Baseline stimulus level at second SPECT (mA) Follow-up (mo) Seizure frequency (CPS/mo) Before VNS At second SPECT % Change At maximum follow-up % Change 1 1.50 28 30 20 −33 20 −33 2 — 7 30 — — 20 −33 3 — 22 180 — — 60 −67 4 1.75 23 15 4 −73 4 −73 5 — 15 90 — — 3 −97 6 — 7 50 — — 50 0 7 — 30 12 — — 9 −25 8 1.75 26 10 5 −50 0 −100 9 1.50 15 30 25 −17 25 −17 10 — 4 5 — — 0 −100 11 — 5 8 — — 6 −25 12 — 44 8 — — 4 −50 13 — 5 4 — — 4 0 14 1.50 29 3 1 −67 1 −67 15 — 48 16 — — 5 −69 16 — 40 200 — — 0 −100 17 — 4 4 — — 1 −75 18 1.25 26 4 4 0 2 −50 19 2.00 25 30 15 −50 15 −50 20 1.50 5 4 3 −25 3 −25 21 1.00 5 8 6 −25 6 −25 22 — 12 10 — — 8 −20 23 1.25 7 30 15 −50 15 −50 - TABLE 3
VOI Comparison for VNS Epilepsy Patients in Acute Phase (Group A) and for Patients Who Underwent Activation in Chronic Situation (Group B)
Area VOI size (voxels) Acute Chronic, group B (n = 10) Group A (n = 23) Group B (n = 10) Ratio (on-to-off) SD t (df = 22) P (2-tailed) Ratio (on-to-off) SD t (df = 9) P (2-tailed) Ratio (on-to-off) SD t (df = 9) P (2-tailed) Left parahippocampus* (BA 19, 35, 36) 104 0.978 0.059 −1.79 0.09† 0.992 0.067 −0.39 NS 0.998 0.049 −0.12 NS Left amygdala (BA 34) 44 1.011 0.133 0.38 NS 1.018 0.121 0.47 NS 1.008 0.073 0.35 NS Left hippocampus 67 1.002 0.073 0.13 NS 1.012 0.061 0.62 NS 1.031 0.068 1.44 NS Left thalamus 131 0.969 0.049 −2.98 0.007 0.971 0.046 −1.96 0.08† 1.044 0.030 4.59 0.001 Right parahippocampus* (BA 19, 35, 36) 105 0.973 0.036 −3.57 0.002 0.969 0.033 −2.91 0.017 0.990 0.035 −0.91 NS Right amygdala (BA 34) 47 1.025 0.112 1.07 NS 1.038 0.133 0.90 NS 1.037 0.068 1.71 NS Right hippocampus 74 0.966 0.059 −2.78 0.011 0.964 0.057 −1.98 0.08† 0.961 0.050 −2.33 0.048 Right thalamus 120 0.990 0.069 −0.66 NS 1.008 0.031 0.82 NS 1.008 0.041 0.64 NS Brain stem 137 1.006 0.060 0.47 NS 1.012 0.038 0.91 NS 1.012 0.056 0.65 NS - TABLE 4
Regional Prestimulus, Interictal z Score Versus Healthy Volunteers and Pearson Correlation with Acute Perfusion Changes Caused by VNS
Area Acute Chronic, group B (n = 10) Group A (n = 23) Group B (n = 10) z t (22 df) Pz r Pr z t (9 df) Pz r Pr z t (9 df) Pz Left parahippocampus (BA 19, 35, 36) 0.8 2.9 0.008 −0.51 0.01 0.5 1.2 NS −0.56 NS 0.8 2.9 0.016 Left amygdala (BA 34) 1.1 2.7 0.01 −0.71 0.001 1.3 1.3 NS −0.46 NS 1.5 2.2 0.06* Left hippocampus 0.6 2.7 0.02 −0.51 0.013 0.5 0.9 NS −0.26 NS 0.5 1.6 NS Left thalamus 0.9 3.1 0.005 −0.50 0.015 1.0 2.5 0.038 −0.82 0.006 0.1 0.2 NS Right parahippocampus (BA 19, 35, 36) 0.1 0.7 NS −0.26 NS 0.6 2.2 0.06* −0.64 0.06* 0 −0.2 NS Right amygdala (BA 34) 0.3 1.3 NS −0.49 0.02 0.0 0.0 NS −0.73 0.02 −0.3 −0.5 NS Right hippocampus 0.6 2.9 0.008 −0.24 NS 0.8 2.2 0.06* −0.53 NS 0.4 1.1 NS Right thalamus 0.5 1.4 NS −0.51 0.01 0.6 1.5 NS −0.72 0.02 0.2 0.5 NS Brain stem 0.2 0.5 NS −0.18 NS 0.8 1.5 NS −0.62 0.07* 0.7 1.5 NS ↵* Two-tailed significance level: P < 0.05; values up to P = 0.10 are displayed; NS = P > 0.10 (not statistically significant).
df = degrees of freedom; Pz = P for Z score; Pr = P for Pearson correlation coefficient; BA = Brodmann’s area.
- TABLE 5
Chronic Changes Caused by VNS in 10 Patients and Correlation with Follow-Up and with Initial Prestimulus Interictal z Score
Area Group B (n = 10) activity ratio, chronic vs. pre-VNS Correlations Clinical efficacy, second SPECT Clinical efficacy, maximum follow-up Prestimulus z score Ratio, 3/1 SD t (9 df) P r P r P r P Left parahippocampus (BA 19, 35, 36) 1.002 0.086 0.06 NS −0.24 NS −0.01 NS −0.30 NS Left amygdala (BA 34) 1.016 0.142 0.35 NS 0.11 NS 0.25 NS −0.86 0.006 Left hippocampus 0.990 0.110 −0.28 NS 0.41 NS 0.28 NS −0.84 0.009 Left thalamus 0.947 0.062 −2.69 0.025 0.28 NS 0.01 NS −0.23 NS Right parahippocampus (BA 19, 35, 36) 0.974 0.066 −1.23 NS 0.38 NS 0.12 NS −0.81 0.009 Right amygdala (BA 34) 0.968 0.159 −0.60 NS 0.66 0.05 0.70 0.04 −0.70 0.05 Right hippocampus 0.945 0.096 −1.71 NS 0.58 0.09* 0.85 0.004 −0.76 0.03 Right thalamus 0.966 0.046 −2.35 0.044 0.11 NS 0.53 NS 0.29 NS Brain stem 0.994 0.065 −0.29 NS 0.08 NS 0.26 NS −0.41 NS ↵* Two-tailed significance level: P < 0.05; values up to P = 0.10 are displayed; NS = P > 0.10 (not statistically significant).
df = degrees of freedom; BA = Brodmann’s area.
