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Research Article| Volume 13, ISSUE 6, P366-374, September 2004

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Abnormal quantitative EEG scores identify patients with complicated idiopathic generalised epilepsy

Open ArchiveDOI:https://doi.org/10.1016/j.seizure.2003.09.012
Abnormal quantitative EEG scores identify patients with complicated idiopathic generalised epilepsy
Previous ArticleObituary to Pierre Loiseau
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      Abstract

      Objective: To investigate the relationship between quantitative EEG (QEEG) scores and “complicating factors” (psychopathology, true pharmacoresistance, neurological symptoms) in idiopathic generalised epilepsy (IGE). Methods: 35 newly referred, newly diagnosed, unmedicated IGE patients were collected in a prospective and random manner. Standard neuro-psychiatric and EEG examination was done. The patients were treated and controlled at regular visits. After 2 years of follow-up, clinical data were summarised and were compared to QEEG results. Clinical target items were neurologic and psychiatric abnormalities, proven pharmacoresistance. Patients with at least one of these items were labelled “complicated”, whereas patients without these additional handicap were labelled as “uncomplicated”. The 12 QEEG target variables were: Z-transformed absolute power values for three (anterior, central, posterior) brain regions and four frequency bands (1.5–3.5; 3.5–7.5; 7.5–12.5; 12.5–25.0 Hz). QEEG scores outside the ±2.5 Z range were accepted as abnormal. The overall QEEG result was classified as normal (0–2 abnormal scores), or pathological (3 or more abnormal scores). Clinical and QEEG results were correlated. Results: All patients with psychopathology showed 4–8 positive pathological scores (power excess not confined to a single cortical region or frequency band). The two patients with pure pharmacoresistance showed pathological negative values (delta power deficit) all over the scalp. Statistically significant (P<0.001) association was found between patients with uncomplicated IGE and normal QEEG, and between complicated IGE and pathological QEEG. Patients with neurological items had normal QEEG. Conclusion: Higher degree of cortical dysfunction (as assessed in the clinical setting) is reflected by higher degree of QEEG abnormalities. QEEG analysis can differentiate between IGE patients with or without psychopathology. Forecasting psychopathology may be the practical application of the findings.

      Keywords

      Introduction

      Idiopathic generalised epilepsy (IGE) syndromes are overlapping electro-clinical entities. According to the definition elaborated by an ILAE Committee, “the patient usually has a normal interictal state, without neurologic and neuroradiologic signs”.

      ILAE Commission on Classification and Terminology: proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389–99.

      The majority of IGE patients can be successfully treated with standard antiepileptic drugs.
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      • de la Cruz N.
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      Monotherapy with valproate in primary generalised epilepsies.
      Epilepsia. 1987; 28: S8-S11
      Diagnosis and treatment is not always easy, however, 15.5% of juvenile myoclonic epilepsy patients are resistant to antiepileptic drugs despite correct therapy and lifestyle.
      • Genton P.
      • Gelisse P.
      • Thomas P.
      • Bartolomei F.
      • Rey M.
      • Dravet C.
      Clinical factors of drug-resistance in patients with juvenile myoclonic epilepsy.
      Epilepsia. 1999; 40: 212
      . About 25% of these patients has psychiatric and psychological problems that can counteract therapeutic efforts.

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      , 
      • Gelisse P.
      • Genton P.
      • Raybaud C.
      • Thomas P.
      • Dravet C.
      Structural brain lesions do not influence the prognosis of juvenile myoclonic epilepsy.
      Acta. Neurol. Scand. 2000; 102: 188-191
      . The negative impact of cognitive and personality disturbances on seizure control and quality of life has been confirmed repeatedly. Besides average intelligence, these young people are inclined to follow their momentary feelings and impulsions which results in instable, childish behaviour sometimes reaching the degree of levity. Planning their own future is often lacking because they are “… more inclined to take things as they come than to act in accordance with an independent line of conduct” as Janz wrote.

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      This sort of personality disturbance results in neglecting and dissimulating seizures, irregular intake of medication, ignoring proven seizure-provoking factors like sleep deprivation. In this way the patients are likely to suffer of self-provoked seizures and, in turn, self-perpetuated social maladjustment.

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      , 

      Janz D. Pitfalls in the diagnosis of grand mal on awakening. In: Wolf P, editor. Epileptic seizures and syndromes. John Libbey Co., Ltd.; 1994. p. 213–20.

      , 
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      Frontal functions in juvenile myoclonic epilepsy.
      Neuropsychiat. Neuropsychol. Behav. Neurol. 1997; 10: 243-246
      , 

      Janz D, Durner M. Juvenile myoclonic epilepsy. In: Engel J, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven Publishers; 1997. p. 2389–400.

      . Neurological signs and abnormal radiological findings (in standard CT and MRI scans) may occur but have no impact on treatment and prognosis.
      • Genton P.
      • Gelisse P.
      • Thomas P.
      • Bartolomei F.
      • Rey M.
      • Dravet C.
      Clinical factors of drug-resistance in patients with juvenile myoclonic epilepsy.
      Epilepsia. 1999; 40: 212
      , 
      • Gelisse P.
      • Thomas P.
      • Samuelian J.
      • Roger J.
      • Genton P.
      Psychiatric disorders in patients with juvenile myoclonic epilepsy.
      Epilepsia. 1999; 40: 273
      Focal features in IGE patients can hinder correct diagnosis, however.
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      • Asconapé J.J.
      • Kiffin Penry J.
      Clinical and EEG asymmetries in juvenile myoclonic epilepsy.
      Epilepsia. 1994; 35: 302-306
      Early recognition of these difficulties, in particular, psychopathology, can promote planning of effective treatment strategies.

      Janz D. Pitfalls in the diagnosis of grand mal on awakening. In: Wolf P, editor. Epileptic seizures and syndromes. John Libbey Co., Ltd.; 1994. p. 213–20.

      , 

      Janz D, Durner M. Juvenile myoclonic epilepsy. In: Engel J, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven Publishers; 1997. p. 2389–400.

      The problem is that recognition of these complicating factors is not always easy. Neurological signs and mental retardation can be recognised at the first examination. In contrast, a peculiar personality trait that highly counteracts effective treatment

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      may be unrecognised at the first visit. Usually, analysis of recurrent therapeutic failures highlights that psychopathology is the cause of pseudoresistance. In cases of “pseudoresistance”, the causes of persistent seizures are irregular intake of the drug and/or ignoring appropriate lifestyle by the patients. Also true pharmacoresistance cannot be diagnosed at the first visit.
      Advanced neuroimaging studies and neuropathology revealed that the brain of IGE patients is not entirely normal in terms of structure and function.
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      Central benzodiazepine/gamma-aminobutyric acid A receptors in idiopathic epilepsy: an [Math Eq]flumazenil positron emission study.
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      Quantitative MRI in patients with idiopathic generalised epilepsy. Evidence of widespread cerebral structural changes.
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      Specific features of disturbance of cortical development in generalised epilepsies.
      Epilepsia. 1999; 40: 74
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      Epilepsia. 1999; 40: P44
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      Valproate monotherapy in juvenile myoclonic epilepsy: dose-related effects on electroencephalographic and other neurophysiological tests.
      Ther. Drug Monit. 1999; 21: 91-96
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      • Savic I.
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      • Helms G.
      MR spectroscopy shows reduced frontal lobe concentrations of N-acetylaspartate in patients with juvenile myoclonic epilepsy.
      Epilepsia. 2000; 41: 290-296
      . Mild cortical pathology not detected by routine MRI probably contributes to neuro-psychiatric problems.
      • Devinsky O.
      • Gershengorn J.
      • Brown E.
      • Perrine K.
      • Vazquez B.
      • Luciano D.
      Frontal functions in juvenile myoclonic epilepsy.
      Neuropsychiat. Neuropsychol. Behav. Neurol. 1997; 10: 243-246
      , 
      • Swartz B.E.
      • Simpkins F.
      • Helgren E.
      • Mandelkern M.
      • Brown C.
      • Krisdakumtorn T.
      • et al.
      Visual working memory in primary generalised epilepsy: an 18FDG-PET study.
      Neurology. 1996; 47: 1203-1212
      Interestingly, the percentage of IGE patients with psychiatric disturbances

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      , 
      • Gelisse P.
      • Genton P.
      • Raybaud C.
      • Thomas P.
      • Dravet C.
      Structural brain lesions do not influence the prognosis of juvenile myoclonic epilepsy.
      Acta. Neurol. Scand. 2000; 102: 188-191
      . is roughly equal to the percentage of IGE patients with significant cortical abnormalities detected by voxel-based MRI.
      • Woermann F.G.
      • Free S.L.
      • Koepp M.J.
      • Sisodiya S.M.
      • Duncan J.S.
      Abnormal cerebral structure in juvenile myoclonic epilepsy demonstrated with woxel-based analysis of MRI.
      Brain. 1999; 122: 2101-2108
      Some indirect evidence suggest that cortical pathology might contribute to pharmacoresistance, too.
      • Genton P.
      • Gelisse P.
      • Thomas P.
      • Bartolomei F.
      • Rey M.
      • Dravet C.
      Clinical factors of drug-resistance in patients with juvenile myoclonic epilepsy.
      Epilepsia. 1999; 40: 212
      , 
      • Fernando-Dongas M.C.
      • Radtke R.A.
      • VanLandingham K.E.
      • Husain A.M.
      Characteristics of valproic acid resistant juvenile myoclonic epilepsy.
      Seizure. 2000; 9: 385-388
      . In the light of these findings, it is reasonable to suppose that IGE patients with complicating factors have higher degree of cortical dysfunction than IGE patients without such additional handicaps. For several reasons, sophisticated neuroimaging can hardly be used as a routine screening method for cerebral abnormalities that are associated with psychopathology and pharmacoresistance. In contrast, quantitative EEG (QEEG) analysis is a proven tool to assess the degree and pattern of cortical dysfunction.
      • Nuwer M.
      Quantitative EEG: 1. Techniques and problems of frequency analysis and topographic mapping.
      J. Clin. Neurophysiol. 1988; 5: 1-43
      , 
      • John E.R.
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      In a prior study we found that a group of IGE patients showed significant diffuse quantitative EEG alterations as compared to a healthy control group.
      • Clemens B.G.
      • Szigeti Z.
      Barta: EEG frequency profiles of idiopathic generalised epilepsy syndromes.
      Epilepsy Res. 2000; 42: 105-115
      . In that study we did not address the distribution of the QEEG abnormalities across the patients. Now we formulated and tested the hypotheses that (1) IGE patients do not have the same degree of QEEG abnormality, (2) higher degree of cortical dysfunction (as assessed in the clinical setting) might be reflected by higher degree of QEEG abnormalities.

      Methods

      The design of this study was approved by the Local Ethics Committee of the Institution. In a period of 2.5 years, all the newly referred patients who fulfilled inclusion criteria entered this investigation. Inclusion criteria were as follows: (1) newly diagnosed IGE (juvenile absence epilepsy, juvenile myoclonic epilepsy, epilepsy with generalised tonic-clonic seizures on awakening). The diagnosis was based on concordant clinical and EEG results.

      ILAE Commission on Classification and Terminology: proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389–99.

      Definition of the term “newly diagnosed” was a seizure history of 1 year or less. (2) No systemic or neuro-psychiatric illness except IGE. (3) No regular alcohol or drug use or misuse (contraceptives were allowed). (4) Freedom from any medications in the 5 days before EEG investigation. (5) Standard EEG record of good quality, according to recommendations for quantitative EEG studies.
      • Nuwer M.
      • Lehmann D.
      • Lopes da Silva F.
      • Matsuoka S.
      • Sutherling W.
      Jean-Francois Vibert: IFCN guidelines for topographic and frequency analysis of EEGs and EPs. Report of an IFCN committee.
      Electroencephalogr. Clin. Neurophysiol. 1994; 91: 1
      . Patients who had got generalised tonic-clonic seizures in the 3 days before EEG, or took any medication in the 5 days before EEG investigation, were excluded. All the patients were diagnosed, treated, and followed at the Outpatient Service of our Institution. History taking, routine neuro-psychiatric evaluation, conventional EEG evaluation were done at the first visit. Indications of cranial MRI were the presence of neurological items, and later, pharmacoresistance. Treatment with valproate was indicated in all the patients. No extra investigation was done, no treatment was postponed or tapered off for study purposes. Patients were followed at regular visits. In case of therapeutic failure, potential causes were analysed. In difficult-to-treat cases other drugs (lamotrigine, ethosuximide) or combinations of these drugs were administered. In cases of personality disturbances and pseudoresistance, psychotherapy was indicated. Final evaluation of the patients was done after 2 years of follow-up. Based on the clinical data accumulated in this period, patients were classified as uncomplicated (no neurologic or mental problems interictally, responders to drugs), or complicated (any cerebral damage in the patient’s history, neurological symptoms, psychiatric symptoms, personality disorder, pharmacoresistance). In this paper, the term “personality disorder” refers to the peculiar trait that is characteristic to IGE patients,

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      as described in the Introduction section of this paper. Part of this personality disturbance is neglecting and dissimulating seizures, irregular intake of medication, ignoring proven seizure-provoking factors. As a consequence, the patients are prone to self-perpetuated social maladjustment. This condition should be recognised in the clinical setting as soon as possible; psychological testing is not necessary.

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      , 

      Janz D. Pitfalls in the diagnosis of grand mal on awakening. In: Wolf P, editor. Epileptic seizures and syndromes. John Libbey Co., Ltd.; 1994. p. 213–20.

      , 

      Janz D, Durner M. Juvenile myoclonic epilepsy. In: Engel J, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven Publishers; 1997. p. 2389–400.

      All the EEG recordings were done in the forenoon hours, in the same semi-isolated room, with the same equipment (Brain Quick BQ240) by trained personnel, according to recommended standards for quantitative EEG studies.
      • Nuwer M.
      • Lehmann D.
      • Lopes da Silva F.
      • Matsuoka S.
      • Sutherling W.
      Jean-Francois Vibert: IFCN guidelines for topographic and frequency analysis of EEGs and EPs. Report of an IFCN committee.
      Electroencephalogr. Clin. Neurophysiol. 1994; 91: 1
      . Silver–silver chloride electrodes were placed according to the 10–20 system, fixed by appropriate adhesive and conductive gel. Impedances did not exceed 5 kΩ. 19-channel EEG was recorded against a linked ears reference. In addition, two bipolar derivations were used to identify oculographic and myogenic artefacts. 12-bit on-line digitisation was used. Sampling frequency was 128 s−1. Forty minutes EEG was recorded in the resting, eyes-closed condition. The patients

      ILAE Commission on Classification and Terminology: proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389–99.

      level of vigilance was verbally checked during the recording. EEG records were stored on optical disc. Off-line frequency analysis started with data file conversion to the format of the Neurometric Analysis System (NAS, Version 23.5). Sixty 2-s epochs reflecting relaxed–waking state of the subjects were selected for spectral analysis. Sample selection and analysis was done blindly, without knowing the patient’s name and clinical data. Our standardised epoch selection protocol was used. Epoch inclusion criteria were: (1) presence of continuous physiological (“waking” or “resting”) alpha activity with alpha voltage maximum in posterior regions; (2) absence of artefacts, epileptiform or other nonstationary elements; (3) absence of patterns indicating drowsiness or arousal. After final visual revision of the edited epochs, they were submitted to Fast Fourier Transform (FFT). Leakage was reduced by Hanning window. Data of the 60 epochs were averaged. Absolute band power was computed for 19 monopolar derivations and four frequency bands (delta: 1.5–3.5 Hz, theta: 3.5–7.5 Hz, alpha: 7.5–12.5 Hz, beta: 12.5–25.0 Hz). NAS evaluated all neurometric parameters relative to its own normative database, using age-regression equations. Independent of age, sex and derivation, deviations of the individual values from the normative mean were expressed in Z-score.

      John E, Prichep L, Ahn H, Kaye H, Brown D, Easton P, et al. Neurometric evaluation of brain function in normal and learning disabled children. Ann Arbour: University of Michigan Press; 1989.

      In order to get regional spectral variables, electrode-related values were compressed by averaging. Delta, theta, alpha, beta power was computed for anterior region (ANT, composed of Fp1, Fp2, F3, F4, F7, F8, Fz values), central region (CENT, composed of T3, T4, C3, C4, Cz values), and posterior region (POST, composed of P3, P4, Pz, T5, T6, O1, O2 values).
      Deviation of these 12 EEG variables from the mean (Z=0) were evaluated in all the patients. Deviations of (Z>±2.5) were scored as abnormal. The number and distribution of abnormal neurometric scores were compared in the patients with and without complicating factors.
      Depending on the amount of abnormal scores, the QEEG finding was classified as “normal QEEG” (less than two abnormal scores), or, “pathological QEEG” (two or more abnormal scores). Binomial distributions were analysed by means of Fisher’s exact test (GraphPad Prism 2.0). Differences with P≤0.05 were accepted as statistically significant.

      Results

      Thirty-five patients were investigated, treated and controlled (16 males, 19 females, age limits: 12–24 years, average: 17 years). Their clinical data are summarised in Table 1. Eleven patients were classified as complicated. Neurological items were found in three patients; their cranial MRI was within normal limits, however. Minor psychiatric disturbances were diagnosed in two patients (mild mental retardation and compulsive self-stimulation, respectively) at the first investigation. Personality disorder of the Janz type

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      was found in three patients who had juvenile myoclonic epilepsy. It was never identified at the initial investigation, but could be recognised at follow-up visits, within 2 years after the first visit. One patient displayed absence-like pseudoseizures in the course of the illness. Treatment was effective in 32 patients. Despite difficulties due to non-compliance, also two patients with personality disorder could be treated successfully. One patient with personality disorder and two patients without neuro-psychiatric items showed proven pharmacoresistance to valproate, lamotrigine, ethosuximide, and combinations.
      Table 1Clinical and quantitative EEG data of the patients.
      BandClinical itemsANTCENTPOST
      Patient 1
       Delta0.310880.8476080.491416
       Theta1.4248241.658450.016648
       Alpha1.9291231.470671.001024
       Beta1.8029241.2651550.904999
      Patient 2
       DeltaRight central facial palsy−1.63885−0.82875−1.03608
       Theta0.3776880.8287890.524203
       Alpha0.7636510.4385860.205375
       Beta0.0163730.089472−0.03316
      Patient 3
       Delta0.0127590.166161−0.1496
       Theta1.4818741.495891.556829
       Alpha0.9441880.8070050.425343
       Beta0.8226540.5125870.349063
      Patient 4
       DeltaMild mental retardation3.0653052.2493431.729534
       Theta4.2861083.0398442.625455
       Alpha3.2283472.889061.33583
       Beta4.0161992.518911.786904
      Patient 5
       DeltaPersonality disorder1.8018163.3229292.595404
       Theta4.9233134.6202772.823014
       Alpha3.0267512.7275111.438308
       Beta2.2382731.8228961.173346
      Patient 6
       Delta−0.01440.6957210.792229
       Theta0.9108410.66090.389974
       Alpha−0.44227−0.18263−0.18567
       Beta2.2938351.0866190.10202
      Patient 7
       Delta−0.65629−0.395420.871796
       Theta0.0151210.408711.008864
       Alpha1.3000821.511351.028962
       Beta1.2802311.1959371.125488
      Patient 8
       DeltaPersonality disorder and pharmacoresistance2.4292492.2780494.02887
       Theta5.3046214.4467735.390082
       Alpha3.1512682.5769962.080613
       Beta3.5120752.4224832.736306
      Patient 9
       Delta−0.92326−0.91705−0.5878
       Theta0.7248190.3497411.124451
       Alpha−0.1259−0.34973−0.15741
       Beta−0.27367−0.79593−0.78858
      Patient 10
       Delta−0.76201−0.79149−1.0714
       Theta−0.029190.105787−0.50964
       Alpha0.8445120.7454940.386925
       Beta0.8679550.332503−0.27622
      Patient 11
       Delta1.0102490.8195161.376778
       Theta2.6114842.3854911.844083
       Alpha2.1610552.010151.441971
       Beta0.4588820.3897950.329511
      Patient 12
       DeltaPharmacoresistance−3.20185−2.71718−2.67932
       Theta−1.50301−0.90068−1.67703
       Alpha−1.23073−1.14346−1.19992
       Beta−1.25992−1.36071−1.56627
      Patient 13
       Delta−1.03946−0.57796−0.64287
       Theta−0.21173−0.22574−0.24023
       Alpha0.3141340.3542420.272119
       Beta0.1161820.050746−0.17668
      Patient 14
       DeltaCerebral concussion in patient’s history−2.5971−1.69692−2.05564
       Theta−1.11202−0.70517−1.1994
       Alpha1.3611250.192236−0.50236
       Beta0.9347950.778545−0.10705
      Patient 15
       DeltaPersonality disorder2.2268242.4121442.901531
       Theta4.6028684.4713174.344932
       Alpha2.1403562.3995881.517922
       Beta2.3595711.9978741.360339
      Patient 16
       Delta0.1876240.2467730.78972
       Theta0.8053230.9116771.421761
       Alpha2.3541461.8968851.781106
       Beta0.7912410.895161.085975
      Patient 17
       Delta0.6784671.2766341.280058
       Theta1.8854251.8546981.767609
       Alpha2.0395361.8968081.519539
       Beta2.4058042.1367652.14372
      Patient 18
       Delta−1.52188−0.86952−0.93473
       Theta−0.74972−0.52789−0.88522
       Alpha1.0360040.8476840.8332
       Beta0.9779960.6866310.548921
      Patient 19
       Delta1.2541991.4292181.59811
       Theta4.1544913.8075532.410176
       Alpha2.7403113.0051221.925584
       Beta2.4682152.309591.717678
      Patient 20
       Delta0.4338560.4857731.189957
       Theta1.5442731.371241.232523
       Alpha2.2344891.8544331.371282
       Beta0.6726310.4554360.32823
      Patient 21
       DeltaPharmacoresistance−3.23486−3.05815−2.93852
       Theta−2.16056−2.17171−2.15926
       Alpha−1.97948−1.85067−1.73364
       Beta0.232642−1.09746−1.21954
      Patient 22
       Delta−1.5739−1.57027−1.73257
       Theta−0.30775−0.43832−0.80225
       Alpha1.5820121.082660.356632
       Beta0.24162−0.04525−0.45494
      Patient 23
       Delta−0.89126−0.05732−0.11697
       Theta0.2033970.5325690.348521
       Alpha0.30830.385621−0.2029
       Beta0.486740.5060830.457137
      Patient 24
       Delta0.554791.0854190.941792
       Theta2.2791212.3933411.572294
       Alpha0.6942750.7366350.168982
       Beta1.3316641.0569810.519622
      Patient 25
       Delta1.334011.5983672.673381
       Theta2.2771342.2370143.041324
       Alpha1.8637921.8581972.192263
       Beta2.0858142.1496432.478859
      Patient 26
       Delta−2.14925−0.67237−0.94602
       Theta−0.442570.3121790.000849
       Alpha1.2193332.2722731.081031
       Beta0.2051170.7802740.741893
      Patient 27
       DeltaSelf-induction of seizures2.3761851.9961732.346125
       Theta3.1644082.339832.66294
       Alpha2.7676841.79872.04938
       Beta3.3114012.0411462.795052
      Patient 28
       DeltaPerinatal hypoxya−0.044890.3254361.295653
       Theta−0.27276−0.012530.727034
       Alpha2.248291.4289221.882709
       Beta1.1896960.982671.827979
      Patient 29
       Delta−1.75831−1.37801−1.48549
       Theta−0.39165−0.79838−1.07742
       Alpha0.0363730.081404−0.20156
       Beta−0.8614−0.97133−1.35139
      Patient 30
       Delta0.7203291.6074321.382499
       Theta2.055312.0796731.776112
       Alpha2.185632.026641.539772
       Beta3.6345512.4903411.698804
      Patient 31
       Delta−0.077720.39282−0.10401
       Theta1.5842891.595081.298563
       Alpha0.4994981.0916640.356403
       Beta0.5999890.576474−0.08987
      Patient 32
       Delta−0.660.7616511.680449
       Theta0.1275220.8605990.970948
       Alpha1.4404791.3031.179837
       Beta0.608530.8910970.750859
      Patient 33
       DeltaAbsence-like pseudoseizures1.2368461.020431.292326
       Theta2.7958353.3503032.982875
       Alpha1.8398782.2350021.408266
       Beta3.6148393.1218212.404069
      Patient 34
       Delta0.8114271.1421380.810987
       Theta2.3617772.4183652.104271
       Alpha2.0337282.1767131.464969
       Beta2.9640852.4619921.675566
      Patient 35
       Delta0.4384450.5219190.679708
       Theta2.3889421.9249811.802096
       Alpha1.0399270.7766190.824221
       Beta0.4847220.140263−0.16644
      Z-transformed absolute power data for four frequency bands and three cortical regions (ANT: anterior, CENT: central, POST: posterior). Bold numerals indicate (Z>±2.5) scores.
      Neurometric analysis and consecutive data compression resulted in 12 neurometric scores in each patient. The distribution of pathological scores across patients, cortical regions, and frequency bands is tabulated in Table 1. The results can be summarised as follows:
      • 1.
        Clusters of positive abnormal values were found in all the patients with psychiatric items (patients no. 4, 5, 8, 15, 27, and 33). Abnormal scores did not show specific linkage to any cortical region or frequency band. Rather, they involved all cortical regions and 2–4 frequency bands.
      • 2.
        Two patients with neurological items had completely normal scores, the third (patient no. 14) had a single abnormal one. This girl had a documented history of cerebral concussion, many years before the first absence seizure. However, no residual damage was present by neurological investigation and the recent cranial MRI was normal, too.
      • 3.
        Patients with true pharmacoresistance but no neuro-psychiatric items (patients no. 12 and 21) showed selective involvement of the delta band: unusually low negative delta scores were found in all regions. Patient no. 18 with pharmacoresistance and psychopathology showed abnormal positive scores.
      • 4.
        In the group of the uncomplicated IGE patients, 23/24 had normal QEEG. Out of them, 19 patients had not abnormal scores at all one, or two abnormal scores were found in 3 and 1 patients, respectively. Pathological QEEG (as defined above) was found in one uncomplicated patient (patient no. 19). The reason for this pathological QEEG finding remained hidden.
      • 5.
        The comparison of the clinically uncomplicated and complicated groups showed that the former is associated with normal QEEG while the latter with abnormal QEEG (Table 2, P<0.001).
        Table 2Relationship of clinical and QEEG findings (for definitions, see text).
        IGE patients
        ComplicatedUncomplicatedAll
        Normal QEEG32326
        Pathological QEEG819
        All112435
        Chi-square test (P<0.001).

      Discussion

      In this prospectively, randomly collected sample of newly diagnosed, unmedicated IGE patients, so-called complicating factors (neurological, psychiatric symptoms, pathological personality traits, true pharmacoresistance) were present in 11/35. Roughly the same proportion of patients with these complicating factors was reported by other authors.
      • Genton P.
      • Gelisse P.
      • Thomas P.
      • Bartolomei F.
      • Rey M.
      • Dravet C.
      Clinical factors of drug-resistance in patients with juvenile myoclonic epilepsy.
      Epilepsia. 1999; 40: 212
      , 

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      , 
      • Gelisse P.
      • Genton P.
      • Raybaud C.
      • Thomas P.
      • Dravet C.
      Structural brain lesions do not influence the prognosis of juvenile myoclonic epilepsy.
      Acta. Neurol. Scand. 2000; 102: 188-191
      , 
      • Fernando-Dongas M.C.
      • Radtke R.A.
      • VanLandingham K.E.
      • Husain A.M.
      Characteristics of valproic acid resistant juvenile myoclonic epilepsy.
      Seizure. 2000; 9: 385-388
      We found that some sorts of psychopathology (personality disorder, pseudoseizures) were not recognised at the first clinical visit. Our impression was that psychological support contributed to effective treatment of our patients with psychopathology. Thus, we agree that these conditions should be recognised and managed as soon as possible.

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      , 

      Janz D, Durner M. Juvenile myoclonic epilepsy. In: Engel J, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven Publishers; 1997. p. 2389–400.

      The QEEG method we used is simple and can be reproduced without difficulty. Standard data acquisition and sampling allow 80–90% reproducibility of the univariate QEEG variables.

      John E, Prichep L, Ahn H, Kaye H, Brown D, Easton P, et al. Neurometric evaluation of brain function in normal and learning disabled children. Ann Arbour: University of Michigan Press; 1989.

      . This degree of reproducibility is roughly equal to test–retest variability of the same spectral parameters.
      • Gasser T.
      • Bacher P.
      • Steinberg H.
      Test–retest reliability of spectral parameters of the EEG.
      Electroencephalogr. Clin. Neurophysiol. 1985; 60: 312-319
      . It was disclosed that one can rely on the normative means of the NAS database independent of race and geographical differences.

      John E, Prichep LS. Principles of neurometric analysis of EEG and evoked potentials. In: Niedermeyer E, Lopes da Silva FH, editors. Electroencephalography. Basic principles, clinical applications, and related fields. 3rd ed. Williams and Wilkins; 1993. p. 989–1003.

      Our results confirmed the hypotheses that (1) IGE patients do not have the same degree of QEEG-defined cortical dysfunction, and (2) higher degree of QEEG abnormality corresponds to higher degree of cortical dysfunction. All but one (23/24) uncomplicated IGE patients with lesser degree of cortical dysfunction (as presumed by clinical results) had normal QEEG. In contrast, one group of the patients with presumed higher degree of cortical dysfunction (all the patients with psychopathology and/or pharmacoresistance) had pathological QEEG. Our results indicate that QEEG may be a useful method in differentiating between IGE patients with and without psychopathology at the beginning of the illness. QEEG alterations are not specific, however. The pattern of the spectral alterations (in terms of topography and frequency band) cannot differentiate between patients with diverse psychopathology like personality disorder,

      Janz D. Epilepsy and the sleep–waking cycle. In: Vinke PJ, Bruyn GW, editors. Handbook of clinical neurology, vol. 15. North Holland: Elsevier; 1974. p. 457–88.

      mental subnormality, or a tendency toward developing pseudoseizures or self-stimulation. Introduction of multivariate QEEG parameters might contribute to this issue.

      John E, Prichep L, Ahn H, Kaye H, Brown D, Easton P, et al. Neurometric evaluation of brain function in normal and learning disabled children. Ann Arbour: University of Michigan Press; 1989.

      , 

      John E, Prichep LS. Principles of neurometric analysis of EEG and evoked potentials. In: Niedermeyer E, Lopes da Silva FH, editors. Electroencephalography. Basic principles, clinical applications, and related fields. 3rd ed. Williams and Wilkins; 1993. p. 989–1003.

      An alternative possibility is that mild diffuse derangement of cortical functions may be a non-specific predisposition to a variety of psychopathological disturbances.
      • Herrmann B.P.
      Neuropsychological function and psychopathology in epilepsy.
      Psychol. Rep. 1985; 57: 275-278
      The neurophysiological basis of the association between psychopathology and abnormal QEEG has not been clarified yet. Increased volume of cortical grey matter,
      • Woermann F.G.
      • Free S.L.
      • Koepp M.J.
      • Sisodiya S.M.
      • Duncan J.S.
      Abnormal cerebral structure in juvenile myoclonic epilepsy demonstrated with woxel-based analysis of MRI.
      Brain. 1999; 122: 2101-2108
      seemingly subtle developmental abnormalities
      • Meencke H.J.
      Specific features of disturbance of cortical development in generalised epilepsies.
      Epilepsia. 1999; 40: 74
      can indicate the presence of widespread anomalous neuronal connections in IGE patients. Altered networks can be the pathological basis of enhanced neuronal synchronisation,

      Farrel MA, Vinters HV. General neuropathology of epilepsy. In: Engel J, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven Publishers; 1997. p. 157–67.

      and in turn, increased spectral power. According to another hypothesis, aspecific “thalamocortical dysrhythmia” governed by T-type Ca2+ channels may be common to a few neurological conditions including epilepsy.
      • Llinás R.L.
      Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography.
      PNAS. 1999; 96: 15222-15227
      Interestingly, valproate, a drug that blocks T-type Ca2+ channels
      • Kelly K.M.
      • Gross R.A.
      • MacDonald R.L.
      Valproic acid selectively reduces the low-threshold (T) calcium current in rat nodose neurons.
      Neurosci. Lett. 1990; 116: 233-238
      partly reversed pathological delta–theta power excess in IGE patients.
      • Clemens B.
      • Barta Z.
      Valproate treatment normalises EEG frequency profiles in idiopathic (primary) generalised epilepsy.
      Clin. Neurosci/Ideggy. Szle. 1999; 52 ([in Hungarian; English abstract]): 307-317
      In contrast to psychopathology, neurological items were not accompanied by abnormal QEEG. Pathological items in medical history and mild neurological signs do not necessarily indicate significant cortical dysfunction, however.
      Both patients with pure pharmacoresistance showed the same unique finding, significant delta power decrease all over the scalp. This pattern of abnormal QEEG was not found in other IGE patients. The results of two patients cannot be managed as a proven scientific finding, however. In order to elaborate this issue, a long-term prospective study is underway.

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      DOI: https://doi.org/10.1016/j.seizure.2003.09.012

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