Clinical Significance of Secondary Epileptogenesis

Abstract: A possible existence of secondary epileptogenesis in humans was examined encephalographically and clinically. In the study of 128 patients with temporal foci who were followed up for about five years, the EEG foci changed from unilateral to bilateral (in 25/84) and from bilateral to unilateral (in 17/44). After status epilepticus, a new focus was found encephalographically in addition to the previous foci in one of the patients. The patients with bitemporal foci were found to be more therapy-resistant than those with a unitemporal focus. The mode of evolution of partial seizures was investigated in long-term histories of four patients with visual seizures and complex partial seizures who had occipital and temporal foci independently in the interictal EEG. In one patient the visual seizure at onset combined with a complex partial seizure after the fifth year, although only former seizure events had been documented on videotape. Through careful observations of a number of simultaneous video recordings of clinical and encephalographic features, not one patient showed two different partial seizures originating at separate foci. Therefore, we failed to obtain the definitive evidence of clinieoencephalographic secondary epileptogenesis, despite the fact that the existence of encephalographic secondary epileptogenesis seemed to be possible.     

Localization of epileptic foci with postictal single photon emission computed tomography

Effective surgical treatment of patients with intractable complex partial seizures depends on accurate preoperative seizure focus localization. We evaluated seizure localization with interictal and immediate postictal single photon emission computed tomographic images of cerebral perfusion using technetium-99m-hexamethyl-propyleneamineoxime (99mTc-HMPAO) in comparison with conventional ictal electroencephalographic (EEG) localization. Thirty-two patients with intractable complex partial seizures were studied. The mean delay from seizure onset to injection was 6.3 +/- 5.3 (SD) minutes. Independent blinded observers assessed the scans for interictal hypoperfusion and postictal focal hyperperfusion. Interictal scans alone were unreliable, indicating the correct localization in 17 patients (53%) and an incorrect site in 3 (9%). When interictal and postictal scans were interpreted together, the focus was correctly localized in 23 patients (72%). There was 1 false-positive study, and 8 patients had inconclusive changes, including 2 with inconclusive depth EEG studies. Postictal hyperperfusion was predominantly mesial temporal and frequently associated with hypoperfusion of lateral temporal cortex. Secondarily generalized seizures tended to show focal hyperperfusion less often than complex partial seizures did (Fisher's exact test p = 0.09). Combined interictal and immediate postictal single photon emission computed tomography with 99mTc-HMPAO is a useful noninvasive technique for independent confirmation of electrographic seizure localization. It may provide a suitable alternative to the use of depth electrode studies for confirmation of surface EEG findings in many patients with complex partial seizures.     

Usefulness of Unilateral Interictal Sharp Waves of Temporal Lobe Origin in Prolonged Video-EEG Monitoring Studies

The value of EEG interictal epileptiform activity in predicting location of the seizure focus remains controversial. In 64 patients, scalp video-EEG monitoring studies showed one or two ipsilateral interictal foci in the temporal lobe. The site of these interictal foci correlated with location of the seizure focus recorded during prolonged video-electrocorticography (ECoG) with use of subdural grids placed under the mesiobasal temporal region and over the lateral temporal convexity. Our findings suggest that unilateral anterotemporal interictal foci can accurately predict location of seizure onset. This is also true in patients with two ipsilateral temporal interictal foci, provided that the dominant focus is localized in anterotemporal regions. We believe that in such patients invasive recordings are not warranted, but we caution against sole use of interictal epileptiform criteria for localization of the seizure focus. Correlation with clinical information, ictal EEG, neuropsychometric, and neu-roimaging studies is required before performance of epilepsy surgery.     

MRI and EEG findings in surgically treated patients with partial seizures due to neuronal migration disorders, their relations to each other and to surgery outcome

OBJECTIVES: To evaluate magnetic resonance imaging (MRI) and electro-encephalogram (EEG) findings of patients with therapy-resistant partial seizures due to neuronal migration disorders (NMD), and compare them with each other and with surgery outcome. MATERIAL AND METHODS: The MRI, interictal and ictal EEG findings, and their relations to each other in 41 patients with NMD were compared with class IA surgery outcome. RESULTS: The patients showed an MRI lesion in decreasing frequency from the frontal to the occipital areas. A predominantly extratemporal location of the interictal EEG foci (73.3%) and ictal patterns (82.4%) was therefore apparent, also showing a diminishing frequency from the anterior to the posterior areas. Comparing the EEG foci with the MRI lesions, the same location of the interictal foci was found in 68.4% and of the ictal foci in 52.7%, including several cases with a more widespread EEG focus or MRI lesion. The same location of interictal as well as ictal foci was evident in 85.7%. The most favourable surgery outcome (class IA) was, on average, apparent in patients with an MRI lesion (28.6% vs 25%), a main interictal EEG focus (50% vs 18%) and an ictal seizure pattern (37.5% vs 16.7%) located in the temporal area; likewise, if the interictal focus (30.8% vs 18.2%) and the ictal pattern (31.8% vs 12.5%) showed the same location as the MRI lesion, as well as when the interictal and ictal EEG changes had an equal location (30% vs 20%). CONCLUSION: MRI and EEG recordings show relatively close relations to each other and might be important methods to predict surgery outcome in NMD patients.     

Consistent localization of interictal epileptiform activity on EEGs of patients with tuberous sclerosis complex

PURPOSE: We addressed consistent localization of focal interictal epileptiform activity on EEGs of patients with tuberous sclerosis complex (TSC) and epilepsy. METHODS: Twenty-one patients with TSC with a 10-year history of epilepsy and interictal epileptiform activity in three or more EEG recordings were included. None of the patients had undergone epilepsy surgery. Local maxima of interictal epileptiform activity were measured from 76 EEG traces and 33 EEG reports. Information about the patients' clinical course was extracted from their medical records. Magnetic resonance imaging (MRI) and neuropsychological examinations were performed. Statistical analysis was performed with the Mann-Whitney U test. RESULTS: In eight patients, interictal epileptiform activity was consistently detected in one or two regions (group 1), and in 13 patients, epileptiform activity was detected in three or more regions (group 2). The number of foci increased throughout the disease course in both groups. Age at seizure onset and IQ were significantly higher in group 1. Complex partial seizures occurred more often in the patients of group 1. In 19 of the 21 patients, the most consistent epileptiform activity was localized in the frontotemporal region. CONCLUSIONS: Ninety percent of patients with TSC showed at least one region of consistent interictal epileptiform activity. Patients with one or two regions of epileptiform activity were older at seizure onset, often experienced complex partial seizures, and had mild or no mental deficits. These patients may be candidates for epilepsy surgery.     

脑电偶极子分析在痫灶切除术中的定位价值

目的探讨长程视频脑电监测和偶极子分析在痫灶切除术中的定位价值。方法对35例开颅痫灶切除术患者术前行常规脑电和长程视频脑电监测,脑电痫性放电进行偶极子分析,并与手术中硬膜下电极记录的脑电相对照。结果35例患者视频脑电图监测异常35例,有痫性放电者35例;常规脑电图异常28例,有痫性放电者18例;行常规脑电图监测无典型癫痫发作出现。两者之间脑电异常率、痫性放电阳性率、典型临床发作率都有统计学意义。以术中硬膜下电极记录为标准,头皮脑电偶极子定位异常放电灶的准确率为97%,切除病灶病理检查异常率86%。偶极子定位误差一般<15mm。结论长程视频脑电监测和头皮脑电偶极子定位癫痫起源灶可为开颅痫灶切除手术提供有价值的信息。     

The Absence of Interictal Spikes with Documented Seizures Suggests Extratemporal Epilepsy

PURPOSE: To determine the demographic and clinical characteristics of patients who have documented epileptic seizures on long-term video-EEG monitoring who do not have interictal spikes. METHODS: The records of 1,223 monitoring studies from 919 patients who underwent noninvasive long-term video-EEG monitoring were reviewed. In 28 patients (3.0% of monitored patients, 4.4% of patients with electrographic evidence of epilepsy), no interictal spikes were found despite the occurrence of at least one recorded electrographic seizure. The demographic, medical, neuropsychological, and EEG data of these patients were compared with those of 28 matched control patients with documented interictal spikes. RESULTS: Extratemporal seizures were significantly more frequent in the patients with at least one recorded epileptic seizure but without interictal spikes compared with patients with epileptic seizures and interictal spikes (p = 0.031). The only other significant difference between the groups (p = 0.016) was a later age at seizure onset (18.3 vs. 10.7 years) for the patients without interictal spikes. Age at evaluation, gender, handedness, clinical seizure type, family history of epilepsy, history of febrile seizures, neuropsychological testing, and neurologic and psychiatric history did not differ between the two groups. CONCLUSIONS: In patients with documented epilepsy without interictal spikes on EEG monitoring, the possibility of an extratemporal focus should be considered.     

What is the Relationship Between Arachnoid Cysts and Seizure Foci?

Summary: Purpose: Arachnoid cysts are sometimes encountered in MRIs performed for a variety of reasons. In patients with epilepsy, particularly those with refractory epilepsy, arachnoid cysts are often assumed to be related to their seizure focus. We conducted a study to investigate this putative relationship.
Methods: A retrospective study on the incidence of arachnoid cysts was performed in patients seen in our Epilepsy Clinic who had CT or MRI scans, interictal EEGs or ictal EEGS. Locations of seizure foci in these patients were defined from clinical and electrophysiologic data.
Results: Seventeen of 867 patients had arachnoid cysts. Twelve patients had temporal lobe cysts and only 3 of them had temporal lobe seizures. Four patients had frontal lobe cysts and only 1 had frontal lobe seizures ipsilateral to the cyst. One patient had a cerebellopontine angle cyst and frontal lobe seizures. Thus, clinical manifestations of seizures and EEG findings (interictal and/or ictal) indicated that the seizure focus was adjacent to the cysts in only 4 patients (23.5%).
Conclusions: Our findings suggest that arachnoid cysts are often an incidental finding in patients with epilepsy and do not necessarily reflect the location of the seizure focus.     

Functional partial epilepsies in childhood

Out of the 314 children with partial epilepsies below the age of 15 who had been followed for more than 5 years, 122 children with functional partial epilepsies (FPE) were the subjects of this study. The specific modality of interictal EEG findings reminiscent of that of the Rolandic spikes (Dalla Bernardina, 1982, 1984) was compared between functional and organic partial epilepsies. The results were: 1) One hundred and twenty-two patients were found to have FPE out of a total of 314 patients (39%). 2) Fifty-five patients were diagnosed as typical benign epilepsy of children with centro-temporal EEG foci (BECCT) of the 122 functional cases (45%). The remaining 67 patients who defied the diagnostic criteria of BECCT were; 9 cases with frontal EEG focus (7%), 11 cases with central and/or midtemporal EEG foci (9%), 10 cases with occipital EEG focus (8%) and 14 cases with multiple foci (11%). 3) Unfavorable seizure control was observed in cases with frontal foci (44%) and with multiple EEG foci (64%) compared with those whose EEG focus was located in the centro-midtemporal area, (including BECCT; 98%) and in the occipital region (80%). 4) It was noteworthy that the recurrent interictal spikes similar to those of the Rolandic spikes (Dalla Bernardina) were found in more than 50% of the patients not only with functional but with organic partial epilepsies. Our results, at least at the present time, appear to indicate that the recurrent spikes never did signify the benignancy of the seizure prognosis. The importance of differential diagnosis of BECCT from FPE was specifically stressed.     

Functional Partial Epilepsies in Childhood

Abstract: Out of the 314 children with partial epilepsies below the age of 15 who had been followed for more than 5 years, 122 children with functional partial epilepsies (FPE) were the subjects of this study. The specific modality of interictal EEG findings reminiscent of that of the Rolandic spikes (Dalla Bernardina, 1982, 1984) was compared between functional and organic partial epilepsies.
The results were: 1) One hundred and twenty-two patients were found to have FPE out of a total of 314 patients (39%). 2) Fifty-five patients were diagnosed as typical benign epilepsy of children with centra-temporal EEG foci (BECCT) of the 122 functional cases (45%). The remaining 67 patients who defied the diagnostic criteria of BECCT were; 9 cases with frontal EEG focus (7%), 11 cases with central and/or mid-temporal EEG foci (9%), 10 cases with occipital EEG focus (8%) and 14 cases with multiple foci (11%). 3) Unfavorable seizure control was observed in cases with frontal foci (44%) and with multiple EEG foci (64%) compared with those whose EEG focus was located in the centro-midtemporal area, (including BECCT; 98%) and in the occipital region (80%). 4) It was noteworthy that the recurrent interictal spikes similar to those of the Rolandic spikes (Dalla Bernardina) were found in more than 50% of the patients not only with functional but with organic partial epilepsies. Our results, at least at the present time, appear to indicate that the recurrent spikes never did signify the benignancy of the seizure prognosis. The importance of differential diagnosis of BECCT from FPE was specifically stressed.     

Clinical Value of "Ictal" FDG-Positron Emission Tomography and the Routine Use of Simultaneous Scalp EEG Studies in Patients with Intractable Partial Epilepsies

Summary: Purpose: EEG is widely used during positron emission tomography (PET) to confirm the interictal state of the patient and assist in scan interpretation when a seizure occurs. Ictal scans usually reflect mixed interictal-ictal-postictal metabolic activity as seizures are brief in comparison to the 30-min uptake period of the tracer. We wished to determine whether routine EEG is justified and if seizures commonly affect the diagnostic information of the PET scan.
Methods: We examined the PET scans of 6 of 236 outpatients with intractable epilepsy with clinical and electrical evidence of a seizure during tracer uptake. We performed semi-quantitative analysis in 2 patients who had "ictal" and control interictal scans.
Results: Patients with single seizures lasting 23 s to 4 min [four complex partial seizures (CPS) and one absence seizure (AS)] had focal hypometabolism concordant with results of other investigations. One patient with complex partial status had irregular cortical uptake and focal hypometabolism, but the site of the ictal focus could not be confirmed.
Conclusions: In this group of patients, seizures occurred infrequently during tracer uptake. The interpretation of the PET scan when single seizures occurred did not appear to be influenced by the continuous scalp EEG (CSEEG) recordings. The value of routine CSEEG in outpatients treated with medication should be reappraised, with potential cost savings. In rare circumstances in which a true ictal study occurs (complex partial status, epilepsia partialis continua, and repetitive CPS), PET scanning may be inconclusive and repeat interictal scanning should be pursued.     

Ictal Scalp EEG in Unilateral Mesial Temporal Lobe Epilepsy

Summary: Purpose: We wished to determine the predictive significance of unilateral hippocampal atrophy and interictal spikes on localization of ictal scalp EEG changes and assess whether ictal EEG provides information that might change treatment or influence prognosis in patients with such characteristics of epilepsy.
Methods: We analyzed EEG seizure patterns in 118 seizures in 24 patients with unilateral mesial temporal lobe epilepsy (MTLE) defined by typical clinical seizure semiology, unilateral hippocampal atrophy on magnetic resonance imaging (MRI) and unitemporal spikes on interictal EEG. Two blinded electroencephalographers independently determined morphology, location, and time course of ictal EEG changes.
Results: Lateralization was possible in 88.4–92.0% of seizures and always corresponded to the side of the interictal spike focus and of hippocampal atrophy on MRI. Although only 30.4–33.9% of seizures were lateralized at onset, a later significant pattern emerged (12.6–13.3 s after EEG seizure onset) that allowed lateralization in 82.4–91.O% of seizures with non-lateralized onset. Interobserver reliability for lateralization was excellent, with a K-value of 0.85. In most patients, either all (79.2–83.3%) or >50% (8.3–16.7%) of seizures were lateralized. In only a small proportion of patients (4.2–8.3%) were 40% of seizures lateralized. In 1 patient, no seizure could be lateralized by 1 electroencephalographer. The results of ictal EEG recordings did not alter the surgical approach and did not correlate with surgical outcome.
Conclusions: We conclude that unilateral hippocampal atrophy on MRI and unitemporal interictal spikes can predict localization of ictal scalp EEG changes with a high degree of reliability and that ictal EEG provides no additional localizing information in this particular patient group.     

The lateralizing significance of version of head and dystonic limb posturing in epileptic seizures

Several clinical signs have been described for lateralization and localization of seizure focus in complex partial seizures; however, the specificity of each of these has been widely debated upon. The present study was done to evaluate 'dystonic unilateral limb posturing' and 'versive head movements' for lateralization and localization of epileptic foci in patients with intractable partial complex seizures, being investigated with long term Video-EEG monitoring. Fifteen patients with 46 seizures, studied with long term Video EEG, had either one or both of these signs. The video recordings of the clinical behaviour were noted and later compared with the corresponding EEG. Unilateral dystonic limb posturing and versive head movements had good lateralising value in complex partial seizures, suggestive of temporal lobe origin, contralateral to the seizure focus, with a specificity of 87.5% and 86% respectively. In addition, turning of the whole body to one side was associated with a contralateral seizure focus in 100% cases. Appendicular automatisms were found to be of no lateralising significance, as they occurred on either side with equal frequency. These motor phenomena should, therefore, be enquired about in detail, during history taking for lateralization or localization of seizure focus.     

无创性定位手段在颞叶内侧癫(癎)患者癫(癎)灶定位中的价值

目的 评价多种无创性定位手段在颞叶内侧癫(癎)患者术前癫(癎)灶定位中的可靠性.方法 选择2002年5月至2005年5月间在我院行前颞叶内侧切除,随访1年以上,预后为Engle I级的40例患者,回顾性地总结这组病例发作间期和发作期脑电图、发作症状、头颅MRI、发作问期SPECT所提供的定侧定位信息,分析其在癫疴灶定位中的价值.结果 (1)发作间期颞前尖波:出现单侧独立尖波者37例(92.5%),其中35例(94.6%)与癫(癎)灶侧别相符;(2)发作期脑电图:32例获取了发作期脑电图,26例(81.2%)的发作期脑电图可提供定侧信息,其中25例(96.2%)与癫(癎)灶的侧别相符;(3)发作症状:23例(57.5%)患者的发作症状可以提供癫(癎)灶侧别信息,其中19例(82.6%)提供的侧别信息与癫(癎)灶侧别一致;(4)头颅MRI:38例(95.0%)头颅MRI提示一侧海马及颞叶的信号或结构异常,其中37例(97.4%)与癫(癎)灶侧别相符;(5)发作间期SPECT:23例患者行同位素检查,22例(95.7%)可提供癫(癎)灶侧别信息,其中18例(81.8%)与癫(癎)灶侧别相符.结论 颞叶内侧癫(癎)术前无创性定位定侧方法中,提供定侧信息比较敏感的方法依次为SPECT、MRI、发作问期脑电图、发作期脑电图和发作症状,而定侧信息可靠性的高低依次为头颅MRI、发作期脑电图、发作间期脑电图、发作症状和SPECT.     

Ictal/postictal SPECT in the pre-surgical localisation of complex partial seizures.

Single photon emission computed tomography (SPECT) used in conjunction with HM-PAO (Ceretec-Amersham International) was used to image regional cerebral blood flow (rCBF) in 28 patients with medically intractable complex partial seizures during or soon after a seizure, and interictally. Changes from interictal rCBF were seen in 26/28 (93%) patients. The main findings were; 1) During the seizure--hyperperfusion of the whole temporal lobe; 2) Up to 2m postically--hyperperfusion of the hippocampus with hypoperfusion of lateral temporal structures; 3) From 2-15m postically--hypoperfusion of the whole temporal lobe. When compared with EEG and MRI data, correct localisation to one temporal lobe was obtained in 23 patients. In one further patient bilateral temporal foci, and in a further two patients frontal foci, were correctly identified. There were no disagreements between EEG and SPECT localisation. Temporal lobe surgery was successful (by the criterion of at least 90% reduction in seizure frequency) in all but one of the 23 patients operated on. It is concluded that ictal/postictal SPECT is a reliable technique for the presurgical localisation of complex partial seizures. The data indicate a likely sequence of changes in rCBF during and after complex partial seizures of temporal lobe origin.     

Interictal and ictal magnetoencephalographic study in patients with medial frontal lobe epilepsy

PURPOSE: To determine whether magnetoencephalography (MEG) has any clinical value for the analysis of seizure discharges in patients with medial frontal lobe epilepsy (FLE). METHODS: Four patients were studied with 74-channel MEG. Interictal and ictal electroencephalographic (EEG) and MEG recordings were obtained. The equivalent current dipoles (ECDs) of the MEG spikes were calculated. RESULTS: In two patients with postural seizures, interictal EEG spikes occurred at Cz or Fz. The ECDs of interictal MEG spikes were localized around the supplementary motor area. In the other two patients with focal motor or oculomotor seizures, interictal EEG spikes occurred at Fz or Cz. The ECDs of interictal MEG spikes were localized at the top of the medial frontal region. The ECDs detected at MEG ictal onset were also localized in the same area as those of the interictal discharges. CONCLUSIONS: In medial FLE patients, interictal and ictal MEG indicated consistent ECD localization that corresponded to the semiology of clinical seizures. Our findings demonstrate that MEG is a useful tool for detecting epileptogenic focus.     

The magnetic field of complex partial seizures agrees with intracranial localizations

The magnetoencephalogram (MEG) was recorded during 63 complex partial seizures in 4 patients. The MEG showed large biomagnetic signals occurring at the same time as discharges recorded from scalp electroencephalogram (EEG). These MEG signals had the same morphology and frequency as the discharges from the EEG. The location of the seizure focus was verified by depth electrode recordings in 2 patients and by lesions shown on computed tomographic scan and magnetic resonance imaging in the other 2. In each patient, MEG localization estimates were consistent with the location of the seizure focus shown by other methods. When seizures were recorded repeatedly and mapped with a single-channel magnetometer placed at different scalp locations in a single patient, the MEG localization agreed with the electrographic seizure focus localized from depth electrodes. In the maps, the MEG resolved an ambiguity in the scalp EEG and therefore increased the confidence of localization. MEG recordings of seizures may help localize epileptic foci noninvasively.     

A practical guide for routine EEG studies in epilepsy

Know what is not epilepsy! An electroencephalographer can do much more damage by overinterpreting than by underinterpreting an EEG tracing. Epilepsy is a clinical, not an EEG, diagnosis, but the EEG, when used appropriately, can greatly aid the diagnostic process. Use activating techniques such as hyperventilation, photic stimulation, and natural sleep. Take advantage of seizures in the laboratory--this is a unique opportunity to make a diagnosis. If the ictal event is not accompanied by an EEG abnormality, and pseudoseizures are suspected, remember that patients with hysterical epilepsy often have real seizures as well. Use the EEG to help differentiate between generalized and partial epileptic conditions, and to identify benign epileptic syndromes. These diagnoses have important prognostic and therapeutic implications. The EEG can help determine whether a patient is deteriorating due to increased seizure activity (undermedicated) or increased side effects (overmedicated). Postictal slowing must be differentiated from progressive or drug induced changes. The best candidates for resective surgical therapy are otherwise healthy young adults with medically intractable partial complex seizures, no psychosis, and unilateral or bilaterally independent interictal anterior temporal EEG spike foci. Patients with multifocal or bilaterally synchronous interictal EEG spikes combined with mental retardation are less likely to benefit from resective surgery, although they may be helped by corpus callosum section.     

Clinical and electroencephalographic characteristics of midline parasagittal foci

We report the clinical and electroencephalographic (EEG) characteristics of 14 patients with midline parasagittal epileptogenic foci. Montages not including the vertex electrodes demonstrated the abnormal activity poorly or not at all. The clinical manifestations were diverse and included tonic-clonic, atypical absence, and partial seizures. In the majority, no cause could be established. The interictal EEG abnormality did not predict the pattern of clinical attack. Half the patients had evidence of structural brain disease. Four patients had no history of seizures.     

Correlation of abnormalities of interictal n-isopropyl-p-iodoamphetamine single-photon emission tomography with focus of seizure onset in complex partial seizure disorders

Single-photon emission tomography (SPECT) scanning with n-isopropyl-p-iodoamphetamine (IMP) was performed on 23 patients with complex partial seizures undergoing long-term video electroencephalographic (EEG) seizure monitoring. Twenty-one of the 23 patients had abnormalities on SPECT scanning consisting of areas of decreased activity reflecting diminished cerebral blood flow. In 15 of these 21 patients, there was good correlation between the site of the abnormality on SPECT scan and the site of origin of seizures monitored by EEG. Of the six remaining patients, four had multifocal SPECT abnormalities, with one of the abnormal areas corresponding with an ictal site. The two remaining patients had SPECT abnormalities and major ictal EEG foci in entirely different areas. In contrast to the high proportion of abnormal SPECT scans, only 10 of 23 focal abnormalities were discovered on magnetic resonance imaging (MRI) scans. Three patients who had seizures within 2 h of an initial scan were rescanned 4-5 h after injection. Focal areas of increased blood flow were noted on all three scans, although not always at the ictal site. The SPECT scan appears to be useful in interictal localization of seizure foci. Postictal scans may also be useful, although our numbers are too small to draw conclusions.