Typical childhood absence seizures are associated with thalamic activation.

Functional MRI with simultaneously acquired EEG (fMRI/EEG) can identify areas of signal change associated with interictal discharges. We report the fMRI/EEG study of a child with newly-diagnosed IGE, performed prior to the start of antiepileptic medication. The 7-years-old girl had very frequent absences, associated with eyelid myoclonia. Her EEG showed frequent, typical 3/sec discharges. Functional MRI was performed with a 3T scanner using whole brain gradient echo-planar imaging, and the EEG was recorded with 18, non-metallic, scalp electrodes. Ten bursts of generalized discharges were captured during 30 minutes fMRI/EEG acquisition. The bursts lasted 3.4 (SD +/- 0.6) seconds. Event-related analysis was performed with SPM2 and iBrain software. Functional MRI showed prominent, bilateral thalamic activation, and less pronounced areas of cortical activation and deactivation. This study demonstrates thalamic activation in typical, untreated childhood absence epilepsy. The cortical signal change may be related to a thalamo-cortical circuit.

Men may be more vulnerable to seizure-associated brain damage.

BACKGROUND: Repetitive seizures may be associated with progressive neuronal damage measurable by quantitative MRI. OBJECTIVE: To investigate whether gender is a risk factor for this damage. METHODS: Sixty patients with refractory temporal lobe epilepsy (TLE) (28 men, 32 women) and 54 healthy controls (28 men, 26 women) were compared by quantitative MRI methods. RESULTS: Male patients had ipsilateral hemicranial volume loss of 12% (CI 8% to 16%) and contralateral volume loss of 7% (CI:3% to 11%) compared with male controls (p < or =0.004, analysis of variance). Female patients were 4% (CI:0.3% to 8%, p = 0.04) smaller than controls in the ipsilateral hemicranium, and not different contralaterally. The patient-to-control difference was greater in men than in women for the ipsilateral (p = 0.003) and contralateral hemicranial volume (p = 0.02). In men, 14% of the ipsilateral (F = 4.7, p = 0.004) and 16% of the contralateral (F = 5.1, p = 0.03) hemicranial volume loss could be attributed to generalized tonic clonic seizures. Compared with controls, patients averaged a 29% smaller ipsilateral and a 5% smaller contralateral hippocampus. CONCLUSION: Men with TLE have more brain atrophy than women with TLE. Seizure frequency is a factor contributing to reduced brain volumes in men but not in women. Men, therefore, may be more vulnerable to seizure-associated brain abnormalities.

Seizures in family members of patients with hippocampal sclerosis.

OBJECTIVE: To characterize seizures in family members of patients with refractory temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). METHODS: The authors systematically investigated family history (FH) of seizures in 66 probands with histologically proven HS, and in 51 control subjects. A positive FH was defined as at least one first-to-third-degree relative being affected. The odds ratio (OR) to be affected with seizures was calculated for siblings, parents, and aunts/uncles. RESULTS: An FH of seizures was found in 58% of patients, and in 24% of control subjects (p = 0.02). A variety of seizure types were found. Siblings of patients were more likely to be affected than siblings of control subjects (OR 11.5; 95% CI = 1.5 to 86.9 p = 0.003), with febrile convulsions occurring in 5.8% of the siblings of patients. The OR of being affected was 5.7 for parents of patients, and 1.9 for aunts/uncles of patients (p = NS). CONCLUSION: FH of seizures, particularly febrile convulsions, are a risk factor for TLE with HS. These data suggest that a variety of genes contributing to epilepsy phenotypes in relatives may be involved in the pathogenesis of HS.

Hippocampal sclerosis following brief generalized seizures in adulthood.

This report describes a patient who had a first generalized tonic clonic seizure (GTCS) at the age of 18 years. The initial MRI scan was normal on visual and quantitative examination. After a further six GTCS, a second MRI scan showed reduced hippocampal volume and increased hippocampal T2 signal, which was confirmed in a third scan. Therefore, hippocampal sclerosis may be acquired in adulthood after brief GTCS.

Hippocampal sclerosis studied in identical twins.

OBJECTIVE: To test both the genetic and acquired hypotheses for the etiology of hippocampal sclerosis (HS) by studying with optimized and quantitative MRI three monozygous (MZ) twin pairs in which the index twin had temporal lobe epilepsy and HS. BACKGROUND: There is conflicting evidence in the literature regarding whether HS is genetic or acquired prenatally, perinatally, or as a consequence of prolonged childhood seizures. METHODS: We compared three MZ pairs with 30 age-matched control subjects who had no history of a neurologic disorder; we also used the twins as matched samples to assess subtle differences between the affected and the unaffected twins. RESULTS: All of the affected twins had prolonged seizures with fever in early childhood, which stood out as the unique factor common to all affected twins and was absent in all the unaffected twins. HS was present in all affected twins but was absent in the unaffected twin on visual, volumetric, and T2 relaxometry criteria. Comparison of the affected twin with the co-twin revealed that intracranial volume ipsilateral to the HS was relatively small in two of three affected twins. CONCLUSIONS: The absence of HS in the unaffected twin is strong evidence against a genetic hypothesis for HS. Neither perinatal problems nor birth order were factors in determining the presence of HS. This twin study supports the notion of HS as an acquired lesion secondary to prolonged seizures in early childhood and suggests that regional abnormalities of intracranial volume are associated with HS.

TLE patients with postictal psychosis: mesial dysplasia and anterior hippocampal preservation.

The authors studied six patients with refractory temporal lobe epilepsy and postictal psychosis using quantitative MRI and histopathology, and compared the results with 45 patients with temporal lobe epilepsy without postictal psychosis. Total hippocampal volumes were not different between the two groups. However, patients with postictal psychosis had a relatively preserved anterior hippocampus, and temporal lobe dysplasia was more frequent (p = 0.006, chi-square test). These findings may be associated with the clinical symptoms.

APOE epsilon4 genotype is associated with an earlier onset of chronic temporal lobe epilepsy.

The authors analyzed the association between APOE epsilon4 genotype and clinical and MRI findings in 43 refractory temporal lobe epilepsy patients. The distribution of the alleles were normal. Ten patients (23%) had an APOE epsilon 4 allele and had an earlier onset of habitual seizures (with epsilon4 5 +/- 5 years; without epsilon4 15 +/- 10 years). Quantitative MRI findings were not influenced by the APOE epsilon4 genotype. APOE epsilon4 may shorten the latency between an initial injury and seizure onset.

Pathologic and physiologic function in the subcortical band of double cortex.

Double cortex is a neuronal migration disorder, associated with impaired cognitive function and seizures, and characterized by a subcortical band of neurons. Using functional MRI, we assessed the involvement of the subcortical band in language function and with interictal discharges. In both girls assessed, language-associated activation was in typical cortical areas, as well as in parts of the subcortical band. Interictal discharges were associated with deactivation in the subcortical band. This suggests involvement of the subcortical neurons in physiologic and pathologic functions.

Relationship between language lateralization and handedness in left-hemispheric partial epilepsy.

OBJECTIVE: To investigate the relationship between language lateralization and handedness in patients with epilepsy and a left-sided seizure focus and in healthy control subjects. METHODS: We recruited a consecutive series of 74 patients and 70 control subjects. Functional MRI, using a noun-verb generation task, was performed to establish the language laterality index (LI). Handedness was quantified using the Edinburgh Handedness Inventory. RESULTS: Patients showed a shift toward atypical language lateralization (0.43 +/- 0.47; controls 0.57 +/- 034; p < or = 0.05) and left-handedness (55 +/- 57; controls 74 +/- 39; p < or = 0.05). The LI and handedness were correlated in patients (r = 0.54; F = 25.9; p < 0.001) but not in control subjects (r = 0.1; F = 0.64; NS). A combination of left-handedness and atypical LI was more frequent in patients (12%) than control subjects (0%; p < or = 0.05). Crossed hemispheric specialization (e.g., right-handedness associated with atypical LI) was equally frequent in patients (20%) and control subjects (16%; NS). CONCLUSION: In epilepsy patients with a left-sided seizure focus, language lateralization is correlated to handedness. The increased frequency of left-handedness and associated atypical language lateralization is most likely related to the left-hemispheric seizure focus, influencing hemispheric specialization for both domains.

Idiopathic generalized epilepsies: do sporadic and familial cases differ?

PURPOSE: Genetic factors are the only identified cause of idiopathic generalized epilepsies (IGEs), but the majority of cases do not have affected first-degree relatives. Here we investigate whether subjects with sporadic and familial IGE differ in terms of antecedent events and clinical and EEG features. Differences would support the hypothesis of a different etiology for sporadic cases, which has implications for choice of subjects for genetic association studies. METHODS: We analyzed 98 patients with IGE, diagnosed on clinical and EEG criteria. All patients and, if possible, one relative were interviewed, with special emphasis on potential antecedent events and family history. Patients with first-degree relatives affected with epileptic seizures were regarded as "familial," and the other patients were regarded as "sporadic." RESULTS: Of the 98 IGE patients, 32 (33%) patients were familial. The risk for seizures was 13.2% for siblings, and 7.7% for parents. The distribution of the IGE subsyndromes, the presence of antecedent events, and other electroclinical features did not differ between familial and sporadic IGE groups. CONCLUSIONS: No differences were found between familial and sporadic IGE patients. This does not the support the hypothesis that sporadic and familial IGE cases have separate etiologies.

Blink reflex excitability is abnormal in patients with periodic leg movements in sleep.

The excitability of the late component of the blink reflex was measured in 19 patients with periodic leg movements in sleep (PLMS) and in 18 control patients with other sleep complaints. PLMS patients were not different from controls regarding age, body mass index, and apneas and hypopneas per hour of sleep. The latencies of the R1 and R2 components of the blink reflex were not different between the groups. However, in PLMS, the excitability of the R2 response was markedly enhanced: The second R2 response to a pair of stimuli given at an interval of 500 ms was in PLMS 59.5% (range 21-87%) of the first R2 response and in controls 18.8% (range 2-79%) (p < 0.0001, Mann-Whitney U test). These results provide further evidence of an altered motor control in PLMS, which is likely to be located subcortically and possibly related to the dopaminergic striatopallidal system.

Comparison of hippocampal volumetry at 1.5 tesla and at 3 tesla.

PURPOSE: Hippocampal volumetry using magnetic resonance imaging (MRI) is a common clinical study in epilepsy patients. Most clinical MR scans operate at 1.5 tesla (T); however, there is increasing use of scanners of a higher field strength. We analyzed whether control data of hippocampal volumes can be used across different field-strength scanners. METHODS: We studied eight adult healthy controls twice at both 1.5 and 3 T. Bilateral hippocampal volumes were measured by manual outlining. Measurement error was analyzed based on the variability between two measurements at the same field strength, and intrascanner variability was analyzed based on the difference between measurements obtained at 1.5 and at 3 T. RESULTS: The measurement error was 4.0% (+/-3.1) at 1.5 T, and 3.4% (+/-2.5) at 3 T. The intrascanner variability between measurements at 1.5 and at 3 T was 6% (+/-3.9). The intrascanner variability was not different from the measurement error. CONCLUSIONS: Control hippocampal volume measurements obtained at 1.5 and at 3 T were not different.

Causes of epilepsies: insights from discordant monozygous twins.

Whereas some patients with epilepsy have known acquired or genetic causes, in many the cause is unknown. By analyzing monozygotic twins, discordant for epilepsy, subtle etiological factors may be detected. We analyzed 12 monozygotic, discordant twins for factors explaining discordancy. These factors were presence of major clinical risk factors, presence of possibly epileptogenic lesions on brain magnetic resonance imaging (MRI), and quantitative brain volume abnormalities. Major risk factors, with associated acquired lesions were found in 4 of 12 twins. An MRI lesion without a major risk factor was found in a further 4 of 12 twins. Two of these had unilateral malformations of cortical development, 1 had bilateral periventricular heterotopia, and 1 had focal atrophy. Significant twin-twin differences in MRI volumes without obvious MRI lesions or major risk factors were found in 2 of 12 twins. Both had larger volumes than their co-twins, and idiopathic generalized epilepsy. No clinical or MRI findings accounting for discordance for epilepsy were found in 2 of 12 twins. In 10 of 12 pairs a clinical or MR correlate of epilepsy was found; some of those were subtle and only apparent by twin-twin comparison. They may be due to occult acquired factors, such as prenatal insults, or to genetic abnormalities resulting from postfertilization genetic processes.

Brain reorganisation in cerebral palsy: a high-field functional MRI study.

Early brain damage may induce alternative organisation of cortical brain functions. This may happen even if there is no damage to the cortex. We assessed a 15-year-old girl with a perinatal left-sided subcortical lesion without cortical damage by functional MRI at 3 Tesla. The patient had congenital hemiparesis, mirrored limb movements and normal language function. Functional MRI was used to assess language using orthographic-lexical retrieval and noun-verb generation tasks, and demonstrated right-sided language dominance. Functional MRI of motor function was assessed for both hands separately, by squeezing a rubber balloon. Both hand movements induced asymmetric bilateral activation of the motor cortex, with a predominance of contralateral activation. Language-associated activity is usually left-hemispheric, but was found in the undamaged right-sided hemisphere. Motor function was associated with the unusual pattern of bilateral cortical activation. The MR findings explain the clinical features and suggest widespread alternative cortical organisation in the presence of a focal lesion confined to subcortical structures.

Autoantibody-associated sensory neuronopathy and intestinal pseudo-obstruction without detectable neoplasia.

A 60-year-old patient presenting with the typical features of progressive sensory neuronopathy and subsequent intestinal pseudo-obstruction was found to have antineuronal nuclear antibodies (ANNA-I or Anti-Hu). These findings were suggestive of a paraneoplastic syndrome, but neither clinically nor at autopsy could a neoplasm be detected. Neuropathological findings were identical with those known for carcinoma-associated forms with marked neuron loss of spinal sensory ganglia and myenteric plexus. Therefore, ANNA-I and intestinal pseudo-obstruction may in rare cases occur without detectable underlying cancer.

Patterns of muscle activity in legs in sleep apnea patients before and during nCPAP therapy.

Nocturnal muscle activity in legs (MAL) was studied in 19 patients with sleep apnea syndrome before and during nCPAP. We distinguished periodic (P-MAL) and nonperiodic (N-MAL) as well as apnea-associated and independent MALs. N-MALs were strongly associated with apneas and disappeared during nasal continuous positive airway pressure (nCPAP). P-MALs showed a rather long intermovement interval (IMI) of about 54 s when associated with respiratory disturbances and a shorter one of about 38 s when occurring independently. In 5 patients with predominantly independent P-MALs and a short IMI before and during nCPAP an incidental coexistence of sleep apnea with periodic leg movements in sleep syndrome (PLMS) was postulated. Five patients with an equal number of apnea-associated and independent MALs before nCPAP had a long IMI which shortened under nCPAP, while the majority of MALs become independent. This could indicate a facilitating or an unmasking effect of nCPAP on PLMS. Four patients with predominantly apnea-associated MALs with a long IMI before nCPAP showed an unchanged MAL pattern under nCPAP, despite the disappearance of apneas. Since some arousals persisted in these patients, insufficient nCPAP pressure with an upper airway resistance syndrome was suspected. We conclude that when P-MALs persist under nCPAP therapy a long IMI may indicate an upper airway resistance syndrome, whereas a short IMI may indicate a coexisting or even induced PLMS.

Spike-triggered fMRI in reading epilepsy: involvement of left frontal cortex working memory area.

OBJECTIVE: To determine the origin of epileptiform activity in reading epilepsy (RE) and the association between these regions and regions activated by reading, and to assess brain morphometry in these areas. METHODS: In two subjects with RE, EEG was recorded inside the three tesla MRI while subjects read silently. Spike-triggered fMRI images were compared to baseline. In a second fMRI study, 30 seconds of silent reading was compared to visual fixation. Morphometry of these areas was assessed using curvilinear surface reconstruction. Left central sulcal patterns in three subjects with RE were compared to three subjects with idiopathic generalized epilepsy (IGE) and 12 normal controls. RESULTS: One subject with RE showed spike-related activity (17 spikes) in the left precentral gyrus, and bilaterally in the central sulcus and globus pallidus. The other showed no definite activation owing to low spike numbers (4 spikes). In both subjects, the block reading task recruited normal visual and language areas including the left posterior middle frontal gyrus. Two subjects with RE showed an unusual gyrus branching anteriorly off the left central sulcus. A similar sulcal pattern was seen in none of the subjects with IGE and only 1 of 12 controls. CONCLUSION: Spike activity overlapped with reading activity in the left middle frontal gyrus, a structure recruited during working memory cognitive tasks. The authors postulate that, because of a local structural anomaly, the spikes of reading epilepsy spread from working memory areas into adjacent motor cortex, activating a cortical subcortical circuit.

Twins with different temporal lobe malformations: schizencephaly and arachnoid cyst.

The etiology and relationships between different forms of malformations of cortical development are poorly understood. Schizencephaly is generally regarded as unrelated to arachnoid cysts. As part of a systematic study of epilepsy in twins we observed a monozygotic twin pair discordant for temporal lobe epilepsy where the twin with epilepsy had unilateral temporal schizencephaly and periventricular heterotopia. The twin without epilepsy had an arachnoid cyst in the same temporal lobe. Although an incidental association is possible, this observation, together with occasional reports of schizencephaly and arachnoid cysts within one individual, suggests a shared pathogenic mechanism. Schizencephaly can be caused by both genetic and acquired factors. We propose that our observations in this twin pair are best explained by a genetic factor present in both twins, with an additional environmental insult resulting in schizencephaly in only one of the pair.

Hemicranial volume deficits in patients with temporal lobe epilepsy with and without hippocampal sclerosis.

PURPOSE: In patients with refractory temporal lobe epilepsy, studies have suggested volume deficits measured by MRI of brain structures outside the epileptogenic hippocampus. Hippocampal sclerosis (HS) is a frequent, but not obligate, finding in such patients. The present study examines the influence of the presence of HS on quantitative magnetic resonance imaging (MRI) measurements. METHODS: We analyzed 47 patients and 30 controls by quantitative MRI, including intracranial volume (ICV), hemicranial volume, hippocampal volume (HCV), and T2 relaxometry. MRI results were compared with histological findings in the resected temporal lobe. RESULTS: Histology documented HS in 35 patients (HS group) and other findings in 12 patients (no-HS group). In both groups, the hemicranial volume ipsilateral to the epileptogenic focus was significantly smaller than on the contralateral side (p < 0.004). The HCV on both sides was smaller in the HS group compared with patients without HS (p < or = 0.004). Unilateral hippocampal atrophy and increased T2 value were found in 71% of patients with HS, and bilaterally normal HCV and T2 value were found in 67% of patients without HS. CONCLUSIONS: The smaller hemicranial volume on the focus side, irrespective of the presence or absence of HS suggests a different pathogenic mechanism for the additional hemicranial volume deficit, compared to HS itself. The contralateral HCV deficit depends on the presence of HS, indicating a pathogenic connection between damage to both hippocampi.