Hippocampal volume and depression: insights from epilepsy surgery.

BACKGROUND: Major depression is common after epilepsy surgery. It has previously been suggested that surgical removal of limbic system structures such as the hippocampus may contribute to this comorbidity. Recent magnetic resonance imaging studies have found smaller hippocampal volumes in depressed patients in comparison with controls. AIMS: The current study examined whether preoperative hippocampal volumes were associated with depression experienced after epilepsy surgery. Patients undergoing mesial (n = 26) and non-mesial (n = 16) temporal lobe resections were assessed preoperatively, and for 1 year postoperatively. Assessment included a clinical interview and the Beck Depression Inventory. Hippocampal volumes were measured on the preoperative T1-weighted magnetic resonance imaging scans of the patients and 41 neurologically normal controls. RESULTS: A similar proportion of mesial and non-mesial temporal patients had a preoperative history of major depression. Postoperatively, 42% of mesial and 19% of non-mesial temporal patients were depressed. There was no relationship between hippocampal volume and preoperative depression in either group. Depression after surgery was associated with significantly smaller hippocampal volumes contralateral to the resection in the mesial temporal group (p = 0.005). This effect was seen in mesial temporal patients who developed de novo depression (p = 0.006). Hippocampal volume was unrelated to postoperative depression in the non-mesial group. CONCLUSION: This study highlights the role of neurobiological factors in the development of postoperative depression. These initial findings have implications for understanding depression following epilepsy surgery as well as the pathogenesis of depression more generally.

The electroencephalogram and acute ischemic stroke. Distinguishing cortical from lacunar infarction.

One hundred consecutive cases of clinically diagnosed, acute forebrain infarction were studied using computerized tomography (CT) and electroencephalography (EEG). Computed tomography confirmed brain infarction in 91 patients and was normal in the remaining nine. Each EEG was read independently by two experienced electroencephalographers without knowledge of CT or clinical details and their findings were compared with those of CT. Lateralized theta and/or delta activity predicted ipsilateral cortical infarction with a sensitivity of 76% and specificity of 82%. In contrast, cerebral hemisphere lacunae produced similar EEG abnormalities in only a few cases (9%). Electroencephalography is particularly useful following stroke if the initial CT excludes hemorrhage but does not detect infarction. In conjunction with clinical details, the EEG can then be used to indicate the likelihood of cortical involvement and thus suggest the likely pathophysiologic mechanism of infarction.

Striatocapsular infarction: large infarcts in the lenticulostriate arterial territory.

A specific form of deep cerebral hemisphere infarction was identified in 11 of 1,600 stroke register patients. Despite the CT finding of a deep striatocapsular lesion, these patients showed evidence of both cortical and capsular abnormalities. Angiography showed significant proximal carotid artery lesions as well as evidence of occlusive or obstructive lesions in the region of the T junction of the internal carotid artery. The combination of these pathologic entities would explain this particular clinical picture.

Human brain, plasma, and cerebrospinal fluid concentration of sodium valproate after 72 hours of therapy.

Nine neurosurgical patients suffering from a variety of brain tumors were studied. Sodium valproate was given for 3 days before surgery. At craniotomy, sections of brain and samples of cerebrospinal fluid (CSF) and plasma were obtained and assayed for sodium valproate concentrations. Brain levels were 6.8 to 27.9% of plasma concentrations, and CSF levels were 7.6 to 25.0% of plasma levels. There was a significant correlation between brain and CSF levels and plasma on Spearman ranking. These results confirm that valproate is not selectively concentrated in brain fractions, and the concentration in brain is related to the free anticonvulsant level in plasma.

A prospective study of lacunar infarction using computerized tomography.

Sequential computed tomography (CT) scans were performed for up to 7 months on patients who presented with clinical evidence of lacunar infarction or ischemia. Sixty-nine percent of the patients showed lacunar infarction, and a negative scan did not suggest a better prognosis in stroke patients. Of patients with transient ischemic attacks (TIA) (lacunar), those with repeated bursts of hemiplegia (capsular warning syndrome) were more likely to be CT-positive (p less than 0.01). The clinical features of patients with lacunar infarction were examined and correlated with the features of infarction. Partial syndromes were found in 32% of the cases and included examples of monoparesis and dysarthria alone.

The capsular warning syndrome: pathogenesis and clinical features.

Transient ischemic attacks (TIAs) are not homogeneous and may consist of subsets with mechanisms as varied as their stroke counterparts. We describe a form of TIA in 50 patients where crescendo episodes of ischemia were restricted to the region of the internal capsule, usually causing symptoms affecting face, arm, and leg. These patients composed 4.5% of a consecutive series of patients admitted with TIAs over a 15-year period and 33% of all TIAs classified as subcortical. We believe that the ischemia was most often due to hemodynamic phenomena in diseases, single, small penetrating vessels. When cerebral infarction developed, it was usually lacunar and involved a single penetrating vessel, although occasionally striatocapsular or anterior choroidal artery territory infarction occurred. There was no evidence of artery-to-artery or heart-to-artery embolism. Resistance to various forms of therapy, including hemodiluting, anticoagulant, and thrombolytic agents, was common. Because of dramatic and easily recognizable clinical presentation, apparent specific pathophysiologic mechanism, and the development of early capsular stroke in a high proportion of cases (42%), we have termed this the "capsular warning syndrome."

Patterns of postictal cerebral blood flow in temporal lobe epilepsy: qualitative and quantitative analysis.

We used single-photon emission computed tomography (SPECT) to study postictal cerebral blood flow (CBF) in 51 patients with temporal lobe epilepsy. There were 78 seizures studied, 77 by early postictal injection of Tc-99m HMPAO (delay from seizure onset = 4.3 +/- 4.5 min) and one by ictal injection. Increased focal temporal lobe uptake, predominantly confined to the anteromesial region, was present in 83% and declined rapidly over 5 minutes. Reduced activity in the lateral temporal lobe accompanied the mesial increase in 80% of studies, extending over much of the ipsilateral hemisphere and closely associated with the degree and extent of postictal EEG slow waves. These patterns enabled correct seizure localization by blinded analysis in 69% (31/45) of the patients with a unilateral EEG focus. The remainder showed bilateral or no changes. One of six patients with bitemporal EEG foci had unilateral perfusion changes. The positive predictive value for the correct localization of a unilateral focus by postictal SPECT was 97% (31/32). Postictal CBF imaging with SPECT can be used to support noninvasive electrographic localization and may decrease the need for invasive electrode studies.

Rectal administration of sodium valproate in status epilepticus.

Six patients suffering from status epilepticus were refractory to parenteral treatment with either diazepam, amobarbital or both, and were given sodium valproate 200 to 800 mg every 6 hours. The drug was administered rectally as 200 mg lipid-based suppositories, thereby avoiding impaired absorption, which occurs in the presence of paralytic ileus. Plasma levels of sodium valproate in all patients reached the therapeutic range within 36 hours of starting therapy. Seizures were totally controlled in five patients and a 75 percent reduction was noted in the sixth. In two patients, the route of administration was changed from rectal to an equivalent oral dose with continuing control of seizures and minimal change in plasma levels, suggesting that bioavailability is similar for the two forms of the drug. The rectal route of administration was effective in achieving systemic absorption of sodium valproate in the treatment of status epilepticus.

Primary intraventricular hemorrhage: clinical and neuropsychological findings in a prospective stroke series.

Seven cases of primary intraventricular hemorrhage (PIVH) constituted 3.1% of intracerebral hemorrhages in a prospective stroke series of 2,950 patients. All patients collapsed suddenly and had a depressed state of consciousness. Focal signs, if present, were minimal and contralateral to the major site of hematoma. Angiography in four patients revealed three intracranial arteriovenous malformations and one moyamoya. We conclude that PIVH may be readily diagnosed radiologically and underlying vessel malformations should be sought by angiography. Survival is common (five of seven cases), but a severe amnesic state may be a persisting deficit.

Valproate prevents the recurrence of absence status.

We assessed the value of valproate in the prevention of recurrent attacks of absence status in 25 patients. Eighteen patients had primary generalized epilepsy with a mean frequency of attacks of absence status of 5.7 per year. After a mean follow-up period of 4.4 years, the attack frequency was reduced to 0.6 per year (p less than 0.0005); 14 patients had no recurrence, 3 had rare attacks with noncompliance, and 1 had an incomplete response probably due to gastrointestinal intolerance. Patients with evidence of generalized cerebral damage (n = 2) or with EEG evidence of focalization (n = 5) did not respond as favorably. Valproate is the drug of choice for the prevention of recurrence of absence status. Moreover, the response can be predicted on the basis of the electroclinical subtype of absence status.

Preoperative MRI predicts outcome of temporal lobectomy: an actuarial analysis.

We used actuarial methods to study outcome after temporal lobectomy in 135 consecutive patients classified into subgroups according to preoperative MRI findings. Sixty months after surgery, 69% of patients with foreign tissue lesions, 50% with hippocampal sclerosis, and 21% with normal MRIs had no postoperative seizures. An eventual seizure-free state of 2 years or more, whether the patient was seizure-free since surgery or not, was achieved by 80% of patients with foreign tissue lesions, 62% of those with hippocampal sclerosis, and 36% of those with normal MRIs. Outcome was worse in those with normal MRIs than in the other two groups. Early postoperative seizures with later remission (the "running down" phenomenon) occurred in all groups. Late seizure recurrence was present only in the hippocampal sclerosis group. These data show that preoperative MRI is a useful predictor of outcome and that actuarial analysis provides insight into different longitudinal patterns of outcome in MRI subgroups. This information can now be used in preoperative counseling.

Parietal lobe epilepsy: clinical features and seizure localization by ictal SPECT.

We studied clinical and ictal single-photon emission computed tomography (SPECT) features in 14 patients with parietal lobe epilepsy, nine of whom had structural parietal lobe lesions. Thirteen patients had simple partial seizures of somatosensory (eight), psychic (four), and motor (nine) types. Complex partial seizures (CPS) occurred in seven patients; six were psychoparetic (prominent staring, relative immobility) and one had hyperkinetic activity. Seizures lasted 7 to 110 seconds; 99mTc-HMPAO (hexamethylpropylene amine oxime) was injected ictally, 7 to 89 seconds from seizure onset and 0 to 74 seconds (mean, 21.0 +/- 24.4 seconds) before seizure termination. Ictal SPECT demonstrated focal areas of parietal hyperperfusion in all 14 cases and corresponded with sites of the structural lesions. Parietal hyperperfusion was anterior in eight, posterior in four, and diffuse in two. Quantitative analysis revealed increases in parietal side-to-side perfusion ratios on ictal compared with interictal scans of 11 to 51% (mean, 25.5 +/- 14.4%). Ictal SPECT localization correlated with two main clinical seizure patterns: an anterior syndrome characterized by sensorimotor manifestations and a posterior syndrome characterized by CPS of the psychoparetic type. Ictal SPECT is helpful for localization of parietal seizures. Parietal hyperperfusion is discrete and short-lived, demanding true ictal injections for diagnostic studies.

Hippocampal sclerosis can be reliably detected by magnetic resonance imaging.

Two independent blinded observers reported the preoperative MRIs in a series of 81 consecutive patients with intractable temporal lobe epilepsy who were undergoing temporal lobectomy. We then compared the nature and lateralization of the MRI abnormalities with the pathologic diagnosis and the side of lobectomy. The MRI criteria of hippocampal sclerosis were an increased T2-weighted signal and the signal's confinement to a unilaterally small hippocampus. Imaging was performed in coronal and axial planes, specially orientated along and perpendicular to the long axis of the hippocampal body. We found diagnostic MRI abnormalities in 25 of the 27 cases with pathologically proven hippocampal sclerosis (sensitivity 93%, specificity 86%). In addition, we detected all 13 foreign tissue lesions on MRI. Overall, we detected lateralized lesions on MRI that correctly predicted the side of the epileptogenic temporal lobe in 72 cases (89%), with 2 possible errors. A learning effect in appreciating the relatively subtle MRI changes of hippocampal sclerosis was apparent in our later cases, as shown by an improved correlation between the 2 observers. This study demonstrates that hippocampal sclerosis can be identified on MRI with a high degree of sensitivity and specificity.

Dystonia, clinical lateralization, and regional blood flow changes in temporal lobe seizures.

We analyzed the lateralizing value of ictal dystonia and head-turning in temporal lobe epilepsy, and sought the biologic basis of these clinical signs by studying the regional changes in perfusion with ictal single-photon emission computed tomography (SPECT). We identified unilateral temporal lobe epilepsy in 40 of 42 patients undergoing evaluation for temporal lobe surgery, and with ictal SPECT all 40 showed striking hyperperfusion of the epileptogenic temporal lobe. Twenty-five of the 40 patients showed unilateral or predominantly unilateral upper limb dystonia, which was opposite the epileptic temporal lobe in all cases. Analysis of regional count ratios in cases with ictal dystonia, compared with those without, showed significant changes only in the basal ganglia. Specifically, we found that ictal dystonia was associated with a relative increase in perfusion of the basal ganglia opposite the dystonic limb. Although we found 26 cases with head-turning, the sign was of no lateralizing value, even when only those with major or "tonic" versions (n = 11) were analyzed. Slight increases in cortical blood flow on the side opposite the direction of version were associated with head-turning, irrespective of the side of seizure focus. In clinical practice, ictal SPECT is a highly accurate aid in the lateralization of temporal lobe foci, in addition to providing a new method to investigate the pathophysiology of clinical signs in focal seizures.

Gelastic seizures and hypothalamic hamartomas: evaluation of patients undergoing chronic intracranial EEG monitoring and outcome of surgical treatment.

We retrospectively studied 12 consecutive patients with gelastic seizures and hypothalamic hamartomas who, because of intractable epilepsy, underwent chronic intracranial EEG monitoring or epilepsy surgery. All patients had medically refractory seizures that included laughter as an ictal behavior (gelastic seizures). The hypothalamic hamartomas were identified with neuroimaging studies (12 of 12) and by pathologic verification (four of 12). Associated clinical features included behavioral disorders (n = 5), developmental delay (n = 4), and precocious puberty (n = 2). Interictal extracranial EEG predominantly showed bi-hemispheric epileptiform changes suggesting a secondary generalized epileptic disorder. Intracranial EEG recordings, performed in eight patients, indicated the apparent focal onset of seizure activity (anterior temporal lobe [n = 7] and frontal lobe [n = 1]). None of the seven patients who underwent a focal cortical resection, however, experienced a significant reduction in seizure tendency. An anterior corpus callosotomy, performed in two patients with symptomatic generalized epilepsy, resulted in a worthwhile reduction in drop attacks. Results of this study may modify the surgical strategies in patients with gelastic seizures and hypothalamic hamartomas.

Post-ictal recognition memory predicts laterality of temporal lobe seizure focus: comparison with post-operative data.

Standardized verbal and visuo-spatial memory recognition were obtained on 15 patients with unilateral temporal lobe epilepsy (TLE), using a reference group of 43 (12 males, 31 females) subjects with no previous history of neurological disease. Inter-ictal measures on these two tasks failed to differentiate between those patients with left vs right seizure foci. When eight of these patients were tested post-ictally (within 1 hr of seizure), seven showed the expected selective memory impairment when compared to inter-ictal performance. Left TLE patients showed a relative lowering of verbal memory, whereas patients with right TLE showed a relative visuo-spatial memory impairment. A similar result was also found in the patients when a comparison between pre-operative (inter-ictal) and post-operative performance was made, thereby further substantiating the validity of the tasks. This significant association between side of seizure focus and selective impairment of post-ictal memory performance provides evidence of a more direct method of neuropsychological diagnosis in TLE patients prior to surgery.

Visual and quantitative analysis of interictal SPECT with technetium-99m-HMPAO in temporal lobe epilepsy.

Interictal 99mTc-HMPAO SPECT images were compared to ictal EEG localization in 51 patients with intractable temporal lobe epilepsy to determine their usefulness for preoperative seizure focus localization. Both quantified temporal lobe asymmetry and blinded visual detection of temporal lobe hypoperfusion were employed. Visual analysis detected ipsilateral hypoperfusion in 18 (39%) of the 46 patients with a unilateral focus and contralateral hypoperfusion in 3. None of the five patients with bitemporal foci had unilateral hypoperfusion. The positive predictive value of unilateral temporal lobe hypoperfusion was 86% (18/21). Quantified anterior temporal lobe asymmetry, greater than a previously derived normal range, correctly identified the focus in 22 (48%) but gave the wrong side in 5, resulting in a predictive value of 81%. The degree of asymmetry correlated inversely with age of seizure onset, but not with other clinical parameters, histology, or verbal and nonverbal memory. The usefulness of interictal 99mTc-HMPAO SPECT for pre-operative seizure focus localization is limited by low sensitivity when performed with a conventional rotating gamma camera. This suggests that ictal or immediate postictal imaging may be necessary for this purpose.

Outcome of temporal lobectomy: expectations and the prediction of perceived success.

PURPOSE: This study examined the independent contributions of medical and psychosocial factors to perceived surgical success. We aimed to develop a multidimensional model predictive of perceived surgical outcome. METHODS: Fifty anterior temporal lobectomy (ATL) patients were prospectively assessed, using a formally coded, semistructured clinical interview. This has been routinely administered pre- and post-operatively as part of a larger, nationwide study of Australian ATL patients. The interview covers a broad range of epileptological, psychiatric, neuropsychological and psychosocial issues. Variables from these domains were examined in relation to the patient's perception of surgical success at the 6-month post-operative review. RESULTS: Variables that correlated with success were analysed using principal components analysis and multiple regression. A predictive model of perceived surgical success emerged, which highlighted the multidimensionality of outcome. Independent effects were observed for both medical and psychosocial factors. These included the patients' pre-operative expectations of surgery, their post-operative seizure outcome, and affective state. The findings also highlighted the importance of discarding sick role behaviours associated with chronic epilepsy, after surgery. CONCLUSIONS: Traditional outcome measures (seizure frequency, post-operative affect) are significant in the patient's evaluation of surgical success. These traditional measures, however, do not account for the process of psychosocial adjustment surrounding seizure surgery. This process involves two major components: (1) positive anticipation of change prior to surgery, and (2) learning to discard roles associated with chronic epilepsy after surgery.

Rey figure distortions reflect nonverbal recall differences between right and left foci in unilateral temporal lobe epilepsy.

Recall of the Rey Complex Figure (RCF) by patients with left (N = 26) or right (N = 18) temporal lobe epilepsy was scored in terms of the qualitative approach developed by Loring, Lee, and Meador. Patients with right temporal lobe epilepsy exhibited significantly more qualitative errors on recall of the RCF than patients with left temporal foci, whereas standard RCF scores failed to differentiate the groups. A linear discriminant function analysis showed that 66% of patients were correctly classified into lateral focus groups on the basis of qualitative scores, with a sensitivity of 50% and specificity of 77%. Although unsuitable for clinical use in its present form, the qualitative approach appears to be a promising one. The findings offer support for the position that some aspects of nonverbal memory are critically dependent on the integrity of the right temporal lobe. The implications of this for reorganization of cerebral representation are examined.

Patient readmission and support utilization following anterior temporal lobectomy.

The aim of this study was to examine factors precipitating patient readmission, following anterior temporal lobectomy (ATL) for refractory epilepsy. A second aim was to explore the use of hospital outpatient and community support services ('outpatient services') by this patient population. These aims served the more general goal of identifying patients most likely in need of services additional to those routinely provided by our Seizure Surgery Follow-up and Rehabilitation Programme. The medical records of 100 consecutive ATL patients were retrospectively examined for the incidence and diagnoses precipitating acute readmission, and the utilization of additional outpatient services. Twenty-one patients (21%) required readmission post-ATL, totalling 47 readmissions between them. Psychiatric diagnoses were the most prevalent (53%), including anxiety, depression and/or post-ictal psychosis. Epileptological diagnoses were the other main precipitant (28%). Additional outpatient services were predominantly utilized for ongoing psychological support. Of the 21 patients requiring readmission, 10(10%) also needed additional outpatient services. These patients were predominantly female or unemployed, in contrast to male or employed patients who tended to require readmission only. Seventeen patients (17%) were maintained within the community using additional outpatient services only. Characteristics of these patients included disrupted family dynamics, limited social networks, and/or a psychiatric history. These patients were also more frequently beyond the 24-month follow-up period of the programme. A profile of patients most in need of additional support services can be constructed to assist team planning of proactive management strategies for the rehabilitation phase of ATL.