Cystic meningioangiomatosis in neurofibromatosis type 2: an MRI-pathological study.

We report cerebral cystic meningioangiomatosis in a patient with neurofibromatosis type 2. An 18-year-old woman presented with progressive hemiparesis secondary to a meningioma at the foramen magnum. Her MR examination also demonstrated three small cortical and subcortical cystic lesions. She underwent surgery for the meningioma, but died from brainstem infarction. Post-mortem histopathological examination of the cystic lesions showed enlarged subcortical perivascular spaces with overlying meningioangiomatosis. The unusual features and possible pathogenesis are discussed.

Longitudinal study of MRS metabolites in Rasmussen encephalitis.

This study analyses the evolution of metabolite changes in an 8-year-old boy with focal Rasmussen encephalitis. Five MRI examinations, including magnetic resonance spectroscopy (MRS) were performed over 9 months. Following complex partial status, T2-weighted imaging showed transient dramatic signal increase in the left superior temporal gyrus and mesial temporal structures. Subsequent scans showed resolution of the swelling and signal normalization, with development of slight focal atrophy. MRS after status showed a reduction in N-acetylaspartate, total creatine and trimethylamines. Subsequent scans showed complete resolution of these metabolite abnormalities, followed later by development of further abnormal metabolite values. Lactate and glutamine/glutamate were elevated after status. After surgery, ex vivo high-field (1)H and (31)P MRS confirmed metabolite abnormalities (elevated choline and decreased aspartate, N-acetylaspartate, [(1)H]glutamate together with altered [(31)P]phospholipid ratios. These findings suggested active disease process in the anterior region of the excised superior temporal gyrus. We conclude that Rasmussen encephalitis is a combination of progressive encephalitic damage and fluctuating seizure effects, in which neuronal injury and recovery can occur. MRS measurements at a single time point should consider the fluctuating metabolite profile related to seizure activity.

Idiopathic generalized epilepsy: lack of significant microdysgenesis.

BACKGROUND: The idiopathic generalized epilepsies (IGE) are classically regarded as due to a functional abnormality. However, microscopic microdysgenetic changes have been reported in the majority of cases by one group. OBJECTIVE: To independently evaluate the microscopic microdysgenetic changes in a controlled, blinded study. METHODS: Five brains with IGE and five age-matched control brains were collected. Blocks were taken from nine standardized Brodmann areas, both hippocampi, and cerebellum. Slides were examined independently by two neuropathologists blinded to patient group, who qualitatively scored microdysgenetic features on standardized data sheets. The results were compared and any discrepancies were rescored by the pathologists together using a double-header microscope. Quantitative neuronal profile counts in the molecular layer in standardized Brodmann areas of frontal cortex and in deep frontal white matter were performed. RESULTS: Microdysgenetic features in nine Brodmann areas, hippocampi, and cerebellum were not increased in brains from subjects with IGE compared with control brains. Quantitative neuronal profile counts in the molecular layer of frontal cortex and deep frontal white matter were not increased in IGE compared with controls. CONCLUSIONS: This controlled, blinded study did not replicate the results of previous reports of microdysgenesis in IGE. Although factors such as syndrome heterogeneity and sample size may explain the discrepancy, technical factors could also play a role. The current ion channel hypothesis for the pathogenesis of IGE does not preclude microscopic or ultramicroscopic abnormalities and the search for these should continue.

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.

Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study.

OBJECTIVE: To examine the nature and frequency of anterior temporal lobe (AT) abnormalities that occur in intractable temporal lobe epilepsy (TLE). METHODS: We reviewed the MR scans and clinical histories of 50 consecutive patients with intractable TLE. Histopathology was available in 42 surgically treated cases. RESULTS: MRI demonstrated loss of the gray-white matter differentiation and decreased T1- and increased T2-weighted signal in the ipsilateral AT in 58% of the 50 patients. This appearance was observed in 64% of the 36 patients with hippocampal sclerosis (HS) but was also seen in patients without HS. These changes were associated with temporal lobe atrophy, a higher hippocampal T2 relaxation time, and a history of febrile convulsions. Pathologic examination showed that the MRI appearances were not caused by dysplasia, degenerative abnormalities, or inflammatory change. Histologic quantitation showed increased glial cell nuclei counts in the intractable TLE cases compared with controls. There was no difference in glial cell numbers between cases with AT abnormality and those without this appearance. Presence or absence of changes was not predictive of preoperative neuropsychology, postoperative change in neuropsychology, or seizure outcome after surgery. CONCLUSIONS: These frequently seen ipsilateral changes are not caused by gliosis and may reflect a nonspecific increase in water content in the temporal lobe. This may be due to myelin abnormalities or some other as yet unidentified pathologic factor.

Perfusion patterns during temporal lobe seizures: relationship to surgical outcome.

We sought to determine whether patterns of ictal hyperfusion demonstrated using [99mTC]HMPAO (hexamethylpropylene amine oxime) single photon emission computed tomography (SPECT) predict outcome of temporal lobectomy; in particular, whether the more extensive patterns of ictal hyperperfusion are associated with poor outcome. We studied 63 patients who had ictal SPECT studies prior to temporal lobectomy. Hyperperfusion on ictal SPECT scans was lateralized, and classified into: (i) 'typical', (ii) 'typical with posterior extension', (iii) 'bilateral' and (iv) 'atypical' patterns. Outcome (minimum of 2 years follow-up) was classified as either seizure free, or not seizure free. Actuarial analysis was used to test the relationship of SPECT patterns with outcome. There were 35 cases with the typical ictal SPECT pattern, 13 posterior, nine bilateral and six atypical cases. The atypical pattern was associated with lack of pathology in the surgical specimen. Outcome was similar for the typical, posterior and bilateral with 60%, 69% and 67% seizure free, respectively. In contrast, the atypical group had a worse outcome with only 33% seizure free. Actuarial analysis showed a significant difference in outcome between patients with the typical pattern, and patients with the atypical pattern (P = 0.04). We conclude that extended patterns of ictal perfusion in temporal lobe epilepsy do not predict poor outcome, indicating that extended hyperperfusion probably represents seizure propagation pathways rather than intrinsically epileptogenic tissue. Atypical patterns of hyperperfusion are associated with poor outcome and may indicate diffuse or extra-temporal epileptogenicity.

Developmental genetics of deleted mtDNA in mitochondrial oculomyopathy.

Heteroplasmic populations of mtDNA, consisting of normal mtDNA and mtDNA with large deletions, are found in the skeletal muscle and other tissues of certain patients with mitochondrial respiratory chain deficiencies, particularly in those with the CPEO (chronic progressive external ophthalmoplegia) phenotype. To study the developmental genetics of this mitochondrial disorder, the distribution of the deleted mtDNA in a wide range of tissues of different embryonic origins (total 34 samples from 27 tissues obtained at autopsy) was investigated in a patient with the CPEO syndrome. Three species of partially deleted mtDNA were observed, with deletions of 2.3 kb, 5.0 kb and 6.4 kb. Their tissue distribution suggests that the mtDNA deletions have occurred very early during embryonic development, prior to the differentiation events that lead to the formation of the three primary embryonic germ layers, and that the partially deleted mtDNA species were segregated during development mainly to the skeletal muscle and to tissues of the central nervous system.

Temporal lobe epilepsy subtypes: differential patterns of cerebral perfusion on ictal SPECT.

PURPOSE: We studied cerebral perfusion patterns in the various subtypes of TLE, as determined by pathology and good outcome after temporal lobectomy (as confirmation of temporal origin). METHODS: We studied clinical features and ictal technetium 99m hexamethyl-propyleneamineoxime (99mTc-HM-PAO) single-photon emission-computed tomography (SPECT) in four subgroups of patients with intractable temporal lobe epilepsy (TLE) treated with surgery: hippocampal sclerosis (group 1, n = 10), foreign-tissue lesion in mesial temporal lobe (group 2, n = 8), foreign-tissue lesion in lateral temporal lobe (group 3, n = 7), and normal temporal lobe tissue with good surgical outcome (group 4, n = 5). RESULTS: No major clinical differences in auras, complex partial seizures or postictal states were identified among the groups. Ictal SPECT showed distinct patterns of cerebral perfusion in these subtypes of TLE. In groups 1 and 2, hyperperfusion was seen in the ipsilateral mesial and lateral temporal regions. In group 3, hyperperfusion was seen bilaterally in the temporal lobes with predominant changes in the region of the lesion. Hyperperfusion was restricted to the ipsilateral anteromesial temporal region in group 4. Ipsilateral temporal hyperperfusion in mesial onset seizures can be explained by known anatomic projections between mesial structures and ipsilateral temporal neocortex. Bilateral temporal hyperperfusion in lateral onset seizures can be explained by the presence of anterior commissural connections between lateral temporal neocortex and the contralateral amygdala. CONCLUSIONS: We conclude that the perfusion patterns seen on ictal SPECT are helpful for subclassification of temporal lobe seizures, whereas clinical features are relatively unhelpful. These perfusion patterns provide an insight into preferential pathways of seizure propagation in the subtypes of TLE.

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.

Concurrent adjacent meningioma and astrocytoma: a report of three cases and review of the literature.

Three patients presenting with an adjacent meningioma and astrocytoma are described. A review of the literature discusses several modes of neuroimaging and the difficulties in diagnosing simultaneous adjacent tumors. Aspects of the pathology and etiology of these tumors are also reviewed.

Seizure outcome and pathological findings following temporal lobectomy in patients with complex partial seizures and foreign tissue lesions seen only on MRI.

11 patients with foreign tissue lesions (FTL) in the temporal lobe associated with complex partial seizures (CPS) were studied. All had lesions clearly definable on magnetic resonance imaging (MRI) but not seen on computerised tomographic (CT) scans. All cases showed seizure reduction following temporal lobectomy with 10 becoming seizure free. Pathology showed 9 tumours, 1 hamartoma and 1 cavernous angioma. Hippocampus was available for examination in 7 cases, showing abnormalities in 6. Our findings suggest MRI be mandatory in screening patients with CPS and that following surgery, outcome should be excellent.

Dopa resistance in multiple-system atrophy: loss of postsynaptic D2 receptors.

Postmortem autoradiography was used to explore the mechanisms underlying L-dopa resistance in 2 patients with multiple-system atrophy. Indices of striatal presynaptic dopamine terminal loss and dopamine (D1 and D2) receptors were provided by 3H-mazindol, 3H-SCH 23390, and 125I-sulpiride binding. Neuronal loss, gliosis, and loss of postsynaptic D2 receptors preferentially involved the middle and posterior of the putamen, that region of the striatum most intimately involved in motor function. Loss of D1 receptors in the same area occurred in only 1 patient. These findings suggest that in multiple-system atrophy, resistance to L-dopa is due to a loss of putamental D2 receptors. The differential effects on D1 and D2 receptors in 1 patient implies that different subpopulations of striatal neurons were selectively involved.

Lateralization of verbal memory and unilateral hippocampal sclerosis: evidence of task-specific effects.

This study retrospectively investigated the effect of left (LHS) versus right (RHS) hippocampal sclerosis on verbal memory, measured by means of the Paired Associate Learning and Logical Memory subtests of the Wechsler Memory Scale (WMS) administered as part of a routine preoperative assessment. Patients were selected for the presence of unilateral hippocampal sclerosis by means of preoperative magnetic resonance imaging (MRI) and postoperative neuropathology. The LHS patients (n = 20) were significantly worse on paired associate learning than RHS patients (n = 18), the performance of RHS patients being consistent with normative standards. In contrast, no laterality effect was seen on the immediate and delayed recall of passages; the evidence suggests that both groups performed at a mildly impaired level. It was suggested that the laterality of verbal memory is conditional upon specific task demands in patients with damage to mesial temporal structures.

Localised neuronal migration disorder and intractable epilepsy: a prenatal vascular aetiology.

Localised neuronal heterotopias are an increasingly recognised cause of intractable focal epilepsies. The aetiology of these circumscribed disorders of neuronal migration is often unknown although in some instances proximity to areas of prenatal infarction suggests that severe ischaemia was responsible. A patient is described with intractable complex partial seizures associated with heterotopic grey matter and cerebral hypoplasia confined to the territory of the left posterior cerebral artery; the left hippocampus was spared. Angiography showed a normal left anterior choroidal artery but a hypoplastic left posterior cerebral artery, implicating prenatal ischaemia without frank infarction as the aetiology of the malformation.

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.

Distribution of catecholamine uptake sites in human brain as determined by quantitative [3H] mazindol autoradiography.

Because of the importance of the catecholamine system in Parkinson's disease and its relevance to a variety of clinical movement disorders, catecholamine uptake sites were mapped in the human brain using [3H] mazindol autoradiography. Displacement studies with known dopamine (DA) and noradrenaline (NA) uptake blockers showed that binding in the striatum was to dopamine uptake sites; binding in the locus coeruleus was to noradrenergic uptake sites. By using the selective noradrenergic uptake blocker desmethylimipramine (DMI), a comprehensive map of both DA and NA uptake sites was generated. In general, catecholamine uptake sites were better seen in terminals than in cells of origin or axonal projections. In some areas, such as the locus coeruleus, punctate binding could be seen over individual pigmented cells. A variegated pattern of binding was seen in caudate nucleus and putamen and some correspondence of patches of low binding with striosomes was observed in the caudate. The highest levels of binding to DA uptake sites was observed in the striatum, where regional differences in binding occurred. The most dense binding was seen in the ventral striatum, and a rostral-to-caudal decrement in binding levels in caudate nucleus and putamen was evident. Binding was more intense in the putamen compared to the caudate and within the caudate lower values were seen laterally. The highest levels of binding to noradrenergic uptake sites were in the locus coeruleus and dorsal raphé, although these sites may be on terminals from other projections. Whereas uptake sites were more often evident in known catecholamine pathways, [3H] mazindol binding was seen in some areas where catecholamine neurons or terminals had not been identified previously. These maps of the catecholamine uptake system add further information concerning the nature of the distribution of catecholamines in human brain and provide an important baseline for the study of disease and ageing processes.

Evidence for plasticity of the dopaminergic system in parkinsonism.

A series of compensatory mechanisms within the dopaminergic system have been shown to maintain clinical function in the presence of dopamine loss. Experimental evidence for increased presynaptic dopamine turnover owing to increased dopamine synthesis, release, and reduced reuptake exists. Direct evidence that these mechanisms maintain extracellular dopamine levels is provided by intracerebral microdialysis techniques. Postsynaptic denervation supersensitivity clearly occurs with D2 dopamine receptors, although this is less evident with D1 receptors. Similarly, mechanisms of plasticity have been shown to be relevant in human postmortem and Positron Emission Tomographic studies of patients with Parkinson's disease. However, although presynaptic increases in dopamine turnover are well documented, postsynaptic D1 and D2 receptor changes have been more difficult to establish, mainly because of methodological difficulties. D2, but not D1, receptor increases have been documented in drug naive Parkinsonian patients with PET techniques. In transplantation of adrenal gland to striatum in animal models and patients with Parkinsonism where clinical improvement occurs, plasticity of host response may be as important as plasticity of the graft. Although some elements of the compensatory mechanism of dopamine plasticity may be deleterious, such as dyskinesias owing to dopamine receptor supersensitivity, the overall effect of delay and minimization of the clinical expression of disease is advantageous. An even greater understanding of the mechanisms involved may assist in developing future therapeutic strategies.