Renate M Kalnins

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.

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.

Cerebellar infarction: natural history, prognosis, and pathology.

Using clinical and computed tomography (CT) criteria, an analysis of 2,000 consecutive stroke unit patients from 1977 to 1984 revealed 30 patients with cerebellar infarction. The case fatality rate was 23%, higher than for any other location of brain infarction studied over the same period. Death was most often due to concomitant brainstem infarction. Obstructive hydrocephalus occurred in 4 patients (13%), and in 2 cases diagnosis, facilitated by urgent CT scanning, allowed early surgical intervention that was life saving. Patients who survived the acute phase were followed for an average of 21 months, and over that time 22% sustained further brainstem infarction, representing a 13% stroke rate per year. Over the latter 3 years of the clinical study, an autopsy survey revealed 11 cases of cerebellar infarction that had been clinically unrecognized. None of these died as a direct result of their infarction. Mechanisms of infarction inferred from autopsy included in situ thrombosis, embolism, watershed, and lacunar infarction, with in situ thrombosis being the most common. We conclude that the case fatality rate of cerebellar infarction is greater than of any other form of brain infarction, but it may be reduced by prompt recognition of those patients who will benefit from surgical decompression. In survivors, a high risk of subsequent hindbrain stroke exists. More attention needs to be paid to this entity in terms of early diagnosis and prevention of subsequent stroke.

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

Summary: 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).

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria

Abstract. The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimers disease but low agreement for cases with possible Alzheimers disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimers disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

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

Article abstract 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.

Catecholamine uptake sites in mouse brain: distribution determined by quantitative [3H]mazindol autoradiography

Because of the importance of the mouse brain catecholamine system in the study of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and because little information is available concerning the chemical neuroanatomy of the mouse, catecholamine uptake sites were mapped in C57 black mouse brain using [3H]mazindol autoradiography. Displacement studies with known dopamine (DA) and noradrenaline (NA) uptake blockers showed that binding in the striatum was entirely to DA uptake sites, while binding in the locus coeruleus was to NA uptake sites only. By using the selective noradrenergic uptake blocker desmethylimipramine (DMI), a complete map of both DA and NA uptake sites was generated. The mesostriatal DA system was the most clearly labelled and uptake sites were seen better in striatal terminals than the substantia nigra. Within the noradrenergic system, highest binding levels were seen over the locus coeruleus, although it was unclear whether these uptake sites were on cell bodies or terminals from the lateral tegmental noradrenergic system. These maps of the catecholamine uptake system in mouse brain provide a baseline for study of newly discovered neurotoxins 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 Parkinsons 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.

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.