Teresa Burke

Microdysgenesis in resected temporal neocortex Incidence and clinical significance in focal epilepsy

Fifty patients underwent superficial temporal lobectomy for intractable temporal lobe epilepsy. Total cure rate was 52%, and significant improvement was achieved in 88%. Cytoarchitectural changes in gray and white tissue were analyzed under light microscopy. Neuronal dysgenesis was correlated with the duration of seizure disorder, age of onset, and other etiologic factors, and with clinical outcome. Temporal lobes from 33 neurologically normal autopsy brains which were age- and sex-matched with patients were examined as controls. Severe neuronal ectopia (> 8 neurons/2 mm2 white matter) was present in 42% of patients with epilepsy and in none of controls. There was neuronal clustering in 28% of those with epilepsy, and Chaslins (subpial) gliosis in 38%. Controls did not have these changes. The presence of severe neuronal ectopia and clustering was predictive of a favorable clinical outcome following surgery (p < 0.05). No correlation was found between microdysgenesis and other factors. These findings suggest that the presence of neuronal dysgenesis may be of significance in the clinical outcome following surgery, and that the abnormal tissue may be important as a morphologic substrate for seizures in some patients.

Topographical disorientation following unilateral temporal lobe lesions in humans.

Studies of the non-human temporal lobe, particularly the hippocampus, confirm its significant role in learning and memory, particularly allocentric spatial mapping of the environment. The role of the human temporal lobes in topographical orientation was investigated by examining the formation of representations of a large-scale real-world environment after unilateral left and right temporal lobe surgery. Patients and normal control subjects viewed videotape presentations of overlapping routes through a novel urban area. Topographical orientation was then assessed across a range of parameters. Right temporal lobe lesions alone gave rise to deficits in making proximity judgements. However, on all other topographical orientation tasks both right and left temporal lobe lesion groups were impaired relative to the normal control group, but the two patient groups did not differ significantly from each other. These findings suggest that such is the nature of remembering and way-finding in the environment that the integrity of both human temporal lobes is required.

Predictors of compliance with neuroleptic medication among inpatients with schizophrenia: a discriminant function analysis.

OBJECTIVE To identify clinically useful predictors of adherence to medication among persons with schizophrenia. METHOD We evaluated levels of compliance with neuroleptic medication among 32 consecutive admissions with DSM-III-R schizophrenia from a geographically defined catchment area using a compliance interview. We also assessed symptomatology, insight, neurological status and memory. RESULTS Less than 25% of consecutive admissions reported being fully compliant. Drug attitudes were the best predictor of regular compliance, symptomatology the best predictor of noncompliance, and memory the best predictor of partial compliance with neuroleptic medication. CONCLUSIONS These data emphasise the complexity of factors that influence whether a person adheres to his medication regimen. Furthermore, they suggest that these factors may vary within the same person over time.

Schizophrenia and neurological soft signs: Gender differences in clinical correlates and antecedent factors

Although it is recognized that patients with schizophrenia demonstrate more neurological soft signs (NSS) than control subjects, the significance and clinical correlates of these signs remain poorly defined. The present study examined 48 patients with DSM-III-R schizophrenia for evidence of NSS. The majority (98%) of patients demonstrated at least one NSS, although the range of scores was wide. There was no relationship between current dosage of neuroleptic medication and NSS score. Among males, there was a significant relationship between NSS and duration of illness. Males whose mothers experienced obstetric complications had higher NSS scores, while females with a family history of schizophrenia exhibited higher scores. These relationships in schizophrenia between NSS and factors of etiological importance wuch as obstetric complications and family history require further evaluation. The present findings are in accord with a body of evidence which suggests that gender may influence the impact of genetic and environmental factors on the neurology of the disorder.

Amnesic syndrome with bilateral mesial temporal lobe involvement in Hashimoto’s encephalopathy

Article abstract A 25-year-old woman presented with a subacute confusional state, headaches, unsteadiness, myoclonus, seizures, and an amnesic syndrome as a manifestation of Hashimoto’s encephalopathy. Investigations showed biochemical hypothyroidism, raised thyroid microsomal antibodies, and weakly positive antineuronal antibodies. A T2-weighted MRI of the brain showed bilateral symmetric areas of increased signal in the mesial temporal lobes and hippocampi that had a low signal intensity on T1-weighted imaging. Despite clinical and radiologic improvement after steroid and thyroid hormone replacement therapy, a severe amnesic syndrome with associated localized MRI abnormalities persists.

Detection of prospective memory deficits in mild cognitive impairment of suspected Alzheimer's disease etiology using a novel event-based prospective memory task.

We investigated the relative discriminatory efficacy of an event-based prospective memory (PM) task, in which specificity of the instructions and perceptual salience of the PM cue were manipulated, compared with two widely used retrospective memory (RM) tests (Rivermead Paragraph Recall Test and CERAD-Word List Test), when detecting mild cognitive impairment of suspected Alzheimers disease etiology (MCI-AD) (N = 19) from normal controls (NC) (N = 21). Statistical analyses showed high discriminatory capacity of the PM task for detecting MCI-AD. The Non-Specific-Non-Salient condition proved particularly useful in detecting MCI-AD, possibly reflecting the difficulty of the task, requiring more strategic attentional resources to monitor for the PM cue. With a cutoff score of <4/10, the Non-Specific-Non-Salient condition achieved a sensitivity = 84%, and a specificity = 95%, superior to the most discriminative RM test used (CERAD-Total Learning: sensitivity = 83%; specificity = 76%). Results suggest that PM is an early sign of memory failure in MCI-AD and may be a more pronounced deficit than retrospective failure, probably reflecting the greater self-initiated retrieval demands involved in the PM task used. Limitations include the relatively small sample size, and the use of a convenience sample (i.e. memory clinic attenders and healthy active volunteers), reducing the generalizability of the results, which should be regarded as preliminary. (JINS, 2009, 15, 154-159.).

Temporal neocorticectomy in management of intractable epilepsy : long-term outcome and predictive factors

Summary: We report the results of a long‐term follow‐up study of 50 patients who underwent removal of temporal neocortex with preservation of deeper limbic structures as surgical therapy for intractable temporal lobe epilepsy. The follow‐up period ranged from 3 to 15 years. Preoperative EEG investigations were based on interictal discharges alone. Three factors were predictive of a good outcome: (a) A clear unilateral anterior‐midtemporal focus (p < 0.01), (b) stereotypical onset of temporal lobe seizure (p < 0.005), and (c) greater volume of tissue removed at operation (p < 0.05). Overall results showed that 62% of patients experienced an outcome of “cure” or “almost cure,” as classified according to a modified version of Crandalls criteria (Crandalls I and II). Those who experienced a significant reduction in seizures but who continued to have intractable epilepsy (Crandalls III) were not considered to have had a good result. Overall outcome compares favorably with other that of centers using different surgical approaches and indicates that neocorticectomy is a suitable procedure in a highly selected population even when limited resources are available.

Linkage of AD HSP and cognitive impairment to chromosome 2p: haplotype and phenotype analysis indicates variable expression and low or delayed penetrance

We report linkage of a family affected with autosomal dominant hereditary spastic paraparesis (HSP) and/or cognitive impairment to the HSP locus on chromosome 2p. To date all families linked to this locus have been affected with ‘pure’ HSP. The specific pattern of cognitive impairment in this family is characterised primarily by deficits in visuo-spatial functions. We also present genetic studies that indicate variable expression and low or delayed penetrance. We have constructed a haplotype flanked by polymorphic markers D2S400 and D2S2331 that was present in 12 individuals affected with spastic paraparesis. The severity of spasticity varied markedly among these individuals. In addition four of these individuals (aged 62–70) also had a specific form of cognitive impairment. The disease haplotype was also present in an individual (age 57) who had an identical pattern of cognitive impairment as the only sign of the disease supporting the hypothesis that spastic paraparesis and cognitive impairment are the result of variable expression of a single gene (rather than a co-incidental occurrence). Haplotype reconstruction for all participating family members revealed the presence of this disease haplotype in six individuals who had normal neurological and neuropsychological examinations. All six are below the maximal age of onset in the family – 60 years. This is evidence for low or late penetrance of the AD HSP gene in this family. The identification of normal individuals carrying the disease haplotype demonstrates the importance of genetic studies in combination with clinical examination when counselling at risk family members.

Letter and Category Fluency in Alzheimer's Disease: A Prognostic Indicator of Progression?

This study investigated differential patterns of performance by 40 Alzheimers disease (AD) patients on standardised letter and category fluency tests. The performance of 24 age and education matched controls was used to classify patients as relatively more letter fluency impaired (L < C, n = 15) or more category fluency impaired (C < L, n = 25), and clinical features distinguishing these patient subgroups were investigated. Category performance was equally impaired in both patient subgroups, whereas the L < C subgroups were particularly impaired on letter fluency. The subgroups differed significantly in duration of illness (24 months for L < C group, 47 months for C < L group; t = 2.69, p = 0.01) but did not differ in global dementia severity, age, education, general language ability, or functional status. Data on annual rate of change (ARC) on the Mini-Mental State Examination were available for 26 patients. While not statistically significant, subgroup ARC differences were suggestive of more rapid decline in the L < C patients, consistent with the finding of shorter duration of illness in this group. Word fluency tests may have potential as early predictors of rate of progression in AD.

A qualitative exploration of how individuals reconstruct their sense of self following acquired brain injury in comparison with spinal cord injury

Abstract Primary objective: The present study aimed to investigate the specific ways in which individuals reconstruct their sense of self following injury to the nervous system, by comparing individuals with acquired brain injury (ABI) and individuals with spinal cord injury (SCI), two groups that have experienced a sudden-onset injury with life-changing repercussions. Research design: Phenomenological qualitative research. Methods and procedures: Nine individuals with ABI and 10 individuals with SCI took part in an interview exploring the ways in which individuals reconstruct their sense of self following injury. Data were analysed using interpretative thematic analysis. Main outcomes and results: Findings showed similar themes identified within the interview data of the ABI and SCI groups. Both groups developed positive and negative self-narratives. Individuals employed strategies that facilitated the reconstruction of positive self-narratives. In addition, individuals described their sense of self as simultaneously continuous and changing. Discussion: Findings are discussed in relation to proposed models of self-reconstruction post-injury to the nervous system.