Biomedical subjects

I R Mackenzie

Publications and source records attributed to I R Mackenzie.

32 records · Page 2Linked to original sources

PubMed1996

Prospective neuropsychological assessment of nondemented patients with biopsy proven senile plaques.

Senile plaques are characteristic of Alzheimer's disease but also occur as an age-related change in some neurologically normal individuals at autopsy. The significance of these "incidental" senile plaques, with regard to the development of dementia, is unknown and cannot be assessed by postmortem studies. Patients with biopsy proven senile plaques offer an important opportunity for prospective followup. We identified senile plaques in temporal lobectomy specimens, removed in the surgical treatment of intractable epilepsy, from 11 patients. Review of preoperative neuropsychological test results showed no suggestion of dementia in any of the patients with senile plaques and no significant difference compared with controls. Postoperative followup ranged from 2 to 7 years (mean, 3.7 yr). There was no evidence of generalized cognitive deterioration in any of the study patients. These findings indicate that an abundance of senile plaques may be present without associated dementia and without cognitive deterioration for at least several years.

Adult↗

PubMed1995

Achromatic neurons in the cortex of progressive supranuclear palsy.

Achromatic neurons (AN) in the cerebral cortex are a characteristic feature of several neurodegenerative conditions including Pick's disease, corticobasal degeneration and some cases of primary progressive aphasia. Although AN are occasionally seen in some other diseases, their presence in progressive supranuclear palsy (PSP) has not been previously documented. We found significant numbers of AN in the cerebral cortex of five out of seven cases which had been diagnosed pathologically as PSP. The identification of AN was greatly facilitated by the use of neurofilament immunohistochemistry. The entorhinal and transentorhinal cortices were most frequently involved, but in several cases AN were also seen throughout the neocortex. The presence and number of AN roughly correlated with a history of clinical dementia. This suggests that cortical AN may be a common and important pathological finding in PSP.

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PubMed1995

Chronic myelopathy associated with human herpesvirus-6.

Human herpesvirus-6 (HHV-6) is implicated in a variety of neurologic diseases. We report a previously healthy elderly woman with progressive spastic paraparesis. At autopsy the spinal cord showed widespread demyelination, axonal loss, and chronic inflammation. HHV-6 DNA was amplified, using polymerase chain reaction, from spinal cord tissue, and glial cells were immunoreactive with an HHV-6 antibody. These findings suggest that HHV-6 may cause myelopathy.

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PubMed1994

Senile plaques in temporal lobe epilepsy.

Senile plaques (SP) are one of the characteristic pathological lesions of Alzheimer's disease (AD). They are also seen in the brains of some non-demented individuals as an age-related change. Identification of clinical conditions associated with these "incidental" SP could provide insight into AD pathogenesis. We have examined the presence of SP in lobectomy specimens (n = 101) removed in the surgical treatment of temporal lobe epilepsy (TLE). SP were present in 10 specimens from epileptic patients aged 36 to 61 years and the presence of SP correlated positively with patient age. No other significant AD-related pathology was identified and no patients showed any evidence of dementia on neuropsychological testing. When compared with temporal lobe tissue from non-demented, non-epileptic autopsy controls (n = 406), the density and distribution of SP was the same. The age-related incidence of SP however, was significantly greater in the epileptics. This suggests that some aspects of TLE has a positive influence on the formation of SP.

Adult↗

PubMed1994

Senile plaques do not progressively accumulate with normal aging.

Senile plaques (SP) are one of the pathologic hallmarks of Alzheimer's disease (AD). Models of SP formation, particularly the early stages, could provide valuable insight into AD pathogenesis. One such model may be provided by non-demented elderly individuals in whom some SP are a common incidental finding. This study has examined post-mortem brain tissue from a large number of such neurologically normal patients in an attempt to better understand the temporal sequence of SP formation. SP were identified in modified Bielschowsky-stained sections of mesial temporal lobe in 122 (30%) of 402 cases. The prevalence of SP in the temporal neocortex correlated strongly with patient age. Surprisingly, however, neither the mean nor maximum SP density showed any increase with age. This suggests that SP do not progressively accumulate in normal aging but develop over a limited time period after which their number stabilizes at a constant level. In most cases, all SP were of the diffuse type. In 37 cases (9%), however, some neuritic SP (NP) were also seen. Although the NP density did not show a significant increase with age either, the proportion of SP which were neuritic (NP/SP), did. This suggests that changes in SP morphology may be more important than total SP numbers in normal aging.

Adult↗

PubMed1994

The pathology and nosology of primary progressive aphasia.

We present three cases of primary progressive aphasia (PPA) with Pick-variant pathology to support a hypothesis of an underlying nosologic relatedness. Neuropathologic examination demonstrated focal brain atrophy with corresponding neuronal loss and gliosis, accompanied by superficial spongiosis. Specific histologic findings were ballooned neurons (Pick cells) in the atrophic areas, and in two of the cases, Pick bodies. They were immunoreactive for tau. In contrast to classic Pick's disease, there were no Pick bodies in the hippocampus. The intense neurofilament immunoreactivity of the perikarya of the ballooned neurons greatly facilitated their recognition. Based on our cases and a critical review of the literature, we hypothesize that the common underlying pathology of PPA is a variant of Pick's disease. Furthermore, we propose the concept of "Pick complex" to include other neurodegenerative diseases characterized by focal cortical degeneration, such as PPA, frontal lobe dementia, ALS with PPA, and corticonigral and corticobasal ganglionic degenerations.

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PubMed1993

Primary cerebral fibrosarcomas. Clinicopathologic study and review of the literature.

BACKGROUND: Primary of the brain and meninges are uncommon tumors. Information regarding optimum treatment is limited due to their rarity, and the best form of therapy is not yet known. METHODS: Nine patients between the ages of 22 and 61 years with primary fibrosarcomas confined to the brain and meninges were studied clinicopathologically. Tumors were superficially located in five patients and intracerebrally or deep in four patients. Treatment consisted of maximum feasible surgical resection (seven patients, gross total; one, subtotal; one, no surgery before death) and radiation therapy (45-60 Gy conventional fractionation) in eight of nine patients. RESULTS: Fibrosarcomas were moderate or high grade in seven of nine patients (78%). Immunohistochemical reactions with antisera to glial fibrillary acid protein (GFAP), cytokeratin, vimentin, desmin, and S-100 demonstrated vimentin positivity in five of nine patients and cytokeratin positivity in two of nine patients. Individual GFAP-positive cells were seen in two cases, thought to represent trapped reactive astrocytes. None were S-100-positive or desmin-positive. Eight patients have died, with a median survival time of 7.5 months (range, 1 day-96 months). Local recurrence developed in eight patients and distant recurrence in six patients. Systemic metastases developed in four patients (50%) and meningeal seeding in four patients (50%). Longer survival was observed in superficially located tumors (range, 7.5 months-96 months) compared with intracerebral tumors (range, 1 day-9 months). CONCLUSIONS: Primary fibrosarcomas of the brain are uncommon tumors, usually of high histologic grade, with a high rate of local recurrence. Their propensity for meningeal and distant relapse distinguishes them from tumors of glial origin. Immunohistochemistry is of limited diagnostic value, although it may facilitate exclusion of other diagnoses. Because the prognosis after conventional surgery with 50-60 Gy external beam radiation therapy is relatively poor, the authors recommend more aggressive therapy with maximal feasible resection followed by external beam radiation therapy to doses of 64-66 Gy. When effective chemotherapy is established for soft tissue sarcomas of the extremities, this should be evaluated in view of the high incidence of distant metastases.

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PubMed1991

Cysts of the neuraxis of endodermal origin.

Five colloid cysts of the third ventricle were compared with two spinal enterogenous cysts to examine the hypothesis that these entities have the same origin from primitive endodermal tissue. All the lesions showed cuboidal and columnar epithelium with mucus containing goblet cells and cilia. Immunohistochemistry for cytokeratin, EMA and CEA was positive in all the colloid cyst and enterogenous cyst epithelium. S-100 was focally positive in three of the colloid and one of the enterogenous cysts while vimentin and GFAP were negative in both. The anatomical distribution of both colloid and enterogenous cysts is reviewed. An illustrative case of an identical cyst within the fourth ventricle is presented. This suggests that the similarities between colloid and enterogenous cysts and the presence of identical lesions along the neuroaxis indicate that these structures are derived from primitive foregut endoderm.

Adult↗

PubMedDate not supplied

Role of microglia in senile plaque formation.

To assess the role of microglial cells in senile plaque (SP) formation, we examined the density and distribution of microglia in the temporal neocortex of three groups of nondemented individuals, chosen to represent sequential stages of SP formation (no SP, n = 14; diffuse plaques (DP) only, n = 12; both DP and neuritic plaques (NP), n = 14) and patients with Alzheimer's disease (AD, n = 11). The mean density of microglia was significantly greater in the AD group. In nondemented individuals, the presence of NP but not DP was associated with an increased number of microglial cells. Most NP (91%) were focally associated with microglial cells. DP less commonly contained microglia, however, individuals with some NP had microglia within a greater proportion of their DP (47%) than did those with only DP (19%). These findings suggest that: (a) microglia are not involved in the formation of DP; (b) the presence of NP is associated with both an overall increase in microglia and the focal aggregation of cells around NP; (c) microglia may be locally involved in the conversion of DP into NP. This final point represents the most significant aspect of this study, providing the first quantitative evidence to support a specific role for microglia in the formation of NP from DP.

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PubMedDate not supplied

Inflammation and Alzheimer's disease.

Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid beta peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.

Alzheimer Disease↗

PubMedDate not supplied

Postmortem studies of the effect of anti-inflammatory drugs on Alzheimer-type pathology and associated inflammation.

Examining postmortem tissue is the most direct way of evaluating the effect of antemortem drug use on the pathological processes believed to be important in Alzheimer's disease (AD). A small number of studies have recently been published in which data from human autopsy tissue and animal models provides important insight into the mechanisms by which anti-inflammatory (AI) agents may protect against AD. These indicate that certain classes of AI drugs may be capable of reducing the chronic inflammation which is consistently seen in AD brain tissue. In addition, a recent study using a transgenic mouse model of AD, suggests that AI therapy may also influence the accumulation of senile plaques and dystrophic neurites. The results of these and future postmortem studies will be invaluable in the development of optimum treatment strategies.

Alzheimer Disease↗

PubMedDate not supplied

Xanthoma disseminatum with massive intracranial involvement.

We present the case of a man who died 11 years after the onset of xanthoma disseminatum. His course was marked by numerous, large recurrent intracranial dural-based xanthomatous tumors requiring repeated neurosurgical intervention. Late in his course there was progressive quadriparesis, ataxia, ophthalmoplegia and bulbar palsy as a result of intraparenchymal brainstem involvement. At autopsy, there was extensive meningeal and intraparenchymal CNS disease and widespread systemic infiltrates. The gross and microscopic pathology are presented with immunohistochemical, ultrastructural and biochemical details. The present case is discussed in the context of the current classification scheme and the recent literature, where it is exceptional for the extent of CNS disease. Xanthoma disseminatum is currently classified as a non-X histiocytopathy, the pathogenesis of which remains uncertain. CNS involvement carries a poor prognosis in this otherwise benign condition.

Adult↗

PubMedDate not supplied

Symptomatic osteolipoma of the tuber cinereum.

Intracranial osteolipomas are rare lesions which occur in the region of the tuber cinereum. All cases reported to date have been incidental autopsy findings. We describe a patient who presented with a variety of neurological symptoms and had a typical osteolipoma surgically removed.

Adult↗

PubMedDate not supplied

Cerebral amyloid angiopathy with extensive mineralization.

Cerebral amyloid angiopathy (CAA, congophilic angiopathy) occurs with aging, Alzheimer's disease, and certain rare familial syndromes. It is an important risk factor for spontaneous intracerebral hemorrhage. In addition to the accumulation of amyloid within the walls of cortical and leptomeningeal blood vessels, CAA is often accompanied by other vascular changes (CAA-associated vasculopathies, CAA-AV). This case report describes the unusual finding of extensive vascular mineralization with CAA, a rare form of CAA-AV which was detected during life.

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