Basal ganglia calcification in BB/E rats with diabetes.

Human diabetes is associated with cognitive impairment and structural abnormalities in the brain such as cerebral atrophy. The aetiology of these abnormalities is not known. The BB/E rat is a well-established model of type 1 (insulin dependent) diabetes. A cohort of 34 BB/E rats with diabetes was divided into three sub-groups according to age (and duration of diabetes). Basal ganglia calcification (BGC) was present in the brains of more than 50% of diabetic animals, but not in any of 37 non-diabetic BB/E rats. BGC occurred more commonly in those animals which had the longest duration of diabetes (p=0.001), such that BGC was present in only 8% of animals with diabetes for 20 weeks, but in 100% of animals with diabetes for 60 weeks. There were no other significant light microscopic neuropathologic changes in diabetic animals. It will be important to investigate the mechanism of brain calcification, whether a similar process occurs in humans with diabetes, and its possible relationship to cognitive decline.

Venous angioma of the facial nerve: a case report.

BACKGROUND: Lower motor neurone type facial nerve palsy is a common condition that is very rarely caused by a neoplastic lesion. CASE DESCRIPTION: This case report describes a progressive facial palsy in a 62-year-old man because of a vascular tumor of the facial nerve. Histologic examination confirmed it to be a venous angioma. CONCLUSION: Meticulous imaging of the facial nerve is required to diagnose cases of progressive facial nerve palsy caused by a neoplastic lesion.

Cerebrovascular responses to pathophysiological insult in diabetic rats.

Diabetes mellitus is associated with altered cerebrovascular responsiveness and this could contribute to the pathology of stroke in diabetic patients. In these studies, we used a model of haemorrhagic stroke (intrastriatal injection of 50 microl blood) to examine subacute perilesional perfusion and blood-brain barrier (BBB) integrity in spontaneously diabetic rats. Volumes of striatal oligaemia (blood flow < 35 ml 100 g(-1) min(-1)) were significantly increased (>300%) in diabetic rats with intrastriatal blood, compared to either non-diabetic rats with blood or control diabetic rats with striatal injection of silicon oil. However, the increase in BBB permeability was both qualitatively and quantitatively similar in diabetic and control rats. Poorer outcomes following haemorrhagic stroke in diabetic patients may thus result from dysfunctional cerebrovascular control, and particularly decreased dilatatory reserve.

Pathology of small vessel stroke.

Disease of small intracerebral vessels is widely assumed to be responsible for the majority of small, deep-seated (lacunar) infarcts and primary intracerebral haemorrhages. Our present, limited understanding of the pathogenesis of these stroke subtypes, which together constitute up to one-third of all strokes, is based on a limited number of detailed pathology studies, supported by clinical, risk factor and imaging data. Further progress using these traditional approaches has been prevented by a variety of largely technical obstacles. It is suggested that advances in our understanding of the genetic basis of established and new animal stroke models, in turn linked to more focused human genetic stroke surveys, may hold the key to further insights.

The significance of intratumoural neurones and neuronal differentiation in diffuse gliomas: a case series.

We describe four patients, ranging from 26-40 years of age, who presented with seizures and large, poorly circumscribed cerebral tumours on magnetic resonance imaging. The resected tumours demonstrated a histopathology similar to low-grade glioma, but with admixed mature neurones. Immunohistochemistry demonstrated expression of putative neuronal antigens in the neuronal component as well as in tumour cells which did not show neuronal morphology. These tumours did not have the usual radiological and pathological features typical of gangliogliomas, but demonstrated an infiltrative pattern of growth and subsequent progressive behaviour. The term ganglioglioma, with its implication of good prognosis, is therefore inappropriate for tumours of this type. The expression of "neuronal" antigens by astrocytomas requires further investigation.

Cerebral infarction in adult AIDS patients: observations from the Edinburgh HIV Autopsy Cohort.

BACKGROUND AND PURPOSE: Autopsy series of patients with AIDS have found a 4% to 29% prevalence of cerebral infarction. Little is known of the prevalence of cerebral infarction when not associated with non-HIV central nervous system (CNS) infection, lymphoma, or cardioembolic sources. Clinical correlation has seldom been available. We describe the pathological and clinical features of patients from the Edinburgh HIV Cohort Study found to have had cerebral infarcts without evidence of non-HIV CNS infection, CNS lymphoma, or cardioembolic sources at autopsy. METHODS: From 183 autopsy cases, 26 without evidence of opportunistic cerebral infection or lymphoma were selected. These 26 cases went through a second selection process in which the presence of cerebral infarction, in the absence of the conditions mentioned, was verified. Histology and clinical records for the remaining patients were reviewed. RESULTS: Ten (5.5%) cases fulfilled the inclusion criteria and demonstrated similar hypoxic-ischemic lesions. Small-vessel thickening was seen in all cases, and perivascular space dilatation, rarefaction, and pigment deposition, with vessel wall mineralization and perivascular inflammatory cell infiltrates, were seen in some cases. Vasculitis was not found. One patient had had a transient ischemic attack, and no patient had had a stroke. CONCLUSIONS: Cerebral infarcts in HIV-infected patients are not common in the absence of cerebral non-HIV infection, lymphoma, or embolic sources. We found an HIV-associated vasculopathy with similar features in all risk groups. In AIDS patients presenting with stroke or transient ischemic attack, potentially treatable causes, such as cerebral coinfection or tumor, should be sought.

Stress-related primary intracerebral hemorrhage: autopsy clues to underlying mechanism.

BACKGROUND: Research into the causes of small-vessel stroke has been hindered by technical constraints. Cases of intracerebral hemorrhage occurring in unusual clinical contexts suggest a causal role for sudden increases in blood pressure and/or cerebral blood flow. CASE DESCRIPTION: We describe a fatal primary thalamic/brain stem hemorrhage occurring in the context of sudden emotional upset. At autopsy, the brain harbored several perforating artery fibrinoid lesions adjacent to and remote from the hematoma as well as old lacunar infarcts and healed destructive small-vessel lesions. CONCLUSIONS: We postulate that the emotional upset caused a sudden rise in blood pressure/cerebral blood flow, mediating small-vessel fibrinoid necrosis and rupture. This or a related mechanism may underlie many small-vessel strokes.

What pathological components indicate carotid atheroma activity and can these be identified reliably using ultrasound?

OBJECTIVE: The aim of this project was to determine whether histological features of 'active' plaque as described in the coronary circulation following acute myocardial infarction were similar in the carotid circulation, and whether these factors could be detected ultrasonically. METHOD: Endarterectomy specimens were prospectively collected, and examined histologically and assessed by two observers for ulceration, inflammation, size of necrotic core, thickness of fibrous cap, haemorrhage and luminal thrombosis. Ultrasound of the plaque obtained preoperatively was similarly coded (blind to pathology) and compared with the pathology. RESULTS: In 42 endarterectomy specimens, there was a highly significant relationship between a thin fibrous cap and a large necrotic core (P<0.002), irregular plaque contour (P<0.05) and ulceration (P<0.01) and between a large necrotic core (P<0.002) and ulceration and inflammation (P<0.05). Increasing amounts of necrosis were associated with more surface thrombosis (P<0.02). Ultrasound detected the thickness of the fibrous cap and 'any necrosis or haemorrhage' with some reliability (kappas are 0.53 and 0.5, respectively), but not ulceration, necrosis or haemorrhage on their own. CONCLUSION: Features corresponding to active atheromatous plaque are similar in the carotid and coronary arteries, and some of these, namely lucent areas in the plaque (corresponding to necrosis or haemorrhage) and the thickness of the fibrous cap, can be determined reliably with ultrasound.

Imaging features of leptomeningeal metastases.

AIMS: To assess the range of appearances, and accuracy of various methods of diagnosing leptomeningeal metastases. MATERIALS AND METHODS: In a retrospective study, the notes and imaging of all patients with a radiological and/or CSF cytological diagnosis of leptomeningeal metastasis (LM) were identified, and assessed for the following: age and sex, primary tumour type, presenting symptoms, initial radiological and cytological diagnosis, radiological appearances and length of survival following diagnosis. Discordance between the CSF cytology and radiological diagnosis of LM was also noted. RESULTS: 41 positive cases (36 female) of LM were identified over a 2.7 year period (diagnosis based on: imaging only--19 cases, cytology only--6, both--16 cases). The average age was 48 years, and the most frequent primary tumour was breast carcinoma (27/41). Two thirds of patients presented with at least one cranial or spinal nerve palsy. Where performed, contrast-enhanced CT was normal in 40% (10/25), with LM mistaken for parenchymal disease in a further 24% (6/25). CSF cytology was positive in 85% (22/26). Gadolinium-enhanced MRI was positive in all cases where it was performed (25/25). Pial enhancement and nodularity was the commonest finding (67%), but other manifestations included nodular disease, neural enhancement and white matter changes. Prognosis was uniformly poor. CONCLUSION: Leptomeningeal metastatic disease has a poor prognosis, and treatment regimen may differ from those of parenchymal CNS metastases. CT is normal or misleading in two thirds of patients, and CSF cytology may also be negative. Gadolinium-enhanced T1-weighted MRI complements CSF cytology, and is the investigation of choice in patients with a non-haematological primary tumour and suspected LM.

Inverse relation between Braak stage and cerebrovascular pathology in Alzheimer predominant dementia.

The most common neuropathological substrates of dementia are Alzheimer's disease, cerebrovascular disease, and dementia with Lewy bodies. A preliminary, retrospective postmortem analysis was performed of the relative burden of each pathology in 25 patients with predominantly Alzheimer's disease-type dementia. Log linear modelling was used to assess the relations between ApoE genotype, Alzheimer's disease, and cerebrovascular disease pathology scores. Sixteen of 18 cases (89%) with a Braak neuritic pathology score

Intracerebral haemorrhage and cerebral amyloid angiopathy: CT features with pathological correlation.

AIMS: To review the computed tomography (CT) features of intracerebral haemorrhage pathologically proven to be associated with cerebral amyloid angiopathy in order to facilitate recognition of the presence of cerebral amyloid angiopathy in life. METHODS: We prospectively collected the clinical and brain imaging records of patients dying following an intracerebral haemorrhage who underwent a post-mortem examination and were found to have cerebral amyloid angiopathy. We reviewed the brain imaging to highlight features of the haemorrhage and of the rest of the brain common to these cases. RESULTS: Seven patients aged 60-86 years were examined over a 30-month period. On CT, the notable features were that the haemorrhages appeared large, lobar, often extended through the cortex to the subarachnoid space or into the ventricles, and were multiple and recurrent in patients who survived the initial bleed. The high density (blood) within the haematoma tended to sediment posteriorly. CONCLUSIONS: There are features on CT of cerebral amyloid angiopathy associated with spontaneous intracerebral haemorrhage which should raise the possibility of this underlying diagnosis. We suspect this condition is under-recognized in life, and should perhaps be considered more widely.

Neuropathologic characterization of a rodent model of closed head injury--addition of clinically relevant secondary insults does not significantly potentiate brain damage.

We have characterized the early brain pathology in Sprague-Dawley rats subjected to a modified Richmond impact acceleration model of closed head injury (CHI). This model was modified to produce maximal traumatic brain injury (TBI) in the absence of skull fracture, extracerebral or intracerebral hemorrhage, or brain contusion. We then used this model to assess the neuropathologic effects of superimposed secondary insults, which were designed to reflect a clinically relevant combination of hypotension and pyrexia. Acute neuronal injury, blood-brain barrier (BBB) integrity, axonal injury (AI), and glial activation were studied 4 1/2 hours following either CHI (group A), CHI plus secondary insults (group B), secondary insults alone (group C), or sham control injury (group D). There was evidence of limited AI following CHI in the lower medulla and upper cervical cord region, which was not modified by addition of secondary insult. Loss of dendritic microtubule-associated protein MAP2 immunoreactivity proved a reliable marker of acute neuronal damage, which was confined to subimpact and inferolateral cortical locations following CHI and was widespread after secondary insult. The pattern of plasma protein extravasation paralleled that of acute neuronal injury. We found no evidence of microglial activation, either local or generalized, by 4 1/2 hours. However, by this time CHI and secondary insults had combined to produce evidence of subimpact astrocyte activation, which was not apparent with either insult or injury alone. We conclude that in this modified Richmond model of CHI, when combined with secondary insults, there is no convincing potentiation of brain damage with the minor exception of astrocyte activation.

Recently occluded intracranial and extracranial carotid arteries. Relevance of the unstable atherosclerotic plaque.

BACKGROUND AND PURPOSE: It is now widely accepted that thrombotic coronary artery occlusion usually follows rupture of an unstable atherosclerotic plaque. The significance of such instability in arteries supplying the brain is less well appreciated. We therefore describe the clinical and pathological features of recent, symptomatic internal carotid artery occlusion to examine the pathogenetic role of plaque instability at both extracranial and intracranial sites. METHODS: Cases were selected from a consecutive series of 188 adult neuropathology autopsies. In 90 of these, the principal neuropathological abnormality was cerebral infarction, in 14 cases due to recent occlusion of 1 or more segments of the internal carotid artery. In each case, a full systemic, cardiovascular, and neuropathological autopsy was performed. Plaque instability was assessed by the presence or absence of a large, necrotic, lipid core; a thin, fibrous cap; and superficial inflammation. RESULTS: Of the 14 cases, 3 showed extracranial (carotid sinus), 7 intracranial, and 4 both extracranial and intracranial carotid artery occlusion. In 6 of the 7 occluded carotid sinuses, thrombus overlay an ulcerated, unstable, atherosclerotic plaque. In 1 extracranial and all 11 intracranial occlusions, there was either no atheroma or a mildly stenotic, stable, fibrous plaque, and in these cases, the cause of occlusion was embolism (8 cases), giant-cell arteritis (1 case), and unknown (3 cases). CONCLUSIONS: Coronary-type rupture of an unstable atherosclerotic plaque is the usual cause of fatal occlusion of the carotid sinus, but other causes usually underlie intracranial carotid occlusion. The nature and consequences of intracranial atherosclerosis require further study.

Evaluation of serum markers of neuronal damage following severe hypoglycaemia in adults with insulin-treated diabetes mellitus.

BACKGROUND: Neurone-specific enolase (NSE) and protein S-100 (S-100) may be used as markers of acute neuronal damage in humans with neurological disorders. METHOD: To evaluate their use following a single episode of severe hypoglycaemia (defined as an episode requiring external assistance to aid recovery), serum concentrations of NSE and S-100 were measured following hypoglycaemia which had not caused persistent neurological impairment in 16 patients with insulin-treated diabetes (the 'hypo' subjects), and in three diabetic patients who died following severe hypoglycaemia. The serum proteins were also measured in 10 subjects with insulin-treated diabetes who had not experienced an episode of severe hypoglycaemia within the preceding year (the 'control' subjects). RESULTS: No differences in serum concentrations of NSE and S-100 were observed between the 'control' and the 'hypo' subjects at either 36 hours or seven days after the episode of severe hypoglycaemia (p>0.05). However, in two of the three subjects who died following hypoglycaemia, serum concentrations of the markers were markedly elevated. CONCLUSIONS: Any neuronal injury occurring during severe hypoglycaemia that is not associated with persistent neurological deficit is insufficient to provoke elevation of these serum markers. However, the measurement of serum concentrations of NSE and S-100 may have a prognostic role in evaluating clinical outcome following severe hypoglycaemia which is associated with neurological damage.

Atherosclerotic plaque at the carotid bifurcation: CT angiographic appearance with histopathologic correlation.

BACKGROUND AND PURPOSE: The likelihood that carotid plaque will give rise to cerebral ischemia probably relates to the degree of arterial stenosis and to plaque morphology. The aim of this study was to assess whether features seen at CT angiography might be used to predict carotid plaque stability by comparing CT angiograms with histopathologic examinations of the carotid artery bifurcation. METHODS: Nine patients with symptomatic severe carotid stenosis at intraarterial angiography had CT angiography of the carotid bifurcation before carotid endarterectomy. After endarterectomy, multiple sections of the specimens through the carotid bifurcation were examined histologically. Plaque characteristics recorded included the proportion of necrotic/lipid core, presence of hemorrhage, extent of fibrosis, ulceration, calcification, inflammatory cell infiltrate, and fibrous cap thickness. Corresponding CT angiograms were assessed for plaque size, distribution, and radiodensity as well as presence of calcific density and ulceration. Histologic findings and CT angiograms were compared. RESULTS: Plaque with a large necrotic/lipid core, which was often hemorrhagic, was found in 16 of 23 sections, and in 15 of these this histologic appearance corresponded with patchy or homogeneous low density on CT angiograms. Six of seven predominantly fibrous plaques were of soft-tissue density on CT angiograms. High density consistent with calcification was seen more frequently on CT angiograms than it was detected histologically, but CT angiography depicted plaque ulceration poorly (four ulcers at histology; two false-positive and two false-negative findings at CT angiography). CONCLUSION: CT angiography is a promising method for assessing the lumen and wall of the carotid artery. The apparent correlation between histologic appearance and plaque density on CT angiograms has important implications for the prediction of plaque stability, even though ulceration is shown inconsistently.

Small centrum ovale infarcts--a pathological study.

There are limited data, mainly clinical and radiological, on small centrum ovale infarcts (SCOIs). From a consecutive series of 159 autopsy brains we identified 12 cases which on gross pathological examination harboured a total of 21 SCOIs. In the majority of lesions histology revealed a significant component of incompletely infarcted brain. Clinicopathological data suggested that the underlying mechanism was likely to have been cardioembolic in 3 cases, and possibly embolic from heart or aortic arch in a further 5. Two cases were due to ipsilateral carotid artery atheroma (i.e. 10 of 12 cases had possible embolic sources). The majority of lesions appeared to lie in arterial borderzones. The combined data suggest that SCOIs are pathologically and pathogenetically heterogeneous, and therefore that the term 'lacune' is inappropriate because this implies intrinsic small vessel disease as the underlying cause. Clinically, potentially treatable cardiac and large vessel pathology should be excluded.

Dsyembryoplastic neuroepithelial tumour with discrete bilateral multifocality: further evidence for a germinal origin.

We report the case of a middle aged woman who developed refractory complex partial seizures in her early twenties. She had a right coloboma and neurological examination was normal. Neuropsychological assessments revealed mild impairments of non-verbal memory, and visuospatial and constructional difficulties. Serial CT and MRI showed multiple nodular abnormalities in her mid-brain, diencephalon, subependymal region and both mesial temporal lobes. EEG recording revealed a right medial temporal focus. She underwent en bloc temporal lobectomy. The surgical pathology revealed mesial temporal dysembryoplastic neuroepithelial tumour (DNET) in association with extensive, contiguous neocortical dysplasia. The proliferation marker MIB-1 revealed up to 2% labelling in tumour areas resembling conventional oligodendroglioma. In the two years since surgery she has been seizure free and the remaining MR brain abnormalities have not changed. The very unusual centripetal MRI pattern of discrete multifocal lesions with the characteristic T1 and T2 features of DNET would support the dysembyroplastic germinal origin that was proposed by Daumas-Duport et al. (1988) in their original description of the lesion. The neuroradiological, neuropathological and clinical features of this case are compared with the two previous cases of multifocal DNET.