Imaging beta-amyloid burden in aging and dementia.

OBJECTIVE: To compare brain beta-amyloid (Abeta) burden measured with [(11)C]Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias. METHODS: Thirty-three subjects with dementia (17 AD, 10 dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects (HCs) were studied. Abeta burden was quantified using PIB distribution volume ratio. RESULTS: Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or normal pattern. Binding was greatest in the precuneus/posterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis. CONCLUSIONS: Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if Abeta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that Abeta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce Abeta may benefit this condition.

Dominant intermediate Charcot-Marie-Tooth neuropathy maps to chromosome 19p12-p13.2.

The hereditary disorders of peripheral nerve form one of the most common groups of human genetic diseases, collectively called Charcot-Marie-Tooth (CMT) neuropathy. Using linkage analysis we have identified a new locus for a form of CMT that we have called "dominant intermediate CMT" (DI-CMT). A genomewide screen using 383 microsatellite markers showed strong linkage to the short arm of chromosome 19 (maximum LOD score 4.3, with a recombination fraction (straight theta) of 0, at D19S221 and maximum LOD score 5.28, straight theta=0, at D19S226). Haplotype analysis performed with 14 additional markers placed the DI-CMT locus within a 16.8-cM region flanked by the markers D19S586 and D19S546. Multipoint linkage analysis suggested the most likely location at D19S226 (maximum multipoint LOD score 6.77), within a 10-cM confidence interval. This study establishes the presence of a locus for DI-CMT on chromosome 19p12-p13.2.

Miller Fisher syndrome mimicking stroke in immunosuppressed patient with rheumatoid arthritis responding to plasma exchange.

A patient with rheumatoid arthritis on immunosuppressive therapy was admitted to hospital with the sudden onset of diplopia and ataxia. Because of the history, a stroke was thought most likely. However, as he progressed a diagnosis of the Miller Fisher syndrome was established. He responded to plasma exchange. This presentation is highly unusual and has not previously been described. In addition, the possibility of immune dysregulation setting the stage for the development of this syndrome is discussed. The role of plasma exchange for this condition is also reviewed.

Doppler diagnosis in cases of acute stroke.

Ultrasound techniques are employed increasingly for the evaluation of patients with cerebrovascular disease. We determined the accuracy of carotid Doppler ultrasonography, which incorporated spectral analysis and periorbital directional Doppler assessment, by comparison with conventional or digital-subtraction arteriography in 93 patients (186 vessels). We also reviewed our experience with the Doppler technique in consecutive patients who were admitted to hospital with established carotid-territory stroke. The Doppler technique had a sensitivity of 93% and a specificity of 97% as a screening test for the presence of carotid stenosis, and a high level of precision. The arteriography rate in patients with completed stroke was 40% before the introduction of Doppler ultrasonography but decreased to 24% after its introduction, and to 16% in the last 100 cases. The proportion of cases in whom an underlying cause for stroke could not be identified decreased from 31% of cases to 21% of cases. Extracranial carotid stenosis was implicated in only 22 of the last 100 patients with carotid-territory stroke. Doppler ultrasonography is a valuable diagnostic tool in patients with completed stroke. It aids in the selection of patients for arteriography and provides clues to the pathogenesis of stroke in patients in whom arteriography is inappropriate.

Subcortical arteriosclerotic encephalopathy: Binswanger's disease.

Binswanger, in his 1894 dissertation on the differential diagnosis of general paresis of the insane, described a slowly progressive dementia associated with macroscopic loss of white matter. In recent years interest in Binswanger's disease was rekindled with CT demonstration of extensive white matter low densities in some patients. To define the clinical spectrum, we reviewed 22 consecutive cases in which the CT appearances suggested a diagnosis of Binswanger's disease. Two patients had focal neurological deficits at presentation, but recent anoxic or hypoglycaemic insults could not be excluded as the cause of the CT abnormalities. The 20 remaining patients were demented and showed variable combinations of corticobulbar dysfunction and gait dyspraxia. The duration of symptoms ranged from a few months to several years. Sixty per cent of this group gave a history of discrete stroke events and focal cortical and/or lacunar infarcts were a frequent CT finding. Binswanger's disease is probably due to chronic or acute-on-chronic white matter ischaemia. The association with lacunar and cortical infarctions suggests that a combination of large and small vessel disease produces diffuse ischaemia maximal in white matter watershed zones. Binswanger's disease is clinically differentiated from multi-infarct dementia by its time course.

Intravenous pulse methyl prednisolone in the successful treatment of severe sarcoid polyneuropathy with pulmonary involvement.

Severe widespread sarcoid polyneuropathy with associated pulmonary involvement was treated successfully in a 26 year old man using "pulse' methyl prednisolone. After he had failed to respond clinically to a two months course of high-dose oral prednisolone, a regimen of intravenous methyl prednisolone 1 g once a week for eight weeks was instituted, along with 10 mg prednisolone orally daily. Neurological improvement began after the third dose with complete remission achieved after the eighth week. More than 12 months after cessation of treatment he remains in good health with no clinical or laboratory evidence of sarcoidosis.

Adrenomyeloneuropathy--clinical and biochemical diagnosis.

Adrenomyeloneuropathy (AMN) is an X-linked storage disease of very-long-chain fatty acids that presents as primary adrenocortical failure combined with spastic paraparesis and peripheral neuropathy. This disorder was diagnosed in three unrelated adult males. Definitive diagnosis was made by finding elevated very-long-chain fatty acids in plasma and skin biopsy samples. Biochemical characterisation of this disease has elucidated its genetics, clarified its relationship with adrenoleukodystrophy of children and other phenotypic variants, and allowed heterozygote identification, accurate genetic counselling and prenatal diagnosis.

Cerebral blood flow after surgery for recent subarachnoid haemorrhage.

243 measurements of cerebral blood flow by a noninvasive (133)Xe clearance technique have been made in 45 patients undergoing surgery for a recently ruptured cerebral aneurysm. Two groups of patients have been defined by the presence or absence of a postoperative rise in cerebral blood flow which showed a significant correlation with level of consciousness after operation.

Effect of tinofedrine (Homburg D8955) on cerebral blood flow in multi-infarct dementia.

Tinofedrine, a new derivative of l-norephedrine, was examined for cerebral vasodilator activity in man. Ten patients with reduced cerebral blood flow (CBF) and multi-infarct dementia were given the drug intravenously. Cerebral blood flow increased significantly by 28% from a mean of 43.3 to 55.5 ml/100 g/min.

Xenon-133 inhalation method for regional cerebral blood flow measurements: normal values and test-retest results.

The purpose of this investigation is to determine the normal values for regional cerebral blood flow (rCBF) as determined by the xenon inhalation method of Obrist. Normal values for all rCBF parameters were measured in 15 healthy individuals. Our data are compared with the normal data obtained by other investigators. In addition, test-retest rCBF measurements were performed to determine the reproducibility of the method. Our results show that the method is highly reproducible when carried out in serial studies over a short period of time.

Doppler ultrasound scanning of the carotid bifurcation.

The results of Doppler scanning of 146 carotid bifurcations in 86 patients were correlated with carotid arteriography. The correlations for normal carotid arteries ranged from 63% to 98%; the correlation for occlusions of carotid arteries was 100%. The Doppler scan correlated in 70% to 85% of stenoses of the internal or external carotid arteries near their origins. The technique may be performed by a well-trained technician or physician.

Mechanisms in cerebral lesions in trauma to high cervical portion of the vertebral artery--rotation injury.

Three cases have been described illustrating the mechanisms and effects of lesions from acute rotation injury to the vertebral artery. These indicate that the portion of artery at risk is in the C1 to C2 region, where stretching and shearing strains can produce intramural dissection and haemorrhage. Such changes can radically alter flow to produce acute arterial obliteration or later cerebral embolism. Such alteration can also produce a change in relationships between artery and surrounding structures and thus cause intermittent occlusion of a vertebral artery upon cervical rotation.

Fluctuations of plasma phenytoin levels on single dose and twice daily dose regimes.

Eight chronic refractory epileptics were studied with regard to frequency of administration of phenytoin. There were no excessive fluctuations in plasma levels when the total drug dose was given as a single daily dose, and the clinical state of the patients was unchanged from that on twice daily dosage.

Frontal agraphia, (including a case report).

Frontal agraphia has always been a subject of interest, although very few documented case reports have been published. A 57 year old male clerk, suffering from adenocarcinoma of the signoid colon, presented with mild headache and difficulty in writing. Minor features of dysphasia could be detected, but there were no alexia, agnosia or apraxia. Brain scan and angiography confirmed a metastasis in the posterior part of the left prefrontal region. The patient was able to write single letters, and had no difficulty with automatic writing or copying. The writing of words and of sentences was more affected. After a brief review of the literature and discussion, the authors concluded that frontal agraphia is related to frontal lobe diorders, especially the inability to translate verbal signals into motor behaviour (i.e. writing).