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Delirium in Alzheimer disease.

Advanced age and dementia are well-known risk factors for delirium, and most studies of delirium have concentrated on hospitalized populations. We reviewed the records of 199 community-dwelling Alzheimer disease (AD) patients and identified 43 (22%) who had had episodes of delirium during their dementing illness. These patients were matched for age, gender, and disease duration to AD patients without previous episodes of delirium. Variables examined included causes of delirium, Mini-Mental State Examination scores, Clinical Dementia Rating scores. Blessed Activities of Daily Living (ADL) scores, years of education, neuropsychological performance, and incidence of behavioral symptoms on the Brief Psychiatric Rating Scale. In six of 198 (3%) patients delirium was an initial symptom of AD. Conditions associated with onset of delirium were urinary tract infections, stressful events, surgery, medical illnesses, and medications. No significant differences were found between groups on neuropsychological testing. Patients with previous episodes of delirium had worse ADL scores and higher disease-course incidences of hallucinations and paranoid delusions, mostly occurring during the delirious episode. We conclude that delirium is common in AD, but it is an unusual initial symptom and it occurs in diverse clinical settings. Measures of behavioral symptoms and ADLs are more likely to reflect the impact of delirium on clinical status than measures of cognition or stage of dementia.

Aged↗

Encephalopathy associated with bismuth subgallate therapy.

A 74-year-old man developed paranoid ideation, memory impairment, and defective gustatory and olfactory function while on bismuth subgallate therapy for use as a colostomy deodorant. Twenty-four-hour urine bismuth was elevated at 889 micrograms/day, and whole blood bismuth concentration was 67 micrograms/L. The patient improved after discontinuation of bismuth subgallate; there was resolution of paranoid behavior and gustatory and olfactory functions improved. Follow-up whole blood bismuth concentration was 21 micrograms/L 4 weeks after cessation. Altered gustatory and olfactory function have not been previously reported with bismuth intoxication.

Aged↗

Temporal patterns of uncoupling between oxidative metabolism and regional cerebral blood flow demonstrated by functional magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Brain activation can be detected by functional magnetic resonance imaging. Termination of stimulation can cause drop of postactivation signal below preactivation baseline; the nature of this "undershoot" remains controversial. The authors investigated postactivation signal after stimulation of the visual cortex with photic stimuli of different duration. METHODS: Activation of visual cortex in 11 healthy subjects was studied. The authors underwent short and long stimulation. The relation between activation and postactivation signal was investigated after both durations of stimulation. RESULTS: Average postactivation signal after short stimulation was -1.71 +/- 2.66% and after long stimulation 0.82 +/- 1.59% (P < or = 0.01). Significant "undershoot" was detected after short stimulation in the majority of cases, although this was typically absent after long stimulation. CONCLUSIONS: The authors propose that "undershoot" is caused by decreased oxygen content in venous blood compared with the preactivation level and may reflect increased extraction of oxygen as a result of glycolytic metabolism. The absence of "undershoot" after longer stimulation suggests a gradual shift from uncoupling between regional cerebral blood flow and oxygen consumption toward a steady state.

Adult↗

Cortical localization of human sustained attention: detection with functional MR using a visual vigilance paradigm.

PURPOSE: Our goal was to determine whether functional MRI on a standard 1.5 T system can localize activation during a visual vigilance sustained attention task and whether this corresponds to results described in a PET investigation of a similar task. METHOD: Sixteen volunteers were studied on a 1.5 T system using a gradient echo technique. A single axial section was oriented within a stereotaxic coordinate space, 40 mm superior to the anterior-posterior commissure line. Images with eyes closed were followed by images during subject concentration on a small dim spot. Motion correction and pixel-by-pixel statistical analysis were performed. Talairach grids were applied for summary statistical analysis and comparison to PET data, with analysis using a series of planned contrasts within a repeated measures analysis of variance. RESULTS: Predominantly right-sided frontal and parietal activation was observed, with statistical significance across subjects in the right frontal lobe (F > or = 5.9, p < or = 0.041). Comparison with previously reported PET data yielded a very similar pattern of activation (F = 13.2; df = 1,8; p = 0.007). CONCLUSION: Activation of the right middle frontal gyrus and right parietal lobe during visual vigilance is detectable across functional imaging modalities.

Adult↗

Autosomal dominant lateral temporal epilepsy: two families with novel mutations in the LGI1 gene.

PURPOSE: Mutations in the leucine rich, glioma inactivated gene (LGI1) were recently described in a small number of families with autosomal dominant lateral temporal epilepsy (ADLTE). ADLTE is characterized by partial seizures with symptoms suggestive of a lateral temporal onset, including frequent auditory aura. Here we report the results of clinical and genetic analyses of two newly identified families with ADTLE. METHODS: We identified two families whose seizure semiology was suggestive of ADLTE. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. The coding sequence of the LGI1 gene from affected subjects from both families was analyzed for evidence of mutation. RESULTS: Each patient had a history of partial seizures, often with secondary generalization earlier in the course. Auditory aura was reported by approximately two thirds of affected patients in each pedigree. Novel mutations in LGI1 were detected in both families. A heterozygous single-nucleotide deletion at position 329 (del 329C) was detected in affected individuals from one family, whereas patients from the second family had a nonsynonymous variation, corresponding to C435G. CONCLUSIONS: We identified two novel mutations in the LGI1 gene. The phenotype of these two families was similar to that of other kindreds with ADLTE, as auditory aura was absent in one third of affected individuals. Our results further support that LGI1 mutations should be considered in patients with a history of partial seizures if the semiology of seizures is consistent with the onset in the lateral temporal lobe.

Adult↗

High incidence of sensitization to ornamental plants in allergic rhinitis.

BACKGROUND: A few indoor plants have been described as potential allergens, in single case reports of allergic rhinitis. There is no data evaluating the prevalence of allergic sensitization to these plants. AIM: The relationship between owning indoor ornamental plants with the risk to be sensitized has been evaluated in atopic rhinitis. METHODS: A group of 59 patients with allergic rhinitis were submitted to skin prick tests (SPT) using both the leafs of their own plant and commercial extracts of the most frequent airborne allergens. A control group of 15 healthy subjects was tested with the same allergens. RESULTS: While no subject from the control group developed a significant SPT to any of the tested plants, 78% of allergic rhinitis had positive SPT to at least one plant, the most frequent sensitization being Ficus benjamina, yucca, ivy and palm tree. CONCLUSION: In allergic rhinitis, indoor plants should be considered as potential allergens.

Adolescent↗

Identification of a novel locus for febrile seizures and epilepsy on chromosome 21q22.

PURPOSE: To report results of linkage analysis in a large family with autosomal dominant (AD) febrile seizures (FS) and epilepsy. BACKGROUND: AD FS and epilepsy is clinically and genetically a heterogeneous group of epilepsies, frequently inherited. The most notable, generalized epilepsy with febrile seizures plus (GEFS+), is characterized by heterogeneous phenotypes including FS persisting beyond the usual age of remission or coexisting with afebrile seizures. Mutations in three subunits of sodium channel genes and one GABA(A)-receptor subunit gene have been identified in some GEFS+ pedigrees. Six genetic loci for FS have been reported so far, but the molecular basis of FS remains unknown. METHODS: We identified a five-generation family with 13 individuals affected by FS. Evidence was found for coexisting afebrile seizures in some affected individuals. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. After excluding previously identified loci associated with FS and epilepsy, a genome-wide search was performed. RESULTS: Two affected individuals reported only a single FS, whereas the other affected individuals had a history of repeated FS. Coexisting afebrile seizures developed in three individuals. The mode of inheritance was consistent with AD inheritance with an incomplete penetrance. Tight linkage to a group of markers on chromosome 21q22 was identified with flanking markers D21S1909 and D21S1444, and maximum 2-point lod score 3.35 for markers D21S1910 and D21S1894. We excluded four ion-channel genes within this 6.5-cM locus as a cause of FS and epilepsy in this family. CONCLUSIONS: We report a novel locus on chromosome 21q22 for AD FS. Identification of the gene causing epilepsy on chromosome 21q22 will advance our understanding of inherited epilepsy and FS, and possibly other types of epilepsies.

Adult↗

Blood flow velocities in basilar artery during rotation of the head.

The authors measured blood flow velocities with transcranial Doppler ultrasonography in the basilar artery after extreme rotations of the head. Studied subjects were divided in two groups according to the degree of asymmetry of the vertebral artery lumens. Rotation of the head caused significant reduction of the mean flow velocity in the basilar artery in the subjects with asymmetry of the vertebral arteries of more than 75%. The decline occurred only after the rotation ipsilaterally to the hypoplastic vertebral artery. This study confirms the importance of the collateral flow in the compensation of dynamic compression of the vertebral artery.

Adult↗

Stroke risk factors and development of collateral flow in carotid occlusive disease.

BACKGROUND AND PURPOSE: Blood flow through collateral vessels compensates for reduced blood flow through stenotic or occluded extracranial carotid arteries. Previous studies have shown that extent of collateral flow influences likelihood of stroke and its outcome. Here we analyzed the relationship between stroke risk factors (hypertension, coronary artery disease, diabetes mellitus, tobacco smoking and hypercholesterolemia) and number of patent intracranial collaterals detected by transcranial Doppler ultrasonography. SUBJECTS AND METHODS: We studied 182 patients with various degrees of angiography proven unilateral stenosis of the internal carotid artery. Contribution of the anterior and posterior communicating arteries to the perfusion of the cerebral hemisphere on the side of the stenosis or occlusion was evaluated by a series of compression tests performed during continuous insonation of the middle cerebral artery. The number of detected collateral vessels was correlated with analyzed stroke risk factors. RESULTS: Subjects with stenosis more than 75% or occlusion of the internal carotid artery had a higher frequency of two major intracranial collateral vessels (P< or =0.01 and P< or =0.001, respectively). Hypertensive patients with stenosis more than 75% or total carotid occlusion were more likely to have only a single collateral vessel than patients without hypertension (P< or =0.01 and P< or =0.05, respectively). Other risk factors did not influence the patency of preformed collateral vessels. CONCLUSIONS: Hypertension hindered the development of preformed intracranial collateral vessels in our patients with carotid occlusive disease.

Aged↗

Neuroimaging of vessel amyloid in Alzheimer's disease.

Despite extensive recent advances in understanding Alzheimer's disease (AD) we are unable to noninvasively establish a definite diagnosis during life and cannot monitor the cerebral deposition of amyloid beta protein (A beta) in living patients. We evaluated the use of 10H3, a monoclonal antibody Fab targeting A beta protein 1-28 labeled with Tc-99m. Six subjects with probable AD were studied using single-photon emission computed tomography (SPECT) at times from 0-24 hours following injection. Curves of radioactivity in blood demonstrate a half-life of the injected Fab of 2-3 hours. Images show uptake around the head in the scalp or bone marrow in all subjects. There is no evidence of cerebral uptake of the antibody. Scalp biopsies in all six patients demonstrate diffuse staining with 10H3 of the scalp, a pattern indistinguishable from that found in controls. Evidence of amyloid deposition in the scalp in AD is not seen with other anti-A beta antibodies, suggesting that 10H3 is cross-reacting with another protein. Further studies with anti-A beta antibodies will require longer-lived radionuclides to detect cerebral uptake at later times after injection to allow for complete clearance from the blood. Alternately, imaging using labeled A beta itself may provide a means for noninvasive targeting of cerebral amyloid.

Alzheimer Disease↗

Amyloid-beta protein angiopathies masquerading as Alzheimer's disease?

Current evidence from genetic and epidemiological studies supports the view that Alzheimer's disease (AD) is a heterogeneous disorder. While the disease is pathologically defined by the presence of specified lesions in form of amyloid plaques and neurofibrillary tangles within the parenchyma, other features of pathology are often either neglected or considered coincidental. Our studies suggest that cerebrovascular pathology is inherently part of the disorder, which could be an important factor in a cause or effect manner. We have recently identified subjects having died with severe amyloid beta (A beta) protein cerebral amyloid angiopathy (CAA) in the absence of a profound Alzheimer pathology. These subjects, diagnosed with dementia had a late onset disease and were found at autopsy to exhibit severe CAA but paucity of typical AD changes. Immunocytochemical studies showed numerous microvascular abnormalities as well as characteristic degeneration of the vascular smooth muscle in both surface and intracortical vessels. The pathology was also characterized by occasional intracerebral hemorrhages and multiple infarcts. Further assessment of the abnormalities and amyloid infiltrated cerebral vessels with antibodies to the carboxyl terminus of A beta indicated that the longer, more pathogenic form of A beta(1-42) was found to be highly associated with intracerebral hemorrhages. Our observations suggest that these mild AD cases with a predominantly vascular pathology are variants of AD and bear resemblance to the familial Dutch and Flemish versions of cerebral amyloidosis. We propose that AD is a group of diseases with a variable pathology analogous to the prion diseases, in which a vascular variant also exists.

Aged↗