Regional ß-amyloid burden does not correlate with cognitive or language deficits in Alzheimer's disease presenting as aphasia.

BACKGROUND AND PURPOSE: A subset of patients with Alzheimer's disease (AD) present with early and prominent language impairment (aphasic AD). Our previous study demonstrated an association between global ß-amyloid burden measured on [(11)C] Pittsburgh compound B (PiB) positron emission tomography and general cognitive impairment, but not with aphasia, in such subjects. As a follow-up, whether there is any association between regional ß-amyloid burden, atrophy on magnetic resonance imaging (MRI) and global cognitive impairment, aphasia or other cognitive and functional impairment in aphasic AD is assessed. METHODS: Forty-four aphasic AD subjects who underwent PiB scanning and volumetric MRI and were determined to be positive for ß-amyloid deposition were analyzed. All had completed detailed neurological, neuropsychological and language batteries. Spearman's rank-order correlation was utilized to assess for associations. RESULTS: Greater visuospatial impairment was associated with increased ß-amyloid burden in the primary visual cortex (P = 0.001). Although there were many trends for associations between neurocognitive and language deficits and regional ß-amyloid burden, there were no strong associations that survived correction for multiple comparisons. However, neurocognitive and language impairment in these subjects strongly correlated with the degree of left lateral temporal and inferior parietal atrophy (P < 0.004). CONCLUSIONS: The findings from this study suggest a close relation between the severity of regional atrophy and cognitive and language impairment, but argue against a strong association between regional ß-amyloid burden and such deficits in aphasic AD subjects. Hence, other pathological factors may be driving the previously identified association between global ß-amyloid deposition and general cognitive impairment in aphasic AD.

Amyloid burden correlates with cognitive decline in Alzheimer's disease presenting with aphasia.

BACKGROUND AND PURPOSE: A subset of patients with Alzheimer's disease (AD) present with early and prominent language deficits. It is unclear whether the burden of underlying ß-amyloid pathology is associated with language or general cognitive impairment in these subjects. METHODS: The relationship between cortical ß-amyloid burden on [(11) C]Pittsburgh compound B (PiB) positron emission tomography (PET) and performance on the Montreal Cognitive Assessment (MoCA), the Wechsler Memory Scale - Third Edition (WMS-III), the Boston Naming Test (BNT) and the Western Aphasia Battery (WAB) was assessed using regression and correlation analyses in subjects presenting with aphasia who showed ß-amyloid deposition on PiB PET. RESULTS: The global PiB ratio was inversely correlated with MoCA (P = 0.02) and the WMS-III Visual Reproduction (VR) subtest (VR I, P = 0.02; VR II, P = 0.04). However, the correlations between PiB ratio, BNT (P = 0.13), WAB aphasia quotient (P = 0.11) and WAB repetition scores (P = 0.34) were not significant. CONCLUSION: This study demonstrates that an increased cortical ß-amyloid burden is associated with cognitive impairment, but not language deficits, in AD subjects presenting with aphasia. The results suggest that ß-amyloid deposition could be partly contributing to impaired cognition in such patients whilst language dysfunction may be more influenced by other pathological mechanisms, perhaps downstream pathways of ß-amyloid deposition.

Timing of prophylactic antibiotic at cesarean section: a double-blinded, randomized trial.

OBJECTIVE: The purpose was to determine the effect of the timing of prophylactic antibiotics for cesarean section on post-operative infectious complications. STUDY DESIGN: This was a prospective, double-blinded, randomized controlled trial in which patients were randomized to receive cefazolin or clindamycin either before skin incision or after cord clamp. The primary outcome was maternal infectious morbidity at 6 weeks postpartum, a composite infectious outcome, which included endometritis, urinary tract infection, wound infection and pneumonia. RESULT: Data on 896 women were analyzed; 449 randomized to skin incision, 447 to cord clamp. Postpartum infections were seen in a total of 8.4% of patients. Timing of antibiotic administration did not significantly affect any maternal postpartum infection rates or selected neonatal outcomes. CONCLUSION: Our results suggest that, in a largely non-laboring population, the timing of prophylactic antibiotic administration does not impact post-operative infectious complications of the mother. Despite being one of the largest randomized controlled trials to address this question, our study still lacked sufficient power to make definitive conclusions.

Neuroimaging comparison of primary progressive apraxia of speech and progressive supranuclear palsy.

BACKGROUND AND PURPOSE: Primary progressive apraxia of speech, a motor speech disorder of planning and programming, is a tauopathy that has overlapping histological features with progressive supranuclear palsy. We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes. METHODS: Sixteen primary progressive apraxia of speech subjects were age- and gender-matched to 16 progressive supranuclear palsy subjects and 20 controls. All subjects were prospectively recruited, underwent neurological and speech evaluations and 3.0-Tesla magnetic resonance imaging. Grey and white matter atrophy was assessed using voxel-based morphometry and atlas-based parcellation, and white matter tract degeneration was assessed using diffusion tensor imaging. RESULTS: All progressive supranuclear palsy subjects had typical oculomotor/gait impairments, but none had speech apraxia. Both syndromes showed grey matter loss in supplementary motor area, white matter loss in posterior frontal lobes and degeneration of the body of the corpus callosum. Whilst lateral grey matter loss was focal, involving superior premotor cortex, in primary progressive apraxia of speech, loss was less focal extending into prefrontal cortex in progressive supranuclear palsy. Caudate volume loss and tract degeneration of superior cerebellar peduncles were also observed in progressive supranuclear palsy. Interestingly, area of the midbrain was reduced in both syndromes compared to controls, although this was greater in progressive supranuclear palsy. CONCLUSIONS: Although neuroanatomical differences were identified between these distinctive clinical syndromes, substantial overlap was also observed, including midbrain atrophy, suggesting these two syndromes may have common pathophysiological underpinnings.

Sensitivity of a Giardia antigen test in persistent giardiasis following an extensive outbreak.

The utility of a rapid antigen test for diagnosing cases of persistent giardiasis, as defined by detection of cysts by conventional microscopy following standard formalin-ether concentration or the positive rapid antigen test, was investigated following a large, waterborne outbreak of giardiasis. The sensitivity and specificity of the rapid test as compared with microscopy were 60.7% and 96.7%, respectively, in this patient group. The low sensitivity contrasts with previous reports, and may be partly explained by low cyst numbers.

Treatment-ladder and genetic characterisation of parasites in refractory giardiasis after an outbreak in Norway.

OBJECTIVES: To evaluate the efficacy of a treatment ladder in metronidazole-refractory giardiasis, and to compare genetic characteristics of the parasites. METHODS: A clinical observational study was carried out in 38 adult patients with metronidazole-refractory giardiasis, during an outbreak in Norway with more than 1200 cases. All patients were treated with albendazole in combination with metronidazole. Those who failed were treated with paromomycin. Those who failed on paromomycin were treated with quinacrine in combination with metronidazole. Giardia isolates from 17 patients were characterised by PCR and sequencing at two separate genes. RESULTS: Metronidazole in combination with albendazole was effective in 30 (79%) out of 38 patients. Paromomycin was effective in three out of six patients. Quinacrine in combination with metronidazole was effective in 3 patients. Molecular characterisation of the Giardia isolates revealed that these parasites were identical at two different gene segments, while sequence profiles from isolates at the peak of the outbreak were more heterogenous. CONCLUSIONS: Albendazole and quinacrine both in combination with metronidazole were effective in treating metronidazole-refractory giardiasis in this cohort. Paromomycin was less effective. Particular Giardia sub-genotypes may have been associated with the treatment-refractory giardiasis in these patients, although other undefined factors are probably also of importance.

Progressive aphasia secondary to Alzheimer disease vs FTLD pathology.

BACKGROUND: The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD). OBJECTIVE: To compare clinicopathologic and MRI features of subjects with progressive aphasia and AD pathology to subjects with aphasia and FTLD-U pathology and subjects with typical AD. METHODS: We identified 5 subjects with aphasia and AD pathology and 5 with aphasia and FTLD-U pathology with an MRI from a total of 216 aphasia subjects. Ten subjects with typical AD clinical features and AD pathology were also identified. All subjects with AD pathology underwent pathologic reanalysis with TDP-43 immunohistochemistry. Voxel-based morphometry (VBM) was used to assess patterns of gray matter atrophy in the aphasia cases with AD pathology, aphasia cases with FTLD-U, and typical AD cases with AD pathology, compared with a normal control group. RESULTS: All aphasic subjects had fluent speech output. However, those with AD pathology had better processing speed than those with FTLD-U pathology. Immunohistochemistry with TDP-43 antibodies was negative. VBM revealed gray matter atrophy predominantly in the temporoparietal cortices, with notable sparing of the hippocampus in the aphasia with AD subjects. In comparison, the aphasic subjects with FTLD-U showed sparing of the parietal lobe. Typical AD subjects showed temporoparietal and hippocampal atrophy. CONCLUSIONS: A temporoparietal pattern of atrophy on MRI in patients with progressive fluent aphasia and relatively preserved processing speed is suggestive of underlying Alzheimer disease pathology rather than frontotemporal lobar degeneration with ubiquitin-only immunoreactive changes.

Anisakiasis presenting as an obstructive duodenal tumor. A Scandinavian case.

A case of chronic anisakiasis presenting as an occluding duodenal tumor is described. Significant falls in Anisakis simplex-specific serum IgE and total IgE occurred after resection of the lesion. Histopathologic examination showed a chronic eosinophilic granulomatous infiltrate and a tubular sclerotic structure in the antral submucosa consistent with, but not diagnostic for, an A. simplex larva.

Long-term phonatory instability in individuals with multiple sclerosis.

This paper uses a new approach to describe and quantify the long-term phonatory instability of speakers with MS. Sustained vowel phonations of 20 individuals with a definite diagnosis of multiple sclerosis (MS) and 20 age- and gender-matched individuals with normal speech were recorded. The phonations were f0 and intensity analyzed and subjected to spectral analysis using the Fast Fourier Transform. Three methods for analyzing the instabilities are presented, compared, and related to perceptual judgments: (a) coefficients of variation, (b) magnitude-based analysis of spectral energy, and (c) frequency-based analysis of spectral components. All measures reliably distinguished between individuals with MS and persons with normal speech. A single factor based on a linear discriminant analysis of the frequency-based measures was especially useful in distinguishing these groups. Critical frequency bands of instability, corresponding to wow (1-2 Hz), tremor (around 8 Hz), and flutter (17-18 Hz), distinguished the MS group from those of the control group.

Effects of length and linguistic complexity on temporal acoustic measures in apraxia of speech.

The purpose of this study was to examine the effects of varying length and linguistic utterance types on temporal acoustic characteristics of the imitative speech of apraxic speakers. Vowel duration and two between-word segment durations were examined during the production of three response types: words, word-strings, and sentences. Three length conditions were studied in words, two length conditions for word-strings, and three length conditions for sentences, yielding eight experimental conditions. Apraxic speakers exhibited significantly longer vowel and between-word segment durations than control speakers in all conditions. Apraxic speakers consistently produced longer vowel and between-word segment durations in sentence contexts than in word contexts. Further, intrasubject and intersubject variability for between-word segment durations were substantially greater for the apraxic speakers in sentences compared to word conditions, whereas control speakers exhibited greater homogeneity in sentence production. The differences in duration and variability in sentence production versus word or word-string production imply different mechanisms for executing motor programs for varying linguistic stimuli.

Management of oral-pharyngeal dysphagia symptoms in amyotrophic lateral sclerosis.

Oral and pharyngeal dysphagia is a common symptom in patients with amyotrophic lateral sclerosis (ALS) and is the result of a progressive loss of function in bulbar and respiratory muscles. Clinicians involved in the management of ALS patients should be familiar with the common clinical findings and the usual patterns of temporal progression. The prevention of secondary complications, such as nutritional deficiency and dehydration that compound the deteriorating effects of the disease, requires careful monitoring of each patient's functional status and timely intervention with appropriate management techniques.

Differential phonatory characteristics of four women with amyotrophic lateral sclerosis.

Patients with specific neural subsystem involvement are often reported to present with particular perceptual characteristics of voice. This has been true for diseases such as amyotrophic lateral sclerosis (ALS), a progressive disease in which mixed neurologic signs are present. This article reports acoustic data on the phonatory performance of four women diagnosed with ALS who had initial bulbar signs and progressive phonatory deterioration. The data presented here demonstrate that the phonatory characteristics of women with ALS are not uniform, but in fact may vary greatly from patient to patient.

The programming and execution of movement sequences in Parkinson's disease.

Parkinsonian and neurologically normal subjects performed a finger-tapping task in which different sequence lengths had to be executed as rapidly as possible. For each response sequence, reaction time (RT), inter-tap-intervals (ITIs) and error patterns were recorded. It was found that the RT-sequence length relationship as well as the group ITI data were different for the two groups, indicative of impaired programming in the Parkinsonian subjects. This conclusion was supported by a relative dissociation of the first and subsequent taps and by a pattern of progressively increasing errors with longer tap sequences in the Parkinsonians.

Movement preparation in Parkinson's disease. The use of advance information.

The effects of advance information on movement planning in parkinsonism were assessed by means of movement precuing. Using this technique, the response latencies of identical sets of movements were compared across conditions in which the degree and type of advance movement information were manipulated. Specifically, prior information concerning three movement dimensions (the direction and extent of forthcoming movements, as well as the limb to be used) was or was not provided. Eight patients with Parkinson's disease and 8 neurologically normal age-matched controls served as subjects. The experiment showed that the elevated reaction times of the Parkinsonian subjects are not primarily caused by delays in response selection. Estimates of specification times for each of the three dimensions showed only a modest slowing in parkinsonians. The specification of those movement dimensions unknown before the response signal appears to occur serially, and can occur in a variable order as in normals. Since parkinsonians can initiate movements with shorter latencies when partial or complete information is available, albeit more slowly than normals, we conclude that response selection and specification processes preceding rapid discrete movements are relatively unaffected by the disease. The overall slowness in movement initiation in parkinsonians as compared with normals may in part be caused by excessive delays in motor time and, in general, to those 'input' and/or 'output' processes which are unaffected by advance information.

An agarose plate method for detecting alloantisera to coagulant factor IX and factor IX antigen.

An agarose plate method for detecting human alloantibodies (inhibitors) to coagulant factor IX has been developed. The assay is based on the ability of such antisera to inhibit the coagulation of a mixture of haemophilia B plasma, normal plasma and platelet subsitute in an agarose matrix. The agarose plate method was also adopted to measure levels of FIX antigen (IX:Ag) in plasma. Using this technique, 12 of 17 obligate carriers of haemophilia B demonstrated reduced levels of IX:Ag. Three of the five carriers with normal IX:Ag levels were members of kindred in which affected individuals had normal or near normal levels of IX:Ag.