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Biomedical subjects

I Litvan

Publications and source records attributed to I Litvan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Language disturbances in corticobasal degeneration.

To characterize the language deficits in corticobasal degeneration (CBD) and their relation to neuroradiologic findings, the authors administered a standardized battery of neurobehavioral tests and performed MRI studies on 15 patients with CBD. Eight patients (53%) had classifiable aphasias, including anomic, Broca's and transcortical motor aphasias. The aphasias were associated primarily with left frontal and parietal cortical damage and subcortical white matter and corpus callosum abnormalities. Our findings demonstrate that language disturbances in CBD are more frequent than previously considered.

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PubMed2000

Mitochondrial dysfunction in cybrid lines expressing mitochondrial genes from patients with progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative movement disorder of unknown etiology. We hypothesized that mitochondrial DNA (mtDNA) aberration could occur in this disease and contribute to its pathogenesis. To address this we created transmitochondrial cytoplasmic hybrid (cybrid) cell lines expressing mitochondrial genes from persons with PSP. The presence of cybrid mtDNA aberration was screened for by biochemical assay of mitochondrial gene products. Relative to a control cybrid set, complex I activity was reduced in PSP cybrid lines (p<0.005). Antioxidant enzyme activities were elevated in PSP cybrid lines. These data suggest that mtDNA aberration occurs in PSP, causes electron transport chain pathology, and can produce oxidative stress. Further study of mitochondrial dysfunction in PSP may yield insights into why neurodegeneration occurs in this disease.

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PubMed2000

Neuropsychiatric aspects of corticobasal degeneration.

Neuropsychiatric symptoms are present in the majority of patients with CBD. Depression is common in this group of patients and contributes to the morbidity of the disease. Depression is more severe in CBD than in many other neurologic disorders. Neuropsychiatric symptoms should be assessed in all patients with CBD to enhance symptom detection and improve management.

Basal Ganglia Diseases↗
PubMed1999

Accuracy of four clinical diagnostic criteria for the diagnosis of neurodegenerative dementias.

OBJECTIVE: To evaluate the inter-rater reliability and validity of clinical diagnostic criteria for neurodegenerative dementias. BACKGROUND: Inter-rater accuracy of the diagnosis of AD has been explored, but there are few accuracy studies for progressive supranuclear palsy (PSP) and frontotemporal lobe dementia (FTD). Furthermore, there have been no simultaneous accuracy studies in a mixed sample of patients with cortical and subcortical neurodegenerative processes. METHODS: Four experienced clinicians reviewed first-visit clinical data abstracted from the records of 40 pathologically diagnosed demented subjects. They were asked to apply the NINCDS-ADRDA criteria for AD, the NINDS-SPSP clinical criteria for PSP, the Lund and Manchester criteria for FTD, and the Consensus Guidelines for the Clinical Diagnosis of Dementia with Lewy Bodies (DLB). RESULTS: The generalized K for AD was 0.73, for PSP 0.82, for FTD 0.75, and for DLB 0.37. The K pool test showed a statistically significant difference between DLB and the other disease processes, and no differences were observed among AD, FTD, and PSP. The mean sensitivity for AD was 95%, for PSP 75%, for FTD 97%, and for DLB 34%. The mean specificity for AD was 79%, for PSP 98.5%, for FTD 97%, and for DLB 94%. CONCLUSIONS: We found improved inter-rater reliability for the diagnosis of AD among clinicians compared with earlier studies. Similarly, there was a near-perfect and substantial inter-rater agreement for the diagnosis of PSP and FTD. The sensitivity for the diagnosis of AD was high, although clinicians overdiagnosed this condition. However, there was a reasonable accuracy for the diagnosis of PSP and FTD. Heterogeneity of the clinical presentation of DLB significantly affected inter-rater agreement and accuracy. The use of multiple diagnostic criteria for cortical and subcortical dementia increases the level of clinical diagnostic accuracy.

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PubMed1999

Consensus statement on the diagnosis of multiple system atrophy.

We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.

Autonomic Nervous System Diseases↗
PubMed1999

A lack of the R406W tau mutation in progressive supranuclear palsy and corticobasal degeneration.

Linkage disequilibrium studies suggest that progressive supranuclear palsy (PSP) is an autosomal recessive condition that maps to a polymorphism in the tau gene. These results provide evidence that homozygous mutations in the tau gene may cause PSP. Recently, a missense mutation in exon 13 of one tau allele (R406W) was found in a single family with an atypical clinicopathologic form of dominantly inherited PSP. The authors report that the R406W mutation is lacking in 25 unrelated individuals with PSP and in six unrelated individuals with another tauopathy-corticobasal degeneration.

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PubMed1999

Progression of falls in postmortem-confirmed parkinsonian disorders.

Although falls are known to occur in several parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of this feature have not been studied systematically in pathologically confirmed cases. Seventy-seven cases with pathologically confirmed parkinsonian disorders (PD: n = 11, MSA: n = 15, DLB: n = 14, CBD: n = 13, PSP: n = 24), collected up to 1994, formed the basis for a multicenter clinicopathologic study organized by the National Institute of Neurological Disorders and Stroke to improve differential diagnosis of parkinsonian disorders. In the present study, we determined the time course, that is, the duration from first symptom to onset (latency) and duration from onset to death, of recurrent falls. Furthermore, we analyzed the diagnostic validity of a predefined latency to onset of recurrent falls within 1 year of symptom onset. Significant group differences for latency, but not duration, of recurrent falls were observed. Latencies to onset of falls were short in PSP patients, intermediate in MSA, DLB, and CBD, and long in PD. Recurrent falls occurring within the first year after disease onset predicted PSP in 68% of the patients. Our study demonstrates for the first time that latency to onset, but not duration, of recurrent falls differentiates PD from other parkinsonian disorders. Whereas early falls are important for the diagnosis of PSP, the addition of other features increases its diagnostic predictive value.

Accidental Falls↗
PubMed1999

Clinical features differentiating patients with postmortem confirmed progressive supranuclear palsy and corticobasal degeneration.

Progressive supranuclear palsy (PSP) and cortocobasal degeneration (CBD) are often clinically confused with each other because they share a rapid disease progression, parkinsonism that responds poorly or transiently to levodopa therapy, and associated signs (e.g., ocular abnormalities, pyramidal signs and cognitive involvement). To improve the accuracy in diagnosing these disorders, this study examined the clinical features of 51 patients pathologically diagnosed with PSP and CBD. Logistic regression analysis identified two sets of predictors (models) for CBD patients, one consisting of asymmetric parkinsonism, cognitive disturbances at onset and instability and falls at first clinic visit, and the other one of asymmetric parkinsonism, cognitive disturbances at symptom onset and speech disturbances. While PSP patients often had severe postural instability at onset, symmetric parkinsonism, vertical supranuclear gaze palsy, speech and frontal lobe-type features, CBD patients presented with lateralized motor (e.g., parkinsonism, dystonia or myoclonus) and cognitive signs (e.g., ideomotor apraxia, aphasia or alien limb). On the other hand, CBD patients presenting with an alternate phenotype characterized by early severe frontal dementia and bilateral parkinsonism were generally misdiagnosed. PSP patients without vertical supranuclear gaze palsy were misdiagnosed. Recognizing the features which differentiate these disorders and the less obvious disease presentations as well as developing an increased index of suspicion will improve the diagnostic accuracy of these disorders.

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PubMed1999

Effects of physostigmine on swallowing and oral motor functions in patients with progressive supranuclear palsy: A pilot study.

The purpose of this pilot study was to investigate whether cholinergic stimulation reduces swallowing and oral motor disturbances in patients with progressive supranuclear palsy (PSP). A controlled, double-blind crossover trial of physostigmine, a centrally active cholinesterase inhibitor, and placebo was conducted. Patients were randomized to a 10-day crossover placebo-controlled double-blind trial of physostigmine at their previously determined best dose administered orally every 2 hr, six times per day. Patients were evaluated with ultrasound imaging of the oropharynx and an oral motor examination at baseline and during the third or fourth days of each study phase (placebo and drug). Under the double-blind placebo-controlled conditions, patients showed no statistically significant improvement in oral motor functions or swallow durations. Because patients with PSP have increased sensitivity to cholinergic blockade compared with control subjects, studies with newer, more potent cholinergic stimulating agents need further exploration. Suggestions for future research include the evaluation of newer direct cholinergic agonists in the treatment of the less-impaired PSP patients who may have a greater number of cholinergic neurons preserved and the evaluation of combined therapies.

Cholinesterase Inhibitors↗
PubMed1999

Association of an extended haplotype in the tau gene with progressive supranuclear palsy.

We describe two extended haplotypes that cover the human tau gene. In a total of approximately 200 unrelated caucasian individuals there is complete disequilibrium between polymorphisms which span the gene (which covers approximately 100 kb of DNA). This suggests that the establishment of the two haplotypes was an ancient event and either that recombination is suppressed in this region, or that recombinant genes are selected against. Furthermore, we show that the more common haplotype (H1) is significantly over-represented in patients with progressive supranuclear palsy (PSP), extending earlier reports of an association between an intronic dinucleotide polymorphism and PSP.

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