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Biomedical subjects

A D Korczyn

Publications and source records attributed to A D Korczyn.

At least 73 records · Page 4Linked to original sources

Demented patients' participation in a clinical trial: factors affecting the caregivers' decision.

Clinical trials for Alzheimer's disease take place in medical centers all over the world. Patients and caregivers have to decide whether or not to agree to participate in clinical trials. This study aimed to investigate the motivation that determines the caregivers' choice. Nineteen caregivers of demented patients who consented to participate in a clinical trial in our Memory Clinic and 10 caregivers who refused to participate were interviewed. The data were gathered by a self-report questionnaire covering various aspects of the caregivers' decision-making process. Among the reasons for agreeing to participate in the clinical trial were the respondents' belief that it would improve or help to maintain the patients' condition. Most of the respondents of both groups indicated that information regarding side effects and success probability was adequately provided in advance. The primary reason for refusal was the potential side effects of the drug. The implications of the findings are discussed.

Aged↗

Risk factors for dementia, depression and psychosis in long-standing Parkinson's disease.

OBJECTIVES: To study the relationships between clinical features of Parkinson's disease (PD) and the development of dementia, depression or psychosis in patients with long-standing disease. BACKGROUND: The natural history of dementia and depression in PD, and its relation to psychosis in long standing PD, are unclear. METHOD: 172 consecutive patients (99 men and 73 women, mean age at symptoms onset 58.3 +/- 13.2 years) with 5 years or more of PD (mean symptom duration of 11.8 +/- 5.6 years) were studied. Clinical data were collected during the last office visit through physical examination, detailed history, review of patient charts and outside documents. Dementia and depression were diagnosed according to DSM-IV criteria, while psychosis was diagnosed if hallucinations or delusions were present. Chi-square and t tests were used to compare the patient characteristics among those with vs. those without mental complications of the disease at different disease stages. Logistic regression was used for the comparison of associations between the presence of dementia or depression (dependent variable) and age at onset of PD, duration of PD and disease staging (explanatory variables). RESULTS: The study population consisted of 45 patients at Hoehn & Yahr (H&Y) stage < or = 2.5 (26%), 104 patients at stage 3 (60.5%) and 23 patients at H&Y stage 4-5 (13.5%). Sixty one patients (36%) had dementia, 55 patients had depression (33%) and 50 patients (27%) had psychosis. Dementia and depression were significantly associated with disease severity as reflected in the H&Y scale (P = 0.0003, Z = 3.59; P = 0.006, Z = 3.22, respectively). These associations were significant also for the older age of PD onset (> or = 59 years n = 89) subgroup (p = 0.001, Z = 3.2 for dementia and p = 0.02, Z = 2.9 for depression), but not for younger onset cases (< 59 years n = 83). Dementia was significantly associated with older age of PD onset (beta = 0.04, p = 0.009) while depression was inversely associated with age of PD onset (beta = -0.04, p = 0.02). The presence of dementia was also significantly associated with depression (beta = 1.49, p = 0.0006). Dementia and depression were found to be independent explanatory variables for the development of psychosis (logistic regression, odds ratio (OR) = 26.0, p < 0.0001; OR = 10.2, p < 0.0001, respectively). In patients with younger age of PD onset, depression more than dementia was strongly correlated with the appearance of psychosis. CONCLUSION: Dementia in PD was related to older age of symptoms onset and old age. Depression was associated with dementia or early age of PD onset. Depression seemed to contribute to the appearance of psychosis even more than dementia, especially in patients with younger age of symptoms onset.

Age Distribution↗

Sound lateralization and interaural discrimination. Effects of brainstem infarcts and multiple sclerosis lesions.

Subjects with brainstem lesions due to either an infarct or multiple sclerosis (MS) underwent two types of binaural testing (lateralization testing and interaural discrimination) for three types of sounds (clicks and high and low frequency narrow-band noise) with two kinds of interaural differences (level and time). Two major types of abnormalities were revealed in the lateralization performances: perception of all stimuli, regardless of interaural differences (time and/or level) in the center of the head (center-oriented), or lateralization of all stimuli to one side or the other of the head (side-oriented). Similar patterns of abnormal lateralization (center-oriented and side-oriented) occurred for MS and stroke patients. A subject's pattern of abnormal lateralization testing was the same regardless of the type of stimulus or type of interaural disparity. Lateralization testing was a more sensitive test than interaural discrimination testing for both types of subjects. Magnetic resonance image (MRI) scanning in three orthogonal planes of the brainstem was used to detect lesions. A semi-automated algorithm superimposed the auditory pathway onto each MRI section. Whenever a lesion overlapped the auditory pathway, some binaural performance was abnormal and vice versa. Given a lateralization test abnormality, whether the pattern was center-oriented or side-oriented was mainly determined by lesion site. Center-oriented performance was principally associated with caudal pontine lesions and side-oriented performance with lesions rostral to the superior olivary complex. For lesions restricted to the lateral lemniscus and/or inferior colliculus, whether unilateral or bilateral, just noticeable differences (JNDs) were nearly always abnormal, but for caudal pontine lesions JNDs could be normal or abnormal. MS subjects were more sensitive to interaural time delays than interaural level differences particularly for caudal pontine lesions, while stroke patients showed no differential sensitivity to the two kinds of interaural differences. These results suggest that neural processing of binaural stimuli is multilevel and begins with independent interaural time and level analyzers in the caudal pons.

Adult↗

The diagnostic aid of routine EEG findings in patients presenting with a presumed first-ever unprovoked seizure.

Data are available on the yield of a single EEG recording in patients with epilepsy but there is little information on EEG findings as an aid in supporting the diagnosis of an epileptic event in patients presenting with a first-ever event suspected of being an unprovoked seizure. We retrieved files of patients above the age of 15 years admitted through the emergency room during 1991-1995 with presumed first-ever unprovoked seizure. There were 91 patients (age 50+/-24; 52 males), of whom 66% had a presumed seizure of unknown origin and 34% had presumed remote symptomatic seizures. About 80% had generalized seizures (primarily or secondarily). In all the patients an EEG had been performed within 48 h of the event. Abnormal EEGs were obtained in 69%, with epileptiform activity in 21% (10% focal, 9% generalized and 2% focal and generalized), slowing in 58% (21% focal, 31% generalized and 7% focal and generalized), and both epileptiform activity and slowing in 10%. Epileptiform activity was most common in younger patients with seizures of unknown origin, compared with older individuals with symptomatic seizures (34, 38 vs. 27%, 7%, P=0.001). We conclude that following a single unprovoked presumed seizure, adults commonly exhibit abnormalities in an EEG recorded close in time to the event. The EEG is particularly helpful in supporting the epileptic nature of the event in younger patients and in those with seizures of unknown origin.

Adolescent↗

Physically traumatic events in patients with epilepsy compared with non-epileptic subjects.

To determine the incidence of traumatic events among epileptic patients compared with non-epileptic individuals, we distributed a questionnaire on physically traumatic events occurring during the preceding three months to consecutive epileptic patients and to age- and sex-matched controls. There were 145 epileptic patients, 121 with seizures (age 36 +/- 15 y, 60 males) and 24 who were seizure free during this period (age 39 +/- 17 y, 13 males), and 145 controls (age 36 +/- 15 y, 73 males). There was no significant difference in the duration of epilepsy between the two groups of patients with epilepsy. Traumatic events (n= 27, three of them unrelated to seizure) were most common in patients with seizures, followed by controls (n= 20), and absent in seizure-free patients (P< 0.001). Patients with epilepsy most commonly injured the head while the extremities were more usually involved in controls. Patients with epilepsy had significantly more traumatic events at home, whereas controls underwent most traumatic events at work and in public areas. There was no significant difference in the type and severity of trauma between the two groups. We conclude that physically traumatic events not related to seizures are fewer among patients with epilepsy with and without seizures compared with controls, probably because of increased cautiousness.

Accidents↗

Use of the selective serotonin 3 receptor antagonist ondansetron in the treatment of neuroleptic-induced tardive dyskinesia.

OBJECTIVE: The authors examined the efficacy, tolerability, and safety of ondansetron, a selective serotonin 3 receptor antagonist, in patients with tardive dyskinesia. METHOD: Twenty patients with schizophrenia who had neuroleptic-induced tardive dyskinesia were given 12 mg/day of ondansetron for 12 weeks in an open-label study. RESULTS: Administration of ondansetron resulted in a statistically significant improvement in tardive dyskinesia and psychotic symptoms. CONCLUSIONS: Ondansetron may be an effective and safe therapy to control tardive dyskinesia and psychosis in patients with schizophrenia.

Adult↗

Muscarinic M(1) agonists in the treatment of Alzheimer's disease.

The treatment of Alzheimer's disease attempts to correct cholinergic deficiency in the brain. In addition to the established, but restricted, efficacy of acetylcholinesterase inhibitors, attempts are being made to develop agents which will stimulate muscarinic receptors directly. This approach is logical and was found efficacious in several animal models of the disease; however none of these agents succeeded in clinical studies. Several reasons might account for this failure, which are discussed, as well as the prospects for the future.

Acetylcholine↗

Creutzfeldt-Jakob disease profile in patients homozygous for the PRNP E200K mutation.

We identified 70 Creutzfeldt-Jakob disease patients with the previously described E200K mutation in the prion protein gene. The purpose of this study was to define the clinical features of E200K homozygous patients (n = 5), compared with heterozygotes. We found a statistically significant younger age at disease onset for the homozygous patients, although the average age at onset in this group was still in midlife. Disease features were not statistically different in the two groups. Possible explanations are discussed.

Adult↗

Hereditary juvenile-onset craniocervical predominant generalized dystonia with parkinsonism.

OBJECTIVE: To report a unique hereditary, juvenile onset, craniocervical predominant, generalized dystonia and parkinsonism affecting four members of one family. FAMILY DESCRIPTION: A father and three of his four daughters presented to us over the past 30 years with a similar picture of generalized dystonia, starting in the craniocervical region in the second or third decade of life. They later developed moderate parkinsonism, mainly manifesting bradykinesia, rigidity and abnormal postural reflexes. Biochemical and genetic tests excluded Wilson's disease, Huntington's disease and Oppenheim's dystonia. CONCLUSION: This is a new type of familial dystonia-parkinsonism where the craniocervical dystonic symptoms are most prominent in the early stages while parkinsonism becomes the predominant problem later in life. A search for the genetic mutation in this family is underway.

Adolescent↗

Preliminary evidence for anticipation in genetic E200K Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) linked to the E200K mutation of the prion protein (PrP) gene presents within a wide range of phenotypic heterogeneity, including the age at disease onset. We report an earlier disease onset for mutation carriers of the offspring generation when compared with that of their parents, suggesting the possibility of anticipation. A still unidentified environmental or genetic element may affect the age at onset in mutation carriers of different generations.

Age Factors↗

A 3-year randomized trial of ropinirole and bromocriptine in early Parkinson's disease. The 053 Study Group.

OBJECTIVE: To compare the long-term efficacy and safety of ropinirole with bromocriptine over 3 years in patients with early PD with limited or no previous dopaminergic therapy. METHODS: In this prospective, double-blind, parallel-group study, 335 patients were randomized to 0.75 mg ropinirole or 1.25 mg bromocriptine titrated upward at weekly intervals--maximum permitted daily doses were 24 mg ropinirole, 40 mg bromocriptine. RESULTS: Approximately one third of patients in each group withdrew prematurely, mostly because of adverse experiences; 61/102 (60%) of ropinirole-treated and 59/112 (53%) of bromocriptine-treated patients completed the study on the dopamine agonist alone. Mean doses for all patients at completion were 12 mg (SD 6) ropinirole and 24 mg (SD 8) bromocriptine. Occurrence of adverse experiences in both groups was similar. Emergence of dyskinesias was low. Both treatments induced marked improvements in Unified Parkinson's Disease Rating Scale activities of daily living (ADL, Part II) and motor (Part III) scores over the first 12 weeks, which were maintained during the study. After 3 years, patients in the ropinirole group had a mean improvement in motor score of 31% compared with 22% in the bromocriptine group (p = 0.086) and a significantly better ADL score (treatment difference 1.46 points, p = 0.009) [corrected]. CONCLUSIONS: Both dopamine agonists are effective in the early treatment of a high proportion of PD patients; effectiveness persists for at least 3 years. Those who completed the study had a significantly better functional status on ropinirole than on bromocriptine.

Activities of Daily Living↗

Antibodies to prothrombin in patients with Sneddon's syndrome.

Antiprothrombin antibodies (aPT), a new serologic marker of antiphospholipid syndrome, were studied in 46 patients randomly selected from 73 with Sneddon's syndrome and 20 matched normal controls. aPT were elevated in 26 patients (57%) and were not found in any of the controls. The addition of aPT data increased the proportion of Sneddon's syndrome patients with at least one type of antiphospholipid syndrome marker from 65 to 78%. The finding that aPT are common in Sneddon's syndrome supports the hypothesis that Sneddon's syndrome is a form of antiphospholipid syndrome.

Adolescent↗

[Prevalence of APO e4 allele in Israeli ethnic groups].

The 4 allele of the APOE gene, coding for apo-lipoprotein E, is the most common genetic risk factor for Alzheimer's disease and a significant risk factor for coronary atherosclerosis. There is therefore much interest in studying its frequency in different ethnic groups. We examined its frequency in Jews originating from Libya, Buchara and Ethiopia and in Jews of Sepharadi and Ashkenazi origins. Its frequency among Ethiopian immigrants was 0.27, significantly higher than in the other groups, in which the frequency was between 0.067 and 0.10. These differences in allele frequency may serve as a basis for future studies in Israel to assess the relative contributions of genetic and environmental factors to the incidence of dementia.

Africa↗

Intermittent rhythmic delta activity (IRDA) morphology cannot distinguish between focal and diffuse brain disturbances.

IRDA (intermittent rhythmic delta activity) is an abnormal generalized EEG pattern that is not specific to any single etiology and can occur with diffuse or focal cerebral disturbances. To determine whether different electrographic features of IRDA and associated EEG findings can differentiate underlying focal from diffuse brain disturbances, we performed a blind analysis of 58 consecutive EEGs with an IRDA pattern, recorded from 1993 until 1996, in which we evaluated posterior background activity, focal slowing and IRDA characteristics (frequency, distribution, duration, symmetry and abundance). The clinical diagnosis, state of consciousness and CT brain findings were retrieved from the patients' hospital records. There were 58 patients (33 females; mean age, 58+/-21 years). Twelve (21%) had only focal brain lesions, while 46 (79%) had diffuse brain abnormalities, (15 diffuse structural, 19 metabolic abnormalities, 12 postictal). Normal consciousness and focal EEG slowing were more frequent in patients with focal abnormalities, however, this was not statistically significant. Of the patients with focal abnormality, 11 (92%) had normal posterior background activity either bilaterally (n=4) or contralateral to the focal lesion (n=7). Bilaterally normal posterior background activity was observed in about 30% in both groups. Bilaterally abnormal posterior background activity was apparent in one patient (8%) with focal brain lesion and in 31 patients (67%) with diffuse brain abnormalities (P<0.0001). There were no significant differences in IRDA electrographic features between the focal group and the group with diffuse brain disturbances. We conclude that IRDA morphology cannot distinguish between focal and diffuse brain abnormalities.

Adolescent↗

Preliminary observations on APOE epsilon4 allele and progression of disability in multiple sclerosis.

BACKGROUND: Apolipoprotein E expression is increased in regenerating neural tissue and the APOE epsilon4 allele is associated with impaired neuronal repair. Since repair is essential for the restoration of central nervous system function following multiple sclerosis (MS) relapses, APOE genotype may influence clinical progression of the disease. OBJECTIVE: To examine the association of the APOE genotype with disease susceptibility and progression in MS. PATIENTS AND METHODS: APOE genotyping was determined by polymerase chain reaction and restriction enzyme digestion in 47 patients with MS who had been followed up every 3 months for 2 years as part of an open-label clinical trial with glatiramer acetate. The Expanded Disability Status Scale (EDSS) was used to assess clinical progression. RESULTS: Nine patients were heterozygous and 1 patient was homozygous for the APOE epsilon4 allele, for a frequency of 12% (11/94), which is similar to that of the general Israeli population. The APOE epsilon4 carriers had a mean +/- SE EDSS score of 3.10+/-0.45 at entry, which was not significantly different from the remaining 37 patients (2.62+/-0.25). During the observation period, the EDSS score of the APOE epsilon4 carriers deteriorated to 4.00+/-0.63 while the other patients remained stable with an EDSS score of 2.74+/-0.31. The interaction of genotype with disability over time was significant (P = .02 by repeated-measures analysis of variance). There were no differences in the number of relapses occurring in the 2 groups. CONCLUSIONS: These preliminary observations suggest that APOE genotype may influence disease progression in MS. The APOE epsilon4 allele was not associated with an increased risk of MS or relapses.

Adult↗