Biomedical subjects

D M Maraganore

Publications and source records attributed to D M Maraganore.

At least 37 records · Page 2Linked to original sources

PubMed1999

Pathologic heterogeneity in clinically diagnosed corticobasal degeneration.

BACKGROUND: Early reports suggested that corticobasal degeneration (CBD) is a distinct clinicopathologic entity. Because patients have had a fairly consistent constellation of clinical and laboratory findings, many have proposed that the pathologic diagnosis can be surmised with confidence during life. OBJECTIVE: To analyze the pathologic findings in a large series of cases with clinically diagnosed CBD. METHODS: Using the medical research linkage system of the Mayo Clinic for the period January 1990 to December 1997, we identified cases diagnosed during life with CBD who subsequently underwent autopsy. All patients had progressive asymmetric rigidity and apraxia (except one with rigidity but no apraxia) with other findings, suggesting additional cortical and basal ganglionic dysfunction. All cases underwent standardized neuropathologic examination with the distribution and severity of the pathologic changes determined for each case and the pathologic diagnoses based on currently accepted criteria. RESULTS: Thirteen cases were identified. The pathologic diagnoses were CBD in seven, AD in two, and one each for progressive supranuclear palsy, Pick's disease, nonspecific degenerative changes, and Creutzfeldt-Jakob disease. Two cases had negligible basal ganglia and nigral degeneration despite previously having obvious extrapyramidal signs. However, all patients had focal or asymmetric cortical atrophy with coexisting neuronal loss and gliosis with or without status spongiosis, which was maximal in the parietal and frontal cortical regions. CONCLUSIONS: The constellation of clinical features considered characteristic of CBD is associated with heterogeneous pathologies. Furthermore, this syndrome can occur in the absence of basal ganglia and nigral degeneration. The one invariable pathologic abnormality in patients with this syndrome, however, is asymmetric parietofrontal cortical degeneration. At present, accurate diagnosis of CBD requires tissue examination.

Aged↗

PubMed1999

Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990.

OBJECTIVE: Limited information is available on the frequency and distribution of parkinsonism as a syndrome. We studied the incidence of parkinsonism and its specific types among residents of Olmsted County, MN, for the period from 1976 through 1990. METHODS: We used the medical records linkage-system of the Rochester Epidemiology Project to identify all individuals whose records contained documentation of any form of parkinsonism, related neurodegenerative diseases, or tremor of any type. A nurse abstractor screened the records, and, when applicable, a neurologist reviewed them to determine the presence of parkinsonism using specified diagnostic criteria and to define the year of onset. RESULTS: We found 364 incident cases of parkinsonism: 154 with PD (42%), 72 with drug-induced parkinsonism (20%), 61 unspecified (17%), 51 with parkinsonism in dementia (14%), and 26 with other causes (7%). The average annual incidence rate of parkinsonism (per 100,000 person-years) in the age group 50 to 99 years was 114.7; incidence increased steeply with age from 0.8 in the age group 0 to 29 years to 304.8 in the age group 80 to 99 years. The cumulative incidence of parkinsonism assuming no competing causes of death was 7.5% to age 90 years. PD was the most common type of parkinsonism, followed by parkinsonism in dementia in men and drug-induced parkinsonism in women. Men had higher incidence than women at all ages for all types of parkinsonism except drug-induced. CONCLUSIONS: Parkinsonism is a common disease among the elderly; its incidence increases steeply with advancing age and is consistently higher in men. The distribution by type changes with age and gender.

Age Distribution↗

PubMed1999

The effect of dopamine agonist therapy on dopamine transporter imaging in Parkinson's disease.

Single-photon emission computed tomography (SPECT) imaging with the dopamine transporter ligand, [123I] beta-CIT (2beta-carboxymethoxy-3beta-[4-iodophenyl] tropane), has been proposed as a means of measuring Parkinson's disease (PD) progression. To be useful in this role, however, [123I] beta-CIT imaging should not be influenced by the medications used to treat PD, including the dopamine agonist drugs such as pergolide. We assessed the effect of adjunctive pergolide administration on [123I] beta-CIT uptake in 12 patients with PD, who were being treated with levodopa, initiating pergolide therapy for motor fluctuations. Patients underwent [123I] beta-CIT imaging at baseline, subsequently while on pergolide therapy (6 weeks), and again 4 weeks after pergolide wash-out. Uptake in the striatum was averaged for the two sides and expressed as (striatum - occipital)/occipital, with similar calculations for putamen and caudate. Consistent with PD, the patients' mean striatal and putamen uptake ratios at baseline were significantly less (p <0.001) than the mean values from 26 normal control subjects of similar age. During pergolide treatment, the striatal and putamen [123I] beta-CIT uptake ratios were each statistically similar to baseline, although there was a slight trend toward an increased striatal value (8% higher on pergolide; p = 0.105). Caudate [123I] beta-CIT uptake was 11% higher on pergolide therapy (nominal p = 0.042, but not significant when adjusted for multiple comparisons: p = 0.126). After pergolide wash-out, the striatal, putamen, and caudate uptake ratios did not differ from baseline. Therefore, we found that pergolide therapy did not significantly affect [123I] beta-CIT SPECT imaging but we cannot exclude a small influence.

Aged↗

PubMed1999

Primary torsion dystonia: the search for genes is not over.

A GAG deletion in the DYT1 gene accounts for most early, limb onset primary torsion dystonia (PTD). The genetic bases for the more common adult onset and focal PTD are less well delineated. Genetic loci for an "intermediate dystonia" phenotype and for torticollis, named DYT6 and DYT7 respectively, have recently been mapped in single families. To evaluate the contribution of these genetic loci to other families with familial "non-DYT1" dystonia five large families with dystonia were studied using genetic markers spanning the DYT6 and DYT7 regions. There was no evidence of linkage to either locus in any family. These findings illustrate the genetic heterogeneity of the dystonias and indicate the existence of one or more as yet unmapped genes for dystonia. Large collaborative efforts will be required to identify these, and additional genes, causing PTD.

Adolescent↗

PubMed1999

The incidence and prevalence of myoclonus in Olmsted County, Minnesota.

OBJECTIVE: To study the incidence and prevalence of diagnosed myoclonus in Olmsted County, Minnesota. Little is known about the frequency and distribution of myoclonus in the general population. DESIGN: Descriptive study with case ascertainment through a records-linkage system. PATIENTS AND METHODS: We used a medical records-linkage system to identify all subjects whose records contained documentation of myoclonus or of diseases known to exhibit myoclonus. The records of all potential patients were reviewed by a neurologist, and only patients with pathologic and persistent myoclonus were included. Population denominators were derived from census data. RESULTS: The average annual incidence rate of pathologic and persistent myoclonus for 1976 through 1990 was 1.3 cases per 100,000 person-years. The rate increased with advancing age and was consistently higher in men. Symptomatic myoclonus was the most common type, followed by epileptic and essential myoclonus; dementing diseases were the most common cause of symptomatic myoclonus. The lifetime prevalence of myoclonus, as of January 1, 1990, was 8.6 cases per 100,000 population, and the prevalence increased with advancing age. CONCLUSION: Although our figures are probably under-estimated, they are the first attempt, to our knowledge, to measure myoclonus morbidity in the general population. We found clinical features and age and sex distributions different from those previously described in clinical series.

Adolescent↗

PubMed1999

Detection of preclinical Parkinson disease in at-risk family members with use of [123I]beta-CIT and SPECT: an exploratory study.

OBJECTIVE: To explore whether the radioligand 2 beta-carboxymethoxy-3 beta-(4-[123I] iodophenyl) tropane ([123I]beta-CIT) and single-photon emission computed tomography (SPECT) can detect decreased striatal uptake in at-risk relatives of patients with Parkinson disease (PD). PATIENTS AND METHODS: Ten PD patients, 10 at-risk first-degree relatives of PD patients, and 10 controls underwent [123I]beta-CIT and SPECT brain imaging. Their striatal uptake ratios were compared. RESULTS: Age-adjusted specific to nonspecific striatal uptake ratios were lower in patients compared with controls and with relatives; however, ratios were similar in relatives and controls. Among relatives, ratios were consistently lower in subgroups postulated to be at higher risk for preclinical PD. CONCLUSION: Our findings provide preliminary support that [123I]beta-CIT and SPECT may detect decreased striatal uptake in relatives of PD patients postulated to be at higher risk for PD.

Adult↗

PubMed1999

Quantitation of iodine-123-beta-CIT dopamine receptor uptake in a phantom model.

OBJECTIVE: The purpose of this study was to determine the effects of technical factors such as collimation and filtration on the measurement of 123I-beta-CIT uptake in the striatum. METHODS: All SPECT studies were performed using a brain phantom containing striata within a bone- and tissue-equivalent skull. The effects of collimator resolution and septal penetration were assessed from 99mTc and 123I studies containing variable activities in the striata and background regions. Optimum attenuation coefficients (mu) were determined from studies containing uniform activity in the brain. RESULTS: For 99mTc, mu was 0.095 cm-1 and 0.07 cm-1 for parallel-hole and fanbeam collimators, respectively. For 123I, these values dropped to 0.09 cm-1 and 0.00 cm-1 (zero) for medium-energy and fanbeam collimators, respectively. Striatal uptake was significantly underestimated, particularly for medium-energy and general-purpose collimators. With 99mTc, fanbeam collimation gave a 50% increase in the measured striatal uptake, compared to medium-energy collimation. However, with 123I, this gain was eliminated by septal penetration and scatter. Increasing transaxial slice thickness, ROI size and decreasing filter cutoff frequency all degraded apparent striatal uptake. CONCLUSION: Partial volume effects, combined with the averaging effects of increasing slice thickness and ROI size, are the most significant factors affecting measurement of striatal uptake of 123I-beta-CIT. The increased resolution of low-energy high-resolution collimators, compared to a medium-energy collimator, is offset by the increased septal penetration and scatter.

Brain↗

PubMed1998

Clinical presentation and pharmacological therapy in corticobasal degeneration.

BACKGROUND: To date, to our knowledge, there is no systematic presentation of treatment outcome in large series of patients clinically diagnosed as having corticobasal degeneration. OBJECTIVE: To evaluate the clinical presentation and treatment outcome of patients clinically diagnosed as having corticobasal degeneration. SUBJECTS: We gathered case patients seen in 8 major movement disorder clinics during the last 5 years who were diagnosed as having corticobasal ganglionic degeneration. METHODS: Using a chart review method, we recorded the clinical presentation, medications used, response to medications, and adverse effects. RESULTS: A total of 147 case patients were reviewed, 7 were autopsy proven. Parkinsonian features were present in all, other movement disorders in 89%, and higher cortical dysfunction in 93%. The most common parkinsonian sign was rigidity (92%), followed by bradykinesia (80%), gait disorder (80%), and tremor (55%). Other movement disorders were dystonia in 71% and myoclonus in 55%. Higher cortical dysfunction included dyspraxia (82%), alien limb (42%), cortical sensory loss (33%), and dementia (25%). Ninety-two percent of the case patients received dopaminergic drugs, which resulted in a beneficial effect for 24%. Parkinsonian signs were the elements improving the most and levodopa was the most effective drug. Benzodiazepines, primarily clonazepam, were administered to 47 case patients, which resulted in improvement of myoclonus in 23% and dystonia in 9%. The most frequent disabling adverse effects of drug trials in these case patients were somnolence (n = 24), gastrointestinal complaints (n = 23), confusion (n = 16), dizziness (n =12), hallucinations (n = 5), and dry mouth (n = 5). CONCLUSIONS: Pharmacological intervention was largely ineffective in the management of corticobasal degeneration, and new treatments are needed for ameliorating the symptoms of this syndrome.

Antiparkinson Agents↗

PubMed1998

Hereditary form of parkinsonism--dementia.

In four generations of a family, 13 members were afflicted with an autosomal dominant disorder characterized by young age at onset, early weight loss, and rapidly progressive dopa-responsive parkinsonism, followed later by dementia and, in some, by hypotension. Intellectual dysfunction began with subjective memory loss and objective visuospatial dysfunction and was followed later by decline of frontal lobe cognitive and memory functions. Neuropathological examination in 4 autopsied cases showed neuronal loss in the substantia nigra and locus ceruleus and widespread Lewy bodies, many of them in the cerebral cortex; those in the hypothalamus and locus ceruleus were often of bizarre shapes. Other findings were vacuolation of the temporal cortex, unusual neuronal loss and gliosis in the hippocampus (CA 2/3), and neuronal loss in the nucleus basalis. There were no neuritic plaques, neurofibrillary tangles, or amyloid deposits. Positron emission tomography in 3 patients showed decreased striatal uptake of fluorodopa. Neurochemical analysis of an autopsied brain showed a pronounced decrease in choline acetyltransferase activity in the frontal and temporal cortices and hippocampus and a severe depletion of striatal dopamine with a pattern not typical of classic Parkinson's disease.

Adult↗

PubMed1998

Case ascertainment uncertainties in prevalence surveys of Parkinson's disease.

Using unpublished data from five completed prevalence surveys of Parkinson's disease (PD), we investigated case ascertainment uncertainties that potentially have a direct effect on prevalence. These uncertainties arise from the choice of diagnostic criteria, the choice of screening method, and the amount of information lost because of nonresponse. The surveys were conducted in Argentina, India, China, Italy, and the Netherlands. Our analyses consisted of simple comparisons of prevalence results, positive predictive values (a screening measure), and nonresponse percentages. We found that (a) prevalence comparisons between surveys have diminished value if the surveys used different diagnostic criteria for PD; (b) screening performance may be affected adversely if symptom questions are answered by one family member for the entire family living together rather than by each family member individually; and (c) nonresponse from refusal or unavailability does not necessarily lead to bias, but special caution may be appropriate with prevalence results pertaining to elderly women.

Aged↗

PubMed1998

A double-blind, placebo-controlled study of intranasal apomorphine spray as a rescue agent for off-states in Parkinson's disease.

Nine patients with advanced levodopa-responsive Parkinson's disease were enrolled in a double-blind, placebo-controlled crossover trial of intranasal apomorphine as rescue therapy for parkinsonian off-states. Patients were assigned in random order to each of four possible combinations of apomorphine, trimethobenzamide antiemetic, and their matched placebos and received detailed in-office motor scoring during each of the four study periods. Patients also completed diaries describing the effectiveness of the nasal spray for reversing off-states. A statistically significant reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score was seen following active apomorphine during in-office evaluation visits but not following placebo nasal spray. Patient diaries revealed that active apomorphine had a latency to onset of 11 minutes and a duration of 50 minutes. Significant nausea from apomorphine spray was seen in only one patient whereas nasal irritation was disabling in three and mild in two. We conclude that intranasal apomorphine is an effective rescue agent for parkinsonian off-states although nasal irritation is a limiting factor.

Administration, Intranasal↗

PubMed1998

Validation of a telephone questionnaire for Parkinson's disease.

As part of a genetic study, we investigated the accuracy of a telephone questionnaire to diagnose or screen for Parkinson's disease (PD). We studied 20 PD patients randomly selected among all incident cases in Olmsted County, Minnesota, for the period 1970 through 1988. Each patient was matched by age and sex to a subject free of PD or parkinsonism residing in the same county. In addition, we studied 20 patients with PD referred to our institution from outside of Olmsted County between 1991 and 1993. Medical record documentation of disease status for both affected and unaffected subjects served as the standard for comparison. A trained interviewer kept unaware of disease status administered nine symptom questions via telephone to all study subjects (or their proxy). Seventeen PD cases from Olmsted County, all 20 referral cases, and 16 unaffected subjects participated in the interview (total = 37 with PD and 16 unaffected subjects); 36 interviews (24 PD) were with a proxy and 17 (13 PD) were direct. Questions regarding "poor balance," "trouble buttoning," and "trouble arising" had the highest sensitivity; questions regarding "shaking," "feet stuck to the floor," "softer voice," and "smaller writing" had the highest specificity. A combination of any four symptoms yielded the best balance between sensitivity (89%) and specificity (88%). Although the questionnaire appears to be useful both as a screening and as a diagnostic tool, it failed to reach complete accuracy, and it should be used in the context of a more complex case-finding strategy.

Female↗

PubMed1998

Childhood-onset schizophrenia associated with parkinsonism in a patient with a microdeletion of chromosome 22.

The deletion of a gene or genes on chromosome 22q11 is responsible for the velocardiofacial syndrome (VCFS), which is associated with cardiac anomalies, short stature, palate abnormalities, learning disabilities, and developmental delay. Herein we describe a 30-year-old man with VCFS in whom a chronic psychotic disorder originated during childhood. A 10% rate of psychotic disorders has been reported in association with this genetic syndrome. In our patient, the clinical manifestation was complicated by extrapyramidal symptoms that predated the onset of psychotic symptoms. To our knowledge, extrapyramidal symptoms have not previously been reported in a patient with VCFS. The diagnosis of VCFS was confirmed with the fluorescence in situ hybridization probe for VCFS. The role of the atypical antipsychotic drug clozapine is discussed with respect to treating this patient who has severe psychotic symptoms coexisting with extrapyramidal symptoms and seizures. In light of the observation that patients with VCFS have an unexpectedly high rate of psychotic disorders, issues concerning the genetics of schizophrenia are intriguing.

Abnormalities, Multiple↗

PubMed1998

Drug-induced parkinsonism as a risk factor for Parkinson's disease: a historical cohort study in Olmsted County, Minnesota.

OBJECTIVE: To investigate whether subjects who experienced a reversible episode of drug-induced parkinsonism have an increased risk of subsequent Parkinson's disease. DESIGN: We undertook a historical cohort study based on the medical records-linkage system of the Rochester Epidemiology Project in Olmsted County, Minnesota. MATERIAL AND METHODS: All subjects in whom drug-induced parkinsonism developed between 1955 and 1990 and was indexed in the medical records-linkage system were identified. In the 24 eligible subjects, follow-up for the subsequent development of Parkinson's disease consisted of a total of 192.7 person-years. The observed number of cases of Parkinson's disease was compared with the expected number of cases in an age- and sex-matched cohort from the general population. RESULTS: In 2 of 24 subjects with drug-induced parkinsonism, Parkinson's disease later developed. A comparison with the expected number of cases in the general population (0.08) yielded a relative risk of 24.3 (95% confidence interval, 2.9 to 87.5; P = 0.006). CONCLUSION: Our findings suggest that drug-induced parkinsonism is associated with an increased risk of Parkinson's disease. Clarification of the mechanisms of this association may have preventive implications.

Adult↗

PubMed1997

Dopaminergic function in familial Parkinson's disease: a clinical and 18F-dopa positron emission tomography study.

There is increasing evidence for familial aggregation in Parkinson's disease (PD). It is possible that some asymptomatic relatives of PD patients have subclinical nigral Lewy body pathology and their identification could help determine the true prevalence of the disease. We used 18F-dopa positron emission tomography to investigate nigrostriatal dopaminergic terminal function in asymptomatic members of 7 unrelated kindreds in which at least 2 members had parkinsonism. Eight (25%) of the 32 asymptomatic relatives showed abnormal putamen 18F-dopa uptake (2.5 standard deviations below the normal mean). When discriminant function analysis was applied, all of these 8 subjects plus another 3 were classified with high probability as having PD. On neurological examination, 5 of the 32 relatives scanned had an isolated mild postural tremor and 2 of these 5 had reduced putamen uptake. Our findings provide further support for a role of inheritance in the etiology of PD and suggest that the penetrance for nigrostriatal dopaminergic dysfunction in familial clusters of PD is higher than the prevalence of clinical parkinsonism reported in epidemiological surveys.

Adult↗

PubMed1997

Treatment of putative immune-mediated and idiopathic cervical dystonia with intravenous methylprednisolone.

A young pregnant woman developed a persistent dystonic head tremor a few days after Rho (D) immune globulin administration; further deterioration occurred after a second administration of Rh(o) (D) immune globulin with the development of marked retrocollis. This persisted and she was treated 2 months later with a 5-day course of intravenous (1 g daily) methylprednisolone (IVMP) with resolution of her condition. We proceeded to treat similarly the next four patients with idiopathic cervical dystonia who were seen in our practice and who had current symptoms of less than 6 months duration. One also experienced persistent resolution and another had a marked, but transient, improvement after each of two separate courses of IVMP. The other two patients did not have improvement. This suggests a possible autoimmune pathogenesis for a limited subset of cervical dystonia. However, identifying which cases of recent-onset cervical dystonia will respond to IVMP therapy has yet to be determined.

Adult↗

PubMed1997

A population perspective on diagnostic criteria for Parkinson's disease.

For Parkinson's disease (PD), little is known about how the choice of diagnostic criteria affects research results. Using data on PD from three community studies (from Argentina, the Netherlands, Italy), we compared the impact on prevalence of several sets of diagnostic criteria. Each set was based on cardinal signs--resting tremor, bradykinesia, rigidity, impaired postural reflexes--and required that other parkinsonism be excluded. Some sets had additional requirements related to duration of symptoms, asymmetry of signs, or response to medication. In terms of prevalence, much lower estimates were associated with the requirements of asymmetry of signs and response to medication. The assessment of these clinical features may not be practical in community studies. Impaired postural reflexes, as a cardinal sign, seemed superfluous. For community studies of PD, we recommend the following diagnostic criteria: at least two of resting tremor, bradykinesia, or rigidity, in the absence of other apparent causes of parkinsonism.

Age Distribution↗

PubMed1997

Guamanian neurodegenerative disease: are diabetes mellitus and altered humoral immunity clues to pathogenesis?

On the western Pacific island of Guam, parkinsonism, dementia, and amyotrophic lateral sclerosis are highly prevalent but the cause is not known. To assess the possibility that the pathologic process extends beyond the nervous system, we studied patients with Guamanian neurodegenerative disease (N = 16) and Guamanian Chamorro control subjects (N = 16) in the Clinical Research Center of the Mayo Clinic, Rochester, MN. The principal abnormalities found in those with neurodegenerative disease included diabetes mellitus in 44%, elevated levels of serum immunoglobulin A (IgA) in 50%, and elevated IgG in 44%. The mean serum IgM level in the patient group was significantly lower than in the control group. Diabetes mellitus and elevated IgA and IgG levels were also present in 31% of neurologically normal Guamanian subjects. Some of these control subjects, however, probably have preclinical neurodegenerative disease, as found in previously published postmortem studies. Extensive serologic testing did not reveal any consistent profile of autoimmunity. Other blood and urine studies failed to identify hematologic, nutritional, renal, hepatic, or metabolic abnormalities that distinguished patients. Whether diabetes mellitus or abnormalities of immune regulation share common etiopathology with Guamanian neurodegenerative disease deserves further study.

Adult↗