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Steven Frucht

Publications and source records attributed to Steven Frucht.

18 recordsLinked to original sources
PubMed2007

Regional metabolic changes in parkinsonian patients with normal dopaminergic imaging.

Dopaminergic imaging has been found to be normal in approximately 15% of parkinsonian patients enrolled in neuroprotective trials. We used (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) to determine the metabolic basis for this finding. We reviewed scans from 185 patients with clinical signs of Parkinson's disease (PD) who underwent (18)F-fluorodopa PET imaging for diagnostic confirmation. Of this group, 27 patients (14.6%) had quantitatively normal scans; 8 of these patients were additionally scanned with FDG PET. Pattern analysis was performed on an individual scan basis to determine whether the metabolic changes were consistent with classic PD. Computer-assisted single-case assessments of the FDG PET scans of these 8 patients did not disclose patterns of regional metabolic change compatible with classical PD or an atypical parkinsonian variant. Similarly, network quantification revealed that PD-related pattern expression was not elevated in these patients as it was in an age- and duration-matched cohort with classical PD (P < 0.0001). None of these patients developed clinical signs of classical PD or of an atypical parkinsonian syndrome at a follow-up visit conducted 3 years after imaging. The results suggest that parkinsonian subjects with normal dopaminergic imaging do not have evidence of classical PD or an atypical parkinsonian syndrome.

Brain↗
PubMed2006

Case-control study of the parkin gene in early-onset Parkinson disease.

BACKGROUND: Mutations in parkin are estimated to account for as much as 50% of familial Parkinson disease (PD) and 18% of sporadic PD. Single heterozygous mutations in parkin in both familial and sporadic cases may also increase susceptibility to PD. To our knowledge, all previous studies have been restricted to PD cases; this is the first study to systematically screen the parkin coding regions and exon deletions and duplications in controls. OBJECTIVE: To determine the frequency and spectrum of parkin variants in early-onset PD cases (aged < or =50 years) and controls participating in a familial aggregation study. PATIENTS AND METHODS: We sequenced the parkin gene in 101 cases and 105 controls. All cases and controls were also screened for exon deletions and duplications by semiquantitative multiplex polymerase chain reaction. RESULTS: Thirteen (12.9% [95% confidence interval, 7%-21%]) of the 101 cases had a previously described parkin mutation: 1 was homozygous, 11 were heterozygous, and 1 was a compound heterozygote. The mutations Arg42Pro (exon 2) and Arg275Trp (exon 7) were recurrent. The previously reported synonymous substitution Leu261Leu (c.884A>G) was identified in 4 (3.9%) of 101 cases and 2 (2%) of 105 controls (P = .44). Excluding the synonymous substitution Leu261Leu (heterozygotes), 10 (9.9% [95% confidence interval, 4.6%-17.5%]) carried mutations. CONCLUSIONS: The frequency of mutations among cases that were not selected based on family history of PD is similar to what has previously been reported in sporadic PD. The similar frequency of Leu261Leu in cases and controls suggests it is a normal variant rather than a disease-associated mutation. We confirmed that heterozygous parkin mutations may increase susceptibility for early-onset PD.

Age of Onset↗
PubMed2006

Essential tremor associated with pathologic changes in the cerebellum.

BACKGROUND: Although essential tremor (ET) is one of the most common neurologic disorders, there have been few postmortem studies. We recently reported postmortem changes (torpedoes and Bergmann gliosis) in the cerebellar cortex in a few ET cases. OBJECTIVE: To describe more extensive postmortem changes in the cerebellum in another ET case. DESIGN: Case report. RESULTS: A 90-year-old woman had a 30-year history of ET. At postmortem examination, there was segmental loss of Purkinje cells, presence of torpedoes, and Bergmann gliosis in the cerebellar cortex. Moreover, there were extensive changes in the dentate nucleus, in the form of neuronal loss, neuronal atrophy, microglial clusters, and reduction in the number of efferent fibers (ie, pallor of the hilum). CONCLUSIONS: The brain in the current case exhibited more marked cerebellar pathologic features than noted in previously reported ET cases and thereby extends the described cerebellar findings in this common, yet pathologically poorly characterized, neurologic disorder.

Aged, 80 and over↗
PubMed2006

Movement disorders fellowship training program at Columbia University Medical Center in 2001-2002.

Data regarding the clinical experience of movement disorders subspecialty training are currently not available. In order to provide information to help design a well-rounded clinical experience, we reviewed the number and types of patients seen by all clinical movement disorders fellows over the course of 1 year at Columbia University Medical Center (CUMC). We conducted a retrospective analysis of all patients seen by four full-time clinical fellows and one part-time fellow during the 2001-2002 academic year, using billing records to tabulate all clinic visits and patient charts to certify diagnosis. One thousand six hundred sixty-two patients (1,132 new and 530 follow-ups) were seen by five fellows. Each full-time fellow evaluated and treated a mean of 263 new patients, 116 follow-up patients, and 15 in-patient consultations. The part-time clinical fellow evaluated and treated 81 new patients and 65 follow-up patients. Approximately half of the new patients had idiopathic Parkinson's disease. Full-time fellows saw equivalent numbers of patients but they evaluated few patients with uncommon movement disorders. Weekly video rounds allowed all fellows to see many more patients, aiding the recognition of movement phenomenology and enhancing understanding of diagnoses and treatment strategies. Thus, CUMC fellows evaluate a large number of patients with a wide range of diagnoses within a 1-year period. Video rounds allow greater exposure to uncommon diagnoses. Similar data from other movement disorder training programs are needed to help create guidelines for formal accreditation and to improve clinical training in this subspecialty.

Academic Medical Centers↗
PubMed2006

Movement disorders after resuscitation from cardiac arrest.

It is difficult to predict precisely the final neurologic outcome from cardiac arrest and accompanying cerebral hypoxia. Although rare, several movement disorders may arise as a consequence of hypoxic injury, including myoclonus, dystonia, akinetic-rigid syndromes, tremor, and chorea. Dys-function of various portions of the central nervous system, including the basal ganglia, thalamus, midbrain, and cerebellum, is implicated in the pathogenesis of these posthypoxic movement disorders. The development of animal models of posthypoxic movement disorders and of newer imaging techniques applied to human patients who have movement disorders after hypoxic episodes has improved understanding of the pathophysiology of posthypoxic movement disorders and has suggested newer treatments. Many outstanding questions remain, however. What factors promote susceptibility to the development of posthypoxic movement disorders? Why do patients who have similar clinical hypoxic insults develop markedly dis-similar movement disorders? Why are the basal ganglia especially vulnerable to cerebral hypoxia? Why do some movement disorders occur in delayed fashion and progress for years after the hypoxic insult? Is the pathogenesis of progressive posthypoxic movement disorders related to that of neurodegenerative diseases? What are the most effective medications for the various posthypoxic movement disorders? Is there a role for deep brain stimulation in the treatment of posthypoxic movement disorders? We anticipate that current and future research in the area of posthypoxic movement disorders will reveal answers to some of these important questions.

Brain Ischemia↗
PubMed2005

Contribution of aging to the severity of different motor signs in Parkinson disease.

BACKGROUND: Evidence does not support the view that Parkinson disease (PD) represents an accelerated aging process; however, the additional contribution of aging to the severity of different motor signs in patients with PD is not known. This knowledge may have implications for clinical trials of neuroprotective agents in PD. OBJECTIVE: To investigate the contribution of aging to the severity of the different motor signs of idiopathic PD. SETTING: Center for Parkinson Disease and Other Movement Disorders of the Columbia University Medical Center and a neurology clinic that primarily served individuals from the Washington Heights-Inwood community in New York City. PATIENTS: Sample of patients with a wide range of disease duration and age. DESIGN: Cross-sectional clinic-based study. Patients with PD were evaluated using the Unified Parkinson Disease Rating Scale (UPDRS). The total UPDRS motor score was divided into 6 motor domains (tremor, rigidity, bradykinesia, facial expression, speech, and axial impairment) and 2 subscores that represented predominantly dopaminergic (subscore A: tremor, rigidity, bradykinesia, and facial expression) and nondopaminergic (subscore B: speech and axial impairment) deficiency. Analyses were performed using linear regression models with the UPDRS motor domains and subscores as the outcomes. The variation (adjusted R(2)) of the outcome variables explained by the inclusion of disease duration in the models, adjusting for sex, years of education, levodopa dosage, and use of other antiparkinsonian medications, was calculated. The additional variation explained by adding age at examination to the models was used to gauge the contribution of aging to each motor domain and subscore of the UPDRS. RESULTS: A total of 451 patients participated in the study. Mean age at examination was 62.0 years (SD, 12.6 years; median, 62.0 years; range, 18-93 years), and mean disease duration was 7.2 years (SD, 5.9 years; median, 5.6 years; range, 0.1-41.6 years). The additional variation of the outcome variable explained by including age in the models was higher for subscore B (14.3%; 95% confidence interval [CI], 9.9%-20.4%) than subscore A (4.7%; 95% CI, 2.0%-9.1%). Among the 6 motor domains, the additional variation of the outcome variable explained by including age in the models was highest for axial impairment (13.6%; 95% CI, 9.4%-19.6%). CONCLUSION: Axial (gait and postural) impairment in PD may result from the combined effect of the disease and the aging process on nondopaminergic subcortical structures.

Adolescent↗
PubMed2005

Pilot association study of the beta-glucocerebrosidase N370S allele and Parkinson's disease in subjects of Jewish ethnicity.

Mutations in the beta-glucocerebrosidase gene cause Gaucher's disease, one of the most common lysosomal lipid storage diseases in the Ashkenazi Jewish population. The occurrence of parkinsonism in patients with Type 1 Gaucher's disease has been noted previously. In this pilot study, we evaluated a possible association between Parkinson's disease (PD) and the beta-glucocerebrosidase gene N370S allele (nt.1226 A>G) in 160 Parkinson's disease patients and 92 controls of Jewish ethnicity. We observed a higher frequency of the N370S genotype in PD cases (NS and SS, 10.7%) compared to controls (NS and SS 4.3%); however, the difference was not statistically significant (chi(2) = 3.4, P = 0.2). A total of 17 PD cases carry the N370S allele, including 2 homozygotes and 15 heterozygotes. The N370S allele (nt.1226 A>G) may be associated with PD in patients of Jewish ethnicity and should be examined in a larger study.

Aged↗
PubMed2005

Association between male gender and pediatric essential tremor.

Approximately 5% of new essential tremor (ET) cases arise during childhood. The goal of the current report was to examine the possible association between male gender and pediatric ET, using data from 95 pediatric ET cases seen at three medical centers (two in the United States and one in Spain). The odds of ET in our sample of cases were threefold higher in boys compared to girls. Whether this association between male gender and pediatric ET represents a selection bias or a true gender-mediated biological difference in disease expression is not known, although some data support the latter possibility.

Adolescent↗
PubMed2004

Lack of familial aggregation of Parkinson disease and Alzheimer disease.

OBJECTIVE: To investigate the risk of Alzheimer disease (AD) in first-degree relatives of patients with Parkinson disease (PD) compared with first-degree relatives of controls. DESIGN: Case-control study, family history method, and reconstructed cohort approach. METHODS: Probands with PD without dementia and control probands, matched by age strata, sex, and ethnicity, were examined in person and enrolled without knowledge of family history of PD and other neurological disorders. Disease status in first-degree relatives of probands with PD and control probands was ascertained through a structured family history interview administered to the proband and a second informant (self-report or another informant). Cox proportional hazards models with double-censoring techniques for missing information on age of onset of AD were used to analyze the risk of AD in first-degree relatives of patients with PD compared with first-degree relatives of controls. RESULTS: Four hundred eighty-seven probands with PD and 409 control probands provided family history information on 4819 first-degree relatives older than 30 years (2534 relatives of probands with PD and 2285 relatives of control probands). One hundred thirteen first-degree relatives (2.3%; 61 relatives [2.4%] of patients with PD and 52 relatives [2.3%] of controls) were diagnosed with AD. The risk of AD was not increased in relatives of patients with PD compared with relatives of controls (hazard ratio, 1.1; 95% confidence interval, 0.7-1.6; P =.65). Similarly, no significantly increased risk of AD was observed when comparing relatives of patients with early-onset (< or =50 years) and late-onset (>50 years) PD with relatives of controls. CONCLUSION: The lack of familial aggregation of PD and AD does not support the hypothesis of major shared genetic contributions to the etiology of the 2 most common neurodegenerative disorders.

Adult↗
PubMed2004

Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations.

The frequency and relative contribution of DJ-1 mutations in early-onset Parkinson's disease (EOPD) is currently unknown. We analyzed a cohort of 89 EOPD patients (mean age at onset of PD +/- SD, 41.5 +/- 7.2 years), ascertained independent of family history, who participated in a study of the genetic epidemiology of PD. This study includes sequence analysis of the DJ-1 gene in addition to assaying the 14,082-bp deletion spanning exons 1 to 5, previously identified in a Dutch kindred, in 89 EOPD cases. A heterozygous missense mutation in exon 5 (A104T) was identified in an EOPD case of Asian ethnicity; this sequence variant was absent in 308 control chromosomes. We identified additional sequence variation in the DJ-1 gene, including a polymorphism in the coding region in exon 5 (R98Q), three polymorphisms in the 5' untranslated region (exon 1A/1B), and two polymorphisms in intronic regions (IVS1 and IVS5). Mutations in the DJ-1 gene are rare in EOPD in both sporadic and familial cases.

Adult↗
PubMed2003

Familial aggregation of early- and late-onset Parkinson's disease.

The role of heredity in early- versus late-onset Parkinson's disease (PD) is controversial. We estimated the degree of increased risk of PD in first-degree relatives of 221 PD probands with age of onset 50 years or younger and 266 PD probands with age of onset older than 50 years compared with the first-degree relatives of 409 control probands. Risk of PD was similar among first-degree relatives of early-onset PD probands (risk ratio [RR], 2.9; 95% confidence interval [CI], 1.6-5.0; p = 0.0002) and late-onset PD probands (RR, 2.7; 95% CI, 1.6-4.4; p = 0.0002) when each was compared with first-degree relatives of controls. However, siblings of early-onset PD probands were at markedly increased risk of PD compared with siblings of controls (RR, 7.9; 95% CI, 2.5-25.5; p = 0.0005), whereas parents of early-onset PD probands were not at significantly increased risk compared with parents of controls (RR, 1.7; 95% CI, 0.9-3.3; p = 0.2). In late-onset families, both siblings (RR, 3.6; 95% CI, 1.3-10.3; p = 0.02) and parents (RR, 2.5; 95% CI, 1.4-4.6; p = 0.003) were at increased risk compared with control relatives. This pattern is consistent with an autosomal recessive contribution to the inheritance of early but not late-onset PD. Genetic factors are important in both early- and late-onset PD, but specific genes and mode of inheritance may differ between the two groups.

Adult↗
PubMed2003

Factors associated with increased risk of head tremor in essential tremor: a community-based study in northern Manhattan.

Head tremor is one of the major expressions of essential tremor (ET). It is not well understood why some patients develop head tremor, whereas others do not. A study of the characteristics of patients with head tremor has not been undertaken. Our goal was to estimate the prevalence of head tremor and to identify demographic and clinical characteristics associated with an increased risk of head tremor in ET. Cases were ascertained from a community-based study of ET in northern Manhattan, New York. Arm tremor severity was rated with a total tremor score. Logistic regression analyses resulted in odds ratios (OR). Head tremor was present in 37 (34.9%) of 106 ET cases. Female gender was associated with a fourfold increased risk of head tremor (OR = 3.73; P = 0.005). Total tremor score was divided into quartiles; individuals in the lowest or highest quartile were four times more likely to have head tremor (OR = 4.16; P = 0.001). Individuals with both risk factors (female gender and lowest or highest total tremor score quartile) were 16 times more likely to have head tremor (OR = 15.88; P = 0.0006). Being related to a proband with head tremor marginally increased the risk of head tremor (OR = 11.30; P = 0.08). Age and tremor duration did not influence the risk of head tremor. We identified several factors that were associated with an increased risk of head tremor in ET; female gender, coexisting arm tremor that was either very mild or extremely severe, and relation to an ET case with head tremor. These disease associations require further exploration, and might provide insight into the mechanisms underlying head tremor.

Adult↗
PubMed2003

Toxic pediatric parkinsonism: report of a child with metabolic studies and response to treatment.

We successfully treated a child with parkinsonism secondary to cytosine arabinoside with levodopa/carbidopa and attempted to elucidate the pathogenesis of the disorder by sequential analysis of cerebrospinal fluid biogenic amines, sequential magnetic resonance imaging, and fluorodopa positron emission tomography, which revealed both permanent and reversible biochemical and structural alterations. The parkinsonian disorder resolved in 9 months. Metabolic changes and structural abnormalities on imaging studies were chronologically correlated with the clinical course.

Antimetabolites, Antineoplastic↗
PubMed2002

Levetiracetam in the treatment of paroxysmal kinesiogenic choreoathetosis.

Anticonvulsants are frequently used in the treatment of paroxysmal kinesiogenic choreoathetosis (PKC). Although they are often extremely effective in eliminating paroxysmal movements, short- and long-term side-effects may limit their use in young patients. Levetiracetam (Keppra), a novel antiepileptic drug approved for the treatment of partial seizures is well tolerated in patients with epilepsy. We report on the use of levetiracetam in the treatment of PKC. Levetiracetam was effective in eliminating paroxysmal events and should be considered as an alternative to standard antiepileptic medications in this disorder.

Adult↗
PubMed2002

Dystonia, athetosis, and epilepsia partialis continua in a patient with late-onset Rasmussen's encephalitis.

Rasmussen's encephalitis is a rare autoimmune disorder characterized by intractable epilepsy and progressive hemispheric dysfunction. The disorder usually affects children, although cases have been reported with symptom onset in late adolescence or adulthood. Myoclonus is common in Rasmussen patients, usually occurring as part of epilepsia partialis continua (EPC); however, other hyperkinetic movements are rare. This report documents a 19-year-old woman with Rasmussen's encephalitis whose clinical presentation was dominated by foot dystonia, arm athetosis, and EPC. Intravenous immunoglobulin improved both hyperkinetic movements and EPC, but benefit was transient. The clinical significance and implications of these findings are discussed.

Adult↗
PubMed2002

Volumetric measurements in the detection of reduced ventricular volume in patients with normal-pressure hydrocephalus whose clinical condition improved after ventriculoperitoneal shunt placement.

OBJECT: The syndrome of normal-pressure hydrocephalus (NPH) refers to the clinical triad of gait disturbance, dementia, and urinary incontinence in association with idiopathic ventriculomegaly and normal intracranial pressure. Ventriculoperitoneal (VP) shunt placement often yields significant clinical improvements, sometimes without apparent reduction of ventricular size. The authors hypothesized that careful volumetric measurements would show a decrease in ventricular volume in these patients. METHODS: Twenty consecutive patients with NPH underwent placement of VP shunts equipped with programmable valves. In 11 patients pre- and postoperative neuroimaging was performed, which allowed volumetric analysis. Volumetric measurements of the lateral ventricles were calculated in triplicate by National Institutes of Health image-processing software to assess standard computerized tomography (CT) scans (eight patients) or magnetic resonance (MR) images (three patients) obtained before and after shunt placement. Ventricular volumes were also assessed by an independent neuroradiologist. Postoperative studies were performed at a time of clinical improvement, between 1 and 9 months postsurgery (mean 5 months). Preoperative and postoperative Unified Parkinson's Disease Rating Scale evaluations were performed in four patients. Significant clinical improvement occurred in all patients after shunt placement (mean follow-up period 17.5 months). Although 10 (91%) of 11 patients demonstrated a calculable decrease in volume in the lateral ventricles (mean decrease 39%), formal interpretation of neuroimages indicated a definite decrease in lateral ventricular volume in only three (27%) of 11 patients. CONCLUSIONS: Volumetric measurements obtained to compare preoperative and postoperative CT or MR studies obtained in patients with NPH in whom clinical improvement was seen after shunt placement surgery show a demonstrable decrease in ventricular size. Volumetric measurements may be helpful in clinical assessment postoperatively and in guiding programmable valve pressure settings.

Aged↗