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Biomedical subjects

Christopher G Goetz

Publications and source records attributed to Christopher G Goetz.

At least 37 records · Page 2Linked to original sources
PubMed2005

Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004.

The objective of this study is to update a previous evidence-based medicine (EBM) review on Parkinson's disease (PD) treatments, adding January 2001 to January 2004 information. The Movement Disorder Society (MDS) Task Force prepared an EBM review of PD treatments covering data up to January 2001. The authors reviewed Level I (randomized clinical trials) reports of pharmacological and surgical interventions for PD, published as full articles in English (January 2001-January 2004). Inclusion criteria and ranking followed the original program and adhered to EBM methodology. For Efficacy Conclusions, treatments were designated Efficacious, Likely Efficacious, Non-Efficacious, or Insufficient Data. Four clinical indications were considered for each intervention: prevention of disease progression; treatment of Parkinsonism, as monotherapy and as adjuncts to levodopa where indicated; prevention of motor complications; treatment of motor complications. Twenty-seven new studies qualified for efficacy review, and others covered new safety issues. Apomorphine, piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Non- efficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non-efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner.

Amantadine↗
PubMed2005

Transcultural comparison of psychogenic movement disorders.

Prompted by the lack of cross-cultural comparative data, and because a better understanding in the different clinical presentations of psychogenic movement disorders (PMDs) is relevant to neurological assessment and interventions, we compared the phenomenology, anatomical distribution, and functional impairment of PMDs in the United States and Spain. Consecutive patients diagnosed with PMD by a movement disorder specialist from one US site and from eight Spanish university centers were included in the study. The two groups were similar in their movement types, anatomical distribution, and functional impairment. PMDs were more prevalent in women than in men and were most common in upper and lower extremities. Gait and speech dysfunctions were distributed similarly in both countries. We found action tremor to be the most frequent PMD in both countries.

Adult↗
PubMed2005

Rating scale for psychogenic movement disorders: scale development and clinimetric testing.

We developed and tested the clinimetric properties of a scale for psychogenic movement disorders (PMDs). PMDs are disabling but lack any generally accepted treatment strategies. To develop treatments, means of assessing disease severity must be provided. No scale to assess PMDs existed. The PMD scale developed here rates 10 phenomena (rest tremor, action tremor, dystonia, chorea, bradykinesia, myoclonus, tics, athetosis, ballism, cerebellar incoordination), 2 functions (gait, speech), and 14 body regions. To study interrater agreement, three movement disorder neurologists independently rated 88 videotapes of PMD patients. Data analysis was performed using a kappa coefficient of agreement, Kendall's coefficient of concordance, Spearman correlations, and intraclass correlation coefficients. Validity and scale responsiveness were tested as well. All phenomena and speech and gait dysfunction occurred in the patient sample. A wide range of affected body regions, severity, and incapacitation was captured. Ratings showed excellent interrater reliability for presence or absence of each phenomenon (kappa range, 0.63 to 0.86). Kendall's concordance coefficients for phenomenology, function, and total PMD scores were 0.92, 0.93, and 0.91. Spearman correlations between raters ranged from 0.86 to 0.90. The scale was responsive to changes that occurred as a result of a neuropsychiatric intervention. The PMD scale adequately captures the complex movements of PMDs and can be used to assess PMDs and test the efficacy of intervention strategies.

Adolescent↗
PubMed2005

Non-linearity of Parkinson's disease progression: implications for sample size calculations in clinical trials.

BACKGROUND: Estimation of sample size for long-term studies of neuroprotection in Parkinson's disease requires information on expected clinical decline. Values may be obtained by analyzing existing long-term data sets or by prediction models of clinical decline applied to available data from shorter-term trials. The most commonly used measure to track clinical decline is the Unified Parkinson's Disease Rating Scale (UPDRS) but this measure is also affected by symptomatic therapy. Models can help better understand behavior of the UPDRS after initiation of symptomatic therapy when scores will improve and eventually start deteriorating again. PURPOSE: To understand how UPDRS scores progress after initiation of symptomatic therapy and how this progression impacts sample size calculations. METHODS: We developed a non-linear model of UPDRS after introduction of symptomatic therapy. The model is specified as a non-linear mixed effects model and is applied to three different data sets from clinical trials. The model is then used to produce estimates for the change in UPDRS and its associated variance for a period of up to five years of follow-up. The estimates produced by the model serve as the basis for sample-size calculations for different lengths of follow-up (one through five years) and for different values of clinically meaningful change in UPDRS. RESULTS: Despite differences in the short-term benefit of the dopaminergic drugs, after a period of approximately six months UPDRS scores progress linearly at an estimated rate of approximately three points a year. The sample size that is required for a clinical trial where the baseline coincides with initiation of symptomatic therapy is very large. On the other hand, if baseline is set at six months after initiation of symptomatic therapy then the sample size required decreases with length of follow-up. LIMITATIONS: Model specification and estimation is based on a set of simplifying assumptions regarding the progression of individual level UPDRS scores. CONCLUSIONS: Sample size calculations based on these estimates indicate a substantial reduction in sample size if patients are required to be on symptomatic treatment for a period of time before being randomized to a neuroprotective trial.

Antiparkinson Agents↗
PubMed2004

The origins of scientific cinematography and early medical applications.

OBJECTIVE: To examine the neurologic cinematographic contributions of Gheorghe Marinescu. BACKGROUND: Near the end of the 19th century, cinematography developed and was immediately recognized as a new technique applicable to medical documentation. After studying with several prominent European neurologists and deeply influenced by Jean-Martin Charcot, Marinescu returned to Bucharest in 1897 and applied moving picture techniques to the study of neurologic patients. METHODS: The Romanian State Archives were researched for original Marinescu films, and related publications were translated from Romanian and French. RESULTS: Between 1899 and 1902, Marinescu perfected the use of cinematography as a research method in neurosciences and published five articles based on cinematographic documents. He focused his studies particularly on organic gait disorders, locomotor ataxia, and hysteria. He adapted Charcot's method of lining up several patients with the same disorder and showing them together to permit appreciation of archetypes and formes frustes. He decomposed the moving pictures into sequential tracings for publication. He documented treatment results with cases filmed before and after therapy. Processed and digitized excerpts of these films accompany this manuscript. CONCLUSIONS: Marinescu's cinematographic studies led to several original contributions in clinical neurology. Remaining film archives include examples of many neurologic diseases, his examination techniques, and the working medical environment of the young founder of the Romanian school of neurology.

Biomechanical Phenomena↗
PubMed2004

Medical-legal issues in Charcot's neurologic career.

OBJECTIVE: Trace the medical-legal involvement of the 19th century clinical neurologist Jean-Martin Charcot. BACKGROUND: The two major neurologic concerns of the 1800s that involved legal questions were topics of particular academic interest to Charcot: post-traumatic neurologic syndromes and the behavioral consequences of hysteria and hypnotism. Although Charcot's medical views influenced several nonmedical fields, including art, poetry, and drama, his impact on medical-legal issues has not been examined. METHODS: Original documents from the Bibliothèque Charcot at the Salpêtrière Hospital in Paris, legal documents, and publications from Charcot's era were examined. RESULTS: Although his involvement in medical-legal affairs was a modest element of Charcot's multifaceted career, he was involved in four different types of medical-legal activities: as a cited authority in the medical-legal literature, as an author of articles within medical-legal contexts, as a subpoenaed expert consultant, and as an expert examiner. CONCLUSIONS: Charcot's involvement demonstrates the long tradition of an interface between neurology and legal medicine and provides a model for highly limited but authoritative involvement by academic neurologists in medical-legal affairs.

Adult↗
PubMed2004

Genetic polymorphisms in Parkinson disease subjects with and without hallucinations: an analysis of the cholecystokinin system.

BACKGROUND: Hallucinations in patients with Parkinson disease (PD), occurring in about one third of those receiving long-term dopaminergic therapy, contribute to morbidity and mortality. In matched Chinese PD subjects with and without hallucinations, the presence of the -45 C/T locus in the cholecystokinin (CCK) gene, particularly when combined with the CCK receptor, CCKAR (cholecystokinin A receptor), C polymorphism, was associated with increased hallucination risk. Because CCK gene polymorphisms vary across ethnic groups, the presence of similar associations in white PD subjects merits investigation. OBJECTIVE: To determine whether polymorphisms of CCK and CCK receptor genes are associated with hallucinations in white PD subjects. DESIGN: Case-control study of PD subjects with and without chronic hallucinations matched for age and dopaminergic medication. Genomic DNA was analyzed for CCK, CCKAR, and CCKBR (cholecystokinin B receptor) polymorphisms by polymerase chain reaction. Genotype distributions and allele frequencies were compared between groups and in matched pairs. RESULTS: Comparing matched pairs, we found more frequent representation of the CCK T allele in hallucinating PD subjects, although this finding was not statistically significant (P =.06). Of 5 cases with both CCK T and CCKAR C alleles, 4 were hallucinators. Cases and controls did not differ in CCKAR or CCKBR polymorphisms. CONCLUSIONS: Our study supports a previous association of hallucinations in PD subjects with the CCK T allele and the combined CCK T and CCKAR C allele, suggesting that the CCK system may influence the development of hallucinations in PD subjects. The lower representation of the T allele in our white sample limited our statistical power. Further assessment of the T allele as a risk factor for hallucinations would include longitudinal study of nonhallucinators to detect the evolution of hallucinations relative to T allele frequency.

Aged↗
PubMed2004

Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations.

The Movement Disorder Society Task Force for Rating Scales for Parkinson's disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scale's mixing of impairment and disability and its non-linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2-4). Although a "modified HY scale" that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should "rate what you see" and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five-point scales should be maintained.

Feasibility Studies↗
PubMed2004

Assuring interrater reliability for the UPDRS motor section: utility of the UPDRS teaching tape.

We assessed rates of successful certification on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRSm) after training with the UPDRS Teaching Tape. The most frequently used clinical scale for PD is the UPDRS, and most clinical trials rely on the motor examination as the primary outcome measure. Whereas the Movement Disorder Society's UPDRS Teaching Tape has been used widely as a training format, outcome data are lacking. We examined data sets from four multicenter studies that required raters to pass the certification exercise of the UPDRS Teaching Tape. Raters viewed the Teaching Tape showing examples of all rating levels for all items (38 minutes), and then took the certification exercise, rating 4 subjects with PD (20 minutes). Certification required scores on all 4 subjects that fit within the 95% confidence interval range established by three experts. We calculated the numbers of raters successfully certified after one or more rating attempts. Only one-half of 226 raters that participated successfully completed certification on their first attempt, but all completed by the third attempt. North American raters scored better than Europeans raters. The most difficult case to rate was the subject with the least impairment. Standardized methods for training UPDRSm application are essential to ensure that raters use the scale uniformly. Raters have the greatest difficulty with the mildest impairment, making training especially important to studies of early PD.

Certification↗
PubMed2004

Short-term and practice effects of metronome pacing in Parkinson's disease patients with gait freezing while in the 'on' state: randomized single blind evaluation.

OBJECTIVE: In a randomized single blind parallel study, we tested the efficacy of an auditory metronome on walking speed and freezing in Parkinson's disease (PD) patients with freezing gait impairment during their 'on' function. BACKGROUND: No pharmacological treatment is effective in managing 'on' freezing in PD. Like visual cues that can help overcome freezing, rhythmic auditory pacing may provide cues that help normalize walking pace and overcome freezing. DESIGN/METHODS: Non-demented PD patients with freezing during their 'on' state walked under two conditions, in randomized order: unassisted walking and walking with the use of an audiocassette with a metronome recording. The walking trials were randomized and gait variables were rated from videotapes by a blinded evaluator. Outcome measures were total walking time (total trial time-total freezing time), which was considered the time over a course of specified length, freezing time, average freeze duration and number of freezes. All outcomes were averaged across trials for each person and then compared across conditions using Signed Rank tests. RESULTS: Twelve non-demented PD patients with a mean age of 65.8 +/- 11.2 years, and mean PD duration of 12.4 +/- 7.3 years were included. The use of the metronome slowed ambulation and increased the total walking time (P < 0.0005) only during the first visit, without affecting any freezing variable. In the nine patients who took the metronome recording home and used it daily for 1 week while walking, freezing remained unimproved. CONCLUSIONS: Though advocated in prior publications as a walking aid for PD patients, auditory metronome pacing slows walking and is not a beneficial intervention for freezing during their 'on' periods.

Acoustic Stimulation↗
PubMed2003

Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.

We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of 'genomic convergence' to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1beta. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.

Age of Onset↗
PubMed2003

The prefaces by Charcot: leitmotifs of an international career.

The objective of this article was to examine the prefaces that Jean-Martin Charcot wrote for other colleagues' books and to evaluate these short essays from three perspectives: scientific material discussed, medicopolitical strategies revealed, and larger thematic issues developed. Charcot (1825-1893) was the most celebrated clinical neurologist of his epoch. In his mid and late career, he wrote very few manuscripts, delegating such work to junior colleagues or to Bourneville, who compiled Charcot's Complete Works. One particular source of direct writing from Charcot's mature career is the group of prefaces he composed for selected monographs authored by other colleagues. The prefaces from the Gasser tabulation (Bibliothèque Charcot, Paris) of Charcot's works were examined and analyzed in the context of Charcot's career. Of the 21 prefaces, 10 concerned books by other colleagues with whom he had not worked, and 11 introduced books of his students or direct colleagues. The prefaces concerned primarily two topics of direct medical interest to Charcot: localization studies of cortical and spinal cord diseases, and the combined subject of hysteria and hypnotism. In placing the works in scientific context, Charcot systematically emphasized the contributions of French neurologists, largely focusing on the Salpêtrière school and its (his) discoveries. Charcot used these prefaces to summarize the major thematic elements of his career, drafting the essays in the context of such topics as medical specialization, the concept of experimental medicine, and the prioritization of human studies over experimental laboratory medicine. Although an exhaustive reading of Charcot's entire opus is needed to provide a comprehensive view of his ideas, the short and pithy prefaces, comprising fewer than 60 pages, coalesce and distill the primary themes of his international career.

Cooperative Behavior↗
PubMed2003

Progression of gait, speech and swallowing deficits in progressive supranuclear palsy.

OBJECTIVE: To identify outcome measures for clinical trials in progressive supranuclear palsy (PSP), the authors determined the time to key motor impairments in a well-defined patient cohort. METHODS: The records of consecutive patients with probable PSP, defined by National Institute of Neurological Disorders and Stroke-Society for Progressive Supranuclear Palsy workshop criteria on first visit to a tertiary care center, were selected for study if the patients were seen regularly at 3- to 6-month intervals, had at least 24 months of care at the Rush movement disorder center, and were originally seen in the movement disorder center before any of the following key motor impairments developed: unintelligible speech, no independent walking, inability to stand unassisted, wheelchair-bound, or recommendation for feeding tube placement. Using standardized criteria from the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr stages taken at each clinic visit, the authors recorded the time that each patient reached the key motor impairments and death. Median months from first symptom onset and from first consultation at the movement disorder center to each motor impairment were derived from Kaplan-Meier curves. RESULTS: Fifty subjects, mean age at study entry 64.2 years, were followed to death (n = 21, mean duration of surveillance 53.6 months) or in ongoing fashion (n = 29, mean duration of surveillance 46.2 months). Eighty-eight percent of the sample met at least one milestone. The median time from disease onset to the first key motor impairment was 48 months, 24 months after first consultation. The three gait items occurred temporally close, and the authors considered them thereafter as a single milestone, occurring at a median disease duration of 57 months, 34 months after first consultation. Unintelligible speech occurred at a median disease duration of 71 months, median 44 months after first consultation. As a composite end point, speech/gait accounted for 98% of the sample's first key motor impairment. Need for nasogastric tube was rarely the first milestone (8%). CONCLUSIONS: Gait impairment and unintelligible speech are milestones that occur rapidly in PSP and can be monitored with standardized rating scales. The authors suggest that clinical trials use these indices to assess how interventions alter anticipated progression of clinical deterioration in PSP.

Adult↗
PubMed2003

Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease.

Mitochondrial (mt) impairment, particularly within complex I of the electron transport system, has been implicated in the pathogenesis of Parkinson disease (PD). More than half of mitochondrially encoded polypeptides form part of the reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme. To test the hypothesis that mtDNA variation contributes to PD expression, we genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34-0.91; P=.02) or K (OR 0.52; 95% CI 0.30-0.90; P=.02) demonstrated a significant decrease in risk of PD versus individuals carrying the most common haplogroup, H. Furthermore, a specific SNP that defines these two haplogroups, 10398G, is strongly associated with this protective effect (OR 0.53; 95% CI 0.39-0.73; P=.0001). SNP 10398G causes a nonconservative amino acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men (OR 0.43; 95% CI 0.27-0.71; P=.0009). In addition, SNP 9055A of ATP6 demonstrated a protective effect for women (OR 0.45; 95% CI 0.22-0.93; P=.03). Our results suggest that ND3 is an important factor in PD susceptibility among white individuals and could help explain the role of complex I in PD expression.

DNA, Mitochondrial↗
PubMed2003

Parkinson disease with old-age onset: a comparative study with subjects with middle-age onset.

BACKGROUND: To our knowledge, no prior study has focused on subjects with Parkinson disease (PD) with elderly disease onset, and there is little evidence-based knowledge of treatment outcomes in these patients. OBJECTIVE: To compare the clinical presentation, comorbidities, treatment, and evolution of PD in patients with old-age onset with those of patients with middle-age onset in one US university center. DESIGN: In the Rush Movement Disorder Database, we retrieved 43 patients with PD with onset at 78 years or older. By using a case-control design, we assigned each patient with old-age PD onset 1 (n = 5) or 2 (n = 38) patients with middle-age PD onset, matched for disease duration but with disease onset between the ages of 43 and 66 years. We compared the groups on several clinical measures using conditional logistic regression. RESULTS: At a comparable length of PD duration (mean, 5.1 years for patients with old-age PD onset and 5.5 years for patients with middle-age PD onset), the total Unified Parkinson's Disease Rating Scale motor score was significantly higher in those with old-age PD onset than in those with middle-age PD onset (33.3 vs 21.2; P<.001). The patients with old-age onset had higher scores for rigidity (5.2 vs 4.3; P =.03), bradykinesia (13.0 vs 9.6; P =.001), and axial impairment (12.8 vs 5.2; P<.001), but not for tremor (2.2 vs 2.0; P =.68). They were more likely to have at least one comorbid condition compared with patients with middle-age onset (24 [56%] of 43 patients vs 20 [25%] of 81 patients; P =.002), but even when adjusting for comorbidities, they still maintained higher motor scores than controls. When treating patients with old-age PD onset, clinicians used levodopa monotherapy more frequently than in patients with middle-age PD onset (34 patients [79%] vs 16 patients [20%]; P<.001), and agonists were prescribed less frequently (5 patients [12%] vs 29 patients [36%]; P =.005). CONCLUSIONS: At the same disease duration, patients with old-age PD onset have greater motor impairment than patients with middle-age PD onset. This difference may be due to more rapid disease progression, less aggressive or less potent medical treatment, the elderly age of the subjects with old-age PD onset at study end independent of disease onset, or yet-to-be elucidated influences of comorbid conditions. Focused research on old-age PD onset is important to delineate the confounding influences of aging and comorbidities and to establish the safety and efficacy of new treatments for this group of patients.

Adult↗
PubMed2003

Association study of Parkin gene polymorphisms with idiopathic Parkinson disease.

BACKGROUND: Previously, we detected linkage of idiopathic Parkinson disease (PD) to the region on chromosome 6 that contains the Parkin gene (D6S305; logarithm of odds score, 5.47) in families with at least one individual with age at onset younger than 40 years (families with early-onset disease). Further study demonstrated the presence of Parkin mutations in this data set. However, previous case-control studies have reported conflicting results regarding the role of more common Parkin polymorphisms as susceptibility alleles for idiopathic PD. OBJECTIVE: To investigate the association of 7 previously studied Parkin single-nucleotide polymorphisms (SNPs) throughout the promoter and most of the open reading frame with PD in a large cohort of patients with primarily late-onset PD. METHODS: One promoter, 3 intronic, and 3 exonic Parkin SNPs were genotyped in 1580 individuals belonging to 397 families, and their association with PD was evaluated using family-based association tests. RESULTS: No significant association (P>.05) between PD and any Parkin SNP allele or genotype was detected. Haplotype analysis and stratification by age at onset or family history also failed to produce significant results. CONCLUSIONS: These results suggest that these common variants of Parkin are not associated with PD in white patients, although Parkin mutations are known to cause early- and late-onset PD.

Adolescent↗
PubMed2003

Tremor and ataxia in fragile X premutation carriers: blinded videotape study.

Fragile X premutation carriers do not have typical fragile X syndrome (FXS) although late-onset progressive action tremor and gait disorder with CNS atrophy was recently reported in male carriers. We compared tremor, gait disorder and parkinsonian signs in FXS premutation subjects (age 50 or more) and a similar control population, using a standardized videotaping protocol. Videotapes were rated using standard scales for tremor (CRST), ataxia (ICARS), and parkinsonian signs (UPDRS) by an investigator blinded to premutation status. Compared to all other groups pooled (n = 30), the male premutation carrier group (n = 7) had significantly higher scores on the CRST (p = 0.0008), ICARS (p = 0.001), and UPDRS (p = 0.0094). On the CRST, rest, postural and kinetic tremor scores were all higher in the male carriers. The elevated total UPDRS and ICARS scores mainly resulted from markedly higher scores for tremor and limb ataxia, respectively. The female carrier (n = 14) and control groups (n = 8) did not differ on any measure. The FMR1 premutation is associated with increased levels of CGG repeat-containing FMR1 mRNA, which may predispose to these symptoms by interfering with nuclear mechanisms. Given the relatively high population frequency of the FMR1 premutation, this mutation may be a significant cause of late-onset "idiopathic" progressive tremor.

Aged↗