PubMed Health⌕ Search

Biomedical subjects

Ali Samii

Publications and source records attributed to Ali Samii.

At least 19 recordsLinked to original sources
PubMed2007

Holmes-like tremor of the lower extremity following brainstem hemorrhage.

Holmes tremor is an arrhythmic, 2- to 5-Hz resting, postural, and kinetic upper extremity movement disorder that occurs weeks to months after acute mesencephalic pathology. We present a patient who developed tremor in three body parts postbrainstem hemorrhage with subsequent hypertrophic olivary degeneration and discuss the relevant clinical evolution. Our case is unique because in addition to expected upper extremity and cervical dystonic head tremors, the patient also developed a severe lower extremity movement disorder, which we believe to be a form of Holmes tremor. Tremor involving the lower extremity in this setting has not been previously reported.

Acute Disease↗
PubMed2006

LRRK2 G2019S in families with Parkinson disease who originated from Europe and the Middle East: evidence of two distinct founding events beginning two millennia ago.

The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic determinant of Parkinson disease (PD) identified to date. It accounts for 1%-7% of PD in patients of European origin and 20%-40% in Ashkenazi Jews and North African Arabs with PD. Previous studies concluded that patients from these populations all shared a common Middle Eastern founder who lived in the 13th century. We tested this hypothesis by genotyping 25 microsatellite and single-nucleotide-polymorphism markers in 22 families with G2019S and observed two distinct haplotypes. Haplotype 1 was present in 19 families of Ashkenazi Jewish and European ancestry, whereas haplotype 2 occurred in three European American families. Using a maximum-likelihood method, we estimated that the families with haplotype 1 shared a common ancestor 2,250 (95% confidence interval 1,650-3,120) years ago, whereas those with haplotype 2 appeared to share a more recent founder. Our data suggest two separate founding events for G2019S in these populations, beginning at a time that coincides with the Jewish Diasporas.

Africa, Northern↗
PubMed2006

Parkinson's disease and LRRK2: frequency of a common mutation in U.S. movement disorder clinics.

The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography; to determine carrier frequency in a large and well-characterized control population; to examine segregation of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1,425 patients and one of 1,647 controls had the mutation. Carrier frequency (+/- 2SE) in patients was 0.013 +/- 0.006 overall, 0.030 +/- 0.019 in familial PD, 0.007 +/- 0.005 in nonfamilial PD, 0.016 +/- 0.013 in early-onset PD, and 0.012 +/- 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date.

Adolescent↗
PubMed2006

Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study.

BACKGROUND: A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson's disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. METHODS: Investigators from three Michael J Fox Foundation for Parkinson's Research-funded genetics consortia-comprising 14 teams-contributed DNA samples from 5526 patients with Parkinson's disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. FINDINGS: In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0.89 to 1.09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0.95 to 1.08); there was little heterogeneity except for SNP rs7520966. INTERPRETATION: Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease.

Aged↗
PubMed2006

Validity and utility of a LRRK2 G2019S mutation test for the diagnosis of Parkinson's disease.

The G2019S mutation in the LRRK2 gene, the most common known cause of Parkinson's disease (PD), will soon be widely available as a molecular clinical test for PD. The objective of this study was to assess performance characteristics of G2019S as a clinical test for PD in the setting of typical movement disorder clinics in the United States. Subjects included 1,518 sequentially recruited PD patients from seven movement disorder clinics in the United States, and 1,733 unaffected subjects. All 3,251 subjects were genotyped for the G2019S mutation using a TaqMan assay, and mutations were verified by direct sequencing. Test validity estimates were calculated using standard methods. A total of 20/1518 patients and 1/1733 controls carried the G2019S mutation. Specificity was 99.9% (95% CI, 99.6-100%), sensitivity was 1.3% (0.8-2.1%), and the positive likelihood ratio was 22.8. A positive family history of PD increased the positive likelihood ratio to 82.5. Information on gender, age at disease onset, or age at testing did not improve test performance. The gene test was highly accurate in classifying mutation carriers as PD, but it performed poorly in predicting the phenotype of non-mutation carriers. A G2019S molecular test for PD would be highly specific, technically simple, and inexpensive. Test interpretation is straightforward when used for diagnosis of symptomatic individuals, but is more complex for risk assessment and predictive testing in asymptomatic individuals. Test results can have psychological, social, and economical ramifications; thus, proper counseling is essential.

Adolescent↗
PubMed2006

Challenges and opportunities for pharmacoepidemiology in drug-therapy decision making.

Pharmacoepidemiology is a relatively new and evolving science that attempts to quantify mainly adverse drug events and patterns of drug use in a large population. The strength of pharmacoepidemiology over randomized trials is the ability to quantify rare adverse events that may occur over long periods. Recently, discordance in the results of pharmacoepidemiologic studies has made it difficult for clinicians and policy makers to make informed drug-therapy decisions. This commentary addresses the strength of pharmacoepidemiology and the advances in the methodology of pharmacoepidemiologic studies over the years. We also discuss the potential problem of discordant results and urge pharmacoepidemiologists to develop good practice guidelines for the conduct of pharmacoepidemiologic studies.

Adverse Drug Reaction Reporting Systems↗
PubMed2006

Telemedicine for delivery of health care in Parkinson's disease.

We have used telemedicine at the Seattle Veterans Administration Medical Center to deliver follow-up care to patients with Parkinson's disease (PD). Patients were located at eight facilities which were 67-2400 km from the medical centre. Each facility had videoconferencing equipment (connected by Internet Protocol at 384 kbit/s), and computer terminals that could access the patient's electronic medical record. Over a three-year period, we used telemedicine for 100 follow-up visits on 34 PD patients. Visits lasted 30-60 min. Patients and providers were satisfied with the use of the technology. Savings amounted to approximately 1500 attendant travel hours, 100,000 travel kilometres, and US 37,000 dollars in travel and lodging costs. For the first 82 telemedicine visits, the video quality was inadequate for scoring all components of the motor Unified Parkinson Disease Rating Scale (UPDRS). For the last 18 visits, a different videoconferencing unit produced better video quality, which was satisfactory for motor UPDRS measurements, except for components that required physical contact with the patient (rigidity and retropulsion testing). Our experience shows that telemedicine can be used effectively for follow-up visits with selected PD patients who are unable to travel.

Computer Terminals↗
PubMed2006

Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders.

Biomarkers are needed to assist in the diagnosis and medical management of various neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy body (DLB). We have employed a multiplex quantitative proteomics method, iTRAQ (isobaric Tagging for Relative and Absolute protein Quantification), in conjunction with multidimensional chromatography, followed by tandem mass spectrometry (MS/MS), to simultaneously measure relative changes in the proteome of cerebrospinal fluid (CSF) obtained from patients with AD, PD, and DLB compared to healthy controls. The diagnosis of AD and DLB was confirmed by autopsy, whereas the diagnosis of PD was based on clinical criteria. The proteomic findings showed quantitative changes in AD, PD, and DLB as compared to controls; among more than 1,500 identified CSF proteins, 136, 72, and 101 of the proteins displayed quantitative changes unique to AD, PD, and DLB, respectively. Eight unique proteins were confirmed by Western blot analysis, and the sensitivity at 95% specificity was calculated for each marker alone and in combination. Several panels of unique makers were capable of distinguishing AD, PD and DLB patients from each other as well as from controls with high sensitivity at 95% specificity. Although these preliminary findings must be validated in a larger and different population of patients, they suggest that a roster of proteins may be generated and developed into specific biomarkers that could eventually assist in clinical diagnosis and monitoring disease progression of AD, PD and DLB.

Alzheimer Disease↗
PubMed2005

Unilateral subthalamic nucleus deep brain stimulation contralateral to thalamic stimulation in Parkinson disease.

The effects of unilateral subthalamic nucleus (STN) stimulation contralateral to thalamic stimulation in Parkinson disease (PD) have not been previously reported. We are reporting a patient who developed left arm tremor in 1994, at age 62, as her first PD symptom. She underwent right thalamic DBS surgery in 1999 that resulted in complete resolution of left arm tremor. Her PD symptoms progressed and she developed severe motor fluctuations and disabling dyskinesias. In 2003, she underwent left STN electrode implantation. Left STN stimulation improved contralateral motor scores in the medication OFF state, and allowed for reduced medication doses and less dyskinesia. However, there was no significant improvement in activities of daily living (ADL), motor scores in the medication ON state, gait, or postural stability.

Deep Brain Stimulation↗
PubMed2005

Deep brain stimulation in a patient on immunosuppressive therapy after renal transplant.

We performed thalamic deep brain stimulation (DBS) surgery to treat severe essential tremor in a 36 year-old woman who had undergone cadaveric renal transplant four years earlier. She was receiving chronic immunosuppressive therapy. Post-operative healing was normal and there have been no infections of the DBS hardware. There were no peri-operative complications and no rejection of the transplanted kidney. She remains on the same systemic immunosuppressive agents as pre-operatively: prednisone, cyclosporine, and mycophenolate mofetil (CellCept). DBS surgery may be safely performed in carefully selected patients on systemic immunosuppression after renal transplant.

Adult↗
PubMed2005

Positron emission tomography after fetal transplantation in Huntington's disease.

Huntington's disease (HD) is a progressive disorder with no known cure. We report two-year postoperative positron emission tomography (PET) data from 7 HD patients who underwent intrastriatal fetal transplantation. Patients showed widespread reductions in glucose uptake with no significant change over 2 years. Dopamine receptor binding was significantly reduced in HD striatum. D1 binding did not change significantly following transplantation, but there was a significant loss of D2 binding. These findings may reflect loss of graft viability and/or disease progression. There was no significant relationship between changes in PET and clinical function. In summary, there was no benefit from transplantation.

Analysis of Variance↗
PubMed2005

Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis.

We studied the effect of vitamin C, vitamin E, and beta carotene intake on the risk of Parkinson's disease (PD). We did a systematic review and meta-analysis of observational studies published between 1966 and March 2005 searching MEDLINE, EMBASE, and the Cochrane Library. Eight studies were identified (six case-control, one cohort, and one cross-sectional). We found that dietary intake of vitamin E protects against PD. This protective influence was seen with both moderate intake (relative risk 0.81, 95% CI 0.67-0.98) and high intake (0.78, 0.57-1.06) of vitamin E, although the possible benefit associated with high intake of vitamin E was not significant. The studies did not suggest any protective effects associated with vitamin C or beta carotene. We conclude that dietary vitamin E may have a neuroprotective effect attenuating the risk of PD. These results require confirmation in randomised controlled trials.

Ascorbic Acid↗
PubMed2004

Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies.

OBJECTIVE: To explore the association between migraine and risk of ischaemic stroke. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Observational studies published between 1966 and June 2004 (identified through Medline and Embase) that examined the association between migraine and risk of ischaemic stroke. RESULTS: 14 studies (11 case-control studies and 3 cohort studies) were identified. These studies suggest that the risk of stroke is increased in people with migraine (relative risk 2.16, 95% confidence interval 1.89 to 2.48). This increase in risk was consistent in people who had migraine with aura (relative risk 2.27, 1.61 to 3.19) and migraine without aura (relative risk 1.83, 1.06 to 3.15), as well as in those taking oral contraceptives (relative risk 8.72, 5.05 to 15.05). CONCLUSIONS: Data from observational studies suggest that migraine may be a risk factor in developing stroke. More studies are needed to explore the mechanism of this potential association. In addition, the risk of migraine among users of oral contraceptives must be further investigated.

Adolescent↗
PubMed2004

Coexistence of tuberous sclerosis and Friedreich ataxia.

Tuberous sclerosis (TS) is caused by point mutations in the TSC1 or TSC2 genes on chromosomes 9q33-34 or 16p13, respectively. Clinical manifestations can be quite variable but are primarily limited to cutaneous, neurologic, and cardiovascular abnormalities. Phenotypes range from neurologically devastated to those with silent lesions. A 34-year-old patient with genetically documented TSC1 developed progressive ataxia over a decade, without TS lesions to correlate with this finding. After evaluation of common causes including long-term antiepileptic regimens, DNA testing for hereditary ataxias was performed and revealed the presence of an additional mutation on chromosome 9. The patient was homozygous for the Friedreich ataxia (FA) mutation, with 500 and 700 GAA repeats in the FRDA gene on chromosome 9q13. There is no established relationship between these two disorders and the occurrence of two mutations on the same chromosome is probably coincidental but emphasizes the importance of searching for additional genetic causes when the phenotype does not fit with an established genetic diagnosis.

Adult↗
PubMed2004

Parkinson's disease.

Parkinson's disease is the most common serious movement disorder in the world, affecting about 1% of adults older than 60 years. The disease is attributed to selective loss of neurons in the substantia nigra, and its cause is enigmatic in most individuals. Symptoms of Parkinson's disease respond in varying degrees to drugs, and surgery offers hope for patients no longer adequately controlled in this manner. The high prevalence of the disease, and important advances in its management, mean that generalists need to have a working knowledge of this disorder. This Seminar covers the basics, from terminology to aspects of diagnosis, treatment, and pathogenesis.

Brain↗