Puiu Nisipeanu

Retinal nerve fiber layer thinning in Parkinson disease.

Retinal dopamine loss in Parkinson disease (PD) is reflected by visual neurophysiological dysfunction. We measured the thickness of the circumpapillary retinal nerve fiber layer (RNFL) in PD patients using optical coherence tomography. The thickness in the inferior quadrant of PD patients (147 +/- 20 microns) was significantly thinner than that of controls (173 +/- 12 microns; p=0.002), while the inferotemporal area was the thinnest (146 +/- 24 vs. 191 +/- 21 microns; p=0.0003). The results show significant loss of RNFL thickness in PD at specific sites.

Homozygotes for oculopharyngeal muscular dystrophy have a severe form of the disease

Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) usually begins with ptosis or dysphagia during the fifth or sixth decade of life. We studied 7 patients with OPMD symptoms starting before the age of 36 years. All were found to be homozygotes for the dominant (GCG)9 OPMD mutation. On average, disease onset was 18 years earlier than in heterozygotes, and patients had a significantly larger number of muscle nuclei containing intranuclear inclusions (INIs) (9.4 vs 4.9%). Ann Neurol 1999;46:115–118

Practice parameter: Initiation of treatment for Parkinson’s disease: An evidence-based review

To the Editor: We have read with interest the practice parameter by Miyasaki et al.1 concerning the use of dopamine agonists (DA) in the treatment of patients with early Parkinson’s disease (PD). The authors stressed in this evidence-based review that cabergoline, pramipexole, and ropinirole were shown to be superior to levodopa in delaying the motor fluctuations and dyskinesias. However, they did not recommend any of the three DA as the first choice of treatment, arguably because there have been no adequate trials comparing these drugs with each other as monotherapy in early PD. To address this issue we compared the three …

Cabergoline, pramipexole and ropinirole used as monotherapy in early Parkinson's disease: an evidence-based comparison.

Dopamine agonists have been widely used as add-on to levodopa in the treatment of Parkinson’s disease with motor fluctuations. However, the use of dopamine agonists in early Parkinson’s disease and levodopa-naive patients is controversial. Although dopamine agonists have been compared with levodopa, no studies exist which directly compare one dopamine agonist with another. This evidence-based review compares the results of large published studies of early treatment of Parkinson’s disease with dopamine agonists (cabergoline, ropinirole or pramipexole) with similar studies using levodopa.Because of their design, the common variables analysed in all studies were the proportion of patients who developed dyskinesia, those withdrawn from the trial and the mean change from baseline in Unified Parkinson’s Disease Rating Scale (UPDRS) parts II and III scores.Cabergoline, pramipexole and ropinirole were similarly effective in reducing the risk for dyskinesia relative to levodopa (p < 0.01 for all three). The reduction in risk for dyskinesia was slightly more evident for pramipexole and ropinirole (p < 0.0001) than cabergoline (p = 0.0074). Odds ratios (95% confidence intervals [CI]) relative to levodopa were 0.38 (0.19–0.78) for cabergoline, 0.25 (0.13–0.47) for pramipexole and 0.31 (0.18-0.53) for ropinirole. The absolute risk reductions (95% CI) were, respectively, 8% (2.2–13.7), 20% (11.7–29.8) and 25% (13.6–36.7), ropinirole reducing the risk significantly more than cabergoline. The mean change from baseline UPDRS was similar for pramipexole and ropinirole (not evaluated for cabergoline). The proportion of withdrawn patients and the adverse effect profiles of the three agonists were similar to each other, with the exception of oedema, which was less prominent for ropinirole than for the other two agonists.Cabergoline, pramipexole and ropinirole are comparable choices for the delay of dyskinesia. Their adverse effect profiles are also similar, but they are less well tolerated than levodopa. The motor antiparkinsonian benefit of dopamine agonists is somewhat smaller than that of levodopa.

Autosomal-recessive juvenile parkinsonism in a Jewish Yemenite kindred: Mutation of Parkin gene

We report a Jewish family of Yemenite origin in which three brothers born from a consanguineous marriage had juvenile parkinsonism. The DNA samples from three affected brothers and one healthy brother were analyzed for the linkage to markers covering the autosomal-recessive juvenile parkinsonism (AR-JP) locus. A perfect homozygous cosegregation to the markers was found, giving a maximal lod score of 3.11 at D6S1579, D6S305, and D6S411, all of which are 0 cm apart from each other (nonparametric linkage score, 8.041; p = 0.000977). Exon 3 of the Parkin gene was homozygously deleted in all patients. The AR-JP gene also exists in the Jewish population.

A locus for complicated hereditary spastic paraplegia maps to chromosome 1q24-q32.

We updated the clinical features of a consanguineous Arab Israeli family, in which four of seven children were affected by spastic paraplegia complicated by skin pigmentary abnormalities. A genomewide linkage screen performed for the family identified a new locus (SPG23) for this form of hereditary spastic paraplegia, in an approximately 25cM region of chromosome 1q24‐q32, with a peak logarithm of odds score of 3.05. Ann Neurol 2003;54:796–803

Camptocormia, axial dystonia, and parkinsonism: phenotypic heterogeneity of a parkin mutation.

Autosomal recessive juvenile parkinsonism (AR-JP) is a young-onset parkinsonism caused by mutations in the parkin gene.1 Exonic deletions or multiplications and truncating and missense mutations have been described.2,3⇓ The phenotype encompasses juvenile-, early-, and late-onset patients.2 We describe a large kindred with different phenotypic expressions of a mutation in the parkin gene. The patients belonged to two branches of an Arabic Israeli family (figure). Patients in Branch A have been previously described.4 The consanguinity of the branches was established to the seventh ancestral generation. Figure. The pedigree. Square symbols = men, circles = women, diagonal lines = deceased persons, ✓ = genotyped. The consanguinity of the branches of the family was established to the seventh ancestral generation. Four brothers (black squares) in Branch A (right) and two first-degree cousins (black square and circle) in Branch B (middle) are affected. All patients showed homozygous one adenine deletion at nucleotide position 202. The horizontal shaded symbols represent patients with tremor only who were clinically examined. The patient with an asterisk was genotyped …

Inspiratory muscle training and the perception of dyspnea in Parkinson's disease.

BACKGROUND Pulmonary and respiratory muscle function impairment are common in patients with Parkinsons disease (PD). Inspiratory muscle training may improve strength, dyspnea and functional capacity in healthy subjects and in those with chronic obstructive pulmonary disease. This study investigated the effect of specific inspiratory muscle training (SIMT) on pulmonary functions, inspiratory muscle performance, dyspnea and quality of life, in patients with PD. PATIENTS AND METHODS Twenty patients with PD (stage II and III Hoehn and Yahr scale) were recruited for the study and were divided into two groups: (a) ten patients who received SIMT and (b) ten patients who received sham training, for three months. Pulmonary functions, the respiratory muscle strength and endurance, the perception of dyspnea (POD) and the quality of life were studied before and within one week after the training period. All subjects trained daily, six times a week, each session consisting of 1/2 hour, for 12 weeks. RESULTS Following the training period, there was a significant improvement, in the training group but not in the control group, in the following parameters: inspiratory muscle strength, (PImax, increased from 62.0 +/- 8.2 to 78.0 +/- 7.5 cm of H2O (p < 0.05), inspiratory muscle endurance (increased from 20.0 +/- 2.8 to 29.0 +/- 3.0 cm of H2O (p < 0.05), and the POD (decreased from 17.9 +/- 3.2 to 14.0 +/- 2.4 units (p < 0.05). There was a close correlation between the increase in the inspiratory muscle performance and the decrease in the POD. CONCLUSIONS The inspiratory muscle performance may be improved by SIMT in patients with PD. This improvement is associated with a significant decrease in their POD.

Respiratory Muscle Performance and the Perception of Dyspnea in Parkinson's Disease

BACKGROUND Pulmonary and respiratory muscle function impairment are common in patients with Parkinsons disease (PD). However, dyspnea is not a frequent complaint among these patients, although it is well documented that the intensity of dyspnea is related to the activity and the strength of the respiratory muscles. PATIENTS AND METHODS We studied pulmonary function, respiratory muscle strength and endurance and the perception of dyspnea (POD) in 20 patients with PD (stage II and III Hoehn and Yahr scale) before and after their first daily L-dopa dose. Respiratory muscle strength was assessed by measuring the maximal inspiratory and expiratory mouth pressures (PImax and PEmax), at residual volume (RV) and total lung capacity (TLC) respectively. The POD was measured while the subject breathed against progressive load and dyspnea was rated using a visual analog scale. RESULTS Respiratory muscle strength and endurance were decreased and the POD was increased during the off medication period compared to normal subjects. There was a nonsignificant trend to an increase in Plmax, PEmax and endurance after L-dopa intake. The POD of PD patients decreased (p<0.05) following medication, although, it remained increased (p<0.01) as compared to the normal subjects. Even if patients had spirometry data showing a mild restrictive pattern, before medication, both forced vital capacity (FVC) and forced expiratory volume (FEV)1 remained almost identical after L-dopa intake. CONCLUSIONS Patients with PD have higher POD, compared to normal subjects and this increased perception is attenuated when the patients are on dopaminergic medication. The change in the POD is not related to changes in respiratory muscle performance or pulmonary functions. A central effect or a correction of uncoordinated respiratory movements by L-dopa may contribute to the decrease in POD following L-dopa treatment.

Clinical features of oculopharyngeal muscular dystrophy among Bukhara Jews

Oculopharyngeal muscular dystrophy (OPMD), a late onset autosomal dominant myopathy, is common among the French-Canadians and the Jews from Bukhara (Uzbekistan); most clinical histologic and genetic data published until now, as well as the recently suggested diagnostic criteria, are based on studies among the former. We studied 79 patients with OPMD belonging to the newly described Jewish-Bukhara cluster. The disease began between the ages of 21 and 78 yr (median 53 yr). In 11 patients (15%) it began before the age of 40. Ptosis was the first symptom in 59 patients and dysphagia in the remaining 20. Eight patients (10%) were monosymptomatic (ptosis) after more than 7 yr from the start of the disease; however, other family members had additional signs/symptoms. The patients belong to 29 families; in 26 age-dependent autosomal dominant inheritance could be documented. Among them there is certain evidence for genetic anticipation. This clinical study is the largest published concerning patients other than French-Canadians.