Hsin Fen Chien

ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease

Objective: To assess the prevalence, nature, and associated phenotypes of ATP13A2 gene mutations among patients with juvenile parkinsonism (onset <21 years) or young onset (between 21 and 40 years) Parkinson disease (YOPD). Methods: We studied 46 patients, mostly from Italy or Brazil, including 11 with juvenile parkinsonism and 35 with YOPD. Thirty-three cases were sporadic and 13 had positive family history compatible with autosomal recessive inheritance. Forty-two had only parkinsonian signs, while four (all juvenile-onset) had multisystemic involvement. The whole ATP13A2 coding region (29 exons) and exon-intron boundaries were sequenced from genomic DNA. Results: A novel homozygous missense mutation (Gly504Arg) was identified in one sporadic case from Brazil with juvenile parkinsonism. This patient had symptoms onset at age 12, levodopa-responsive severe akinetic-rigid parkinsonism, levodopa-induced motor fluctuations and dyskinesias, severe visual hallucinations, and supranuclear vertical gaze paresis, but no pyramidal deficit nor dementia. Brain CT scan showed moderate diffuse atrophy. Furthermore, two Italian cases with YOPD without atypical features carried a novel missense mutation (Thr12Met, Gly533Arg) in single heterozygous state. Conclusions: We confirm that ATP13A2 homozygous mutations are associated with human parkinsonism, and expand the associated genotypic and clinical spectrum, by describing a homozygous missense mutation in this gene in a patient with a phenotype milder than that initially associated with ATP13A2 mutations (Kufor-Rakeb syndrome). Our data also suggest that ATP13A2 single heterozygous mutations might be etiologically relevant for patients with YOPD and further studies of this gene in Parkinson disease are warranted.

The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson’s disease and originates from a common ancestor

Background: Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2) were recently identified as the cause of PARK8 linked autosomal dominant Parkinson’s disease. Objective: To study recurrent LRRK2 mutations in a large sample of patients from Italy, including early (<50 years) and late onset familial and sporadic Parkinson’s disease. Results: Among 629 probands, 13 (2.1%) were heterozygous carriers of the G2019S mutation. The mutation frequency was higher among familial (5.1%, 9/177) than among sporadic probands (0.9%, 4/452) (p<0.002), and highest among probands with one affected parent (8.7%, 6/69) (p<0.001). There was no difference in the frequency of the G2019S mutation in probands with early v late onset disease. Among 600 probands, one heterozygous R1441C but no R1441G or Y1699C mutations were detected. None of the four mutations was found in Italian controls. Haplotype analysis in families from five countries suggested that the G2019S mutation originated from a single ancient founder. The G2019S mutation was associated with the classical Parkinson’s disease phenotype and a broad range of onset age (34 to 73 years). Conclusions: G2019S is the most common genetic determinant of Parkinson’s disease identified so far. It is especially frequent among cases with familial Parkinson’s disease of both early and late onset, but less common among sporadic cases. These findings have important implications for diagnosis and genetic counselling in Parkinson’s disease.

Neurological manifestations in Wilson's disease: Report of 119 cases

We describe the neurological manifestations of 119 patients with WD (93 index cases and 26 affected family members) seen between 1963 and 2004. The mean age at symptoms onset was 19.6 years (range, 7–37 years). Medical records were reviewed for the patients first neurological examination. The most frequent neurological manifestations observed were dysarthria (91%), gait disturbance (75%), risus sardonicus (72%), dystonia (69%), rigidity (66%), tremor (60%), and dysphagia (50%). Less frequent manifestations were chorea (16%) and athetosis (14%). Rare neurological presentations were seizures (4.2%), and pyramidal signs (3%).

DNAJC6 Mutations Associated with Early-Onset Parkinson's Disease

DNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age < 11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair‐bound within ∼10 years from onset). Here, for the first time, we report DNAJC6 mutations in early‐onset Parkinsons disease (PD).

Botulinum toxin a in the treatment of blepharospasm: a 10-year experience.

To evaluate the long-term effect of botulinum toxin type A (BTX) in the treatment of blepharospasm, a retrospective analysis was conducted from the patients seen at the Movement Disorders Clinic of the Department of Neurology, Hospital das Clínicas, University of São Paulo School of Medicine from 1993 to 2003. A total of 379 treatments with BTX were administered to 30 patients with blepharospasm. Sixty six per cent of the subjects had used oral medication for dystonia and only 15% of them reported satisfactory response to this treatment. Ninety three per cent of the patients showed significant improvement after the first BTX injection. There was no decrement in response when compared the first and the last injection recorded. Adverse effects, mostly minor, developed at least once in 53% of patients. Six patients (20%) discontinued the treatment but there was no case of secondary resistance.

Botulinum toxin type A in the treatment of hemifacial spasm: an 11-year experience

In order to evaluate the long-term effect of botulinum toxin type A (BTX) in the treatment of hemifacial spasm (HFS), a retrospective analysis of patients treated at the Movement Disorders Unit of the Division of Neurology, Clinical Hospital, University of São Paulo, School of Medicine from 1993 to 2004 was made. A total of 808 injections with BTX were administered to 54 patients with HFS. The mean duration of improvement per application was 3.46 months and the mean rate of improvement using subjective judgement by the patient was of 83%. Adverse effects, mostly minor, were observed in 64.8% of patients at least once along the period of follow-up and the most frequent of them was orbicularis oris paralysis (38.8%). There was no decrement in response when compared the first and the last injection recorded.

Clinical changes of cervical dystonia pattern in long-term botulinum toxin treated patients.

Cervical dystonia (CD) is a complex disorder but the response to long-term botulinum toxin (BTX) therapy is satisfactory in most cases. Bad results are attributed by some authors to changes in muscle activation. Our purpose is to verify if the change in head deviation affects negatively the response to BTX therapy in a long-term follow-up, and if there are any differences in clinical parameters of these patients in comparison to those with stable pattern. From a total of 88 patients evaluated at the Movement Disorders Clinics of Hospital das Clinicas - University of São Paulo School of Medicine between January 1993 and December 2005, 67 were included. In 24 (35.8%) change in pattern of CD was observed, in a medium follow-up period of 80 months. The time between onset of dystonia and the diagnosis of pattern change was 9.7 years. Comparing with patients with no changes in CD pattern, there were no significant statistical differences. Improvement of symptoms around 60% was reported in both groups. In conclusion, the change in head deviation observed in CD was not responsible for bad response to therapy with BTX and there were no significant differences between both groups.

Influence of Educational Status on Executive Function and Functional Balance in Individuals with Parkinson Disease

Objective:This study investigated whether educational status influenced how people with Parkinson disease (PD) performed on Parts A, B, and DELTA of the Trail Making Test (TMT) and on the Berg Balance Scale (BBS). Background:Recent studies have shown that educational status may influence cognitive and motor test performance. Methods:We gave the TMT and the BBS to assess executive function and functional balance in 28 people with PD (Hoehn and Yahr score between 2 and 3) and 30 healthy elderly people. Participants reported their number of years of formal education. We divided each group of participants by educational status: low (4 to 10 years of education) or high (≥11 years). Results:In both the PD (P=0.018) and control (P=0.003) groups, participants with low educational status performed worse on the TMT Part B than did those with high educational status. Within the PD group, the less-educated participants scored worse on the BBS than did the more educated (P<0.001); this difference was not significant between the more- and less-educated controls (P=0.976). Conclusions:Whether or not they had PD, less-educated people performed worse than more-educated people on the TMT Part B. Educational status affected executive function, but PD status did not. Among individuals with PD, educational status influenced functional balance.

Paroxysmal exercise-induced dystonia within the phenotypic spectrum of ECHS1 deficiency

ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, ECHS1 mutations were shown to cause a new severe metabolic disorder presenting as Leigh or Leigh‐like syndromes. The objective of this study was to describe a family with 2 siblings affected by different dystonic disorders as a resulting phenotype of ECHS1 mutations.

Síndrome de Gilles de la Tourette: estudo clínico de 58 casos

Gilles de la Tourettes syndrome (GTS) is a neuropsychiatric disorder with a childhood onset and is characterized by motor and vocal tics. Fifty-eight patients with GTS were evaluated during a period of three years. Thirty-six patients were male and twenty two female, with an age range of 7 to 51 years (mean 20.33 years). The male to female ratio was 1.6:1. The age of onset ranged from 3 to 15 years (mean 7.81 years). Seventy nine percent of the patients presented motor tics as the initial symptom of the disease. In terms of complex tics, coprolalia was present in 27.6% of the patients; copropraxia in 20.1%; palilalia in 20.1%; ecolalia in 27.6%; and ecopraxia in 27,6%. Associated manifestations, such as attention deficit, hyperactivity disorder and obsessive-compulsive disorder were present in 25.8% and 39.6%, respectively. Sensory phenomena were present in 54.8% of the patients.