Long-Term Abobotulinumtoxin A Treatment of Cervical Dystonia.

Botulinum toxin is considered as first-line therapy for cervical dystonia, but few papers have addressed these issues in the long term. Aim of this study was to investigate the long-term efficacy and safety of abobotulinumtoxin A (A/Abo) in patients with primary cervical dystonia. Consecutive patients who received at least six injections with A/Abo were included. Safety was assessed on patients' self-reports. Efficacy was assessed by recording the total duration of benefit, duration of maximum efficacy, disease severity measured by means of the Tsui score, and pain intensity evaluated by means of the visual analog scale (VAS). Thirty-nine patients with PCD were included. The mean dose injected was 701.5 ± 280.6 U. The mean duration of the clinical improvement was 93.0 ± 30.7 days, while the mean duration of the maximum clinical improvement was 77.1 ± 27.1 days. The mean VAS before and 4 weeks after injection was 4.4 ± 1.8 and 1.8 ± 1.6, respectively. The mean Tsui score before and 4 weeks after treatment was 5.7 ± 1.8 and 3.5 ± 1.5, respectively. Doses of A/Abo and duration of the maximum clinical improvement significantly increased over time, while the Tsui score and VAS displayed a tendency to decrease along time. Side effects occurred in 19.6% of all the treatments but were severe in only four injections. The results of our study confirm the effectiveness and safety profile of A/Abo for the long-term treatment of primary cervical dystonia.

Fifteen-year experience in treating blepharospasm with Botox or Dysport: same toxin, two drugs.

OBJECTIVES: To compare the clinical characteristics and the long-term outcome of a large series of patients with blepharospasm (BS) treated with the two most used brands of BoNT-A over the last 15 years. METHODS: We have reviewed the clinical charts of 128 patients with BS who received botulinum neurotoxin (BoNT) in 1341 treatments (Botox in 1009, Dysport in 332) over the last 15 years. RESULTS: Mean dose per session was 34U +/- 15 for Botox and 152U +/- 54 for Dysport. Mean latency of clinical effect was 4.5 +/- 4.6 days for Botox and 5.0 +/- 5.7 days for Dysport (P > 0.05). Mean duration of clinical improvement was higher for Dysport than Botox: 80.1 +/- 36.3 and 66.2 +/- 39.8 days, respectively (P < 0.01). In a six-point scale (0: no efficacy, 6: remission of BS), the mean efficacy of both treatments was 3.60 +/- 1.3; 3.51 +/- 1.4 (Botox) and 3.85 +/- 1.2 (Dysport), P < 0.01. The doses of Botox (beta = 0.40) and Dysport (beta = 0.16) were significantly increased over time. Side effects occurred in 325 out of 1341 treatments (24.2%): 21.8% of the patients who had received Botox, and in 31.6% of those who had received Dysport (P < 0.01). CONCLUSIONS: Both brands are effective and safe in treating blepharospasm; efficacy is long lasting. The differences in outcome and side effects suggest that, albeit the active drug is the same, Botox and Dysport should be considered as two different drugs.

Outcome predictors, efficacy and safety of Botox and Dysport in the long-term treatment of hemifacial spasm.

BACKGROUND AND PURPOSE: To review the clinical characteristics and the long-term outcome of patients with hemifacial spasm (HFS) who received botulinum neurotoxin (BoNT) over the past 10 years. RESULTS: A total of 108 patients received 665 treatments. Mean latency of clinical effect was 5.4 +/- 5.3 days for Botox and 4.9 +/- 4.6 days for Dysport (P > 0.05). Mean duration of clinical improvement was higher after the injection of Dysport than Botox: 105.9 +/- 54.2 and 85.4 +/- 41.6 days respectively (P < 0.01). The percentage of treatment failures was 6.5% for Botox and 4.6% for Dysport (P > 0.05). The doses of Botox significantly increased over time (beta = 0.35, P < 0. 001) whilst Dysport dose remained unchanged (beta = 0.16, n.s.). The duration of clinical benefit slightly increased with Botox (beta = 0.12; P < 0.01), but remained constant for Dysport. Side effects occurred in 17.4% of treatments: 16.7% of patients who had received Botox, and in 19.7% who had received Dysport (P > 0.05). The most common side effects were palpebral ptosis and lacrimation; ptosis and lagophtalmos was more common in Dysport treatments (P < 0.005). CONCLUSIONS: Both brands are effective and safe in treating HFS; efficacy is long-lasting. The differences in outcome and side effects confirm that, albeit the active drug is the same, Botox and Dysport should be considered as two different drugs.

Onset and progression of primary torsion dystonia in sporadic and familial cases.

Four hundred and sixty records of patients with primary torsion dystonia (296 women and 164 men) were evaluated. The mean age at disease onset was 48.3 +/- 17.7 years; 13 patients carried the DYT1 CAG deletion. The distribution of age at onset was represented by a bi-modal curve, with a nadir at 21 year separating early onset from late onset cases. In 15.9% of cases there was a positive family history of dystonia. Cranial, cervical or lower limb onset was more common amongst women (M:F ratios were 1:2.7, 1:1.9, and 1:3); by contrast, onset in the upper limb was more common in men (M:F ratio 2.2:1). As expected, disease progression was more pronounced in cases with early onset; it was reckoned that onset at or above 32 years was associated with a negligible likelihood to progress to a generalized form. The mean age at onset of familial cases was 44.8 +/- 11.2 years, significantly lower than the mean age at onset of sporadic cases (53.5 +/- 13.4 years). Familial cases were characterized by more sites involved throughout disease course. Familial cases had a higher tendency to progress to a segmental or generalized form than sporadic cases.

Phenotypic characterisation of autosomal recessive PARK6-linked parkinsonism in three unrelated Italian families.

The clinical features of nine patients (three women and six men) affected by PARK6-linked parkinsonism, belonging to three unrelated Italian families, are reported. The occurrence of affected men and women within one generation suggested an autosomal recessive mode of inheritance in all three families. Mean age at disease onset was 36 +/- 4.6 years; all cases except one presented with asymmetrical signs, consisting of tremor and akinesia of one upper limb or unilateral short step gait. Affected individuals had a mean age of 57 +/- 8.5 years, and average disease duration was 21 +/- 7.8 years. Parkinsonian features included benign course, early onset of drug-induced dyskinesias, and a good and persistent response to levodopa. There were no other associated features (i.e., pyramidal or cerebellar signs, dysautonomia, or diurnal fluctuations unrelated to drug treatment). Cognition was unaffected. The clinical picture was remarkably similar in all patients; no relevant family-related differences were found. PARK6 disease is a new form of early-onset parkinsonism without other atypical clinical features.

Identification of a novel primary torsion dystonia locus (DYT13) on chromosome 1p36 in an Italian family with cranial-cervical or upper limb onset.

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous group of movement disorders, usually inherited in an autosomal dominant fashion. Three PTD loci (DYT1, DYT6 and DYT7) have been identified to date. However, in several PTD families linkage to the known loci has been excluded. We identified an Italian PTD family with 11 definitely affected members. Phenotype was characterised by juvenile or early-adult onset, prominent cranial-cervical and upper limb involvement, mild course and occasional generalisation. A genome-wide search performed in the family identified a novel PTD locus (DYT13) within a 22-cM interval on the short arm of chromosome 1, with a maximum lod score of 3.44 (theta = 0) between the disease and marker D1S2667.

DYT13, a novel primary torsion dystonia locus, maps to chromosome 1p36.13--36.32 in an Italian family with cranial-cervical or upper limb onset.

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous group of movement disorders, usually inherited in an autosomal dominant fashion with reduced penetrance. The DYT1 gene on chromosome 9q34 is responsible for most cases of early limb-onset PTD. Two other PTD loci have been mapped to date. The DYT6 locus on chromosome 8 is associated with a mixed phenotype, whereas the DYT7 locus on chromosome 18p is associated with adult onset focal cervical dystonia Several families have been described in which linkage to the known PTD loci have been excluded. We identified a large Italian PTD family with 11 definitely affected members. Phenotype was characterized by prominent cranial-cervical and upper limb involvement and mild severity. A genome-wide search was performed in the family. Linkage analysis and haplotype construction allowed us to identify a novel PTD locus (DYT13) within a 22 cM interval on the short arm of chromosome 1, with a maximum lod score of 3.44 between the disease and marker D1S2667.

Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36.

The cause of Parkinson disease (PD) is still unknown, but genetic factors have recently been implicated in the etiology of the disease. So far, four loci responsible for autosomal dominant PD have been identified. Autosomal recessive juvenile parkinsonism (ARJP) is a clinically and genetically distinct entity; typical PD features are associated with early onset, sustained response to levodopa, and early occurrence of levodopa-induced dyskinesias, which are often severe. To date, only one ARJP gene, Parkin, has been identified, and multiple mutations have been detected both in families with autosomal recessive parkinsonism and in sporadic cases. The Parkin-associated phenotype is broad, and some cases are indistinguishable from idiopathic PD. In > or = 50% of families with ARJP that have been analyzed, no mutations could be detected in the Parkin gene. We identified a large Sicilian family with four definitely affected members (the Marsala kindred). The phenotype was characterized by early-onset (range 32-48 years) parkinsonism, with slow progression and sustained response to levodopa. Linkage of the disease to the Parkin gene was excluded. A genomewide homozygosity screen was performed in the family. Linkage analysis and haplotype construction allowed identification of a single region of homozygosity shared by all the affected members, spanning 12.5 cM on the short arm of chromosome 1. This region contains a novel locus for autosomal recessive early-onset parkinsonism, PARK6. A maximum LOD score 4.01 at recombination fraction .00 was obtained for marker D1S199.