Approximately 3.6% of patients with Parkinson's disease develop symptoms before age 45. Early-onset Parkinson's disease (EOPD) patients have a higher familial recurrence risk than late-onset patients, and 3 main recessive EOPD genes have been described. We aimed to establish the prevalence of mutations in these genes in a UK cohort and in previous studies. We screened 136 EOPD probands from a high-ascertainment regional and community-based prevalence study for pathogenic mutations in PARK2 (parkin), PINK1, PARK7 (DJ-1), and exon 41 of LRRK2. We also carried out a systematic review, calculating the proportion of cases with pathogenic mutations in previously reported studies. We identified 5 patients with pathogenic PARK2, 1 patient with PINK1, and 1 with LRRK2 mutations. The rate of mutations overall was 5.1%. Mutations were more common in patients with age at onset (AAO) < 40 (9.5%), an affected first-degree relative (6.9%), an affected sibling (28.6%), or parental consanguinity (50%). In our study EOPD mutation carriers were more likely to present with rigidity and dystonia, and 6 of 7 mutation carriers had lower limb symptoms at onset. Our systematic review included information from >5800 unique cases. Overall, the weighted mean proportion of cases with PARK2 (parkin), PINK1, and PARK7 (DJ-1) mutations was 8.6%, 3.7%, and 0.4%, respectively. PINK1 mutations were more common in Asian subjects. The overall frequency of mutations in known EOPD genes was lower than previously estimated. Our study shows an increased likelihood of mutations in patients with lower AAO, family history, or parental consanguinity.

We have seen 32 patients with "apraxia of lid opening" (ALO) in the following clinical settings: as an isolated condition (3 patients), idiopathic blepharospasm (BSP, 20 patients, including 4 familial cases), progressive supranuclear palsy (PSP, 7 patients), and dystonic parkinsonian syndrome (2 patients). Twenty-nine patients treated with botulinum toxin into the orbicularis oculi muscle were rated before and after treatment and 83% of the patients improved on a clinical scale. Best results were obtained with injections directed toward the junction of the preseptal and pretarsal parts of the palpebral orbicularis oculi. Several patients also improved on anticholinergic drugs. Besides medical treatment, lid crutches, in conjunction with botulinum toxin injections, were useful in some patients. ALO is not a true apraxia; it constitutes an eyelid dystonia as shown by its clinical and electrophysiological features as well as pharmacological reactions and is encountered in a clinical spectrum ranging from an isolated form to predominant BSP. It was an important cause of treatment failures in botulinum toxin-treated BSP but by modifying our injection strategy and by adding anticholinergic drugs and also lid crutches, we obtained a good functional benefit.

SUMMARY Twenty-three children (aged less than 18 years) and 17 adults with severe widespread dystonia were treated with high doses of benzhexol (up to 130 mg daily introduced slowly over many weeks). Children tolerated higher doses (median 30 mg/day) than adults (median 20 mg/ day). 52% of the children gained useful benefit, many (43%) without unwanted side effects. Such an approach was less successful in adults; 41% gained benefit, but only 35% had no side effects. Twelve adults with severe axial dystonia, and two children with life-threatening generalised dystonia were treated with a combination of a low constant dose of tetrabenazine to which were added pimozide and benzhexol as necessary. The dose of tetrabenazine was aimed at 75 mg daily; pimozide was increased (6 to 25 mg/day) until the dystonia was relieved or Parkinsonism and other side-effects prevented further increments; if necessary benzhexol (6 to 30 mg/day) then was added to control side-effects and to provide additional benefit.

This study shows that RBD and dementia have a significant coincidence in the course of PD, and RBD not only precedes or coincides with the motor signs, but can occur during the course of the progression of the PD, suggesting a degenerative process of the dopaminergic and cholinergic neurons of the brainstem nuclei, progressing at a different pace in each patient.