Arianna Guidubaldi

Botulinum toxin A versus B in sialorrhea: A prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson's disease†

Background: Either botulinum toxins (BoNTs) A and B have been used for improving drooling in different neurological conditions. Methods: Consecutive patients affected by Amyotrophic Lateral Sclerosis (ALS) or Parkinsons Disease (PD) accompanied by severe drooling were randomized to receive botulinum neurotoxin type A (BoNT‐A) or B (BoNT‐B) injections into the salivary glands. Following the first treatment, when sialorrhea returned to baseline (at least three months after the first injection), subjects were re‐treated with the other serotype. Ultrasound‐guided injections into parotid and submandibular glands were bilaterally performed: total doses were 250 U BoNT‐A (Dysport) and 2500 U BoNT‐B (Neurobloc). Objective (cotton roll weight) and subjective (ad hoc clinical scales) evaluations were performed at baseline, after 1 and 4 weeks, and every 4 weeks until drooling returned to baseline. Results: Twenty‐seven patients (15 ALS and 12 PD) were enrolled, fourteen completed the study. BoNT‐A and BoNT‐B treatments gave both subjective and objective improvements in all patients. The latency was significantly shorter after BoNT‐B treatments (3.2 ± 3.7 days) compared to BoNT‐A (6.6 ± 4.1 days; P = 0.002). The mean benefit duration was similar at 75 and 90 days for BoNT‐A and BoNT‐B, respectively (P = NS). The only toxin‐related side effect was a change to saliva thickness. Conclusions: Either 250 U Dysport or 2500 U Neurobloc have similar effectiveness and safety in controlling sialorrhea. BoNT‐B has a shorter latency and comparable duration. Cost analysis, considering the doses used in this study protocol favored BoNT‐B treatment.

The long-term effect of tetrabenazine in the management of Huntington disease

Objectives: To enhance the knowledge on the long-term efficacy and safety of tetrabenazine (TBZ) in managing chorea. Methods: We analyzed 68 Huntington disease patients (mean disease duration, 55.8 ± 34.7 months) who had been treated with TBZ for a mean period of 34.4 ± 25.2 months (median, 34 months; mode, 48 months; range, 3-104 months). We measured the variation from pretreatment of the motor score of Unified Huntingtons Disease Rating Scale at the first follow-up visit and at the latest. Results: Mean Unified Huntingtons Disease Rating Scale-chorea underscore at the time of the pretreatment visit was 10.4 ± 4.1 (range, 0-28). At the first follow-up, 9.7 ± 7.8 months after the prescription of TBZ (mean dose, 35.3 ± 14.7 mg), mean score of chorea was 8.2 ± 4.1 (−21% compared with baseline), whereas at the latest follow-up visit (mean dose, 57.5 ± 14.7 mg), it was 9.5 ± 5.0 (9%). During the follow-up, the clinical benefit persisted, but the magnitude was reduced despite a progressive increase of the doses (up to 60%). Motor improvement was not influenced by sex, or doses or duration of therapy; age at onset was the only predictor of a good outcome. Five patients (7%) did not gain any improvement, and TBZ was discontinued. There were 2 withdrawals because of side effects; 34 patients reported at least 1 side effect. Conclusions: Tetrabenazine was well tolerated and produced long-term improvement of motor symptoms in Huntington disease patients, although a slight reduction of benefit occurred during the course of treatment. Abbreviations: HD, Huntington disease, TBZ, tetrabenazine

Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa responsive parkinsonism

Background: Autosomal recessive hereditary spastic paraplegia with thin corpus callosum is a neurodegenerative disorder characterized by spastic paraparesis, cognitive impairment, and peripheral neuropathy. The neuroradiologic hallmarks are thin corpus callosum and periventricular white matter changes. Mutations in the SPG11 gene have been identified to be a major cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and recently also proven to be responsible for juvenile parkinsonism associated with spastic paraplegia.

Tremor in primary adult-onset dystonia: prevalence and associated clinical features

Objective To investigate the frequency and the main clinical features of tremor in primary adult-onset dystonia (PAOD). Methods This cross-sectional study was conducted on 429 patients with PAOD from eight Italian movement disorder centres. Results Of the 429 dystonic patients, 72 (16.7%) had tremor. Although sex and age at dystonia onset were similar in dystonic patients who had tremor and those who did not, patients who had tremor were affected more often by focal cervical dystonia and less often by focal blepharospasm. Dystonia had a greater tendency to spread in patients with tremor. According to the Movement Disorder Society Consensus Statement, tremor was classified as dystonic tremor (DT) in 43 patients and tremor associated with dystonia (TAWD) in 23 patients. Six patients had both types of tremor. Taking into account potential confounding by age at onset and body distribution of the corresponding dystonia type, all the clinical features in patients with DT and in those with TAWD were comparable except the tendency of dystonia to spread, which was greater in patients with DT. Conclusions Tremor is a relatively common feature occurring in about 17% of patients with primary late-onset dystonia. The association between tremor and dystonia spread suggests that this form of tremor may be a dystonic manifestation. Similarities in phenotypic features of DT and TAWD predominated over differences, suggesting that the two forms of tremor may be manifestations of the same disease. Differences in gender and body distribution of tremor between patients with dystonia and tremor and those of patients with essential tremor also suggest that tremor in dystonia and essential tremor are different entities.

Punding and computer addiction in Parkinson's disease

Punding is a stereotypical behavior in which there is an intense fascination with repetitive handling and examining of mechanical objects, such as taking apart watches and radios or arranging common objects (lining up pebbles, rocks, or other small objects). This disabling condition, different from both obsessive–compulsive disorder and mania, is probably underreported. Punding is thought to be related to dopaminergic stimulation, although only a few observations of this condition in patients with Parkinsons disease (PD) under therapy has been reported. We report a man with PD who developed an unusual, severe, repetitive behavior characterized by spending most of his time on his computer; this abnormal behavior was concomitant with the introduction of L‐dopa (400 mg per day) and was not associated to a pattern of chronic inappropriate overuse of dopaminergic medication or other psychiatric symptoms. The patient had the feeling he was forced into a disruptive and unproductive behavior, and he made several attempts to quit without succeeding.

Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a 123I-FP-CIT SPECT study.

PurposePsychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of 123I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson’s disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity.MethodsEnrolled in the study were 21 patients with Parkinson’s disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific 123I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects.ResultsAs expected, DAT availability was significantly decreased in patients with Parkinson’s disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson’s disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = −0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = −0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = −0.71, p = 0.004, and r = −0.75, p = 0.002, respectively). There were no correlations between psychometric scores and 123I-FP-CIT uptake ratios in healthy subjects.ConclusionWe found association between presynaptic dopaminergic function and affective symptoms in different movement disorders. Interestingly, the inverse correlation was present in each group of patients, supporting the fascinating perspective that common subcortical substrates may be involved in both anxiety and depression dimensions and movement disorders.

Olfactory dysfunction in Parkinsonism caused by PINK1 mutations

Hyposmia is a common nonmotor feature of Parkinsons disease (PD) and has been variably detected in monogenic Parkinsonisms. To assess olfactory dysfunction in PINK1‐related Parkinsonism, we evaluated olfactory detection threshold, odor discrimination, and odor identification in five groups of subjects: sporadic PD (n = 19), PINK1 homozygous (n = 7), and heterozygous (n = 6) parkinsonian patients, asymptomatic PINK1 heterozygous carriers (n = 12), and Italian healthy subjects (n = 67). All affected subjects and all healthy heterozygotes but one resulted hyposmic, with most patients in the range of functional anosmia or severe hyposmia. Detection threshold was more preserved and discrimination more impaired in patients with PINK1 mutations than in PD cases. Alterations of detection and discrimination were observed also in PINK1 asymptomatic heterozygotes. On the contrary, odor identification appeared to be mostly related to the disease status, as it was impaired in nearly all patients (including PD and PINK1 cases) and preserved in healthy heterozygotes. Our data indicate that olfactory dysfunction is common in PINK1 Parkinsonism and consists typically in defective odor identification and discrimination. A milder olfactory deficit, mostly involving discrimination, can be found in asymptomatic heterozygotes, possibly indicating an underlying preclinical neurodegenerative process.

Phenotypic Variability of PINK1 Expression: 12 Years' Clinical Follow-up of Two Italian Families

Mutations in the PINK1 gene are the second most frequent cause of autosomal recessive early‐onset parkinsonism.

Age at onset and symptom spread in primary adult-onset blepharospasm and cervical dystonia

The site of dystonia onset is known to affect the risk of spread in primary adult‐onset focal dystonia, but other factors possibly influencing spread are unknown. This study explored the relationship between age and spread of dystonia in primary adult‐onset focal dystonia.

Lower limb involvement in adult-onset primary dystonia: frequency and clinical features.

Background and purpose:  Despite the growing number of reports describing adult‐onset primary lower limb dystonia (LLD) this entity has never been systematically evaluated in the general population of patients with primary adult‐onset dystonia.