Objective: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism. Methods: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1 coding region was sequenced from genomic DNA; cDNA was analyzed in selected cases. Results: Homozygous pathogenic mutations were identified in 4 of 90 Italian sporadic cases, including the novel Gln456Stop mutation; single heterozygous truncating or missense mutations were found in another 4 Italian sporadic cases, including two novel mutations, Pro196Leu and Gln456Stop. Pathogenic mutations were not identified in the familial cases. Novel (Gln115Leu) and known polymorphisms were identified with similar frequency in cases and controls. In cases carrying single heterozygous mutation, cDNA analysis detected no additional mutations, and revealed a major pathogenic effect at mRNA level for the mutant C1366T/Gln456Stop allele. All patients with homozygous mutations had very early disease onset, slow progression, and excellent response to l-dopa, including, in some, symmetric onset, dystonia at onset, and sleep benefit, resembling parkin-related disease. Phenotype in patients with single heterozygous mutation was similar, but onset was later. Conclusions: PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. The role of mutations found in single heterozygous state is difficult to interpret. Our study suggests that, at least in some patients, these mutations are disease causing, in combination with additional, still unknown factors.

Introduction. Telerehabilitation enables patients to access remote rehabilitation services for patient-physiotherapist videoconferencing in their own homes. Home-based virtual reality (VR) balance training has been shown to reduce postural instability in patients with Parkinson’s disease (PD). The primary aim was to compare improvements in postural stability after remotely supervised in-home VR balance training and in-clinic sensory integration balance training (SIBT). Methods. In this multicenter study, 76 PD patients (modified Hoehn and Yahr stages 2.5–3) were randomly assigned to receive either in-home VR telerehabilitation (n=38) or in-clinic SIBT (n=38) in 21 sessions of 50 minutes each, 3 days/week for 7 consecutive weeks. VR telerehabilitation consisted of graded exergames using the Nintendo Wii Fit system; SIBT included exercises to improve postural stability. Patients were evaluated before treatment, after treatment, and at 1-month follow-up. Results. Analysis revealed significant between-group differences in improvement on the Berg Balance Scale for the VR telerehabilitation group (p=0.04) and significant Time × Group interactions in the Dynamic Gait Index (p=0.04) for the in-clinic group. Both groups showed differences in all outcome measures over time, except for fall frequency. Cost comparison yielded between-group differences in treatment and equipment costs. Conclusions. VR is a feasible alternative to in-clinic SIBT for reducing postural instability in PD patients having a caregiver.

Patients with Parkinson disease (PD) often complain of painful sensations that may involve body parts affected and unaffected by dystonia.^1-7 Pain in nondystonic body parts may have cramping and arthralgic features, as well as features of peripheral or central neuropathic pain.^1,6 The high frequency of these pain disorders in the general population makes it hard to establish whether pain is more frequent among people with PD than among age-matched controls. Although the 3 pertinent controlled studies (1 published in abstract form alone)^5-7 found a higher frequency of pain among PD patients than among controls, they provided inconclusive results, owing to limitations in study design. Most important, they failed to distinguish between dystonic and nondystonic pain, used as controls a relatively small group of participants with diseases who may not have fully represented the variable of interest in the source population, and did not take into account the time between pain and PD onset.^5,6 Finally, 2 of 3 studies focused on back pain alone.^5,6

Background. Postural instability (PI) is a disabling sign of Parkinson’s disease (PD) not easily amenable to treatment with medication. Objective. To evaluate the effects of balance training on PI in patients with PD. Methods. A total of 64 patients with PI were randomly assigned to the experimental group (n = 33) for balance training or to the control group (n = 31) for general physical exercises. Each patient received 21 treatment sessions of 50 minutes each. Patients were evaluated by a blinded rater before and after treatment as well as 1 month posttreatment using the Berg Balance Scale (BBS), Activities-Specific Balance Confidence Scale (ABC), postural transfer test, self-destabilization of the center of foot pressure test, number of falls, Unified Parkinson’s Disease Rating Scale (UPDRS), modified Hoehn and Yahr (H&Y) Staging Scale, and Geriatric Depression Scale (GDS). Results .At the end of treatment, the experimental group showed significant improvements in all outcome measures, except for the UPDRS and the H&Y scale. Improvement was maintained at the 1-month follow-up in all outcome measures except for the GDS. No significant changes in performance were observed in the control group. Conclusions. A program of balance training can improve PI in patients with PD.

Several observations suggest impaired central sensory integration in dystonia. We studied median and ulnar nerve somatosensory evoked potentials (SEPs) in 10 patients who had dystonia involving at least one upper limb (six had generalized, two had segmental and two had focal dystonia) and in 10 normal subjects. We compared the amplitude of spinal N13, brainstem P14, parietal N20 and P27 and frontal N30 SEPs obtained by stimulating the median and ulnar nerves simultaneously (MU), the amplitude value being obtained from the arithmetic sum of the SEPs elicited by stimulating the same nerves separately (M + U). Throughout the somatosensory system, the MU : (M + U) ratio indicates the interaction between afferent inputs from the two peripheral nerves. No significant difference was found between SEP amplitudes and latencies for individually stimulated median and ulnar nerves in dystonic patients and normal subjects, but recordings in patients yielded a significantly higher percentage ratio [MU : (M + U)×100] for spinal N13 brainstem P14 and cortical N20, P27 and N30 components. The SEP ratio of central components obtained in response to stimulation of the digital nerves of the third and fifth fingers was also higher in patients than in controls but the difference did not reach a significant level. The possible contribution of subliminal activation was ruled out by recording the ratio of SEPs in six normal subjects during voluntary contraction. This voluntary contraction did not change the ratio of SEP suppression. These findings suggest that the inhibitory integration of afferent inputs, mainly proprioceptive inputs, coming from adjacent body parts is abnormal in dystonia. This inefficient integration, which is probably due to altered surrounding inhibition, could give rise to an abnormal motor output and might therefore contribute to the motor impairment present in dystonia.

Aims: To study the association of pain with motor complications in 117 patients with Parkinson’s disease. Methods: Patients were asked to refer any pain they experienced at the time of study and lasting since at least 2 months. Basic parkinsonian signs and motor complications (including motor fluctuations and dyskinesia) were assessed and Unified Parkinson’s Disease Rating Scale (UPDRS) motor score part III (during on) and part IV were calculated. Information on age, sex, duration of disease, use of dopamine agonists and levodopa, years of levodopa treatment and current levodopa dosage, medical conditions possibly associated with pain, and depression were collected. Single and multiple explanatory variable logistic regression models were used to check the association of pain with the investigated variables. Results: Pain was described by 47 patients (40%) and could be classified into dystonic (n.19) and non dystonic pain (n.16); in 12 patients both types coexisted. Multiple explanatory variable logistic regression models indicated a significant association of pain with motor complications (adjusted OR, 5.7; 95% CI, 2 to 16.5; p = 0.001). No association was found between pain, dystonic or non dystonic, and the other investigated variables including medical conditions known to be associated to pain in the general population. There was a significant correlation (r = 0.31, p<0.05) between severity of pain (measured on a Visual Analogue Scale) and severity of motor complications (UPDRS part IV). Conclusions: Pain may be a representative feature of Parkinson’s disease frequently associated with motor complications. The association is independent of a number of potentially relevant demographic and clinical variables.