Trials of GDNF in Parkinson’s disease have yielded inconsistent results. In a randomised controlled trial, Whone et al. administer GDNF using a paradigm designed to optimize delivery to the putamen. [ 18 F]DOPA PET reveals putamen-wide uptake, but GDNF does not differ from placebo in its effects on motor function.

Background: Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson's disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [ 18 F]DOPA uptake throughout the entire putamen. Objective: This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks. Methods: Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo). The primary outcome was the percentage change from baseline to Week 80 in the OFF state Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Results: All 41 parent study participants were enrolled. The primary outcome decreased by 26.7 ± 20.7% in patients on GDNF for 80 weeks (GDNF/GDNF; N = 21) and 27.6 ± 23.6% in patients on placebo for 40 weeks followed by GDNF for 40 weeks (placebo/GDNF, N = 20; least squares mean difference: 0.4%, 95% CI:-13.9, 14.6, p = 0.96). Secondary endpoints did not show significant differences between the groups at Week 80 either. Prespecified comparisons between GDNF/GDNF at Week

Objective Evaluate the relationship between falls, freezing of gait, and swallowing disturbance in Parkinson’s disease (PD). Background Dysphagia is a common symptom in PD, and is often thought of as an axial feature along with falls and gait disturbance. It is of interest to examine the relationship between these symptoms in PD, given the possibility of shared pathophysiology due to non-dopaminergic and extranigral dysfunction. Methods We recruited 29 consecutive non-demented patients with idiopathic PD and at least one clinically determined impairment in swallowing, falls, or freezing of gait. Swallow dysfunction was assessed using the Swallowing Disturbance Questionnaire (SDQ). The Falls Efficacy Scale and Freezing-of-gait questionnaire were recorded. Correlation analysis and multiple regression were used to determine the relationship between swallow and gait disturbance. Results Total SDQ score correlated strongly with the falls efficacy scale (Spearman’s rho = 0.594; P = 0.001), but not with the freezing-of-gait score. Linear regression controlling for other factors associated with dysphagia identified falls efficacy score as a significant predictor of swallow dysfunction. Conclusions The severity of dysphagia in PD is closely related to severity of falls, but not gait freezing. This may be helpful to more precisely determine the anatomical substrate of levodopa-resistant axial symptoms in PD and provide clues to further management.

No abstract

A previously well 16-year-old boy developed a rapid-onset hypokinetic syndrome, coupled with a radiological appearance of extensive and highly symmetrical basal ganglia and white matter change. The diagnostic process was challenging and we systematically considered potential causes. After excluding common causes of this clinico-radiological picture, we considered common disorders with this unusual radiological picture and vice versa, before finally concluding that this was a rare presentation of a rare disease. We considered the broad categories of: metabolic; toxic; infective; inflammatory, postinfective and immune-mediated; neoplastic; paraneoplastic and heredodegenerative. Long-term follow-up gave insight into the nature of the insult, confirming the monophasic course. During recovery, and following presumed secondary aberrant reinnervation, his disorder evolved from predominantly hypokinetic to hyperkinetic. Here, we explore the process of finding a 'best-fit' diagnosis: in this case, acute necrotising encephalopathy.

No abstract

No abstract

We read with interest the report by Poisson and colleagues, concluding that rest tremor in classical galactosemia may be linked to dopaminergic denervation. 1 The authors describe a galactosemia patient who in his mid-50s was found to have a parkinsonian phenotype and a striatal reduction in 123 I-FP-CIT DAT uptake. 1 Based on our own "new observation," reported below, we concur that striatal dopaminergic denervation may indeed be present in the late-onset tremor seen in galactosemia, although in our case the tremor was of the more typical postural and kinetic type than the predominantly rest tremor described by Poisson. 1,2 A 40-year old right-handed woman was referred to our center for consideration of deep brain stimulation for treatment of tremor that had reached a severity rendering her no longer able to feed, wash, or dress herself. Tremor of the head and tongue was causing progressive swallowing difficulties. She had been born after a normal pregnancy from nonconsanguineous parents and was diagnosed with classical galactosemia at 10 days of age after staphylococcal septicemia. Despite dietary restriction, she exhibited psychomotor developmental delay and ovarian failure. Since the age of 30 she had suffered progressively worsening dystonia and tremor. In addition to generalized dystonic posturing, clinical examination revealed a severe, low-frequency, wideamplitude, flexion-extension, asymmetric, rest, postural, and kinetic tremor involving the upper more than the lower limbs. The limb tremor involved both the proximal and the distal segments and had an added element of intention tremor. The head tremor disappeared with full head support. There was a mild degree of rigidity in both upper limbs but no bradykinesia.Given that the tremor phenomenologically most resembled Holmes tremor, for which L-dopa is known to be partially effective, 3 a trial of dispersible L-dopa 1 benserazide was initiated. Immediate benefit was observed even on low starting doses (L-dopa 150 mg per day), with complete resolution of the head and tongue tremor and 75% improvement of limb action tremor on L-dopa 450 mg per day. After 3 months, the patient developed wearing-off phenomena with breakthrough tremor at the end of each dosing period, necessitating an additional fourth dose. On one occasion when she attended clinic, her latest L-dopa dose had not yet kicked in, and she was exhibiting the same severe postural and kinetic tremor. Thirty minutes later as she switched "on," she demonstrated brief oromandibular dystonia, following which her head tremor entirely resolved and the limb tremor was markedly improved (see video).It is worth noting that although the case presented by Poisson showed evidence of presynaptic dopaminergic degeneration, indicating nigrostriatal dysfunction, they saw only a minimal response to L-dopa. 1 However, our patient with a tremor phenotype more suggestive of Holmes tremor 3 is likely to have involvement of the cerebellothalamocortical and/or dentaterubro-olivary pathways as well as the nigrostriatal trac...