Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [(18)F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.

We have shown previously that intraparenchymal infusion of glial cell line-derived neurotrophic factor (GDNF) continuously into the posterior putamen in five Parkinson's disease patients is safe and may represent a new treatment option. Here, we report a continuation of this phase I study. After 2 years of continual GDNF infusion, there were no serious clinical side effects and no significant detrimental effects on cognition. Patients showed a 57% and 63% improvement in their off-medication motor and activities of daily living subscores of the Unified Parkinson's Disease Rating Scale, respectively, and health-related quality-of-life measures (Parkinson's Disease Questionnaire-39 and Short Form-36) showed general improvement over time.

The features of this case are set into the context of recent conceptualizations of AN and the clinical implications for identifying individuals with underlying organic causes.

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Purpose -Mild traumatic brain injury (mTBI) is a common occurrence. For most people recovery is quick and complete. For a minority disability persists. This paper aims to discuss the factors that likely give rise to this on-going disability and discuss the current evidence-based approaches to treatment. Design/methodology/approach -A selective review of the contemporaneous research literature was undertaken.Findings -On-going disability following mTBI is likely to be secondary to a combination of factors, namely subtle organic damage, psychological factors and situational/motivational factors. These factors likely operate to different degrees in different individuals and may vary over time in individual cases. Treatment in the form of a multi-disciplinary assessment, accurate sign-posting to appropriate services and cognitivebehavioural psychotherapy is likely to improve outcomes for some with on-going disability following mTBI. Research limitations/implications -Future research should aim to identify at an early stage post-injury those individuals at risk of developing on-going disability following mTBI and the efficacy of different treatment approaches. Practical implications -Earlier identification of individuals not making the expected rapid recovery from mTBI, followed by appropriate multi-disciplinary assessment and intervention would likely improve outcomes for patients at risk of developing on-going disability following mTBI. Originality/value -This paper is of value to healthcare professionals who encounter individuals reporting on-going symptoms and problems following an apparently mild traumatic brain injury.

A prospective, randomised, controlled trial to evaluate the efficacy and safety of endoscopic choroid plexus coagulation with third ventriculostomy in the treatment of idiopathic normal pressure hydrocephalus [ISRCTN29863839]