Brain structure in movement disorders: a neuroimaging perspective.

Purpose of review: An overview of recent advances in structural neuroimaging and their impact on movement disorders research is presented. Recent findings: Novel developments in computational neuroanatomy and improvements in magnetic resonance image quality have brought further insight into the pathophysiology of movement disorders. Sophisticated automated techniques allow for sensitive and reliable in-vivo differentiation of phenotype/genotype related traits and their interaction even at presymptomatic stages of disease. Summary: Voxel-based morphometry consistently demonstrates well defined patterns of brain structure changes in movement disorders. Advanced stages of idiopathic Parkinson's disease are characterized by grey matter volume decreases in basal ganglia. Depending on the presence of cognitive impairment, volume changes are reported in widespread cortical and limbic areas. Atypical Parkinsonian syndromes still pose a challenge for accurate morphometry-based classification, especially in early stages of disease progression. Essential tremor has been mainly associated with thalamic and cerebellar changes. Studies on preclinical Huntington's disease show progressive loss of tissue in the caudate and cortical thinning related to distinct motor and cognitive phenotypes. Basal ganglia volume in primary dystonia reveals an interaction between genotype and phenotype such that brain structure changes are modulated by the presence of symptoms under the influence of genetic factors. Tics in Tourette's syndrome correlate with brain structure changes in limbic, motor and associative fronto-striato-parietal circuits. Computational neuroanatomy provides useful tools for in-vivo assessment of brain structure in movement disorders, allowing for accurate classification in early clinical stages as well as for monitoring therapy effects and/or disease progression.

Genetics of Parkinson's disease: the yield.

The discovery of genes implicated in familial forms of Parkinson's disease (PD) has provided new insights into the molecular events leading to neurodegeneration. Clinically, patients with genetically determined PD can be difficult to distinguish from those with sporadic PD. Monogenic causes include autosomal dominantly (SNCA, LRRK2, VPS35, EIF4G1) as well as recessively (PARK2, PINK1, DJ-1) inherited mutations. Additional recessive forms of parkinsonism present with atypical signs, including very early disease onset, dystonia, dementia and pyramidal signs. New techniques in the search for phenotype-associated genes (next-generation sequencing, genome-wide association studies) have expanded the spectrum of both monogenic PD and variants that alter risk to develop PD. Examples of risk genes include the two lysosomal enzyme coding genes GBA and SMPD1, which are associated with a 5-fold and 9-fold increased risk of PD, respectively. It is hoped that further knowledge of the genetic makeup of PD will allow designing treatments that alter the course of the disease.

Comparison of C-reactive protein and white blood cell count with differential in neonates at risk for septicaemia.

We prospectively compared the diagnostic value of C-reactive protein (CRP) and white blood cell counts for detection of neonatal septicaemia. Sensitivity and specifity in receiver operating characteristics, and positive and negative predictive value of CRP and white blood cell count were compared in 195 critically ill preterm and term newborns clinically suspected of infection. Blood cultures were positive in 33 cases. During the first 3 days after birth CRP elevation (sensitivity 75%, specifity 86%), leukopenia (67%/90%), neutropenia (78%/80%) and immature to total neutrophil count (I/T) ratio (78%/73%) were good diagnostic parameters, as opposed to band forms with absolute count (84%/66%) or percentage (79%/71%), thrombocytopenia (65%/57%) and toxic granulations (44%/94%). Beyond 3 days of age elevated CRP (88%/87%) was the best parameter. Increased total (84%/66%) or percentage band count (79%/71%) were also useful. Leukocytosis (74%/56%), increased neutrophils (67%/65%), I/T ratio (79%/47%), thrombocytopenia (65%/57%) and toxic granulations had a low specifity. The positive predictive value of CRP was 32% before and 37% after 3 days of age, that of leukopenia was 37% in the first 3 days. CONCLUSION: During the first 3 days of life CRP, leukopenia and neutropenia were comparably good tests while after 3 days of life CRP was the best single test in early detection of neonatal septicaemia. Serial CRP estimations confirm the diagnosis, monitor the course of infection and the efficacy of antibiotic treatment.

Subthalamic nucleus deep brain stimulation for Parkinson's disease : "Are we where we think we are ?

ABSTRACT High frequency electrical deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a worldwide recognized therapy for the motor symptoms of Parkinson's disease in fluctuating patients who are progressively disabled despite medical treatment adjustments. However, such improvements emerge despite a lack of understanding of either the precise role of STN in human motor control or the mechanism(s) of action of DBS. Through the question "are we where we think we are", this thesis is first dedicated to the control of the position of the preoperatively defined target and of the implanted electrodes on magnetic resonance imaging (MRI). This anatomical approach will provide a way to identify more precisely the structure(s) involved by electrical stimulation. Then, a study of the correlation existing between the position of the preoperative target and the position of the electrode is performed. In this part, a unique opportunity is given to identify factors that may affect these correlation results. Finally, the whole work represents a « quality assessment » of the crucial steps of STN DBS: first, the target and the implanted electrode localisation procedures that have been developed in collaboration with the Radiological department; second the implantation procedure that has been performed nowadays on more than 50 parkinsonian patients in the Neurosurgical department of the Centre Hospitalier Universitaire Vaudois in collaboration with the Neurological department. This work is especially addressed to the multidisciplinary medical team involved in the surgical treatment of movement disorders, including also neurophysiologists, neuropsychologists and psychiatrists. RESUME La stimulation électrique à haute fréquence du noyau sous-thalamique est à ce jour mondialement reconnue pour le traitement des symptômes moteurs de la maladie de Parkinson chez des patients sévèrement atteints et chez qui la réponse fluctuante au traitement médicamenteux ne peut être améliorée de façon satisfaisante. Cependant, les résultats observés surviennent malgré une compréhension approximative et controversée du rôle réel du noyau sous-thalamique dans le contrôle du mouvement volontaire aussi bien que des mécanismes d'action de la stimulation cérébrale profonde. A travers la question « sommes-nous où nous pensons être », cette thèse est tout d'abord consacrée à l'étude du contrôle de la position de la cible définie avant l'intervention et de la position des électrodes implantées sur l'imagerie par résonance magnétique (IRM). Cette approche anatomique permettra d'identifier plus précisément la (les) structure(s) influencées par la stimulation électrique. Ensuite, une étude de la corrélation existant entre la position de la cible préopératoire et la position des électrodes implantées est effectuée. Elle a pour but de mettre en évidence les facteurs influençant les résultats de cette corrélation. Enfin, le travail dans son ensemble est un « contrôle de qualité » des étapes cruciales de la stimulation du noyau sous-thalamique : premièrement, des méthodes de localisation de la cible et des électrodes implantées effectuées sur IRM, développées en collaboration avec le service de Radiologie ; deuxièmement, de la méthode d'implantation utilisée à ce jour chez plus de 50 patients dans le service de Neurochirurgie du Centre Hospitalier Universitaire Vaudois en collaboration avec le service de Neurologie. Ce travail s'adresse spécialement aux équipes médicales pluridisciplinaires impliquées dans le traitement chirurgical des mouvements anormaux, incluant également des neurophysiologistes, des neuropsychologues et des psychiatres.

Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson's disease with severe motor fluctuations: a 2-year follow-up review.

OBJECT: The aim of this study was to evaluate the long-term safety and efficacy of bilateral contemporaneous deep brain stimulation (DBS) in patients who have levodopa-responsive parkinsonism with untreatable motor fluctuations. Bilateral pallidotomy carries a high risk of corticobulbar and cognitive dysfunction. Deep brain stimulation offers new alternatives with major advantages such as reversibility of effects, minimal permanent lesions, and adaptability to individual needs, changes in medication, side effects, and evolution of the disease. METHODS: Patients in whom levodopa-responsive parkinsonism with untreatable severe motor fluctuations has been clinically diagnosed underwent bilateral pallidal magnetic resonance image-guided electrode implantation while receiving a local anesthetic. Pre- and postoperative evaluations at 3-month intervals included Unified Parkinson's Disease Rating Scale (UPDRS) scoring, Hoehn and Yahr staging, 24-hour self-assessments, and neuropsychological examinations. Six patients with a mean age of 55 years (mean 42-67 years), a mean duration of disease of 15.5 years (range 12-21 years), a mean "on/off' Hoehn and Yahr stage score of 3/4.2 (range 3-5), and a mean "off' time of 40% (range 20-50%) underwent bilateral contemporaneous pallidal DBS, with a minimum follow-up period lasting 24 months (range 24-30 months). The mean dose of levodopa in these patients could not be changed significantly after the procedure and pergolide was added after 12 months in five patients because of recurring fluctuations despite adjustments in stimulation parameters. All but two patients had no fluctuations until 9 months. Two of the patients reported barely perceptible fluctuations at 12 months and two at 15 months; however, two patients remain without fluctuations at 2 years. The mean improvements in the UPDRS motor score in the off time and the activities of daily living (ADL) score were more than 50%; the mean off time decreased from 40 to 10%, and the mean dyskinesia and complication of treatment scores were reduced to one-third until pergolide was introduced at 12 months. No significant improvement in "on" scores was observed. A slight worsening after 1 year was observed and three patients developed levodopa- and stimulation-resistant gait ignition failure and minimal fluctuations at 1 year. Side effects, which were controlled by modulation of stimulation, included dysarthria, dystonia, and confusion. CONCLUSIONS: Bilateral pallidal DBS is safe and efficient in patients who have levodopa-responsive parkinsonism with severe fluctuations. Major improvements in motor score, ADL score, and off time persisted beyond 2 years after the operation, but signs of decreased efficacy started to be seen after 12 months.

Robotic Gait Training Is not Superior to Conventional Treadmill Training in Parkinson Disease: A Single-Blind Randomized Controlled Trial.

BACKGROUND: The use of robots for gait training in Parkinson disease (PD) is growing, but no evidence points to an advantage over the standard treadmill. METHODS: In this randomized, single-blind controlled trial, participants aged <75 years with early-stage PD (Hoehn-Yahr <3) were randomly allocated to 2 groups: either 30 minutes of gait training on a treadmill or in the Lokomat for 3 d/wk for 4 weeks. Patients were evaluated by a physical therapist blinded to allocation before and at the end of treatment and then at the 3- and 6-month follow-up. The primary outcome measure was the 6-minute walk test. RESULTS: Of 334 screened patients, the authors randomly allocated 30 to receive gait training with treadmill or the Lokomat. At baseline, the 2 groups did not differ. At the 6-month follow-up, both groups had improved significantly in the primary outcome measure (treadmill: mean = 490.95 m, 95% confidence interval [CI] = 448.56-533.34, P = .0006; Lokomat: 458.6 m, 95% CI = 417.23-499.96, P = .01), but no significant differences were found between the 2 groups (P = .53). DISCUSSION: Robotic gait training with the Lokomat is not superior to treadmill training in improving gait performance in patients with PD. Both approaches are safe, with results maintained for up to 6 months.

Long-term cognitive profile and incidence of dementia after STN-DBS in Parkinson's disease

An effect of subthalamic nucleus deep brain stimulation (STN-DBS) on cognition has been suspected but long-term observations are lacking. The aim of this study was to evaluate the long-term cognitive profile and the incidence of dementia in a cohort of Parkinson's disease (PD) patients treated by STN-DBS. 57 consecutive patients were prospectively assessed by the mean of a neuropsychological battery over 3 years after surgery. Dementia (DSM-IV) and UPDRS I to IV were recorded. 24.5% of patients converted to dementia over 3 years (incidence of 89 of 1,000 per year). This group of patients cognitively continuously worsened over 3 years up to fulfilling dementia criteria (PDD). The rest of the cohort remained cognitively stable (PD) over the whole follow-up. Preoperative differences between PDD and PD included older age (69.2 +/- 5.8 years; 62.6 +/- 8 years), presence of hallucinations and poorer executive score (10.1 +/- 5.9; 5.5 +/- 4.4). The incidence of dementia over 3 years after STN-DBS is similar to the one reported in medically treated patients. The PDD presented preoperative risk factors of developing dementia similar to those described in medically treated patients. These observations suggest dementia being secondary to the natural evolution of PD rather than a direct effect of STN-DBS.

The White Cane Magazine, Winter 2010, Vol. 1, no. 1

Quarterly newsletter produced by the Iowa Department of Blind, about the information and activities that are on going in the department.

The White Cane Magazine, Spring 2010, Vol. 1, no. 2

Quarterly newsletter produced by the Iowa Department of Blind, about the information and activities that are on going.

The White Cane Magazine, Fall 2010, Vol.1, no. 4

Newsletter produced by Iowa Department of the Blind.

On-shoe wearable sensors for gait and turning assessment of patients with Parkinson's disease.

Assessment of locomotion through simple tests such as timed up and go (TUG) or walking trials can provide valuable information for the evaluation of treatment and the early diagnosis of people with Parkinson's disease (PD). Common methods used in clinics are either based on complex motion laboratory settings or simple timing outcomes using stop watches. The goal of this paper is to present an innovative technology based on wearable sensors on-shoe and processing algorithm, which provides outcome measures characterizing PD motor symptoms during TUG and gait tests. Our results on ten PD patients and ten age-matched elderly subjects indicate an accuracy ± precision of 2.8 ± 2.4 cm/s and 1.3 ± 3.0 cm for stride velocity and stride length estimation compared to optical motion capture, with the advantage of being practical to use in home or clinics without any discomfort for the subject. In addition, the use of novel spatio-temporal parameters, including turning, swing width, path length, and their intercycle variability, was also validated and showed interesting tendencies for discriminating patients in ON and OFF states and control subjects.