Novel synthetic (poly)glycerolphosphate-based antistaphylococcal conjugate vaccine.

Staphylococcal infections are a major source of global morbidity and mortality. Currently there exists no antistaphylococcal vaccine in clinical use. Previous animal studies suggested a possible role for purified lipoteichoic acid as a vaccine target for eliciting protective IgG to several Gram-positive pathogens.

The midbrain to pons ratio: a simple and specific MRI sign of progressive supranuclear palsy.

Objectives: MRI-based measurements used to diagnose progressive supranuclear palsy (PSP) typically lack pathologic verification and are not easy to use routinely. We aimed to develop in histologically proven disease a simple measure of the midbrain and pons on sagittal MRI to identify PSP.

Methods: Measurements of the midbrain and pontine base on midsagittal T1-weighted MRI were performed in confirmed PSP (n = 12), Parkinson disease (n = 2), and multiple system atrophy (MSA) (n = 7), and in controls (n = 8).

Uncertainty about mapping future actions into rewards may underlie performance on multiple measures of impulsivity in behavioral addiction: evidence from Parkinson's disease.

A subset of patients with Parkinson's disease (PD) develops behavioral addictions, which may be due to their dopamine replacement therapy. Recently, several groups have been comparing PD patients with and without behavioral addictions on tasks that are thought to measure aspects of impulsivity. Several of these experiments, including information sampling, a bias toward novel stimuli and temporal discounting, have shown differences between PD patients with and without behavioral addictions.

Erich Harnack (1852-1915) and a short history of apomorphine.

Apomorphine, now established as an efficacious therapy for refractory motor fluctuations in levodopa-treated Parkinson's disease, has a long and chequered history in medical and veterinary therapeutics. The preclinical in vivo pharmacological effects of apomorphine were first studied about 150 years ago following which the drug was introduced for the treatment of behavioural vices in domesticated animals. Erich Harnack's early pharmacological studies in Dorpat (now Tartu, Estonia), where he belonged to the pharmacological dynasty of Buchheim and Schmiedeberg, are of particular historical significance as he emphasised that while apomorphine had potent emetic effects, the drug also had complex effects on the central nervous system.

Pisa syndrome in Parkinson's disease: a mobile or fixed deformity?

Background: Although Pisa syndrome and scoliosis are sometimes used interchangeably to describe a laterally flexed postural deviation in Parkinson's disease (PD), the imaging findings of Pisa syndrome in PD have not been previously studied in detail.

Methods: Patients with PD and Pisa syndrome (lateral flexion >10° in the standing position) were examined clinically and underwent radiological assessment using standing radiograph and supine CT scan of the whole spine.

Results: Fifteen patients were included in this observational study.

Demographic and motor features associated with the occurrence of neuropsychiatric and sleep complications of Parkinson's disease.

Objective: To determine whether four key neuropsychiatric and sleep related features associated with Parkinson's disease (PD) are associated with the motor handicap and demographic data.

Background: The growing number of recognised non-motor features of PD makes routine screening of all these symptoms impractical. Here, we investigated the hypothesis that standard demographic data and the routine assessment of motor signs is associated with the presence of dementia, psychosis, clinically probable rapid eye movement (REM) sleep behavior disorder (cpRBD) and restless legs syndrome (RLS).

Parkin disease: a clinicopathologic entity?

Importance: Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss.

Objective: To investigate whether parkin-linked parkinsonism is a different clinicopathologic entity to Parkinson disease (PD).

α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy?

We report a British family with young-onset Parkinson's disease (PD) and a G51D SNCA mutation that segregates with the disease. Family history was consistent with autosomal dominant inheritance as both the father and sister of the proband developed levodopa-responsive parkinsonism with onset in their late thirties. Clinical features show similarity to those seen in families with SNCA triplication and to cases of A53T SNCA mutation.

Primary progressive aphasia with parkinsonism.

A 65-year-old man presented with word-finding difficulty and gait disturbance. His speech was nonfluent with word retrieval impairment and difficulties with sentence repetition. Other cognitive domains were intact initially.

Shell shock at Queen Square: Lewis Yealland 100 years on.

This article reviews the treatment of functional neurological symptoms during World War I by Lewis Yealland at the National Hospital for the Paralysed and Epileptic in London. Yealland was among the first doctors in Britain to incorporate electricity in the systematic treatment of shell shock. Our analysis is based on the original case records of his treatment of 196 soldiers with functional motor and sensory symptoms, functional seizures and somatoform disorders.

Neural response to visual sexual cues in dopamine treatment-linked hypersexuality in Parkinson's disease.

Hypersexuality with compulsive sexual behaviour is a significant source of morbidity for patients with Parkinson's disease receiving dopamine replacement therapies. We know relatively little about the pathophysiology of hypersexuality in Parkinson's disease, and it is unknown how visual sexual stimuli, similar to the portrayals of sexuality in the mainstream mass media may affect the brain and behaviour in such susceptible individuals. Here, we have studied a group of 12 patients with Parkinson's disease with hypersexuality using a functional magnetic resonance imaging block design exposing participants to both sexual, other reward-related and neutral visual cues.

Clinical features of childhood-onset paroxysmal kinesigenic dyskinesia with PRRT2 gene mutations.

Aim: To define better the phenotype and genotype of familial and sporadic cases of paroxysmal kinesigenic dyskinesia (PKD) caused by mutations in the PRRT2 gene presenting in the paediatric age group.

Method: We report the detailed clinical and molecular genetic features of 11 patients (six females, five males) with childhood-onset PRRT2-mutation-positive PKD.

Results: Mean age at disease onset was 8 years 7.

Availability of olfactory bulb: experience from a British Brain Bank.

The olfactory bulb and tract (OB/OT) are among the earliest structures in the brain to undergo pathological changes in many neurodegenerative conditions. The availability of OB/OT samples from brain specimens in brain banks therefore assumes importance. We collected data from 5 years (2006-2010) regarding the presence or absence of OB/OT material in cases received by the Queen Square Brain Bank (QSBB) for Neurological Disorders, UCL Institute of Neurology, UK, to estimate availability of OB/OT material at the brain bank and also to look for possible associations.

Neuropathological findings in benign tremulous parkinsonism.

Benign tremulous parkinsonism, a tremor dominant syndrome with a relatively slow rate of deterioration, is recognized by clinicians although its pathological basis is not well understood. A systematic review of Queen Square Brain Bank donors was carried out to determine the natural history and pathology of individuals who had tremor dominant parkinsonism with mild non-tremor components and minimal gait disability for at least 8 years. We identified 16 cases of pathologically proved benign tremulous Parkinson's disease (PD); another 5 individuals conformed to the definition but did not have the pathology of PD.

Increased reflection impulsivity in patients with ephedrone-induced Parkinsonism.

Aims: To examine a syndrome of chronic manganism that occurs in drug addicts in eastern Europe who use intravenous methcathinone (ephedrone) contaminated with potassium permanganate. In many cases the basal ganglia, especially the globus pallidus and the putamen, are damaged irreversibly. Routine neuropsychological assessment has revealed no cognitive deficits, despite widespread abnormalities on brain imaging studies and severe extrapyramidal motor handicap on clinical examination.

The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease.

Background: Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD.

Methods: One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing.

MM2 subtype of sporadic Creutzfeldt-Jakob disease may underlie the clinical presentation of progressive supranuclear palsy.

The classical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) is rapid progressive dementia often associated with myoclonus and ataxia followed by death in less than a year from diagnosis. The few patients in the literature who presented with parkinsonism and who were suspected to have progressive supranuclear palsy (PSP) all ran a malignant course and most of them died within 3 years of diagnosis. We screened the Queen Square Brain Bank database and, among 213 patients with a clinical diagnosis of PSP, we found ten patients with 3 years or less disease duration, including one patient with CJD pathology.

Normal pressure hydrocephalus or progressive supranuclear palsy? A clinicopathological case series.

Idiopathic normal pressure hydrocephalus (iNPH) is a poorly understood condition, which typically presents with the triad of balance impairment, urinary incontinence and subacute cognitive decline, while brain imaging shows a marked enlargement of the cerebral ventricles. Few patients with iNPH have come to post-mortem. We identified four patients from the Queen Square Brain Bank archival collection, who had received a diagnosis of iNPH during life, and reviewed their clinical, radiological and pathological characteristics.

Gowers' Queen Square case notes on chorea: a 21st century re-appraisal.

Objective: To analyze the case notes of 127 patients with chorea admitted to the National Hospital at Queen Square, London, under the care of William Richard Gowers and review his contribution to the study of choreas.

Methods: We consulted the case books available at the Queen Square Library, from 1878 to 1911, comprising 42 volumes.

Results: 97 patients (76.

PRRT2 gene mutations: from paroxysmal dyskinesia to episodic ataxia and hemiplegic migraine.

Objective: The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such as epilepsy, migraine, and paroxysmal movement disorders, often coexist and are thought to have a shared channel-related etiology. To investigate further the frequency, spectrum, and phenotype of PRRT2 mutations, we analyzed this gene in 3 large series of episodic neurologic disorders with PKD/IC, episodic ataxia (EA), and hemiplegic migraine (HM).

Meta-analysis of early nonmotor features and risk factors for Parkinson disease.

Objective: To evaluate the association between diagnosis of Parkinson disease (PD) and risk factors or early symptoms amenable to population-based screening.

Methods: A systematic review and meta-analysis of risk factors for PD.

Results: The strongest associations with later diagnosis of PD were found for having a first-degree or any relative with PD (odds ratio [OR], 3.