A plasma proteomics-based candidate biomarker panel predictive of amyotrophic lateral sclerosis.

Identifying a reliable biomarker for amyotrophic lateral sclerosis (ALS) is crucial for clinical practice. Here, in this cross-sectional study, we used the Olink Explore 3072 platform to investigate plasma proteomics as a biomarker tool for this neurodegenerative condition. Thirty-three proteins were differentially abundant in the plasma of patients with ALS (n = 183) versus controls (n = 309).

Persistent GDNF Expression 45 Months after Putaminal Infusion of AAV2-GDNF in a Patient with Parkinson's Disease.

Objective: Gene therapy by convection-enhanced delivery of type 2 adeno-associated virus-glial cell derived neurotrophic factor (AAV2-GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD).

Methods: A 63-year-old man with advanced PD received AAV2-GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later.

A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease.

Background: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD).

Objective: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG).

Electrophysiological Characterization of a Variant with Tremor Phenotype.

Background: The concept of a myopathy with associated tremor ("myogenic tremor") in humans has been previously described for specific (Myosin-Binding Protein C) variants. Here we report for the first time an individual with tremor who was found to have a de-novo likely pathogenic variant in Myosin Heavy Chain 7 (MYH7

Unlabelled: We provide a detailed electrophysiological characterization of the tremor syndrome in a human individual with a myopathy and this pathogenic MYH7 variant to provide further insight in the phenotypic spectrum and pathomechanism of myogenic tremors in skeletal sarcomeric myopathies.

Methods: Electromyographic recordings were obtained from facial muscles, as well as bilateral upper and lower extremities.

Long-term safety of MRI-guided administration of AAV2-GDNF and gadoteridol in the putamen of individuals with Parkinson's disease.

Direct putaminal infusion of adeno-associated virus vector (serotype 2) (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene was studied in a phase I clinical trial of participants with advanced Parkinson's disease (PD). Convection-enhanced delivery of AAV2-GDNF with a surrogate imaging tracer (gadoteridol) was used to track infusate distribution during real-time intraoperative magnetic resonance imaging (iMRI). Pre-, intra-, and serial postoperative (up to 5 years after infusion) MRI were analyzed in 13 participants with PD treated with bilateral putaminal co-infusions (52 infusions in total) of AAV2-GDNF and gadoteridol (infusion volume, 450 mL per putamen).

Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson's disease.

Objective: To investigate the safety and tolerability of convection-enhanced delivery of an adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor into the bilateral putamina of PD patients.

Methods: Thirteen adult patients with advanced PD underwent adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor and gadoteridol (surrogate MRI tracer) coinfusion (450 μL/hemisphere) at escalating doses: 9 × 10 vg (n = 6); 3 × 10 vg (n = 6); and 9 × 10 vg (n = 1). Intraoperative MRI monitored infusion distribution.

Functional neuroimaging and chorea: a systematic review.

Chorea is a hyperkinetic movement disorder consisting of involuntary irregular, flowing movements of the trunk, neck or face. Although Huntington's disease is the most common cause of chorea in adults, chorea can also result from many other neurodegenerative, metabolic, and autoimmune conditions. While the pathophysiology of these different conditions is quite variable, recent advances in functional imaging have enabled the development of new methods for analysis of brain activity and neuronal dysfunction.

The phenomenology and treatment of idiopathic adult-onset truncal dystonia: a retrospective review.

Background: Focal dystonia is the most common type of adult-onset dystonia; however, it infrequently affects truncal musculature. Although commonly attributed to secondary etiologies such as a neurodegenerative illness or tardive syndromes, the entity of idiopathic adult-onset truncal dystonia has only been previously described in a few case reports and small case series. Here we characterize seven cases of adult-onset primary truncal dystonia and present them within the scope of the existing literature.

Molecular alterations in the cerebellum of the plasma membrane calcium ATPase 2 (PMCA2)-null mouse indicate abnormalities in Purkinje neurons.

PMCA2, a major calcium pump, is expressed at particularly high levels in Purkinje neurons. Accordingly, PMCA2-null mice exhibit ataxia suggesting cerebellar pathology. It is not yet known how changes in PMCA2 expression or activity affect molecular pathways in Purkinje neurons.