Uncovering genetic mimics in multiple sclerosis: A single-center clinical exome sequencing study.

Background: Multiple sclerosis (MS) shares clinical/radiological features with several monogenic diseases that can mimic MS.

Objective: We aimed to determine if exome sequencing can identify monogenic diseases in patients diagnosed with MS according to the McDonald criteria thus uncovering them as being misdiagnosed.

Methods: We performed whole exome sequencing in a cohort of 278 patients with MS, clinically or radiologically isolated syndrome without cerebrospinal fluid-specific oligoclonal bands (CSF-OCBs) (n = 228), a positive family history of MS (n = 44), or both (n = 6), thereby focusing on individuals potentially more likely to have underlying monogenic conditions mimicking MS.

Patients' and caregivers' perception of multidimensional and palliative care in amyotrophic lateral sclerosis - protocol of a German multicentre study.

Introduction: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS).

Symptomatic intracranial hypertension in an adult patient with spinal muscular atrophy and arachnoid cysts receiving nusinersen.

 In patients with spinal muscular atrophy (SMA) headache after intrathecal administration of nusinersen is usually attributed to post-lumbar puncture syndrome. However, lumbar puncture opening pressure (LOP) has also been reported to be increased in children with SMA, both before and after treatment with nusinersen, although symptoms associated with increased LOP were not observed. We report to our knowledge the first case of symptomatic intracranial hypertension in an adult SMA patient.

Parkinson's disease therapy: what lies ahead?

The worldwide prevalence of Parkinson's disease (PD) has been constantly increasing in the last decades. With rising life expectancy, a longer disease duration in PD patients is observed, further increasing the need and socioeconomic importance of adequate PD treatment. Today, PD is exclusively treated symptomatically, mainly by dopaminergic stimulation, while efforts to modify disease progression could not yet be translated to the clinics.

Current State and Future Directions in the Diagnosis of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurons, resulting in progressive weakness of all voluntary muscles and eventual respiratory failure. Non-motor symptoms, such as cognitive and behavioral changes, frequently occur over the course of the disease. Considering its poor prognosis with a median survival time of 2 to 4 years and limited causal treatment options, an early diagnosis of ALS plays an essential role.

The Mutation Matters: CSF Profiles of GCase, Sphingolipids, α-Synuclein in PD.

Background: With pathway-specific trials in PD associated with variants in the glucocerebrosidase gene (PD ) under way, we need markers that confirm the impact of genetic variants in patient-derived biofluids in order to allow patient stratification merely based on genetics and that might serve as biochemical read-out for target engagement.

Objective: To explore GBA-pathway-specific biomarker profiles cross-sectionally (TUEPAC-MIGAP, PPMI) and longitudinally (PPMI).

Methods: We measured enzyme activity of the lysosomal glucocerebrosidase, CSF levels of glucosylceramides (upstream substrate of glucocerebrosidase), CSF levels of ceramides (downstream product of glucocerebrosidase), lactosylceramides, sphingosines, sphingomyelin (by-products) and CSF levels of total α-synuclein in PD patients compared to PD patients.

The longevity gene Klotho and its cerebrospinal fluid protein profiles as a modifier for Parkinson´s disease.

Background: Parkinson´s disease (PD) has a large phenotypic variability, which may, at least partly, be genetically driven including alterations of gene products. Candidates might not only be proteins associated with disease risk but also pathways that play a role in aging.

Objective: To evaluate phenotype-modifying effects of genetic variants in Klotho, a longevity gene.

CSF NFL in a Longitudinally Assessed PD Cohort: Age Effects and Cognitive Trajectories.

Background: Neurofilament light protein is an unspecific biofluid marker that reflects the extent of neuronal/axonal damage and thereby offers the chance monitor disease severity and progression. The objective of this study was to investigate cerebrospinal fluid (CSF) levels of neurofilament light protein in Parkinson's disease (PD) patients with clinical trajectories of motor and cognitive function longitudinally.

Methods: CSF neurofilament light protein levels were assessed in 371 PD , 126 genetic PD patients (91 PD , 8 PD , 21 PD , 6 PD ), and 71 healthy controls.

Orthostatic hypotension as a risk factor for longitudinal deterioration of cognitive function in the elderly.

Background And Purpose: Orthostatic hypotension is frequent with aging with a prevalence of 20%-30% in people aged 65 or older and is considered to increase the risk for coronary events, strokes and dementia. Our objective was to characterize the association of orthostatic hypotension and cognitive function longitudinally over 6 years in a large cohort of the elderly aged over 50 years.

Methods: In all, 495 participants were assessed longitudinally with the Schellong test and comprehensive cognitive testing using the extended CERAD neuropsychological test battery at baseline and after 6 years.

Dementia with lewy bodies: GBA1 mutations are associated with cerebrospinal fluid alpha-synuclein profile.

Background: Patients with dementia with Lewy bodies reveal a variable pathology including alpha-synuclein, amyloid-beta, and Tau. Mutations in GBA1 are specifically associated with synucleinopathies. PD patients with GBA1 mutations show reduced CSF levels of total alpha-synuclein.

Polygenic load: Earlier disease onset but similar longitudinal progression in Parkinson's disease.

Objectives: In order to evaluate the influence of the genetic load of 49 genetic variants known to be associated with PD on the age at onset as well as on clinical outcome parameters.

Background: PD patients show a large variability in phenotype and progression reflecting interindividual heterogeneity. This might be influenced by a diverse genetic architecture.

The Therapeutic Potential of Metformin in Neurodegenerative Diseases.

The search for treatments for neurodegenerative diseases is a major concern in light of today's aging population and an increasing burden on individuals, families, and society. Although great advances have been made in the last decades to understand the underlying genetic and biological cause of these diseases, only some symptomatic treatments are available. Metformin has long since been used to treat Type 2 Diabetes and has been shown to be beneficial in several other conditions.

Deterioration of executive dysfunction in elderly with REM sleep behavior disorder (RBD).

REM sleep behavior disorder (RBD) represents a major and relatively specific prodromal marker for synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies, and multisystem atrophy. Because PD patients primarily suffer from executive dysfunction, we hypothesized that individuals with RBD show an impairment in the nonamnestic executive domain rather than in amnestic domains. To address this question, we investigated a cohort of 1145 healthy elderly (183 with RBD) cross-sectionally and a subgroup of 544 of them longitudinally (144 with RBD) over 6 years.

Validation of a novel Montreal Cognitive Assessment scoring algorithm in non-demented Parkinson's disease patients.

Introduction: The early diagnosis of mild cognitive impairment (PD-MCI) in Parkinson's disease (PD) is essential as it increases the future risk for PD dementia (PDD). Recently, a novel weighting algorithm for the Montreal Cognitive Assessment (MoCA) subtests has been reported, to best discriminate between those with and without cognitive impairment in PD. The aim of our study was to validate this scoring algorithm in a large sample of non-demented PD patients, hypothesizing that the weighted MoCA would have a higher diagnostic accuracy for PD-MCI than the original MoCA.

Diagnostic exome sequencing in early-onset Parkinson's disease confirms VPS13C as a rare cause of autosomal-recessive Parkinson's disease.

Parkinson's disease (PD) is a genetically heterogeneous disorder and new putative disease genes are discovered constantly. Therefore, whole-exome sequencing could be an efficient approach to genetic testing in PD. To evaluate its performance in early-onset sporadic PD, we performed diagnostic exome sequencing in 80 individuals with manifestation of PD symptoms at age 40 or earlier and a negative family history of PD.

[Congenital poikiloderma of the verrucous type in Thomson syndrome with associated myopathy].

This report deals with a 15-year-old girl suffering from the verrucous type of Thomson's syndrome. Initial poikilodermatous skin changes developed on both cheeks at the age of 3 months. Subsequently, rapid generalization of typical skin findings was observed.