Current Opinion In Neurology[JOURNAL]
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200 papers
Congenital myasthenic syndromes: increasingly complex.
Ramdas S, Beeson D, Dong YY
Curr Opin Neurol · 2024 Oct · PMID 39051439 · Full text
PURPOSE OF REVIEW: Congenital myasthenia syndromes (CMS) are treatable, inherited disorders affecting neuromuscular transmission. We highlight that the involvement of an increasing number of proteins is making the unders...
PURPOSE OF REVIEW: Congenital myasthenia syndromes (CMS) are treatable, inherited disorders affecting neuromuscular transmission. We highlight that the involvement of an increasing number of proteins is making the understanding of the disease mechanisms and potential treatments progressively more complex. RECENT FINDINGS: Although early studies identified mutations of proteins directly involved in synaptic transmission at the neuromuscular junction, recently, next-generation sequencing has facilitated the identification of many novel mutations in genes that encode proteins that have a far wider expression profile, some even ubiquitously expressed, but whose defective function leads to impaired neuromuscular transmission. Unsurprisingly, mutations in these genes often causes a wider phenotypic disease spectrum where defective neuromuscular transmission forms only one component. This has implications for the management of CMS patients. SUMMARY: Given the widening nonneuromuscular junction phenotypes in the newly identified forms of CMS, new therapies need to include disease-modifying approaches that address not only neuromuscular weakness but also the multisystem involvement. Whilst the current treatments for CMS are highly effective for many subtypes there remains, in a proportion of CMS patients, an unmet need for more efficacious therapies.
Muscle ultrasound in myopathies.
Vicino A, Veltsista D, van Alfen N
Curr Opin Neurol · 2024 Oct · PMID 39051427 · Full text
PURPOSE OF REVIEW: This review highlights recent developments in the field of muscle ultrasound (MUS) for the diagnosis and follow up of muscle disorders. RECENT FINDINGS: The diagnostic screening capacity of quantitativ...
PURPOSE OF REVIEW: This review highlights recent developments in the field of muscle ultrasound (MUS) for the diagnosis and follow up of muscle disorders. RECENT FINDINGS: The diagnostic screening capacity of quantitative grayscale analysis is still sufficient to assess children suspected of a neuromuscular disorder. A combination of visual and quantitative assessment is advised for optimal interpretation. MUS was more sensitive but less specific than MRI for detecting pathology in limb girdle dystrophies and inflammatory myopathies. New techniques such as shearwave elastography and artificial intelligence algorithms for automated image segmentation show promise but need further development for use in everyday practice.Muscle ultrasound has high correlations with clinical measures of function in skeletal and respiratory muscles and the orofacial region, in most of the myopathies and dystrophies studied. Over time, imaging changes precede changes in clinical status, making them attractive for biomarker use in trials. In Duchenne muscular dystrophy MUS was also responsive to the effects of steroid treatment. SUMMARY: Muscle ultrasound is a sensitive technique to diagnose and follow up of skeletal, facial and respiratory muscles in neuromuscular disorders. Its role is both complementary to and partially overlapping with that of MRI.
Ways to think about vasculitic neuropathy.
Kapoor M, Reddel SW
Curr Opin Neurol · 2024 Oct · PMID 39046107 · Publisher ↗
PURPOSE OF REVIEW: Vasculitis as a pathomechanism for neuropathy can be isolated to the peripheral nervous system, a part of a systemic autoimmune condition or a component of another syndrome. This review aims to discuss...
PURPOSE OF REVIEW: Vasculitis as a pathomechanism for neuropathy can be isolated to the peripheral nervous system, a part of a systemic autoimmune condition or a component of another syndrome. This review aims to discuss the broad range of diagnoses in which vasculitic neuropathy can be encountered, highlight the progress in imaging techniques in identifying vasculitis, and the new drugs developed for other autoimmune diseases that may be applied to neurological conditions. RECENT FINDINGS: Advances in imaging modalities, ultrasound, MRI and FDG-PET scanning for neuromuscular applications has redefined many aspects of vasculitic neuropathies. The benefit of dividing vasculitides by vessel size is becoming less absolute as diagnostic approaches advance. MRI and FDG-PET are widely used in diagnosis, defining extent of involvement of disease and monitoring. In neuralgic amyotrophy, the identification of hourglass-like constrictions on imaging has changed the treatment paradigm to include surgical interventions. These diagnostic approaches are supported by new immunomodulating and immunosuppression techniques. SUMMARY: Vasculitic neuropathies are a broad group of conditions with a range of causes and associations. Increased use of imaging techniques impacts our traditional definitions and classifications. The growth in treatment options for other autoimmune conditions are likely to infiltrate the neurological landscape.
Diagnostic criteria for amyotrophic lateral sclerosis.
Timmins HC, Thompson AE, Kiernan MC
Curr Opin Neurol · 2024 Oct · PMID 39037015 · Publisher ↗
PURPOSE OF REVIEW: The present review will discuss the evolution of diagnostic criteria for amyotrophic lateral sclerosis (ALS) and biomarker considerations. RECENT FINDINGS: To address the limitations of existing ALS di...
PURPOSE OF REVIEW: The present review will discuss the evolution of diagnostic criteria for amyotrophic lateral sclerosis (ALS) and biomarker considerations. RECENT FINDINGS: To address the limitations of existing ALS diagnostic criteria, a consortium of key stakeholders developed the Gold Coast consensus criteria (GCC). The GCC has similar or greater sensitivity compared with the revised El Escorial (rEEC) and Awaji criteria (AC), particularly for atypical phenotypes, maintained across disease duration, severity, and site of onset. In addition to improving diagnostic sensitivity, using the GCC in clinical trials may promote an increased enrolment of up to 50% of ALS patients who do not currently meet the full diagnostic eligibility requirements of the rEEC. Future inclusion of genetic biomarkers may mitigate some limitations of the GCC, to further improve diagnostic utility. In advance of such a process, validation of these biomarkers will be required before inclusion as additional criteria. SUMMARY: The GCC are simpler to use than previous consensus criteria, with demonstrated greater sensitivity and, enabling an earlier and more definitive ALS diagnosis, thereby facilitating wider enrolment into clinical trials. Broader implementation of the GCC in clinical trial settings is currently underway, globally.
Current advance on distal myopathy genetics.
Ranta-Aho J, Johari M, Udd B
Curr Opin Neurol · 2024 Oct · PMID 39017652 · Full text
PURPOSE OF REVIEW: Distal myopathies are a clinically heterogenous group of rare, genetic muscle diseases, that present with weakness in hands and/or feet at onset. Some of these diseases remain accentuated in the distal...
PURPOSE OF REVIEW: Distal myopathies are a clinically heterogenous group of rare, genetic muscle diseases, that present with weakness in hands and/or feet at onset. Some of these diseases remain accentuated in the distal muscles whereas others may later progress to the proximal muscles. In this review, the latest findings related to genetic and clinical features of distal myopathies are summarized. RECENT FINDINGS: Variants in SMPX , DNAJB2, and HSPB6 have been identified as a novel cause of late-onset distal myopathy and neuromyopathy. In oculopharyngodistal myopathies, repeat expansions were identified in two novel disease-causing genes, RILPL1 and ABCD3. In multisystem proteinopathies, variants in HNRNPA1 and TARDBP , genes previously associated with amyotrophic lateral sclerosis, have been shown to cause late-onset distal myopathy without ALS. In ACTN2 -related distal myopathy, the first recessive forms of the disease have been described, adding it to the growing list of genes were both dominant and recessive forms of myopathy are present. SUMMARY: The identification of novel distal myopathy genes and pathogenic variants contribute to our ability to provide a final molecular diagnosis to a larger number of patients and increase our overall understanding of distal myopathy genetics and pathology.
Late-onset myopathies.
Salort-Campana E, Attarian S
Curr Opin Neurol · 2024 Oct · PMID 39017649 · Publisher ↗
PURPOSE OF REVIEW: Late-onset myopathies are defined as muscle diseases that begin after the age of 50 years. Some myopathies present classically in the elderly, whereas others may have a variable age of onset, including...
PURPOSE OF REVIEW: Late-onset myopathies are defined as muscle diseases that begin after the age of 50 years. Some myopathies present classically in the elderly, whereas others may have a variable age of onset, including late-onset presentation. The purpose of this review is to summarize and comment on the most recent evidence regarding the main diagnosis of late-onset myopathies focusing on genetic causes. RECENT FINDINGS: Although late-onset myopathies (LOM) are expected to be predominantly acquired myopathies, some common genetic myopathies, such as facioscapulohumeral muscular dystrophy (FSHD), can present late in life, usually with an atypical presentation. In addition, metabolic myopathies, which are classically early-onset diseases, are also diagnoses to be considered, particularly as they may be treatable. Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) has recently been identified as a cause of subacute LOM with a dramatic response to riboflavin supplementation. SUMMARY: Inclusion body myositis is the most frequent of all LOM. Myotonic dystrophy type 2, FSHD and oculopharyngeal muscular dystrophy are the most frequent causes of genetic LOM. We summarize the major differential diagnoses and the clinical features on clinical examination that are suggestive of a genetic diagnosis to provide a diagnostic approach.
Update on RYR1-related myopathies.
Ogasawara M, Nishino I
Curr Opin Neurol · 2024 Oct · PMID 38994695 · Publisher ↗
PURPOSE OF REVIEW: RYR1-related myopathy (RYR1-RM) is a group of myopathies caused by mutations in the RYR1 gene, which encodes the ryanodine receptor 1 (RYR1). This review discusses recent advances in the clinical featu...
PURPOSE OF REVIEW: RYR1-related myopathy (RYR1-RM) is a group of myopathies caused by mutations in the RYR1 gene, which encodes the ryanodine receptor 1 (RYR1). This review discusses recent advances in the clinical features, pathology, pathogenesis, and therapeutics of RYR1-RM. RECENT FINDINGS: Although treatments such as salbutamol, pyridostigmine, and N-acetylcysteine have been explored as potential therapies for RYR1-RM, none have been conclusively proven to be effective. However, recent clinical trials of Rycal ARM210 in patients with RYR1-RM have shown promising results, including reduced fatigue and improved proximal muscle strength.Recent advances in three-dimensional structural analysis of RYR1 channels, facilitated by cryo-electron microscopy (cryo-EM), have elucidated the distinct molecular mechanisms underlying RYR1 functionality. Additionally, high-throughput screening methods, including FRET-based and endoplasmic reticulum Ca 2+ -based assays, have been successful in identifying potential candidates for the treatment of RYR1-RM. SUMMARY: Recent advances in clinical and pathological understanding have provided new insights into RYR1-RM. Novel pathomechanisms elucidated by cryo-EM and rapid screening methods have led to the identification of several promising drug candidates. We are hopeful about the potential of Rycal, other new drugs, and gene therapy, offering a promising outlook for the future.
Recent insights in striated muscle laminopathies.
Leconte M, Bonne G, Bertrand AT
Curr Opin Neurol · 2024 Oct · PMID 38989655 · Publisher ↗
PURPOSE OF REVIEW: To highlight recent insights in different aspects of striated muscle laminopathies (SMLs) related to LMNA mutations. RECENT FINDINGS: Clinical and genetic studies allow better patient management and di...
PURPOSE OF REVIEW: To highlight recent insights in different aspects of striated muscle laminopathies (SMLs) related to LMNA mutations. RECENT FINDINGS: Clinical and genetic studies allow better patient management and diagnosis, with confirmation of ventricular tachyarrhythmias (VTA) risk prediction score to help with ICD implantation and development of models to help with classification of LMNA variants of uncertain significance. From a pathophysiology perspective, characterization of lamin interactomes in different contexts revealed new lamin A/C partners. Expression or function modulation of these partners evidenced them as potential therapeutic targets. After a positive phase 2, the first phase 3 clinical trial, testing a p38 inhibitor targeting the life-threatening cardiac disease of SML, has been recently stopped, thus highlighting the need for new therapeutic approaches together with new animal and cell models. SUMMARY: Since the first LMNA mutation report in 1999, lamin A/C structure and functions have been actively explored to understand the SML pathophysiology. The latest discoveries of partners and altered pathways, highlight the importance of lamin A/C at the nuclear periphery and in the nucleoplasm. Modulation of altered pathways allowed some benefits, especially for cardiac involvement. However, additional studies are still needed to fully assess treatment efficacy and safety.
The genetics of amyotrophic lateral sclerosis.
Nijs M, Van Damme P
Curr Opin Neurol · 2024 Oct · PMID 38967083 · Full text
PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) has a strong genetic basis, but the genetic landscape of ALS appears to be complex. The purpose of this article is to review recent developments in the genetics of A...
PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) has a strong genetic basis, but the genetic landscape of ALS appears to be complex. The purpose of this article is to review recent developments in the genetics of ALS. RECENT FINDINGS: Large-scale genetic studies have uncovered more than 40 genes contributing to ALS susceptibility. Both rare variants with variable effect size and more common variants with small effect size have been identified. The most common ALS genes are C9orf72 , SOD1 , TARDBP and FUS . Some of the causative genes of ALS are shared with frontotemporal dementia, confirming the molecular link between both diseases. Access to diagnostic gene testing for ALS has to improve, as effective gene silencing therapies for some genetic subtypes of ALS are emerging, but there is no consensus about which genes to test for. SUMMARY: Our knowledge about the genetic basis of ALS has improved and the first effective gene silencing therapies for specific genetic subtypes of ALS are underway. These therapeutic advances underline the need for better access to gene testing for people with ALS. Further research is needed to further map the genetic heterogeneity of ALS and to establish the best strategy for gene testing in a clinical setting.
Pathological insights derived from neuroimaging in amyotrophic lateral sclerosis: emerging clinical applications.
Tu S, Vucic S, Kiernan MC
Curr Opin Neurol · 2024 Oct · PMID 38958573 · Publisher ↗
PURPOSE OF REVIEW: Neuroimaging has been instrumental in shaping current understanding of the pathoanatomical signature of amyotrophic lateral sclerosis (ALS) across clinically well defined patient cohorts. The potential...
PURPOSE OF REVIEW: Neuroimaging has been instrumental in shaping current understanding of the pathoanatomical signature of amyotrophic lateral sclerosis (ALS) across clinically well defined patient cohorts. The potential utility of imaging as an objective disease marker, however, remains poorly defined. RECENT FINDINGS: Increasingly advanced quantitative and computational imaging studies have highlighted emerging clinical applications for neuroimaging as a complementary clinical modality for diagnosis, monitoring, and modelling disease propagation. Multimodal neuroimaging has demonstrated novel approaches for capturing primary motor disease. Extra-motor subcortical dysfunction is increasingly recognized as key modulators of disease propagation. SUMMARY: The neural signature of cortical and subcortical dysfunction in ALS has been well defined at the population level. Objective metrics of focal primary motor dysfunction are increasingly sensitive and translatable to the individual patient level. Integrity of extra-motor subcortical abnormalities are recognized to represent critical pathways of the ALS disease 'connectome', predicting pathological spread. Neuroimaging plays a pivotal role in capturing upper motor neuron pathology in ALS. Their potential clinical role as objective disease markers for disease classification, longitudinal monitoring, and prognosis in ALS have become increasingly well defined.
Editorial: Update on movement disorders.
Svenningsson P
Curr Opin Neurol · 2024 Aug · PMID 38953966 · Publisher ↗
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Describing and assessing behavioural symptoms in amyotrophic lateral sclerosis with and without frontotemporal dementia: a scoping review.
Trucco AP, Backhouse T, Mioshi E
Curr Opin Neurol · 2024 Oct · PMID 38946579 · Publisher ↗
PURPOSE OF REVIEW: Alongside motor and cognitive symptoms, amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal dementia (ALSFTD) present with behavioural symptoms, which can be challenging for all affected by...
PURPOSE OF REVIEW: Alongside motor and cognitive symptoms, amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal dementia (ALSFTD) present with behavioural symptoms, which can be challenging for all affected by the disease. A scoping review of studies published between 2011 and 2024 was conducted to present the breadth of behavioural symptoms in ALS and ALSFTD, explore how they are described and assessed, and identify patterns in the literature. FINDINGS: This scoping review identified 3939 articles, with 111/3939 meeting eligibility criteria. Most studies were from Australia (23.22%), Italy (16.94%) and the UK (14.29%); 75.67% were cross-sectional. Sample size ranged from 1 to 1013, as case studies were included. Overall mean age (100/111 studies) was 61.32 (SD = 4.15). Proportion of male patients (reported 102/111 studies) was 61.49%; mean disease duration (reported in 86/111 records) was 32.63 months (SD = 24.72). Papers described a broad range of behavioural symptoms (465 examples), which were thematically collated into seven categories: disinhibition (27.74%), apathy (25.16%), perseverative/compulsive behaviours (17.42%), hyperorality (10.53%), loss of sympathy or empathy (8.6%), psychotic symptoms (7.74%), and loss of insight about disease and changes (2.8%). Most studies (78.37%) used validated behavioural assessments that elicited carer's perspectives. SUMMARY: Despite extensive evidence of behavioural symptoms in ALS, implementation of assessments and management of behavioural symptoms in clinical care remain limited. Clinicians must assess behavioural symptoms, as these can negatively affect disease prognosis, patient treatment engagement and increase family distress. Measures capturing carers' perspectives through interviews are ideal as they can reveal anosognosia, lack of sympathy and lack of empathy.
Advances in functional and structural imaging of the brainstem: implications for disease.
Cai J, Wang Y, McKeown MJ
Curr Opin Neurol · 2024 Aug · PMID 38884636 · Publisher ↗
PURPOSE OF REVIEW: The brainstem's complex anatomy and relatively small size means that structural and functional assessment of this structure is done less frequently compared to other brain areas. However, recent years...
PURPOSE OF REVIEW: The brainstem's complex anatomy and relatively small size means that structural and functional assessment of this structure is done less frequently compared to other brain areas. However, recent years have seen substantial progress in brainstem imaging, enabling more detailed investigations into its structure and function, as well as its role in neuropathology. RECENT FINDINGS: Advancements in ultrahigh field MRI technology have allowed for unprecedented spatial resolution in brainstem imaging, facilitating the new creation of detailed brainstem-specific atlases. Methodological improvements have significantly enhanced the accuracy of physiological (cardiac and respiratory) noise correction within brainstem imaging studies. These technological and methodological advancements have allowed for in-depth analyses of the brainstem's anatomy, including quantitative assessments and examinations of structural connectivity within both gray and white matter. Furthermore, functional studies, including assessments of activation patterns and functional connectivity, have revealed the brainstem's roles in both specialized functions and broader neural integration. Notably, these investigations have identified alterations in brainstem structure and function associated with various neurological disorders. SUMMARY: The aforementioned developments have allowed for a greater appreciation of the importance of the brainstem in the wider context of neuroscience and clinical neurology.
Gene therapies for CMT neuropathies: from the bench to the clinic.
Stavrou M, Kleopa KA
Curr Opin Neurol · 2024 Oct · PMID 38873808 · Publisher ↗
PURPOSE OF REVIEW: Charcot-Marie-Tooth (CMT) neuropathies are rare, genetically heterogeneous and progressive diseases for which there are no approved treatments and their management remains mostly supportive and symptom...
PURPOSE OF REVIEW: Charcot-Marie-Tooth (CMT) neuropathies are rare, genetically heterogeneous and progressive diseases for which there are no approved treatments and their management remains mostly supportive and symptomatic. This review is intended to provide an update on recent developments in gene therapies for different CMT neuropathies. RECENT FINDINGS: Increasing knowledge of disease pathomechanisms underlying several CMT types has facilitated the development of promising viral and nonviral gene therapy approaches. Some of these therapies are currently approaching the crucial step of moving from the bench to the clinic, having passed the proof-of-concept stage in rodent models and some also in larger animals. However, questions of optimal delivery route and dose, off-target effects, and possible payload toxicity remain to be clarified for several of these approaches. Furthermore, limited resources, the rarity of most CMT subtypes, and issues of safety and regulatory requirements, create the need for consensus guidelines and optimal clinical trial design. SUMMARY: Promising gene therapies have been developed for several CMT neuropathies, with proof-of-principle demonstrated in relevant disease models. Advantages and drawbacks of each approach are discussed and remaining challenges are highlighted. Furthermore, we suggest important parameters that should be considered in order to successfully translate them into the clinic.
New chronic inflammatory demyelinating polyneuropathy/Guillain-Barré syndrome guidelines - impact on clinical practise.
Allen JA
Curr Opin Neurol · 2024 Oct · PMID 38873801 · Publisher ↗
PURPOSE OF REVIEW: There is no diagnostic biomarker that can reliably detect Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnosis relies upon integrating key clinical chara...
PURPOSE OF REVIEW: There is no diagnostic biomarker that can reliably detect Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnosis relies upon integrating key clinical characteristics and relevant supportive data. Consequently, misdiagnosis and delayed diagnosis are common. Diagnostic criteria have proven valuable resources to improve diagnosis, but are underutilized during routine clinical care. RECENT FINDINGS: In 2021, the EAN/PNS CIDP criteria was published, and were followed by the EAN/PNS GBS criteria in 2023. Both guidelines utilized GRADE methodology to formulate evidence-based recommendations that are intended to be used by adult and paediatric clinicians across diverse care settings to optimize diagnostic accuracy and improve patient outcomes during routine clinical care. SUMMARY: The EAN/PNS GBS and CIDP criteria detail specific clinical, electrophysiological, and laboratory features that raise diagnostic confidence, and call attention to diagnostic mimics. The sensitivity of EAN/PNS and other modern criteria to detect GBS and CIDP is high, but utilization during clinical practice is low. Complexity is one factor limiting widespread application. Strategies are needed to optimize criteria adoption during routine clinical care such that GBS and CIDP diagnosis can be achieved with greater speed and accuracy.
Obesity-related neuropathy: the new epidemic.
Elafros MA, Reynolds EL, Callaghan BC
Curr Opin Neurol · 2024 Oct · PMID 38864534 · Full text
PURPOSE OF REVIEW: To examine the evidence evaluating the association between obesity and neuropathy as well as potential interventions. RECENT FINDINGS: Although diabetes has long been associated with neuropathy, additi...
PURPOSE OF REVIEW: To examine the evidence evaluating the association between obesity and neuropathy as well as potential interventions. RECENT FINDINGS: Although diabetes has long been associated with neuropathy, additional metabolic syndrome components, including obesity, are increasingly linked to neuropathy development, regardless of glycemic status. Preclinical rodent models as well as clinical studies are shedding light on the mechanisms of obesity-related neuropathy as well as challenges associated with slowing progression. Dietary and surgical weight loss and exercise interventions are promising, but more data is needed. SUMMARY: High-fat-diet rodent models have shown that obesity-related neuropathy is a product of excess glucose and lipid accumulation leading to inflammation and cell death. Clinical studies consistently demonstrate obesity is independently associated with neuropathy; therefore, likely a causal risk factor. Dietary weight loss improves neuropathy symptoms but not examination scores. Bariatric surgery and exercise are promising interventions, but larger, more rigorous studies are needed. Further research is also needed to determine the utility of weight loss medications and ideal timing for obesity interventions to prevent neuropathy.
Recent insights into haematology and peripheral nerve disease.
Tomkins O, Lunn MP
Curr Opin Neurol · 2024 Oct · PMID 38861221 · Publisher ↗
PURPOSE OF REVIEW: The association between clonal haematological disorders and peripheral nerve disease is recognized. Paraproteinaemic phenomena are the most common mechanism, but direct neural lymphomatous infiltration...
PURPOSE OF REVIEW: The association between clonal haematological disorders and peripheral nerve disease is recognized. Paraproteinaemic phenomena are the most common mechanism, but direct neural lymphomatous infiltration is seen and can be challenging to diagnose. Traditional and novel anticancer therapies have neuropathic side effects. RECENT FINDINGS: Novel studies using sensitive techniques are refining the incidence of peripheral neuropathy in patients with a monoclonal gammopathy, and the pathogenesis of IgM Peripheral neuropathy (PN) and POEMS syndrome. Recent series give insight into the characteristics and diagnostic challenges of patients with neurolymphomatosis and amyloid light chain amyloidosis. There is an increasing repertoire of effective anticancer drugs in haematological oncology, but chemotherapy-related neuropathy remains a common side effect. SUMMARY: This review of the current literature focuses on recent updates and developments for the paraproteinaemic neuropathies, and the evaluation, diagnosis and treatment of peripheral nerve disease due to high-grade and low-grade lymphomas and lymphoproliferative disorders.
An update on multiple system atrophy.
Stankovic I, Kuijpers M, Kaufmann H
Curr Opin Neurol · 2024 Aug · PMID 38828714 · Full text
PURPOSE OF REVIEW: Multiple system atrophy (MSA) is a rapidly progressive synucleinopathy characterized by autonomic failure, parkinsonism, and cerebellar ataxia. Here, we provide an update on α-synuclein's role in MSA p...
PURPOSE OF REVIEW: Multiple system atrophy (MSA) is a rapidly progressive synucleinopathy characterized by autonomic failure, parkinsonism, and cerebellar ataxia. Here, we provide an update on α-synuclein's role in MSA pathophysiology and review the new Movement Disorders Society (MDS) diagnostic criteria and the utility of α-synuclein-based biomarkers. We also highlight ongoing efforts toward clinical trial readiness and review potential disease-modifying therapies undergoing clinical trials. RECENT FINDINGS: A role of urinary tract infections in triggering α-synuclein aggregation and contribution of genes implicated in oligodendroglial development have been suggested in the MSA pathophysiology. The clinically probable MSA category of the new diagnostic criteria shows improved accuracy in early disease stages. Predictors of phenoconversion from pure autonomic failure to MSA are now better defined. Alpha-synuclein strains in CSF and serum, phosphorylated α-synuclein deposits in the skin, and brain α-synuclein pathology visualized using PET ligand [18F]ACI-12589 are emerging as valuable diagnostic tools. Clinical trials in MSA investigate drugs targeting α-synuclein aggregation or preventing α-synuclein expression, along with stem cell and gene therapies to halt disease progression. SUMMARY: New MSA diagnostic criteria and α-synuclein-based biomarkers may enhance diagnostic accuracy while promising therapies are in development to address disease progression.
Freezing of gait: pharmacological and surgical options.
Gámez-Leyva G, Cubo E
Curr Opin Neurol · 2024 Aug · PMID 38828625 · Publisher ↗
PURPOSE OF REVIEW: The primary aim of this review is to describe and update the pathophysiological and relevant therapeutic strategies for freezing of gait (FoG) in patients with Parkinson's disease (PD). RECENT FINDINGS...
PURPOSE OF REVIEW: The primary aim of this review is to describe and update the pathophysiological and relevant therapeutic strategies for freezing of gait (FoG) in patients with Parkinson's disease (PD). RECENT FINDINGS: FoG presumably involves dysfunction of multiple cortical and subcortical components, including dopaminergic and nondopaminergic circuits. In this regard, levodopa and physical therapy represent the first-choice therapeutic options for PD patients with FoG. However, the relationship between FoG and levodopa is not fully predictable. For those patients with levodopa-resistant FoG, there is promising but still controversial data on the benefits of bilateral high-frequency transcranial magnetic stimulation and deep brain stimulation on the subthalamic nuclei, substantia nigra pars reticulata, pedunculopontine nucleus, and the Fields of Forel. On the other hand, general exercise, gait training with a treadmill, focus attention on gait training, and conventional physiotherapy have demonstrated moderate to large benefits in FoG. SUMMARY: FOG requires different treatment strategies. The inclusion of adequate detection and prediction of FoG combined with double-blind, and statistically powered protocols are needed to improve patients' quality of life, the motor and nonmotor symptoms and societal burden associated with FoG.
PET-based brain molecular connectivity in neurodegenerative disease.
Hanania JU, Reimers E, Bevington CWJ … +1 more , Sossi V
Curr Opin Neurol · 2024 Aug · PMID 38813843 · Publisher ↗
PURPOSE OF REVIEW: Molecular imaging has traditionally been used and interpreted primarily in the context of localized and relatively static neurochemical processes. New understanding of brain function and development of...
PURPOSE OF REVIEW: Molecular imaging has traditionally been used and interpreted primarily in the context of localized and relatively static neurochemical processes. New understanding of brain function and development of novel molecular imaging protocols and analysis methods highlights the relevance of molecular networks that co-exist and interact with functional and structural networks. Although the concept and evidence of disease-specific metabolic brain patterns has existed for some time, only recently has such an approach been applied in the neurotransmitter domain and in the context of multitracer and multimodal studies. This review briefly summarizes initial findings and highlights emerging applications enabled by this new approach. RECENT FINDINGS: Connectivity based approaches applied to molecular and multimodal imaging have uncovered molecular networks with neurodegeneration-related alterations to metabolism and neurotransmission that uniquely relate to clinical findings; better disease stratification paradigms; an improved understanding of the relationships between neurochemical and functional networks and their related alterations, although the directionality of these relationships are still unresolved; and a new understanding of the molecular underpinning of disease-related alteration in resting-state brain activity. SUMMARY: Connectivity approaches are poised to greatly enhance the information that can be extracted from molecular imaging. While currently mostly contributing to enhancing understanding of brain function, they are highly likely to contribute to the identification of specific biomarkers that will improve disease management and clinical care.
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