Orthostatic dizziness and lightheadedness are frequent complaints in patients age 60 and above, whereas various common and uncommon etiologies need to be considered, including medication side effects, cardiovascular and metabolic causes and neurologic disorders. Autonomic dysfunction is a common etiology that warrants comprehensive medical and neurologic evaluations for identification of neurogenic orthostatic hypotension, prodromal Parkinson's disease, Lew body dementia, pure autonomic failure and others. In this article, key historical details, physical exam findings and diagnostic investigations for orthostatic dizziness are discussed. Patients' report of chronic and persistent orthostatic intolerance, even in the absence of objective orthostatic hypotension, should serve as a reliable and sufficient key feature should prompt an evaluation for autonomic and neurodegenerative disorders.

Existing evidence from cohort studies of atypical parkinsonism has demonstrated that median time from symptom onset to diagnosis is 3.4 years for progressive supranuclear palsy (PSP) and 3.1 years for multiple system atrophy (MSA). This compares to only 1.0-1.2 years in Parkinson's disease (PD). Earlier diagnosis is essential to facilitate recruitment to disease-modifying treatment trials. In the Early Assessment, Diagnosis and Treatment of Parkinsonism and Related Syndromes study, we will prospectively assess patients across the UK with incident parkinsonism and determine the best predictors to improve early diagnosis of the 'Parkinson-plus' syndromes (PPS) and build a trial-ready cohort.

To provide an update on the pathophysiology, phenotyping, and management of post-traumatic headache (PTH) following mild traumatic brain injury (mTBI), and to propose a phenotype-guided framework for evaluation and treatment.

Introduction: Adult-onset Alexander disease (AOAD) is a rare astrocytopathy linked to the glial fibrillary acidic protein (GFAP) gene, which is known for its clinical heterogeneity and common misdiagnosis. In adults, it may present with bulbar dysfunction, pyramidal signs, ataxia, dysautonomia, cognitive decline, or parkinsonism, which often mimics atypical parkinsonian syndromes like multiple system atrophy (MSA). The purpose of this case series was to define practical clinical, radiological, and genetic cues for suspecting AOAD in adults with atypical parkinsonism, autonomic dysfunction, or paroxysmal focal symptoms, particularly when genetic findings are inconclusive. Case Presentation: Four patients, aged 40 to 59 years, had progressive and varied neurological symptoms, like gait disturbance, lower limb weakness, dysarthria, dysphagia, autonomic dysfunction, parkinsonism, cognitive decline, and paroxysmal focal deficits. Initial diagnoses were parkinsonian syndrome, stroke, transient ischemic attack (TIA), and MSA. Diagnostic Assessment and Intervention: Brain magnetic resonance imaging (MRI) in all patients showed characteristic lower brainstem abnormalities, particularly atrophy of the medulla oblongata and upper cervical spinal cord, consistent with the "tadpole sign." GFAP sequencing identified one likely pathogenic variant (p.Arg70Trp) and three variants of uncertain significance: p.Glu122_Arg124del, p.Met415Ile, and p.Glu195Val. Management was mainly symptomatic; one patient showed significant motor improvement after repetitive transcranial magnetic stimulation (rTMS). Conclusions: AOAD should be considered in adults with parkinsonism-plus syndromes or unexplained combinations of bulbar symptoms, pyramidal signs, autonomic dysfunction, and cognitive decline. Recognizing the tadpole sign on MRI may improve diagnostic accuracy, particularly when genetic results are inconclusive.

Background and Objectives: Parkinson's disease (PD) includes a prodromal phase characterized by non-motor symptoms (NMS). We investigated whether sleep disturbances co-aggregate with other NMS in suspected prodromal PD (p-PD) to refine early phenotyping and risk stratification. Materials and Methods: A population-based survey was conducted in Kaunas, Lithuania. Participants from the Kaunas City preventive health screening cohort (2024-2025) were screened using the Innsbruck REM Sleep Behaviour Disorder Inventory (RBD-I). Sixty-two individuals were included: 31 with suspected p-PD and 31 controls. Demographic characteristics, clinical features, sleep symptoms, olfactory function, autonomic symptoms, cognition, and mood were assessed. Between-group comparisons and within-group correlation analyses were performed. Results: Groups did not differ in age, sex, education, lifestyle exposures, or family history (all p > 0.05). Compared with controls, individuals with suspected p-PD had a higher prevalence of insomnia (71.0% vs. 12.9%, p < 0.001), pathological daytime sleepiness (22.6% vs. 0%, p = 0.005), cognitive impairment (54.8% vs. 16.1%, p = 0.001), and constipation (32.3% vs. 0%, p = 0.002). As expected from the predefined enrichment strategy, hyposmia and orthostatic hypotension (OH) were observed only among suspected p-PD participants. Within the suspected p-PD group, the Non-Motor Symptoms Questionnaire (NMSQ) scores correlated with depressive/anxiety symptoms (r = 0.578, p = 0.001). Olfactory dysfunction correlated with cognitive impairment (r = 0.410, p = 0.001) and depressive/anxiety symptoms (r = 0.396, p = 0.001). Conclusions: Sleep disturbances, particularly insomnia and excessive daytime sleepiness, co-occurred with cognitive, affective, and gastrointestinal non-motor manifestations in individuals with suspected p-PD, supporting the concept of a broader prodromal phenotype. Comprehensive screening in individuals with RBD symptoms may improve early PD risk stratification beyond single-marker approaches.

Multiple system atrophy (MSA) is a rare and rapidly progressive neurodegenerative disorder characterized by a variable combination of autonomic failure, parkinsonism, and cerebellar ataxia, with a median survival of 8-10 years from symptom onset. Its aetiology remains poorly understood, as most cases are sporadic and environmental contributors remain unclear. Neuropathologically, MSA is defined by the accumulation of α-synuclein within oligodendroglial cells, forming glial cytoplasmic inclusions that drive widespread neurodegeneration in striatonigral and olivopontocerebellar systems. Recent advances in diagnostic criteria and biomarker development have improved disease recognition; however, early diagnosis remains challenging, particularly during the prodromal phase, when clinical features overlap with other α-synucleinopathies. Advances in fluid biomarkers and multimodal imaging are expected to facilitate earlier detection, improve diagnostic accuracy, and provide more robust tools for monitoring disease progression. Therapeutic development has largely focused on targeting α-synuclein pathology, but these approaches have not yet demonstrated consistent clinical benefit, highlighting the biological complexity of MSA. In the absence of curative treatments, management remains largely supportive, aimed at symptom control, particularly addressing autonomic dysfunction and motor impairment. Emerging care models, including telemedicine and multidisciplinary management, are reshaping clinical practice and may improve access to specialized care. Bridging advances in pathophysiology with patient-centred care will be essential for improving outcomes in MSA.

ObjectiveTo investigate the association of cardiac autonomic dysfunction with clinical staging and disease progression rate upon diagnosis of amyotrophic lateral sclerosis (ALS), and its impact on survival.Methods24-hour Holter was performed in 95 ALS patients at diagnosis and 39 controls. Patients were grouped by King's Clinical Staging and progression rate (ΔFS, median cut-off 0.67). Heart rate variability parameters were compared across groups. A survival-based cut-point optimization approach was used to determine the cut-off value of standard deviation of all normal-to-normal intervals (SDNN). Kaplan-Meier estimator and multivariable Cox regression analysis were used to evaluate of the effect of SDNN on survival during a median follow-up of 21.5 months.ResultsΔFS in ALS patients in King's Stage 4 upon diagnosis was faster (P=0.007) compared to that of those diagnosed in earlier stages, featuring a higher incidence of respiratory (P<0.001) and bulbar symptoms (P<0.001). In addition, ALS patients in King's Stage 4 exhibited elevated HR-min (P=0.007) and decreased RR intervals (RRI) (P=0.032), SDNN (P=0.004), and standard deviation of the averages of NN intervals in all 5-min segments (SDANN) values (P=0.020) compared to controls. Patients in the ΔFS-fast group had a higher HR-min than those in the ΔFS-slow group (P=0.013) and controls (P=0.003) and lower SDNN (P=0.018) than controls. Both Kaplan-Meier estimator (P=0.03) and multivariable Cox regression analysis (P=0.019) showed that lower SDNN (cut-off value: 111 ms) was associated with poor survival in ALS patients.ConclusionUpon diagnosis, ALS patients in King's Stage 4 and with faster disease progression demonstrated significantly diminished cardiac autonomic control. Lower SDNN was associated with poor survival in ALS.

N-methyl-D-aspartate (NMDA) receptor encephalitis stands as the most common form of autoimmune encephalitis in young adults, characterized by a spectrum of distressing symptoms such as seizures, behavioral disruptions, autonomic dysfunction, and memory impairment. We present a noteworthy case involving a young adult male exhibiting seizures and renal failure, initially prompting an evaluation for vasculitis, hyperuricemia-induced acute kidney injury (AKI), and rhabdomyolysis-induced AKI. However, subsequent findings revealed the presence of NMDA receptor antibodies, and a renal biopsy confirmed tubulointerstitial nephritis. This case sheds light on the association between renal failure and NMDA receptor antibody-associated encephalitis, marking a rare instance in our knowledge.

Frontotemporal dementia (FTD) and Lewy body dementia (LBD) are distinct neurodegenerative disorders that rarely co-occur. However, their overlapping features can obscure diagnosis and complicate management. We present the case of a 65-year-old man with a history of alcohol use disorder, diabetes, and blindness who developed acute behavioral changes, catatonia, and fluctuating mental status. He exhibited signs consistent with a behavioral variant FTD, including disinhibition, executive dysfunction, and hypersexuality, as well as features associated with LBD, including visual hallucinations, autonomic instability, and waxing-and-waning impairment in cognition. His hospital course was marked by episodic disorientation, variable language use, and persecutory delusions. Neuroimaging, cerebrospinal fluid analysis, and serial neuropsychological testing yielded mixed and inconclusive results, contributing to the diagnostic ambiguity. Treatment included lorazepam, which improved catatonic symptoms but was discontinued due to risk of delirium, and aripiprazole, which was tapered due to suspected neuroleptic sensitivity. The patient was ultimately discharged to memory care with a diagnosis of an unspecified dementia. This case underscores the challenges of diagnosing and managing patients with overlapping features of multiple neurodegenerative disorders. Recognizing points of overlap between syndromes like FTD and LBD is key to tailoring interventions and avoiding harm. Serial cognitive assessments, functional neuroimaging, and biomarker analysis may improve diagnostic accuracy, although these tools have limitations. A deeper understanding of the pathophysiology of overlapping dementia syndromes is crucial for improving diagnostic clarity and guiding treatment strategies.