Annals of Clinical and Translational Neurology最新文献

Uniparental isodisomy (UPiD) can cause mixed phenotypes of imprinting disorders and autosomal-recessive diseases. We present the case of a 3-year-old male with a blended phenotype of TECPR2-related hereditary sensory and autonomic neuropathy (HSAN9) and Temple syndrome (TS14) due to maternal UPiD of chromosome 14, which includes a loss-of-function founder variant in the TECPR2 gene [NM_014844.5: c.1319del, p.Leu440Argfs*19]. This case illustrates challenges associated with a mixed phenotype of ultra-rare disorders and underscores the importance of investigating recessive conditions in homozygosity regions when atypical clinical features occur in patients with well-characterized imprinting disorders.

Objective: To describe peripheral neuropathy associated with familial Creutzfeldt-Jakob disease.

Methods: We report two unrelated patients with genetic Creutzfeldt-Jakob disease with demyelinating peripheral neuropathy as initial presentation, with a comprehensive clinical, electrophysiological and neuropathological description.

Results: Both patients exhibited gait disturbance and paresthesia. Electrodiagnostic studies revealed demyelinating abnormalities with motor conduction blocks suggestive of chronic inflammatory demyelinating polyradiculoneuropathy, with abnormal plexus MRI and elevated CSF protein levels. One of them had pes cavus and a late-onset Charcot-Marie-Tooth (CMT) disease was also initially hypothesized. Central nervous system involvement manifested 1-2 years after the onset of peripheral symptoms. Both patients had a heterozygous E200K mutation in the PRNP gene. Postmortem neuropathological examinations showed PrP^Sc deposits in the peripheral nervous system, particularly in Schwann cells.

Interpretation: Peripheral neuropathy in E200K genetic forms of Creutzfeldt-Jakob disease can be inaugural and mimic chronic inflammatory demyelinating polyradiculoneuropathy.

Objective: We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).

Methods: Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (n = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates. Age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised ALS functional rating scale (ALSFRS-r) total score, and forced vital capacity, from baseline were included as covariates.

Results: Baseline higher GI and GL were associated with less decline of ALSFRS-r total score at 3-month follow-up in the riluzole treatment group (RTG) but not in the no-riluzole group (NRG). When quartile groups were used, GI second [β = -1.9, 95% CI (-4.1, -0.2), p = 0.07], third [β = -3.0, 95% CI (-5.1, -0.8), p < 0.01] and fourth [β = -2.2, 95% CI (-4.3, -0.01), p < 0.05] quartile groups were associated with less ALSFRS-r decline at 3-months compared to the first quartile group (GI < 47.2) among the RTG. Similarly, GL fourth quartile group (GL > 109.5) was associated with less ALSFRS-r decline at 3 months compared to the first quartile group [β = -2.6, 95% CI (-4.7, -0.5), p < 0.05] among the RTG. In NRG, no statistically significant differences in ALSFRS-r decline were found among GI/GL quartile groups.

Interpretation: High dietary GI and GL are associated with a slower functional decline only among ALS patients taking riluzole.

Objective: Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and disease stabilization with recovery of function in some patients. We report our clinical experience with treating patients with SOD1 ALS and the effects of tofersen on outcome measures.

Methods: This was a single-center observational study of patients with SOD1 ALS receiving treatment with tofersen. The effects of tofersen treatment on neurofilament levels, muscle strength, and clinical outcome measures were assessed. Several patients had outpatient neuromuscular rehabilitation in addition to tofersen treatment and we report changes in functional outcomes.

Results: Seven SOD1 ALS patients received treatment at our institution. All patients showed robust and sustained declines in serum NfL and CSF pNFH (mean change serum NfL: -57.9%; mean change CSF pNFH: -67.6%). There was apparent disease stabilization as assessed by the ALSFRS-R total score, mean change 1.1 (SD = 0.7). There was notable improvement in functional independence measured by the FIM motor score, mean change 5.13 points (SD = 3.85).

Interpretation: This study provides evidence that tofersen treatment in SOD1 ALS can lead to meaningful preservation of function and suggestions of sustained improvement in neurologic function in some patients, and strongly supports the role of neurofilaments as therapeutic biomarkers.

Objective: Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.

Methods: This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia.

Results: In our cohort of 642 patients, 318 (49.6%) had psychiatric symptoms at the time of initial presentation, including 78.2% with autoimmune etiologies and 35.2% with viral etiologies (P < 0.001). Those with psychiatric symptoms were younger (median age 47.5 vs. 51.5; P < 0.001), and more likely to have a history of documented psychiatric disorders, as well as longer lengths of hospital stay, and poorer discharge outcomes. Of patients initially admitted to a psychiatric service (n = 28), most had autoimmune causes, although 3 out of 28 (10.7%) had herpes viral infections; admission to a psychiatric service was associated with substantially longer interval to initiation of antivirals and immunotherapy. Autoimmune and infectious etiologies differed in the spectrum and frequency of psychiatric manifestations.

Interpretation: Psychiatric symptoms are common across etiologies of encephalitis and are associated with longer lengths of hospital stay and worse clinical outcomes. Specific patterns and dimensionality of psychiatric symptoms distinguish autoimmune from infectious causes.

Episodic memory is a critical cognitive function that enables the encoding, storage, and retrieval of new information. Memory consolidation, a key stage of episodic memory, stabilizes this newly encoded information into long-lasting brain "storage." Studies using fMRI to investigate post-encoding awake rest holds promise to shed light on early, immediate consolidation mechanisms. Here, we review fMRI studies during episodic memory to document common methods to investigate post-encoding consolidation, such as multivoxel pattern analysis (MVPA) and functional connectivity, and the current state of the science in both healthy younger and older adults. In young adults, post-encoding reactivation of stimuli-specific neural patterns in the hippocampus and its connectivity with cortical and subcortical areas (e.g., visual-temporal cortex, medial prefrontal, and medial parietal cortex) correlate with subsequent memory performance. Conversely, studies in older adults highlight the importance of large-scale brain networks during post-encoding rest, particularly the default mode network (DMN). Alterations in connectivity between the DMN and task-positive networks may help older adults maintain episodic memory. Furthermore, non-invasive brain stimulation techniques can enhance these post-encoding consolidation processes and improve memory performance in both younger and older adults. Notably, a lack of studies has investigated post-encoding memory consolidation in neurodegenerative disorders. This review underscores the importance of understanding how post-encoding neural reactivation and connectivity evolve with age to partially explain age-related declines in episodic memory performance and how such declines can be restored.

Objective: Evidence for an association between psoriasis and dementia is limited and conflicting. We aimed to investigate the association using large and representative population-based data and describe risk by dementia subtype and over time.

Methods: We compared dementia risk between people with and without psoriasis using an age-, sex- and primary care practice-matched cohort of adults aged ≥40 years from the Clinical Practice Research Datalink Aurum in England (1997-2021) linked to hospital admissions data, analysed with stratified Cox regression.

Results: Among 360,014 individuals with psoriasis and 1,799,617 without, psoriasis was associated with a small increased risk of all-cause dementia (adjusted hazard ratio [aHR] 1.06, 95% CI 1.04-1.08; absolute rate difference 24 per 100,000 person-years). Strength of association increased with time since psoriasis diagnosis (e.g. aHR 0.99, 0.96-1.03 within 0 to 5 years; 1.20, 1.05-1.37 within 20 to 25 years). The association was stronger for vascular dementia (aHR 1.10, 1.06-1.14) than Alzheimer's dementia (aHR 1.03, 1.00-1.06). Hazard ratios were larger for severe psoriasis (all-cause aHR 1.32, 1.25-1.39; vascular aHR 1.58, 1.44-1.74; Alzheimer's aHR 1.11, 1.02-1.21).

Interpretation: Long-term risk of all-cause dementia and vascular dementia, but not Alzheimer's dementia, was slightly higher in people with psoriasis, but absolute risk differences were small. Risks were more substantially raised with time since psoriasis diagnosis and in severe psoriasis compared to mild to moderate psoriasis, suggesting a potential dose-response relationship.

This study evaluated disease activity in people with Multiple Sclerosis (PwMS) who received immune checkpoint inhibitors (ICIs) compared to PwMS not treated with ICIs. There were 108 PwMS included (27 PwMS+ICIs and 81 PwMS controls), matched on age, sex, disease duration, DMTs, and MS disease course. Of 27 PwMS+ICIs, one (4%) had a relapse and four (15%) developed new MRI lesions without clinical symptoms. Time to relapse and MRI activity were compared using Kaplan-Meier curves and Cox regression models. There was no significant difference for either time to relapse (p = 0.34) or MRI activity (p = 0.15) in PwMS+ICIs compared to controls.