Neurology. Clinical practice最新文献

Objectives: The aim of this study was to evaluate the causes of suspected neurodegeneration in adults with histiocytic neoplasms.

Methods: Patients with histiocytic neoplasms were identified. Inclusion criteria were (1) diagnosis of histiocytic neoplasm; (2) the treating hematologist suspected neurodegeneration; and (3) patients age 18 years or older. Active CNS histiocytic neoplasm was defined as new or enlarging T2 lesions, or gadolinium enhancing lesions on MRI.

Results: Neurodegeneration was suspected in 23 of 478 patients. A progressive neurologic disorder was confirmed in 15 of 23 patients and was associated with an underlying active (12/15) or inactive (3/15) histiocytic neoplasm. Of the 8 patients without a progressive neurologic disorder, diagnoses included fixed deficit from histiocytic neoplasm (3/8), depression (2/8), fatigue (1/8), pain (1/8), and stroke (1/8). Of the 3 of 15 patients with progressive neurologic dysfunction and inactive CNS histiocytic neoplasm, all had progressive pontocerebellar dysfunction. Progressive pontocerebellar atrophy on MRI was present in 10 of 13 patients with progressive symptoms, and 2 of 6 patients with no progressive symptoms.

Discussion: Progressive neurologic dysfunction in adult patients with histiocytic neoplasms is most frequently because of an active histiocytic neoplasm or nonhistiocytic etiology. A minority of patients have presumed nonneoplastic progressive neurologic dysfunction, primarily associated with pontocerebellar atrophy.

Background and objectives: Intravenous ketamine is increasingly used for refractory and super-refractory status epilepticus (RSE/SRSE), yet its efficacy and optimal use remain uncertain. We therefore aimed to synthesize the available evidence to quantify the effectiveness of ketamine in achieving seizure cessation and to explore differences in treatment characteristics between patients who respond and those who do not.

Methods: We conducted a systematic review and meta-analysis to estimate the pooled seizure cessation rate associated with intravenous ketamine. Secondary analyses compared ketamine initiation timing, dosing, and infusion duration between patients who achieved seizure cessation (responders) and those who did not (nonresponders).

Results: Fourteen studies comprising 388 adult patients (249 responders, 139 nonresponders) were included. The pooled seizure cessation rate with ketamine was 64% (95% CI 49%-76%) with moderate heterogeneity (I ² = 54.1%). Sensitivity analysis showed no single study substantially influenced results, supporting robustness. Responders received ketamine earlier (3.2 ± 2.6 days) than non-responders (4.3 ± 2.6 days), mean difference of -0.90 days (95% CI: -1.31 to -0.49; p < 0.0001). The mean maintenance dose was 2.5 ± 1.4 mg/kg/hr (responders: 2.5 ± 1.3; nonresponders: 2.6 ± 1.4), with no significant difference between groups (mean difference -0.14 mg/kg/hr; 95% CI -0.45 to 0.18; p = 0.39). Infusion duration averaged 5.0 ± 4.2 days in both groups, with no significant difference (mean difference -0.07 days; 95% CI -1.02 to 0.88; p = 0.88). Ketamine discontinuation due to adverse events was rare (0.7%, 3/55 patients).

Discussion: Intravenous ketamine demonstrates consistent effectiveness and safety as an adjunctive therapy in RSE/SRSE. However, the timing of initiation cannot be reliably linked to improved clinical outcomes given current methodological limitations and heterogeneity across studies. Future prospective research using standardized definitions and rigorous temporal data collection is needed to clarify whether the timing of ketamine initiation independently influences therapeutic success and to define its optimal integration within established status epilepticus (SE) treatment algorithms.

Registration: The systematic review was registered (June 7, 2024) with the International Prospective Register of Systematic Reviews (PROSPERO, CRD42024549523).

Background and objectives: Spontaneous intracranial hypotension (SIH) profoundly affects quality of life. We aimed to identify and quantify various aspects of patients' experiences with SIH.

Methods: We piloted an "SIH Impact Inventory," a cross-sectional survey developed in collaboration with patients, family members, and caregivers. Potential participants were identified from a single center using diagnosis and procedure codes. Participants completed the inventory online using REDCap between December 2021 and April 2022.

Results: Ninety-eight adult patients completed the inventory. The mean age was 50.6 years, and 69.4% were female. Sixty-three percent had a confirmed diagnosis of SIH, and 36.7% had clinically suspected but unconfirmed SIH. The mean time to diagnosis was 2.0 (interquartile range: 0.5-4.8) years; 25.5% went undiagnosed for 5 or more years, and 75% were initially misdiagnosed. The 3 most common symptoms were head pain, neck pain, and "brain fog." Of those undergoing epidural blood patch procedures, 22% experienced relief of symptoms for a median time of 1.3 months; those with a confirmed diagnosis had more prolonged relief. 58.2% reported experiencing rebound intracranial hypertension after a therapeutic procedure. Surgical repair of the leak was most likely to result in a symptom-free status (p = 0.003) than nonsurgical treatments. Of those working for compensation when they developed SIH, 95.2% indicated that the condition affected their ability to work and 65.1% stopped working. The financial burden was substantial for 65.3% of our cohort, with medical expenses (98.4%) and travel for health care (65.6%) being the most prevalent expenses. SIH negatively affected personal and family relationships for most patients.

Discussion: Individuals with confirmed and suspected SIH experience difficulties related to the disorder itself and the lengthy process of diagnosis and treatment. Our findings demonstrate the marked impact of SIH on employment, education, interpersonal relationships, and finances. Compared with previous studies, our cohort reported considerable cognitive difficulties, with rates approaching those of head pain. Heightened awareness of SIH, referral to a center with expertise in SIH, increasing the number and geographic distribution of SIH centers, and advances in diagnostic and treatment modalities can help alleviate some of the challenges that patients face.

Background and objectives: Migraine is a significant disabling neurologic headache disorder globally. Evaluating patient-related outcomes (PROs) is necessary to assess the impact of therapeutic interventions in preventive therapy. An exploratory analysis of data from the EMPOwER study examined the effect of erenumab on PROs in patients with episodic migraine (EM) in regions underrepresented in the pivotal Phase 3 trials of erenumab, specifically Asia, the Middle East, and Latin America.

Methods: Patients (N = 900) were randomized (2:3:3) to receive monthly subcutaneous injections of erenumab 140 mg, erenumab 70 mg, or placebo. Adjusted mean changes from baseline in the Headache Impact Test (HIT-6), Migraine Physical Function Impact Diary (MPFID), modified Migraine Disability Assessment (mMIDAS), and EuroQoL 5-dimension 5-level scale (EQ-5D-5L) scores were assessed during the double-blind treatment phase of 3 months.

Results: A statistically significant reduction from baseline in the HIT-6 total score was observed for erenumab 140 mg (-9.34, p < 0.001) and 70 mg (-8.39, p = 0.004) vs placebo (-6.62) at Month 3. Improvement in MPFID scores was also greater in the erenumab groups vs the placebo group (Everyday Activity: 140 mg, -5.61 [p = 0.002]; 70 mg, -4.94 [p = 0.011]; placebo, -3.19; Physical Impairment: 140 mg, -4.27 [p = 0.014]; 70 mg, -3.95 [p = 0.021]; placebo, -2.31) at Month 3. Similar findings were observed for mMIDAS scores (140 mg -8.99 [p < 0.001], 70 mg -8.11 [p = 0.011] vs placebo [-6.59]) and the EQ-5D-5L quality-of-life visual analog scale scores (140 mg 8.13 [p = 0.017], 70 mg 7.08 [p = 0.088] vs placebo [5.22]), although no meaningful between-group difference was noted for index values.

Discussion: Erenumab showed favorable effects on PROs when compared with placebo in patients with EM. These results enhance the evidence for erenumab as an effective preventive therapy for patients with EM.

Trial registration information: Clinicaltrials.gov/study/NCT03333109.

Biologic therapeutics have revolutionized treatment of disorders for which there were previously limited options. Biologic products are typically very expensive. However, the emergence of biosimilars (a biologic product that is nearly identical to a Food and Drug Administration [FDA]-approved "branded" version) offers an opportunity to reduce costs after the branded product's period of patent protection ends. Despite the promise of biosimilars, some physicians have expressed concern regarding interchangeability, especially in specific patient populations. The American Academy of Neurology (AAN) supports the cost-saving potential of biosimilar therapeutics while emphasizing the importance of a balance between reducing costs, maintaining clinical efficacy, and preserving the integrity of the physician-patient relationship. This position statement from the AAN offers a framework to aid neurologists in deciding whether to switch a patient from a branded biologic product to a biosimilar therapeutic. This framework aligns with broader AAN policies on drug pricing and medical decision-making autonomy.

Purpose of review: There is no consensus or standardized framework to characterize disease activity in CNS neurosarcoidosis, and the existing literature is highly heterogeneous. Here, we aimed to aggregate all longitudinal monitoring metrics in neurosarcoidosis through a systematic review. The review protocol is registered in PROSPERO (ID:533857). Articles were included if they incorporated at least 1 longitudinal monitoring or outcome metric relevant to neurosarcoidosis disease activity. In addition, we aimed to establish an evidence-based clinical framework for characterizing, monitoring, and communicating neurosarcoidosis disease activity, applicable to both clinical care and research.

Recent findings: Of 387 articles initially identified, 67 met the inclusion criteria. Most studies focused on metrics within a single domain (clinical, imaging, or laboratory) or analyzed multiple domains independently. Often, the definitions were not formally outlined. Only 11 studies included a multidomain monitoring metric. Our proposed framework integrates 3 critical domains for assessing the neurosarcoidosis disease activity: (1) clinical, (2) imaging, and (3) laboratory and supports a standardized characterization of the disease, especially when domain results are discordant. The overarching goal in defining the elements of each domain was to prioritize specificity in attributing activity to neurosarcoidosis while minimizing the risk of misattribution. Each domain includes criteria for 4 categories of disease status: "improved," "stable," "worsened," or "resolved." The overall disease status of activity or inactivity is then determined by reconciling the independent domains into a summary disease activity assessment, communicated with additional clinical context, including immune treatment status and neuroanatomic localization. Sustained clinical stability of persistent neurologic symptoms or signs in the absence of MRI or CSF activity is considered in the summary assessment to reflect inactive disease with sustained neurologic deficits.

Summary: A systematic review highlighted substantial heterogeneity in how CNS neurosarcoidosis disease activity is measured, with many studies lacking formal definitions and often reporting activity only within isolated domains. This proposed framework integrates multiple domains to comprehensively characterize CNS neurosarcoidosis disease activity. With further validation, this approach has the potential to standardize research practices and improve clinical reasoning and communication.

Purpose of review: Idiopathic normal pressure hydrocephalus (iNPH) is a treatable condition characterized by impaired gait, cognition, and bladder function. Neuropsychiatric symptoms may be important in iNPH but are poorly understood. We report the first systematic review and meta-analysis estimating the prevalence, severity, and treatment responsiveness of neuropsychiatric symptoms and diagnoses in iNPH. We searched PubMed, CINAHL, Embase, Ovid, MEDLINE, Cochrane, and PsycINFO from inception until October 23, 2024, for peer-reviewed, original studies in adults with definite, probable, or possible iNPH that reported neuropsychiatric features using validated tools or clinician diagnosis (PROSPERO CRD42021287293). Case studies and series, as well as studies where diagnostic criteria for iNPH were unclear, were excluded. Study quality assessment and data extraction were independently performed by 2 authors, according to a proforma developed iteratively. Random-effects meta-analysis was used to pool proportions and standardized mean differences. Meta-regression, subgroup analysis, and sensitivity analysis were performed.

Recent findings: Twenty-two studies were included, of which 1 was a randomized-controlled trial. For our primary outcome, we found a high prevalence of apathy (69.2%, 95% CI 63.1-74.6, n = 293) and depression (30.1%, 20.1-42.3, n = 7,670) in iNPH. Agitation (22.6%, 11.8-39.1), anxiety (21.9%, 13.2-34.2), disinhibition (21.0%, 11.8-34.7), and psychotic syndromes (8.0%, 3.3-18.3) were relatively less prevalent. Depression scores were higher in patients with iNPH than in controls (Hedge's g 1.31, 0.39-2.23). Treatment of iNPH was associated with a reduction in depression scores (-0.30, -0.62 to 0.01), although the confidence interval contained the null. A total of 12 of 22 studies were rated 'low' quality.

Summary: Apathy and depression are highly prevalent in iNPH, maybe more so than in other neurodegenerative conditions. Little is known about other neuropsychiatric features in iNPH. Treatment of iNPH may reduce neuropsychiatric symptoms, particularly depression. However, our study was limited by heterogeneity in populations and assessment tools and a lack of baseline data on neuropsychiatric symptoms before iNPH diagnosis. These findings highlight the urgent need for further research into neuropsychiatric features in iNPH, their mechanisms, and their potential response to treatment.

Background and objectives: Vesicular monoamine transporter 2 inhibitors (VMAT2is) have demonstrated effectiveness in attenuating motor symptoms of Huntington disease (HD). However, evidence regarding their long-term safety and overall efficacy in this population remains limited. The aim of this study was to investigate the efficacy and safety of VMAT2is in the treatment of HD.

Methods: We performed a meta-analysis of placebo-controlled, randomized controlled trials (RCTs) of VMAT2is in patients with HD. PubMed, Embase, and Cochrane databases were searched for trials up to February 8, 2025. Data were extracted from published reports, and quality assessment was performed per Cochrane recommendations. Binary end points were compared using odds ratios (ORs) while continuous end points were compared using mean difference (MD) and standardized MD (SMD), with 95% CIs for all measures. The analysis end points included changes in the Unified Huntington's Disease Rating Scale-Total Maximal Chorea (UHDRS-TMC), improvements in the Clinical Global Impression of Change (CGI-C), incidence of adverse effects, and alterations in depression scale scores.

Results: Of 336 database results, 3 RCTs and 302 patients were included; 163 (53.97%) received VMAT2is. The UHDRS-TMC (MD -2.98; 95% CI [-4.21 to -1.75]; p = 0.009; I ² = 0%) and CGI-C (OR 5.36; CI 95% [2.94-9.76]; p = 0.007; I ² = 0%) scores were significantly improved in the intervention group. In addition, the therapy did not influence the adverse effects (OR 1.89; CI 95% [0.47-7.70]; p = 0.19 I ² = 28%) and depression scale scores (SMD -0.40; 95% CI [-1.20 to 0.41]; p = 0.17; I ² = 59%).

Discussion: In patients with HD, treatment with VMAT2is improved chorea (UHDRS-TMC and CGI-C), with no significant changes in adverse effects or depressive symptoms. These findings indicate that VMAT2is may be a promising and safe treatment option for the disease.

Objectives: Thrombotic thrombocytopenic purpura (TTP) is rare, life-threatening autoimmune disorder characterized by microvascular thrombosis, severe thrombocytopenia, and hemolytic anemia. It can lead to organ ischemia and increase the risk of thromboembolic events, including acute ischemic stroke (AIS). Caplacizumab, an essential adjunct in TTP management, rapidly inhibits platelet aggregation and prevents disease progression.

Methods: We present 3 cases of TTP diagnosed in patients with AIS. Treatment included plasma exchange (PLEX), corticosteroids, and caplacizumab.

Results: All 3 patients exhibited acute neurologic deficits, with brain MRI confirming AIS. Laboratory tests revealed thrombocytopenia, hemolytic anemia, and ADAMTS-13 activity <1%, confirming TTP. Two patients initially treated only with PLEX and corticosteroids experienced thrombocytopenia exacerbation, requiring caplacizumab for stabilization. The third patient, treated with caplacizumab from stroke onset, maintained stable platelet counts without exacerbation. No adverse events or deaths occurred, emphasizing caplacizumab's role in sustained hematologic recovery.

Discussion: This case series underscores caplacizumab's potential role in stabilizing platelet counts, reducing exacerbation rates, and improving clinical outcomes in TTP-associated AIS. Although all patients experienced favorable neurologic outcomes, a faster recovery cannot be directly attributed to caplacizumab given the multimodal treatment approach. These findings are suggestive of its early use as first-line adjunct, potentially optimizing treatment strategies and improving prognosis.

Background and objectives: Neurocysticercosis is the most common parasitic infection of the CNS and remains a significant, yet often neglected, public health issue in endemic regions. High-quality evidence suggests that albendazole monotherapy leads to superior clinical outcomes compared with placebo or praziquantel. However, there is still insufficient evidence regarding the efficacy and safety of combined albendazole-praziquantel therapy. This systematic review and meta-analysis aims to compare combined antiparasitic therapy with albendazole and praziquantel with albendazole monotherapy, evaluating whether dual therapy offers superior therapeutic benefits in the management of neurocysticercosis while maintaining an acceptable safety profile.

Methods: We searched MEDLINE, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published until April 2024 that compared combined albendazole-praziquantel therapy with albendazole monotherapy for the treatment of neurocysticercosis. Statistical analysis was performed using Review Manager 5.4.1, with odds ratios (ORs) and 95% confidence intervals (CIs) reported. A random-effects model was applied to all end points. The risk of bias was assessed for each study, and the certainty of evidence was evaluated using the GRADE approach.

Results: Five RCTs were included, comprising a total of 320 patients, 49% of whom received combined therapy. Complete cyst resolution was significantly more frequent in patients treated with combined albendazole-praziquantel therapy compared with albendazole monotherapy (OR = 3.06; 95% CI [1.81-5.19]; p = 0.0001; I ² = 5%; high-certainty evidence). In a subgroup analysis restricted to patients with 1-2 cysts (248 patients), no statistically significant difference in complete cyst resolution was observed (OR = 1.98; 95% CI [0.92-4.27]; p = 0.08; I ² = 34%; very-low-certainty evidence). There was no significant difference in seizure recurrence between treatment strategies (OR = 1.28, 95% CI [0.56-2.91], p = 0.55, I ² = 0%; moderate-certainty evidence). Similarly, the incidence of adverse effects did not differ significantly between groups (OR = 1.40, 95% CI [0.72-2.72], p = 0.30, I ² = 0%; moderate-certainty evidence).

Discussion: This systematic review and meta-analysis demonstrated a threefold increase in complete cyst resolution among patients receiving combined therapy, suggesting its superiority over albendazole monotherapy for the management of neurocysticercosis. In addition, no significant differences were observed between treatment strategies regarding seizure or adverse events.