Search Results (14)

Background: Episodic ataxia type 2 (EA2) is the most common subtype of episodic ataxia and is primarily caused by pathogenic variants in the CACNA1A gene. Although classically characterized by paroxysmal ataxia, CACNA1A-related disorders are increasingly recognized as an age-dependent phenotypic continuum that extends beyond episodic cerebellar dysfunction to include fluctuating weakness, persistent neurological signs, and neurodevelopmental impairments. Case report: A 12-year-old boy presented with episodic vertigo. His medical history was notable for infantile paroxysmal tonic upward gaze beginning at 6 months of age. From the age of 7 years, he developed frequent episodes of vertigo and ataxia lasting 2 to 3 h. At 10 years of age, he experienced an episode of acute lower limb weakness with diminished deep tendon reflexes, without prominent ataxia. Guillain–Barré syndrome was initially suspected, and he received two courses of intravenous immunoglobulin, with only transient improvement. Neurophysiological studies were largely unremarkable, except for an isolated decremental response on repetitive nerve stimulation. In addition to paroxysmal events, he exhibited persistent interictal cerebellar signs, including dysmetria, dysdiadochokinesia, and downbeat nystagmus. Neuropsychological testing revealed mild intellectual disability with prominent visuospatial deficits. Trio-based whole-exome sequencing identified a de novo CACNA1A splice donor variant (c.978 + 1G > A), confirming the diagnosis of EA2. Treatment with acetazolamide resulted in marked improvement in episodic ataxic events. Conclusions: This case highlights EA2 as part of a broader CACNA1A-related phenotypic continuum rather than a purely paroxysmal disorder. Awareness of atypical and age-dependent manifestations is crucial to avoid diagnostic pitfalls and to facilitate the timely initiation of targeted therapy and appropriate developmental support. Full article

Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). While it is known to affect the autonomic nervous system, the relationship between left atrial (LA) remodeling and PVI-mediated neuromodulation remains unclear. We aimed to assess the neuromodulatory effects of PVI using skin sympathetic nerve activity (SKNA). SKNA was recorded one day before and 2–3 days after PVI in 28 paroxysmal AF (PAF) and 33 persistent AF (PerAF) groups. Baseline low frequency to high frequency (LF/HF) ratio was higher in the PAF group (1.23 [interquartile range {IQR}: 0.79–1.76] vs. 0.74 [IQR: 0.49–1.38], p = 0.017). After PVI, the PAF group demonstrated significant reductions in burst amplitude (1.46 [IQR: 1.04–2.84] vs. 1.09 [IQR: 0.78–2.17] μV, p = 0.015) and LF/HF ratio (0.91 [IQR: 0.73–1.52] vs. 0.71 [IQR: 0.48–1.21], p = 0.012), whereas the PerAF group exhibited no such changes. A weak positive correlation was observed between the percentage change in LF/HF ratio and LA volume index in the PAF group (r = 0.572, p = 0.002). PVI significantly decreased SKNA in PAF patients but not in PerAF. LA remodeling may hinder the effectiveness of PVI-mediated neuromodulation. Full article

Flow cytometry plays a fundamental role in the diagnosis of leukemias and lymphomas, as well as in the follow-up and evaluation of minimally measurable disease after treatment. In some instances, such as in the case of acute promyelocytic leukemia (APL), rapid diagnosis is required to avoid death due to serious blood clotting or bleeding complications. Given that promyelocytes do not express the glycophosphatidylinositol (GPI)-anchored protein CD16 and that deficient CD16 expression is a feature of some CD16 polymorphisms and paroxysmal nocturnal hemoglobinuria (PNH), we included the GPI anchor probe FLAER aerolysin in the APL flow cytometry probe panel. Initial tests showed that FLAER binding was absent in pathological promyelocytes from APL patients but was consistently detected with high intensity in healthy promyelocytes from control bone marrow. FLAER binding was studied in 71 hematologic malignancies. Appropriate control cells were obtained from 16 bone marrow samples from patients with idiopathic thrombocytopenic purpura and non-infiltrated non-Hodgkin’s lymphoma. Compared with the positive FLAER signal in promyelocytes from healthy bone marrow, malignant promyelocytes from APL patients showed weak or negative FLAER binding. The FLAER signal in APL promyelocytes was also lower than that in control myeloid progenitors and precursors from patients with other forms of acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, or myelodysplastic syndrome. Minimal measurable disease studies performed in APL patients after treatment found normal promyelocyte expression when minimal measurable disease was negative and FLAER-negative promyelocytes when disease relapse was detected. The inclusion of FLAER in the flow cytometry diagnosis and follow-up of APL could be very helpful. Decreased FLAER binding was found in all cases of APL, confirmed by the detection of the PML-RARA fusion transcript and, to a lesser extent, in the other AMLs studied. This study also revealed FLAER differences in other acute leukemias and even between different precursors (myeloid and lymphoid) from healthy controls. However, the reason for FLAER’s non-binding to the malignant precursors of these leukemias remains unknown, and future studies should explore the possible relation with an immune escape phenomenon in these leukemias. Full article

Primary cardiac tumours are relatively uncommon (75% are benign). Across the other 25%, representing malignant neoplasia, sarcomas account for 75–95%, and primary cardiac intimal sarcoma (PCIS) is one of the rarest findings. We aimed to present a comprehensive review and practical considerations from a multidisciplinary perspective with regard to the most recent published data in the specific domain of PCIS. We covered the issues of awareness amid daily practice clinical presentation to ultra-qualified management in order to achieve an adequate diagnosis and prompt intervention, also emphasizing the core role of MDM2 immunostaining and MDM2 genetic analysis. An additional base for practical points was provided by a novel on-point clinical vignette with MDM2-positive status. According to our methods (PubMed database search of full-length, English publications from January 2021 to March 2023), we identified three studies and 23 single case reports represented by 22 adults (male-to-female ratio of 1.2; male population with an average age of 53.75 years, range: 35–81; woman mean age of 55.5 years, range: 34–70) and a 4-year-old child. The tumour-related clinical picture was recognized in a matter of one day to ten months on first admission. These non-specific data (with a very low index of suspicion) included heart failure at least NYHA class II, mitral regurgitation and pulmonary hypertension, acute myocardial infarction, ischemic stroke, obstructive shock, and paroxysmal atrial fibrillation. Awareness might come from other complaints such as (most common) dyspnoea, palpitation, chest pressure, cough, asthenia, sudden fatigue, weakness, malaise, anorexia, weight loss, headache, hyperhidrosis, night sweats, and epigastric pain. Two individuals were initially misdiagnosed as having endocarditis. A history of prior treated non-cardiac malignancy was registered in 3/23 subjects. Distant metastasis as the first step of detection (n = 2/23; specifically, brain and intestinal) or during follow-up (n = 6/23; namely, intestinal, brain and bone, in two cases for each, and adrenal) required additional imagery tools (26% of the patients had distant metastasis). Transoesophageal echocardiography, computed tomography (CT), magnetic resonance imagery, and even ¹⁸F-FDG positronic emission tomography-CT (which shows hypermetabolic lesions in PCIS) represent the basis of multimodal tools of investigation. Tumour size varied from 3 cm to ≥9 cm (average largest diameter of 5.5 cm). The most frequent sites were the left atrium followed by the right ventricle and the right atrium. Post-operatory histological confirmation was provided in 20/23 cases and, upon tumour biopsy, in 3/23 of them. The post-surgery maximum free-disease interval was 8 years, the fatal outcome was at the earliest two weeks since initial admission. MDM2 analysis was provided in 7/23 subjects in terms of MDM2-positive status (two out of three subjects) at immunohistochemistry and MDM2 amplification (four out of five subjects) at genetic analysis. Additionally, another three studies addressed PCISs, and two of them offered specific MDM2/MDM2 assays (n = 35 patients with PCISs); among the provided data, we mention that one cohort (n = 20) identified a rate of 55% with regard to MDM2 amplification in intimal sarcomas, and this correlated with a myxoid pattern; another cohort (n = 15) showed that MDM2-positive had a better prognostic than MDM2-negative immunostaining. To summarize, MDM2 amplification and co-amplification, for example, with MDM4, CDK4, HMGA3, CCND3, PDGFRA, TERT, KIT, CCND3, and HDAC9, might improve the diagnosis of PCIS in addition to MDM2 immunostaining since 10–20% of these tumours are MDM2-negative. Further studies are necessary to highlight MDM2 applicability as a prognostic factor and as an element to be taken into account amid multi-layered management in an otherwise very aggressive malignancy. Full article

Volcanic emissions (ash, gas, aerosols) dispersed in the atmosphere during explosive eruptions generate hazards affecting aviation, human health, air quality, and the environment. We document for the first time the contamination of airspace by very fine volcanic ash due to sequences of transient ash plumes from Mount Etna. The atmospheric dispersal of sub-10 μm (PM10) ash is modelled using the WRF-Chem model, coupled online with meteorology and aerosols and offline with mass eruption rates (MERs) derived from near-vent Doppler radar measurements and inferred plume altitudes. We analyze two sequences of paroxysms with widely varied volcanological conditions and contrasted meteorological synoptic patterns in October–December 2013 and on 3–5 December 2015. We analyze the PM10 ash dispersal simulation maps in terms of time-averaged columnar ash density, concentration at specified flight levels averaged over the entire sequence interval, and daily average concentration during selected paroxysm days at these flight levels. The very fine ash from such eruption sequences is shown to easily contaminate the airspace around the volcano within a radius of about 1000 km in a matter of a few days. Synoptic patterns with relatively weak tropospheric currents lead to the accumulation of PM10 ash at a regional scale all around Etna. In this context, closely interspersed paroxysms tend to accumulate very fine ash more diffusively at a lower troposphere and in stretched ash clouds higher up in the troposphere. Low-pressure, high-winds weather systems tend to stretch ash clouds into ~100 km wide clouds, forming large-scale vortices 800–1600 km in diameter. Daily average PM10 ash concentrations commonly exceed the aviation hazard threshold, up to 1000 km downwind from the volcano and up to the upper troposphere for intense paroxysms. Vertical distributions show ash cloud thicknesses in the range 0.7–3 km, and PM10 sometimes stagnates at ground level, which represent a potential health hazard. Full article

Heterozygous variants in the ATP1A3 gene are linked to well-known neurological phenotypes. There has been growing evidence for a separate phenotype associated with variants in residue Arg756—fever-induced paroxysmal weakness and encephalopathy (FIPWE) or relapsing encephalopathy with cerebellar ataxia (RECA). With only about 20 cases being reported, the clinical features associated with mutations at Arg756 have not been fully elucidated. We report a case of FIPWE with a p.Arg756Cys change in the ATP1A3 gene and a comparison of the clinical features, including electrophysiological examination, with previous cases. The 3-year-old male patient had normal psychomotor development, presenting with recurrent symptoms of generalized hypotonia with loss of gait, mutism, and dystonic movements only during febrile illnesses since 19 months of age. At 2.7 years of age, a third neurological decompensation episode occurred, during which electroencephalography (EEG) did not reveal high voltage slow waves or epileptiform discharge. Nerve conduction studies (NCS) also did not show latency delay or amplitude reduction. ATP1A3 exon sequencing showed a heterozygous p.Arg756Cys mutation. While the patient experienced repeated encephalopathy-like episodes, including severe hypotonia during febrile illness, EEG and NCS did not reveal any obvious abnormalities. These electrophysiological findings may represent an opportunity to suspect FIPWE and RECA. Full article

Background: Prior studies evaluating post-atrial fibrillation (AF) ablation pulmonary vein (PV) ostial gaps via magnetic resonance imaging (MRI) have shown circumferential PV fibrosis in a minority of patients, and their correlation with AF recurrence was weak. These studies were mostly based on radio-frequency AF ablations. Aim: We aimed to assess cryoballoon ablation-induced PV fibrosis via MRI and its correlation with AF recurrence. Methods and Results: This was a prospective study of consecutive patients with symptomatic AF who underwent pre- and post-ablation MRI to assess baseline and ablation-induced fibrosis, respectively. Post-ablation PV gaps were assessed by new semi-quantitative visual analysis assisted by computerized ADAS analysis. AF recurrence monitored via multiple ECGs and event monitoring at 6 and 12 months post ablation. Nineteen patients with 80 PVs were included, age 56 ± 11, with paroxysmal and persistent AF in 17/19 and 2/19 patients, respectively. Baseline MRI showed minimal LA fibrosis. All patients underwent successful cryoballoon PV electrical isolation. Post-ablation MRI revealed circumferential PV fibrosis among 63/80 (78.8%) PVs and partial fibrosis with major gaps among 17/80 (21.2%) PVs. AF recurred within one year in 5/9 (55.5%) patients with partial PV fibrosis, while no AF recurred among the 10 patients in whom all PVs had circumferential fibrosis (p < 0.01). Similarly, there were significantly more PVs without circumferential fibrosis (due to major gaps) among patients with AF recurrence as compared with patients without AF recurrence (42.9% vs. 13.5%; p < 0.01). Conclusion: Cryoballoon AF ablation results in circumferential PV fibrosis in the majority of PVs, as assessed by a new clinically relevant MRI-LGE analysis. Significant correlation was found between major PV gaps on post-ablation MRI and AF recurrence, suggesting that MRI might have the ability to predict AF recurrence. Full article

We aimed to evaluate the overall clinical characteristics of patients treated by a neuro-emergency expert dedicated to the emergency department (ED) as an attending neurologist during the COVID-19 pandemic. We included adult patients who visited the ED between 1 January and 31 December 2020 and were treated by a neuro-emergency expert. We retrospectively obtained and analyzed the data on patients’ clinical characteristics and outcome. The neuro-emergency expert treated 1155 patients (mean age, 62.9 years). The proportion of aged 18–40 years was the lowest, and the most common modes of arrival were public ambulance (50.6%) and walk-in (42.3%). CT and MRI examinations were performed in 94.4 and 33.1% of cases, respectively. The most frequent complaints were dizziness (31.8%), motor weakness (24.2%), and altered mental status (15.8%). The ED diagnoses were acute ischemic stroke (19.8%), benign paroxysmal positional vertigo (14.2%), vestibular neuritis (9.9%), and seizure (8.8%). The mean length of stay in the ED was 207 min. Of the patients, 55.0% were admitted to the hospital, and 41.8% were discharged for outpatient follow-up. Despite the longer stay and the complexity and difficulty of neurological diseases during the COVID-19 pandemic, the accurate diagnosis and treatment provided by a neuro-emergency expert can be presented as a good model in the ED. Full article

Multi-sensor strategies are key to the real-time determination of eruptive source parameters (ESPs) of explosive eruptions necessary to forecast accurately both tephra dispersal and deposition. To explore the capacity of these strategies in various eruptive conditions, we analyze data acquired by two Doppler radars, ground- and satellite-based infrared sensors, one infrasound array, visible video-monitoring cameras as well as data from tephra-fallout deposits associated with a weak and a strong paroxysmal event at Mount Etna (Italy). We find that the different sensors provide complementary observations that should be critically analyzed and combined to provide comprehensive estimates of ESPs. First, all measurements of plume height agree during the strong paroxysmal activity considered, whereas some discrepancies are found for the weak paroxysm due to rapid plume and cloud dilution. Second, the event duration, key to convert the total erupted mass (TEM) in the mass eruption rate (MER) and vice versa, varies depending on the sensor used, providing information on different phases of the paroxysm (i.e., unsteady lava fountaining, lava fountain-fed tephra plume, waning phase associated with plume and cloud expansion in the atmosphere). As a result, TEM and MER derived from different sensors also correspond to the different phases of the paroxysms. Finally, satellite retrievals for grain-size can be combined with radar data to provide a first approximation of total grain-size distribution (TGSD) in near real-time. Such a TGSD shows a promising agreement with the TGSD derived from the combination of satellite data and whole deposit grain-size distribution (WDGSD). Full article

There have been no reports regarding nystagmus observed immediately after the end of an acute vertiginous attack in patients with Meniere’s disease. The aim of this study was to demonstrate positional direction-changing nystagmus in patients with Meniere’s disease, and to discuss the mechanism that underlies this nystagmus. Video-nystagmography was recorded in two patients with definite Meniere’s disease, who showed positional direction-changing nystagmus during the period immediately after a vertigo attack. In one patient, video-nystagmographic recording was conducted 5 h after an episode of vertigo attack, and it showed very weak, persistent positional geotropic direction-changing nystagmus. In the other patient, video-nystagmographic recording was conducted 23 h after an episode of vertigo attack, and it showed very weak, persistent positional apogeotropic direction-changing nystagmus. Our patients exhibited very weak, persistent positional direction-changing nystagmus, which was geotropic in one and apogeotropic in the other. This type of positional nystagmus has been reported in other inner ear disorders and it cannot be clearly explained by typical benign paroxysmal positional vertigo. The change in chemical composition and/or electrolyte concentration of the inner ear fluid, although still unclear, may underlie the production of this characteristic nystagmus in these patients. Full article

Paroxysmal symptoms are well-recognized manifestations of multiple sclerosis (MS). These are characterized by multiple, brief, sudden onset, and stereotyped episodes. They manifest as motor, sensory, visual, brainstem, and autonomic symptoms. When occurring in the setting of an established MS, the diagnosis is relatively straightforward. Conversely, the diagnosis is significantly more challenging when they occur as the initial manifestation of MS. The aim of this review is to summarize the various forms of paroxysmal symptoms reported in MS, with emphasis on the clinical features, radiological findings and treatment options. Full article

Paroxysmal nocturnal hemoglobinuria (PNH) is a disease which diagnosis may be delayed due to variable clinical findings. We describe herein a case of PNH in a 21 year old woman who admitted with complaints of chronic weakness, intermittent spontaneous ecchymoses, and an intermittent abdominal pain. On laboratory tests thrombocytopenia and iron deficiency anemia without any clinical findings were found. Flow cytometric evaluations showed a PNH clone of 15% for erythrocytes, 64% for monocytes, and 60% for granulocytes. The patient was diagnosed with PNH and an eculizumab therapy was initiated. Following initiation of eculizumab therapy, the frequency of abdominal pain attacks decreased, hemoglobin level normalized, and platelet values increased slightly. In patients submitting with a triad of symptoms such as thrombocytopenia, iron deficiency anemia, and abdominal pain attacks of unknown etiology we suggest considering PNH. We also encourage physicians to share their similar observations in order to raise the knowledge on infrequent presentations of PNH. Full article

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by intravascular hemolysis. Real-world experience of PNH management is largely unreported. A retrospective analysis was undertaken based on medical records from six patients with PNH [two with aplastic anemia (AA)] treated at our center, Dicle University, Turkey. Diagnosis was based on granulocyte PNH clones, ranging from 93% to 66%. All patients had symptoms consistent with PNH. One patient was managed adequately with supportive measures only. Five were treated with the complement inhibitor eculizumab. Follow-up data (<1 year) were available in four cases (the fifth had received only three infusions by final follow-up). Hemoglobin level in these four patients increased from 4.1–7.2 g/dL to 8.3–13.0 g/dL. Lactate dehydrogenase, a marker for hemolysis, decreased profoundly in the two non-AA patients, with more minor improvements in the two AA patients. Weakness and fatigue improved in all eculizumab-treated patients. Four of the five treated patients became transfusion independent, including the patient given only three infusions. In the remaining case, a patient with AA, transfusion requirement decreased, and abdominal pain and dysphagia resolved. No adverse events occurred. PNH can be successfully managed in routine practice. Full article