A Comprehensive Examination of Clinical Characteristics and Determinants of Long-Term Outcomes in Pediatric Cerebral Sinus Venous Thrombosis.

BACKGROUND: To analyze the clinical and neuroimaging features, risk factors, treatment choices, and long-term clinical outcomes in children with cerebral sinus venous thrombosis (CSVT). METHODS: This is a retrospective cohort study of children diagnosed with CSVT between 2002 and 2018 at Texas Children's Hospital. RESULTS: A total of 183 children (male: 62.3%) with CSVT were included. The average presenting age was 7.7 years (S.D.: 5.6). The mean follow-up duration was 33.7 months (S.D.: 38.6). The most common presenting clinical feature was headache (36.6%). Head and neck infections other than meningitis (36.6%) were the most common risk factors. Prevalent neurological examination findings included motor deficit (21.3%) and altered mental status (AMS, 20.2%). Neuroimaging features included hemorrhagic infarction (19.6%), ischemic infarction (8.2%), and intracranial hemorrhage without infarction (5.5%). The most common site of thrombosis was the superior sagittal sinus (37.2%), with 78.2% of patients demonstrating involvement of multiple sinuses. Treatment of choice was low-molecular-weight heparin in 69.4% of patients. Factors associated with worse clinical outcomes included head and neck infections, malignancy (other than hematologic), cardiac disease, and recent surgery; seizure and dehydration on initial presentation; motor abnormalities and AMS on initial examination; ischemic infarct only; and involvement of vein of Trolard on neuroimaging. Thrombus condition on repeat imaging, receiving any anticoagulant/antithrombotic treatment, treatment duration, or follow-up duration was not associated with severity of long-term outcome. CONCLUSIONS: CSVT may lead to unfavorable long-term outcomes in a remarkable portion of pediatric patients. Thus, a high index of suspicion and early and appropriate management of pediatric CSVT is imperative.

The Effect of Smartphone Video on Lead Time to Diagnosis of Infantile Spasms.

OBJECTIVE: To assess whether access to smartphone video capture of infantile spasms at initial presentation is associated with improved time to diagnosis and treatment. METHODS: We conducted a collaborative retrospective cohort study of 80 consecutive infants with confirmed infantile epileptic spasms syndrome initially presenting from 2015 to 2021 at 2 US pediatric centers. Statistical methods used included Mann-Whitney U test to assess the difference in lead times to electroencephalogram (EEG), diagnosis, and treatment between groups with and without video capture. A χ2 analysis was used to assess differences in demographics, clinical characteristics, and treatment outcomes between groups. Multivariate regression analysis was used to account for etiology types and infantile spasms capture on EEG. RESULTS: Patients with smartphone video infantile spasms capture initially presented a median of 9 days earlier (P = .02), had their first EEG 16 days earlier (P = .007), and were diagnosed and started treatment 17 days earlier (P = .006 and P = .008, respectively) compared with the nonvideo group. The video group had a 25% greater response to initial standard treatment (P = .02) and a 21% greater freedom from infantile spasms at long-term follow-up (P = .03), although this long-term outcome lost statistical significance after adjustment for etiology type (P = .07) and EEG capture of infantile spasms (P = .059). CONCLUSION: Our findings suggest a benefit of smartphone video capture of infantile spasms in reduced time to diagnosis and initial standard treatment, which are associated with improved treatment response rates. Substantial differences in lead times and treatment response highlight the clinical importance of pediatricians recommending caregivers to obtain smartphone video of events concerning for infantile spasms.

KCNA1 gain-of-function epileptic encephalopathy treated with 4-aminopyridine.

Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage-gated K+ channel subunit KV 1.1. So far, loss-of-function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain-of-function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4-aminopyridine. Clinical use of 4-aminopyridine was associated with reduced seizure burden, enabled simplification of co-medication and prevented rehospitalization.

Clinical Profile and Long-Term Outcome in Neonatal Cerebral Sinus Venous Thrombosis.

BACKGROUND: Neonatal cerebral sinus venous thrombosis (CSVT) causes high morbidity and mortality. Factors associated with either favorable or unfavorable long-term outcomes have not been clearly established. This study aimed to determine the factors involved in long-term neurological outcomes in patients with neonatal CSVT. METHODS: This was a retrospective cohort study of patients with neonatal CSVT at a single institution. Clinical factors associated with long-term neurological outcomes were examined. RESULTS: A total of 67 patients met study inclusion criteria for radiologically confirmed neonatal CSVT. The mean patient follow-up duration was four years (range one week to 16 years, median six years). We observed a favorable neurological outcome defined by a pediatric stroke outcome measures (PSOM) score of 0 to 0.5 in 26 (53%) of osurviving patients at follow-up. An unfavorable neurological outcome as defined by PSOM score >0.5 was observed in 23 survivors (47%). Death was reported in 18 (27%) patients, of which 10 patients died due to direct complications of CSVT. Congential heart disease and genetic disease were associated with significantly increased odds for all-cause death. Cardiorespiratory failure and altered mental status during the initial neurological examination were significantly associated with increased odds of death due to CSVT. Among surviving patients, higher PSOM scores were associated with premature birth (i.e., gestational age < 37 weeks), traumatic birth, site of thrombosis in the straight sinus, site of thrombosis in the internal cerebral veins, and hemorrhagic infarct. In contrast, lower PSOM scores were associated with a normal neurological examination at presentation, thrombosis in only superficial sinuses, and hemorrhage without infarct. There was no statistically significant association between the type and duration of CSVT treatment. CONCLUSIONS: The major factors influencing outcome of neonates following CSVT included comorbid medical conditions, abnormal neurological examination at presentation, location of venous thrombosis, and type of cerebral injury. These results can help guide further studies in neonatal CSVT aiming to decrease morbidity and mortality with the goal of improving long-term neurological outcomes.