Mean Age Of Onset Research Articles

A Comparative Study between Ultrasound-guided Concomitant Infraclavicular Plus Distal Median, Radial, and Ulnar Nerve Blockade Versus Infraclavicular Block Alone

Abstract Background: Peripheral nerve blocks can be used alone as the sole “surgical” anesthetic technique as the initial step in providing prolonged postoperative analgesia. There are studies, where accurate deposition of local anesthetic perineurally has the potential to improve the success rate and reduce the incidence of complications of the infraclavicular block. We hypothesized whether a combined block of the infraclavicular brachial plexus and distal median, radial, and ulnar nerves would accelerate upper extremity anesthesia compared with an infraclavicular block alone. Materials and Methods: This study was a prospective randomized control study conducted among 60 patients undergoing elective and emergency wrist and hand surgeries. A group of 30 patients received an infraclavicular block with 30 mL of a local anesthetic mixture containing 1% lignocaine with adrenaline and 0.25% bupivacaine from Group A. Group B received an infraclavicular block with 15 mL of local anesthetic mixture containing 1% lignocaine with adrenaline and 0.25% bupivacaine along with distal median, radial, and ulnar nerve blockade with 5 mL each of local anesthetic mixture containing 1% lignocaine with adrenaline and 0.25% bupivacaine. Pain score, assessment of sensory and motor functions, block performance time, and surgical anesthesia were observed. Results: The mean block performance time of Group A was 10.9 ± 1.1 min and Group B was 14.7 ± 0.5 min. The difference between the two groups’ block performance minutes was statistically significant (P < 0.001). The difference in the onset of the sensory block between the two groups was statistically significant (P < 0.001). The mean onset of motor blockade between the two groups was statistically very highly significant (P < 0.001). The mean of Group A was 5.0 ± 0.2 and Group B was 2.1 ± 0.4. Conclusion: From this study, we conclude that using an approximately equivalent dose of local anesthetics, combining ultrasound-guided infraclavicular block with distal median, radial, and ulnar nerve blockade shortens the onset time of sensory and motor block with improved block consistency compared to infraclavicular block alone.

Phenotypic, Electrophysiologic, and Imaging Spectrum of Hirayama Disease from Northern India.

Cervical flexion-induced myelopathy, also known as Hirayama disease (HD), is a lower motor neuron disorder seen mainly in adolescents and young adults, affecting the C7-T1 myotomes, presenting as asymmetric weakness with wasting of one or both the distal upper limbs. We aimed to describe the clinical features, electrophysiology, and radiologic features of HD in a tertiary care institute in northern India. One hundred and forty patients between 2017 and 2022 with clinical and imaging features consistent with HD were retrospectively reviewed from the All India Institute of Medical Sciences-Comprehensive Neuromuscular Diseases center database. Majority were males with the mean age of onset of illness being 17.8 years. The median duration of the symptoms was 3 (1.5-4) years. Sixty-nine (49%) patients had unilateral involvement, and the disease was actively progressing in 88 (63%) patients at presentation. Two families had history of HD in two (1.4%) siblings. Electromyography showed abnormal findings in the clinically involved limb in all the patients and in the clinically uninvolved limb in 17/50 (34%) patients. Flexion magnetic resonance imaging (MRI) demonstrated forward dural displacement in 134 (96%) patients and asymmetric cord flattening in 124 (88.5%) patients. Disability was graded as mild, moderate, and severe; 12 (13%) had severe disability. The majority were managed conservatively, and four underwent surgery for HD. A high index of suspicion of HD needs to be kept in a young male presenting with distal upper limb weakness and atrophy. Dynamic MRI of the cervical spine in young adults presenting with hand wasting is inevitable. This disease needs to be managed aggressively and early to prevent serious dysfunction and loss of productivity.

Clinical and pathological analysis of cutaneous mixed tumors.

In this study we aimed to understand and summarize the clinical and pathological characteristics of cutaneous mixed tumors. A retrospective analysis was conducted on the clinical and pathological data of 20 patients diagnosed with cutaneous mixed tumors in our outpatient department between January 2014 and April 2024. The study comprised 20 patients with a male-to-female ratio of 3:2. The mean age of onset was 52.10 ± 15.46 years. All patients presented with solitary cutaneous lesions ranging from 2 to 30mm in diameter. Notably, none of the patients received a preoperative diagnosis of cutaneous mixed tumor. The clinical manifestations of cutaneous mixed tumors are nonspecific, necessitating histopathological examination for a definitive diagnosis.

Clinical and neurophysiological characterization of p.Gly59Ser mutation in DCTN1: a study in a Thai family and a brief review.

Mutations in the Dynactin 1 (DCTN1) gene lead to various neurodegenerative disorders. The p.Gly59Ser mutation, the first pathogenic mutation identified in DCTN1, was initially reported in a family with distal hereditary motor neuropathy and early vocal cord paralysis. Since its discovery in 2003, this mutation has been documented in only three families worldwide, to the best of our knowledge. This study examines six patients from a Thai family carrying the p.Gly59Ser mutation in DCTN1 and includes a literature review. Five of the patients were female. The mean age of onset was 32.6 ± 1.9 years. Thai patients showed early involvement of intrinsic hand, facial, and bulbar muscles, with vocal cord impairment manifesting later in the disease course. Tongue fasciculations, not previously reported with this mutation, were observed in most Thai patients. Bilateral split-hands were consistently noted. Arytenoidectomy and cordotomy have proven beneficial in relieving upper airway obstruction and preventing life-threatening upper airway complications from vocal cord paralysis. The p.Gly59Ser mutation in DCTN1 presents with autosomal-dominant, adult-onset, lower motor neuronopathy/neuropathy. Compared to earlier reports, Thai patients exhibited more widespread involvement, including facial, bulbar, tongue, vocal cord, and limb muscles. In addition to vocal cord paralysis, the split-hand phenomenon emerges as another clinical hallmark of this condition.

7534 Characterizing The Presentation Of Non-Classical Congenital Adrenal Hyperplasia

Abstract Disclosure: S. Patel: None. M. Skamagas: None. A.C. Levine: None. M. Yau: None. Introduction: 21-hydroxylase deficiency, due to CYP21A2 gene mutations, is the most common steroidogenic enzymatic defect causing congenital adrenal hyperplasia (CAH). Disease severity is categorized into the classical and milder, non-classical (NCAH) form. Many patients go undiagnosed due to variable presentation and delayed onset. We aim to investigate the specific presenting concerns, age of onset, and genotypes associated with NCAH. Methods: A retrospective chart review of 285 patients with CAH seen over the past 2 years at our academic pediatric and adult endocrine clinics was performed. Records were reviewed for presenting concerns and age of symptom onset. CYP21A2 gene analysis was performed commercially via multiplex ligation-dependent probe amplification or next generation sequencing. Results: Of the 165 patients classified with NCAH, genotypes were available for 124 patients. Of the patients with a V281L allele, 43 were homozygous and 49 were heterozygous. 7 patients had the P30L allele and 7 had other allele combinations. The overall most common presenting concerns were early pubarche (29%), hirsutism (28%), and irregular menses (26%). In V281L homozygotes, family history most commonly led to diagnosis (30%). In patients with V281L heterozygosity or the P30L allele, the predominant concern was early pubarche (37% and 43% respectively). 15% of patients were screened prenatally or only due to family history and were asymptomatic at diagnosis. Patients’ age at diagnosis ranged from 0-40 years, with the mean age at diagnosis for the total group being 13.3 ± 8.9 years. Mean age of onset in symptomatic V281L homozygotes (15.4 ± 7.9 years) trended toward an older age compared to symptomatic V281L heterozygotes (15.1 ± 10.5 years) (P value = 0.90). Those who were heterozygous for V281L/P30L or undetermined whether homozygous for V281L or heterozygous with a deletion were excluded from age of onset comparisons. Discussion: The mean age of symptom onset was in adolescence and did not differ significantly between V281L homozygotes and heterozygotes. Early pubarche is a frequent presenting symptom in children with NCAH, and our data support this finding. P30L has been associated with a more severe phenotype than V281L, and in our cohort, the only patient presenting in adrenal crisis had a genotype with a P30L mutation. As NCAH is one of the most common autosomal recessive disorders in humans and there is an allelic predominance of V281L in NCAH patients, it is not surprising that a large percentage of V281L homozygotes were diagnosed due to family history prior to developing symptoms. Such patients need to be followed clinically and our data describing symptom onset could be useful in counseling these families and those with prenatal diagnoses. Presentation: 6/1/2024

Evaluating estimated health care resource utilization and costs in patients with myelofibrosis based on transfusion status and anemia severity: A retrospective analysis of the Medicare Fee-For-Service claims data.

Myelofibrosis (MF) is a rare but aggressive myeloproliferative neoplasm that commonly affects older patients, with a mean age of onset of older than 60 years. At least a third of patients with primary MF are anemic at diagnosis, and nearly all patients become anemic over time; approximately half require red blood cell transfusions within a year of diagnosis. Anemia and transfusion dependence are leading negative prognostic factors for overall survival and are associated with diminished quality of life and increased health care-related economic burden in patients with MF. To describe baseline characteristics, health care resource utilization (HCRU), and costs as a function of transfusion status and anemia severity in patients diagnosed with MF among the US Medicare Fee-For-Service (FFS) population. This retrospective cohort study included patients diagnosed with MF appearing in the 100% Medicare FFS database enrolled between January 1, 2012, and December 31, 2020. Patients were segmented into hemoglobin level cohorts (no, mild, moderate, and severe anemia) and transfusion status cohorts (transfusion independent [TI], transfusion requiring [TR], or transfusion dependent [TD]). Across cohorts, demographics and disease characteristics were assessed at baseline; per patient per month all-cause HCRU and medical and pharmacy costs were reported during follow-up. All results were summarized descriptively. The transfusion status cohort (N = 1,749) included TI (n = 980), TR (n = 559), and TD (n = 210) patients; the anemia severity cohort (N = 365) included patients with no (n = 100), mild (n = 128), moderate (n = 99), and severe (n = 38) anemia. On average, TR and TD patients or those with moderate or severe anemia had numerically higher Deyo-Charlson Comorbidity Index scores than those who were TI or had mild or no anemia. TR and TD cohorts reported numerically greater all-cause outpatient, inpatient, and emergency department utilization vs the TI cohort. All-cause costs were numerically higher in the TD and TR cohorts vs the TI cohort ($14,655 and $14,249 vs $8,191). Incremental increases in HCRU and costs were also observed with increasing anemia severity. All-cause medical and pharmacy costs for no, mild, moderate, and severe anemia cohorts were $4,689, $7,268, $10,439, and $13,590, respectively. This retrospective analysis of the US Medicare FFS database descriptively evaluated patients by transfusion status and anemia severity and showed that costs and HCRU were numerically lower for patients with transfusion independence compared with those with transfusion dependence. Similar trends were seen when comparing patients based on anemia status, with numerically lower HCRU and cost observed with decreasing anemia severity.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific protease 25, a key member of the deubiquitinating enzyme family that is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown aetiology. Five heterozygous USP25 variants, including two de novo and three co-segregated variants, were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared with the East Asian population and all populations in the gnomAD database. The mean age at onset of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom, except that one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was expressed ubiquitously in mouse brain with two peaks, on embryonic Days 14-16 and postnatal Day 21, respectively. In human brain, likewise, USP25 is expressed in the fetus/early childhood stage and with a second peak at ∼12-20 years old, consistent with the seizure onset age in patients during infancy and in juveniles. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knockout mice, which showed increased seizure susceptibility compared with wild-type mice in a pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we used multiple functional detections. In HEK293 T cells, the variant associated with a severe phenotype (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed stable truncated dimers with an increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del variants increased neuronal excitability in mouse brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating that USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play an epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have a profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

Using cancer phenotype sex-specificity to enable unbiased penetrance estimation of SMARCA4 pathogenic variants for small cell carcinoma of the ovary, hypercalcemic type (SCCOHT)

PurposeSmall cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an extremely rare, highly aggressive cancer (mean age of onset, 24 years). Nearly all cases are associated with somatic or germline pathogenic variants (GPVs) in SMARCA4. Early bilateral oophorectomy is recommended for unaffected females with a SMARCA4 GPV. However, the penetrance of SMARCA4 GPVs for SCCOHT is highly uncertain and subject to ascertainment bias. MethodsLeveraging the early-onset, sex-specific, highly morbid nature of SCCOHT, we hypothesized that the penetrance for SCCOHT could be quantified from the deficit in SMARCA4 GPVs in females compared with males in UK Biobank, a population cohort for which recruitment was restricted to those age 40 to 69. We also analyzed pedigrees ascertained internationally by the Montreal-based SCCOHT-SMARCA4 Registry. ResultsWe observed SMARCA4 GPVs in 8/210,182 (0.0038%) female and 18/179,210 (0.0100%) male participants in UK Biobank (P = .028), representing a male:female odds ratio of 2.64 (95%CI 1.09-7.02), implying a penetrance of 62% for SCCOHT (given the absence of other SMARCA4-related female-specific early morbid diseases). A deficit of GPVs in females in UK Biobank was also demonstrated for BRCA1 and TP53. ConclusionOur findings support bilateral oophorectomy in early adulthood as a rational choice for at-risk females with SMARCA4 GPVs.

Clinical Characteristics of Egyptian Patients with Active Secondary Progressive Multiple Sclerosis

Abstract Background Many challenges exist in the precise definition of secondary progressive multiple sclerosis (SPMS). Early diagnosis of active SPMS is getting more important as pharmaceutical treatment options are developed. Objectives This study aimed to assess the clinical characteristics of patients with active SPMS enrolled in a new registry in Egypt and compare it with 6-month follow-up assessment. Methods It is a longitudinal, hospital-based study, conducted in the multiple sclerosis unit of Ain Shams University Hospital, forty-six patients were enrolled in this study who fulfilled the 2017 McDonald criteria for MS, as well as that of active secondary progressive multiple sclerosis (SPMS). All patients are subjected to a full personal history, primary clinical assessment was done using EDSS, Symbol Digit Modalities test (SDMT), and timed 25-Foot Walk Test (T25FWT) and were followed up and compared by a 6-month assessment. Results The mean age of the studied group was 43.543 ± 8.326 (SD). Females represented 69 %. The mean age of MS onset was 29.565 ± 8.010 (SD), mean age of SPMS onset was 40.109±7.892 (SD). EDSS mean value at baseline assessment was 5.8 and increased to 6 in the 6-month follow-up with a significant difference between the two assessments (p < 0.001). SDMT mean value in baseline assessment was 24 and deteriorated to 21 in the 6-month follow-up. With p-value <0.001. Regarding T25FWT baseline mean value was 16 seconds and increased to 18 seconds during the 6-month follow-up with a significant p-value of 0.013. Conclusion This study showed the importance of highlighting other aspects than motor to detect progression in patients with MS and the importance of entangling different techniques for better and more accurate assessment and earlier detection of progression.

Impact of early onset colorectal cancer on mental and physical health: A comparative analysis of self-reported mental and physical health outcomes using the PROMIS framework in the NIH All of Us Research Program.

241 Background: Patients with early-onset colorectal cancer (EOCRC) have complex psycho-social needs that can impact their overall health and well-being. With the increasing incidence of EOCRC, it is essential to investigate the effects of this diagnosis on patients' mental and physical health. This study uses the Patient-Reported Outcomes Measurement Information System (PROMIS) framework to compare patients' self-reported mental and physical health perceptions with EOCRC and those with late-onset colorectal cancer (LOCRC). Methods: We utilized the National Institutes of Health's (NIH) All of Us database Registered Tier Dataset v7, which includes 266,520 participants who agreed to share their EHR information, for analysis. Participants completed PROMIS surveys for physical health (PROMIS-PH) and mental health (PROMIS-MH). We categorized patients with colorectal cancer into EOCRC (age at diagnosis <50) and LOCRC (age at diagnosis >=50) using ICD 9/10 codes. We calculated the raw summed scores for PROMIS-PH and PROMIS-MH for each group. We transformed the raw summed score into a T-score. The study compared scores in EOCRC and LOCRC using the Mann-Whitney U test with a significance level of P<0.05. We used the R programming language in the web-based Jupyter Notebook platform for data analysis. Results: Our study revealed 1764 colorectal cancer patients, with 408 cases of EOCRC (mean age of onset: 42.13 years, SD: 7.0) and 1356 cases of LOCRC (mean age: 63.72 years, SD: 8.35). Analysis of PROMIS Global scores showed that EOCRC patients had a mean PROMIS-MH score of 13.90 (SD: 3.42, T-score: 45.8, 95% CI: 38.74-52.86) and mean PROMIS-PH score of 13.95 (SD: 3.38, T-score: 42.3, 95% CI: 34.07-50.53). In contrast, LOCRC patients had mean PROMIS-MH and PROMIS-PH scores of 14.47 (SD: 3.37, T-score: 48.3, 95% CI: 41.05-55.55) and 14.24 (SD: 3.35, T-score: 44.9, 95% CI: 36.47-53.33), respectively. The PROMIS-MH scores were significantly higher in LOCRC than in EOCRC (p-value <0.001). However, there was no significant difference between the PROMIS-PH scores in both groups (p-value= 0.191). Conclusions: The study suggests that patients with EOCRC have a lower level of perceived mental health compared to LOCRC. Also, the EOCRC had a lower level of perceived physical health, although not statistically significant. These findings emphasize the significance of age-specific approaches in cancer research and underscore the importance of focused interventions to meet the unique mental and physical health needs of patients with EOCRC.

Risk Factors for the Development of Ocular Complications in Herpes Zoster Ophthalmicus and Zoster Vaccine Utilization in a Large, Urban Health System

To characterize the epidemiology of herpes zoster (HZ) and herpes zoster ophthalmicus (HZO) in an urban hospital system and determine risk factors associated with developing ocular complications in HZO. To report the frequency of shingles vaccination and HZ reactivation following shingles vaccination in this population. A retrospective cohort study was conducted on patients seen at the University of Illinois Hospital system from January 1, 2010 to December 1, 2021 with HZ and HZO identified by diagnosis code. Charts of HZO patients seen within 1 year of diagnosis were abstracted. Multivariable logistic regression analysis identified factors associated with the development of ocular complications in HZO. During the study period, 3283 patients had HZ; mean age of onset was 52.3 years, 61.6% were female, and 37% were Black. HZO with ocular involvement was seen in 110 (3.4%) patients. Ocular complications developed in 40 (36.4%) patients; the most common complication was corneal scarring (70%). Age (odds ratio [OR] 1.04, 95%CI 1.0-1.1), female gender (OR 2.86, 95%CI 1.0-8.1), steroids at initial visit (4.46, 95%CI 1.4-14.6), and stromal keratitis (OR 3.45, 95% CI 1.2, 9.8) were associated with developing ocular complications. Of eligible populations, 5333 (1.5%) received shingles vaccination; 43 patients developed reactivation of HZ following vaccination. In HZO, age, female gender, steroids at initial visit, and stromal keratitis are strongly associated with developing ocular complications. Shingles vaccination rates were low in this study population. Understanding potential for complications in HZ/HZO and vaccination uptake can help identify at risk populations to prevent disease. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Dancing with disorder: chorea – an unusual and neglected manifestation of antiphospholipid syndrome

ObjectivesChorea, characterised by involuntary, irregular movements, is a rare neurological manifestation of antiphospholipid syndrome (APS). The specific clinical features remain unclear. This study aimed to summarise the available evidence on...

Demographics and Clinical Assessment of Familial Multiple Sclerosis Patients in Ain Shams University Hospitals

Abstract Background Multiple sclerosis (MS) is the most seen demyelinating disease. The exact cause of MS is still uncertain; many genes significantly increase the disease susceptibility along with several well-defined environmental factors. Genetic factors play an important role in the pathogenesis and clinical presentations of MS. Aim of the Work This study aims to detect the prevalence of familial multiple sclerosis among Egyptian patients suffering from MS at Ain Shams University hospitals, to register the demographics and the clinical characteristics of familial multiple sclerosis patients and to demonstrate the effect of inheritance on the severity and progression. Patients and Methods This study aimed to detect the prevalence of familial multiple sclerosis among Egyptian patients suffering from MS at Ain Shams University hospitals, to register the demographics and the clinical characteristics of familial multiple sclerosis patients and to demonstrate the effect of inheritance on the severity and progression. The current study showed that the prevalence of familial multiple sclerosis among MS Egyptian at Ain Shams University hospitals was 6,4%. Female to male percentages were found to be (73.8%) to (26.2%) respectively. Results The mean age of onset among the FMS cases was found to be (26.1±7.8). The mean time elapsed between symptoms onset and diagnosis was found to be (19.9±34.0) months and it was found that time from disease onset to MS diagnosis is significantly shorter in the 2nd and 3rd family-members diagnosed in familial cases compared to 1st family member diagnosed with MS. Regarding focality of presentation at the first attack, in this study there was found that monofocal presentation was more common than multifocal presentation (64.4%). The current study also showed that affection of the pyramidal functional system is significantly the most frequent in cases with an affected relative of first degree while it was least frequent in cases with an affected relative of third-degree consanguinity. Sensory affection in the first attack was the most common functional system affected. Most of the familial MS cases showed relapsing remitting pattern of the disease (76.6%) that was followed by SPMS (20.9%) and the least frequent form was PPMS (2.3%) with no significant relation between the degree of consanguinity between the relatives affected within the same family and the pattern of progression of the disease. Conclusion The number of exacerbations per year in the studied cases was 0.9±0.8 and the mean MSSS of the studied cases was (4.9±2.5) and there were significant agreement between type in cases and relatives indicating that the presence of a family member diagnosed with a certain MS clinical phenotype can be a predictor to the clinical phenotype in the patient calling for special consideration to the choice of treatment for the patient.

Magnesium Sulphate Versus Fentanyl as Adjuncts to Epidural Anaesthesia for Lower Limb Orthopaedic Surgeries: A Comparative Study

Abstract Introduction: Pain relief for lower limb orthopaedic surgeries is achievable with epidural anaesthesia. This study compared the analgesic effects of epidural anaesthesia with magnesium sulphate or fentanyl adjuvant in patients scheduled for elective lower limb orthopaedic surgeries. Patients and Methods: A double-blind randomisation study was carried out on 96 patients categorised into three groups; M, F, and C. All participants received 18 mL of 0.5% bupivacaine plus 1.5 mL of 75 mg magnesium sulphate in Group M or 50 mg of fentanyl in Group F or normal saline in Group C via the lumbar epidural route. Variables including the onset time of sensory and motor blockade, duration of anaesthesia, and time for postoperative Numerical Rating Scale (NRS) score of 3 were summarised using mean, median, standard deviation, and percentages as appropriate. A P value of <0.05 was considered statistically significant. Results: Mean onset time for the sensory blockade at T8 was 23.7 ± 5.3, 20.5 ± 3.4, and 17.9 ± 5.6 min for groups C, F, and M, respectively (P = 0.001). The onset time for the motor blockade (Bromage score 3) was 29.8 ± 4.0, 26.6 ± 3.5, and 24.5 ± 5.3 min in groups C, F, and M, respectively (P = 0.001). The duration of epidural anaesthesia was 121.6 ± 31.5, 145.9 ± 29.6, and 167.0 ± 27.0 min in groups C, F, and M, respectively (P = 0.001). The time to attain an NRS pain score of 3 was 133.2 ± 27.7, 151.8 ± 32.4, and 172.0 ± 30.9 min in groups C, F, and M, respectively (P = 0.001). Conclusion: Magnesium sulphate is better as an epidural adjuvant compared to fentanyl in patients undergoing lower limb orthopaedic surgeries.

Epidemiology of traumatic spinal cord injury in Ireland, 2017-2022.

Retrospective population based study on traumatic spinal cord injury (SCI) in Ireland. To gather the most recent epidemiological data prior to the implementation of a new national trauma strategy. Also, to consider if the COVID-19 pandemic impacted on SCI epidemiology in Ireland. Republic of Ireland. All patients with TSCI discharged from the National Rehabilitation Hospital (NRH), the national acute SCI unit and two neurosciences centres were included. The International Spinal Cord Injury Core Data Set was collected on all patients at discharge from rehabilitation between 2017 and 2022. Overall crude incidence of TSCI was 14 per million per year, ranging between 11.3 and 18.4. 12.7% of patients did not survive to discharge from hospital. In those completing rehabilitation, the mean age of injury onset was 50.1 years (SD 19.9). Males accounted for 75.7%. The most common impairment was incomplete tetraplegia, 45.3% of all TSCI. Leading aetiology was falls, 53.9% of injuries. Patients with incomplete tetraplegia and those whose cause of injury were falls were older than those with all other impairments and injury aetiologies (p < 0.001). Overall incidence of TSCI is similar to our previous studies. Also similar is the predominant pattern of older people sustaining falls resulting in incomplete tetraplegia.

The prevalence of neuropsychiatric symptoms and correlation with MRI findings in CADASIL patients.

To assess the prevalence, timing, and functional impact of neuropsychiatric symptoms in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to assess whether these neuropsychiatric symptoms are associated with magnetic resonance imaging (MRI) features of the patients. Our study included a total of 78 patients with CADASIL. To assess neuropsychiatric symptoms, we evaluated the caregivers using the Neuropsychiatric Inventory (NPI). Patients were considered to have an irritability, depression, apathy, aggression, or anxiety disorder if they scored ≥1 in the NPI. Subsequently, we conducted a more detailed assessment of irritability, depression, apathy, aggression, and anxiety. Multivariate logistic regression was employed to analyze the relationships between neuropsychiatric symptoms and clinical/MRI features in the patients. Overall, 57.69% of patients with CADASIL experienced neuropsychiatric symptoms. Among these symptoms, irritability was the most prevalent (52.56%), followed by depression (19.23%), apathy (17.95%), aggression (7.69%), and anxiety (6.41%). The mean age of onset for irritability was the youngest, followed by anxiety, apathy, aggression, and depression. Among patients with both stroke/TIA and neuropsychiatric symptoms, 31.03% reported experiencing neuropsychiatric symptoms prior to stroke/TIA. Furthermore, both irritability and apathy had a negative impact on the patients' daily functioning. Additionally, there was a correlation between the presence of neuropsychiatric symptoms and the patients' MRI lesion burden. Our study has discovered that neuropsychiatric symptoms are highly prevalent in patients with CADASIL and may occur before cerebrovascular events, suggesting that neuropsychiatric symptoms of CADASIL deserve more attention and earlier exploration.

Frequency of Variants in Mendelian Alzheimer's Disease Genes within the Alzheimer's Disease Sequencing Project (ADSP).

Prior studies using the ADSP data examined variants within presenilin-2 (PSEN2), presenilin-1 (PSEN1), and amyloid precursor protein (APP) genes. However, previously-reported clinically-relevant variants and other predicted damaging missense (DM) variants have not been characterized in a newer release of the Alzheimer's Disease Sequencing Project (ADSP). To characterize previously-reported clinically-relevant variants and DM variants in PSEN2, PSEN1, APP within the participants from the ADSP. We identified rare variants (MAF <1%) previously-reported in PSEN2, PSEN1, and APP in the available ADSP sample of 14,641 individuals with whole genome sequencing and 16,849 individuals with whole exome sequencing available for research-use (Ntotal = 31,490). We additionally curated variants in these three genes from ClinVar, OMIM, and Alzforum and report carriers of variants in clinical databases as well as predicted DM variants in these genes. We detected 31 previously-reported clinically-relevant variants with alternate alleles observed within the ADSP: 4 variants in PSEN2, 25 in PSEN1, and 2 in APP. The overall variant carrier rate for the 31 clinically-relevant variants in the ADSP was 0.3%. We observed that 79.5% of the variant carriers were cases compared to 3.9% were controls. In those with AD, the mean age of onset of AD among carriers of these clinically-relevant variants was 19.6 ± 1.4 years earlier compared with noncarriers (p-value=7.8×10-57). A small proportion of individuals in the ADSP are carriers of a previously-reported clinically-relevant variant allele for AD and these participants have significantly earlier age of AD onset compared to noncarriers.

Investigating the genetic basis of hereditary spastic paraplegia and cerebellar Ataxia in Pakistani families

BackgroundHereditary Spastic Paraplegias (HSPs) and Hereditary Cerebellar Ataxias (HCAs) are progressive neurodegenerative disorders encompassing a spectrum of neurogenetic conditions with significant overlaps of clinical features. Spastic ataxias are a group of conditions that have features of both cerebellar ataxia and spasticity, and these conditions are frequently clinically challenging to distinguish. Accurate genetic diagnosis is crucial but challenging, particularly in resource-limited settings. This study aims to investigate the genetic basis of HSPs and HCAs in Pakistani families.MethodsFamilies from Khyber Pakhtunkhwa with at least two members showing HSP or HCA phenotypes, and who had not previously been analyzed genetically, were included. Families were referred for genetic analysis by local neurologists based on the proband’s clinical features and signs of a potential genetic neurodegenerative disorder. Whole Exome Sequencing (WES) and Sanger sequencing were then used to identify and validate genetic variants, and to analyze variant segregation within families to determine inheritance patterns. The mean age of onset and standard deviation were calculated to assess variability among affected individuals, and the success rate was compared with literature reports using differences in proportions and Cohen’s h.ResultsPathogenic variants associated with these conditions were identified in five of eight families, segregating according to autosomal recessive inheritance. These variants included previously reported SACS c.2182 C > T, p.(Arg728*), FA2H c.159_176del, p.(Arg53_Ile58del) and SPG11 c.2146 C > T, p.(Gln716*) variants, and two previously unreported variants in SACS c.2229del, p.(Phe743Leufs*8) and ZFYVE26 c.1926_1941del, p.(Tyr643Metfs*2). Additionally, FA2H and SPG11 variants were found to have recurrent occurrences, suggesting a potential founder effect within the Pakistani population. Onset age among affected individuals ranged from 1 to 14 years (M = 6.23, SD = 3.96). The diagnostic success rate was 62.5%, with moderate effect sizes compared to previous studies.ConclusionsThe findings of this study expand the genotypic and phenotypic spectrum of HSPs and HCAs in Pakistan and emphasize the importance of utilizing exome/genome sequencing for accurate diagnosis or support accurate differential diagnosis. This approach can improve genetic counseling and clinical management, addressing the challenges of diagnosing neurodegenerative disorders in resource-limited settings.

Short-term effectiveness and side effects of ketogenic diet for drug-resistant epilepsy in children with genetic epilepsy syndromes.

Drug-resistant epilepsy (DRE) impacts a significant portion, one-third, of individuals diagnosed with epilepsy. In such cases, exploring non-pharmacological interventions are crucial, with the ketogenic diet (KD) standing out as a valuable option. KD, a high-fat and low-carb dietary approach with roots dating back to the 1920s for managing DRE, triggers the formation of ketone bodies and modifies biochemistry to aid in seizure control. Recent studies have increasingly supported the efficacy of KD in addressing DRE, showcasing positive outcomes. Furthermore, while more research is needed, limited data suggests that KD May also be beneficial for specific genetic epilepsy syndromes (GESs). This study aimed to assess the short-term efficacy of KD among pediatric patients diagnosed with GESs. This is a multi-center retrospective analysis of pediatric patients with GESs diagnosed using next-generation sequencing. The enrolled patients followed the keto-clinic protocol, and the KD efficacy was evaluated at 3, 6, and 12-month intervals based on seizure control and compliance. The collection instrument included demographic, baseline, and prognostic data. The collected data was coded and analyzed promptly. We enrolled a cohort of 77 patients with a mean current age of 7.94 ± 3.83 years. The mean age of seizure onset was 15.5 months. Notably, patients experienced seizures at a younger age tended to have less positive response to diet. Overall, 55 patients responded favorably to the diet (71.4%) while 22 patients (28.6%) showed no improvement. Patients with genetic etiology showed a significantly more favorable responses to the dietary intervention. Patients with Lennox-Gastaut syndrome showed the most significant improvement (14/15) followed by patients with Dravet syndrome (6/8), and West syndrome (3/4). The number of used anti-seizure medications also played a significant role in determining their response to the diet. While some patients experienced mild adverse events, the most common being constipation, these occurrences were not serious enough to necessitate discontinuation of the diet. The study revealed a high improvement rate in seizure control, especially among younger patients and those with later seizure onset. The success of dietary treatment hinges greatly on early intervention and the patient's age. Certain genetic mutations responded favorably to the KD, while efficacy varied among various genetic profiles.

Update on Palmar Fasciitis and Polyarthritis Syndrome: A systematic review

ObjectivesThis systematic review aims to (1) summarize the clinical, laboratory, and imaging characteristics of Palmar Fasciitis and Polyarthritis Syndrome (PFPAS) patients and (2) evaluate the effectiveness of different treatments. MethodsWe conducted a systematic search of three electronic databases (Scopus, Embase, and PubMed) from inception to December 31, 2023. We presented demographic and clinical features, along with laboratory factors and imaging examinations of PFPAS patients. Additionally, we outline main treatments and evaluate therapeutic effectiveness. ResultsA total of 121 patients were included in the analysis, with a mean onset age of 61.4 years. Swelling or thickening (49.6%, n=60/121) and pain (41.3%, n=50/121) were characteristic musculoskeletal symptoms of the hands. The median time between onset of PFPAS symptoms and detection of malignancy was 4 months, with a median survival of 13.0 months (range=2 to 69). The abnormal rate of ultrasound, magnetic resonance imaging, and bone scan of the musculoskeletal system was more than 80%. Effective therapeutic responses were observed in 66.0% (n=33/50) of cases treated with chemotherapies and 79.2% (n=19/24) with operations. Two patients who received biologics achieved partial remission. ConclusionPFPAS is a rare paraneoplastic condition, and early recognition of its distinctive symptoms may lead to the detection of underlying malignancy and timely treatments, potentially saving lives.