Subcutaneous sodium valproate in palliative care: A systematic review.

BACKGROUND: Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish to avoid intravenous access, subcutaneous infusions may be employed. Options for antiseizure medications that can be provided subcutaneously may be limited. Subcutaneous sodium valproate may be an additional management strategy. AIM: To evaluate the published experience of subcutaneous valproate use in palliative care, namely with respect to effectiveness and tolerability. DESIGN: A systematic review was registered (PROSPERO CRD42023453427), conducted and reported according to PRISMA reporting guidelines. DATA SOURCES: The databases PubMed, EMBASE and Scopus were searched for publications until August 11, 2023. RESULTS: The searches returned 429 results, of which six fulfilled inclusion criteria. Case series were the most common study design, and most studies included <10 individuals who received subcutaneous sodium valproate. There were three studies that presented results on the utility of subcutaneous sodium valproate for seizure control, which described it to be an effective strategy. One study also described it as an effective treatment for neuropathic pain. The doses were often based on presumed 1:1 oral to subcutaneous conversion ratios. Only one study described a local site adverse reaction, which resolved with a change of administration site. CONCLUSIONS: There are limited data on the use of subcutaneous sodium valproate in palliative care. However, palliative symptoms for which subcutaneous sodium valproate have been used successfully are seizures and neuropathic pain. The available data have described few adverse effects, supporting its use with an appropriate degree of caution.

A 20-year multicentre retrospective review of optic nerve sheath fenestration outcomes.

Background: Optic nerve sheath fenestration (ONSF) longitudinal outcomes remain unclear and are vital in the assessment of vision failure in patients with raised intracranial pressure (ICP). Furthermore, limited observational data exists regarding its use in other causes of raised ICP. Objective: To determine the efficacy and safety of ONSF for idiopathic intracranial hypertension (IIH), cerebral venous sinus thrombosis (CVST), and other indications. Method: Multicentre study from a tertiary hospital and specialty eye referral hospital in Melbourne, Australia, from July 2000 to December 2020. A total of 116 eyes from 70 patients undergoing ONSF were retrospectively reviewed with patient demographics, surgery indications, visual acuity (VA), visual fields, fundus photos of optic discs, retinal nerve fibre layer (RNFL) thickness, average thickness of optic discs on optical coherence tomography (OCT), and complications recorded. Parametric tests were used to compare the treatment groups pre- and post-operatively. Results: A total of 116 eyes from 70 patients underwent ONSF, which involved 92 eyes with IIH, 9 eyes with CVST, and 15 eyes with other aetiologies ('Other'). Post ONSF, there was a best corrected visual acuity (BCVA) improvement or stabilisation in 84% of patients in all groups, with 50% achieving a BCVA of 6/6 or better at the final follow-up. RNFL, visual fields, and fundus grades all trended towards improvement, with most improvement noted by day 360. Common complications included transient diplopia (n = 29, 25%) and worsening of visual function requiring further cerebrospinal fluid (CSF) diversion procedures (n = 20, 17%). Complications were most significant in the 'Other' group with 1/3 of eyes requiring further CSF diversion procedures. Conclusion: Our data demonstrates effectiveness in the use of ONSF in papilloedema with visual failure due to IIH or CVST and when other CSF diversion procedures or medical therapies have failed.

Systematic review and meta-analysis of ipsilateral and contralateral carotid web prevalence in embolic supratentorial strokes of undetermined source.

OBJECTIVES: A carotid web isdefined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. Its presence may be an under-recognised source of embolic stroke of undetermined source (ESUS). The aim of this study was to investigate its prevalence in previously reported studies. MATERIALS AND METHODS: A systematic literature review of Pubmed, EMBASE, and Scopus was conducted up until the 4/12/2021 using variations of the search terms - 'carotid web' and 'ischemic stroke'. Inclusion criteria were studies reporting carotid web prevalence in an ESUS cohort aged >18 years with adequate imaging. Secondary measures such as age, gender, ethnicity, and laterality were recorded. A meta-analysis of proportions was used to summarise the prevalence of webs along with a random-effects model to calculate the relative risk of ipsilateral and contralateral webs in ESUS. RESULTS: The initial search yielded 361 articles, with 11 remaining post the inclusion and exclusion criteria. A meta-analysis of allage groups yielded a total carotid web prevalence among patients with stroke of unknown cause of 9.58 % (95 % CI 5.62 - 15.85). Carotid webs were more often detected in females (76.5 % ± 22.3 %), and in those of African heritage (58 % ± 39 %). In comparison with patients without an ischemic stroke, there was a significant association found for an ipsilateral carotid web (risk ratio of 2.74 (95 % CI: 2.14 - 3.51)) but no association found for contralateral webs (risk ratio of 1.50 (95 % CI: 0.94 - 2.40)). CONCLUSION: The prevalence of ipsilateral carotid webs associated with ESUS is substantial, and may be more common in females and in individuals of African descent.

Clinical correlates of movement disorders in adult Niemann-Pick type C patients measured via a Personal KinetiGraph.

BACKGROUND: Niemann-Pick type C (NPC) is an autosomal recessive progressive neurodegenerative disorder caused by mutations in the NPC1 or NPC2 genes. Patients with this disorder have variable phenotypic presentations that often include neuropsychiatric manifestations, cognitive decline, and movement disorders. There is considerable interpatient variation in movement disorders, with limited quantitative measurements describing the movements observed. Objective measurements using wearable sensors provide clinically applicable monitoring of patients with Parkinson's disease, and hence may be utilized in patients with NPC. OBJECTIVE: To explore the relationship between objective measurements of movement obtained via the use of the Personal KinetiGraph (PKG) with the clinical information obtained via questionnaires and clinical rating tools of patients with Niemann-Pick type C. METHODS: Twelve patients with Niemann-Pick type C were recruited who wore the PKG for 6 days during regular activities. A 6-day output was provided by the manufacturer, which provided bradykinesia (BK) and dyskinesia (DK) scores. BK and DK scores were further divided into their interquartile ranges. A fluctuation score (FDS), percentage time immobile (PTI), and percent time with tremors (PTT) were also provided. Clinical assessments included Abnormal Involuntary Movement Scale (AIMS), Epworth Sleepiness Score (ESS), Falls, Neuropsychiatric Unit Assessment Tool (NUCOG), Parkinson's disease questionnaire (PDQ), and modified Unified Parkinson's Disease Rating Scale (UPDRS) which were performed over telehealth within 2 weeks of PKG use. Pearson's correlation analyses were utilized to explore the relationship between DK and BK quartiles and clinical measures. RESULTS: We found bradykinesia to be a feature among this cohort of patients, with a median BKS of 22.0 (7.4). Additionally, PTI scores were elevated at 4.9 (8.2) indicating elevated daytime sleepiness. Significant correlations were demonstrated between BK25 and Falls (r = - 0.74, 95% CI = [- 0.95, - 0.08]), BK50 and Falls (r = - 0.79, 95% CI = [- 0.96, - 0.19]), and BK75 and Falls (r = - 0.76, 95% CI = [- 0.95, - 0.11]). FDS correlated with PDQ (r = - 0.7, 95% CI = [- 0.92, - 0.18]), UPDRS IV (r = - 0.65, 95% CI = [- 0.90, - 0.09]), UPDRS (r = - 0.64, 95% CI = [- 0.9, - 0.06]), and AIMS (r = - 0.96, 95% CI = [- 0.99, - 0.49]). DK25 in comparison with NUCOG-A (r = 0.72, 95% CI = [0.17, 0.93]) and DK75 in comparison with NUCOG (r = 0.64, 95% CI = [0.02, 0.91]) and NUCOG-A (r = 0.63, 95% CI = [0.01, 0.90]) demonstrated significant correlations. Additionally, duration of illness in comparison with PTI (r = 0.72, 95% CI = [0.22, 0.92]) demonstrated significance. CONCLUSIONS: Utilization of PKG measures demonstrated that bradykinesia is under recognized among NPC patients, and the bradykinetic patients were less likely to report concerns regarding falls. Additionally, the FDS rather than the DKS is sensitive to the abnormal involuntary movements of NPC-reflecting a differing neurobiology of this chorea compared to levodopa-induced dyskinesias. Furthermore, dyskinetic individuals performed better in cognitive assessments of attention which may indicate an earlier timepoint within disease progression.