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 systematic review of the symptomatic management of Lhermitte's phenomenon.

INTRODUCTION: Lhermitte's phenomenon (LP) is a transient shock-like sensation that radiates down the spine into the extremities, usually with neck flexion. The potential efficacy and tolerability of various symptomatic therapies in the management of LP have not been systematically reviewed previously. METHOD: A systematic review was conducted using PubMed, EMBASE, and the Cochrane Library from inception to August 2022 for peer-reviewed articles describing the treatment of patients with Lhermitte's phenomenon. The review adheres to the PRISMA guidelines and was registered on PROSPERO. RESULTS: This systematic review included sixty-six articles, which included 450 patients with LP. Treatment of the underlying cause varied by aetiology. Whilst LP is most commonly considered in the context of structural pathology of the cervical cord, medication-induced LP was a common theme in the literature. The most common cause of medication-induced LP was platinum-based chemotherapy agents such as cisplatin and oxaliplatin. In medication-induced LP, symptoms typically resolved with cessation of the causative agent. Non-pharmacological treatment options were associated with mild-moderate symptomatic improvement. The most commonly used agents to treat patients with LP were carbamazepine and gabapentin, which resulted in variable degrees of symptomatic benefit. CONCLUSIONS: No randomised studies currently exist to support the use of symptomatic therapies to treat LP. Observational data suggest that some therapies may yield a symptomatic benefit in the management of LP. However, this systematic review identified a significant paucity of evidence in the literature, which suggests that further controlled studies are needed to investigate the optimal management of this common neurologic phenomenon.

Single count breath test for the evaluation of respiratory function in Myasthenia Gravis: A systematic review.

BACKGROUND: Myasthenia gravis (MG) can have a variety of respiratory presentations, ranging from mild symptoms through to respiratory failure. The evaluation of respiratory function in MG can be limited by accessibility to testing facilities, availability of medical equipment, and facial weakness. The single count breath test (SCBT) may be a useful adjunct in the evaluation of respiratory function in MG. METHOD: A systematic review of the databases PubMed, EMBASE, and the Cochrane Library was conducted from inception to October 2022 in accordance with PRISMA guidelines and was registered on PROSPERO. RESULTS: There were 6 studies that fulfilled the inclusion criteria. The described method of evaluating SCBT involves inhaling deeply, then counting at two counts per second, in English or Spanish, sitting upright, with normal vocal register, until another breath needs to be taken. The identified studies support that the SCBT has a moderate correlation with forced vital capacity. These results also support that SCBT can assist the identification of MG exacerbation, including via assessment over the telephone. The included studies support a threshold count of ≥ 25 as consistent with normal respiratory muscle function. Although further analysis is needed, the included studies describe the SCBT as a quick bedside tool that is inexpensive and well tolerated. CONCLUSIONS: The results of this review support the clinical utility of the SCBT in assessing respiratory function in MG and describe the most current and effective methods of administration.

Magnetic resonance-guided laser interstitial thermal therapy for drug-resistant epilepsy: A systematic review and individual participant data meta-analysis.

Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has emerged as a popular minimally invasive alternative to open resective surgery for drug-resistant epilepsy (DRE). We sought to perform a systematic review and individual participant data meta-analysis to identify independent predictors of seizure outcome and complications following MRgLITT for DRE. Eleven databases were searched from January 1, 2010 to February 6, 2021 using the terms "MR-guided ablation therapy" and "epilepsy". Multivariable mixed-effects Cox and logistic regression identified predictors of time to seizure recurrence, seizure freedom, operative complications, and postoperative neurological deficits. From 8705 citations, 46 studies reporting on 450 MRgLITT DRE patients (mean age = 29.5 ± 18.1 years, 49.6% female) were included. Median postoperative seizure freedom and follow-up duration were 15.5 and 19.0 months, respectively. Overall, 240 (57.8%) of 415 patients (excluding palliative corpus callosotomy) were seizure-free at last follow-up. Generalized seizure semiology (hazard ratio [HR] = 1.78, p = .020) and nonlesional magnetic resonance imaging (MRI) findings (HR = 1.50, p = .032) independently predicted shorter time to seizure recurrence. Cerebral cavernous malformation (CCM; odds ratio [OR] = 7.97, p < .001) and mesial temporal sclerosis/atrophy (MTS/A; OR = 2.21, p = .011) were independently associated with greater odds of seizure freedom at last follow-up. Operative complications occurred in 28 (8.5%) of 330 patients and were independently associated with extratemporal ablations (OR = 5.40, p = .012) and nonlesional MRI studies (OR = 3.25, p = .017). Postoperative neurological deficits were observed in 53 (15.1%) of 352 patients and were independently predicted by hypothalamic hamartoma etiology (OR = 5.93, p = .006) and invasive electroencephalographic monitoring (OR = 4.83, p = .003). Overall, MRgLITT is particularly effective in treating patients with well-circumscribed lesional DRE, such as CCM and MTS/A, but less effective in nonlesional cases or lesional cases with a more diffuse epileptogenic network associated with generalized seizures. This study identifies independent predictors of seizure freedom and complications following MRgLITT that may help further guide patient selection.

Dual ankyrinG and subpial autoantibodies in a man with well-controlled HIV infection with steroid-responsive meningoencephalitis: A case report.

Neuroinvasive infection is the most common cause of meningoencephalitis in people living with human immunodeficiency virus (HIV), but autoimmune etiologies have been reported. We present the case of a 51-year-old man living with HIV infection with steroid-responsive meningoencephalitis whose comprehensive pathogen testing was non-diagnostic. Subsequent tissue-based immunofluorescence with acute-phase cerebrospinal fluid revealed anti-neural antibodies localizing to the axon initial segment (AIS), the node of Ranvier (NoR), and the subpial space. Phage display immunoprecipitation sequencing identified ankyrinG (AnkG) as the leading candidate autoantigen. A synthetic blocking peptide encoding the PhIP-Seq-identified AnkG epitope neutralized CSF IgG binding to the AIS and NoR, thereby confirming a monoepitopic AnkG antibody response. However, subpial immunostaining persisted, indicating the presence of additional autoantibodies. Review of archival tissue-based staining identified candidate AnkG autoantibodies in a 60-year-old woman with metastatic ovarian cancer and seizures that were subsequently validated by cell-based assay. AnkG antibodies were not detected by tissue-based assay and/or PhIP-Seq in control CSF (N = 39), HIV CSF (N = 79), or other suspected and confirmed neuroinflammatory CSF cases (N = 1,236). Therefore, AnkG autoantibodies in CSF are rare but extend the catalog of AIS and NoR autoantibodies associated with neurological autoimmunity.

Little evidence for an effect of smoking on multiple sclerosis risk: A Mendelian Randomization study.

The causes of multiple sclerosis (MS) remain unknown. Smoking has been associated with MS in observational studies and is often thought of as an environmental risk factor. We used two-sample Mendelian randomization (MR) to examine whether this association is causal using genetic variants identified in genome-wide association studies (GWASs) as associated with smoking. We assessed both smoking initiation and lifetime smoking behaviour (which captures smoking duration, heaviness, and cessation). There was very limited evidence for a meaningful effect of smoking on MS susceptibility as measured using summary statistics from the International Multiple Sclerosis Genetics Consortium (IMSGC) meta-analysis, including 14,802 cases and 26,703 controls. There was no clear evidence for an effect of smoking on the risk of developing MS (smoking initiation: odds ratio [OR] 1.03, 95% confidence interval [CI] 0.92-1.61; lifetime smoking: OR 1.10, 95% CI 0.87-1.40). These findings suggest that smoking does not have a detrimental consequence on MS susceptibility. Further work is needed to determine the causal effect of smoking on MS progression.

Precuneal epilepsy: Clinical features and surgical outcome.

OBJECTIVE: The precuneus is a complex and highly connected structure located in the medial portion of the superior parietal lobule. The clinical presentation of precuneal epilepsy is poorly characterized, mostly because these patients have seldom been distinguished from those with other types of parietal lobe epilepsy. The present study aims to improve the understanding of precuneal epilepsy by detailing its clinical features and surgical outcomes. METHODS: Six previously unreported cases of drug-resistant precuneal epilepsy investigated between 2002 and 2014 were retrospectively studied. Seizure focus was confirmed by presence of a lesion, intracranial monitoring, or post-operative seizure control when applicable. RESULTS: Seizures arising from the precuneus have heterogeneous presentations, including body movement sensation, visual auras, eye movements, vestibular manifestations, and complex motor behaviors. Two patients with an anterior precuneus lesion described body movement sensations whereas two others with a posterior precuneus lesion experienced visual symptoms. Two of the five patients who underwent epilepsy surgery achieved good seizure control (Engel IA). One patient underwent gamma knife surgery with an Engel IV outcome. Surgical complications included contralateral visual field impairment, limb hypoesthesia and hemispatial neglect. One patient developed late-onset epilepsia partialis continua from a Rolandic subdural grid-related contusion. SIGNIFICANCE: In absence of a clear precuneal epileptogenic lesion, recognition of a precuneal focus is challenging. Magnetoencephalography may sometimes localize the generator but invasive EEG remains in well-selected cases necessary to identify the seizure focus. Surgical failures may be explained by the widespread connectivity of the precuneus with distant and adjacent structures. Different ictal manifestations of precuneal epilepsy in this series provide a clinical correlate to the described functional subdivisions of the precuneus.

Association of postoperative furosemide use with a reduced blood transfusion rate in sagittal craniosynostosis surgery.

OBJECT A major challenge in sagittal craniosynostosis surgery is the high transfusion rate (50%-100%) related to blood loss in small pediatric patients. Several approaches have been proposed to prevent packed red blood cell (PRBC) transfusion, including endoscopic surgery, erythropoietin ortranexamic acid administration, and preoperative hemodilution. The authors hypothesized that a significant proportion of postoperative anemia observed in pediatric patients is actually dilutional. Consequently, since 2005, at CHU Sainte-Justine, furosemide has been administered to correct the volemic status and prevent PRBC transfusion. The purpose of this study was to evaluate the impact of postoperative furosemide administration on PRBC transfusion rates. METHODS This was a retrospective study of 96 consecutive patients with sagittal synostosis who underwent surgery at CHU Sainte-Justine between January 2000 and May 2012. The mean age at surgery was 4.9 ± 1.5 months (range 2.8-8.7 months). Patients who had surgery before 2005 constituted the control group. Those who had surgery in 2005 or 2006 were considered part of an implementation phase because furosemide administration was not routine. Patients who had surgery after 2006 were part of the experimental (or furosemide) group. Transfusion rates among the 3 groups were compared. The impact of furosemide administration on transfusion requirement was also measured while accounting for other variables of interest in a multiple logistic regression model. RESULTS The total transfusion rate was significantly reduced in the furosemide group compared with the control group (31.3% vs 62.5%, respectively; p = 0.009), mirroring the decrease in the postoperative transfusion rate between the groups (18.3% vs 50.0%, respectively; p = 0.003). The postoperative transfusion threshold remained similar throughout the study (mean hemoglobin 56.0 g/dl vs 60.9 g/dl for control and furosemide groups, respectively; p = 0.085). The proportion of nontransfused patients with recorded hemoglobin below 70 g/dl did not differ between the control and furosemide groups (41.7% vs 28.6%, respectively; p = 0.489). Surgical procedure, preoperative hemoglobin level, estimated blood loss, and furosemide administration significantly affected the risk of receiving a postoperative PRBC transfusion. When these variables were analyzed in a multiple logistic regression model, furosemide administration remained strongly associated with a reduced risk of being exposed to a blood transfusion (OR 0.196, p = 0.005). There were no complications related to furosemide administration. CONCLUSIONS A significant part of the postoperative anemia observed in patients who underwent sagittal craniosynostosis surgery was due to hypervolemic hemodilution. Correction of the volemic status with furosemide administration significantly reduces postoperative PRBC transfusion requirements in these patients.

Prognostic tests and antiepileptic drug withdrawal after epilepsy surgery.

Approximately one in three patients with a successful epilepsy surgery will have seizure recurrence following antiepileptic drugs (AED) withdrawal. The value of postoperative testing for predicting seizure relapse after AED tapering is not clear. The purpose of this study was to review the literature for evidence on the use of postoperative investigations before AED discontinuation after successful epilepsy surgery. We were unable to identify studies on the prognostic value of postoperative magnetic resonance imaging and AED blood levels. The literature review yielded seven studies on the predictive value of electroencephalography. Four studies found no association between interictal discharges (IED) and seizure relapse. These studies suffered from various limitations due to their retrospective design and generally small cohorts. Two of the three studies reporting a positive association were prospective and provided strong evidence of an increased risk of seizure recurrence with presence of postoperative IED in successfully operated patients undergoing AED withdrawal.

Somatosensory and pharyngolaryngeal auras in temporal lobe epilepsy surgeries.

Purpose. Somatosensory (SSA) and pharyngolaryngeal auras (PLA) may suggest an extratemporal onset (e.g., insula, second somatosensory area). We sought to determine the prognostic significance of SSA and PLA in temporal lobe epilepsy (TLE) patients undergoing epilepsy surgery. Methods. Retrospective review of all patients operated for refractory TLE at our institution between January 1980 and July 2007 comparing outcome between patients with SSA/PLA to those without. Results. 158 patients underwent surgery for pharmacoresistant TLE in our institution. Eleven (7%) experienced SSA/PLA as part of their seizures. All but one had lesional (including hippocampal atrophy/sclerosis) TLE. Compared to patients without SSA or PLA, these patients were older (P = 0.049), had a higher prevalence of early ictal motor symptoms (P = 0.022) and prior CNS infection (P = 0.022), and were less likely to have a localizing SPECT study (P = 0.025). A favorable outcome was achieved in 81.8% of patients with SSA and/or PLA and 90.4% of those without SSA or PLA (P > 0.05). Conclusion. Most patients with pharmacoresistant lesional TLE appear to have a favorable outcome following temporal lobectomy, even in the presence of SSA and PLA.

Temporal lobe epilepsy surgery failures: a review.

Patients with temporal lobe epilepsy (TLE) are refractory to antiepileptic drugs in about 30% of cases. Surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20-30% of TLE patients. Several reasons have been identified to explain these surgical failures. This paper will address the five most common causes of TLE surgery failure (a) insufficient resection of epileptogenic mesial temporal structures, (b) relapse on the contralateral mesial temporal lobe, (c) lateral temporal neocortical epilepsy, (d) coexistence of mesial temporal sclerosis and a neocortical lesion (dual pathology); and (e) extratemporal lobe epilepsy mimicking TLE or temporal plus epilepsy. Persistence of epileptogenic mesial structures in the posterior temporal region and failure to distinguish mesial and lateral temporal epilepsy are possible causes of seizure persistence after TLE surgery. In cases of dual pathology, failure to identify a subtle mesial temporal sclerosis or regions of cortical microdysgenesis is a likely explanation for some surgical failures. Extratemporal epilepsy syndromes masquerading as or coexistent with TLE result in incomplete resection of the epileptogenic zone and seizure relapse after surgery. In particular, the insula may be an important cause of surgical failure in patients with TLE.