Symptoms and signs did not predict outcome after surgery: a prospective study of 143 patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE: To determine the utility of symptoms, signs, comorbidities and background variables for the prediction of outcome of treatment in iNPH. METHODS: A prospective observational study of consecutively included iNPH patients, who underwent neurological, physiotherapeutic and neuropsychological assessments before and after shunt surgery. The primary outcome measure was the total change on the iNPH scale, and patients were defined as improved postoperatively if they had improved by at least five points on that scale. RESULTS: 143 iNPH patients were included, and 73% of those were improved after surgery. None of the examined symptoms or signs could predict which patients would improve after shunt surgery. A dominant subjective complaint of memory problems at baseline was predictive of non-improvement. The reported comorbidities, duration of symptoms and BMI were the same in improved and non-improved patients. Each of the symptom domains (gait, neuropsychology, balance, and continence) as well as the total iNPH scale score improved significantly (from median 53 to 69, p < 0.001). The proportions of patients with shuffling gait, broad-based gait, paratonic rigidity and retropulsion all decreased significantly. DISCUSSION: This study confirms that the recorded clinical signs, symptoms, and impairments in the adopted clinical tests are characteristic findings in iNPH, based on that most of them improved after shunt surgery. However, our clinical data did not enable predictions of whether patients would respond to shunt surgery, indicating that the phenotype is unrelated to the reversibility of the iNPH state and should mainly support diagnosis. Absence of specific signs should not be used to exclude patients from treatment.

Adherence to anti-seizure medications in the Swedish Prospective Regional Epilepsy Database and Biobank for Individualized Clinical Treatment (PREDICT).

The aim of this study was to describe the extent of, and risk factors for, non-adherence to anti-seizure medications (ASMs) in adult people with epilepsy (PWE) in Sweden. A cross-sectional multi-centre study was performed of PWEs in western Sweden, with data from medical records, and a questionnaire filled in by the participants including self-reports on how often ASM doses had been forgotten during the past year. Participants were categorized into adherent if they forgot at 0-1 occasion, and non-adherent if they forgot at 2-10 or >10 occasions. Demographic and clinical factors were compared by Chi2- or Fisher's test and a logistic regression model was used to find risk factors for non-adherence. In the cohort of 416 PWE aged median 43, IQR 29-62 years, 398 patients were prescribed ASM treatment at inclusion, and 39 % (n = 154) were in the non-adherent group. Significant factors in the multivariable analysis were: younger age, seizure freedom the past year, valproate treatment and experiencing side effects. The rate of self-reported non-adherence was high, illustrating a need for continuous focus on fundamental aspects of epilepsy care. The identified risk factors could enable quality improvement projects and patient education to be directed to those at risk of non-adherence.

Prevalence and nature of patient-reported antiseizure medication side effects in a Swedish regional multi-center study.

PURPOSE: Side effects is one of the major clinical problems in epilepsy care. We assessed the prevalence of ASM side effects in participants in a large regional multicenter observational study in western Sweden and aimed to identify risk factors and inventory the nature of side effects with different ASM regimes. METHODS: Cross-sectional analysis of survey answers and clinical characteristics of 406 adult participants recruited to a regional observational study between December 2020 and March 2023. Half of the participants had been seizure free for one year. Second-generation or newer ASMs were the most common. RESULTS: A total of 164 (40 %, 95 %CI: 36-45) patients reported side effects. Patients reporting side effects were younger (median 41 vs 47 years, p = 0.015), had more frequently experienced a seizure in the last year (p = 0.02), and were more often on ASM polytherapy (p < 0.01). ASM polytherapy and age were significant risk factors in regression models, but the explanatory value was low. The most common side effect was tiredness followed by cognitive symptoms. CONCLUSIONS: Our findings show that side effects are still common in epilepsy care and suggests that unnecessary polypharmacy should be avoided. Apart from number or ASMs, predicting who will experience side effects is difficult and more research on individual vulnerability is needed.

Antiseizure medication selection and retention for adult onset focal epilepsy in a Swedish health service region: A population-based cohort study.

OBJECTIVE: Historically, approximately half of those with newly diagnosed epilepsy have responded to and tolerated the first antiseizure medication (ASM), but there are few contemporary real-world data. Third-generation ASMs have improved tolerability and are increasingly used according to prescription data. We aimed to describe current ASM selection and retention in adult onset focal epilepsy in western Sweden. METHODS: A multicenter retrospective cohort study was performed at five public neurology care providers in western Sweden (nearly complete coverage in the area). We reviewed 2607 medical charts and included patients diagnosed with nongeneralized epilepsy after January 1, 2020 who had a seizure onset after age 25 years (presumed focal onset) and were started on ASM monotherapy. RESULTS: A total of 542 patients (median age at seizure onset = 68 years, interquartile range = 52-77) were included. Most patients received levetiracetam (62%) or lamotrigine (35%), with levetiracetam being more common among men and those with structural causes or short epilepsy duration. During follow-up (median = 471.5 days), 463 patients (85%) remained on the first ASM. Fifty-nine (18%) patients discontinued levetiracetam, and 18 (10%) ended treatment with lamotrigine (p = .010), most commonly because of side effects. In a multivariable Cox regression model, the discontinuation risk was higher for levetiracetam than lamotrigine (adjusted hazard ratio = 2.01, 95% confidence interval = 1.16-3.51). SIGNIFICANCE: Levetiracetam and lamotrigine were the dominating first ASMs for adult onset focal epilepsy in our region, indicating good awareness of problems with enzyme induction or teratogenicity of older drugs. The most striking finding is the high retention rates, perhaps reflecting a shift toward an older epilepsy population, higher tolerability of newer ASMs, or suboptimal follow-up. The finding that treatment retention differed among patients receiving levetiracetam and lamotrigine aligns with the recent SANAD II results. It suggests lamotrigine may be underutilized in our region and that education efforts are needed to ensure it is considered the first choice more often.

Early shunt surgery improves survival in idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: To examine the effect of delayed compared to early planning of shunt surgery on survival, in patients with idiopathic normal pressure hydrocephalus (iNPH), a long-term follow-up case-control study of patients exposed to a severe delay of treatment was performed. METHODS: In 2010-2011 our university hospital was affected by an administrative and economic failure that led to postponement of several elective neurosurgical procedures. This resulted in an unintentional delay of planning of treatment for a group of iNPH patients, referred to as iNPHDelayed (n = 33, waiting time for shunt surgery 6-24 months). These were compared to patients treated within 3 months, iNPHEarly (n = 69). Primary outcome was mortality. Dates and underlying causes of death were provided by the Cause of Death Registry. Survival was analysed by Kaplan-Meier plots and a Cox proportional hazard model adjusted for potential confounders. RESULTS: Median follow-up time was 6.0 years. Crude 4-year mortality was 39.4% in iNPHDelayed compared to 10.1% in iNPHEarly (p = 0.001). The adjusted hazard ratio in iNPHDelayed was 2.57; 95% confidence interval 1.13-5.83, p = 0.024. Causes of death were equally distributed between the groups except for death due to malignancy which was not seen in iNPHDelayed  but in 4/16 cases in iNPHEarly (p = 0.044). CONCLUSIONS: The present data indicate that shunt surgery is effective in iNPH and that early treatment increases survival.

Survival in treated idiopathic normal pressure hydrocephalus.

OBJECTIVE: To describe survival and causes of death in 979 treated iNPH patients from the Swedish Hydrocephalus Quality Registry (SHQR), and to examine the influence of comorbidities, symptom severity and postoperative outcome. METHODS: All 979 patients operated for iNPH 2004-2011 and registered in the SHQR were included. A matched control group of 4890 persons from the general population was selected by Statistics Sweden. Data from the Swedish Cause of Death Registry was obtained for patients and controls. RESULTS: At a median 5.9 (IQR 4.2-8.1) year follow-up, 37% of the iNPH patients and 23% of the controls had died. Mortality was increased in iNPH patients by a hazard ratio of 1.81, 95% CI 1.61-2.04, p < 0.001. More pronounced symptoms in the preoperative ordinal gait scale and the Mini-mental State Examination were the most important independent predictors of mortality along with the prevalence of heart disease. Patients who improved in both the gait scale and in the modified Rankin Scale postoperatively (n = 144) had a similar survival as the general population (p = 0.391). Deaths due to cerebrovascular disease or dementia were more common in iNPH patients, while more controls died because of neoplasms or disorders of the circulatory system. CONCLUSIONS: Mortality in operated iNPH patients is 1.8 times increased compared to the general population, a lower figure than previously reported. The survival of iNPH patients who improve in gait and functional independence is similar to that of the general population, indicating that shunt surgery for iNPH, besides improving symptoms and signs, can normalize survival.

The phenotype of idiopathic normal pressure hydrocephalus-a single center study of 429 patients.

INTRODUCTION: Idiopathic Normal Pressure Hydrocephlaus (iNPH) is, despite a vastly improved knowledge of the disorder since its first description still underdiagnosed and undertreated. Because of this, there is a need for further large studies describing the typical symptomatology and reversibility of symptoms in iNPH, which was the aim of this study. METHODS: In all, 429 patients (mean age 71 years) were included. Detailed pre- and postoperative examinations of symptoms and signs were analyzed. A composite outcome measure was constructed. RESULTS: Sixty-eight % improved after surgery. Preoperatively, 72% exhibited symptoms from three or four of the assessed domains (gait, balance, neuropsychology and continence) while 41% had symptoms from all four domains. Ninety % had gait disturbances, of which 75% had broad-based gait, 65% shuffling gait and 30% freezing of gait. These disturbances coexisted in most patients preoperatively, but were more likely to appear as isolated findings after surgery. Impaired balance was seen in 53% and retropulsion in 46%. MMSE <25 was seen in 53% and impaired continence in 86%. Improvements were seen in all symptom domains postoperatively. CONCLUSIONS: The iNPH phenotype is characterized by a disturbance in at least 3/4 symptom domains in most patients, with improvements in all domains after shunt surgery. Most patients present with a broad-based and shuffling gait as well as paratonia. Present symptoms in all domains and a shuffling gait at the time of diagnosis seem to predict a favorable postoperative outcome, whereas symptom severity does not.

Long-term effects of complications and vascular comorbidity in idiopathic normal pressure hydrocephalus: a quality registry study.

BACKGROUND: There is little knowledge about the factors influencing the long-term outcome after surgery for idiopathic normal pressure hydrocephalus (iNPH). OBJECTIVE: To evaluate the effects of reoperation due to complications and of vascular comorbidity (hypertension, diabetes, stroke and heart disease) on the outcome in iNPH patients, 2-6 years after shunt surgery. METHODS: We included 979 patients from the Swedish Hydrocephalus Quality Registry (SHQR), operated on for iNPH during 2004-2011. The patients were followed yearly by mailed questionnaires, including a self-assessed modified Rankin Scale (smRS) and a subjective comparison between their present and their preoperative health condition. The replies were grouped according to the length of follow-up after surgery. Data on clinical evaluations, vascular comorbidity, and reoperations were extracted from the SHQR. RESULTS: On the smRS, 40% (38-41) of the patients were improved 2-6 years after surgery and around 60% reported their general health condition to be better than preoperatively. Reoperation did not influence the outcome after 2-6 years. The presence of vascular comorbidity had no negative impact on the outcome after 2-6 years, assessed as improvement on the smRS or subjective improvement of the health condition, except after 6 years when patients with hypertension and a history of stroke showed a less favorable development on the smRS. CONCLUSION: This registry-based study shows no negative impact of complications and only minor effects of vascular comorbidity on the long-term outcome in iNPH.

Cerebrospinal fluid markers of neuronal and glial cell damage in patients with autoimmune neurologic syndromes with and without underlying malignancies.

Autoimmune neurologic syndromes can be paraneoplastic (associated with malignancies and/or onconeural antibodies), or non-paraneoplastic. Their clinical presentation is often similar. As prognosis is related to malignancy treatment, better biomarkers are needed to identify patients with malignancy. We investigated cerebrospinal fluid (CSF) markers of neuronal (neurofilament light chain, NFL and total tau protein, T-tau) and glial (glial fibrillary acidic protein) damage. CSF-NFL and T-tau were increased in both paraneoplastic and non-paraneoplastic autoimmune syndromes. Patients with manifest malignancies were older, had less epilepsy, more focal central and peripheral neurological signs and symptoms, and worse long-term outcome, than those without malignancy. CSF-NFL-levels predicted long-term outcome but were not diagnostic for malignancy, after age adjustment.

Natural course of idiopathic normal pressure hydrocephalus.

OBJECTIVES: The natural course of idiopathic normal pressure hydrocephalus (iNPH) has not been thoroughly studied. The consequences of postponing shunt treatment are largely unknown. We aimed to describe the effects of waiting for more than 6 months before surgery and to compare the outcome with that seen in patients who waited for less than 3 months. METHODS: 33 patients (iNPHDelayed) underwent an initial investigation (Pre-op 1), followed by re-examination, just prior to surgery, after waiting for at least 6 months (Pre-op 2). Outcome was evaluated after 3 months of treatment. 69 patients who were surgically treated within 3 months after Pre-op 1 and who were also evaluated after 3 months of treatment constituted a comparison group (iNPHEarly). Evaluations were done with the iNPH scale and the modified Rankin Scale (mRS). iNPHDelayed patients were prospectively studied with regard to outcome, whereas the comparison group iNPHEarly was defined and analysed retrospectively. RESULTS: iNPHDelayed patients deteriorated significantly during their wait for surgery, with progression of symptom severity ranging from +7 to -47 on the iNPH scale, and from 0 to +3 on the mRS (both p<0.001). The magnitude of change after surgery was similar in the groups, but since the symptoms of iNPHDelayed patients had worsened while waiting, their final outcome was significantly poorer. CONCLUSIONS: The natural course of iNPH is symptom progression over time, with worsening in gait, balance and cognitive symptoms. This deterioration is only partially reversible. To maximise the benefits of shunt treatment, surgery should be performed soon after diagnosis.