Documentation of neurological status in patients admitted to an intensive care unit after cardiac arrest: A 10-year cohort study.

OBJECTIVE: The objective of this study was to describe the documented neurological assessment and investigations for neuroprognostication in patients after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of adult patients after cardiac arrest, admitted to a tertiary intensive care unit (ICU), between January 2009 and December 2018. MAIN OUTCOME MEASURES: The main outcome measures were the proportion of patients with a documented Glasgow Coma Scale (GCS) score and investigations for neuroprognostication. RESULTS: Four hundred twenty-seven patients formed the study cohort. The GCS score was documented for 267 (63%) patients at some time during their ICU stay. The proportion of patients with the GCS score documented decreased each day of ICU stay (59% at day 1, 20% at day 5). Pupil reflex to light was recorded in 352 (82%), corneal reflex in 155 (36%), and limb reflexes in 216 (51%) patients. Twenty-eight (6.6%) patients underwent brain magnetic resonance imaging, 10 (2.3%) an electroencephalogram, and two somatosensory evoked potentials. Withdrawal of life-sustaining treatments occurred in 166 (39%) patients, and 221 (52%) patients died in hospital. CONCLUSIONS: In this single-centre study of patients admitted to the ICU after cardiac arrest, the GCS score was inconsistently documented, and investigations for neuroprognostication were infrequent.

Long-term mood, quality of life, and seizure freedom in intracranial EEG epilepsy surgery.

OBJECTIVES: To determine the long-term outcomes in patients undergoing intracranial EEG (iEEG) evaluation for epilepsy surgery in terms of seizure freedom, mood, and quality of life at St. Vincent's Hospital, Melbourne. METHODS: Patients who underwent iEEG between 1999 and 2016 were identified. Patients were retrospectively assessed between 2014 and 2017 by specialist clinic record review and telephone survey with standardized validated questionnaires for: 1) seizure freedom using the Engel classification; 2) Mood using the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E); 3) Quality-of-life outcomes using the QOLIE-10 questionnaire. Summary statistics and univariate analysis were performed to investigate variables for significance. RESULTS: Seventy one patients underwent iEEG surgery: 49 Subdural, 14 Depths, 8 Combination with 62/68 (91.9%) of those still alive, available at last follow-up by telephone survey or medical record review (median of 8.2 years). The estimated epileptogenic zone was 62% temporal and 38% extra-temporal. At last follow-up, 69.4% (43/62) were Engel Class I and 30.6% (19/62) were Engel Class II-IV. Further, a depressive episode (NDDI-E > 15)was observed in 34% (16/47), while a 'better quality of life' (QOLIE-10 score < 25) was noted in 74% (31/42). Quality of life (p < 0.001) but not mood (p = 0.24) was associated with seizure freedom. SIGNIFICANCE: Long-term seizure freedom can be observed in patients undergoing complex epilepsy surgery with iEEG evaluation and is associated with good quality of life.

Efficacy and tolerability of adjuvant perampanel: an Australian multicenter real-world observational study in refractory focal and generalized epilepsy syndromes.

PURPOSE: To explore the efficacy and tolerability of adjuvant perampanel (PER) and their associated risk factors in late add-on drug-resistant epilepsy. METHOD: Retrospective multicenter 'real-world' observational study. Consecutively identified patients commenced on PER, with mixed epilepsy syndromes, from nine Australian epilepsy centers. Primary efficacy endpoints were at least 50% reduction in seizure frequency (responders), seizure freedom, and retention at 6 and 12 months, following a 3-month titration period. Tolerability endpoints were cessation of PER for any reason, cessation of PER due to treatment-emergent adverse events (TEAE), or cessation due to inefficacy. Outcomes were assessed for a-priori risk factors associated with efficacy and tolerability. RESULTS: Three-hundred and eighty seven adults were identified and followed up for a median of 12.1 months (IQR 7.0-25.2). Focal epilepsy accounted for 79.6% (FE), idiopathic generalized epilepsy (IGE), 10.3% and developmental epileptic encephalopathy (DEE) 10.1%, of the cohort. All patients had drug-resistant epilepsy, 71.6% had never experienced six months of seizure freedom, and the mean number of antiepileptic medications (AEDs) prior to starting PER was six. At 12 months, with missing cases classified as treatment failure, retention was 40.0%, responder 21.7%, and seizure freedom 9.0%, whereas, using last outcome carried forward (LOCF), responder and seizure freedom rates were 41.3% and 14.7%, respectively. Older age of epilepsy onset was associated with a marginal increase in the likelihood of seizure freedom at 12-month maintenance (OR 1.04, 95% CI 1.02, 1.06). Male sex (adjusted OR [aOR] 2.06 95% CI 1.33, 3.19), lower number of prior AEDs (aOR 0.84, 95% CI 0.74, 0.96) and no previous seizure-free period of at least 6-month duration (aOR 2.04 95% CI 1.21, 3.47) were associated with retention. Perampanel combined with a GABA receptor AED was associated with a lower responder rate at 12 months but reduced cessation of PER. The most common TEAEs were neuropsychiatric (18.86%), followed by dizziness (13.70%), and sleepiness (5.68%). CONCLUSIONS: Adjuvant PER treatment, even in late-add on drug-resistant epilepsy is an effective and well-tolerated treatment for drug-resistant epilepsy.

Improved irritability, mood, and quality of life following introduction of perampanel as late adjunctive treatment for epilepsy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and tolerability of perampanel (PER) in late adjunctive treatment of focal epilepsy. We assessed outcomes 1) according to patients' clinical profiles and the broad mechanism of action (MoA) of concomitant antiepileptic drugs (AEDs) and 2) the effects of PER on adverse events, irritability, mood, and quality of life (QOL). METHODS: Consecutive patients commenced on PER at two epilepsy centers in Melbourne, Australia were identified. A nested cohort underwent detailed prospective assessment, while the remainder were retrospectively analyzed. Six- and 12-month efficacy endpoints were at least a 50% reduction in seizure frequency (responders) and complete seizure freedom. The prospective cohort underwent standardized validated questionnaires at 0, 1, 3, 6, and 12 months using the modified semi-structured seizure interview (SSI), Liverpool Adverse Events Profile (LAEP), Quality of Life in Epilepsy-Patient-Weighted (QOLIE-10-P), Neurological Disorders Depression Inventory Epilepsy (NDDI-E), and an Irritability Questionnaire. RESULTS: One hundred sixty patients were followed for a median of 6 months: the mean number of prior AEDs was 6, 99% had drug-resistant epilepsy, and 72% had never experienced a prior seizure-free period of at least 6 months (=continuously refractory epilepsy). Perampanel was associated with responder and seizure freedom rates of 30.6% and 9.4% at 6 months and 19.4% and 4.4% (5.6% adjusted for the titration period) at 12 months. Having "continuously refractory epilepsy" was associated with a reduced likelihood of seizure freedom at 6 months (5% vs. 30%; p = 0.001) and 12 months (3% vs. 13%; p = 0.058). Quality of Life in Epilepsy-Patient-Weighted, irritability, and NDDI-E showed mean improvement at 6 months from baseline. SIGNIFICANCE: Even when used as late add-on adjunctive therapy in patients with highly refractory focal epilepsy, PER can result in 12-month seizure freedom of 5.6%. The likelihood of seizure freedom was associated with prior "continuous medication refractoriness". Six months after introduction of PER patients reported improved mood, QOL, and decreased irritability.

Receive + Heart = Love. Bidirectional Nourishment in the Practice of Medicine.

Attitudinal considerations are so important in the practice of meeting the patient as whole person, and in our literature, these are underexamined. Where does love sit in the transactionality of medical practice? Is this an uncomfortable question? In times which challenge intention and resolve, could the reflection be in some way nourishing?

Neurological Health: Not Merely the Absence of Disease: Current Wellbeing Instruments Across the Spectrum of Neurology.

OBJECTIVE: Well-being and quality of life can vary independently of disease. Instruments measuring well-being and quality of life are commonly used in neurology, but there has been little investigation into the extent in which they accurately measure wellbeing/quality of life or if they merely reflect a diseased state of an individual. DESIGN: Systematic searches, thematic analysis and narrative synthesis were undertaken. Individual items from instruments represented in ≥ 5 publications were categorised independently, without prior training, by five neurologists and one well-being researcher, as relating to 'disease-effect' or 'Well-being' with a study-created instrument. Items were additionally categorised into well-being domains. DATA SOURCES: MEDLINE, EMBASE, EMCARE and PsycINFO from 1990 to 2020 were performed, across the 13 most prevalent neurological diseases. RESULTS: 301 unique instruments were identified. Multiple sclerosis had most unique instruments at 92. SF-36 was used most, in 66 studies. 22 instruments appeared in ≥ 5 publications: 19/22 'well-being' outcome instruments predominantly measured disease effect (Fleiss kappa = .60). Only 1/22 instruments was categorised unanimously as relating to well-being. Instruments predominantly measured mental, physical and activity domains, over social or spiritual. CONCLUSIONS: Most neurological well-being or quality-of-life instruments predominantly measure disease effect, rather than disease-independent well-being. Instruments differed widely in well-being domains examined.

Cognitive impairment and vitamin B12: a review.

BACKGROUND: This review examines the associations between low vitamin B12 levels, neurodegenerative disease, and cognitive impairment. The potential impact of comorbidities and medications associated with vitamin B12 derangements were also investigated. In addition, we reviewed the evidence as to whether vitamin B12 therapy is efficacious for cognitive impairment and dementia. METHODS: A systematic literature search identified 43 studies investigating the association of vitamin B12 and cognitive impairment or dementia. Seventeen studies reported on the efficacy of vitamin B12 therapy for these conditions. RESULTS: Vitamin B12 levels in the subclinical low-normal range (<250 ρmol/L) are associated with Alzheimer's disease, vascular dementia, and Parkinson's disease. Vegetarianism and metformin use contribute to depressed vitamin B12 levels and may independently increase the risk for cognitive impairment. Vitamin B12 deficiency (<150 ρmol/L) is associated with cognitive impairment. Vitamin B12 supplements administered orally or parenterally at high dose (1 mg daily) were effective in correcting biochemical deficiency, but improved cognition only in patients with pre-existing vitamin B12 deficiency (serum vitamin B12 levels <150 ρmol/L or serum homocysteine levels >19.9 µmol/L). CONCLUSION: Low serum vitamin B12 levels are associated with neurodegenerative disease and cognitive impairment. There is a small subset of dementias that are reversible with vitamin B12 therapy and this treatment is inexpensive and safe. Vitamin B12 therapy does not improve cognition in patients without pre-existing deficiency. There is a need for large, well-resourced clinical trials to close the gaps in our current understanding of the nature of the associations of vitamin B12 insufficiency and neurodegenerative disease.

The multiple mini-interview: how long is long enough?

OBJECTIVES: The multiple mini-interview (MMI) overcomes the limitations of the traditional panel interview by multiple sampling to provide improved objectivity and reliability. Reliability of the MMI is affected by number of stations; however, there are few data reporting the influence of interview duration on MMI outcome and reliability. We aimed to determine whether MMI stations can be shortened without affecting applicant rankings or compromising test reliability. METHODS: A total of 175 applicants were interviewed and assessed at 10 8-minute stations. Applicants were scored once after 8 minutes at five control stations and twice after 5 minutes and 8 minutes at five experimental stations. Scores at 5 and 8 minutes were compared using t-tests and correlation coefficients. Rankings of applicants based on 5- and 8-minute scores were compared using Spearman's rank order coefficient. The reliability of the MMI was examined for 5- and 8-minute scores using generalisability theory. RESULTS: Mean scores at 5 minutes were lower than mean scores at 8 minutes. Cumulative scores at 5 minutes were also lower. There were highly significant correlations between 5- and 8-minute scores at all experimental stations (0.82-0.91; P < 0.01) and between the cumulative scores at 5 and 8 minutes (0.92; P < 0.01). There was a strong correlation between applicant rankings based on cumulative 5- and 8-minute scores (Spearman's rank order coefficient 0.92). Reliability was not affected. CONCLUSIONS: Reducing the duration of MMI stations from 8 to 5 minutes conserves resources with minimal effect on applicant ranking and test reliability.

The extent of resection of FDG-PET hypometabolism relates to outcome of temporal lobectomy.

A significant minority of patients undergoing surgery for medically refractory non-lesional temporal lobe epilepsy (TLE) continue to have seizures, but the reasons for this are uncertain. Fluorodeoxyglucose (FDG) PET shows hypometabolism in a majority of patients with non-lesional TLE, even in the absence of hippocampal atrophy. We examined whether the extent of resection of the area of FDG-PET hypometabolism influenced outcome following surgery for non-lesional TLE. Twenty-six patients who underwent temporal lobectomy for medically refractory TLE with at least 12 months follow-up were studied. The preoperative FDG-PET was compared with 20 non-epileptic controls using SPM99 to identify regions of significant hypometabolism (P < 0.0005, cluster > 200). This image was then co-registered to the postoperative MRI scan. The volume of the FDG-PET hypometabolism that lay within the area of the resected temporal lobe was calculated. The volume of temporal lobe resected was also calculated. Patients with a good outcome had a greater proportion of the total FDG-PET hypometabolism volume resected than those with a poor outcome (24.1% versus 11.8%, P = 0.02). There was no significant difference between the groups in the volume of temporal lobe resected (P = 0.86). Multivariate regression demonstrated that the extent of resection of the hypometabolism significantly correlated with outcome (P = 0.03), independent of the presence of hippocampal sclerosis (P = 0.03) and total brain volume of hypometabolism (P = 0.45). The extent of resection of the region of hypometabolism on the preoperative FDG-PET is predictive of outcome following surgery for non-lesional TLE. Strategies that tailor resection extent to regional hypometabolism may warrant further evaluation.

Characteristics of motor vehicle crashes associated with seizure: Car crash semiology.

OBJECTIVE: To examine the characteristics of seizure-related vehicle crashes (SRC). METHOD: Using a nested case-control design, we identified and compared cases of SRC involving confirmed epilepsy patients with 137,126 non-seizure-related crash controls (NSRC) in the Australian state of Victoria. SRC were identified from approximately 20,000 epileptologist medical records by cross-referencing this source with the Victorian Police Traffic Incident database and the Road Crash Information System Database (RCISD). RESULTS: Seventy-one SRC involving 62 patients with epilepsy were identified. Thirty-seven SRC resulted in injury and could be identified in the RCISD and compared to NSRC. Seizure-related crashes typically involved a single vehicle (57% vs 29%, p < 0.001) carrying a sole occupant (95% vs 48%, p = 0.001). Most SRC began with an "out of control movement" (51% vs 10%, p < 0.001) and the subsequent collision type differed significantly between the groups (p < 0.001). The majority of SRC were a "collision with a fixed object" (54% vs 17%, p < 0.001) involving an "off path on straight" mechanism (48% vs 10%, p < 0.001). Regarding all 71 SRC, generalized as compared with focal epilepsy crashes involved younger drivers (p < 0.001), seizure-provoking factors (p = 0.033), and occurred earlier in the day (p = 0.004). CONCLUSIONS: Given the distinct SRC features, we propose that clinicians, crash investigators, and driver licensing authorities incorporate collision characteristics into the overall assessment of suspected SRC. Further research should examine restricting driving immediately after risk periods as a harm-minimization strategy.