Treating status epilepticus in adults. / Behandling av status epilepticus hos voksne.

This clinical review examines the treatment of status epilepticus, a condition in which epileptic seizures are prolonged and pose a significant risk of brain damage and death. International guidelines recommend the use of benzodiazepines as first-line treatment, and these should be administered promptly and in appropriate doses. Second-line treatment involves the use of high-dose anti-seizure medications to stop and prevent seizures. If seizure activity persists, general anaesthesia should be administered as soon as possible. All neurological hospital departments should have established and rehearsed protocols for treating status epilepticus.

A woman in her sixties with epilepsy and syncope. / En kvinne i 60-årene med epilepsi og synkope.

BACKGROUND: A woman in her sixties had been diagnosed with generalised epilepsy twenty years earlier. The diagnosis was confirmed by EEG, and an MRI scan revealed hippocampal sclerosis, which is not uncommon in patients with epilepsy. Treatment with carbamazepine was initiated. CASE PRESENTATION: Due to a rise in the patient's cholesterol, carbamazepine was replaced with oxcarbazepine. At a follow-up, the patient reported a recent episode with loss of consciousness. Unstable epilepsy was suspected and the oxcarbazepine dose increased. The patient had had a minor stroke shortly before the check-up. As part of the diagnostic workup, a 24-hour ECG was performed. On removal of the apparatus, the patient described an episode with loss of consciousness that same morning. The ECG showed asystole at that point in time due to total AV block. A pacemaker was implanted, and the patient has had no episodes since. INTERPRETATION: The patient retrospectively reported recurrent episodes with loss of consciousness over many years. The diagnosis of epilepsy was convincing, but was the heart condition linked to her epilepsy, her medication or was it a separate entity? When seizures become more frequent or change character in a previously stabilised patient with epilepsy, it is important to look for non-epileptic causes, and cardiac arrhythmias should be high on the list.

Neuropsychological Performance 1 Year After Status Epilepticus in Adults.

OBJECTIVES: Status epilepticus (SE) may lead to or worsen cognitive dysfunction. Few studies have evaluated magnitude and profile of cognitive dysfunction in patients after SE. Characterization of cognitive deficits may be important for rehabilitation and follow-up. We assessed cognitive function in a consecutive, non-selected group of relatively healthy survivors with a comprehensive neuropsychological test battery. METHODS: A total of 33 patients (24 men, 9 women; mean age 54,9 years, mean education 11,8 years) were tested 1 year after SE with Wechsler Adult Intelligence Scale Fourth edition (WAIS-IV), Rey Auditory Verbal Learning Test, subtests from the Wechsler Memory Scale-Revised, Phonemic and Semantic word list generation, and the Halstead-Reitan Battery. Premorbid IQ was estimated with a Norwegian version of the National Adult Reading Test (NART). Results were compared to published norms. Regression analyses and independent groups t-tests were performed to assess the influence of background variables. RESULTS: Mean performance generally was about one standard deviation below average. Full scale IQ (WAIS-IV) was significantly reduced compared to estimated premorbid IQ (NART). Negative influence on cognition of brain lesions visible on computed tomography or magnetic resonance imaging and duration of SE >30 min was shown by group comparisons. CONCLUSIONS: SE represents a marker for possible cognitive dysfunction, and follow-up with neuropsychological assessment and cognitive rehabilitation seems warranted in most patients. Complex problem-solving abilities with high general sensitivity to brain impairment showed the most prominent reduction. Otherwise, no specific profile of domain affection was found. Structural brain lesions and duration of SE over 30 min represent risk factors for cognitive deficit.

Cognitive function after status epilepticus versus after multiple generalized tonic-clonic seizures.

OBJECTIVES: Status epilepticus (SE) is considered a risk for cognitive impairment. Studies have indicated that SE cause more cognitive decline than multiple lifetime generalized tonic clonic (GTC) seizures. The aim of the study was to investigate whether patients suffering from SE or from multiple lifetime GTC seizures have cognitive dysfunction, and if the disabilities differ between these groups. MATERIALS AND METHODS: Patients suffering from SE were evaluated shortly after the clinical post-ictal phase and again after one year. Their follow-up results were compared to results from patients with ≥10 GTC seizures and a group of control subjects. Tests from Cambridge Neuropsychological Test Automated Battery (CANTAB) were used. Motor Screening Test (MOT) assessed motor speed, Delayed Matching to Sample (DMS) and Paired Associates Learning (PAL) assessed memory, and Stockings of Cambridge (SOC) assessed executive function. Estimated premorbid IQ and radiologically visible brain lesions were controlled for in adjusted results. Outcome measures were z-scores, the number of standard deviations a score deviates from the mean of a norm population. Negative z-scores indicate poor performance. RESULTS: After the clinical post-ictal phase, performances of SE patients were poor on all domains (n = 46). Mean z-scores with 95% confidence intervals were below zero for tests of psychomotor speed, executive thinking times and memory. Both SE patients at follow-up (n = 39) and patients with multiple GTC seizures (n = 24) performed poorer than controls (n = 20) on tests of memory. These group differences remained significant after covariate adjustments. SE patients at follow-up scored below patients with multiple GTC seizures on tests of psychomotor speed (mean difference -0.59, P = 0.020), but after adjusting for covariates this difference was no longer significant. CONCLUSIONS: Our data do not allow a firm conclusion as to whether SE is a more pronounced risk factor for cognitive dysfunction than repeated generalized tonic clonic seizures. In both patient groups, memory and learning dysfunction remained significant after adjusting for estimated premorbid IQ and structural brain lesions.

Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K+ channel properties.

OBJECTIVE: To comprehensively describe the new syndrome of myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK), including cellular electrophysiological characterization of observed clinical improvement with fever. METHODS: We analyzed clinical, electroclinical, and neuroimaging data for 20 patients with MEAK due to recurrent KCNC1 p.R320H mutation. In vitro electrophysiological studies were conducted using whole cell patch-clamp to explore biophysical properties of wild-type and mutant KV 3.1 channels. RESULTS: Symptoms began at between 3 and 15 years of age (median = 9.5), with progressively severe myoclonus and rare tonic-clonic seizures. Ataxia was present early, but quickly became overshadowed by myoclonus; 10 patients were wheelchair-bound by their late teenage years. Mild cognitive decline occurred in half. Early death was not observed. Electroencephalogram (EEG) showed generalized spike and polyspike wave discharges, with documented photosensitivity in most. Polygraphic EEG-electromyographic studies demonstrated a cortical origin for myoclonus and striking coactivation of agonist and antagonist muscles. Magnetic resonance imaging revealed symmetrical cerebellar atrophy, which appeared progressive, and a prominent corpus callosum. Unexpectedly, transient clinical improvement with fever was noted in 6 patients. To explore this, we performed high-temperature in vitro recordings. At elevated temperatures, there was a robust leftward shift in activation of wild-type KV 3.1, increasing channel availability. INTERPRETATION: MEAK has a relatively homogeneous presentation, resembling Unverricht-Lundborg disease, despite the genetic and biological basis being quite different. A remarkable improvement with fever may be explained by the temperature-dependent leftward shift in activation of wild-type KV 3.1 subunit-containing channels, which would counter the loss of function observed for mutant channels, highlighting KCNC1 as a potential target for precision therapeutics. Ann Neurol 2017;81:677-689.

Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.

Neuroleptic malignant syndrome is an unpredictable iatrogenic neurologic emergency condition, mainly arising as an idiosyncratic reaction to antipsychotic agent use. It is characterized by distinctive clinical features including a change in mental status, generalized rigidity, hyperpyrexia, and dysautonomia. It can be lethal if not diagnosed and treated properly. Mortality and morbidity attributed to this syndrome have recently declined markedly due to greater awareness, earlier diagnosis, and intensive care intervention. In most cases, the syndrome occurs as a result of a rapid increase in a dose of neuroleptic, especially one of the long-acting ones. Pathophysiology behind this syndrome is attributed to a dopamine receptor blockade inside the neurons rendered by the offending drug and excessive calcium release from the sarcoplasmic reticulum of skeletal myocytes. Laboratory tests, although not diagnostic, may assist in assessing the severity of the syndrome and also the consequent complications. The syndrome has been described in all age groups and occurs more in males than in females. Genetics appears to be central regarding the etiology of the syndrome. Stopping the use of the offending agent, cold intravenous fluids, and removal of the causative agent and its possible active metabolites is the cornerstone of treatment. Periodic observation of psychotic patients recently started on antipsychotic medications, especially those being treated with depot preparations, may aid to an early diagnosis of the syndrome and lead to early treatment.

Codeine is associated with poor prognosis in acute stroke.

Background: The aim of this study was to investigate how the use of analgesics, sleeping drugs, and sedatives relates to prognosis and complications in stroke patients in the acute care phase (≤48 hr) after a stroke. Materials and Methods: Patients with ischemic stroke, hemorrhagic stroke, and transient ischemic attack were included. The study is based on gathering of data on medication from 921 patient records belonging to patients included in the Bergen NORSTROKE registry, 12.2009-02.2012. In this database risk factors, stroke severity, etiology, and blood analyses were prospectively registered. We have retrospectively registered if patients received one drug or more from a list of analgesics, sleeping drugs, and sedatives within the first 48 hr after admission. Results: In total, 921 patients were included in the study, 408 females and 513 males. Mean age was 71.0 years. In total, 101 patients were given sleeping drugs, 97 patients sedatives and 140 patients analgesics. Of the group given analgesics, 90 patients were given codeine-containing analgesics. Logistic regression analyses showed that codeine-containing analgesics were associated with an increased occurrence of pneumonia (OR = 3.8, p < .001), stroke worsening (OR = 2.7, p = .001), and a higher mRS-score (OR = 2, p = .024) day 7. The study did not show any relation between poorer prognosis or increased occurrence of complications and the use of other analgesics, sedatives and/or sleeping drugs. Conclusion: Use of codeine-containing analgesics is associated with a poorer short-term prognosis and an increased occurrence of complications in the acute phase after a stroke. The highly significant findings suggest that codeine has a negative effect on acute stroke patients. The study reflects exploratory analyses and prospective studies are necessary to determine the background of the association observed in our study.

Life satisfaction in women with epilepsy during and after pregnancy.

OBJECTIVE: The aim of this study was to investigate life satisfaction in women with epilepsy during and after pregnancy. METHODS: The study was based on the Norwegian Mother and Child Cohort Study, including 102,265 women with and without epilepsy from the general population. Investigation took place at pregnancy weeks 15-19 and 6 and 18months postpartum. Women with epilepsy were compared with a reference group without epilepsy. RESULTS: The proportion of women with epilepsy was 0.6-0.7% at all three time points. Women with epilepsy reported lower life satisfaction and self-esteem both during and after pregnancy compared with the references. Single parenting correlated negatively with life satisfaction in epilepsy during the whole study period. Epilepsy was associated with lower levels of relationship satisfaction and higher levels of work strain during pregnancy and lower levels of self-efficacy and satisfactory somatic health 18months postpartum. Adverse life events, such as divorce, were more common in women with epilepsy compared with the references, and fewer women with epilepsy had a paid job 18months postpartum. SIGNIFICANCE: Reduced life satisfaction associated with epilepsy during and after pregnancy showed that, even in a highly developed welfare society, women with epilepsy struggle. Mothers with epilepsy and their partners should be examined for emotional complaints and partnership satisfaction during and after pregnancy. Validated screening tools are available for such measures.

Prognostic factors of status epilepticus in adults.

AIM: Status epilepticus (SE) can lead to sequelae or even death. Identifying characteristics associated with poor outcome is crucial in guiding patient treatment. Based on our retrospective patient cohorts, potential prognostic factors were analysed. METHODS: Patients consecutively treated for refractory convulsive status epilepticus (CSE) between 2001 and 2010 and non-convulsive status epilepticus (NCSE) between 2004 and 2009 were studied. Outcome was compared to prognostic variables. Index SE episodes were used for the statistical analyses. Crosstabs and independent samples t-test were applied. Due to sample size, logistic regression was performed for the combined groups. RESULTS: In total, 50% (9/18) of index refractory CSE and 42% (16/38) of index NCSE episodes led to sequelae. Refractory CSE requiring narcosis for >20 hours was associated with poor outcome (p=0.05). De novo presentation (p=0.0001), long-lasting SE (>2 hours) (p=0.014), age >65 years (p=0.002), and refractory SE (p=0.047) were predictors of poor outcome following NCSE. Based on logistic regression for combined refractory CSE and NCSE, de novo presentation was identified as the strongest predictor of sequelae. CONCLUSIONS: Older age and de novo SE are predictors of sequelae following NCSE. Prolonged SE is a risk factor for poor outcome, both for refractory CSE and NCSE. Aggressive initial treatment to terminate seizures during the early phase is therefore essential.

Status epilepticus secondary to glioma.

PURPOSE: Epilepsy is common in glioma patients, but clinical data on the course of status epilepticus (SE) in this group are sparse. The aim of this study was to investigate the relationship of SE to tumor grading, seizure semiology, trigger factors, treatment response, recurrence and outcome of SE in patients with glioma. METHODS: Adult patients with SE and glioma WHO grade II-IV were identified from a prospective clinical study at two neurological departments. We identified 31 SE in 20 patients during a period of 7 years. RESULTS: SE was more frequent in patients with high-grade glioma. Half of the seizures were secondary generalized. Patients with a clinical and radiological stable glioma had SE as often as patients with untreated tumor or tumor in progression. The majority of patients had a well-controlled epilepsy prior to SE. SE responded well to first and second line treatment. Patients with SE and tumor progression were not more refractory to treatment than patients without progression. CONCLUSION: SE secondary to glioma responded well to treatment and should be treated aggressively regardless of the oncological prognosis. Seizures during tumor progression were not more treatment refractory than SE in patients with stable glioma disease.

Combined variants in reading epilepsy; coexisting anterior and posterior variants camouflaged as heat cramps where the patient finds his own diagnosis searching the internet.

Reading epilepsy is a form of reflex-induced seizures. Two entities are postulated as part of a clinical spectrum; one anterior variant with jaw jerks and orofacial myoclonia and another posterior variant with visual symptoms and alexia or dyslexia. We present a case with suggestible evidence of both conditions coexisting within the same patient, a finding that, to our knowledge, has not been previously reported. The diagnosis in this specific case was contributed to by the patient searching the internet.

Psychiatric Comorbidity, Social Aspects and Quality of Life in a Population-Based Cohort of Expecting Fathers with Epilepsy.

OBJECTIVES: To investigate psychiatric disorders, adverse social aspects and quality of life in men with epilepsy during partner's pregnancy. METHOD: We used data from the Norwegian Mother and Child Cohort Study, including 76,335 men with pregnant partners. Men with epilepsy were compared to men without epilepsy, and to men with non-neurological chronic diseases. RESULTS: Expecting fathers in 658 pregnancies (mean age 31.8 years) reported a history of epilepsy, 36.9% using antiepileptic drugs (AEDs) at the onset of pregnancy. Symptoms of anxiety or depression were increased in epilepsy (7.0% and 3.9%, respectively) vs. non-epilepsy (4.6% and 2.5%, respectively, p = 0.004 and 0.023), and so were new onset symptoms of depression (2.0% vs. 1.0%, p < 0.031) and anxiety (4.3% vs. 2.3%, p = 0.023). Low self-esteem (2.5%) and low satisfaction with life (1.7%) were more frequent among fathers with epilepsy compared to fathers without epilepsy (1.3% and 0.7%, respectively, p = 0.01 and 0.010). Adverse social aspects and life events were associated with epilepsy vs. both reference groups. Self-reported diagnoses of ADHD (2.2%) and bipolar disorder (1.8%) were more common in epilepsy vs. non-epilepsy (0.4% and 0.3%, respectively, p = 0.002 and 0.003) and non-neurological chronic disorders (0.5% and 0.5%, respectively, p = 0.004 and 0.018). A screening tool for ADHD symptoms revealed a higher rate compared to self-reported ADHD (9.5% vs. 2.2%, p < 0.001). CONCLUSION: Expecting fathers with epilepsy are at high risk of depression and anxiety, adverse socioeconomic aspects, low self-esteem, and low satisfaction with life. Focus on mental health in fathers with epilepsy during and after pregnancy is important. The use of screening tools can be particularly useful to identify those at risk.

Epilepsy and recommendations for breastfeeding.

PURPOSE: The objective of this paper is to provide a synopsis of benefits and potential harmful effects of exposure to antiepileptic drugs (AEDs) via breastmilk, and present recommendations for breastfeeding in women with epilepsy. METHODS: The article is based on a discretionary selection of English language articles retrieved by a literature search in the PubMed database, the LactMed database, and the authors' clinical experience. RESULTS: Breastfeeding is associated with benefits for the infant, including nutrition, protection against infectious and immunological disease, and promotion of development and psychological attachment. Exposure to AEDs via breastmilk could potentially produce side effects or negatively affect development. Most studies on AED transfer through breastmilk report infant serum levels well below the limit of an expected pharmacological effect. Some drugs have the potential to reach significant serum levels in breastfed infants, such as barbiturates, benzodiazepines, lamotrigine, and ethosuximide. Thus, breastfed infants should be monitored for side effects. Still, adverse symptoms are rarely reported in breastfed infants of mothers taking AEDs, and prospective studies have failed to demonstrate any negative developmental effects in children that have been exposed to AEDs via breastmilk. The nursing infant's degree of drug exposure can be minimized by breastfeeding when drug concentrations in the milk are low, reducing maternal AED dosage to prepregnancy levels, and administering mixed nutrition. CONCLUSION: Most AEDs are considered safe or moderately safe during breastfeeding. Mothers with epilepsy should be encouraged to breastfeed, provided careful monitoring of the infant.

Depression and anxiety during pregnancy and the postpartum period in women with epilepsy: A review of frequency, risks and recommendations for treatment.

PURPOSE: To review available data and provide treatment recommendations concerning peripartum depression, anxiety and fear of birth in women with epilepsy (WWE). METHOD: The PubMed, the LactMed, the DART and the Cochrane database were searched for original articles concerning psychiatric disease in the peripartum period in WWE. RESULTS: Point prevalence of depression from 2nd trimester to 6 months postpartum ranged from 16 to 35% in women with epilepsy compared to 9-12% in controls. The highest estimates were found early in pregnancy and in the perinatal period. Anxiety symptoms 6 months postpartum were reported by 10 and 5%, respectively. Fear of birth symptoms were increased in primiparous WWE compared to controls. Previous psychiatric disease, sexual/physical abuse, antiepileptic drug (AED) polytherapy, and high seizure frequency emerged as strong risk factors. Depressed WWE rarely used antidepressive medication during pregnancy. No evidence was available concerning treatment effects or impact on the developing child. CONCLUSION: Peripartum depression is frequent in WWE and seldom medically treated. Health personnel should screen WWE for psychiatric disease and risk factors during pre-pregnancy planning, pregnancy and postpartum follow up. Treatment decisions should rely on efficacy and safety data in peripartum patients without epilepsy and non-pregnant people with epilepsy. Consequences of in utero exposure to AED therapy in combination with antidepressants are not known, and non-pharmacological treatment should be tried first.

A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy.

Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation, c.959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Eleven unrelated exome-sequenced (13%) and two affected individuals in a secondary cohort (7%) had this mutation. KCNC1 encodes KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, which are major determinants of high-frequency neuronal firing. Functional analysis of the Arg320His mutant channel showed a dominant-negative loss-of-function effect. Ten cases had pathogenic mutations in known PME-associated genes (NEU1, NHLRC1, AFG3L2, EPM2A, CLN6 and SERPINI1). Identification of mutations in PRNP, SACS and TBC1D24 expand their phenotypic spectra to PME. These findings provide insights into the molecular genetic basis of PME and show the role of de novo mutations in this disease entity.

Depression and anxiety in women with epilepsy during pregnancy and after delivery: a prospective population-based cohort study on frequency, risk factors, medication, and prognosis.

OBJECTIVE: To assess incidence, prevalence, risk factors, and prognosis of peripartum depression and anxiety in a prospective study of women with epilepsy. METHOD: Pregnancies in women with epilepsy (n=706) were compared to pregnancies in all women without epilepsy (n=106,511) including women with specified nonepileptic chronic diseases (n=8,372) in the Norwegian Mother and Child Cohort Study. The database was linked to the Medical Birth Registry of Norway. Depression and anxiety were assessed with validated questionnaires five times from the second trimester to 36 months after delivery. Blood was drawn for analysis of antiepileptic drug (AED) concentrations. RESULTS: Women with epilepsy more often had peripartum depression (26.7%) or anxiety (22.4%) than women without epilepsy (18.9% and 14.8%, respectively, p<0.001 for both comparisons) and women with other chronic diseases (23.1% and 18.4%, respectively, p=0.03 and 0.01). Women using AEDs during pregnancy were especially at risk regardless of AED type. The risk further increased with the use of multiple AEDs and with high doses and/or plasma levels. Risk factors associated with peripartum depression and/or anxiety in the epilepsy cohort were high seizure frequency, a history of physical and/or sexual abuse, adverse socioeconomic factors, previous loss of a child, AED use, unplanned pregnancy, and prepregnancy depression and/or anxiety. The recovery rate 3 years after delivery was lower for women with epilepsy with a history of depression/anxiety or physical/sexual abuse than for women without epilepsy. Depressed women with epilepsy were less frequently treated with antidepressive drugs during pregnancy than women without epilepsy. SIGNIFICANCE: Women with epilepsy frequently have depression and anxiety during and after pregnancy. Patients at risk should be identified before delivery as depressive symptoms could be undertreated in this group.