Are seizures predictors of mortality in critically ill patients in the intensive care unit (ICU)?

PURPOSE: This study aimed to determine if seizures in critically ill patients are predictive of in-hospital mortality. METHODS: Patients above the age of 55 who underwent continuous electroencephalogram (cEEG) monitoring between 2015 and 2018 at the Hackensack Meridian Health and JFK Neuroscience Institute were included in the present study. Patients were subdivided into those with and without seizures. Age, sex, seizure types, CNS disorders, and other associated comorbidities were collected by chart review. After descriptive analysis, we used multiple logistic regression analyses to evaluate if seizures and mortality were associated. P-values less than 0.05 were considered statistically significant. RESULTS: One hundred and one critically ill patients (62.4% female) were included in this study. Sixty-six (65.3%) were between 55 and 75 years of age, while 35 (34.7%) were above 75 years of age. Most patients (n = 31, 83.8%) had focal-onset seizures, and 10 had nonconvulsive status epilepticus (NCSE). Twelve (11.9%) patients with seizures did not survive. However, seizures were not independently associated with mortality in either unadjusted (OR 1.13, CI 0.47-2.72, p = 0.773) or adjusted (OR 1.20, CI 0.35-4.05, p = 0.760) regression models. Secondary predictors of mortality included mechanical ventilation (OR 5.36, CI 1.69-16.96, p = 0.001) and acute ischemic stroke (OR 2.77, CI 1.08-7.09, p = 0.034). CONCLUSION: Seizures did not predict in-hospital mortality in critically ill patients. Larger prospective studies are needed to confirm our current findings.

Lateralizing and localizing value of seizure semiology: Comparison with scalp EEG, MRI and PET in patients successfully treated with resective epilepsy surgery.

PURPOSE: To evaluate the lateralizing and localizing value of seizure semiology in patients who became completely seizure free after resective epilepsy surgery. METHODS: We analyzed seizures of patients who were seizure free after focal resection limited to the temporal lobe (30 patients), frontal lobe (27 patients), parietal lobe (8 patients) and occipital lobe (8 patients). Three investigators independently analyzed video segments of seizures blinded to clinical information and attempted to lateralize and localize the seizure focus, based on pre-defined criteria. Inter-observer agreement measured and positive predictive value were calculated and compared with scalp interictal, ictal EEG, MRI and PET. RESULTS: Seizure semiology correctly lateralized 19/30 (63%) temporal lobe epilepsy patients (kappa = 0.64); lobar localization was correct in 27/30 patients (90%) (Kappa = 0.6). Twenty of 27 (74%) frontal lobe patients were correctly lateralized (kappa = 0.55) and localized (Kappa = 0.41). Seven of 8 (87%) of parietal lobe patients were correctly lateralized (kappa = 0.83) and lobar localization was correct in 3/8 patients (37%) (Kappa = 0.5). Seven of 8 (87%) occipital lobe patients were correctly lateralized (kappa = 0.67) and lobar localization was correct in 7/8 patients (87%) (Kappa = 0.67). Collectively, seizure semiology was correctly lateralizing in 74% and correctly localizing in 77% of patients. Lateralization in secondarily generalized seizures was significantly higher compared to seizures that did not generalize (p = 0.0001). In non-lesional patients, lateralization was correct in 81% while localization was correct in 88% of patients. CONCLUSION: Seizure semiology has high lateralizing and localizing value, on par with interictal/ictal scalp EEG and MRI.

Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG.

We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized.

Memory performance in older adults before and after temporal lobectomy for pharmacoresistant epilepsy.

Little is known about the effects of epilepsy surgery on memory in older adults. The purpose of this study was to determine if older adults exhibit greater memory decline than younger adults after anterior temporal lobectomy (ATL). Patients 55 years and older at time of surgery (23 left, 14 right ATL, range 55-66 years) were compared to patients age 25-35 years (44 left, 33 right ATL) to assess differences in preoperative to postoperative change in WMS-III index scores. Repeated-measures ANOVAs and ANCOVAs revealed that older patients did not demonstrate greater decline than younger patients across any of the memory indices. Rather, in the left ATL group, older patients showed less decline than younger patients on the Auditory Delayed Memory Index. Similarly, in the right ATL group, older patients showed less decline than younger patients on the Visual Delayed Memory Index. These patterns were also apparent in frequency of individual change. Results provide preliminary evidence that older adults who are good candidates for ATL are not at greater risk for memory decline when measured at 7 months postoperatively.

Seizure semiology and aging.

The incidence of epilepsy is high in older individuals. However, epilepsy in the elderly may be underdiagnosed and undertreated because of diagnostic difficulties. The main goal of this study was to determine whether seizure semiology differs between older and younger adults with epilepsy in the outpatient setting. Fifty patients with focal epilepsy aged 55 years and older and 50 patients aged between 18 and 45 years were included. Review of medical records contained detailed seizure description. There were no differences in seizure semiology between groups, except that subtle perceptions of transient confusion were seen in older patients but not in younger patients (P=0.0028). Older patients had less generalized motor seizures, but the differences between groups did not reach significance (P=0.01). Older patients may present with subtle symptoms of seizures characterized by brief periods of confusion, which may contribute to greater difficulty diagnosing seizures in the elderly.

Temporal lobe epilepsy surgery failures: predictors of seizure recurrence, yield of reevaluation, and outcome following reoperation.

OBJECT: The authors provide a systematic analysis of electroclinical characteristics in patients with persistent seizures following temporal lobe epilepsy (TLE) surgery and identify ideal candidates for reoperation. METHODS: The authors retrospectively reviewed the records of 68 adult patients (mean follow-up 8.7 years) who underwent a video electroencephalography evaluation and high-resolution imaging after failed TLE surgery performed between 1990 and 2004 at The Cleveland Clinic. Multivariate logistic regression analyses were performed to identify predictors of the yield of a repeat evaluation, location of the recurrence focus, and outcome following reoperation. RESULTS: Although a focus of recurrence was identified in 44 patients, only 15 underwent reoperation, and only 6 of these became seizure free. Localized foci of recurrence were successfully identified in patients with early (within 1 postoperative year) and frequent (≥4 per month) recurrent seizures (yield of 100% if both conditions were fulfilled). Predictors of contiguity of the focus of recurrence to the initial surgical bed were variable depending on the type of the initial surgery: patients with baseline contralateral temporal spiking were 6 times (OR 6.34, p<0.05) more likely to experience seizure recurrence from the contralateral temporal lobe after a "standard" temporal lobectomy, while the need to use subdural electrodes and the timing of recurrence were more significant following limited temporal resections. The focus of recurrence was distant to the original surgical bed when subdural electrodes were used prior to first surgery (OR 28.0, p=0.01) or when seizures recurred early (within <6 postoperative months; OR 12.5, p=0.04). With reoperation, only patients with mesial and basal extension of the temporal resections became seizure free. Interestingly, seizure freedom was achieved with medical therapy alone in 42% of patients with a nonidentifiable recurrence focus as opposed to 4% of those with an unoperated identifiable focus. CONCLUSIONS: The timing and frequency of recurrent seizures following unsuccessful TLE surgery provide useful guidelines for the yield of a surgical reevaluation, and potentially for the mechanisms of surgical failure.

Prevalence of stroke in Restless Legs Syndrome: Initial Results Point to the Need for More Sophisticated Studies.

BACKGROUND: Recent studies suggest a potential relationship between Restless Legs Syndrome (RLS) and hypertension and heart disease. Acute clinical stroke has been linked to the immediate onset of RLS, and epidemiological studies suggest the possibility that RLS may also lead to stroke. METHODS: MRI scans from 26 RLS cases and 241 controls from the population based MEMO-Study (Memory and Morbidity in Augsburg Elderly) were assessed for the presence of clinical stroke, silent infarction, subcortical lesions and cortical atrophy. T1, T2, proton density images were obtained and infarcts and their characteristics were determined by visual inspection. RLS status was assessed according to the minimal criteria of the International RLS Study Group. Scans from the 26 RLS patients and a subset of 26 age and sex matched controls were reexamined by a separate rater using the same methodology. Descriptive statistics, logistic and linear regression models were used to determine the risk of the three types of CNS changes associated with RLS case status. RESULTS: Among the 267 participants there was no difference in the prevalence of cardiovascular diseases or risk factors between RLS patients and the 241 controls. The prevalences of cerebrovascular events of all types, were greater in RLS patients, as were the amounts of cortical atrophy and the volume of subcortical lesions. However, these differences were not statistically significant. When age, sex and co-morbidities were taken into account in a logistic regression model, there was a statistically non-significant greater risk for stroke (Odds Ratio 2.46 with 95% CI 0.97-6.28, p = .06) associated with RLS case status. CONCLUSIONS: Future similar studies need to be performed on younger patients without other potential vascular risk factors, using Flair images and computerized programs for detection of cerebral ischemia. Improved methods for detection may allow for a reasonable sample size.

Spontaneous recurrent seizure following status epilepticus enhances dentate gyrus neurogenesis.

It is known that evoked seizures can increase neurogenesis in the dentate gyrus in adult rats. Whether spontaneous seizures occurring after status epilepticus (SE) also results in alterations in neurogenesis is not known. Here, we measured neurogenesis in rats with and without spontaneous seizures following SE. Lithium-pilocarpine was used to induce seizures in postnatal (P) day 20 rats. Spontaneous seizure frequency was assessed 2 months using video monitoring. Rats then received bromodeoxyuridine to label dividing DNA and were sacrificed 24 h later. Animals with spontaneous seizures (n = 9) had a modest increase in neurogenesis compared to animals with SE (n = 6) and no spontaneous seizures and control rats (n = 10). These findings demonstrate that the hippocampus is capable of generating new neurons weeks following SE and further that recurrent seizures enhance the production of new neurons. These alterations in neurogenesis may contribute to ongoing pathological changes week and months following SE.

Effects of lesions of basal forebrain cholinergic neurons in newborn rats on susceptibility to seizures.

The cholinergic system modulates cerebral excitability. We recently reported that immunolesions of the basal forebrain (BF) cholinergic neurons in adult rats increase the susceptibility to generalized seizures. In this study we investigated the effects of lesions of the BF cholinergic neurons in neonatal rats on seizure susceptibility and cognitive function. Neonatal rats at postnatal day (P) 7 received intracerebroventricular (i.c.v.) injections of 192 IgG-saporin (SAP) or phosphate-buffered saline. Following 3 weeks after the injection the first group of rats was implanted with hippocampal electrodes for electroencephalogram (EEG) recordings while the second group of rats was tested for visual spatial memory using the hidden platform version of the water maze test. The first group of rats was then tested for seizure susceptibility using flurothyl 1 week after the electrode implantation. Rats that received immunolesions of the BF cholinergic neurons at P7 had significantly shorter latencies to onset of myoclonic jerks and tonic-clonic seizures than controls. However, no significant differences were found in the duration of seizures, or EEG ictal duration. No significant deficits in spatial learning were found between rats that received i.c.v. injections of SAP at P7 and controls. As in adult rats, lesions of the BF cholinergic system in rat pups result in subsequent increase in seizure susceptibility.

Effect of topiramate following recurrent and prolonged seizures during early development.

Topiramate, an antiepileptic drug with a number of mechanisms of action including inhibition of glutamate activity at the AMPA and KA receptors, was assessed as a neuroprotective agent following seizures. We administered topiramate, 80 mg/kg, or saline for 4 weeks following a series of 25 neonatal seizures or status epilepticus (SE) induced by lithium-pilocarpine in postnatal day 20 rats. Age-matched control rats without a history of seizures were administered topiramate or saline. Following completion of the topiramate injections, animals were tested in the water maze for spatial learning and the brains examined for cell loss and sprouting of mossy fibers. While there was a trend for improved visual-spatial performance in the water maze following topiramate therapy in rats with neonatal seizures, no differences were found in the histological examination of the hippocampus. Neonatal rats exposed to 4 weeks of topiramate did not differ from non-treated controls in water maze performance or histological examination. In weanling rats subjected to SE, topiramate provided a moderate degree of neuroprotection, with topiramate-treated rats performing better in the water maze than rats receiving saline. However, no differences in cell loss or mossy fiber sprouting were found in the histological examination of the brains. These findings demonstrate that chronic treatment with topiramate following SE improves cognitive function. In addition, long-term administration of high-dose topiramate in the normal developing rat brain does not appear to impair cognitive performance.

Memory impairment following status epilepticus in immature rats: time-course and environmental effects.

Status epilepticus (SE) has a high mortality and morbidity rate in children. Disturbances in learning and memory are frequently associated with SE although it is not clear when the cognitive deficits occur. If cognitive dysfunction occurs immediately following the seizure, the window of opportunity for therapeutic intervention is limited. The first goal of this study was to determine the timing of cognitive dysfunction following SE in weanling rats. As there is evidence that enriching the environment can improve cognitive and motor deficits following brain injury, our second goal was to determine whether environmental enrichment improves cognitive function following SE. Rats underwent lithium-pilocarpine-induced SE at postnatal (P) day 20 and were then tested for visual-spatial memory in the water maze at P22, P25, P30, or P50. Rats with SE performed significantly worse in the water maze than control rats at all time points. Once the time-courses of visual-spatial memory deficits were determined, a second group of P20 rats were subjected to SE and were then placed in an enriched environment (enriched group) or remained in standard cages in the vivarium (nonenriched group) for 28 days. Following environmental manipulation, the animals were tested in the water maze. Rats housed in an enriched environment following the SE performed substantially better in the water maze than rats housed in standard cages. However, no differences were found between the enriched and nonenriched groups in EEG or histological evaluation. Although SE results in cognitive impairment within days of the seizure, housing in an enriched environment after SE has a beneficial effect on cognitive performance in rats.

The expression of Fos following kainic acid-induced seizures is age-dependent.

The expression of limbic seizures following kainic acid (KA) administration starts at approximately postnatal day (P) 19 in rats. In this study we investigated whether the expression of Fos-like immunoreactivity (Fos-IR) in limbic regions occurs concomitantly with the behavioural expression of limbic seizures. Immunohistochemistry for c-Fos protein was examined 1, 2, 4, 12 and 24 h following seizure onset (KA-treated rats) or saline injections (controls) in immature and adult rats at P7, P13, P20 and P60. The expression of Fos-IR in limbic structures following KA-induced seizures is age-dependent. There is a strong and selective induction of Fos-IR in the CA3 region of the hippocampus following KA-induced seizures in rats at P7. However, the expression of Fos-IR in KA-treated rats at P13, P20 and P60 involved other hippocampal structures in addition to CA3. Abundant induction of Fos-IR was found in the CA1, CA3 and dentate gyrus (DG) in KA-treated rats at P13, P20 and P60. While immature rats at P7 and P13 showed very few or no Fos-IR neurons in most amygdala nuclei, rat pups at P20 showed strong induction of Fos-IR in the amygdala. Our results demonstrated that the induction of Fos-IR in most amygdala nuclei and the full expression of behavioural limbic seizures occur at the same developmental age, which is consistent with the idea that the amygdala may play a role in the modulation of limbic seizures.

Interictal hyposexuality in male patients with epilepsy

The purpose of this study was to compare the serum levels of androgens between hyposexual and non-hyposexual patients with epilepsy. Adult male patients with epilepsy were investigated. Serum levels of testosterone (T) and free-T, estradiol, and sex hormone binding globulin (SHBG) were measured and the free androgen index (FAI) was calculated. While there were no differences between hyposexual and non-hyposexual patients in the serum levels of T, free-T, and estradiol, or to the FAI, the serum levels of SHBG were significantly higher in hyposexual patients than in non-hyposexual patients. Thus, the effects of increased SHBG upon serum levels of testosterone biologically active in patients with epilepsy and hyposexuality were not detected by the methods used in this study. Four (44 percent) of nine hyposexual patients who were re-evaluated after two years follow-up improved sexual performance. Thus, clinical treatment that results in good seizure control may improve sexual performance in some patients with epilepsy

Sexual dysfunction in epilepsy: identifying the psychological variables

In order to evaluate the psychological variables that affect sexual dysfunction (SD) in epilepsy, where compared 60 epileptics (Group 1) with 60 healthy individuals (Group 2), through the State-Trait Anxiety Inventory (Spielberger et al., 1970), Beck Depression Inventory (Beck, 1974) and Sexual Behavior Interview (Souza, 1995). Sexual dysfunction (SD), anxiety and depression were found more frequently in Group 1 than in Group 2 and were not related to sex. Variables such as the onset duration and frequency of seizures as well as the use to medication were not associated with SD. Temporal lobe epilepsy was related to SD (p = 0.035) but not to anxiety or depression. Anxiety and depression were related to SD in both groups. Perception in controlling the seizures was closely related to anxiety (p = 0) and depression (p = 0.009). We conclude that psychological factors play an important role in the alteration of sexual behavior in epileptics and that suitable attention must be given to the control of these variables.

Evoluçäo eletrencefalográfica em mulheres com epilepsia de difícil controle / Electroencephalographic evolution in women with refractary epilepsy

Foram revistos 444 traçados eletrencefalográficos realizados durante o acompanhamento de 62 mulheres do Ambulatório de Epilepsia Catamenial do Hospital das Clínicas da UNICAMP com diagnóstico de epilepsia de difícil controle, que compareceram a esse ambulatório regularmente por um período mínimo de cinco anos. Dos 350 (78,84 por cento) traçados anormais, 273 mostraram atividade epileptiforme e 77 anormalidades "näo-epileptiformes". Segundo definiçöes adotadas em relaçäo à freqüência das crises, encontramos 18 pacientes (29 por cento) que apresentavam crises freqüentes, 16 (25,8 por cento) com crises muito freqüentes, 12 (19,3 por cento) com crises esporádicas e 16 (25,8 por cento) com crises que se tornaram controladas durante o período de acompanhamento. Em relaçäo aos achados de EEG, quatro pacientes (6,5 por cento) mostraram EEGs sempre normais, 30 (48,4 por cento) tiveram EEGs normais e anormais e 28 (45,2 por cento) apenas EEGs anormais. Entre aquelas cujos EEGs sempre foram normais, duas estavam com crises controladas, uma com crises esporádicas e uma com crises freqüentes. Das 30 pacientes com EEGs normais e anormais, 10 estavam controladas, 5 tinham crises esporádicas, 9 tinham crises freqüentes e 6 tinham crises muito freqüentes. No grupo de pacientes com EEGs sempre anormais, 4 estavam controladas, 6 tinham crises esporádicas, 8 tinham crises freqüentes e 10 tinham crises muito freqüentes. Em relaçäo ao último EEG, ele foi normal em 7 (43,7 por cento) das 16 pacientes que estavam controladas, em 3 (25 por cento) das 12 pacientes com crises muito freqüentes. Os pacientes que persistem com EEGs normais parecem ter melhor evoluçäo que aqueles que persistem com EEGs anormais. Pela análise deste estudo, pode-se sugerir um papel relativo do EEG quanto ao prognóstico a longo prazo no controle das crises epilépticas, pois as pacientes que persistiram com EEGs normais aparentemente tiveram evoluçäo clínica mais favorável que aquelas que persistiram com os EEGs alterados

Início de crises epilépticas na menarca / Beginning of epileptic seizures in menarche

Nove pacientes com início das crises epilépticas coincidindo com a menarca foram avaliadas. Duas tinham crises generalizadas e 7 crises com início parcial. O exame físico e neurológico foram normais em todas, exceto em uma que tinha estenose aórtica. O EEG mostrou ondas agudas focais nas regiöes temporais em 4 pacientes, ondas lentas intermitentes generalizadas em uma e foi normal nas outras 4. Sete das 9 pacientes que tiveram a primeira crise na menarca apresentavam excerbaçäo das crises epilépticas no período perimenstrual, o que poderia sugerir estarem estas pacientes mais sujeitas a aumento na frequencia das crises nesse período em ciclos subsequentes. Este achado necessita de estudo mais amplo para confirmaçäo e pode contribuir para melhor orientaçäo terapêutica nessas mulheres

Crises focais na hiperglicemia näo cetótica / Focal seizures in nonketotic hyperglycemia

Os casos de três pacientes com crises focais associadas a hiperglicemia näo cetótica (HNC) säo relatados. Os dois primeiros tiveram epilepsia parcial contínua (EPC) motora. No primeiro paciente a EPC foi a manifestaçäo inicial do diabetes mellitus. O exame neurológico mostrou-se normal em todos os pacientes. TC de crânio e exame do LCR foram normais, quando realizados. O EEG, durante a EPC em um caso, mostrou atividade crítica epileptiforme nas regiöes temporais bilateralmente, a despeito da manifestaçäo clínica ser unilateral. Os níveis glicêmicos foram de 455, 660 e 439 mg/dl. Dois pacientes apresentavam hiponatremia concomitante. Nenhum dos pacientes respondeu à hidantalizaçäo ou ao uso de benzodiazepínicos; em um deles houve acentuaçäo das crises após sua administraçäo. O controle das crises só ocorreu com insulinoterapia e correçäo hidroeletrolítica. O reconhecimento da HCN como causa de EPC, sem lesäo estrutural evidenciável, é de grande importância no sentido de orientar a terapêutica adequada para o controle das crises e de evitar evoluçäo para síndrome de NHC com hiperosmolaridade e alteraçäo de consciência, o que leva a mortalidade significante

Manifestaçöes cursivas e gelásticas das epilepsias / Cursive and gelastic manifestations of epilepsy

Os autores descrevem dois pacientes com manifestaçöes gelásticas e sete pacientes com manifestaçöes cursivas de crises epilépticas, documentadas com eletrencefalograma intercrítico e tomografia computadorizada craniana. Todos os pacientes apresentavam crises parciais complexas seguidas ou näo de crises tônico-clônicas generalizadas. Discutem o tema a respeito da fisiopatologia e questionam a importância nosológica destas formas de epilepsias