Non-convulsive status epilepticus: mimics and chameleons.

Non-convulsive status epilepticus (NCSE) is an enigmatic condition with protean manifestations. It often goes unrecognised, leading to delays in its diagnosis and treatment. The principal reason for such delay is the failure to consider and request an electroencephalogram (EEG), although occasional presentations have no scalp or surface electroencephalographic correlate. In certain settings with limited EEG availability, particularly out-of-hours, clinicians should consider treating without an EEG. Patients need a careful risk-benefit analysis to assess the risks of neuronal damage and harm versus the risks of adverse effects from various intensities of therapeutic intervention. Specialists in EEG, intensive care or epilepsy are invaluable in the management of patients with possible NCSE.

Hidden in plain sight: Non-convulsive status epilepticus-Recognition and management.

Non-convulsive status epilepticus (NCSE) is an electroclinical state associated with an altered level of consciousness but lacking convulsive motor activity. It can present in a multitude of ways, but classification based on the clinical presentation and electroencephalographic appearances assists in determining prognosis and planning treatment. The aggressiveness of treatment should be based on the likely prognosis and the underlying cause of the NCSE.

Early predictors of refractory status epilepticus: an international two-center study.

BACKGROUND AND PURPOSE: Status epilepticus (SE) refractory to first- and second-line antiepileptic drugs carries high mortality. Little is known on early prediction of refractory SE (RSE)­an essential tool for planning appropriate therapy. Our aim was to identify and validate independent early RSE predictors in adults. METHODS: Clinical and laboratory data on consecutive intensive care unit patients with SE from two academic care centers (a derivation data set from a Swiss center and a validation data set from a US center) were assessed. Multivariable analysis was performed with the derivation set to identify RSE predictors at SE onset. Their external validity was evaluated with an independent validation set. Measures of calibration and discrimination were assessed. RESULTS: In all, 302 patients were analyzed (138 with and 164 without RSE), 171 in the derivation data set and 131 in the validation data set. Acute SE etiology, coma/stupor and serum albumin <35 g/l at SE onset were independent predictors for RSE in the derivation data set [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.01-4.07; OR 4.83, 95% CI 2.42-9.68; OR 2.45, 95% CI 1.16-5.16]. The prediction model showed good measures of calibration (Hosmer-Lemesow goodness-of-fit test P = 0.99) and discrimination (area under the receiver operating characteristic curve 0.8) on the derivation data set­results that were similar in the validation data set (Hosmer-Lemeshow P = 0.24; area under the receiver operating characteristic curve 0.73). CONCLUSIONS: This study confirms the independent prognostic value of readily available parameters for early RSE prediction. Prospective studies are needed to identify additional robust predictors, which could be added to the proposed model for further optimization towards a reliable prediction scoring system.

Uncovering clinical and radiological associations of triphasic waves in acute encephalopathy: a case-control study.

BACKGROUND AND PURPOSE: Triphasic waves (TWs) are archetypal waveforms seen on electroencephalography (EEG) in some forms of encephalopathy. Their particular underlying pathological substrates are largely unexplored. This case-control study was designed to identify and quantify specific clinical and neuroradiological associations underlying TWs and to determine if TWs predicate outcome. METHODS: From 2004 to 2012, adult encephalopathic patients with TWs (cases) were matched 1:1 with encephalopathic patients without TWs (controls) by Glasgow Coma Scale (GCS) and the frequency range of EEG background activity. Clinical characteristics, neuroimaging and outcomes were assessed. RESULTS: The mean age of 190 patients (95 with and 95 without TWs) was 66.6 years (±15.6). In multivariable analyses, patients with TWs had significantly higher odds for liver insufficiency [odds ratio (OR) = 8.10, 95% confidence interval (CI) 1.98-33.08], alcohol abuse (OR = 3.65, 95% CI 1.25-10.63), subcortical brain atrophy (OR = 2.82, 95% CI 1.39-5.71) and respiratory tract infections (OR = 1.28, 95% CI 1.01-4.71). With each additional independent predictor, the odds increased for the occurrence of TWs (1 predictor, OR = 2.40, 95% CI 1.16-5.13; ≥2 predictors, OR = 9.20, 95% CI 3.27-25.62). Mortality was 15% and tended to be higher in patients with TWs (19% with vs. 11% without TWs). CONCLUSIONS: Alcohol abuse, liver insufficiency, infections and subcortical brain atrophy were independently associated with TWs in patients matched for clinical and EEG features of encephalopathy. These associations strengthen the hypothesis that TWs evolve from an interplay of pathological neurostructural, metabolic and toxic conditions. When matched for EEG background activity and GCS, TWs were not associated with death.

Electroencephalographic sleep elements and outcome in acute encephalopathic patients: a 4-year cohort study.

BACKGROUND AND PURPOSE: Acute encephalopathy in hospitalized patients is common and associated with high mortality. Preservation of physiological sleep has been associated with favorable outcomes in acute brain injury. It is hypothesized that electroencephalographic presence of sleep elements is associated with good outcome in encephalopathic adults. METHODS: This observational study was performed at an academic tertiary medical care center. Clinical data, electroencephalogram (EEG) characteristics and outcome of critically ill patients with acute encephalopathy were assessed. EEGs were interpreted regarding the presence of sleep elements (K-complexes, vertex sharp-waves and sleep spindles). Associations between sleep elements and outcome (graded by the Glasgow Outcome Scale, GOS) were analyzed. RESULTS: One hundred and forty-two consecutive patients with a median age of 64.5 years (range 18-98) and mean Glasgow Coma Scale 10.4 (± 3.8) were included. Leading etiologies were infections (47.2%), intracranial hemorrhages (14.1%) and ischaemic strokes (10.6%). All EEGs demonstrated encephalopathy patterns and 38% had ≥ 1 sleep element (27.5% K-complexes, 31.7% vertex sharp-waves and 33.8% sleep spindles). Patients without sleep elements were older (P = 0.010) and septic shock was more common (P = 0.014). Amongst sleep elements, K-complexes were significantly associated with good outcome, even after adjusting for possible confounders (odds ratio for GOS 5 = 2.79, 95% confidence interval 1.16-6.69) and without significant effect modification across subgroups. CONCLUSIONS: Whilst EEG sleep elements were detected more frequently in patients with favorable outcome, only K-complexes were significantly and independently associated with good outcome in intensive care unit patients with acute encephalopathy, findings that need to be confirmed in larger prospective studies.

Psychogenic amnesia and self-identity: a multimodal functional investigation.

BACKGROUND: Patients with psychogenic amnesia generally suffer from episodic memory deficits associated with an impairment of self-identity. While the first is generally attributed to limbic dysfunction, the latter might be related to posterior parietal cortex. METHODS AND RESULTS: In a patient with acute repetitive psychogenic amnesia, three different functional investigations (fMRI, electrical-neuroimaging, PET) during both resting-state and a behavioural paradigm testing 'time-travel' showed left posterior parietal activation, unlike in 12 control subjects. CONCLUSION: Impairment of self-identity and episodic memory in psychogenic amnesia may be associated with functional alterations of left posterior parietal cortex.

Antiepileptic drugs modify power of high EEG frequencies and their neural generators.

BACKGROUND: The clinical and molecular effects of antiepileptic drugs (AEDs) have been extensively investigated. Much less is known about their effects on human electrophysiology. METHODS: Topographic analysis in the frequency domain has been used to analyze 104 electroencephalogram (EEG) epochs of 52 patients presenting with first-ever generalized seizure, with normal MRI and EEG. Patients were treated with valproate, arbamazepine, or lamotrigine in monotherapy (each group n = 13). Thirteen patients without medication served as a control group. RESULTS: Carbamazepine and lamotrigine, both sodium-channel modulators, altered brain topography in the gamma range in the same frequency bands (50-60 Hz). Valproate, which has multiple actions on sodium and calcium channels as well as GABA turnover, modified brain topography in the low gamma range (30-40 Hz). No such changes were found in the control group. For all AEDs, the neural generators were shifted more anteriorly in medial temporal through to inferior frontal regions. CONCLUSION: Decreased gamma-power and anterior shift of neural generators after AED introduction reflect AED influence on human electrophysiology.

Clinical utility of EEG in diagnosing and monitoring epilepsy in adults.

Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE.

A continuing controversy: magnesium sulfate in the treatment of eclamptic seizures.

It would appear from the above that Pritchard agrees with the use of some agents other than magnesium sulfate that have known anticonvulsant properties. We believe that the subject at issue is whether magnesium sulfate should be used in treating the seizures of eclampsia. In our "Controversies" article, we do not address the issue of whether magnesium sulfate modifies pathophysiological factors leading to preeclampsia, but restrict ourselves to the treatment of the seizure per se, once seizures supervene, and the avoidance of their recurrence. The pathophysiological mechanisms and optimal treatment of preeclampsia and of eclampsia (excepting seizures) remain to be determined, as does the use of magnesium sulfate in this condition. Eclamptic seizures are clinically and electroencephalographically indistinguishable from generalized tonic-clonic seizures. Whether seizures arise in or out of the setting of preeclampsia, they should be treated as are other seizures, with known anticonvulsants. Controlled clinical trials are needed to address the effectiveness of alternative antiseizure regimens.

Neurophysiologic and clinical correlations of epileptic nystagmus.

Epileptic nystagmus (EN) is a rare sign of seizure activity. We describe eight patients with horizontal EN and hypothesize that the frequency of ictal discharge, anatomic localization of ictal activity, and level of consciousness determine its occurrence and mechanism. We believe that EN is due to epileptic activation of a cortical saccade region; in each case, quick phases were generated away from the side of the focus, and both quick and slow phases were totally confined to the field contraversive to the seizure focus.

Vertical and horizontal epileptic gaze deviation and nystagmus.

Periods of epileptic nystagmus consisting of rightward eye deviation and right-beating nystagmus, alternating with upward eye deviation and upbeating nystagmus, occurred in a comatose patient with a left hemisphere subdural hematoma and seizures. The periods of upbeating nystagmus were associated with symmetric, low-voltage 3 to 4 Hz bifrontal spikes. Rightward eye deviation and right-beating nystagmus occurred with diffuse, predominantly left hemispheric 4 to 6 Hz sharp waves. No eye movements occurred in the absence of spike and wave activity. These correlations agree with current concepts of the cortical control of saccadic eye movements in monkeys studied by electrical stimulation.

Somatosensory evoked potentials in adrenomyeloneuropathy.

Adrenomyeloneuropathy (AMN) is an X-linked metabolic disorder causing accumulation of very-long-chain fatty acids with multifocal nervous system demyelination of the peripheral nerves, spinal cord, and cerebrum. The extent to which the disorder affects upper versus lower limbs or peripheral versus CNS has not been electrophysiologically defined in a large population nor differentiated in men and women. To determine patterns of nervous system demyelination and define gender differences, we studied 83 AMN patients with short latency median and posterior tibial nerve somatosensory evoked potentials (SSEPs). Most women (10/16) had abnormal median SSEPs all involving central pathways, whereas most men (59/67) had abnormal median SSEPs involving both peripheral and central pathways. Tibial SSEPs were abnormal in both sexes (14/15 women, 67/67 men), with either peripheral or central pathway involvement. This study demonstrates the frequent widespread involvement of both peripheral nerve and central somatosensory pathways in men with AMN and the predominantly central involvement in women.

Ipsiversive eye deviation and epileptic nystagmus.

We studied an 11-year-old boy with focal seizures in the right temporo-occipital cortex. During the seizure, there was a 1- to 2-second period of ipsiversive (rightward) conjugate eye deviation, followed by 10 to 15 seconds of horizontal jerk nystagmus with slow phases that were directed to the right and appeared linear. The patient was conscious throughout the seizure. These findings fit the description of epileptic nystagmus. We postulate that the eye deviation and slow phases of the nystagmus in this patient were induced by epileptic activation of a cerebral smooth pursuit pathway originating from temporoccipital cortex.

Reversible dementia with idiopathic hypereosinophilic syndrome.

A 66-year-old woman with hypereosinophilic syndrome became rapidly demented. Evaluation revealed CSF eosinophilia, background slowing on EEG, and periventricular MRI abnormalities. Following steroid therapy, there was rapid resolution of the dementia and normalization of CSF and EEG. These findings support the concept of a direct neurotoxic effect on the human CNS produced either by eosinophils or possibly by eosinophil-derived neurotoxins.

Acute steroid-induced tetraplegia following status asthmaticus.

A 10-year-old girl was treated for an acute asthmatic attack with ventilation and a high-dose steroids regimen. An areflexic paralysis of the four limbs was noted when artificial ventilatory support was withdrawn. Electromyography and a muscle biopsy revealed marked myopathic features. We discuss the unusual presentation of an acute steroid-induced myopathy in an asthmatic patient.

A double-blind, placebo-controlled study of the treatment of periodic limb movements in sleep using carbidopa/levodopa and propoxyphene.

We studied the relative benefits of carbidopa/levodopa (25/100 mg and 50/200 mg) and propoxyphene (100 mg and 200 mg) in six subjects with periodic limb movements (PLM) using a randomized, double-blind, placebo-controlled, cross-over design with a 4-day placebo wash-out period between test medications. Each subject received, for successive 2-week periods, 4 days of placebo followed by 5 days of low-dose and then 5 days of high-dose medication. Outcome was measured with polysomnograms and sleep latency tests on the last night of the high dose, and leg activity was monitored for each night of the study. Carbidopa/levodopa normalized PLM and improved sleep, particularly in the first 3 hours in most subjects. Propoxyphene had marginal benefit and significantly decreased arousals and mildly decreased leg movements for leg activity monitoring, but not for PLM on the polysomnograms. Subjects reported better sleep and alertness on carbidopa/levodopa than on propoxyphene or placebo. Our results support the premise of a central dopaminergic abnormality in PLM.

Clinical correlates and prognosis in early spindle coma.

OBJECTIVE: To determine the prognostic significance of spindle coma (SC) according to etiology and EEG reactivity. METHODS: We reviewed 15 patients with SC due to various causes within 8 days of coma to determine the prognostic significance of this EEG pattern. RESULTS: The outcome among survivors was favorable: among 13 survivors, 9 were independent in all activities of daily living (ADLs) at 6 months; 3 were dependent in all ADLs; and one remained in coma. EEG reactivity to noxious stimuli best predicted outcome: All patients (whatever the coma etiology) with EEG reactivity survived; conversely, not all patients without EEG reactivity died. CONCLUSION: In our patients, EEG reactivity independent of etiology predicted survival, neurological examination did not predict outcome. Most SC survivors had a meaningful recovery achieving all ADLs. From the literature, the cause of SC was predictive of outcome: encephalopathy, seizures and trauma had the best prognosis while hypoxia, CRA and structural lesions carried the worst. Literature review revealed that 23% of patients [56/242] died or remained in a persistent vegetative state (PVS). Best outcomes occurred when SC was due to drugs, encephalopathy or seizures: (0/14 died or were in a PVS). With trauma 15% [25/169] died or were in a PVS). Intermediate outcomes occurred with hypoxia and cardio-respiratory arrest (CRA): 33% [7/21] died or were in a PVS. The gravest outcomes occurred with brain-stem and cerebral infarctions, and tumors: 73% [22/30] died or were in a PVS.

Etiology, neurologic correlations, and prognosis in alpha coma.

OBJECTIVE: To determine the factors affecting prognosis in alpha coma (AC). METHODS: Retrospective review of 36 study patients, 36 control coma patients matched for age and etiology, and meta-analysis of 335 cases in the world literature. RESULTS: Principal causes were cardiorespiratory arrest (CRA) (21 patients); infection, metabolic dysfunction, head trauma (3 each); and drugs, stroke and hypoxia (2 each). Outcome was predicated by EEG reactivity to noxious stimuli. Fourteen of the 15 patients with reactive EEGs, had measurable outcome, 8 awoke - all but two had etiologies other than CRA. Fourteen of 19 patients without EEG reactivity died; two had support discontinued and 3 awoke. Following CRA, 16/21 patients died and 3 had support discontinued. Only 3 patients made a good recovery - all with toxic or metabolic etiologies. Literature meta-analysis of 335 cases showed that overall, AC carried a poor prognosis (76% died). CRA (226 cases) had an 88% mortality; strokes (29 cases), a 90% mortality; hypoxia without cardiac arrest (28 cases), a 61% mortality; drug-induced AC (25 cases), an 8% mortality. CONCLUSIONS: Although the cause of AC largely predicts outcome, EEG reactivity in AC predicted survival: most patients with reactivity awoke; most of those without, died. Few survivors had meaningful recovery.

Assessing the outcomes in patients with nonconvulsive status epilepticus: nonconvulsive status epilepticus is underdiagnosed, potentially overtreated, and confounded by comorbidity.

Nonconvulsive status epilepticus (NCSE) is characterized by behavioral or cognitive change from baseline for at least 30 minutes with EEG evidence of seizures. Categorized into complex partial status epilepticus (with lateralized seizures), and generalized nonconvulsive status epilepticus (bilateral diffuse synchronous seizures), there is debate regarding the diagnosis and morbidity of NCSE. Because EEG is needed for diagnosis, only a high index of suspicion leads to a request for the study, whereas EEG is often unavailable after hours or on weekends. Furthermore, the cognitive changes during NCSE are often incorrectly ascribed to a postictal state, intoxication, psychogenic or psychotic states, and mental retardation. Regarding categorization, present classifications address EEG features but fail to distinguish among depths of coma. Deeply comatose patients (with coma etiologies that themselves carry poor prognoses) are mixed with lightly obtunded patients with no morbidity, confusing the prognosis. Thus, a classification that subsumes depth of coma, and possibly etiology, is sorely warranted. Regarding treatment, comatose NCSE patients treated with benzodiazepines may worsen, whereas generalized nonconvulsive status epilepticus patients may suffer iatrogenically from aggressive treatment (hypotension and respiratory depression) necessitating balancing the potential neurologic morbidity of NCSE against the possible morbidity of IV antiepileptic drugs. A high index of suspicion is needed to initiate EEG studies. Better stratification of level of consciousness will be needed to distinguish among morbidity due to underlying conditions, treatment, and the effects of status epilepticus, proper.