Motor impairment in liver cirrhosis without and with minimal hepatic encephalopathy

Butz M, Timmermann L, Braun M, Groiss SJ, Wojtecki L, Ostrowski S, Krause H, Pollok B, Gross J, Südmeyer M, Kircheis G, Häussinger D, Schnitzler A. Motor impairment in liver cirrhosis without and with minimal hepatic encephalopathy.
Acta Neurol Scand: 2010: 122: 27–35.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Aim – Manifest hepatic encephalopathy (HE) goes along with motor symptoms such as ataxia, mini‐asterixis, and asterixis. The relevance of motor impairments in cirrhotics without and with minimal HE (mHE) is still a matter of debate. Patients and methods – We tested three different groups of patients with liver cirrhosis: no signs of HE (HE 0), mHE, and manifest HE grade 1 according to the West Haven criteria (HE 1). All patients (n = 24) and 11 healthy control subjects were neuropsychometrically tested including critical flicker frequency (CFF), a reliable measure for HE. Motor abilities were assessed using Fahn Tremor Scale and International Ataxia Rating Scale. Fastest alternating index finger movements were analyzed for frequency and amplitude. Results – Statistical analyses showed an effect of HE grade on tremor and ataxia (P < 0.01). Additionally, both ratings yielded strong negative correlation with CFF (P < 0.01, R = ?0.5). Analysis of finger movements revealed an effect of HE grade on movement frequency (P < 0.03). Moreover, decreasing movement frequency and increasing movement amplitude parallel decreasing CFF (P < 0.01, R = 0.6). Conclusion – Our results indicate that ataxia, tremor, and slowing of finger movements are early markers for cerebral dysfunction in HE patients even prior to neuropsychometric alterations becoming detectable.     

Status epilepticus as a manifestation of hepatic encephalopathy

OBJECTIVES: Seizures have been described as a rare manifestation of hepatic encephalopathy. MATERIAL AND METHODS: We present a 54-year-old female, with 6-year history of decompensated, hepatitis B liver cirrhosis, admitted with generalized seizures. She reported a history of recurrent episodes of hepatic encephalopathy, spontaneous bacterial peritonitis, tense ascites and variceal hemorrhage. Neurologic examination revealed a comatose patient, without papilledema. Laboratory examinations were suitable with cirrhosis and mild renal failure. Blood gas examination revealed severe metabolic acidosis and hypoxemia. Plasma NH3+ levels upon admission were twice normal. Brain computed tomography and magnetic resonance imaging were normal. Electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy, grades III-IV. RESULTS: Status epilepticus was refractory to continuous antiepileptic treatment. However, it was resolved after 24-h therapy with lactulose. Blood NH3 levels were simultaneously normalized with clinical improvement. CONCLUSIONS: We consider the status epilepticus of our patient to be a rare manifestation of hepatic encephalopathy.     

Anesthetic drugs for the treatment of status epilepticus

Worsening pharmacoresistance to antiseizure drugs is common with ongoing excitotoxic neuronal and systemic injury. Early initiation of anesthetic drugs in refractory status epilepticus (RSE) may halt these processes while allowing time for treatment targeting the cause of the seizures. Current guidelines support the use of anesthetic drugs as the third line pharmacologic therapy in generalized convulsive status epilepticus but do not clearly define the indications for these drugs in other types of status epilepticus. There is wide practice variation in choice of third line therapy for RSE, but there is overall consensus that anesthetics should be initiated earlier in generalized convulsive status epilepticus than in nonconvulsive forms. More recently, doubt has been cast on the appropriateness of anesthetic treatment of RSE following a series of studies associating their use with higher mortality and morbidity. This suggests that efforts should focus on determination of who benefits most, optimal use, and prevention of refractoriness. The risk‐benefit ratio of anesthetic use is discussed, with specific indications proposed. In addition, anesthetic dosing, supportive neurocritical care, electroencephalogram suppression target, and weaning of anesthesia are reviewed.     

Cerebrospinal fluid and blood biomarkers of status epilepticus

Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures and require urgent administration of antiepileptic drugs. Refractory status epilepticus requires anesthetics drugs and may lead to brain injury with molecular and cellular alterations (eg, inflammation, and neuronal and astroglial injury) that could induce neurologic sequels and further development of epilepsy. Outcome scores based on demographic, clinical, and electroencephalography (EEG) condition are available, allowing prediction of the risk of mortality, but the severity of brain injury in survivors is poorly evaluated. New biomarkers are needed to predict with higher accuracy the outcome of patients admitted with status in an intensive care unit. Here, we summarize the findings of studies from patients and animal models of status epilepticus. Specific protein markers can be detected in the cerebrospinal fluid and the blood. One of the first described markers of neuronal death is the neuron-specific enolase. Gliosis resulting from inflammatory responses after status can be detected through the increase of S100-beta, or some cytokines, like the High Mobility Group Box 1. Other proteins, like progranulin may reflect the neuroprotective mechanisms resulting from the brain adaptation to excitotoxicity. These new biomarkers aim to prospectively identify the severity and development of disability, and subsequent epilepsy of patients with status. We discuss the advantages and disadvantages of each biomarker, by evaluating their brain specificity, stability in the fluids, and sensitivity to external interferences, such as hemolysis. Finally, we emphasize the need for further development and validation of such biomarkers in order to better assess patients with severe status epilepticus.     

Mental illness and admission to general hospitals: a register investigation

Admissions to psychiatric departments and general hospitals in an 8-year period were studied for the 17- to 49-year-old population in 2 Danish municipalities. Information was extracted from the National Patient Register and the Danish Psychiatric Register, registers containing information on all admissions to nonpsychiatric and psychiatric departments, respectively, in Denmark. Fourteen percent of the patients who had been admitted at least once to a general hospital (or 7.5% of the background population) had an indication of a mental disorder. They comprised one fourth of all general admissions of the population during the 8-year period. Patients who had been admitted to a general hospital had a 4 times greater risk of having been admitted to a psychiatric department than the rest of the population and the risk increased markedly with number of general admissions. A pronounced association was found between the number of admissions to general hospitals and psychiatric departments; i.e., both types of admissions clustered in some individuals. The excessive general admissions of psychiatric patients were found to be correlated to all types of psychiatric diagnoses, but was less prominent in nonorganic psychoses. The implication is that there is a very close association between somatic and psychiatric morbidity and that the mentally disturbed use a great part of the nonpsychiatric health services.     

Season of birth and season of hospital admission in bipolar depressed female patients

The season of birth and season of hospital admission of 50 bipolar I and 42 bipolar II female patients were analyzed. Significant differences were found in the seasonal distribution of births in the two subgroups. The birth dates of most bipolar I patients showed a tendency to peak during spring and autumn, while bipolar II patients were born mostly in summer and winter. Bipolar I patients were hospitalized for mania mainly in spring and autumn, and for depression mainly in summer and winter. Examination of the seasonal variation of hospital admission for depression also revealed significant difference between bipolar I and bipolar II patients. The results support the validity of the bipolar I-bipolar II distinction and are in agreement with earlier findings.     

Pathophysiology of mitochondrial disease causing epilepsy and status epilepticus

Epilepsy is part of the clinical phenotype in nearly 40% of children with mitochondrial disease, yet the underlying molecular mechanisms remain poorly understood. Energy depletion has been postulated as the cause of mitochondrial epilepsy, but if this were the case, then 100% of patients with mitochondrial disease would be expected to present with seizures. This review explores other potential disease mechanisms underlying mitochondrial epilepsy, including oxidative stress, impaired calcium homeostasis, immune dysfunction, and deficiency of vitamins, cofactors, reducing equivalents, and other metabolites. Different mechanisms are likely to predominate in different mitochondrial disorders, since mitochondrial function varies between neurons and astrocytes, between different types of neurons, and in different brain regions. Systematic studies in cell and animal models of mitochondrial disease are needed in order to develop effective therapies for mitochondrial epilepsy.This article is part of a Special Issue entitled “Status Epilepticus”.     

Significance of atypical triphasic waves for diagnosing nonconvulsive status epilepticus

The aim of the study described here was to analyze findings in 15 cases who were admitted with nonconvulsive status epilepticus (NCSE) and whose EEGs featured atypical triphasic waves (ATWs). We also investigated whether ATWs are useful for diagnosing this condition. Mental status was assessed, and EEGs were recorded during/after the antiepileptic drug treatment. Eight patients had metabolic disorders and nine had intracranial pathology. The ATWs were unilateral focal in 5 cases and bilaterally asymmetrical focal in 10 cases. In 11 of the 15 cases, the ATWs disappeared and mental status improved after treatment. NCSE should be considered in any individual who presents in an acute confusional state and whose EEG reveals either unilateral or bilaterally asymmetric ATWs.     

The effectiveness of intravenous benzodiazepine for status epilepticus in Dravet syndrome

PurposeWe aimed to evaluate choice and efficacy of intravenous antiepileptic drugs (AEDs) for status epilepticus (SE) in Dravet syndrome and to find predictable clinical features demonstrating the effectiveness of benzodiazepine (BZD) for SE.MethodsWe retrospectively investigated the medical records in patients with Dravet syndrome and evaluated the effectiveness rate of intravenous AEDs and the rate of adverse effects. To find the clinical features of BZD-effective SE, we divided the SE episodes into the following two groups: BZD effective group and BZD non-effective group. The choice of treatment was dependent on physicians’ discretion according to the protocol for SE in our institution.ResultsSixty-eight SE episodes in 10 patients were assessed. The median age at SE was 31 months. Of 68 episodes, 42 episodes (61.8%) were in the BZD effective group and 26 (38.2%) in the BZD non-effective group. There were no significant differences in clinical features. In the BZD non-effective group, the effective rates of continuous midazolam, phenobarbital, phenytoin/fosphenytoin were 9/9 episodes (100%), 14/17 (82.4%), and 2/5 (40.0%), respectively. Adverse effects were identified in 19/68 episodes (27.9%), including 11/42 episodes in the BZD effective group and 8/26 in the BZD non-effective group, which was no statistical difference between the two groups. Respiratory suppression was found in all 19 episodes and the incidence of endotracheal intubation in the BZD non-effective group (15.4%) was higher than that in the BZD effective group (2.4%) (p = 0.046).ConclusionBZD may be used as first choice, and phenobarbital prior to continuous midazolam as second choice for SE with Dravet syndrome. There might be no predictable clinical features showing that BZD will be effective.     

Treatment gap for convulsive status epilepticus in resource‐poor countries

The magnitude of the treatment gap (TG) for convulsive status epilepticus (CSE) in resource‐poor countries is unknown. Hospital‐based cohort studies from developing countries revealed that the management of CSE was usually suboptimal due to lack of advanced diagnostic and treatment facilities, significant delay in patient's presentation at hospital, and shortages of essential antiepileptic drugs (AEDs). However, there were no significant differences in the proportion of refractory status epilepticus, short‐term mortalities, and morbidities of CSE between the developed and the developing countries. Therefore, the presence of significant TG for CSE in developing countries is still an assumption without evidence. We conducted an expert survey in Asia for potential sources of TG. Experts from 16 Asian countries responded to the questionnaire. An injectable form of diazepam was available in all 16 countries even at the primary care level, but intravenous lorazepam was available only in four countries. Second‐line AEDs were widely available at tertiary care hospitals, but not at primary care hospitals. Lack of second‐line AEDs at primary care hospitals, significant delay in patient transportation to the hospital, shortages of intensive care unit facilities, and absence of trained physicians were important contributing factors to TG in Asia.     

Parental socio-economic status and risk of first admission with schizophrenia

Abstract.Background: We examined the relationships between measures of parental and personal socio-economic status and risk of first admission with schizophrenia in order to identify whether low socio-economic status in cases is a consequence of the illness process or is a familial risk factor.Methods: A national population-based nested case-control study based on Danish longitudinal registers was conducted. The sample included 7704 first admissions with ICD-8 or ICD-10 schizophrenia admitted to a psychiatric facility in Denmark between 1981 and 1998 and 192 590 individually time-, age- and gender-matched population controls identified through national registers, and their parents and siblings. Socio-economic indicators measured in the year prior to admission and background factors for cases, controls, and parents were included.Results: Risk of schizophrenia was associated with unemployment, low educational attainment, being single, lower wealth status, low income, and being childless. Increased risk was associated with a family history of psychiatric disorders, birth in urban areas, birth outside of Denmark, and having three of more siblings. Increased risk of schizophrenia was associated with parental unemployment and parental lower income, but was not associated with parental wealth. Risk for schizophrenia was associated with higher education in parents.Conclusions: Increased risk of first admission was associated with socio-economic disadvantage in cases. Although we found some associations between parental unemployment and parental higher education and risk of schizophrenia, there was little evidence that low parental socio-economic status increases the risk of schizophrenia.     

A girl with Cardio-facio-cutaneous syndrome complicated with status epilepticus and acute encephalopathy

We report a six-year-old girl with Cardio-facio-cutaneous (CFC) syndrome who developed acute encephalopathy after the recurrence of status epilepticus. While epileptic encephalopathy and severe epilepsy have been mentioned as frequent complications of the CFC syndrome, no previous reports have shown a case of the CFC syndrome complicated with acute encephalopathy. Here we discuss the possibility for the linkage between the development of acute encephalopathy and CFC syndrome which is generally susceptible to seizures or epilepsy.     

脑炎后癫痫持续状态进展为难治性癫痫持续状态及超级难治性癫痫持续状态的早期预测因素

目的 探讨脑炎后癫痫持续状态(SE)进展为难治性SE(RSE)及超级RSE(SRSE)的早期预测因素.方法 根据疾病进展情况将89例脑炎后SE患者分为非RSE组、RSE组及SRSE组.比较各组临床资料.结果 非RSE组、RSE组及SRSE组年龄、SE严重程度评分量表(STESS)评分、基于流行病学SE病死率评分(EMS...     

Fosphenytoin vs. continuous midazolam for pediatric febrile status epilepticus

Background

Fosphenytoin (fPHT) and continuous intravenous midazolam (cMDL) had commonly been used as second-line treatments for pediatric status epilepticus (SE) in Japan. However, there is no comparative study of these two treatments.

Complex partial status epilepticus as a manifestation of Hashimoto''s encephalopathy

Epileptic seizures are a frequent manifestation of Hashimoto's encephalopathy. However, status epilepticus associated with Hashimoto's encephalopathy are not well characterized in medical literature. We described here a 16-year-old girl who presented with complex partial status epilepticus associated with elevated anti-thyroid antibodies. Ictal EEG showed lateralized high amplitude rhythmic delta waves over the right hemisphere and ictal single-photon emission computed tomography revealed regional hyperperfusion of the right parietal and temporal lobes. The patient was unresponsive to antiepileptic drug therapy but responded to intravenous steroid treatment. Screening of serum anti-thyroid antibodies for unexplained encephalopathy with epileptic seizures is suggested, as early recognition and prompt steroid treatment may lead to a favorable prognosis.