Loss of network efficiency associated with cognitive decline in chronic epilepsy.

OBJECTIVE: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. METHODS: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. RESULTS: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. CONCLUSIONS: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.

Early treatment after stroke for the prevention of late epileptic seizures: a report on the problems performing a randomised placebo-controlled double-blind trial aimed at anti-epileptogenesis.

INTRODUCTION: Epileptic seizures in stroke patients are a common complication and adversely affect neurological outcome. We tried to perform a trial aimed at preventing the development of late poststroke seizures using levetiracetam. Levetiracetam is assumed to have anti-epileptogenic properties and might be suitable to prevent late epileptic seizures in stroke patients. METHODS: Stroke patients with a cortical syndrome and a modified Rankin score ≥ 3 or NIHSS ≥ 6 were treated with either levetiracetam 1500 mg daily divided in two doses or placebo during 12 weeks following stroke. Treatment was started within 7 days following stroke onset. RESULTS: Only 16 patients were included in this trial. Problems during the execution of this prophylactic trial concerned the assessment of the occurrence of epileptic seizures, a very slow inclusion rate, the use of anticonvulsive co-medication, continuation of the trial medication after discharge, and the evaluation of possible side effects of the trial medication. DISCUSSION: Due to too few participants, no conclusions could be drawn regarding the ability of levetiracetam to prevent poststroke seizures. The problems encountered during execution of this trial seem to be inherent to performing a trial aimed at preventing the development of epileptic seizures in stroke patients. CONCLUSIONS: A prophylactic trial in stroke patients aimed at preventing poststroke seizures and epilepsy seems not feasible.

Functional connectivity and language impairment in cryptogenic localization-related epilepsy.

BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.

Adjustment of treatment increases quality of life in patients with epilepsy: a randomized controlled pragmatic trial.

BACKGROUND AND PURPOSE: Complaints about side-effects of antiepileptic drugs (AEDs) may be overlooked in clinical practice. We assessed the value and risks of an active intervention policy for reported complaints in a randomized controlled pragmatic trial. METHODS: This randomized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals. They were considered well-managed by their treating physician, but reported moderate to severe complaints on a questionnaire (SIDAED, assessing SIDe effects in AED treatment). The intervention was adjustment of AED treatment (53 patients), either reduction of dose or switch of AED, versus continuation of treatment unchanged (58 control patients) during 7 months. Primary outcomes were quality of life (Qolie-10) and complaints score. Secondary outcome measures were the occurrence of seizures or adverse events. RESULTS: After 7 months, the relative risk (RR) for improvement in quality of life was 1.80 (1.04-3.12) for the intervention group compared to control and the RR of decrease in complaints was 1.34 (0.88-2.05). In 58% of patients randomized to adjustment, the medication had indeed been changed. DISCUSSION: In conclusion, despite a possible risk of seizure recurrence, adjustment of drug treatment in well-managed patients with epilepsy, who report considerable complaints, improves the quality of life.

[Carpal tunnel syndrome: diagnosis, treatment, prevention and its relevance to dentistry]. / Diagnostiek en behandeling van het carpaletunnelsyndroom.

Nocturnal pins and needles and other sensory disturbances in the median nerve innervated fingers are caused by local pressure on this nerve in the carpal tunnel. Carpal tunnel syndrome is the most frequently encountered peripheral nerve entrapment. In The Netherlands, the prevalence of carpal tunnel syndrome is estimated 9% among adult women and 0.6% among adult men. Several risk factors have been identified. For dental professionals, the most relevant seem forceful use of the hand during scaling and extractions, use of vibrating ultrasonic equipment and frequent working with the wrist in flexion or in extension. The diagnosis of carpal tunnel syndrome is based on the characteristic complaints, confirmed preferably by abnormal electrophysiological tests. Depending on the degree of impact on daily functioning, treatment for carpal tunnel syndrome may be expectative, conservative or surgical. Adjustment of the working conditions may prevent the development of a carpal tunnel syndrome.

Cognitive fMRI and soluble telencephalin assessment in patients with localization-related epilepsy.

Objectives - The use of telencephalin as a possible marker for altered cortical function as demonstrated by functional MRI was investigated in a pilot study with 16 patients with localization-related epilepsy and secondarily generalized seizures. Materials and methods - Functional MRI of verbal working memory performance (Sternberg paradigm) and self-regulatory control processes (Stroop paradigm) was used to examine cortical activation in 16 patients with localization-related epilepsy and secondarily generalized seizures. Additionally, blood serum concentrations of soluble telencephalin (marker for neuronal damage) were determined. Results - In three patients (one temporal and two frontal focus), telencephalin was detected. All three patients had lower functional MRI activation in the frontotemporal region (P = 0.04), but not in other regions (P > 0.35) compared with patients without detectable telencephalin. Additionally, an association of levetiracetam and frontotemporal activation was observed. Conclusions - These preliminary data in a heterogeneous group suggest an association between decreased frontotemporal activation on fMRI and both detectable telencephalin serum levels and levetiracetam use. Future longitudinal studies with larger patient groups are required to confirm these observations. It is hypothesized that altered local function of the frontotemporal cortex in localization-related epilepsy might be better predicted by the biochemical marker telencephalin than epilepsy characteristics such as seizure focus.

[Guideline 'Diagnosis and treatment of carpal tunnel syndrome']. / Richtlijn 'Diagnostiek en behandeling van het carpale-tunnelsyndroom'.

--Carpal tunnel syndrome (CTS) is the most frequently encountered peripheral nerve entrapment: about 10% of adult women and less than 1% of adult men in the Netherlands have a clinically and electrophysiologically confirmed CTS. --All medical and paramedical disciplines involved in the diagnosis and treatment of CTS in the Netherlands contributed to the development of a guideline for the diagnosis and treatment ofCTS. --Clinical diagnosis of CTS is based on a history of nocturnal pins and needles, numbeness and/or pain in the median nerve innervated area of the fingers and hand, which often causes the patient to awake. --Provocative tests do not contribute to the clinical diagnosis of CTS. --If invasive therapy is considered, such as corticosteroid injection or surgery, the clinical diagnosis must be confirmed by abnormal findings in electrophysiological tests. --Ultrasound or MRI of the wrist may be of diagnostic value when structural abnormalities in the carpal tunnel are suspected. Given the special expertise needed for ultrasound testing and the limited availability of MRI for CTS diagnostic purposes, these methods are not the first preference. --Depending on the degree of impact on daily functioning, treatment for CTS may be expectative, conservative (wrist splint or local steroid injections) or surgical (endoscopic or open techniques). --If CTS does not restrict daily functioning, adjustment of the working conditions will do. --Furthermore measures aimed at CTS prevention and treatment of an already existing work-related CTS are discussed.

The ictal bradycardia syndrome.

The ictal bradycardia syndrome is an uncommon diagnosis in which bradycardia is accompanied by simultaneous epileptic discharges in the EEG. We describe a patient who was referred to the emergency ward because of syncope. Ictal semeiology and EEG-EG findings are discussed and compared with those published in the literature. Therapeutic options are discussed in relation with those published in the literature. The ictal bradycardia syndrome is probably underdiagnosed, while its recognition is of utmost importance because of potential life threatening complications such as asystole. Up to now, its aetiology is poorly understood, its ictal semeiology is often described insufficiently and its therapy is still discussed.

Sudden unexpected death in epilepsy patients: Risk factors. A systematic review.

INTRODUCTION: Several risk factors for sudden unexplained death in epilepsy patients (SUDEP) have been proposed, but subsequent work has yielded conflicting data. The relative importance of various risk factors for SUDEP was never explored. The aim of this study is to review systematically risk factors for SUDEP and also to determine their relevance for SUDEP by calculating relative risk factor ratios. METHODS AND MATERIALS: Authors performed a literature-search on "SUDEP" in Medline, the Cochrane Library and EMBASE. Studies with unknown number of SUDEP cases or with less than five SUDEP cases and reviews were excluded from further analysis. The value of each paper was assessed, based on the quality of the study and the reliability of the diagnosis of SUDEP. This value ranged from 1 (low quality) to 10 (high quality). Papers with a value below 7 were eliminated for further analysis. For each analysed factor, a risk factor ratio was determined, with a higher ratio for a stronger risk factor. RESULTS: A number of strong risk factors for SUDEP: young age, early onset of seizures, the presence of generalized tonic clonic seizures, male sex and being in bed. Weak risk factors for SUDEP: prone position, one or more subtherapeutic bloodlevels, being in the bedroom, a strucural brain lesion and sleeping. CONCLUSIONS: In this study, authors have designed a quality scale to select papers. The relative importance of risk factors for SUDEP is demonstrated.

SUDEP in the Netherlands: a retrospective study in a tertiary referral center.

OBJECTIVE: To evaluate risk factors for sudden and unexpected death in epilepsy (SUDEP) in a high-risk population, i.e. patients treated in a Dutch tertiary referral center for epilepsy. METHODS: All patients who died between January 1999 and April 2004 while under treatment of the epilepsy center were identified. Based on clinical data, deaths were classified as definite, probable, possible or non-SUDEP. Potential risk factors were compared in SUDEP cases and non-SUDEP cases. RESULTS: SUDEP incidence was 1.24 per 1000 patient years. SUDEP patients died at a younger age than patients from the control group of non-SUDEP deaths with epilepsy and had an earlier onset of epilepsy. However, the frequently mentioned factors in previous studies, i.e. male sex, generalized tonic-clonic seizures, high seizure frequency, specific AEDs, polytherapy with several AEDs, mental retardation, psychiatric illness and psychotropic comedication, were not found to be correlated with SUDEP. CONCLUSIONS: Even in this high-risk population of patients with refractory epilepsy, treated in a tertiary referral center, SUDEP is not a frequently occurring phenomenon. Specific risk factors could not be identified within an already high-risk population.

A cross-sectional study of subjective complaints in patients with epilepsy who seem to be well-controlled with anti-epileptic drugs.

OBJECTIVES: Side-effects of anti-epileptic drugs (AEDs) may be overlooked in patients with epilepsy in everyday clinical practice. The aim of this study was to assess the prevalence and severity of subjective complaints in patients who were considered to be well-controlled and to assess whether these complaints are related to medication, personality traits, or other determinants. METHODS: We included patients with epilepsy who were considered to be well-controlled in a cross-sectional study in seven hospitals in the Netherlands. Their medication had not been changed for six months and an apparent reason to change the medication was lacking at the time of enrolment. Subjective complaints were assessed with a 46-item questionnaire. Using multivariable linear regression modeling, we assessed whether patient characteristics, epilepsy characteristics, medication, quality of life (Qolie-10), and personality traits (SCL-90) explained the presence and severity of complaints. RESULTS: Of 173 included patients, 67% reported moderate to severe subjective complaints on the questionnaire. Cognitive complaints were reported most frequently. Multivariate modeling showed that 61% of the variance in reported complaints could be explained by included determinants. The prevalence and severity of complaints was associated with AED polytherapy and higher scores on psycho neuroticism. CONCLUSIONS: Patients who were considered to be well-controlled proved to report an unexpectedly high number of subjective complaints. Both medication and aspects of personality contributed to the level of complaints. Our study illustrates that subjective side-effects are easily overlooked in everyday clinical practice, possibly because in practice a generally phrased question is used to detect side-effects.

[The hot summer of 2003: heat stroke in Maastricht]. / De hete zomer van 2003: hitteberoerte in Maastricht.

Two male patients, 46 and 62 years of age, were brought to the emergency department on a hot summer's day. Both wore excessive clothing. The first patient had a temperature of 43 degrees C and was comatose. Heteroanamnesis indicated that he was suffering from schizophrenia. Although the prognosis seemed to be poor, his condition improved after treatment in intensive care, consisting of cooling and supportive treatment, but the patient had considerable permanent neurological impairment. The second patient had a temperature of 40.3 degrees C, was confused and had an atactic gait. He was cooled immediately and recovered swiftly without complications. Heat stroke is a life-threatening illness, which is defined as a body temperature above 40 degrees C and central nervous-system dysfunction. Heat stroke may be attended by many serious complications, including multi-organ failure and residual brain damage. Prompt recognition and rapid treatment, consisting of adequate cooling, are required.

Psychological characteristics of patients with newly developed psychogenic seizures.

OBJECTIVES: To assess psychopathological symptoms and history of childhood trauma in patients with newly developed psychogenic seizures. METHODS: Using validated scales, 178 patients from the general population diagnosed with newly developed seizures were assessed, at a point in time when the nature of their seizures was yet unknown to either doctors or patients. After standardised neurological examination, 138 patients were diagnosed with non-psychogenic seizures (NPS), while 40 patients were found to have psychogenic seizures (PS). To evaluate possible differences between the genders and the diagnostic groups, univariate analyses of variance were done. RESULTS: PS patients reported significantly more comorbid psychopathological complaints, dissociative experiences, anxiety, and self-reported childhood trauma than NPS patients. In addition, PS patients had lower quality of life ratings than NPS patients. These effects were not modulated by gender. CONCLUSIONS: The results of the present study indicate that patients with newly developed PS constitute a group with complex psychopathological features that warrant early detection and treatment.

Prognostic value of MRI findings in sciatica.

The natural course of sciatica due to disc herniation is generally favourable but individually unpredictable. Some patients recover only after prolonged conservative therapy or surgery. This study aims to ascertain whether magnetic resonance (MR) imaging features can be used to predict outcome of sciatica and help to identify patients unlikely to respond to conservative management. For a transversal diagnostic study 274 primary care patients underwent early MR imaging for leg pain. One hundred and thirty-three patients with sciatica were followed for 3 months, both patients and physicians being unaware of MR imaging findings. At 12 weeks a favourable prognosis was indicated by the following features: annular rupture (P= 0.02) and nerve root compression on MR imaging (P = 0.03). Poor prognosis was indicated by disc herniation in the foramen (P = 0.004). Our findings show that early MR imaging features are related to prognosis. However, the associations are not strong enough to justify routine use of early MR imaging to predict the prognosis of sciatica.

Diagnostic value of history and physical examination in patients suspected of lumbosacral nerve root compression.

OBJECTIVE: To evaluate patient characteristics, symptoms, and examination findings in the clinical diagnosis of lumbosacral nerve root compression causing sciatica. METHODS: The study involved 274 patients with pain radiating into the leg. All had a standardised clinical assessment and magnetic resonance (MR) imaging. The associations between patient characteristics, clinical findings, and lumbosacral nerve root compression on MR imaging were analysed. RESULTS: Nerve root compression was associated with three patient characteristics, three symptoms, and four physical examination findings (paresis, absence of tendon reflexes, a positive straight leg raising test, and increased finger-floor distance). Multivariate analysis, analysing the independent diagnostic value of the tests, showed that nerve root compression was predicted by two patient characteristics, four symptoms, and two signs (increased finger-floor distance and paresis). The straight leg raise test was not predictive. The area under the curve of the receiver-operating characteristic was 0.80 for the history items. It increased to 0.83 when the physical examination items were added. CONCLUSIONS: Various clinical findings were found to be associated with nerve root compression on MR imaging. While this set of findings agrees well with those commonly used in daily practice, the tests tended to have lower sensitivity and specificity than previously reported. Stepwise multivariate analysis showed that most of the diagnostic information revealed by physical examination findings had already been revealed by the history items.

Predicting the outcome of sciatica at short-term follow-up.

BACKGROUND: The prognostic value of the clinical findings elicited in the patient presenting with sciatica is unknown. AIM: To investigate whether history and physical examination findings can predict outcome. DESIGN OF STUDY: Prospective study of prognostic factors. SETTING: A sample of primary care patients with sciatica. METHOD: Short-term favourable outcome was registered as improvement perceived by the patient after two weeks. Long-term failure was defined as eventual surgery or lack of improvement after three months. RESULTS: The signs and symptoms that most consistently predicted an unfavourable outcome were: a disease duration of more than 30 days; increased pain on sitting; and more pain on coughing, sneezing or straining. The straight leg raising test and, to a lesser degree the reversed straight leg raising test, were the most consistent examination findings associated with poor outcome. Chances of short-term improvement were also related to the body weight relative to the length. CONCLUSION: The predictors in this study can indicate the prognosis of patients with sciatica at an early stage. Knowledge of these prognostic factors may help to fine tune treatment decisions and improve patient selection in trials of conservative therapy strategies.

Estimating the costs of epilepsy: an international comparison of epilepsy cost studies.

PURPOSE: To compare systematically the national and per capita estimates of the cost of epilepsy in different countries. METHODS: Studies for this literature review were selected by conducting a Medline literature search from January 1966 to March 2000. Key methodologic, country-related, and monetary issues of the selected epilepsy cost studies were evaluated to compare their direct cost estimates and to explore their distribution. The results of the selected studies were made comparable by converting them with different types of conversion factors and expressing them as a proportion of the national expenditure on health care. RESULTS: Ten epilepsy cost studies were reviewed. The proportion of national health care expenditure on epilepsy shows a range of 0.12-1.12% or 0.12-1.05% depending on the type of conversion factor. The list of cost components included in the estimation of the direct costs of epilepsy differs from study to study. A comprehensive list is associated with a decrease in the contribution of drug and hospital costs to the total direct costs of epilepsy. CONCLUSIONS: This study highlights the importance of studying the economic consequences of epilepsy and of interpreting the results on the international level. The results of epilepsy cost studies can provide insight into the distribution of the costs of epilepsy and the impact of epilepsy on the national expenditure on health care.