The retention of lacosamide in patients with epilepsy and intellectual disability in three specialised institutions.

PURPOSE: We describe the effectiveness of lacosamide as adjunctive therapy in patients with epilepsy and an intellectual disability. This information is relevant, as few data exist pertaining to this population with a high prevalence of (intractable) epilepsy. METHODS: We performed a retrospective study in three specialised institutions. Inclusion criteria were (1) focal onset or symptomatic generalized (2) therapy-resistant epilepsy, (3) intellectual disability and (4) residence in a care-facility for people with intellectual disabilities (PWID). The primary outcome variables were the retention rates of lacosamide, estimated through Kaplan-Meier survival analysis. Secondary outcomes were reported seizure control, side effects and clinical factors influencing discontinuation. RESULTS: One hundred and thirty-two patients were included. The median retention time of lacosamide in our cohort was four years. The estimated one-, two- and three-year retention rates of lacosamide were 64%, 57% and 56% respectively. Severity of intellectual disability and seizure type did not influence whether lacosamide was continued. In 48.5% of patients, a reduction of seizure activity was reported. Side effects were at least part of the reason for discontinuing treatment in 26.5% of all patients. Common side effects were tiredness/somnolence (in 30.3%), aggression/agitation (24.2%), and instable gait (15.2%). Five deaths during follow-up were considered unlikely to be related to the use of lacosamide. One patient died unexpectedly within two months of treatment onset, probably this was a case of SUDEP. CONCLUSION: These retention rates of lacosamide in PWID are similar to rates of previously registered anti-epileptic drugs in PWID. Behavioural side effects were noted in a high proportion compared to the general literature on lacosamide. Other side effects were in line with this literature. Lacosamide seems effective and safe for PWID and refractory epilepsy.

Treatment of epilepsy in daily clinical practice: have outcomes improved over the past 10 years?

In the past decade, many new antiepileptic drugs have become available, but their influence on patient outcomes in daily practice is not well known. In a community-based study, we assessed changes in epilepsy treatment and outcomes over a 10-year period. We compared two cross-sectional community-based samples that were obtained from the same Dutch suburban region in 2000 and 2010 using pharmacy records for recruitment, including 344 and 248 epilepsy patients, respectively. The main outcome was self-reported quality of life (QoL, using the QOLIE-31). Potential predictors of QoL (adverse effects, seizure control, seizure acceptability, demographic, epilepsy- or treatment-related determinants) were assessed by multivariable linear regression. New antiepileptic drugs were used by 9 % of patients in 2000 and 34 % in 2010, P < 0.001. More than 80 % in both samples reported to be treated by a neurologist. We found no significant differences in QOLIE-31 scores (72.57 vs. 72.44), or in the proportion of patients with complete seizure control (51 vs. 54 %), between the two study samples. Seizure control and adverse effects were important independent predictors of quality of life, explaining 58 % of the variance. We found no evidence that in this community the QoL of epilepsy patients has improved in the last decade, despite unrestricted availability of healthcare resources, including accessibility to new AEDs. The relatively low proportion with complete seizure control and the high rate of adverse effects in these community-based samples suggest that the effectiveness of epilepsy treatment is still far from optimal.

Headache and epilepsy.

Headache and epilepsy often co-occur. Epidemiologic studies conducted in the past few years reinforce the notion of a bi-directional association between migraine and epilepsy. Data on an association between headache (in general) and epilepsy, however, are less clear. Peri-ictal headache often presents with migraine-like symptoms and can be severe. A correct diagnosis and management are paramount. It was demonstrated that cortical hyperexcitability may underlie both epilepsy and migraine. A recent study linked spreading depolarisation, the supposed underlying pathophysiological mechanism of migraine with aura, to epilepsy. Although this study was carried out in patients who had suffered a subarachnoid haemorrhage, the finding may shed light on pathophysiological mechanisms common to epilepsy and migraine.

[Bad aftertaste caused by pine nuts]. / Een vieze smaak in de mond door pijnboompitten.

BACKGROUND: Dysgeusia caused by the consumption of pine nuts is not widely reported in the medical literature, although much is written about this condition on the Internet. CASE DESCRIPTION: We present the case of a 46-year-old male who complained of metallic and bitter dysgeusia that started 2 days after the ingestion of approximately 70 grams of pine nuts. A literature search revealed only 3 case reports on this subject. In all cases including ours, the complaints began a few days after the ingestion of pine nuts and had spontaneously resolved after a week. No medical sequelae are known, but patients may suffer social consequences. CONCLUSION: The cause of this condition is unknown. Possible causes include the presence of toxic or inedible components in the pine nuts. Physicians should be aware of this phenomenon in order to be able to reassure patients about this benign disorder.

[Epilepsy from seizure to care]. / Epilepsie van aanval tot zorg.

Epilepsy is very common. The prevalence in the Netherlands is 5:1000 inhabitants. The diagnosis is mostly made on clinical grounds and often incorrectly. If there are doubts about the diagnosis, the patient can be referred to a specialised centre for a seizure registration with an EEG and video recording. The disorder generally responds well to treatment with anti-epileptics. Some 60-70% of patients treated with these remain free of seizures. If medicinal treatment fails then a surgical intervention can be considered. For patients with temporal epilepsy in particular, there is quite a high chance that a surgical intervention will resolve the symptoms. Where it proves difficult to satisfactorily adjust the medication of a patient, stimulation of the left vagus nerve can be considered. Paying more attention to the side effects of the medication and the limitations imposed on the patients can reduce the negative influence of epilepsy on the quality of life.

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.

Retention of new AEDs in institutionalized intellectually disabled patients with epilepsy.

PURPOSE: To assess the long-term usefulness of 'new anti-epileptic drugs (AEDs)' (lamotrigine, topiramate, levetiracetam, gabapentin and pregabalin) in institutionalized intellectually disabled patients. Information from RCTs is lacking in this population with severe intellectual and behavioural disabilities. METHODS: Retrospective study. Data from the medical files and the pharmacy databases of 118 institutionalized intellectually disabled patients who had ever used at least one of the new AEDs were analyzed. The main evaluation parameters were the duration of use (using Kaplan-Meier survival estimates) and the reason for discontinuation (lack of efficacy, occurrence of adverse events, or both) of the new AEDs. Drug continuation was based on the evaluation of treatment results by experienced epileptologists, and not on fixed criteria. RESULTS: New AEDs were generally tried only after a substantial number of other regimens (with classic AEDs) had failed. The most frequently used new AEDs were lamotrigine (68%) and levetiracetam (58%), followed by topiramate (28%) and gabapentin (8%). The 3-year retention rates were 70% (lamotrigine), 52% (levetiracetam), 51% (topiramate) and 33% (gabapentin). Discontinuation due to "lack of efficacy" occurred in 61% (topiramate), 60% (lamotrigine) and 42% (levetiracetam) of the cases. Discontinuation due to adverse events occurred in 42% (levetiracetam), 33% (topiramate) and 28% (lamotrigine). CONCLUSIONS: Treatment of epilepsy with new AEDs was quite often successful in this very therapy-resistant 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.

Complaints associated with the use of antiepileptic drugs: results from a community-based study.

BACKGROUND: Few data exist with respect to the occurrence of chronic side effects due to antiepileptic drugs (AED) in routine clinical practice. OBJECTIVE: To evaluate the prevalence of subjective complaints which patients with epilepsy regard as side effects of their AED treatment in a community-based population. METHODS: Cross-sectional study. Subjects were identified through the database of AED-use in the pharmacies in a suburban area in The Netherlands. Respondents completed a brief questionnaire about their epilepsy, including a checklist with 30 complaints, which are common in AED users. RESULTS: We present data of 346 responding adults with treated epilepsy from a population of 107,000 adult inhabitants. Eighty percent was using monotherapy, with few patients taking new AEDs. Almost 60% of the patients reported complaints probably due to side effects in at least three domains. General CNS-related side effects were reported most often; memory problems (21.4% of the patients) and fatigue (20.3%) were dominant. Polytherapy was associated with more side effects than monotherapy. We identified differences in profiles of complaints between valproate, carbamazepine and phenytoin monotherapy. Complaints were not substantially associated with ongoing seizures or other treatment factors. CONCLUSIONS: The majority of patients taking AEDs for epilepsy think they have side effects form their drugs, even when seizures were in remission and when monotherapy was used. Our findings suggest a need to improve monitoring of complaints of side effects of AEDs and to explore the feasibility of interventions aimed at reduction of such complaints in everyday clinical practice.

[Antiepileptic primidone shortly to be withdrawn from sale: change medication now]. / Anti-epilepticum primidon binnenkort uit de handel: nu medicatie herzien.

The antiepileptic drug primidone is to be withdrawn from sale by January 2004. After this date, the drug will still be available for a time, but only on a limited basis. Most primidone users are elderly patients who have been prescribed this drug for many years. Changing to a new drug constitutes a health risk for them. If primidone treatment is discontinued too quickly, withdrawal seizures may appear, some of which may be severe. In patients who have not suffered an epileptic seizure for many years, discontinuing medication may be considered. Whenever continuation of anticonvulsive treatment is desirable, it may probably be a good idea to switch over to some newer antiepileptic drug. If a simple and quick substitution is essential, primidone may be replaced by its main metabolite: phenobarbital. General practitioners and neurologists are strongly advised to alter patients' medication in good time.

Placebo adverse events in headache trials: headache as an adverse event of placebo.

We analysed the adverse events of placebo in acute and preventive randomized, double-blind, placebo-controlled studies for migraine treatment. Fifty-seven trials (oral triptans, non-steroidal anti-inflammatory drugs, nasal ergot alkaloids and preventive agents) were included. From 10 to 30% of subjects reported adverse events after placebo. Most common were features associated with a migraine attack, such as nausea, phono- and photophobia. Other frequent complaints resembled those of the active drug (e.g. chest pressure in triptan trials). A third group of adverse events appeared to be coincidental (e.g. sleep disturbance). Adverse events following placebo are probably related to the drug under study and the symptomatology of migraine; some have no obvious explanation.

Efficacy of sumatriptan nasal spray in recurrent migrainous headache: an open prospective study.

OBJECTIVE: To evaluate the effectiveness of sumatriptan 20 mg via nasal spray and 100-mg tablets in treating migrainous headache in patients without a concomitant migraine diagnosis. METHODS: We prospectively investigated the efficacy of sumatriptan 20 mg via nasal spray and 100-mg tablets in patients with a history of at least 5 moderate to severe headache attacks lasting 2 to 72 hours that consistently did not meet the International Headache Society (IHS) criteria for migraine or episodic tension-type headache. RESULTS: Nineteen headache attacks classifiable as migrainous disorder without aura (IHS 1.7) were evaluated in 13 patients using 20-mg sumatriptan nasal spray within a 10-week period. A 2-point decrease in headache severity on a four-point scale was achieved in 74% (95% confidence interval [CI], 50% to 89%) of the attacks within 2 hours. The pain-free incidence (a reduction in headache severity from moderate or severe to none) was 37% (95% CI, 17% to 63%) after 2 hours. Ten patients completed the second part of the study, taking oral sumatriptan for 14 migrainous attacks: a 2-point decrease in headache severity was achieved in 38% (95% CI, 13% to 71%) of the attacks within 2 hours and in 77% (95% CI, 48% to 92%) within 4 hours. CONCLUSION: This is the first prospective study to show that intranasal or oral sumatriptan may be effective in patients experiencing moderate to severe headache attacks which consistently do not fulfill the IHS criteria for migraine or episodic tension-type headache.

Coactivation of the ulnar nerve in motor tests for carpal tunnel syndrome.

Coactivation of the ulnar nerve at the wrist can be a source of error in tests for carpal tunnel syndrome (CTS). We compared the effects of coactivation in two tests for CTS: the abductor pollicis brevis-distal motor latency (APB-DML) and lumbrical-interosseus-distal motor latency difference (2LI-DML). We studied 33 hands of 25 consecutive patients referred for suspected CTS. In severe CTS, when selective supramaximal stimulation of the median nerve was impossible, all APB-compound muscle action potentials (CMAP) showed abnormalities, indicating volume conduction of ulnar muscle activation. 2LI-DML in these hands led to falsely normal test results, as two identical CMAP were obtained after median and ulnar stimulation. In less severe CTS, warning signs indicating coactivation were observed in APB-DML virtually as often as in 2LI-DML. Undetected coactivation was more likely to be associated with false normal test results in 2LI-DML than in APB-DML.

The diagnostic yield of a second EEG after partial sleep deprivation: a prospective study in children with newly diagnosed seizures.

PURPOSE: To assess the diagnostic yield of a repeated EEG (REPEEG) after partial sleep deprivation (SD) in children and adolescents with one or more seizures who previously had had a standard EEG (STDEEG) without epileptiform abnormalities (EAs). In the literature, 32-75% of such REPEEGs after SD were reported to show EA. METHODS: In a prospective, multicentred study, we selected children aged 1 month to 16 years with one or more idiopathic or remote symptomatic newly diagnosed seizures. A REPEEG was recorded in children without EAs in their STDEEG. RESULTS: Of 552 children and adolescents who entered the study, 243 (44%) had a STDEEG without EAs. In 177 (73% of eligible children), REPEEGs were recorded after SD. We found EAs in 61 (34.5%) REPEEGs and new nonepileptiform abnormalities in five (1%). In 552 children in the total cohort, the REPEEG thus added 11% with EAs to the 56% with EAs in the STDEEG. Of REPEEGs, 81% included sleep compared with 20% of STDEEGs. In about half the REPEEGs, EAs occurred during sleep only. One child had tonic-clonic seizures probably related to the SD. CONCLUSIONS: One third of REPEEGs yielded new diagnostic information. Partial, age-dependent SD was highly effective in inducing sleep, which is important because in many cases EAs were found only during EEG recording in sleep. The procedure was safe and convenient.

Seizure severity in children with epilepsy: a parent-completed scale compared with clinical data.

PURPOSE: We wished to compare a parent-completed scale quantifying seizure severity (SS) in children with various seizure types with the clinicians' impression of SS and other clinical data. METHODS: The parents of 117 children with recurrent seizures completed a 13-item, subjective scale (The Hague Seizure Severity Scale, HASS). Eight treating neurologists quantified SS on a 10-point Visual Analog Scale (VAS) and supplied other clinical data. RESULTS: Both the HASS and the VAS assessments of SS showed considerable variation within one seizure type. Significant differences were noted between groups with (a) absences and simple partial seizures (SPS), (b) complex partial seizures (CPS), and (c) generalized tonic-clonic seizures (GTCS). The correlation coefficient between the neurologists' and the parents' scores was 0.45 but did not exceed 0.26 after stratification for seizure type. The parents' score was not substantially influenced by various other clinical variables. The neurologists' score was correlated with resistance to treatment and presence of mental retardation. CONCLUSIONS: The SS ratings of the parents and the neurologists were not substantially correlated. The consideration that parents, as eyewitnesses to the seizures, are probably better judges of SS than clinicians may favor the use of a parent-completed scale to quantify SS. The HASS is a valid and reliable measure of parent-perceived SS that can be useful as an outcome measure in childhood epilepsy.