Psychosocial functioning of adult siblings of Dutch very long-term survivors of childhood cancer: DCCSS-LATER 2 psycho-oncology study.

OBJECTIVE: To describe psychosocial outcomes among adult siblings of very long-term childhood cancer survivors (CCS), to compare these outcomes to reference populations and to identify factors associated with siblings' psychosocial outcomes. METHODS: Siblings of survivors (diagnosed <18 years old, between 1963 and 2001, >5 years since diagnosis) of the Dutch Childhood Cancer Survivor Study DCCSS-LATER cohort were invited to complete questionnaires on HRQoL (TNO-AZL Questionnaire for Adult's HRQoL), anxiety/depression (Hospital Anxiety and Depression Scale), post-traumatic stress (Self-Rating Scale for Post-traumatic Stress Disorder), self-esteem (Rosenberg Self-Esteem Scale) and benefit and burden (Benefit and Burden Scale for Children). Outcomes were compared to a reference group if available, using Mann-Whitney U and chi-Square tests. Associations of siblings' sociodemographic and CCS' cancer-related characteristics with the outcomes were assessed with mixed model analysis. RESULTS: Five hundred five siblings (response rate 34%, 64% female, mean age 37.5, mean time since diagnosis 29.5) of 412 CCS participated. Siblings had comparable HRQoL, anxiety and self-esteem to references with no or small differences (r = 0.08-0.15, p < 0.05) and less depression. Proportions of symptomatic PTSD were very small (0.4%-0.6%). Effect sizes of associations of siblings' sociodemographic and CCS cancer-related characteristics were mostly small to medium (ß = 0.19-0.67, p < 0.05) and no clear trend was found in the studied associated factors for worse outcomes. CONCLUSIONS: On the very long-term, siblings do not have impaired psychosocial functioning compared to references. Cancer-related factors seem not to impact siblings' psychosocial functioning. Early support and education remain essential to prevent long-term consequences.

T-type Ca2+ and persistent Na+ currents synergistically elevate ventral, not dorsal, entorhinal cortical stellate cell excitability.

Dorsal and ventral medial entorhinal cortex (mEC) regions have distinct neural network firing patterns to differentially support functions such as spatial memory. Accordingly, mEC layer II dorsal stellate neurons are less excitable than ventral neurons. This is partly because the densities of inhibitory conductances are higher in dorsal than ventral neurons. Here, we report that T-type Ca2+ currents increase 3-fold along the dorsal-ventral axis in mEC layer II stellate neurons, with twice as much CaV3.2 mRNA in ventral mEC compared with dorsal mEC. Long depolarizing stimuli trigger T-type Ca2+ currents, which interact with persistent Na+ currents to elevate the membrane voltage and spike firing in ventral, not dorsal, neurons. T-type Ca2+ currents themselves prolong excitatory postsynaptic potentials (EPSPs) to enhance their summation and spike coupling in ventral neurons only. These findings indicate that T-type Ca2+ currents critically influence the dorsal-ventral mEC stellate neuron excitability gradient and, thereby, mEC dorsal-ventral circuit activity.

Psychosocial functioning of parents of Dutch long-term survivors of childhood cancer.

OBJECTIVE: To describe health-related quality of life (HRQoL), post-traumatic stress and post-traumatic growth of parents of long-term survivors of childhood cancer (CCS) and study associated factors. METHODS: Parents of survivors of the Dutch Childhood Cancer Survivor Study LATER cohort below 30 years and diagnosed 1986-2001 were invited to complete the TNO-AZL Questionnaire for Adult's HRQoL (e.g., sleep and aggressive emotions), Self-Rating Scale for Post-traumatic Stress Disorder, Post-traumatic Growth Inventory, and Illness Cognition Questionnaire. HRQoL domain scores were compared to references using Mann-Whitney U tests. Correlations between post-traumatic stress, growth and HRQoL were evaluated. Medical characteristics of their child and illness cognitions were studied as associated factors of HRQOL, post-traumatic stress and growth. p < 0.05 was considered statistically significant. RESULTS: Parents (n = 661 of n = 448 survivors, 56% female, mean time since child's diagnosis: 21.3 [SD: 3.3] years) reported better HRQoL in social functioning and aggressive emotions than references (r = .08-0.17). Mothers additionally reported better HRQoL in pain, daily activities, sexuality, vitality, positive and depressive emotions (r = .07-0.14). Post-traumatic stress was symptomatic in 3%, and associated with worse HRQoL (r = -0.27-0.48). Post-traumatic growth was positively associated to post-traumatic stress and better HRQoL (r = 0.09-0.12). Cancer recurrence was associated to better HRQoL (ß = 0.37-0.46). Acceptance illness cognitions were associated to better (ß = 0.12-0.25), and helplessness to worse outcomes (ß = 0.14-0.38). CONCLUSIONS: HRQoL of parents of young adult survivors of CCS is comparable to references or slightly better. Only a small proportion reports symptomatic post-traumatic stress. Improving acceptance and reducing feelings of helplessness may provide treatment targets for parents with psychosocial problems.

Pore structure evolution in andesite rocks induced by freeze-thaw cycles examined by non-destructive methods.

In this paper, we compare the values of petrophysical properties before and after 100 freeze-thaw (F-T) cycles, as well as recorded length change behaviour and temperature development on a vacuum-saturated fractured andesite rock sample taken from the Babina Quarry in Slovakia using a specially-constructed thermodilatometer, VLAP 04, equipped with two HIRT-LVDT sensors. We also used non-destructive visualization of the rock pore network by µCT imaging in order to study the development of the pore structure and fracture network in pyroxene andesites during the freeze-thaw process. The results show that the andesite rock samples, due to good fabric cohesion, low porosity, and low pore interconnection, showed good resistance against frost-induced damage. However, it must be stated that the main process causing disintegration of this type of rock is fracture opening, which is caused by internal stresses induced by water-ice phase transition. The overall residual strain recorded after 100 F-T cycles was not significant, however, the increase of 31 pp in volume of the fracture showed us that repeated freezing and thawing can lead to long term deterioration in terms of subcritical crack growth in brittle-elastic solids like pyroxene-andesite rocks.

[Simultaneous Bilateral Femoral Osteotomies in Neurogenic Hip Instability: a Feasibility Study]. / Simultánní oboustranné femorální osteotomie u neurogenních kycelních instabilit: studie proveditelnosti.

PURPOSE OF THE STUDY The study aimed to evaluate the intraoperative and early postoperative response to simultaneous bilateral femoral osteotomy usually accompanied by soft tissue release of hip joints, or open reduction, capsuloplasty, pelvic osteotomy or extraarticular shelf procedure. MATERIAL AND METHODS A bilateral surgery was performed in 16 children. Twelve children suffered from (spastic) cerebral palsy and there was one case of paralytic dislocation in a patient with myelomeningocele, while the remaining patients suffered from chromosome I aberrations, Dandy-Walker syndrome and merosin-deficient muscular dystrophy. GMFCS Level IV and V prevailed. The patients with femoral head deformity or severe adduction contracture were removed from the study group. In all cases the LCP Pediatric Hip Plate 3.5 or 5.0 (Synthes) was used for osteosynthesis. The postoperative fixation by a hip spica cast was applied for 6 weeks, after which in most cases SWASH orthosis was used at night. The age of the patient, the hip joint finding, the GMFCS level and the type of procedure were recorded. RESULTS The evaluation took into account the use of general anaesthesia only or a combination of general and epidural anaesthesia, most often through caudal block, duration of surgery, time when blood transfusion was necessary and the volumes of blood needed, duration of stay in the Anaesthesiology and Resuscitation Unit, or Intensive Care Unit. As a response to surgery, the changes in haemoglobin levels in g/l and VAS pain score were studied. In four patients only the operative time exceeded 3 hours. Blood transfusion was necessary in 13 patients, with one blood unit being always sufficient. Two patients were admitted to the Anaesthesiology and Resuscitation Unit, the remaining patients spent 1-3 days after surgery in the ICU. The average length of hospital stay did not exceed a week. The postoperative decrease in haemoglobin levels quickly improved. The pain intensity was regularly recorded postoperatively and on day 3-4 it was evaluated as moderate, with patients responding well to common analgesics (VAS 4-7). DISCUSSION The evaluation of duration of simultaneous bilateral procedure, postoperative recovery based on the need for blood transfusion, changes in blood count and VAS scores indicated that the procedure performed on both hip joints simultaneously does not significantly exceed the reasonable limits in terms of the patient s burden. In literature, we found only a single article on a topic of this sort, the conclusions of which are very similar. CONCLUSIONS The simultaneous bilateral femoral osteotomy can be considered a fairly safe procedure. Key words: hip joint instability, simultaneous femoral osteotomy, cerebral palsy.

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels as Drug Targets for Neurological Disorders.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are voltage-gated ion channels that critically modulate neuronal activity. Four HCN subunits (HCN1-4) have been cloned, each having a unique expression profile and distinctive effects on neuronal excitability within the brain. Consistent with this, the expression and function of these subunits are altered in diverse ways in neurological disorders. Here, we review current knowledge on the structure and distribution of the individual HCN channel isoforms, their effects on neuronal activity under physiological conditions, and how their expression and function are altered in neurological disorders, particularly epilepsy, neuropathic pain, and affective disorders. We discuss the suitability of HCN channels as therapeutic targets and how drugs might be strategically designed to specifically act on particular isoforms. We conclude that medicines that target individual HCN isoforms and/or their auxiliary subunit, TRIP8b, may provide valuable means of treating distinct neurological conditions.

Psychometric Properties of the Pediatric Patient-Reported Outcomes Measurement Information System Item Banks in a Dutch Clinical Sample of Children With Juvenile Idiopathic Arthritis.

OBJECTIVE: To assess the psychometric properties of 8 pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) item banks in a clinical sample of children with juvenile idiopathic arthritis (JIA). METHODS: A total of 154 Dutch children (mean ± SD age 14.4 ± 3.0 years; range 8-18 years) with JIA completed 8 pediatric version 1.0 PROMIS item banks (anger, anxiety, depressive symptoms, fatigue, pain interference, peer relationships, physical function mobility, physical function upper extremity) twice and the Pediatric Quality of Life Inventory (PedsQL) and the Childhood Health Assessment Questionnaire (C-HAQ) once. Structural validity of the item banks was assessed by fitting a graded response model (GRM) and inspecting GRM fit (comparative fit index [CFI], Tucker-Lewis index [TLI], and root mean square error of approximation [RMSEA]) and item fit (S-X2 statistic). Convergent validity (with PedsQL/C-HAQ subdomains) and discriminative validity (active/inactive disease) were assessed. Reliability of the item banks, short forms, and computerized adaptive testing (CAT) was expressed as the SE of theta (SE[θ]). Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) and smallest detectable change. RESULTS: All item banks had sufficient overall GRM fit (CFI >0.95, TLI >0.95, RMSEA <0.08) and no item misfit (all S-X2 P > 0.001). High correlations (>0.70) were found between most PROMIS T scores and hypothesized PedsQL/C-HAQ (sub)domains. Mobility, pain interference, and upper extremity item banks were able to discriminate between patients with active and inactive disease. Regarding reliability, PROMIS item banks outperformed legacy instruments. Post hoc CAT simulations outperformed short forms. Test-retest reliability was strong (ICC >0.70) for all full-length item banks and short forms, except for the peer relationships item bank. CONCLUSION: The pediatric PROMIS item banks displayed sufficient psychometric properties for Dutch children with JIA. PROMIS item banks are ready for use in clinical research and practice for children with JIA.

Digital Breast Tomosynthesis as a Tool in Confirming Negative Surgical Margins in Non-palpable Breast Lesions.

Breast cancer is one of the leading killers among women the world over. Widespread mammographic screening programs have led to almost 20% of breast cancers being detected when they are radiologically visible but clinically impalpable. For the localization of these cancers before surgical excision, the Kopan hook wire is the standard technique, but the extent of margins excised still needs to be determined. In this study, we have evaluated the accuracy of specimen mammogram (SM) with digital breast tomosynthesis (DBT) for margin assessment by comparing it to the excised margins as measured in final histopathology. This is a prospective observational study of patients with radiologically suspicious impalpable breast lesions. The patients underwent ultrasound-guided hook wire placement followed by excision of the lesion, subjected to digital tomosynthesis mammogram, and margins were revised on table when indicated. These findings were correlated with final histopathological margin. Our study included 30 patients and out of the 6 lesions, which showed positive margins on specimen mammography, 4 were histologically confirmed to have tumour at the surgical margin and 2 were confirmed to be tumour free. All DBT-positive margins were re-excised at the time of primary surgery. Individual comparison of the margins revealed a good agreement and high level of correlation between DBT and histopathology margins. None of the cases required a second surgery for margin revision. It can be concluded that specimen mammogram with DBT can be used as a reliable tool for intraoperative surgical margin assessment in non-palpable breast lesions to reduce rate of margin revision as well as reduce the volume of breast excised without compromising the oncological safety of the procedure.

Clostridium difficile infection and colonisation in children under 3 years of age: prospective comparative study.

AIMS: Despite an increasing trend in Clostridium difficile infections (CDI) and high C. difficile colonization rate especially among younger children, infants remain quite resistant to the disease. The goals of this study were to distinguish whether there exists a difference in CDI between children with or without diarrhoea, ascertain the prevalence of CDI, and assess CDI severity in children under 3 years with diarrhoea in our institution. METHODS: A prospective study was conducted from May 2015 to June 2016. Children 3 years of age or younger were enrolled and into two groups. Every faecal sample was tested using a diagnostic two-step screening algorithm including an immunochromatographic test and polymerase chain reaction. RESULTS: The study enrolled 147 children with diarrhoea and 75 control patients. The prevalence of CDI in children with diarrhoea was 2% (3/147), the prevalence of toxigenic C. difficile in the diarrhoeal group compared to the control group was 11.6 % (17/147) vs. 10.6% (8/75) (p.

Clinical and microbiological characteristics of Clostridium difficile infection in children hospitalized at the Departement of Paediatric Infectious Diseases in Brno between 2013 and 2017.

AIMS: Clostridium difficile (C. difficile) plays a minor but important role in paediatrics. The aims of this study were to objectivise data, to show their significance in clinical practice, and to present our experience with the treatment of paediatric patients. MATERIALS AND METHODS: A retrospective study was conducted in patients (0-19 years of age) hospitalized for Clostridium difficile infection (CDI) in the Department of Paediatric Infectious Diseases, University Hospital in Brno between 2013 and 2017. Each patient was tested using a two-step diagnostic screening algorithm including immunochromatography and polymerase chain reaction assays. RESULTS: Thirty-five patients with a median age of 10.3 years (range 1-17.5 years) were enrolled in the study. Almost 70% of patients were aged between 6 and 19 years. No risk factor was identified in one patient, 41.6% of cases were patients with malignancy or inflammatory bowel disease, and 2.5% of patients had short bowel syndrome. After targeted CDI treatment, the median time to resolution of diarrhoea was 2.5 days. Metronidazole was used in more than half of cases. Five patients received fidaxomicin, which was well tolerated. Metronidazole failed in three cases. Recurrence after incomplete treatment with metronidazole occurred in one patient. Health care-associated CDI was recorded in 86% of cases. Recurrent CDI was reported in four children (two with malignancy, one with inflammatory bowel dissease, and one with short bowel syndrome). CONCLUSIONS: The course of CDI is generally mild in the paediatric population. CDI without a risk factor is rare. Paediatric patients respond well to metronidazole. Fidaxomicin was well tolerated by all patients. We prefer the treatment with fidaxomicin in high-risk groups (immunocompromised condition, inflammatory bowel disease, and short bowel syndrome).

The subthreshold-active KV7 current regulates neurotransmission by limiting spike-induced Ca2+ influx in hippocampal mossy fiber synaptic terminals.

Little is known about the properties and function of ion channels that affect synaptic terminal-resting properties. One particular subthreshold-active ion channel, the Kv7 potassium channel, is highly localized to axons, but its role in regulating synaptic terminal intrinsic excitability and release is largely unexplored. Using electrophysiological recordings together with computational modeling, we found that the KV7 current was active at rest in adult hippocampal mossy fiber synaptic terminals and enhanced their membrane conductance. The current also restrained action potential-induced Ca2+ influx via N- and P/Q-type Ca2+ channels in boutons. This was associated with a substantial reduction in the spike half-width and afterdepolarization following presynaptic spikes. Further, by constraining spike-induced Ca2+ influx, the presynaptic KV7 current decreased neurotransmission onto CA3 pyramidal neurons and short-term synaptic plasticity at the mossy fiber-CA3 synapse. This is a distinctive mechanism by which KV7 channels influence hippocampal neuronal excitability and synaptic plasticity.

HCN1 channels reduce the rate of exocytosis from a subset of cortical synaptic terminals.

The hyperpolarization-activated cyclic nucleotide-gated (HCN1) channels are predominantly located in pyramidal cell dendrites within the cortex. Recent evidence suggests these channels also exist pre-synaptically in a subset of synaptic terminals within the mature entorhinal cortex (EC). Inhibition of pre-synaptic HCN channels enhances miniature excitatory post-synaptic currents (mEPSCs) onto EC layer III pyramidal neurons, suggesting that these channels decrease the release of the neurotransmitter, glutamate. Thus, do pre-synaptic HCN channels alter the rate of synaptic vesicle exocytosis and thereby enhance neurotransmitter release? To address this, we imaged the release of FM1-43, a dye that is incorporated into synaptic vesicles, from EC synaptic terminals using two photon microscopy in slices obtained from forebrain specific HCN1 deficient mice, global HCN1 knockouts and their wildtype littermates. This coupled with electrophysiology and pharmacology showed that HCN1 channels restrict the rate of exocytosis from a subset of cortical synaptic terminals within the EC and in this way, constrain non-action potential-dependent and action potential-dependent spontaneous release as well as synchronous, evoked release. Since HCN1 channels also affect post-synaptic potential kinetics and integration, our results indicate that there are diverse ways by which HCN1 channels influence synaptic strength and plasticity.

Recording Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Currents (Ih) in Neurons.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are voltage-gated ion channels that play a crucial role in many physiological processes such as memory formation and spatial navigation. Alterations in expression and function of HCN channels have also been associated with multiple disorders including epilepsy, neuropathic pain, and anxiety/depression. Interestingly, neuronal HCN currents (Ih) have diverse biophysical properties in different neurons. This is likely to be in part caused by the heterogeneity of the HCN subunits expressed in neurons. This variation in biophysical characteristics is likely to influence how Ih affects neuronal activity. Thus, it is important to record Ih directly from individual neurons. This protocol describes voltage-clamp methods that can be used to record neuronal Ih under whole-cell voltage-clamp conditions, in cell-attached mode, or with outside-out patches. The information obtained using this approach can be used in combination with other techniques such as computational modeling to determine the significance of Ih for neuronal function.

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Currents in Neurons.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are voltage-gated ion channels that activate at potentials more negative than -50 mV and are predominantly permeable to Na(+) and K(+) ions. Four HCN subunits (HCN1-4) have been cloned. These subunits have distinct expression patterns and biophysical properties. In addition, cyclic nucleotides as well as multiple intracellular substances including various kinases and phosphatases modulate the expression and function of the subunits. Hence, the characteristics of the current, Ih, are likely to vary among neuronal subtypes. In many neuronal subtypes, Ih is present postsynaptically, where it plays a critical role in setting the resting membrane potential and the membrane resistance. By influencing these intrinsic properties, Ih will affect synaptic potential shapes and summation and thereby affect neuronal excitability. Additionally, Ih can have an effect on resonance properties and intrinsic neuronal oscillations. In some neurons, Ih may also be present presynaptically in axons and synaptic terminals, where it modulates neuronal transmitter release. Hence the effects of Ih on neuronal excitability are complex. It is, however, necessary to fully understand these as Ih has a significant impact on physiological conditions such as learning as well as pathophysiological states such as epilepsy.

Cholinergic afferent stimulation induces axonal function plasticity in adult hippocampal granule cells.

Acetylcholine critically influences hippocampal-dependent learning. Cholinergic fibers innervate hippocampal neuron axons, dendrites, and somata. The effects of acetylcholine on axonal information processing, though, remain unknown. By stimulating cholinergic fibers and making electrophysiological recordings from hippocampal dentate gyrus granule cells, we show that synaptically released acetylcholine preferentially lowered the action potential threshold, enhancing intrinsic excitability and synaptic potential-spike coupling. These effects persisted for at least 30 min after the stimulation paradigm and were due to muscarinic receptor activation. This caused sustained elevation of axonal intracellular Ca(2+) via T-type Ca(2+) channels, as indicated by two-photon imaging. The enhanced Ca(2+) levels inhibited an axonal KV7/M current, decreasing the spike threshold. In support, immunohistochemistry revealed muscarinic M1 receptor, CaV3.2, and KV7.2/7.3 subunit localization in granule cell axons. Since alterations in axonal signaling affect neuronal firing patterns and neurotransmitter release, this is an unreported cellular mechanism by which acetylcholine might, at least partly, enhance cognitive processing.

Cortical HCN channels: function, trafficking and plasticity.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated potassium ion channels. They are, however, activated by hyperpolarizing potentials and are permeable to cations. Four HCN subunits have been cloned, of which HCN1 and HCN2 subunits are predominantly expressed in the cortex. These subunits are principally located in pyramidal cell dendrites, although they are also found at lower concentrations in the somata of pyramidal neurons as well as other neuron subtypes. HCN channels are actively trafficked to dendrites by binding to the chaperone protein TRIP8b. Somato-dendritic HCN channels in pyramidal neurons modulate spike firing and synaptic potential integration by influencing the membrane resistance and resting membrane potential. Intriguingly, HCN channels are present in certain cortical axons and synaptic terminals too. Here, they regulate synaptic transmission but the underlying mechanisms appear to vary considerably amongst different synaptic terminals. In conclusion, HCN channels are expressed in multiple neuronal subcellular compartments in the cortex, where they have a diverse and complex effect on neuronal excitability.

Recording dendritic ion channel properties and function from cortical neurons.

Dendrites emerging from the cell bodies of neurons receive the majority of synaptic inputs. They possess a plethora of ion channels that are essential for the processing of these synaptic signals. To fully understand how dendritic ion channels influence neuronal information processing, various patch-clamp techniques that allow electrophysiological recordings to be made directly from dendrites have been developed. In this chapter, I describe one such method that is suitable for making electrophysiological recordings from the apical dendrites of hippocampal and cortical pyramidal neurons.

The LIM homeodomain protein Lhx6 regulates maturation of interneurons and network excitability in the mammalian cortex.

Deletion of LIM homeodomain transcription factor-encoding Lhx6 gene in mice results in defective tangential migration of cortical interneurons and failure of differentiation of the somatostatin (Sst)- and parvalbumin (Pva)-expressing subtypes. Here, we characterize a novel hypomorphic allele of Lhx6 and demonstrate that reduced activity of this locus leads to widespread differentiation defects in Sst(+) interneurons, but relatively minor and localized changes in Pva(+) interneurons. The reduction in the number of Sst-expressing cells was not associated with a loss of interneurons, because the migration and number of Lhx6-expressing interneurons and expression of characteristic molecular markers, such as calretinin or Neuropeptide Y, were not affected in Lhx6 hypomorphic mice. Consistent with a selective deficit in the differentiation of Sst(+) interneurons in the CA1 subfield of the hippocampus, we observed reduced expression of metabotropic Glutamate Receptor 1 in the stratum oriens and characteristic changes in dendritic inhibition, but normal inhibitory input onto the somatic compartment of CA1 pyramidal cells. Moreover, Lhx6 hypomorphs show behavioral, histological, and electroencephalographic signs of recurrent seizure activity, starting from early adulthood. These results demonstrate that Lhx6 plays an important role in the maturation of cortical interneurons and the formation of inhibitory circuits in the mammalian cortex.

HCN and KV7 (M-) channels as targets for epilepsy treatment.

Voltage-gated ion channels are important determinants of cellular excitability. The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) and KV7 (M-) channels are voltage-gated ion channels. Both channels are activated at sub-threshold potentials and have biophysical properties that mirror each other. KV7 channels inhibit neuronal excitability. Thus, mutations in KV7 channels that are associated with Benign Familial Neonatal Convulsions (BFNC) are likely to be epileptogenic. Mutations in HCN channels have also been associated with idiopathic epilepsies such as GEFS+. In addition, HCN channel expression and function are modulated during symptomatic epilepsies such as temporal lobe epilepsy. It is, though, unclear as to whether the changes in HCN channel expression and function associated with the various forms of epilepsy promote epileptogenesis or are adaptive. In this review, we discuss this as well as the potential for KV7 and HCN channels as drug targets for the treatment of epilepsy. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.