Sandra J. Petty

Anti-epileptic medication and bone health

BackgroundEpilepsy is a common chronic neurological disorder, usually requiring long-term treatment with anti-epileptic drugs (AED). Many studies have reported that AED therapy is associated with metabolic bone disease and is a major iatrogenic risk factor for fractures. There remains uncertainty about the type(s) of bone disease due to AED treatment, and the pathogenesis of AED-associated fractures.RationaleDeficits in bone mineral density (BMD) are widely reported in AED-treated patient populations. However, much of the research conducted to date has been limited by factors such as small sample size, potentially biased subject selection, a lack of selection of appropriate control data, and failure to take account of important confounding influences. The pathogenesis of AED-associated fractures is likely to be multifactorial, due to factors including reduced BMD, impaired bone quality (due to osteoporosis and/or osteomalacia), increased propensity to fall, and fractures associated with seizures or loss of consciousness.RecommendationsPatients receiving long-term AED should be monitored for indices of bone health, including BMD and vitamin D status. Lifestyle factors should be optimized, vitamin D status maintained, and fall prevention strategies introduced as appropriate. Good seizure control is important. The use of additional, specific osteoporosis therapy is not evidence-based in this setting, but would appear reasonable in patients with clinically significant decreases in BMD, applying current treatment guidelines for osteoporosis.ConclusionThere is a pressing need for improved understanding of the pathogenesis of AED-associated bone disease, for better definition of the risk associated with specific AED regimens, and for the development of evidence-based preventive and treatment approaches in this common but neglected disorder.

Effect of antiepileptic medication on bone mineral measures

Objective: Long-term antiepileptic drug (AED) use has been associated with bone disease, but many previous studies have been limited by inadequate control subjects. We used a cotwin affected sib-pair model to investigate this issue. Methods: The authors studied 31 female twin (15 monozygous and 16 dizygous) and four sibling pairs (<3 years age difference) aged 21 to 75 years, in which one member had >12 months of AED treatment. Areal bone mineral density (ABMD, g/cm2) was measured at the lumbar spine (LS), total hip (TH), femoral neck (FN), and total forearm (FA). Three primary a priori defined subgroups were analyzed: a) use for >2 years, b) use of enzyme-inducing AEDs, or c) age older than 40 years. Results: For all pairs (n = 35), there were no significant within-pair differences in any ABMD measure. However, in Subgroup a (n = 27), there was a within-pair difference at the FA (0.513 vs 0.534, −3.9%, p = 0.016). In Subgroup b (n = 29), there was also a within-pair difference at the FA for AED user vs nonuser (0.508 vs 0.529, −3.8%, p = 0.010). In Subgroup c (n = 15), there were within-pair differences at the FA (0.492 vs 0.524, −6.1%, p = 0.017) and the LS (0.884 vs 0.980, −9.8%, p = 0.036). Conclusions: Patients using AEDs for >2 years, in particular those taking enzyme-inducing AEDs and those older than 40 years, have significantly lower bone mineral density at clinically relevant fracture risk sites.

Balance impairment in chronic antiepileptic drug users: A twin and sibling study

Purpose:  Patients taking antiepileptic drugs (AEDs) have an increased incidence of fractures. This study investigated chronic AED use and physical contributors to falls risk using an AED‐discordant, twin and sibling matched‐pair approach, and assessed clinically relevant subgroups: AED polytherapy; longer‐duration AED; and falls history.

Acute encephalomyelitis syndromes associated with H1N1 09 influenza vaccination

### Case reports. #### Case 1. A previously healthy 38-year-old man presented with acute urinary retention and constipation after 4 days of progressive weakness affecting all 4 limbs and patchy sensory disturbance over the trunk and upper arms. Ten days prior to the onset of symptoms, he had received H1N1 09 influenza (Panvax H1N1, CSL Biotherapies, Parkville, Australia) vaccination and had experienced a spontaneously resolving febrile reaction 24–48 hours following administration. MRI of the brain, cervical, thoracic, and lumbar spine was performed (figure,A). Several areas of central cord T2 signal hyperintensity were demonstrated, extending from C3 to C6 and from T7 to L1, and a diagnosis of longitudinally extensive transverse myelitis was made. Serologic investigations for infective and autoimmune etiologies were unremarkable. CSF demonstrated an inflammatory pattern, with 80 × 106/L lymphocytes and 0.78 g/L total protein. Figure MRI from clinical cases (A) MRI thoracic spine, demonstrating extensive longitudinal intramedullary T2 hyperintensity. (B) MRI cervical spine, demonstrating multilevel cord edema and hyperintensity of proximal thoracic segments. The patient received IV methylprednisolone (1 g/d for 3 days), with resolution in power and sphincter function over the following 10 days. #### Case 2. A previously healthy 19-year-old …

Osteoporosis Associated with Epilepsy and the Use of Anti-Epileptics—a Review

The increased rate of fractures associated with epilepsy has been long recognised but remains incompletely understood. Study quality and study results have varied, with some but not all studies showing bone diseases including osteoporosis and/or osteomalacia, and a high prevalence of vitamin D insufficiency and deficiency are also noted. Falls risk can also be higher in patients with epilepsy taking anti-epileptic medications, potentially leading to fracture. Larger research collaborations are recommended to further advance understanding in this field, particularly to examine underlying genetic and pharmacogenomic associations of epilepsy and anti-epileptic medication usage and its association with bone diseases and fractures, as well as further investigation into optimal management of bone health in epilepsy.

Weight and fat distribution in patients taking valproate: a valproate-discordant gender-matched twin and sibling pair study.

Chronic treatment with valproate (VPA) is commonly associated with weight gain, which potentially has important health implications, in particular increased central fat distribution. We utilized a VPA‐discordant same‐sex, twin and matched sibling pair study design to primarily examine for differences in fat distribution between patients with epilepsy treated with VPA compared to their matched twin or sibling control. Weight, blood pressure, and leptin levels were assessed.

The antiepileptic medications carbamazepine and phenytoin inhibit native sodium currents in murine osteoblasts.

Fracture risk is a serious comorbidity in epilepsy and may relate to the use of antiepileptic drugs (AEDs). Many AEDs inhibit ion channel function, and the expression of these channels in osteoblasts raises the question of whether altered bone signaling increases bone fragility. We aimed to confirm the expression of voltage‐gated sodium (NaV) channels in mouse osteoblasts, and to investigate the action of carbamazepine and phenytoin on NaV channels.

Changes in balance function with chronic antiepileptic drug therapy: a twin and sibling study

To investigate cross‐sectional and longitudinal differences in static and dynamic standing balance measures and lower limb muscle strength in patients who are treated chronically with antiepileptic drugs (AEDs).

Balance and Gait Impairment in Transient Ischemic Attack and Minor Stroke

BACKGROUND There has been little research into gait and balance impairment in transient ischemic attack (TIA) and minor stroke, despite these conditions affecting large numbers of people and the potential impact on function. The aim of this study was to determine the impact of TIA and minor stroke on gait and balance. METHODS Twelve people with TIA or minor stroke without previous gait/balance problems and 12 age- and sex-matched controls were recruited. Participants (mean age 67 years) underwent a comprehensive assessment including physiological, balance, and gait measures (clinical and computerized [NeuroCom/GAITRite]). Matched-pairs analysis was undertaken. RESULTS Groups were similar in body mass index, vision, leg proprioception/strength, and reaction time. Cognition was worse in the TIA/minor stroke group: mean Montreal Cognitive Assessment score 22.2 versus 26.6, P = .001. People with TIA/minor stroke were significantly worse on all but one clinical test. Median scores for TIA/minor stroke versus control were as follows: Timed Up and Go (TUG), 9.4 versus 7.6 seconds, P = .019; TUG dual task, 12.3 versus 8.5 seconds, P = .012; Four Square Step Test, 10.9 versus 7.2 seconds, P = .006. Mean Step Test score for TIA/minor stroke versus control was 14.1 versus 17.7, P = .021. The TIA/minor stroke group also had significantly worse performance on computerized tests: increased turn time/sway, increased step length, slower comfortable/fast gait speeds, and greater proportion of gait cycle spent in double support. CONCLUSIONS This study found that people with TIA/minor stroke have gait and balance dysfunction despite having no obvious physiological impairments. Intervention studies aimed at improving balance and gait in this population are needed.

Eliciting and responding to patient histories of abuse and trauma: challenges for medical education.

raumatic experiences such as childhood abuse, family violence, elder abuse and combat T exposure influence both physical and mental health, health-related behaviour, and the ways in which patients interact with medical practitioners. Despite greater knowledge of the pervasive sequelae of psychological trauma, the implications for medical practice and for medical education are not well articulated. Many doctors lack confidence and remain ill-informed or avoidant when dealing with patients’ psychological trauma. The consequences of this include non-recognition of somatisation and of psychiatric disorders, delay in instituting proper treatment, and costs to the patient and health care system of unnecessary investigations and treatments. Here, we discuss why and how we should better train doctors to elicit and respond to patient histories of trauma.