John W. Dunne

First seizure presentation: Do multiple seizures within 24 hours predict recurrence?

We compared clinical features and prognosis of 72 adults with a first-ever seizure presentation comprising multiple discrete seizures within 24 hours to 425 patients presenting with a single seizure. Those presenting with multiple seizures were no more likely to have seizure recurrence, irrespective of etiology or treatment. Hence, a presentation with multiple seizures within 24 hours should be regarded as a single event, in keeping with the International League Against Epilepsy recommendations.

Velocity dependent passive plantarflexor resistive torque in patients with acquired brain injury.

OBJECTIVES This study sought to determine whether factors other than stretch reflex excitability contribute to velocity dependent passive plantarflexor resistive torque following brain injury. BACKGROUND In patients with acquired brain injury increased resistance to passive muscle lengthening commonly results from abnormal muscle contraction, secondary to disinhibition of descending motor pathways, in addition to rheologic changes within the musculo-tendinous unit. Hyper-excitable tonic stretch reflex responses (spasticity) have traditionally been considered to be the main factor influencing resistance that is velocity dependent. METHODS Ten adults with brain injury and eighteen age matched controls were studied. A computer controlled torque measurement system was utilised to evaluate resistance to dorsiflexion stretches at two velocities (5 degrees and 25 degrees s(-1)). Only stretches which did not evoke muscle contraction were included in the data analysis. The mean difference and 95% confidence limits in passive plantarflexor resistive torque at two stretch velocities, measured over a defined portion of the test movement, were compared between subject groups. RESULTS A velocity dependent increase in passive plantarflexor resistive torque was evident when the ankle was dorsiflexed past the neutral position in both subjects with brain injury and controls. However, the mean difference was approximately 10 times greater in neurologically impaired limbs compared with control values. CONCLUSIONS These data indicate that an important component of velocity dependent resistance to passive muscle lengthening in adults with brain injury can be mechanical, and unrelated to stretch induced reflex muscle contraction. RELEVANCE Increased resistive torque during rapid muscle lengthening may represent a compensatory adaptation for reduced distal motor control following brain injury. A velocity dependent increase in passive plantarflexor resistive torque has the potential to improve stability during gait and provide mechanical resistance to sudden external perturbations.

Non-surgical management of ankle contracture following acquired brain injury

Background and purpose: The purpose of this study was to document the outcome of non-surgical management of equinovarus ankle contracture in a cohort of patients with acquired brain injury admitted to a specialist Neurosurgical Rehabilitation Unit. Methods: This prospective descriptive study examined all patients with a new diagnosis of moderate to severe acquired brain injury (Glasgow Coma Scale score ⩽ 12) admitted for rehabilitation over a 1 year period. Ankle dorsiflexion range and plantarflexor/invertor muscle activity were evaluated weekly during the period of hospitalization. Contracture was defined as maximal passive range of motion ⩽ 0° dorsiflexion, with the knee extended, on a minimum of two measurement occasions. Patients were retrospectively allocated to one of four treatment outcome categories according to ankle dorsiflexion range, type of intervention required and response to treatment. Results: Ankle contracture was identified in 40 of the 105 patients studied. Contracture resolved with a standard physiotherapy treatment programme, including prolonged weight-bearing stretches and motor re-education, in 23 patients. Contracture persisted or worsened in 17 of 40 cases, all of whom exhibited dystonic muscle overactivity producing sustained equinovarus posturing. Ten of 17 cases required serial plaster casting ( ± injection of botulinum toxin type A) in order to achieve a functional range of ankle motion. Remediation of ankle contracture was not considered a priority in the remaining seven patients due to the severity of their overall disability. Conclusion: The incidence of ankle contracture identified in this population was considerably less than previously reported. Reduced dorsiflexion range was remediated with standard physiotherapy treatment in over half of the cases. Additional treatment with serial casting ± botulinum toxin type-A injection was required to correct persistent or worsening contracture in one quarter of cases. Dystonic extensor muscle overactivity was a major contributor to persistent or progressive ankle contracture.

A prospective, multicentre, randomized, double-blind, placebo-controlled trial of onabotulinumtoxinA to treat plantarflexor/invertor overactivity after stroke:

Objective: To examine the safety and efficacy of onabotulinumtoxinA (Botox) for plantarflexor overactivity following stroke. Design: Double-blind randomized controlled trial, open-label extension phase. Setting: Neurology rehabilitation facilities. Subjects: Eighty-five subjects with lower limb hypertonia received 200 U (n = 28) or 300 U (n = 28) of onabotulinumtoxinA or saline (n = 29) injection. Primary measures: Plantarflexor Ashworth scores at 12 weeks post injection and adverse events. Secondary measures: self-reported spasm frequency and pain, physician rating of hypertonia severity, gait quality and active dorsiflexion. Results: Differences were not seen between onabotulinumtoxinA groups; hence data were pooled. Incidence of adverse events was not different between groups (P = 0.61). Reduction in hypertonia was not different between groups at 12 weeks (P = 0.53); however for subjects with Ashworth scores of >3 at baseline, 14/31 in the onabotulinumtoxinA group demonstrated a reduction of >1 grade versus 1/17 receiving placebo injection (P = 0.01). Overall, onabotulinumtoxinA-injected subjects demonstrated significantly greater improvement in spasm frequency (22/54 versus 4/29, P = 0.01), pain reduction (8/54 versus 1/29, P = 0.02), active dorsiflexion (8/54 versus 1/29 P = 0.03) and gait quality (17/54 versus 6/29, P = 0.02) than controls. In the open-label phase, a second onabotulinumtoxinA injection was associated with greater hypertonia reduction (P = 0.005) and gait quality (P = 0.002) compared with single injection. Conclusions: OnabotulinumtoxinA injection for ankle flexor overactivity after stroke was safe and well tolerated but did not alter local spasticity at 12 weeks; it did reduce spasms and improve gait quality. There were no detectable differences between higher and lower doses. A second injection may be associated with greater change.

The role of botulinum toxin injections in the management of muscle overactivity of the lower limb

Muscle overactivity is common in patients with adult onset central nervous system damage. It can produce significant disablement in conjunction with other impairments such as adaptive soft tissue shortening and loss of muscle strength. Muscle overactivity is not evenly distributed throughout the body; across joints there is frequently imbalance between agonist and antagonist, producing abnormal joint postures and movement patterns. Due to the asymmetric nature of the abnormal activity across joints, in general we recommend local treatment targeting the more overactive of the two agonists, rather than systemic treatment. Considerable experience with the use of botulinum toxin, both serotypes A and B, in the treatment of muscle overactivity has been accumulated in the last two decades through pragmatic clinical practice and open label studies, supported by an increasing number of randomized controlled trials. In most cases, it is important to use botulinum toxin injection for treatment of muscle overactivity in the setting of wider rehabilitation goals and interventions. Focal and partial blocks with botulinum toxin should be used as a component of a general neurorehabilitation programme rather than as an alternative to other treatments. We review the evidence supporting the use of botulinum toxin to treat muscle overactivity in the lower limb, present practical guidelines on when and how to use botulinum toxin and provide direction for future research.

Amphetamine-associated seizures: Clinical features and prognosis

Forty‐four patients presenting with first‐ever seizure within 24 h of illicit use of amphetamine or related analogs (amphetamine‐associated seizures, AAS) were identified over 8 years. Patients with AAS were compared to control groups of other first‐ever seizure patients (provoked n = 126 and unprovoked n = 401). Cumulative probability of recurrence was calculated using Kaplan‐Meier analysis. Seizure recurrence and development of epilepsy were less likely in patients with AAS compared to provoked or unprovoked controls. Forty percent of patients with AAS had clinical risk factors for epilepsy, epileptiform abnormalities on electroencephalography (EEG), or an epileptogenic lesion on neuroimaging. Sleep deprivation was more frequently present in those with AAS. AAS likely relate to an intrinsic proconvulsant effect of these drugs combined with patient susceptibility and environmental factors.

AUStralian Study of Titration to Effect Profile of Safety (AUS-STEPS): High-Dose Gabapentin (Neurontin) in Partial Seizures

Summary:  Purpose: To evaluate the safety, tolerability, efficacy, and impact on quality of life of gabapentin (Neurontin; GBP) as adjunctive therapy in patients with refractory partial seizures.

When is it safe to return to driving following first-ever seizure?

Objectives The risk of recurrence following a first-ever seizure is 40–50%, warranting driving restriction during the early period of highest risk. This restriction must be balanced against the occupational, educational and social limitations that result from patients being ineligible to drive. The recommended duration of non-driving after a first seizure varies widely between jurisdictions, influenced by various factors including the community perception of an acceptable relative level of risk for an accident (the accident risk ratio; ARR). Driving restrictions may be based on individualised risk assessments or across-the-board guidelines, but these approaches both require accurate data on the risk of seizure recurrence. Methods 1386 patients with first-ever seizure were prospectively analysed. Seizure recurrence was evaluated using survival analysis. The duration of non-driving required for a range of risks of seizure recurrence and ARRs was calculated. Additionally, the actual occurrence of seizures while driving was prospectively determined during follow-up. Results For a risk of seizure recurrence to fall to 2.5% per month, corresponding to a monthly risk of a seizure while driving of 1.04 per thousand and an ARR of 2.6, non-driving periods of 8 months are required for unprovoked first-ever seizure, and 5 months for provoked first-ever seizure. Of patients with a seizure recurrence, 14 (2%) occurred while driving, with the monthly risk falling to less than 1/1000 after 6 months. Conclusions Our data provide a quantitative approach to decisions regarding a return to driving in patients with first-ever provoked or unprovoked seizure.

Are seizures in the setting of sleep deprivation provoked

It is generally accepted that sleep deprivation contributes to seizures. However, it is unclear whether a seizure occurring in the setting of sleep deprivation should be considered as provoked or not and whether this is influenced by seizure type and etiology. This information may have an important impact on epilepsy diagnosis and management. We prospectively analyzed the influence of sleep deprivation on the risk of seizure recurrence in patients with first-ever unprovoked seizures and compared the findings with patients with first-ever provoked seizures. Of 1026 patients with first-ever unprovoked seizures, 204 (20%) were associated with sleep deprivation. While the overall likelihood of seizure recurrence was slightly lower in sleep-deprived patients with first-ever seizures (log-rank p=0.03), sleep deprivation was not an independent predictor of seizure recurrence on multivariate analysis. Seizure recurrence following a first-ever unprovoked seizure associated with sleep deprivation was far more likely than for 174 patients with a provoked first-ever seizure (log-rank p<0.0001). Our findings support the International League Against Epilepsy recommendation that seizures occurring in the setting of sleep deprivation should not be regarded as provoked.

First seizure in the older patient: Clinical features and prognosis

PURPOSE The prognosis of first seizure in the elderly has rarely been studied. Despite this, anti-epileptic drug treatment following first seizure is often recommended in older adults due to the perception that recurrence is inevitable and associated with significant morbidity. This study aims to establish whether older patients presenting with first-ever seizure are more likely to have a second seizure or not, and to examine their clinical features including seizure-related morbidity. METHODS Prospective observational study of adults seen by a hospital-based first seizure service between 2000 and 2011. The prognosis and clinical features of older (aged ≥65 years) and younger (aged 16-64 years) patients were compared. KEY FINDINGS 139 of 1008 patients with first-ever unprovoked seizure were aged ≥65 years (mean age 74 years). The majority of these older patients were healthy (95% ambulant, 81% Rankin score ≤2). The likelihood of a second seizure at one year was 53% (95% CI 45-62) in older patients and 48% (95% CI 44-51) in younger patients. Independent predictors of seizure recurrence were remote symptomatic etiology, first seizure arising from sleep, epileptiform abnormality on EEG and partial seizures but not age. Older patients were less likely to suffer a seizure-related injury with both the presenting seizure and the first recurrence. CONCLUSIONS With first-ever seizure age is not an independent predictor of seizure recurrence and older patients are less likely to sustain a seizure-related injury. Treatment decisions in older patients presenting with first-ever seizure should be based on established risk factors for seizure recurrence rather than age.