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Objectives Randomized studies in drug-resistant epilepsy (DRE) typically involve addition of a new anti-seizure medication (ASM). However, in clinical practice, if the patient is already taking multiple ASMs, then substitution of one of the current ASMs commonly occurs, despite little evidence supporting this approach. Methods Longitudinal prospective study of seizure outcome after commencing a previously untried ASM in patients with DRE. Multivariable time-to-event and logistic regression models were used to evaluate outcomes by whether the new ASM was introduced by addition or substitution. Results A total of 816 ASM changes in 436 adult patients with DRE between 2010 and 2018 were analyzed. The new ASM was added on 407 (50.1%) occasions and substituted on 409 (49.9%). Mean patient follow-up was 3.2 years. Substitution was more likely if the new ASM was enzyme-inducing or in patients with a greater number of concurrent ASMs. ASM add-on was more likely if a γ-aminobutyric acid (GABA) agonist was introduced or if the patient had previously trialed a higher number of ASMs. The rate of discontinuation due to lack of tolerability was similar between the add-on and substitution groups. No difference between the add-on and substitution ASM introduction strategies was observed for the primary outcome of ≥50% seizure reduction at 12 months. Significance Adding or substituting a new ASM in DRE has the same influence on seizure outcomes. The findings confirm that ASM alterations in DRE can be individualized according to concurrent ASM therapy and patient characteristics.

Epileptic seizures and nonconvulsive status (NCSE) are common in the critically ill, but non- epileptic movements and posturing are even more common. EEG can provide clarification when seizures are suspected. Different EEG patterns form a continuum of non-seizure to seizure activity, and over- interpretation of these patterns may lead to inappropriate advice and treatment. Recurrent seizures are easiest to recognise, with rhythmic discharges having spatiotemporal evolution in frequency (>4Hz), morphology and distribution. Periodic patterns are the most difficult. Generalised periodic discharges (GPDs) may or may not be ictal, and the specific EEG findings combined with the clinical context determines the approach. Severe myoclonic encephalopathy may occur after cardiac arrest, and the EEG may show burst suppression, unreactive GPDs separated by isoelectric intervals, ± electrographic seizures. The prognosis is extremely poor irrespective of treatment. Lateralised periodic discharges (i.e. PLEDs) may be an interictal finding in epilepsy and after any acute cerebral insult such as stroke or herpes encephalitis, and usually indicates a predisposition to seizures rather than ongoing seizure activity. Generalised triphasic waves are mainly seen with metabolic and toxic encephalopathies and are usually not an ictal finding. Whilst they can be sharply contoured, they are recognised by their other characteristics including morphology, state-dependent reactivity, and lag in phase and/or morphology changes from front to back. Triphasic waves (and almost all periodic patterns) are suppressed by benzodiazepines, along with consciousness and respiration. Such EEG suppression, in the absence of clinical improvement, does not diagnose NCSE. Ambiguous patterns can also be seen, with stimulus-induced rhythmic, periodic or evolving discharges. Whilst non-convulsive seizures and NCSE may be detected in comatose patients, prognosis is largely determined by the underlying aetiology and its complications. Unresolved questions include what particular EEG patterns should consistently prompt aggressive treatment. It is not always possible to be certain that an EEG pattern is ictal or non- ictal, and in the correct clinical context (especially patients presenting with seizures or with a history of epilepsy) a treatment trial may be indicated to see if temporally associated clinical improvement occurs. EEG interpretation needs to be made within the clinical context by an expert reporter.

EEG records the electrical activity of the cerebral cortex, mainly from large pyramidal neurons close to the surface, and this activity is influenced by subcortical structures. At least 6 cm2 of synchronised cortical activity is required to be recorded by scalp EEG. Surface electrodes are placed equidistantly over the scalp according to an international convention (10–20 System), ensuring good electrical contact, with electrode impedances Digital EEG amplifiers then use analogue-to-digital converters to translate the recorded voltage differences into numerical values, requiring an amplitude resolution of at least 12 bits (usually ≥16 bits), and with the number of measurements per second (sampling rate) at least three times the highest frequency being recorded (≥256 Hz). Filtering highlights activity that is biologically relevant, using a bandpass of 0.5–70 Hz for routine diagnostic EEG, but filtering distorts raw data and is no substitute for good technique. Digital EEG recording uses a system reference electrode separate from the 10–20 recording electrodes and stores the voltage measurements for each recording electrode relative to this system reference electrode. This allows reformatting of EEG channels and montages after the recording simply by combining any electrode pair to create the channel. At least longitudinal bipolar, transverse bipolar and referential montages should be used to read EEG. Unfortunately, EEG is commonly misinterpreted, leading to misdiagnosis. Age and state dependency dramatically influence the normal EEG, and there are many variations of normal, especially during drowsiness and sleep. ECG, careful clinical observation and video recording (routine if possible) are required throughout the recording to recognise artefacts and other important changes. For EEG to be useful, comprehensive knowledge, training and experience are required under the supervision of a skilled mentor. When in doubt, it is best to assume that background slowing is related to drowsiness/sleep, and every sharply contoured wave is an artefact or normal variant until proven otherwise.

OBJECTIVE: To examine the factors and reasons influencing treatment initiation decisions in patients with newly diagnosed epilepsy. METHODS: We assessed antiseizure medication initiation decisions in adults with newly diagnosed epilepsy seen at first seizure clinics in Western Australia between 1999 and 2016 and followed to 2018. RESULTS: Of 610 patients (median age 40 years, 61.0% male), 426 (69.8%) were diagnosed after two or more seizures and 184 (30.2%) after a single seizure with risk factors for recurrence. Treatment was commenced in 427 patients (70.0%) at diagnosis, 112 (18.4%) during follow-up, mostly after further seizures, whereas 71 (11.6%) remained untreated at last follow-up. Elders (≥65 years, odds ratio [OR] = 3.06, 95% confidence interval [CI]: 1.62-5.80), more seizures (OR = 3.48, 95% CI: 2.03-5.96), and epileptogenic lesions on neuroimaging (OR = 2.15, 95% CI: 1.26-3.68) had a higher likelihood of treatment at diagnosis. Patients with less than one seizure per year within the preceding year (OR = 0.40, 95% CI: 0.21-0.73) and of higher socioeconomic status (OR = 0.985, 95% CI: 0.977-0.994) were less likely to be treated. For 93 patients (15.2%), treatment was not recommended at diagnosis, most commonly because only a single seizure had occurred. Ninety patients (14.8%) declined recommended treatment, mostly because they were unconvinced of the need for treatment or the diagnosis. SIGNIFICANCE: Thirty percent of adults with newly diagnosed epilepsy were not immediately treated. Treatment initiation in this real-world cohort was influenced by age, number of seizures prior to diagnosis, imaging findings, patient preferences, and socioeconomic status.

Baclofen has been reported to cause both a metabolic encephalopathy and nonconvulsive status epilepticus. Baclofen is typically used in the management of muscle spasticity but is being increasingly used to manage alcohol withdrawal and opiate dependency. Given the increasing use of baclofen we describe the clinical and electrographical features of baclofen neurotoxicity seen at our institution.The clinical and EEG features of patients with an encephalopathy in the setting of baclofen therapy were analyzed. Patients were identified via our hospital EEG database.Fourteen patients were identified having presented with an acute confusional state without identifiable cause other than baclofen use. Five patients took a deliberate overdose, three of whom were baclofen naive, two patients presented after medication prescription error, and seven patients were on stable doses (30-140 mg daily). All patients presented with an encephalopathy, one patient was reported to have clinical seizures, and seven had multifocal myoclonus. EEGs were abnormal in all patients and showed moderate to severe generalized slowing. Generalized triphasic waves occurring at 1 to 2 Hz, sometimes with an anterior to posterior phase lag, were present in 10 patients (71%), and intermittent generalized suppression of the background was seen in three patients. Three patients received small doses of intravenous benzodiazepines, resulting in a marked depression of consciousness and respiration. All patients recovered within 48 hours of baclofen discontinuation.Baclofen toxicity can produce an acute encephalopathy even at modest doses, with the EEG showing generalized slowing and triphasic waves consistent with a toxic encephalopathy. Management consists of supportive care and cessation of baclofen. Patients with baclofen neurotoxicity exhibit a marked vulnerability to the depressant effects of benzodiazepines.

There has recently been a marked rise in the medicinal use of cannabis for epilepsy and multiple other conditions. While seizures have been reported in association with synthetic cannabinoids, the clinical features and prognosis have not been studied. Thirty patients with a history of seizures occurring within 24 h of synthetic cannabinoid use were identified from a first seizure clinic database in Perth, Western Australia between 2011 and 2016. Eight had a prior history of seizures, three related to synthetic cannabinoid use, with an additional three patients having risk factors for seizures. The presenting event was a tonic–clonic seizure in 27 patients (90%). “Kronic” was the synthetic cannabinoid used by 16 patients. Absorption was via smoking in all cases, with seizures occurring within 30 min of inhalation in 14 patients (46%). Electroencephalography (EEG) showed epileptiform abnormalities in 11%, and neuroimaging revealed epileptogenic lesions in 12%. Nine of 24 patients with follow-up had subsequent seizures, occurring in the setting of further synthetic cannabinoid use in two patients. This seizure recurrence rate is similar to seizures provoked by other acute systemic insults. In conclusion, smoking of some synthetic cannabinoids is associated with seizures, and this may relate to an intrinsic proconvulsant effect.

Metabolic encephalopathy and Non-Convulsive Status Epilepticus (NCSE) have been reported with cephalosporin use, particularly cefepime. We aimed to analyze the clinical and EEG findings in patients with cephalosporin-related neurotoxicity (CRN) at our hospital identified via the hospital EEG database, and to critically review CRN case reports in the literature. A Medline search was performed to identify CRN cases where a representative sample of EEG was provided. EEGs were analyzed using published criteria differentiating NCSE from triphasic waves (TW). Eleven patients at our hospital were identified with CRN (9 cefepime, 2 ceftriaxone): all had an encephalopathy with decreased consciousness and/or confusion. One patient had clinical seizures and 6 had multifocal myoclonus. All patients had abnormal EEGs, all with moderate to severe generalized slowing and 10 also with TW. Recovery was related to cephalosporin withdrawal rather than antiepileptic therapy. Analysis of 37 EEG samples of CRN patients reported in the literature as NCSE (30) or TW (7) revealed that most did not meet criteria for NCSE, with 33 showing TW, 1 showing generalised epileptiform discharges and 3 being uninterpretable. CRN usually produces a toxic encephalopathy rather than NCSE, and is commonly associated with triphasic waves on EEG. In most patients anti-epileptic and/or sedative drugs do not hasten clinical improvement.

Objective Epilepsy has recently been redefined to include a single unprovoked seizure if the probability of recurrence is ≥60% over the following 10 years. This definition is based on the estimated risk of a third seizure after two unprovoked seizures, using the lower-limit 95% confidence interval (CI) at 4 years, and does not account for the initially high recurrence rate after first-ever seizure that rapidly falls with increasing duration of seizure freedom. We analyzed long-term outcomes after the first-ever seizure, and the influence of duration of seizure freedom on the likelihood of seizure recurrence, and their relevance to the new definition of epilepsy. Methods Prospective analysis of 798 adults with a first-ever unprovoked seizure seen at a hospital-based first seizure clinic between 2000 and 2011. The likelihood of seizure recurrence was analyzed according to the duration of seizure freedom, etiology, electroencephalography (EEG), and neuroimaging findings. Results The likelihood of seizure recurrence at 10 years was ≥60% in patients with epileptiform abnormalities on EEG or neuroimaging abnormalities, therefore, meeting the new definition of epilepsy. However, the risk of recurrence was highly time dependent; after a brief period (≤12 weeks) of seizure freedom, no patient group continued to fulfill the new definition of epilepsy. Of 407 patients who had a second seizure, the likelihood of a third seizure at 4 years was 68% (95% CI 63-73%) and at 10 years was 85% (95% CI 79-91%). Significance The duration of seizure freedom following first-ever seizure substantially influences the risk of recurrence, with none of our patients fulfilling the new definition of epilepsy after a short period of seizure freedom. When a threshold was applied based on the 10-year risk of a third seizure from our data, no first-seizure patient group ever had epilepsy. These data may be utilized in a definition of epilepsy after a 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.

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 p0.0001). Our findings support the International League Against Epilepsy recommendation that seizures occurring in the setting of sleep deprivation should not be regarded as provoked.

Summary 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.

The role of neuroimaging in the assessment of a first-ever seizure has not been well-defined, in particular the utility of MRI when CT is normal. The results of neuroimaging (CT brain, MRI brain, or both) in 1,013 adults with first-ever unprovoked seizure were correlated with clinical features and seizure outcome. Epileptogenic lesions were identified in 29%. Of patients with a normal CT who also had MRI, 12% had an epileptogenic lesion on MRI, the strongest independent predictor of which was a focal abnormality on EEG. Patients with an epileptogenic lesion had a higher risk of seizure recurrence, including when this was only evident on MRI.

Objectives This randomised controlled crossover trial examined the efficacy of botulinum toxin type A (BoNT-A) injection, plus an exercise programme, to remediate chronic anterior knee pain (AKP) associated with quadriceps muscle imbalance. Methods 24 individuals with refractory AKP received either BoNT-A (500 U Dysport) or the same volume saline injection to the vastus lateralis (VL) muscle and performed home exercises focusing on re-training the vastus medialis (VM) muscle. All subjects were offered open-label injection at 12 weeks. Knee-related disability (anterior knee pain scale; AKPS) and activity-induced pain (10 cm visual analogue scale) at 12 weeks were the primary outcomes. Peak isometric extensor force was recorded and normalised VL:VM ratios were derived from simultaneous surface electromyography. Selfreported pain and disability measures were collected at six time points to a mean of 20±8 months. Results 14 subjects received BoNT-A and 10 placebo injection. Improvement at 12 weeks was significantly greater for BoNT-A compared with placebo-injected subjects for the AKPS (p

Intramuscular injection of botulinum toxin (BoNT) produces reversible blockade of neuromuscular transmission. In animal experimental models, recovery begins within four weeks and is usually complete by twelve weeks. We present evidence of prolonged denervation following BoNT injection of the vastus lateralis (VL) muscle to correct quadriceps muscle imbalance in patients with chronic anterior knee pain. Needle electromyography data were obtained from 10 subjects who had received a single BoNT treatment 5 to 19 months earlier as part of a clinical trial. Insertional and spontaneous activity, recruitment, and motor unit action potentials were examined. Clear differences between the injected and non-injected VL muscles, which correlated with the time since injection, were identified in all subjects. All 10 subjects studied with needle EMG showed evidence of persisting denervation in the BoNT-A injected VL muscle beyond the period of neuromotor recovery expected from animal experimental studies.

To examine the effect of intramuscular injection of botulinum toxin type A [Dysport] to reduce relative overactivity of the vastus lateralis [VL] muscle, in conjunction with re-training of vastus medialis [VM] muscle as an adjunct to rehabilitation for chronic anterior knee pain.Eight females with chronic (6 months) history of anterior knee pain, who had failed conservative management, were studied in this open label pilot study. Intramuscular Dysport injection [300 - 500 units] to the distal third of VL muscle was followed by a 12-week customized home exercise programme to improve recruitment of VM muscle and functional knee control. VL and VM muscle cross sectional area from a standardized spiral CT sequence, isometric quadriceps strength (dynamometry), timed stair task, self-reported pain and disability were assessed.Subjects reported reduced knee pain and brace dependency and increased participation in sporting and daily living activities. Isometric quadriceps muscle strength was maintained or improved despite significant atrophy, evident on CT, of the distal component of VL in the treated limb. Time taken to ascend and descend a flight of stairs improved in all subjects. Subjective and objective improvements were maintained at 24-week follow-up.These pilot data provide preliminary support for the role of Dysport as an adjunct to non-surgical management of individuals with chronic anterior knee pain. Larger double blind, randomized, placebo-injection controlled studies of this novel approach to improving patellofemoral mechanics are needed to establish the efficacy of this intervention.

Singer BJ, Jegasothy GM, Singer KP, Allison GT, Dunne JW. Incidence of ankle contracture after moderate to severe acquired brain injury. Arch Phys Med Rehabil 2004;85:1465–9. Objective To examine an adult population undergoing rehabilitation after brain injury to determine the incidence of ankle contracture and factors contributing to the development of this deformity. Design Descriptive study Setting Specialist inpatient neurosurgical rehabilitation unit in Australia. Participants Patients (N=105) admitted with a new diagnosis of moderate to severe brain injury over a 12-month period. Interventions Not applicable. Main outcome measures Maximal ankle dorsiflexion range and the presence of abnormal muscle tone affecting the lower limb(s) were evaluated at weekly intervals. Ankle contracture was defined as maximal passive range of less than 0° dorsiflexion with the knee in extension. Patients were grouped into 3 muscle tone categories: normal, predominantly spastic, or predominantly dystonic. Age, sex, mechanism and severity of brain injury, time to onset of ankle contracture, total length of hospital stay, and discharge mobility status data were also recorded. Results Muscle tone was designated as normal in 68 (64.7%), as spastic in 14 (13.3%), and as dystonic in 23 (21.9%) patients. The incidence of ankle contracture was 16.2% (17/105 cases). Ankle deformity correlated closely with muscle tone category. Of 23 cases with dystonic muscle overactivity, 17 developed contracture at some point between 1 and 16 weeks after brain injury, although no subject with normal tone or spasticity developed the deformity. There was a weak association between the severity of brain injury and development of ankle contracture. Conclusions The incidence of ankle contracture was much lower than previously reported. Dystonic overactivity of the plantarflexor and invertor muscles is a major predisposing factor to ankle contracture.

Diabetic amyotrophy is a distinctive form of diabetic neuropathy usually characterized by the abrupt onset of pain and asymmetric proximal leg weakness and wasting. Involvement of the upper limbs is unusual, and prognosis is said to be good. We describe two patients, each with type II diabetes mellitus, who presented with diabetic amyotrophy progressing to severe quadriparesis. One patient remains severely disabled. The clinical spectrum of diabetic amyotrophy includes progression to severe quadriparesis.

Objective. 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° and 25° 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. Conclusion. 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.

Objective. To examine changes in muscle length and resistance to passive lengthening in the triceps surae muscles in patients with recently acquired brain injury. Background. Increased passive resistance in the triceps surae muscles is common following acquired brain injury. Adaptive shortening secondary to relative immobility, and increased stiffness due to rheologic changes within the musculo-tendinous unit, may be exacerbated by plantarflexor muscle overactivity related to the brain injury itself. Design. Three variables representing resistance to passive lengthening and soleus muscle length were compared between subjects with recent brain injury and age matched normal controls. Comparison between limbs was made for subjects with unilateral neurological impairment. Methods. Slow passive dorsiflexion stretches were performed using a computer controlled dynamometer. Muscle stiffness in the initial and latter portion of the range, and the angles achieved at torques of 5 and 10 N m were determined from torque–angle curves. Maximal ankle dorsiflexion with the knee flexed was considered to reflect soleus muscle length. Results. Significant differences were demonstrated for all variables, except passive stiffness near the end of available range. The limb ipsilateral to unilateral brain injury differed from control limbs in that significantly less passive range of dorsiflexion was available and initial resistance to passive stretch was significantly less. Conclusions. The reduction in soleus muscle length evident in subjects with recent acquired brain injury, even in neurologically unaffected limbs, may reflect the influence of relative immobility. Although plantarflexor muscle overactivity was found to be associated with increased resistance to slow passive stretch, the mechanism was unable to be elucidated from these data. The limb ipsilateral to unilateral neurological impairment cannot be considered to be a `normal' control for comparative purposes. Relevance Adaptive shortening and increased resistance to passive lengthening limit active ankle dorsiflexion, and alter ankle biomechanics. Tonic muscle overactivity has the potential to exacerbate these changes. Prophylactic management of inappropriate muscle activity and maintenance of muscle length may facilitate the achievement of rehabilitation goals and reduce subsequent disability following acquired brain injury.

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. Methods: AUS-STEPS was an open-label, multicenter, prospective study in patients experiencing partial seizures who were inadequately controlled with one to three concurrent antiepileptic drugs (AEDs). GBP treatment was titrated to a maximum of 4,800 mg/day, over a treatment period of 24 weeks, to achieve an efficacious and tolerable dosage. Efficacy was assessed by seizure-frequency data. Quality of life was evaluated by using the QOLIE-10 questionnaire, and safety was assessed by adverse-event reports and clinical laboratory findings. Results: A total of 176 patients received treatment with GBP, with 174 evaluable for intention-to-treat (ITT) efficacy analysis. A reduction of >50% in overall seizure frequency was observed in 93 patients (53%). There was a small (4.6%) overall improvement in QOLIE-10 score. The most frequent adverse events were dizziness (31%), fatigue (29%), somnolence (27%), headache (21%), and ataxia (20%), with no major increase seen in adverse events necessitating discontinuation as the dose of GBP was titrated upward. Conclusions. This study indicates that patients with partial epilepsy may be effectively treated with GBP at dosages of 4,800 mg/day, without altering the safety profile of the drug.

Assessment of medical fitness to drive can be a sensitive and difficult task, particularly when it involves a condition such as epilepsy, where impairment is intermittent. The patient, their doctor and the driver licensing authority (DLA) each have responsibilities, both to the patient and to the wider community of road users. DLAs in Australia have shifted most of the responsibility for determining fitness to drive to the treating doctor. This creates a conflict of interest and may lead to unsafe decisions, damage to the doctor-patient relationship, interference with medical management and legal vulnerability for the doctor. Australian neurologists have argued for a system in which the treating doctor provides objective information about the patient's condition, rather than an opinion on fitness to drive, and the DLA uses that information to determine fitness. This must be supported by an expert review process. Although drivers are legally obliged to notify the DLA when they become unfit, most people are unaware of this law. However, passing this responsibility to doctors in the form of mandatory reporting is counterproductive to road safety. Language: en

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.

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.

OBJECTIVES: To determine the clinical features, response to treatment and outcome of petrol sniffers presenting to Perth's teaching hospitals. DESIGN: Retrospective study of all admissions to Perth's tertiary referral hospitals that were related to petrol sniffing from 1 January 1984 to 31 December 1991. RESULTS: Twenty-five patients (22 male and 3 female) were admitted with a diagnosis of intentional petrol sniffing. Five presented with acute petrol intoxication as the result of an isolated action. The remaining 20 patients were "chronic petrol sniffers". The mean age was 17.7 years (range, 5-27 years). Twenty patients were Australian Aborigines, including 18 of 20 chronic petrol sniffers and the three females. In the chronic petrol sniffers, a high prevalence of seizures and an alarmingly high case fatality ratio (8 of 20), usually by sudden death, were found. An altered mental state was universal, manifesting as drowsiness, delirium or stupor. Generalised tonic-clonic seizures occurred in 14, three with status epilepticus. Myoclonus (9), chorea (8) and cerebellar ataxia (appendicular and truncal) (13) were common. High blood lead levels on presentation were associated with a poor prognosis (survivors v. deaths, P = 0.002). Eighteen of the 20 patients were treated with specific agents to reduce the lead load, but the results were extremely disappointing. CONCLUSION: Petrol sniffing is an important cause of sickness and death in young people from some rural Aboriginal communities. It can cause sudden death or irreversible encephalopathy. Those severely affected have a poor prognosis, despite treatment. Effective strategies for prevention are needed. Language: en

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.

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.

Intramuscular injection of botulinum toxin (BoNT) produces reversible blockade of neuromuscular transmission. In animal experimental models, recovery begins within four weeks and is usually complete by twelve weeks. We present evidence of prolonged denervation following BoNT injection of the vastus lateralis (VL) muscle to correct quadriceps muscle imbalance in patients with chronic anterior knee pain. Needle electromyography data were obtained from 10 subjects who had received a single BoNT treatment 5 to 19 months earlier as part of a clinical trial. Insertional and spontaneous activity, recruitment, and motor unit action potentials were examined. Clear differences between the injected and non-injected VL muscles, which correlated with the time since injection, were identified in all subjects. All 10 subjects studied with needle EMG showed evidence of persisting denervation in the BoNT-A injected VL muscle beyond the period of neuromotor recovery expected from animal experimental studies.

Increased calf muscle stiffness is a common impairment following acquired brain injury. This study examined the immediate effects of cyclic ankle stretching at two stretch velocities on calf stiffness in individuals with hemiparesis (n=17) and control subjects (n=10).Cyclic ankle stretching was applied for 3min at velocities of 5 degrees s(-1) and 25 degrees s(-1) using a purpose-built dynamometer. Surface electromyography was employed to ensure stretches were passive. Peak plantarflexor resistive torque was derived from torque-angle curves. Comparisons were made between groups, velocities, and between limbs for hemiparetic subjects.At baseline, mean peak plantarflexor resistive torque was greater in the affected limbs of hemiparetic subjects than their contralateral limbs (P0.001), however there was no significant difference between groups. Plantarflexor resistive torque was reduced in all limbs following cyclic stretching regardless of stretch velocity (P0.005). Two distinct patterns of response were observed in hemiparetic subjects. In nine cases the affected limb responses did not differ from the contralateral limb or control data. In the remaining eight cases mean peak plantarflexor resistive torque in the affected limb was greater than the contralateral limb and control values. In this subgroup, peak plantarflexor resistive torque was significantly affected by stretch velocity and showed the greatest reduction following cyclic stretching.Cyclic stretching has been shown to produce a short term reduction in calf stiffness in a subgroup of individuals with hemiplegia. Further investigation is required to elaborate the characteristics of those most likely to respond optimally to this intervention.

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.

Objective: To analyze seizure control and treatment in pregnant women with epilepsy. Methods: Seizure control and treatment were recorded prospectively in 1,956 pregnancies of 1,882 women with epilepsy participating in EURAP, an international antiepileptic drugs (AEDs) and pregnancy registry. Results: Of all cases, 58.3% were seizure-free throughout pregnancy. Occurrence of any seizures was associated with localization-related epilepsy (OR: 2.5; 1.7 to 3.9) and polytherapy (OR: 9.0; 5.6 to 14.8) and for tonic-clonic seizures, with oxcarbazepine monotherapy (OR: 5.4; 1.6 to 17.1). Using first trimester as reference, seizure control remained unchanged throughout pregnancy in 63.6%, 92.7% of whom were seizure-free during the entire pregnancy. For those with a change in seizure frequency, 17.3% had an increase and 15.9% a decrease. Seizures occurred during delivery in 60 pregnancies (3.5%), more commonly in women with seizures during pregnancy (OR: 4.8; 2.3 to 10.0). There were 36 cases of status epilepticus (12 convulsive), which resulted in stillbirth in one case but no cases of miscarriage or maternal mortality. AED treatment remained unchanged in 62.7% of the pregnancies. The number or dosage of AEDs were more often increased in pregnancies with seizures (OR: 3.6; 2.8 to 4.7) and with monotherapy with lamotrigine (OR: 3.8; 2.1 to 6.9) or oxcarbazepine (OR: 3.7; 1.1 to 12.9). Conclusions: The majority of patients with epilepsy maintain seizure control during pregnancy. The apparently higher risk of seizures among women treated with oxcarbazepine and the more frequent increases in drug load in the oxcarbazepine and lamotrigine cohorts prompts further studies on relationships with pharmacokinetic changes. Risks associated with status epilepticus appear to be lower than previously reported.

A 58-year-old man with progressive supranuclear palsy (PSP) developed two episodes of respiratory failure associated with laryngeal spasm. It was revealed he had adductor laryngeal breathing dystonia, a relatively unrecognized complication of PSP.

To examine an adult population undergoing rehabilitation after brain injury to determine the incidence of ankle contracture and factors contributing to the development of this deformity.Descriptive studySpecialist inpatient neurosurgical rehabilitation unit in Australia.Patients (N=105) admitted with a new diagnosis of moderate to severe brain injury over a 12-month period.Not applicable.Maximal ankle dorsiflexion range and the presence of abnormal muscle tone affecting the lower limb(s) were evaluated at weekly intervals. Ankle contracture was defined as maximal passive range of less than 0 degrees dorsiflexion with the knee in extension. Patients were grouped into 3 muscle tone categories: normal, predominantly spastic, or predominantly dystonic. Age, sex, mechanism and severity of brain injury, time to onset of ankle contracture, total length of hospital stay, and discharge mobility status data were also recorded.Muscle tone was designated as normal in 68 (64.7%), as spastic in 14 (13.3%), and as dystonic in 23 (21.9%) patients. The incidence of ankle contracture was 16.2% (17/105 cases). Ankle deformity correlated closely with muscle tone category. Of 23 cases with dystonic muscle overactivity, 17 developed contracture at some point between 1 and 16 weeks after brain injury, although no subject with normal tone or spasticity developed the deformity. There was a weak association between the severity of brain injury and development of ankle contracture.The incidence of ankle contracture was much lower than previously reported. Dystonic overactivity of the plantarflexor and invertor muscles is a major predisposing factor to ankle contracture.

Ninety randomly selected general practitioners from the Perth metropolitan area completed a self-administered postal questionnaire aiming to examine the extent of their involvement with epilepsy and how closely their management mirrored best practice guidelines. GPs saw a median of 6 patients with epilepsy, mainly adults. They perceived complementary roles for GPs and neurologists: the GP providing ongoing support and education, monitoring treatment and making dosage adjustments; with the neurologist largely making the formal diagnosis and other management decisions. Only 42% regarded their knowledge of epilepsy as adequate for their practice. About half advised patients on the existence of the Epilepsy Association. Some respondents overestimated the usefulness of EEG. Plasma antiepileptic drug (AED) measurements were overvalued, with 69% of respondents performing plasma levels without regard to symptoms, and 20% would alter AED doses solely on the basis of plasma levels. GPs may tolerate very frequent seizures before referring their patients for more specialised evaluation.

The purpose of this open study was to find out whether botulinum toxin A (BTX-A) relieves the signs and symptoms of chronic limb spasticity. The study comprised 40 patients, aged 12-82 years, with moderate to severe spasticity of the upper (13) or lower limbs (27) refractory to conventional physical and medical treatments. Outcome measures were clinical and blinded videotape assessments of spasticity and motor function. Electromyography guided BTX-A injections were given in one or two sessions at total doses averaging 175 U in the upper limb (range 70-270 U) and 221 U in the lower limb (range 100-500 U). Thirty four patients (85%) derived worthwhile benefit, with improved limb posture and increased range of passive motion in 31, pain reduction in 28 of 31 with pain, and improved function in 16. Side effects were limited to local and usually mild discomfort from the injections (19), symptomatic local weakness (one), and local infection (one). Preliminary experience indicates that BTX-A is a promising adjunctive treatment for selected patients with spasticity.

Background Familial adult myoclonic epilepsy (FAME) is an autosomal dominant syndrome characterized by a core triad of cortical tremor, multifocal myoclonus, and generalized tonic-clonic seizures. Objectives To expand the phenotypic spectrum of FAME, to highlight diagnostic pointers to this underrecognized disorder, and to refine the FAME2 genetic locus. Design Observational family study. Setting The study was coordinated in a tertiary academic hospital, with data acquired in diverse primary, secondary, and tertiary care settings. Participants Consenting members of a single large family. Results A 6-generation FAME kindred of European descent was ascertained in New Zealand and Australia. Affected family members (N = 55) had fine hand tremor, with onset typically in adolescence (median age, 15 years; age range, 4-60 years). Proximal myoclonus was present in 44 of 55 (80%), arising later than hand tremor (median age, 17 years; age range, 5-60 years). Generalized tonic-clonic seizures occurred in 8 of 55 (15%), with a median age at onset of 43.5 years (age range, 18-76 years). Neurophysiological testing confirmed features of cortical reflex myoclonus. Genetic mapping narrows the FAME2 (OMIM 607876) locus on chromosome 2 to a 13.3-megabase interval, harboring 99 known protein-coding genes. Conclusions The most common FAME phenotype in this large family is mild postural hand tremor resembling essential tremor, combined with subtle proximal myoclonus. Generalized tonic-clonic seizures are uncommon and occur around sleep onset following severe generalized myoclonus.

Phenelzine associated sensorimotor peripheral neuropathy is reported in two patients. Symptoms were predominantly sensory, and improvement occurred after withdrawal of phenelzine. Electrophysiologic findings were consistent with an axonal process.

To quantify velocity dependent and position related properties of increased muscle tone measured during a constant velocity stretch.Elbow flexors were vertically stretched under four different velocities (40, 80, 120, and 160 degrees /s) through a 75 degrees range of motion in 12 patients with hemiparesis, 16 with parkinsonism, and 12 normal controls. From reactive torque measurement, a linear second order model was adopted to dissociate velocity dependent viscous and velocity independent elastic components. The averaged speed dependent reflex torque (ASRT)--defined as the deviation of measured torque from baseline torque--was used to quantify the viscous component of hypertonia. Velocity sensitivity of ASRT (VASRT) and segmented ASRT (SASRT), derived from the slope of the regression line among ASRT velocity plots and from segmentations of reactive torque, respectively, were used to differentiate the increased muscle tone of spasticity and rigidity.ASRT and VASRT were significantly higher in both spasticity and rigidity than in normal controls. SASRT analysis showed three different position related patterns among spasticity, rigidity, and normal groups: spasticity showed progressively increasing muscle tension relative to position; rigidity showed increased (relative to the norm) but constant muscle tone over the entire stretch range; the normal control group showed a consistently low reactive torque over the entire range.Velocity dependence analysis indicates that rigidity and spasticity have approximately equal velocity dependent properties. For differentiating these two types of hypertonia, position dependent properties my be employed.