Patients' Experiences of Remote Neurology Consultations during the COVID-19 Pandemic.

Telemedicine has been widely implemented during the COVID-19 global pandemic to enable continuity of care of chronic illnesses. We modified our general neurology clinic to be conducted using remote audio-only telephone consultations. We included all patients over a 10-week period who agreed to both a telephone consultation and a questionnaire afterwards in order to ascertain the patient's perspective of the experience. There were 212 participants consisting of men (43.8%) and women (56.2%). The mean ± standard deviation of age was 47.8 ± 17.0 (range 17-93) years. For the most part, patients found remote consultations either "just as good" (67.1%) or "better" (9.0%) than face-to-face consultations. Those who deemed it to be "not as good" were significantly older (52.3 ± 17.9 years vs. 46.6 ± 16.6 years, p =0.045) or were more likely to have a neurological disorder that required clinical examination, namely, a neuromuscular condition (66.7%, p = 0.002) or an undiagnosed condition (46.7%, p = 0.031). At the height of the COVID-19 global pandemic, most patients were satisfied with remote consultations. The positive feedback for remote consultations needs to be verified outside of this unique scenario because the results were likely influenced by the patients' apprehension to attend the hospital amongst other factors.

Very-late-onset Friedreich's ataxia: diagnosis in a kindred with late-onset cerebellar ataxia.

Friedreich's ataxia is classically considered a disease with onset in the first or second decade. However, late-onset (age of onset 25-39 years) and very-late-onset (age of onset >40 years) forms do occur rarely. Misdiagnosis is common, particularly because the later onset forms of Friedreich's ataxia commonly do not show characteristic features of the disorder (areflexia, dysarthria, sensory neuropathy, extensor plantars, amyotrophy, cardiac involvement, diabetes mellitus, scoliosis). Also, there may be atypical features such as spasticity, brisk reflexes and laryngeal dystonia. We present the clinical, imaging and genetic findings of a kindred with very-late-onset Friedreich's ataxia and discuss the pitfalls and risk of misdiagnosis.

Diverse phenotype of hypokalaemic periodic paralysis within a family.

Hypokalaemic periodic paralysis typically presents with intermittent mild-to-moderate weakness lasting hours to days. We report a case with an uncommon phenotype of late-onset myopathy without episodic paralytic attacks. Initial work-up including muscle biopsy was inconclusive. A subsequent review of the right deltoid biopsy, long exercise testing and repeated family history was helpful, followed by appropriate genetic testing. We identified a heterozygous pathogenic mutation in calcium ion channel (CACNA1S:c.1583G>A p.Arg528His) causing hypokalaemic periodic paralysis. Myopathy can present without episodic paralysis and the frequency of paralytic episodes does not correlate well with the development and progression of a fixed myopathy. Our report also highlights the intrafamilial phenotypic variation of hypokalaemic periodic paralysis secondary to a CACNA1S gene mutation.

Advice following a possible first seizure: what do patients attending for EEG remember?

PURPOSE: This study was designed to assess the knowledge of patients following their first seizure or blackout of unknown cause. We aimed to compare the advice our cohort of patients recalled against that suggested in the current literature. BACKGROUND: 5 % of the population will experience a non- febrile seizure in their lifetime. Education and advice for the patient and their family is an important aspect of their care. METHOD: After reviewing the recommended guidelines from both the Scottish Intercollegiate Guidelines Network and the National Institute for Health and Care Excellence, a questionnaire was developed. From 1st May 2020 to 1st September 2022, a questionnaire was given to eligible patients attending St. James's Hospital for an electroencephalogram (EEG) following their first possible seizure or blackout of unknown cause. The patients were provided with a list of topics and were asked to select which, if any, were discussed with them. RESULTS: A total of 50 eligible adults participated in the study. Driving was the topic most frequently recalled as having been discussed at 66 % followed by family education. CONCLUSION: It has been recognised that patients remember as little as a fifth of information initially discussed, failing to recall 40-80 % of content within medical encounters and our study supports this. This highlights the need to review the information delivered and how this is achieved as well as using new methods to help increase the retention of this vital information.

Sudden unexpected death in epilepsy: people with nocturnal seizures may be at highest risk.

PURPOSE: Most people with epilepsy who die suddenly and whose death is attributed to sudden unexpected death in epilepsy (SUDEP) are found in or by the bed for unknown reasons. We assessed whether those with sleep-related SUDEP were more likely to have nocturnal seizures, and whether seizure patterns (diurnal vs. nocturnal) differed from people dying suddenly and living controls with epilepsy. METHODS: Seizure patterns in a cohort of 154 people with epilepsy who died suddenly and after autopsy conformed to the definition of SUDEP and 616 controls living with epilepsy were classified as having "exclusively diurnal" or "nocturnal seizures." Comparisons were made between the groups. SUDEP was classified as sleep-related or non-sleep-related based on eyewitness accounts and the circumstances surrounding death. KEY FINDINGS: SUDEP was primarily a sleep-related (58%) and unwitnessed (86%) event. If sleep-related, SUDEP was more likely to be unwitnessed [odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-12]. Those with sleep-related SUDEP were more likely to have a history of nocturnal seizures than those who had non-sleep-related SUDEP (OR 3.6, 95% CI 1.4-9.4). Those who died were more likely to have a history of nocturnal seizures than living controls (OR 3.9, 95% CI 2.5-6.0). After correction for previously established SUDEP risk factors (Langan et al., 2005), the presence of nocturnal seizures remained significant (OR 2.6, 95% CI 1.3-5.0). SIGNIFICANCE: Nocturnal seizures seem to be an independent risk factor for SUDEP. These findings underscore the importance of preventive measures, which may include night supervision.

Do antiepileptic drugs or generalized tonic-clonic seizure frequency increase SUDEP risk? A combined analysis.

PURPOSE: In an analysis of four case-control studies of sudden unexpected death in epilepsy (SUDEP), we found that yearly frequency of generalized tonic-clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy were associated with an increased risk for SUDEP. The prior analysis, however, did not evaluate AEDs and GTCS frequency concurrently. METHODS: We combined data from the three case-control studies with information on the frequency of GTCS and AED therapy, that is, carbamazepine, phenytoin, valproic acid, and other AED therapy. Number of AEDs was also considered. Lamotrigine and GTCS frequency were considered separately in two of the case-control studies. Logistic regression analysis was used to evaluate GTCS frequency, each of the AEDs, and number of AEDs. Adjusted analysis of the different AEDs accounted for study, age at death, gender, and GTCS frequency. KEY FINDINGS: In crude analysis, GTCS frequency, AED polytherapy, and number of AEDs were associated with an increased risk for SUDEP. Analysis of individual AEDs and of number of AEDs, adjusting for GTCS frequency, revealed no increased risk associated with AEDs as monotherapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP. SIGNIFICANCE: Our findings-that none of the AEDs considered were associated with increased SUDEP risk as monotherapy or as polytherapy when GTCS frequency was taken into account-provide a consistent message that number of GTCS increases SUDEP risk and not AEDs. These results suggest that prevention of SUDEP must involve increased efforts to decrease GTCS frequency in order to avert the occurrence of this devastating epilepsy outcome.

Combined analysis of risk factors for SUDEP.

PURPOSE: To pool data from four published case-control studies of sudden unexpected death in epilepsy (SUDEP) with live controls, to increase the power to determine risk factors. METHODS: Case-control studies from the United States, Sweden, Scotland, and England were combined. SUDEP was defined as (1) a history of epilepsy (>1 epileptic seizure during a period of < 5 years); (2) death occurring suddenly; (3) death unexpected (i.e., no life-threatening illness); and (4) death remained unexplained after all investigative efforts, including autopsy. Definite SUDEP required all criteria. Logistic regression analyses adjusted for study. Further analysis simultaneously adjusted for study, age at death, gender, and duration of epilepsy. KEY FINDINGS: Of the risk factors that could be analyzed across some or all studies, those that were statistically significant were increased frequency of generalized tonic-clonic seizures (GTCS), use of polytherapy, duration of epilepsy, young age at onset, gender, symptomatic etiology, and lamotrigine therapy. Results persisted when epilepsy onset was younger than 16 years and when it was 16 years or older. In univariate analysis, lamotrigine therapy was associated with significantly increased risk for SUDEP among individuals with idiopathic generalized epilepsy. SIGNIFICANCE: This analysis refines the identification of people with epilepsy that are at particular risk of SUDEP. The emerging profile indicates that people with early onset refractory symptomatic epilepsy with frequent GTCS and antiepileptic drug (AED) polytherapy are at higher risk. The results suggest that reduction of the number of GTCS is a priority, of more importance than reducing the number of AEDs. The role of AEDs and other treatment should be analyzed further in future studies.

Amnesia for loss of consciousness is common in vasovagal syncope.

AIMS: The aim of this study was to determine the prevalence of amnesia for loss of consciousness (A-LOC) in those who have a history suggestive of vasovagal syncope (VVS) and who develop syncope on head-up tilt (HUT) table testing. Furthermore, we wished to determine if A-LOC is an age-dependent phenomenon in VVS and whether haemodynamic parameters on tilting can predict for A-LOC. METHODS AND RESULTS: Patients were recruited in a dedicated syncope unit and underwent neurocardiovascular evaluation as indicated under European Society of Cardiology guidelines to illicit a diagnosis of VVS. A set protocol of questioning occurred following induced syncope to determine the presence of A-LOC. The prevalence of A-LOC following syncope on tilting was 28% (44/159). Forty-two per cent of those≥60 years of age vs. 20%<60 years of age experienced amnesia post-induced syncope (P=0.003). However, regression analysis did not show age to be an independent predictor for A-LOC. Blood pressure change between those without amnesia and those with amnesia showed no significant difference (P=0.687). There was a significant difference in heart rate response; those experiencing amnesia had reduced bradycardic response on HUT compared with those without amnesia (P=0.001). CONCLUSION: Amnesia for loss of consciousness is common in VVS. Although more prevalent, it is not unique to older age-groups. Absence of syncope associated bradycardia during HUT testing predicts for A-LOC.

Possible N-methyl-D-aspartate receptor antibody-mediated encephalitis in the setting of HIV cerebrospinal fluid escape.

Discordant elevations of cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) ribonucleic acid (RNA) in chronically treated patients known as 'CSF escape' may present as acute encephalitis. Infectious encephalitis caused by herpes simplex virus (HSV) and other neurotropic viruses have been identified as potential triggers of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Autoantibody-mediated encephalitis has been infrequently reported in HIV infected patients and may mimic HIV encephalitis. We report two adults infected with HIV presenting with encephalopathy and seizures. Case 1 had a monophasic encephalopathy with detection of NMDAR antibodies in the context of HIV CSF escape. There was a clinical response to immunotherapy and anti-retroviral therapy adjustment. Case 2 initially presented in non-convulsive status epilepticus associated with HIV CSF escape. He responded to treatment with anti-epileptic drugs and anti-retroviral therapy alteration, but had two further neurological relapses. NMDAR antibodies were detected during the relapses and a clinical response was observed following treatment with immunotherapy. Clinicians should consider autoimmune encephalitis in HIV infected patients presenting with encephalopathy and seizures, particularly in cases with concomitant HIV CSF escape.

The role of alcohol dependency in deaths among people with epilepsy recorded by the National Drug-Related Deaths Index (NDRDI) in Ireland, 2004-2013.

PURPOSE: The aim of this study was to investigate deaths among individuals with epilepsy recorded on the National Drug-Related Deaths Index (NDRDI). METHOD: A descriptive analysis of individuals with a known history of epilepsy in the NDRDI from 2004 to 2013 was undertaken. RESULTS: Between 2004 and 2013, 225 (2%) of the recorded cases had a documented history of epilepsy, 82 (36%) of whom had epilepsy recorded as the cause of death. Of these 82 deaths, the majority were male (60-73%) and half (median age) were aged 47 years or younger. A post mortem toxicology report was available for 65 (79%) of these deaths, of which over two thirds (44-68%) did not have any antiepileptic drugs present on toxicology. Over two thirds of these deaths, (31-70%) were among people known to be alcohol dependent. CONCLUSION: The high percentage of individuals with a diagnosis of alcohol dependency that died as a result of epilepsy and who have no antiepileptic drugs in their system at the time of their death, highlights the need for preventative measures for this at-risk group.

Talampanel, a new antiepileptic drug: single- and multiple-dose pharmacokinetics and initial 1-week experience in patients with chronic intractable epilepsy.

PURPOSE: Talampanel (LY300164), a potent and selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-receptor antagonist, is a potential new antiepileptic drug (AED). This study examines the single- and multiple-dose pharmacokinetics, safety, and tolerability of talampanel in patients with intractable epilepsy and assesses the potential for pharmacokinetic interaction. METHODS: Eleven of 14 patients entered into the study completed. Fourteen patients were evaluated for safety, 13 patients were used in the single-dose, and 11 patients in the multiple-dose pharmacokinetic analysis. Each patient initially received a single 35-mg dose of talampanel followed by the measurement of pharmacokinetic profiles. A 21-day t.i.d. dosing regimen was then determined for each patient based on his or her initial pharmacokinetic profile. Adverse events were recorded by patients or their carers. RESULTS: After oral ingestion, talampanel was rapidly absorbed, with maximal plasma concentrations achieved within 1-3 h. Talampanel concentrations in patients taking enzyme-inducing AEDs were 50% lower than those seen in healthy volunteers. Mean talampanel t1/2 values were 3.0 h compared with 4.2 h in healthy volunteers. After multiple-dose and steady-state, talampanel t1/2 values were increased to 5.6 h Talampanel and valproic acid (VPA) appear to inhibit each other's metabolism mutually. Talampanel had no effect on plasma concentrations of other AEDs. Multiple-dose talampanel administration was associated with nonlinear pharmacokinetics. No serious adverse events were reported; the most frequently reported being dizziness, ataxia, drowsiness, and headaches CONCLUSIONS: Talampanel dosing strategies may be reliant on concomitant AED medication, as enzyme-inducing AEDs enhance, whereas VPA inhibits its metabolism. Talampanel was well tolerated, although adverse events occurred at lower doses compared with those in healthy subjects, probably because of the additive effect of concomitant AEDs.