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Biallelic variants of the gene encoding for the zinc-finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders.

PurposeCannabidiol has been licensed in the UK for those with refractory seizures associated with Lennox Gastaut Syndrome (LGS). However, characterizing LGS in adults can be challenging. Patients are frequently too agitated to tolerate EEG monitoring. Many patients are monitored by carers whose expertise may be variable; identifying seizures, particularly non convulsive manifestations such as atonic head drops or sleep-related tonic seizures, is therefore unreliable. We sought to ascertain whether those with an LGS-type syndrome – refractory multifocal epilepsy with cognitive impairment and multiple seizure types arising in childhood, would benefit from Cannabidiol. These patients did not have the typical elec- troclinical phenotype for LGS.MethodIndividual Funding Requests were made for five patients. Four had genetically defined syndromes- Alternating Hemiplegia of Childhood, Batten’s disease (CLN5), CHD2 related epileptic encephalopathy and Tuberous Sclerosis. One had Febrile Related Epilepsy Syndrome (FIRES) of unknown aetiology. Patients were commenced on adjunctive Cannabidiol between March and December 2021. All patients were prescribed Clobazam.ResultsCannabidiol at a maximum dose of 5mg/kg lead to significant seizure reduction (>50%) in 3 patients. Our patient with Tuberous Sclerosis was the only one who did not experience a reduction in seizure intensity.ConclusionCannabidiol is potentially efficacious in adult patients with severe refractory epilepsy ‘outside’ the typical LGS phenotype.

Queen Elizabeth HospitalIntroductionCannabidiol (CBD) is approved for the treatment of refractory epilepsy associated with Dravet and Lennox-Gastaut syndromes. Affected individuals have co-morbid intellectual disability, making serum monitoring challenging. Those prescribed CBD at the Queen Elizabeth Hospital underwent at least one face to face appointment in the twelve months preceding treatment. Many were initiated on CBD remotely, in keeping with trust guidance to reduce the burden of face-to-face consultations during the Pandemic.NICE recommends liver function test (LFT) monitoring in those prescribed CBD at baseline, 1, 3 and 6 months, then periodically thereafter 2. All patients initiating CBD were offered LFT on site, with a recom- mendation to GPs to continue LFT monitoring in the community.Aim To assesses whether CBD patients undergo LFT monitoring in keeping with NICE guidance.ResultsOf thirty patients prescribed Cannabidiol for a minimum of six months, sixteen (53%) had LFTs undertaken at least once. Twelve (75%) were conducted by their GP. Three patients had abnormal LFT at some stage which normalised within six months of initiation of treatment.RecommendationsRegular liaison with community healthcare providers about LFT protocols and access to finger prick testing (both on site and community) would potentially facilitate regular serum monitoring.

We present a 50-year-old lady with 6-months’ history of episodes of feeling weak with legs giving way triggered by sudden change of position or head-turning and no loss of consciousness. She had left tinnitus for years and one year worsening migraines with fortification spectra, visual blurring, and vertigo. ENT made a diagnosis of vestibular migraines.Her neurological examination was normal and attempted provocation of attacks with sudden changes in position and Dix-Hallpike was unsuccessful. Brain MRI revealed a large lesion obstructing foramina of Luschka-Magendie giving rise to obstructive hydrocephalus.Neuro-ophthalmology review showed bilateral papilledema and no evidence of Parinaud’s syndrome (no convergence retraction nystagmus or tectal pupils). Tumour biomarkers (bHCG-AFP-AlkPh-LDH) and body CT scan were normal. She underwent urgent CSF diversion. MDTs confirmed radiological diagnosis of epidermoid cyst awaiting debulking.Episodic headaches/vertigo with head-turning are described in Bruns syndrome manifesting as abrupt headaches, vertigo, vomiting provoked by changes in head position due to intermittent obstructive hydrocephalous (mass lesion and ball-valve mechanism). We propose patient’s acute episodes of lower limb weakness were similar phenomenon highlighting importance of imaging in stereotypical attacks after triggers.

1. A 42-year-old female developed status ten days following admission for alcohol-related liver disease. MRI brain showed symmetrical medial temporal high signal. No cause was identified.Though the convulsive seizures settled, focal seizures persisted. A second MRI showed extensive multi- lobar signal change, presumed inflammatory in nature. Pulsed methylprednisolone and plasma exchange were ineffective.Tocilizumab was administered ten weeks following onset of seizures.Sequential MRIs showed resolution of inflammatory changes. The patient was discharged to rehabilitation- Modified Rankin Score 3.2. A 79-year-old female presented with convulsive NORSE, 24hours after first dose of Pfizer COVID vaccine. She had a background of vascular dementia.The patient never recovered her GCS. Convulsive seizures were replaced by epilepsy partialis continua. Sequential MRIs showed diffuse left parietal cortical high signal. An inflammatory aetiology was presumed, pulsed methylprednisolone and the ketogenic diet (3 months) were ineffective.Anakinra was administered on week twelve. Subsequent MRIs showed progression of confluent white matter disease, now bi-hemispheric. She remains symptomatic, a year post presentation.We hypothesise that both patients had NORSE arising from an unidentified inflammatory aetiology. Age and premorbid function are known to influence recovery. Early use of monoclonal antibodies may be beneficial, including in those with systemic disease.

Initiation of anti-epileptic drugs is increasingly relevant to daily neurosurgical practice. Intracranial pathologies ranging from brain tumours to subarachnoid haemorrhage and traumatic brain injury are commonly associated with the subsequent development of seizures. The scope and range of anti-epileptic drugs available has increased dramatically in recent years and understanding the evidence base behind this class of drugs in addition to their interaction/side effect profiles is essential. In this review we aim to generate a practical guide for neurosurgeons regarding the use of different anti-epileptic medications in common neurosurgical conditions, including considerations for their use in pregnancy.

In light of the COVID 19 pandemic, outpatient services have been restructured to facilitate remote con- sultations. As the pandemic has entered second and third ‘phases’, patients’ perspectives regarding remote consultation are essential.MethodsQuestionnaires were sent to PWE and carers attending tertiary epilepsy services at University Hospitals Birmingham. 25% of the population is from an ethnic minority.Results378 questionnaires were analysed- 278 in phase A, 100 in phase B. 57.0% respondents were female, 42.9% over 50 years. 8.2% had comorbid non epileptic attacks.55.8% respondents preferred telephone consultation in phase A, 66% in phase B. 34.9% preferred face to face in phase A, dropping to 32% by phase B, the majority being non-white.6.83% selected video consultation in phase A, none in phase B.The proportion citing ‘safety’ as a reason for remote consultation in phase A (23%) was greater than in B (5%) PThe proportion citing ‘ease of access’ as key increased by phase B, though non significantly p=0.03.ConclusionEase of access continues to drive preferences for telephone consultations with infection risk in outpatients becoming less of a concern. Translating services are essential if remote consultation is to be accessible to all.smritibose55@gmail.com64

BackgroundThe co-existence of non epileptic attacks (NEAD) in patients with brain tumour related epilepsy (BTRE) is poorly described. Non epileptic attacks (NEAD) co-occur in up to 30% of patients with epilepsy (PWE) [SS1] . Adverse life events are associated with development of NEAD; their co-occurrence in those with BTRE is potentially un-surprising .MethodsClinical trajectories of patients with BTRE and co-existing NEAD were characterised. The diagnosis of NEAD was based on specialist’s observation of attacks and/or capture of attacks on video. Patients had been referred because of persisting symptoms in spite of escalating antiepileptic therapy.ResultsOf seven patients, six developed NEAD following development of BTRE. One developed NEAD de novo following tumour biopsy. Onset of NEAD was not temporally linked with the diagnosis of a brain tumour. In five, NEAD onset occurred when seizures were controlled (< 1 seizure/month). All seven nev- ertheless reported fear of developing uncontrolled seizures and identified their NEAD as more disabling than their epilepsy.Six were initially misdiagnosed with escalating seizures. Patients were eventually managed with polytherapy (two found adjunctive clobazam helpful) and behavourial strategies including mindfulness.ConclusionNEAD can co-occur with BTRE and should be considered where seizure type symptoms are escalating.[SS1]S.R. Benbadis, W.A. HauserAn estimate of the prevalence of psychogenic non-epileptic seizures.Seizure, 9 (2000), pp. 280–281 shani@doctors.org.uk

Epileptic seizures are well recognized as a presenting symptom in patients with brain tumors, however much less is known about coexisting nonepileptic attack disorder (NEAD) in this population. Establishing a diagnosis of NEAD can be challenging, especially in those with concomitant epilepsy. Nonepileptic attack disorder is associated with a high rate of morbidity, often due to coexisting psychological factors which may require the input of multiple services. In an era where early aggressive management of tumors is enabling patients to live longer, the associated psychological impact of adjusting to physical disease is increasingly apparent. In this case series, we present a narrative summary of 9 patients referred to neurology with brain tumor-related epilepsy (BTRE) over a five-year period (2015-2020) who also experienced NEAD. We describe their tumor characteristics, treatment course, and factors potentially contributing to their presentation. We conducted a case note review of patients presenting to the epilepsy service with BTRE, in whom NEAD was diagnosed based on clinical features and correlation with their EEG. Patients ranged in age from 26 to 63 years. Two patients were diagnosed with grade 1, three with grade 2 and four with grade 3 tumors. Tumors localized to frontal or temporal regions in seven cases. All patients presented initially with BTRE and developed nonepileptic seizures subsequently. Four patients developed NEAD within 1 month of their tumor diagnosis. One patient developed NEAD 79 months following diagnosis. The diagnosis of NEAD was established in 8 patients by direct visualization of attacks (two during concomitant EEG recording). In the remaining patient, diagnosis was based on history (patient and witness). Six patients were diagnosed with concomitant low mood and/ or anxiety and three were commenced on antidepressant medication. At the time of last review, the predominant attacks were nonepileptic in all but one patient.

Objective\ud \ud The management of Chiari malformations in pregnancy is challenging due to the perceived risk of adverse maternal neurological outcomes and raising intracranial pressure during labour. Our aim was to evaluate the management and health outcomes of pregnant women cared for at a regional referral center and highlight elements of best practice.\ud \ud Study Design\ud \ud A retrospective case series of all pregnant women diagnosed with Chiari malformation over fourteen years (January 2004- June 2018) at the Birmingham Women’s Hospital – UK.\ud \ud Results\ud \ud Twenty-one women (23 pregnancies) with Chiari malformation were included, four had syringomyelia (4/21,19%) and six had previously undergone craniovertebral decompression (6/21, 29%). The median age was 34-years (range 20-41), the median gravidity was two (range 1-8), the median parity was one (range 0-6), and the median extent of tonsillar herniation was 11 mm (range 9-18). The majority of women received their preferred mode of delivery (15 normal vaginal deliveries (15/23, 65.2%) and 6 elective Caesarean sections (6/23, 26.1%)) with two pregnancies ending with an emergency caesarean section for obstetric complications (2/23, 8.7%). Five Caesarean section were performed under general anaesthetic, two under spinal (2/23, 8.7%) and one under epidural anaesthesia (1/23, 4.3%) with no neurological sequelae. There were no adverse neurological outcomes at discharge postnatally.\ud \ud Conclusions\ud \ud Offering normal vaginal delivery with effective analgesia, for women with Chiari malformation, appears to be safe. Pregnancy care should be provided by a multi-disciplinary team with experience in managing Chiari malformation.

Purpose To compare the efficacy of AspireSR ® to preceding VNS battery models for battery replacements, and to determine the efficacy of the AspireSR ® for new implants. Methods Data were collected retrospectively from patients with epilepsy who had VNS AspireSR ® implanted over a three-year period between June 2014 and June 2017 by a single surgeon. Cases were divided into two cohorts, those in whom the VNS was a new insertion, and those in whom the VNS battery was changed from a previous model to AspireSR ® . Within each group, the seizure burden was compared between the periods before and after insertion of AspireSR ® . Results Fifty-one patients with a newly inserted AspireSR ® VNS model had a significant reduction in seizure frequency (p ® , 71% (n = 44) reported a further reduction of ≥50% in their seizure burden. The size of this reduction was at least as large as that resulting from the insertion of their existing VNS in 98% (61/62) of patients. Conclusion The results suggest that approximately 70% of patients with existing VNS insertions could have significant additional benefit from cardiac based seizure detection and closed loop stimulation from the AspireSR ® device. For new insertions, the AspireSR ® device has efficacy in 59% of patients. The ‘rule of thirds' used in counseling patients may need to be modified accordingly.

Aims The co-existence of non-epileptic attacks (NEAD) in patients with brain tumour related epilepsy (BTRE) is poorly described. Non epileptic attacks (NEAD) co-occur in up to 30% of patients with epilepsy PWE. Adverse life events are associated with development of NEAD; their co-occurrence in those with BTRE is potentially un-surprising. We sought to characterise the evolution of symptoms in this cohort. Method Clinical trajectories of patients with BTRE and co-existing NEAD were characterised. The diagnosis of NEAD was based on the epilepsy specialist’s observation of attacks and /or capture of attacks on video. Some patients had additional video EEG correlate. Patients had been referred because of persisting symptoms in spite of escalating antiepileptic therapy. Results Of eight patients, six were initially misdiagnosed with escalating seizures. One patient developed NEAD de novo following tumour biopsy, the remaining patients developed NEAD following onset of BTRE. Onset of NEAD was not temporally linked with the diagnosis of a brain tumour. In five patients, NEAD onset occurred when seizures were controlled (< 1 seizure/ month). All patients reported fear of developing uncontrolled seizures as being associated with their symptoms and identified their NEAD as more disabling than their epilepsy. Patients were eventually managed with polytherapy -two found adjunctive clobazam helpful and four were offered antidepressant/ anxiolytic medication. Behavourial strategies including mindfulness were also discussed. At time of last follow up, seven patients had on-going NEAD symptoms in spite of good seizure control. Conclusion NEAD can co-occur with BTRE and should be considered in those with rapidly escalating symptoms in spite of antiepileptic therapy and radiologically stable lesions. Both making the diagnosis of NEAD and providing ongoing support is challenging. These patients require a multidisciplinary approach with support from allied specialties including neuropsychiatry and neuropsychology.

To compare the efficacy of AspireSRData were collected retrospectively from patients with epilepsy who had VNS AspireSRFifty-one patients with a newly inserted AspireSRThe results suggest that approximately 70% of patients with existing VNS insertions could have significant additional benefit from cardiac based seizure detection and closed loop stimulation from the AspireSR

BackgroundThe longer-term trajectory of seizures associated with autoimmune encephalitis (AIE) is not clear. Recent data in NMDA AIE suggests seizures manifest early and are generally short lived, but in LGI1 AIE they occur later and continue longer. We characterised seizure semiology and associated prognosis in two cohorts of AIE patients.MethodsCase note review of 14 patients with a ‘definite’ diagnosis of anti-NMDAR AIE and 14 patients with LGI1 AIE showed the latter to occur in older adults. Patients were categorized as having seizures within one month of presentation or no seizures and the semiology was classified as focal or generalised onset.ResultsIn the NMDA group A, 3/7 patients (23%) had focal onset compared to 6/11 patients (55%) in the LGI1 group, with predominantly faciobrachial dystonic seizures. NMDA patients were more likely to be seizure-free at 6 months (9/12, 75%) compared to LGI1 patients (6/14, 43%). Similarly, much fewer NMDAR patients remained on ant-epileptic medications at 1 year compared to the LGI1 patients. Neither seizure semiology at presentation nor presence of inflammation on MRI correlated with longer term seizure trajectory in both groups.ConclusionSeizures are common presenting symptoms in these AIE groups. More NMDA patients were seizure-free at 6 months and did not require AEDs after 1 year compared to the LGI1 patients. LGI1 patients represented a more susceptible group of AIE patients to epilepsy.

ObjectivesTo identify predictors of poor response to cardiac based seizure detection (CBSD) VNS therapy.DesignData was collected retrospectively for patients with epilepsy who had VNS Aspire SR implanted between June 2014 and June 2017. 51 patients who reached a therapeutic level of stimulation were included. We compared those who achieved significant seizure reduction (at least 50%) with the remainder to identify potential factors predicting response.Subjects51 patients achieving therapeutic stimulation (1.5mA) with the VNS Aspire SR.MethodsWe reviewed patients’ electronic records over the period between June 2014 and June 2018.Results32 (63%) patients achieved significant seizure reduction. The following factors applied equally to both responders and non-responders: patient age, duration of epilepsy prior to VNS insertion, seizure type, the presence of a causative structural abnormality and the presence of a carer. Co-existing learning disability and/or non-epileptic attacks were commoner among poor responders. Polytherapy (3 or more AEDs) and non-compliance with medical treatment were also commoner among the poor responders; none of these factors was statistically significant.ConclusionsFactors potentially predicting response to resective surgery (including patients’ age and duration of epilepsy) do not necessarily predict response to VNS therapy. The presence of a learning disability and the extent of seizure refractoriness may influence response to VNS therapy; a larger study is needed to assess their significance.

Introduction: Breast cancer is exceptionally associated with anti–collapsin response mediator protein 5 (anti-CRMP5) antibody or demyelinating neuropathy. This paraneoplastic antibody is itself not associated with demyelinating neuropathy. Methods: Herein we describe a patient with a predominantly sensory ataxic demyelinating neuropathy associated with an IgG-kappa monoclonal gammopathy of uncertain significance (MGUS). Further investigations led to identification of anti-CRMP5 antibodies. An initial search for a malignancy proved negative. No immunomodulatory therapy was administered. Results: The patient developed breast carcinoma 2 years after the initial neurological symptoms, which was effectively treated by surgery, chemotherapy, hormone therapy, and radiotherapy. At neurological follow-up, 16 months after cancer treatment, she remained in remission and had made substantial neurological recovery. Electrophysiology showed significant amelioration, and serum anti-CRMP5 antibodies were undetectable. MGUS paraprotein level was unchanged. Conclusion: This case widens the range of paraneoplastic manifestations of breast carcinoma to include anti-CRMP5 antibody–positive sensory ataxic demyelinating neuropathy, which, in this patient, improved after cancer treatment. Muscle Nerve, 2011

Introduction NICE guidance recognises that the care of patients with CNS malignancy needs to be coordinated. However the pathway for managing BTRE differs across hospitals, with patients presenting to a number of clinicians. Method Local guidelines for managing BTRE were established in 2015. Weekly BTRE clinic appointments enabled the neurologist to accept referrals primarily from neuro-oncology and neurosurgery. Results 42 new referrals were seen over 24 months; 40 patients experienced both focal and generalised seizures. The neurologist modified the AED regimen in 18 (42.9%) patients. Addition of a second AED, most commonly Valproate, was recommended by neurology for 6 (14.3%) patients. This was done primarily to manage focal symptoms, which was successful in 50% cases. Withdrawal of an AED, commonly phenytoin or clobazam, was recommended for 12 (28.5%) patients. Co-existing non epileptic attacks were diagnosed in 3 (7.1%) patients. 32 (76.2%) patients had been prescribed Levetiracetam by the referring clinician, reflecting local guidelines. Conclusions Establishing local guidelines for the management of BTRE has changed practice regarding the choice of AEDs used, with drugs such as Levetiracetam becoming first line. The neurologist9s role is in refining AED regimens and clarifying diagnostic uncertainty. Balancing multiple treatments with quality of life is essential.

A 24-year-old previously healthy farm worker was out shooting rabbits in the field when he accidentally dropped his gun. The gun fired, shooting him in the left foot. He presented to the hospital hours later and was found to have entry and exit gunshot wounds to the foot. Multiple fractures of the talus, calcaneum and distal fibula were confirmed on x-ray and subsequent CT. He was admitted to the theatre for a washout. On entering the recovery room, the patient initially coughed appropriately when extubation was attempted. However, he then lapsed into an unrousable state and was noted to be decorticate to painful stimuli. …

A 39-year-old right-handed community nurse presented to us on the neurology ward in April, 2005, after a telephone call from her work colleagues. They expressed concern that she had appeared subdued before starting the afternoon shift and that, when asked, she could not recall her home address. She had apparently carried out her morning duties as normal and could not understand her colleagues’ concerns. However, she agreed to be reviewed. The nurse’s symptoms had begun 48 h previously, when she woke with a bitemporal headache, similar in character to previous episodes of migraine. Her vision then “fl ipped 180°” so that all images appeared inverted. She was able to crawl back to bed and on waking 6 h later, her vision had returned to normal and the headache had subsided. There were no further symptoms, and she continued engagements over the weekend as planned. She had experienced a similar episode while at work 12 years previously. Her vision had “fl ipped”, again occurring in combination with a migraine. The symptoms resolved within hours. Apart from a long history of infrequent migraines for which she had not received any treatment, there was no other signifi cant medical history. She was a non-smoker, was not taking any medications (including oral contraceptives), and denied alcohol or illicit drug use. On presentation, she appeared withdrawn. General medical examination was unremarkable, and she was normotensive. There were no focal abnormalities on neurological examination. She was still unable to recall her home address, although she was able to give a detailed account of her activities over the preceding 48 h, including dates and times of consultations with patients. We did an Addenbrooke’s cognitive assessment, which showed a score of 66/100, with marked defi cits in anterograde memory and verbal fl uency. EEG showed a moderate number of slow delta transients and theta slowing in the left temporal region. MRI showed a defi ned lesion on T2 imaging in the left medial thalamus, with high signal on FLAIR and diff usion-weighted imaging (fi gure). There was a much smaller lesion in the right thalamus, without corresponding acute signal change. These images were consistent with an acute left medial thalamic and older right thalamic infarct. The focus of high signal on the diff usion-weighted imaging trace showed hypointensity on the apparent diff usion coeffi cient map (not shown), confi rming an area of restricted diff usion indicating an acute infarction. On MR angiography, both vertebral and carotid arteries appeared normal. A transoesophageal echocardiogram showed an aneurysmal interatrial septum with a large patent foramen ovale. Plasma homo cysteine concentration, and results of a thrombophilia and an extended autoantibody screen were normal, so anticoagulant treatment with warfarin was started. Although she continued to experience anterograde memory disturbance after discharge, this improved substantially. She was last reviewed in January, 2006; she had no new symptoms and had returned to work. The subtle changes in our patient’s behaviour and memory could easily have been missed by her colleagues. Such changes are well recognised with anteromedian thalamic infarcts; a loss of self-activation and initiative has been described, with patients appearing to “resemble robots”. Anterograde memory disturbance, usually accompanied by dysphasia or aphasia, is another established feature with dominant hemisphere involvement. The infarct is likely to have arisen from embolisation of thrombus within the aneurysmal septum or a paradoxical embolus from a venous source. Patients with both a patent foramen ovale and an atrial septal aneurysm are at increased risk of recurrent stroke compared with patients presenting with either one of these abnormalities. Longterm oral anticoagulation or surgical closure of the foramen ovale is therefore recommended. Our patient described a 180° rotation of her vision, known as reversal of vision metamorphopsia, which was fi rst described by Winslow in 1868—the exact mechanism remains unclear. Our case highlights an atypical presentation of acute stroke and the value of a cognitive assessment as part of the neurological examination.