Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection.

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.

A DM1 patient with CCG variant repeats: Reaching the diagnosis.

We report the case of a male patient presenting in his 50s with ptosis, facial and distal limb muscle weakness, clinical and electrical myotonia, and a prior history of cataract extraction. He had a dominant family history in keeping with a similar phenotype. Myotonic dystrophy type 1 was clinically suspected. Triplet-primed polymerase chain reaction in a diagnostic laboratory did not identify a typical CTG repeat expansion on two separate blood samples. However, subsequent genetic testing on a research basis identified a heterozygous repeat expansion containing CCG variant repeats. Our case highlights the point that variant repeats are not detectable on triplet-primed polymerase chain reaction and result in a milder phenotype of myotonic dystrophy. It is crucial to maintain a high clinical index of suspicion of this common neuromuscular condition.

Psychogenic nonepileptic seizures that remit when the diagnosis is given: Just good luck?

OBJECTIVE: Some patients with psychogenic nonepileptic seizures (PNES) remit when given the diagnosis. It is not realistically possible to test this potential therapeutic effect in an Randomized Controlled Trial (RCT) so we aim to statistically demonstrate it using the temporal relationship between the communication of the diagnosis and the timing of remission. METHOD: Re-analysis of data from a study of PNES, where diagnosis was communicated, and outcomes recorded in 54 patients. Making conservative assumptions and using the binomial distribution, the Poisson distribution and the chi-squared test distribution, we calculated likelihoods of the null hypothesis: that communication of the diagnosis and remission of seizures had occurred in random temporal relationship. RESULTS: Remission occurred in the week following communication of the diagnosis in 15 out of 54 patients. The χ2 test assigned this result a p value of <0.00001. Binomial and Poisson distribution calculations also indicated that remission was highly unlikely to have occurred by chance and that, in a dataset similar to ours, was unlikely to be due to chance if occurring in more than 9 patients (16.7%). CONCLUSIONS: We showed that the observed remissions were highly unlikely to be due to chance. Where an intervention is 'short and sharp' and the outcome can be measured with reasonable temporal acuity, then this type of method may provide an alternative to RCT methodology when the latter is impracticable.

'Breaking Good News': Neurologists' experiences of discussing SUDEP with patients in Scotland.

Since the findings of a Fatal Accident Inquiry (FAI) in 2010, clinicians working in Scotland have been advised to discuss the risk of Sudden Unexpected Death in Epilepsy (SUDEP) with patients immediately or soon after a diagnosis of epilepsy is made. A thematic analysis was used to describe the experiences discussing SUDEP of 10 clinicians (six Consultant Neurologists and four Neurology Registrars) working in Scotland. Contrary to previous research, clinicians appear to be routinely discussing SUDEP in a standardized fashion with newly diagnosed patients and the FAI appears to have instigated this change in practice. Clinicians are ambivalent about the practice and whether this is a Breaking Bad News (BBN) experience. Clinicians appear to anticipate that patients will be anxious or distressed discussing SUDEP, despite their experiences that patients do not react this way. There are further concerns that the pressure to discuss SUDEP, as a result of the FAI, hinders effective communication of the SUDEP message. Implications for guideline development are discussed.

Healthcare resource utilization after medium-term residential assessment for epilepsy and psychogenic nonepileptic seizures.

INTRODUCTION: Epilepsy and epilepsy mimics may lead to high healthcare resource utilization (HRU) including diagnostic resources. The William Quarrier Scottish Epilepsy Centre (SEC) provides medium-term residential assessment (MTRA; average length of stay: 28days) and treatment for complex presentations of epilepsy and related conditions (principally psychogenic nonepileptic seizures, PNES). We studied the effect of MTRA on HRU in a defined health board area in Scotland. METHODS: A retrospective audit of individuals admitted to the SEC from a defined health board area using SEC and health board medical records. Neurological HRU assessed included emergency department visits, hospital admissions, outpatient clinic appointments, and brain imaging prior to and post-MTRA. Healthcare resource utilization was also compared with individuals referred but not admitted to the SEC because of individual circumstances and choice. RESULTS: Seventy-three individuals (51 female, average age: 37.51; 22 men, average age: 43.72) were identified from three years of admissions (1st April 2010 to 31st March 2013). Final diagnosis was epilepsy (ES), 32; ES and psychogenic nonepileptic seizures (ES+PNES), 17; and PNES alone, 24. Twenty-two individuals were identified as a comparison group (8 men, 14 women; average age: 37.21 and 43.90, respectively). Total average contacts per patient per year (CPY) was significantly different pre- and post-MTRA (4.16 vs. 1.32; t(72)=6.11, p<.0001, d=.72). Comparison of HRU in the first year of baseline and last full year of follow-up showed a post-MTRA reduction in HRU for PNES of 92.28%, for ES of 46.81%, and for ES+PNES of 28.3%. During the course of follow-up, PNES CPY continued to drop (1.13 first year vs. 0.10 at 3years post-MTRA). For individuals with epilepsy (with or without PNES), HRU use dropped significantly in the year after admission, and these gains remained stable (total first vs. third postdischarge CPY, 1.74 vs. 1.29). The participants in the comparison group, who were not admitted, had no comparable drop across the study period and were using significantly more resources at each follow-up point than those in the admitted group (F (1, 48)=44.45, p<.01, ηp(2)=.49). CONCLUSION: Medium-term residential assessment is associated with sustained reduction in HRU especially in patients with PNES. Overall HRU reduction was 68.27% following admission (d=.72). This suggests benefit from the MTRA model for people with complex presentations.

Rare neurological diseases: a practical approach to management.

Although neurologists are frequently faced with the management of rare diseases, there is little generic guidance for the approach to management. There are complexities with respect to diagnosis, counselling, treatment and monitoring which are idiosyncratic to rare diseases. Here we use a case report as the basis for discussion of the management of rare neurological diseases. We discuss current issues, guidance from regulatory bodies, and offer practical tips for diagnosis, treatment and monitoring, including the use of decision tree analysis. We offer a generic algorithm to aid neurologists when facing rare conditions.

Accelerated long-term forgetting in temporal lobe epilepsy: verbal, nonverbal and autobiographical memory.

Patients with temporal lobe epilepsy (TLE) often present with memory complaints despite performing within normal limits on standard memory tests. One possible explanation for this phenomenon is accelerated long-term forgetting (ALF). The present study investigated material-specific ALF in patients with unilateral TLE and also examined whether ALF could be demonstrated on a novel, standardized anterograde autobiographical memory (ABM) task. Fourteen patients with TLE and 17 controls were administered verbal, nonverbal and ABM event memory tasks. The participants were tested for immediate recall, recall and recognition at 30-minute delay, and recall and recognition after four weeks. The extent of ALF was calculated based on the percentage decay of memory from the 30-minute delay trial to the four-week delay trial. Patients with left TLE showed significantly greater ALF for verbal material and a trend towards greater forgetting of ABM. Patients with right TLE showed a non-significant trend towards greater ALF for nonverbal material. Patients with unilateral hippocampal abnormalities showed greater ALF compared to patients without hippocampal abnormalities. Patients with seizures that generalize had more global memory deficits and greater ALF. We conclude that patients with unilateral TLE show material-specific ALF, which appears to be more pronounced with an abnormal hippocampus or seizures that secondarily generalize.

N-methyl D-aspartate receptor antibody encephalitis associated with myelitis.

Encephalitis associated with antibodies to the N-methyl D-aspartate receptor (NMDA-R) was first described in young women with ovarian teratoma. It has subsequently been described in men, children and in those without an underlying tumour. Characteristic clinical features include neuropsychiatric symptoms, seizures, movement disorders, hypoventilation and autonomic instability. Spinal cord disease in association with other typical clinical features has been described in only one patient previously. We report a patient presenting with myelitis, with typical features of NMDA-R associated encephalitis manifesting 3 months later.

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: an important cause of stroke in young people.

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes is a progressive, multisystem mitochondrial disease affecting children and young adults. Patients acquire disability through stroke-like episodes and have an increased mortality. Eighty per cent of cases have the mitochondrial mutation m.3243A>G which is linked to respiratory transport chain dysfunction and oxidative stress in energy demanding organs, particularly muscle and brain. It typically presents with seizures, headaches and acute neurological deficits mimicking stroke. It is an important differential in patients presenting with stroke, seizures, or suspected central nervous system infection or vasculitis. Investigations should exclude other aetiologies and include neuroimaging and cerebrospinal fluid analysis. Mutation analysis can be performed on urine samples. There is no high quality evidence to support the use of any of the agents reported in small studies. This article summarises the core clinical, biochemical, radiological and genetic features and discusses the evidence for a number of potential therapies.

Newly diagnosed psychogenic nonepileptic seizures: health care demand prior to and following diagnosis at a first seizure clinic.

Patients with psychogenic nonepileptic seizures (PNES) are heavy users of emergency and nonemergency health care. We performed a 1-year prospective audit of use of a group of PNES-related health care items in patients with newly diagnosed (mean duration: 7.3 months) PNES from PNES onset to diagnosis and from diagnosis to 6 months postdiagnosis. Twenty-eight patients (20 women, age: 34±16 years) were responsible for 14 general practitioner home visits, 31 ambulance calls, 34 emergency department visits, 21 hospital admissions (66 inpatient days), 8 MRI scans, 24 CT scans, 2 standard EEGs, 28 short video EEG recordings, and 5 ambulatory EEG recordings. In the 6 months following diagnosis, there were 2 emergency department visits (94.1% reduction), no hospital admissions (100% reduction), 2 ambulance calls, no general practitioner visits, 1 MRI scan, and no CT scans or EEGs. The immediacy of this marked health care demand reduction suggests that the relationship between presentation of diagnosis and health care demand reduction is causal.

Multidetector computed tomography angiography: Application in vertebral artery dissection.

BACKGROUND AND PURPOSE: Multidetector computed tomography angiography (MDCTA) is a minimally invasive radiological technique providing high-resolution images of the arterial wall and angiographic images of the lumen. We studied the radiological features of vertebral artery dissection (VAD) in a consecutive series of patients investigated for acute stroke and subarachnoid hemorrhage (SAH) in order to confirm and define the diagnostic features of VAD on MDCTA. PATIENTS AND METHODS: Review of patients identified prospectively over a 4-year period with VAD assessed by MDCTA was conducted. Radiological features of VAD on MDCTA were reanalyzed utilising previously reported criteria for VAD. RESULTS: Thirty-five patients (25 males, mean age 49.6 years) with a total of 45 dissected vertebral arteries were reviewed. MDCTA features of VAD included increased wall thickness in 44/45 (97.7%) arteries and increased total vessel diameter in 42/45 arteries (93.3%). All dissected arteries had either lumen stenosis (21/45) or associated segmental occlusion (24/45). An intimal flap was detected in 6/45 (13.3 %) vessels. Twenty-five patients had follow-up imaging, 14/32 vessels returned to normal, 4 showed improvement in stenosis but did not return to normal and 14 demonstrated no change. The majority of non-occluded vessels became normal or displayed improved patency. Only 4/17 occluded arteries demonstrated re-establishment of flow. No adverse effects were recorded. CONCLUSIONS: MDCTA is a safe and reliable technique for the diagnosis of VAD. Increased wall thickness (97.7%) and increased vessel wall diameter (93.3%) were the most frequently observed features.

Newly presenting psychogenic nonepileptic seizures: incidence, population characteristics, and early outcome from a prospective audit of a first seizure clinic.

There are few published population-based data for psychogenic nonepileptic seizures (PNES). We prospectively identified first presentations of PNES from a population of 367,566, over 3 years. PNES were diagnosed in 68 patients, in 54 of whom the diagnosis was confirmed by video/EEG recording, indicating an incidence of 4.90/100,000/year. Median diagnostic delay was 0.6 ± 0.2 year. At presentation with PNES, our patients already had high rates of psychological morbidity, medically unexplained symptoms other than PNES, and economic dependence. At 3 months postdiagnosis, 27 of 54 patients (50.0%) were spell free. For 24 of the 27 patients (88.9%), spells ceased immediately on communication of the diagnosis. At 6 months, 24 of 54 patients (44.4%) were spell free. Poor early outcome was predicted by unemployment. Our data suggest that early outcome is good in patients with recent-onset PNES, but some patients relapse quickly.

Driving regulations and psychogenic non-epileptic seizures: perspectives from the United Kingdom.

The Driver and Vehicle Licensing Agency (DVLA) in the United Kingdom provides guidance on fitness to drive for patients with a number of medical illnesses, including epilepsy and psychogenic non-epileptic seizures (PNES). The Association of British Neurologists circulates a monthly electronic newsletter to its membership by email. We used this newsletter to survey its recipients on the driving advice they offer patients with PNES, and their awareness of current DVLA guidelines. 54 replies were received (19/54 were epilepsy specialists). 11/54 respondents were unaware of any DVLA guidance regarding PNES. Of 43/54 aware of DVLA guidance, only 7% felt that it was sufficient. 40% of respondents did not recommend any driving restriction. 68% of epilepsy specialists recommended driving restriction as compared to 54% of non-epilepsy specialists. 2 respondents reported patients with PNES who had an accident as a consequence of a non-epileptic attack. The risk of motor vehicle accidents in patients with PNES needs further study. Until the establishment of evidence-based guidelines, there is a need to seek consensus and provide sufficient guidance regarding driving for both patients with PNES and their clinicians.

Reading epilepsy.

Reading epilepsy is a rare epilepsy syndrome triggered by language related activity, in particular reading. Here we describe a patient with reflex seizures brought on specifically by reading in Arabic. The types of reading epilepsy, their typical clinical features, probable pathophysiology and management are discussed.

Syphilis presenting with headache and papilloedema.

A 41-year-old homosexual man presented with a 10-week history of headache without pressure features commencing 10 weeks after a new sexual contact. Three days after the headache onset he noticed intermittent, bilateral visual blurring, worse in the right eye. The visual disturbance persisted intermittently and led to his referral to a local ophthalmology department where he was found to have bilateral papilloedema. There were no other abnormal signs on full examination of other systems and no other abnormal ocular findings. Cerebral imaging studies were normal. A lumbar puncture revealed a raised opening pressure of 35 mm cerebrospinal fluid (CSF) with a white cell count of 58 cells/mcl (mainly lymphocytes). Venereal disease research laboratory (VDRL), Treponema pallidum haemagglutination (TPHA) and Inno-LIA tests confirmed the presence of neurosyphilis. HIV testing was negative. He was treated with CSF pressure reduction via repeat lumbar puncture and acetozolamide and procaine penicillin intramuscularly. He recovered and remains symptom free at 1 year.

Single gene disorders causing ischaemic stroke.

Stroke is the third most common cause of death and the leading cause of long-term neurological disability in the world. Conventional vascular risk factors for stroke contribute approximately to only forty to fifty percent of stroke risk. Genetic factors may therefore contribute to a significant proportion of stroke and may be polygenic, monogenic or multi-factorial. Monogenic (single gene) disorders may potentially account for approximately one percent of all ischaemic stroke. Monogenic stroke disorders include conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) and hereditary endotheliopathy, retinopathy, nephropathy and stroke (HERNS). In addition, other monogenic conditions such as sickle cell and Fabry disease also lead to stroke. These monogenic disorders cause either small vessel or large vessel stroke (or a combination of both) and serve as useful models for understanding and studying conventional stroke and cerebrovascular disease and its accompaniments such as vascular dementia.