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Background Multiple sclerosis (MS) is frequently diagnosed in people of reproductive age, many of whom will become pregnant following diagnosis. Although many women report an improvement in symptoms and relapses during pregnancy, symptoms such as fatigue and spasticity are commonly reported and can worsen. Prescribing medications during pregnancy and breastfeeding presents unique challenges and guidance on the use of symptomatic therapies is limited. Objectives This paper aims to provide a consensus on the current evidence base to facilitate informed decision-making and optimise pre-conception counselling. Methods A list of most commonly prescribed medications for symptom management in MS was created using pregnancy and MS-related READ codes in the Welsh GP Dataset, followed by a review by MS neurologists. Results A final list of 24 medications was generated for review. Searches were performed on each medication, and evidence graded using standardised criteria. Evidence-based recommendations were developed and distributed to experts in the field and revised according to feedback using modified Delphi criteria. Conclusions Our guidelines provide evidence-based recommendations on the safety of symptomatic therapies during pregnancy and breastfeeding for general practitioners and specialist teams working with people with MS who are hoping to embark on pregnancy or are currently pregnant. Individual risk–benefit ratios should be considered during pre-conception counselling to optimise symptom burden and minimise harm to both parent and child.

Neurologists increasingly use anti-CD20 therapies, including for women of childbearing age, despite these medications being unlicensed for use in pregnancy. Current evidence suggests that women can safely conceive while taking anti-CD20 therapy. Women should not be denied treatment during pregnancy when it is clinically indicated, although they should be counselled regarding live vaccinations for their infant. Women receiving regular ocrelizumab for multiple sclerosis should preferably wait 3 months before trying to conceive. There are few data around ofatumumab in pregnancy, and while there is probably a class effect across all anti-CD20 therapies, ofatumumab may need to be continued during pregnancy to maintain efficacy. We recommend that anti-CD20 therapies can be safely given while breast feeding. It is important to make time to discuss treatments with women of childbearing age to help them choose their most suitable treatment. Outcomes should be monitored in pregnancy registries.

ObjectiveTo identify factors predictive of relapse risk and disability in myelin oligodendrocyte glycoprotein associated disease (MOGAD).SettingPatients were seen by the neuromyelitis optica spectrum disorders (NMOSD) service in Liverpool, UK, a national referral centre for adult patients with MOGAD, NMOSD and related conditions.ParticipantsPatients with MOGAD=76 from England, Northern Ireland and Scotland were included in this cohort study.ResultsRelapsing disease was observed in 55% (42/76) of cases. Steroid treatment >1 month (OR 0.2, 95% CI 0.05 to 0.80; p=0.022), transverse myelitis (TM) at first attack (OR 0.03, 95% CI 0.004 to 0.23; p=0.001) and male sex (OR 0.16, 95% CI 0.04 to 0.68; p=0.014) were associated with monophasic disease (area under the curve=0.85). Male sex (HR 0.46, 95% CI 0.24 to 0.89; p=0.011) and TM at disease onset (HR 0.42, 95% CI 0.22 to 0.82; p=0.011) were also associated with an increased latency to first relapse. 45% (32/71) of patients became MOG-antibody negative and in relapsing patients negative seroconversion was associated with a lower relapse risk (relative risk 0.11 95% CI 0.05 to 0.26; pConclusionsMale patients with spinal cord involvement at disease onset have a lower risk of relapsing disease and longer latency to first relapse. Steroid treatment for at least 1 month at first attack was also associated with a monophasic disease course. MOG-antibody negative seroconversion was associated with a lower risk of relapse and may help inform treatment decisions and duration.

IntroductionPsychological distress is a major issue in multiple sclerosis (MS), having a significant impact on quality of life. Antidepressants are generally unhelpful for subsyndromal symptomatology, and psychological treatment approaches often not accessible or too cognitively demanding for some patients. There is an urgent need for low-cost interventions to improve wellbeing in MS.MethodsThis was a pilot randomised controlled trial (RCT) of Positive Mental Training (PosMT), a low intensity intervention providing training in positivity, optimism and resilience previously shown to improve anxious and depressive symptomotology. 28 patients with MS were randomised to the intervention and 30 to the control group.ResultsFollow-up data was obtained from 39 patents. The majority of participants receiving PosMT reported that they had used the intervention, with few reporting side effects. The intervention group reported a significant improvement in self-rated health as measured by the EuroQual visual analogue scale, F(4,34) = 3.204, p = 0.025, R2 = 0.274.DiscussionThis preliminary RCT found that PosMT in its current form could be used by patients with MS with little difficulty. Despite the small size of the study, allocation to the intervention was found to be associated with a significant improvement in self-rated health. Given the low cost of PosMT and its easy availability (it can simply be downloaded from a website), this pilot RCT suggests it could be a useful tool for MS patients. We believe this intervention warrants further study, ideally in a large multi-centre RCT.

BackgroundWe present baseline data on the first 50 participants recruited to the UK MS Pregnancy Register.MethodsData collected via questionnaires from consenting participants until 20th December 2021 were included.Results50 participants (all with relapsing remitting MS; mean age at diagnosis 28.0 years; mean age at recruitment 33.0 years) were included. Median EDSS was 2.5 (n=16). Gestation at recruitment ranged from 2 to 40 weeks. 78% had discussed their pregnancy in advance with their MS team. 90% of patients had ever taken DMT. Of the patients that stopped DMT (n=23), 16 reported stopping for pregnancy-related reasons. Of these, 39% stopped before pregnancy and 30% following conception. 15 women are continuing DMT during their current pregnancy, taking the following DMT: Glatiramer acetate (n=5), natalizumab (n=7), Peginterferon beta-1a (n=2), not recorded (n=1). In those with prior pregnancies, 61% (14/23) reported pregnancy loss with 1 case of a rare genetic condition in the baby. None of the prior pregnancy losses happened whilst on DMT. One participant reported previous PPH and foetal macrosomia and another reported previous pre-eclampsia.ConclusionsThese results show that a patient-facing pregnancy MS registry is feasible and can collect previous adverse pregnancy outcomes. Future results will inform clinicians and women about the safety of DMT and adjunctive medication during pregnancy and postpartum.

BackgroundThere is limited evidence to guide DMT prescribing prior to and during pregnancy, leading to wide variation in practice. In 2019, ABN consensus guidelines were published to address this. We set out to establish what impact these have had.MethodsAn online questionnaire was cascaded to UK MS neurologists. Individuals completed the ques- tionnaire anonymously.Results85 responses were obtained; 76 from DMT prescribers in a variety of settings. 74/76 (97%) were aware of the ABN guidelines. 74% reported a recent change in prescribing IFN-B and 70% in prescribing natalizumab around pregnancy, compared to 5% for alemtuzumab and 1% for teriflunomide and fingoli- mod. The ABN guidelines were the most commonly cited reason for change (58 individuals), followed by SmPC changes and influence from peers.There was significant variation in natalizumab prescribing - 51% ‘normally continue to prescribe’ until 34/40, 12% stop when pregnancy confirmed and 11% stop prior to conception. 58% encourage breastfeeding on natalizumab whilst 34% discourage this.ConclusionsThere remains significant variation in advice given to women with MS considering pregnancy. This is most marked with higher efficacy DMT, where risk-benefit decision making is complex. Additional data and resources for women with MS, including a UK MS Pregnancy register, are urgently needed.ruth.dobson@qmul.ac.uk

Objective: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Methods: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). Results: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3–14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3–24.9) months. In this ‘relapsing group’, relapse rate declined by 37% (95%CI=19–52%, p Conclusion: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.

International audience; Recombinant interferon alpha is used to treat several immunological, oncological, and infectious diseases,1 and various serious side-effects have been associated with its therapeutic use. We want to bring attention to the development of neuromyelitis optica spectrum disorder (NMOSD) [...]

Background The ABN Multiple Sclerosis (MS) pregnancy guidelines set out to combine best current evidence with expert consensus. They were developed to provide a practical framework to support neurologists when counselling women with MS regarding pregnancy. A key objective was to reduce variation in practice and increase clarity for patients in an area of uncertainty. Methods In order to assess the impact of these guidelines on practice, and assess ongoing areas of need, we conducted an online survey about MS and pregnancy. This survey was cascaded via email to UK neurologists between December 2019 and January 2020. Individuals completed this questionnaire anonymously. Results The majority of respondents reported changing their prescribing practice with interferon-beta preparations (IFN-B) and natalizumab. The ABN guidelines were the most commonly cited reason for change (76%). However, there was considerable variation in advice regarding the use of both DMTs in pregnancy. Conclusions There is substantial variation in advice given to women with MS around pregnancy, and this is reflected in prescribing practice by UK Neurologists. Awareness of national guidelines is good, and these have driven change in a majority of MS neurologists. There remains the need to continually update and communicate these guidelines, particularly as recommendations evolve with increasing evidence.

Biologic immunotherapies have transformed the treatment landscape of multiple sclerosis. Such therapies include recombinant proteins (interferon beta), as well as monoclonal antibodies (natalizumab, alemtuzumab, daclizumab, rituximab and ocrelizumab). Monoclonal antibodies show particular efficacy in the treatment of the inflammatory phase of multiple sclerosis. However, the immunological perturbations caused by biologic therapies are associated with significant immunological adverse reactions. These include development of neutralising immunogenicity, secondary immunodeficiency and secondary autoimmunity. These complications can affect the balance of risks and benefits of biologic agents, and 2018 saw the withdrawal from the market of daclizumab, an anti-CD25 monoclonal antibody, due to concerns about the development of severe, unpredictable autoimmunity. Here we review established and emerging risks associated with multiple sclerosis biologic agents, with an emphasis on their immunological adverse effects. We also discuss the specific challenges that multiple sclerosis biologics pose to drug safety systems, and the potential for improvements in safety frameworks.

The diagnosis and treatment of breast cancer can involve a series of life-altering, traumatic experiences, leading to distress, reduced quality of life, and long-standing fears of recurrence. Distress may exacerbate physical symptoms, impair coping, impact health behaviors, and reduce compliance with cancer treatment. Psychological treatments have focused on alleviating distress and improving quality of life. Given the growing evidence of the role of stress and behavior on cancer outcomes, a biobehavioral approach to treatment may serve to achieve these traditional treatment goals while also impacting disease course. Shapiro’s (2001) eye movement desensitization and reprocessing (EMDR) protocol for illness and somatic disorders was greatly informed by her interest in mind–body approaches to health and the newly emerging (1992) field of psychoneuroimmunology. The protocol includes first identifying and addressing the realistic fears and challenges a woman faces. Once appropriate, EMDR therapy turns to the reprocessing of past memories, present triggers, and the development of positive future templates of health. This article focuses on situations, usually in the early diagnosis and intensive phases of cancer treatment, when the reprocessing phases of EMDR therapy need to be delayed because of the demands of cancer treatment or insufficient client stability. Resourcing interventions that are compatible with biobehavioral goals are provided, with brief clinical examples.

Prion diseases are unique in medicine as in humans they occur in sporadic, genetic, and acquired forms. The most common human prion disease is sporadic Creutzfeldt-Jakob disease (CJD), which commonly presents as a rapidly progressive dementia (RPD) with behavioral, cerebellar, extrapyramidal, and some pyramidal features, with the median survival from symptom onset to death of just a few months. Because human prion diseases, as well as other RPDs, are relatively rare, they can be difficult to diagnose, as most clinicians have seen few, if any, cases. Not only can prion diseases mimic many other conditions that present as RPD, but some of those conditions can present similarly to prion disease. In this article, the authors discuss the different etiologic categories of conditions that often present as RPD and also present RPDs that had been misdiagnosed clinically as CJD. Etiologic categories of conditions are presented in order of the mnemonic used for remembering the various categories of RPDs: VITAMINS-D, for vascular, infectious, toxic-metabolic, autoimmune, mitochondrial/metastases, iatrogenic, neurodegenerative, system/seizures/sarcoid, and demyelinating. When relevant, clinical, imaging, or other features of an RPD that overlap with those of CJD are presented.

Prion diseases are unique in medicine as in humans they occur in sporadic, genetic, and acquired forms. The most common human prion disease is sporadic Creutzfeldt-Jakob disease (CJD), which commonly presents as a rapidly progressive dementia (RPD) with behavioral, cerebellar, extrapyramidal, and some pyramidal features, with the median survival from symptom onset to death of just a few months. Because human prion diseases, as well as other RPDs, are relatively rare, they can be difficult to diagnose, as most clinicians have seen few, if any, cases. Not only can prion diseases mimic many other conditions that present as RPD, but some of those conditions can present similarly to prion disease. In this article, the authors discuss the different etiologic categories of conditions that often present as RPD and also present RPDs that had been misdiagnosed clinically as CJD. Etiologic categories of conditions are presented in order of the mnemonic used for remembering the various categories of RPDs: VITAMINS-D, for vascular, infectious, toxic-metabolic, autoimmune, mitochondrial/metastases, iatrogenic, neurodegenerative, system/seizures/sarcoid, and demyelinating. When relevant, clinical, imaging, or other features of an RPD that overlap with those of CJD are presented.

Neuromyelitis optica typically presents at a median age of 40-50 years. The myelitis is usually of acute onset, long (>3 vertebral segments) and causes severe sensorimotor and bladder and bowel disturbances. We describe a 73-year-old Caucasian woman with aquaporin-4 antibody-positive neuromyelitis optica whose index event was intermittent paroxysmal tonic spasms (and no other myelitis features) that recurred for 6 months and was associated with a short spinal cord lesion on MRI. This case reiterates recent observations that neuromyelitis optica can occur in older persons, and its myelitis can be 'short' and clinically mild.

“Translating Research Into Practice” is a new regular journal feature in which clinicians share clinical case examples that support, elaborate, or illustrate the results of a specific research study. Each column begins with the abstract of that study, followed by the clinician’s description of their own application of standard eye movement desensitization and reprocessing (EMDR) procedures with the population or problem treated in the study. The column is edited by the EMDR Research Foundation with the goal of providing a link between research and practice and making research findings relevant in therapists’ day-to-day practices. In this issue’s column, Katy Murray references Sprang’s (2001) study, which investigated EMDR treatment of complicated mourning and describes how she used EMDR with three challenging cases—a mother mourning for her young adult son who died by suicide, a woman struggling with the loss of her mother to Alzheimer’s disease, and a young mother whose baby was stillborn. Case examples are followed with a comprehensive discussion.

The Clinical column is a regular Journal of EMDR Practice and Research feature in which master clinicians answer a question posed by a reader who is requesting assistance with clinical challenges. In this issue’s column, the response is written by Katy Murray, who is a licensed independent clinical social worker and an EMDRIA-approved consultant in Olympia, Washington. Readers can send questions for future issues to journal@emdria.org.

Introduction Establishing an early clinical diagnosis in variant Creutzfeldt–Jakob disease (vCJD) can be difficult, resulting in extended periods of uncertainty for many families and sometimes a view that patients have been subjected to unnecessary investigations. This issue is accentuated by the progressive nature of vCJD and by the difficulty in achieving a confident clinical diagnosis before an advanced stage of illness. Although diagnostic delay may be a result of the non-specific early clinical features, a systematic analysis of the process of diagnosis was undertaken, with the aim of trying to achieve earlier diagnosis of vCJD. Methods Retrospective case file analysis was undertaken of the first 150 definite and clinically probable cases of vCJD identified by the UK surveillance system. Results There is a significant interval between illness onset and presentation to a primary care physician, which is influenced by the nature of the initial clinical features. Neurological review is invariably sought following the development of clinical signs and a diagnosis is then established relatively quickly. Despite the progressive clinical course, a confident clinical diagnosis is not usually achieved until a relatively advanced stage of illness (mean time to diagnosis 10.5 months) with a more rapid clinical progression accounting for those cases diagnosed earlier after symptom onset. Conclusions Early clinical diagnosis in vCJD is not possible in the great majority of cases because of non-specific initial symptoms. Once neurological signs develop, a diagnosis is usually made promptly but this is often at a relatively advanced stage of illness. The inherent delays in the diagnosis of vCJD have implications for those involved in both public health and therapeutics.

Objective Although surgical transmission of Creutzfeldt–Jakob disease (CJD) has been demonstrated, these iatrogenic cases account for only a small proportion of all CJD cases. The majority are sporadic CJD (sCJD) cases of unknown cause. This study investigated whether some cases classified as sCJD might have an unrecognized iatrogenic basis through surgical or other medical procedures Methods This study compared medical risk factors from 431 sCJD cases referred 1998 to 2006 with 454 population control subjects. Possible geographic and temporal links between neurological and gynecological operations in 857 sCJD cases referred from 1990 to 2006 were investigated Results A reported history of ever having undergone surgery was associated with increased risk for sCJD (odds ratio, 2.0; 95% confidence interval, 1.3–2.1; p = 0.003). Increased risk was not associated with surgical categories chosen a priori but was confined to the residual category “other surgery,” in which the increase in risk appeared most marked for three subcategories: skin stitches, nose/throat operations, and removal of growths/cysts/moles. No convincing evidence was found of links (same hospital, within 2 years) between cases undergoing neurosurgery or gynecological surgery Interpretation It is unlikely that a high proportion of UK sCJD cases are the result of transmission during surgery, but we cannot exclude the possibility that such transmission occurs occasionally. A study based on accurate surgical histories obtained from medical records is required to determine whether the increased risk associated with reported surgical history reflects a causal association or recall bias. Ann Neurol 2007

Background: Sporadic Creutzfeldt–Jakob disease (CJD) is a condition predominantly affecting older age groups, with cases aged less than 45 years rare and an age at onset or death of less than 20 years exceptional. Methods: Data from the systematic study of sporadic CJD in the UK are available from 1970 onwards. Clinical and pathological data are reviewed in order to identify atypical cases, including those at the extremes of the age range of sporadic CJD. Detailed analysis of atypical cases is undertaken, and in selected cases laboratory transmission studies are carried out in order to provide information on the characteristics of the infectious agent. Results: In the UK, two cases of sporadic CJD in adolescents have been identified, dying at ages 16 and 20 years. The first case predated the epidemic of bovine spongiform encephalopathy and the characteristics of the second case, including laboratory transmission studies, are consistent with a diagnosis of sporadic rather than variant CJD. Conclusion: The cases in this report indicate that sporadic CJD can develop at a very young age, that variant CJD is not the only form of CJD occurring in this age group and that neuropathological examination is essential for accurate diagnosis of human prion disease.

Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low (p o = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher (p o = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder.

A young man in his late teens presented with a four week history of malaise, vomiting, anorexia, and 7 kg weight loss. He was dehydrated and barium follow through revealed a band like obstruction of the 3rd and 4th parts of the duodenum. Following rehydration and normalisation of his biochemistry he had three generalised tonic-clonic seizures and was started on sodium valproate. This failed to control his seizures and phenytoin was added. He also experienced visual hallucinations, for instance seeing toilet seats being swallowed up. Laparotomy confirmed duodenal obstruction secondary to Wilkie’s syndrome (obstruction between the angle of the aorta and superior mesenteric artery, seen in association with weight loss). A duodeno-jejunal anastamosis was performed. Postoperatively his neurological condition deteriorated with increasing confusion, headache, and left sided myoclonus and weakness so he was transferred to the neurology service. The past medical history was revisited. He had had a normal birth and childhood milestones but he had always been thin and weak with reduced exercise tolerance compared to his two siblings. He had complained of intermittent abdominal pain and vomiting since the age of 5. He had no family history of neurological or gastrointestinal disease. It also turned out that he had been bitten by a tick three weeks before admission. On examination he was underweight at 40 kg with generalised muscle wasting and bilateral pes cavus. The most striking finding was epilepsia partialis continua (EPC) affecting the left arm and leg. He had a left homonymous hemianopia, dysarthria, and horizontal nystagmus on right gaze. In addition he had a left hemiparesis (MRC grade 2) and left sided sensory impairment (all modalities). Upper limb reflexes were normal but lower limb reflexes were absent. He had a very large number of investigations during the course of this admission and these are summarised …

Objectives The possibility of vertical transmission of variant Creutzfeldt–Jakob disease (vCJD) has been raised because of the widespread distribution of infectivity in vCJD and the demonstration that this condition can be transmitted through blood transfusion. The aim of this study is to search for evidence of this type of transmission of vCJD. Methods A national surveillance system for CJD has been established in the UK since 1990. Through this register, details were extracted of all children born to vCJD cases up to March 2009. This list was checked against the CJD register and cases identified through the UK study of Progressive Intellectual and Neurological Deterioration in children to determine whether any of the children of vCJD cases had themselves developed a progressive neurological disorder or vCJD. Results 125 children were born to parents with a diagnosis of vCJD. Nine of these children were born to females with vCJD who were symptomatic at conception, birth or within a year of clinical onset. Only one woman was known to have breast fed her child. None of the children of vCJD cases have been referred to the National CJD Surveillance Unit as suspected vCJD and none have been classified as suffering from a progressive neurodegenerative disorder through the Progressive Intellectual and Neurological Deterioration study. One of the children has been investigated by the National Prion Unit (see accompanying case report). Interpretation To date there is no evidence of vertical transmission of vCJD. However, the incubation period through this mechanism might be prolonged and it will be many years before observational data can exclude this possibility.

We report the first cases of Edwardsiella ictaluri causing epizootics in laboratory populations of Zebrafish Danio rerio. Edwardsiella ictaluri is primarily recognized as a disease of catfish species and is known to cause an economically important bacterial disease of farm-raised catfish in the USA and abroad; however, it has been isolated on occasion from 10 other genera of nonictalurid fishes. We isolated E. ictaluri from moribund Zebrafish held in quarantine at two different universities in two states and from a research facility in a third state between February 23 and December 6, 2011. Edwardsiellosis in Zebrafish can be described as a severe systemic disease characterized by tissue necrosis and the presence of large numbers of extracellular and intracellular bacteria, often within macrophages. The kidneys (pronephros and mesonephros), spleen, nares, and forebrain were the most commonly and severely affected tissues. In outbreaks, mortality was acute and numerous fish died over a 1–2 week period. Mortality continued until the majority of the population was lost, at which time the remaining fish were euthanized. In addition to these cases, four cultures of bacteria isolated from Zebrafish by another diagnostic laboratory were submitted to the Louisiana Aquatic Diagnostic Laboratory for identification and were confirmed as E. ictaluri. In total, eight cultures of E. ictaluri from Zebrafish from Louisiana, Massachusetts, Pennsylvania, and Florida were identified. The isolates were confirmed as E. ictaluri by biochemical phenotype, API 20E (bioMérieux), and amplification and sequencing of a portion of the 16S rRNA gene. Edwardsiella ictaluri isolates from Zebrafish are believed to comprise a unique group and were differentiated from catfish isolates by exhibiting weaker motility, autoaggregation in broth, a different plasmid profile (two plasmids of 4.0 and 3.5 kb), a different API 20E code (4204000), and lack of lipopolysaccharide recognition with Mab Ed9.

Objective Variant Creutzfeldt–Jakob disease (vCJD), a novel form of human prion disease, was recognized in 1996. The disease affected a younger cohort than sporadic CJD, and the early clinical course was dominated by psychiatric and sensory symptoms. In an attempt to aid diagnosis and establish standardization between surveillance networks, diagnostic criteria were established. These were devised from the features of a small number of cases and modified in 2000 as the clinical phenotype was established. Since then, only minor changes have been introduced; revalidation of the criteria in the current format is overdue. Methods Included in this study are autopsy/cerebral biopsy-proven cases of vCJD referred to the National CJD Surveillance Unit (NCJDSU) between 1995 and 2004 and suspect cases in which an alternative diagnosis was identified following autopsy/cerebral biopsy. Results Over the 10-year period, 106 definite cases of vCJD and 45 pathologically confirmed “noncases” were identified from the archives of the NCJDSU. The median age at onset of the cases was significantly younger than that of the noncases (27 years [range, 12–74 years] vs 43 years [range, 10–64 years]), and the median duration of illness was significantly shorter (14 months [range, 6–39 months] vs 22 months [range, 2–139 months]). The most commonly identified core clinical feature in cases was dementia; persistent painful sensory symptoms were the least frequent. Eighty-eight of 106 (83%) vCJD cases were retrospectively classified as probable in life, 6 cases were classified as possible. Most cases were classified as probable on the basis of core clinical features and brain magnetic resonance imaging. To date, the diagnostic criteria remain 100% specific, with no autopsy/cerebral biopsy-proven noncases classified as probable in life. Interpretation This study confirms that the diagnostic criteria for vCJD are sensitive and specific and provide a useful standard framework for case classification in a surveillance setting. ANN NEUROL 2010

Objective: To determine the frequency, in the UK, of sporadic Creutzfeldt–Jakob Disease (sCJD) with a cerebellar ataxic onset, and to describe the clinical features of the syndrome. Methods: A retrospective review of autopsy-proved cases of sCJD cases in the UK, 1990–2005, identifying those presenting with cerebellar features without early cognitive decline. Results: 29 of 618 (5%) patients with sCJD had an isolated cerebellar onset. Mean illness duration was 9 months. Subsequently, 21 (72%) developed myoclonus and 23 (79%) developed pyramidal features. Magnetic resonance imaging showed high signal in the basal ganglia in 11 of 14 (79%) patients. 7 of 15 (47%) patients were valine homozygotic at prion protein gene ( PRNP )-129. Only 8 (28%) cases were referred to the surveillance unit after death. Conclusion: A better definition of sCJD presenting with an isolated cerebellar syndrome might improve future case recognition and contribute to the determination of its cause.

Background: The Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD) is commonly understood to represent cases with early, prominent visual complaints. The term is clarified to represent those who present with isolated visual symptoms. This group may pose diagnostic difficulties and often present to ophthalmologists where they may undergo needless invasive procedures. Method: A retrospective review of 594 pathologically proved sCJD cases referred to the UK National CJD Surveillance Unit over a 15 year period to identify Heidenhain cases. Results: 22 cases had isolated visual symptoms at onset with a mean illness duration of 4 months. The mean age at disease onset was 67 years. Most displayed myoclonus, pyramidal signs, and a delay in the onset of dementia for some weeks. 17 (77%) were referred initially to ophthalmology. Two underwent cataract extraction before diagnosis. All tested cases were homozygous for methionine at codon 129 of the prion protein gene. Conclusions: This rare, but clinically distinct, group of patients with sCJD may cause diagnostic difficulties. Because ocular intervention carries with it the risk of onward transmission awareness of this condition among ophthalmologists is important.