BACKGROUND:Cognitive dysfunction may be a sequelae of N-Methyl-D-Aspartate receptor encephalitis (NMDAR encephalitis) with working memory commonly affected. This study examined cognitive outcomes in patients treated for NMDAR encephalitis using a neurocognitive test battery and a working memory paradigm, compared with healthy controls & patients with schizophrenia. METHODS:Adult patients previously treated for NMDAR encephalitis were assessed using the Cambridge Automated Neuropsychological Test Battery (CANTAB) for working memory & episodic memory. Patients completed the N-back task during functional MRI (fMRI) scanning. Results were compared to patients with schizophrenia and healthy controls from a prior study. RESULTS:Twelve patients were recruited [11 women; mean (SD) age 37(12) years; Mean (SD) duration until immunotherapy treatment 7.09 (2.43) weeks]. Data were compared to 14 patients with schizophrenia [10 women; mean (SD) age 39 (12) years] and 14 healthy controls [7 women; mean (SD) age 30 (6) years]. Significant differences in letter number sequencing, spatial working memory, logical memory I, 1-back, and 2-back performance were observed (Cohen's d = 0.766 to 1.254, p< 0.05), driven by poorer performance by patients with schizophrenia. While patients with NMDAR encephalitis exhibited slightly lower performance compared with healthy controls, none of these differences were statistically significant. No significant differences in neural activation during 1-back or 2-back performance were observed. CONCLUSIONS:Study findings suggest cognitive performance in patients treated for NMDAR encephalitis approaches normal over time. Prompt treatment with immunotherapy is associated with improved cognitive outcomes. Psychiatric services should be aware of the clinical features of autoimmune encephalitis.

To report the first Irish family with Salla disease; to expand the phenotype by the first description of myoclonus in this condition; to report new radiological features.

Introduction Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) represent an over- lapping spectrum characterised pathologically by TDP-43 positive inclusions in the Central Nervous System. C9orf72 repeat expansions are the most frequent causes of familial FTD/ALS. We present a case which demonstrates the increasingly recognised clinical heterogeneity associated with this genetic alteration. Case A 64-year-old male presented with progressive neuropsychiatric decline over four weeks. He had no known family history of neurodegeneration. At initial review, he had non fluent speech, confusion, marked rigidity, and upper limb myoclonus. He rapidly became increasingly unresponsive and immobile. His genetic testing detected a pathogenic repeat expansion in C9orf72. He died within 6 months of initial presentation. Postmortem showed TDP43 inclusions in the striatum and substantia nigra, and p62 pathology in the temporal and frontal neocortex, hippocampus, striatum and cerebellum consistent with C9Orf72 repeat expansion pattern. Discussion This case adds to the literature detailing a range of phenotypic variability associated with C9orf72 expansions. In addition to the classic ALS/FTD presentation, C9orf72 can cause other dementia syndromes, parkinsonism and more complex movement disorders. This case was particularly remarkable for its fulminant course. We suggest C9orf72 expansion should be considered in patients with a rapidly progressive dementia.

Haploinsufficiency of the methyl-CpG-binding domain protein 5 (MBD5) gene causes a neurodevelopmental disorder that includes intellectual disability, developmental delay, speech impairment, seizures, sleep disturbances, and behavioral difficulties. Microdeletion of 2q23.1 is the most common cause of haploinsufficiency, although MBD5 haploinsufficiency may also cause this genetic disorder. We report a family harboring a heterozygous loss-of-function variant in MBD5 (NM_018328.5:c.728delC; p.Pro243Hisfs*26), which includes three affected siblings with varying phenotypic features. Both parents were phenotypically normal but deep coverage sequencing of the parents showed germline mosaicism in the mother.

Cork University Hospital acts as the tertiary referral centre for the HSE southern area, with a catchment population of 1.2 million [1]. The neurology registrars receive telephone consultations from hospitals and primary care practices in the region. While there have been a number of studies examining inpatient neurology consultations in Irish hospitals [2–6], there is a paucity of data examining the support provided by tertiary referral centres to other acute hospitals and primary care centres in their region. The aim of this study is to define the workload of the neurology registrar with respect to telephone consultations and to examine the quality of these referrals. All calls received from the 19th of October 2021 to the 25th of February 2022 were logged by the receiving registrar. Information collected pertained to the nature of the consult and completeness of the referral. The average volume of calls during the study period was six per week. The median call duration was 8 min. The cumulative time spent resolving outside calls during the study period was at least 41.25 hours. Sixty-three per cent of calls were from other acute hospitals in the region. Thirty-nine per cent of referrals were deemed incomplete with respect to either history, collateral history or examination. This is a necessary service in a system that is not adequately resourced to provide specialist led care in all hospitals. A greater emphasis on complete and accurate referrals, along with robust communication and documentation, could reduce the inherent risk associated with such consultations.

Pain is an often-reported symptom in Multiple Sclerosis (MS); however, pain management is often described as being inadequate. Emerging evidence suggests that cannabinoids may be effective in the treatment of MS related pain. This research aimed to determine the prevalence and patterns of use of medications and cannabinoids for pain relief in a sample of Irish patients with MS.

A 23- year-man post female to male (FTM) gender transition was found to have bilateral papilloedema at a routine optician visit. The patient was referred on for formal ophthalmological and neurological assessments. Optical coherence tomography (OCT) confirmed the presence of bilateral papilloedema. The patient was entirely asymptomatic and had no medical history. He took testosterone intramuscularly once per month. Neurological examination was otherwise normal. Investigations including routine blood panels, CT brain, MRI brain and cerebral MR venogram were all normal. Lumbar puncture yielded cerebrospinal fluid (CSF) normal in appearance but demonstrated raised intracranial pressure. In the absence of other causative aetiologies a diagnosis of idiopathic intracranial hypertension (IIH) was made. Treatment was commenced with acetazolamide and the patient was discharged with outpatient ophthalmological and neurological follow-up.

Acquired vocal cord paralysis (VCP) is caused by dysfunction or injury of one or both recurrent laryngeal nerves. Here we report a 41-year-old man with spinocerebellar atrophy, autosomal recessive type 10 (SCAR10) due to an autosomal recessive mutation in the ANO10 gene, with VCP as the presenting symptom. He later developed ataxia and speech disturbance.

Next generation sequencing provides an important opportunity for improved diagnosis in epilepsy. To date, the majority of diagnostic genetic testing is conducted in the paediatric arena, while the utility of such testing is less well understood in adults with epilepsy. We conducted whole exome sequencing (WES) and copy number variant analyses in an Irish cohort of 101 people with epilepsy and co-morbid intellectual disability to compare the diagnostic yield of genomic testing between adult and paediatric patients. Variant interpretation followed American College of Medical Genetics and Genomics (ACMG) guidelines. We demonstrate that WES, in combination with array-comparative genomic hybridisation, provides a diagnostic rate of 27% in unrelated adult epilepsy patients and 42% in unrelated paediatric patients. We observe a 2.7% rate of ACMG-defined incidental findings. Our findings indicate that WES has similar utility in both adult and paediatric cohorts and is appropriate for diagnostic testing in both epilepsy patient groups.

Ataxia pancytopenia (ATXPC) syndrome due to gain-of-function pathogenic variants in theSAMD9Lgene has been described in 38 patients to date. It is characterized by variable neurological and hematological phenotypes including ataxia, pyramidal signs, cytopenias, and hematological malignancies. Peripheral neuropathy with slowing of conduction velocities has been reported in only two affected individuals. We describe a female with childhood onset neuropathy diagnosed as Charcot-Marie-Tooth disease type 1 with onset of cerebellar ataxia in her 50s. Cerebellar, pyramidal, and neuropathic features were found on examination. Additionally, she also had conjunctival telangiectasia. Nerve conduction studies confirmed a demyelinating neuropathy. MRI brain showed cerebellar atrophy with diffuse white matter hyperintensities. OCT demonstrated global thinning of the retinal nerve fiber layer (RNFL). Full blood count has always been normal. A previously described pathogenic variant inSAMD9L[c.2956C>T p.(Arg986Cys)] was identified on whole exome sequencing. This case extends the previously described phenotype to include conjunctival telangiectasia and RNFL thinning and suggests that ATXPC syndrome should be considered in the differential for inherited demyelinating neuropathies.

A 24-year-old woman presented with bilateral blurring of her distance vision and ‘dizzy spells’. She had no other neurological symptoms or medical history. She consulted an optometrist, and optical coherence tomography (OCT) was performed, which demonstrated papilloedema. She was referred to the local eye clinic for assessment and from there was referred for neurological assessment.Her initial investigations revealed no abnormalities, and brain imaging was reported to be normal. In the absence of an alternative diagnosis, idiopathic intracranial hypertension (IIH) was considered and a lumbar puncture was performed. This showed elevated protein but normal cerebrospinal fluid (CSF) pressure. MRI of the brain the next day revealed a large cerebellopontine lesion in keeping with vestibular schwannoma. She was referred to neurosurgery for operative management.This case highlights three interesting points: the aetiology of her papilloedema without raised intracranial pressure, the decision to perform a lumbar puncture in suspected IIH and community OCT as a clinical adjunct.

Genomics is revolutionizing biomedical research, medicine and healthcare globally in academic, public and industry sectors alike. Concrete examples around the world show that huge benefits for patients, society and economy can be accrued through effective and responsible genomic research and clinical applications. Unfortunately, Ireland has fallen behind and needs to act now in order to catch up. Here, we identify key issues that have resulted in Ireland lagging behind, describe how genomics can benefit Ireland and its people and outline the measures needed to make genomics work for Ireland and Irish patients. There is now an urgent need for a national genomics strategy that enables an effective, collaborative, responsible, well-regulated, and patient centred environment where genome research and clinical genomics can thrive. We present eight recommendations that could be the pillars of a national genomics health strategy.

Genomics is revolutionizing biomedical research, medicine and healthcare globally in academic, public and industry sectors alike. Concrete examples around the world show that huge benefits for patients, society and economy can be accrued through effective and responsible genomic research and clinical applications. Unfortunately, Ireland has fallen behind and needs to act now in order to catch up. Here, we identify key issues that have resulted in Ireland lagging behind, describe how genomics can benefit Ireland and its people and outline the measures needed to make genomics work for Ireland and Irish patients. There is now an urgent need for a national genomics strategy that enables an effective, collaborative, responsible, well-regulated, and patient centred environment where genome research and clinical genomics can thrive. We present eight recommendations that could be the pillars of a national genomics health strategy.

Background: Late-onset Tay-Sachs disease (LOTS) is an autosomal-recessive lysosomal storage disease caused by deficient beta-hexosaminidase A activity. LOTS is rare in the Ashkenazi Jews, but even rarer in the non-Jewish population. Cases: We report an Irish family expanding the LOTS phenotype (ataxia, diffuse muscle wasting, dystonia, chorea, belly dancer's dyskinesia, and neuropsychiatric features) associated with the known HEXA variant 1073 + 1G > A and a novel variant c.459 + 24G > C. Conclusions: LOTS should be considered in patients with similar symptoms and cerebellar atrophy on brain imaging.