Genetic landscape of ALS in Malta based on a quinquennial analysis.

Genetic risk for amyotrophic lateral sclerosis (ALS) is highly elevated in genetic isolates, like the island population of Malta in the south of Europe, providing a unique opportunity to investigate the genetics of this disease. Here we characterize the clinical phenotype and genetic profile of the largest series of Maltese ALS patients to date identified throughout a 5-year window. Cases and controls underwent neuromuscular assessment and analysis of rare variants in ALS causative or risk genes following whole-genome sequencing. Potentially damaging variants or repeat expansions were identified in more than 45% of all patients. The most commonly affected genes were ALS2, DAO, SETX and SPG11, an infrequent cause of ALS in Europeans. We also confirmed a significant association between ATXN1 intermediate repeats and increased disease risk. Damaging variants in major ALS genes C9orf72, SOD1, TARDBP and FUS were however either absent or rare in Maltese ALS patients. Overall, our study underscores a population that is an outlier within Europe and one that represents a high percentage of genetically explained cases.

Immune-mediated ophthalmoparesis with anti-GD1a antibodies.

A young woman presented to neurology with a 1 month history of progressive diplopia on lateral gaze and a 1 week history of headaches. On examination she was found to have complex ophthalmoparesis with binocular horizontal diplopia, failure of abduction bilaterally and limited upgaze with convergence-retraction nystagmus. The rest of the neurological examination was normal. She was admitted for investigations: blood, CT brain, MR brain and lumbar puncture results were normal. Anti-GD1a antibodies were strongly positive; anti-GM1, anti-GM2 and anti-GD1b were also positive. On follow-up 3 weeks later, the complex ophthalmoplegia persisted. It was decided to treat with intravenous immunoglobulins (IVIgs) with good response but recurrence at 2 weeks post infusion. She was treated with 4 weekly IVIg courses and remains responsive and controlled over 1 year since presentation but becomes symptomatic in the week running up to each dose; thus, disease modifying treatment is currently being considered.

Late-onset radiation-induced brachial plexopathy.

The late-onset variant of radiation-induced brachial plexopathy is most often seen after treatment for breast or lung cancers. It has an insidious onset, with symptoms noted years after receiving radiotherapy, and the condition gradually continues to deteriorate with time. We present the case of an elderly man who we saw in view of worsening paraesthesias and weakness of his left arm with associated prominent muscle wasting along the left shoulder girdle. Fifteen years prior to this, he had received radiotherapy for the treatment of nasopharyngeal carcinoma.

Guillain-Barré syndrome after COVID-19 vaccination.

We report a case of Guillain-Barré syndrome (GBS) occurring soon after the first dose of Vaxzevria (previously known as COVID-19 vaccine AstraZeneca). Thus far, there has been no evidence of an increased risk of GBS resulting from either COVID-19 infection nor from COVID-19 vaccines; however, individual cases and population cohorts should be scrutinised, in order to ensure the constant evaluation of such risks. It is as yet not possible to draw conclusions about any significant association between COVID-19 vaccination and GBS. A temporal correlation does not imply, and should not be deemed to signify, causality. However, it is important to remain vigilant, so that any potential increased risk is properly evaluated. The specific presentation of bifacial weakness as the initial symptom may be a characteristic feature of GBS in the context of recent COVID-19 vaccination.

Eagle's syndrome: a piercing matter.

We present an unusual case of Eagle's syndrome with bilateral internal carotid artery dissection in a 45-year-old man. Initial symptomatology included ipsilateral headaches and facial sensory symptoms. A right horner's syndrome was present on clinical examination. Radiological imaging revealed an old infarct, with bilateral carotid dissections and bilateral elongated styloid processes consistent with Eagle's syndrome. Despite initiation of secondary prevention with antiplatelet therapy, he had two further ischaemic events. The case highlights the symptomatology and complications of Eagle's syndrome, with its management discussed through a review of similar case reports.

Anti-HMGCR antibody-associated necrotising myopathy and its association with statin use.

A 66-year-old man presented with chest pain and a 1-year history of generalised weakness, accompanied with generalised aches and pains. Symptoms worsened when he was initiated on statins. Investigations yielded high creatine kinase, high HMG-coenzymeA reductase (HMGCR) antibody titre, myopathic features on electromyography and muscle biopsy, and muscle atrophy on MRI. These results were in keeping with anti-HMGCR antibody myopathy. The patient responded well to immunosuppressive therapy.

MRI-verified "asleep" deep brain stimulation in Malta through cross border collaboration: clinical outcome of the first five years.

INTRODUCTION: Deep Brain Stimulation (DBS) requires a specialist multidisciplinary approach and lifelong follow-up. Patient access can be a challenge for small nation states. Malta is an island nation with a population of just under 450 000. The number of patients likely to benefit from DBS is around 5 to 10 per year. This study explores the outcome of a cross border collaboration between specialist services at Queen Square, London and a tertiary centre in Malta. MATERIAL AND METHODS: Between 2011 and 2015, 35 patients underwent MRI-Guided and MRI-Verified DBS with 29 receiving bilateral subthalamic nucleus (STN) DBS for Parkinson's Disease under general anaesthesia. Pre-operative motor function was compared with one year post-operative motor function assessments in 26 patients (16 male; age 60 ± 9, range 32-70; disease duration 8.8 ± 2.7). Pre-operative and post-operative quality of life scores were also completed in 24 patients. RESULTS: There was significant improvement in off-medication Unified Parkinson's Disease Rating Scale (UPDRS) III motor function (41.7%), reduction in Levodopa Equivalent Dose (LED) (30.6%) and improvement in quality of life as measured by the Parkinson's Disease Questionnaire (PDQ-39) (52.3%) (p < .001). All PDQ-39 dimensions showed significant improvement except communication, with greatest benefit in activities of daily living (ADLs) (72.4%) and stigma (66.3%). Surgical complications did not lead to any permanent deficit. Patients receiving DBS to other targets and for different indications also benefitted from surgery. CONCLUSION: An MRI-guided and MRI-verified approach to DBS was successfully implemented through cross border collaboration with achievement of expected clinical results. This healthcare collaboration developed out of necessity and opportunity, taking advantage of a UK-based neurosurgeon from Malta. The UK healthcare system benefits from numerous immigrants at Consultant level. Such a mutually beneficial arrangement could enable such individuals to offer their expertise to citizens in the UK as well as their country of origin.

An unusual case of Parinaud's syndrome.

A 25-year-old man presented with blurred vision, headache and dizziness. On questioning, there was also a history of a preceding diarrhoeal illness. Initial investigations were normal. However, after a week, he represented with a Parinaud's syndrome. In view of the preceding diarrhoea, the transient unsteadiness and the areflexia on examination, anti-GQ1b antibodies were requested. The resulting titre was positive confirming the suspected diagnosis of Miller Fisher syndrome. He responded to intravenous immunoglobulins with full resolution of his symptoms and signs. Although various unusual neuro-ophthalmological signs have been reported localising to the brainstem, to our knowledge, this is the first case report of Parinaud's syndrome being the presenting symptom of Miller Fisher syndrome.