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.

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.

Pure red cell aplasia and myasthenia gravis: a patient having both autoimmune conditions in the absence of thymoma.

This is a patient who was presented initially with symptoms of malaise, tiredness and exertional dyspnoea and found to have a severe normocytic normochromic anaemia with low reticulocyte counts. Bone marrow confirmed the diagnosis of pure red cell aplasia (PRCA) and at the time serology for recent parvovirus infection was positive. He was successfully treated with transfusions and intravenous Ig. Six years later, he had a mild relapse of his PRCA and subsequently developed severe dysphagia and dysarthria which were fatigable. Positive antiacetylcholine receptor antibodies confirmed the diagnosis of myasthenia gravis. The two conditions are both known to be associated with thymoma. Imaging and resection of the thymus gland showed only the presence of a thymic cyst. Treatment with pyrdistogmine and intravenous Ig have kept the patient asymptomatic and in remission. The rare association of the two autoimmune conditions associated in the same patient without thymoma is discussed.

Postintervention acute opsoclonus myoclonus syndrome.

Opsoclonus myoclonus syndrome (OMS) is a rare, neurological condition affecting 1 in 10 000 000 people annually. Opsoclonus, defined as involuntary rapid, multivectorial oscillations of the eyes, together with ataxia and myoclonus are usually present. OMS may be paraneoplastic: often associated with occult neuroblastoma in childhood and with breast carcinoma or small cell lung carcinoma in adults. Other aetiologies include viral or toxic agents. The pathogenesis is thought to be immune mediated. A 37-year-old woman with previous inflammatory cranial mononeuropathies was admitted for elective dilatation and curettage (D&C). Immediately after she complained of left-sided paraesthesia and later became disoriented, with incoherent speech, inability to obey commands, opsoclonus of the eyes and myoclonic jerks. Investigations including onconeuronal antibodies, cerebrospinal fluid analysis, and imaging were normal. She was treated with intravenous methylprednisolone with rapid improvement. Previous surgeries with anaesthesia were uncomplicated. The anaesthetic agents used for the D&C were fentanyl and propofol.

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.