Tim Lynch

Mater Misericordiae University Hospital | MMUH · Department of Neurology

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of cl...

Background: Though uncommon, primary movement disorders can occur in pregnancy, the most common being restless legs syndrome and chorea gravidarum [1]. New onset dystonia in pregnancy has been reported four times previously with a resolution of symptoms within six months of delivery [2345]. Exacerbation of pre-existing movement disorders and the o...

Background: Progressive supranuclear palsy (PSP)-Richardson's syndrome (RS) presents with a distinctive clinical phenotype of supranuclear ophthalmoplegia, parkinsonism, postural instability with falls, and cognitive impairment. Several rare neurological conditions have been described that mimic PSP, and the co-occurrence of dual pathologies has a...

Parkinson’s disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B (CTSB) in susceptibility to PD. A typical PD family was identified and...

Autosomal dominant epilepsy with auditory features (OMIM 600512) is characterised by focal seizures with distinctive auditory auras and/or ictal aphasia. We describe a 17-year-old girl with recurrent attacks of ictal aphasia and rare nocturnal convulsions. She had a four-generation paternal family history of epilepsy. Her father and aunt perceived...

Presentation A 63-year-old man developed polyarthritis two months post recovery from COVID-19 infection. Diagnosis We concluded that the diagnosis was rheumatoid arthritis based upon raised inflammatory markers, positive rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Treatment His symptoms improved with naproxen, corticosteroid...

We selected several “imaging pearls” presented during the Movement Disorder Society (MDS) Video Challenge for this review. While the event, as implicated by its name, was video‐centered, we would like to emphasize the important role of imaging in making the correct diagnosis. We divided this anthology into two parts: genetic and acquired disorders....

Whipple’s disease is a rare, treatable, multisystem bacterial infection with protean manifestations. The causative bacilliform bacterium, Tropheryma whipplei, was once considered rare, but recent evidence demonstrates that it is actually a common commensal. Exposure to the pathogen and asymptomatic gut carriage is frequent; progression to a disease...

Background: Apomorphine is a potent dopamine agonist used in the treatment of advanced and fluctuating Parkinson's Disease. However the need for its subcutaneous infusion can lead to skin reactions. Phenomenology shown: We illustrate necrotic ulcers at infusion sites as a rare event during continuous subcutaneous apomorphine infusion. Education...

Parkinson’s disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson’s disease....

Background Mutations in SPG7 are increasingly identified as a common cause of spastic ataxia. We describe a cohort of Irish patients with recessive SPG7-associated phenotype.Methods Comprehensive phenotyping was performed with documentation of clinical, neurophysiological, optical coherence tomography (OCT) and genetic data from individuals with SP...

Background Mutations in SPG7 are increasingly identified as a common cause of spastic ataxia. We describe a cohort of Irish patients with recessive SPG7-associated phenotype. Methods Comprehensive phenotyping was performed with documentation of clinical, neurophysiological, optical coherence tomography (OCT) and genetic data from individuals with S...

Introduction There have been no specific guidelines regarding which genes should be tested in the clinical setting for PD or parkinsonism. We evaluated the types of clinical genetic testing offered for Parkinson’s disease (PD) as the first step of our gene curation. Methods The National Institutes of Health (NIH) Genetic Testing Registry (GTR) was...

Presentation: An 85-year-old farmer developed disabling progressive proximal limb weakness and dysphagia after 10 years of statin therapy. Diagnosis: Creatine kinase was elevated, and electromyography demonstrated myopathic abnormalities. A muscle biopsy confirmed a necrotising myopathy. Serum 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGC...

Background: α-synuclein aggregates in the form of Lewy bodies and Lewy neurites are the pathological hallmark of Parkinson disease (PD) and dementia with Lewy bodies (DLB). Autopsy studies suggest that α-synuclein aggregates appear in localized areas of the central nervous system before spreading in a sequential pattern from the brainstem to the c...

Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. // Methods: We performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at...

Background: "Ondine's curse" or central hypoventilation, induces an apparently spontaneous failure of automatic respiratory drive, henceforth necessitating a conscious effort to breathe and sleep induced hypoventilation. It is typically seen in congenital central hypoventilation syndrome, but may be acquired. Objectives: To highlight Ondine's cu...

Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. Methods: We performed the first genome-wide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases a...

We report the first clinical-radiological-genetic-molecular-pathological study of a kindred with c.823-10G>T MAPT intronic variant (rs63749974) associated with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We describe the clinical spectrum within this family and emphasize the association between MAPT gene variants and...

OBJECTIVE: Parkinson's disease (PD) is a complex neurodegenerative disorder. Males are on average ~ 1.5 times more likely to develop PD compared to females with European ancestry. Over the years genome-wide association studies (GWAS) have identified numerous genetic risk factors for PD, however it is unclear whether genetics contribute to disease e...

Background Variants in PARKIN, PINK1, and DJ1 are associated with early-onset Parkinson’ disease (EOPD, age-at-onset < 45). We previously reported a single PINK1 and a single DJ1 heterozygous variant carrier. PurposeWe aimed to expand upon our previous EOPD studies and investigate for any genotype–phenotype correlations in Irish PD. Methods Three h...

Sleep and circadian rhythm disturbances are central features of many movement disorders, exacerbating motor and non-motor symptoms and impairing quality of life. Understanding these disturbances to sleep is clinically important and may further our understanding of the underlying movement disorder. This review evaluates the current anatomical and ne...

Freezing of gait in people with Parkinson’s disease (PwP) is associated with executive dysfunction and motor preparation deficits. We have recently shown that electrophysiological markers of motor preparation, rather than decision-making, differentiate PwP with freezing of gait (FOG +) and without (FOG −) while sitting. To examine the effect of loc...

Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. Methods: We performed the first genome-wide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at t...

Clinical, neuropathological and neuroimaging research suggests that pathological changes in Parkinson’s disease (PD) start many years before the emergence of motor signs. Since disease-modifying treatments are likely to be most effective when initiated early in the disease process, there has been significant interest in characterizing prodromal PD....

Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although...

The diagnosis of a paroxysmal dyskinesia is difficult and status dystonicus is a rare life threatening movement disorder characterised by severe, frequent or continuous episodes of dystonic spasms. A 25 year old woman with chronic ataxia and paroxysmal dyskinesia presented with facial twitching, writhing of arms, oculogyric crisis and visual and au...

People living with Parkinson's disease (PwP) experience a wide range of motor and non-motor symptoms associated with increasing complexity of care delivery. A multispecialty approach has been presented as an intuitive solution for tailored and comprehensive care delivery. Nevertheless, past trials of both multidisciplinary or interdisciplinary care...

FRM1 premutation carriers exhibit various subtle deficits in balance and stability, prior to the development of the movement disorder Fragile X Associated Tremor/Ataxia Syndrome (FXTAS). Force plate posturography has increasingly been combined with the temporal sensitive imaging methods such as EEG to offer insight into the neural mechanisms which...

Multiple studies implicate heterozygous GBA mutations as a major genetic risk factor for Parkinson's disease (PD); however, the frequency of mutations has never been examined in PD patients from the Irish population. We prospectively recruited 314 unrelated Irish PD patients (UK Brain Bank Criteria) and 96 Irish healthy controls (without any signs...

Background: Frontotemporal dementia (FTD) is the second most common cause of early-onset neurodegenerative dementia. Several studies have focused on early imaging changes in FTD patients, but once subjects meet full criteria for the FTD diagnosis, structural changes are generally widespread. Objective: This study aims to determine the earliest s...

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Background: We describe the clinical and neuropathological features of a patient with T-cell-mediated paraneoplastic limbic encephalitis, parkinsonism, hypothermia, and narcolepsy-like presentation associated with endometrial carcinoma. Objectives: This patient with prominent parkinsonism and narcolepsy broadens the phenotype of known paraneopla...

Clinical history: A 57-year old woman presented with left hand pain, periodic leg movement during sleep, gradual onset of stiffness, clumsiness, and falls. Neurological examination showed: generalized rigidity and bradykinesia. There was left hand dystonic posturing and ideomotor apraxia, as well as mirror movements of upper limbs and stimulus-sen...

Background: Thalamotomy and deep brain stimulation of the ventralis intermedius nucleus are effective symptomatic treatments for tremor, irrespective of the underlying diagnosis. Methods and results: Herein we describe six tremor patients (2 Parkinson's disease, 1 dystonic tremor, 2 Essential tremor plus dystonia, 1 Essential tremor plus ataxia)...

Background: Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative movement disorder characterized by tremor, ataxic gait, and balance issues resulting from a premutation of the Fragile X Mental Retardation 1 (FMR1) gene. No biomarkers have yet been identified to allow early diagnosis of FXTAS, however, recent studies have repo...

A diagnosis of primary mitochondrial disease was traditionally arrived at on the basis of clinical and biochemical features including abnormal respiratory chain analysis on muscle biopsy and/or identification of other ‘mitochondrial disease markers’. With the increased availability of genetic testing, in particular massive parallel sequencing, alte...

SCA 17 is a rare, autosomal dominant disorder caused by TBP gene CAG/CAA repeat expansion. Ataxia and dementia are common. The presence of frontal dysfunction at outset of the disease may mimic frontotemporal dementia (FTD). Parkinsonism, chorea, dystonia, and pyramidal signs may occur. We report an Irish family with autosomal dominant partially pe...

Objectives: The cognitive indicators of preclinical behavioral variant Frontotemporal Dementia (bvFTD) have not been identified. To investigate these indicators, we compared cross-sectional performance on a range of cognitive measures in 12 carriers of pathogenic MAPT mutations not meeting diagnostic criteria for bvFTD (i.e., preclinical) versus 3...

Background: CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effe...

Background: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion. Methods: In this meta-analysis of in...

A 42-year-old man, returning to Europe after a 2-month stay in China, reported cough and runny nose. Five days later, he developed neck discomfort and rapidly evolving weakness, spreading from his arms to the facial, bulbar and neck muscles, and then the legs. He developed dysphagia and breathlessness, and was intubated in the emergency department....

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Objective: Differentiating Parkinson's disease (PD) from atypical parkinsonian disorders (APD) such as Multiple System Atrophy, parkinsonian type (MSA-p) or Progressive Supranuclear Palsy (PSP-RS) can be challenging. Early signs of postural Instability and gait disability (PIGD) are considered clues that may signal presence of APD. However, it rem...

Encephalopathy associated with autoimmune thyroid disease (EAATD), also known as Hashimoto's encephalopathy, is a rare neurological condition that may occur in patients with clinical or sub-clinical autoimmune thyroid disease. The pathogenesis of EAATD has been not clearly elucidated yet. The diagnostic criteria include neurological or psychiatric...

Genetics is the backbone of Neurology, where a number of disorders have a genetic aetiology and are complex, requiring a dedicated Neurogenetics clinic. Genetics in the Republic of Ireland is under-resourced, with the lowest number of consultants per million of population in Europe. In November 2014, we established the monthly adult Neurogenetics c...

Objective To characterise psychiatric symptoms in preclinical and early behavioural-variant frontotemporal dementia (bvFTD), a neurodegenerative disorder whose symptoms overlap with and are often mistaken for psychiatric illness. Methods The present study reports findings from a systematic, global, prospective evaluation of psychiatric symptoms in...

Objectives To study the phenotype and establish the genetic background of familial Parkinson’s disease (PD) in Ireland. Background 10% of PD patients have a PD family history. Familial studies have led to the identification of causative gene mutations at 7 chromosome loci. Methods We expanded upon a 12 year familial PD study and identified a furt...

SCA 17 is a rare, autosomal dominant ataxia caused by CAG/CAA repeat expansion in TBP gene. Dementia can occur. Parkinsonism, chorea, dystonia and pyramidal signs may occur. We report an Irish family with autosomal dominant partially penetrant frontal dementia with cerebellar atrophy due to SCA17. A 44-year-old doctor presented with 18–month histor...

Current diagnosis of Parkinson’s disease is clinical. A DaTscan may be helpful in complex cases. Both false positive DAT scan results (1.4%) and false negative (4.8%) are uncommon. We present a 50 year old woman who had a seven-year history of a right hand tremor, slowing, forgetfulness and hesitant speech. Past medical history included bipolar dis...

Mutations in GNAL (DYT25) are a rare cause of adult-onset focal or segmental dystonia. Phenotypic heterogeneity is evident in the few cases described to date. We present a case of familial, early-onset dystonia and myoclonus due to a novel GNAL mutation. An eighteen-year-old right-handed woman first presented in early childhood with mild action tre...

Aims: We studied the referral practice, reporting standards, and the impact of 123 ioflupane single photon emission computed tomogram dopamine transporters (DAT-SPECT) scans conducted for the diagnosis and clinical management of patients. Settings and designs: The present study was a retrospective, non-interventional study. Materials and method...

Autosomal recessive hereditary spastic paraparesis is rare.We present 4 patients with slowly progressive predominantly lower limb spasticity and ataxia. Only one patient had family history of ataxia but without any underlying diagnosis. All of them proved negative for the mutation of Spinocerebelalr ataxia genes SCA 1,2,3 and 6. All had mutation in...

Rapid-onset dystonia-parkinsonism (DYT12) is an autosomal dominant combined dystonia associated with mutations of the ATP1A3 gene. Onset is precipitated abruptly by physical/psychological stressors. Dystonia displays a rostrocaudal distribution with prominent orofacial and upper limb involvement. Symptoms remain refractory to dopaminomimetic or GAB...