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Orla Hardiman

Publications and source records attributed to Orla Hardiman.

17 recordsLinked to original sources
PubMed2006

Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD.

BACKGROUND: A new locus for amyotrophic lateral sclerosis--frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p. METHODS: We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2) and undertook mutational screening of candidate genes within this locus. RESULTS: Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (IFT74) gene in family 476 (F476), but no mutation was detected within IFT74 in family 2 (F2). While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 (predicted to truncate the protein by 258 amino acids) led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases (n = 420). An additional sequence variant (G58D) was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples. CONCLUSION: Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families.

Amyotrophic Lateral Sclerosis↗
PubMed2006

ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis.

We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.

Adult↗
PubMed2004

Use of Sniff nasal-inspiratory force to predict survival in amyotrophic lateral sclerosis.

Respiratory muscle weakness is the usual cause of death in amyotrophic lateral sclerosis. The prognostic value of the forced vital capacity (FVC), mouth-inspiratory force, and sniff nasal-inspiratory force were established in a group of 98 patients with amyotrophic lateral sclerosis who were followed trimonthly for 3 years. Sniff nasal-inspiratory force correlated with the transdiaphragmatic pressure (r = 0.9, p < 0.01). Sniff nasal-inspiratory force was most likely to be recorded at the last visit (96% of cases), compared with either the FVC or mouth-inspiratory force (86% and 81%, respectively, p < 0.01). A sniff nasal-inspiratory force less than 40 cm H(2)O was significantly related with nocturnal hypoxemia. When sniff nasal-inspiratory force was less than 40 cm H(2)O, the hazard ratio for death was 9.1 (p = 0.001), and the median survival was 6 +/- 0.3 months. The sensitivity of FVC < 50% for predicting 6-month mortality was 58% with a specificity of 96%, whereas sniff nasal-inspiratory force less than 40 H(2)O had a sensitivity of 97% and a specificity of 79% for death within 6 months. Thus the sniff nasal-inspiratory force test is a good measure of respiratory muscle strength in amyotrophic lateral sclerosis, it can be performed by patients with advanced disease, and it gives prognostic information.

Adult↗
PubMed2004

Oropharyngeal dysphagia in amyotrophic lateral sclerosis: neurological and dysphagia specific rating scales.

BACKGROUND: Oropharyngeal dysphagia is highly prevalent in amyotrophic lateral sclerosis (ALS). Patients with dysphagia and weight loss are frequently offered gastrostomy. Although the neurological basis of dysphagia in ALS is complex, there are currently no specifically validated scales for dysphagia in ALS, and the reliability of existing generic scales has not been assessed. METHODS: We undertook a prospective study of 25 patients who fulfilled the criteria for definite or probable ALS. We examined the reliability of the Dysphagia Outcome Severity Scale (DOSS) and the Aspiration-Penetration Rating Scale (APRS) and the correlation between these scales and the Norris ALS Scale and ALS Functional Rating Scale-R (ALS FRS-R). RESULTS: Using the Pearson Product-Moment Correlation, an expected high linear association between the two disease specific neurological scales was demonstrated. Both dysphagia scales were found to be reliable. Interrelationship evaluation showed a low association between Norris and ALS FRS-R scores and DOSS and APRS. However, examination found specific subsections to be significantly correlated, particularly the Norris bulbar sections (NBS) and the DOSS. CONCLUSIONS: Generic dysphagia scales are reliable indicators of dysphagia in ALS. The bulbar components of the ALS specific scales is sensitive to dysphagia. The bulbar section of the Norris scale can be utilised as an independent and reliable indicator of the severity of dysphagia in ALS. In the absence of availability of detailed swallowing assessment using videofluoroscopy, these scales, i.e., the Norris and to a lesser degree the ALS FRS-R bulbar sections, are adequate to diagnose and follow clinically significant dysphagia in ALS, and can be used as an indicator for dysphagia treatment initiation.

Adult↗
PubMed2004

Recovery of the upper limb post ischaemic stroke and the predictive value of the Orpington Prognostic Score.

OBJECTIVE: To document upper limb recovery in stroke patients and investigate whether the Orpington Prognostic Score (OPS) performed within 48 hours of admission to hospital post ischaemic stroke was a predictor of upper limb function at six months and two years. DESIGN: Inception cohort design. SETTING: Teaching Hospital. SUBJECTS: One hundred and fourteen patients hospitalized with acute ischaemic stroke were stratified into three groups based on their OPS within 48 hours of admission post stroke and underwent further assessments at two weeks, six months and two years after stroke onset. MAIN MEASURES: Rivermead Arm Score (RAS), Nine Hole Peg Test (NHPT) and grip strength (GS). RESULTS: Patients with a good OPS and intermediate OPS showed significant recovery in all outcome measures for up to six months post stroke (p < 0.05), while those with a poor OPS at 48 hours showed no significant improvement (p > 0.05). The OPS score at 48 hours was the most highly correlated variable with upper limb outcome at six months (r= -0.728) and at two years (r= -0.712) compared with other variables such as age, class of stroke, sensation, grip strength and RAS. CONCLUSION: Stroke patients demonstrate differential upper limb recovery patterns which need to be taken in consideration when designing studies that investigate efficacy of rehabilitation, and the OPS is highly correlated with upper limb recovery at six months and two years.

Aged↗
PubMed2003

Polymyositis masquerading as motor neuron disease.

BACKGROUND: Several conditions have been reported to mimic motor neuron disease (MND), and misdiagnosis remains a common clinical problem. OBJECTIVE: To report a case of bulbar-onset polymyositis where the initial clinical presentation was suggestive of MND. CASE DESCRIPTION: A 73-year-old woman was admitted for investigation of acute-onset dysphagia without dysarthria. Examination revealed nasal dysphonia and severe oropharyngeal weakness. Subtle upper-limb weakness, brisk tendon reflexes, and fasciculations in the right deltoid muscle were also demonstrated. A clinical diagnosis of MND was entertained. The serum creatine kinase value was within the reference range. Findings from electromyographic studies, however, were suggestive of a myopathic rather than a neurodegenerative process, and a muscle biopsy specimen was diagnostic of polymyositis. The dysphagia rapidly resolved upon treatment with corticosteroids and azathioprine. CONCLUSIONS: Bulbar-onset polymyositis may mimic MND, particularly in the absence of inflammatory markers or elevated muscle enzyme levels. Caution should be exercised in the clinical diagnosis of bulbar dysfunction, and further investigations such as electromyography and muscle biopsy are indicated to confirm the diagnosis.

Adrenal Cortex Hormones↗
PubMed2003

An outcome study of riluzole in amyotrophic lateral sclerosis--a population-based study in Ireland, 1996-2000.

Riluzole is the only therapy proven in clinical trials to prolong amyotrophic lateral sclerosis (ALS) survival (approximately three months). Questions remain concerning riluzole's effectiveness in everyday practice, the appropriate duration of treatment, which certain subtypes of ALS specifically benefit from the medication, and whether early administration prolongs survival in ALS patients. We report the results of a population-based outcome study of riluzole in the Irish ALS population over a five-year period. Using data from the Irish ALS Register, we examined the survival of patients diagnosed with ALS between 1 January 1996 and 31 December 2000 who attended a general neurology clinic (n = 264 patients, MD = 16). An intention to treat analysis is employed. 149 (61 %) patients were prescribed riluzole and the remaining 99 (39 %) were not. Riluzole therapy reduced mortality rate by 23 % and 15 % at 6 and 12 months respectively and prolonged survival by approximately four months. This beneficial effect was lost in prolonged follow-up. Suspected or possible ALS patients receiving riluzole experienced similar improvement in survival as the overall cohort. Survival benefit was more marked among patients with bulbar-onset disease. Multivariate analysis did not show riluzole to be an independent predictor of survival. We conclude that riluzole therapy improves ALS survival in everyday clinical practice by a short period of time. This beneficial effect is transient and stopping the medication in advanced ALS should be reconsidered. Bulbar-onset patients appear to particularly benefit from riluzole for unclear reasons. Our initial observations support riluzole use in early ALS.

Adult↗
PubMed2003

Differing central amine receptor sensitivity in different migraine subtypes? A neuroendocrine study using buspirone.

Despite the importance of the 5HT1A receptor in regulating central serotonergic tone, there is a dearth of research examining its role in migraine. In this study, we examined the hypothesis that there would be altered neuroendocrine responses to a 5HT1A agonist challenge in different migraine subtypes. Prolactin (PRL) responses to the 5HT1A receptor agonist drug buspirone were compared in 30 female subjects with migraine (ten migraine with aura, MA; ten migraine without aura, MO and ten chronic/transformed migraine, CM), and ten healthy controls matched for age, gender and menstrual status. None of the subjects were taking psychotropic medication or migraine prophylactic treatment and those with formal psychiatric disorder were excluded. Endocrine responses were determined by measuring differences between baseline PRL and maximum increases post-buspirone (deltaPRL). There was no difference in baseline PRL between groups. MA subjects did not differ in their PRL responses to buspirone compared to healthy controls. The MO group had a four-fold increase in mean deltaPRL responses compared to healthy controls. Mean deltaPRL was also increased in the CM group compared to controls, but the difference was less exaggerated. This study indicates that there is supersensitive central amine receptor function in MO and CM, but not in MA. These findings support the hypothesis that central 5HT function differs among the migraine subtypes. The results also suggest that migrainous 'transformation' may be associated with adaptive changes in central 5HT receptor sensitivity. The relative contribution of 'state' and 'trait' receptor function to these findings as well as the possible role of dopamine receptors is discussed.

Adult↗
PubMed2003

Factors associated with burden of primary headache in a specialty clinic.

OBJECTIVE: To examine factors associated with social, occupational, and psychological burden of common primary headache (migraine and tension-type headache). BACKGROUND: The personal and social burden of primary headache is high. Health, occupational, social, and psychological factors contributing to burden in people with disabling headache have not been fully unravelled. METHODS: One hundred eighty consecutive patients with either migraine or tension-type headache attending a specialty headache outpatient clinic for the first time were evaluated over a 9-month period. Headache subtype was operationally defined according to International Headache Society criteria. Headache frequency, duration, and severity were recorded. Occupational and social disability were quantified using the Migraine Disability Assessment questionnaire. Psychological burden was quantified using the 28-item General Health Questionnaire, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. Premorbid vulnerability to life stress was quantified using the neuroticism subscale of the Eysenck Personality Inventory. RESULTS: Patients with frequent (chronic) headache scored higher on the Migraine Disability Assessment questionnaire and had higher Beck Depression Inventory and General Health Questionnaire depression scores than those with less frequent (episodic) headache. Frequency of headache, but not pain severity, duration, or diagnosis, predicted both Migraine Disability Assessment total disability and General Health Questionnaire/Beck Depression Inventory depression. Neuroticism was predictive of depression but not disability. Patients with chronic migraine had the highest depression and disability scores. CONCLUSION: The number of days per month with headache is a key determinant of headache-related burden in those attending specialty clinics. Frequent (chronic) headache is associated with significantly higher psychopathology scores and general social impairment, but the direction of this relationship is not clear. Those with migraine and chronicity are the most impaired.

Adolescent↗
PubMed2003

Maximum voluntary isometric contraction: investigation of reliability and learning effect.

Maximum Voluntary Isometric Contraction (MVIC) is a standardised, objective and sensitive tool for the measurement of muscle strength. The purpose of this study was to investigate different aspects of reliability of MVIC and to determine if a learning effect existed in a relatively new user of the system. Two clinical investigators participated in the study. The inter- and intra-rater reliability of MVIC of 11 muscle groups was tested on healthy subjects (n=35). Intra-class correlation co-efficients (ICCs) were calculated and the statistical methods described by Bland and Altman were applied to the data. ICCs were higher for the more experienced investigator and a learning effect was demonstrated in a relatively new user of the system. Inter-rater reliability was acceptable but lower than intra-rater reliability. Upper limb tests generally yielded higher ICCs and lower ranges of error. The ICC was similar regardless of whether the maximum or average of the two values was taken in a single session. Utilising the statistical methods proposed by Bland and Altman allows estimation of the magnitude of error of MVIC and gives additional information to the ICC. These methods may be useful in the training of investigators and in clinical interpretation of MVIC values.

Adaptation, Physiological↗
PubMed2002

The "spray can" sign: validation of a clinical observation in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: The presentation of chronic inflammatory neuropathies is variable. The decision regarding when to intervene with treatment is ideally determined by identifying early markers of loss of function. OBJECTIVE: To test the hypothesis that an observation of functional impairment, defined by a patient with demyelinating neuropathy, can be used as a reproducible and reliable measure of improvement with intravenous immune globulin. DESIGN: A 28-year-old woman presented with a chronic inflammatory demyelinating polyneuropathy. Her first complaint was the inability to use her deodorant spray because of hand weakness. A calibrated pincer gauge fixed on top of her usual spray can was used to objectively test finger flexion. Tip grip and lateral pinch were also measured. A calibrated dynamometer was used to measure grip strength. RESULTS: Power and precision grip force were reproducible in normal control subjects by means of the spray can test. This test proved to be a reliable indicator of reduced muscle strength in the patient and improved after treatment with intravenous immune globulin. CONCLUSIONS: The spray can test objectively quantified the daily function, nominated by the patient, of operating an aerosol can. This measurement, drawn from a functional loss observed by the patient, proved to be a portable and reliable indicator of decline and recovery in chronic inflammatory demyelinating polyneuropathy.

Adult↗
PubMed2002

"True" sporadic ALS associated with a novel SOD-1 mutation.

Mutations in the Cu/Zn superoxide dismutase gene (SOD-1) are reported in 20% of familial amyotrophic lateral sclerosis (ALS) cases, but no definite report of a mutation in a "truly" sporadic case of ALS has been proved. We present the first case of a novel SOD-1 mutation in a patient with genetically proven sporadic ALS. This mutation (H80A) is believed to alter zinc ligand binding, and its functional significance correlates well with the aggressive clinical course and postmortem findings observed in this patient.

Adult↗
PubMed2002

Models of care for motor neuron disease: setting standards.

Models of care for people with motor neuron disease (MND) must be designed in a patient-centered format, with an in-built flexibility and responsiveness that reflect the evolving nature of the condition. Diagnosis should be made as early as possible. Patients should have early access to centres with specialist knowledge of amyotrophic lateral sclerosis (ALS). Services should be flexible and responsive to the needs of the patient, and operate to best advantage when functioning as a coordinated team that cross-refers internally. Patients with ALS should be empowered to make rational end-of-life decisions based on maximizing quality of life and maintaining dignity. All models of care should be designed to cater for the sudden change from health to chronic illness, and should aim to provide a core of specialties that are patient-oriented, flexible and responsive. Ultimately, models of care should be assessed based on their outcomes.

Diagnosis, Differential↗
PubMed2002

Amyotrophic lateral sclerosis: enteral nutrition provision--endoscopic or radiologic gastrostomy?

PURPOSE: To retrospectively evaluate gastrostomy placement in patients with amyotrophic lateral sclerosis (ALS) to determine the insertion method of choice. MATERIALS AND METHODS: During 3(1/2) years, 36 patients with ALS (19 men, 17 women; mean age, 54 years; age range, 37-69 years) underwent gastrostomy. Twenty patients were primarily referred for percutaneous endoscopic gastrostomy (PEG) and 16 for percutaneous radiologic gastrostomy (PRG). Gastrostomy method, success rate of each technique, and reason for procedure failure were reviewed in each patient. Forced vital capacity (FVC) prior to gastrostomy was recorded. PEG was performed with a pull-through technique after transillumination of the abdominal wall. PRG was performed with fluoroscopic guidance and T-fastener gastropexy. A log-rank test was used to compare survival rates after PRG and PEG, and a Wilcoxon rank sum test was used to evaluate the influence of declining FVC on PEG success. The Kaplan-Meier product limit method was used to estimate survival probabilities. RESULTS: Of the 20 patients referred for PEG, 11 had successful results. The nine failures (45%) resulted from failure to transilluminate the abdominal wall. All 16 patients primarily referred for PRG underwent successful gastrostomy. The nine patients in whom PEG failed underwent subsequent successful PRG. In patients with diaphragmatic palsy and a high subcostal stomach, an angled subcostal approach (n = 6) or intercostal approach (n = 2) was required at PRG. One death occurred in the PEG group (9%) because of procedure-related aspiration, and a second patient from the PEG group required laparotomy for postprocedural peritonitis. One death occurred in the PRG group (4%) because of inadvertent placement of the feeding tube in the peritoneal cavity. There was no significant difference between PEG and PRG in patient survival. FVC did not have a statistically significant influence on PEG failure. CONCLUSION: Results show PRG to be the method of choice.

Adult↗