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Biomedical subjects

N P Quinn

Publications and source records attributed to N P Quinn.

At least 19 recordsLinked to original sources
PubMed2004

Anti-basal ganglia antibodies in patients with atypical dystonia and tics: a prospective study.

Anti-basal ganglia antibodies (ABGA) are associated with movement disorders in children, but have not been assessed in adult onset movement disorders. In a prospective assessment ABGA were positive in 65% of a group of 65 patients with atypical movement disorders, but were very rare in healthy adults and adults with idiopathic dystonia. An autoimmune mechanism may underlie a proportion of cases of atypical movement disorders.

Adolescent↗
PubMed2002

Striatal contribution to cognition: working memory and executive function in Parkinson's disease before and after unilateral posteroventral pallidotomy.

The basal ganglia are intimately connected to the frontal cortex via five fronto-striatal circuits. While the role of the frontal cortex in cognition has been extensively studied, the contribution of the basal ganglia to cognition has remained less clear. In Parkinson's disease, posteroventral pallidotomy (PVP) involves surgical lesioning of the internal section of the globus pallidus (GPi, the final output pathway from the basal ganglia) to relieve the motor symptoms of the disorder. PVP in Parkinson's disease provides a unique opportunity to investigate the impact of disruption of striatal outflow to the frontal cortex on cognition. We assessed executive function and working memory after withdrawal of medication in 13 patients with Parkinson's disease before and 3 months after unilateral PVP compared to 12 age- and IQ-matched normals assessed twice with an interval of 3 months. The tests used were: Wisconsin Card Sorting (WCST), Self-Ordered Random Number Sequences, Missing Digit Test, Paced Visual Serial Addition Test (PVSAT), and Visual Conditional Associative Learning Test (VCALT). After PVP, the patients performed significantly better on the Self-Ordered Random Number Sequences and the WCST, an improvement that was also observed in the normals across the two assessment and is therefore likely to reflect practice effects. Relative to the normals, the patients showed significant differential change following PVP on the Missing Digit Test and PVSAT, on which they performed worse after compared to before surgery, while the controls performed better on the second assessment. For the patients, performance on the VCALT also indicated deterioration after PVP, but the changes approached significance. The side of PVP had no effect on the results. The pattern of change observed 3 months after PVP was maintained at 15-month follow-up. The results suggest that striatal outflow to the frontal cortex may be essential for those aspects of executive function that showed deterioration after PVP.

Adult↗
PubMed2001

Effect of ApoE and tau on age of onset of progressive supranuclear palsy and multiple system atrophy.

In addition to allelic association between genetic polymorphisms and diseases, modulation of age of onset is a well recognised effect of disease susceptibility genes. The ApoE epsilon4 allele is associated with an earlier age of onset of sporadic and familial Alzheimer's disease. It has been suggested that the tau genotype influences the age of onset of progressive supranuclear palsy (PSP), a form of atypical parkinsonism caused by tau neurofibrillary tangle deposition. We have therefore analysed the relationship between tau and ApoE genotypes and the age of onset of PSP and another form of atypical parkinsonism, multiple system atrophy (MSA). We have not found any effect of possession of the tau H1 haplotype or the ApoE epsilon4 allele on the age of onset of MSA or PSP.

Age of Onset↗
PubMed2001

Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype.

OBJECTIVE: To analyze the association of polymorphisms in the tau gene with pathologically confirmed corticobasal degeneration (CBD). BACKGROUND: The authors previously described an extended tau haplotype (H1) that covers the human tau gene and is associated with the development of progressive supranuclear palsy (PSP). The authors now extend this analysis to CBD, a neurodegenerative condition with clinical and neuropathologic similarities to PSP. Like PSP, CBD is associated with accumulation of aggregates containing the 4-repeat isoforms of tau. Because of difficulty in diagnosis of CBD, the authors only analyzed cases with pathologically confirmed CBD. METHODS: The authors collected 57 unrelated, neuropathologically confirmed cases of CBD. Tau sequencing in these cases failed to show the presence of pathogenic mutations. Polymorphisms that spanned the tau gene were analyzed in all CBD cases and controls. RESULTS: Analyzing tau polymorphisms in CBD cases showed that the frequency of H1 and H1/H1 was significantly increased when analyzing all cases and when separating by country of origin. H1 frequency in all CBD cases was 0.921, compared with a control frequency of 0.766 (X(2) = 9.1, p = 0.00255 [1df], OR 3.56 [8.43 > CI 95% > 1.53]). The H1/H1 frequency was also significantly higher at 0.842 compared with 0.596 in age-matched controls (X(2) = 17.42, p = 0.00016, 2df), OR 3.61 [7.05 > CI 95% > 1.85]). CONCLUSIONS: The CBD tau association described here suggests that PSP and CBD share a similar cause, although the pathogenic mechanism behind the two diseases leads to a different clinical and pathologic phenotype.

Genotype↗
PubMed2001

Spontaneously changing muscular activation pattern in patients with cervical dystonia.

The objective of this study was to determine stability of the neck muscle activation pattern in a given dystonic head position in patients with cervical dystonia (CD). We assessed 26 patients with CD and botulinum toxin (BT) treatment failure before surgical denervation. None of them had received BT injections for at least 4 months. To relate dystonic head position to underlying neck muscle activity, we used synchronised video and poly-electromyographic (EMG) recording over a period of 10 minutes. The muscle activation pattern during constant ("stable") maximal dystonic excursions was analysed. EMG data of nine patients was excluded from the analysis, as these patients had a constantly changing head position or marked head tremor. In the remaining 17 patients, who had a fairly stable dystonic position, muscular activation patterns during the recording spontaneously changed in nine (Group A) while in eight it remained stable (Group B). There was no significant difference in demographic variables between the two groups other than a male predominance in Group A. However, the retrospectively determined initial response to BT treatment (before BT treatment failure had occurred) was significantly worse in Group A as compared with Group B. Neck muscle activation patterns can spontaneously change in CD patients despite constant dystonic head position, implying an inherent variability of the underlying central motor program in some patients. This should be considered when BT treatment response is unsatisfactory, and should also be taken into account when interpreting results of EMG recordings of neck muscles in these patients.

Adult↗
PubMed2001

What contributes to depression in Parkinson's disease?

BACKGROUND: Depression is a common problem in patients with Parkinson's disease, but its mechanism is poorly understood. It is thought that neurochemical changes contribute to its occurrence, but it is unclear why some patients develop depression and others do not. Using a community-based sample of patients with Parkinson's disease, we investigated the contributions of impairment, disability and handicap to depression in Parkinson's disease. METHODS: Ninety-seven patients seen in a population-based study on the prevalence of Parkinson's disease completed the Beck Depression Inventory (BDI). Clinical and historical information on symptoms and complications of Parkinson's disease were obtained from the patients by a neurologist. In addition, clinician and patient ratings of disability on the Schwab and England scale were obtained and a quality of life questionnaire was completed. RESULTS: Moderate to severe depression (BDI > or = 18) was reported by 19.6% of the patients. Higher depression scores were associated with advancing disease severity, recent self-reported deterioration, higher akinesia scores, a mini-mental score of < 25 and occurrence of falls. Disability as rated by the neurologist accounted for 34% of the variance of depression scores. Self-reported impairment of cognitive function and the feeling of stigmatization accounted for > 50% of the variance of depression scores. CONCLUSIONS: Depression in patients with Parkinson's disease is associated with advancing disease severity, recent disease deterioration and occurrence of falls. Regression analysis suggests that depression in Parkinson's disease is more strongly influenced by the patients' perceptions of handicap than by actual disability. The treatment of depression should therefore be targeted independently of treatment of the motor symptoms of Parkinson's disease, and consider the patients' own perception of their disease.

Aged↗
PubMed2001

Abnormal interaction between vestibular and voluntary head control in patients with spasmodic torticollis.

The functional status of vestibulo-collic reflexes in the sternocleidomastoid (SCM) muscles was investigated in 24 patients with spasmodic torticollis using small, abrupt 'drops' of the head. None had been treated with botulinum toxin injections during at least 4 months preceding the study. Eight of the patients, four of whom had been studied before surgery, were also studied after selective peripheral denervation of neck muscles. The reflex was of normal latency and duration in the 'passive drop' condition, in which subjects were instructed not to oppose the fall of the head. To study voluntary interaction with the reflex response, subjects were then asked to flex the neck as quickly as possible after onset of the head drop ('active drop'). In this condition, voluntary responses in patients were delayed, smaller and less effective in counteracting the head fall than in normal subjects. The same abnormalities were also found in patients after surgery when the head posture was improved. Somatosensory/auditory voluntary reaction times in SCM were normal, as was the latency of the startle reflex. We conclude that voluntary interaction with the vestibulo-collic reflex is disrupted in patients with spasmodic torticollis, a finding which corroborates the patients' aggravation of their symptoms by head or body perturbations. Lack of effective interaction between two major systems controlling head position may contribute to torticollis.

Adult↗
PubMed2001

Prospective study of selective peripheral denervation for botulinum-toxin resistant patients with cervical dystonia.

We have carried out a prospective study of selective peripheral denervation (SPD) in cervical dystonia (CD) patients with primary or secondary botulinum toxin (BT) treatment failure using independent standardized assessment. Patients referred for surgery had a standardized clinical examination, neck muscle EMG, videofluoroscopic swallow and CT of the cervical spine, and were selected for surgery on the basis of the results of these investigations. CD severity, disability and pain were assessed preoperatively and at 3, 6, 9, 12 and 18 months postoperatively using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Severity of head tremor and dysphagia were scored using established rating scales. Additionally, psychosocial function was assessed in a representative subsample of patients (n = 12) using several established questionnaires. Of the 62 patients who were assessed, 22 (35.5%) were not offered surgery, most commonly because of widespread dystonia. Of the remaining 40 patients, 37 have so far had surgery, 31 of whom have been followed up for at least 1 year, and 15 for 18 months after surgery (mean follow-up duration 16.7 months). Using the TWSTRS global outcome score, 68% of patients derived functionally relevant improvement at 12 months after surgery. In the entire operated group, total TWSTRS scores were reduced by 30% at 6 and 12 months after surgery (P < 0.0001). The subscores for severity, disability and pain were reduced by 20, 30 and 40%, respectively, at 6 months (P < or = 0.01) and 20, 40 and 30%, respectively, at 12 months (P < 0.01). Pain increased over time, which appeared to result from muscle reinnervation. TWSTRS scores were not significantly improved in the six patients with primary BT treatment failure. Head tremor did not change. There was a significant improvement of body concept, perceived disfigurement, stigma, and quality of life in the 12 patients whose psychosocial function was assessed. Preoperative disability and restriction of head movement were negatively correlated and the initial response to BT treatment positively correlated with global outcome score. Spread or deterioration of dystonia elsewhere in the body occurred in three patients, with unpleasant sensory symptoms in denervated posterior cervical segments occurring in 14. Ten patients developed mild to moderate dysphagia, and two developed severe dysphagia. We conclude that SPD is an effective treatment for patients with secondary, but probably not for those with primary, BT treatment failure. Reinnervation is not infrequent and can compromise outcome. Postoperative morbidity is low, but there is a risk of dysphagia.

Botulinum Toxins↗
PubMed2001

Arm tremor in cervical dystonia differs from essential tremor and can be classified by onset age and spread of symptoms.

The pathophysiology of arm tremor in patients with cervical dystonia (CD) and its relationship to other types of tremor is unclear. In the present study, we have compared the tremor in these patients with that seen in patients with essential tremor (ET) using two neurophysiological techniques: the triphasic EMG pattern accompanying ballistic wrist flexion movements; and reciprocal inhibition between forearm muscles. During ballistic wrist flexion movements, the latency of the second agonist EMG burst was later in ET than CD patients. This suggests that the mechanism of the arm tremor in CD may differ from that in ET. There was no group difference between reciprocal inhibition in patients with ET or CD. However, there was much more variability in the data from patients with CD. Because of this, we subdivided the CD patients into two groups, group A with normal levels of presynaptic inhibition and group B with reduced or absent presynaptic inhibition. A posteriori, it turned out that the patients in these two subgroups had similar clinical symptoms, but different clinical histories. The arm tremor of patients in group A started simultaneously with torticollis (mean onset age of arm tremor 40 years +/- 20.7 SD, interval between onset of arm tremor and torticollis 0 +/- 2.9 years) whereas it began much earlier (mean onset age 14 years +/- 6 SD) and preceded onset of torticollis by a longer interval (21.6 +/- 17.5 years) in patients of group B. Patients in group A also had less co-contraction in their ballistic wrist movements between the first agonist and the antagonist burst than those patients in group B. We conclude that arm tremor in patients with CD may have a mechanism different from that seen in patients with ET. Moreover, the data imply that there are two subgroups of CD patients with arm tremor, one with a late and simultaneous onset of arm tremor and torticollis (group A), and another with an early onset of arm tremor and later development of torticollis (group B). These groups do not correspond to the currently proposed clinical subdivision of 'dystonic tremor' and 'tremor associated with dystonia'.

Adult↗
PubMed2001

Levodopa reversible loss of the Piper frequency oscillation component in Parkinson's disease.

OBJECTIVES: Although Parkinson's disease is typically characterised by bradykinesia, rigidity, and rest tremor, the possibility that two additional motor deficits are manifest during small hand muscle activity was explored-namely, weakness and abnormal physiological tremor. METHODS: A paradigm previously used in normal subjects reliably records the strength, tremor and surface EMG of index finger abducting contractions against a compliant (elastic) resistance. In addition to the well known physiological tremor at around 10 Hz, there are other co existing peak tremor frequencies at around 20 and 40 Hz; the last of these frequencies corresponds to the range of EMG Piper rhythm. The same technique was used to study parkinsonian patients while on and off dopaminergic medication. RESULTS: The maximum strength of finger abduction produced by first dorsal interosseous contraction was considerably lower when patients were off medication (mean (SD) 6.27 (1.49) N when off v 12.33 (3.64) N when on). There was also a marked reduction in the power of Piper frequency finger tremor (p<0.0005) and EMG (p<0.0005) oscillations that did not simply result from weaker contraction. CONCLUSION: As the components of physiological tremor at higher frequencies are thought to derive from CNS oscillations important in motor control, their loss in parkinsonism in association with severe off symptoms may represent an important pathophysiological link between dopaminergic depletion and parkinsonian motor deficits.

Electromyography↗
PubMed2001

Prospective study of swallowing function in patients with cervical dystonia undergoing selective peripheral denervation.

OBJECTIVE: To characterise swallowing function in patients with cervical dystonia with botulinum toxin treatment failure, before and after selective peripheral denervation surgery. METHODS: Twelve patients with cervical dystonia had a thorough examination including standardised assessment for cervical dystonia, scoring of subjective dysphagia, and videofluoroscopic swallow. Videofluoroscopy was scored by consensus opinion between a speech and language therapist and an independent blinded radiologist using a validated scoring system. RESULTS: Seven patients with cervical dystonia experienced no subjective dysphagia either before or after surgery, although in all these patients there was objective videofluoroscopic evidence of underlying mild to moderate oropharyngeal dysphagia preoperatively and postoperatively. The most common finding was delayed initiation of swallow. Three other patients, also without subjective dysphagia before surgery, developed postoperative dysphagia. In these patients, videofluoroscopy showed a delayed swallow reflex before surgery, which was worse postoperatively in two. The remaining two patients had mild subjective dysphagia before surgery that improved postoperatively in one and deteriorated in the other. In the first, videofluoroscopy was normal preoperatively and postoperatively, and in the second, oral bolus preparation was moderately abnormal preoperatively and swallow initiation was delayed postoperatively. Mean subjective dysphagia scores did not change significantly. Apart from a significant improvement of tongue base retraction, videofluoroscopic scores were not significantly different after surgery. Postoperatively there was significant improvement of overall cervical dystonia severity and abnormal head rotation in the group as a whole. There was no correlation between age, duration of symptoms of cervical dystonia, preoperative or postoperative cervical dystonia severity, subjective dysphagia scores, or videofluoroscopic scores. However, in the five patients with persisting anterior sagittal head shift as part of the torticollis, tongue base retraction was less likely to improve after surgery compared with those without head shift. CONCLUSION: Surgical denervation of dystonic neck muscles, leading to improved neck posture, can also improve tongue base retraction, which is a key component of normal bolus propagation. However, delayed swallow initiation, a common feature in patients with cervical dystonia, can be further compromised by surgery, leading to subjective dysphagia. In general, selective peripheral denervation seems to be a safe procedure with no major compromise of swallowing function.

Adult↗
PubMed2001

Polymyography combined with time-locked video recording (video EMG) for presurgical assessment of patients with cervical dystonia.

We assessed 26 patients with cervical dystonia, in whom botulinum toxin (BT) injections had failed, before selective peripheral denervation. We decided to base the decision which muscle should be denervated on both clinical information and EMG data and focussed on the following features: activity at onset or during 'dystonic spasms' (according to the concept of the 'leading' dystonic muscle), paradoxical activity during voluntary head movements causing restriction of head movements opposite the side of head turn or tilt and activity when symptoms deteriorated during walking. To identify these muscles we developed a new recording system that integrates simultaneous video-taping and polymyography (video EMG) by means of a digital counter, driven by the recording software (resolution 0.1 s), that was fixed in view of the video camera. This system time-locked clinical signs with relevant EMG activity thus allowing demonstration of the above features. These were found in 68% of dystonic muscles with each of them being present in approximately 40%. Video EMG allows an integrated approach to identify overactive neck muscles in patients with cervical dystonia taking into account both relevant clinical findings and EMG data.

Adult↗
PubMed2000

Multiple system atrophy/progressive supranuclear palsy: alpha-Synuclein, synphilin, tau, and APOE.

Article abstract-Alpha synuclein, tau, synphilin, and APOE genotypes were analyzed in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and controls. The predisposing effect of the tau insertion polymorphism to the development of PSP is confirmed. However, no effect of alpha-synuclein, synphilin, or APOE variability on the development of PSP, or of tau, alpha-synuclein, APOE, or synphilin gene variability on the development of MSA, are demonstrated.

Apolipoproteins E↗
PubMed2000

Firing patterns of pallidal cells in parkinsonian patients correlate with their pre-pallidotomy clinical scores.

It is unclear how the disordered activity of cells in the basal ganglia contributes to the symptoms of Parkinson's disease (PD). We recorded from single neurons extracellularly in 3 regions of the globus pallidus (GPe, GPie and GPii) in patients undergoing pallidotomy for PD. Movement-related cell firing patterns, analysed using hidden Markov models, were significantly correlated with patients' preoperative clinical scores (off drugs). Responses of cells in GPii correlated best with the scores for specific motor tasks, rather than general ones related to activities of daily living, but the reverse was true for responses from GPe. In both GPii and GPe, a higher score (i.e. greater parkinsonian severity) was associated with greater variability in cell firing rather than an increase in firing rate itself.

Activities of Daily Living↗