1/69. A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy.Recently intronic and exonic mutations in the Tau gene have been found to be associated with familial neurodegenerative syndromes characterized not only by a predominantly frontotemporal dementia but also by the presence of neurological signs consistent with the dysfunction of multiple subcortical neuronal circuitries. Among families, the symptomatology appears to vary in quality and severity in relation to the specific Tau gene mutation and often may include parkinsonism, supranuclear palsies, and/or myoclonus, in addition to dementia. We carried out molecular genetic and neuropathological studies on two patients from a French family presenting, early in their fifth decade, a cognitive impairment and supranuclear palsy followed by an akinetic rigid syndrome and dementia. The proband died severely demented 7 years after the onset of the symptoms; currently, his brother is still alive although his disease is progressing. In both patients, we found a Tau gene mutation in exon 10 at codon 279, resulting in an asparagine to lysine substitution (N279K). Neuropathologically, widespread neuronal and glial tau accumulation in the cortex, basal ganglia, brain stem nuclei as well as in the white matter were the hallmark of the disease. These deposits were shown by immunohistochemistry and immunoelectron microscopy, using a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes present in multiple tau regions. In the neocortex, tau-immunopositive glial cells were more numerous than immunopositive neurons; the deeper cortical layers as well as the white matter adjacent to the cortex contained the largest amount of immunolabeled glial cells. In contrast, some brain stem nuclei contained more neurons with tau deposits than immunolabeled glial cells. The correlation of clinical, neuropathological and molecular genetic findings emphasize the phenotypic heterogeneity of diseases caused by Tau gene mutations. Furthermore, to test the effect of the N279K mutation and compare it with the effect of the P301L exon 10 mutation on alternative splicing of Tau exon 10, we used an exon amplification assay. Our results suggest that the N279K mutation affects splicing similar to the intronic mutations, allowing exon 10 to be incorporated more frequently in the Tau transcript.- - - - - - - - - - ranking = 1keywords = palsy (Clic here for more details about this article) |
2/69. Bilateral contemporaneous posteroventral pallidotomy for the treatment of Parkinson's disease: neuropsychological and neurological side effects. Report of four cases and review of the literature.The authors report the underestimated cognitive, mood, and behavioral complications in patients who have undergone bilateral contemporaneous pallidotomy, as seen in their early experience with functional neurosurgery for Parkinson's disease (PD) that is accompanied by severe motor fluctuations before pallidal stimulation. Four patients, not suffering from dementia, with advanced (Hoehn and Yahr Stages III-IV), medically untreatable PD featuring severe "on-off" fluctuations underwent bilateral contemporaneous posteroventral pallidotomy (PVP). All patients were evaluated according to the Core Assessment Program for Intracerebral Transplantations (CAPIT) protocol without positron emission tomography scans but with additional neuropsychological cognitive, mood, and behavior testing. For the first 3 to 6 months postoperatively, all patients showed a mean improvement of motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS), in the best "on" (21%) and worst "off" (40%) UPDRS III motor subscale, a mean 30% improvement in the UPDRS II activities of daily living (ADL) subscore, and 60% on the UPDRS IV complications of treatment subscale. Dyskinesia disappeared almost completely, and the mean daily duration of the off time was reduced by an average of 60%. Despite these good results in the CAPIT scores, one patient experienced a partially regressive corticobulbar syndrome with dysphagia, dysarthria, and increased drooling. No emotional lability was found in this patient, but he did demonstrate severe bilateral postoperative pretarsal blepharospasm (apraxia of eyelid opening), which interfered with walking and which required treatment with high-dose subcutaneous injections of botulinum toxin. No patient showed visual field defects or hemiparesis, but postoperative depression, changes in personality, behavior, and executive functions were seen in two individuals. Postoperative abulia was reported by the family of one patient, who lost his preoperative aggressiveness and drive in terms of ADL, speech, business, family life, and hobbies, and became more sleepy and fatigued. One patient reported postoperative mental automatisms, such as compulsive mental counting, and circular thoughts and reasoning during off phases; postoperative depression was found in two patients. However, none of the patients demonstrated these symptoms during intraoperative microelectrode stimulation. These findings are compatible with previous reports on bilateral pallidal lesions. A progressive lowering of UPDRS subscores was seen after 12 months, consistent with the progression of the disease. Bilateral simultaneous pallidotomy may be followed by emotional, behavioral, and cognitive deficits such as depression, obsessive-compulsive disorders, and loss of psychic autoactivation-abulia, as well as disabling corticobulbar dysfunction and apraxia of eyelid opening, in addition to previously described motor and visual field deficits, which make this surgery undesirable even though significant improvement in motor deficits can be achieved.- - - - - - - - - - ranking = 0.67058843446248keywords = dysarthria (Clic here for more details about this article) |
3/69. Treatment of Parkinson hypophonia with percutaneous collagen augmentation.OBJECTIVES: It has been estimated that more than 70% of patients with parkinson disease experience voice and speech disorders characterized by weak and breathy phonation, and dysarthria. This study reports on the efficacy of treating Parkinson patients who have glottal insufficiency. STUDY DESIGN AND methods: Thirty-five patients underwent collagen augmentation of the vocal folds for hypophonia associated with parkinson disease, using a new technique of percutaneous injection with fiberoptic guidance. Patient response to the collagen augmentation was determined by telephone survey. RESULTS AND CONCLUSIONS: The procedure required minimal patient participation and was safely performed on all the patients who were studied. Results of the survey indicated that 75% of patient responses demonstrated satisfaction with the technique, compared with 16% of patient ratings reflecting dissatisfaction. These results were moderately correlated with the duration of improvement of the dysphonia. Results of this preliminary evaluation demonstrate that voice deficits in parkinson disease are amenable to vocal fold augmentation. Because this procedure requires minimal patient participation and can be safely performed in an office setting, it may also be useful in other severely debilitating neuromotor diseases that result in glottal insufficiency and hypophonia.- - - - - - - - - - ranking = 0.67058843446248keywords = dysarthria (Clic here for more details about this article) |
4/69. Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese.OBJECTIVE: To describe the clinical and molecular genetic analysis of a large family of northern Chinese descent with a mutation at the SCA2 locus causing carbidopa-levodopa-responsive parkinsonism. BACKGROUND: Most causes of parkinsonism remain unknown. However, molecular genetic analysis of families with parkinsonism has recently identified five distinct loci and pathogenic mutations in four of those. Additionally, some of the spinocerebellar ataxia syndromes (SCA), particularly Machado-Joseph syndrome (SCA3), are known to cause parkinsonism. Spinocerebellar ataxia type 2 (SCA2) has not previously been described as causing a typical dopamine-responsive asymmetric PD phenotype. methods: A large family was evaluated clinically and molecularly for apparent autosomal dominant parkinsonism. RESULTS: The phenotype includes presentation consistent with typical dopamine-responsive parkinsonism. Other presentations in this family include a parkinsonism/ataxia phenotype, which is classic for SCA2 and parkinsonism, resembling progressive supranuclear palsy. CONCLUSIONS: patients presenting with a family history of parkinsonism, including familial progressive supranuclear palsy and PD, should be tested for the spinocerebellar ataxia type 2 expansion.- - - - - - - - - - ranking = 0.4keywords = palsy (Clic here for more details about this article) |
5/69. Parkinson's disease associated with argyrophilic grains clinically resembling progressive supranuclear palsy: an autopsy case.A 70-year-old male began to show akinesia, rigidity of extremities, finger tremor, disturbed vertical external ocular movement, and nuchal dystonia, which progressed slowly. Brain CT scan and magnetic resonance images showed slight atrophy of the frontal lobe and slight enlargement of the lateral ventricles. Hasegawa's dementia rating scale-revised version gave a moderate score of 11/30 points. He died of pneumonia at the age of 76. The clinical diagnosis was progressive supranuclear palsy (PSP). However, there were no neuropathological characteristics of PSP. Neuropathologically, Parkinson's disease was diagnosed. In addition, many argyrophilic grains (ArGs) in the gray matter were stained, especially in the insula, amygdala, hippocampus, parahippocampal gyrus, lateral occipitotemporal gyrus, and substantia nigra, by the Gallyas-Braak method. We consider that ArGs could modify the symptoms of Parkinson's disease and that Parkinson's disease with ArGs may show a PSP-like clinical course.- - - - - - - - - - ranking = 1keywords = palsy (Clic here for more details about this article) |
6/69. Rapid-onset dystonia-parkinsonism: a clinical and genetic analysis of a new kindred.BACKGROUND: Rapid-onset dystonia-parkinsonism (RDP) is an autosomal dominant disorder linked to chromosome 19q13 that is characterized by sudden onset of primarily bulbar and upper limb dystonia with parkinsonism. methods: The authors evaluated 12 individuals from three generations of an Irish family and obtained detailed medical records on a deceased member. The authors describe the clinical, psychiatric, and genetic features of the affected individuals. RESULTS: Five of eight affected members developed sudden-onset (several hours to days) dystonia with postural instability. Four of the five also had bulbar symptoms. Two have stable focal or segmental limb dystonia. One has intermittent hemidystonia with dysarthria that comes on abruptly in times of stress or anxiety. Three had a history of profound difficulty socializing, and at presentation two developed depression. Three patients had a trial of dopamine agonists without benefit. Genetic analysis suggests linkage to chromosome 19 with lod score of 2.1 at zero recombination. CONCLUSION: This is the third reported family with chromosome 19q13 rapid-onset dystonia-parkinsonism. Psychiatric morbidity appeared common in affected members of this family and may be part of the RDP phenotype.- - - - - - - - - - ranking = 0.67058843446248keywords = dysarthria (Clic here for more details about this article) |
7/69. A case of frontotemporal dementia and parkinsonism of early onset with progressive supranuclear palsy-like features.We report a patient with frontotemporal degeneration and parkinsonism with mental retardation. The patient was a 54-year-old man who had parkinsonism that resembled progressive supranuclear palsy, frontotemporal degeneration and myoclonus. His family included many affected members. Neuropathologically, there was degeneration of the frontal and temporal cortices, the basal ganglia, the brainstem and the cerebellum. Microscopically, neuronal loss was severe in the frontal and temporal cortex, the globus pallidus, substantia nigra, red nucleus and dentate nucleus. Fibrillary changes were found in neurons and glia that were immunostained for tau. Although we could not define the genetic abnormalities, we thought that this case might have involved frontotemporal dementia and parkinsonism linked to chromosome 17.- - - - - - - - - - ranking = 1keywords = palsy (Clic here for more details about this article) |
8/69. Progressive supranuclear palsy on guam.This is the first report demonstrating that progressive supranuclear palsy (PSP) exists on guam. This 75-year-old Guamanian Chamorro patient with slight dementia and rigidity with restriction of ocular up gaze was diagnosed as parkinsonism-dementia complex (PDC) of guam clinically. However, neurofibrillary tangles (NFTs) were scarcely seen in the cerebral cortices and hippocampus, but many NFTs, composed of 15-17 nm straight tubules, were detected in the subthalamic nucleus and brain stem. A large number of tuft-shaped astrocytes were observed in the putamen and motor cortex, and numerous argyrophilic grains were seen in the CA1 and subiculum. These pathological findings are different from those of PDC and consistent with PSP. The present case indicates that PSP and PDC clinically resemble each other, and that precise neuropathological examination is indispensable for the final diagnosis of the patient with parkinsonism, dementia and disturbance of vertical external ocular movement.- - - - - - - - - - ranking = 1keywords = palsy (Clic here for more details about this article) |
9/69. Complications of gamma knife surgery for parkinson disease.BACKGROUND: Many medical centers throughout the world offer radiosurgery with the gamma knife (GK) for pallidotomy and thalamotomy as a safe and effective alternative to radiofrequency ablative surgery and deep brain stimulation for parkinson disease (PD). The reported incidence of significant complications varies considerably, and the long-term complication rate remains unknown. DESIGN: We describe 8 patients seen during an 8-month period referred for complications of GK surgery for PD. RESULTS: Of the 8 patients, 1 died as a result of complications, including dysphagia and aspiration pneumonia. Other complications included hemiplegia, homonymous visual field deficit, hand weakness, dysarthria, hypophonia, aphasia, arm and face numbness, and pseudobulbar laughter. In all patients, lesions were significantly off target. CONCLUSIONS: The 8 patients with PD seen in referral at our center for complications of GK surgery highlight a spectrum of potential problems associated with this procedure. These include lesion accuracy and size and the delayed development of neurological complications secondary to radiation necrosis. Gamma knife surgery may have a higher complication rate than has been previously appreciated due to delayed onset and underreporting. We believe that the risk-benefit ratio of the GK will require further scrutiny when considering pallidotomy or thalamotomy in patients with PD. physicians using this technique should carefully follow up patients postoperatively for delayed complications, and fully inform patients of these potential risks.- - - - - - - - - - ranking = 145.37087037772keywords = pseudobulbar, dysarthria (Clic here for more details about this article) |
10/69. Effect of speech task on intelligibility in dysarthria: a case study of Parkinson's disease.This study assessed intelligibility in a dysarthric patient with Parkinson's disease (PD) across five speech production tasks: spontaneous speech, repetition, reading, repeated singing, and spontaneous singing, using the same phrases for all but spontaneous singing. The results show that this speaker was significantly less intelligible when speaking spontaneously than in the other tasks. Acoustic analysis suggested that relative intensity and word duration were not independently linked to intelligibility, but dysfluencies (from perceptual analysis) and articulatory/resonance patterns (from acoustic records) were related to intelligibility in predictable ways. These data indicate that speech production task may be an important variable to consider during the evaluation of dysarthria. As speech production efficiency was found to vary with task in a patient with Parkinson's disease, these results can be related to recent models of basal ganglia function in motor performance.- - - - - - - - - - ranking = 3.3529421723124keywords = dysarthria (Clic here for more details about this article) |
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