1/5. pantothenate kinase-associated neurodegeneration initially presenting as postural tremor alone in a Japanese family with homozygous N245S substitutions in the pantothenate kinase gene.We describe a 24-year-old Japanese woman with pantothenate kinase-associated neurodegeneration (PKAN) whose only early symptom was postural tremor in the right hand at around 18 years of age, leading to a diagnosis of essential tremor at age 21. Although she was treated with arotinolol hydrochloride and clonazepam, she gradually progressed to extrapyramidal and pyramidal signs several years later. T2-weighted magnetic resonance images (MRI) showed bilaterally marked hypointensity with a central region of hyperintensity in the globus pallidus, or the so-called "eye-of-the-tiger" sign. Six years have passed since the initial appearance of postural tremor, whereas she has not shown choreoathetosis, retinitis pigmentosa, optic atrophy, or seizure. Direct sequencing of the patient's genomic dna revealed homozygous base substitutions in the pantothenate kinase gene (PANK2): the A764-->G substitution (N245S) due to consanguinity of her parents. Although the heterozygous form of this mutation has already been reported among several families, this is the first report of the homozygous mutation in a patient with atypical-type PKAN. This detailed description of the clinical features of a Japanese patient with PKAN arising from homozygous N245S mutations in PANK2 would be useful for elucidating the pathogenesis of PKAN.- - - - - - - - - - ranking = 1keywords = globus pallidus, pallidus, globus (Clic here for more details about this article) |
2/5. Paraneoplastic degeneration of the substantia nigra with dystonia and parkinsonism.A 42-year-old woman suffered unexplained weight loss followed by action tremor and difficulty initiating gait. Three months after onset of symptoms, infiltrating ductal carcinoma of the breast, metastatic to liver and lymph nodes, was diagnosed and treated briefly with cyclophosphamide, methotrexate, and 5-flourouracil (5FU). Severe symmetric action and postural tremor with a myoclonic component developed, with minimal rest tremor, severe dysarthria and dysphagia, small-stepped and slightly ataxic gait progressing to a bedbound state, and severe widespread dystonic posturing. The latter began as a typical parkinsonian posture of trunk and upper extremities and progressed to a fixed and painful flexion of the elbows and wrists and extension of fingers and neck. Sinemet, anticholinergics, baclofen, diazepam, and plasmapheresis gave no benefit. The patient died of complications of immobility 5 months after neurologic symptom onset. autopsy revealed many pigment-laden macrophages in substantia nigra and moderate loss of pigmented neurons. inflammation, lewy bodies, and tumor were absent. Cerebellar purkinje cells were moderately depleted. Mild neuronal loss and gliosis were present in globus pallidus and cerebellar cortex. Stains for anti-human IgG, IgM, kappa, and lambda were negative. This, to our knowledge, is the first report of paraneoplastic degeneration of substantia nigra or paraneoplastic parkinsonism.- - - - - - - - - - ranking = 1keywords = globus pallidus, pallidus, globus (Clic here for more details about this article) |
3/5. autopsy-proven progressive supranuclear palsy in two siblings.Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is generally considered to be nonfamilial. We report a brother and sister with clinical and pathologic findings characteristic of PSP. Both developed parkinsonism in the eighth decade of life and within 5 years exhibited severe postural instability, bradykinesia, rigidity, dystonia, dysarthria, dysphagia, urinary incontinence, pseudobulbar palsy, and supranuclear oculomotor dysfunction but no tremor. Neither responded to levodopa and/or carbidopa. Their mother and, possibly, maternal grandfather reportedly suffered from a parkinsonian syndrome. essential tremor occurred in the siblings' father and in two of the brother's three children. autopsy in the brother at age 81 years and sister at age 79 years revealed changes typical of PSP with atrophy and neurofibrillary tangles in the globus pallidus, subthalamic nucleus, and rostral tegmental brainstem. No lewy bodies were present. These cases are the first pair of relatives reported with autopsy confirmation of PSP in both and raise the question of genetic predisposition to PSP.- - - - - - - - - - ranking = 1keywords = globus pallidus, pallidus, globus (Clic here for more details about this article) |
4/5. High-frequency stimulation of the globus pallidus internalis in Parkinson's disease: a study of seven cases.The effectiveness of ventroposterolateral pallidotomy in the treatment of akinesia and rigidity is not a new discovery and agrees with recent investigations into the pathogenesis of Parkinson's disease, which highlight the role played by the unbridled activity of the subthalamic nucleus (STN) and the consequent overactivity of the globus pallidus internalis (GPi). Because high-frequency stimulation can reversibly incapacitate a nerve structure, we applied stimulation to the same target. Seven patients suffering from severe Parkinson's disease (Stages III-V on the Hoehn and Yahr scale) and, particularly, bradykinesia, rigidity, and levodopa-induced dyskinesias underwent unilateral electrode implantation in the posteroventral GPi. Follow-up evaluation using the regular Unified Parkinson's disease Rating Scale has been conducted for 1 year in all seven patients, 2 years in five of them, and 3 years in one. In all cases high-frequency stimulation has alleviated akinesia and rigidity and has generally improved gait and speech disturbances. In some cases tremor was attenuated. In a similar manner, the authors observed a marked diminution in levodopa-induced dyskinesias. This could be an excellent primary therapy for younger patients exhibiting severe bradykinesia, rigidity, and levodopa-induced dyskinesias, which would allow therapists to keep ventroposterolateral pallidotomy in reserve as a second weapon.- - - - - - - - - - ranking = 5keywords = globus pallidus, pallidus, globus (Clic here for more details about this article) |
5/5. Dynamics of tremor-related oscillations in the human globus pallidus: a single case study.Physiological evidence indicates that the resting tremor of Parkinson's disease originates in oscillatory neural activity in the forebrain, but it is unknown whether that activity is globally synchronized or consists of parallel, independently oscillating circuits. In the present study, we used dual microelectrodes to record tremor-related neuronal activity from eight sites in the internal segment of the globus pallidus (GPi) from an awake Parkinson's disease patient undergoing stereotaxic pallidotomy. We utilized spectral analysis to evaluate the temporal correlations between multiunit activity at spatially separated sites and between neural and limb electromyographic activity. We observed that some GPi neural pairs oscillated synchronously at the tremor frequency, whereas other neural pairs oscillated independently. Additionally, we found that GPi tremor-related activity at a given site could fluctuate between states of synchronization and independence with respect to upper limb tremor. Consistent with this finding, some paired recording sites within GPi showed periods of transient synchronization. These observations support the hypothesis of independent tremor-generating circuits whose coupling can fluctuate over time.- - - - - - - - - - ranking = 5keywords = globus pallidus, pallidus, globus (Clic here for more details about this article) |