1/12. Idiopathic familial facial nerve paralysis.A 26-year-old man was seen one day after developing a left facial palsy of unknown aetiology. He had previously had a left facial palsy at age 14 and a right facial palsy at 19, both with minimal residual paresis. Both his mother and grandmother have had facial palsies. The role of hereditary influences in idiopathic facial paralysis, as well as the treatment of this condition, is discussed.- - - - - - - - - - ranking = 1keywords = paralysis (Clic here for more details about this article) |
2/12. An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous exon 4 deletion in the parkin gene.We report the neuropathologic and genetic features of a 70-year-old man with autosomal-recessive juvenile parkinsonism (AR-JP). At the age of 32 years, he developed a dystonic gait, followed by hand tremor, rigidity, bradykinesia, and impaired postural reflex. levodopa was effective in ameliorating these symptoms. Pathologic examination of autopsy specimens from this patient revealed loss of pigmented neurons and gliosis in the substantia nigra pars compacta (SNPC), being most pronounced in the medial and ventrolateral regions, and locus ceruleus (LC). The melanin content of the remaining SNPC neurons was low. This feature was less marked in the LC. There were no lewy bodies, as confirmed by immunostaining for alpha-synuclein. An additional, significant finding in this patient was neuronal loss and fibrillary gliosis in the substantia nigra pars reticulata; this feature has not been reported previously in AR-JP. Gene analysis revealed that this autopsied patient and his siblings had the parkin gene mutation (homozygous exon 4 deletion) that is responsible for the disease.- - - - - - - - - - ranking = 735.54145672232keywords = parkinsonism (Clic here for more details about this article) |
3/12. Clinical-molecular study of a family with essential tremor, late onset seizures and periodic paralysis.We report the clinical features of, and the molecular study performed on, a Spanish family with essential tremor (ET), late onset epilepsy and autosomal dominant hypokalemic periodic paralysis (hypoPP). The presence of hypoPP in this kindred suggested an ion channel as a candidate gene for ET. Our study identified an Arg528His CACNL1A3 mutation in patients with hypoPP, and excluded this mutation as the cause of tremor or epilepsy in this kindred.- - - - - - - - - - ranking = 1keywords = paralysis (Clic here for more details about this article) |
4/12. Neuropathology of two members of a German-American kindred (family C) with late onset parkinsonism.We present genealogical and longitudinal clinical observations and autopsy findings of a previously reported kindred, family C (German-American), with late-onset autosomal dominant parkinsonism with evidence for linkage on chromosome 2p13. The clinical phenotype includes the cardinal features of idiopathic Parkinson's disease. In addition, postural tremor and dementia are detected in some individuals. Two members of the kindred, one affected and one unaffected have recently come to autopsy. The unaffected family member was an 82-year-old woman whose brain showed only mild age-related pathology and no evidence of subclinical lewy body disease. In contrast, the affected family member was an 83-year-old man whose brain had neuronal loss, gliosis and lewy bodies in the substantia nigra and other monoaminergic brain stem nuclei, as well as the basal forebrain and amygdala. lewy bodies and Lewy neurites had a distribution typical of cases of idiopathic Parkinson's disease. Thus, the clinical and pathological findings in this family with autosomal dominant parkinsonism are similar to those of sporadic Parkinson's disease.- - - - - - - - - - ranking = 882.64974806679keywords = parkinsonism (Clic here for more details about this article) |
5/12. A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis.Hypokalemic Periodic Paralyses comprise diverse diseases characterized by acute and reversible attacks of severe muscle weakness, associated with low serum potassium. The most common causes are Familial hypokalemic periodic paralysis (FHypoKPP), an autosomal dominant disease, and Thyrotoxic hypokalemic periodic paralysis (THypoKPP), secondary to thyrotoxicosis. Symptoms of paralysis are similar in both diseases, distinguished by thyrotoxicosis present in THypoKPP. FHypoKPP is caused by mutations in ionic channel genes calcium (CACN1AS), sodium (SCN4A) and potassium (KCNE3). Since both diseases are similar, we tested the hypothesis that THypoKPP could carry the same mutations described in FHypoKPP, being the paralysis a genetically conditioned complication of thyrotoxicosis. In 15 patients with THypoKPP, using target-exon PCR, CSGE screening, and direct sequencing, we excluded known mutations in CACN1AS and SCN4A genes. On the other hand, we were able to identify the R83H mutation in the KCNE3 gene in one sporadic case of THypoKPP, a man who had been asymptomatic until developing thyrotoxicosis caused by Graves' disease; we confirmed the disease-causing mutation in 2 of 3 descendants. R83H was recently found in two FHypoKPP unrelated families, in which the mutant decreased outward potassium flux, resulting in a more positive resting membrane potential. We, therefore, identified the first genetic defect in THypoKPP, a mutation in the KCNE3 gene.- - - - - - - - - - ranking = 1.2keywords = paralysis (Clic here for more details about this article) |
6/12. SCA2 may present as levodopa-responsive parkinsonism.Some kindreds with familial parkinsonism exhibit genetic anticipation, suggesting possible involvement of trinucleotide repeat expansion. Recent reports have shown trinucleotide repeat expansions in the spinocerebellar ataxia 2 (SCA2) gene in patients with levodopa-responsive parkinsonism. We tested 136 unrelated patients with familial parkinsonism for SCA2 mutations. Two probands had borderline mutations; the rest were normal. (- - - - - - - - - - ranking = 1176.8663307557keywords = parkinsonism (Clic here for more details about this article) |
7/12. The PINK1 phenotype can be indistinguishable from idiopathic parkinson disease.Mutations in the PINK1 gene cause autosomal recessive parkinsonism characterized by early onset and a variable phenotypic presentation. A patient homozygous for the Ala168Pro mutation has been fully characterized clinically. Apart from onset at age 39 years and the excellent and sustained response to levodopa, all clinical and laboratory features, including SPECT and assessment of autonomic function, were indistinguishable from typical idiopathic parkinson disease.- - - - - - - - - - ranking = 147.10829134446keywords = parkinsonism (Clic here for more details about this article) |
8/12. Familial Bell's palsy in females: a phenotype with a predilection for eyelids and lacrimal gland.The authors report a family with familial Bell's palsy affecting seven individuals, six of whom are females. This is a distinct subtype of Bell's palsy with a predilection for juvenile females, previously reported only very rarely. In conjunction with a review of the literature, this case suggests that this phenotype carries with it a greater risk of serious complications affecting the eyelids and lacrimal gland. These carry significant functional and cosmetic implications owing to aberrant regeneration of the seventh, sixth and possibly third cranial nerves, chronicity and relapses. Clinical features include synkinesis of the eyelids with the orbicularis oris causing synkinetic ptosis, recurrent paralytic ectropion, paralysis of facial muscles of expression with dry eye, hyperlacrimation (crocodile tears), and transient strabismus. Clinically, the decision to offer surgery in place of conservative treatment should consider the natural history of chronicity and relapses often seen with this subtype of familial Bell's palsy. Botulinum toxin injections are especially versatile in managing the complications associated with this phenotype.- - - - - - - - - - ranking = 0.2keywords = paralysis (Clic here for more details about this article) |
9/12. dopamine transporter imaging study in parkinsonism occurring in fragile X premutation carriers.The authors studied four patients with parkinsonism carrying the fragile X premutation using SPECT with ([23)I]FP-CIT. They found evidence of preserved presynaptic nigrostriatal function, suggesting that parkinsonism in the X fragile premutation might be related to postsynaptic dopaminergic changes or different neurotransmitter alterations.- - - - - - - - - - ranking = 882.64974806679keywords = parkinsonism (Clic here for more details about this article) |
10/12. Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome.BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1. This study sought to analyse KCNJ2 in patients with familial ATS and to determine the functional characteristics of the mutated gene. methods AND RESULTS: We screened a family with inherited ATS for the mutation in KCNJ2, using direct dna sequencing. A missense mutation (T75R) of Kir2.1, located in the highly conserved cytoplasmic N-terminal domain, was identified in three affected members of this family. Using the xenopus oocyte expression system and whole cell voltage clamp analyses, we found that the T75R mutant was non-functional and possessed a strong dominant negative effect when co-expressed with the same amount of wild type Kir2.1. Transgenic (Tg) mice expressing the mutated form of Kir2.1 in the heart had prolonged QTc intervals compared with mice expressing the wild type protein. Ventricular tachyarrhythmias were observed in 5 of 14 T75R-Tg mice compared with 1 of 7 Wt-Tg and none of 6 non-transgenic littermates. In three of five T75R-Tg mice with ventricular tachycardia, their ECG disclosed bidirectional tachycardia as in our proband. CONCLUSIONS: The in vitro studies revealed that the T75R mutant of Kir2.1 had a strong dominant negative effect in the xenopus oocyte expression system. It still preserved the ability to co-assemble and traffic to the cell membrane in mammalian cells. For in vivo studies, the T75R-Tg mice had bidirectional ventricular tachycardia after induction and longer QT intervals.- - - - - - - - - - ranking = 0.2keywords = paralysis (Clic here for more details about this article) |
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