| 41. |
- Puschmann, Andreas, et al.
(författare)
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A family with parkinsonism, essential tremor, restless legs syndrome, and depression
- 2011
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X. ; 76:19, s. 1623-1630
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous epidemiologic and genetic studies have suggested a link between Parkinson disease (PD), essential tremor (ET), and restless legs syndrome (RLS). Methods: We describe the clinical, PET, and pathologic characteristics of an extensive kindred from Arkansas with hereditary PD, ET, and RLS. The pedigree contains 138 individuals. Sixty-five family members were examined neurologically up to 3 times from 2004 to 2010. Clinical data were collected from medical records and questionnaires. Genetic studies were performed. Five family members underwent multitracer PET. Two individuals with PD were examined postmortem. Results: Eleven family members had PD with generally mild and slowly progressive symptoms. Age at onset was between 39 and 74 years (mean 59.1, SD 13.4). All individuals treated with L-dopa responded positively. Postural or action tremor was present in 6 individuals with PD, and in 19 additional family members. Fifteen persons reported symptoms of RLS. PET showed reduced presynaptic dopamine function typical of sporadic PD in a patient with PD and ET, but not in persons with ET or RLS. The inheritance pattern was autosomal dominant for PD and RLS. No known pathogenic mutation in PD-related genes was found. Fourteen of the family members with PD, ET, or RLS had depression. Neuropathologic examination revealed pallidonigral pigment spheroid degeneration with ubiquitin-positive axonal spheroids, TDP43-positive pathology in the basal ganglia, hippocampus, and brainstem, and only sparse Lewy bodies. Conclusion: Familial forms of PD, ET, RLS, and depression occur in this family. The genetic cause remains to be elucidated. Neurology (R) 2011; 76: 1623-1630
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| 42. |
- Puschmann, Andreas, et al.
(författare)
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A Swedish family with de novo alpha-synuclein A53T mutation: Evidence for early cortical dysfunction.
- 2009
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1873-5126 .- 1353-8020. ; 15, s. 627-632
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Tidskriftsartikel (refereegranskat)abstract
- A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected, but was not associated with disease state.
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| 43. |
- Puschmann, Andreas, et al.
(författare)
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Alpha-synuclein multiplications with parkinsonism, dementia or progressive myoclonus?
- 2009
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1873-5126 .- 1353-8020. ; 15:5, s. 390-392
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Tidskriftsartikel (refereegranskat)abstract
- Duplications and triplications of the alpha-synuclein (SNCA) gene have been reported in Parkinson's disease patients belonging to the Southern Swedish "Lister family". Further genealogical research has now shown that these individuals are descended from a large kindred characterized by Herman Lundborg in 1901-1913. In the expanded pedigree, a total of 25 individuals had Parkinson's disease with an autosomal dominant pattern of inheritance. Hereditary dementia, and, historically, dementia praecox have been described in other family members. Furthermore, an autosomal recessively inherited pediatric disease with nocturnal tonic-clonic fits, subsequent progressive myoclonus, startle reactions, tremor and muscle rigidity was described by Lundborg in the same pedigree. The entity was later designated Unverricht-Lundborg disease (ULD) or progressive myoclonus epilepsy type 1 (EPM1). However, Lundborg's clinical description of this disease, based on 17 patients within this kindred, differs from the modern definition of EPM1, which relies on patients with a mutation in the cystatin B (CSTB) gene. We hypothesize that the former pediatric disease, as well as the parkinsonism and dementia phenotypes, are associated with duplications, triplications and possibly higher-order multiplications of the alpha-synuclein (SNCA) gene. This hypothesis is supported by the distribution of afflicted family members within the pedigree and by recently obtained genealogical information.
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| 44. |
- Puschmann, Andreas, et al.
(författare)
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An African-American family with dystonia.
- 2011
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1873-5126 .- 1353-8020. ; 17, s. 547-550
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Tidskriftsartikel (refereegranskat)abstract
- The genetic cause of late-onset focal and segmental dystonia remains unknown in most individuals. Recently, mutations in Thanatos-associated protein domain containing, apoptosis associated protein 1 (THAP1) have been described in DYT6 dystonia and associated with some cases of familial and sporadic late-onset dystonia in Caucasians. We are not aware of any previous descriptions of familial dystonia in African-Americans or reports of THAP1 mutations in African-Americans. Herein, we characterize an African-American (AA) kindred with late-onset primary dystonia, clinically and genetically. The clinical phenotype included cervical, laryngeal and hand-forearm dystonia. Symptoms were severe and disabling for several family members, whereas others only displayed mild signs. There were no accompanying motor or cognitive signs. In this kindred, age of onset ranged from 45 to 50 years and onset was frequently sudden, with symptoms developing within weeks or months. DYT1 was excluded as the cause of dystonia in this kindred. The entire genomic region of THAP1, including non-coding regions, was sequenced. We identified 13 sequence variants in THAP1, although none co-segregated with dystonia. A novel THAP1 variant (c.-237-3G>T/A) was found in 3/84 AA dystonia patient alleles and 3/212 AA control alleles, but not in 5870 Caucasian alleles. In summary, although previously unreported, familial primary dystonia does occur in African-Americans. Genetic analysis of the entire genomic region of THAP1 revealed a novel variant that was specific for African-Americans. Therefore, genetic testing for dystonia and future studies of candidate genes must take genetic background into consideration.
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| 45. |
- Puschmann, Andreas, et al.
(författare)
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CHCHD2 and Parkinson's disease
- 2015
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Ingår i: Lancet Neurology. - : Lancet Publishing Group. - 1474-4465. ; 14:7, s. 679-679
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Tidskriftsartikel (refereegranskat)
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| 46. |
- Puschmann, Andreas, et al.
(författare)
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Clinically meaningful parameters of progression and long-term outcome of Parkinson disease: An international consensus statement.
- 2015
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1873-5126 .- 1353-8020. ; 21:7, s. 675-682
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson disease (PD) is associated with a clinical course of variable duration, severity, and a combination of motor and non-motor features. Recent PD research has focused primarily on etiology rather than clinical progression and long-term outcomes. For the PD patient, caregivers, and clinicians, information on expected clinical progression and long-term outcomes is of great importance. Today, it remains largely unknown what factors influence long-term clinical progression and outcomes in PD; recent data indicate that the factors that increase the risk to develop PD differ, at least partly, from those that accelerate clinical progression and lead to worse outcomes. Prospective studies will be required to identify factors that influence progression and outcome. We suggest that data for such studies is collected during routine office visits in order to guarantee high external validity of such research. We report here the results of a consensus meeting of international movement disorder experts from the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium, who convened to define which long-term outcomes are of interest to patients, caregivers and clinicians, and what is presently known about environmental or genetic factors influencing clinical progression or long-term outcomes in PD. We propose a panel of rating scales that collects a significant amount of phenotypic information, can be performed in the routine office visit and allows international standardization. Research into the progression and long-term outcomes of PD aims at providing individual prognostic information early, adapting treatment choices, and taking specific measures to provide care optimized to the individual patient's needs.
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| 47. |
- Puschmann, Andreas, et al.
(författare)
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Diagnosis and Treatment of Common Forms of Tremor
- 2011
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Ingår i: Seminars in Neurology. - : Georg Thieme Verlag. - 0271-8235 .- 1098-9021. ; 31:1, s. 65-77
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Tidskriftsartikel (refereegranskat)abstract
- Tremor is the most common movement disorder presenting to an outpatient neurology practice and is defined as a rhythmical, involuntary oscillatory movement of a body part. The authors review the clinical examination, classification, and diagnosis of tremor. The pathophysiology of the more common forms of tremor is outlined, and treatment options are discussed. Essential tremor is characterized primarily by postural and action tremors, may be a neurodegenerative disorder with pathologic changes in the cerebellum, and can be treated with a wide range of pharmacologic and nonpharmacologic methods. Tremor at rest is typical for Parkinson's disease, but may arise independently of a dopaminergic deficit. Enhanced physiologic tremor, intention tremor, and dystonic tremor are discussed. Further differential diagnoses described in this review include drug- or toxin-induced tremor, neuropathic tremor, psychogenic tremor, orthostatic tremor, palatal tremor, tremor in Wilson's disease, and tremor secondary to cerebral lesions, such as Holmes' tremor ( midbrain tremor). An individualized approach to treatment of tremor patients is important, taking into account the degree of disability, including social embarrassment, which the tremor causes in the patient's life.
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| 48. |
- Puschmann, Andreas, et al.
(författare)
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First neuropathological description of a patient with Parkinson's disease and LRRK2 p.N1437H mutation.
- 2012
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1873-5126 .- 1353-8020. ; 18:4, s. 332-338
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Tidskriftsartikel (refereegranskat)abstract
- The c.4309A>C mutation in the LRRK2 gene (LRRK2 p.N1437H) has recently been reported as the seventh pathogenic LRRK2 mutation causing monogenic Parkinson's disease (PD). So far, only two families worldwide have been identified with this mutation. By screening DNA from seven brains of PD patients, we found one individual with seemingly sporadic PD and LRRK2 p.N1437H mutation. Clinically, the patient had levodopa-responsive PD with tremor, and developed severe motor fluctuations during a disease duration of 19 years. There was severe and painful ON-dystonia, and severe depression with suicidal thoughts during OFF. In the advanced stage, cognition was slow during motor OFF, but there was no noticeable cognitive decline. There were no signs of autonomic nervous system dysfunction. Bilateral deep brain stimulation of the subthalamic nucleus had unsatisfactory results on motor symptoms. The patient committed suicide. Neuropathological examination revealed marked cell loss and moderate alpha-synuclein positive Lewy body pathology in the brainstem. There was sparse Lewy pathology in the cortex. A striking finding was very pronounced ubiquitin-positive pathology in the brainstem, temporolimbic regions and neocortex. Ubiquitin positivity was most pronounced in the white matter, and was out of proportion to the comparatively weaker alpha-synuclein immunoreactivity. Immunostaining for tau was mildly positive, revealing non-specific changes, but staining for TDP-43 and FUS was entirely negative. The distribution and shape of ubiquitin-positive lesions in this patient differed from the few previously described patients with LRRK2 mutations and ubiquitin pathology, and the ubiquitinated protein substrate remains undefined.
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| 49. |
- Puschmann, Andreas
(författare)
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Genetics of Parkinson's
- 2012
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Ingår i: Life with Parkinson's. Accurate Diagnosis, Treatment and Care. - : European Parkinson's Disease Association. ; , s. 88-90
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Bokkapitel (populärvet., debatt m.m.)
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| 50. |
- Puschmann, Andreas
(författare)
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Genetiska orsaker till Parkinsons sjukdom
- 2013
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Ingår i: Neurologi i Sverige. - : Pharma Industry Publishing. - 2000-8538. ; :2, s. 28-34
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Tidskriftsartikel (populärvet., debatt m.m.)
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