Neuropathology of primary adult-onset dystonia

Holton, Janice L.; Schneider, Susanne A.; Ganesharajah, T; Gandhi, Sonia; Strand, Catherine; Shashidharan, P.; Barreto, José Fernando; Wood, Nicholas W.; Lees, A. J.; Bhatia, Kailash P.; Révész, Tamás

doi:10.1212/01.wnl.0000302175.76229.f0

Cited by 43 publications

(28 citation statements)

References 18 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, abnormal striatal plasticity may play a stronger role in patients with early onset generalized dystonia and a relatively weaker (but still critical) role in patients with adult onset focal dystonia. This concept is consistent with recent suggestions that inclusion body pathology may be more prominent in early onset generalized forms of dystonia (Holton et al, 2008; Wichmann, 2008), because cellular pathologies in dopaminergic and cholinergic brain stem nuclei could have severe adverse effects on plastic processes throughout the striatum.…”

Section: Discussionsupporting

confidence: 91%

“…Historically, there is very limited evidence for structural or histological abnormalities in postmortem analyses of brain tissues from patients with primary dystonia (Holton et al, 2008), with only a few case reports of neuronal loss or astrocytic gliosis in striatum (Gibb et al, 1992; Waters et al, 1993). However, dystonia can be secondary to putamenal lesions with (Starostarubinstein et al, 1987) or without Wilson’s disease, and the symptomatic expression is proportional to the lesion extent (Bhatia and Marsden, 1994; Palfi et al, 2000).…”

Section: The Striatum and Dystoniamentioning

confidence: 99%

See 1 more Smart Citation

Convergent evidence for abnormal striatal synaptic plasticity in dystonia

Peterson

Sejnowski

Poizner

2010

Neurobiology of Disease

101

View full text Add to dashboard Cite

Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor "use" may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes linking etiology to pathophysiology of the disease.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: The Striatum and Dystoniamentioning

confidence: 99%

Convergent evidence for abnormal striatal synaptic plasticity in dystonia

Peterson

Sejnowski

Poizner

2010

Neurobiology of Disease

101

View full text Add to dashboard Cite

show abstract

“…Our neuropathological investigation of these DYT6 cases utilized a similar IHC approach to that previously applied in DYT1-related dystonia cases [11,12] and adult-onset dystonia cases [22] with the specific aim of determining whether brainstem neuronal cytoplasmic inclusions are a common hallmark of isolated dystonias [11]. We were unable to identify such inclusions in our study and, indeed, we found no neuropathological features that could be regarded as specific to DYT6 dystonia in either case.…”

Section: Discussionmentioning

confidence: 99%

DYT6 Dystonia: A Neuropathological Study

Paudel¹,

Li²,

Hardy³

et al. 2015

Neurodegener Dis

View full text Add to dashboard Cite

Background: Mutations in the thanatos-associated protein domain containing apoptosis-associated protein 1 gene (THAP1) are responsible for adult-onset isolated dystonia (DYT6). However, no neuropathological studies of genetically proven DYT6 cases have been previously reported. Objective: We report the first detailed neuropathological investigation carried out on two DYT6 brains. Methods: Genetic screening for THAP1 gene mutations using standard Sanger polymerase chain reaction sequencing identified 2 cases, 1 with a known pathogenic mutation and the other with a novel mutation. A detailed neuropathological assessment of the cases was performed. Results: Both DYT6 cases showed no significant neurodegeneration and no specific disease-related pathology. Conclusions: No neuropathological features that could be defined as hallmark features of DYT6 dystonia were identified. Our study supports the notion that in isolated dystonia, there is no significant neurodegeneration or morphological lesions that can be identified using routine methods.

show abstract

“…Injury to the brainstem, basal ganglia, striatum and thalamus affects GABA synthesis or transportation leading to dystonia and other movement disorders. Normally the basal ganglia provide the memory for controlled or skilled movements (38, 83, 84). The thalamus creates a zone of inhibition modulating descending signals from the motor cortex.…”

Section: Medical Management Of Motor Disorders In Ambulatory Patientsmentioning

confidence: 99%

New Clinical and Research Trends in Lower Extremity Management for Ambulatory Children with Cerebral Palsy

Damiano

Alter

Chambers

2009

Physical Medicine and Rehabilitation Clinics of North America

View full text Add to dashboard Cite

SynopsisCerebral palsy is the most prevalent physical disability in childhood and includes a group of disorders with varying manifestations and levels of capability in individuals given this diagnosis. This chapter will focus on current and future intervention strategies for improving mobility and participation over the lifespan for ambulatory children with cerebral palsy (CP). The provision and integration of physical therapy, medical and orthopedic surgery management focused primarily on the lower extremities will be discussed here. Some of the newer trends are: more intense and task-related exercise strategies, greater precision in tone identification and management, and a shift towards musculoskeletal surgery that focuses more on promoting dynamic bony alignment and less on releasing or lengthening tendons. Advances in basic and clinical science and technology development are changing existing paradigms and offering renewed hope for improved functioning for children with CP who are currently facing a lifelong disability with unique challenges at each stage in life.

show abstract

Neuropathology of primary adult-onset dystonia

Cited by 43 publications

References 18 publications

Convergent evidence for abnormal striatal synaptic plasticity in dystonia

Convergent evidence for abnormal striatal synaptic plasticity in dystonia

DYT6 Dystonia: A Neuropathological Study

New Clinical and Research Trends in Lower Extremity Management for Ambulatory Children with Cerebral Palsy

Contact Info

Product

Resources

About