This review explores recent developments in understanding the neurobiological mechanism of functional (psychogenic) movement disorders (FMDs). This is particularly relevant given the resurgence of ...academic and clinical interest in patients with functional neurological symptoms and the clear shift in diagnostic and treatment approaches away from a pure psychological model of functional symptoms.
Recent research findings implicate three key processes in the neurobiology of FMD (and by extension other functional neurological symptoms): abnormal attentional focus, abnormal beliefs and expectations, and abnormalities in sense of agency. These three processes have been combined in recent neurobiological models of FMD in which abnormal predictions related to movement are triggered by self-focused attention, and the resulting movement is generated without the normal sense of agency that accompanies voluntary movement.
New understanding of the neurobiology of FMD forms an important part of reappraising the way that patients with FMD (and other functional disorders) are characterized and treated. It also provides a testable framework for further exploring the pathophysiology of these common causes of ill health.
This clinical commentary discusses the phenomenology and treatment of paroxysmal dyskinesia in patients with multiple sclerosis. It calls for a consensus on the definition as well as for larger ...studies to better understand this unusual clinical association.
Functional movement disorders are commonly seen in neurology services and may coexist with other neurological diseases. This combination is known as “functional overlay” and an increasing interest on ...this topic has emerged in the past decade as the field of functional neurological disorders has moved forward. Some neurological diseases may be more prone to develop “functional overlay” than others, and within the field of movement disorders, most studies have focused on patients with Parkinson's disease. This review comprehensively summarizes the current body of knowledge on this topic and provides an expert opinion to equip clinicians with a pragmatic approach to recognize functional movement disorders in patients with Parkinson's disease, to communicate the diagnosis and to become familiar with potential therapies in this complex clinical scenario. Potential underlying mechanisms and risk factors that may play a role in increasing the vulnerability of Parkinson's disease patients to develop functional movement disorder comorbidity are also discussed within the framework of modern neurobiological theories of brain functioning.
•Functional movement disorder (FMD) comorbidity is common in Parkinson's Disease (PD).•FMD can occur at any time during the disease course, even prior to PD diagnosis.•Frequent phenotypes include gait disturbance and tremor.•Recognition is based on positive signs from clinical history and neurological exam.•Diagnosis of FMD comorbity is important to treat accordingly and avoid iatrogenesis.
Pyruvate dehydrogenase complex (PDC) deficiency caused by mutations in the X-linked
PDHA1
gene has a broad clinical presentation, and the pattern of X-chromosome inactivation has been proposed as a ...major factor contributing to its variable expressivity in heterozygous females. Here, we report the first set of monozygotic twin females with PDC deficiency, caused by a novel, de novo heterozygous missense mutation in exon 11 of
PDHA1
(NM_000284.3: c.1100A>T). Both twins presented in infancy with a similar clinical phenotype including developmental delay, episodes of hypotonia or encephalopathy, epilepsy, and slowly progressive motor impairment due to pyramidal, extrapyramidal, and cerebellar involvement. However, they exhibited clear differences in disease severity that correlated well with residual PDC activities (approximately 60% and 20% of mean control values, respectively) and levels of immunoreactive E1α subunit in cultured skin fibroblasts. To address whether the observed clinical and biochemical differences could be explained by the pattern of X-chromosome inactivation, we undertook an androgen receptor assay in peripheral blood. In the less severely affected twin, a significant bias in the relative activity of the two X chromosomes with a ratio of approximately 75:25 was detected, while the ratio was close to 50:50 in the other twin. Although it may be difficult to extrapolate these results to other tissues, our observation provides further support to the hypothesis that the pattern of X-chromosome inactivation may influence the phenotypic expression of the same mutation in heterozygous females and broadens the clinical and genetic spectrum of PDC deficiency.
•Motor fluctuations and dyskinesia remains a challenging problem in PD.•Safinamide is effective in fluctuating PD patients without increasing dyskinesia.•Glutamatergic modulation with safinamide ...seems to increase with higher doses.•Increasing safinamide >100 mg improved motor control without dyskinesia worsening.•Safinamide >100 mg may be considered when off time and dyskinesia coexist.
A Bayesian account of 'hysteria' Edwards, Mark J; Adams, Rick A; Brown, Harriet ...
Brain (London, England : 1878),
11/2012, Letnik:
135, Številka:
Pt 11
Journal Article
Recenzirano
Odprti dostop
This article provides a neurobiological account of symptoms that have been called 'hysterical', 'psychogenic' or 'medically unexplained', which we will call functional motor and sensory symptoms. We ...use a neurobiologically informed model of hierarchical Bayesian inference in the brain to explain functional motor and sensory symptoms in terms of perception and action arising from inference based on prior beliefs and sensory information. This explanation exploits the key balance between prior beliefs and sensory evidence that is mediated by (body focused) attention, symptom expectations, physical and emotional experiences and beliefs about illness. Crucially, this furnishes an explanation at three different levels: (i) underlying neuromodulatory (synaptic) mechanisms; (ii) cognitive and experiential processes (attention and attribution of agency); and (iii) formal computations that underlie perceptual inference (representation of uncertainty or precision). Our explanation involves primary and secondary failures of inference; the primary failure is the (autonomous) emergence of a percept or belief that is held with undue certainty (precision) following top-down attentional modulation of synaptic gain. This belief can constitute a sensory percept (or its absence) or induce movement (or its absence). The secondary failure of inference is when the ensuing percept (and any somatosensory consequences) is falsely inferred to be a symptom to explain why its content was not predicted by the source of attentional modulation. This account accommodates several fundamental observations about functional motor and sensory symptoms, including: (i) their induction and maintenance by attention; (ii) their modification by expectation, prior experience and cultural beliefs and (iii) their involuntary and symptomatic nature.
Task-specific dystonia is a form of isolated focal dystonia with the peculiarity of being displayed only during performance of a specific skilled motor task. This distinctive feature makes ...task-specific dystonia a particularly mysterious and fascinating neurological condition. In this review, we cover phenomenology and its increasingly broad-spectrum risk factors for the disease, critically review pathophysiological theories and evaluate current therapeutic options. We conclude by highlighting the unique features of task-specific dystonia within the wider concept of dystonia. We emphasise the central contribution of environmental risk factors, and propose a model by which these triggers may impact on the motor control of skilled movement. By viewing task-specific dystonia through this new lens which considers the disorder a modifiable disorder of motor control, we are optimistic that research will yield novel therapeutic avenues for this highly motivated group of patients.
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