Anna Latorre

Pathophysiology of pain and fatigue in Parkinson's disease

In Parkinsons disease (PD), nigral degeneration determines an altered neuronal ouput from the subthalamic nucleus and globus pallidus, and as a consequence functional changes in the motor circuits linking basal ganglia to the motor cortical areas. Movement slowness, rigidity and tremor are among the principal motor symptoms of PD. Studies of movement execution have shown that PD patients have difficulty in performing simultaneous and sequential movements. In executing sequential movements the abnormalities of PD patients worsen as the sequence progresses. This phenomenon, called sequential effect, may be one of the mechanisms underlying the fatigue of PD patients. Cortical deafferentation is thought to be responsible for the motor disturbances of PD and studies using transcranial magnetic stimulation showed that in PD patients there are abnormalities in cortical plasticity and in cortical connectivity. Sensorimotor integration refers to the processes that link sensory input to motor output to produce appropriate voluntary movements. Sensory information is important for motor preparation and execution in parkinsonian patients, and PD patients have greater difficulty in performing movements when no external cues are provided. Investigating the role of sensory information, several studies provided evidence that PD patients have numerous somatosensory deficits, including tactile temporal discrimination threshold. Neurophysiological testing in PD has also found altered central somatosensory processing. Finally PD patients may experience painful sensations after the onset of the disease and various evidence suggests an abnormal nociceptive input processing in the central nervous system that might predispose PD patients to developing pain.

Abnormal Salivary Total and Oligomeric Alpha-Synuclein in Parkinson’s Disease

In Parkinson’s disease (PD), alpha-synuclein (a-syn) can be detected in biological fluids including saliva. Although previous studies found reduced a-syn total (a-syntotal) concentration in saliva of PD patients, no studies have previously examined salivary a-syn oligomers (a-synolig) concentrations or assessed the correlation between salivary a-syntotal, a-synolig and clinical features in a large cohort of PD patients. Is well known that a-synolig exerts a crucial neurotoxic effect in PD. We collected salivary samples from 60 PD patients and 40 age- and sex-comparable healthy subjects. PD was diagnosed according to the United Kingdom Brain Bank Criteria. Samples of saliva were analyzed by specific anti-a-syn and anti-oligomeric a-syn ELISA kits. A complete clinical evaluation of each patient was performed using MDS-Unified Parkinsons Disease Rating Scale, Beck Depression Inventory, Montreal Cognitive Assessment and Frontal Assessment Battery. Salivary a-syntotal was lower, whereas a-synolig was higher in PD patients than healthy subjects. The a-synolig/a-syntotal ratio was also higher in patients than in healthy subjects. Salivary a-syntotal concentration negatively correlated with that of a-synolig and correlated with several patients’ clinical features. In PD, decreased salivary concentration of a-syntotal may reflect the reduction of a-syn monomers (a-synmon), as well as the formation of insoluble intracellular inclusions and soluble oligomers. The combined detection of a-syntotal and a-synolig in the saliva might help the early diagnosis of PD.

Parkinsonian patients and poor awareness of dyskinesias

The question of whether the awareness of levodopa-induced dyskinesias (LID) is reduced, or altogether missing, in patients with Parkinson’s disease (PD) has been attracting growing interest. Why is this topic important? Firstly, as studies addressing the efficacy of drugs on LID employ patients’ motor diaries as an outcome measure, poor LID self-awareness might interfere with data collection in clinical trials; secondly, poor LID self-awareness may result in increased doses of dopaminergic drugs, which could in turn be associated with an enhanced risk of side effects such as LID. Lastly, understanding this phenomenon may shed light on some pathophysiological aspects of LID in PD.

Are studies of motor cortex plasticity relevant in human patients with Parkinson’s disease?

Over the last decade, electrophysiological studies in parkinsonian animals have shown that there are abnormalities of synaptic plasticity in motor areas of cortex and basal ganglia. In humans with Parkinsons disease (PD), cortical plasticity has been widely investigated using transcranial magnetic stimulation. A number of studies have reported abnormal responses to several different conditioning protocols, but their relationship to altered basal ganglia output and dopaminergic loss is still not entirely clear. Thus in the near future it seems unlikely that measures of cortical plasticity could be used as a biomarker of disease severity and progression. In this review we provide an overview on current knowledge of abnormalities of plasticity in PD in the light of recent advances in parkinsonian animal models. Finally we will discuss the relevance of abnormalities of plasticity in the clinical context of PD.

Dyskinesias and motor symptoms onset in Parkinson disease

PURPOSE To assess, using a longitudinal follow-up study design, the relationship between the body site of motor symptoms onset and that of dyskinesias (LID) onset in 70 PD patients in whom LID were absent at the baseline but appeared at one of the follow-up visits; to investigate the demographic and clinical features associated with different sites of LID onset. METHODS Motor symptoms onset was retrospectively determined by asking patients which body part had first been affected by motor impairment. The site of LID onset was determined objectively in one of the follow-up visits. RESULTS Motor symptoms started in the limbs in all patients (unilaterally in 91.4% and bilaterally in 8.6% of the patients). LID started unilaterally in the limbs in 25.8%, bilaterally in the limbs in 7.1%, in the cranio-cervical-axial region in 40% and in both the cranio-cervical-axial region and limbs in 27.1% of the patients. No significant association emerged between the site of motor symptoms onset and that of LID onset; a correlation did emerge between the site of motor symptoms onset and that of LID onset in patients with unilateral onset of both motor symptoms and LID. No differences were detected when the subgroups of patients with LID onset in different body regions were compared. CONCLUSIONS The partial association between the body site of motor symptoms and of LID onset likely reflects pathophysiological mechanisms underlying LID.

Reappraisal of cortical myoclonus: A retrospective study of clinical neurophysiology

Myoclonus is defined as a brief and jerky shock-like involuntary movement caused by abrupt muscle contraction or sudden cessation of ongoing muscular activity. Physiological classification of myoclonus is of both pathophysiological and practical importance given that myoclonus is managed differently according to its presumed generators. Thus, by definition, FIG. 1. MRI findings and clinical findings. (A) Before the first surgery, left foot inversion significantly interfered with walking. (B) An MRI obtained before the second surgery showing a coagulated lesion on the Vo nucleus of the right thalamus

The Effect of L-Dopa/Carbidopa Intestinal Gel in Parkinson Disease Assessed Using Neurophysiologic Techniques.

BackgroundBy providing a stable and smooth L-dopa plasmatic level, L-dopa/carbidopa intestinal gel reproduces the physiological continuous dopaminergic receptor stimulation in patients with Parkinson disease (PD), and it therefore represents a suitable tool to investigate the role of the altered dopaminergic neurotransmission in the pathophysiology of motor and sensory abnormalities in this condition. MethodsWe studied 11 patients with advanced PD being treated with L-Dopa/carbidopa intestinal gel (LCIG) and 11 age-matched healthy subjects. Bradykinesia was measured by kinematic recording of repetitive finger movements (finger tapping), whereas sensory abnormalities were evaluated using the somatosensory tactile discrimination threshold. All the patients were studied off and on medication, in 2 different experimental sessions. ResultsParkinson disease patients were very slow and hypokinetic during finger tapping, with no progressive reduction in amplitude or speed being observed during movement repetition. Somatosensory temporal discrimination threshold values were higher in PD patients than in healthy subjects. The neurophysiologic assessment of the effects of LCIG in advanced PD patients demonstrates an improvement, although not normalization, of motor and sensory abnormalities. ConclusionsThe study provides an objective evaluation of the effects of LCIG on motor and sensory abnormalities in PD. The results suggest that besides dopaminergic mechanisms motor and sensory abnormalities in PD reflect a varying combination of pathophysiologic mechanisms.

Quick Flicks: Association of Paroxysmal Kinesigenic Dyskinesia and Tics: PKD & Tics

Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterised by brief attacks of chorea, dystonia, or mixed forms precipitated by sudden movement.

Combined dystonia with self-mutilation in PTPS deficiency: a case report: Self-mutilation in PTPS deficiency

Monoamine-related neurotransmitter diseases refer to several neurological syndromes caused by primary and secondary defects in the biosynthesis, degradation, or transport of catecholamines and serotonin. Tetrahydrobiopterin (BH4) deficiency exemplifies such a disease. BH4 is an essential cofactor for levodopa, serotonin, and tyrosine syntheses. 6-Pyruvoyl-tetrahydropterin synthase (PTPS) is involved in BH4 biosynthesis and its deficiency is the most common BH4 disorder, causing an autosomal-recessive condition clinically characterized by neurodevelopmental delay, truncal hypotonia, extrapyramidal features, and swallowing difficulties. Behavioral problems, such as irritability, obsessive-compulsive disorder, and aggressiveness, are also common. PTPS deficiency can be prevented by presymptomatic diagnosis, by means of neonatal screening test for hyperphenylalaninemia, and treatment. Here, we present a case of PTPS deficiency with combined dystonia and marked behavioral problems and self-mutilation, a feature typically observed in other conditions, such as LeschNyhan syndrome (LNS) and chorea-acanthocytosis (ChAc).

Cervical Dystonia Following Injury to the Cerebellar Pontine Angle: An Instructive Case: Cervical Dystonia Following CPA Injury

A 38‐year‐old woman presented with cervical dystonia in the context of a recent surgery to remove a vestibular schwannoma. She initially presented to neurology with pain in the right arm, and MRI of the brain showed an incidental right‐sided vestibular schwannoma (Video 1 , Segment 1). An elective gamma‐knife procedure was performed, which failed. Hydrocephalus requiring ventriculoperitoneal shunt insertion developed, and 3 years following the initial procedure the lesion was surgically excised. Surgery was further complicated by right middle cerebellar peduncle injury, extending to the cerebellopontine angle and marginally to the right pontine tegmentum, with subsequent mass effect on cerebellum displayed on follow‐up MRI (Video 1 , Segment 2).