Lucia Ricciardi

Status dystonicus: Predictors of outcome and progression patterns of underlying disease

Status dystonicus (SD) is a rare, life‐threatening disorder characterized by acute worsening of generalized dystonia.

The role of alexithymia in the development of functional motor symptoms (conversion disorder)

Background The mechanisms leading to the development of functional motor symptoms (FMS) are of pathophysiological and clinical relevance, yet are poorly understood. Aim The aim of the present study was to evaluate whether impaired emotional processing at the cognitive level (alexithymia) is present in patients affected by FMS. We conducted a cross-sectional study in a population of patients with FMS and in two control groups (patients with organic movement disorders (OMD) and healthy volunteers). Methods 55 patients with FMS, 33 patients affected by OMD and 34 healthy volunteers were recruited. The assessment included the 20-item Toronto Alexithymia Scale (TAS-20), the Montgomery-Asberg Depression Rating Scale, the Reading the Mind in the Eyes’ Test and the Structured Clinical Interview for Personality Disorders. Results Alexithymia was present in 34.5% of patients with FMS, 9.1% with OMD and 5.9% of the healthy volunteers, which was significantly higher in the FMS group (χ2 (2)=14.129, p<0.001), even after controlling for the severity of symptoms of depression. Group differences in mean scores were observed on both the difficulty identifying feelings and difficulty describing feelings dimensions of the TAS-20, whereas the externally orientated thinking subscale score was similar across the three groups. Regarding personality disorder, χ2 analysis showed a significantly higher prominence of obsessive-compulsive personality disorder (OCPD) in the FMS group (χ2 (2)=16.217, p<0.001) and 71.4% of those with OCPD also reached threshold criteria for alexithymia. Conclusions Because alexithymia is a mental state denoting the inability to identify emotions at a cognitive level, one hypothesis is that some patients misattribute autonomic symptoms of anxiety, for example, tremor, paraesthesiae, paralysis, to that of a physical illness. Further work is required to understand the contribution of OCPD to the development of FMS.

Management of punding in Parkinson’s disease: an open-label prospective study

Punding, a peculiar stereotyped behavior characterized by intense fascination with complex, excessive, non-goal-oriented, repetitive activities, is a quite rare condition complicating Parkinson’s disease (PD). It is triggered by dopaminergic therapy and could have a strong impact on patient quality of life. No study has specifically investigated medical management of this condition, and only a few anecdotal reports have provided therapeutic hints. Given the suggested similarities to drug-induced dyskinesias, we have previously suggested a multistep algorithm for management of punding. We conducted a prospective open-label study on ten PD punders aimed at testing its validity. In two cases, reduction of levodopa therapy was efficacious; amantadine was effective in controlling punding in four cases; in the remaining cases, quetiapine was employed, with mild efficacy in two cases.

Premonitory urge to tic in Tourette's is associated with interoceptive awareness.

A contribution of aberrant interoceptive awareness to the perception of premonitory urges in Gilles de la Tourette syndrome (GTS) has been hypothesized.

Neuropsychological features of patients with Parkinson's disease and impulse control disorders

Impulse control disorders (ICDs) are frequent in Parkinson’s disease (PD). Aim of the present study was to investigate cognition and behaviour in PD patients with and without ICDs, in order to identify potential early clinical features which might be associated to the development of ICDs. We recruited 17 PD patients with ICDs and 17 without ICDs, matched for several clinical variables, without clinically significant cognitive deficits. Assessments included behavioural scales and a neuropsychological battery, including the Iowa Gambling Task (IGT). In patients with ICDs, the total score of the BIS and the Motor Impulsivity subscore were significantly higher than in patients without ICDs. In patients with ICDs, we observed only statistical trends towards a worse performance on neuropsychological tasks (go-no-go subtest of the Frontal Assessment Battery, oral verb naming task, copying of drawings with landmarks) sensitive to frontal lobe dysfunction (FLD) and on the IGT (loss of a greater amount of money, more risky choices). As compared to patients without ICDs, they reported a more than threefold number of errors on the interference subtest of Stroop test, which is also sensitive to FLD. Although this study did not show any significant difference between PD patients presenting ICDs as compared with patients without ICDs on neuropsychological variables, some preliminary evidence was detected suggesting a trend toward a worse performance of the PD-ICD group on few neuropsychological tasks which are at least partially sensitive to frontal lobe dysfunction, including tasks sensitive to dysfunction of ventral fronto-striatal loops.

Impairment of sensory-motor integration in patients affected by RLS

Much evidence suggests that restless legs syndrome (RLS) is a disorder characterized by an unsuppressed response to sensory urges due to abnormalities in inhibitory pathways that specifically link sensory input and motor output. Therefore, in the present study, we tested sensory-motor integration in patients with RLS, measured by short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI). SAI and LAI were determined using transcranial magnetic stimulation before and after 1month of dopaminergic treatment in RLS patients. Ten naïve patients with idiopathic RLS and ten healthy age-matched controls were recruited. Patients with secondary causes for RLS (e.g. renal failure, anaemia, low iron and ferritin) were excluded, as well as those with other sleep disorders. Untreated RLS patients demonstrated deficient SAI in the human motor cortex, which proved revertible toward normal values after dopaminergic treatment. We demonstrated an alteration of sensory-motor integration, which is normalized by dopaminergic treatment, in patients affected by RLS. It is likely that the reduction of SAI might contribute significantly to the release of the involuntary movements and might account for the sensory urge typical of this condition.

Anhedonia in Parkinson's disease patients with and without pathological gambling: A case-control study

Anhedonia is present in Parkinsons Disease (PD) as well as in addictive behaviors. Pathological Gambling (PG) and other Impulse Control Disorders (ICDs) have emerged as iatrogenic complications associated with dopamine replacement therapy. We studied 154 PD patients, divided into three groups: 11 with PG, 23 with other ICDs (compulsive buying, hypersexuality, binge eating), 120 without ICDs. All patients underwent a thorough clinical, neuropsychological and psychiatric evaluation. The PG-group, compared to the ICDs-group and PD-controls, reported a significantly higher incidence of anhedonia (45% vs. 9% vs. 14% respectively), higher Snaith-Hamilton Pleasure Scale (SHAPS) scores (2.0±1.3 vs. 1.0±1.1 vs. 1.0±1.2), higher levels of impulsivity traits as measured by the Barratt Impulsiveness Scale (70.0±10.6 vs. 64.8±11 vs. 60.9±9.3) and more severe frontal dysfunctions (Frontal Assessment Battery, FAB: 12.4±4.9 vs. 15.5±1.6 vs. 14.4±3). A model for PG (incorporating anhedonia, impulsivity levels and frontal impairment) is discussed in the context of the pathophysiology of addictive behaviors. The impairment of hedonic capacity, possibly resulting from an underlying neuropsychological dysfunction, might facilitate loss of control over reward-related behavior, thus favoring the shift towards predominantly habit-based compulsive behaviors.

Randomised Feasibility Study of Physiotherapy for Patients with Functional Motor Symptoms

Objective To determine the feasibility of conducting a randomised controlled trial of a specialist physiotherapy intervention for functional motor symptoms (FMS). Methods A randomised feasibility study was conducted recruiting patients with a clinically established diagnosis of FMS from a tertiary neurology clinic in London, UK. Participants were randomised to the intervention or a treatment as usual control. Measures of feasibility and clinical outcome were collected and assessed at 6 months. Results 60 individuals were recruited over a 9-month period. Three withdrew, leaving 29 intervention and 28 controls participants in the final analysis. 32% of patients with FMS met the inclusion criteria, of which 90% enrolled. Acceptability of the intervention was high and there were no adverse events. At 6 months, 72% of the intervention group rated their symptoms as improved, compared to 18% in the control group. There was a moderate to large treatment effect across a range of outcomes, including three of eight Short Form 36 (SF36) domains (d=0.46–0.79). The SF36 Physical function was found to be a suitable primary outcome measure for a future trial; adjusted mean difference 19.8 (95% CI 10.2 to 29.5). The additional quality adjusted life years (QALY) with intervention was 0.08 (95% CI 0.03 to 0.13), the mean incremental cost per QALY gained was £12 087. Conclusions This feasibility study demonstrated high rates of recruitment, retention and acceptability. Clinical effect size was moderate to large with high probability of being cost-effective. A randomised controlled trial is needed. Trial registration number NCT02275000; Results.

Clinical differences between botulinum neurotoxin type A and B

In humans, the therapeutic use of botulinum neurotoxin A (BoNT/A) is well recognized and continuously expanding. Four BoNTs are widely available for clinical practice: three are serotype A and one is serotype B: onabotulinumtoxinA (A/Ona), abobotulinumtoxinA (A/Abo) and incobotulinumtoxinA (A/Inco), rimabotulinumtoxinB (B/Rima). A/Abo, A/Inco, A/Ona and B/Rima are all licensed worldwide for cervical dystonia. In addition, the three BoNT/A products are approved for blepharospasm and focal dystonias, spasticity, hemifacial spasm, hyperhidrosis and facial lines, with remarkable regional differences. These toxin brands differ for specific activity, packaging, constituents, excipient, and storage. Comparative literature assessing the relative safety and efficacy of different BoNT products is limited, most data come from reports on small samples, and only a few studies meet criteria of evidence-based medicine. One study compared the effects of BoNT/A and BoNT/B on muscle activity of healthy volunteers, showing similar neurophysiological effects with a dose ratio of 1:100. In cervical dystonia, when comparing the effects of BoNT/A and BoNT/B, results are more variable, some studies reporting roughly similar peak effect and overall duration (at a ratio of 1:66, others reporting substantially shorter duration of BoNT/B than BoNT/A (at a ratio 1/24). Although the results of clinical studies are difficult to compare for methodological differences (dose ratio, study design, outcome measures), it is widely accepted that: BoNT/B is clinically effective using appropriate doses as BoNT/A (1:40-50), injections are generally more painful, in most of the studies on muscular conditions, efficacy is shorter, and immunogenicity higher. Since the earliest clinical trials, it has been reported that autonomic side effects are more frequent after BoNT/B injections, and this observation encouraged the use of BoNT/B for sialorrhea, hyperhidrosis and other non-motor symptoms. In these indications the efficacy of toxins A and B are comparable and dose ratio is 1:25-30.

A POSITIVE DIAGNOSIS OF FUNCTIONAL (PSYCHOGENIC) TICS

Functional tics, also called psychogenic tics or pseudo‐tics, are difficult to diagnose because of the lack of diagnostic criteria and their clinical similarities to organic tics. The aim of the present study was to report a case series of patients with documented functional tics and to describe their clinical characteristics, risk factors and psychiatric comorbidity. Also clinical tips are suggested which might help the differential diagnosis in clinical practice.