Davide Martino

Cortical Excitability is Abnormal in Patients with the Fixed Dystonia Syndrome

A form of fixed dystonia (FD) without evidence of basal ganglia lesions or neurodegeneration has been recently characterized (Schrag et al., Brain 2004;127:2360‐2372), which may overlap the clinical spectrum of either complex regional pain syndrome or psychogenic dystonia. Transcranial magnetic stimulation studies in typically mobile dystonia revealed abnormal motor cortical excitability and sensori‐motor integration. We compared 12 patients with limb FD to 10 patients with primary adult‐onset typically mobile dystonia and 11 age‐matched healthy volunteers. Measurements at the first digital interosseus representation area on both hemispheres included: short intracortical inhibition (SICI), contralateral silent period (cSP), and short and long afferent inhibition (SAI and LAI). Repeated measure ANOVA and post‐hoc t‐tests were used for statistical analysis. SICI was significantly reduced in both hemispheres of patients with “typical” and FD, compared to healthy subjects. For both hemispheres, cSP duration was shorter in both fixed and “typical” dystonia patients. SAI and LAI did not significantly differ between the three groups. The abnormal cortical excitability observed in FD might represent an underlying trait predisposing to different clinical forms of dystonia.

The prognosis of fixed dystonia: a follow-up study.

BACKGROUND The syndrome of fixed dystonia includes both CRPS-dystonia and psychogenic dystonia. The underlying mechanisms are unclear, but a high prevalence of neuropsychiatric illness has previously been reported. METHODS Clinical and neuropsychiatric follow-up study by telephone and self-administered instruments (HADS, SDQ-20, DES II, EQ-5D), on 41 patients with fixed dystonia after a mean of 7.6 (+/-3.6) years. RESULTS We obtained information on clinical outcome in 35 (85.4%) patients and neuropsychiatric questionnaire data in 22 (53.7%). Eighty-three percent were women. Thirty-one percent had worsened, 46% were the same and 23% had improved, of whom 6% had major remissions. At follow-up, mean duration of illness was 11.8 (+/-4.9) years and mean age 43.2 (+/-14.8) years. Except for 1 patient who was re-diagnosed with corticobasal degeneration, the diagnosis remained unchanged in others. Forty-one percent had scores indicating anxiety and 18% indicating depression; 18% scored within the range of dissociative/somatoform disorders on DES II and 19% on SDQ-20. The mean EQ-5D index and VAS scores were 0.34 and 56.1%. Comparison between the 3 outcome groups revealed significant difference only in the EQ-5D (p=0.003). Only baseline CRPS predicted a worse outcome (chi(2)=0.006). CONCLUSIONS Our findings revealed that the prognosis of this syndrome is poor, with improvement in less than 25% of patients, major remission in only 6% and continued worsening in a third. A high rate of neuropsychiatric findings was noted and new neuropsychiatric features had occurred in some. Average health status was poor. Of the baseline parameters, only CRPS predicted poorer outcome.

Anti-basal ganglia antibodies in patients with atypical dystonia and tics: A prospective study

Anti-basal ganglia antibodies (ABGA) are associated with movement disorders in children, but have not been assessed in adult onset movement disorders. In a prospective assessment ABGA were positive in 65% of a group of 65 patients with atypical movement disorders, but were very rare in healthy adults and adults with idiopathic dystonia. An autoimmune mechanism may underlie a proportion of cases of atypical movement disorders.

Antineuronal antibody status and phenotype analysis in Tourette's syndrome.

The Gilles de la Tourette syndrome (GTS) spectrum includes psychiatric comorbidities, mainly obsessive–compulsive disorder (OCD) and attention‐deficit‐hyperactivity disorder (ADHD). The role of environmental factors, e.g., antineuronal antibodies (ANeA), remains unclear. We compared the clinical features of ANeA‐positive and ANeA‐negative patients in 53 children and 75 adults with GTS. All diagnoses were made according to DSM‐IV‐TR criteria. A positive ANeA Western immunoblot showed bands for at least 1 of 3 reported striatal antigens (40, 45, and 60 kDa). Twelve children (23%) and 18 adults (25%) with GTS were ANeA‐positive. Disease duration, tic phenomenology and severity, frequency of echo/pali/coprophenomena, self‐injurious and aggressive behavior, or frequency of OCD comorbidity did not significantly differ between ANeA‐positive and negative patients. Similar findings were obtained analyzing separately the three different antibody reactivities. A comorbid diagnosis of ADHD was significantly less frequent in GTS patients positive for the anti‐60 kDa antibody only. Using a multivariate logistic regression model, adjusting for age, gender, and age at disease onset, a comorbid diagnosis of ADHD remained inversely associated with anti‐60 kDa antibodies (odds ratio = 0.14; P = 0.002; 95% confidence interval 0.04–0.49). ANeA status does not differentiate a specific phenotype of GTS.

Soluble adhesion molecules in Gilles de la Tourette's syndrome

To investigate the immune-mediated response in TS, and its relationship with streptococcal infection, we measured serum levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in patients with TS, compared to healthy and diseased controls. Soluble VCAM-1 and sE-selectin were significantly elevated in children and adults with TS, and sVCAM-1 was higher among anti-basal ganglia antibodies (ABGA)-positive adults with TS. No correlation of adhesion molecule levels to clinical severity or anti-streptococcal antibodies was observed. Children with Sydenhams chorea and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) showed an increased level of sICAM-1, but not sVCAM-1 and sE-selectin. These results provide initial evidence for a role of adhesion molecules and systemic inflammation in TS, and support the hypothesis of an ongoing immune-mediated process in this condition.

The entity of young onset primary cervical dystonia.

Primary cervical dystonia is typically an adult onset condition with symptom onset usually in the fifth and sixth decade. Young onset (<28 years) is uncommon. We report 76 patients with cervical dystonia as a presenting or predominant feature, with disease onset before the age of 28. Male to female ratio was 1.24:1 and the mean onset age was 21 (3–28) years. A family history of tremor and/or dystonia was noted in 26.3%. Depression and anxiety attacks were present in 23.7%.Prior injury or surgery involving the neck was noted in 17.1%. 23 (30.3%) experienced spontaneous partial or complete remissions within the first 5 years of onset, but all relapsed. Cervical dystonia was predominantly rotational torticollis. 30% developed extra‐nuchal dystonia and tremor affecting contiguous parts but in only one there was spread to affect the legs. All 15 patients tested for the DYT1 gene were negative. 74% responded favorably to botulinum toxin injections, whereas none of the 13 patients treated with L‐Dopa preparations had a beneficial response. The distinctive features of this entity are discussed.

Development and clinimetric assessment of a nurse-administered screening tool for movement disorders in psychosis

Background Movement disorders associated with exposure to antipsychotic drugs are common and stigmatising but underdiagnosed. Aims To develop and evaluate a new clinical procedure, the ScanMove instrument, for the screening of antipsychotic-associated movement disorders for use by mental health nurses. Method Item selection and content validity assessment for the ScanMove instrument were conducted by a panel of neurologists, psychiatrists and a mental health nurse, who operationalised a 31-item screening procedure. Interrater reliability was measured on ratings for 30 patients with psychosis from ten mental health nurses evaluating video recordings of the procedure. Criterion and concurrent validity were tested comparing the ScanMove instrument-based rating of 13 mental health nurses for 635 community patients from mental health services with diagnostic judgement of a movement disorder neurologist based on the ScanMove instrument and a reference procedure comprising a selection of commonly used rating scales. Results Interreliability analysis showed no systematic difference between raters in their prediction of any antipsychotic-associated movement disorders category. On criterion validity testing, the ScanMove instrument showed good sensitivity for parkinsonism (90%) and hyperkinesia (89%), but not for akathisia (38%), whereas specificity was low for parkinsonism and hyperkinesia, and moderate for akathisia. Conclusions The ScanMove instrument demonstrated good feasibility and interrater reliability, and acceptable sensitivity as a mental health nurse-administered screening tool for parkinsonism and hyperkinesia. Declaration of interest None.