Giovanni Defazio

Pain as a nonmotor symptom of Parkinson disease: evidence from a case-control study

OBJECTIVE To determine whether pain is more frequent among people with Parkinson disease (PD) than among age-matched controls. DESIGN Case-control study. PATIENTS AND METHODS Logistic regression models taking into account type of pain, time between pain and PD onset, and possible confounders were used to compare 402 PD patients with 317 age-matched healthy control subjects. RESULTS The overall frequency of pain was significantly greater in PD patients than in controls (281 [69.9%] vs 199 [62.8%]; P = .04), mainly because the healthy control group lacked dystonic pain. Conversely, the frequency of nondystonic pain was similar among PD patients and controls (267 [66.4%] vs 199 [62.8%]; P = .28). Nevertheless, we observed a significant association between PD and nondystonic pain, beginning after the onset of parkinsonian symptoms (odds ratio, 2.1; 95% confidence interval, 1.4-2.9). Cramping and central neuropathic pain were more frequent among PD patients than controls. About one-quarter of patients who experienced pain reported pain onset before starting antiparkinsonian therapy. CONCLUSION These data support the hypothesis that pain begins at clinical onset of PD or thereafter as a nonmotor feature of PD.

Pain and motor complications in Parkinson's disease

Aims: To study the association of pain with motor complications in 117 patients with Parkinson’s disease. Methods: Patients were asked to refer any pain they experienced at the time of study and lasting since at least 2 months. Basic parkinsonian signs and motor complications (including motor fluctuations and dyskinesia) were assessed and Unified Parkinson’s Disease Rating Scale (UPDRS) motor score part III (during on) and part IV were calculated. Information on age, sex, duration of disease, use of dopamine agonists and levodopa, years of levodopa treatment and current levodopa dosage, medical conditions possibly associated with pain, and depression were collected. Single and multiple explanatory variable logistic regression models were used to check the association of pain with the investigated variables. Results: Pain was described by 47 patients (40%) and could be classified into dystonic (n.19) and non dystonic pain (n.16); in 12 patients both types coexisted. Multiple explanatory variable logistic regression models indicated a significant association of pain with motor complications (adjusted OR, 5.7; 95% CI, 2 to 16.5; p = 0.001). No association was found between pain, dystonic or non dystonic, and the other investigated variables including medical conditions known to be associated to pain in the general population. There was a significant correlation (r = 0.31, p<0.05) between severity of pain (measured on a Visual Analogue Scale) and severity of motor complications (UPDRS part IV). Conclusions: Pain may be a representative feature of Parkinson’s disease frequently associated with motor complications. The association is independent of a number of potentially relevant demographic and clinical variables.

Epidemiology of primary dystonia

The prevalence estimates for primary dystonia range from two to 50 cases per million for early-onset dystonia and from 30 to 7320 cases per million for late-onset dystonia. From analysis of methodological information from 14 selected studies, we concluded that all studies on the basis of treatment settings or record-linkage systems, and two population-based surveys were probably flawed by incomplete ascertainment; the third population-based study provided the largest prevalence for late-onset dystonia but probably overestimated the prevalence of the disorder. Age and ethnic differences among study populations further biased comparisons of estimates. On the basis of methodologically more robust service-based studies and the likely percentage of underdiagnosis in a given area, more accurate prevalence estimates may be 111 per million for early-onset dystonia in Ashkenazi Jews from New York area, 600 per million for late-onset dystonia in northern England, and 3000 per million for late-onset dystonia in the Italian population over age 50 years.

Changes of serum sICAM-1 and MMP-9 induced by rIFNβ-1b treatment in relapsing-remitting MS

OBJECTIVE To correlate changes in serum levels of intercellular adhesion molecule-1 (sICAM-1) and matrix metalloproteinases (MMP) with clinical and MRI evidence of disease activity in MS patients receiving treatment with interferon-beta (rIFNbeta)-1b. BACKGROUND rIFNbeta reduces the frequency of gadolinium-enhancing (Gd+) MRI in relapsing-remitting MS (RRMS). Its mechanism of action on improving the integrity of the blood-brain barrier remains unclear. METHODS sICAM-1 and MMP-9 and MMP-2 serum levels were longitudinally (24 months) investigated (ELISA; zymography) in correlation with the modifications of the integrated area under the curve of Expanded Disability Status Scale scores normalized to entry baseline (deltaEDSS AUC) and of GD+ MRI scans, and with neutralizing antibodies (NAB) to rIFNbeta-1b production (MxA) in 36 RRMS patients. RESULTS During the first 12 months of treatment, levels of sICAM-1 increased and MMP-9 decreased significantly. After 12 months, levels returned toward baseline. Levels of sICAM-1 and MMP-9 were significantly negatively correlated. MMP-2 levels did not change significantly during the same period. During the second semester of the study, deltaEDSS AUC was significantly reduced. The percentage of patients with Gd+ MRI decreased significantly in the first (33%), second (29%), third (20%), and fourth (28%) semesters of treatment compared to baseline (62%). The NAB+ patients (14%) tended to have lower sICAM-1 levels at the ninth month; a higher MMP-9 activity at the sixth, 12th, and 18th months; and a greater deltaEDSS AUC in the third semester of treatment in comparison with the NAB- patients. CONCLUSIONS These results show that rIFNbeta-1b therapy increases sICAM-1 serum levels and reduces serum MMP-9 activity.

Camptocormia in Parkinson disease: an epidemiological and clinical study

Background: Camptocormia is an abnormal flexion of the thoracolumbar spine during standing and walking that abates in the recumbent position. Methods: In a single-centre epidemiological and clinical study, the prevalence of camptocormia in Parkinson disease (PD) and its relationship with the clinical features of PD were investigated. A total of 275 consecutive outpatients were systematically screened for camptocormia with a clinical evaluation. Patients who screened positive for camptocormia were subsequently reassessed by formal goniometric analysis. The demographic and clinical features of the patients with and without camptocormia were then compared. Results: A 6.9% (19/275, 95% CI, 4.2 to 10.6) prevalence of camptocormia was found. Camptocormia was found in patients with more severe PD, as clinically assessed by the Hoehn–Yahr (HY) staging and the motor Unified Parkinson Disease Rating Scale (UPDRS) part III, longer l-dopa treatment duration and greater l-dopa daily dose and presence of DSM-IV dementia. Camptocormia was reported to develop after the clinical onset of PD. No correlation was found between the degree of trunk flexion and age, duration of PD, UPDRS motor score, HY staging, and l-dopa treatment duration and dose. As a risk factor, the study identified previous vertebral surgery. Conclusions: Camptocormia, a relatively common sign in PD seems to be related to the clinical severity of PD.

Possible risk factors for primary adult onset dystonia: a case-control investigation by the Italian Movement Disorders Study Group

OBJECTIVES Little is known about the aetiology of idiopathic adult onset dystonia. The Italian Movement Disorders Study Group promoted a case-control study on some hypothetical risk factors including past medical events, life events, life habits, occupational hazards, and family hystory of dystonia, parkinsonism, and tremor. METHODS Cases affected by idiopathic adult onset dystonia (age at symptom onset >20 years, duration of disease >one year and <five years) were selected among consecutive outpatients attending 14 Italian centres. Control outpatients matched for age (±5 years), sex, and referral centre were identified among diagnostic categories thought to be unassociated with study exposures. Information was obtained by a standardised questionnaire administered by medical interviewers. Conditional logistic univariate and multivariate regression analyses were performed by a standard statistical package. RESULTS Multivariate analysis on 202 cases and 202 age and sex matched control outpatients indicated that head or facial trauma with loss of consciousness, family history of dystonia, and family history of postural tremor independently increased the risk of developing adult onset dystonia, whereas hypertension and cigarette smoking exerted a protective effect. The findings also suggested a positive association between local body injury—for example, previous ocular diseases and neck or trunk trauma—and dystonia of the same body part. CONCLUSIONS The results support the idea that environmental and genetic factors may both be important in the aetiology of adult onset dystonia, and suggest aetiological clues worthy of further analytical investigation.

Correlation between cortical plasticity, motor learning and BDNF genotype in healthy subjects

There is good evidence that synaptic plasticity in human motor cortex is involved in behavioural motor learning; in addition, it is now possible to probe mechanisms of synaptic plasticity using a variety of transcranial brain-stimulation protocols. Interactions between these protocols suggest that they both utilise common mechanisms. The aim of the present experiments was to test how well responsiveness to brain-stimulation protocols and behavioural motor learning correlate with each other in a sample of 21 healthy volunteers. We also examined whether any of these measures were influenced by the presence of a Val66Met polymorphism in the BDNF gene since this is another factor that has been suggested to be able to predict response to tests of synaptic plasticity. In 3 different experimental sessions, volunteers underwent 5-Hz rTMS, intermittent theta-burst stimulation (iTBS) and a motor learning task. Blood samples were collected from each subject for BDNF genotyping. As expected, both 5-Hz rTMS and iTBS significantly facilitated MEPs. Similarly, as expected, kinematic variables of finger movement significantly improved during the motor learning task. Although there was a significant correlation between the effect of iTBS and 5-Hz rTMS, there was no relationship in each subject between the amount of TMS-induced plasticity and the increase in kinematic variables during motor learning. Val66Val and Val66Met carriers did not differ in their response to any of the protocols. The present results emphasise that although some TMS measures of cortical plasticity may correlate with each other, they may not always relate directly to measures of behavioural learning. Similarly, presence of the Val66Met BDNF polymorphism also does not reliably predict responsiveness in small groups of individuals. Individual success in behavioural learning is unlikely to be closely related to any single measure of synaptic plasticity.

Somatosensory temporal discrimination in patients with primary focal dystonia

Purposes: To determine whether somatosensory temporal discrimination will reliably detect subclinical sensory impairment in patients with various forms of primary focal dystonia. Methods: The somatosensory temporal discrimination threshold (STDT) was tested in 82 outpatients affected by cranial, cervical, laryngeal and hand dystonia. Results were compared with those for 61 healthy subjects and 26 patients with hemifacial spasm, a non-dystonic disorder. STDT was tested by delivering paired stimuli starting with an interstimulus interval of 0 ms followed by a progressively increasing interstimulus interval. Results: STDT was abnormal in all the different forms of primary focal dystonias in all three body regions (eye, hand and neck), regardless of the distribution and severity of motor symptoms. Receiver operating characteristic curve analysis calculated in the three body regions yielded high diagnostic sensitivity and specificity for STDT abnormalities. Conclusions: These results provide definitive evidence that STDT abnormalities are a generalised feature of patients with primary focal dystonias and are a valid tool for screening subclinical sensory abnormalities.

The Focal Dystonias: Current Views and Challenges for Future Research

The most common forms of dystonia are those that develop in adults and affect a relatively isolated region of the body. Although these adult‐onset focal dystonias are most prevalent, knowledge of their etiologies and pathogenesis has lagged behind some of the rarer generalized dystonias, in which the identification of genetic defects has facilitated both basic and clinical research. This summary provides a brief review of the clinical manifestations of the adult‐onset focal dystonias, focusing attention on less well understood clinical manifestations that need further study. It also provides a simple conceptual model for the similarities and differences among the different adult‐onset focal dystonias as a rationale for lumping them together as a class of disorders while at the same time splitting them into subtypes. The concluding section outlines some of the most important research questions for the future. Answers to these questions are critical for advancing our understanding of this group of disorders and for developing novel therapeutics.

Abnormal processing of the nociceptive input in Parkinson's disease : A study with CO2 laser evoked potentials

&NA; Since a number of patients with Parkinson’s Disease (PD) complain of painful sensations, we studied whether the central processing of nociceptive inputs is abnormal in PD. To test this hypothesis, we recorded scalp CO2 laser evoked potentials (LEPs) to hand skin stimulation in 18 pain‐free PD patients with unilateral bradykinetic‐rigid syndrome (hemiparkinson) during the off state and in 18 healthy subjects. This technique allows us to explore non‐invasively the functional status of some cerebral structures involved in nociceptive input processing. In both PD patients and control subjects, CO2 laser stimulation gave rise to a main negative N2 potential followed by a positive P2 response at vertex peaking at a latency of about 200 and 300 ms, respectively. These potentials are thought to originate from several brain structures devoted to nociceptive input processing, including the cingulate gyrus and insula. PD patients and normal subjects showed comparable N2 and P2 latencies, whereas the N2/P2 peak‐to‐peak amplitude was significantly lower in PD patients (regardless of the clinically affected body side) than in controls. LEPs were even recorded after acute L‐dopa administration in 7 additional PD patients. L‐dopa administration yielded no significant change in N2/P2 amplitude as compared to the off state. These results suggest an abnormal nociceptive input processing in pain‐free PD patients which appears to be independent of clinical expression of parkinsonian motor signs and is not affected by dopaminergic stimulation.