Environmental risk factors and clinical phenotype in familial and sporadic primary blepharospasm.

BACKGROUND: Although environmental and genetic factors may contribute to the etiology of blepharospasm, their relative contribution in causing familial and sporadic blepharospasm is unknown. METHODS: First-degree relatives of 122 patients with primary blepharospasm were examined with a validated 2-step diagnostic procedure, including a screening questionnaire and examination of some relatives. Examiners were blinded to the questionnaire data for family history of probands. Data for demographic and clinical features, prior ophthalmologic complaints, and nondecaffeinated coffee intake were collected from probands before family investigation. RESULTS: Dystonia was diagnosed in 27 relatives from 23 families (20% rate of family history for dystonia). No significant differences were found between familial and sporadic cases in the frequency of coffee drinking and eye diseases or in sex, age at onset, or tendency to spread. Multivariable conditional logistic analysis testing of 67 case patients and 127 family-matched unaffected siblings yielded a significant positive association between blepharospasm and prior eye diseases (adjusted odds ratio [OR] 2.5; 95% confidence interval [CI] 1.1-6.1; p = 0.03) and a significant inverse association between case status and ever coffee drinking (adjusted OR 0.23; 95% CI 0.1-0.8; p = 0.02). CONCLUSIONS: The new information from this large family-based study on primary blepharospasm strongly supports eye diseases and coffee as risk factors for blepharospasm. The finding that the 2 environmental exposures exerted a similar influence on familial and sporadic blepharospasm, together with the convergent phenotypic expression in familial and sporadic cases, implies that familial and sporadic blepharospasm probably share a common etiologic background.

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.

Quality of sleep in primary focal dystonia: a case-control study.

BACKGROUND: Sleep disturbances are common in patients with movement disorders. Evaluating quality of sleep is of primary importance because of the effect that nocturnal and daytime sleep abnormalities exert on general health status. However, quality of sleep has never been addressed in detail in patients with dystonia. The aim of this case-control study was to analyse quality of sleep in patients with the two most common forms of primary focal dystonia, blepharospasm (BSP) and cervical dystonia (CD). METHODS: We evaluated quality of sleep (Pittsburgh Sleep Quality Index, PSQI) and excessive daytime sleepiness (Epworth Sleepiness Scale, ESS) in 98 patients with focal adult-onset dystonia (52 with BSP; 46 with CD) and in a group of 56 age-and gender-matched healthy subjects. The Beck Depression Inventory (BDI) was used for the evaluation of depressive symptomatology. RESULTS: Quality of sleep was impaired (significantly higher PSQI scores) in both groups of patients. However, differences in PSQI scores between patients with CD and control subjects were partly confounded by BDI scores, whereas differences in PSQI scores between patients with BSP and control subjects were not influenced by BDI. Excessive daytime sleepiness was not significantly more frequent than in control subjects in either patients with BSP or patients with CD. CONCLUSIONS: This study suggests that the assessment and treatment of insomnia-related complaints should be considered in global management plans of patients with focal dystonia, particularly in those affected by BSP.

Influence of coffee drinking and cigarette smoking on the risk of primary late onset blepharospasm: evidence from a multicentre case control study.

Prior coffee and smoking habits were investigated in a multicentre case control study involving 166 patients presenting with primary late onset blepharospasm (BSP), 228 hospital control patients with primary hemifacial spasm and 187 population control subjects from five Italian centres. Information on age at disease onset, smoking and coffee drinking status at the reference age and average number of cups of coffee drunk/cigarettes smoked per day reached high and similar test-retest reproducibility in case and control patients. Unadjusted logistic regression analysis yielded a significant inverse association of prior coffee drinking and cigarette smoking with case status for the control groups. After adjustment for age, sex, referral centre, disease duration, years of schooling and ever coffee drinking/cigarette smoking, as appropriate, the smoking estimate lacked significance whereas the association of coffee intake and BSP did not (cases vs hospital control patients: OR 0.37 (95% CI 0.20 to 0.67); cases vs population control subjects: OR 0.44 (95% CI 0.23 to 0.85)). The strength of the inverse association between BSP and coffee intake tended to increase with the average number of cups drunk per day. There was a significant correlation between age of BSP onset and number of cups per day (adjusted regression coefficient 1.73; p = 0.001) whereas no correlation was found with number of packs of cigarettes per day. Coffee drinking may be inversely associated with the development of primary BSP and this association may partly depend on the amount consumed.

A family study on primary blepharospasm.

BACKGROUND: Previous family studies provided evidence that blepharospasm (BSP) can aggregate in families but did not give accurate and reliable information on the characteristics and degree of familial clustering. AIM: To evaluate the proportion of familial and non-familial BSP cases, the clinical expression of dystonia within families, the inheritance pattern, and the extent of penetrance. METHODS: The study was based on the examination of the first degree relatives of 56 probands with primary BSP. RESULTS: The 56 families produced a potential population of 436 first degree relatives of whom 296 were alive and 233 were examined. The proportion of index patients with at least one first degree relative affected by BSP, or adult onset dystonia other than BSP, was 27%. There was a remarkable degree of phenotypic variability of dystonia within families. Similar segregation ratios were calculated for probands' siblings and children. Under the assumption of autosomal dominant transmission of adult onset dystonia, penetrance was about 20%. CONCLUSIONS: The findings of this family study are relevant for accurately counselling the families of patients with BSP and may help identify the most appropriate study design to explore genetic susceptibility in BSP.

Frequency of familial aggregation in primary adult-onset cranial cervical dystonia.

Family history of definite/probable dystonia was studied in 36 probands with primary adult-onset cranial/cervical dystonia. Of the 157 relatives who were examined, 8 from 7 families and 11 from 10 families were diagnosed as having definite or probable dystonia, respectively. The frequency of familial occurrence of definite dystonia was 19.4%, 33% when considering both definite and probable dystonia. There was a tendency for relatives affected by either definite or probable dystonia to have the same type of dystonia as the index patient. Similar segregation ratios were found for parents, siblings, and children with either definite or probable dystonia. These observations raise the possibility that probable dystonia represents formes frustes/mild phenotypes of dystonia rather than another movement disorder.

Influence of age on the association between primary hemifacial spasm and arterial hypertension.

OBJECTIVE: To investigate the association between primary hemifacial spasm and arterial hypertension. SUBJECTS: 114 patients with primary hemifacial spasm and 228 neurological controls, matched for age, sex, and referral centre, were recruited during an 18 month period from consecutive outpatients attending two neurological institutions. DESIGN: The association between exposure variables and case/control status was examined in conditional logistic regression models, adjusting simultaneously for disease duration and education level. RESULTS: Hypertension was more common among the patients with primary hemifacial spasm than among the controls. The association was independent of age, disease duration, years of schooling, and other diseases (adjusted odds ratio (OR) 2.76 (95% confidence interval (CI), 1.43 to 5.33); p = 0.002). Hypertension was associated with hemifacial spasm in both the left sided group (adjusted OR, 2.76 (1.18 to 6.44); p = 0.02) and the right sided group (adjusted OR, 3.02 (1.13 to 8.1); p = 0.03). The association of hypertension with hemifacial spasm was apparently greater in the age group < 60 years (adjusted OR, 4.2 (1.4 to 12); p = 0.008) than in the age group >/= 60 years (adjusted OR, 2.5 (CI 1.3 to 4.6); p = 0.005), but the difference in the OR estimates between the two age groups was not significant. Among hypertensive patients, mean age at the diagnosis of hypertension was significantly lower than mean age at the onset of hemifacial spasm in the age group >/= 60 years, but not significantly different in the age group < 60 years. CONCLUSIONS: The findings support the hypothesised association of primary hemifacial spasm with hypertension and raise the possibility that a different mechanism underlies the association in different age groups.

Agreement among neurologists on the clinical diagnosis of dystonia at different body sites.

OBJECTIVE: To study the reliability of the diagnosis of blepharospasm, oromandibular dystonia, cervical dystonia, and writer's cramp among neurologists. METHODS: 12 patients with adult onset focal segmental dystonia were videotaped in a standardised way. The tape was sent to six neurologists who are involved in clinical practice without a specific interest in movement disorders (general neurologists), and to four neurologists expert in movement disorders. The observers had to recognise whether the patients were affected by dystonia and to distinguish among blepharospasm, oromandibular dystonia, cervical dystonia, and writer's cramp. Interobserver reliability was assessed by kappa statistics, and the degree of agreement was classified according to the Landis classification. RESULTS: The 10 neurologists reached slight to moderate agreement on the diagnosis of these four disorders. When the observers were subdivided according with their professional experience in the field, a moderate to perfect agreement on the diagnosis was achieved by specialists in movement disorders, and a fair to moderate agreement by the general neurologists. CONCLUSIONS: Neurologists may have different ability to recognise adult onset focal dystonia, depending on their experience and on the type of dystonia.

Frequency of apraxia of eyelid opening in the general population and in patients with extrapyramidal disorders.

We ascertained the prevalence of apraxia of eyelid opening (AEO) in a community located in Puglia, a region of southern Italy. The crude prevalence rate was 59 per million (95% confidence interval, 24-173). AEO coexisted with adult onset blepharospasm in 75% of cases, with atypical parkinsonism in 25% of cases. Among the overall patient population seen at our movement disorders clinic from 1987 to 1997, AEO was isolated in 10 otherwise healthy individuals, associated with adult-onset dystonia in 13 cases, and associated with a parkinsonian syndrome in 9 cases. The frequency of AEO was 10.8% in the dystonia group, and 2.1% in the overall parkinsonian group (Parkinson's disease, 0.7%; progressive supranuclear palsy, 33.3%). In two patients with possible progressive supranuclear palsy, AEO worsened after increasing levodopa dosage or acute apomorphine challenge and disappeared following levodopa discontinuation. AEO developing in the setting of a parkinsonian syndrome may be either disease- or drug-related.