Angelo Fabio Gigante

Midbrain SERT in degenerative parkinsonisms: a 123I-FP-CIT SPECT study.

SPECT imaging is widely used for the differential diagnosis of degenerative parkinsonisms by exploiting the high affinitiy of the radiotracer 123I‐FP‐CIT for the dopamine transporter. Reduced levels of DAT are found in Parkinson Disease (PD), Dementia with Lewy Bodies (DLB), and Progressive Supranuclear Palsy (PSP) compared to in Essential Tremor (ET) and Healthy Controls (HC). However, the extent of the neurodegenerative process may extend beyond nigrostriatal system. We have exploited the affinity of the same radiotracer 123I‐FP‐CIT for the serotonin transporter to investigate SERT levels in the midbrain of patients with PD, DLB, PSP, and ET compared to HC. Using MRI images as anatomical templates for midbrain uptake quantification, we found a mild decrease in SERT levels in PD compared to ET and HC, with marked inter‐individual variability; on the other side, PSP and DLB patients displayed markedly reduced to undetectable levels of SERT, respectively. These findings show that the neurodegenerative process affects serotoninergic neurons in parkinsonisms, with much more severe involvement in DLB than in PD patients, despite the comparable loss of striatal DAT. SERT‐dependent 123I‐FP‐CIT uptake may allow a more comprehensive assessment of neurochemical disturbances in degenerative parkinsonisms and may have a value for differential diagnosis.

Is tremor in dystonia a phenotypic feature of dystonia

To understand better the features and mechanisms distinguishing tremor in dystonia, we reviewed the epidemiologic, clinical, and neurophysiologic data in patients with dystonia and tremor. Clinical studies suggest that tremor starts at or after dystonia onset in body parts affected or unaffected by dystonia. Tremor in dystonia manifests during posture or voluntary movements even though some dystonic patients may have tremor at rest. Prevalence rates for tremor in dystonia are higher in patients with adult-onset dystonia and cervical dystonia than in other dystonias and highest in patients in whom dystonia spreads. Neurophysiologic investigations in patients with dystonia and tremor show reduced reciprocal inhibition between agonist and antagonist upper limb muscles, a lack of brainstem interneuronal inhibition, and abnormal sensory integration. The neurophysiologic abnormalities in patients with dystonia and tremor resemble those in dystonia but differ from those described in essential tremor. Tremor is a phenotypic motor feature in dystonia.

Tremor in primary adult-onset dystonia: prevalence and associated clinical features

Objective To investigate the frequency and the main clinical features of tremor in primary adult-onset dystonia (PAOD). Methods This cross-sectional study was conducted on 429 patients with PAOD from eight Italian movement disorder centres. Results Of the 429 dystonic patients, 72 (16.7%) had tremor. Although sex and age at dystonia onset were similar in dystonic patients who had tremor and those who did not, patients who had tremor were affected more often by focal cervical dystonia and less often by focal blepharospasm. Dystonia had a greater tendency to spread in patients with tremor. According to the Movement Disorder Society Consensus Statement, tremor was classified as dystonic tremor (DT) in 43 patients and tremor associated with dystonia (TAWD) in 23 patients. Six patients had both types of tremor. Taking into account potential confounding by age at onset and body distribution of the corresponding dystonia type, all the clinical features in patients with DT and in those with TAWD were comparable except the tendency of dystonia to spread, which was greater in patients with DT. Conclusions Tremor is a relatively common feature occurring in about 17% of patients with primary late-onset dystonia. The association between tremor and dystonia spread suggests that this form of tremor may be a dystonic manifestation. Similarities in phenotypic features of DT and TAWD predominated over differences, suggesting that the two forms of tremor may be manifestations of the same disease. Differences in gender and body distribution of tremor between patients with dystonia and tremor and those of patients with essential tremor also suggest that tremor in dystonia and essential tremor are different entities.

Impaired cognitive functions in adult-onset primary cranial cervical dystonia

BACKGROUND Adult-onset primary dystonia is thought to be a purely motor disorder. Nevertheless, several studies provided evidence that sensory and psychiatric disturbances may contribute to the clinical spectrum of of dystonia, whereas evidence supporting cognitive impairment is still limited. METHODS A set of neuropsychological tests was administered to non depressed, non demented patients with cranial-cervical dystonia and healthy control subjects. The test battery included n-Back Task, Wechsler Memory Scale, Trail Making Test version A and B, and Wisconsin Card Sorting Test. RESULTS As compared with healthy control subjects of similar age, sex and socio-economic status, patients with cranial-cervical dystonia showed deficit on working memory functions revealed by n-Back task, impairment of mental control and visual reproduction subtests of Wechsler memory scale, deficit on information processing speed and set-shifting capacity revealed by Trail Making Test A and B. CONCLUSION Patients with cranial-cervical dystonia may have impairment in specific cognitive domains relative to working memory, processing speed, visual motor ability and short term memory. Probably, these deficits are not dependent on the clinical expression of dystonia but might rather reflect the cortical and subcortical changes highlighted by functional and VBM imaging studies in patients with different forms of dystonia.

The epidemiology of pain in Parkinson’s disease

Pain occurring in Parkinson’s disease (PD) may affect a large proportion of patients. Based on the results of the methodologically more robust case–control studies that detected a significantly greater frequency of pain in PD patients than in control subjects, pain should now be considered as a non-motor symptom of PD. The heterogeneous quality of pain, the variable relationship of pain with parkinsonian motor signs, and the mixed response of pain to dopaminergic drugs suggest complex mechanisms for pain in PD. Some evidence raises the possibility of common mechanisms shared by pain patients, regardless of the clinical heterogeneity of pain and its variable relationship with motor signs.

Development and validation of a clinical scale for rating the severity of Blepharospasm

Existing scales for rating the severity of blepharospasm (BSP) are limited by a number of potential drawbacks. We therefore developed and validated a novel scale for rating the severity of BSP. The development of the scale started with careful examination of the clinical spectrum of the condition by a panel of experts who selected phenomenological aspects thought to be relevant to disease severity. Thereafter, selected items were first checked for reliability, then reliable items were combined to generate the scale, and clinimetric properties of the scale were evaluated. Finally, the confidence with which the scale could be used by people without high levels of movement disorders skill was assessed. The new scale, based on objective criteria, yielded moderate to almost perfect reliability, acceptable internal consistency, satisfactory scaling assumptions, lack of floor and ceiling effects, partial correlations with a prior severity scale and with a quality of life scale, and good sensitivity to change. Despite a few limitations, the foregoing features make the novel scale more suitable than existing scales to assess the severity of BSP in natural history and pathophysiologic studies as well as in clinical trials.

Action tremor in Parkinson's disease: frequency and relationship to motor and non‐motor signs

Action tremor may occur in patients with Parkinsons disease and cause misdiagnosis with other movement disorders such as essential tremor and dystonia. Data on the frequency of action tremor in Parkinsons disease and on the relationships with other motor and non‐motor signs are limited.

Rest tremor in idiopathic adult-onset dystonia

Tremor in dystonia has been described as a postural or kinetic abnormality. In recent series, however, patients with idiopathic adult‐onset dystonia also displayed rest tremor.

The environmental epidemiology of primary dystonia.

Background Dystonia is a movement disorder characterized by involuntary muscle contractions that cause twisting movements and abnormal postures. Primary dystonia is the most common form and is thought to be a multifactorial condition in which one or more genes combine with environmental factors to reach disease. Methods We reviewed controlled studies on possible environmental risk factors for primary early- and late-onset dystonia. Results Environmental factors associated with primary early-onset dystonia are poorly understood. Early childhood illnesses have been reported to be more frequent in patients with DYT1 dystonia than in subjects carrying the DYT1 mutation that did not manifest dystonia, thus raising the possibility that such exposures precipitate dystonia among DYT1 carriers. Conversely, several environmental factors have been associated with primary adult-onset focal dystonias compared to control subjects. Namely, eye diseases, sore throat, idiopathic scoliosis, and repetitive upper limb motor action seem to be associated with blepharospasm (BSP), laryngeal dystonia (LD), cervical dystonia (CD), and upper limb dystonia, respectively. In addition, an inverse association between coffee drinking and BSP has been observed in both case-unrelated control and family-based case-control studies. Additional evidence supporting a causal link with different forms of primary late-onset dystonia is only available for diseases of the anterior segment of the eye, writing activity, and coffee intake. Conclusion There is reasonable epidemiological evidence that some environmental factors are risk-modifying factors for specific forms of primary adult-onset focal dystonia.

Planning genetic studies on primary adult-onset dystonia: Sample size estimates based on examination of first-degree relatives

Primary adult-onset dystonia is thought to be partly genetic, but families large enough for a genome wide search are difficult to find. We examined the first-degree relatives of 76 primary adult-onset dystonia patients to assess the feasibility of model-free nonparametric methods that allow either screening of candidate loci (case-control design, transmission disequilibrium test [TDT], and sibling-TDT [S-TDT]) or identification of novel genes (affected sib-pair [ASP] method). Among the examined relatives, 1/34 parents, 13/149 siblings and 10/125 offspring were affected by adult-onset dystonia. The predicted sample sizes to detect a gene conferring an Odds ratio of 3.0 were 99 for case-control and TDT methodology, 148 for S-TDT, and 107 to 173 for an ASP study assuming three major loci. Based on our family structure, TDT, S-TDT, and ASP methods would required screening of about 220, 700, and 580 to 939 probands respectively. Analysing subpopulations with different types of dystonia, TDT required fewer probands with cervical/hand dystonia, S-TDT needed fewer probands with cranial dystonia. These sample size estimates suggest that the S-TDT may be feasible, whereas collection of cases for both TDT and ASP approaches would represent a major collaborative challenge.