Clinical correlates of "pure" essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of "pure" essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of "pure" ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) "pure" ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of "pure" ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of "pure" ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

Clinical correlates of “pure” essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of “pure” essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of “pure” ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) “pure” ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of “pure” ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of “pure” ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

Changes in laser-evoked potentials during hypnotic analgesia for chronic pain: a pilot study

BACKGROUND: Hypnotic analgesia is one of the most effective nonpharmacological methods for pain control. Hypnosis and distraction of attention from pain might share similar mechanisms by which brain responses to painful stimulation could be similarly reduced in both states. There is ample evidence for the efficacy of clinical hypnosis as a psychological intervention in the treatment of acute or chronic pain. Results are conflicting, however, with some studies showing an increase, others a reduction, and others still no change in the amplitude of event-related brain potentials during hypnosis as compared to control conditions. Here we compared the effects of clinical hypnosis to simple distraction of attention during recording of laser-evoked potentials (LEPs) in patients with chronic pain. METHODS: The dominant hand in ten patients with chronic pain was tested with LEPs during: (I) resting state; (II) clinical hypnosis, and (III) distraction of attention. Nociceptive responses elicited by LEPs were graded on a numerical rating scale (NRS), and the change in N2-P2 complex amplitude during the three experimental conditions was analyzed. RESULTS: N2-P2 amplitudes were significantly decreased during the hypnotic state as compared to the resting state and distraction of attention. CONCLUSIONS: Hypnosis is a modified state of consciousness that may differ from mental relaxation or distraction of attention from pain. A reduction in N2-P2 amplitude may result from the modulation of diverse brain networks, particularly the frontolimbic pathways, which could modify noxious stimuli input processing during hypnotic analgesia. Our findings indicate that several different brain mechanisms may act together in hypnosis and distraction of attention during pain processing and that clinical hypnosis may provide a useful non-invasive pain relief therapy

Late-onset multiple sclerosis presenting with cognitive dysfunction and severe cortical/infratentorial atrophy.

OBJECTIVE: Although cognitive dysfunction is a relevant aspect of multiple sclerosis (MS) from the earliest disease phase, cognitive onset is unusual thus jeopardizing early and accurate diagnosis. Here we describe 12 patients presenting with cognitive dysfunction as primary manifestation of MS with either mild or no impairment in non-cognitive neurological domains.METHODS: Twelve patients with cognitive onset who were subsequently diagnosed with MS (CI-MS) were included in this retrospective study. Twelve cognitively normal MS patients (CN-MS), 12 healthy controls and four patients having progressive supranuclear palsy (PSP) served as the reference population.RESULTS: Ten CI-MS patients had progressive clinical course and all patients had late disease onset (median age = 49 years; range = 40-58 years). Among cognitive functions, frontal domains were the most involved. Compared to CN-MS and healthy controls, significant cortical and infratentorial atrophy characterized CI-MS patients. Selective atrophy of midbrain tegmentum with relative sparing of pons, known as "The Hummingbird sign," was observed in eight CI-MS and in three PSP patients.DISCUSSION: Our observation suggests that MS diagnosis should be taken into consideration in case of cognitive dysfunction, particularly when associated with slowly progressive disease course and severe cortical, cerebellar and brainstem atrophy even in the absence of other major neurological symptoms and signs

Imaging of the dopamine transporter predicts pattern of disease progression and response to levodopa in patients with schizophrenia and parkinsonism: a 2-year follow-up multicenter study

Similarly to subjects with degenerative parkinsonism, (123)I-FP-CIT SPECT has been reported either normal or abnormal in patients with drug-induced parkinsonism (DIP), challenging the notion that parkinsonism might be entirely due to post-synaptic D2-receptors blockade by antipsychotic drugs. In a previous multicenter cross-sectional study conducted on a large sample of patients with schizophrenia, we identified 97 patients who developed parkinsonism with a similar bi-modal distribution of DAT-SPECT. In this longitudinal study, we reported clinical and imaging features associated with progression of motor disability over 2-year follow-up in 60 out of those 97 patients with schizophrenia and parkinsonism who underwent (123)I-FP-CIT SPECT at baseline evaluation (normal SPECT=33; abnormal SPECT=27). As second end-point, chronic response to levodopa over a 3-month period was tested in a subgroup of subjects. Motor Unified Parkinson's Disease Rating Scale (UPDRS) at follow-up significantly increased in patients with abnormal SPECT. Specifically, a 6-point worsening was demonstrated in 18.5% of the subjects with abnormal SPECT and in none of the subjects with normal SPECT. Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT. After adjustment for possible confounders, linear regression analysis demonstrated that abnormal SPECT findings at baseline were the only predictor of motor disability progression and of better outcome of levodopa treatment. Our results support the notion that a degenerative disease might underlie parkinsonism in a minority of schizophrenic patients chronically exposed to antipsychotics. Functional imaging of the dopamine transporter can be helpful to select this patient sub-group that might benefit from levodopa therapy

Impulse control disorders in advanced Parkinson's disease with dyskinesia: The ALTHEA study

Impulse control disorders and dyskinesia are common and disabling complications of dopaminergic treatment in Parkinson's disease. They may coexist and are possibly related. The objectives of this study were to assess the frequency and severity of impulse control disorders in Parkinson's disease patients with dyskinesia

A Bayesian approach to Essential Tremor plus: A preliminary analysis of the TITAN cohort

Background: The construct of Essential Tremor plus (ET-plus) refers to patients who also have rest tremor and/or mild neurologic signs of unknown significance. It is unclear whether soft signs represent confounding factors or are useful in suspecting an alternative condition. Methods: Using a Bayesian approach to ET-plus patients recruited in The ITAlian tremor Network (TITAN), we analyzed the probability that these patients do not have ET. Results: The data of 274 ET-plus patients were extracted from the TITAN database. The majority of patients (240/274; 87.5%) had a single soft sign. The post-test probability of not having ET was different according to the specific soft sign: namely, 0.64 (rest tremor); 0.46 (questionable dystonia); 0.85 (questionable bradykinesia); 0.19 (soft gait impairment); and 0.09 (questionable cognitive issues). In patients with multiple soft signs, the post-test probability of not having ET was higher than 50% for 7 out of 11 combinations, accounting for 44.1% of subjects. Overall, the post-test probability of not having ET was higher than 50% in up to 71.5% of ET-plus patients. Discussion: We have here shown that: 1) the soft signs differently contribute in modulating the probability that a patient does not have ET; and 2) the effect of multiple soft signs are not always addictive. Future studies are needed to collect prevalence figures of soft signs in different neurological disorders as well as in the elderly and to calculate their value in predicting the development of an alternative tremor syndrome