Tremor in motor neuron disease may be central rather than peripheral in origin

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition

“Hard to say, hard to understand, hard to live”: possible associations between neurologic language impairments and suicide risk

In clinical practice, patients with language impairments often exhibit suicidal ideation (SI) and suicidal behavior (SB, covering the entire range from suicide attempts, SA, to completed suicides). However, only few studies exist regarding this subject. We conducted a mini-review on the possible associations between neurologic language impairment (on the motor, comprehension, and semantic sides) and SI/SB. Based on the literature review, we hypothesized that language impairments exacerbate psychiatric comorbidities, which, in turn, aggravate language impairments. Patients trapped in this vicious cycle can develop SI/SB. The so-called “affective prosody” provides some relevant insights concerning the interaction between the different language levels and the world of emotions. This hypothesis is illustrated in a clinical case that we reported, consisting of the case of a 74-year old woman who was admitted to a psychiatric emergency department (ED) after a failed SA. Having suffered an ischemic stroke two years earlier, she suffered from incomplete Broca’s aphasia and dysprosody. She also presented with generalized anxiety and depressive symptoms. We observed that her language impairments were both aggravated by the exacerbations of her anxiety and depressive symptoms. In this patient, who had deficits on the motor side, these exacerbations were triggered by her inability to express herself, her emotional status, and suffering. SI was fluctuant, and—one year after the SA—she completed suicide. Further studies are needed to ascertain possible reciprocal and interacting associations between language impairments, psychiatric comorbidities, and SI/SB. They could enable clinicians to better understand their patient’s specific suffering, as brought on by language impairment, and contribute to the refining of suicide risk detection in this sub-group of affected patients

Neurology and the COVID-19 emergency

Following the COVID-19 outbreak, significant changes have been implemented on a national level in the organization of neurology units and associated stroke units. Regionallydesignated COVID-19 hospitals have implemented an aggressive policy to relocate as many beds as possible to COVID-19 patients. In order to do so, the preferred strategy has been to reduce the number of beds in neurology units, and in some cases several units have been consolidated into one. In other cases, particularly in the northern regions

The effect of stimulation frequency on transcranial evoked potentials

Introduction - Transcranial magnetic stimulation-evoked electroencephalography potentials (TEPs) have been used to study motor cortical excitability in healthy subjects and several neurological conditions. However, optimal recording parameters for TEPs are still debated. Stimulation rates could affect TEP amplitude due to plasticity effects, thus confounding the assessment of cortical excitability. We tested whether short interpulse intervals (IPIs) affect TEP amplitude.Methods - We investigated possible changes in TEP amplitude and global mean field amplitude (GMFA) obtained with stimulation of the primary motor cortex at IPIs of 1.1-1.4 s in a group of healthy subjects.Results - We found no differences in TEP amplitude or GMFA between the first, second and last third of trials.Discussion - Short IPIs do not affect TEP size and can be used without the risk of confounding effects due to short-term plasticity

May Bradykinesia Features Aid in Distinguishing Parkinson's Disease, Essential Tremor, and Healthy Elderly Individuals?

Background: Bradykinesia is the hallmark feature of Parkinson's disease (PD); however, it can manifest in other conditions, including essential tremor (ET), and in healthy elderly individuals. Objective: Here we assessed whether bradykinesia features aid in distinguishing PD, ET, and healthy elderly individuals. Methods: We conducted simultaneous video and kinematic recordings of finger tapping in 44 PD patients, 69 ET patients, and 77 healthy elderly individuals. Videos were evaluated blindly by expert neurologists. Kinematic recordings were blindly analyzed. We calculated the inter-raters agreement and compared data among groups. Density plots assessed the overlapping in the distribution of kinematic data. Regression analyses and receiver operating characteristic curves determined how the kinematics influenced the likelihood of belonging to a clinical score category and diagnostic group. Results: The inter-rater agreement was fair (Fleiss K=0.32). Rater found the highest clinical scores in PD, and higher scores in ET than healthy elderly individuals (p<0.001). In regard to kinematic analysis, the groups showed variations in movement velocity, with PD presenting the slowest values and ET displaying less velocity than healthy elderly individuals (all ps<0.001). Additionally, PD patients showed irregular rhythm and sequence effect. However, kinematic data significantly overlapped. Regression analyses showed that kinematic analysis had high specificity in differentiating between PD and healthy elderly individuals. Nonetheless, accuracy decreased when evaluating subjects with intermediate kinematic values, i.e., ET patients. Conclusion: Despite a considerable degree of overlap, bradykinesia features vary to some extent in PD, ET, and healthy elderly individuals. Our findings have implications for defining bradykinesia and categorizing patients

Clinical and Kinematic Features of Valproate-Induced Tremor and Differences with Essential Tremor

Tremor is a common movement disorder that can be induced by medications, including valproate, which is used for the treatment of epilepsy. However, the clinical and neurophysiological features of valproate-induced tremor are still under-investigated. We performed a clinical and kinematic assessment of valproate-induced tremor by considering tremor body distribution and activation conditions. We investigated possible correlations between demographic and clinical data and kinematic features. Valproate-induced tremor results were also compared with those collected in a large sample of patients with essential tremor. Sixteen valproate-induced tremor patients and 93 essential tremor patients were enrolled. All participants underwent a standardised neurological examination and video recording. Patients also underwent an objective assessment of postural, kinetic and rest tremor of the upper limbs and head tremor through kinematic analysis. Nonparametric tests were used for statistical comparisons between the two groups. Clinical evaluation showed a higher occurrence of rest tremor as well as head or voice, and lower limb involvement in patients with valproate-induced tremor. Kinematic analysis showed a substantial variability in the tremor features of patients with valproate-induced tremor. Compared to essential tremor, we found a higher occurrence of rest tremor of the upper limbs and the involvement of more body segments in valproate-induced tremor patients. Valproate-induced tremor has distinctive clinical and kinematic features, which may suggest that valproate interferes with the cerebellar functions

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular

Core Depressive Symptoms In Depressed Cancer OutpatientsB

Objective: This study aimed to estimate the prevalence of core depressive symptoms among cancer outpatients diagnosed with depressive or adjustment disorders with depressed mood. We also aimed to detect potential differences between patient self-assessment and psychiatrist evaluation in classifying the severity of depression. Methods: Fifty-two outpatients diagnosed with solid tumor malignancy and depressive or adjustment disorder with depressed mood were assessed using the Hamilton Depression Rating Scale (HAMD-17) (and its shortened version the HAMD-7) and the Zung Self-Rating Depression Scale (ZSDS) (and its shortened version BZSDS). Results: Based on HAMD-7 results, the prevalence of moderate depression was low (7.7%); using the BZSDS moderate depression was absent. Mild depression was identified in 82.3% and 73% of our subjects using the HAMD-7 and the BZSDS, respectively. The strength of agreement between psychiatrist and patients' self-evaluation for mild depression was "slight", employing the original and the abbreviated versions of both scales. Conclusion: Our findings suggest that the prevalence of core depressive symptoms is very low in cancer patients diagnosed with depressive disorder. The lack of a strong agreement between psychiatrist and patient in classifying the severity of depression highlights the importance of factors such as well-being and functional status among depressed cancer patients in their self assessment of depression. © Massimo et al

Plasticity and dystonia: a hypothesis shrouded in variability.

Studying plasticity mechanisms with Professor John Rothwell was a shared highlight of our careers. In this article, we discuss non-invasive brain stimulation techniques which aim to induce and quantify plasticity, the mechanisms and nature of their inherent variability and use such observations to review the idea that excessive and abnormal plasticity is a pathophysiological substrate of dystonia. We have tried to define the tone of our review by a couple of Professor John Rothwell's many inspiring characteristics; his endless curiosity to refine knowledge and disease models by scientific exploration and his wise yet humble readiness to revise scientific doctrines when the evidence is supportive. We conclude that high variability of response to non-invasive brain stimulation plasticity protocols significantly clouds the interpretation of historical findings in dystonia research. There is an opportunity to wipe the slate clean of assumptions and armed with an informative literature in health, re-evaluate whether excessive plasticity has a causal role in the pathophysiology of dystonia

Diagnostic accuracy of the primary care screener for affective disorder (PC-SAD) in primary care

Background: Depression goes often unrecognised and untreated in non-psychiatric medical settings. Screening has recently gained acceptance as a first step towards improving depression recognition and management. The Primary Care Screener for Affective Disorders (PC-SAD) is a self-administered questionnaire to screen for Major Depressive Disorder (MDD) and Dysthymic Disorder (Dys) which has a sophisticated scoring algorithm that confers several advantages. This study tested its performance against a ‘gold standard’ diagnostic interview in primary care. Methods: A total of 416 adults attending 13 urban general internal medicine primary care practices completed the PC-SAD. Of 409 who returned a valid PC-SAD, all those scoring positive (N=151) and a random sample (N=106) of those scoring negative were selected for a 3-month telephone follow-up assessment including the administration of the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I) by a psychiatrist who was masked to PC-SAD results. Results: Most selected patients (N=212) took part in the follow-up assessment. After adjustment for partial verification bias the sensitivity, specificity, positive and negative predictive value for MDD were 90%, 83%, 51%, and 98%. For Dys, the corresponding figures were 78%, 79%, 8%, and 88%. Conclusions: While some study limitations suggest caution in interpreting our results, this study corroborated the diagnostic validity of the PC-SAD, although the low PPV may limit its usefulness with regard to Dys. Given its good psychometric properties and the short average administration time, the PC-SAD might be the screening instrument of choice in settings where the technology for computer automated scoring is available