Background
Diagnosis of focal dystonia is based on clinical grounds and is therefore open to bias. To date, diagnostic guidelines have been only proposed for blepharospasm and laryngeal dystonia. To ...provide practical guidance for clinicians with less expertise in dystonia, a group of Italian Movement Disorder experts formulated clinical diagnostic recommendations for cervical, oromandibular, and limb dystonia.
Methods
A panel of four neurologists generated a list of clinical items related to the motor phenomenology of the examined focal dystonias and a list of clinical features characterizing neurological/non-neurological conditions mimicking dystonia. Thereafter, ten additional expert neurologists assessed the diagnostic relevance of the selected features and the content validity ratio was calculated. The clinical features reaching a content validity ratio > 0.5 contributed to the final recommendations.
Results
The recommendations retained patterned and repetitive movements/postures as the core feature of dystonia in different body parts. If present, a sensory trick confirmed diagnosis of dystonia. In the patients who did not manifest sensory trick, active exclusion of clinical features related to conditions mimicking dystonia (features that would be expected to be absent in dystonia) would be necessary for dystonia to be diagnosed.
Discussion
Although reliability, sensitivity, and specificity of the recommendations are yet to be demonstrated, information from the present study would hopefully facilitate diagnostic approach to focal dystonias in the clinical practice and would be the basis for future validated diagnostic guidelines.
Abstract
Familial adult myoclonic epilepsy type 2 is a hereditary condition characterized by cortical tremor, myoclonus and epilepsy. It belongs to the spectrum of cortical myoclonus and the ...sensorimotor cortex hyperexcitability represents an important pathogenic mechanism underlying this condition. Besides pericentral cortical structures, the impairment of subcortical networks seems also to play a pathogenetic role, mainly via the thalamo-cortical pathway. However, the mechanisms underlying cortical–subcortical circuits dysfunction, as well as their impact on clinical manifestations, are still unknown. Therefore, the main aims of our study were to systematically study with an extensive electrophysiological battery, the cortical sensorimotor, as well as thalamo-cortical networks in genetically confirmed familial adult myoclonic epilepsy patients and to establish reliable neurophysiological biomarkers for the diagnosis.
In 26 familial myoclonic epilepsy subjects, harbouring the intronic ATTTC repeat expansion in the StAR-related lipid transfer domain-containing 7 gene, 17 juvenile myoclonic epilepsy patients and 22 healthy controls, we evaluated the facilitatory and inhibitory circuits within the primary motor cortex using single and paired-pulse transcranial magnetic stimulation paradigms. We also probed the excitability of the somatosensory, as well as the thalamo-somatosensory cortex connection by using ad hoc somatosensory evoked potential protocols. The sensitivity and specificity of transcranial magnetic stimulation and somatosensory evoked potential metrics were derived from receiver operating curve analysis. Familial adult myoclonic epilepsy patients displayed increased facilitation and decreased inhibition within the sensorimotor cortex compared with juvenile myoclonic epilepsy patients (all P < 0.05) and healthy controls (all P < 0.05). Somatosensory evoked potential protocols also displayed a significant reduction of early high-frequency oscillations and less inhibition at paired-pulse protocol, suggesting a concomitant failure of thalamo-somatosensory cortex circuits. Disease onset and duration and myoclonus severity did not correlate either with sensorimotor hyperexcitability or thalamo-cortical measures (all P > 0.05). Patients with a longer disease duration had more severe myoclonus (r = 0.467, P = 0.02) associated with a lower frequency (r = −0.607, P = 0.001) and higher power of tremor (r = 0.479, P = 0.02). Finally, familial adult myoclonic epilepsy was reliably diagnosed using transcranial magnetic stimulation, demonstrating its superiority as a diagnostic factor compared to somatosensory evoked potential measures. In conclusion, deficits of sensorimotor cortical and thalamo-cortical circuits are involved in the pathophysiology of familial adult myoclonic epilepsy even if these alterations are not associated with clinical severity. Transcranial magnetic stimulation-based measurements display an overall higher accuracy than somatosensory evoked potential parameters to reliably distinguish familial adult myoclonic epilepsy from juvenile myoclonic epilepsy and healthy controls.
Dubbioso et al. report that sensory–motor cortical hyperexcitability, as well as thalamo-cortical disconnection are involved in familial adult myoclonic epilepsy type 2 pathophysiology. Transcranial magnetic stimulation-based measurements display a higher diagnostic accuracy than somatosensory evoked potential parameters to reliably distinguish familial adult myoclonic epilepsy type 2 from juvenile myoclonic epilepsy and healthy controls.
Graphical Abstract
Graphical Abstract
Purpose
To assess disease-related patterns of in vivo pathology in 11 patients with Corticobasal Syndrome (CBS) compared to 20 healthy controls and 33 mild cognitive impairment (MCI) patients due to ...Alzheimer’s disease.
Methods
We assessed tau aggregates with
18
FAV1451 PET, amyloid-β depositions with
18
FAV45 PET, and volumetric microstructural changes with MRI. We validated for
18
FAV1451 standardised uptake value ratio (SUVRs) against input functions from arterial metabolites and found that SUVRs and arterial-derived distribution volume ratio (DVRs) provide equally robust measures of
18
FAV1451 binding.
Results
CBS patients showed increases in
18
FAV1451 SUVRs in parietal (
P
< 0.05) and frontal (
P
< 0.05) cortices in the affected hemisphere compared to healthy controls and in precentral (
P
= 0.008) and postcentral (
P
= 0.034) gyrus in the affected hemisphere compared to MCI patients. Our data were confirmed at the histopathological level in one CBS patient who underwent brain biopsy and showed sparse tau pathology in the parietal cortex co-localizing with increased
18
FAV1451 signal. Cortical and subcortical
18
FAV45 uptake was within normal levels in CBS patients. In parietal and frontal cortices of the most affected hemisphere we found also grey matter loss (
P
< 0.05), increased mean diffusivity (
P
< 0.05) and decreased fractional anisotropy (
P
< 0.05) in CBS patients compared to healthy controls and MCI patients. Grey matter loss and white matter changes in the precentral gyrus of CBS patients were associated with worse motor symptoms.
Conclusions
Our findings demonstrate disease-related patterns of in vivo tau and microstructural pathology in the absence of amyloid-β, which distinguish CBS from non-affected individuals and MCI patients.
Background and aim
Neurodegeneration with brain iron accumulation (NBIA) and Wilson’s disease (WD) is considered the prototype of neurodegenerative disorders characterised by the overloading of iron ...and copper in the central nervous system. Growing evidence has unveiled the involvement of these metals in brain cortical neurotransmission. Aim of this study was to assess cortical excitability profile due to copper and iron overload.
Methods
Three patients affected by NBIA, namely two patients with a recessive hereditary parkinsonism (PARK9) and one patient with aceruloplasminemia and 7 patients with neurological WD underwent transcranial magnetic stimulation (TMS) protocols to assess cortical excitability. Specifically, we evaluated the motor thresholds that reflect membrane excitability related to the voltage-gated sodium channels in the neurons of the motor system and the ease of activation of motor cortex via glutamatergic networks, and ad hoc TMS protocols to probe inhibitory-GABAergic (short interval intracortical inhibition, SICI; short-latency afferent inhibition, SAI; cortical silent period, CSP) and excitatory intracortical circuitry (intracortical facilitation, ICF).
Results
Patients with NBIA exhibited an abnormal prolongation of CSP respect to HC and WD patients. On the contrary, neurological WD displayed higher motor thresholds and reduced CSP and SICI.
Conclusion
Hereditary conditions due to overload of copper and iron exhibited peculiar cortical excitability profiles that can help during differential diagnosis between these conditions. Moreover, such results can give us more clues about the role of metals in acquired neurodegenerative disorders, such as Parkinson disease, Alzheimer disease, and multiple sclerosis.
Depression is characterized by feelings of sadness, loss, or anger that may interfere with everyday activities. Such a neuropsychiatric condition is commonly reported in multiple neurodegenerative ...disorders, which are quite different from each other. This study aimed at investigating the brain networks involved in depression in patients with frontotemporal dementia (FTD) and Parkinson's disease (PD) as compared to healthy controls (HC). Fifty participants were included in the study: 17 depressed FTD/PD patients; 17 non-depressed FTD/PD patients; and 16 non-depressed HCs matched for age and gender. We used the Beck depression inventory (BDI-II) to measure depression in all groups. On the same day, 3T brain magnetic resonance with structural and resting-state functional sequences were acquired. Differences in resting-state functional connectivity (FC) between depressed and non-depressed patients in all the experimental groups were assessed by using seed-to-seed and network-to-network approaches. We found a significant seed-to-seed hyperconnectivity patterns between the left thalamus and the left posterior temporal fusiform cortex, which differentiated FTD/PD depressed patients from the HCs. Network-to-network analysis revealed a significant hyperconnectivity among the default-mode network (left lateral-parietal region), the medial prefrontal cortex and the left lateral prefrontal cortex (i.e., part of the central executive network). We investigated whether such FC patterns could be related to the underlying neurodegenerative disorder by replicating the analyses with two independent samples (i.e., non-depressed PD and non-depressed FTD patients) and adding clinical parameters as covariates. We found no FC differences in these groups, thus suggesting how the FC pattern we found may signal a common depression-related neural pathway implicated in both the neurocognitive disorders.
Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven ...approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to "a priori" classifications and clinical overlapping.
Data were obtained by the Italian Registry of Functional Motor Disorders. Patients identified with multiple or "combined" FMDs by standardized clinical assessments were selected to be analyzed. Non-hierarchical cluster analysis was performed based on FMDs phenomenology. Multivariate analysis was then performed after adjustment for principal confounding variables.
From a study population of
= 410 subjects with FMDs, we selected
= 188 subjects women: 133 (70.7%); age: 47.9 ± 14.4 years; disease duration: 6.4 ± 7.7 years presenting combined FMDs to be analyzed. Based on motor phenotype, two independent clusters were identified: Cluster C1 (
= 82; 43.6%) and Cluster C2 (
= 106; 56.4%). Cluster C1 was characterized by functional tremor plus parkinsonism as the main clinical phenotype. Cluster C2 mainly included subjects with functional weakness. Cluster C1 included older subjects suffering from anxiety who were more treated with botulinum toxin and antiepileptics. Cluster C2 included younger subjects referring to different associated symptoms, such as pain, headache, and visual disturbances, who were more treated with antidepressants.
Using a data-driven approach of clinical data from the Italian registry, we differentiated clinical subtypes among combined FMDs to be validated by prospective studies.
Apathy is a neuropsychiatric condition characterized by reduced motivation, initiative, and interest in daily life activities, and it is commonly reported in several neurodegenerative disorders. The ...study aims to investigate large-scale brain networks involved in apathy syndrome in patients with frontotemporal dementia (FTD) and Parkinson’s disease (PD) compared to a group of healthy controls (HC). The study sample includes a total of 60 subjects: 20 apathetic FTD and PD patients, 20 non apathetic FTD and PD patients, and 20 HC matched for age. Two disease-specific apathy-evaluation scales were used to measure the presence of apathy in FTD and PD patients; in the same day, a 3T brain magnetic resonance imaging (MRI) with structural and resting-state functional (fMRI) sequences was acquired. Differences in functional connectivity (FC) were assessed between apathetic and non-apathetic patients with and without primary clinical diagnosis revealed, using a whole-brain, seed-to-seed approach. A significant hypoconnectivity between apathetic patients (both FTD and PD) and HC was detected between left planum polare and both right pre- or post-central gyrus. Finally, to investigate whether such neural alterations were due to the underlying neurodegenerative pathology, we replicated the analysis by considering two independent patients’ samples (i.e., non-apathetic PD and FTD). In these groups, functional differences were no longer detected. These alterations may subtend the involvement of neural pathways implicated in a specific reduction of information/elaboration processing and motor outcome in apathetic patients.
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