[How to explore a cervical dystonia]. / Comment j'explore une dystonie cervicale.

Cervical dystonia is one of the most frequent form of focal dystonia. However, there's a great lack of awareness of this condition : a long delay to diagnosis is quite common and misdiagnosis is often seen. Nevertheless, this pathology is invalidating and improving diagnosis could have an impact on the treatment and the patient's quality of life.

Trop souvent méconnue, la dystonie cervicale (parfois appelée torticolis spasmodique) est pourtant une des formes les plus fréquentes de dystonie focale. Les errances diagnostiques sont fréquentes et le délai pour établir le bon diagnostic est souvent long. Il s'agit pourtant d'une pathologie invalidante pour laquelle un traitement est envisageable et susceptible de soulager le patient.

Data set of healthy old people assessed for three walking conditions using accelerometric and opto-electronic methods.

BACKGROUND: Gait patterns of healthy aging are needed to allow a comparison with pathological situations. However, little data is available. OBJECTIVE: To present gait pattern of healthy older specially selected to be "healthy walkers". METHOD: Fifty-seven older people benefited from a geriatric assessment including clinical and functional evaluations to include only those without gait disorders. Gait data were simultaneously recorded using a tri-axial accelerometer placed on the waist and four 3D position markers placed on the feet at the level of the heel and the toe. Volunteers walked at comfortable self-selected speed (CW), fast self-selected speed (FW), and finally in dual task walking condition (DTW). The extracted gait parameters were: gait speed, stride length, stride frequency, regularity and symmetry, swing, stance and double support time and ratio and minimum toe clearance. Gait speed and stride length were normalized to the right leg length. RESULTS: Fifty-seven older people with a mean age of 69.7 ± 4.2 years old (range from 65 to 82 years) were included. Data were analyzed according to the gender and according to the age (<70 or ≥70 years old). After normalization to leg length, the main significant differences were shown for stride length and minimum toe clearance in CW, FW and in DTW that were shorter in women. The regularity in FW was significantly lower among older volunteers. CONCLUSIONS: This work provides a data set considering 14 gait parameters obtained from 57 healthy old people strictly selected and assessed for three walking conditions and shows that GS, SL and MTC have to be related to the gender. The age-related impact on gait performances appears reduced in this cohort.

[Impulse control behaviors associated with antiparkinsonian medications]. / Les troubles du contrôle des impulsions associés au traitement dopaminergique substitutif antiparkinsonien.

In some patients, impulse control behaviours can be triggered by dopaminergic replacement therapy, particularly dopamine agonist drugs: hobbyism, punding (stereotyped behaviours), compulsive buying, binge eating disorder, pathological gamgling, hypersexuality, hedonistic homeostatic dysregulation syndrome ... The pathogenesis of these behaviours: is not well understood, but likely involves aberrant changes in the dopaminergic pathways that mediate motivation i.e., a dopaminergic "overdose" in meso-cortico-limbic circuits, An early diagnosis is difficult, but mandatory to prevent the occurrence of devastating familial, marital, professional, socio-economic, medical and medico-legal consequences. Their management is not yet well standardized. Patients and caregivers should be warned about impulse control behaviours before starting dopamine agonists and monitoring for such behaviours while on therapy is requested.

[Dementia in Parkinson's disease: risk factors, diagnosis and treatment]. / La démence chez le patient parkinsonien: facteurs de risque, diagnostic et traitement.

Aside from limb tremor, bradykinesia, rigidity and gait disturbances, Parkinson's disease (PD) is also characterized by non-motor symptoms. A cognitive decline can occur early in the disease course and undoubtedly impact of the patient's quality of life. Dementia affects 80% of patients 20 years after disease onset but a small subgroup of patients remain free of dementia even after decades with PD. Risk factors and diagnosis of dementia can be easily assessed using bed-side clinical instruments. Advances in genetics and imagery will allow improving the diagnosis and therapeutic strategy dementia in Parkinson's disease.

Gesture subtype-dependent left lateralization of praxis planning: an event-related fMRI study.

Ideomotor apraxia is a disorder mainly of praxis planning, and the deficit is typically more evident in pantomiming transitive (tool related) than intransitive (communicative) gestures. The goal of the present study was to assess differential hemispheric lateralization of praxis production using event-related functional magnetic resonance imaging. Voxel-based analysis demonstrated significant activations in posterior parietal cortex (PPC) and premotor cortex (PMC) association areas, which were predominantly left hemispheric, regardless of whether planning occurred for right or left hand transitive or intransitive pantomimes. Furthermore, region of interest-based calculation of mean laterality index (LI) revealed a significantly stronger left lateralization in PPC/PMC clusters for planning intransitive (LI = -0.49 + 0.10, mean + standard deviation [SD]) than transitive gestures (-0.37 + 0.08, P = 0.02, paired t-tests) irrespective of the hand involved. This differential left lateralization for planning remained significant in PMC (LI = -0.47 + 0.14 and -0.36 + 0.13, mean + SD, P = 0.04), but not in PPC (-0.56 + 0.11 and -0.45 + 0.12, P = 0.11), when both regions were analyzed separately. In conclusion, the findings point to a left-hemispheric specialization for praxis planning, being more pronounced for intransitive gestures in PMC, possibly due to their communicative nature.

[Treatment of early Parkinson's disease]. / La vignette thérapeutique de l'etudiant. La maladie de Parkinson débutante.

We present a discussion on the treatment options in the case of a patient seen at the outpatient abnormal movement clinic for a resting tremor of both hands. Signs and symptoms of the parkinsonian syndrome are summarized as well as the current treatment options of early Parkinson's disease.

[Preserve brain function...through physical exercice?]. / Préserver le fonctionnement du cerveau...par la pratique d'une activité physique?

Over the last few years, there has been an increasing interest in the relationship between brain function and physical exercise. Preliminary evidence from observational and interventional studies in humans suggests a positive and robust effect of chronic aerobic exercise on several brain functions across the entire lifespan. Physical activity and exercise might also serve to reduce the risk of age-associated neurological disorders such as Alzheimer's and Parkinson's diseases. The mechanisms underlying these beneficial effects remain poorly understood. More scientific work is needed before disseminating more specific recommendations to the general population.

Assessing gait parameters with accelerometer-based methods to identify older adults at risk of falls: a systematic review.

PURPOSE: The purpose of this study was to perform a systematic review to assess the utility of accelerometric methods to identify older adults at risk of falls. METHODS: The Preferred Reporting Item for Systematic review and Meta-Analysis (PRISMA) guidelines were followed during all steps of this systematic review. Cross sectional and longitudinal studies assessing gait parameters in older adults using accelerometric devices, and comparing groups based on the risk of falls or fall history were identified from studies published in the MEDLINE, SCOPUS and Cochrane Database of Systematic Reviews databases between January 1996 and January 2017. Study selection and data extraction were performed independently by two reviewers. The quality of the methodology used in the studies included was assessed using the Newcastle-Ottawa Scale. RESULTS: In total, 354 references were identified through the database search. After selection, ten studies were included in this systematic review. According to the cross sectional studies, people who fall or are at risk of fall are slower, and walk with shorter steps, lower step frequency, worse stride and step regularity in terms of time, position and acceleration profiles. One longitudinal study suggests considering harmonic ratio of upper trunk acceleration in the vertical plane. Two other longitudinal studies highlight the importance of considering more than one gait parameter, and sophisticated statistical tools to discern older adults at risk for future fall(s). CONCLUSION: This systematic review essentially highlights the lack of available literature providing strong evidence that gait parameters obtained using acceleration-based methods could be useful to discern older people at risk of fall. Available literature is encouraging, but further high quality studies are needed to highlight the cross-sectional and longitudinal relationships between gait parameters and falls in older adults.

Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study.

Little is known about the neural correlates of tics and associated urges. In the present study, we aimed to explore the neural basis of tics in patients with Tourette syndrome by using event-related functional MRI (fMRI). Ten patients (6 women, 4 men; age: mean +/- SD = 31 +/- 11.2) were studied while spontaneously exhibiting a variety of motor and vocal tics. On the basis of synchronized video/audio recordings, fMRI activities were analysed 2 s before and at tic onset irrespective of the clinical phenomenology. We identified a brain network of paralimbic areas such as anterior cingulate and insular cortex, supplementary motor area (SMA) and parietal operculum (PO) predominantly activated before tic onset (P < 0.05, corrected for multiple comparisons). In contrast, at the beginning of tic action, significant fMRI activities were found in sensorimotor areas including superior parietal lobule bilaterally and cerebellum. The results of this study indicate that paralimbic and sensory association areas are critically implicated in tic generation, similar to movements triggered internally by unpleasant sensations, as has been shown for pain or itching.

[Therapeutic armamentarium in neurology: the birth of a new era]. / L'arsenal thérapeutique en neurologie: une nouvelle ère voit le jour.

The field of neurology was long infamous for a lack of therapeutic options. How many of you have once thought: "Neurologists don't cure the disease, they admire it". But those days have passed into history, and the field is now vibrant with new treatments and hope even for patients with the worst neurodegenerative diseases. We summarized in the present review the latest major advances in therapeutic principles and practice for some of the most frequent chronic neurological disorders such as headaches, epilepsy, multiple sclerosis, dementias, Parkinson's disease, sleep/wake disturbances and peripheral neuropathies. We cannot cure or prevent, but we can now halt or control symptoms and disease progression to provide physical and psychological relief, and a better quality of life for patients who suffer from these otherwise devastating neurological conditions.

Cerebral metabolic correlates of four dementia scales in Alzheimer's disease.

Different scales can be used to evaluate dementia severity in Alzheimer's disease (AD). They do assess different cognitive or functional abilities, but their global scores are frequently in mutual correlation. Functional imaging provides an objective method for the staging of dementia severity. Positron emission tomography was used to assess the relationship between brain metabolism and four dementia scales that reflect a patient's global cognitive abilities (mini mental state), caregiver's evaluation of cognitive impairment (newly designed scale), daily living functioning (instrumental activities of daily living) and global dementia (clinical dementia rating). We wondered whether different clinical dementia scales would be related to severity of metabolic impairment in the same brain regions, and might reflect impairment of common cognitive processes. 225 patients with probable AD were recruited in a prospective multicentre European study. All clinical scales were related to brain metabolism in associative temporal, parietal or frontal areas. A factorial analysis demonstrated that all scales could be classified in a single factor. That factor was highly correlated to decrease of cerebral activity in bilateral parietal and temporal cortices, precuneus, and left middle frontal gyrus. This finding suggests that global scores for all scales provided similar information on the neural substrate of dementia severity. Capitalizing on the neuroimaging literature, dementia severity reflected by reduced metabolism in posterior and frontal associative areas in AD might be related to a decrease of controlled processes.

Neural and cognitive bases of upper limb apraxia in corticobasal degeneration.

OBJECTIVE: To investigate the neural and cognitive bases of upper limb apraxia in corticobasal degeneration (CBD). METHODS: Eighteen patients with CBD underwent a cognitive neuropsychological assessment of apraxia and resting [(18)F]-fluorodeoxyglucose PET scanning. Two complementary measures of apraxia were computed for each modality of gesture production. First, a performance score measured error frequency during gesture execution. Second, as a more stringent test of the integrity of the praxis system, the correction score measured the patient's ability to correct his or her errors on a second attempt. For each measure type, a cut-off score for the presence of apraxia was defined with regard to healthy controls. Using each cut-off score, the regional cerebral glucose metabolism of patients with CBD with apraxia (i.e., performing below cut-off score) was compared with that of patients with CBD without apraxia. RESULTS: Mean performance scores were below normal values in all modalities. Anterior cingulate hypometabolism predominated in patients with CBD who performed below the cut-off performance score. At variance, mean correction scores were below normal values for gesture imitation only. Hypometabolism in superior parietal lobule and supplementary motor area characterized patients with CBD who were unable to correct their errors at the same rate as control subjects did. CONCLUSIONS: Distinct neural networks underlie distinct aspects of the upper limb apraxic deficits in CBD. Extending previous findings of gesture production deficits in CBD, the use of complementary measures of apraxic behavior discloses a visuoimitative upper limb apraxia in CBD, underlain by a metabolic decrease in a parietofrontal neural network.

Fluorodopa uptake and glucose metabolism in early stages of corticobasal degeneration.

Fluorodopa (FDOPA) and fluorodeoxyglucose (FDG) PET was performed in six patients in early stages of corticobasal degeneration (CBD) and compared to Parkinson's disease (PD) patients with a similar degree of bradykinesia and rigidity and to healthy controls. Statistical parametric mapping analysis comparing CBD to controls showed metabolic decrease in premotor, primary motor, supplementary motor, primary sensory, prefrontal, and parietal associative cortices, and in caudate and thalamus contralateral to the side of clinical signs. Except for the prefrontal regions a similar metabolic pattern was observed when CBD was compared to PD. Putamen FDOPA uptake was decreased in both CBD and PD. Caudate FDOPA uptake in CBD patients was decreased contralateral to clinical signs when compared to controls, but was higher than in PD. In early stages of CBD, FDOPA and FDG PET patterns differed from those observed in PD. In CBD the asymmetry in FDOPA uptake was less pronounced than that of clinical signs or metabolic impairment.

Medial temporal lobe metabolic impairment in dementia associated with motor neuron disease.

In the course of their disease certain patients with frontotemporal dementia (FTD) develop clinical features compatible with a motor neuron disease (FTD-MND). Previous reports have suggested that the functional pattern is similar in FTD and FTD-MND. However, some neuropathological studies suggest greater involvement of medial temporal regions in FTD-MND than in FTD. Using statistical parametric mapping (SPM96), we compared the metabolic patterns obtained at rest with positron emission tomography in 10 FTD patients and three FTD-MND patients with those obtained from 46 healthy subjects (HS). Mean age, duration of illness and dementia stage did not differ statistically between the FTD and FTD-MND groups. In comparison with HS, both groups showed frontal and anterior temporal hypometabolism at P<0.001. When the FTD-MND group was compared to the FTD group, significant hypometabolism was only observed in bilateral amygdala, bilateral hippocampus, and bilateral enthorinal and parahippocampal regions (Brodmann's areas, BA 28/36) at P<0.005. We found no significant differences in regional glucose uptake when FTD patients were contrasted to FTD-MND patients. Our results suggest statistically comparable frontal and lateral temporal hypometabolism in both conditions but greater impairment of medial temporal lobe activity in FTD-MND. Our results and a review of the literature support the hypothesis that there is a functional continuum between classical motor neuron disease (cMND), FTD-MND, and FTD.

Brain perfusion patterns in familial frontotemporal lobar degeneration.

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and pathologically heterogeneous disorder. The aim of this study was to compare clinical features and perfusion patterns on SPECT of patients with familial FTLD-TAR DNA binding protein 43 kDa (TDP) and MAPT mutations. METHODS: Patients were included if they had MAPT or GRN mutations, positive family history with pathologically proven FTLD in the patient or first-degree relative, or were part of FTD-MND families. All patients and 10 age- and gender-matched controls underwent measurement of brain perfusion using (99m)Tc-HMPAO SPECT. We used SPM8 to perform image processing and voxel-based group analyses (p < 0.001). Gender and age were included as nuisance variables in the design matrices. RESULTS: Of the 29 patients with familial FTLD, 19 had familial FTLD-TDP (GRN mutations in 6), and 10 had MAPT mutations. At clinical presentation, familial FTLD-TDP patients were older at onset (p = 0.030) and had more memory deficits (p = 0.011), whereas patients with MAPT had more naming deficits (p < 0.001) and obsessive-compulsive behavior (p = 0.001). The between-groups SPECT analyses revealed significantly less perfusion in the right frontal lobe, precuneus, cuneus, and inferior parietal lobule in familial FTLD-TDP, whereas significantly less perfusion was found in the left temporal and inferior frontal gyri in MAPT. Post hoc analysis of familial FTLD-TDP with unknown genetic defect vs MAPT revealed less perfusion in the right frontal and parietal lobe. CONCLUSION: Familial FTLD-TDP shows relatively more posterior hypoperfusion, including the precuneus and inferior parietal lobule, possibly related to significant memory impairment. Patients with MAPT were characterized by impaired perfusion of the temporal regions and naming deficits.

Levodopa increases memory encoding and dopamine release in the striatum in the elderly.

Normal aging is associated with a decrease in dopaminergic function and a reduced ability to form new motor memories with training. This study examined the link between both phenomena. We hypothesized that levodopa would (a) ameliorate aging-dependent deficits in motor memory formation, and (b) increase dopamine availability at the dopamine type 2-like (D2) receptor during training in task-relevant brain structures. The effects of training plus levodopa (100mg, plus 25mg carbidopa) on motor memory formation and striatal dopamine availability were measured with [(11)C]raclopride (RAC) positron emission tomography (PET). We found that levodopa did not alter RAC-binding potential at rest but it enhanced training effects on motor memory formation as well as dopamine release in the dorsal caudate nucleus. Motor memory formation during training correlated with the increase of dopamine release in the caudate nucleus. These results demonstrate that levodopa may ameliorate dopamine deficiencies in the elderly by replenishing dopaminergic presynaptic stores, actively engaged in phasic dopamine release during motor training.

Neuroimaging of neuronal circuits involved in tic generation in patients with Tourette syndrome.

OBJECTIVE: To identify brain regions generating tics in patients with Tourette syndrome using sleep as a baseline. METHODS: We used [15O]H2O PET to study nine patients with Tourette syndrome and nine matched control subjects. For patients, conditions included tic release states and sleep stage 2; and for control subjects, rest states and sleep stage 2. RESULTS: Our study showed robust activation of cerebellum, insula, thalamus, and putamen during tic release. CONCLUSION: The network of structures involved in tics includes the activated regions and motor cortex. The prominent involvement of cerebellum and insula suggest their involvement in tic initiation and execution.

Comparison of impaired subcortico-frontal metabolic networks in normal aging, subcortico-frontal dementia, and cortical frontal dementia.

Normal aging, progressive supranuclear palsy (PSP), and frontotemporal dementia (FTD) are characterized by different degrees of decline in frontal lobe functions. We used (18)FDG-PET and statistical parametric mapping (SPM96) to compare relative subcorticofrontal metabolic impairment at rest in 21 healthy elderly subjects (HES), 20 PSP patients, and 6 FTD patients. When HES were compared to 22 healthy young subjects, widespread decrease in metabolism was observed in bilateral medial prefrontal areas including anterior cingulate cortices, in dorsolateral prefrontal areas, in left lateral premotor area, in Broca's area, and in left insula. In PSP compared to the 43 healthy subjects (HS), we observed subcorticofrontal metabolic impairment including both motor and cognitive neural networks. Impairment of functional connections between midbrain tegmentum and cerebellar, temporal and pallidal regions was demonstrated in PSP as compared to HS. When comparing FTD to HS, glucose uptake was primarily reduced in dorsolateral and ventrolateral prefrontal cortices and in frontopolar and anterior cingulate regions. There was also bilateral anterior temporal, right inferior parietal, and bilateral striatal hypometabolism. Finally, FTD showed more severe striatofrontal metabolic impairment than PSP, while mesencephalothalamic involvement was only observed in PSP. Our data suggest that subcorticofrontal metabolic impairment is distributed in distinct subcorticocortical networks in normal aging, PSP, and FTD. Subcorticofrontal dementia in PSP is related to hypometabolism in discrete frontal areas, which are probably disconnected from certain subcortical structures. The concept of subcortical dementia is reinforced by our data, which show disrupted functional connections between mesencephalon and cerebellar cortex, inferior and medial temporal regions, and pallidum.