Frédéric Bloch

Bio: Frédéric Bloch is an academic researcher from Pierre-and-Marie-Curie University. The author has contributed to research in topics: Camptocormia & Medicine. The author has an hindex of 9, co-authored 9 publications receiving 618 citations. Previous affiliations of Frédéric Bloch include University of Paris & French Institute of Health and Medical Research.

REM sleep behavior disorder and REM sleep without atonia in patients with progressive supranuclear palsy.

Abstract: STUDY OBJECTIVE To compare sleep characteristics, rapid eye movement (REM) sleep without atonia, and REM sleep behavior disorder (RBD) in patients with progressive supranuclear palsy (tauopathy), patients with Parkinson's disease (a synucleinopathy), and control subjects. DESIGN Sleep interview, overnight polysomnography, and Multiple Sleep Latency Tests. PATIENTS Forty-five age- and sex-matched patients with probable progressive supranuclear palsy, (n=15, aged 68 +/- 8 years, 7 men), patients with Parkinson disease (n=15), and control subjects (n=15). SETTINGS Tertiary-care academic hospital. INTERVENTION N/A. RESULTS Compared to the 2 other groups, patients with progressive supranuclear palsy had a longer duration of wakefulness after sleep onset and twice as much sleep fragmentation and percentage of stage 1 sleep but had similar apnea-hypopnea indexes, periodic leg movements indexes, and mean daytime sleep latencies. REM sleep percentage was as low in patients with progressive supranuclear palsy (8% +/- 6% of total sleep time) as in patients with Parkinson disease (10% +/- 4%), versus 20% +/- 6% in controls (analysis of variance, P < .0001). Interestingly, patients with progressive supranuclear palsy had percentages of REM sleep without atonia (chin muscle activity: 33% +/- 36% of REM sleep) similar to those of patients with Parkinson disease (28% +/- 35%) and dramatically higher than those of controls (0.5% +/- 1%, analysis of variance, P = .008). Four (27%) patients with progressive supranuclear palsy had more than 50% REM sleep without atonia (as did a similar number of patients with Parkinson disease), and 2 of them (13%, vs 20% of patients with Parkinson disease) had clinical RBD. The four patients with progressive supranuclear palsy with excessive daytime sleepiness slept longer at night than the 11 patients with progressive supranuclear palsy who were alert (442 +/- 14 minutes vs 312 +/- 74 minutes, student t tests, P = .004), suggesting a primary nonnarcoleptic hypersomnia. CONCLUSION REM sleep without atonia and RBD were as frequent in patients with progressive supranuclear palsy as in patients with Parkinson disease. It suggests that the downstream cause of parkinsonism, rather than its primary neuropathology (synucleinopathy vs tauopathy), is a key factor for REM sleep behavior disorder.

Parkinson’s disease with camptocormia

Abstract: Background: Camptocormia is defined as an abnormal flexion of the trunk that appears when standing or walking and disappears in the supine position. The origin of the disorder is unknown, but it is usually attributed either to a primary or a secondary paravertebral muscle myopathy or a motor neurone disorder. Camptocormia is also observed in a minority of patients with parkinsonism. Objective: To characterise the clinical and electrophysiological features of camptocormia and parkinsonian symptoms in patients with Parkinson’s disease and camptocormia compared with patients with Parkinson’s disease without camptocormia. Methods: Patients with parkinsonism and camptocormia (excluding patients with multiple system atrophy) prospectively underwent a multidisciplinary clinical (neurological, neuropsychological, psychological, rheumatological) and neurophysiological (electromyogram, ocular movement recording) examination and were compared with age-matched patients with Parkinson’s disease without camptocormia. Results: The camptocormia developed after 8.5 (SD 5.3) years of parkinsonism, responded poorly to levodopa treatment (20%) and displayed features consistent with axial dystonia. Patients with camptocormia were characterised by prominent levodopa-unresponsive axial symptoms (ie, axial rigidity, gait disorder and postural instability), along with a tendency for greater error in the antisaccade paradigm. Conclusion: We suggest that (1) the salient features of parkinsonism observed in patients with camptocormia are likely to represent a specific form of Parkinson’s disease and camptocormia is an axial dystonia and (2) both camptocormia and parkinsonism in these patients might result from additional, non-dopaminergic neuronal dysfunction in the basal ganglia.

Gait and balance disorders in Parkinson's disease: impaired active braking of the fall of centre of gravity.

Abstract: Gait and balance disorders are common in Parkinson's disease (PD), but its pathophysiology is still poorly understood. Step length, antero-posterior, and vertical velocities of the center of gravity (CG) during gait initiation were analyzed in 32 controls and 32 PD patients, with and without levodopa, using a force platform. Brain volumes and mesencephalic surface area were measured in PD patients. During the swing limb period, controls showed a fall in the CG, which was reversed before foot-contact indicating active braking of the CG fall. In PD patients, without levodopa, step length and velocity were significantly reduced and no braking occurred before foot-contact in 22 patients. With levodopa, step length and velocity increased in all patients and 7 patients improved their braking capacity. PD patients with normal braking (n = 17) had significantly lower gait and balance disorder scores and higher normalized-mesencephalic surface areas compared to patients with impaired braking (n = 15). The decreased step length and velocity, characteristic of PD, mainly result from degeneration of central dopaminergic systems. The markedly decreased braking capacity observed in half the PD patients contributes to their gait disorders and postural instability, perhaps as a result of nondopaminergic lesions, possibly at the mesencephalic level.

Disease Severity and Progression in Progressive Supranuclear Palsy and Multiple System Atrophy: Validation of the NNIPPS – PARKINSON PLUS SCALE

Abstract: BACKGROUND The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study. METHODS AND FINDINGS Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α ≥ 0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80-0.93), and moderate (Intra-class coefficient = 0.54-0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho ≥ 0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall severity and progression was similar. CONCLUSIONS The NNIPPS-PPS has suitable validity, is reliable and sensitive, and therefore is appropriate for use in clinical studies with PSP or MSA. TRIAL REGISTRATION ClinicalTrials.gov NCT00211224.

Parkinson’s disease: clinical features and diagnosis

Abstract: Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

Standards for educational and psychological testing

Abstract: Pedagosko i psiholosko testiranje i procjenjivanje spadaju među najvažnije doprinose znanosti o ponasanju nasem drustvu i pružaju temeljna i znacajna poboljsanja u odnosu na ranije postupke. Iako se ne može ustvrditi da su svi testovi dovoljno usavrseni niti da su sva testiranja razborita i korisna, postoji velika kolicina informacija koje ukazuju na ucinkovitost kvalitetnih instrumenata u onim situacijama u kojima je njihovo koristenje potkrijepljeno validacijskim podacima. Pravilna upotreba testova može dovesti do boljih odluka o pojedincima i programima nego sto bi to bio slucaj bez njihovog koristenja, a također i ukazati na put za siri i pravedniji pristup obrazovanju i zaposljavanju. Međutim, losa upotreba testova može dovesti do zamjetne stete nanesene ispitanicima i drugim sudionicima u procesu donosenja odluka na temelju testovnih podataka. Cilj Standarda je promoviranje kvalitetne i eticne upotrebe testova te uspostavljanje osnovice za ocjenu kvalitete postupaka testiranja. Svrha objavljivanja Standarda je uspostavljanje kriterija za evaluaciju testova, provedbe testiranja i posljedica upotrebe testova. Iako bi evaluacija prikladnosti testa ili njegove primjene trebala ovisiti prvenstveno o strucnim misljenjima, Standardi pružaju okvir koji osigurava obuhvacanje svih relevantnih pitanja. Bilo bi poželjno da svi autori, sponzori, nakladnici i korisnici profesionalnih testova usvoje Standarde te da poticu druge da ih također prihvate.

Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease

Abstract: REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep with prominent motor activity accompanying dreaming. The terminology relating to RBD, and mechanisms underlying REM sleep without atonia and RBD based on data in cat and rat are presented. Neuroimaging data from the few published human cases with RBD associated with structural lesions in the brainstem are presented, in which the dorsal midbrain and pons are implicated. Pharmacological manipulations which alter RBD frequency and severity are reviewed, and the data from human neuropathological studies are presented. An anatomic framework and new schema for the pathophysiology of RBD are proposed based on recent data in rat regarding the putative flip-flop switch for REM sleep control. The structure in man analogous to the subcoeruleus region in cat and sublaterodorsal nucleus in rat is proposed as the nucleus (and its associated efferent and afferent pathways) crucial to RBD pathophysiology. The association of RBD with neurological disease ('secondary RBD') is presented, with emphasis on RBD associated with neurodegenerative disease, particularly the synucleinopathies. The hypothesized pathophysiology of RBD is presented in relation to the Braak staging system for Parkinson's disease, in which the topography and temporal sequence of synuclein pathology in the brain could explain the evolution of parkinsonism and/or dementia well after the onset of RBD. These data suggest that many patients with 'idiopathic' RBD are actually exhibiting an early clinical manifestation of an evolving neurodegenerative disorder. Such patients may be appropriate for future drug therapies that affect synuclein pathophysiology, in which the development of parkinsonism and/or dementia could be delayed or prevented. We suggest that additional clinicopathological studies be performed in patients with dementia or parkinsonism, with and without RBD, as well as in patients with idiopathic RBD, to further elucidate the pathophysiology and also characterize the clinical and pathophysiological relevance of RBD in neurodegenerative disease. Furthermore, longitudinal studies in patients with idiopathic RBD are warranted to characterize the natural history of such patients and prepare for future therapeutic trials.

Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson's disease: a randomised, multicentre study

Abstract: Summary Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinson's disease (PD) and improves their quality of life; however, the effect of DBS on cognitive functions and its psychiatric side-effects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment. Methods 156 patients with advanced Parkinson's disease and motor fluctuations were randomly assigned to have DBS of the STN or the best medical treatment for PD according to the German Society of Neurology guidelines. 123 patients had neuropsychological and psychiatric examinations to assess the changes between baseline and after 6 months. The primary outcome was the comparison of the effect of DBS with the best medical treatment on overall cognitive functioning (Mattis dementia rating scale). Secondary outcomes were the effects on executive function, depression, anxiety, psychiatric status, manic symptoms, and quality of life. Analysis was per protocol. The study is registered at ClinicalTrials.gov, number NCT00196911. Findings 60 patients were randomly assigned to receive STN-DBS and 63 patients to have best medical treatment. After 6 months, impairments were seen in executive function (difference of changes [DBS–best medical treatment] in verbal fluency [semantic] −4·50 points, 95% CI −8·07 to −0·93, Cohen's d =−;0·4; verbal fluency [phonemic] −3·06 points, −5·50 to −0·62, −0·5; Stroop 2 naming colour error rate −0·37 points, −0·73 to 0·00, −0·4; Stroop 3 word reading time −5·17 s, −8·82 to −1·52, −0·5; Stroop 4 colour naming time −13·00 s, −25·12 to −0·89, −0·4), irrespective of the improvement in quality of life (difference of changes in PDQ-39 10·16 points, 5·45 to 14·87, 0·6; SF-36 physical 16·55 points, 10·89 to 22·21, 0·9; SF-36 psychological 9·74 points, 2·18 to 17·29, 0·5). Anxiety was reduced in the DBS group compared with the medication group (difference of changes in Beck anxiety inventory 10·43 points, 6·08 to 14·78, 0·8). Ten patients in the DBS group and eight patients in the best medical treatment group had severe psychiatric adverse events. Interpretation DBS of the STN does not reduce overall cognition or affectivity, although there is a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after the treatment. These changes do not affect improvements in quality of life. DBS of the STN is safe with respect to neuropsychological and psychiatric effects in carefully selected patients during a 6-month follow-up period. Funding German Federal Ministry of Education and Research (01GI0201).

Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson’s disease

Abstract: Background: Long term effects of subthalamic nucleus (STN) stimulation on cognition, mood, and behaviour are unknown. Objective: This study evaluated the cognitive, mood, and behavioural effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson's disease (PD) followed up for three years. Methods: A consecutive series of 77 PD patients was assessed before, one, and three years after surgery. Mean (SD) age at surgery was 55 (8). Seven patients died or were lost for follow up. Neuropsychological assessment included a global cognitive scale, memory, and frontal tests. Depression was evaluated using the Beck depression inventory. Assessment of thought disorders and apathy was based on the unified Parkinson's disease rating scale. Reports of the behavioural changes are mainly based on interviews done by the same neuropsychologist at each follow up. Results: Only two cognitive variables worsened (category fluency, total score of fluency). Age was a predictor of decline in executive functions. Depression improved whereas apathy and thought disorders worsened. Major behavioural changes were two transient aggressive impulsive episodes, one suicide, four suicide attempts, one permanent apathy, one transient severe depression, four psychoses (one permanent), and five hypomania (one permanent). Conclusions: Comparing baseline, one year, and three year postoperative assessments, STN stimulation did not lead to global cognitive deterioration. Apathy scores mildly increased. Depression scores mildly improved. Behavioural changes were comparatively rare and mostly transient. Single case reports show the major synergistic effects of both medication and stimulation on mood and behaviour, illustrating the importance of a correct postoperative management.