[Brain function in complex regional pain syndrome†: implications for pain management]. / Syndrome douloureux régional complexe†: rôle du système nerveux central et implications pour la prise en charge.

The International Association for the Study of Pain (IASP) proposed the current diagnostic description of complex regional pain syndrome (CRPS) for the distinct and complex chronic pain condition in 1994. Since this classification, studies on the syndrome have led to a better understanding of the underlying pathophysiological mechanisms, epidemiology and therapeutic approaches. F. Luthi of SUVA Care reviewed CRPS in detail in 2014 and 2019 issues of the Revue médicale suisse. The purpose of this article is to provide an update of results on the neural mechanisms involved in this syndrome and how this helps management of CRPS, in particular bringing awareness to physicians of all specialties of the first symptoms with practical advice for investigations and treatment.

Le syndrome douloureux régional complexe (SDRC) a été défini en 1994 par l'International Association for the Study of Pain (IASP). Depuis cette définition, les études concernant ce syndrome ont permis une meilleure compréhension quant aux mécanismes physiopathologiques sous-jacents, à l'épidémiologie et aux approches thérapeutiques. Le SDRC a déjà été bien décrit dans deux numéros de la Revue médicale suisse de 2014 et 2019 par F. Luthi de la Clinique romande de réadaptation (SUVACare). Le but de cet article est de rapporter les connaissances récentes sur les mécanismes neuronaux impliqués dans ce syndrome et impactant la prise en charge. Nous souhaitons sensibiliser les médecins de toutes spécialités à la reconnaissance des premiers symptômes et diffuser des conseils pratiques quant aux investigations et aux traitements.

[Abnormal movements and internal medicine pathologies]. / Mouvements anormauxet médecine interne.

Hyperkinesias can be revelaed by an internal medicine pathology. An acute chorea can be found in association with non ketotic hypergycemia, lupus, antiphospholipid syndrome, endocrinopathies, pregnancy or oral contraceptive initiation, or psychostimulant medication. Acute dystonic syndromes are found in association with the initiation of an old generation neuroleptic, metoclopramide, oral contraceptive and pregnancy. It should be differentiated from hyper- or hypo-calcémie tetany. Tremors are found in association with many drugs and hormones. Akathisisc syndromes, classically found in association with chronic neuroleptic use, include restless legs, found in association with iron deficiency anemia, pregnancy, many drugs and polyneuropathies, as well as in the withdrawal syndrome of benzodiazepines and opiates.

Des hypercinésies (ou dyskinésies) peuvent évoquer une maladie de médecine interne. Une chorée aiguë peut être causée par une hyperglycémie non cétosique, un lupus, un syndrome antiphospholipide, une endocrinopathie, une grossesse, l'initiation d'un contraceptif, une polyglobulie, ou la prise de psychostimulants. Les syndromes dystoniques aigus se rencontrent avec l'initiation d'un neuroleptique, de métoclopramide, d'un contraceptif ou d'une grossesse et doivent se distinguer de la tétanie hyper- ou hypo-calcémique. Les tremblements orientent vers les médicaments ou les hormones. Les myoclonies se voient classiquement dans les encéphalopathies métaboliques (hépatiques, rénales) ou médicamenteuses. Les syndromes akathisiques, associés à la prise chronique de neuroleptiques, incluent le syndrome des jambes sans repos, lié aux anémies ferriprives, à la grossesse, à certains médicaments, aux neuropathies et au sevrage des benzodiazépines ou d'opiacés.

[Capgras delusion and Alzheimer disease]. / Syndrome de Capgras et maladie d'Alzheimer.

Capgras delusion is classified with the misidentification syndromes. In dementia it associates cognitive deficiency of memory and facial recognition (prosopoagnosia) with delirious idea of substitution by a double. The first reported case in the paper describes the important affective and comportmental reactions due to the identification of a double perceived as an imposter, affecting both the suffering person and his family. Rarely, as reported in the second case, misrecognition concerns the person itself (autoprosopagnosia) who can have the illusion to be in front of a twin brother (« auto-Capgras ¼). We discuss data from the literature concerning prevalence, results of cerebral imaging and functional prognosis associated with this curious syndrome.

Le syndrome de Capgras fait partie des troubles de l'identification des personnes. Dans la démence, il associe des déficits cognitifs de la mémoire et de la reconnaissance des visages (prosopagnosie) et des idées délirantes de substitution par des sosies. La première situation rapportée dans l'article décrit les importantes réactions affectives et comportementales engendrées par l'identification d'un sosie qui est perçu comme un imposteur, affectant à la fois le malade et son entourage. Rarement, comme rapporté dans la deuxième situation, la fausse reconnaissance concerne la personne elle-même (autoprosopagnosie) qui peut avoir l'illusion d'avoir en face d'elle un frère jumeau (« auto-Capgras ¼). Nous discutons de données issues de la littérature concernant la prévalence, les résultats de l'imagerie cérébrale ainsi que le pronostic fonctionnel liés à ce curieux syndrome.

Combined thalamic and subthalamic deep brain stimulation for tremor-dominant Parkinson's disease.

Deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) or the subthalamic nucleus (STN) reportedly improves medication-refractory Parkinson's disease (PD) tremor. However, little is known about the potential synergic effects of combined Vim and STN DBS. We describe a 79-year-old man with medication-refractory tremor-dominant PD. Bilateral Vim DBS electrode implantation produced insufficient improvement. Therefore, the patient underwent additional unilateral left-sided STN DBS. Whereas Vim or STN stimulation alone led to partial improvement, persisting tremor resolution occurred after simultaneous stimulation. The combination of both targets may have a synergic effect and is an alternative option in suitable cases.

[Dementia with motor and language disorders]. / Démences avec troubles moteurs et du langage.

Memory is not the only core diagnostic criteria in Alzheimer's disease and many dementias are characterized by other cognitive deficits. Moreover dementias are often associated with multiple and complex motor signs. The first part of this reviewcovers parkinsonism in diffuse Lewy Body Disease and other neurodegenerative diseases, corticobasal syndrome, or motor deficit in the motoneurone disease-frontotemporal dementia spectrum. In the second part, primary progressive aphasia and its three variants including basic clinical evaluation are described. These complex clinical syndromes involving motor and language systems are important for the clinical practice since they are part of diagnostic criteria of several neurodegenerative diseases and can be considered as phenotypical markers of neurodegeneration.

Visual signs and symptoms in patients with the visual variant of Alzheimer disease.

BACKGROUND: Prominent visual symptoms can present in the visual variant of Alzheimer's disease (VVAD). Ophthalmologists have a significant role to play in the early diagnosis of VVAD. METHODS: We retrospectively reviewed the files of ten consecutive patients diagnosed with VVAD. All patients had a full neuro-ophthalmologic examination, a formal neurological and neuro-psychological testing, and cerebral MRI to confirm diagnosis. In addition, functional neuroimaging was obtained in seven patients. RESULTS: The common primary symptom at presentation with all patients was difficulty with near vision (reading difficulty n = 8, "visual blur" in near vision n = 2), and difficulty writing (n = 3). Following assessment, impaired reading and writing skills were evident in 9/10 and 8/10 patients respectively. Median distance visual acuity was 20/25 and at near the median visual acuity was J6. Partial homonymous visual field defect was detected in 80 % (8/10) of the patients. Color vision was impaired in all patients when tested with Ishihara pseudoisochromatic plates, but simple color naming was normal in 8/9 tested patients. Simultanagnosia was present in 8/10 patients. Vision dysfunction corresponded with cerebral MRI findings where parieto-occipital cortical atrophy was observed in all patients. PET scan (5 patients) or SPECT (2 patients) revealed parieto-occipital dysfunction (hypometabolism or hypoperfusion) in all 7 tested patients CONCLUSIONS: Visual difficulties are prominent in VVAD. Dyslexia, incomplete homonymous hemianopia, preserved color identification with abnormal color vision on Ishihara, and simultanagnosia were all symptoms observed frequently in this patient series. Ophthalmologists should be aware of the possibility of neurodegenerative disorders such as VVAD in patients with unexplained visual complaints, in particular reading difficulties.

VPS35 mutations in Parkinson disease.

The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 ± 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.

[Mirror behaviors in dementia: the many mirror signs]. / Conduites spéculaires dans les démences: les multiples signes du miroir.

Mirror behaviors in advanced dementia are: the mirror sign of Abely and Delmas, where the patient stares at his face (environment-driven behavior of Lhermitte); non recognition of the self in the mirror (autoprosopagnosia and/or delirious auto-Capgras); mirror agnosia of Ramachandran and Binkofski where the patient do not understand the concept of mirror and its use; the psychovisual reflex, or reflex pursuit of the eyes when passively moving a minrror in front of a patient (intact vision); mirror writing (procedural learning). We describe four demented patients with mirror behaviors assessing brain mechanisms of self recognition, social brain and mental and visuo-spatial manipulation of images and objects.

[Acute amnestic syndrome: left thalamo-polar infarct]. / Syndrome amnésique aigu: AVC thalamo-polaire gauche.

An 80-year old American patient was found wandering in a mountain village of Switzerland, with an anterograde, prospective, retrograde, dyschronologic amnesic syndrome without confabulation, paramnesia or false recognitions, disoriented, slightly confused, with no focal sensory, motor, ataxic or visual field deficit, with a mild dysexecutive syndrome. The MR imaging showed an acute thalamo-polar artery infarct. A dysconnection of the mamillo-othalamic and thalamo-temporal pathways is felt at the origin of the amnesic syndrome. A brief review of the other presentation of this chamelon syndrome is presented, together the main etiologies at its origin.

Case report: Pallidal deep brain stimulation for treatment of tardive dystonia/dyskinesia secondary to chronic metoclopramide medication.

Objectives: Tardive dystonia/dyskinesia (TDD) occurs as a side effect of anti-dopaminergic drugs, including metoclopramide, and is often refractory to medication. While pallidal deep brain stimulation (DBS) has become an accepted treatment for TDD secondary to neuroleptic medication, there is much less knowledge about its effects on metoclopramide-induced TDD. Methods: We present the case of a woman with metoclopramide-induced TDD, whose symptoms were initially misjudged as "functional." After 8 years of ineffective medical treatments, she received bilateral implantation of quadripolar electrodes into the posteroventral lateral globus pallidus internus (GPi). Results: GPi DBS led to significant symptom reduction [Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score 24/44 at admission and 7/44 at discharge]. Chronic stimulation led to full recovery from TDD symptoms 9 years after surgery. The BFMDRS motor score decreased to 0.5 (98% improvement). Discussion: Pallidal DBS may result in sustained improvement of TDD secondary to chronic metoclopramide intake in the long term.

Management Strategy of Intracranial Complications of Sinusitis: Our Experience and Review of the Literature.

Objective: Sinusitis or rhinosinusitis is a very common disease worldwide, and in some cases, it leads to intracranial complications (ICS). These are more common in immunocompromised patients or with underlying comorbidities, but even healthy individuals, can be affected. Nowadays, ICS have become less common thanks to improved antibiotic therapies, radiological diagnostic methods, surgical techniques and skills. Nonetheless, they can still cause significant morbidity and mortality. For this reason, management of these complications requires a multidisciplinary approach to plan and customize treatment options. This paper presents our strategy in the management of a series of intracranial complications induced by acute sinusitis and compares our experience and outcomes with the literature. Study design: Single institute experience, retrospective analysis of cases series and literature review. Methods: Adult and child patients who were treated for ICS in the Department of Otorhinolaryngology at Sion Hospital, in Switzerland from 2016 to 2020 were included. Their symptoms, medical history, clinical and radiological findings, treatment, and outcome were documented. Results: Eight patients (6 males- 2 females) aged from 14 to 88 y.o., were enrolled. None had any previous history of chronic, or recurrent sinusitis. Moreover, very few presented specific rhinological symptoms, but with neurological or other symptoms. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) were used to confirm the diagnosis of all ICS. All types of known intracranial complications were observed in our cohort with a wide range of extension and severity of sinusitis. A multidisciplinary approach with individual treatments was tailored to each patient. Outcomes were favorable in almost all patients with neither recurrence, nor neurological sequels being observed in the follow-up. Only one patient was lost due to fatal complications of advanced lung cancer. Conclusion: ICS remain a challenging clinical problem due to substantial associated morbidity and mortality. The incidence of these complications is relatively low. Therapeutical management guidelines are lacking. Early detection and multidisciplinary approach are key to successful treatment.

Inhibition in early Alzheimer's disease: an fMRI-based study of effective connectivity.

Changes of functional connectivity in prodromal and early Alzheimer's disease can arise from compensatory and/or pathological processes. We hypothesized that i) there is impairment of effective inhibition associated with early Alzheimer's disease that may lead to ii) a paradoxical increase of functional connectivity. To this end we analyzed effective connectivity in 14 patients and 16 matched controls using dynamic causal modeling of functional MRI time series recorded during a visual inter-hemispheric integration task. By contrasting co-linear with non co-linear bilateral gratings, we estimated inhibitory top-down effects within the visual areas. The anatomical areas constituting the functional network of interest were identified with categorical functional MRI contrasts (Stimuli>Baseline and Co-linear gratings>Non co-linear gratings), which implicated V1 and V3v in both hemispheres. A model with reciprocal excitatory intrinsic connections linking these four regions and modulatory inhibitory effects exerted by V3v on V1 optimally explained the functional MRI time series in both subject groups. However, Alzheimer's disease was associated with significantly weakened intrinsic and modulatory connections. Top-down inhibitory effects, previously detected as relative deactivations of V1 in young adults, were observed neither in our aged controls nor in patients. We conclude that effective inhibition weakens with age and more so in early Alzheimer's disease.

Robot-induced hallucinations in Parkinson's disease depend on altered sensorimotor processing in fronto-temporal network.

Hallucinations in Parkinson's disease (PD) are disturbing and frequent non-motor symptoms and constitute a major risk factor for psychosis and dementia. We report a robotics-based approach applying conflicting sensorimotor stimulation, enabling the induction of presence hallucinations (PHs) and the characterization of a subgroup of patients with PD with enhanced sensitivity for conflicting sensorimotor stimulation and robot-induced PH. We next identify the fronto-temporal network of PH by combining MR-compatible robotics (and sensorimotor stimulation in healthy participants) and lesion network mapping (neurological patients without PD). This PH-network was selectively disrupted in an additional and independent cohort of patients with PD, predicted the presence of symptomatic PH, and associated with cognitive decline. These robotics-neuroimaging findings extend existing sensorimotor hallucination models to PD and reveal the pathological cortical sensorimotor processes of PH in PD, potentially indicating a more severe form of PD that has been associated with psychosis and cognitive decline.

Nonepileptic seizures under levetiracetam therapy.

We describe two patients with epilepsy who presented with nonepileptic seizures (NES) when started on levetiracetam (LEV), which disappeared or significantly decreased when LEV was discontinued. NES are traditionally attributed to psychic trauma often after physical or sexual abuse, whereas the psychiatric side effects of levetiracetam largely encompass depression, hallucinations, and psychosis. We conclude that NES are a rare side effect of LEV treatment and part of the spectrum of behavioral changes observed with LEV treatment.

[What's new in neurology]. / Neurologie.

This article summarize principal news about treatments in the different specialities in neurology. We don't pretend to be exhaustive and to make a detailed analyse of all treatments, and preferred to present pertinent therapeutic advances, with an evidence-based point of view. We also mentioned some negative studies, to balance our purpose.

How non-drug interventions affect the quality of life of patients suffering from progressive cognitive decline and their main caregiver.

BACKGROUND: In the absence of cure for age-related neurodegenerative diseases, non-drug interventions (NDIs) represent useful options. Quality of life (QOL) is a multidimensional concept progressively affected by cognitive decline. How single or multiple NDIs impact QOL is unknown. RESULTS: We found no significant effect of multiple over single NDI on QOL. Socio-demographic variables influenced patients' (age, gender, caregivers' occupational status, management of patients' financial affairs) and caregivers' (gender, occupational status, patients' severity of cognitive decline) QOL. When dyads interrupted interventions after 6 months, their QOL was lower and caregivers' anxiety, depression and physical symptoms were higher at the end of the study. CONCLUSIONS: While the type and number of interventions do not appear to be critical, the continuity of adapted interventions in the long-term might be important for maintaining QOL of patients and caregivers. METHODS: This is a multicenter (7 Swiss Memory Clinics), quasi-experimental, one-year follow-up study including 148 subjects (mild cognitive impairment or mild dementia patients and their caregivers). Primary outcome was the effect of multiple vs single NDIs on QOL. Secondary outcome included NDIs effect on patients' cognitive impairment and functional autonomy, caregivers' burden, severity of patients' neuropsychiatric symptoms and dyads' anxiety and depression.

Peripheral neuropathy and cognitive impairment associated with a novel monoallelic HARS variant.

BACKGROUND: A 49-year-old male presented with late-onset demyelinating peripheral neuropathy, cerebellar atrophy, and cognitive deficit. Nerve biopsy revealed intra-axonal inclusions suggestive of polyglucosan bodies, raising the suspicion of adult polyglucosan bodies disease (OMIM 263570). METHODS AND RESULTS: While known genes associated with polyglucosan bodies storage were negative, whole-exome sequencing identified an unreported monoallelic variant, c.397G>T (p.Val133Phe), in the histidyl-tRNA synthetase (HARS) gene. While we did not identify mutations in genes known to be associated with polygucosan body disease, whole-exome sequencing revealed an unreported monoallelic variant, c.397G>T in the histidyl-tRNA synthetase (HARS) gene, encoding a substitution (Val133Phe) in the catalytic domain. Expression of this variant in patient cells resulted in reduced aminoacylation activity in extracts obtained from dermal fibroblasts, without compromising overall protein synthesis. INTERPRETATION: Genetic variants in the genes coding for the different aminoacyl-tRNA synthases are associated with various clinical conditions. To date, a number of HARS variant have been associated with peripheral neuropathy, but not cognitive deficits. Further studies are needed to explore why HARS mutations confer a neuronal-specific phenotype.

Localization of electrodes in the subthalamic nucleus on magnetic resonance imaging.

OBJECT: The authors describe a new method of localizing electrodes on magnetic resonance (MR) images and focus on the positions of both the most efficient contact and the electrode related to the MR imaging target. METHODS: Thirty-one patients who had undergone bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) were included in this study. Target coordinates were calculated in the anterior commissure-posterior commissure referential. A study of the correlation between the artifact and the related contact allowed one to deduce the contact position from the identification of the distal artifact on MR imaging. The best stimulation point corresponded with the contact resulting in the best Unified Parkinson's Disease Rating Scale (UPDRS) motor score improvement. It was compared (Student t-test) with the dorsal margin of the STN (DM STN), which was determined electrophysiologically. The distance between the target and the electrode was calculated individually in each axis. The best stimulation point was located at anteroposterior -2.34 +/- 1.63 mm, lateral 12.04 +/- 1.62 mm, and vertical -2.57 +/- 1.68 mm. This point was not significantly different from the DM STN (p < 0.05). The postoperative UPDRS motor score was 28.07 +/- 12.16, as opposed to the preoperative score of 46.27 +/- 13.89. The distance between the expected and actual target in the x- and y-axes was 1.34 +/- 1.02 and 1.03 +/- 0.76 mm, respectively. In the z-axis, 39.7% of the distal contacts were located proximal to the target. CONCLUSIONS: This approach proposed for the localization of the electrodes on MR imaging shows that DBS is most effective in the dorsal and lateral part of the STN and indicates that the DBS electrode can be located more proximally than originally expected because of the caudal brain shift that may occur during the implantation procedure.