Dissociative amnesia: Disproportionate retrograde amnesia, stressful experiences and neurological circumstances.

Dissociative amnesias have been reported in neurological episodes mild enough to not cause any visible lesions on morphological examination. Disproportionate retrograde amnesia with or without identity loss happens in the context of psychological trauma (known or not). In metabolic imaging studies, some authors have reported functional alterations, particularly in the bilateral hippocampus, right temporal regions and inferolateral prefrontal cortex, despite normal morphological imaging. To avoid the presumption of an organic, psychogenic or mixed origin for such changes, De Renzi et al. suggested the term 'functional amnesia' to describe the condition. Patients have sometimes recovered during events similar to those preceding the amnesia in either a spectacular fashion or never. Also, in some cases, distraction or sedation may trigger the start of recovery. During psychotherapy, one patient remembered seeing a car on fire when he was a boy, and his amnesia started when his house was on fire. This suggests control by the frontal cortex, with repression blocking amnesic traces in the new emotional and biological context.

Long-lasting active lifestyle and successful cognitive aging in a healthy elderly population: The PROOF cohort.

OBJECTIVES: The aim of this study was to determine whether cognitive reserve in the elderly affects the evolution of cognitive performance and what its relationship is with active lifestyles in later life. METHODS: Cognitive performance was evaluated at baseline and 8 years later in 543 participants of the PROOF cohort, initially aged 67 years. Subjects were categorized as Cognitively Elite (CE), Cognitively Normal (CN) or Cognitively Impaired (CI) at each evaluation. At follow-up, demographic data and lifestyle, including social, intellectual and physical behaviors, were collected by questionnaires. RESULTS: As much as 69% (n=375) remained unchanged, while 25.5% (n=138) decreased and 5.5% (n=30) improved. When present, the reduction in cognitive status was most often limited to one level, but was dependent on the initial level, affecting up to 73% of the initially CN, but only 58% of the initially CE. Cognitive stability was significantly associated with the degree of social engagement at follow-up (CE: P=0.009; CN: P=0.025). CONCLUSION: In the healthy elderly, high cognitive ability predicts both cognitive ability and social involvement in later life. Cognitive decline by only one level may also extend the time to reach impairment, underlining the importance of the so-called cognitive reserve.

[American Academy of Neurology, Washington, 18-25 April 2015]. / American Academy of Neurology, Washington, 18-25 avril 2015.

CEREBROVASCULAR DISEASES: The benefit of the thrombectomy using stents retrievers in the acute stroke phase is now demonstrated when there is a proximal occlusion of an intracranial artery, whatever its mechanism. The place of the anticoagulants in the management of cervical artery dissections remains uncertain, while the benefit of the blood pressure control in the secondary prevention of deep and lobar intracerebral hemorrhages is critical. The development of cardiac MRI, prolonged cardiac monitoring and transcranial doppler seems to improve the diagnosis of cardio-embolic sources of stroke. EPILEPSY: A specialized urgent-access single seizure clinic represents a model which reduces wait-times and improves patient access after a first fit. Co-locating a psychiatrist within outpatient epilepsy center leads to a reduction in psychiatric symptoms and people with psychogenic non-epileptic seizures. When neurologists around the world assess identical case scenarios for the diagnosis of epilepsy, concordance is between moderate and poor, showing that epilepsy diagnosis remains difficult. More than one third of elderly with new-onset epilepsy of unknown etiology exhibit temporal lobe atrophy on brain imaging. MOVEMENT DISORDERS: There is no major progress in the therapeutic approach of Parkinson's disease but the discovery of new genetic markers such as glucocerebrosidase mutations may greatly change our knowledge of the disease process and may induce new therapeutic strategies in the future. The natural history of the disease is also better understood from the prodromal phase to the post-mortem analysis of the brain and the classification of the processes based on abnormal protein deposits. DEMENTIA: The respective value of biomarkers (amyloid imaging versus CSF biomarkers) for in vivo diagnosis of Alzheimer's disease (AD) has been detailed. Therapeutic expectations mainly rely on anti-Aß immunization trials performed in preclinical (and no longer prodromal) stages of AD, with the aim of slowing the evolution of neuronal loss. Besides a lot of communications on dementia genetics or physiopathogeny, fascinating and promising results were presented on deep brain stimulation for depression resistant to medical treatment. PERIPHERAL NEUROPATHY: Ibudilast, administered with riluzole, is safe and tolerable in patients with amyotrophic lateral sclerosis (ALS), improves ALS function and delays progression. Patients with painful small fiber neuropathy have a high rate of mutations in the SCN9A gene, coding for Nav1.7 voltage-gated sodium-channels. Peripheral nerve lymphoma (NL) is a multifocal painful neuropathy that causes endoneurial inflammatory demyelination: primary NL is less severe than secondary NL, which occurs after remission, suggesting that nerve may be considered a "safe lymphoma haven". MULTIPLE SCLEROSIS (MS): Biotin in progressive forms of MS and daclizumab in relapsing-remitting forms appear to be promising treatments. In case of failure of current first-line and/or second-line therapeutics, alemtuzumab may be an interesting alternative treatment. Teriflunomide, dimethyl fumarate and fingolimod are oral treatments with confirmed efficacy and acceptable safety. Besides vitamin D insufficiency and smoking, which are confirmed risk factors for the disease, testosterone insufficiency (in males) and obesity are emerging risk factors, which could also be corrected.

[Post anoxia impairment of autobiographical memory and time estimation]. / Déficit de mémoire autobiographique et d'estimation du temps après une anoxie cérébrale.

A case of episodic amnesia with impairment of time perception is described; it illustrates the link between time perception and autobiographical memory. This woman suffered from a Sheehan syndrome with anoxia at the age of 36 and since that date has had a strong and isolated difficulty to estimate the date and duration of events in a range of weeks, months or years. Conversely, short duration time spans are correctly evaluated. The patient's complaints also involve episodic memory. She reports many events from her biography very imprecisely while the semantic autobiographical data are preserved. The patient has difficulty in recalling the date of public events and the period of celebrity of well-known people. That observation confirms the specificity of time organization for long periods and the link with the episodic memory where the context of the dating task is crucial. The results are discussed in reference to autobiographical memory that involves mental wandering in time-space and the constitution of self over a time continuum.

High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease.

Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations. These mutations were not retrieved in 1500 controls of same ethnic origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample. Using in silico predictions, we conclude that these seven private mutations are likely to have a pathogenic effect. SORL1 encodes the Sortilin-related receptor LR11/SorLA, a protein involved in the control of amyloid beta peptide production. Our results suggest that besides the involvement of the APP and PSEN genes, further genetic heterogeneity, involving another gene of the same pathway is present in ADEOAD.

Exploration of verbal and non-verbal semantic knowledge and autobiographical memories starting from popular songs in Alzheimer's disease.

BACKGROUND: In mild Alzheimer's disease (AD), a deficit in episodic memory, particularly autobiographical memory, is clearly established. Several recent studies have also shown impaired semantic memory from the onset of the disease. Musical memory capacities may be especially preserved and listening to music might encourage autobiographical recall. The aim of this study was to explore recall of popular songs in AD. METHODS: We tested 12 patients with mild AD and 12 control subjects. We created a tool made up of old French popular songs: POP 10. This tool is a questionnaire composed of several subtests: melodic free recall, chorus free recall, melodic recognition, chorus recognition, semantic knowledge, autobiographical recall about the song, and autobiographical recall about the interpreter. RESULTS: We used non-parametric tests, the Mann-Whitney test (M-W), the Friedman test, and the a posteriori Wilcoxon test. Results of AD patients were rather similar to those of control participants for melodic memory. Concerning chorus memory (except recognition), semantic knowledge, and autobiographical recall about the interpreter, results of AD patients were significantly weaker than those of control participants. The most important result concerned autobiographical recall about the song: we found no impairment-related differences between the two groups. CONCLUSION: Our findings demonstrate that popular songs can be excellent stimuli for reminiscence, such as the ability to produce an autobiographical memory related to a song. Thus, we confirm that musical semantic knowledge associated with a song may be relatively preserved in the early stages of AD. This leads to new possibilities for cognitive stimulation.

[Diagnosis of psychocognitive complaints or disorders after de novo consultation in a university hospital specialized memory unit]. / Situations de plaintes ou de déficits psychocognitifs observées lors d'une première consultation de mémoire en CM2R.

Psychiatric diagnoses are frequent in memory units, but most neurologists do not feel comfortable about making the diagnosis of psychopathologic cognitive complaint or disorder. The full diagnosis usually requires careful history taking and a neuropsychological examination followed by a clear joint explanation to the patient. There are no good validated clinical signs to distinguish organic memory complaints from psychological disorders, but a nonorganic pattern, as seen in somatic conversion disorder, can be suggestive of a "cognitivoform" disorder. Cognitive doubt is a frequent symptom of anxiety. Bradypsychia is a frequent symptom of depression. We report 50 patients attending their first neurological memory consultation in university hospital for whom a de novo diagnosis of psychopathologic disorder was established on the basis of the clinical setting, observation, examination and neuropsychological tests. These psychopathologic disorders accounted for 40.3% of first-consultation diagnoses. In 76% of cases, the neuropsychological examination was normal. Nine subjects had mild cognitive impairment, concerning executive functions in six and several domains in three. Simulation with atypical neuropsychological pattern was distinguished in three patients. The diagnoses were:psychosis (n=9), traumatic stress (n=5), depression (n=7), anxiety or obsession/compulsion (n=13), hypochondria and "cognitivoform" disorders (n=13). In this study, few patients consulted with a known psychiatric diagnosis. Psychiatric co-morbidity was common. In the memory unit, listening carefully to ascertain the psychic, somatic and social situation of each individual patient appears to be as important as evaluating cognition. The neurologist can rule out organic disorders or an exaggeration of somatic symptoms and determine the precise etiology in order to build a rationale for treatment. The neurologist can also avert an overconsumption of complementary explorations. In conclusion, this study shows first that psychopathologic disorders are commonly encountered in a neurological memory unit, emphasizing the need for training for the neurologist and collaboration with a psychiatrist, and secondly that the role of the memory unit cannot be limited to the diagnosis of Alzheimer's disease.

[Sneddon syndrome: a rare cause of vascular dementia]. / Le syndrome de Sneddon: une cause rare de démence vasculaire.

Few vascular dementias are diagnosed in memory clinic consultations. One type, a rare etiology, Sneddon syndrome, can lead patients to consult for an isolated memory complaint. We report the cases of two patients, aged 63 and 66 years, who presented frontocortical cognitive profile and behavior disorders. Seronegative Sneddon syndrome, complicated with dementia, was diagnosed in each case by noticing an association between, on MRI, an atrophy and several ischemic cerebrovascular accident aftermaths, and a livedo racemosa. Management of vascular risks factors improves the prognosis.

Neuropsychological assessment and cerebral vascular disease: the new standards.

Vascular cognitive impairment (VCI) includes vascular dementia (VaD), vascular mild cognitive impairment (VaMCI) and mixed dementia. In clinical practice, VCI concerns patients referred for clinical stroke or cognitive complaint. To improve the characterization of VCI and to refine its diagnostic criteria, an international group has elaborated a new standardized evaluation battery of clinical, cognitive, behavioral and neuroradiological data which now constitutes the reference battery. The adaption of the battery for French-speaking subjects is reported as well as preliminary results of the on-going validation study of the GRECOG-VASC group [Clinical Trial NCT01339195]. The diagnostic accuracy of various screening tests is reviewed and showed an overall sub-optimal sensitivity (<0.8). Thus, the general recommendation is to perform systematically a comprehensive assessment in stroke patients at risk of VCI. Furthermore,the use of a structured interview has been shown to increase the detection of dementia. In addition to the well known NINDS-AIREN criteria of VaD, criteria of VCI have been recently proposed which are based on the demonstration of a cognitive disorder by neuropsychological testing and either history of clinical stroke or presence of vascular lesion by neuroimaging suggestive of a link between cognitive impairment and vascular disease. A memory deficit is no longer required for the diagnosis of VaD as it is based on the cognitive decline concerning two or more domains that affect activities of daily living. Both VaMCI and VaD are classified as probable or possible. These new criteria have yet to be validated. Considerable uncertainties remain regarding the determinant of VCI, and especially the lesion amount inducing VCI and VaD. The interaction between lesion amount and its location is currently re-examined using recent techniques for the analysis of MRI data. The high frequency of associated Alzheimer pathology is now assessable in vivo using amyloid imaging. The first studies showed that about a third of patients with VaD due to small vessel disease or with poststroke dementia have amyloid PET imaging suggestive of AD. These new techniques will examine the interaction between vascular lesions and promotion of amyloid deposition. Although results of these on-going studies will be available in few years, these data indicate that efforts should be done in clinical practice to reduce underdiagnosis of VCI; VCI should be examined using a specific protocol which will be fully normalized soon for French-speaking patients; the sub-optimal sensitivity of screening tests prompts to use a structured interview to grade Rankin scale and to perform systematically a comprehensive assessment in stroke patients at risk of VCI; poststroke dementia occurring after 3 months poststroke may be preventable by treatment of modifiable vascular risk factors and secondary prevention of stroke recurrence according to recent recommendations.

DAD-6: A 6-ltem version of the Disability Assessment for Dementia scale which may differentiate Alzheimer's disease and mild cognitive impairment from controls.

BACKGROUND: The need to detect early changes in instrumental activities of daily life led us to modify the Disability Assessment for Dementia Scale (DAD) by focusing on executive components of 6 instrumental items (DAD-6). AIM: To evaluate the relevance of the DAD-6 for detecting early impairment in a nondemented population. METHODS: The DAD-6 was administered to informants of 84 patients: 31 with mild dementia (MD), 53 with mild cognitive impairment (MCI) and 55 healthy controls. RESULTS: DAD-6 scores gradually decreased with increasing severity of the cognitive status [18 in healthy controls vs. 15.1 ± 3.2 in MCI versus 9.6 ± 3.5 in MD, p < 0.0001). Receiver-operating characteristic curve analyses yielded an optimal cut score of 14 to distinguish MCI from MD with a sensitivity of 0.83 (95% confidence interval 0.74-0.92) and a specificity of 0.84 (0.71-0.94), and a cut score of 15 to distinguish single-domain MCI from multi-domain MCI with a sensitivity of 0.96 (0.90-0.99) and a specificity of 0.54 (0.33-0.75). CONCLUSION: The DAD-6 reliably detects early loss of autonomy due to cognitive impairment.

[Somatoform disorders in neurology visits: history and circumstances: retrospective study of 124 cases]. / Symptômes somatomorphes en consultation de neurologie : expression, soubassement et occasion : étude rétrospective de 124 situations.

We report 124 cases of somatoform disorders, considering psychogenic disorders at the same level as neurological disorders. We noted any psychic, somatic or social condition (history taking) and facilitating circumstances. The patients were aged 16 to 84 years old; 71.7% were women. We observed pain (35.4%), psychogenic headache (25%), sensorimotor loss (27.4%), gait and psychogenic tremor (17.7%), cognitive disorders (11.8%), ocular symptoms (7.2%), and urogenital symptoms (2.4%). Delay to consultation ranged from a few days to 20 years. Psychiatric comorbidity was noted in 30.6% of the cases. In 55.6% of 124 cases, we observed a psychological background. It was a childhood trauma in 15.3% of these cases. In one-third of the 124 situations, we noted an underlying somatic or social condition. Facilitation conditions were frequently mixed. Somatic and/or psychological conditions were noted in one-third of the 124 cases and social conditions in half of them. The neurologist is faced with the challenge of naming the symptom (most often labelled a functional disorder) and of making the decision to stop or limit investigations. Visits by patients with psychogenic disorders make up a significant percentage of neurology speciality appointments. The neurologist should not limit the consultation to differentiating "real" symptoms from psychogenic somatoform disorders, but should also propose a straightforward compassionate approach for effective therapeutic care. By carefully listening to the patient's dialogue, the neurologist can help the patient give meaning to the symptoms, and progress towards improved well-being.

Marc Dax and the discovery of the lateralisation of language in the left cerebral hemisphere.

In 1836, Marc Dax presented a revolutionary conclusion based on both his clinical observations and reports from the literature: the localisation of language in the left hemisphere. Twenty-seven years later, his son, Gustave Dax, extended and enriched his work. Their involvement in 19th century neuropsychology is impressive and recognition should have been considerable. However, according to the vast majority of historians of neurology, neuropsychology and aphasiology, the priority in establishing the dominance of the left brain hemisphere for speech goes to Paul Broca in an undivided way. Is it possible that Marc Dax's and his son, Gustave Dax's works were entirely unknown? Were they known and utterly forgotten? Were they ignored? How did we get to know that they existed? The aim of the present paper is to try to answer those and other questions and to demonstrate that there is abundance of data pointing out that the priority of the discovery of left hemisphere dominance for speech ought to be, at least, shared by Dax and Broca.

[Pure progressive amnesia, isolated for 16 years with focal hippocampus atrophy]. / Amnésie pure progressive isolée pendant 16ans et atrophie focalisée de l'hippocampe.

INTRODUCTION: Pure progressive amnesia is a rare and unusual syndrome involving long preservation of autonomy and absence of progression in other cognitive domains. CASE REPORT: We report a case which remained quiescent for 16 years characterized by severe isolated episodic amnesia and preservation of spatial, semantic and implicit memory and autonomy. MRI revealed bilateral focal atrophy of the hippocampus. CONCLUSION: This specific pattern of impairment differs from other types of amnesic syndromes. It is important to identify this kind of amnesia because of its specific course. Studying the topography of the brain lesions may contribute to a better understanding of the neural systems involved in declarative memory.

[Diagnosis contribution of biomarkers in Alzheimer disease: A case of frontotemporal dementia]. / Apport diagnostic des marqueurs biologiques de la maladie d'Alzheimer (MA) dans une observation de dégénérescence lobaire fronto-temporale (DLFT).

INTRODUCTION: Cerebrospinal fluid biomarkers are a fundamental contribution for the diagnosis of Alzheimer disease, in particular for young people. CASE REPORT: We report a case of Alzheimer disease of a 51-years old man whose clinical presentation corresponded to frontotemporal behavioural criteria. The clinical evaluation noticed some troubles in verbal memory. Only the CSF biomarkers confirmed the diagnosis. CONCLUSION: There are different phenotypes of presenile Alzheimer disease and among them we note frontotemporal dementia. It is very important to identify them to introduce a specific treatment.

[Semantic knowledge in MCI and Alzheimer's disease: the French version of the New Words Interview]. / Connaissance des nouveaux mots de la langue française dans les troubles cognitifs légers de type amnésique et la maladie d'Alzheimer.

INTRODUCTION: The first decline in cognitive performance in Alzheimer's disease can appear when assessing semantic memory and can be detected long before the typical symptoms of Alzheimer's disease (AD), appearing with Mild Cognitive Impairment (MCI). PATIENTS AND METHOD: We propose the French version of the New Words Interview (fNWI) using 22 words to investigate semantic knowledge. The fNWI uses 11 words, which entered the French dictionary between 1996 and 1997, and 11 other words, which entered between 2006 and 2007. Words were paired according to orthographic and semantic criteria. Each word was associated with three sub-tests: free evocation, discrimination of the best definition from three propositions, and recognition of the accurate word context (two sentences were proposed). Regarding evocation, we distinguished conceptual definition, life situation examples or examples by use. We tested 12 patients with AD, 12 patients with amnesic Mild Cognitive Impairment (aMCI) and 72 controls (12 were paired with patients for age and education level). RESULTS: MCI patients and AD patients exhibited lower performance than controls in the three sub-tests and for the words of both periods. From the early stage of MCI, the patients were more impaired in the fNWI than in the context recognition task, and they failed to provide conceptual definitions of new words. Therefore, MCI patients suffer from semantic impairments before obvious clinical signs of AD. CONCLUSION: In patients with AD, performance worsened on all subtests, and more strongly in the definition discrimination task, which suggests the impairment of stored semantic knowledge. They provided fewer conceptual definitions and failed to use the strategy observed in MCI patients, who compensated for conceptual difficulties by providing examples.

[Atypical Lewy body disease revealed by burning mouth syndrome and a pseudo-psychiatric syndrome]. / Démence à corps de Lewy atypique révélée par une glossodynie et des troubles pseudo-psychiatriques.

INTRODUCTION: Among the degenerative diseases of the nervous system, Lewy body disease has the most psychiatric symptoms especially hallucinations, delusion and identification disorders. CASE REPORT: We report a case of Lewy body disease that started with a burning mouth syndrome for three year as the only symptom before the development of a pseudo-psychiatric syndrome (melancholy and Capgras). None of the usual cardinal criteria were present. MRI, cerebrospinal fluid, and DAT scan findings enabled the diagnosis. CONCLUSION: The dopaminergic hypothesis put forward in some cases of burning mouth syndrome might explain this symptom in Lewy body disease.

[Diagnostic criteria for mild cognitive impairment in a cohort of 100 subjects]. / Critères diagnostiques des troubles cognitifs légers dans une cohorte de 100 patients.

INTRODUCTION: Tracking can be proposed for subjects with prodromal sates of Alzheimer disease (AD) or people with mild cognitive impairment (MCI) at risk to develop dementia who present a memory complaint. PATIENTS AND METHODS: We present a cohort of 100 subjects who attended a French memory unit with a diagnostic of MCI. We applied the different definitions used in daily practice. We used the following diagnostic criteria: amnestic MCI (MCIa), multiple domain impairment (MDI), single non-memory dysfunction impairment (SDI), and prodromal Alzheimer's disease (Prod-AD), using only the neuropsychological episodic memory criteria. We also analyzed the population of subjects presenting MCI and vascular risk factors. RESULTS: Ninety-nine subjects met the criteria of MCIa, 43 met the criteria of isolated MCIa; 56 met the criteria of MDI; one met the criteria of SDI; 40 met the criteria of MAPD; 58 met the criteria of MCI with vascular risk factors. DISCUSSION: Using the diagnostic criteria of MCI can lead to clinical ambiguity because the population recruited on the bases of memory complaint is highly variable. Moreover, many subjects meet many definitions. This overlap of the classifications further complicates the decision to favor one criterion over another. In clinical practice, a classification system using the concepts of MCI, MDI and SDI seems to be quite operational but cut-offs are necessary for the tests applied, in addition to a clarified choice of which tests to use.

Autobiographic memory: phenomenological aspects, personal semantic knowledge, generic events and characters (one case of pure retrograde memory recovery).

Tulving et al. [Brain Cogn 8 (1988) 3-20] proposed an operational distinction concerning memory between a semantic component consisting of general information about the individual's past and an episodic component, containing memories of specific events that can be situated in space and time. After a mild head trauma and in the context of professional troubles, patient FF displayed a pure retrograde amnesia concerning both his biographical identity and semantic memories. The patient could no longer access his memories. However, these did not seem completely lost since his answers to tests concerning historical events were better than random, his answers to a television quiz were automatic, he showed temporal transfer phenomena (ecmnesia) and since he retrieved the entirety of his memories within nine months. The patient FF illustrates the loss of retrograde autobiographic memory and the recovery of episodic memories, which requires three elements: a sense of subjective time, an autonoetic awareness (the ability to be aware of subjective time) and a "self" that can travel in subjective time.