Suspected neurodevelopmental disorders in adult patients of memory clinics: Start at the beginning. GREDEV proposals for clinical practice.

Neurodevelopmental disorders are frequent but underestimated in adult populations, even though the cognitive profile of those affected remains atypical throughout adulthood and the disorders can cause significant impairment in activities of daily living. Retrospective diagnosis in this population is challenging. In this article, the GREDEV (working group for the assessment of neurodevelopmental disorders in adults) proposes a brief screening questionnaire for patients with suspected neurodevelopmental disorders, a checklist to facilitate taking the patient history, a list of self-administered questionnaires, and the different key steps of diagnosing neurodevelopmental disorders in adults.

Different clinical outcomes between cerebral amyloid angiopathy-related inflammation and non-inflammatory form.

OBJECTIVE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare manifestation related to CAA, thought to be more severe. We aimed to compare the clinical and radiological outcomes of CAA-ri and non-inflammatory CAA. MATERIALS AND METHODS: We retrospectively included all patients with CAA-ri from 13 French centers. We constituted a sex- and age-matched control cohort with non-inflammatory CAA and similar disease duration. Survival, autonomy and cognitive evolution were compared after logistic regression. Cerebral microbleeds (CMB), intracerebral hemorrhage, cortical superficial siderosis and hippocampal atrophy were analyzed as well as CSF biomarker profile and APOE genotype when available. Outcomes were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Data from 48 CAA-ri patients including 28 already reported and 20 new patients were analyzed. Over a mean of 3.1 years, 11 patients died (22.9%) and 18 (37.5%) relapsed. CAA-ri patients were more frequently institutionalized than non-inflammatory CAA patients (30% vs 8.3%, p < 0.001); mortality rates remained similar. MMSE and modified Rankin scale scores showed greater severity in CAA-ri at last follow-up. MRI showed a higher number of CMB at baseline and last follow-up in CAA-ri (p < 0.001 and p = 0.004, respectively). CSF showed lower baseline levels of Aß42 in CAA-ri than non-inflammatory CAA (373.3 pg/ml vs 490.8 pg/ml, p = 0.05). CAA-ri patients more likely carried at least one APOE ε4 allele (76% vs 37.5%, adjusted p = 0.05) particularly as homozygous status (56% vs 6.2%, p < 0.001). INTERPRETATION: CAA-ri appears to be more severe than non-inflammatory CAA with a significant loss of autonomy and global higher amyloid burden, shown by more CMB and a distinct CSF profile. This burden may be partially promoted by ε4 allele.

Visual agnosia and focal brain injury.

Visual agnosia encompasses all disorders of visual recognition within a selective visual modality not due to an impairment of elementary visual processing or other cognitive deficit. Based on a sequential dichotomy between the perceptual and memory systems, two different categories of visual object agnosia are usually considered: 'apperceptive agnosia' and 'associative agnosia'. Impaired visual recognition within a single category of stimuli is also reported in: (i) visual object agnosia of the ventral pathway, such as prosopagnosia (for faces), pure alexia (for words), or topographagnosia (for landmarks); (ii) visual spatial agnosia of the dorsal pathway, such as cerebral akinetopsia (for movement), or orientation agnosia (for the placement of objects in space). Focal brain injuries provide a unique opportunity to better understand regional brain function, particularly with the use of effective statistical approaches such as voxel-based lesion-symptom mapping (VLSM). The aim of the present work was twofold: (i) to review the various agnosia categories according to the traditional visual dual-pathway model; and (ii) to better assess the anatomical network underlying visual recognition through lesion-mapping studies correlating neuroanatomical and clinical outcomes.

17q21.31 duplication causes prominent tau-related dementia with increased MAPT expression.

To assess the role of rare copy number variations in Alzheimer's disease (AD), we conducted a case-control study using whole-exome sequencing data from 522 early-onset cases and 584 controls. The most recurrent rearrangement was a 17q21.31 microduplication, overlapping the CRHR1, MAPT, STH and KANSL1 genes that was found in four cases, including one de novo rearrangement, and was absent in controls. The increased MAPT gene dosage led to a 1.6-1.9-fold expression of the MAPT messenger RNA. Clinical signs, neuroimaging and cerebrospinal fluid biomarker profiles were consistent with an AD diagnosis in MAPT duplication carriers. However, amyloid positon emission tomography (PET) imaging, performed in three patients, was negative. Analysis of an additional case with neuropathological examination confirmed that the MAPT duplication causes a complex tauopathy, including prominent neurofibrillary tangle pathology in the medial temporal lobe without amyloid-ß deposits. 17q21.31 duplication is the genetic basis of a novel entity marked by prominent tauopathy, leading to early-onset dementia with an AD clinical phenotype. This entity could account for a proportion of probable AD cases with negative amyloid PET imaging recently identified in large clinical series.

[Specificities of the logopenic variant of primary progressive aphasia]. / Particularités du variant logopénique au sein des aphasies progressives primaires.

The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved.

Oropharyngeal dysphagia in amyotrophic lateral sclerosis alters quality of life.

Dysphagia is one of the most important complications encountered in amyotrophic lateral sclerosis (ALS). Our aim was to determine whether oropharyngeal dysphagia impacted the quality of life (QoL) of patients with ALS. Thirty consecutive patients were recruited (31-82 years, 18 men). Swallowing function was evaluated using a standardised videofluoroscopic barium swallow. All the patients completed a specific questionnaire on quality of life in dysphagia (SWAL-QoL) immediately after the videofluoroscopy. The results of dysphagia outcome severity scale separated 14 patients with oropharyngeal dysphagia and 16 with normal swallowing function. There was no difference in the average age, weight and body mass index of the two groups (dysphagic patients: 68 ± 11 kg versus non-dysphagic patients: 69 ± 14 kg). Most of the dysphagic patients had a bulbar affection based on their Norris scores which determine the importance of cranial nerves illness (20 ± 8), significantly lower than those of the non-dysphagic patients (35 ± 5) (P < 0·0001). There was no difference in the neurological peripheral symptoms evaluated by Amyotrophic Lateral Sclerosis Functional Rating Scale scores (dysphagic patients: 26 ± 7 versus non-dysphagic patients: 27 ± 8) (ns). The swallowing quality of life questionnaire revealed that the dysphagic patients had significant burden (P < 0·001). They were affected by the necessity to applied a food selection (P < 0·01), by the increase in eating duration (P < 0·05) and described a decrease in eating desire (P < 0·05). They complained of fear regarding the risk of dysphagia (P < 0·05). They also described difficulties with oral communication (P < 0·001). All of those complained about dysphagia which impacted directly mental health (P < 0·05) and social life (P < 0·05). In conclusion, oropharyngeal dysphagia is a common symptom accompanying ALS, which alters the patient's QoL, especially social health.

Clinical screening of oropharyngeal dysphagia in patients with ALS.

OBJECTIVE: It is a major issue to diagnose and detect oropharyngeal dysphagia in the early stage of ALS in order to avoid pulmonary and nutritional complications. The aim of this study was to validate a simple clinical test, the Volume-Viscosity Swallow Test (V-VST), to detect oropharyngeal dysphagia in this population. PATIENTS AND METHODS: Twenty patients were included in this study (mean age: 66.1 ± 8.13, six women). All patients had their swallowing function assessed by videofluoroscopy and V-VST. RESULTS: Among these 20 patients, 15 presented oropharyngeal dysphagia, diagnosed by videofluoroscopy, and five had normal swallowing. Norris score was lower in patients with oropharyngeal dysphagia compared to the patients with normal swallowing (27 ± 6 versus 36 ± 2; P=0.003). Among the 15 patients with oropharyngeal dysphagia, 14 had abnormal V-VST, and only one had normal V-VST. The sensibility of V-VST to detect oropharyngeal dysphagia in these patients with ALS was of 93%, and the specificity was of 80% (P=0.007). There was no significant difference between the two populations for ALSFRS score (22 ± 6 versus 20 ± 6) and body mass index (BMI) (26 ± 6 versus 26 ± 6 kg/m(2)). CONCLUSION: The V-VST presented good sensibility and specificity. It may be interesting to use it systematically for the detection of oropharyngeal dysphagia in ALS, after confirming these results on a wider patient sample.

Detailed neuropsychological evaluation in a patient with Floating Harbor syndrome.

The Floating Harbor syndrome is a rare genetic disease characterized by a triad of clinical signs: specific dysmorphic facial features, short stature with delayed bone age, and language and speech disorders. These signs are, in most cases, associated with borderline normal intelligence to moderate delay concerning intellectual functioning. We report an extensive neuropsychological evaluation for an adult female patient and show, in particular, a severe visuospatial impairment. We discuss this deficit in the light of the previous reported cases and suggest that visuospatial abilities should be explored more systematically.

Superior interhemispheric approach for midline meningioma from the anterior cranial base.

BACKGROUND: For suprasellar meningioma, the fronto-basal exposure is considered the standard approach. The superior interhemispheric (IH) approach is less described in the literature. OBJECTIVE: To assess the surgical complications, functional outcome (visual, olfaction), morbidity and mortality rates and late recurrence, after resection by superior IH approach of midline skull base meningioma. METHODS: Between 1998 and 2008, 52 consecutive patients with midline meningioma on the anterior portion of the skull base (mean age: 63.8 ± 13.1; sex ratio F/M: 3.7) were operated on via the superior IH approach. After a mean follow-up of 56.9 ± 32.9 months, an independent neurosurgeon proposed a prospective examination of functional outcome to each patient, as well as a visual and olfactory function assessment. RESULTS: Fifty-two patients were divided into a group with olfactory groove meningioma (n=34) and another with tuberculum sellae meningioma (n=18). The outcome was characterized by postoperative complications in 13 patients (25%), mortality rate in two (3.8%) and long-term morbidity at in 17 (37%) of 50 surviving patients. Based on multivariate analysis, no prognosis factor was significant as regards the favorable outcome. The mean postoperative KPS score (86.6 ± 9.4) was significantly improved. However, dysexecutive syndrome was observed in four patients (8%), hyposmia-anosmia in 34 (68%) and visual acuity deteriorated in one (2%). CONCLUSION: The superior IH approach could be considered a safe anteriorly orientated midline approach for removal OGM and TSM meningioma.

Clinical imaging and neuropathological correlations in an unusual case of cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder due to a deficiency of the mitochondrial enzyme sterol 27-hydroxylase (CYP 27) with reduced or no chenodeoxycholic synthesis. This deficiency leads to an accumulation of cholestanol in different sites such as the eye lens, central nervous system or tendons. We report a 64-year-old female patient with a progressive gait disorder associated with cognitive decline since the age of 59. The patient had no mental retardation, cataract or chronic diarrhea. Her family reported increasing behavioral modifications 10 years previously. Clinical examination revealed a spastic paraplegia and bilateral xanthomas on the Achilles tendons. Cerebral magnetic resonance imaging (MRI) revealed diffuse hyperintense T2 abnormalities in the pyramidal tracts from the internal capsules to the cerebral peduncles also Technetium-99m-ECD brain SPECT showed a severe cerebellar hypoperfusion. Serum cholestanol analysis was 7 µmol/l (N). After 2 years, she was bedridden and died of aspiration pneumonia. The neuropathological study confirmed the CTX diagnosis and the sequencing analysis revealed that she was compound heterozygous for two mutations in the CYP27A1 gene: 1435 C > T (exon 7) on one allele and a new mutation, 1017 G > C (exon 5) on the other. The interest of the present case is to report neuropathology findings strongly correlated with the MRI and SPECT abnormalities.

[Argyrophilic grain disease: synergistic component of dementia?]. / Maladie des grains argyrophiles: composante synergique de la démence ?

INTRODUCTION: Argyrophilic grain disease (AGD) is one cause of neurodegenerative dementia with a variable clinical spectrum. A neuropathology study is required for diagnosis. CASE REPORT: We report the case of a 68-year-old patient presenting with cognitive decline associating with frontal dysfunction and parkinsonism. Death occurred two years after onset. The neuropathology study revealed a status criblosus in the basal ganglia, neurofibrillary tangles and AGD. DISCUSSION: We suggest that AGD could explain the atypical course of this dementia considering the fast cognitive decline, the clinical expression and the topography of the lesions. CONCLUSION: This case illustrates the possible synergistic deleterious effect of this pathology on other causes of dementia.

Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease.

BACKGROUND: Frontotemporal dementia associated with motor neuron disease (FTD-MND) is a rare neurodegenerative disorder that may be inherited by autosomal dominant trait. No major gene has been identified but a locus was mapped on chromosome 9 (9p21.3-p13.3). METHODS: Ten French families with FTD-MND were tested for linkage to the 9p21.3-p13.3 region. We report extensive mutation screening in 9p-linked families and their clinical characteristics. RESULTS: We identified six new families with evidence for linkage to the chromosome 9p. Cumulative multipoint LOD score values were positive between markers D9S1121 and D9S301, reaching a peak of 8.0 at marker D9S248. Haplotype reconstruction defined the telomeric boundary at marker AFM218xg11, slightly narrowing the candidate interval. We found no disease-causing mutations by sequencing 29 candidate genes including IFT74 and no copy number variations in the 9p region. The mean age at onset was 57.9 +/- 10.3 years (range, 41-84), with wide heterogeneity within and among families suggesting age-dependant penetrance. The patients presented isolated FTD (32%), isolated MND (29%), or both disorders (39%). The general characteristics of the disease did not differ, except for an older age at onset and shorter disease duration in the 9p-linked compared to nonlinked families. TDP-43-positive neuronal cytoplasmic inclusions were found in cortex and spinal cord in 3 patients. CONCLUSIONS: This study increases the number of 9p-linked families now reported and shows that this locus may have a major effect on frontotemporal dementia (FTD) and motor neuron disease (MND). Considering our results, the causative gene might be implicated in at least 60% of the families with FTD-MND disorder.

Anatomy of executive deficit following ruptured anterior communicating artery aneurysm.

BACKGROUND AND PURPOSE: To evaluate behavioral and cognitive deficits following anterior communicating artery aneurysm rupture and determine critical lesion locations. METHODS: We investigated 74 patients with standardized cognitive tests and behavioral inventory. Two examiners rated MRI signal abnormalities in 51 predetermined regions of interest. Classification tree analysis was used to select regions associated with each cognitive deficit. RESULTS: Eleven patients presented behavioral executive deficits and 10 had cognitive executive deficit. Their presence depended on left hemisphere lesions only: (i) ventral striatum lesion was associated with behavioral executive deficit (P = 0.04), reduction of activities (P = 0.01), and hyperactivity (P = 0.02); (ii) superior frontal gyrus lesion, with cognitive executive deficit (P = 0.01), action initiation deficit (P = 0.02), and rule deduction deficit (P = 0.02); (iii) anterior half of centrum semiovale lesion, with Stroop inhibition deficit (P = 0.02); (iv) medial superior and middle frontal gyri lesions, with task coordination deficit (P = 0.01); and (v) middle frontal gyrus lesion, with words generation deficit (P = 0.02). CONCLUSION: This study supports that (i) cognitive executive deficits depend mostly on lateral prefrontal lesions, (ii) with locations varying according to executive process, and (iii) behavioral executive deficits are mainly due to left ventral striatum lesion in post-aneurysmal damage.

[An aphasic reader]. / Une lectrice aphasique.

Nonsemantic reading is the capacity to read without understanding by impairment of the lexical-semantic pathway. We report the case of a female steno secretary with nonsemantic reading capacity associated with severe aphasia caused by a left hemisphere ischemic stroke in Broca's area. Arguments in favor of a right hemisphere contribution to the reading ability are presented.

[Pineal cyst: usefulness of endoscopic treatment]. / Kyste épithélial de la région pinéale: intérêt de la fenestration endoscopique.

Glial cysts of the pineal gland are usually benign and asymptomatic. They develop from the pineal parenchyma and contain liquid. The diagnosis is made by magnetic resonance imaging. In contrast large cysts can be symptomatic due to compression of the aqueduct of Sylvius, compression of the midbrain tectum or mass effect in the posterior fossa. We report the case of a symptomatic cyst treated by an endoscopic procedure.

Frontotemporal dementia, motor neuron disease and tauopathy: clinical and neuropathological study in a family.

We report a familial disorder occurring in three patients that presented as frontotemporal dementia (FTD). A neuropathological study was performed in a 58-year-old patient, who developed FTD 2 years prior to the onset of motor neuron disease (MND), and died at age 62. Lesions indicative of associated MND were observed: neuronal loss in the anterior horns of the spinal cord, Bunina bodies, axonal spheroids, degeneration of the pyramidal tracts, and of FTD: decreased neuronal density and laminar microvacuolation of layers II and III in the frontal and temporal cortex. Ubiquitin-only-immunoreactive changes were found in the spinal cord and medulla, but were absent from the temporal and frontal cortex. There were also widespread deposits of various neuronal and glial inclusions containing abnormally phosphorylated tau protein, the Western blotting pattern of which was characterized by two major bands of 64 and 69 kDa. There were no abnormalities of the entire coding sequences of microtubule-associated protein tau (MAPT) and copper-zinc superoxide dismutase (SOD(1)) genes. Our results suggest that FTD associated with MND can be caused by a larger spectrum of neuropathological lesions than commonly accepted.

[Anti-Ri paraneoplastic syndrome associated with ophtalmoplegia, blepharospasm and palilalia]. / Ophtalmoplégie, blépharospasme et palilalie associés à des anticorps anti-Ri.

INTRODUCTION: Anti-Hu and anti-Yo are the most well-known anti-neuronal antibodies. The anti-Ri antibodies, which are less common, are generally found in subjects with opsoclonus-myoclonus, often associated with breast cancer. CASE REPORT: A 54-year-old woman presented anti-Ri antibodies associated with a paraneoplastic syndrome and unusual symptoms of ophthalmoplegia, blepharospasm, palilalia and ataxia. Adenocarcinoma of the breast was also found. After chemotherapy, radiotherapy, and several immunoglobulin infusions, the patient did not improve ten months after tumor surgery. CONCLUSION: Anti-Ri antibodies associated with paraneoplastic syndrome can be observed in patients who develop a rapidly progressive brainstem tumor. Breast or lung cancer and conduct to search a breast or pulmonary cancer.