How autoimmunity changed our diagnostic practice in epileptology?

Since few years, a new etiology of epilepsy emerges with the labelling of new autoantibodies against the central nervous system. In 2017, the International League Against Epilepsy (ILAE) concluded that autoimmunity is one of six etiologies contributing to epilepsy and that autoimmune epilepsy is directly caused by immune disorders in which seizures constitute a core symptom. Epileptic disorders of immune origin are now distinguished in two different entities: acute symptomatic seizures secondary to autoimmune (ASS) and autoimmune-associated epilepsy (AAE) with different expected clinical outcome under immunotherapy. If acute encephalitis is usually related to ASS with a classic good control of the disease under immunotherapy, clinical phenotype characterized by isolated seizures (new onset seizures and chronic focal epilepsy patients) may be due to either ASS or to AAE. Decision of Abs testing and early immunotherapy initiation needs the development of clinical scores able to select patients with high risk of positive Abs testings. If this selection is now included in the usual medical care of encephalitic patients, specifically with NORSE, the actual bigger challenge is in patients with non or only mild encephalitic symptoms followed for new onset seizures or chronic focal epilepsy patients of unknown origin. The emergence of this new entity provides new therapeutic strategies with specific etiologic and probably anti epileptogenic medication rather than the usual and nonspecific ASM. In the world of the epileptology, this new autoimmune entity appears as a big challenge with an exciting chance to improve or even definitely cure patients of their epilepsy. However, the detection of these patients has to be done in the early phase of the disease to offer the best outcome.

Visual phenomena and anatomo-electro-clinical correlations in occipital lobe seizures.

BACKGROUND: Occipital lobe seizure are underrepresented in epilepsy surgery cases series. This may reflect the fear for post-surgical functional deficits but also the doubt about the ability of anatomo-electro-clinical correlations to localize precisely the epileptogenic zone in occipital lobe seizure. METHODS: In this expert opinion paper, we review first the general clinical characteristics of occipital lobe seizures, describe the repertoire of visual phenomena and oculo-motor signes in occipital seizures, describe inter-ictal and ictal EEG and finally the possible schemes of epileptogenic zone organization. RESULTS: Visual and oculo-motor semiology points towards occipital onset seizures but is neither pathognomonic nor constant. Eyes version and unilateral ictal discharge have a strong lateralizing value but inter-ictal spikes as well as eyes version can be falsely lateralizing. CONCLUSION: Although visual and oculo-motor phenomena are characteristic of occipital lobe seizures, they may be discrete, overlooked and should therefore be carefully assessed. There are no clear electro-clinical correlations of a sublobar organization of occipital seizures but the clinical pattern of propagation might help to differentiate complex occipito-temporal from occipito-parietal initial epileptogenic network.

Long-term cognitive outcomes in patient with epilepsy.

In contrast to short-term cognitive outcomes, long-term cognitive outcomes (over 5 years) has been scarcely assessed so far. Yet, predicting long-term outcomes at any time point of the epilepsy, from initial diagnosis, to medically intractability is very important for therapeutic decision-making, patient information, and orientation. Assessing long-term cognitive outcomes in patients with epilepsy would ideally require longitudinal studies and a comparison with a healthy controls group. This issue has been addressed extensively, but with controversial results. However, there is a general consensus about the fact that cognitive outcome is not the same in all groups of patients with epilepsy. Possible prognostic factors include age at onset, duration of epilepsy, syndrome and etiology, seizure outcome and therapeutics. The multiplicity of factors makes it very difficult to assess their relative weight in individuals. Although long-term cognitive outcome studies are scarce, this issue has been specifically studied in newly diagnosed epilepsies and in focal drug-resistant epilepsies. In the first clinical setting, i.e. newly diagnosed epilepsy, it appears that cognitive deficits are already present at epilepsy onset in a significant proportion of patients but seem to remain stable over time. In focal drug-resistant epilepsies, cognitive deficits (mainly verbal memory) were generally shown to remain stable provided that seizures were controlled either by medication or by surgery. Beyond the possible correlation between seizure and cognitive outcome, no causal link however has been demonstrated between these two important outcomes.

Experiences of self-conscious emotions in temporal lobe epilepsy.

Self-conscious emotions (SCEs) with a negative valence (such as shame and guilt) or a positive valence (such as pride) are moral emotions that emerge from self-reflection and self-evaluation processes in social contexts. In some neurologic and psychiatric disorders, experiences of SCEs are dysregulated. The objectives of the present study were to (i) evaluate whether patients with temporal lobe epilepsy (TLE) experience SCEs in the same way as nonclinical (control) participants and (ii) probe the relationships between experiences of SCEs on the one hand and the psychological symptoms frequently diagnosed in patients with TLE (anxiety and depression), the patients' clinical characteristics, and their functional outcomes in everyday life on the other. Sixty-one patients with TLE and 61 matched controls completed a self-questionnaire (the Positive and Negative Affect Schedule (PANAS)) that enabled us to evaluate the extent to which they experienced shame, guilt, and pride. Demographic data, cognitive data, the severity of anxiety symptoms, and the severity of depressive symptoms were recorded for all participants. In patients with TLE, data of clinical characteristics and quality of life were also evaluated. Relative to controls, patients with TLE were more likely to experience negative-valence SCEs to a higher extent and positive SCEs to a lesser extent. The patients who experienced negative-valence SCEs to a higher extent (rather than to a lesser extent) had a higher frequency of seizures, more severe anxiety and depressive symptoms, and a greater prevalence of anxiety and depressive disorders. Furthermore, patients who experienced positive-valence SCEs to a lesser extent (rather than to a higher extent) displayed a higher level of anxiety. Lastly, differences in experiences of SCEs by patients with TLE were associated with a lower quality of life. In conclusion, experiences of SCEs can be dysregulated in patients with TLE. This dysregulation is linked to the patients' clinical and psychological symptoms and quality of life. In this context, SCEs might be a target of interest in the management of epilepsy.

Is long-term electroencephalogram more appropriate than standard electroencephalogram in the elderly?

OBJECTIVE: To compare the diagnostic accuracy of standard (st) and long-term video (lt) EEG in elderly patients with suspected non-convulsive seizures. METHODS: Over a 12-month period, we prospectively included all elderly (over-65) hospitalized patients having undergone lt-EEG for suspected non-convulsive seizures (n=43). st-EEG was defined as the first 20min of each lt-EEG. We recorded the patients' clinical and imaging characteristics and final diagnosis and assessed the respective diagnostic values of st-EEG and lt-EEG. RESULTS: Epileptiform discharges were detected on standard EEG in only 7% of patients and in 28% of patients on Lt-EEG (p=0.004). Non-convulsive seizures were recorded in 1 case vs. 4, respectively. Nine of 40 negative standard EEG showed later epileptiform activities. The median time to occurrence of the first epileptiform activities was 46.5min (interquartile range: 36.5-239.75min). Epileptiform activity occurred during sleep only in 33% patients with a negative st-EEG. Dementia was associated with a positive lt-EEG (p:0.047). CONCLUSION: Lt-EEG was clearly superior to standard EEG for detecting epileptiform activity in elderly when suspecting non convulsive seizures. SIGNIFICANCE: St-EEG has a low diagnostic yield in elderly patients with suspected non-convulsive seizures and so lt-EEG is preferable in this situation.

Somatosensory evoked potentials in the assessment of peripheral neuropathies: Commented results of a survey among French-speaking practitioners and recommendations for practice.

BACKGROUND: Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have yet been established in this specific application. STUDY AIM: To determine the relevant indication criteria and optimal technical parameters for SSEP recording in peripheral neuropathy investigation. METHODS: A survey was conducted among the French-speaking practitioners with experience of SSEP recording in the context of peripheral neuropathies. The results of the survey were analyzed and discussed to provide recommendations for practice. RESULTS: SSEPs appear to be a second-line test when electroneuromyographic investigation is not sufficiently conclusive, providing complementary and valuable information on central and proximal peripheral conduction in the somatosensory pathways. CONCLUSIONS: Guidelines for a standardized recording protocol, including the various parameters to be measured, are proposed. CLINICAL RELEVANCE: We hope that these proposals will help to recognize the value of this technique in peripheral neuropathy assessment in clinical practice.

The endophyte Verticillium Vt305 protects cauliflower against Verticillium wilt.

AIMS: To investigate the interaction between cauliflower and the isolate VerticilliumVt305, obtained from a field suppressive to Verticillium wilt of cauliflower, and to evaluate the ability of VerticilliumVt305 to control Verticillium wilt of cauliflower caused by V. longisporum. METHODS AND RESULTS: Single and combined inoculations of VerticilliumVt305 and V. longisporum were performed on cauliflower seedlings. Symptom development was evaluated, and fungal colonization was measured in the roots, hypocotyl and stem with real-time PCR. No symptoms were observed after single inoculation of VerticilliumVt305, although it colonized the plant tissues. Pre-inoculation of VerticilliumVt305 reduced symptom development and colonization of plant tissues by V. longisporum. CONCLUSIONS: VerticilliumVt305 is an endophyte on cauliflower plants and showed effective biological control of V. longisporum in controlled conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This work can contribute to the development of a sustainable control measure of V. longisporum in Brassicaceae hosts, which is currently not available. Additionally, this study provides evidence for the different roles of Verticillium species present in the agro-ecosystem.

[Susceptibility weighted magnetic resonance sequences "SWAN, SWI and VenoBOLD": technical aspects and clinical applications]. / Séquences IRM « SWAN, SWI et VenoBOLD ¼ exploitant le phénomène de susceptibilité magnétique : principes techniques et applications cliniques.

Susceptibility-weighted MR sequences, T2 star weighted angiography (SWAN, General Electric), Susceptibility weighted imaging (SWI, Siemens) and venous blood oxygen level dependant (VenoBOLD, Philips) are 3D spoiled gradient-echo sequence that provide a high sensitivity for the detection of blood degradation products, calcifications, and iron deposits. For all these sequences, an appropriate echo time allows for the visualization of susceptibility differences between adjacent tissues. However, each of these sequences presents a specific technical background. The purpose of this review was to describe 1/the technical aspects of SWAN, VenoBOLD and SWI sequences, 2/the differences observed in term of contrast within the images, 3/the key imaging findings in neuroimaging using susceptibility-weighted MR sequences.

Thalamic nuclei activity in idiopathic generalized epilepsy: an EEG-fMRI study.

OBJECTIVE: Idiopathic generalized epilepsies (IGE) are characterized by specific EEG changes including 3- to 5-Hz generalized spike-and-wave discharges. The thalamus and its cortical interactions are considered essential in the production and propagation of spike-and-wave discharges. In animal studies, corticoreticular and limbic system property changes have been observed in absence seizures and during spike-and-wave discharges and suggest the involvement of different types of thalamic nuclei. With the development of deep brain stimulation in epilepsy, the role of the thalamic nuclei needs to be clarified in human IGE. METHODS: Ten patients with IGE were recorded using 3T EEG-fMRI during spike-and-wave discharges. Hemodynamic response functions were calculated for 4 regions of interest corresponding to the anterior thalamic and centromedian and parafascicular (CM-Pf) nuclei of each thalamus. The time to peak of the hemodynamic response function was compared within thalamic structures (left compared to right) and between structures (anterior thalamic compared to CM-Pf nucleus). RESULTS: CM-Pf and anterior nucleus are both activated during GSWDs. However, the positive time to peak in the CM-Pf (4.4 +/- 2.5 s) occurred significantly earlier than in the anterior nucleus (7.6 +/- 3.2 s). CONCLUSIONS: We demonstrated in humans the involvement of the centromedian and parafascicular part of the corticoreticular system and of the anterior nucleus part of the limbic system during generalized spike-and-wave discharges. The different time courses suggest that the posterior intralaminar nuclei may be involved in epileptic discharge initiation or early propagation, while the anterior nucleus may only play a role in its maintenance. These results may help to understand the clinical effect of deep brain stimulation within thalamic nuclei in intractable idiopathic generalized epilepsy patients.

EEG-fMRI: adding to standard evaluations of patients with nonlesional frontal lobe epilepsy.

OBJECTIVE: In patients with nonlesional frontal lobe epilepsy (FLE), the delineation of the epileptogenic zone is difficult. Therefore these patients are often not considered for surgery due to an unclear seizure focus. The aim of this study was to investigate whether EEG-fMRI can add useful information in the preoperative evaluation of these patients. METHODS: Nine nonlesional FLE patients were studied with EEG-fMRI using a 3 T scanner. Spike-related blood oxygen level dependent (BOLD) signal changes were compared to the topography of the spikes and to PET and SPECT results if available. The structural MRIs were reviewed for subtle abnormalities in areas that showed BOLD responses. For operated patients, postoperative resection and histology were compared to BOLD responses. RESULTS: Concordance between spike localization and positive BOLD response was found in 8 patients. PET and SPECT investigations corresponded with BOLD signal changes in 6 of 7 investigations. In 2 cases, reviewing the structural MRI guided by EEG-fMRI data resulted in considering a suspicious deep sulcus. Two patients were operated. In 1, the resected cortex corresponded with the suspicious sulcus and fMRI results and histology showed cortical dysplasia. In another, histology revealed an extended microdysgenesis not visible on structural MRI. EEG-fMRI had shown activation just adjacent to the resected pathologic area. CONCLUSIONS: Our study provides different types of support (topography, concordance with PET and SPECT, structural peculiarities, postoperative histology) that EEG-fMRI may help to delineate the epileptic focus in patients with nonlesional frontal lobe epilepsy, a challenging group in the preoperative evaluation.

A-delta and C-fibres function in primary restless legs syndrome.

STUDY AIMS: The sensory symptoms that are reported in restless legs syndrome (RLS) suggest involvement of the peripheral nervous system (PNS) in general and of the small-fibre system in particular. We aimed to study the status of the small-fibre system in primary RLS. PATIENTS AND METHODS: We investigated 10 patients with idiopathic RLS (mean time since disease onset: 11.4 +/- 12 years, mean International Restless Legs Syndrome Study Group [IRLSSG] score: 23.4 +/- 8). Five had a family history. All had normal results for laboratory tests, neurological examination, and a sural/deep-peroneal nerve conduction study. Lower-limb thulium YAG laser-evoked potentials (LEP) and skin sympathetic reflexes (SSR) were performed. The results were compared with data from 10 healthy subjects. RESULTS: The nociceptive thresholds were 293 +/- 62 mJ for patients and 333 +/- 77 mJ for controls. For patients, the vertex N2 and P2 latencies were 208 +/- 25 ms and 366 +/- 51 ms, respectively (controls: N2 = 235 +/- 41 ms; P2 = 373 +/- 44 ms). The N2-P2 amplitude was 19 +/- 6 microV for patients and 18 +/- 7 microV for controls. SSR were normal in all patients. No significant differences between patients and healthy subjects were observed. CONCLUSION: We failed to demonstrate any significant involvement of small fibres and spinothalamic tracts in idiopathic RLS. Even though sufferers of this specific form of RLS report sensory symptoms, pathogenesis appears to be dissociated from a PNS alteration.

Afferent-induced facilitation of primary motor cortex excitability in the region controlling hand muscles in humans.

Sensory inputs from cutaneous and limb receptors are known to influence motor cortex network excitability. Although most recent studies have focused on the inhibitory influences of afferent inputs on arm motor responses evoked by transcranial magnetic stimulation (TMS), facilitatory effects are rarely considered. In the present work, we sought to establish how proprioceptive sensory inputs modulate the excitability of the primary motor cortex region controlling certain hand and wrist muscles. Suprathreshold TMS pulses were preceded either by median nerve stimulation (MNS) or index finger stimulation with interstimulus intervals (ISIs) ranging from 20 to 200 ms (with particular focus on 40-80 ms). Motor-evoked potentials recorded in the abductor pollicis brevis (APB), first dorsalis interosseus and extensor carpi radialis muscles were strongly facilitated (by up to 150%) by MNS with ISIs of around 60 ms, whereas digit stimulation had only a weak effect. When MNS was delivered at the interval that evoked the optimal facilitatory effect, the H-reflex amplitude remained unchanged and APB motor responses evoked with transcranial electric stimulation were not increased as compared with TMS. Afferent-induced facilitation and short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) mechanisms are likely to interact in cortical circuits, as suggested by the strong facilitation observed when MNS was delivered concurrently with ICF and the reduction of SICI following MNS. We conclude that afferent-induced facilitation is a mechanism which probably involves muscle spindle afferents and should be considered when studying sensorimotor integration mechanisms in healthy and disease situations.

Cortical involvement in the sensory and motor symptoms of primary restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is characterized by closely interrelated motor and sensory disorders. Two types of involuntary movement can be observed: periodic leg movements during wakefulness (PLMW) and periodic leg movements during sleep (PLMS). Basal ganglia dysfunction in primary RLS has often been suggested. However, clinical observations raise the hypothesis of sensorimotor cortical involvement in RLS symptoms. Here, we explored cortical function via movement-related beta and mu rhythm reactivity. METHODS: Twelve patients with idiopathic, primary RLS were investigated and compared with 10 healthy subjects. In the patient group, we analyzed event-related beta and mu (de)synchronization (ERD/S) for PLMS and PLMW during a suggested immobilization test (SIT). An ERD/S analysis was also performed in patients and controls during self-paced right ankle dorsal flexion at 8:30 PM (i.e., the symptomatic period for patients) and 8:30 AM (the asymptomatic period). RESULTS: Before PLMS, there was no ERD. Intense ERS was recorded after PLMS. As with voluntary movement, cortical ERD was always observed before PLMW. After PLMW, ERS had a diffuse scalp distribution. Furthermore, the ERS and ERD amplitudes and durations for voluntary movement were greater during the symptomatic period than during the asymptomatic period and in comparison with healthy controls, who presented an evening decrease in these parameters. Patients and controls had similar ERD and ERS patterns in the morning. CONCLUSION: On the basis of a rhythm reactivity study, we conclude that the symptoms of RLS are related to cortical sensorimotor dysfunction.

Different structures involved during ictal and interictal epileptic activity in malformations of cortical development: an EEG-fMRI study.

Malformations of cortical development (MCDs) are commonly complicated by intractable focal epilepsy. Epileptogenesis in these disorders is not well understood and may depend on the type of MCD. The cellular mechanisms involved in interictal and ictal events are notably different, and could be influenced independently by the type of pathology. We evaluated the relationship between interictal and ictal zones in eight patients with different types of MCD in order to better understand the generation of these activities: four had nodular heterotopia, two focal cortical dysplasia and two subcortical band heterotopia (double-cortex). We used the non-invasive EEG-fMRI technique to record simultaneously all cerebral structures with a high spatio-temporal resolution. We recorded interictal and ictal events during the same session. Ictal events were either electrical only or clinical with minimal motion. BOLD changes were found in the focal cortical dysplasia during interictal and ictal epileptiform events in the two patients with this disorder. Heterotopic and normal cortices were involved in BOLD changes during interictal and ictal events in the two patients with double cortex, but the maximum BOLD response was in the heterotopic band in both patients. Only two of the four patients with nodular heterotopia showed involvement of a nodule during interictal activity. During seizures, although BOLD changes affected the lesion in two patients, the maximum was always in the overlying cortex and never in the heterotopia. For two patients intracranial recordings were available and confirm our findings. The dysplastic cortex and the heterotopic cortex of band heterotopia were involved in interictal and seizure processes. Even if the nodular gray matter heterotopia may have the cellular substrate to produce interictal events, the often abnormal overlying cortex is more likely to be involved during the seizures. The non-invasive BOLD study of interictal and ictal events in MCD patients may help to understand the role of the lesion in epileptogenesis and also determine the potential surgical target.

[Neurophysiology of corticobasal degeneration]. / Neurophysiologie de la dégénérescence corticobasale.

INTRODUCTION: Corticobasal degeneration (CBD) is a neurodegenerative disorder of mid- to late-adult life. From a clinical standpoint, CBD is characterized by (i) an insidious onset and a slowly progressing, unilateral, levodopa-unresponsive parkinsonian syndrome with dystonia or myoclonus and (ii) cerebral features such as apraxia, alien limb phenomena and cortical sensory loss. Decisive clinical diagnostic criteria are not available and thus a neuropathological study remains essential for accurate CBD diagnosis. Consequently, additional non-clinical criteria must be identified in order to improve diagnosis while patients are still alive. BACKGROUND: Electrophysiological exploration can yield functional information on a number of brain structures (both cortical and sub-cortical) involved in CBD. The disorder features a specific cortical (frontoparietal) alteration which could help with differential diagnoses for other extrapyramidal syndromes. Hence, exploration of a patient's myoclonus can provide some specific arguments for CBD. Indeed, myoclonus displays a number of clinical and electromyographical characteristics which are consistent with a cortical origin (a shorter latency of the cortical C response, for example). However, some typical cortical features are missing (giant somesthesic evoked potentials, and cortical potentials preceding myoclonus in jerk-locked back-averaging studies). Some authors explain these abnormalities in terms of a sub-cortical origin for the myoclonus. The frontoparietal alteration in CBD has also been explored in studies of oculomotor movement. Indeed, asymmetric lengthening of the lateral ocular saccade latency argues more in favour of CBD than progressive supranuclear palsy. Moreover, cognitive function is also compromised in the early stages of CBD, although it is sometimes difficult to distinguish between CBD, PSP and frontotemporal dementia. Studying cognitive potentials enables one to confirm subcorticofrontal abnormalities and to dissociate CBD patterns from PSP patterns. Other electrophysiological tests (such as the exploration of dysautonomia, the palmomental reflex and the blink reflex) produce results which overlap with those seen in extrapyramidal syndromes and synucleinopathies (polysomnography), prompting discussion of the physiopathological mechanisms of these various diseases. CONCLUSION: Electrophysiological exploration is of value for diagnosing CBD in general and for studying specific, frontoparietal dysfunctions in particular. These techniques could also significantly contribute to our understanding of the physiopathology of CBD.

Low frequency repetitive transcranial magnetic stimulation over premotor cortex can improve cortical tremor.

OBJECTIVE: To examine the effects of a 30 min, 1 Hz subthreshold rTMS in a case of cortical tremor which is caused by hyperexcitability of sensorimotor cortex. METHODS: Stimulation was applied over primary and, in a second time, over premotor cortex (M1 and PMC, respectively). Tremor was monitored by accelerometers placed on the index fingers of hands outstretched, before and several times after rTMS. Each rTMS session consisted of 1800 pulses delivered at 1 Hz with an intensity of 90% of resting motor threshold. RESULTS: PMC but not M1 stimulation led to a decrease of the postural tremor (90% decrease of acceleration total spectral power). This functional benefit was associated to normalization of electrophysiologic parameters (short-interval intracortical inhibition and cortical silent period duration). Moreover, when stimulating PMC during two daily sessions, improvement of the tremor was longer than one day stimulation and this benefit was associated with functional improvement. CONCLUSIONS: This study shows that 1 Hz rTMS over premotor cortex can improve cortical tremor. SIGNIFICANCE: These results raise the interest of the motor cortical stimulation as a possible therapeutic target for treatment of action tremor.

The effect of repetitive transcranial magnetic stimulation on dystonia: a clinical and pathophysiological approach.

Dystonia is characterized by sustained muscle contraction, which frequently causes repetitive, twisting movements or abnormal posture. The precise pathophysiological mechanisms of dystonia are still unknown. Several studies did demonstrate that, although motor cortex hyperexcitability appears to be responsible for abnormal co-contraction and overflow to adjacent muscles, plasticity mechanisms and integrative sensorimotor processing are also likely to be involved in this condition. Current dystonia treatments are based on oral medication, injection of botulinum toxin and, in a low proportion of cases, bi-pallidal deep brain stimulation. However, treatment outcome is generally disappointing. A few researchers have reported the application of repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex or the premotor cortex, with the goal of decreasing motor cortex hyperexcitability. This article reviews all studies using this technique in dystonia and discusses rTMS therapeutic impact and its possible mechanisms of action in this indication. Currently, the premotor cortex seems to be the best target for rTMS in dystonia. Rather than merely reducing the hyperexcitability of the primary motor cortex, this technique's clinical benefit seems to result from modifications in plasticity and restoration of sensorimotor integration. The corollary technique for chronic rTMS is electrical cortical stimulation. Even though this new therapeutic tool may have therapeutic promise, more studies are required to confirm it. In particular, we need to broaden our knowledge of rTMS impact on the various forms of dystonia and to optimize target localization.

[Presentation of Niemann-Pick type C disease with psychiatric disturbance in an adult]. / Troubles psychiatriques révélateurs d'une maladie de Niemann-Pick de type C à l'âge adulte.

INTRODUCTION: Niemann-Pick Type C disease (NPC) is an autosomal recessive neurovisceral lysosomal lipid storage disorder. CASE REPORT: A 31-year-old right-handed woman had suffered from schizophrenia for 13 years. At 25 years of age, she developed a gait disorder with a static and kinetic cerebellar syndrome, dysarthria, vertical supranuclear gaze palsy and cognitive impairment. Brain MRI was normal. Abdominal ultrasonography was performed because of hypercholesterolemia and elevated transaminases and revealed hepatosplenomegaly, which in conjunction with other signs and symptoms, suggested the diagnosis of NPC. The diagnosis was confirmed by demonstration of lysosomal storage of unesterified cholesterol (filipin staining) and of a reduced rate of LDL-induced cholesterol esterification. Implication of the NPC1 gene was assessed by genetic complementation analysis. DISCUSSION: The phenotypic presentation of NPC is remarkably variable. The rarer adult-onset form has a slowly progressive course. Psychotic manifestations are often prominent and may precede neurologic symptoms. Exposure to neuroleptics delays the diagnosis of NPC. CONCLUSION: Psychotic manifestations associated with cerebellar syndrome, vertical supranuclear gaze palsy, and splenomegaly are very suggestive of NPC disease which can be reliably diagnosed on cultured skin fibroblasts by filipin staining.

[The presentation of small-cell lung cancer with metastatic carcinomatous encephalitis in a non-Hodgkin's lymphoma patient]. / Encéphalite carcinomateuse métastatique révélatrice d'un cancer pulmonaire à petites cellules associé à un lymphome non hodgkinien.

BACKGROUND: Carcinomatous encephalitis or milary cerebral metastases characterized by signs of diffuse encephalopathy is a rare form of brain metastases. Tiny tumor nodules are seen throughout the cortical and subcortical gray matter. OBSERVATION: We report the case of a patient with a history of non-Hodgkin lymphoma who developed carcinomatous encephalitis probably secondary to small-cell lung cancer. This case is discussed in light of findings of 16 cases of carcinomatous encephalitis reported in the literature. We discuss clinical, radiological, histological, pathophysiological characteristics and the survival of this form. CONCLUSION: The frequency of carcinomatous encephalitis is underestimated because clinical expression is non specific. Brain magnetic resonance imaging must be performed in all patients presenting encephalopathy without an obvious cause.

[Peripheral and central neurological manifestations in a case of Churg Strauss syndrome]. / Manifestations neurologiques périphériques et centrales révélatrices d'un syndrome de Churg et Strauss.

In Churg and Strauss syndrome, the central nervous system is rarely affected. We describe the case of a 47-year-old woman who developed signs of altered health status, bradypsychie, and motor axonal multiple mononeuropathy. The context of paranasal sinusitis, asthma and chronic abdominal pains in addition to hypereosinophilia and antimyeloperoxydase antineutrophil cytoplasmic antibodies contributed to the diagnosis of Churg and Strauss syndrome. CT scan and magnetic resonance imaging of the brain revealed a left parieto-occipital and a right occipital hematoma and a right subarachnoid hemorrhage. The cerebral vasculitis was explained by the central manifestation as shown with arteriography. The patient was treated with corticosteroids and immunosuppressors.