Cerebrovascular events as presenting manifestations of Myeloproliferative Neoplasm.

AIM: To determine the incidence and main characteristics of cerebrovascular events as the presenting manifestations of myeloproliferative neoplasm (MPN). METHODS: The Hematology in Lyon (HEMILY) registry is a prospective database (763 patients) of all cases of MPN diagnosed since 2005 in the Rhône-Alpes district of France. The MPN cases were divided into four groups: polycythemia vera (PV); essential thrombocythemia (ET); myelofibrosis (MF); and atypical MPN. The ischemic stroke subtype was classified according to TOAST criteria. RESULTS: A stroke history revealed MPN in 35 (4.3%) patients: 22 (63%) had an ischemic stroke; eight (23%) had a transient ischemic attack; four (11%) had cerebral venous thrombosis; and one (3%) had hemorrhagic stroke. All patients had hemoglobin and/or platelet count abnormalities. In addition, 12 (34%) patients had PV, 21 (60%) had ET, one (3%) had MF and one (3%) had atypical/unclassified MPN. The JAK2 V617F mutation was found in 83% of patients. In 18 (51%) patients, an additional mechanism of stroke was present (atherosclerosis in 10 patients, atrial fibrillation in one patient and dissection in another). The median NIHSS score at entry was 2, and the median modified Rankin Scale score at 3 months was 0. Compared with the general MPN population, stroke-MPN patients presented with significantly higher levels of hemoglobin (P<0.001) and were more frequently positive for the JAK2 V617F mutation (P=0.044). CONCLUSION: Stroke revealing MPN is rare. However, careful attention should still be paid to blood counts even in patients with obvious stroke etiologies, as early diagnosis permits prompt treatment and decreases the risk of recurrence, thus limiting morbidity and mortality.

Towards an earlier diagnosis of Alzheimer's disease presenting with visuospatial disorders (posterior cortical atrophy).

Progressive visual complaints related to visuospatial disorders, and less often to visuoperceptual disorders, may be the presenting and isolated manifestation of a focal degeneration in the posterior cortical areas, called posterior cortical atrophy (PCA). PCA is a clinical syndrome corresponding to a focal variant of Alzheimer's disease in 80% of cases. The predominant dysfunction in the occipitoparietal pathways results in predominant visuospatial disorders, manifesting primarily as dorsal simultanagnosia, alone or associated with other symptoms of Balint's syndrome. PCA is rare and affects young patients who are fully aware of their deficits. Diagnosis of PCA is often delayed, due to insidious onset and development of symptoms, and to poor awareness of the condition in the medical community. An earlier diagnosis requires both better knowledge of PCA among ophthalmologists and neurologists and better recognition of visual complaints, leading to simple bedside tasks that can tackle the syndrome.

[Balint syndrome and spatial functions of the parietal lobe]. / Syndrome de Balint et fonctions spatiales du lobe pariétal.

Balint's syndrome corresponds to the combination of optic ataxia, simultanagnosia and gaze apraxia. It generally results from a bilateral dysfunction of the posterior parietal cortex. Since its early descriptions the syndrome has been subject to many interpretations and controversies. In this article we will reconsider the current concept of Balint's syndrome. A first part will develop the clinical aspects, causes, description of symptoms, examination techniques and neuroanatomical correlations. In a second part, we will discuss how this syndrome can be included in the background of visual neurosciences, particularly through a visual attentional aspect. We will discuss the phenomenon of remapping and some recent data that may contribute to explain the pathophysiology of manifestations as optic ataxia, simultanagnosia or gaze apraxia.

[Idiopathic vasospastic angiopathy of the internal carotid arteries: A rarely recognized cause of ischemic stroke in young individuals]. / Angiopathie vasospastique idiopathique de l'artère carotide interne : une cause peu connue d'accident vasculaire du sujet jeune.

INTRODUCTION: Idiopathic vasospastic angiopathy of the internal carotid arteries is a rare and largely unknown cause of ischemic stroke. METHODS: We report the case of a 39-year-old man with migraine treated by beta-blockers, who had been suffering from progressive right visual impairment and headache for one week. He then experienced a seizure and left hemiparesis. Ophthalmological examination revealed right retinal ischemia and partial left homonymous hemianopia. MRI revealed a long stenosis of both carotid arteries and a recent ischemic stroke in the territory of the right middle cerebral artery. The diagnosis of vasospastic angiopathy of the internal carotid arteries was made based on a second MRI and colored duplex sonography which showed a decrease in the stenosis and no intraparietal hematoma confirming the vasospasm mechanism for stenosis. The clinical course was favorable with calcium channel blockers and aspirin. Use of vasoconstrictor treatments was contraindicated. DISCUSSION/CONCLUSION: Idiopathic vasospastic angiopathy of the internal carotid arteries has been rarely documented. Association with migraine has been mentioned but remains unclear in the literature. This etiology for stroke is probably under-diagnosed due to lack of rapid and repeated examinations of the cervical arteries (angio-MR and colored duplex sonography) to confirm the vasospasm mechanism. Recurrences have been reported justifying a specific secondary preventive treatment to induce vasodilatation. Vasoconstrictor treatments should be contraindicated.

Stenting of a cerebral venous thrombosis.

Cerebral venous and sinus thrombosis (CVT) is a rare but potentially alarming condition, which remains a diagnostic and therapeutic challenge. Endovascular procedure may be a therapeutic option when evolution is unfavourable despite medical treatment, but the use of stenting is rarely reported in CVT treatment. We report the case of a man who presented a jugular vein thrombosis responsible for severe intracranial hypertension. Because of clinical worsening despite intravenous heparin and symptomatic treatment, endovascular procedure including the placement of five venous stents, thrombolysis and balloon angioplasty, was performed and led to venous recanalization with successful clinical outcome. The patient is still asymptomatic 3 years later. Our report shows that venous stenting could represent an efficient alternative in the management of decoagulation refractory CVT.

Optic ataxia errors depend on remapped, not viewed, target location.

Optic ataxia is a disorder associated with posterior parietal lobe lesions, in which visually guided reaching errors typically occur for peripheral targets. It has been assumed that these errors are related to a faulty sensorimotor transformation of inputs from the 'ataxic visual field'. However, we show here that the errors observed in the contralesional field in optic ataxia depend on a dynamic gaze-centered internal representation of reach space.

[Refractory neurosarcoidosis and infliximab: a growing experience]. / Neurosarcoïdose réfractaire et infliximab : une expérience grandissante.

Neurosarcoidosis is a rare disease that can involve all the nervous system with variable clinical onset and prognosis. The initial therapeutic approach is mainly based on corticosteroids and immunosuppressive agents. Treatment of refractory forms of neurosarcoidosis is not well established and emerging immunomodulating drugs like infliximab have been recently tested. The clinical report of a new case of neurosarcoidosis responding to infliximab is followed by a review of the new therapeutic agents available for the treatment of refractory neurosarcoidosis.

[Homonymous hemianopia and posterior cortical atrophy]. / Hémianopsie latérale homonyme et atrophie corticale postérieure.

INTRODUCTION: Posterior cortical atrophy (PCA) is a clinically and radiologically defined syndrome, in which predominant symptoms focus on higher visual dysfunction with progressive course and association with cortical atrophy or hypometabolism that predominates in the posterior part of the hemispheres. Homonymous hemianopia (HH) has rarely been described in this syndrome. METHODS: We report on six patients (four females, two males, aged 63 to 80) referred for visual disorder which led to demonstration of HH using perimetry testing. These patients were followed for 1 to 5 years after discovery of HH. Brain imaging with MRI or CT scan was obtained in the six cases and a SPECT scan was performed in four cases. RESULTS: HH was left-sided in four cases and right-sided in two cases. Associated symptoms related to higher visual dysfunction were simultagnosia, alone or as part of a full Balint's syndrome, alexia, constructional apraxia, dressing apraxia, visual form agnosia, prosopagnosia and hemispatial neglect. These symptoms were mild at onset but invariably worsened with disease progression. Dementia eventually developed in all cases. The clinical diagnosis was probable Alzheimer's disease in five cases and corticobasal degeneration in one case. Radiology showed posterior cortex atrophy in all cases as well as reduced cerebral blood flow in the same region, with an asymmetrical pattern compatible with the side of HH. CONCLUSION: Elementary cortical lesions in PCA can develop mainly in the associative visual areas and even in the primary visual area, resulting in HH. HH has rarely been documented in PCA, but its prevalence would probably be higher if systematic search was conducted. Apparently isolated HH of insidious onset should suggest PCA and lead to neuropsychological testing and search for discrete atrophic changes of the posterior cortex on MRI as well as for metabolic alterations with SPECT or PET.

Idiopathic intracranial hypertension: a comparison between French and North-American white patients.

OBJECTIVE: To compare French and American white patients with idiopathic intracranial hypertension (IIH), and to determine prognostic factors associated with visual loss. METHODS: Medical records of all consecutive white patients with definite IIH seen between 2001 and 2006 in three French tertiary care medical centers and one American tertiary medical center were reviewed. Demographics, associated clinical features, and visual function at presentation and follow-up were collected. French white patients were compared to American white patients. RESULTS: One hundred and thirty-four patients (66 French, 68 American) were included. American patients were 8.7 times more likely than French patients to have visual acuity 20/60 or worse or visual field constriction (95% CI: 2.1-36.1, p=0.0001). American patients were treated more aggressively than French patients. French patients were older (31 vs. 28 years, p=0.02) and more likely to have anemia (20 vs. 2%, p<0.001). American patients had a longer duration of symptoms prior to diagnosis (12 vs. 4 weeks, p=0.01) and longer follow-up than French patients (26 vs. 11 months, p=0.001). Multivariable analysis found that nationality was an independent risk factor for visual loss. French and American patients did not differ regarding gender proportion, frequency of obesity, sleep apnea, endocrine diseases, or systemic hypertension. Cerebrospinal fluid (CSF) opening pressures were similar in both groups. CONCLUSION: American patients with IIH had worse visual outcomes than French patients despite more aggressive treatment. These differences are not explained by differences in previously known risk factors.

[Motorocular syndromes due to neurogenic hyperactivity and their treatment]. / Les syndromes oculomoteurs par hyperactivité neurogène et leur traitement.

In this chapter we describe a variety of rare but clinically identifiable ocular motor syndromes, including ocular neuromyotonia, superior oblique myokymia, ocular motor synkinesis, third nerve palsy with cyclic spasms, and paroxysmal manifestations of multiple sclerosis. These syndromes share many characteristics. They result from neurogenic hyperactivity, causing episodic spasms of one or several extraocular muscles. The pathophysiology is not fully understood, but it usually includes both a focal and partial lesion of one of the ocular motor nerves and a central rearrangement of neuronal activity in the ocular motor nuclei. Treatment with membrane-stabilizing agents, such as carbamazepine, is usually effective to reduce the symptoms. The above-mentioned syndromes result from a number of different diseases. A proportion of apparently idiopathic cases may be related to a neurovascular compression syndrome.

[Functional anatomy of the vestibular nerve]. / Anatomie fonctionnelle du nerf vestibulaire.

The vestibular system detects head movements such as angular rotation, translation, and head position relative to gravity. It acts to stabilize the eyes and posture through subcortical reflexes. Its signals are also integrated at the cortical level to participate in the elaboration of a body scheme, used for different functions such as spatial orientation and motor control. The vestibular nerve shows a resting discharge rate that is modulated up or down according to head motion or position. Central functioning depends on the detection of an asymmetry between signals coming from a pair of peripheral sensors, one on either side. In pathological cases, unilateral peripheral dysfunction is interpreted by the central system as an asymmetry resulting from a change in head position leading to nystagmus, postural disturbances, and vertigo. The dysfunction can be either a deficit, such as observed in vestibular neuronitis, or hyperactivity such as observed in neurovascular compression syndrome of the VIIIth nerve. Anatomically, the VIIIth nerve has a long Root Entry Zone (REZ) that extends over 10mm before entering the brainstem. The VIIIth nerve is also physiologically close to numerous vessels at the pontocerebellar angle and internal auditory meatus. Therefore, vestibular syndrome resulting from neurovascular compression syndrome of the VIIIth nerve may exist, but it is very difficult to prove using radiological imagery.

[Clinical and functional assessment of the vestibular nerve]. / Expertise clinique et fonctionnelle du nerf vestibulaire.

Clinical and functional assessment of the vestibular nerve is fundamental in demonstrating vestibular signs and searching for associated otological and neurological signs. This may help orient topographic diagnosis toward central or peripheral syndrome and etiologic diagnosis.

[Vertigo treatment according to their mechanisms]. / Traitement des vertiges selon leurs mécanismes.

Vertigo is an illusion of rotatory or linear movement that demonstrates a functional or lesional disturbance of the vestibular system, from periphery to central connections. According to the ANAES report (1997), benign paroxysmal positional vertical vertigo, vestibular neuronitis and Ménière's disease account for 40-50% of all mixed vertigo etiologies. Central etiologies may account for 20-40% of causes and 10-40% remain more difficult to classify, and are usually classified under the term of "peripheral vestibulopathy." These include vertigo due to neurovascular compression syndrome of the VIIIth nerve. Clinical manifestations, differential diagnosis, and treatment of the main etiologies of vertigo will be developed in this chapter. A specific section will discuss the subject of neurovascular compression syndrome of the VIIIth nerve. Even though some publications should be challenged, it appears that neurovascular compression syndrome of the VIIIth nerve might explain some cases of vertigo or chronic instability, with or without cochlear signs. The diagnosis is difficult and must be established on multiple clinical, electrophysiological and radiological arguments. A therapeutic test with antiepileptic drugs is helpful. The treatment includes these drugs as a first option but may require a neurosurgical approach if medical treatment fails.

Visual outcome after surgery for cavernous sinus meningioma.

BACKGROUND: Extension of cavernous sinus meningiomas can compromise vision by compressing the optic nerves and chiasm. Surgical tumour removal aims to protect vision in the long-term. However, the risks of surgery include transient or permanent damage to the anterior visual pathways. This study aims to 1) analyse the visual status in unilateral cavernous sinus meningioma with extra-cavernous extension, before and after removal of the extra-cavernous portion, without any adjuvant treatment with radiotherapy, 2) identify pre-surgical and early post-surgical prognostic factors for long-term visual outcome and 3) compare these results to previous studies. METHODS: This is a retrospective study of 30 consecutive patients who underwent surgery between 1989 and 2004. Visual acuity, visual fields, and fundi were evaluated before surgery and during the mean follow-up period of 2 years. FINDINGS: Total visual loss occurred in the ipsilateral eye following surgery in 10% of patients. There was improvement in vision in 23%, no significant change in 27% and worsening in 50% of patients. Pre-surgical visual acuity was not predictive of final visual outcome, but initial optic disc pallor was a poor prognostic factor. In pre-operatively normal contralateral eyes, 10% developed a mild visual deficit (visual acuity = 20/32 or better, and visual field defect

An 'automatic pilot' for the hand in human posterior parietal cortex: toward reinterpreting optic ataxia.

We designed a protocol distinguishing between automatic and intentional motor reactions to changes in target location triggered at movement onset. In response to target jumps, but not to a similar change cued by a color switch, normal subjects often could not avoid automatically correcting fast aiming movements. This suggests that an 'automatic pilot' relying on spatial vision drives fast corrective arm movements that can escape intentional control. In a patient with a bilateral posterior parietal cortex (PPC) lesion, motor corrections could only be slow and deliberate. We propose that 'on-line' control is the most specific function of the PPC and that optic ataxia could result from a disruption of automatic hand guidance.

[Near a biological diagnosis of Alzheimer's disease and related disorders]. / Vers un diagnostic biologique de la maladie d'Alzheimer et des syndromes apparentés.

PURPOSE: To review the current concepts in the biological diagnosis of Alzheimer's disease (AD) and related disorders. CURRENT KNOWLEDGE AND KEY POINTS: As new therapeutics specific of AD may be available soon, early diagnosis of AD in the context of mild cognitive impairment (MCI) or dementia appears to be challenging. The high amount of atypical clinical forms of AD leads to develop new tools allowing in vivo diagnosis. New CerebroSpinal Fluid (CSF) biomarkers seem to reflect specific aspects of deep neuropathological changes observed in AD, i.e. amyloid deposits and neurofibrillary tangles. Amyloid beta-peptide 1-42 (Abeta(1-42)) and hyperphosphorylated tubulin associated unit (tau) isoforms appear to be the most sensitive and specific CSF biomarkers, the combination of these biomarkers depicting the best diagnosis value for AD. These molecules are also efficient in the prediction of the conversion from the MCI state to the dementia state of AD. Combined to clinical and neuro-imaging information, CSF biomarkers appear thus to be highly relevant in improving the early etiological diagnosis of dementia. FUTURE PROSPECTS AND PROJECTS: The current research focalises on the development of new molecules coming from Abeta and tau protein families, in the CSF and in the serum, as well as molecules reflecting other pathological metabolism changes, as alpha-synuclein in Lewy Body Disease. The diagnosis value of CSF biological markers is so promising that they have been recently included in the research diagnosis criteria of AD.

Grasping the past. delay can improve visuomotor performance.

"Optic ataxia" is caused by damage to the human posterior parietal cortex (PPC). It disrupts all components of a visually guided prehension movement, not only the transport of the hand toward an object's location, but also the in-flight finger movements pretailored to the metric properties of the object. Like previous cases, our patient (I.G.) was quite unable to open her handgrip appropriately when directly reaching out to pick up objects of different sizes. When first tested, she failed to do this even when she had previewed the target object 5 s earlier. Yet despite this deficit in "real" grasping, we found, counterintuitively, that I.G. showed good grip scaling when "pantomiming" a grasp for an object seen earlier but no longer present. We then found that, after practice, I.G. became able to scale her handgrip when grasping a real target object that she had previewed earlier. By interposing catch trials in which a different object was covertly substituted for the original object during the delay between preview and grasp, we found that I.G. was now using memorized visual information to calibrate her real grasping movements. These results provide new evidence that "off-line" visuomotor guidance can be provided by networks independent of the PPC.

[Oscillopsia: pathophysiological mechanisms and treatment]. / Oscillopsies: approches physiopathologique et thérapeutique.

Oscillopsia is an illusion of an unstable visual world. It is associated with poor visual acuity and is a disabling and stressful symptom reported by numerous patients with neurological disorders. The goal of this paper is to review the physiology of the systems subserving stable vision, the various pathophysiological mechanisms of oscillopsia and the different treatments available. Visual stability is conditioned by two factors. First, images of the seen world projected onto the retina have to be stable, a sine qua non condition for foveal discriminative function. Vestibulo-ocular and optokinetic reflexes act to stabilize the retinal images during head displacements; ocular fixation tends to limit the occurrence of micro ocular movements during gazing; a specific system also acts to maintain the eyes stable during eccentric gaze. Second, although we voluntary move our gaze (body, head and eye displacements), the visual world is normally perceived as stable, a phenomenon known as space constancy. Indeed, complex cognitive processes compensate for the two sensory consequences of gaze displacement, namely an oppositely-directed retinal drift and a change in the relationship between retinal and spatial (or subject-centered) coordinates of the visual scene. In patients, oscillopsia most often results from abnormal eye movements which cause excessive motion of images on the retina, such as nystagmus or saccadic intrusions or from an impaired vestibulo-ocular reflex. Understanding the exact mechanisms of impaired eye stability may lead to the different treatment options that have been documented in recent years. Oscillopsia could also result from an impairment of spatial constancy mechanisms that in normal condition compensate for gaze displacements, but clinical data in this case are scarce. However, we suggest that some visuo-perceptive deficits consecutive to temporo-parietal lesions resemble oscillopsia and could result from a deficit in elaborating spatial constancy.