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.

Detection of mild papilloedema using spectral domain optical coherence tomography.

OBJECTIVE: To propose a method of diagnosis of mild papilloedema (PO) using peripapillary total retinal (PTR) thickness measurement by spectral domain optical coherence tomography (OCT). METHODS: 24 eyes in 24 patients with PO caused by increased intracranial pressure and 22 eyes in 22 normal subjects were studied. OCT high-quality fundus images were analysed and graded by three masked observers using the Modified Frisén Scale. Eyes with PO were divided into two subgroups: those with mild PO (n=18) and those with moderate-severe PO (n=6). Two methods of measurements were evaluated and compared: retinal nerve fibre layer (RNFL) thickness measurements using standard optic disc cube 200 × 200 acquisition protocol and PTR thickness measurements using the 'macular' cube 512 × 128 acquisition protocol centred on the optic disc. Thickness values were calculated globally and for each quadrant (temporal, superior, nasal, inferior) and compared among the three groups (control, mild PO, moderate-severe PO). The main outcome measures were RNFL and PTR thickness. RESULTS: Average RNFL and PTR thickness in the moderate-severe PO, mild PO and control groups were 299.3 ± 10.9, 112.4 ± 6.3, 96 ± 5.7 and 804.5 ± 17, 463.1 ± 9.8 and 332.4 ± 8.9 µm, respectively. Moderate-severe PO differed from mild PO and control groups using both RNLF thicknesses and PTR thicknesses measurements. Mild PO did not differ from controls using RNLF thickness measurement (p=0.17), but was statistically different using PTR thickness measurement (p<0.001). CONCLUSION: PTR thickness measurement increases the sensitivity of detection of mild PO compared with conventional RNFL measurement. This new way of using OCT may be useful for clinicians to detect mild PO.

[Saccadic system plasticity mechanisms in Parkinson disease patients]. / Mécanismes de plasticité saccadique chez les patients atteints de maladie de Parkinson.

INTRODUCTION: Voluntary or reactive saccades predominate in rapid eye movements. Their goal is to preserve an active and optimal visual perception of the environment. Saccades cannot be guided once launched. Oculomotor plasticity, or saccadic adaptation, is still partially unknown, in particular the role played by the basal ganglia. New neuro-ophthalmological rehabilitation techniques require understanding the neurophysiological basis and demonstrating the neuronal structures involved in this plasticity. OBJECTIVES: This study assessed the reactive saccade adaptation in patients with idiopathic Parkinson disease, as a model of basal ganglia dysfunction. We predicted that saccadic adaptation would be preserved in this pathology. PATIENTS AND METHODS: Five patients with mild idiopathic hemi-Parkinson disease were included, as well as four age-matched controls. Reactive saccade adaptation was studied using the double-step target paradigm, in patients with OFF-Dopa treatment and in controls. RESULTS: Group analysis demonstrated that patients had a lower level of adaptation than the controls (p<0.05). Individually, two patients did not adapt for bilateral saccades and one for ipsilateral (compared to Parkinson motor clinical syndrome) saccades. Two additional patients adapted on both sides but with a deficit in contralateral saccades when compared to the control group. DISCUSSION: These preliminary results suggest basal ganglia involvement in reactive saccadic adaptation, which remains to be clarified.

Persistent ocular motor manifestations and related visual consequences in multiple sclerosis.

Abnormal eye movements in multiple sclerosis (MS) are often persistent and known to be associated with general disability. However, there is no precise knowledge concerning their incidence and resulting visual handicap. The aim of our study was to describe the persistent ocular motor manifestations in MS and relate them to visual functions tested with visual acuity and with a vision-related questionnaire. We selected 24 MS patients complaining of persistent visual disability associated with ocular motor manifestations without any anterior visual pathway deficit. Internuclear ophthalmoplegia was the most frequently observed symptom, followed by gaze-evoked nystagmus, saccadic hypermetria, and then pendular nystagmus. Pendular nystagmus, saccadic hypermetria, and the association of internuclear ophthalmoplegia and gaze-evoked nystagmus were associated with decreased visual acuity and visual functional scores. There was a correlation between the number of abnormal eye movements and visual functions. This study demonstrates that ocular motor dysfunction in MS induces specific visual dysfunction and handicap.

Acquired pendular nystagmus in multiple sclerosis and oculopalatal tremor.

OBJECTIVE: Acquired pendular nystagmus occurs mainly in multiple sclerosis (MS) and focal brainstem lesions. In the later case, it is part of the syndrome of oculopalatal tremor. Even though pathophysiology of acquired pendular nystagmus has been clearly characterized experimentally in both etiologies, there is a persisting ambiguity in clinical literature, which leads one to consider both clinical conditions as a common entity. The objective of our work was to compare in a prospective study clinical features, eye movement recording, and functional consequences of acquired pendular nystagmus in 14 patients with oculopalatal tremor and 20 patients with MS. METHODS: Besides complete neurologic evaluation, evaluation of visual function, 3-dimensional eye movement recording, and functional scores of the Visual Function Questionnaire were recorded. RESULTS: One patient with oculopalatal tremor and 15 patients with MS disclosed signs of optic neuropathy. The nystagmus in the oculopalatal group showed significant larger mean amplitude (8 deg vs 1 deg), higher mean peak velocity (16 deg/s vs 6 deg/s), lower mean frequency (1-3 Hz vs 4-6 Hz), and larger asymmetry and irregularity of ocular oscillations compared to the MS group. The vision-specific health-related quality of life was more deteriorated in the oculopalatal tremor group than in the MS group. CONCLUSIONS: This study emphasizes the need to consider acquired pendular nystagmus in MS and oculopalatal tremor as 2 different clinical entities. This is of particular importance regarding the future evaluation of potential specific effects of pharmacologic agents.

CSF biomarkers in posterior cortical atrophy.

OBJECTIVE: To describe CSF biomarker profiles in posterior cortical atrophy (PCA), which induces high-order visual deficits often associated with Alzheimer disease (AD) pathology, and relate these findings to clinical and neuropsychological assessment. METHODS: This prospective observational study included 22 patients with PCA who underwent CSF biomarker analysis of total tau (t-tau), phosphorylated tau on amino acid 181 (p-tau181), and amyloid ß (Aß(42)). At group level, the CSF profiles of patients with PCA were compared to those of patients with typical AD and patients with other dementia (OD). Individually, the clinical presentation of patients with PCA was correlated to their CSF profile to assess the predictability of clinical features for diagnosis of underlying AD pathology. RESULTS: At group level, the PCA biomarker profile was not different from that of the AD group, but very different from that of the OD group (p < 0.001). More than 90% of patients with PCA had CSF profiles consistent with AD. All patients with PCA with either isolated higher-order visual deficit (n = 8) or visual deficit associated with memory impairment (n = 11) had CSF profiles consistent with AD. Only one of the 3 patients with PCA with asymmetric motor signs fulfilled biological CSF criteria for AD. CONCLUSIONS: PCA syndrome is usually associated with CSF biomarkers suggestive of AD, as shown by previous neuropathologic studies. This does not apply in case of motor signs suggesting associated corticobasal syndrome. CSF biomarkers help to discriminate AD from non-AD processes associated with this condition.

[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.

[Central retinal vein and artery occlusions related to intraocular involvement of an anaplastic optochiasmatic glioma]. / Occlusion vasculaire mixte de la veine et de l'artère centrale de la rétine liée à l'envahissement intraoculaire d'un gliome anaplasique optochiasmatique.

Malignant optic tract gliomas are very aggressive and extremely rare tumors progressing to blindness and death in a few months. We report here the case of a 73-year-old patient who presented a sudden decrease in visual acuity in his left eye associated with papilledema and headache: it revealed an optochiasmatic anaplastic glioma. A few months later, the glioma had grown, with infiltration of the right optic nerve and right peripapillary intraocular invasion. Through this case, we discuss the importance of achieving imaging for atypical optic neuropathies and stress the exceptional nature of intraocular invasion by a glioma.

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.

[Transient binocular visual loss: a diagnostic approach]. / Troubles visuels binoculaires transitoires: une approche diagnostique.

It is rarer for a patient to present with transient binocular visual loss than transient monocular visual loss. This symptom usually results from a cerebral dysfunction. When transient binocular visual loss results from papilledema, ophthalmological examination is critical for an accurate diagnosis. In other cases, examination may be normal and a thorough history is of paramount importance for making a diagnosis and deciding whether or not imaging is necessary. The three main cerebral causes for transient binocular visual loss are migraine with visual aura, partial seizures occurring in the occipital lobe, and vertebrobasilar ischemia.

[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.