Clinical description of the broad range of neurological presentations of COVID-19: A retrospective case series.

BACKGROUND: Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19. METHODS: In this monocentric retrospective case series, medical records from patients with acute neurological disorders associated with SARS-CoV-2 infection from medicine departments of an academic center in Paris area were collected between March 15th and May 15th 2020. Diagnosis of SARS-CoV-2 was ascertained through specific RT-PCR in nasopharyngeal swabs or based on circulating serum IgG antibodies. RESULTS: Twenty-six patients diagnosed with SARS-CoV-2 infection presented with neurological disorders: encephalitis (N=8), encephalopathy (N=6), cerebrovascular events (ischemic strokes N=4 and vein thromboses N=2), other central nervous system (CNS) disorders (N=4), and Guillain-Barré syndrome (N=2). The diagnosis of SARS-CoV-2 was delayed on average 1.6 days after the onset of neurological disorder, especially in case of encephalitis 3.9 days, encephalopathy 1.0 day, and cerebrovascular event 2.7 days. CONCLUSIONS: Our study confirms that COVID-19 can yield a broad spectrum of neurological disorders. Because neurological presentations of COVID-19 often occur a few days before the diagnosis of SARS-COV-2 infection, clinicians should take preventive measures such as patient isolation and masks for any new admission to avoid nosocomial infections. Anti-SARS-CoV2 antibody detection in RT-PCR SARS CoV-2 negative suspected cases is useful to confirm a posteriori the diagnosis of atypical COVID-19 presentations.

Blood Flow Mimicking Aneurysmal Wall Enhancement: A Diagnostic Pitfall of Vessel Wall MRI Using the Postcontrast 3D Turbo Spin-Echo MR Imaging Sequence.

Our aim was to compare the detectability of aneurysmal wall enhancement in unruptured intracranial aneurysms between conventional and motion-sensitized driven equilibrium-prepared postcontrast 3D T1-weighted TSE sequences (sampling perfection with applicationoptimized contrasts by using different flip angle evolution, SPACE). Twenty-two patients with 30 unruptured intracranial aneurysms were scanned at 3T. Aneurysmal wall enhancement was more significantly detected using conventional compared with motion-sensitized driven equilibrium-prepared SPACE sequences (10/30 versus 2/30, P < .0001). Contrast-to-noise ratio measurements did not differ between conventional and motion-sensitized driven equilibrium-prepared sequences (P = .51). Flowing blood can mimic aneurysmal wall enhancement using conventional SPACE sequences with potential implications for patient care.

[Intracranial dural arteriovenous fistula with perimedullary venous drainage: Anatomical, clinical and therapeutic considerations about one case, and review of the literature]. / Fistule durale intracrânienne à drainage veineux périmédullaire : considérations anatomiques, cliniques et thérapeutiques à propos d'un cas, et revue de la littérature.

Intracranial dural arteriovenous fistulae with perimedullary venous drainage are unusual type of vascular brain malformations. Patients may present with a rapidly progressive ascending myelopathy associated with autonomic dysfunction, which can cause a misdiagnosis and delay the therapeutic management. These clinical signs must be quickly recognized to avoid a poor outcome. The authors report the case of a 60-year-old woman presenting with a progressive myelopathy due to a dural arteriovenous fistula with perimedullary venous drainage. The diagnosis was suspected on brain-spinal MRI and confirmed by brain arteriography visualizing the arteriovenous shunt in the middle segment of the superior petrous sinus. MRI showed edema in the medulla oblongata. The treatment was performed early by endovascular glue embolization of the arteriovenous shunt and of the origin of the vein. Brain arteriography and clinical follow-up, one month later, showed complete disappearance of the dural fistula and regression of clinical symptoms. MRI control showed the reduction of the brain stem edema. Because of the early pejorative prognosis of these kinds of fistulae, early diagnosis and treatment are needed.

Definition of DLPFC and M1 according to anatomical landmarks for navigated brain stimulation: inter-rater reliability, accuracy, and influence of gender and age.

The optimization of the targeting of a defined cortical region is a challenge in the current practice of transcranial magnetic stimulation (TMS). The dorsolateral prefrontal cortex (DLPFC) and the primary motor cortex (M1) are among the most usual TMS targets, particularly in its "therapeutic" application. This study describes a practical algorithm to determine the anatomical location of the DLPFC and M1 using a three-dimensional (3D) brain reconstruction provided by a TMS-dedicated navigation system from individual magnetic resonance imaging (MRI) data. The coordinates of the right and left DLPFC and M1 were determined in 50 normal brains (100 hemispheres) by five different investigators using a standardized procedure. Inter-rater reliability was good, with 95% limits of agreement ranging between 7 and 16 mm for the different coordinates. As expressed in the Talairach space and compared with anatomical or imaging data from the literature, the coordinates of the DLPFC defined by our algorithm corresponded to the junction between BA9 and BA46, while M1 coordinates corresponded to the posterior border of hand representation. Finally, we found an influence of gender and possibly of age on some coordinates on both rostrocaudal and dorsoventral axes. Our algorithm only requires a short training and can be used to provide a reliable targeting of DLPFC and M1 between various TMS investigators. This method, based on an image-guided navigation system using individual MRI data, should be helpful to a variety of TMS studies, especially to standardize the procedure of stimulation in multicenter "therapeutic" studies.

Analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex in neuropathic pain: influence of theta burst stimulation priming.

BACKGROUND: 'Conventional' protocols of high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to M1 can produce analgesia. Theta burst stimulation (TBS), a novel rTMS paradigm, is thought to produce greater changes in M1 excitability than 'conventional' protocols. After a preliminary experiment showing no analgesic effect of continuous or intermittent TBS trains (cTBS or iTBS) delivered to M1 as single procedures, we used TBS to prime a subsequent session of 'conventional' 10 Hz-rTMS. METHODS: In 14 patients with chronic refractory neuropathic pain, navigated rTMS was targeted over M1 hand region, contralateral to painful side. Analgesic effects were daily assessed on a visual analogue scale for the week after each 10 Hz-rTMS session, preceded or not by TBS priming. In an additional experiment, the effects on cortical excitability parameters provided by single- and paired-pulse TMS paradigms were studied. RESULTS: Pain level was reduced after any type of rTMS procedure compared to baseline, but iTBS priming produced greater analgesia than the other protocols. Regarding motor cortex excitability changes, the analgesic effects were associated with an increase in intracortical inhibition, whatever the type of stimulation, primed or non-primed. CONCLUSIONS: The present results show that the analgesic effects of 'conventional' 10 Hz-rTMS delivered to M1 can be enhanced by TBS priming, at least using iTBS. Interestingly, the application of cTBS and iTBS did not produce opposite modulations, unlike previously reported in other systems. It remains to be determined whether the interest of TBS priming is to generate a simple additive effect or a more specific process of cortical plasticity.

Navigated rTMS for the treatment of tinnitus: a pilot study with assessment by fMRI and AEPs.

OBJECTIVE: Repeated transcranial magnetic stimulation (rTMS) of auditory cortex has been proposed to treat refractory chronic tinnitus, but the involved mechanisms of action remain largely unknown. The purpose of this pilot study was to evaluate the impact of rTMS on auditory cortex activity in a series of tinnitus patients, using for the first time both functional magnetic resonance imaging (fMRI) of the brain and auditory evoked potentials (AEPs). METHOD: In six patients with chronic, lateralized refractory tinnitus, we performed five sessions of neuronavigated rTMS delivered at 1Hz over the secondary auditory cortex (defined on morphological MRI), contralateral to tinnitus side. The effects of rTMS were assessed on clinical scales, fMRI, and AEPs (N1 and P2 components). RESULTS: The clinical impact of rTMS on tinnitus was good for three patients (25-50% improvement of tinnitus severity compared to baseline), moderate for two patients (15% improvement), and null for one patient who had the most severe tinnitus at baseline. The changes induced by rTMS on fMRI data varied with the baseline level of auditory cortex activation before rTMS. This baseline level of activation was itself related to the severity of tinnitus. Thus, cortical stimulation increased auditory cortex activation in patients who had less severe tinnitus and low level of activation before rTMS, whereas it decreased auditory cortex activation in patients who had more severe tinnitus and higher level of activation before rTMS. Regarding AEPs, rTMS decreased N1 amplitude in all patients, except in the patient who had the most severe tinnitus at baseline and showed no improvement after rTMS. Conversely, P2 amplitude decreased after rTMS only in patients with severe tinnitus, at least for auditory stimulation contralateral to tinnitus, but increased in patients with less severe tinnitus. CONCLUSIONS: The changes produced by rTMS in auditory cortex activity, as assessed by fMRI and AEPs, appeared to depend on a process of disease-related homeostatic cortical plasticity, regardless of the therapeutic impact of rTMS on tinnitus.

Clinical relevance of flow cytometric immunophenotyping of the cerebrospinal fluid in patients with diffuse large B-cell lymphoma.

BACKGROUND: Central nervous system (CNS) relapse is an uncommon but dramatic complication of diffuse large B-cell lymphoma (DLBCL). Several studies have demonstrated the superiority of cerebrospinal fluid (CSF) flow cytometry (FCM), as compared with conventional cytology (CC), in detecting occult leptomeningeal disease. The clinical relevance of a positive FCM still has to be clarified. PATIENTS AND METHODS: We analyzed CSF from 114 DLBCL patients at diagnosis (n = 95) or at relapse (n = 19) by FCM and CC. Most patients received meningeal prophylaxis. FCM results did not influence treatment strategies. RESULTS: Fourteen samples were FCM+, versus one CC+ (also FCM+). Within all patients without neurological symptoms (n = 101), four (4%) relapsed in the CNS, with a median time to relapse of 5.2 months. Only one-fourth (25%) was FCM+ before relapse. More than one extranodal disease site and elevated lactate dehydrogenase levels were associated with an increased risk of CNS relapse. CONCLUSIONS: FCM gives far more positive results than CC. However, a positive FCM result did not translate into a significant increase in CNS relapse rate in this histologically uniform population receiving CNS prophylaxis.

Comparison of "standard" and "navigated" procedures of TMS coil positioning over motor, premotor and prefrontal targets in patients with chronic pain and depression.

Since about 15 years, transcranial magnetic stimulation (TMS) is used as a technique to investigate the function of specific cortical regions. Single pulse TMS studies have targeted the dorsolateral premotor cortex (dlPMC) to characterize premotor-motor interactions in movement disorders. Repetitive TMS (rTMS) trials have targeted the dorsolateral prefrontal cortex (dlPFC) to treat depression. In almost all previous studies, these targets have been defined according to a "standard" scalp distance to the site of stimulation evoking motor responses of maximal amplitude in the contralateral hand ("hand motor hotspot" corresponding to the primary motor cortex, M1). The "standard" procedure of coil positioning locates the dlPMC and dlPFC as 2-3 and 5cm, respectively, anterior to the "hand motor hotspot". The aim of our study was to compare the locations of M1, dlPMC and dlPFC targets provided by the "standard" procedure of coil positioning and those provided by using a neuronavigation system integrating individual brain magnetic resonance imaging (MRI). Twenty-two patients were enrolled, all being treated for depressive symptoms in the context of chronic pain syndrome. The centers of the dlPMC and dlPFC regions were accurately targeted by the "standard" procedure in 14 and eight patients (64 and 36% of the series), respectively. In the other patients, the "standard" procedure located the dlPMC target on the M1/dlPMC border and the dlPFC target on the dlPMC/dlPFC border. On average, the MRI-guided location of M1, dlPMC, and dlPFC was, respectively, 6.1mm posterior, 31.7mm anterior and 69.0mm anterior to the "hand motor hotspot". The "standard" procedure failed to accurately locate the dlPMC and dlPFC targets by about 1 and 2cm, respectively. A statistical analysis of the MRI coordinates (x, y, z) of the targets revealed that the M1 target was more posterior, the dlPMC target more superficial and the dlPFC target more anterior, lateral, and deeper, using neuronavigation compared to the "standard" procedure. This study confirms that the "standard" procedure of coil positioning is not accurate to target a desired cortical region. Target location can be improved by the use of a navigation system taking individual brain anatomy into account. The present results incline to be cautious on the pathophysiological interpretations of previous results reported in TMS studies based on "standard" targeting, e.g. regarding premotor-motor interactions. Similarly, the inaccuracy of the "standard" procedure of coil positioning could partly explain the between-study variability of the therapeutic effects produced by rTMS in patients with depression. Our results strongly support a more anterior and lateral placement of the TMS coil for dlPFC stimulation in the treatment of depression.

[Sciatica after return from Mali: case report of schistosomal myelopathy]. / Sciatique au retour du Mali.

INTRODUCTION: In spite of the high prevalence of schistosomiasis in Mali, few cases involving neurological complications have been described. The purpose of this report is to present a case associated medullary complications. CASE REPORT: A 29-year-old man was hospitalized for low back pain and difficulty in walking linked to dysesthesia. Five months earlier the patient had been trreated for schistosomiasis contracted during a trip to Dogon region of Mali. Based on radiological and laboratory findings and previous clinical history, the difinitive diagnosis was schistosomal myelopathy. DISCUSSION/CONCLUSION: Neuroschistosomiasis is a rare but serious complication of the schistosomiasis that can only be made after complete parasite identification and careful differential diagnosis. Treatment with antiparasitic agents in association with corticosteroids is mandatory but must only be initiated in state stage of the parasitic infection, i.e., after maturation of larvae into adults.

Subthalamic nucleus stimulation in Parkinson's disease: postoperative CT-MRI fusion images confirm accuracy of electrode placement using intraoperative multi-unit recording.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is increasingly used to treat advanced Parkinson's disease (PD). The optimal method for targeting the STN before implanting the definitive DBS electrode is still a matter of debates. Beside methods of direct visualization of the nucleus based on stereotactic magnetic resonance imaging (MRI), the most often used technique for targeting STN consists in recording single-cell activity along exploratory tracks of 10-15mm in length, centered on the theoretical or MRI-defined target coordinates. Single-unit recordings with a microelectrode present various drawbacks. They are time-consuming if correctly performed and a single-cell precision is probably superfluous, taking into account the size of the implanted electrode. In this study, we present an original method of recording and quantification of a multi-unit signal recorded intraoperatively with a semi-microelectrode for targeting the STN. Twelve patients with advanced PD have been included and assessed clinically before and one year after bilateral STN-DBS electrode implantation guided by multi-unit electrophysiological recordings. After one year of chronic stimulation, all patients showed a marked clinical improvement. The motor score of the unified Parkinson's disease rating scale decreased by more than 57% and the required levodopa-equivalent daily dose by 59.5% in on-stimulation off-medication condition compared to off-stimulation off-medication condition. The accuracy of STN-DBS lead placement was confirmed on postoperative computed tomography (CT) scans, which were fused to preoperative T2-weighted MRI. The boundaries of the STN were easily determined by an increase in multi-unit signal amplitude, which was observed on average from 0.492mm below the rostral border of the STN down to 0.325mm above its caudal border. Signal amplitude significantly increased at the both rostral and caudal STN margins (P<0.05) and the level of neuronal activity easily distinguished inside from outside the nucleus. This study showed that STN boundaries could be adequately determined on the basis of intraoperative multi-unit recording with a semi-microelectrode. The accuracy of our method used for positioning DBS electrodes into the STN was confirmed both on CT-MRI fusion images and on the rate of therapeutic efficacy.

The value of navigation-guided rTMS for the treatment of depression: an illustrative case.

Repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has been thought to have great potential to treat refractory depression since the first studies published ten years ago. However, one of the potential limitations of rTMS is the poor definition of the localization of the prefrontal cortical target, which is based on a rather simplistic anatomical approach, i.e., 5cm anterior to the primary motor cortical representation of the hand. This "standard procedure" does not take into consideration interindividual variations in brain morphology. We report the case of a 40-year-old woman who underwent two weeks of 10Hz-rTMS for the treatment of a major, drug-resistant depressive episode. The rTMS target was determined with the "standard procedure" for the first week and with a dedicated navigation system as the left Brodmann area 46 for the second week. The clinical assessment of antidepressant effects was performed before and after each week of stimulation. Following the first week of stimulation, the patient improved, in particular regarding speech production. Using the navigation system, the location of the target stimulated during the first week was found to correspond to Broca's area, and not to the prefrontal area as intended. Antidepressant effects were more marked after the second week of navigated rTMS. In the present case, the prefrontal target was situated 8.3cm anterior to hand motor cortex. This illustrates that the "standard procedure" may inaccurately target the prefrontal cortex, although resulting in antidepressant-like effects. The use of navigation systems should limit the variability of the results reported so far in the treatment of depression by rTMS.

[MRI evaluation of cervicothoracic CSF hypotension]. / Exploration de l'hypotension de liquide cérébro-spinal à l'étage rachidien en IRM.

We propose studying signs of cervicothoracic CSF hypotension by MRI. Axial T1-weighted GRE sequence with and without saturation bands positioned above and below the selected image plane, MR venography and MR Angiography with contrast administration are helpful to confirm the venous nature of the epidural thickening and to make the differential diagnosis with infectious or neoplastic epiduritis.

Diffusion-weighted MR imaging characteristics of an acute strokelike form of multiple sclerosis.

The characteristics of multiple sclerosis (MS) lesions on diffusion-weighted sequences and apparent diffusion coefficient (ADC) mapping at the very early phase of symptoms have not been clearly described. We report the case of a young woman who presented with a sudden pseudostroke form of MS resulting in hemiplegia and sudden aphasia. MR imaging showed a lesion of the left internal capsule with reduced ADC, which suggests an ischemic stroke. This case shows that very acute MS lesions may have reduced ADC on MR imaging, reflecting cytotoxic and not vasogenic edema.

[Transient ischaemic attacks due to hypoplasia of the internal carotid artery in a patient with congenital Horner's syndrome]. / Accident ischémique transitoire révélant une hypoplasie segmentaire de l'artère carotide interne associée à un syndrome de Claude Bernard Horner congénital.

INTRODUCTION: Hypoplasia of the internal carotid artery (ICA) is a rare developmental anomaly sometime revealed by transient ischaemic attaks (TIA). Association with a Horner's syndrome is very rare. CASE REPORT: We report the case of a 42-year-old woman who presented with a TIA and a cervical murmur. Horner's syndrome with iris hypopigmentation was present shortly after birth. Magnetic resonance imaging showed no dissection but hypoplasia of the ICA. Blood flow in the ICA was antegrade through several branches constituting a rete mirabile across the carotid canal, and via collateral arteries from ipsilateral external carotid artery. CONCLUSION: Horner's syndrome in the setting of TIA evokes a carotid dissection. A skull base CT scan demonstrating carotid canal hypoplasia can rule out an ICA dissection and allows diagnosis of a congenital arterial anomaly.

Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study.

Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.

[Cavernous sinus dural arteriovenous fistula complicated by edematous cerebral lesions from venous etiology]. / FISTULE ARTERIOVEINEUSE DE LA LOGE CAVERNEUSE COMPLIQUEE DE LESIONS CEREBRALES OEDEMATEUSES D'ORIGINE VEINEUSE.

The authors report the case of a 38-year-old woman with a cavernous DAVF resulting in edematous lesions located in the territory of the ipsilateral basal vein. Transarterial embolization led to subtotal regression of the fistula associated with the regression of cerebral abnormalities. The authors discuss the pathophysiology of the cerebral edematous lesions and the therapeutic consequences according to the venous drainage of the cavernous sinus.