Transverse Myelitis in Systemic Lupus Erythematosus: Clinical Features and Prognostic Factors in a Large Cohort of Latin American Patients.

BACKGROUND: Acute transverse myelitis (ATM) is an infrequent but severe complication of systemic lupus erythematosus (SLE). The purpose of study was to describe clinical features and prognostic factors of patients with SLE-related ATM. METHODS: In this medical records review study, data were collected from 60 patients from 16 centers seen between 1996 and 2017 who met diagnostic criteria for SLE and myelitis as defined by the American College of Rheumatology/Systemic International Collaborating Clinics and the Working Group of the Transverse Myelitis Consortium, respectively. Objective neurological impairment was measured with American Spinal Injury Association Impairment Scale (AIS) and European Database for Multiple Sclerosis Grade Scale (EGS). RESULTS: Among patients included, 95% (n = 57) were female, and the average age was 31.6 ± 9.6 years. Myelitis developed after diagnosis of SLE in 60% (n = 36). Symmetrical paraparesis with hypoesthesia, flaccidity, sphincter dysfunction, AIS = A/B, and EGS ≥ 8 was the most common presentation. Intravenous methylprednisolone was used in 95% (n = 57), and 78.3% (n = 47) received intravenous cyclophosphamide. Sensory/motor recovery at 6 months was observed in 75% (42 of 56), but only in 16.1% (9 of 56) was complete. Hypoglycorrhachia and EGS ≥ 7 in the nadir were associated with an unfavorable neurological outcome at 6 months (p < 0.05). A relapse rate during follow-up was observed in 30.4% (17 of 56). Hypoglycorrhachia and hypocomplementemia seem to be protective factors for relapse. Intravenous cyclophosphamide was associated with time delay to relapse. CONCLUSIONS: Systemic lupus erythematosus-related ATM may occur at any time of SLE course, leading to significant disability despite treatment. Relapses are infrequent and intravenous cyclophosphamide seems to delay it. Hypoglycorrhachia, hypocomplementemia, and EGS at nadir are the most important prognostic factors.

Guidance for clinical neurophysiology examination throughout the COVID-19 pandemic. Latin American chapter of the IFCN task force - COVID-19.

On 31st December 2019, China notified the World Health Organization of an outbreak of atypical pneumonia from patients at a local seafood market in Wuhan, Hubei, China, responsible for a new coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that caused COVID-19 disease, which spread rapidly around the world. WHO declared a state of pandemic (11th March, 2020), which has caused more than 1 million infected and more than 110,000 deaths; it was observed that up to 29% of those infected were health care personnel. The main route of transmission of SARS-CoV2 is through respiratory secretions and direct contact with contaminated surfaces and material. The pandemic induced an international saturation of health care services and a rupture in the supply chain of protective equipment for healthcare personnel, which poses a high occupational risk to all. Based on the different healthcare systems, human resources, infrastructure and medical emergencies that will warrant the conduct of clinical neurophysiology studies and the lack of a guide for the management of the situation, it was decided by an expert task force of the Latin American Chapter of the International Federation of Clinical Neurophysiology to carry out these guidelines for the protection of patient and healthcare professionals conducting clinical neurophysiological studies.

Access and unmet needs to multiple sclerosis care in a cohort of Argentinean patients.

BACKGROUND: Multiple sclerosis (MS) has a low prevalence in Argentina. However, MS has a high burden of disease, which implies frequent neurological visits, magnetic resonance images (MRI) use and chronic MS medication during follow-up, with a high impact on the healthcare system. Therefore, MS care is essential to optimize disease management and improve patients' outcome. We aimed to evaluate the access and barriers to MS care and identified differences in treatment and management of MS patients over a period of 12 months in an Argentinean cohort. METHODS: A cross-sectional study based on a self-administered survey was carried out from August to December 2017 in 13 provinces from Argentina. MS patients (n = 219) were divided into three groups as follows: prepaid health insurance (PHI), social health insurance (SHI) and state-run health insurance (SRHI, Public Health Ministry) and they were assessed in order to detect differences in employment, access and barriers to MS care (neurological visit, MRI use and MS medication). RESULTS: A total of 185 (84.5%) MS patients were employed (full-time: 59%), 34 (15.5%) were currently unemployed and 15 (6.8%) retired by MS. In addition, 132 had SHI, 45 PHI and 40 SRHI. No statistical differences were found in disease severity, frequency of neurological visit, waiting time for neurological visit as well as frequency and waiting time for MRI use. MS patients with SRHI experienced a longer waiting time (first prescription and during follow-up) and inappropriate delivery of MS medication during follow-up compared to MS patients with PHI and SHI. A total of 8/45 (17.7%) in PHI, 17/40 (42.5%) in SRHI and 25/132 (18.9%) in SHI did not receive the MS medication as properly as prescribed for their neurologists. PHI was independently associated with appropriate delivery of MS medication (OR = 0.81, p = 0.01). CONCLUSION: This study showed that MS patients had access barriers to receive MS medication properly, especially those with SRHI (public sector).

Aquaporin-4 Serostatus and Visual Outcomes in Clinically Isolated Acute Optic Neuritis.

BACKGROUND: Aquaporin-4 antibodies (AQP4-Ab) are associated with neuromyelitis optica spectrum disorder (NMOSD) and typically this disorder has a poor visual prognosis as a result of optic neuritis (ON). Our aim was to report the clinical features at onset and final visual outcomes at 6 months of patients with ON who were positive for AQP4-Ab vs. those who were negative for AQP4-Ab. METHODS: Retrospective cohort study. AQP4-Ab were tested by indirect immunofluorescence in 57 patients with a first episode of ON. All patients initially were referred for consideration of multiple sclerosis ON (MSON), NMOSD, or any other inflammatory central nervous system disorder during follow-up (41.31 ± 24.32 months). Our patients were diagnosed as having NMOSD, MSON, chronic relapsing inflammatory ON, and single isolated ON. Risk factors associated with visual outcomes of ON patients were assessed through an ordinal regression model. RESULTS: Positive AQP4-Ab were associated with male sex (P = 0.02), earlier age of onset (P = 0.01), and myelitis relapses (P = 0.04). Seronegative group had fewer recurrences of ON than the seropositive group (35% vs 58%, P = 0.14). Patients that were positive for AQP4-Ab did not have worse visual acuity at baseline and after 6 months. However, poor visual acuity during first attack was associated with a worse visual acuity at 6 months (odds ratio = 2.28, 95% CI [1.58-3.28], P = 0.03). CONCLUSIONS: At 6 months, positive AQP4-Ab vs negative AQP4-Ab patients no evidence of poorer visual acuity. Lower visual acuity at baseline was associated with poor visual recovery at 6 months.

Short-segment transverse myelitis lesions in a cohort of Latin American patients with neuromyelitis optica spectrum disorders.

STUDY DESIGN: Multicenter retrospective study. OBJECTIVES: The aim was to determine the frequency and magnetic resonance imaging (MRI) features of short-segment transverse myelitis (STM) in patients with neuromyelitis optica spectrum disorders (NMOSD) during a myelitis attack. SETTING: Latin American diagnostic centres (Neuroimmunology Unit). A multicenter study from Argentina, Brazil and Venezuela was performed. METHODS: Seventy-six patients with NMOSD were included. We analyzed 346 attacks and reviewed spinal cord MRIs performed within 30 days from spinal attack onset. Sagittal and axial characteristics on cervical and thoracic MRI (1.5 tesla) were observed. Demographics, clinical, serological, and disability data were collected. RESULTS: Among the 76 patients with NMOSD, isolated STM was observed in 8% (n = 6), multisegmental lesions (longitudinally extensive transverse myelitis (LETM) + STM) in 28% (n = 21; 13 had at least one STM), LETM in 42% (n = 32), and normal spinal MRI in 22% (n = 17). However, isolated STM was increased by 10% in patients with NMOSD with spinal lesions (6 out of 59) with mean attacks of 2.5 (±0.83) and last follow-up expanded disability status scale (EDSS) of 3.1 (±2.63). Positive aquaporin 4 antibodies (AQP4-ab) were found in 50%. Upper-cervical lesion was most frequently observed (5 out of 6). Myelitis was preceded by ON in all isolated patients with STM. Only one had a positive gadolinium lesion and none of these had asymptomatic spinal cord lesion. CONCLUSION: Isolated STM does not exclude NMOSD diagnosis. Therefore, APQ4-ab testing could be useful during a myelitis attack with STM.

Frequency of brain MRI abnormalities in neuromyelitis optica spectrum disorder at presentation: A cohort of Latin American patients.

BACKGROUND: Brain magnetic resonance imaging (BMRI) lesions were classically not reported in neuromyelitis optica (NMO). However, BMRI lesions are not uncommon in NMO spectrum disorder (NMOSD) patients. OBJECTIVE: To report BMRI characteristic abnormalities (location and configuration) in NMOSD patients at presentation. METHODS: Medical records and BMRI characteristics of 79 patients with NMOSD (during the first documented attack) in Argentina, Brazil and Venezuela were reviewed retrospectively. RESULTS: BMRI abnormalities were observed in 81.02% of NMOSD patients at presentation. Forty-two patients (53.1%) showed typical-NMOSD abnormalities. We found BMRI abnormalities at presentation in the brainstem/cerebellum (n = 26; 32.9%), optic chiasm (n = 16; 20.2%), area postrema (n = 13; 16.4%), thalamus/hypothalamus (n = 11; 13.9%), corpus callosum (n = 11; 13.9%), periependymal-third ventricle (n = 9; 11.3%), corticospinal tract (n = 7; 8.8%), hemispheric white matter (n = 1; 1.2%) and nonspecific areas (n = 49; 62.03%). Asymptomatic BMRI lesions were more common. The frequency of brain MRI abnormalities did not differ between patients who were positive and negative for aquaporin 4 antibodies at presentation. CONCLUSION: Typical brain MRI abnormalities are frequent in NMOSD at disease onset.

Impact of multiple sclerosis on quality of life: Comparison with systemic lupus erythematosus.

OBJECTIVE: To report the impact of multiple sclerosis (MS) on patients' quality of life (QoL) compared to systemic lupus erythematosus (SLE) using the 36-Item Short Form (SF-36) health questionnaire in Argentina. PATIENTS AND METHODS: Cross-sectional study. All consecutive MS patients, SLE and healthy controls (HC) were included. Demographics, clinical and radiological aspects, EDSS and SF-36 were assessed. RESULTS: A total of 191 subjects were included (MS=74, SLE=30 and HC=87). When we compared, using 2 standard deviations below the normal mean, the SF-36 subscales scores between MS and SLE, we found that MS patients experienced significant deterioration in general health (p<0.0001), vitality (p=0.009), current health (p<0.0001) and previous year health perception (p=0.003). Additional evaluated areas did not show significant differences. MS patients scored significantly lower in all categories compared to HC, except for bodily pain. An inverse correlation between EDSS and SF-36 total (R2=0.59, ß -11.08, p<0.0001) and subscale scores was observed after applying regression analysis. CONCLUSION: MS behaves as a systemic disease from the functional point of view. Patient-reported QoL scales scores provide comprehensive additional prognostic information beyond the EDSS score. Therefore, adding the SF-36 questionnaire in clinical practice might be useful for the assessment and follow-up of MS patients.

Longitudinally extensive transverse myelitis immune-mediated in aquaporin-4 antibody negative patients: Disease heterogeneity.

BACKGROUND: Longitudinally extensive transverse myelitis (LETM) is a frequent manifestation of neuromyelitis optica spectrum disorder (NMOSD). However, it can also occur in other immune-mediated diseases of the central nervous system (CNS). Positive aquoporin-4 antibodies (AQP4-ab) predict higher relapse rate after LETM. OBJECTIVE: To assess clinical and brain/spinal cord magnetic resonance imaging (MRI) features of LETM immune-mediated at onset and to compare AQP4-ab negative (N-LETM) with AQP4-ab positive (P-LETM) patients. METHODS: Thirty LETM patients remitted for consideration of inflammatory CNS diseases were included. Demographics, clinical, serological, disability and neuroimaging features at onset we reviewed retrospectively and divided into two groups according to serological status. AQP4-ab were tested using indirect immunofluorescence. RESULTS: Twenty-one patients were N-LETM. We did not find significant differences between both groups as regards gender, age at onset, dysfunction (motor, sensory, bladder/bowel) or disability. However, recurrences (p=0.04) of myelitis and number of relapses (p=0.03) were associated to P-LETM. N-LETM was associated with normal brain MRI (p=0.04) at onset. AQP4-ab positive were only observed in NMOSD patients. N-LETM (24%) and P-LETM (56%) patients had relapses of optic neuritis (ON) during the follow-up. CONCLUSION: LETM at onset is a heterogeneous syndrome with similar clinical and neuroimaging features between both groups. N-LETM displayed a lower relapse rate of myelitis and ON.

Etiologic spectrum and functional outcome of the acute inflammatory myelitis.

Clinical, neuroimaging, and laboratory features are not specific enough to establish the etiological diagnosis of the acute inflammatory myelitis (AIM). Longitudinally extensive transverse myelitis (LETM) seen on magnetic resonance imaging (MRI) has been associated with a poor functional prognosis. The aim of this study was to assess the functional outcomes of a first AIM event comparing patients with LETM vs. no LETM on MRI and to report the differential diagnosis. Clinical, radiological, biochemical aspects were collected, and Winner-Hughes Functional Disability Scale (WHFDS) was performed after 3 and 6 months. Centromedullary lesions were associated with LETM, lateral lesions with partial lesion (PL), and brain MRI lesions with multiple sclerosis and acute encephalomyelitis disseminated. LETM patients were associated with a worse functional outcome as the need of a wheelchair after 3 and 6 months (OR = 7.61 p = 0.01; OR 4.8 p = 0.04, respectively), a walker or cane (OR = 11.0 p = 0.002, OR = 4.3 p = 0.03, respectively). In addition, we found a correlation between LETM and acute complete transverse myelitis and PL with acute partial transverse myelitis (83.3 and 90.9%, respectively; p < 0.0001). In conclusion, AIM is a heterogeneous syndrome from an etiological point of view and LETM patients had worse functional prognosis compared with PL after 3 and 6 months.

Diagnostic Utility of Systematic Aquaporin-4 Antibodies Determination in the First Event of Immune-Mediated Optic Neuritis.

BACKGROUND: Antibodies against aquaporin-4 (AQP4-ab) have diagnostic and prognostic value. However, little is known to date about their utility in the first event of optic neuritis (ON). OBJECTIVE: To evaluate the utility of systematic AQP4-ab determination in a retrospective cohort of patients with a first onset of ON. PATIENTS AND METHODS: All patients (n = 42) were tested for AQP4-ab in the following context: typical ON (TON) and atypical ON (AON). Clinical, radiological and biochemical data were collected; patients with TON vs. AON and AQP4-ab positive vs. negative were compared. RESULTS: The proportion of AQP4-ab seropositive patients was 40% in the TON group vs. 40.9% in the AON group. Visual acuity (VA) at baseline was poor in AON patients (p = 0.02) and these patients were associated with worse VA outcome (p < 0.001) at 6 months compared with TON patients, with a median follow-up of 3.27 ± 1.79 years. Brain MRI with dissemination in space criteria (p < 0.001), spinal cord partial lesions (p < 0.001) and oligoclonal bands (p = 0.02) were associated with the initial stages of TON. VA severity, number of myelitis attacks and ON relapses did not differ significantly between seropositive and seronegative patients. AQP4-ab were detected only in neuromyelitis optica spectrum disorders patients. CONCLUSION: This study showed a high seropositivity for AQP4-ab in TON patients, suggesting that it could diagnostic utility at the onset of ON.

Myelitis in systemic lupus erythematosus: clinical features, immunological profile and magnetic resonance imaging of five cases.

Myelopathy is one of the neuropsychiatric lupus syndromes. In this article, an original series of related lupus myelitis is reported and analyzed. We employed a retrospective chart review and identified all patients who were admitted to a general hospital in Buenos Aires, Argentina, with SLE and myelitis during the period 2007-2014. Five patients were observed, all women. The mean age was 25.4 years (19-39). In three of five cases, myelitis was one of the initial SLE manifestations. The SLE Disease Activity Index was variable (3/5 with high activity). Time to nadir ranged from 6 to 72 h. All had severe impairment, with motor deficit, sensory level and urinary retention. Magnetic resonance imaging was abnormal in all cases, 3/5 presented a longitudinally extensive myelitis. Serum analysis revealed positive antinuclear antibodies at a high titer in all patients, 4/5 had low complement levels and 3/5 had anti-phospholipids positive. The treatment (methylprednisolone and, in some cases, cyclophosphamide, anticoagulation and/or plasmapheresis) produced partial improvement or no benefits. One patient died due to sepsis. The others showed significant disability at 6 months (European Database for Multiple Sclerosis grading scale=6-8). In view of these results, myelitis associated with lupus shows heterogeneity of the clinical, radiological and serological features. In our experience, the cases were severe and with poor response to treatment. Further studies are required to understand this disease and establish a more efficient treatment.

Temporolimbic activation by intracranial electrical stimulation.

BACKGROUND: To evaluate the results of intracranial electrical stimulation (ICES) as a pre-surgical tool in order to select the side of the operation in bitemporal lobe epilepsy (BTLE) patients who underwent depth electrode (DE) implantation. METHODS: We reviewed the files of 77 medically intractable BTLE patients who underwent ICES with positive results through implanted DEs and then were under surgical treatment. One year or more after surgery, we evaluated the outcome. ICES was performed through: 1) Square-wave bipolar stimulation with symmetrical pulses of 60 Hz for 0.5 ms was delivered by a constant current Nuclear Chicago stimulator; 2) An initial intensity of 0.5 mA, and subsequently progressively stronger currents at 1-2 and occasionally 3 or 4 mA; 3) The duration of a single stimulation was usually 5 seconds; 4) The volume of tissue effectively stimulated did not exceed 5 mm. RESULTS: We obtained habitual auras or seizures (clinical responses, CRs) in 74 patients and after-discharges, ADs in 61 of them, according to Engel's classification for post surgery outcomes. If CRs or ADs were obtained by stimulation of only one temporal lobe the result of epilepsy surgery tended to be better (Engel classes I or II) when the operation was done on the same side of positive CRs (15 cases) or ADs (14 cases), and tended to be worse (Engel classes III or IV) when the ICES had provoked bilateral responses or when the side operated on was contra-lateral to positive CRs (33 cases) or ADs (28 cases). Statistical analyses were performed in order to test these results and we found better post-operative results when the resection took place in the same side of positive responses to ICES (CRs: chi2 4.74 and p=0.0295; ADs: chi2 7.57 and p=0.0059). CONCLUSION: In addition to other methods (PET, MRI and neuropsychology) presurgical ICES can provide useful data in the process of identifying the temporal lobe to be targeted for resection in BTLE patients.

Metabotropic glutamate receptors and epilepsy.

Metabotropic glutamate receptors (mGluRs) play an important role in the initiation of ictal discharges by participating in the interictal-ictal transition, and may play a crucial role in recruiting normal brain tissue into synchronized discharges, thereby facilitating propagation of seizure activity. In this article we present a review of mGluRs and epilepsy studies. Structural features of mGluRs offer multiple possibilities for synthetic compounds to modulate their activity, and for many reasons these compounds are good candidates for therapeutic applications. Group I mGluRs enhance excitatory transmission as much as groups II and III mGluRs can modulate those effects. Finally, main avenues to induce epileptogenesis are considered: activation of Ca2+ channels and Ca2+/CaMKII cascade, overexpression of AMPA and/or KA receptors, enhanced NMDARs function, activation of protooncogenes leading to a steady epileptogenic state, enhancement of INaP currents, blockade of A and/or M K(+) currents, calcium channelopathies, diminished number of GABARs or functions, and down-regulation of glutamate transporters. Deregulation of mGluR signaling functions including deficits in groups II and III mGluRs or hyperactivation of group I mGluRs may occur in some forms of epilepsy, therefore targeting these mechanisms with specific pharmacological tools could provide new developments for original therapeutic approaches.

Síncope de origen neurocardiogénico / Syncope of neurocardiogenic origin

El objetivo de este trabajo fue evaluar la utilidad del Tilt Test (TT)para reconocer el origen neurocardiogénico del síncope en pacientes que habían sufrido uno o más de dichos episodios en el año previo y en quienes no se detectó enfermedad orgánica luego de haber sido sometidos a los correspondientes estudios cardiológicos, neurológicos y de laboratorio. Se incluyeron 147 pacientes en los que se realizó TT basal y en alguno de ellos TT bajo estimulación adrenérgica con Isopro-terenol. Luego de 40 minutos con una inclinación de 80º, los hallazgos fueron los siguientes: en 53 pacientes (36,1 por ciento) el TT fue positivo y en 94 (63,9 por ciento) fue negativo sin la ocurrencia de síncope o presíncope. En los pacientes con TT positivo, las respuestas fueron cardioinhibitorias y vasodepresora en 44 (83,1 por ciento) en estado basal y en 9 (16,9 por ciento) con infusión de Isoproterenol. No hubo pacientes con TT positivo y respuesta cardioinhibitoria aislada. Sólo un paciente, presentó respuesta mixta a predominio cardioinhibidor. El síncope se presentó en todos los casos, entre los 2´y 32´ del comienzo del estudio, siendo más precoz en los niños. En todos los pacientes en los que se presentó síncope durante el TT el cuadro revirtió volviendo la camilla a la posición inicial. Entre los pacientes que tuvieron TT negativo, en 5 el examen psiquiátrico y la respuesta efectiva al tratamiento reveló que la causa era síncope de origen psiquiátrico. La sensibilidad y espcificidad del método son difíciles de calcular. Un TT positivo no asegura que el síncope sea de origen neurocardiogénico, aunque esta prueba nos aproxima al diagnóstico

Síncope de origen neurocardiogénico / Syncope of neurocardiogenic origin

El objetivo de este trabajo fue evaluar la utilidad del Tilt Test (TT)para reconocer el origen neurocardiogénico del síncope en pacientes que habían sufrido uno o más de dichos episodios en el año previo y en quienes no se detectó enfermedad orgánica luego de haber sido sometidos a los correspondientes estudios cardiológicos, neurológicos y de laboratorio. Se incluyeron 147 pacientes en los que se realizó TT basal y en alguno de ellos TT bajo estimulación adrenérgica con Isopro-terenol. Luego de 40 minutos con una inclinación de 80º, los hallazgos fueron los siguientes: en 53 pacientes (36,1 por ciento) el TT fue positivo y en 94 (63,9 por ciento) fue negativo sin la ocurrencia de síncope o presíncope. En los pacientes con TT positivo, las respuestas fueron cardioinhibitorias y vaso