Rheumatoid meningitis in a patient with overlap syndrome: The usefulness of anti-citrullinated peptide antibodies determination in CSF.

Rheumatoid meningitis (RM) is a rare complication of rheumatoid arthritis that can manifest as stroke-like episodes. We present the case of a 63-year-old woman with a past history of overlap syndrome and clinical manifestations suggestive of amyopathic dermatomyositis, rheumatoid arthritis, and systemic lupus erythematosus. She presented to the emergency department with sudden onset right-sided clumsiness and numbness, as well as a 2-week history of left hemicranial headache. Laboratory workup revealed positive serum antinuclear antibodies, anti-Ro antibodies, anti-citrullinated peptide antibodies (ACPA), and elevated rheumatoid factor. Lymphocytic pleocytosis, positive ACPA and anti-Ro antibodies with passive diffusion pattern, and negative microbiological studies were demonstrated in the CSF. Brain magnetic resonance imaging showed predominant left fronto-parieto-occipital leptomeningeal and pachimeningeal enhancement. She was diagnosed with RM and received methylprednisolone IV mg/kg once daily. Stroke-like episodes in the setting of a patient with lymphocytic pleocytosis in the cerebrospinal fluid (CSF) and meningeal enhancement should raise suspicion of RM. In this context, serum rheumatoid factor and ACPA levels should always be measured and ACPA should also be measured in CSF. To our knowledge, this is the first reported case of RM in the context of an overlap syndrome. ACPA levels in CSF could be a relevant diagnostic clue in the setting of central nervous system disturbance and overlapping autoimmune conditions that include rheumatoid arthritis. In our case, the presence of a suggestive clinical scenario of RM reinforces the probable pathogenic role of ACPA when it is present in the central nervous system, even without intrathecal synthesis evidence.

Non-severe immunosuppression might be associated with a lower risk of moderate-severe acute respiratory distress syndrome in COVID-19: A pilot study.

The role of immunosuppression among coronavirus disease 2019 (COVID-19) patients has not been elucidated and management may be challenging. This observational study included confirmed COVID-19 patients. The primary endpoint was the development of moderate-severe acute respiratory distress syndrome (ARDS). Time to moderate-severe ARDS, the need for mechanical or noninvasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints. Of 138 patients included, 27 (19.6%) were immunosuppressed (IS) and 95 (68.8%) were male, with a median (IQR) age of 68 (54-78) years. A significantly lower proportion of IS patients (25.9%) compared to non-IS patients (52.3%) developed moderate-severe ARDS, in both unadjusted (0.32; 95% CI, 0.13-0.83; p = .017) and adjusted (aOR, 0.25; 95% CI, 0.08-0.80; p = .019) analyses. After stratifying by pathologies, only IS patients with autoimmune diseases remained significant (aOR 0.25; 95% CI, 0.07-0.98; p = .046). Nonsignificant trends toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected among IS. In our cohort of COVID-19 patients, nonsevere immunosuppression was associated with a lower risk of moderate-severe ARDS, especially among AD. This suggests a potential protective effect from a hypothesized hyper-inflammatory response.

Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.

OBJECTIVE: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). METHODS: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. RESULTS: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). SIGNIFICANCE: PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.

Mnemonic discrimination in patients with unilateral mesial temporal lobe epilepsy relates to similarity and number of events stored in memory.

Mesial temporal lobe epilepsy (mTLE) is a neurological disorder associated with histopathological changes in different subfields of the hippocampus. These alterations have been associated with memory difficulties. In this study, we tested the hypothesis that these difficulties stem on mnemonic discrimination impairment due to a reduced ability to make similar representations more distinct, leading to an increased susceptibility to interference. With this aim, we used a visual mnemonic discrimination task and evaluated the ability of a group of patients with unilateral mTLE, relative to controls, to discriminate between a studied item and a new foil item, as a function of the similarity between them, and of the number of exemplars from a category stored in memory. We found that patients performed worse than controls when the studied item had to be discriminated from a physically similar new object from the same basic-level category. Crucially, reliable differences between groups were observable in the conditions in which more exemplars from a category were held in memory. In the conditions in which the studied item had to be discriminated from a foil from a different basic-level category, there were no differences between groups, with one exception. Neither a general cognitive impairment nor a general memory impairment could account for this pattern of results. Current findings indicate that patients found more difficulties in conditions with higher interference, which poses greater demands for pattern separation. A disruption of pattern separation processes resulting from hippocampal damage provides a reasonable interpretation for these results. Future studies should explore the causal relationship between hippocampal subfields integrity and mnemonic discrimination capacity in mTLE patients.

A novel ATTR L32V mutation causes familial amyloid polyneuropathy in a Bolivian family.

We report a new transthyretin (ATTR) gene c.272C>G mutation and variant protein, p.Leu32Val, in a kindred of Bolivian origin with a rapid progressive peripheral neuropathy and cardiomyopathy. Three individuals from a kindred with peripheral nerve and cardiac amyloidosis were examined. Analysis of the TTR gene was performed by Sanger direct sequencing. Neuropathologic examination was obtained on the index patient with mass spectrometry study of the ATTR deposition. Direct DNA sequence analysis of exons 2, 3, and 4 of the TTR gene demonstrated a c.272 C>G mutation in exon 2 (p.L32V). Sural nerve biopsy revealed massive amyloid deposition in the perineurium, endoneurium and vasa nervorum. Mass spectrometric analyses of ATTR immunoprecipitated from nerve biopsy showed the presence of both wild-type and variant proteins. The observed mass results for the wild-type and variant proteins were consistent with the predicted values calculated from the genetic analysis data. The ATTR L32V is associated with a severe course. This has implications for treatment of affected individuals and counseling of family members.

Substantia Nigra Echogenicity Predicts Response to Drug Withdrawal in Suspected Drug-Induced Parkinsonism.

INTRODUCTION: Response to drug withdrawal in patients with suspected drug-induced parkinsonism (DIP) is of prognostic and therapeutic importance, but cannot be predicted solely on clinical information. The aim of this study was to validate SN hyperechogenicity (SN+) assessed by transcranial sonography as a predictor of response to drug withdrawal in this group of patients. METHODS: Patients were diagnosed according to previously published criteria and prospectively included in the study. All patients were followed until complete recovery of parkinsonian symptoms or at least for 6 months after discontinuation of the offending drug and then diagnosed as DIP or parkinsonism following neuroleptic exposure (PFNE). Transcranial sonography (TCS) findings were compared with the clinical diagnosis. RESULTS: Sixty patients comprised the group for the final analysis. Sixteen patients were classified as PFNE and 44 as DIP. The area of SN echogenicity was significantly increased in the PFNE group (0.23 cm2; standard deviation [SD]: 0.04), compared to the DIP group (0.14 cm2; SD, 0.05; one-way analysis of variance; P < 0.001). Normal SN was significantly associated with complete recovery after withdrawal of the parkinsonism-inducing drug (P < 0.0005). Accuracy of SN+ to distinguish PFNE from DIP was: sensitivity 81.2%; specificity 84.1%; positive predictive value 47.4%; and negative predictive value 96.2%. CONCLUSIONS: We believe that SN+ assessed with TCS is a valid prognostic marker in the setting of suspected DIP. It is a nonexpensive, feasible technique that can be implemented for proper counseling and guidance of treatment decisions.

Sonography for diagnosis of Parkinson disease-from theory to practice: a study on 300 participants.

OBJECTIVES: Hyperechogenicity of the substantia nigra on transcranial sonography is used for diagnosing Parkinson disease (PD). Cutoff values for the substantia nigra echogenic area, defining substantia nigra hyperechogenicity, vary among ultrasound systems from different manufacturers. In this study we wanted to determine the cutoff criterion for a Toshiba (Tokyo, Japan) system and to assess its diagnostic value. METHODS: Three hundred participants (controls, n = 138; patients with PD, n = 105; and patients with essential tremor, n = 57) underwent transcranial sonography following a standardized protocol. RESULTS: The substantia nigra was assessable in 92.7% of all participants. The substantia nigra echogenic area (larger of bilateral measurements) was larger in patients with PD (mean ± SD, 0.24 ± 0.05 cm(2)) than controls (0.14 ± 0.05 cm(2); P < .001) and patients with essential tremor (0.14 ± 0.04 cm(2); P < .001). Substantia nigra echogenicity was larger in male participants (0.20 ± 0.07 cm(2)) than female participants (0.15 ± 0.06 cm(2); P< .001). Age did not correlate with substantia nigra echogenicity in any group. Frontal horn width was larger and lenticular nucleus hyperechogenicity and a discontinuous raphe were more frequent in the PD group than the other groups. On multivariate analysis, only substantia nigra hyperechogenicity was associated with the diagnosis of PD. The 90th-percentile substantia nigra echogenic area in the control group, which defined marked substantia nigra hyperechogenicity, also represented the optimum cutoff value for discrimination of PD from non-PD participants on receiver operating characteristic curve analysis (area under the curve, 0.913; Youden index, 0.73). This cutoff value (≥0.21 cm(2), larger of bilateral measurements) yielded sensitivity of 83% and specificity of 90% for the diagnosis of PD. CONCLUSIONS: Transcranial sonography shows good diagnostic validity for diagnosis of PD when implemented according to a strictly standardized protocol.

Fibrilación auricular desencadenada por crisis epilépticas tónico-clónicas generalizadas / Atrial fibrillation triggered by generalized tonic-clonic epileptic seizures

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Opsoclonus-myoclonus syndrome and limbic encephalitis associated with GABAB receptor antibodies in CSF.

We report a case of a woman who had two consecutive autoimmune neurological disorders, including an opsoclonus-myoclonus syndrome (OMS) and limbic encephalitis (LE), with positive titers of GABAB receptor antibodies. The patient never developed seizures or had an underlying tumor after 4 years of follow-up.

Stroke mimics treated with thrombolysis: further evidence on safety and distinctive clinical features.

BACKGROUND: Patients who present with symptoms mimicking ischaemic stroke (IS), but have a different diagnosis, are known as stroke mimics (SM). The necessity for rapid administration of intravenous thrombolysis in patients with acute IS may lead to treatment of patients with conditions mimicking stroke. A variable proportion of patients with SM (1.4-14%) are currently treated with intravenous tissue plasminogen activator therapy (IV-tPA). The outcome of these patients is generally favourable and complications are rather infrequent. We aimed to determine the frequency, clinical features and prognosis of SM patients treated with IV-tPA in an experienced stroke centre. METHODS: A prospective registry was assembled with patients treated with IV-tPA at our stroke unit from January 2004 to December 2011. We recorded age, gender, baseline National Institutes of Health Stroke Scale (NIHSS) score, treatment delay, vascular risk factors, clinical syndrome and aetiology. We retrospectively analysed the clinical characteristics of SM, safety (symptomatic intracranial haemorrhage and mortality) and outcome measures (modified Rankin Scale at 3 months, mRS) and compared them with IS patients. RESULTS: 621 patients were treated with IV-tPA during the study period, 606 (97.5%) were IS and 15 (2.4%) were SM. The aetiology of SM was somatoform disorders (5), headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome (3), herpetic encephalitis (2), glial tumours (2), and migraine with aura, focal seizure and cortical vein thrombosis in single cases. SM were younger (72 ± 14 vs. 53.7 ± 16 years, p < 0.05), had a lower baseline deficit [NIHSS 13 (9-18) vs. 8 (5-10), p < 0.05], fewer vascular risk factors, and left hemisphere symptoms were predominant (80 vs. 52.4%, p < 0.05). Global aphasia without hemiparesis (GAWH) was the presenting symptom in 8 (54%) SM and 44 (7%) IS (p < 0.05). Multimodal computed tomography was performed in 3 SM patients and showed perfusion deficits in 2 of them. No intracranial haemorrhage or disability (functional outcome at 3 months, mRS >2) was recorded in any SM patient. CONCLUSIONS: The use of intravenous thrombolysis appears to be safe in our SM patients, and prognosis is universally favourable. Somatoform disorder and HaNDL syndrome were prominent causes, and GAWH the most common presentation. The safety of thrombolysis in SM suggests that delaying or withholding treatment may be inappropriate: the benefit of thrombolysis in case of IS may outweigh the risks of treating an SM. Further studies may assess the future role of multimodal computed tomography in the differential diagnosis between IS and SM.

Neurology at the airport.

OBJECTIVES: Neurological problems are reported to be common in air travellers. The authors aimed to study neurological problems which might be associated with air traffic in a systematic way. METHODS: The authors analysed a prospective registry of all the patients referred from Madrid-Barajas International Airport to the emergency department of their tertiary university hospital (Hospital Universitario Ramón y Cajal), for whom a neurological consultation was required, during a period of 21 months. RESULTS: 77 patients with a history of air travel presented with neurological problems and were included in the analysis. Fifty-nine (76.6%) were male, and the mean age was 45.9 (range 8-89, SD 17.5). Onset of symptoms was after landing in 44 subjects (58.7%), during the flight in 31 (41.3%), and unknown in two (5.1%). Thirty-nine (50.9%) had seizures, 18 (23.4%) had a stroke, and 20 (26%) other diagnosis. Sixty-one per cent of the patients with seizures had no previous history of epilepsy. Seizures on presentation were significantly associated with the use of drugs (p = 0.0008), and most of the cases with known epilepsy admitted non-adherence to treatment. Three 'body packers' were admitted with seizures secondary to intra-abdominal cocaine pack rupture. Of eight ischaemic strokes, five had high-grade carotid stenosis, and one case had economy-class stroke syndrome. Six patients with stroke were eligible and treated with intravenous thrombolysis. CONCLUSION: In our series of neurological problems among air travellers, drug-induced seizures and ischaemic strokes due to large-artery atherosclerosis were the commonest observed diagnoses.

Accuracy of CSF and MRI criteria for dissemination in space in the diagnosis of multiple sclerosis.

Demonstration of lesion dissemination in space (DIS) and time (DIT) is necessary for the diagnosis of multiple sclerosis (MS) in clinically isolated syndromes (CIS). The McDonald criteria accepted two methods to demonstrate DIS. The fulfillment of at least three of four MRI Barkhof criteria (MRI-BC) or, alternatively, the finding of at least two MRI lesions on T2-weighted images (T2 lesions) plus the presence of oligoclonal IgG bands (OCGB) in cerebrospinal fluid (CSF). We aimed to evaluate the accuracy of both methods for DIS demonstration to predict conversion of CIS to MS using a new OCGB test. We studied fifty-eight CIS patients with OCGB detection and brain MRI, and followed them up during 6 years. Twenty-eight patients fulfilled MRI-BC. Twenty-five of them converted to MS during follow-up (sensitivity 73.53%, specificity 87.50%, accuracy 79.31%). Thirty-four patients had at least two T2 lesions plus oligoclonal bands. Thirty-three converted to MS during follow-up (sensitivity 94.29%, specificity 95.65%, accuracy 94.82%). The presence of oligoclonal IgG bands plus two T2 lesions accurately predicts CIS conversion to MS. MRI-BC criteria have a high specificity but less sensitivity and accuracy. These results reinforce the role of CSF study in MS diagnosis.