Rituximab Responsive Relapsing-Remitting IgG4 Anticontactin 1 Chronic Inflammatory Demyelinating Polyradiculoneuropathy Associated With Membranous Nephropathy: A Case Description and Brief Review.

ABSTRACT: Nodal/paranodal IgG4-related chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) rarely involves anticontactin (CNTN1) subtype and exceptionally complicates with nephrotic syndrome. A 65-year-old man developed weakness, facial palsy, and balance impairment; after spontaneous recovery, he severely relapsed 1 month later. Electroneuromyography confirmed CIDP. Proteinorachy (462 mg/dL; N < 45), proteinuria (3.5 g/g creatine), and biopsy-proven membranous nephropathy were identified. Intravenous immunoglobulins, corticosteroids, and plasmaphereses did not allow recovery. Anti-CNTN1 immunoglobulin G4 (IgG4) assay was positive. Rituximab (375 mg/m2/week, 4 weeks) provided obvious improvement. Relapsing-remitting anti-CNTN1-CIDP co-occurring with nephrotic syndrome is exceptional, and its identification is essential because efficient therapies such as rituximab are available for this severe condition.

Impact on quitting smoking of cognitive impairment in stroke patients.

INTRODUCTION: Smoking is a well-established risk factor for strokes, leading to a high incidence of cognitive deficits. Since the impact of cognitive impairment on the effectiveness of interventions for smoking cessation is not yet known, we considered important to assess it. METHODS: We compared, from April 2012 to November 2015, the success rate of quitting smoking in two groups of acutely hospitalised adult smokers. The first group consisted of stroke patients (SP, n = 54) with lesions confirmed by cerebral imaging. The second used as a control group (NSP, n = 38), included patients hospitalised for any reason other than stroke and characterised by normal global cognition. All participants were assessed twice, in acute phase (T0) and 3 months later (T1), using exhaled carbon monoxide (CO) and several questionnaires. RESULTS: At T1, we observed in SP group an inverse correlation between the Montreal Cognitive Assessment (MoCA) and CO (r = -0.33, p = 0.015). Amongst patients who continued smoking, a higher increase in CO between T0 and T1 was observed in SP group (average 20 ± 15, p < 0.001) than NSP (average 9 ± 13, p = 0.002). CONCLUSIONS: The inverse correlation between CO and cognitive parameters at T1 in SP group suggests an increased susceptibility to tobacco dependency in case of residual cognitive impairment. The global cognitive assessment should thus be taken into consideration when providing assistance with quitting smoking, especially in case of stroke patients.

Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy.

Primary membranous nephropathy (MN) is an autoimmune glomerular disease in which autoantibodies are directed against podocyte proteins. In about 80% of cases the main targeted antigen is the phospholipase A2 receptor 1 (PLA2R1). Anti-PLA2R1 antibodies are mainly immunoglobulin G type 4 (IgG4). However, the antigenic target remains to be defined in 20% of cases. MN can be associated with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system where a common antigenic target has yet to be identified. To ascertain a possible novel target antigen, we analyzed kidney biopsies from five patients positive for anti-contactin 1 antibodies and presenting with MN combined with chronic inflammatory demyelinating polyneuropathy. Eluted IgG from biopsy sections against contactin 1 and nerve tissue were screened. Western blot revealed contactin 1 expression in normal kidney glomeruli. Confocal microscopic analysis showed the presence and colocalization of contactin 1 and IgG4 on the glomerular basement membrane of these patients. Glomerular contactin 1 was absent in patients with anti-PLA2R1-associated MN or membranous lupus nephritis or a healthy control. The eluted IgG from contactin 1-positive biopsy sections but not the IgG eluted from patients with PLA2R1 MN bound contactin 1 with the main eluted subclass IgG4. Eluted IgG could bind paranodal tissue (myelinated axon) and colocalized with commercial anti-contactin 1 antibody. Thus, contactin 1 is a novel common antigenic target in MN associated with chronic inflammatory demyelinating polyneuropathy. However, the precise pathophysiology remains to be elucidated.

Assessment of a standardized EEG reactivity protocol after cardiac arrest.

OBJECTIVE: Reactivity assessment during EEG might provide important prognostic information in post-anoxic coma. It is still unclear how best to perform reactivity testing and how it might be affected by hypothermia. Our primary aim was to determine and compare the effectiveness, inter-rater reliability and prognostic value of different types of stimulus for EEG reactivity testing, using a standardized stimulation protocol and standardized definitions. Our secondary aims were to assess the effect of hypothermia on these measures, and to determine the prognostic value of a simplified sequence with the three most efficient stimuli. METHODS: Prospective single-center cohort of post-anoxic comatose patients admitted to the intensive care unit of an academic medical center between January 1, 2016 and December 31, 2018 and receiving continuous EEG monitoring (CEEG). Reactivity was assessed using standardized definitions and standardized sequence of stimuli: auditory (mild noise and loud noise), tactile (shaking), nociceptive (nostril tickling, trapezius muscle squeezing, endotracheal tube suctioning), and visual (passive eye opening). Gwet's AC1 and percent agreement (PA) were used to measure inter-rater agreement (IRA). Ability to predict favorable neurological outcome (defined as a Cerebral Performance Category of 1 to 2: no disability to moderate disability) was measured with sensitivity (Se), specificity (Sp), accuracy, and odds ratio [OR]. These were calculated for each stimulus type and at the level of the entire sequence comprising all the stimuli. RESULTS: One-hundred and fifteen patients were included and 242 EEG epochs were analyzed. Loud noise, shaking and trapezius muscle squeezing most frequently elicited EEG reactivity (42%, 38% and 38%, respectively) but were all inferior to the entire sequence, which elicited reactivity in 58% cases. The IRA for reactivity to individual stimuli varied from moderate to good (AC1:58-69%; PA:56-68%) and was the highest for loud noise (AC1:69%; PA:68%), trapezius muscle squeezing (AC1:67%; PA:65%) and passive eye opening (AC1:68%; PA:64%). Mild (odds ratio [OR]:11.0; Se:70% and Sp:86%) and loud noises (OR:27.0; Se:73% and Sp:75%), and trapezius muscle squeezing (OR:15.3; Se:76% and Sp:83%) during hypothermia had the best predictive value for favorable neurological outcome, although each was inferior to the whole sequence (OR:60.2; Se:91% and Sp:73%). A simplified sequence of loud noise, shaking and trapezius muscle squeezing had the same performance for predicting neurological outcome as the entire sequence. Hypothermia did not significantly affect the effectiveness of stimulation, but IRA was slightly better during hypothermia, for all stimuli. Similarly, the predictive value was higher during hypothermia than during normothermia. CONCLUSIONS: Despite a standardized stimulation protocol and standardized definitions, the IRA of EEG reactivity testing in post-anoxic comatose patients was only good at best (AC1 < 70%), and its predictive value for neurological outcome remained imperfect, in particular with Sp values < 90%. While no single stimulus appeared superior to others, a full sequence using all stimuli or a simplified sequence comprising loud noise, shaking and trapezius muscle squeezing had the best combination of IRA and predictive value. SIGNIFICANCE: This study stresses the necessity to use multiple stimulus types to improve the predictive value of reactivity testing in post-anoxic coma and confirms that it is not affected by hypothermia.

Acute Paraparesis after Epidural Corticosteroid Injection Revealing Spinal Dural Arteriovenous Fistula in a HIV Patient.

Spinal dural arteriovenous fistulas (SDAVFs) are often misdiagnosed as their symptoms are non-specific, leading to treatment delay and a poor outcome. We describe the case of a 53-year-old man with a history of progressive paraparesis that worsened abruptly after an epidural corticosteroid injection. We highlight here the need for high diagnostic suspicion for an SDAVF in patients deteriorating after an epidural injection and an indication of repeated spine imaging in such cases. Finally, this is the first reported case of an SDAVF in a HIV-positive patient and it emphasizes the need for a broad differential diagnosis. LEARNING POINTS: Consider an SDAVF in cases of slowly progressive paraparesis and hypoaesthesia, especially if symptoms worsen after an epidural injection.The need for an in-depth work-up including repeated angiographic explorations in cases where no malformation is found in a straightforward manner.In a patient infected with HIV, even though a broad range of neuromuscular diseases can be suspected, non-related aetiologies should not be forgotten.

Flexion MRI in a case of Hirayama disease.

We report the case of an 18-year old male with a history of asymmetric weakness and amyotrophy of distal upper extremities, suggestive of Hirayama disease. Magnetic resonance imaging (MRI) of the cervical spine was obtained both in flexion and neutral position. Flexion MRI showed forward displacement of the dura and subsequent cord compression, with associated marked enlargement and postcontrast enhancement of posterior epidural plexus. These findings are pathognomonic of the disorder. On neutral MRI abnormalities may be subtle: in our case, they included loss of physiological lordosis, asymmetric atrophy and increased T2 signal intensity of the lower anterior cervical cord. The ability to identify abnormalities on neutral MRI however is even more important in that it allows the radiologist to include a flexion sequence in the MRI examination, if not specifically requested by the referring physician, and in cases in which the suspicion of the disorder has not been raised.

Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera.

INTRODUCTION: IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP. METHODS: 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department. RESULTS: IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies). CONCLUSIONS: Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.

The characteristics of patients with bilateral absent evoked potentials after post-anoxic brain damage: A multicentric cohort study.

OBJECTIVES: Patients with bilateral absence of cortical response (N20ABS) to somatosensory evoked potentials (SSEPs) have poor neurological outcome after cardiac arrest (CA). However, SSEPs are not available in all centers. The aim of this study was to identify predictors of N20ABS. METHODS: Retrospective analysis of institutional databases (2008-2015) in three ICUs including all adult admitted comatose patients undergoing SSEPs between 48 and 72 h after CA. We collected clinical (i.e. absence of pupillary reflexes, PLR, myoclonus and absent or posturing motor response and myoclonus on day 2-3), electroencephalographic (EEG; i.e. unreactive to painful stimuli; presence of a highly malignant patterns, such as burst-suppression or flat tracings) findings during the first 48 h, and the highest NSE levels on the first 3 days after CA. Unfavorable neurological outcome (UO) was assessed at 3 months using the Cerebral Performance Categories of 3-5. RESULTS: We studied 532 patients with SSEPs, including 143 (27%) without N20ABS; UO was observed in 334 (63%) patients. Median time to SSEPs was 72 [48-72] h after CA. No patient with absent PLR and myoclonus during the ICU stay had N20 present; similar results were observed with the combination of absent PLR, myoclonus and any EEG pattern (i.e. unreactive or highly malignant). Similar results were observed in the subgroup of patients where NSE was available (n = 303). In a multivariate logistic regression, non-cardiac etiology of arrest, unreactive EEG to painful stimuli, absence of pupillary reflexes and posturing motor response, were independent predictors of N20ABS. When available, the highest NSE was also an independent predictor of N20ABS. CONCLUSIONS: Clinical and EEG findings predicting patients with N20ABS, confirm that N20ABS reflects a severe and permanent cerebral damage after CA.

Electrophysiological features of chronic inflammatory demyelinating polyradiculoneuropathy associated with IgG4 antibodies targeting neurofascin 155 or contactin 1 glycoproteins.

OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) with antibodies against neurofascin 155 (Nfasc155) or contactin-1 (CNTN1) have distinctive clinical features. Knowledge on their electrophysiological characteristics is still scarce. In this study, we are investigating whether these patients have specific electrophysiological characteristics. METHODS: The electrophysiological data from 13 patients with anti-Nfasc155 IgG4 antibodies, 9 with anti-CNTN1 IgG4 antibodies were compared with those of 40 consecutive CIDP patients without antibodies. RESULTS: All the patients with antibodies against Nfasc155 or CNTN1 fulfilled the EFNS/PNS electrodiagnostic criteria for definite CIDP. There was no electrophysiological difference between patients with anti-CNTN1 and anti-Nfasc155 antibodies. Nerve conduction abnormalities were heterogeneously distributed along nerves trunks and roots. They were more pronounced than in CIDP without antibodies. Motor conduction velocity on median nerve <24 m/s or motor velocity on ulnar nerve <26 m/s or motor distal latency on ulnar nerve >7.4 ms were predictive of positive antibodies against the node of Ranvier with a sensitivity of 59% and a specificity of 93%. CONCLUSIONS: Marked conduction abnormalities may suggest the presence of positive antibodies against the node of Ranvier. SIGNIFICANCE: Anti-Nfasc155 and anti-CNTN1 antibodies target the the paranodal axo-glial domain but are associated with nerve conduction abnormalities mimicking a "demyelinating" neuropathy.

Charcot-Marie-Tooth hereditary neuropathy revealed after administration of docetaxel in advanced breast cancer.

Charcot-Marie-Tooth (CMT) neuropathy is the most common hereditary cause of neuropathy. Diagnosis is usually not made during the childhood but in adolescence or late adulthood. It is reported in the literature that some neurotoxic chemotherapeutical agents can reveal an asymptomatic CMT IA hereditary neuropathy. To our knowledge, we report here the first case of CMT IA revealed in a 55-year-old woman after the administration of docetaxel/trastuzumab/pertuzumab for metastatic breast cancer. This case stresses again the necessity to obtain a complete personal and familial anamnesis and to perform a neurologic examination before the administration of neurotoxic chemotherapeutical agents to prevent the clinical expression of these hereditary neuropathies.

Evolution of clinical, electrophysiological, and radiological aspects of the carpal tunnel syndrome before and after surgery.

The aim of the study was to analyze the evolution of the clinical, electrophysiological, and ultrasound aspects of carpal tunnel syndrome (CTS) before and 4 and 8 weeks after surgery. A Boston Carpal Tunnel Questionnaire, an ultrasound scan, and an electrophysiological exam were performed in 14 patients the day of surgery, 4 and 8 weeks after. The nerve conduction study included: median nerve sensory conduction stimulating digit 3 and 4, median motor conduction from the abductor pollicis brevis, ulnar nerve sensory, and motor conduction. A significant improvement of the symptoms and a significant decrease of the median nerve proximal cross-sectional area on the ultrasound scan were observed 4 weeks after surgery. Distal motor latency (DML) was > 4.2 ms in six patients and decreased along the three visits. DML was ≤ 4.2 ms in the eight others and stayed stable after surgery. We observed a significant increase of the sensory median nerve amplitude response at the wrist stimulating the third digit 8 weeks after surgery. When operated patients are referred for control, we recommend to perform: (1) 4 weeks after surgery, an ultrasonography, and a measure of the DML of the median nerve; (2) 8 weeks after surgery, a measure of the sensory conduction velocity of the median nerve.

The potential role of auditory evoked potentials to assess prognosis in comatose survivors from cardiac arrest.

AIM: Few data are available on the use of brainstem auditory evoked potentials (BAEPs) in combination with other electrophysiological tools to assess prognosis of comatose survivors from cardiac arrest (CA). METHODS: Retrospective analysis of data from all adult patients (>18years of age) admitted to our Dept of Intensive Care after CA over a 6-year period who were comatose (Glasgow Coma Scale <9) on admission, had been treated with targeted temperature management and had BAEP testing. We collected variables related to CA, as well as electroencephalography (EEG) findings, N20 somatosensory evoked potentials, and the presence of I, III and/or V waves on BAEP testing. Outcome was assessed at 3 months using the Cerebral Performance Categories (3-5=poor outcome). RESULTS: We studied 65 patients; 48 (74%) had a poor neurological outcome. BAEP assessment was performed day 3 [3,4] after the CA. At least one of the three waves was absent bilaterally in 34 patients (52%); of these patients, 29 (85%) had a poor neurological outcome (sensitivity 60%, specificity 71%, positive predictive value [PPV] 85% and negative predictive value [NPV] 39%). Three patients (5%) had bilateral absence of all three waves, all of whom had a poor neurological outcome. CONCLUSIONS: In this series of patients after CA, at least one of the BAEP waves was absent bilaterally in half the survivors; however, their use for prediction of poor neurological outcome remains limited.

Occipital transcranial magnetic stimulation discriminates transient neurological symptoms of vascular origin from migraine aura without headache.

OBJECTIVES: The diagnosis of transient neurological attacks (TNA) relies on medical history. Transient ischemic attack is often considered until proven otherwise, because of lack of objective paraclinical tools that can help discriminate TIA from differential diagnoses such as migraine aura. This may lead to needless and potentially harmful stroke secondary prevention in many cases. This study aimed at determining the yield of occipital transcranial magnetic stimulation (oTMS) in discriminating TNA of vascular origin from migraine aura without headache (MAWH). METHODS: Ten patients with acute TNA of vascular origin and ten patients with migraine aura without headache (MAWH), without prior history of migrainous headache, were prospectively included. TNA of vascular origin were considered for individuals presenting unilateral focal symptoms with full resolution within 24hours and positive diffusion weighted imaging (DWI+). For individuals with MAWH, diagnostic criteria were either ICHD-III beta or Fischer criteria for a first episode of MAWH. All participants underwent one session of oTMS. Induction and threshold of phosphene induction were recorded. RESULTS: In TNA of vascular origin, MRI disclosed cortical lesions in nine and one sub-cortical lesion. Phosphenes were induced in 9/10 subjects with MAWH with a mean threshold of 66% of the maximal intensity, whereas oTMS induced phosphenes in only one subject with TNA of vascular origin at a threshold of 85%. CONCLUSIONS: In this pilot study, oTMS was found to be an effective tool to discriminate between MAWH and transient neurological symptoms of vascular origin.

HLA genotype as a marker of multiple sclerosis prognosis: A pilot study.

OBJECTIVE: The identification of a biomarker with prognostic value is an unmet need in multiple sclerosis (MS). The objective of this study was to investigate a possible association of HLA genotype with disease status and progression in MS, based on comprehensive and sensitive clinical and magnetic resonance imaging (MRI) parameters to measure disease effects. METHOD: A total of 118 MS patients (79 females, 39 males) underwent HLA typing. Patient MS status was assessed at two time points in a 2-year interval, based on clinical scores (including EDSS, MSSS, T25FW, 9-HPT, SDMT, BVMT, CVLT-II) and MRI evaluations. Quantitative brain MRI values were obtained for whole brain atrophy, FLAIR lesion volume change and number of new lesions using MSmetrix. Predefined HLA patient groups were compared as of disease status and progression. Global assessment was achieved by an overall t-statistic and assessment per measurement by a Welch test and/or Mann Whitney U test. The effects of multiple covariates, including age, gender and disease duration as well as scan parameters, were also evaluated using a regression analysis. RESULTS: The HLA-A*02 allele was associated with better outcomes in terms of MSSS, EDSS and new lesion count (Welch test p-value<0.05). The HLA-B*07 and HLA-B*44 alleles showed a global negative effect on disease status, although none of the measurements reached significance (p-value<0.05). Results for the HLA-DRB1*15, HLA-DQB1*06 and HLA-B*08 alleles were inconclusive. The influence of the confounding variables on the statistical analysis was limited.

Yield of repeated intermittent EEG for seizure detection in critically ill adults.

INTRODUCTION: Seizures are common in critically ill patients and prevalence can exceed 30% in the neuro-intensive care unit (ICU). Continuous EEG monitoring (cEEG) is the gold standard for seizure detection in critically ill patients. OBJECTIVES: To determine the yield of intermittent EEG (iEEG) to detect critically ill adult patients with seizures and to identify the factors that affect this yield. METHODS: We retrospectively analyzed cEEG data and medical records from 977 consecutive critically ill patients undergoing cEEG. We included those presenting at least one electrographic seizure during the first 24hours of cEEG. Patients with hypoxic-ischemic encephalopathy were excluded. For seizure detection, we reviewed six 30-minute epochs on cEEG selected at H0, H3, H6, H12, H18 and H24. RESULTS: Seizures occurred in 10.75% (105/977) of patients. Level of consciousness was impaired in 79 (75%) of patients, with 42 (40%) in coma. Review of the H0 epoch on cEEG permitted to detect seizures in 61 (58%) patients. These figures increased to 70 (67%), 75 (71%), 91 (87%) and 97 (92%) patients for a sampling every 24, 12, 6 and 3hours, respectively (P=0.02). Frequency of seizures on cEEG was the only factor significantly affecting the probability of seizure detection. Sampling every 6hours revealed seizures in all patients with more than six seizures per 24hours. CONCLUSIONS: iEEG repeated every 6hours can accurately detect patients presenting seizures, especially when seizure frequency is greater than six per 24hours. These findings have practical implications for electrographic seizure detection in critically ill patients in settings lacking cEEG.

Quantifying brain volumes for Multiple Sclerosis patients follow-up in clinical practice - comparison of 1.5 and 3 Tesla magnetic resonance imaging.

INTRODUCTION: There is emerging evidence that brain atrophy is a part of the pathophysiology of Multiple Sclerosis (MS) and correlates with several clinical outcomes of the disease, both physical and cognitive. Consequently, brain atrophy is becoming an important parameter in patients' follow-up. Since in clinical practice both 1.5Tesla (T) and 3T magnetic resonance imaging (MRI) systems are used for MS patients follow-up, questions arise regarding compatibility and a possible need for standardization. METHODS: Therefore, in this study 18 MS patients were scanned on the same day on a 1.5T and a 3T scanner. For each scanner, a 3D T1 and a 3D FLAIR were acquired. As no atrophy is expected within 1 day, these datasets can be used to evaluate the median percentage error of the brain volume measurement for gray matter (GM) volume and parenchymal volume (PV) between 1.5T and 3T scanners. The results are obtained with MSmetrix, which is developed especially for use in the MS clinical care path, and compared to Siena (FSL), a widely used software for research purposes. RESULTS: The MSmetrix median percentage error of the brain volume measurement between a 1.5T and a 3T scanner is 0.52% for GM and 0.35% for PV. For Siena this error equals 2.99%. When data of the same scanner are compared, the error is in the order of 0.06-0.08% for both MSmetrix and Siena. CONCLUSIONS: MSmetrix appears robust on both the 1.5T and 3T systems and the measurement error becomes an order of magnitude higher between scanners with different field strength.

Perceptual Accent Rating and Attribution in Psychogenic FAS: Some Further Evidence Challenging Whitaker's Operational Definition.

A 40-year-old, non-aphasic, right-handed, and polyglot (L1: French, L2: Dutch, and L3: English) woman with a 12-year history of addiction to opiates and psychoactive substances, and clear psychiatric problems, presented with a foreign accent of sudden onset in L1. Speech evolved toward a mostly fluent output, despite a stutter-like behavior and a marked grammatical output disorder. The psychogenic etiology of the accent foreignness was construed based on the patient's complex medical history and psychodiagnostic, neuropsychological, and neurolinguistic assessments. The presence of a foreign accent was affirmed by a perceptual accent rating and attribution experiment. It is argued that this patient provides additional evidence demonstrating the outdatedness of Whitaker's (1982) definition of foreign accent syndrome, as only one of the four operational criteria was unequivocally applicable to our patient: her accent foreignness was not only recognized by her relatives and the medical staff but also by a group of native French-speaking laymen. However, our patient defied the three remaining criteria, as central nervous system damage could not conclusively be demonstrated, psychodiagnostic assessment raised the hypothesis of a conversion disorder, and the patient was a polyglot whose newly gained accent was associated with a range of foreign languages, which exceeded the ones she spoke.

Impact of hyponatremia on nerve conduction and muscle strength.

BACKGROUND: Hyponatremia is associated with unstable gait and propensity to falls. The potential contribution of peripheral nervous system dysfunction induced by hyponatremia has not yet been addressed by prospective studies. DESIGN: In the first part of this prospective study, we performed two tests evaluating muscle strength (grip test and quadriceps isometric contraction test) together with a timed up and go (TUG) test in 11 patients with chronic mild-to-moderate hyponatremia before and after the normalization of natremia. In the second part, we measured nerve conduction velocities and F-wave latencies in nine patients with profound hyponatremia (< 125 mmol/L) before and after the normalization of natremia. RESULTS: No significant change in muscle strength was observed when natremia was corrected from 127·7 ± 2·5 to 136·1 ± 1·8 mmol/L, contrary to a significant improvement in TUG from 14·9 ± 5·1 to 12·5 ± 4·7 s (P = 0·006). Nerve conduction velocities and F-wave latencies showed significant improvement in most of the studied nerves when natremia was corrected from 121·9 ± 2·4 to 135·5 ± 3·4 mmol/L (e.g. mean increase of 14·3% for motor nerve conduction and mean decrease of 21·6% for F-wave latency of left peroneal nerve). CONCLUSION: Whereas chronic mild-to-moderate hyponatremia has no impact on muscle strength, we demonstrate for the first time an impact of profound hyponatremia on nerve conduction studies. Further studies are needed to ascertain the contribution of these latter results on gait disturbances, propensity to falls and attention deficits associated with hyponatremia.

The Prognostic Value of 48-h Continuous EEG During Therapeutic Hypothermia After Cardiac Arrest.

BACKGROUND: The aim of this study was to evaluate the prognostic value of continuous electroencephalogram (cEEG) during the first 48 h following cardiac arrest (CA) in patients treated with targeted temperature management (TTM). METHODS: We reviewed data from 92 comatose post-CA patients over a 6 year-period; cEEG recordings were performed during TTM and restoration of normothermia. EEG findings were divided into four time-periods: 0-8, 8-16, 16-24, and 24-48 h after CA. Background EEG findings were defined as moderate encephalopathy (diffuse slowing with reactivity/variability), severe encephalopathy (diffuse slowing without reactivity/variability), burst suppression or suppression, and dichotomized as malignant (suppression/burst suppression/severe encephalopathy) or benign (moderate encephalopathy). Epileptiform activity was defined as the presence of seizures, sporadic epileptiform discharges, or periodic discharges. Neurological outcome was assessed at 3 months using the cerebral performance categories (CPC) score (good outcome: CPC 1-2). RESULTS: 26/92 (28%) patients had a good outcome. Malignant patterns were associated with a poor outcome at all time-points, with a high positive predictive value (94-97%) but a poor negative predictive value (44-56%). Epileptiform activity did not influence the prognostic value of EEG patterns. All patients with moderate encephalopathy and seizures or generalized periodic discharges had a poor outcome. CONCLUSIONS: cEEG can identify patients with poor outcome from the first hours following CA, with limited predictive value for good outcome. Epileptiform activity did not improve the prognostic accuracy of EEG, but seizures and generalized periodic discharges were associated with poor outcome even when developing on a benign EEG pattern.

A novel large deletion in the RYR1 gene in a Belgian family with late-onset and recessive core myopathy.

We report a novel and particularly unusual type of mutation, namely, large deletion in the RYR1 gene, in a Belgian family with myopathy: Patients were found to be compound heterozygous and presented a clinico-pathological phenotype characterized by late-onset and recessive myopathy with cores. We depict the clinical, electrophysiological, pathological and molecular genetic characteristics of family members. To date, large deletions in the RYR1 gene have been reported in only two cases. Both involved different mutations and, in sharp contrast to our cases, presented with a very early-onset, neonatal, and a very severe or lethal phenotype. Overview of reported clinico-pathologic phenotypes, also highlights the rarity of combined late-onset/recessive co-occurrence in this group of myopathies with cores. Finally, this report underlines the broadening spectrum in this group of myopathologic disorders and highlights the concept of 'RYR1-associated/related core myopathies'.