Ophthalmologic manifestations in myasthenia gravis: presentation and prognosis.

We investigated the ophthalmologic manifestations and factors that influence outcomes in patients with myasthenia gravis (MG). We retrospectively analyzed the prevalence of neuro-ophthalmologic findings and clinical and outcome measures of 100 consecutive patients (53 males, 47 females), aged 55.7 ± 17.5 (range 15-85) years with an established diagnosis of MG. Forty-eight patients had purely ocular symptoms at the onset of disease (OMG) and 52 patients presented with generalized symptoms (GMG). Overall, 21 patients presented with extraocular muscle (EOM) weakness. Bilateral EOM weakness was seen in 12 patients, and unilateral EOM weakness was seen in nine patients. Diplopia responded partially to immunosuppressive treatments in 60% of patients with ophthalmoparesis. Twenty-five (52.1%) patients with ocular-onset MG converted to secondary GMG at a mean time of 14.5 months. Patients who developed secondary GMG were younger and had an earlier age of disease onset when compared with patients with pure OMG (p < 0.05). Patients with secondary GMG presented more frequently with ptosis and diplopia (72% vs. 28%) compared with patients with pure ocular MG who presented more frequently with isolated ptosis (66.7% vs. 33.3%) (p = 0.02). Remission and minimal manifestation status were achieved in 50 (79.3%) of all patients with a clinical follow-up ≥ 3 years. Poor outcome was associated with the presence of thymoma (p < 0.05). Myasthenic ophthalmoparesis is bilateral and heterogeneous and partly responds to treatment with immunotherapy. Younger patients with ptosis and diplopia at disease onset had an increased risk of secondary GMG. The presence of thymoma increases the risk for poor prognosis.

Amyotrophic lateral sclerosis with coexisting cancer: a single-center study.

This study investigated the occurrence of malignancy in a cohort of patients with amyotrophic lateral sclerosis (ALS). Forty-three consecutive ALS patients (mean age 61.3 years, 31 men/12 women) admitted between 2015 and 2019 were enrolled. Clinical, electrophysiologic and outcome features that differentiate cancer-associated ALS from classical ALS were investigated. ALS was associated with cancer in 5 (11.6%) patients. Two patients were diagnosed with non-small cell lung, one with endometrium, one with prostate and one with laryngeal carcinoma. One another patient was diagnosed with monoclonal gammopathy of unknown significance, but she did not develop cancer within 12-month follow-up duration. Two patients had a previous diagnosis of cancer before the diagnosis of ALS. In the remaining 3 patients, cancer was diagnosed at the same time or after the onset of ALS. There was no significant difference with respect to mean age of onset, sex, disease duration, clinical and electrophysiological features and outcome between patients with and without malignancy. None of the patients with cancer survived more than two years after the onset of ALS except one who was diagnosed with flail-leg syndrome before the diagnosis of non-small cell lung carcinoma. ALS is not accepted as a classical paraneoplastic neurological syndrome. Although the association of ALS and cancer seems coincidental, a careful investigation for an underlying cancer is important in patients with ALS. In our patient group with cancer-associated ALS, no distinguishing features were identified.

Electroclinical patterns in patients with nonconvulsive status epilepticus: Etiology, treatment, and outcome.

INTRODUCTION: This study investigated the clinical and electroencephalography (EEG) features and prognostic factors of patients with nonconvulsive status epilepticus (NCSE). MATERIALS AND METHODS: We retrospectively reviewed the clinical files and EEG data of 45 (28 females, mean age 54 ±â€¯22.6 years) consecutive patients with NCSE over a five-year period. An EEG interpreter who was blinded to the clinical findings evaluated the EEGs according to the Salzburg Consensus Criteria (SCC) for NCSE. Patient demographics, etiology, neuroimaging and laboratory data, EEG features, treatment, and outcome measures were analyzed. RESULTS: The most common etiology for NCSE was acute symptomatic etiologies (57.8%) and cerebrovascular disease (48.9%). The majority (68.9%) of the patients presented with new-onset status epilepticus (SE). NCSE was refractory to treatment in 31.1% of patients. The most common status pattern consisted of rhythmic delta/theta activity in 62.3% of EEGs. Twenty-five status patterns on the EEGs were classified as definite, 30 as possible, and six as no NCSE according to the SCC. The in-hospital mortality rate was high (33.3%) showing an association with potentially fatal etiology, refractory SE, treatment with continuous I.V. anesthetics and also the presence of multiple status patterns and nonreactivity in EEGs (p < 0.05). CONCLUSIONS: The SCC for NCSE have high diagnostic accuracy but do not affect prognosis. Potentially fatal etiology, multiple status patterns on EEG and non-reactive EEGs may carry significantly greater risk for short-term mortality.

Stimulation-induced ictal vocalisation of left frontal lobe origin.

Pure ictal non-speech vocalisation occurs in frontal and temporal lobe epilepsies. Electrical stimulation of supplementary motor areas is reported to evoke vocalisation in selected patients. Here, we report a patient with focal epilepsy of the left anterior insula who had isolated monotonous vocalisation elicited by electrical stimulation of the left superior frontal gyrus. Quantitative analysis of audio signals was performed and compared with a former patient with left frontal lobe epilepsy who had pure ictal vocalisation. Both patients showed a comparable reduction in frequency variation indicating a monotonous voice. [Published with video sequences on www.epilepticdisorders.com].

Does semiology of status epilepticus have an impact on treatment response and outcome?

OBJECTIVE: This study investigated whether there is an association between semiology of status epilepticus (SE) and response to treatment and outcome. METHOD: Two hundred ninety-eight consecutive adult patients (160 females, 138 males) with SE at the University of Munich Hospital were prospectively enrolled. Mean age was 63.2±17.5 (18-97) years. Patient demographics, SE semiology and electroencephalography (EEG) findings, etiology, duration of SE, treatment, and outcome measures were investigated. Status epilepticus semiology was classified according to a semiological status classification. Patient's short-term outcome was determined by Glasgow Outcome Scale (GOS). RESULTS: The most frequent SE type was nonconvulsive SE (NCSE) (39.2%), mostly associated with cerebrovascular etiology (46.6%). A potentially fatal etiology was found in 34.8% of the patients. More than half (60.7%) of the patients had poor short-term outcome (GOS≤3) with an overall mortality of 12.4%. SE was refractory to treatment in 21.5% of the patients. Older age, potentially fatal etiology, systemic infections, NCSE in coma, refractory SE, treatment with anesthetics, long SE duration (>24h), low Glasgow Coma Scale (GCS) (≤8) at onset, and high Status Epilepticus Severity Score (STESS-3) (≥3) were associated with poor short-term outcome and death (p<0.05). Potentially fatal etiology and low GCS were the strongest predictors of poor outcome (Exp [b]: 4.74 and 4.10 respectively, p<0.05). CONCLUSION: Status epilepticus semiology has no independent association with outcome, but potentially fatal etiology and low GCS were strong predictive factors for poor short-term outcome of SE.

Genital automatisms: Reappraisal of a remarkable but ignored symptom of focal seizures.

OBJECTIVES: Genital automatisms (GAs) are uncommon clinical phenomena of focal seizures. They are defined as repeated fondling, grabbing, or scratching of the genitals. The aim of this study was to determine the lateralizing and localizing value and associated clinical characteristics of GAs. METHODS: Three hundred thirteen consecutive patients with drug-resistant seizures who were referred to our tertiary center for presurgical evaluation between 2009 and 2016 were investigated. The incidence of specific kinds of behavior, clinical semiology, associated symptoms/signs with corresponding ictal electroencephalography (EEG) findings, and their potential role in seizure localization and lateralization were evaluated. RESULTS: Fifteen (4.8%) of 313 patients had GAs. Genital automatisms were identified in 19 (16.4%) of a total 116 seizures. Genital automatisms were observed to occur more often in men than in women (M/F: 10/5). Nine of fifteen patients (60%) had temporal lobe epilepsy (right/left: 4/5) and three (20%) had frontal lobe epilepsy (right/left: 1/2), whereas the remaining two patients could not be classified. One patient was diagnosed as having Rasmussen encephalitis. Genital automatisms were ipsilateral to epileptic focus in 12 patients and contralateral in only one patient according to ictal-interictal EEG and neuroimaging findings. Epileptic focus could not be lateralized in the last 2 patients. Genital automatisms were associated with unilateral hand automatisms such as postictal nose wiping or manual automatisms in 13 (86.7%) of 15 and contralateral dystonia was seen in 6 patients. All patients had amnesia of the performance of GAs. CONCLUSION: Genital automatisms are more frequent in seizures originating from the temporal lobe, and they can also be seen in frontal lobe seizures. Genital automatisms seem to have a high lateralizing value to the ipsilateral hemisphere and are mostly concordant with other unilateral hand automatisms. Men exhibit GAs more often than women.

Delta Brush Pattern Is Not Unique to NMDAR Encephalitis: Evaluation of Two Independent Long-Term EEG Cohorts.

PURPOSE: Although its specificity has not previously been investigated in other cohorts, delta brush pattern (DBP) is increasingly reported in the EEGs of patients with anti- N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHODS: We aimed to investigate the DBP in the EEGs of 2 cohorts; patients with change in consciousness for various causes monitored in the intensive care unit (ICU) (n = 106) and patients with mesial temporal lobe epilepsy (MTLE) with or without antineuronal antibodies (n = 76). RESULTS: These patients were investigated for the presence of DBP, defined as an EEG pattern characterized by delta activity at 1 to 3 Hz with superimposed bursts of rhythmic 12- to 30-Hz activity. Two investigators blindfolded for the clinical and immunological data independently analyzed the EEGs for recognition of this pattern. An EEG picture compatible with DBP was observed in 4 patients; only 1 of them (1.3%) belonged to the MTLE group. She did not bear any of the investigated autoantibodies and was seizure-free after epilepsy surgery. In the ICU group, there were 3 additional patients showing DBP with various diagnoses such as hypoxic encephalopathy, brain tumor, stroke, and metabolic derangements. All of them had died in 1-month period. CONCLUSIONS: Our results underlined that DBP is not unique to NMDAR encephalitis; it may very rarely occur in MTLE with good prognosis after surgery and second, in ICU patients who have high mortality rate. Therefore, the presence of this pattern should alert the clinician for NMDAR encephalitis but other possible etiologies should not be ignored.

Analysis of heart rate variability and risk factors for SUDEP in patients with drug-resistant epilepsy.

BACKGROUND: Cardiac problems have been suggested as causes of sudden unexpected death in epilepsy (SUDEP). Our aim was to investigate possible associations of cardiac autonomic functions based on heart rate variability (HRV) parameters with risk factors of SUDEP in patients with drug-resistant epilepsy. METHODS: Forty-seven patients with drug-resistant seizures and 45 healthy control subjects were enrolled in the study. Interictal time domain parameters of HRV were evaluated with 24-hour Holter recordings. Potential SUDEP risk in patients with epilepsy was estimated using an inventory of seven validated SUDEP risk factors (The SUDEP-7 inventory). RESULTS: When compared with the healthy controls, all time domain measures (SDNN-24, SDNN-index, SDANN-index, RMSSD and pNN50) were significantly suppressed in the patient group. Scores of the SUDEP-7 inventory ranged from 1 to 9 with a median 4 out of a maximum possible risk score of 10. Maximum heart rate value in 24-hour Holter recordings and epilepsy duration were correlated with the SUDEP-7 scores (r=0.3, p=0.03). We found no significant association with HRV measures and SUDEP-7 risk factors. One patient diagnosed with Dravet syndrome died of SUDEP, which was autopsy confirmed; his SUDEP-7 inventory score was 7, HRV measures were significantly diminished, and his maximum heart rate (HR) was 208beats/min (maximum HR is between 104 and 188beats/min in normal subjects). CONCLUSION: Patients with drug-resistant epilepsy present with significantly lower HRV measures, which may increase the risk for sudden cardiac death. Increased heart rate and diminished HRV measures may constitute one of the possible mechanisms underlying SUDEP and should be diagnosed in patients with epilepsy.

Neuronal autoantibodies in mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: Our aim was to investigate the prevalence of neuronal autoantibodies (NAbs) in a large consecutive series with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to elucidate the clinical and laboratory clues for detection of NAbs in this prototype of frequent, drug-resistant epilepsy syndrome. METHODS: Consecutive patients diagnosed with MTLE fulfilling the MRI criteria for HS were enrolled. The sera of patients and various control groups (80 subjects) were tested for eight NAbs after ethical approval and signed consents. Brain tissues obtained from surgical specimens were also investigated by immunohistochemical analysis for the presence of inflammatory infiltrates. The features of seropositive versus seronegative groups were compared and binary logistic regression analysis was performed to explore the differentiating variables. RESULTS: We found antibodies against antigens, contactin-associated protein-like 2 in 11 patients, uncharacterised voltage-gated potassium channel (VGKC)-complex antigens in four patients, glycine receptor (GLY-R) in 5 patients, N-methyl-d-aspartate receptor in 4 patients and γ-aminobutyric acid receptor A in 1 patient of 111 patients with MTLE-HS and none of the control subjects. The history of status epilepticus, diagnosis of psychosis and positron emission tomography or single-photon emission CT findings in temporal plus extratemporal regions were found significantly more frequently in the seropositive group. Binary logistic regression analysis disclosed that status epilepticus, psychosis and cognitive dysfunction were statistically significant variables to differentiate between the VGKC-complex subgroup versus seronegative group. CONCLUSIONS: This first systematic screening study of various NAbs showed 22.5% seropositivity belonging mostly to VGKC-complex antibodies in a large consecutive series of patients with MTLE-HS. Our results indicated a VGKC-complex autoimmunity-related subgroup in the syndrome of MTLE-HS.

Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings.

Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3%) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29%), contactin-associated protein-like 2 (CASPR2) in 5 (29%), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18%), glutamic acid decarboxylase (GAD) in 2 (12%), glycine receptor (GLYR) in one (6%) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6%). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.

Are There Any Specific EEG Findings in Autoimmune Epilepsies?

This study evaluated the EEG findings of patients whose seizures were associated with a possible autoimmune etiology. Our aim was to find clues to distinguish patients with antineuronal antibodies (Ab) through EEG studies. We reviewed our database and identified antineuronal Ab positive epilepsy patients with or without autoimmune encephalitis. These patients had Abs to N-methyl-d-aspartate receptor (NMDAR) (n = 5), glycine receptor (GLY-R) (n = 5), contactin-associated protein-like 2 (CASPR-2) (n = 4), uncharacterized voltage-gated potassium channel complex (VGKC) antigens (n = 2), glutamic acid decarboxylase (GAD) (n = 2), Hu (n = 1), and amphiphysin (n = 1). The control group consisted of 21 seronegative epilepsy or encephalopathy patients with similar clinical features. EEG findings were compared between the groups in a blindfolded design. We did not find any significant difference in EEG findings between antineuronal Ab positive epilepsy patients and seronegative control group. It was remarkable that four seropositive but none of the seronegative patients presented with nonconvulsive status epilepticus (NCSE) or focal motor status epilepticus. Continuous theta and delta rhythms were observed in 5 (71%) seropositive patients with autoimmune encephalitis and 2 (25%) seronegative patients. Eight (40 %) seropositive patients showed a frontal intermittent rhythmic delta activity (FIRDA) pattern as opposed to 5 (24%) seronegative patients. Two patients with NMDAR Ab positivity showed rhythmic delta waves superimposed with beta frequency activity resembling "delta brush" pattern. EEG seems as a limited diagnostic tool in differentiating epilepsy and/or encephalopathy patients with a possible autoimmune etiology from those without. However, antineuronal Abs associated with encephalitis should be considered in the etiology of status epilepticus forms. A possible autoimmune etiology for seizures may be considered in the presence of continuous slow waves, FIRDA, and delta brush pattern in the EEG.

Jitter Values on Voluntary Active Periocular Muscles of Healthy Subjects with Conventional (37 mm) Concentric Needle Electrode.

INTRODUCTION: The aim of this study was to re-evaluate jitter values of healthy subjects in whom pairs of single-fiber-like potentials were recorded from voluntary activated periocular muscles using a disposable 37-mm concentric needle electrode (CNE) with 2-kHz low-cut filtering. METHODS: We reviewed the recordings of 129 subjects (85 women; 44 men; mean age, 43.8±15.3 years). The m. frontalis group included 116 subjects, and the m. orbicularis oculi group included 18 subjects. Jitter values were expressed as the mean consecutive difference (MCD) of 20 different pairs. RESULTS: The mean MCD (n=2680) was 22.5±9.7 µs (range, 5-121 µs), and the upper 95% confidence limit (CL) was 39 µs. The mean of 134 MCD values for each subject was 22.5±3.7 µs (range, 15-33 µs), and the upper 95% CL was 30 µs. The outer limit of the 18th highest MCD values out of 20 recordings for each subject was 31.3±6.5 µs (range, 18-53 µs), with an upper 95% CL of 43.3 µs. CONCLUSION: Using a conventional 37-mm CNE with 2-kHz low-cut filtering may be a cost effective alternative to a single-fiber electrode in periocular muscles if strict criteria are used for acceptable signals. Jitter values of >44 µs that were calculated from single-fiber-like action potential pairs should alert the physician regarding the possibility of neuromuscular junction disorders and constitute an indication for a further diagnostic investigation.

Eye movements differ between ictal ipsilateral and contralateral head turning.

PURPOSE: This study evaluated the relation of head and eye movements during ictal ipsilateral and contralateral head turning in patients with focal epilepsies with regard to lateralization of the epileptogenic zone. METHODS: We reviewed our database and identified patients with ictal head turning ipsilateral and contralateral to the seizure onset as defined by ictal EEG. Twenty-seven seizures of 19 consecutive patients with ipsilateral and 40 seizures of 32 patients with contralateral head turning were investigated. Twenty-four patients had temporal lobe epilepsy (TLE), and 27 patients had extratemporal or multifocal epilepsy. KEY FINDINGS: Eye movement in the same direction preceded contralateral head turning in 90% (36 of 40 seizures) of the seizures, but this was the case in only 33% (9 of 27 seizures) of the ipsilateral ictal head turning. In contrary, head turning preceded the eye movements in 67% (18 of 27 seizures) of the ipsilateral ictal head turning and in only 10% of the contralateral head turning (p < 0.001). The results were similar in TLE and FLE. SIGNIFICANCE: The sequence of head and eye movements is different in ictal ipsilateral and contralateral head turning movements which likely reflects different spread patterns of epileptic activity associated with activation of different generators. The analysis of eye movements adds to the lateralization of ictal head movements.

Assessment of early cognitive impairment in patients with clinically isolated syndromes and multiple sclerosis.

Objective. The aim of our study was to investigate the frequency and pattern of cognitive impairment in patients with clinically isolated syndromes and definite diagnosis of multiple sclerosis within the last 2 years. Methods. We assessed the cognitive status of 46 patients aged 18-49 years with clinically isolated syndromes or definite diagnosis of multiple sclerosis who have onset of their symptoms within the last 2 years. Patients were matched with 40 healthy participants for age, sex, and educational level. Neuropsychological assessment was performed by stroop test, paced auditory serial addition test (PASAT), controlled oral word association test (COWAT), clock drawing test, trail making test (TMT), faces symbol test (FST). Hamilton Depression Scale and Modified Fatigue Impact Scale were used to quantify the severity of any depression and fatigue the subjects might suffer. Results. 19.6% of early MS/CIS group failed at 4 and more tests and had significant cognitive impairment focused on attention, executive functions, memory, and learning. No significant relationship was found between cognitive impairment and disability and fatigue scores. Discussion. Cognitive impairment can be present from the earliest stage of multiple sclerosis. It should be considered among the main manifestations of MS even in the earliest stages of the disease.

Myoclonic status epilepticus in six patients without epilepsy.

Myoclonic status epilepticus (MSE) is defined as prolonged period of myoclonic jerks that are correlated with epileptiform discharges on EEG. We here describe clinical features and video-EEG records of six adult patients with MSE who did not have a prior diagnosis of epilepsy. In four out of six patients, MSE was precipitated by drugs. Two out of four patients had chronic renal disease and received beta lactam group antibiotics. Two other patients, who described chronic pain, developed MSE while taking pregabalin. One patient who had dementia and family history of juvenile myoclonic epilepsy (JME) developed MSE one month after quetiapine was introduced. Another patient, who had a recent ischemic stroke, developed MSE due to an unknown reason. In these last two patients, an immediate triggering factor was not evident. Myoclonic status epilepticus ceased in five out of six patients after withdrawal of the drugs and/or intravenous antiepileptic treatment. Myoclonic status epilepticus is a rare event in patients without epilepsy. A correct diagnosis and prompt drug discontinuation may reverse this severe and life-threatening condition.