Pragmatic computerised perfusion diagnostics for non-convulsive status epilepticus: a prospective observational study.

BACKGROUND: Non-convulsive status epilepticus (NCSE) is a time-dependent neurological disorder often misdiagnosed in the emergency setting. Electroencephalography (EEG) is often not available on a 24/7 basis, and Salzburg criteria may at times miss the diagnosis. Here, we tested the accuracy of hyperperfusion on CT perfusion imaging (CTP) in the identification of NCSE against Salzburg criteria, to define its potential role in a pragmatic diagnostic workflow. METHODS: We enrolled consecutive patients with suspected acute seizure or seizure disorder undergoing brain imaging with CTP and EEG from January 2021 to March 2023. EEG recordings, Salzburg criteria and CTP hyperperfusion were rated and adjudicated by two independent experts blinded to patient status. A reference standard including all clinical, lab, imaging, EEG and therapeutic data was used to adjudicate NCSE diagnosis. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (NPV) were calculated for CTP hyperperfusion and Salzburg criteria versus NCSE adjudicated according to reference standard. RESULTS: Seventy-seven patients were enrolled. Among 21 NCSE cases, 17 were adjudicated according to Salzburg criteria (81%) and 4 received NCSE diagnosis according to reference standard. Agreement between EEG and CTP emerged in 16/21 NCSE cases, reaching sublobar level in 37.5% of cases. Receiver operator curve analysis suggested good accuracy for CTP hyperperfusion for the diagnosis of NCSE (AUROC 0.79, 95% CI 0.69 to 0.89). CTP hyperperfusion had a high NPV for NCSE (NPV 0.97, 95% CI 0.86 to 1). CONCLUSION: CTP hyperperfusion may be implemented in the emergency fast-track to rule out NCSE, given very high NPV. Further validation studies are needed to evaluate CTP application in real-world setting for NCSE codes.

A retrospective multicentric study on the effectiveness of intravenous brivaracetam in seizure clusters: Data from the Italian experience.

OBJECTIVE: Nearly half of people with epilepsy (PWE) are expected to develop seizure clusters (SC), with the subsequent risk of hospitalization. The aim of the present study was to evaluate the use, effectiveness and safety of intravenous (IV) brivaracetam (BRV) in the treatment of SC. METHODS: Retrospective multicentric study of patients with SC (≥ 2 seizures/24 h) who received IV BRV. Data collection occurred from January 2019 to April 2022 in 25 Italian neurology units. Primary efficacy outcome was seizure freedom up to 24 h from BRV administration. We also evaluated the risk of evolution into Status Epilepticus (SE) at 6, 12 and 24 h after treatment initiation. A Cox regression model was used to identify outcome predictors. RESULTS: 97 patients were included (mean age 62 years), 74 (76%) of whom had a history of epilepsy (with drug resistant seizures in 49% of cases). BRV was administered as first line treatment in 16% of the episodes, while it was used as first or second drug after benzodiazepines failure in 49% and 35% of episodes, respectively. On the one hand, 58% patients were seizure free at 24 h after BRV administration and no other rescue medications were used in 75 out of 97 cases (77%) On the other hand, SC evolved into SE in 17% of cases. A higher probability of seizure relapse and/or evolution into SE was observed in patients without a prior history of epilepsy (HR 2.0; 95% CI 1.03 - 4.1) and in case of BRV administration as second/third line drug (HR 3.2; 95% CI 1.1 - 9.7). No severe treatment emergent adverse events were observed. SIGNIFICANCE: In our cohort, IV BRV resulted to be well tolerated for the treatment of SC and it could be considered as a treatment option, particularly in case of in-hospital onset. However, the underlying etiology seems to be the main outcome predictor.

Hyperperfusion Tmax mapping for nonconvulsive status epilepticus in the acute setting: A pilot case-control study.

OBJECTIVE: Nonconvulsive status epilepticus (NCSE) is misdiagnosed in >50% of cases in the emergency department. Computed tomographic perfusion (CTP) has been implemented in the hyperacute setting to detect seizure-induced hyperperfusion. However, the diagnostic value of CTP is limited by the lack of thresholds for hyperperfusion and high interrater variability. This pilot case-control study aims at identifying the diagnostic value of reverse Tmax (rTmax) in differentiating NCSE from acute ischemic stroke in the hyperacute setting. METHODS: We enrolled patients with NCSE (Salzburg criteria-based diagnosis) and stroke cases 1:1 matched for clinical features and time of presentation. CTP standard maps (mean transit time [MTT]-cerebral blood volume-cerebral blood flow [CBF]) and rTmax maps were elaborated and rated by two experts in CTP blinded to the final diagnosis. Hyperperfusion was adjudicated for standard CTP maps as an increase in CBF and a decrease in MTT, and for rTmax as the presence of a black area on 3-, 2-, and 1-s threshold maps. Cronbach alpha was used for interrater agreement; receiver operating curve analysis was run to measure accuracy with area under the curve. RESULTS: Overall, 34 patients were included (17 NCSE, 17 stroke; time from onset to imaging = 2 h for both groups). People with NCSE were older and more frequently had a history of epilepsy. NCSE patients had hyperperfusion on rTmax maps in 11 of 17 cases versus zero of 17 in stroke. Intra- and interrater reliability was higher for rTmax than for standard CTP maps (κ = 1 vs. κ = .6). rTmax was 82% (95%CI = 67-97%) accurate in predicting NCSE versus stroke in the hyperacute setting. Agreement between neuroimaging and electroencephalography (EEG) was limited at a hemispheric level for standard CTP maps, whereas rTMax had agreement with EEG largely reaching the sublobar level. SIGNIFICANCE: rTmax mapping might represent a reliable tool to spot NCSE-induced hyperperfusion with a threshold-based reproducible approach. Further studies are needed for validation and implementation in the differential diagnosis of focal neurological deficit in the hyperacute setting.

GABAA receptor and anti-titin antibody encephalitis in a patient with thymoma.

Autoimmune encephalitis (AE) associated to antibodies against GABA A R is a rare form of encephalitis. On the other hand, thymoma has been linked to antibodies against both muscular and neuronal epitopes, even if concurrent positivity for more than one antibody is exceptional, and their contribution to the clinical course and treatment decision is unclear. We report a case of a 73-year-old male with AE associated with thymoma secreting both anti-GABAaR and anti-titin antibodies. Clinical presentation included status epilepticus, behavioural changes and cognitive decline. While the status was stopped with lacosamide, AE treatment included first- and second-line immunomodulation, in addition to thymoma's removal. Nonetheless, the patient experienced a worsening in cognitive and behavioural status.

Bulbar watershed ischemic stroke: the comma-shaped sign-a case series.

Watershed infarcts can involve the brainstem, with lesions distributed across the terminal supply from the vertebral and cerebellar arteries. Brain imaging can highlight a comma-shaped lesion at the edge of vertebral and posteroinferior cerebellar artery vascularization territory. Such peculiar MRI lesion shape might suggest a watershed hypoperfusion etiology and direct workup towards causes of hemodynamic impairment, including postural hypotension, cardiac failure, or vertebral artery origin occlusion.

The domino effect of acephalgic spontaneous intracranial hypotension.

Spontaneous intracranial hypotension results from a spinal CSF leak and usually presents with orthostatic headache, although acephalgic presentations have anecdotally been reported. The underlying low CSF volume, rarely, leads to serious complications such as cerebral venous thrombosis and coma. We report a patient presenting with cerebral venous thrombosis secondary to acephalgic spontaneous intracranial hypotension. An epidural blood patch was performed; nonetheless, the patient intracracal condition deteriorated to coma and neuroimages showed a deep brain swelling with midbrain distortion, subsequently complicated by intracranial pontine hemorrhage.

Seizures in acute stroke: incidence, risk factors and prognosis.

BACKGROUND AND PURPOSE: Studies on post-stroke seizures have produced conflicting results. Our study aim was to further elucidate the incidence and predictive factors of early post-stroke seizures (ES) and their relationship with outcome. METHODS: relevant clinical data were prospectively collected in 2,053 patients with acute stroke admitted to the Stroke Unit from 2004 to 2008. RESULTS: Sixty-six patients (8 hemorrhagic and 58 ischemic strokes) aged 73-88 years (mean age 82 years) presented seizures in the first week after stroke onset. The type of ischemic stroke was atherothrombotic in 10 patients, cardioembolic in 21, lacunar in 4, undetermined in 19, and of other etiology in 4. Twenty-seven patients had generalized convulsive, 6 had complex partial, and 33 had simple partial seizures. Status epilepticus was observed in 13 patients. The severity of strokes in patients with ES was greater than in those without (National Institutes of Health Stroke Scale >14 in 50 vs. 25%), so mortality (30 days) was higher (29 vs. 14%). Independent seizure predictors were: total anterior circulation infarct, hemorrhagic transformation, hyperglycemia, and the interaction term diabetes × hyperglycemia. CONCLUSIONS: ES may be considered a marker of stroke severity. Cortical location of the lesion, hemorrhagic transformation, and hyperglycemia in patients without diabetes are important predictors of ES.

Association of restless legs syndrome with nocturnal eating: a case-control study.

We investigated the prevalence of nocturnal eating (sleep-related eating disorder-SRED or night-eating syndrome-NES) in patients with restless legs syndrome (RLS). One hundred RLS patients living in Emilia-Romagna (Northern Italy) and 100 matched controls randomly selected from the general population received two telephone interviews, and were investigated for socio-demographic characteristics, general health status, and presence of nocturnal eating. Additionally, subjects underwent interviews for psychopathological traits [by means of the Eating Disorder Inventory-2 (EDI-2), the Maudsley Obsessive-Compulsive Inventory (MOCI), the Beck Depression Inventory (BDI)], excessive daytime sleepiness (EDS), and subjective sleep quality. Compared with controls, RLS patients had more frequently pathological MOCI scores (24% versus 10%, P = 0.03), used significantly more drugs for concomitant diseases and had more nocturnal sleep impairment and EDS. SRED was more prevalent in RLS patients than controls (SRED: 33% versus 1%, P < 0.001). Medication use and pathological MOCI scores were more prevalent in RLS patients with SRED than among RLS patients without SRED. Use of dopaminergic or hypnotic drugs for RLS was not correlated with the presence of SRED. We demonstrate an association between RLS and SRED. Prospective studies are needed to establish the mechanisms underlying such association and whether it is causal.

Detection of sleep onset by analysis of slow eye movements: a preliminary study of MSLT recordings.

BACKGROUND: Excessive daytime sleepiness (EDS) adversely impacts daily activity and quality of life. Evaluation of EDS should be as easy and effective as possible. Multiple sleep latency test (MSLT) represents the standard in EDS evaluation. It is, however, a long and expensive test. Slow eye movements (SEMs) occurring at the wake-sleep transition could be an easy and reliable marker of sleepiness. We have developed an automatic method for the detection of SEMs. In the present preliminary work we compare standard measurement of EDS with visual and automatic detection of SEMs, both performed on MSLT recordings. METHODS: We compared sleep latency, obtained upon standard analysis of MSLT with visually and automatically detected SEM latency, in MSLT tests performed in a population of 20 subjects, (10 Obstructive Sleep Apnea Syndrome (OSAS) patients and 10 patients with normal MSLT). RESULTS: There were no significant differences between SEMs latency and standard determined sleep latency both in OSAS and normal MSLT patients. Automatic and visual analysis of SEMs gave comparable results. Both SEMs latency and sleep latency were significantly shorter in OSAS patients than normal MSLT patients. CONCLUSION: SEMs can be easily detected automatically and represent an effective marker of sleepiness in those conditions usually characterised by sleep onset with NREM sleep. Their performance equals that of standard measurements of sleep onset in MSLT recordings at least for OSAS and normal MSLT patients. Our study is, however, still preliminary and needs confirmation on a larger number of patients and in other clinical conditions characterised by EDS.

Sleep-related faciomandibular myoclonus: A sleep-related movement disorder different from bruxism.

We describe a 33-year-old man who presented with lip and tongue nibbling and bleeding during sleep. Videopolysomnography revealed myoclonic jerks involving the masticatory and facial muscles recurring mainly during NREM sleep. There was no tonic EMG masticatory activity typical of bruxism. EMG analysis demonstrated the recruitment of V- to VII innervated muscles and, in half of the episodes, also the sternocleidomastoideus. Our patient had sleep-related faciomandibular myoclonus (SFMM) with spontaneous jerks of oromasticatory and cervical muscles, occurring only during sleep. Tooth grinding, temporomandibular joint pain, abnormal tooth mobility, tooth wear, and other dental problems were clinically absent. We propose that, on the basis of the clinical and EMG features, SFMM may be considered a distinct disorder and different from sleep bruxism.

Interobserver reliability of video recording in the diagnosis of nocturnal frontal lobe seizures.

BACKGROUND: Nocturnal frontal lobe seizures (NFLS) show one or all of the following semeiological patterns: (1) paroxysmal arousals (PA: brief and sudden recurrent motor paroxysmal behavior); (2) hyperkinetic seizures (HS: motor attacks with complex dyskinetic features); (3) asymmetric bilateral tonic seizures (ATS: motor attacks with dystonic features); (4) epileptic nocturnal wanderings (ENW: stereotyped, prolonged ambulatory behavior). OBJECTIVE: To estimate the interobserver reliability (IR) of video-recording diagnosis in patients with suspected NFLS among sleep medicine experts, epileptologists, and trainees in sleep medicine. METHODS: Sixty-six patients with suspected NFLS were included. All underwent nocturnal video-polysomnographic recording. Six doctors (three experts and three trainees) independently classified each case as "NFLS ascertained" (according to the above specified subtypes: PA, HS, ATS, ENW) or "NFLS excluded". IR was calculated by means of Kappa statistics, and interpreted according to the standard classification (0.0-0.20 = slight agreement; 0.21-0.40 = fair; 0.41-0.60 = moderate; 0.61-0.80 = substantial; 0.81-1.00 = almost perfect). RESULTS: The observed raw agreement ranged from 63% to 79% between each pair of raters; the IR ranged from "moderate" (kappa = 0.50) to "substantial" (kappa = 0.72). A major source of variance was the disagreement in distinguishing between PA and nonepileptic arousals, without differences in the level of agreement between experts and trainees. CONCLUSIONS: Among sleep experts and trainees, IR of diagnosis of NFLS, based on videotaped observation of sleep phenomena, is not satisfactory. Explicit video-polysomnographic criteria for the classification of paroxysmal sleep motor phenomena are needed.

Interobserver reliability of ICSD-R minimal diagnostic criteria for the parasomnias.

OBJECTIVE: To estimate the interobserver reliability (IR) of the minimal diagnostic criteria for the parasomnias provided in the International Classification of Sleep Disorders Revised (ICSD-R). METHODS: Fifty consecutive subjects underwent a structured interview by three doctors based on the ICSD-R minimal criteria for the diagnosis of 13 parasomnias at any time in life. IR was calculated by Kappa statistics and interpreted according to conventional categories. RESULTS: In the group of Arousal Disorders, IR was "substantial" (kappa 0.74) for confusional arousals, "slight" (kappa 0.36) for sleepwalking, "fair" (kappa -0.02) for sleep terrors. In the group of Wake-Sleep Transition Disorders, IR was "substantial" to "almost perfect", but "moderate" for sleep starts (kappa 0.41). In the group of Parasomnias usually associated with REM Sleep, IR was "substantial" (kappa 0.69) for sleep paralysis, "moderate" (kappa 0.46) for RBD, "fair" (kappa 0.25) for nightmares. In the group of Other Parasomnias, IR was "substantial" to "almost perfect" (kappa between 0.73 and 0.93). CONCLUSIONS: When the clinical diagnosis of parasomnias is based on the ICSD-R: 1) the majority of Arousal Disorders and REM sleep parasomnias showed only a "fair" to "moderate" IR; 2) all of the other parasomnias showed a "substantial" to "almost perfect" IR. Nosological entities with unsatisfactory IR share complex motor phenomenology associated with a mental state difficult for the patient to define. The source of disagreement probably lies in the difficulty in interpreting patients' reports. For these parasomnias IR must be verified and possibly improved with training.

Telephone-induced seizures: a new type of reflex epilepsy.

PURPOSE: To report a new form of reflex epilepsy in which the seizures are repeatedly and exclusively triggered by answering the telephone. METHODS: Three patients with a history of telephone-induced seizures were studied in detail by means of clinical, EEG, and neuroradiologic investigations. Intensive video-EEG monitoring to record the reflex seizures also was performed in all cases. RESULTS: The patients (two men, one woman, aged 21 to 30 years) had the onset during early adulthood of complex partial and secondarily generalized seizures exclusively triggered by answering the telephone. The seizures were stereotyped, with subjective auditory or vertiginous auras and inability to speak or understand the spoken voices. In one patient, a telephone-induced seizure arising from the dominant temporal lobe was recorded by means of video-EEG technique. In the interictal EEGs, temporal abnormalities were detected in all cases. The patients had a normal neurologic examination and normal magnetic resonance imaging or computed tomography scans. CONCLUSIONS: We suggest that telephone epilepsy is a previously unrecognized form of reflex epilepsy induced by a complex auditory stimulus involving the lateral temporal areas.

Malformation of cortical development in adult patients.

Few studies have focused on the clinical, neurophysiological and prognostic features of adult epileptic patients with malformation of cortical development. We reviewed the clinical data of a series of sixty adult epileptic patients with different types of malformation of cortical development, who had been followed at the Epilepsy Centre of the Department of Neurological Sciences of the University of Bologna, with particular attention to age at seizure onset, mental retardation, response to therapy, and EEG features. The heterogeneity of our population, especially when divided into the different groups of malformation of cortical development, precluded any general conclusions, but we stress the following aspects: 1). epilepsy due to malformation of cortical development may begin in adolescents and young adults; 2). epileptic seizures with clinical and polygraphic features of infantile spasms may persist into adulthood; 3). complex cortical malformation is not necessarily associated with severe epileptic encephalopathy. In periventricular nodular heterotopias, the largest in our series (nine patients), age at onset of seizures, response to therapy and mental deterioration differed according to the presence of nodules confined to the ventricular wall ('pure' form) or periventricular nodules associated with other cerebral cortical malformations ('plus' form).