A novel scale for suspicion of psychogenic nonepileptic seizures: development and accuracy.

OBJECTIVE: The differential diagnosis between epileptic and psychogenic nonepileptic seizures (PNES) is challenging, yet suspicion of PNES is crucial to rethink treatment strategies and select patients for diagnostic confirmation through video EEG (VEEG). We developed a novel scale to prospectively suspect PNES. METHODS: First, we developed a 51-item scale in two steps, based upon literature review and panel expert opinion. A pilot study verified the applicability of the instrument, followed by a prospective evaluation of 158 patients (66.5% women, mean age 33 years) who were diagnosed for prolonged VEEG. Only epileptic seizures were recorded in 103 patients, and the other 55 had either isolated PNES or both types of seizures. Statistical procedures identified 15 items scored between 0 and 3 that best discriminated patients with and without PNES, with a high degree of consistency. RESULTS: Internal consistency reliability of the scale for suspicion of PNES was 0.77 with Cronbach's Alpha Coefficient and 0.95 with Rasch Item Reliability Index, and performance did not differ according to the patient's gender. For a cut-off score of 20 (of 45) points, area under the curve was 0.92 (95% IC: 0.87-0.96), with an accuracy of 87%, sensitivity of 89%, specificity of 85%, positive predictive value of 77%, and negative predictive value of 94% (95% IC) for a diagnosis of PNES. CONCLUSIONS: The scale for suspicion of PNES (SS-PNES) has high accuracy to a reliable suspicion of PNES, helping with the interpretation of apparent seizure refractoriness, reframing treatment strategies, and streamlining referral for prolonged VEEG.

Control of drop attacks with selective posterior callosotomy: Anatomical and prognostic data.

OBJECTIVE: In a previous proof of concept study, selective posterior callosotomy achieved similar degree of control of drop attacks as total callosotomy, while sparing prefrontal interconnectivity. The present study aims to confirm this finding in a larger cohort and to provide anatomical and prognostic data. METHODS: Fifty-one patients with refractory drop attacks had selective posterior callosotomy and prospective follow up for a mean of 6.4 years. Twenty-seven patients had post-operative magnetic resonance imaging (MRI) and 18 had tractography (DTI) of remaining callosal fibers. Pre and postoperative falls were quantified and correlated with demographic, clinical and imaging data. RESULTS: Mean monthly frequency of drop attacks had a 95 % reduction, from 297 before to 16 after the procedure. Forty- one patients (80 %) had either complete or greater than 90 % control of the epileptic falls. Age and duration of epilepsy at surgery correlated with outcome (p values, respectively, 0.042 and 0.005). Mean index of callosal section along the posterior-to-anterior axis was 53.5 %. Extending the posterior section anterior to the midbody of the corpus callosum did not correlate with seizure control (p 0.91), providing fibers interconnecting the primary motor (M1) and caudal supplementary motor areas (SMA) were sectioned. Only one patient had a notable surgical complication which resolved in two days. CONCLUSIONS: This level III cohort study with objective outcome assessment confirms that selective posterior callosotomy is safe and effective to control epileptic falls. Younger patients with smaller duration of epilepsy have better results. A posterior section contemplating the splenium, isthmus and posterior half of the body (posterior midbody) seems sufficient to achieve complete or almost complete control of drop attacks.

Selective Posterior Callosotomy for Treatment of Epileptic Drop Attacks: Video Documentation of the Surgical Technique: 2-Dimensional Operative Video.

This is a surgical technique video of selective posterior callosotomy (SPC), a novel surgical procedure to alleviate refractory epileptic drop attacks.1 Departing from traditional approaches aiming the anterior half or the entire callosum, SPC sections the posterior half of the callosum sparing prefrontal connectivity.1 Drop attacks are generalized epileptic seizures characterized by sudden falls.1 These seizures are often seen in diffuse brain pathology associated with generalized or multifocal epilepsies, whose electroencephalogram (EEG) "fingerprint" is bilaterally synchronous epileptic discharges.1 Sectioning the callosum to control drop attacks follows the rationale that the rapid synchronization of discharges between motor and premotor regions of both hemispheres is the basis.1 The standard approach to callosotomies always contemplated the anterior fibers of the callosum.2 Literature reports that anterior sections lead to unsatisfactory control of drop attacks, and results are improved when extended into a total callosotomy.2,3 This evidence coupled with diffusion tensor imaging (DTI) findings showing that motor and premotor fibers actually cross through posterior half of the callosum led us to hypothesize that selective section of the posterior half of the callosum would section all relevant motor fibers and control drop attacks to a similar extent to total callosotomies, with the advantage of sparing prefrontal interconnectivity3 and no split-brain syndrome. Both our series, one retrospective, followed by a new prospective study have confirmed SPC to be a safe procedure, leading to complete or greater than 90% control of epileptic falls in 85% of patients.1 The video presented here was recorded during a selective posterior callosotomy performed on a 13-yr-old girl who had hundreds of uncontrollable drop attacks per day. Falls were completely controlled with significant gains in psychomotor development and cognition, after 5 yr of follow-up. The patient provided signed consent to the surgical procedure, video acquisition, photo acquisition, and storage at operations, and the publication of this material.

Posterior reversible encephalopathy syndrome (PRES): Is DWI a prognosis factor?

INTRODUCTION: Posterior reversible encephalopathy syndrome is a clinicoradiologic entity with typical MR imaging showing a white matter vasogenic edema predominantly affecting the occipital and parietal lobes of the brain. The aim of this article is evaluated the importance of DWI as a prognosis factor in patients with PRES. MATERIALS AND METHODS: We reviewed data from 70 patients with PRES (35 with restricted DWI and 35 with no DWI abnormalities), that were admitted to Hospital São Lucas-PUCRS. These two groups were evaluated in age, sex, previous diseases and past medical history, use of medications, the neurologic manifestations, the highest blood pressure during the neurologic presentation and the highest creatinine during the period of observation. RESULTS: Evaluating 70 patients with PRES with a mean age of 25.4 years old (range from 2 to 74 years old; 55 female and 15 male) we identified 35 cases were brain MRI presents with restricted DWI. Restricted DWI was associated with higher mortality in 90 days (14.2% vs 0.0%; p: 0.027). CONCLUSIONS: Few articles present new data that will help clinicians in therapeutic decisions or that modify the knowledge of this syndrome. We suggested that restricted DWI is associated with a worst prognosis in PRES.

Heterotopia or overlaying cortex: What about in-between?

We describe a patient with unilateral periventricular nodular heterotopia (PNH) and drug-resistant epilepsy, whose SEEG revealed that seizures were arising from the PNH, with the almost simultaneous involvement of heterotopic neurons ("micronodules") scattered within the white matter, and subsequently the overlying cortex. Laser ablation of heterotopic nodules and the adjacent white matter rendered the patient seizure free. This case elucidates that "micronodules" scattered in white matter between heterotopic nodules and overlying cortex might be another contributor in complex epileptogenicity of heterotopia. Detecting patient-specific targets in the epileptic network of heterotopia creates the possibility to disrupt the pathological circuit by minimally invasive procedures.

Neuropsychiatric features of the coexistence of epilepsy and psychogenic nonepileptic seizures.

OBJECTIVE: To investigate demographic, epidemiologic and psychiatric features suggestive of the coexistence epilepsy (ES) and psychogenic nonepileptic seizures (PNES) that may contribute to precocious suspicion of the association. METHODS: In this exploratory study, all patients older than 16 years admitted to prolonged video-electroencephalogram monitoring were evaluated about demographic, epileptological and psychiatric features. Detailed psychiatric assessment using M.I.N.I.-plus 5.0, Beck Anxiety Inventory, Beck Depression Inventory and the Childhood Trauma Questionnaire (CTQ) was performed. Data were collected previous to the final diagnosis and patients with ES-only, PNES-only or coexistence of ES/PNES were compared. RESULTS: Of 122 patients admitted to epilepsy monitoring unit, 86 patients were included and 25 (29%) had PNES. Twelve (14%) had PNES-only, 13 (15%) had ES/PNES and the remaining 61 (71%) had only ES. A coexistence of ES and PNES was associated with clinical report of more than one seizure type (p˂0.001), nonspecific white matter hyperintensities on MRI (p < .001) and a past of psychotic disorder (p = .005). In addition, these patients had significantly more emotional abuse and neglect (p < .002 and 0.001, respectively). Somatization (including conversion disorder) was the most common diagnosis in patients with PNES- only (83%) and co-existing of PNES and ES (69.2%), differentiating both from ES-only patients (p < .001). CONCLUSION: The high prevalence of this coexistence ES/PNES in this study reinforces a need to properly investigate PNES, especially in patients with confirmed ES who become refractory to medical treatment with antiepileptic drugs. The neuropsychiatric assessment may help to diagnostic suspicion and in the planning of therapeutic interventions.

Suicide risk, temperament traits, and sleep quality in patients with refractory epilepsy.

OBJECTIVES: The objective of the study was to access the suicide risk (SR) in patients with refractory epilepsy and its association with temperament and sleep quality. METHODS: A total of 50 consecutive patients referred for epilepsy surgery evaluation in the Porto Alegre Epilepsy Surgery Program were included. All patients had a detailed neurologic and psychiatric evaluation, including video-electroencephalogram (VEEG), high-resolution magnetic ressonance imaging (MRI), and neuropsychologic assessment. In addition, structured questionnaires were applied: module C of the MINI-plus (International Neuropsychiatric Interview-Brazilian version 5.0.0), Affective and Emotional Composite Temperament Scale (AFECTS), and Pittsburgh Sleep Quality Index (PSQI). RESULTS: Ten patients (20.0%) showed an increased SR. The most frequent location of the epileptic focus was in the temporal lobe (50%; n=25). Final diagnosis on VEEG comprised epilepsy in 74.0% (n=37), psychogenic nonepileptic seizures (PNES) in 8.0% (n=4), and both in 12%. Thirty patients (60.0%) received surgery indication. Mood disorders were the main psychiatric diagnosis, found in 19 subjects (70.4%), with major depressive disorder (MDD) encountered in 15 patients (55.6%). In the group, SR was more frequent in patients with sleep disorders (p=0.001) and elevated scores of high emotional sensitivity (p=0.003). CONCLUSION: In this cohort of patients with highly refractory epilepsy, there was a significant association between SR, sleep disorders, and high emotional sensitivity. Careful evaluation of these factors should be performed in these patients to fully access SR.

Polymyositis without Beneficial Response to Steroid Therapy: Should Miyoshi Myopathy be a Differential Diagnosis?

BACKGROUND Miyoshi myopathy (MM) is an autosomal-recessive muscle disorder caused by mutations in the DYSF gene. Clinical features and histopathological changes in dysferlinopathies may mimic inflammatory myopathies and a high degree of clinical suspicion is required to guide the genetic investigation. CASE REPORT We report the case of a 16-year-old male who presented with severe bilateral calf pain and elevated CK levels (15 000 IU/l) who was on prolonged steroid therapy prompted by the clinical suspicion of inflammatory myopathy. Three years into his illness, he was referred for neuromuscular evaluation presenting with untreatable muscle pain and progressive weakness. The diagnosis of "refractory polymyositis" was revisited. Targeted exome sequencing revealed homozygous pathogenic mutations in the DYSF gene, confirming a diagnosis of Miyoshi myopathy. CONCLUSIONS Our case illustrates that severe muscle pain may be the initial feature of Miyoshi myopathy and should be considered in the differential diagnosis of inflammatory myopathies. Although the described patient reported partial clinical improvement in muscle pain, steroid treatment is not an effective therapy for dysferlinopathy patients and it did not prevent disease progression. In addition, we confirm the utility of next-generation sequencing approaches to myopathies, particularly in complex or unusual cases when muscle biopsy is not available.

Selective posterior callosotomy for drop attacks: A new approach sparing prefrontal connectivity.

OBJECTIVE: To evaluate a novel approach to control epileptic drop attacks through a selective posterior callosotomy, sparing all prefrontal interconnectivity. METHODS: Thirty-six patients with refractory drop attacks had selective posterior callosotomy and prospective follow-up for >4 years. Falls, episodes of aggressive behavior, and IQ were quantified. Autonomy in activities of daily living, axial tonus, and speech generated a functional score ranging from 0 to 13. Subjective effect on patient well-being and caregiver burden was also assessed. RESULTS: Median monthly frequency of drop attacks decreased from 150 to 0.5. Thirty patients (83%) achieved either complete or >90% control of the falls. Need for constant supervision decreased from 90% to 36% of patients. All had estimated IQ below 85. Median functional score increased from 7 to 10 (p = 0.03). No patient had decrease in speech fluency or hemiparesis. Caregivers rated the effect of the procedure as excellent in 40% and as having greatly improved functioning in another 50%. Clinical, EEG, imaging, and cognitive variables did not correlate with outcome. CONCLUSIONS: This cohort study with objective outcome assessment suggests that selective posterior callosotomy is safe and effective to control drop attacks, with functional and behavioral gains in patients with intellectual disability. Results are comparable to historical series of total callosotomy and suggest that anterior callosal fibers may be spared. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that selective posterior callosotomy reduces falls in patients with epileptic drop attacks.

Mother and daughter with adolescent-onset severe frontal lobe dysfunction and epilepsy / Mãe e filha com disfunção severa do lobo frontal e epilepsia com início na adolescência

ABSTRACT Familial cases of early-onset prominent frontal lobe dysfunction associated with epilepsy have not been reported to date. We report a mother and her only daughter with incapacitating behavioral manifestations of frontal lobe dysfunction and epilepsy of variable severity. The possibility of a hitherto undescribed genetic condition is discussed.

RESUMO Casos familiares de disfunção proeminente do lobo frontal associada a epilepsia com início precoce ainda não foram relatados. Nós descrevemos uma mãe e sua filha única com manifestações comportamentais incapacitantes de disfunção do lobo frontal e epilepsia de severidade variável. A possibilidade de uma condição genética ainda não descrita é discutida.

Posterior Reversible Encephalopathy Syndrome: Clinical Differences in Patients with Exclusive Involvement of Posterior Circulation Compared to Anterior or Global Involvement.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiologic syndrome not yet fully understood and characterized by transient neurologic symptoms in addition to typical radiological findings. There are only a few articles that describe the clinical differences between patients with PRES that involve carotid and vertebrobasilar circulations. Our study aims to further evaluate the differences between predominantly anterior and posterior circulation PRES. METHODS: We review 54 patients who had received the diagnosis of PRES from 2009 to 2015. The patients were divided into 2 groups: (1) exclusively in posterior zones; and (2) anterior plus posterior zones or exclusively anterior zones. Several clinical characteristics were evaluated, including the following: age, sex, previous diseases, the neurologic manifestations, the highest blood pressure in the first 48 hours of presentation, highest creatinine level during symptoms, and the neuroimaging alterations in brain magnetic resonance imaging. RESULTS: Mean age at diagnosis was 28.5 years old (9 men and 45 women) and mean systolic blood pressure among patients with lesions only in posterior zones was 162.1 mmHg compared to 179.2 mmHg in the anterior circulation. The most common symptoms in the 2 groups were headache and visual disturbances. DISCUSSION: PRES may have several radiological features. A higher blood pressure seems to be 1 of the factors responsible for developing widespread PRES, with involvement of carotid vascular territory. This clinical-radiological difference probably occurs because of the larger number of autonomic receptors in the carotid artery in comparison to the vertebral-basilar system.

Variables associated with co-existing epileptic and psychogenic nonepileptic seizures: a systematic review.

PURPOSE: Epileptic seizures (ES) have many mimickers, perhaps the most relevant being psychogenic nonepileptic seizures (PNES). The picture is even more challenging when PNES are associated with ES in a given patient. The aim of this research paper was to delineate the demographic, epileptological and psychiatric profile of that specific population. METHODS: A systematic review was carried out from 2000 to 2015 for articles in English, French, Italian, Spanish and Portuguese in PUBMED and EMBASE. Cohort or case-control studies reporting prospective or retrospective original data comparing patients with co-existing ES and PNES with those who had PNES only and ES only have been included. In retained studies, the presence of PNES was confirmed by video-electroencephalography (V-EEG). Forty-eight abstracts were identified. RESULTS: Nine studies were retained. Most showed that female gender predominated in both groups with PNES. Patients with co-existing ES and PNES take higher number of antiepileptic drugs (AEDs) than PNES alone. Two studies showed association of concomitant ES and PNES with earlier age of seizure onset. Localizing EEG features and ES type were evaluated in only two studies and their association with either group was inconclusive. Somatoform, conversion or cluster B personality disorders were more frequent in subjects with PNES than with ES. DISCUSSION: Patients with concomitant ES and PNES are highly heterogeneous, challenging differentiation on clinical grounds. A diagnosis of conversion or somatoform, anxiety disorders, and the use of a higher number of AEDs than psychiatric medications may have an association with co-existing ES and PNES. Further studies are warranted to differentiate patients who only have PNES from those with co-existing ES and PNES.

Epilepsia partialis continua triggered by traumatic hand injury: a peripheral tuning of brain excitability?

Epilepsia partialis continua is often refractory to antiepileptic medication and its causal relation to peripheral sensory stimuli has only rarely been suggested. We report a man who received surgery for temporal lobe epilepsy 10 years ago, who presented "de novo" epilepsia partialis continua following mild traumatic injury of the left hand. Continuous myoclonus of the left upper limb started the day after injury and persisted unabated for several weeks. Non-invasive evaluation was inconclusive. Acute electrocorticography during surgery under local anaesthesia revealed continuous, rhythmic spiking over the right sensorimotor cortex. Tailored excision of the posterior bank of the motor and adjacent sensory cortex immediately stopped the continuous myoclonus. Histopathology showed abnormal radial lamination and was compatible with focal cortical dysplasia type IA. Epilepsia partialis continua did not recur for seven years. Afferent stimuli from peripheral injury can disinhibit hyperexcitable sensorimotor cortex leading to epilepsia partialis continua. [Published with video sequences online].

Holmes' tremor as a delayed complication of thalamic stroke.

Movement disorders are not commonly associated with stroke. Accordingly, thalamic strokes have rarely been associated with tremor, pseudo-athetosis and dystonic postures. We present a 75-year-old man who developed a disabling tremor 1 year after a posterolateral thalamic stroke. This tremor had low frequency (3-4 Hz), did not disappear on focus and was exacerbated by maintaining a static posture and on target pursuit, which made it very difficult to perform basic functions. MRI demonstrated an old ischemic lesion at the left posterolateral thalamus. Treatment with levodopa led to symptom control. Lesions in the midbrain, cerebellum and thalamus may cause Holmes' tremor. Delayed onset of symptoms is usually seen, sometimes appearing 2 years after the original injury. This may be due to maturation of a complex neuronal network, leading to slow dopaminergic denervation. Further studies are needed to improve our understanding of this unique disconnection syndrome.

Mother and daughter with adolescent-onset severe frontal lobe dysfunction and epilepsy.

Familial cases of early-onset prominent frontal lobe dysfunction associated with epilepsy have not been reported to date. We report a mother and her only daughter with incapacitating behavioral manifestations of frontal lobe dysfunction and epilepsy of variable severity. The possibility of a hitherto undescribed genetic condition is discussed.

Casos familiares de disfunção proeminente do lobo frontal associada a epilepsia com início precoce ainda não foram relatados. Nós descrevemos uma mãe e sua filha única com manifestações comportamentais incapacitantes de disfunção do lobo frontal e epilepsia de severidade variável. A possibilidade de uma condição genética ainda não descrita é discutida.

Dysplastic Cerebellar Epilepsy: Complete Seizure Control Following Resection of a Ganglioglioma.

Subcortical epilepsy has been a controversial issue, partially settled by evidence showing seizure generation in hypothalamic hamartomas and also by reports of seizures caused by cerebellar lesions. We report 4-year-old girl with right hemifacial seizures and autonomic phenomena, in whom MRI showed an irregular mass in the right cerebellar peduncle. Despite several unremarkable video-EEG recordings, seizure origin in the lesion was hypothesized. Complete resection was feasible, histopathology showed a ganglioglioma, and she has been seizure free for 3 years. A fine line separates these developmental tumors from focal cortical dysplasia, and the homogeneous presentation of this entity led us to propose the terminology dysplastic cerebellar epilepsy.