Rani A. Sarkis

Surgical outcome following resection of rolandic focal cortical dysplasia

OBJECTIVE This study evaluates surgical outcomes in patients with balloon cell containing, focal cortical dysplasia (FCD type IIB) in the peri-rolandic region. We also address the question of, postoperative seizure worsening after an incomplete resection in this patient population. METHODS We retrospectively reviewed the clinical data on patients with pathologically proven FCD, who underwent epilepsy surgery over a 12-year period. Seizure outcomes were compared between, patients with rolandic FCD and non-rolandic frontal FCD. RESULTS Seventeen patients with rolandic and 22 patients with non-rolandic FCD were identified. Twelve patients were found to have type IIB lesions (8 rolandic). Seizure freedom at last follow up was, achieved in 59% of the rolandic subset of patients (including 75% seizure freedom in the rolandic type, IIB cases, as opposed to 44% of rolandic non-type IIB and 75% of type IIB outside the rolandic, region). New postoperative neurological deficits occurred in 59% of the rolandic subgroup and were, independent of pathology. Three patients (3/8) with incompletely resected rolandic type IIB lesions, developed status epilepticus postoperatively; all 3 patients became seizure free following a second, more extensive surgical resection. CONCLUSIONS Patients with rolandic FCD can achieve a good surgical outcome after a complete, resection. However, an incomplete surgical resection in this patient population may lead to acute, postoperative seizure worsening.

When is a postoperative seizure equivalent to epilepsy recurrence after epilepsy surgery

Purpose:  Up to one‐half of epilepsy surgery patients will have at least one seizure after surgery. We aim to characterize the prognosis following a first postoperative seizure, and provide criteria allowing early identification of recurrent refractory epilepsy.

Chronic dizocilpine or apomorphine and development of neuropathy in two animal models II: Effects on brain cytokines and neurotrophins

Dopaminergic and glutamatergic mechanisms are involved in the development and modulation of neuropathy. Cytokines and neurotrophins can be also involved in the supraspinal maintenance of neuropathic pain. We assessed the effects of chronic intraperitoneal (ip) injection of dizocilpine (MK-801), a N-methyl-d-Aspartate (NMDA) noncompetitive receptor antagonist, or apomorphine (APO), a dopamine (DA) D1 and D2 receptor agonist, on neuropathic manifestations in the chronic constriction injury (CCI) and the spared nerve injury (SNI) models of neuropathy in rats. Six groups of rats were subjected to SNI or CCI (3 groups each) neuropathy and 5-7 days later received daily ip injections of saline, MK-801, or APO for two weeks. An additional control group was subjected to sham surgery without nerve lesion or injections. Rats were then sacrificed, and levels of IL-1β, IL-6, NGF, BDNF and GDNF were determined in the cingulum, striatum, and hippocampus. In both models, the neuropathy seen in the saline group was associated with decreased BDNF and an increase in IL-1β, IL-6, NGF and GDNF in most brain regions when compared to sham group. Chronic systemic MK-801 or APO injections decreased the neuropathic manifestations in both models, increased the BDNF level and modulated the other cytokines and neurotrophins. This modulation depended on the neuropathy model and the region/side of the brain studied. Our results showed that the changes in surpraspinal cytokines and neurotrophins could parallel neuropathic manifestations. These changes and the observed hyperalgesia can be modulated by chronic systemic injections of NMDA antagonists or DA agonists.

Seizure outcomes following multilobar epilepsy surgery.

Purpose:  Outcomes following unilobar surgeries for refractory epilepsy have been well described. However, little is known about long‐term seizure outcomes following multilobar resections. The aim of the current study was to identify long‐term seizure control and predictors of seizure recurrence in this patient population.

Autonomic changes following generalized tonic clonic seizures: An analysis of adult and pediatric patients with epilepsy

OBJECTIVE Sudden unexpected death in epilepsy (SUDEP) is the most common cause of mortality directly related to epilepsy. Its incidence is higher in adult patients and its pathophysiology remains poorly understood, but likely involves autonomic dysregulation following generalized tonic clonic seizures (GTCS). In the current study, we aimed to analyze post-ictal autonomic changes following GTCS in adult and pediatric patients. METHODS Patients admitted to the epilepsy monitoring unit were prospectively recruited, and wore an electrodermal activity (EDA) wrist sensor that continuously measured sympathetic activity while being monitored with EEG and EKG electrodes. Peri-ictal EDA parameters were assessed as a measure of sympathetic activity. Peri-ictal parasympathetic activity was determined through the high frequency component (HF) analysis of heart rate variability (HRV). The duration of post-ictal generalized EEG suppression (PGES) was also documented. RESULTS Twenty patients with GTCS were included in the study on whom 30 GTCS were recorded. PGES duration strongly correlated with age (r=0.62, p=0.004) and measures of the EDA response. After controlling for PGES duration, we found pediatric patients had greater sympathetic activation measured as log rising portion of the area under the curve of the EDA response (β=+0.67, p=0.034) and a higher degree of vagal suppression measured as maximal percentage change of HF power (β=-12.65, p=0.0036). CONCLUSION Sympathetic activity can be measured in the peri-ictal period, and directly correlates with PGES duration. Age is a significant determinant of the sympathetic and parasympathetic response following a GTCS; given the same PGES duration, pediatric patients demonstrate stronger sympathetic activation and higher vagal suppression. However, the increase in PGES duration with age and the associated autonomic dysregulation may provide clues as to why there is a variable vulnerability to SUDEP across age groups.

Chronic dizocilpine or apomorphine and development of neuropathy in two rat models I: behavioral effects and role of nucleus accumbens.

Dopaminergic and glutamatergic inputs converge on nucleus accumbens (NAC) and affect the neuropathic pain. We tested the effects of daily systemic administration of dizocilpine (MK-801), a N-methyl-d-Aspartate (NMDA) noncompetitive receptor antagonist, or apomorphine (APO), a dopamine (DA) D1 and D2 receptor agonist, on neuropathic manifestations in the chronic constriction injury (CCI) and the spared nerve injury (SNI) models of mononeuropathy in rats. Six groups of rats were subjected to CCI or SNI neuropathy and 5-7 days later received daily intraperitoneal (ip) injections of saline, MK-801, or APO for two weeks. Tests for nociception and motor behaviors were performed at regular intervals. Tactile and cold allodynia were assessed using von Frey hairs or acetone drops, respectively. Heat hyperalgesia was assessed by the paw withdrawal test. Tests were performed before administering the daily injections. Another four groups of rats were subjected to SNI surgery, and then had their NAC (contralateral to the lesioned paw) perfused for two weeks with MK-801, saline, APO+ascorbic acid, or ascorbic acid alone using mini-osmotic pumps. Behavioral manifestations were assessed as above. Systemic daily injections of MK-801 and APO markedly attenuated the neuropathic manifestations in the CCI and SNI models with a minimal effect on cold allodynia. The same results were seen in the SNI model with chronic perfusion of NAC. Our results suggest that daily systemic administration of DA agonists and NMDA antagonists can attenuate neuropathic pain manifestations and that the NAC is involved in the modulation of neuropathic-like behaviors.

Clinical and Neurophysiologic Characteristics of Unprovoked Seizures in Patients Diagnosed With Dementia

Seizures are a common comorbid condition in patients with dementia, but their characteristics have been poorly described. The authors performed a retrospective chart review using ICD-9 diagnosis codes consistent with seizures and with dementia. Seventy-seven patients were identified. Average age at onset was 68.1 years for cognitive symptoms, 71.5 years for dementia, and 73.9 years for seizures. Seizures preceded or followed cognitive symptoms (4.3 years before and 18.7 years after). At last follow-up, 12% of patients continued to have seizures. Findings show that unprovoked seizures can precede or follow the onset of dementia, but these seizures are controlled with medications in the majority of patients.

MRI findings in cryptococcal meningitis of the non-HIV population.

Objectives:Cryptococcal meningitis is an opportunistic infection which can afflict immunocompetent and immunocompromised individuals. Imaging findings in the HIV population are well described; however, few studies have focused on the non-HIV population.The purpose of this study is to characterize clinical and magnetic resonance imaging (MRI) findings in the non-HIV population. Methods:We performed a retrospective chart review of patients with positive CSF cryptococcal antigen (between 1997 and 2009) who were not HIV positive. Only patients with MRIs of the brain were included. Data collected included CSF findings, blood and CSF cryptococcal titers, and information regarding the use of immunosuppressant drugs. Results:Nineteen patients fulfilled study criteria, and 74% of the patients had abnormal imaging.Ten patients were on immunosuppressants due to cancer, organ transplantation, or presumed vasculitis. Four patients had no known risk factors and 2 patients had idiopathic low CD4 counts.MRI findings in cryptococcal meningitis included leptomeningeal enhancement with or without a micronodular pattern, microcystic prominence involving the temporal lobes or basal ganglia, ventriculomegaly, and a brain abscess. Two patients had posterior fossa cysts at the foramen of Luschka. Five patients had a normal MRI. Conclusions:MRI findings in cryptococcal meningitis of the non-HIV population were more common in our series than previously recognized. In this patient population, leptomeningeal enhancement and intraventricular cystic lesions were more common than intraparenchymal findings.

Neuropsychiatric and seizure outcomes in nonparaneoplastic autoimmune limbic encephalitis.

INTRODUCTION Autoimmune limbic encephalitis is an inflammatory condition often associated with an underlying neoplasm. However, a subset of patients does not have an underlying tumor and have a nonparaneoplastic form of this condition. The focus in the literature has been on the acute phase of this illness, but long-term follow-up is lacking. METHODS A retrospective chart review, over a period of 15 years, of patients carrying a diagnosis of encephalitis was performed. Inclusion criteria included a clinical presentation consistent with limbic encephalitis (subacute behavioral change, seizures, or anterograde memory decline) and an identifiable autoantibody, inflammatory CSF (>5 white blood cells/mm(3)), or limbic hyperintensities on MRI. Readmission rates and long-term psychiatric, psychosocial, and seizure outcomes were evaluated. RESULTS A total of 16 patients were identified. Clinical presentation included new-onset seizures in 14 (88%), behavioral changes in 7 (44%), and memory decline in 5 (31%). Four (25%) patients presented with status epilepticus. Five patients had antibodies against NMDAR (N-methyl-D-aspartate receptor) and four against VGKC (voltage gated potassium channel) complex. An inflammatory CSF was noted in 7 (44%) and MRI changes in 9 (56%). Four were readmitted during the follow-up period. Around half the patients continued to have medically drug/treatment-refractory seizures, while 7 (44%) had a new psychiatric diagnosis (mood disorder, anxiety disorder, or impulse control disorder). The majority of the patients continued to reside at home, while 43% of previously employed patients lost employment. CONCLUSION Nonparaneoplastic autoimmune limbic encephalitis is a neuropsychiatric condition presenting with a combination of seizures (sometimes status epilepticus), behavioral changes, and memory decline. After the acute phase, patients are at risk of readmissions, medically refractory seizures, chronic mood and anxiety disorders, and loss of employment.

Predictors of decline in verbal fluency after frontal lobe epilepsy surgery.

Few studies have focused on language changes following frontal lobe epilepsy (FLE) surgery. The aim of the current study is to quantify the role of resection location and size in verbal fluency decline after FLE surgery and to examine its predictors. A retrospective chart review identified 36 adult patients who underwent FLE surgery. Verbal fluency was assessed using the Controlled Oral Word Association Test (COWAT). Nine (25%) of the patients had significant decline. Binary logistic regression incorporating side of resection and preoperative COWAT score significantly predicted decline and accounted for 25% of the variance. A trend was also noted for decliners to have higher postoperative seizure recurrence (p=0.067). There was no effect of size of resection. Patients undergoing FLE surgery are at risk of verbal fluency decline, especially if they have a high presurgical verbal fluency score, undergo a frontal lobe resection in the language dominant hemisphere, and have poor seizure outcome.