What type of FCD is considered the best candidate for curative surgery, even if it involves lesions in brain eloquent areas? a) Type I FCD b) Type IIa FCD c) Type IIb FCD d) Type III FCD What is the most common surgical procedure for FCD that aims to eliminate the source of seizures while minimizing damage to healthy brain tissue? a) Lobectomy b) Vagus Nerve Stimulation (VNS) c) Resection d) Responsive Neurostimulation (RNS) In cases where open surgery might not be suitable, what minimally invasive technique can be used to target and destroy dysplastic tissue? a) Intracranial EEG monitoring b) Laser interstitial thermal therapy (LITT) c) Functional MRI (fMRI) d) PET scan What is the primary goal of resection surgery for FCD? a) Complete removal of healthy brain tissue b) Elimination of all cognitive functions c) Removal of the dysplastic tissue while preserving healthy tissue d) Reducing the size of the dysplastic area Which factor is crucial for achieving seizure freedom following surgery for FCD? a) The type of medications used b) Completeness of resection c) The patient's age at the time of surgery d) The number of electrodes used during surgery What is the purpose of intraoperative electrocorticography (ECOG) during FCD surgery? a) To monitor the patient's blood pressure b) To assess cognitive function c) To pinpoint the exact location of the dysplastic tissue d) To perform laser interstitial thermal therapy In cases where surgery is not feasible, what alternative treatment option involves monitoring brain activity and delivering electrical stimulation to interrupt seizures? a) Intracranial EEG monitoring b) Lobectomy c) Vagus Nerve Stimulation (VNS) d) Responsive Neurostimulation (RNS) What type of preoperative assessment helps in understanding the potential risks and benefits of FCD surgery, particularly regarding cognitive and neurological functions? a) Neuropsychological Assessment b) Physical fitness evaluation c) Blood pressure monitoring d) Dental examination What type of FCD surgery involves inserting a laser fiber into the brain through a small incision to heat and destroy the dysplastic tissue? a) Intracranial EEG monitoring b) Vagus Nerve Stimulation (VNS) c) Lobectomy d) Laser interstitial thermal therapy (LITT) What is the ultimate goal of FCD surgery with respect to cognitive function? a) Preservation of cognitive and neurological functions b) Complete elimination of cognitive function c) Inducing temporary amnesia d) Enhancing cognitive abilities
Epilepsy surgery
Temporal lobe epilepsy
Temporal lobe epilepsy
Mesial temporal sclerosis (MTS) is the most common cause of intractable temporal lobe epilepsy.
Clinical features
Temporal lobe epilepsy (TLE) is a chronic neurological condition characterized by recurrent seizures (epilepsy) which originate in the temporal lobe with progressive neurological disabilities, including cognitive deficit, anxiety and depression.
The seizures involve sensory changes, for example smelling an unusual odour that is not there, and disturbance of memory.
Treatment
Based on the promising results of randomized controlled trials, deep brain stimulation (DBS) and responsive neurostimulation (RNS) are increasingly used in the treatment of patients with drug-resistant epilepsy. Drug-resistant temporal lobe epilepsy (TLE) is an indication of either DBS of the anterior nucleus of the thalamus (ANT) or temporal lobe (TL) RNS, but there are no studies that directly compare seizure benefits and adverse effects associated with these therapies in this patient population.
Mesial temporal lobe epilepsy
Mesial temporal lobe epilepsy.
Neocortical temporal lobe epilepsy
Neocortical temporal lobe epilepsy
Unilateral temporal lobe epilepsy
Unilateral temporal lobe epilepsy
Case series
Sixty patients with drug-resistant temporal lobe epilepsy who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence (n = 7/group). They also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in non-depressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy 1)
Yang et al., therefore, examined all patients who underwent ANT-DBS or TL-RNS for drug-resistant TLE.
They performed a retrospective review of patients who were treated with either ANT-DBS or TL-RNS for drug-resistant TLE with at least 12 months of follow-up. Along with the clinical characteristics of each patient’s epilepsy, seizure frequency was recorded throughout each patient’s postoperative clinical course.
26 patients underwent ANT-DBS implantation, and 32 patients underwent TL-RNS for drug-resistant TLE. Epilepsy characteristics of both groups were similar. Patients who underwent ANT-DBS demonstrated a median seizure reduction of 58% at 12-15 months, compared to a median seizure reduction of 70% at 12-15 months in patients treated with TL-RNS (p > 0.05). The responder rate (percentage of patients with a 50% decrease or more in seizure frequency) was 54% for ANT-DBS and 56% for TL-RNS (p > 0.05). Incidence of complications and stimulation-related side effects did not significantly differ between therapies.
They demonstrated in a single-center experience that patients with drug-resistant TLE benefit similarly from either ANT-DBS or TL-RNS. Selection of either ANT-DBS or TL-RNS may therefore depend more heavily on patient and provider preference, as each has unique capabilities and configurations. Future studies will consider subgroup analyses to determine if specific patients have greater seizure frequency reduction from one form of neuromodulation strategy over another 2).
1)
Li XL, Wang S, Tang CY, Ma HW, Cheng ZZ, Zhao M, Sun WJ, Wang XF, Wang MY, Li TF, Qi XL, Zhou J, Luan GM, Guan YG. Translocation of High Mobility Group Box 1 From the Nucleus to the Cytoplasm in Depressed Patients With Epilepsy. ASN Neuro. 2022 Jan-Dec;14:17590914221136662. doi: 10.1177/17590914221136662. PMID: 36383501.
2)
Yang JC, Bullinger KL, Dickey AS, Karakis I, Alwaki A, Cabaniss BT, Winkel D, Rodriguez-Ruiz A, Willie JT, Gross RE. Anterior Nucleus of the Thalamus Deep Brain Stimulation Versus Temporal Lobe Responsive Neurostimulation for Temporal Lobe Epilepsy. Epilepsia. 2022 Jun 15. doi: 10.1111/epi.17331. Epub ahead of print. PMID: 35704344.
Epilepsy diagnosis
Epilepsy diagnosis
The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences
Imaging
Imaging is pivotal in the evaluation and management of patients with seizure disorders.
Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist the performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment 1).
Magnetic resonance imaging
Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, Low-grade glioma and malformations of cortical development has been demonstrated.
Positron emission tomography in epilepsy
Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of aresearch was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG.
Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2′-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ.
Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data.
Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation 2).
Cerebrospinal fluid analysis
Cerebrospinal fluid analysis for epilepsy
Automatic seizure detection
Genetic testing
Results of a cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes 3).
1)
Cendes F, Theodore WH, Brinkmann BH, Sulc V, Cascino GD. Neuroimaging of epilepsy. Handb Clin Neurol. 2016;136:985-1014. doi: 10.1016/B978-0-444-53486-6.00051-X. PubMed PMID: 27430454.
2)
Avendaño-Estrada A, Velasco F, Velasco AL, Cuellar-Herrera M, Saucedo-Alvarado PE, Marquez-Franco R, Rivera-Bravo B, Ávila-Rodríguez MA. Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy. Stereotact Funct Neurosurg. 2019 Nov 13:1-9. doi: 10.1159/000503692. [Epub ahead of print] PubMed PMID: 31722358.
3)
McKnight D, Morales A, Hatchell KE, Bristow SL, Bonkowsky JL, Perry MS, Berg AT, Borlot F, Esplin ED, Moretz C, Angione K, Ríos-Pohl L, Nussbaum RL, Aradhya S; ELEVIATE Consortium, Haldeman-Englert CR, Levy RJ, Parachuri VG, Lay-Son G, de Montellano DJD, Ramirez-Garcia MA, Benítez Alonso EO, Ziobro J, Chirita-Emandi A, Felix TM, Kulasa-Luke D, Megarbane A, Karkare S, Chagnon SL, Humberson JB, Assaf MJ, Silva S, Zarroli K, Boyarchuk O, Nelson GR, Palmquist R, Hammond KC, Hwang ST, Boutlier SB, Nolan M, Batley KY, Chavda D, Reyes-Silva CA, Miroshnikov O, Zuccarelli B, Amlie-Wolf L, Wheless JW, Seinfeld S, Kanhangad M, Freeman JL, Monroy-Santoyo S, Rodriguez-Vazquez N, Ryan MM, Machie M, Guerra P, Hassan MJ, Candee MS, Bupp CP, Park KL, Muller E 2nd, Lupo P, Pedersen RC, Arain AM, Murphy A, Schatz K, Mu W, Kalika PM, Plaza L, Kellogg MA, Lora EG, Carson RP, Svystilnyk V, Venegas V, Luke RR, Jiang H, Stetsenko T, Dueñas-Roque MM, Trasmonte J, Burke RJ, Hurst ACE, Smith DM, Massingham LJ, Pisani L, Costin CE, Ostrander B, Filloux FM, Ananth AL, Mohamed IS, Nechai A, Dao JM, Fahey MC, Aliu E, Falchek S, Press CA, Treat L, Eschbach K, Starks A, Kammeyer R, Bear JJ, Jacobson M, Chernuha V, Meibos B, Wong K, Sweney MT, Espinoza AC, Van Orman CB, Weinstock A, Kumar A, Soler-Alfonso C, Nolan DA, Raza M, Rojas Carrion MD, Chari G, Marsh ED, Shiloh-Malawsky Y, Parikh S, Gonzalez-Giraldo E, Fulton S, Sogawa Y, Burns K, Malets M, Montiel Blanco JD, Habela CW, Wilson CA, Guzmán GG, Pavliuk M. Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice. JAMA Neurol. 2022 Oct 31. doi: 10.1001/jamaneurol.2022.3651. Epub ahead of print. PMID: 36315135.
Epilepsy surgery indications
Epilepsy surgery indications
Epilepsy surgery is an established safe and effective treatment for selected candidates with drug-resistant epilepsy. In a opinion piece, Hale et al. from the Children’s of Alabama, Great Ormond Street Hospital, Nemours Children’s Hospital outlined the clinical and experimental evidence for selectively considering epilepsy surgery prior to drug resistance. The rationale for expedited surgery is based on the observations that, 1) a high proportion of patients with lesional epilepsies (e.g. focal cortical dysplasia, epilepsy associated tumours) will progress to drug-resistance, 2) surgical treatment of these lesions, especially in non-eloquent areas of brain, is safe, and 3) earlier surgery may be associated with better seizure outcomes. Potential benefits beyond seizure reduction or elimination include less exposure to anticonvulsants (ASM), which may lead to improved developmental trajectories in children and optimize long-term neurocognitive outcomes and quality of life. Further, there exists emerging experimental evidence that brain network dysfunction exists at the onset of epilepsy, where continuing dysfunctional activity could exacerbate network perturbations. This in turn could lead to expanded seizure foci and contribution to the comorbidities associated with epilepsy. Taken together, they rationalize that epilepsy surgery, in carefully selected cases, may be considered prior to drug resistance. Lastly, they outlined the path forward, including the challenges associated with developing the evidence base and implementing this paradigm into clinical care 1).
20% of patients continue to have seizures despite aggressive medical management with antiepileptic drugs AEDs. Many of these patients may be candidates for surgical procedures to control their seizures 2).
Seizure disorder must be severe, medically refractory with satisfactory trials of tolerable medication for at least 1 year, and disabling to the patient. Medically refractory epilepsy is usually considered two attempts of high-dose monotherapy with two distinct AEDs, and one attempt at polytherapy.
The three general categories of patients suitable for seizure surgery have 3):
a) temporal origin: the largest group of surgical candidates (especially mesial temporal lobe epilepsy (MTLE) which is often medically refractory)
b) extratemporal origin
- symptomatic generalized seizures: e.g. Lennox-Gastaut syndrome.
- unilateral, multifocal epilepsy associated with infantile hemiplegia syndrome.
The goal is to eliminate seizures or significantly reduce seizure burden.
In most state-of-the-art epilepsy units, resective epilepsy surgery is currently the standard treatment for intractable epilepsy. Generally, the success rate, defined as a seizure-free status or Engel class I, is between 62% and 71%, as compared to 14% in non-operated cases 4) 5).
Generally, surgery is considered in patients whose seizures cannot be controlled by adequate trials of two different medications. Epilepsy surgery has been performed for more than a century, but its use dramatically increased in the 1980s and ’90s, reflecting its efficacy in selected patients.
Patients with comorbid psychosis and temporal lobe drug-resistant epilepsy may benefit from epilepsy surgery under close psychiatric supervision 6).
Epilepsy surgery is an effective and safe therapeutic modality in childhood. In children with extratemporal epilepsy, more careful interpretation of clinical and investigative data is needed to achieve favorable seizure outcome 7).
Tuberous sclerosis complex surgery
see Tuberous sclerosis complex surgery.
1)
Hale AT, Chari A, Scott RC, Cross JH, Rozzelle CJ, Blount JP, Tisdall MM. Expedited epilepsy surgery prior to drug resistance in children: a frontier worth crossing? Brain. 2022 Jul 27:awac275. doi: 10.1093/brain/awac275. Epub ahead of print. PMID: 35883201.
2)
Engel JJ. Surgery for Seizures. N Engl J Med. 1996; 334:647–652
3)
National Institutes of Health Consensus Development Conference. Surgery for Epilepsy. JAMA. 1990; 264:729–733
4)
Edelvik A, Rydenhag B, Olsson I, et al. Long-term outcomes of epilepsy surgery in Sweden: a national prospective and longitudinal study. Neurology 2013;81:1244–51.
5)
Sarkis RA, Jehi L, Najm IM, et al. Seizure outcomes following multilobar epilepsy surgery. Epilepsia 2012;53:44–50.
6)
D’Alessio L, Scévola L, Fernandez Lima M, Oddo S, Solís P, Seoane E, Kochen S. Psychiatric outcome of epilepsy surgery in patients with psychosis and temporal lobe drug-resistant epilepsy: A prospective case series. Epilepsy Behav. 2014 Jul 15;37C:165-170. doi: 10.1016/j.yebeh.2014.06.002. [Epub ahead of print] PubMed PMID: 25036902.
7)
Kim SK, Wang KC, Hwang YS, Kim KJ, Chae JH, Kim IO, Cho BK. Epilepsy surgery in children: outcomes and complications. J Neurosurg Pediatr. 2008 Apr;1(4):277-83. doi: 10.3171/PED/2008/1/4/277. PubMed PMID: 18377302.
Posterior quadrant disconnection
Posterior quadrant disconnection
Posterior quadrant disconnection (PQD) is surgery for refractory unilateral temporo-parieto-occipital epilepsy to limit the propagation of epileptic discharges. As incomplete disconnection can lead to residual seizures, detailed procedures are presented by Umaba et al. using a cadaveric brain, three-dimensional (3D) reconstruction and simulation models, and intraoperative photographs.
A formalin-fixed adult cadaveric brain was dissected to show each step in PQD. Using 3D preoperative planning software, we reconstructed 3D models from computed tomography and magnetic resonance imaging, and visualized operative views. Intraoperative photographs were taken from the case of a 7-year-old girl with temporo-parieto-occipital epilepsy.
Fronto-temporo-parietal craniotomy is performed. The Sylvian fissure is widely dissected and the insular cortex is exposed. The temporal stem is disconnected along the inferior periinsular sulcus. The disconnection is extended from the limen insulae to the atrium of the lateral ventricle (LV). The fibers between the head of the hippocampus and the amygdala are disconnected. The parietal lobe is disconnected along the postcentral sulcus and the disconnection is connected to the atrium of the LV. At the medial surface of the parietal lobe, the disconnection is continued until reaching the corpus callosum (CC). The splenium of the CC is disconnected via the medial wall of the LV. The fornix is divided in the atrium of the LV. After these steps, disconnection of the unilateral tempo-parieto-occipital lobe is achieved while preserving the arteries and veins.
Inclusion of views from cadaveric brains, 3D reconstruction and simulation models, and intraoperative photographs facilitates a clearer anatomical understanding of PQD 1).
Twenty hemispheres were dissected according to Klingler’s fiber dissection technique illustrating the peri-insular (temporal stem, superior longitudinal fasciculus, corona radiata) and mesial disconnection (mesiotemporal cortex, cingulum, and corpus callosum).
Extensive white matter tract disconnection is obtained after posterior quadrant disconnection. Callosal fibers connecting the anterior most part of the parietal cortex invariably ran through the isthmus of the corpus callosum and need to be disconnected, while frontal lobe connections including the corticospinal tract and the anterior two-thirds of the corpus callosum are spared during the procedure.
The findings suggest the involvement of both the splenium and the isthmus in interhemispheric propagation in posterior cortex epilepsies. Sectioning the total extent of the posterior one-third of the corpus callosum might therefore be necessary to achieve optimal outcomes in posterior quadrant epilepsy surgery 2).
Case series
Nooraine et al. analyzed the data of seven (n = 7) consecutive posterior quadrant epilepsy patients who underwent posterior quadrant disconnection with a mean age of 8.5 years over the last three years of which 4 were male and 3 females. All patients underwent extensive pre-surgical evaluation including detailed history, examination, prolonged video EEG recordings, neuropsychological testing, MRI brain, DTI, PET scan (n = 6), fMRI (n = 4), WADA test (n = 1) and invasive recording (n = 1), Of seven patients four had left sided pathology and three had right sided pathology. All patients except one underwent pure disconnection and one underwent partial resection.
Posterior quadrant disconnection is effective surgical procedure for medically refractory epilepsy arising from the posterior quadrant in carefully selected patients without morbidity or functional disability across various age groups especially in children. In our series, all seven patient had good seizure outcome and none had functional disabilities 3).
Ten patients who were surgically treated using the posterior quadrantectomy (PQT) were enrolled in this study. Surgical outcome was analyzed as seizure-free or not at 2 years after surgery. Psychomotor development was evaluated by the scores of mental developmental index (MDI) and psychomotor developmental index (PDI) in the Bayley Scales of Infant Development II preoperatively, and at 6 and 12 months after the PQT. RESULTS:
Eight of 10 patients were seizure-free. Patients without complete elimination of the angiomatous areas had residual seizures. Average MDI and PDI scores before the surgery were 64.8 and 71.6, respectively. Scores of MDI at 6 and 12 months after the PQT in seizure-free patients were 80.5 and 84.5, respectively (p < 0.01). PDI scores at these postoperative intervals were 87.3 and 86.4, respectively (p < 0.05). Patients with residual seizures did not improve in either MDI or PDI. SIGNIFICANCE:
The PQT achieved good seizure control and improved psychomotor development in patients with SWS. The complete deafferentation of angiomatous areas is required for seizure-free results and psychomotor developmental improvement 4).
There were 3 males and 7 females (median age 8.7 years; range 4.2-22.1 years). The affected hemisphere was the left in 3 patients and the right in 7. The patients’ median age at seizure onset was 3.0 years (range 0.2-8.3 years). The median duration of epilepsy before surgery was 5.2 years (range 1.3-17.2 years). The underlying pathology was TPO malformation of cortical development in 5 patients, and venous infarction, posterior hemispheric quadrant atrophy, Sturge-Weber syndrome, cortical involvement of a systemic lupus erythematosus, and gliosis after cerebral tumor treatment in 1 each. In 6 children, a pure TPO disconnection was performed; in 2 patients, the temporal lobe was resected and parietooccipital disconnection was performed. The 2 remaining patients had had previous epilepsy surgery that was extended to a TPO disconnection: disconnection of the occipital lobe (n = 1) and resection of the temporal lobe (n = 1). The authors encountered no complications while performing surgery. No patient needed blood replacement therapy. No patient developed CSF disturbances that warranted treatment. Nine of 10 patients are currently seizure free since surgery (Wieser Class 1a) at a median follow-up time of 2.1 years (range 4 months to 8.1 years). CONCLUSIONS:
Temporoparietooccipital disconnection is a safe and effective motor-sparing epilepsy surgery in selected cases. Technical adjuncts facilitate a better intraoperative visualization and orientation, thereby enabling a less invasive approach than previously suggested 5).
there were 13 patients with a median age of 17 years. All patients had extensive presurgical evaluation that provided concordant evidence localizing the lesion and seizure focus to the posterior quadrant. The objective of the surgery was to eliminate the effect of the epileptogenic tissue and preserve motor and sensory functions. RESULTS:
During the course of this study period of 15 years, the surgical procedure performed evolved toward incorporating more techniques of disconnection and minimizing resection. Three technical variants were thus utilized in this series, namely, (i) anatomical posterior quadrantectomy (APQ), (ii) functional posterior quadrantectomy (FPQ), and (iii) periinsular posterior quadrantectomy (PIPQ). After a median follow-up period of 6 years, 12/13 patients had Engel’s Class I seizure outcome. CONCLUSION:
The results of surgery for posterior quadrantic epilepsy have yielded excellent seizure outcomes in 92% of the patients in the series with no mortality or major morbidity. The incorporation of disconnective techniques in multilobar surgery has maintained the excellent results obtained earlier with resective surgery 6).
Case reports
An enhanced operative video presents the illustrative case of a total Posterior quadrant disconnection indicated for a 15-year-old boy with Sturge-Weber syndrome suffering from seizure recurrence after a partial PQD. Barrit et al. described the surgical procedure with emphasis on relevant anatomy and multimodal intraoperative guidance in three steps: (i) parieto-occipital disconnection, (ii) posterior callosotomy, and (iii) temporal disconnection/resection. Pearls and pitfalls of surgical management are discussed.
Posterior quadrant disconnection is a less invasive surgical option than typical hemispherectomy for selected indications of posterior multilobar epilepsy 7).
1)
Umaba R, Uda T, Nakajo K, Kawashima T, Tanoue Y, Koh S, Uda H, Kunihiro N, Matsusaka Y, Ohata K. Anatomical understanding of posterior quadrant disconnection from cadaveric brain, 3D reconstruction and simulation model, and intraoperative photographs. World Neurosurg. 2018 Aug 30. pii: S1878-8750(18)31951-X. doi: 10.1016/j.wneu.2018.08.168. [Epub ahead of print] PubMed PMID: 30172981.
2)
Verhaeghe A, Decramer T, Naets W, Van Paesschen W, van Loon J, Theys T. Posterior Quadrant Disconnection: A Fiber Dissection Study. Oper Neurosurg (Hagerstown). 2018 Jan 1;14(1):45-50. doi: 10.1093/ons/opx060. PubMed PMID: 29253283.
3)
Nooraine J, R SK, Iyer RB, Rao RM, Raghavendra S. Posterior quadrant disconnection for refractory epilepsy: A case series. Ann Indian Acad Neurol. 2014 Oct;17(4):392-7. doi: 10.4103/0972-2327.144006. PubMed PMID: 25506159; PubMed Central PMCID: PMC4251011.
4)
Sugano H, Nakanishi H, Nakajima M, Higo T, Iimura Y, Tanaka K, Hosozawa M, Niijima S, Arai H. Posterior quadrant disconnection surgery for Sturge-Weber syndrome. Epilepsia. 2014 May;55(5):683-9. doi: 10.1111/epi.12547. Epub 2014 Feb 22. PubMed PMID: 24621276.
5)
Dorfer C, Czech T, Mühlebner-Fahrngruber A, Mert A, Gröppel G, Novak K, Dressler A, Reiter-Fink E, Traub-Weidinger T, Feucht M. Disconnective surgery in posterior quadrantic epilepsy: experience in a consecutive series of 10 patients. Neurosurg Focus. 2013 Jun;34(6):E10. doi: 10.3171/2013.3.FOCUS1362. PubMed PMID: 23724834.
6)
Daniel RT, Meagher-Villemure K, Farmer JP, Andermann F, Villemure JG. Posterior quadrantic epilepsy surgery: technical variants, surgical anatomy, and case series. Epilepsia. 2007 Aug;48(8):1429-37. Epub 2007 Apr 18. PubMed PMID: 17441997.
7)
Barrit S, Park EH, Madsen JR. Posterior quadrant disconnection for refractory epilepsy: how I do it. Acta Neurochir (Wien). 2022 May 17. doi: 10.1007/s00701-022-05221-x. Epub ahead of print. PMID: 35578117.
Hemispherectomy for Rasmussen’s encephalitis
Hemispherectomy for Rasmussen’s encephalitis
Compared with functional hemispherectomy and hemisphere disconnection, anatomical hemispherectomy elicited better seizure outcomes with an acceptable level of complications. Early-stage operations might lead to better cognitive status, but they are associated with a high risk of IQ decline 1).
Obtaining complete disconnection is critical for favorable seizure outcomes from hemispherectomy, and neurosurgeons should have a low threshold to reoperate in patients with Rasmussen’s encephalitis with recurrent seizures. Rapid progression of motor deficits and bilateral MRI abnormalities may indicate a subpopulation of patients with RE with an increased risk of needing reoperation. Overall, they believe that hemispherectomy is a curative surgery for the majority of patients with RE, with excellent long-term seizure outcomes 2).
The majority of pediatric patients undergoing resection or hemispherectomy for RE achieve good seizure outcome. Although small retrospective cohort studies are inherently prone to bias, the best available evidence utilizing individual participant data suggests hemispheric surgery and younger age at the surgery are associated with good seizure outcomes following epilepsy surgery. Large, multicenter observational studies with long-term follow-up are required to evaluate the risk factors identified in a review 3).
Hemispherotomy remains the gold standard treatment but causes permanent functional impairment. No standardized medical treatment protocol currently exists for patients prior to indication of hemispherotomy, although some immunotherapies have shown partial efficacy with functional preservation but poor antiseizure effect. Some studies suggest a role for tumor necrosis factor alpha (TNF-α) in RE pathophysiology.
1)
Guan Y, Chen S, Liu C, Du X, Zhang Y, Chen S, Wang J, Li T, Luan G. Timing and type of hemispherectomy for Rasmussen’s encephalitis: Analysis of 45 patients. Epilepsy Res. 2017 May;132:109-115. doi: 10.1016/j.eplepsyres.2017.03.003. Epub 2017 Mar 22. PMID: 28399506.
2)
Sundar SJ, Lu E, Schmidt ES, Kondylis ED, Vegh D, Poturalski MJ, Bulacio JC, Jehi L, Gupta A, Wyllie E, Bingaman WE. Seizure Outcomes and Reoperation in Surgical Rasmussen Encephalitis Patients. Neurosurgery. 2022 May 13. doi: 10.1227/neu.0000000000001958. Epub ahead of print. PMID: 35544031.
3)
Harris WB, Phillips HW, Chen JS, Weil AG, Ibrahim GM, Fallah A. Seizure outcomes in children with Rasmussen’s encephalitis undergoing resective or hemispheric epilepsy surgery: an individual participant data meta-analysis. J Neurosurg Pediatr. 2019 Dec 6:1-10. doi: 10.3171/2019.9.PEDS19380. [Epub ahead of print] Review. PubMed PMID: 31812145.
American Society for Stereotactic and Functional Neurosurgery
American Society for Stereotactic and Functional Neurosurgery
Position Statement on Magnetic resonance image-guided laser interstitial thermal therapy for epilepsy
Magnetic resonance image-guided laser interstitial thermal therapy (MRgLITT) is a tool in the neurosurgical armamentarium for the management of drug-resistant epilepsy. Given the introduction of this technology, the American Society for Stereotactic and Functional Neurosurgery (ASSFN), which acts as the joint section representing the field of stereotactic and functional neurosurgery on behalf of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, provides here the expert consensus opinion on evidence-based best practices for the use and implementation of this treatment modality. Indications for treatment are outlined, consisting of failure to respond to, or intolerance of, at least 2 appropriately chosen medications at appropriate doses for disabling, localization-related epilepsy in the setting of well-defined epileptogenic foci, or critical pathways of seizure propagation accessible by MRgLITT. Applications of MRgLITT in mesial temporal lobe epilepsy and hypothalamic hamartoma, along with its contraindications in the treatment of epilepsy, are discussed based on current evidence. To put this position statement in perspective, they detailed the evidence and authority on which this ASSFN position statement is based 1)
Position Statement on Deep Brain Stimulation for Medication-Refractory Epilepsy
A persistent underuse of epilepsy surgery exists. Neuromodulation treatments including deep brain stimulation (DBS) expand the surgical options for patients with epilepsy and provide options for patients who are not candidates for resective surgery. DBS of the bilateral anterior nucleus of the thalamus is an Food and Drug Administration-approved, safe, and efficacious treatment option for patients with refractory focal epilepsy. The purpose of this consensus position statement is to summarize evidence, provide recommendations, and identify indications and populations for future investigation in Deep Brain Stimulation for epilepsy. The recommendations of the American Society for Stereotactic and Functional Neurosurgery are based on several randomized and blinded clinical trials with high-quality data to support the use of DBS to the anterior nucleus of the thalamus for the treatment of refractory focal-onset seizures.
Online surveys
Cabrera et al. designed a 51-question online survey comprising Likert-type, multiple-choice, and rank-order questions and distributed it to members of the American Society for Stereotactic and Functional Neurosurgery (ASSFN). Descriptive and inferential statistical analyses were performed on the data.
They received 38 completed surveys. Half (n = 19) of responders reported devoting at least a portion of their clinical practice to psychiatric neurosurgery, utilizing DBS and treating obsessive compulsive disorder (OCD) most frequently overall. Respondents indicated that psychiatric neurosurgery is more medically effective (OR 0, p = 0.03242, two-sided Fisher’s exact test) and has clearer clinical indications for the treatment of OCD than for the treatment of depression (OR 0.09775, p = 0.005137, two-sided Fisher’s exact test). Seventy-one percent of all respondents (n = 27) supported the clinical utility of ablative surgery in modern neuropsychiatric practice, 87% (n = 33) agreed that ablative procedures constitute a valid treatment alternative to DBS for some patients, and 61% (n = 23) agreed that ablative surgery may be an acceptable treatment option for patients who are unlikely to comply with postoperative care.
This up-to-date account of practices, perceptions, and predictions about psychiatric neurosurgery contributes to the knowledge about evolving attitudes over time and informs priorities for education and further surgical innovation on the psychiatric neurosurgery landscape 2).
Biennial Meetings
2022 AMERICAN SOCIETY FOR STEREOTACTIC AND FUNCTIONAL NEUROSURGERY BIENNIAL MEETING
2016 Biennial Meeting of the American Society for Stereotactic and Functional Neurosurgery, Chicago, IL, USA, June 18-21, 2016: Abstracts 3)
1)
Wu C, Schwalb JM, Rosenow JM, McKhann GM 2nd, Neimat JS; American Society for Stereotactic and Functional Neurosurgeons. The American Society for Stereotactic and Functional Neurosurgery Position Statement on Laser Interstitial Thermal Therapy for the Treatment of Drug-Resistant Epilepsy. Neurosurgery. 2022 Feb 1;90(2):155-160. doi: 10.1227/NEU.0000000000001799. PMID: 34995216.
2)
Cabrera LY, Courchesne C, Kiss ZHT, Illes J. Clinical Perspectives on Psychiatric Neurosurgery. Stereotact Funct Neurosurg. 2019;97(5-6):391-398. doi: 10.1159/000505080. Epub 2020 Jan 17. PMID: 31955163.
3)
2016 Biennial Meeting of the American Society for Stereotactic and Functional Neurosurgery, Chicago, IL, USA, June 18-21, 2016: Abstracts. Stereotact Funct Neurosurg. 2017 Jan 16;94 Suppl 2:1-77. doi: 10.1159/000455386. [Epub ahead of print] PubMed PMID: 28092908.
Subdural Grid Monitoring
Subdural Grid Monitoring
.
Indications
A useful technique for intra-operative functional mapping, for the surgical treatment of epilepsy.
○ Grids are frequently used for extra-operative functional mapping (helpful in children or in the mentally retarded). Subdural grid electrodes are placed with a craniotomy.
○ Surface strip electrodes may be placed through a burr hole.
https://adtechmedical.com/subdural-electrodes.
Disadvantages
Subdural grid monitoring (SDG) has the advantage to provide continuous coverage over a larger area of cortex, direct visualization of electrode location and functional mapping. However, SDG can cause direct irritation of the cortex or postoperative headaches due to cerebrospinal fluid fistula. Epidural grid monitoring (EDG) without opening the dura is thought to reduce the possibility of these complications. Park et al. reported the experience with Epidural grid monitoring.
Placement
Traditionally, for subdural grid electrode placement, large craniotomies have been applied for optimal electrode placement. Nowadays, microneurosurgeons prefer patient-tailored minimally invasive approaches. Absolute figures on craniotomy size have never been reported. To elucidate the craniotomy size necessary for successful diagnostics, Schneider et al. reviewed there single-center experience in the Charité.
Within 3 years, 58 patients with focal epilepsies underwent subdural grid implantation using patient-tailored navigation-based craniotomies. Craniotomy sizes were measured retrospectively. The number of electrodes and the feasibility of the resection were evaluated. Sixteen historical patients served as controls.
In all 58 patients, subdural electrodes were implanted as planned through tailored craniotomies. The mean craniotomy size was 28 ± 15 cm2 via which 55 ± 16 electrodes were implanted. In temporal lobe diagnostics, even smaller craniotomies were applied (21 ± 11 cm2). Craniotomies were significantly smaller than in historical controls (65 ± 23 cm2, p < 0.05), while the mean number of electrodes was comparable. The mean operation time was shorter and complications were reduced in tailored craniotomies.
Craniotomy size for subdural electrode implantation is controversial. Some surgeons favor large craniotomies, while others strive for minimally invasive approaches. For the first time, they measured the actual craniotomy size for subdural grid electrode implantation. All procedures were straightforward. They therefore advocate for patient-tailored minimally invasive approaches – standard in modern microneurosurgery – in epilepsy surgery as well 1).
Subdural strip and grid electrode (SDE) implantations have long been used as the mainstay of intracranial seizure localization in the United States. Stereoelectroencephalography (SEEG) is an alternative approach in which depth electrodes are placed through percutaneous drill holes to stereotactically defined coordinates in the brain. Long used in certain centers in Europe, SEEG is gaining wider popularity in North America, bolstered by the advent of stereotactic robotic assistance and mounting evidence of safety, without the need for catheter-based angiography. Rates of clinically significant hemorrhage, infection, and other complications appear lower with SEEG than with SDE implants. SEEG also avoids unnecessary craniotomies when seizures are localized to unresectable eloquent cortex, found to be multifocal or nonfocal, or ultimately treated with stereotactic procedures such as laser interstitial thermal therapy (LITT), radiofrequency thermocoagulation (RF-TC), responsive neurostimulation (RNS), or deep brain stimulation (DBS). While SDE allows for excellent localization and functional mapping on the cortical surface, SEEG offers a less invasive option for sampling disparate brain areas, bilateral investigations, and deep or medial targets. SEEG has shown efficacy for seizure localization in the temporal lobe, the insula, lesional and nonlesional extra-temporal epilepsy, hypothalamic hamartomas, nodular periventricular heterotopias, and patients who have had prior craniotomies for resections or grids. SEEG offers a valuable opportunity for cognitive neurophysiology research and may have an important role in the study of dysfunctional networks in psychiatric disease and understanding the effects of neuromodulation 2).
Case series
Hamer et al retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997.
From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization.
Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate 3).
From 1987 to 1992, invasive EEG studies using subdural strips, subdural grids or depth electrodes were performed in a total of 160 patients with medically intractable epilepsy, in whom scalp EEG was insufficient to localize the epileptogenic focus. Dependent on the individual requirements, these different electrode types were used alone or in combination. Multiple strip electrodes with 4 to 16 contacts were implanted in 157 cases through burrholes, grids with up to 64 contacts in 15 cases via boneflaps, and intrahippocampal depth electrodes in 36 cases using stereotactic procedures. In every case, localization of the electrodes with respect to brain structures was controlled by CT scan and MRI. Visual and computerized analysis of extra-operative recordings allowed the localization of a resectable epileptogenic focus in 143 patients (89%), who subsequently were referred for surgery, whereas surgery had to be denied to 17 patients (11%). We did not encounter any permanent morbidity or mortality in our series. In our experience, EEG-monitoring with chronically implanted electrodes is a feasible technique which contributes essentially to the exact localization of the epileptogenic focus, since it allows nearly artefact-free recording of the ictal and interictal activity. Moreover, grid electrodes can be used for extra-operative functional topographic mapping of eloquent brain areas 4).
References
1)
Schneider UC, Oltmanns F, Vajkoczy P, Holtkamp M, Dehnicke C. Craniotomy Size for Subdural Grid Electrode Placement in Invasive Epilepsy Diagnostics. Stereotact Funct Neurosurg. 2019 Jul 30:1-9. doi: 10.1159/000501235. [Epub ahead of print] PubMed PMID: 31362296.
2)
Youngerman BE, Khan FA, McKhann GM. Stereoelectroencephalography in epilepsy, cognitive neurophysiology, and psychiatric disease: safety, efficacy, and place in therapy. Neuropsychiatr Dis Treat. 2019 Jun 28;15:1701-1716. doi: 10.2147/NDT.S177804. eCollection 2019. Review. PubMed PMID: 31303757; PubMed Central PMCID: PMC6610288.
3)
Hamer HM, Morris HH, Mascha EJ, Karafa MT, Bingaman WE, Bej MD, Burgess RC, Dinner DS, Foldvary NR, Hahn JF, Kotagal P, Najm I, Wyllie E, Lüders HO. Complications of invasive video-EEG monitoring with subdural grid electrodes. Neurology. 2002 Jan 8;58(1):97-103. PubMed PMID: 11781412.
4)
Behrens E, Zentner J, van Roost D, Hufnagel A, Elger CE, Schramm J. Subdural and depth electrodes in the presurgical evaluation of epilepsy. Acta Neurochir (Wien). 1994;128(1-4):84-7. PubMed PMID: 7847148.
Status epilepticus treatment
Status epilepticus treatment
61% of seizures that persist > 5 mins will continue > 1 hour 1).
The treatment protocol is intensive and includes benzodiazepines, anticonvulsants, and eventually anesthetics to medically induce coma when polypharmacy is exhausted 2).
Acute treatment of SE, and particularly refractory (RSE), and super-refractory status epilepticus (SRSE), is associated with high hospital costs and prolonged LOS. Patients with disabilities are at risk for an unfavorable course of SE, resulting in prolonged LOS. In general, mortality associated with SE is low in children and adolescents, however three or more treatment steps are associated with high treatment costs 3).
General treatment measures for status epilepticus
Treatment success, like morbidity/mortality, may be time-dependent. One review showed that first-line AED therapy aborted SE in 60% of patients if initiated within the first 30 minutes, and efficacy decreased as seizure duration increased. As such, treatment should be initiated as soon as possible and should be directed at stabilizing the patient, stopping the seizure, identifying the cause (determining if there is an acute insult to the brain), and, if possible, also treating the underlying process. Treatment often must be initiated prior to the availability of test results to confirm the diagnosis and may even be initiated in the pre-hospital setting.
- “ABC’s”
a) Airway: oral airway if feasible.Turn the patient on their side to avoid aspiration
b) Breathing: O2 by nasal cannula or bag-valve-mask.Consider intubation if respiration is compromised or if seizure persists > 30 min
c) Circulation: CPR if needed. Large bore proximal IV access (2 if possible: 1 for phenytoin (PHT) (Dilantin®), not necessary if fosphenytoin is available): start with NS KVO
- Simultaneous with ABCs, AEDs should be prepared and/or given if SE suspected
- neurologic exam
-
monitor: EKG & baseline vital signs. Pulse oximeter. Frequent blood pressure checks
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bloodwork: STAT capillary blood (fingerstick) glucose (to R/O hypoglycemia), electrolytes (including glucose), CBC, LFTs, Mg + + , Ca + + , AED levels, ABG
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head CT (usually without contrast)
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correct any electrolyte imbalance (SE due to electrolyte imbalance responds more readily to cor- rection than to AEDs) 8. if CNS infection is a major consideration, perform LP for CSF analysis (especially in febrile children) unless contraindicated. WBC pleocytosis up to 80 × 106/L can occur following SE (benign postictal pleocytosis), and these patients should be treated with antibiotics until infection can be ruled out by negative cultures
-
general meds for unknown patient:
a) glucose:
● in patients with poor nutrition (e.g. alcoholics): giving glucose in thiamine deficiency can precipitate Wernicke’s encephalopathy prior to glucose bolus give thiamine 50– 100 mg IV
● if fingerstick glucose can be obtained immediately and it shows hypoglycemia, or if no fin- gerstick glucose can be done: give 25–50 ml of D50 IV push for adults (2 ml/kg of 25% glu- cose for peds). If at all possible, draw blood for definitive serum glucose first
b) naloxone(Narcan®)0.4mgIVP(in case of narcotics)
c) ± bicarbonate to counter acidosis (1–2 amps depending on length of seizure)
d) forneonate<2years:considerpyridoxine100mgIVpush(pyridoxine-dependent seizures
constitute a rare autosomal recessive condition that generally presents in the early neonatal period
- administer specific anticonvulsants for seizures lasting > 5-10 mins
-
EEG monitor if possible
-
if paralytics are used(e.g.to intubate), use short-acting agents and be aware that muscle paralysis alone may stop visible seizure manifestations, but does not stop the electrical seizure activity in the brain, which can lead to permanent neurologic damage if prolonged
Medications for generalized convulsive status epilepticus
General information
There are no randomized trials for refractory status epilepticus, although there is published data regarding specific treatment options. Numerous protocols exist.
“Peds dosing” refers to patients < 40 kg or approximately 12 yrs of age. Rapid treatment is indicated as delays are associated with neuronal injury and reduced response to medications.
Prehospital phase
- impending SE: may be heralded by a crescendo in Sz. A 1–3 d course of lorazepam may preempt the development of SE 2. SE treatment may be initiated in the home setting with buccal midazolam or rectal diazepam
Hospital phase
Start IV drugs at half the maximal rate, and titrate up to maximal rate if VS stable.
- First line drugs
a) benzodiazepine (main side effect: respiratory depression in ≈12%; be prepared to intubate). Onset of action is rapid (1–2 mins):
● lorazepam (Ativan®) 4 mg IV for adults, 2 mg IV for children @ < 2 mg/min
● OR midazolam (Versed®) 10 mg IM for adults, 5 mg IM for children > 13 kg. Repeat dose of benzodiazepine if necessary after 10 min.
● If no IV access or if midazolam injections not available, diazepam can be given rectally in Diastat® gel formulation (0.2–0.5 mg/kg)
- If seizures persist after the first dose of benzodiazepine, initiate second-line agent in a different IV.
a) load with fosphenytoin (Cerebyx®) or phenytoin (Dilantin®).
Do not worry about acutely overdosing, but do follow dosing rates, monitor BP for hypotension and EKG for arrhythmias. After giving the following loading dose, start on maintenance. Fosphenytoin has the advantage of being less irritating and able to infuse at a faster rate, but phenytoin is less expensive and does not need to be metabolized.
● fosphenytoin: 15–20 mg PE/kg IV @ 150 mg PE/min
● OR phenytoin: 15–20 mg/kg IV @ 50 mg/min
- if no response to loading dose, an additional 10 mg/kg IV may be given after 20 min.
-
if pt is on PHT and a recent level is known: a rule of thumb is giving 0.74 mg/kg to an adult raises the level by ≈ 1 mcg/ml
-
if on PHT and level not known: adult: give 500 mg @ < 50 mg/min
b) There are several good alternatives to fosphenytoin/phenytoin as second-line AEDs:
● Sodium valproate: 20–30 mg/kg IV bolus (max rate: 100 mg/min)—has been shown to be equal or superior to phenytoin in a few small studies
● Phenobarbital: 20 mg/kg IV (start infusing @ 50–100 mg/min) – commonly used 2nd or 3rd line AED. A repeat dose of 25–30 mg/kg can be given 10 min after the first dose.
● Levetiracetam (Keppra®): 20 mg/kg IV bolus of over 15 minutes – evidence for Keppra as a first or second line drug is less clear
- Traditionally, a third-line agent was given prior to continuous infusion therapy (CIT); however, it was successful in only 7%.42 As such, most new protocols proceed directly to anesthetic administration. If seizures are continuing after above therapies have been administered (15–30 min after initial presentation), begin CIT as follows:
● Midazolam: 0.2 mg/kg IV loading dose followed by 0.2–0.6 mg/kg/hr
● OR Propofol: 2 mg/kg IV loading dose followed by 2–10 mg/kg/hr
- At this time, lab results and tests should be available. Ensure that all reversible etiologies have been addressed and that a CT head has been performed.
-
Pentobarbital is often reserved for SE that is refractory to all of the above interventions. If necessary, pentobarbital is administered as follows:
● Pentobarbital: 5 mg/kg IV followed by 1–5 mg/kg/hr
- While some practitioners will try additional drugs (carbamazepine, oxcarbazepine, topiramate, levetiracetam, lamotrigine, gabapentin), these are likely to be of limited utility.
-
Experimental interventions include: lidocaine infusion, inhalational anesthesia, direct brain stimulation, transcranial magnetic stimulation, electroconvulsive therapy (shock therapy), surgical intervention if a seizure focus is identified
Remember: Paralytics stop the visible manifestations of the seizure and they may be useful for intu- bation and/or in order to obtain head imaging; however, they do not stop the abnormal electrical brain activity or the neurological damage that results.
Efficacy of drug therapy
Studies vary widely, but it appears that approximately 2/3 of patients will respond to initial therapy with the other 1/3 progressing to refractory SE.
Medications to avoid in status epilepticus
- narcotics
-
phenothiazines: including promethazine (Phenergan®)
-
neuromuscular blocking agents in the absence of AED therapy: seizures may continue and cause neurologic injury but would not be clinically evident
Medications for non-convulsive status epilepticus
In non-convulsive status epilepticus, the first and second line AEDs should be utilized. However, many practitioners avoid escalating to the anesthetic options (CIT, pentobarbital), instead opting for trials of additional AEDs first (carbamazepine, oxcarbazepine, topiramate, lamotrigine, etc).
Miscellaneous status epilepticus
Myoclonic status
Treatment: valproic acid (drug of choice). Place NG, give 20 mg/kg per NG loading dose. Maintenance: 40 mg/kg/d divided.
Can add lorazepam (Ativan®) or clonazepam (Klonopin®) to help with acute control.
Absence status epilepticus
Almost always responds to diazepam.
Surgery
1)
Abend NS, Dlugos DJ. Treatment of refractory status epilepticus: literature review and a proposed proto- col. Pediatr Neurol. 2008; 38:377–390
2)
D. A. Greenberg, M. J. Aminof, and R. P. Simon, Clinical Neurology, McGraw-Hill Education, New York, NY, USA, 9th edition, 2015.
3)
Schubert-Bast S, Lenders C, Kieslich M, Rosenow F, Strzelczyk A. Costs and cost-driving factors of acute treatment of status epilepticus in children and adolescents: A cohort study from Germany. Seizure. 2022 Mar 19;97:63-72. doi: 10.1016/j.seizure.2022.03.014. Epub ahead of print. PMID: 35344919.
PISCOM
PISCOM
Perissinotti et al. present a modified version of the SISCOM procedure that uses interictal PET instead of interictal SPECT for seizure onset zone localization. Perissinotti et al. called this new nuclear medicine imaging processing technique PISCOM (PET interictal subtracted ictal SPECT coregistered with MRI).
They retrospectively studied 23 patients (age range 4-61 years) with medically refractory epilepsy who had undergone MRI, ictal SPECT, interictal SPECT and interictal FDG PET and who had been seizure-free for at least 2 years after surgical treatment. FDG PET images were reprocessed (rFDG PET) to assimilate SPECT features for image subtraction. Interictal SPECT and rFDG PET were compared using statistical parametric mapping (SPM). PISCOM and SISCOM images were evaluated visually and using an automated volume of interest-based analysis. The results of the two studies were compared with each other and with the known surgical resection site.
SPM showed no significant differences in cortical activity between SPECT and rFDG PET images. PISCOM and SISCOM showed equivalent results in 17 of 23 patients (74%). The seizure onset zone was successfully identified in 19 patients (83%) by PISCOM and in 17 (74%) by SISCOM: in 15 patients (65%) the two techniques showed concordant successful results. The volume of interest-based analysis showed no significant differences between PISCOM and SISCOM in identifying the extension of the seizure onset zone. However, PISCOM showed a lower amount of indeterminate activity due to propagation, background or artefacts.
Preliminary findings of this initial proof-of-concept study suggest that perfusion and glucose metabolism in the cerebral cortex can be correlated and that PISCOM may be a valid technique for identification of the seizure onset zone. However, further studies are needed to validate these results 1)
Children with drug-resistant focal epilepsy have a compromised quality of life. Epilepsy surgery can control or significantly reduce the seizures. Aparicio et al. assessed and compared the usefulness of PISCOM, with SISCOM and 18F-FDG PET (FDG-PET) in pre-surgical evaluation of paediatric drug-resistant focal epilepsy.
Twenty-two children with pharmcorefractory epilepsy, mainly extratemporal, who had undergone pre-surgical assessment including SISCOM and FDG-PET and with postsurgical favorable outcome (Engel class I or II) for at least two years, were included in this proof-of-concept study. All abnormalities observed in SISCOM, FDG-PET and PISCOM were compared with each other and with the known epileptogenic zone (EZ) based on surgical treatment, histopathologic and surgical outcome results. Global interobserver agreement, Cohen’s Kappa coeficient and PABAK statistic were calculated for each technique.
ISCOM concordance with the known EZ was significantly higher than SISCOM (p<0.05), and no statistically differences were found with FDG-PET. PISCOM showed successful identification in 19 of 22 cases (86%), successful concordant with FDG-PET in 17 (77%), and SISCOM in 11 (50%). If we consider PISCOM and FDG-PET results together, both techniques successfully localized the known EZ in all cases. The measures of agreement between two experts in nuclear medicine were higher in PISCOM than in SISCOM and FDG-PET.
PISCOM could provide complementary presurgical information in drug-resistant paediatric focal epilepsy, particularly in cases in which FDG-PET is doubtful or negative, replacing SISCOM and sparing the use of interictal SPECT 2)
1)
Perissinotti A, Niñerola-Baizán A, Rubí S, Carreño M, Marti-Fuster B, Aparicio J, Mayoral M, Donaire A, Sanchez-Izquierdo N, Bargalló N, Rumiá J, Boget T, Pons F, Lomeña F, Ros D, Pavía J, Setoain X. PISCOM: a new procedure for epilepsy combining ictal SPECT and interictal PET. Eur J Nucl Med Mol Imaging. 2018 Dec;45(13):2358-2367. doi: 10.1007/s00259-018-4080-6. Epub 2018 Aug 1. PMID: 30069576; PMCID: PMC6208811.
2)
Aparicio J, Niñerola-Baizán A, Perissinotti A, Rubí S, Muchart J, Candela-Cantó S, Campistol J, Setoain X. Presurgical evaluation of drug-resistant paediatric focal epilepsy with PISCOM compared to SISCOM and FDG-PET. Seizure. 2022 Mar 15;97:43-49. doi: 10.1016/j.seizure.2022.03.010. Epub ahead of print. PMID: 35325841.