Positron emission tomography (PET) of local cerebral glucose metabolism in 13 children with infantile spasms of undetermined cause (cryptogenic spasms) revealed unilateral hypometabolism involving the parieto-occipito-temporal region in 5 female infants. Cranial computed tomography showed normal findings in all infants. Magnetic resonance imaging (MRI) demonstrated a normal appearance in 4 of the 5 infants; in 1 infant, MRI revealed a subtle abnormality consisting of poor demarcation between occipital gray and white matter. Surface electroencephalography (EEG) in 4 showed hypsarrythmia at some time in the patients' courses, but at other times showed localized or lateralized abnormalities corresponding to areas of PET-detected hypometabolism. Because of poor seizure control, 4 infants underwent surgical removal of the cortical focus guided by intraoperative electrocorticography and were seizure free postoperatively. Neuropathological examination of resected tissue in each showed microscopic cortical dysplasia. Our findings indicate that in infants with cryptogenic spasms, PET can effectively identify those due to unsuspected focal cortical dysplasia, for which resective surgery offers improved prognosis.

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Purpose: Established tonic–clonic status epilepticus (SE) does not stop in one-third of patients when treated with an intravenous (IV) benzodiazepine bolus followed by a loading dose of a second antiseizure medication (ASM). These patients have refractory status epilepticus (RSE) and a high risk of morbidity and death. For patients with convulsive refractory status epilepticus (CRSE), we sought to determine the strength of evidence for 8 parenteral ASMs used as third-line treatment in stopping clinical CRSE. Methods: A structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) was performed to identify original studies on the treatment of CRSE in children and adults using IV brivaracetam, ketamine, lacosamide, levetiracetam (LEV), midazolam (MDZ), pentobarbital (PTB; and thiopental), propofol (PRO), and valproic acid (VPA). Adrenocorticotropic hormone (ACTH), corticosteroids, intravenous immunoglobulin (IVIg), magnesium sulfate, and pyridoxine were added to determine the effectiveness in treating hard-to-control seizures in special circumstances. Studies were evaluated by predefined criteria and were classified by strength of evidence in stopping clinical CRSE (either as the last ASM added or compared to another ASM) according to the 2017 American Academy of Neurology process. Results: No studies exist on the use of ACTH, corticosteroids, or IVIg for the treatment of CRSE. Small series and case reports exist on the use of these agents in the treatment of RSE of suspected immune etiology, severe epileptic encephalopathies, and rare epilepsy syndromes. For adults with CRSE, insufficient evidence exists on the effectiveness of brivaracetam (level U; 4 class IV studies). For children and adults with CRSE, insufficient evidence exists on the effectiveness of ketamine (level U; 25 class IV studies). For children and adults with CRSE, it is possible that lacosamide is effective at stopping RSE (level C; 2 class III, 14 class IV studies). For children with CRSE, insufficient evidence exists that LEV and VPA are equally effective (level U, 1 class III study). For adults with CRSE, insufficient evidence exists to support the effectiveness of LEV (level U; 2 class IV studies). Magnesium sulfate may be effective in the treatment of eclampsia, but there are only case reports of its use for CRSE. For children with CRSE, insufficient evidence exists to support either that MDZ and diazepam infusions are equally effective (level U; 1 class III study) or that MDZ infusion and PTB are equally effective (level U; 1 class III study). For adults with CRSE, insufficient evidence exists to support either that MDZ infusion and PRO are equally effective (level U; 1 class III study) or that low-dose and high-dose MDZ infusions are equally effective (level U; 1 class III study). For children and adults with CRSE, insufficient evidence exists to support that MDZ is effective as the last drug added (level U; 29 class IV studies). For adults with CRSE, insufficient evidence exists to support that PTB and PRO are equally effective (level U; 1 class III study). For adults and children with CRSE, insufficient evidence exists to support that PTB is effective as the last ASM added (level U; 42 class IV studies). For CRSE, insufficient evidence exists to support that PRO is effective as the last ASM used (level U; 26 class IV studies). No pediatric-only studies exist on the use of PRO for CRSE, and many guidelines do not recommend its use in children aged <16 years. Pyridoxine-dependent and pyridoxine-responsive epilepsies should be considered in children presenting between birth and age 3 years with refractory seizures and no imaging lesion or other acquired cause of seizures. For children with CRSE, insufficient evidence exists that VPA and diazepam infusion are equally effective (level U, 1 class III study). No class I to III studies have been reported in adults treated with VPA for CRSE. In comparison, for children and adults with established convulsive SE (ie, not RSE), after an initial benzodiazepine, it is likely that loading doses of LEV 60 mg/kg, VPA 40 mg/kg, and fosphenytoin 20 mg PE/kg are equally effective at stopping SE (level B, 1 class I study). Conclusions: Mostly insufficient evidence exists on the efficacy of stopping clinical CRSE using brivaracetam, lacosamide, LEV, valproate, ketamine, MDZ, PTB, and PRO either as the last ASM or compared to others of these drugs. Adrenocorticotropic hormone, IVIg, corticosteroids, magnesium sulfate, and pyridoxine have been used in special situations but have not been studied for CRSE. For the treatment of established convulsive SE (ie, not RSE), LEV, VPA, and fosphenytoin are likely equally effective, but whether this is also true for CRSE is unknown. Triple-masked, randomized controlled trials are needed to compare the effectiveness of parenteral anesthetizing and nonanesthetizing ASMs in the treatment of CRSE.

ABSTRACT. A 6-year-old boy presented with epilepsia partialis continua 6 months after diagnosis of type 1 diabetes. Anti-glutamic acid decarboxylase 65 antibodies were found in his serum and cerebrospinal fluid. Antiepileptic agents did not improve his seizures. High-dose steroids, plasmapheresis, and intravenous immunoglobulin resulted in decreased anti-glutamic acid decarboxylase 65 antibody levels and resolution of his seizures. Pediatrics 2002;109(3). URL: http://www.pediatrics.org/ cgi/content/full/109/3/e50; GAD65 antibody, type 1 diabetes mellitus, Rasmussen encephalitis, seizure, plasmapheresis, autoimmunity.ABBREVIATIONS. GAD, glutamic acid decarboxylase; GABA, ␥ amino butyric acid; SMS, stiff-man syndrome; EPC, epilepsia partialis continua.G lutamic acid decarboxylase 65 (GAD65) is a protein found both in the central nervous system, where it converts glutamic acid to ␥ amino butyric acid (GABA), and in the ␤-cells of pancreatic islets. Antibodies to GAD65 are found in 70% to 80% of patients with new-onset type 1 (autoimmune) diabetes mellitus. 1 They are also found in patients with certain neurologic conditions, particularly, stiff-man syndrome (SMS); however, the antibody titers are 10-to 1000-fold higher than the titers usually seen in type 1 diabetes mellitus. 2 This is the first report of a patient with both type 1 diabetes mellitus and epilepsia partialis continua (EPC) associated with extremely elevated levels of anti-GAD65 antibodies. CASE REPORTThe patient is a previously healthy 6 1 ⁄2-year-old adopted black boy who developed simple partial seizures involving the right hand 6 months after receiving the diagnosis of type 1 diabetes. He progressed rapidly over 3 days to have continuous multifocal right-sided seizures involving the hand, the face, and the leg (EPC). He stabilized transiently after 1 week, but 2 weeks after the initial seizure he became aphasic and obtunded. An electroencephalogram revealed frequent left-sided epileptiform discharges and slowing. He was treated with continuous but changing antiepileptic medications for the first 17 days after onset of seizures, at which time high-dose corticosteroids (2 mg/kg/d intravenous prednisolone) were added. Acyclovir was used for 4 days at the time of presentation but was discontinued when herpes simplex virus polymerase chain reaction and cultures were negative. Intubation and midazolam coma were used between day 17 and day 25 after seizure onset. None of these modalities resulted in improvement of the seizures.His evaluation included cerebrospinal fluid studies that were negative for herpes simplex virus, tuberculosis, fungus, cryptococcal antigen, and routine viral and bacterial pathogens. Serology was negative for herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and Mycoplasma. Coagulation studies, including protime, partial thromboplastin time, protein C and protein S, and antithrombin III, all were normal. Rheumatologic studies, including lupus anticoagulant, antinuclear antibodi...