Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy.

OBJECTIVE: To evaluate a trial of immunotherapy as an aid to diagnosis in suspected autoimmune epilepsy. METHOD: We reviewed the charts of 110 patients seen at our autoimmune neurology clinic with seizures as a chief complaint. Twenty-nine patients met the following inclusion criteria: (1) autoimmune epilepsy suspected based on the presence of ≥ 1 neural autoantibody (n = 23), personal or family history or physical stigmata of autoimmunity, and frequent or medically intractable seizures; and (2) initiated a 6- to 12-week trial of IV methylprednisolone (IVMP), IV immune globulin (IVIg), or both. Patients were defined as responders if there was a 50% or greater reduction in seizure frequency. RESULTS: Eighteen patients (62%) responded, of whom 10 (34%) became seizure-free; 52% improved with the first agent. Of those receiving a second agent after not responding to the first, 43% improved. A favorable response correlated with shorter interval between symptom onset and treatment initiation (median 9.5 vs 22 months; p = 0.048). Responders included 14/16 (87.5%) patients with antibodies to plasma membrane antigens, 2/6 (33%) patients seropositive for glutamic acid decarboxylase 65 antibodies, and 2/6 (33%) patients without detectable antibodies. Of 13 responders followed for more than 6 months after initiating long-term oral immunosuppression, response was sustained in 11 (85%). CONCLUSIONS: These retrospective findings justify consideration of a trial of immunotherapy in patients with suspected autoimmune epilepsy. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with suspected autoimmune epilepsy, IVMP, IVIg, or both improve seizure control.

Comorbidities in pediatric epilepsy: beyond "just'' treating the seizures.

The goal of this review is to discuss the comorbidities reported in specific epilepsy syndromes to examine possible underlying causes or associations and to present data on current therapies for these conditions. Comorbid conditions including cognitive impairment, neuropsychiatric problems, and social difficulties are common in children with epilepsy, and often more disabling than the seizures themselves. Biological factors associated with a greater risk of comorbidity in epilepsy include younger age at seizure onset, cognitive impairment, temporal or frontal lobe onset, and intractability. Social factors correlating with greater risk include lower socioeconomic status, lower parental education level, and poorer family function. These comorbid conditions not only have a significant impact on the child but also are a source of increased stress and burden for families. Increased awareness and early diagnosis of these conditions may affect therapeutic intervention and long-term outcome as well as assist in better understanding of potential risk factors and biological mechanisms.

Acute glomerulonephritis presenting with PRES: a report of 4 cases.

OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) occurs most commonly in the setting of known hypertension or use of immunosuppressive agents. DESIGN AND METHODS: We report four previously-well children who presented acutely with altered mentation, seizures and visual disturbances and were diagnosed with PRES. RESULTS: Only one child had a history of gross hematuria prior to the seizure. All four were discovered to be hypertensive only after onset of their neurological symptoms, and were subsequently diagnosed with glomerulonephritis. All four had rapid resolution of neurological symptoms with adequate treatment of hypertension. CONCLUSIONS: Blood pressure must be measured promptly in all children presenting with these symptoms. If elevated, the diagnosis of PRES should be strongly considered and a workup for renal disease pursued.

Diagnostic inaccuracy in children referred with "first seizure": role for a first seizure clinic.

PURPOSE: To determine (a) the range of diagnoses, and (b) the prevalence of previous seizures in children presenting to a first seizure clinic. METHODS: One hundred twenty-seven children were seen in a tertiary care First Seizure Clinic. Inclusion criteria were age 1 month-17 years with an unprovoked event suggestive of seizure. Data collected included referring physician specialty, child's age, gender, developmental status, and clinical diagnosis of epileptologist (nonepileptic vs. epileptic). For those with epileptic events, seizure type, syndrome (if identifiable), presumed etiology (idiopathic, cryptogenic, and symptomatic), presence of prior afebrile and febrile seizures, provoking factors, family history, pre/perinatal complications and EEG results were recorded. RESULTS: The diagnosis was epileptic in 94 (74%), nonepileptic in 31 (24%) and unclassifiable in two (2%). Pediatricians were more likely to refer true epileptic events (92%) than ED physicians (76%) or family physicians (65%). Mean age at presentation was 8 years. Fifteen percent of children were developmentally delayed and neurological examination was abnormal in 11%. For those diagnosed with epileptic events, 32 presented with generalized while 62 presented with partial onset seizures. An epilepsy syndrome was identifiable in 15 cases. Thirty-eight percent experienced a prior probable seizure which was recognized by the referring physician in only one case. An EEG was done in all children with seizures and was abnormal in 41%. Early EEG was performed in 20% of children and did not show statistical significance. CONCLUSIONS: Diagnostic inaccuracy is common in first seizure. One quarter of children were incorrectly diagnosed as having a seizure while the diagnosis of epilepsy was missed in over one-third of children.

Prolonged seizures exacerbate perinatal hypoxic-ischemic brain damage.

This study was undertaken to clarify whether seizures in the newborn cause damage to the healthy brain and, more specifically, to determine the extent to which seizures may contribute to the brain-damaging effects of hypoxia-ischemia (HI). Seizures were induced in 10-d-old rat pups with kainic acid (KA). Seizure duration was determined electrographically. HI was induced by common carotid artery ligation followed by exposure to 8% oxygen for either 15 or 30 min. Six groups of animals were assessed: 1) controls [neither KA nor HI (group I)]; 2) group II, KA alone; 3) group III, 15 min HI alone; 4) group IV,15 min HI plus KA; 5) group V, 30 min HI alone; and 6) group VI, 30 min HI plus KA. Animals were assessed neuropathologically at 3 (early) and 20 (late) d of recovery. KA injection without hypoxia resulted in continuous clinical and electrographic seizures lasting a mean of 282 min. No neuropathologic injury was seen in groups I (no HI or KA), II (KA alone), III (15 min HI alone), or IV (15 min HI and KA). Animals in group V (30 min HI alone) displayed brain damage with a mean score of 2.3 and 0.60 at 3 and 20 d of recovery, respectively. Animals in group VI (30 min HI and KA) had a mean score of 12.1 and 3.65 at 3 and 20 d of recovery, respectively. Compared with group V, the increased damage as a result of the seizure activity in group VI occurred exclusively in the hippocampus. Status epilepticus in the otherwise "healthy" neonatal brain does not cause neuropathologic injury. However, seizures superimposed on HI significantly exacerbate brain injury in a topographically specific manner.

Prognosis of seizures occurring in the first year.

To determine whether predictors of neurodevelopmental outcome and the course of epilepsy can be identified in infants 1-12 months of age presenting with their first afebrile seizure, we collected demographic data, seizure details (type, frequency, duration, etiology, and treatment), developmental status, neurologic findings at presentation and follow-up, and electroencephalographic (EEG), neuroimaging, metabolic, hematologic, and chemistry test results by chart review, parental interview, and neurologic examination in 40/41 subjects (98%) presenting to our institution between January 1994 and December 1998. The mean duration of follow-up from onset of seizures was 29 months (S.D. = 17; range = 1-64). Predictors of developmental and neurologic abnormalities at follow-up included developmental delay and abnormal neurologic examination at presentation, infantile spasms, lack of response to antiepileptic drugs (AEDs), valproate use, and abnormal EEG or neuroimaging results. Predictors against seizure control and epilepsy remission and for the development of problematic seizures at follow-up included valproate use and lack of response to AEDs. Poor neurodevelopmental outcome of children with new-onset afebrile seizures in the first 1-12 months of age can be accurately predicted at diagnosis with the aid of EEG and neuroimaging studies. The course of epilepsy is more difficult to predict, but failure to respond to the first AED is worrisome.

Seizures in the elderly: etiology and prognosis.

PURPOSE: To determine the etiology, early mortality, predictors of prognosis and diagnostic yields of EEG and CT scans of the head in new-onset seizures in elderly patients. METHODS: EEG records for the north-central region of Saskatchewan, between 01/94 and 12/95 were reviewed to identify all adults aged 60 years or older with new-onset seizures. Information on demographics, seizure type, etiology, EEG and neuroimaging studies, anti-epileptic treatment and course of epilepsy was obtained by review of medical records and interview with the patient and/or family member. RESULTS: Of 88 eligible subjects, 61 (69%) were contacted for follow-up, 19 (22%) were deceased (12 of whom who had a serious underlying etiology to their seizures, which was obvious at the time of initial presentation and led shortly to their demise), 4 (5%) were lost to follow-up and 4 (5%) refused participation. Excluding those refusing participation, 74/84 (88%) patients presented with partial or secondarily generalized seizures. Seizures were cryptogenic in 38/84 (45%), and due to stroke in 19/84 (23%). EEGs were abnormal in 61/84 (73%) cases, with epileptiform discharge in 33/84 (39%). CT scans were abnormal in 57/84 (68%) cases with acute pathology in 29/84 (35%). Of the 61 patients participating in the follow-up interview, 54 (89%) were treated with anti-epileptic medication and seizure control was usually successful. Predictors for ongoing seizures were more than 3 seizures at presentation, epileptiform activity on initial EEG and discontinuation of anti-epileptic medication for lack of efficacy. CONCLUSION: Prognosis of new-onset seizures in elderly patients is favorable if seizures are not symptomatic of a life-threatening disorder.

Benign epilepsy of childhood with centrotemporal spikes.

Benign epilepsy of childhood with centrotemporal spikes (BECT) is the most common partial epilepsy syndrome in the pediatric age group, with an onset between age 3 and 13 years. The typical presentation is a partial seizure with parasthesias and tonic or clonic activity of the lower face associated with drooling and dysarthria. Seizures commonly occur at night and may become secondarily generalized. They are usually infrequent and may not require antiepileptic drugs but, if treated, they tend to be easily controlled. Children with BECT are neurologically and cognitively normal. The EEG shows characteristic high-voltage sharp waves in the centrotemporal regions, which are activated with drowsiness and sleep. In this typical form, BECT is easily recognized. However, atypical cases are common and the definition of BECT can become blurred. Although further investigations are not required in cases with typical clinical and EEG findings and normal neurologic examinations, neuroimaging studies may be required in atypical cases to rule out other pathology. The long-term medical and psychosocial prognosis of BECT is excellent, with essentially all children entering long-term remission by mid-adolescence.

Long-term psychosocial outcome in typical absence epilepsy. Sometimes a wolf in sheeps' clothing.

OBJECTIVES: To determine whether young adults in whom typical absence epilepsy has been diagnosed in childhood have greater psychosocial difficulties than those with a non-neurologic chronic disease and to decide which seizure-related factors predict poor psychosocial outcome. DESIGN: Population-based, inception cohort study. SETTING: The only tertiary care pediatric hospital in the province of Nova Scotia. PATIENTS: All children in whom typical absence epilepsy or juvenile rheumatoid arthritis (JRA) was diagnosed between January 1, 1997, and December 31, 1985, who were aged 18 years or older at follow-up in March 1994 to April 1995. Patients with typical absence epilepsy were identified from centralized electroencephalographic records for Nova Scotia, and those with JRA were identified from discharge diagnoses from the only children's hospital in Nova Scotia. MAIN OUTCOME MEASURE: Patients participated in a structured interview that assessed psychosocial function. RESULTS: Fifty-six (86%) of the 65 patients with absence epilepsy and 61 (80%) of the 76 patients with JRA participated in the interview. The mean age of the patients at the interview was 23 years. Terminal remission occurred in 32 (57%) of the patients with typical absence epilepsy but in only 17 (28%) of the patients with JRA. Factor analysis identified 5 categories of outcome: academic-personal, behavioral, employment-financial, family relations, and social-personal relations. Patients with typical absence epilepsy had greater difficulties in the academic-personal and in the behavioral categories (P < .001) than those with JRA. Those with ongoing seizures had the least favorable outcome. Most seizure-related factors showed minimal correlation with psychosocial functioning. CONCLUSION: Young adults with a history of typical absence epilepsy, particularly those without remission of their seizures, often have poor psychosocial outcomes, considerably worse than those with JRA.

Long-term prognosis of typical childhood absence epilepsy: remission or progression to juvenile myoclonic epilepsy.

OBJECTIVE: To determine the proportion and characteristics of children presenting with childhood absence epilepsy (CAE) who were not taking anti-epileptic drugs (AEDs) and were seizure-free over the last year of long-term follow-up. METHODS: For case finding, centralized EEG records for the province of Nova Scotia allowed identification of all children with typical CAE diagnosed between 1977 and 1985. Follow-up was done in 1994 to 1995. RESULTS: Of 81 children with CAE, 72 (89%) were contacted for follow-up. Mean age at seizure onset was 5.7 years (range, 1 to 14 years) and at follow-up was 20.4 years (range, 12 to 31 years). Forty-seven (65%) were in remission. Twelve others (17%) were not taking AEDs but continued to have seizures. Thirteen (18%) were taking AEDs; five were seizure-free over the last year (in four of these a trial without AEDs had previously failed). Fifteen percent of the total cohort had progressed to juvenile myoclonic epilepsy (JME). Multiple clinical and EEG factors were examined as predictors of outcome. Factors predicting no remission (p < 0.05) included cognitive difficulties at diagnosis, absence status prior to or during AED treatment, development of generalized tonic clonic or myoclonic seizures after onset of AEDs, abnormal background on initial EEG, and family history of generalized seizures in first-degree relatives. CONCLUSIONS: Only 65% of children presenting with CAE had remission of their epilepsy. Forty-four percent of those without remission had developed JME. At the time of diagnosis, remission is difficult to predict accurately in most patients. However, development of generalized tonic-clonic seizures or myoclonic seizures during AED treatment is ominous, predicting both lack of remission of CAE and progression to JME.

Accidental injury is a serious risk in children with typical absence epilepsy.

OBJECTIVES: To determine if young adults with a history of typical absence epilepsy (AE) in childhood have a greater risk of accidental injury than controls with juvenile rheumatoid arthritis (JRA). To assess the nature and severity of these injuries. METHODS: All patients with AE or JRA diagnosed between 1977 and 1985, who were 18 years or older at the onset of the study, were identified from review of pediatric electroencephalographic records for the province of Nova Scotia (AE) or review of the medical records database at the only tertiary care pediatric center for the province (JRA). Fifty-nine (86%) of 69 patients with AE and 61 (80%) of 76 patients with JRA participated in an interview in 1994 or 1995, assessing nature, severity, and treatment of prior accidental injuries. Patients with AE were further questioned about injuries sustained during an absence seizure. RESULTS: Sixteen (27%) of 59 patients with AE reported accidental injury during an absence seizure, with risk of injury being 9% per person-year of AE. Most injuries (81%) occurred during anti-epileptic drug therapy. Although the majority of injuries did not require treatment, 2 (13%) of 16 patients required minor treatment and 2 (13%) of 16 were admitted to hospital. The risk of accidental injury resulting from an absence seizure in person-years at risk was highest in juvenile myoclonic epilepsy (45%), moderate in juvenile AE (14%), and lowest in childhood AE (3%). Patients with AE had a greater number of overall accidental injuries than those with JRA (P<.04), but these differences were particularly marked for bicycle (P<.003) and car accidents (P<.05) and for mild head injuries (P=.05). CONCLUSIONS: Accidental injury is common in AE and usually occurs after anti-epileptic drug treatment is started. Injury prevention counseling is indicated both at diagnosis and follow-up. Bicycle accidents pose a special risk and helmet use should be mandatory.

Will a critical level of hyperventilation-induced hypocapnia always induce an absence seizure?

We wished to determine if the degree of hypocapnia correlates with increased frequency of absence seizures and if there is a critical pCO2 at which absence seizures are reliably provoked. Twelve untreated children with newly diagnosed absence epilepsy were continuously monitored by EEG and end-expiratory CO2 recording during quiet respiration and hyperventilation (to absence seizure or exhaustion) while breathing four gas mixtures: (a) room air, (b) 100% O2, (c) 4% CO2 in room air, or (d) 4% CO2 + 96% O2). In quiet respiration, a reduction in number of spike and wave bursts and total seconds of spike and wave was noted in children breathing supplemental CO2 (gases c and d vs. gases a and b), p < 0.05. Supplemental O2 had no effect. Eight subjects had absence seizures elicited with each trial of hyperventilation. All subjects had their own critical pCO2, ranging from 19 to 28 mmHg. Three children had no seizures, two despite hypocapnia to pCO2 of 19 and 21 and 1 who achieved a pCO2 of only 25. In 1, absence seizures were provoked in only six of nine hyperventilation trials to pCO2 of 17-23. In 67% of subjects, absence seizures were reliably provoked by hypocapnia. Critical pCO2 varied among children with absence. Determination of whether variation in sensitivity to hypocapnia may be helpful in determining response to antiepileptic drugs (AEDs) or remission of seizures will require further study.

Benign rolandic epilepsy: atypical features are very common.

The objective of this study was to determine the frequency of atypical clinical and electrographic features in children with benign rolandic epilepsy. A retrospective case series design was employed in the setting of a tertiary care pediatric hospital. Forty-two children with benign rolandic epilepsy were seen through our neurology department between January 1, 1991, and December 31, 1993. Their charts were reviewed for atypical clinical features, imaging studies and results, total number of seizures at initial presentation and last follow-up, and use of anticonvulsants. Atypical clinical features included status epilepticus, developmental delay, daytime-only seizures, screaming as a seizure component, and postictal Todd's paresis. All children had at least one electroencephalogram, and these records were reviewed for atypical electrographic features such as unusual location, atypical spike morphology, and abnormal background. Atypical clinical features were seen in 50% of patients and atypical electrographic features in 31%. Computed tomographic scans were performed in 15 patients and were consistently normal. Treatment with anticonvulsant medication was initiated in 40%. Although patients with atypical features did not have an increased seizure frequency, they were more likely to undergo imaging studies (P < .01) and to be commenced on anticonvulsant medication (P < .02). Our experience suggests that atypical clinical and electrographic features are the rule rather than the exception in benign rolandic epilepsy. Further work must be done to develop a reliable definition of this common entity.

Massive pericardial effusion as a cause for sudden deterioration of a very low birthweight infant.

We describe the successful resuscitation of a very low birthweight infant after sudden deterioration caused by a massive pericardial effusion. The neonatal course of this 740 gm, 26-week gestational age infant had been complicated by moderate respiratory distress syndrome, apnea, and bronchopulmonary dysplasia. A Silastic catheter was placed percutaneously in the right axillary vein on day 6 of life and documented to be in the superior vena cava prior to continuous parenteral nutrition. On day 38, her cardiorespiratory status abruptly deteriorated, blood return could not be obtained from the central line, and it was removed. Chest radiograph and subsequent echocardiogram confirmed a massive pericardial effusion. Under echocardiographic guidance, an emergency percutaneous pericardiocentesis allowed aspiration of 23 ml of straw-colored fluid. Her vital signs immediately returned to normal and reaccumulation of the effusion did not occur. Despite the high mortality of premature infants from pericardial effusion as a complication of central venous catheterization, early diagnosis and prompt therapy can assure a good outcome. As a cause of sudden deterioration of very low birthweight infants, tamponade must not be forgotten, since it is now a rapidly treatable complication of central venous cannulation.