Response: Seizure Outcome after Anterior Temporal Lobectomy

Epilepsia, 46(4):599–602, 2005 Blackwell Publishing, Inc.
C 2005 International League Against Epilepsy

Comment Letters Variables in Childhood Epilepsy and Scholastic Underachievement

to the first seizures and diagnosis had a negative effect on cognitive functioning (4). The group of Fastenau et al. and our Dutch group agree on the importance of disentangling moderating and mediating factors of a nonillness nature from those directly related to the epilepsy, for a better understanding of the cognitive and behavioral predicament of school children with epilepsy. Both also met limitations when composing a sufficiently large sample of patients. A solution for obtaining representative data certainly lies in international collaboration.

To the Editor: We compliment Dr. Fastenau et al. (2004) on their beautiful elucidation of family factors that moderate the immediate effect of neuropsychological functioning and school achievement of children with epilepsy (1). Indeed, the type of theoretical and practical framework as used by the authors enables one to disentangle the decisive factors, enhances our understanding of the functioning of schoolchildren with epilepsy, and yields a sound basis for counseling. In other illness groups, such as spina bifida, a similar theoretical and statistical approach has already proven to be of great value [see, for instance, Holmbeck et al., 1997 (2)]. Dr. Fastenau et al. applied exploratory factor analysis to achieve data reduction and to identify relevant constructs in their neuropsychological test findings. In this respect, we wish to compliment the authors’ review of the literature. In the segment of the population of children with epilepsy that is similar to that described by Dr. Fastenau et al. (i.e., children with idiopathic or cryptogenic epilepsy), our group studied performances of the children and their parents’ and teachers’ complaints with respect to the behavior of the children, by using principal component analysis. We found ≥70% of the variance explained by five factors covering major domains of neuropsychological functioning (3). We strived for maximal homogeneity of our patient sample (i.e., schoolchildren with newly diagnosed nonsymptomatic epilepsy). Similar to the experience of Fastenau et al., despite a multicentric collaboration, our sample was too small for structural equation modeling (SEM). As could perhaps be expected in a small country such as the Netherlands, it also turned out to be not possible to establish large enough groups to apply conventional regression analyses. Although their succinct literature review is quite exhaustive, Fastenau et al. seem not to be fully aware of published European efforts to get a grip on the manifold interacting variables in the cognitive (and, for that matter, educational) functioning of children with epilepsy. By using repeated measures analysis of variance, we found that adverse psychosocial context and not epilepsy variables influences the outcome after 1 year. By now, we have followed up the majority of the original group for 3.5 years after diagnosis. Rather than primary illness variables (such as etiology, type of epilepsy, seizure remission, or use of antiepileptic drugs), again, school and behavioral history, broken families, and a wavering parenting as a reaction

∗

A. Jennekens-Schinkel † K. J. Oostrom on behalf of the Dutch Study Group of Epilepsy in Childhood ∗ Division of Neuropsychology Wilhelmina Children’s Hospital University Medical Centrum Utrecht Utrecht, The Netherlands † Department of Medical Psychology University Hospital Vrije Universiteit Amsterdam, The Netherlands REFERENCES 1. Fastenau PS, Shen J, Dunn DW, et al. Neuropsychological predictors of academic underachievement in pediatric epilepsy: moderating roles of demographic, seizure, and psychosocial variables. Epilepsia 2004;5:1261–72. 2. Holmbeck GN. Toward terminological, conceptual, and statistical clarity in the study of mediators and moderators: examples from the child-clinical and pediatric psychology literatures. J Consult Clin Psychol 1997;65:599–610. 3. Oostrom KJ, Smeets-Schouten A, Kruitwagen CL, et al. Not only a matter of epilepsy: early problems of cognition and behavior in children with “epilepsy only”. A prospective, longitudinal, controlled study starting at diagnosis. Pediatrics 2003;112:1338–44. 4. Oostrom KJ, van Teeseling H, Smeets-Schouten A, et al. Three to four years after diagnosis: cognition and behaviour in children with “epilepsy only”: a prospective, controlled study. Brain, accepted.

Valproate-induced Proximal Renal Tubular Dysfunction: Clinically Relevant in the Severely Disabled Epileptic Population To the Editor: We read with interest the article by Knorr et al., Fanconi Syndrome Caused by Antiepileptic Therapy with Valproic Acid, Epilepsia 2004;45:868–71, and their observation that this severe proximal renal tubular dysfunction on literature review has occurred almost exclusively in mentally retarded, severely disabled, often wheelchair-bound children. As consultants to several developmental centers, we follow valproic acid (VPA)-treated epilepsy patients 599

600

TO THE EDITOR

with profound mental retardation and other accompanying severe central nervous system disabilities. After observing a septicemic death associated with a reduction in serum albumin to 2.1 g/dl (3.4–5.0 g/dl, normal range) during VPA monotherapy, we systematically monitored these VPA-treated epilepsy patients and not uncommonly observed declining serum albumin levels to well below normal range. Of the first 12 patients (10 women, two men; ages, 16–50 years) so categorized, those supported with enteral nutrition (five of 12) who had weight increase, edema, and reduced serum albumin levels had no change in intake of calories and protein. Pearson correlations did not reveal a relation between the serum albumin levels and the protein intake. Plasma VPA concentrations were found to be within therapeutic range in the entire group, and none had a history of renal or hepatic disease. Serum glutamic oxaloacetic transaminase (SGOT) levels were within normal limits in 10 of 12, but ammonia levels were slightly elevated in seven of 12. The 24-h urine protein levels were found to be elevated, with a range of 115 to 2,850 mg, with a mean serum albumin level of 3.1 g/dl. The blood urea nitrogen (BUN) levels were all within normal limits. On discontinuance of VPA, the serum albumin levels increased to normal range (mean, 3.8 g/dl) within 2 to 3 weeks. We now routinely monitor VPA-treated patients at our developmental centers, discontinuing VPA when serum albumin levels decrease persistently to >2.8–3.0 g/dl, or even slightly higher levels if liver function appears to be problematic as well. Although the full-blown Fanconi syndrome appears rare, in our experience, a significant degree of proximal tubular dysfunction as a result of VPA toxicity with significant reductions in serum albumin is relatively common in this severely disabled epilepsy patient group, both children and adults, and requires systematic attention. Korinthenberg et al. (Renal tubular dysfunction following treatment with anti-epileptic drugs. Eur J Pediatr 1994;153:855–8) documented subclinical VPA (monotherapy)-induced proximal tubular dysfunction in otherwise healthy children with epilepsy. Therefore the superimposed loss of weight-bearing with its multiple endocrine/renal effects in our severely disabled epilepsy patient group could be the predisposing factor producing clinically significant VPA proximal renal tubular toxicity (Regnard et al. Validity of microgravity simulation models on earth. Am J Kidney Dis 2001;38:668–74). Stephen L. Jaffe Louisiana State University School of Medicine Shreveport, Louisiana Martha Sanford Northwest Louisiana Developmental Center Bossier City, Louisiana

Epilepsia, Vol. 46, No. 4, 2005

ATL in Refractory Epilepsy with Normal MRI-volumetric Criteria? To the Editor: P.N. Sylaja, et al., in their article, “Seizure Outcome after Anterior Temporal Lobectomy and Its Predictors in Patients with Apparent Temporal Lobe Epilepsy and Normal MRI” (Epilepsia 2004;45:803–8), reported excellent outcome after anterior temporal lobectomy (ATL) in a subset of patients with normal magnetic resonance imaging (MRI): those with a history of febrile seizures, strictly unilateral anterior interictal epileptiform discharges (IEDs), and concordant type 1 ictal EEG pattern. All of the patients in their group with excellent outcome had histologically proven hippocampal sclerosis. The question, therefore, arises whether subtle asymmetry of hippocampal size was missed, as the MRI criteria did not include quantitative analysis of the hippocampal volumes. Perhaps the authors should look at more patients with apparent temporal lobe epilepsy (TLE) and perform hippocampal volumetry to arrive at the conclusion that the MRI results were truly normal in this subset of patients. Ictal semiology, ictal video-EEG, and interictal EEG may point to a ictal-onset zone but may equally well include the epileptogenic zone, or indicate the area to which the epileptic discharges spread and produce ictal symptoms; the current understanding is that at least one imaging criterion should be met (whether positron emission tomography, singlephoton emission computed tomography, or MRI) before a patient can be submitted for ATL. If one is to change significantly this practice, then one must be certain that even after T2 relaxometry and hippocampal volumetry, a subset of TLE patients with normal MRIs will benefit with ATL. Rajshekher Garikapati Sudhir Kumar Subhashini Prabhakar Apollo Hospital, Neurosciences Department Hyderabad, AP India

Response: Seizure Outcome after Anterior Temporal Lobectomy To the Editor: We appreciate the valuable comments of Dr. Garikapati and colleagues on our report. The aim of our report was to emphasize how to identify a subset of temporal lobe epilepsy patients with favorable postoperative seizure outcome from among those selected for surgery based on a noninvasive protocol, as is usually practiced in developing countries. The assessment of the severity and extent of hippocampal atrophy and sclerosis can be improved by

TO THE EDITOR hippocampal volume measurements and T2 relaxometry, respectively. However, studies have shown that the magnetic resonance images (MRIs) undertaken conforming to the protocol we described and viewed by an experienced radiologist have a sensitivity and specificity comparable to those that have used quantitative analysis (1). We thought that each epilepsy center should evolve their own presurgical evaluation protocol considering the facilities and expertise available and the affordability for the patient population it serves. P. N. Sylaja K. Radhakrishnan C. Kesavadas P. S. Sarma Trivandrum, India

REFERENCE 1. Kuzniecky RI, Bilir E, Gilliam F, et al Multimodality MRI in mesial temporal sclerosis: relative sensitivity and specificity. Neurology 1997;49:774–8.

Epilepsy in Malaria To the Editor: I read with interest the article by Carter et al., “Increased Prevalence of Epilepsy Associated with Severe Falciparum Malaria in Children” (Epilepsia 2004;45:97881). I call attention to the possible pathogenesis of epilepsy in malaria. Epilepsy has long been recognized as a late complication of cerebral malaria. Generalized tonic–clonic seizures as well as partial motor seizures have been recorded (1). In fatal cases, pathological examinations of the brain in late stages have shown the malaric granuloma of Durck formed by an astroglial reaction (2). It is conceivable that these lesions may act as an epileptogenic foci in those who survive, giving rise to chronic epileptic seizures. M. A. Aleem Department of Neurology KAPV Govt. Medical College AGM Hospital and ABC HOSPITAL Trichy. 620018 Tamil Nadu, India

REFERENCES 1. Vietze G. Malaria and other protozoal diseases. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology. Vol 35. Amsterdam: North Holland, 1978:143–60. 2. Toro G, Roman GC. Cerebral malaria: a disseminated vasculomyelinopathy. Arch Neurol 1978;35:271–5.

601

Response: Pathogenesis of Epilepsy after Exposure to Severe Falciparum Malaria To the Editor: The causes of an increased rate of epilepsy in children who have had severe falciparum malaria are currently a matter of speculation. Our study strongly supports an association between falciparum malaria and epilepsy (1). Two complications of falciparum malaria—cerebral malaria and malaria with complicated seizures—were associated with an increased prevalence of epilepsy compared with that in children unexposed to these conditions. Dr. Aleem’s suggestion of granulomas of Durck being a cause of epilepsy in these children is possible. The neuropathology of severe falciparum malaria is discussed in several studies (2,3), which suggest that several pathogenic processes could be involved. The most likely are vascular/ischemic mechanisms (2), because ischemic lesions have been detected in adults with severe malaria (4,5); neurotoxic effects (6); and antibodies against voltage-gated channels (7). We would also raise the possibility of genetic mechanisms (8). In addition, complicated seizures occurring during the acute episode have features similar to those of complicated febrile seizures, which are associated with the subsequent development of epilepsy. Elucidating the mechanism of epileptogenesis will require magnetic resonance studies in children and further investigation of the putative mechanisms mentioned earlier. Julie Carter Neurosciences Unit Institute of Child Health The Wolfson Centre London, U.K. and The Centre for Geographic Medicine Research (Coast) Kenya Medical Research Institute Kilifi, Kenya Brian Neville Neurosciences Unit Institute of Child Health The Wolfson Centre London, U.K. Charles Newton Neurosciences Unit Institute of Child Health The Wolfson Centre London, U.K. and The Centre for Geographic Medicine Research (Coast) Kenya Medical Research Institute Kilifi, Kenya Epilepsia, Vol. 46, No. 4, 2005

602

TO THE EDITOR REFERENCES

1. Carter JA, Neville BG, White S, et al. Increased prevalence of epilepsy associated with severe falciparum malaria in children. Epilepsia 2004;45:978–81. 2. Newton CR, Krishna S. Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment. Pharmacol Ther 1998;79:1–53. 3. Turner G. Cerebral malaria. Brain Pathol 1997;7:569–82. 4. Cordoliani YS, Sarrazin JL, Felten D, et al. MRI of cerebral malaria. Am J Neuroradiol 1998;19:871–4.

Epilepsia, Vol. 46, No. 4, 2005

5. Looareesuwan S, Wilairatana P, Krishna S, et al. Magnetic resonance imaging of the brain in patients with cerebral malaria. Clin Infect Dis 1995;21:300–9. 6. Dobbie M, Crawley J, Waruiru C, et al. Cerebrospinal fluid studies in children with cerebral malaria: an excitotoxic mechanism? Am J Trop Med Hyg 2000;62:284–90. 7. Lang B, Newbold C, Williams G, et al. Antibodies to voltage-gated calcium channels in children with falciparum malaria. J Infect Dis 2005;191:117–21. 8. Versteeg AC, Carter JA, Dzombo J, et al. Seizure disorders among relatives of Kenyan children with severe falciparum malaria. Trop Med Int Health 2003;8:12–6.