490930 research-article2013 EEGXXX10.1177/1550059413490930Huang et alClinical EEG and Neuroscience Article Isolated Aphasic Status Epilepticus as Initial Presentation of Nonketotic Hyperglycemia Clinical EEG and Neuroscience 2014, Vol. 45(2) 126­–128 © EEG and Clinical Neuroscience Society (ECNS) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1550059413490930 eeg.sagepub.com Ling-Chun Huang1, Diane Ruge2, Chin-Ling Tsai3, Meng-Ni Wu1,4, Chung-Yao Hsu1,4, Chiou-Lian Lai1,4, and Li-Min Liou1,3 Abstract Diagnosis of aphasic status epilepticus is sometimes not easy because of its rarity and electroclinical dissociation. Although most cases are associated with organic brain lesions, nonketotic hyperglycemia (NKH)–related aphasic status epilepticus is rare, especially if it is isolated (without other clinical seizure activity). On the other hand, unlike other metabolic disorders, or hypoglycemia-related generalized seizures, focal motor seizure and epilepsia partialis continua can occur in 25% of NKH, with seizures being the initial manifestation in up to 50% of patients. However, the presentation of epileptic aphasia is rare in NKH patients. We report a rare case of NKH presenting initially as persistent and isolated aphasic status epilepticus. Brain magnetic resonance imaging did not reveal any focal lesion, but ictal electroencephalography (EEG) disclosed left frontotemporal continuous theta to delta waves, intermingled with epileptiform discharges. Correcting the hyperglycemia failed to improve the language disorder, and the seizure was controlled only by the addition of carbamazepine. Patients with NKH may initially present with isolated aphasic status epilepticus. Unlike stroke-related aphasia, accurate diagnosis is difficult if based solely on neurologic examination and brain neuroimaging. Use of EEG and blood sugar determination should be helpful in this special condition. Keywords aphasic status epilepticus, carbamazepine, nonketotic hyperglycemia Received November 13, 2012; revised April 5, 2013; accepted April 24, 2013. Introduction In the literature, aphasia occurs in a variety of cerebrovascular, traumatic, epileptic, or neurodegenerative conditions involving critical language areas of the brain, with cerebrovascular disease the leading cause.1 Although aphasia during epileptic seizures (epileptic aphasia) is not uncommon, isolated epileptic aphasia (without other clinical seizure activity) is rare and is often of short duration.2 Unlike other metabolic disorders, or hypoglycemia-related generalized seizures, NKH is classically associated with simple partial seizure, partial motor status, rarely complex partial seizure, or even isolated aphasic seizure.3,4 Isolated aphasic status epilepticus (ASE) without previous epilepsy, or cerebral lesions, is even more rare, especially due to NKH.2 We present a rare case of NKH-related isolated ASE, successfully treated by carbamazepine after correction of hyperglycemia. Case Report A 78-year-old right-handed man experienced acute speech disturbance for 5 days. His speech was scanty and incomprehensible, and he could not understand spoken language when he awoke that morning. However, he was alert, and could express his needs by gesturing. The course was persistent. The patient had no previous health examination. However, polyuria and polydipsia were noted before the event. Neurological examination revealed an alert and cooperative patient who had mixed aphasia with impaired fluency, repetition, comprehension, and naming. Muscle power was full and no spontaneous muscle activity could be found. He would occasionally have spontaneous speech and could follow orders by gesturing. Initial laboratory data showed serum glucose 381 mg/dL, osmolality 297 mOsm/L, and HbA1c 13.5%, without ketonuria or systemic acidosis. An initial diagnosis of NKH was made. Brain magnetic resonance imaging on the sixth day after onset showed mild cortical atrophy but no focal lesion. Cerebrospinal 1 Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, UK 3 Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Department of Neurology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Corresponding Author: Li-Min Liou, Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, No. 482, Shanming Road, Siaogang District, Kaohsiung City 812, Taiwan ROC. Email: liou_lm@yahoo.com.tw Full-color figures are available online at http://eeg.sagepub.com Downloaded from eeg.sagepub.com at SETON HALL UNIV on April 5, 2015 127 Huang et al Figure 1. EEG showed left frontotemporal continuous theta to delta waves intermingled with epileptiform discharges when aphasia persisted (A, B). EEG became normalized when aphasia subsided (C). fluid (CSF) was within normal limits (CSF protein 40 mg/dL; CSF/blood glucose 138/245). EEG on the sixth day of symptoms showed left frontotemporal continuous theta to delta waves intermingled with epileptiform discharges (Figure 1A and B). Aphasic disorder, EEG epileptiform discharges and negative cranial magnetic resonance imaging excluded cerebrovascular disease, but included the possibility of “epileptic aphasia.” A diagnosis of NKH-related isolated ASE was made. The aphasia persisted, although blood sugar was controlled (<200 mg/dL) 3 days after admission, and EEG patterns remained. Carbamazepine (100 mg per day) was started 4 days after correction of hyperglycemia. Carbamazepine was titrated to 200 mg per day 4 days later. Global aphasia gradually shifted to Broca’s aphasia. Speech was restored and EEG normalized 4 days later (Figure 1C). No aphasia or seizures were noted in the following years, even after discontinuing carbamazepine. Discussion We demonstrated a rare case of NKH, initially presenting as isolated ASE. Although hyperglycemia was corrected, aphasia was not controlled until the addition of carbamazepine. The diagnosis of ASE is sometimes not easy because of its rarity and electroclinical dissociation.5 Routine 30-minute EEG demonstrated seizure activity in only 56% of patients, despite the presence of aphasia during the recording.5 EEG abnormalities of ASE include epileptiform discharges, periodic lateralized epileptiform discharges and slow waves in left frontal, temporal and parietal cortex.5 Although most ASE patients have organic brain lesions, such as tumor, vascular abnormalities, stroke, or herpes simplex virus infection, NKH-related ASE is rare, especially if isolated (without other clinical seizure features).5,6 The clinical course and the EEG findings of our patient fits ASE.2 The appearance and disappearance of aphasia, with corresponding EEG findings, confirm ictal but not post-ictal manifestations.7 On literature review, NKH-related ASE seems to have its initial presentation as mixed aphasia,6 the same as in our case. This kind of aphasia is similar to that of patients with left middle cerebral artery infarction, which is the leading cause of isolated aphasia, making it more difficult to establish accurate diagnosis of NKH-related ASE. Interestingly, the recovery course of aphasia after treatment in our case is also similar to that of patients with left middle cerebral artery infarction. Seizures can be found in 25% of NKH patients and may be the first manifestation in up to 50% of NKH patients with seizures.4,8 Tiamkao et al9 have proposed the following diagnostic criteria for NKH-related seizures; plasma glucose >290 mg/dL and osmolarity 288 mOsm/kg. Several mechanisms of NKHrelated seizures have been proposed. Schwechter et al10 reported that hyperglycemia may be proconvulsant per se, even in the absence of organic brain lesions. Decreased local brain blood flow, producing reversible focal ischemia and decreased seizure threshold, were also reported.11 NKH-related seizures, generally considered types of symptomatic seizures, were usually resistant to anticonvulsant treatment but responded well to insulin therapy and rehydration.8 However, correction of hyperglycemia only in our case failed to control NKH-related “epileptic aphasia,” implying it is more than a symptomatic seizure disorder. We hypothesize that NKH-related epileptic aphasia in our case is actually a kind of “status epilepticus”, therefore the use of an anticonvulsant is necessary. Whether NKH-related epileptic aphasia is solely a symptomatic seizure disorder, or is largely based on the degree of cerebral damage caused by NKH, is not known. NKH itself can induce seizure disorders, and poor glycemic control can further aggravate epileptic seizures. Huang et al12 found that patients with diabetic hyperglycemia had more recurrent seizures and status epilepticus than those without, suggesting potential kindling during poor glycemic control. Patients with higher plasma glucose level with poor glycemic control (HbA1c >9%) had significantly higher risk of seizure recurrence.12 In animal studies, a higher glucose level also facilitated amygdala kindling in rats.13 Further detailed investigations on NKH-related epileptic aphasia are warranted. In summary, patients with NKH may initially present with persistent and isolated ASE. Unlike stroke-related aphasia, NKH-related epileptic aphasia is difficult to diagnose accurately if based solely on neurologic examination and cranial neuroimaging. The use of EEG and blood sugar examination should be helpful in all patients presenting with acute aphasia. Declaration of Conflicting Interests The authors declared no conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The authors received no financial support for the research, authorship, and/or publication of this article. References 1. Pedersen PM, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Aphasia in acute stroke: incidence, determinants, and recovery. Ann Neurol. 1995;38:659-666. 2. Grimes DA, Guberman A. De novo aphasic status epilepticus. Epilepsia. 1997;38:945-949. 3. Grant C, Warlow C. Focal epilepsy in diabetic non-ketotic hyperglycaemia. Br Med J (Clin Res Ed). 1985;290:1204-1205. Downloaded from eeg.sagepub.com at SETON HALL UNIV on April 5, 2015 128 Clinical EEG and Neuroscience 45(2) 4. Pro S, Randi F, Pulitano P, Vicenzini E, Mecarelli O. Nonconvulsive status epilepticus characterised exclusively by a language disorder induced by non-ketotic hyperglycaemia. Epileptic Disord. 2011;13:193-196. 5. 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