Reversible splenial lesions during febrile illness with or without white matter lesions.

OBJECTIVE: Reversible splenium lesions during febrile illness (RESLEF) are found in a spectrum. There are two types of corpus callosum (CC) lesions: CC-only type, with limited lesions and the CC (+) type, with extensive white-matter lesions. This retrospective study aimed to describe the differences in clinical findings between CC-only and CC (+) lesions and the association between onset age and clinico-radiological features in RESLEF. METHODS: Fifty-two episodes of CC-only or CC (+) lesions accompanied by neurological symptoms, e.g., seizures, delirious behavior (DB), and disturbance of consciousness (DC), from January 2008 to October 2019 were included. We analyzed the etiology (pathogen), clinical course, laboratory data, magnetic resonance imaging and electroencephalography findings, therapy, and prognosis. RESULTS: The rate of DC in the CC (+) was significantly higher than that in the CC-only group (5/6 [83%] vs 7/46 [15%]; p = 0.0016). The median number of seizures in the CC (+) was also significantly higher than that in the CC-only group (4 [0-7] vs 0 [0-7]; p = 0.034). Further, in RESLEF, the median onset age (months) in the seizure was significantly lower than that in the no-seizure group (39 [12-74] vs 83 [28-174]; p = 0.0007). The median onset age (months) in the DB was significantly higher than that in the no-DB group (74.5 [26-174] vs 28 [12-139]; p = 0.003). CONCLUSIONS: In RESLEF, CC (+) is a more severe neurological symptom than CC-only. Furthermore, the onset age is related to the type of neurological symptoms that appear.

Treatment outcomes for infantile spasms in Japanese children with Down syndrome.

BACKGROUND: The aim of this study was to assess the treatment response to conventional antiepileptic drugs and low-dose adrenocorticotropic hormone therapy for infantile spasms in children with Down syndrome. METHODS: We retrospectively investigated the response and relapse rates, electroencephalography findings, patient characteristics during drug withdrawal, and developmental outcome in 10 children with Down syndrome treated for infantile spasms in our hospital. RESULTS: All patients showed cessation of infantile spasms and achieved electroencephalographic normalization. Spasm relapse occurred in one of 10 patients (10%). Antiepileptic drugs have been withdrawn for seven of 10 patients (70%), none of whom have experienced seizure relapse since drug withdrawal. The median developmental quotient (n = 8) was 20.5, which shows that the developmental outcome was unfavorable. Low-dose adrenocorticotropic hormone therapy achieved a low seizure remission rate of 28.6%. CONCLUSIONS: Elucidation of the optimal treatment for infantile spasms in children with Down syndrome is needed to reduce the duration of infantile spasms and improve the developmental outcome.

Rapid-onset dystonia-parkinsonism with ATP1A3 mutation and left lower limb paroxysmal dystonia.

BACKGROUND: Rapid-onset dystonia-parkinsonism (RDP) is a disease characterized by an abrupt onset of dystonia accompanied by signs of parkinsonism and prominent bulbar symptoms. CASE REPORT: We describe a case of a female patient, born after normal delivery, but diagnosed with mild intellectual disability at age 7. She presented with an abrupt onset of upper limb dystonia and bradykinesia without tremor in parkinsonism, as well as dysarthria and dysphagia caused by prominent bulbar symptoms, at age 9. She had normal findings on brain magnetic resonance imaging, electroencephalography, and blood examination but was diagnosed with a psychogenic disorder. At age 10, she developed left lower limb paroxysmal stiffness with pain, and at 14, she was hospitalized due to lasting paroxysmal symptoms. Whole-exome sequencing was performed for this index case and her parents, and a de novo missense variant c.829G > A, p.Glu277Lys in ATP1A3 was identified. DISCUSSION: This RDP case highlights a rare clinical feature of paroxysmal dystonia that affects the lower left limb and develops after the abrupt onset of permanent dystonia. Currently, there are only three reported RDP cases associated with the same missense mutation, and we summarized the clinical features of all cases including ours, such as onset of age, time for stable, RDP score, relapse and exacerbation. Various symptoms owing to ATP1A3 mutation could develop as ATP1A3-related neurological disorders beyond classical phenotypes such as alternating hemiplegia of childhood (AHC) or RDP. Although RDP is extremely rare during childhood, it is important to understand its clinical characteristics in children.

Clinical findings in patients with febrile seizure after 5 years of age: A retrospective study.

OBJECTIVE: Febrile seizures (FSs) typically occur in infants and children between 6 and 60 months of age. Rarely, FS can occur in late childhood (late FS [LFS]; >5 years of age); however, the clinical features of LFS remain unclear. We aimed to clarify the clinical features of LFS. METHODS: We retrospectively analyzed data from patients with LFS who visited Hirakata City Hospital between January 2004 and December 2014. We defined LFS as a seizure accompanied by fever (temperature ≥38 °C) occurring after 5 years of age, without a central nervous system infection. RESULTS: A total of 505 patients (349 boys, 156 girls: 5-14 years old) were included. A history of FS before 60 months of age was observed in 319 of 460 patients (69.3%) with sufficient information about previous FS history among the 505 patients enrolled. LFS was more likely to occur in males (69.1%). Seizure duration was ≤15 min in 87.4% of cases. A family history of FS in first-degree relatives was observed in 103/327 cases (31.5%). Among LFS cases, 45% occurred at 5 years of age, and 92.1% experienced only one seizure after 5 years of age. The number of seizure episodes gradually lessened with age, decreasing drastically to 5.6% of cases older than 9 years. CONCLUSIONS: Our findings suggest that sex differences, seizure duration, and family history were similar for LFS and FS. Over 90% patients with LFS experienced no recurrence after 5 years of age. Further study is needed to verify the recurrence rate of LFS.

Prognostic factors in the early phase of acute encephalopathy.

BACKGROUND: Neurological sequelae occur in 40% of patients with acute encephalopathy (AE). The early prediction of poor outcomes is critical to the initiation of appropriate treatment. The aim of the present study was therefore to elucidate prognostic factors that can be quickly and feasibly evaluated on hospital admission in patients with AE. METHODS: We analyzed data from 51 AE patients admitted to Hirakata City Hospital between January 2005 and December 2014. Age at onset, sex, underlying disease, status epilepticus (SE), presence of benzodiazepine-resistant SE (BZD-resistant SE), and basic blood serum parameters on admission were evaluated in relation to each patient's outcome. RESULTS: On univariate analysis age at onset, BZD-resistant SE, and serum aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and platelet count varied significantly according to outcome. On multivariate analysis age at onset (≤21 months), presence of BZD-resistant SE, and AST (≥46 IU/L) were identified as independent variables associated with poor outcome. CONCLUSION: Age at onset, presence of BZD-resistant SE, and AST are associated with a poor prognosis in AE.

The efficacy of adrenocorticotropic hormone in a girl with anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Immunomodulatory therapy has shown some therapeutic benefits in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. In this report, we describe the use of adrenocorticotropic hormone (ACTH) immunotherapy with good outcome in a patient with anti-NMDAR encephalitis. SUBJECT AND METHODS: A 4-year-old girl developed convulsions in her right arm and leg without impaired consciousness. These convulsions occurred frequently in clusters of 10-20 events of 10-20 s duration. She was admitted to our hospital on the 6th day following her initial series of convulsions. Flaccid paralysis of the right hand and leg was also found. Interictal electroencephalography showed high-amplitude slow waves. No abnormal findings were shown on MRI. 99mTc-ECD brain SPECT on the 14th day showed hyperperfusion in the left hemisphere, including the left basal ganglia. The convulsions ceased following the oral administration of valproic acid on the 10th day; however, paralysis associated with choreic dyskinesia of the right arm and leg remained. ACTH immunotherapy was then performed on the 15th day. We identified the presence of N-methyl-D-aspartate receptor antibody in CSF samples taken on the 6th day. After ACTH therapy, the patient fully recovered from the paralysis associated with choreic dyskinesia of the right arm and leg. She has not had a relapse and has not required medication for over a year. CONCLUSION: ACTH immunotherapy may be a useful treatment option for patients with anti-NMDAR encephalitis, although further evaluation is required.

Gaze stabilization exercises derive sensory reweighting of vestibular for postural control.

[Purpose] The aim of this study was to investigate whether gaze stabilization exercise derives sensory reweighting of vestibular for upright postural control. [Subjects and Methods] Twenty-three healthy volunteers participated in this study. The center of pressure of the total trajectory length was measured before (pre), immediately after (post), and 10 min after (post10) gaze stabilization exercise, in the static standing position, with the eyes open or closed, on the floor or on foam rubber. The sensory contribution values of the visual, somatosensory, and vestibular systems were calculated using center of pressure of the total trajectory length value in these measuring conditions. [Results] The center of pressure of the total trajectory length on foam rubber in post and post10 were significantly lower than that in the pre. The sensory contribution values of vestibular in post10 stages were significantly higher than that in pre-stage. [Conclusion] Gaze stabilization exercise can improve the static body balance in a condition that particularly requires vestibular function. The possible mechanism involves increasing sensory contribution of the vestibular system for postural control by the gaze stabilization exercise, which may be useful to derive sensory reweighting of the vestibular system for rehabilitation.

Effect of gaze-stabilization exercises on vestibular function during postural control.

Gaze-stabilization exercise (GSE) is often conducted in vestibular rehabilitation, but its effect on vestibular function in postural control is not clear. We investigated whether GSE affects vestibular function during static upright standing and vestibulospinal reflex (VSR) in healthy young adults. First, the center of pressure of the total trajectory length (CoP-L) was measured before each GSE task or control (only standing) task (pre), immediately after (post), and 10 min after (post10) in the static standing position on foam rubber with the eyes open or closed (EC). Second, the H-reflex on the soleus muscle was measured after the onset of ipsilateral anodal galvanic vestibular stimulation before and after a GSE or a control task to estimate the amount of VSR induced by electrical vestibular input. CoP-L for the pre, post, and post10 control tasks and the GSE in EC did not differ significantly; the CoP-L for the post and post10 tasks in EC were significantly lower than that for the pretask. The H-reflex was inhibited by galvanic vestibular stimulation in the pre-GSE tasks. The inhibition increased after GSE, but not during control tasks. These findings suggest that GSE immediately improves the postural stability required for vestibular function and can be mediated by VSR improvements.

Prediction of destination at discharge from a comprehensive rehabilitation hospital using the home care score.

[Purpose] This study investigated whether it is possible to predict return to home at discharge from a rehabilitation hospital in Japan using the home care score of patients with cerebrovascular or osteoarticular disease and low activities of daily living at admission. [Subjects and Methods] The home care score and functional independent measurement were determined for 226 patients at admission and at discharge from five hospitals, and receiver operating characteristic analyses were conducted. [Results] The home care score cutoff point for the prediction of return to home at admission and at discharge was 11, and the area under the curve was more than 0.8. The area under the curve of the home care score was 0.77 for patients with low activities of daily living and within this group, the probability of return to home was approximately 50%, as predicted by the functional independent measurement. The home care score increased after receiving intervention at a rehabilitation hospital. [Conclusion] The home care score is useful for the prediction of return to home from a rehabilitation hospital, although prediction using the functional independent measurement is difficult for patients with low activities of daily living. Moreover, comprehensive interventions provided by the rehabilitation hospitals improve the ability to provide home care of the patient's family, which is assessed by the home care score.

Post-vaccination MDEM associated with MOG antibody in a subclinical Chlamydia infected boy.

The mechanism of post-vaccination acute disseminated encephalomyelitis (ADEM) has been hypothesized as resulting from vaccination-injected antigens cross-reacting with myelin components, however, a precise etiology has been uncertain. In this report, we describe the case of a 6-year-old Japanese boy who had multiphasic disseminated encephalomyelitis (MDEM), and was positive for both anti-myelin oligodendrocyte glycoprotein (MOG) antibodies and Chlamydophila pneumoniae antibodies. After vaccinations that were the second one for measles and rubella, and the booster immunization for Japanese encephalitis, the patient presented with fever, headache, vomiting, and a change in personality. He was treated with a high-dose of intravenous methylprednisolone in the diagnosis of ADEM. However, these symptoms recurred with different magnetic resonance imaging lesion, and he was diagnosed as MDEM. Retrospective testing for pathogens revealed C. pneumoniae IgM and IgG antibodies, and it was considered that he was infected with C. pneumoniae subclinically. The patient's serum indicated a positive response for the anti-MOG antibody from the onset of the ADEM diagnosis and in all recurrent episodes. Chlamydia species infection has been known to play a role in demyelinating diseases. It is also known that the anti-MOG antibody may be present but not exhibit its pathogenesis in the absence of a cell-mediated inflammatory response; however, the precise mechanism of action of the anti-MOG antibodies is not yet determined. We propose the possibility that post-vaccination demyelinating disease may result from the synergistic effects of a preceding anti-MOG antibody, possibly produced in response to a subclinical Chlamydia species infection.

Clinical features of long-term low-dose levetiracetam treatment for epilepsy.

BACKGROUND: The aim of this study was to assess the rate of response to long-term low-dose levetiracetam (LEV) treatment and the clinical factors associated with response. METHODS: The response to low-dose LEV of 43 patients with epilepsy (22 male, 21 female; age range, 5-39 years; median age, 13 years) was retrospectively assessed. Patients aged <15 years received <20 mg/kg/day LEV, whereas those aged ≥15 years received <1000 mg/day LEV. Clinical features were compared between responders to low-dose LEV, responders to the recommended dose, and non-responders. RESULTS: Of the 43 patients who received low-dose LEV, 13 (30%) showed improvement, defined as seizure cessation or >75% seizure reduction over 6 months for patients with monthly, weekly, and daily seizures; and over 1 year for patients with yearly seizures. Efficacy was maintained for >1 year in 10 (77%) of the 13 patients. Long-term response to low-dose LEV was significantly associated with older age at onset and fewer previous treatments with ineffective anti-epileptic drugs. All patients showing long-term response to low-dose LEV developed only focal seizures. CONCLUSIONS: Titration of LEV starting from a low dose may be effective in selected patients. Once patients respond to low-dose treatment, maintenance of the effective dosage may prolong response.

Acute abdominal pain as the only symptom of a thoracic demyelinating lesion in multiple sclerosis.

Multiple sclerosis (MS) is a syndrome characterized by complex neurological symptoms resulting from demyelinating lesions in the central nervous system. We report a child with a relapse of MS whose only presenting symptom was severe abdominal pain. Dysfunctional intestinal mobility was assessed by abdominal computed tomography. Findings resembled paralytic ileus resulting from peritonitis. However, the patient demonstrated no other symptoms of peritonitis. A T2-weighted magnetic resonance image revealed a new demyelinating lesion localized to thoracic segments T4-T12. The lesion presumably affected autonomic efferents involved in intestinal mobility. Treatment with a pulse of methylprednisolone reduced both abdominal pain and lesion size. To our knowledge, this is the first reported case of a pediatric MS patient with a demyelinating lesion associated with an autonomic symptom of altered intestinal mobility in the absence of neurological symptoms. This atypical presentation of MS highlights the need for physicians' vigilance when treating this patient population.

Incidence of febrile seizure in patients with Down syndrome.

BACKGROUND: It is unclear whether the incidence of febrile seizure (FS) in children with Down syndrome (DS) is higher or lower than in the general population. In this study, we investigated the incidence of FS in DS patients using mailed questionnaires. METHODS: The questionnaires were distributed to parents or caregivers of DS patients attending Osaka Medical College Hospital and six other facilities. The questionnaires were returned by mail from February 2012 to September 2013 from 323 families of DS patients (176 male, 147 female; age range, 3 months-47 years; median age, 5.0 years). To assess the incidence of FS in DS, we performed the following two analyses: (i) we calculated the incidence of FS among DS patients between the ages of 4 and 20 years (n = 199; 113 male, 86 female), and (ii) we extracted families with both DS and healthy siblings between the ages of 4 and 20 years (n = 150; 77 male, 73 female) and compared the incidence of FS in these sibling groups. RESULTS: Five DS patients had a past history of FS. The incidence of FS in DS was 2.5%. The incidence of FS was significantly lower in DS patients compared with healthy siblings (P < 0.003; OR, 0.14). CONCLUSION: The incidence of FS is lower in DS patients than in the general population.

Serum N-Terminal Pro-B-Type Natriuretic Peptide (NTproBNP) Levels Are Elevated During the Acute Phase of Acute Encephalopathy-Associated Virus Infection.

Acute virus-associated encephalopathy induces seizures. Serum N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are elevated following febrile and afebrile seizures. However, the role of NTproBNP in acute virus-associated encephalopathy pathology is unknown. We enrolled 10 patients with acute virus-associated encephalopathy and convulsions (E group: 7 boys, 3 girls; median age, 3.10 ± 1.92 years) and 130 patients with febrile seizure (FS group: 80 boys, 50 girls; median age, 3.23 ± 2.44 years). The E group had significantly higher NTproBNP levels (345 ± 141 pg/mL) compared with the FS group (166 ± 228 pg/mL) (P < .0005). Furthermore, subjects with prolonged seizure within the E group had significantly higher NTproBNP levels (303 ± 107 pg/mL) compared with subjects with prolonged seizure within the FS group (134 ± 100 pg/mL) (P < .005). Our findings suggest that serum NTproBNP levels are increased during the acute phase of acute virus-associated encephalopathy associated with convulsion.

ACTH therapy on intractable epilepsy in Hemiconvulsion-Hemiplegia-Epilepsy syndrome.

INTRODUCTION: In the chronic phase of Hemiconvulsion-Hemiplegia-Epilepsy (HHE) syndrome, developing epilepsy may be intractable. Herein, we report a case where adrenocorticotropic hormone (ACTH) ceased an intractable habitual partial seizure in a patient with HHE syndrome. CASE REPORT: A developmentally normal one-year-old girl presented with left focal motor status epilepticus in the clinical course of rotavirus infection. She was diagnosed with HH syndrome. At 4 months after status epilepticus, she developed partial seizures that occurred daily, and which resulted in a stooped posture, head rotation to the right, and contraction of both upper limbs predominantly in the left arm. At this time, she was diagnosed with idiopathic HHE syndrome. Her seizures were not reduced by sodium valproate, clonazepam, clobazam, zonisamide, phenytoin, phenobarbital, topiramate, lamotrigine, or liposteroid. At the age of 7, ACTH therapy was performed. On the 10th day of ACTH therapy, the habitual seizure was ceased. However, partial seizures characterized by left arm contraction then developed. Treatment with 350 mg/day lamotrigine prevented this emerging seizure. She has been free of both seizure types for more than one year, with no serious adverse effects of ACTH therapy. CONCLUSION: We suggest that ACTH therapy may be useful for patients with HHE, although further studies are required.

3-Methyl-1-phenyl-2-pyrazolin-5-one or N-acetylcysteine prevents hippocampal mossy fiber sprouting and rectifies subsequent convulsive susceptibility in a rat model of kainic acid-induced seizure ceased by pentobarbital.

There is accumulating evidence that reactive oxygen species are involved in the development of seizures under pathological conditions, and antioxidant treatments are a novel therapeutic approach for epilepsy. The kainic acid (KA) model of induced seizures has been widely used to study temporal lobe epilepsy. However, research on the use of free radical scavengers following KA-induced status epilepticus (SE) is limited. We examined whether antioxidants already used in humans could reduce hippocampal neuronal cell loss, mossy fiber sprouting and the acquisition of hyperexcitability when administered as a single dose after SE. The antioxidant 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) (30mg/kg) or N-acetylcysteine (NAC) (30mg/kg) was administered after KA-induced SE ceased by pentobarbital. We evaluated neuronal cell viability 1 week after SE, determined the threshold for seizures induced by inhalation of flurothyl ether 12 weeks after SE, and examined the extent of mossy fiber sprouting 12 weeks after SE. We found that edaravone or NAC prevented neuronal cell loss and mossy fiber sprouting, and increased the threshold for seizures induced by flurothyl ether, even when administered after KA-induced SE. These results demonstrate that a single dose of edaravone or NAC can protect against neuronal cell loss and epileptogenesis when administered after SE ceased by pentobarbital.

Partial seizures during ACTH therapy in a cryptogenic West syndrome patient.

BACKGROUND: Partial seizures often develop during the clinical course of infantile spasms. Herein, we report a boy with cryptogenic West syndrome, who developed partial seizures that we suspected were induced by the ACTH therapy. SUBJECT: The patient developed cryptogenic West syndrome at six months of age and ACTH therapy was started. On the tenth day of treatment, he developed frequent partial seizures, characterized by being motionless during the seizure with eye deviation to the right. The partial seizures stopped after the ACTH was discontinued, although oral carbamazepine was commenced at the same time. Thus, a definitive role for carbamazepine in the treatment of the partial seizures was unclear as the timing of the seizure cessation also corresponded to the discontinuation of the ACTH therapy. We suspected that the partial seizures were induced by the ACTH therapy for the following reasons: (1) seizures appeared only during ACTH therapy, (2) no new epileptic focus was revealed by EEG, MRI, or (99m)TcECD SPECT, and (3) the seizures were different from the epileptic spasms. CONCLUSION: Our results suggest that ACTH might induce partial seizures in West syndrome. Further studies are required to confirm this phenomenon.

Lamotrigine for intractable migraine-like headaches in Sturge-Weber syndrome.

We herein report that naratriptan remarkably improved intractable migraine-like headaches in a patient with Sturge-Weber syndrome (SWS) despite his past history of cerebral infarction. In addition, lamotrigine had a prophylactic effect on his visual aura and headaches. An 18-year-old male patient with SWS had intractable migraine-like headaches every several months from the age of 3years. His migraine-like headaches were characterized by pulsating attacks preceded by left homonymous hemianopsia, which persisted after headache disappearance. In addition, after 14years of age, the pulsating headaches were preceded by photophobia without homonymous hemianopsia and occurred almost daily. Headache pains were not improved by acetaminophen or loxoprofen sodium hydrate. Furthermore, various prophylactic drugs were ineffective. After obtaining informed consent, naratriptan was administered. The pain severity was reduced and the duration of headache with homonymous hemianopsia was shortened from several days to several hours. Interestingly, naratriptan also shortened the duration of homonymous hemianopsia to several hours. We confirmed that his headache attacks were not epileptic seizures by ictal electroencephalography. However, 25mg/day of lamotrigine had a prophylactic effect on the frequency of headache. Moreover, lamotrigine led to complete remission of his headache without homonymous hemianopsia. Lamotrigine may have an advantage in terms of reducing the risk of cerebrovascular disease caused by migraine-like headaches and the use of triptans. The most effective management for migraine-like headaches in patients with SWS has not been established. Lamotrigine is a potentially effective option for patients with SWS with migraine-like headaches.

Microdeletions of 5.5 Mb (4q13.2-q13.3) and 4.1 Mb (7p15.3-p21.1) associated with a saethre-chotzen-like phenotype, severe intellectual disability, and autism.

We observed a patient with a Saethre-Chotzen-like phenotype with severe neurological features. Saethre-Chotzen syndrome (acrocephalosyndactyly type III; SCS; OMIM #101400) is an autosomal dominant craniosynostosis syndrome characterized by craniofacial and mild limb abnormalities. The phenotypic features of chromosomal microdeletions involving the 7p21.1, where the twist homolog 1 gene (TWIST1) responsible for SCS is located, are recognized as a contiguous gene deletion syndrome with SCS and other phenotypic manifestations. In this study, we identified microdeletions in 4q13.2 and 7p21.1 in a patient with SCS and severe neurological features including developmental delay and autistic behavior. In comparison to other SCS patients with intragenic mutations or small deletions in 7p21.1, neurological features seen in this patient were extremely severe, likely modified by a concurrent deletion of 4q13.2. Both microdeletions were de novo and paternal in origin. Further information on such concurrent chromosomal deletions should be accumulated for better understanding of the mechanism.

[Efficacy of topiramate for relapsed epileptic spasms with tuberous sclerosis: report of three cases].

Topiramate (TPM) has been shown to be effective for epileptic spasms (ES) in children, but there is little clinical experience with TPM use in Japan. We report three tuberous sclerosis (TS) patients with relapsed ES, who became spasm-free while receiving TPM treatment. All three patients were treated with a starting dose of 0.5 mg/kg/day. The dosage was increased by 0.5 mg/kg/day every 2 weeks. Although the dose of TPM and the period until the relapsed ES subsided differed among these patients, spasm frequency was clearly reduced by a 1 mg/kg/day dose of TPM. Therefore, efficacy against relapsed ES appeared within one month in all three patients. All three became spasm-free, and there have been no ES relapses for more than 5 months to date. In case 2, seizures were well controlled by TPM alone. Cases 2 and 3 were able to discontinue zonisamide treatment. No adverse effects occurred in any of these patients.