Shohei Nomura

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.

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.

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.

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 patients 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.

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.

Prognostic factors in the early phase of acute encephalopathy

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.

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.

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

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.

Clinical features of long‐term epilepsy treatment with low‐dose levetiracetam

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.