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Background and purpose Akinetic mutism is thought to be an appropriate therapeutic end-point in patients with sporadic Creutzfeldt−Jakob disease (sCJD). However, prognostic factors for akinetic mutism are unclear and clinical signs or symptoms that precede this condition have not been defined. The goal of this study was to identify prognostic factors for akinetic mutism and to clarify the order of clinical sign and symptom development prior to its onset. Methods The cumulative incidence of akinetic mutism and other clinical signs and symptoms was estimated based on Japanese CJD surveillance data (455 cases) collected from 2003 to 2008. A proportional hazards model was used to identify prognostic factors for the time to onset of akinetic mutism and other clinical signs and symptoms. Results Periodic synchronous discharges on electroencephalography were present in the majority of cases (93.5%). The presence of psychiatric symptoms or cerebellar disturbance at sCJD diagnosis was associated with the development of akinetic mutism [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.14–1.99, and HR 2.15, 95% CI1.61–2.87, respectively]. The clinical course from cerebellar disturbance to myoclonus or akinetic mutism was classified into three types: (i) direct path, (ii) path via pyramidal or extrapyramidal dysfunction and (iii) path via psychiatric symptoms or visual disturbance. Conclusions The presence of psychiatric symptoms or cerebellar disturbance increased the risk of akinetic mutism of sCJD cases with probable MM/MV subtypes. Also, there appear to be sequential associations in the development of certain clinical signs and symptoms of this disease.

AIM: Some previous studies have shown a positive relation between geomagnetic disturbances and an increased incidence of suicide. If such a relation exists, stronger geomagnetic fields may affect the number of suicides, because stronger geomagnetic fields generally cause larger geomagnetic field disturbances. Therefore, we here investigated the relation between local geomagnetic field magnetic flux density and the standardized morbidity ratios (SMR) for suicide by each prefecture in Japan. METHODS: Monthly suicide data for each prefecture in the period January 1999 to December 2008 was obtained, and it was found that a total of 216 171 male individuals and 85 154 female individuals committed suicide during this period. A multiple linear regression analysis was carried out with a backward elimination procedure. The SMR for suicide by each prefecture was taken as the response variable and the explanatory variables were each prefecture's local geomagnetic field magnetic flux density (nT), north latitude (°), monthly mean unemployment rate (%), monthly mean air pressure (hPa), monthly mean air temperature (°C), monthly mean humidity (%), and monthly total day length (hours). Analyses were carried out separately for each sex. RESULTS: In the multiple linear regression analysis for male subjects, the local geomagnetic field magnetic flux density (nT), monthly mean unemployment rate (%), and monthly mean humidity (%) were associated with the incidence of suicide, but in the multiple linear regression analysis of female subjects, only north latitude was associated with that. CONCLUSION: In this study, we generated a hypothesis that stronger geomagnetic fields affect the number of cases of male suicide. Language: en

Summary: Purpose: We analyzed the short- and long-term effects of adrenocorticotropic hormone (ACTH) therapy for patients with epileptic spasms (ESs) who did not meet the criteria of West syndrome (WS). Methods: The subjects were 30 patients, including 13 boys and 17 girls, who had received ACTH therapy between 1970 and 2003. We excluded patients with WS, but included those with a history of WS who no longer showed hypsarrhythmia at the period of ACTH therapy. The age at onset of ESs and at ACTH therapy ranged from 2 to 82 months with a median of 18 months, and from 11 to 86 months with a median of 29 months, respectively. Results: Excellent and poor responses were obtained in 19 (63%) and 11 (37%) patients, respectively, as a short-term effect. Although the patients could be subclassified into five subgroups according to the previous reports, no difference was seen in shortterm response to ACTH. Among 17 of the 19 patients with excellent short-term outcomes and a follow-up of >1 year after the ACTH therapy, eight patients have continued to be seizure free (29%; excellent long-term effect), whereas the remaining nine patients had a recurrence of seizures (complex partial seizures, four; generalized tonic seizures, three; ESs, two) at 9 months to 198 months (median, 49 months) after ACTH therapy. In addition, nine of the 17 patients demonstrated a localized frontal EEG focus after the ACTH therapy, although most of these had previously shown diffuse epileptic EEG abnormality. Conclusions: ACTH therapy is worth trying for patients with resistant ESs, even without features of WS. However, the longterm effect is uncertain because recurrences of various types of seizures, including focal, were frequently observed. Key Words: Epileptic spasms—ACTH therapy—West syndrome— Hypsarrhythmia—Frontal EEG focus. Epileptic spasms (ESs) are the primary seizure manifestation not only in patients with West syndrome (WS) but also in patients with other forms of generalized or focal epilepsies (1‐4). The latter groups are subdivided largely into patients characterized by early onset of ESs without hypsarrhythmia, those with late onset of ESs and clinicoelectrical features of Lennox‐Gastaut syndrome, and those with focal epilepsy manifesting both partial seizures and ESs (2‐4). Detailed studies focusing on ESs in the latter groups have been conducted by several investigators, who demonstrated that the clinical and EEG characteristics of the attacks were identical to those of WS, whereas the interictal EEG pattern manifested no typical hypsarrhythmia (5‐8). The prognosis of the seizures has been reported to be poor, because ESs without hypsarrhythmia (ESwoH) have been resistant to medical treatment and also to the epileptic surgery attempted in some patients

Reaction of microglial cells as well as DNA fragmentation in pyramidal cells was investigated using immunohisto-chemistry and in situ end-labeling method (TUNEL) in the hippocampus of rats after rapid kindling or kainic acid treatment. In intact rats, no or very little DNA fragmentation was detected in the hippocampus. Resting microglia distributed evenly throughout the hippocampus. Neither major histocompatibility complex antigens class I (MHC I) nor class II (MHC II) immunoreactivity was seen in the hippocampus. In the rapid-kindling model, no DNA fragmentation, reactive microglia or MHC antigen-positive cells were present in the hippocampus. In rats given an intraperitoneal injection of kainic acid (12 mg/kg), reactive microglial cells were seen around pyramidal neurons in the CA1 and CA3 field of the hippocampus as well as in the hilus of the dentate gyrus at 3 h. At that point in time, DNA fragmentation was not detected. DNA fragmentation was clearly observed, mainly in the CA1 region of the hippocampus, from 24 h to 4 weeks after the kainic acid injection. The number of reactive microglia was quickly increased and reached a maximum at 7 days after the injection, and continued until 8 weeks thereafter. During this period, many reactive microglia expressed MHC I and MHC II. The present study indicates that epileptic seizures do not depend on microglial activation and that microglial activation is closely related to the neuronal death process induced by kainic acid.

In this study, we assessed the effects of the acute (a single injection) and repeated (once daily injections for 21 days) administration of the atypical antipsychotic drug clozapine (1.5, 5, or 15 mg/kg i.p.) and the typical antipsychotic drug haloperidol (0.15, 0.5, and 1.5 mg/kg, i.p.) on hippocampal partial seizures generated by low-frequency electrical stimulation in male Wistar rats. The seizure threshold and severity were determined by measuring the pulse number threshold (PNT) and the primary afterdischarge duration (ADD), respectively. A single injection of either 5 or 15 mg/kg of clozapine significantly decreased the PNT and significantly increased the primary ADD, indicating a proconvulsant action. The repeated administration of clozapine (1.5, 5, or 15 mg/kg, i.p.) produced dose-dependent, proconvulsant effects by significantly decreasing the PNT and by significantly increasing the primary ADD. In contrast to clozapine, the acute administration of haloperidol did not significantly alter the PNT or the primary ADD. The repeated administration of haloperidol (0.5 and 1.5 mg/kg, i.p.), unlike clozapine, significantly decreased the primary ADD, but did not alter the PNT. Overall, clozapine produces a greater proconvulsant action than haloperidol in an animal model of hippocampal seizures.

Purpose: This study was conducted to assess the effect of NMDA receptor antagonists (MK-80 I and CPP) and a non-NMDA receptor antagonist (NBQX), administered into inferior colliculus (IC) or into the ambient cistern on audiogenic seizures i n rats neonatally exposed to propylthiourecil (PTU). Furthermore, the role of glutamatc rcceptor subtypes i n audiogenic seizures was cxanincd by analysis of behavioral manifcstations induced hy inttacisternal injection of NMDA or AMPA in naive rats. Methods: I. Rats were exposed to 0.02% PTU through the mother's milk from day 0 to day 19 (PTU rats). Those animals were tested for audiogcnic scizure susceptibility at the age of 10 wccks. PTU rats without generalized tonic-clonic scizurc (GTCS) after auditory stimulation wcrc excluded i n this study. MK-801 at doscs of 2, 20, 40 nmol/side (n = 2, I I, 5), CPP at doscs of 0.04, 0.4, 4 nmol/side (11 = I I, 5, 13), or NBQX at doscs of 2, 20 imnol/side (n = 3, 13) was bilatcrally;idministered into IC. Thiriy minutcs aftcr treatment of drugs, auditory stimulation wiis applied by ringing the emergency bell (1 12 dB) [or 80 scc. The latency to running fit (RF) and GTCS, and the duration 0 1 RF and GTCS wcrc observed i n each tested animal. MKX O I at doses of 0.02, 2, 40 nmol/brain (n = 6, 5, 5), CPP at doses of 0.04, 0.4, 4 nmol/hrain (n = 6, 6, h), or NBQX at doses of 0.5, 5 nmol/brain (n = 6, 6) was administered inio cisterna ambicncc of PTU rats. Five minutes after treatment of drugs, the audiogenic seizures wcrc obscrved as stated above. 2. Naive Spraguc-Dawlcy rats were used at 7 weeks of age. NMDA at doscs of 10, 20 pglbrain (n = 10, 5) or AMPA at doses of 3, 6 pg/brain (11 = 6, 7) was administcrcd into cisterna ambience. After trcatincnt of NMDA or AMPA, the behavioral changes wcrc observed for 30 minutes. Furthermore, aftcr trcatment of NMDA 5 pg/hrain (n = 4) or AMPA 3 @brain (n=6), the behavioral changes were obscrvcd i n cach tested animal during 80 seconds with auditory stimulation. AMPA 3 pg/brain was administered into cisterna arnbiencc after pre-trciitmcnt of systemic administration or MK-801 0.5 mg/kg. The behavioral changes of the prc-treated animals were comparcd with those of non pre-treated animals during 80 scconds with auditory stimulation. Results: I. In PTU rats the microinjection of CPP into 1C at 0.4, 4 nmol/side was found to exhibit significant blocking effects on both RF and GTCS. NBQX at 20 nmollside inhibited only GTCS. 2. intracisternal injection of MK-801, CPP, or NBQX showed significant block-ing effects on both RF and GTCS in PTU rats. 3. Thc intracistcrnal administration of NMDA or AMPA in naive rats dose-dependently elicitcd RF lollowcd by GTCS similar to audiogenic seizurcs in PTU rats. 4. Auditory stimulation augmented both RF and GTCS induced by subclinical dose of AMPA in naive rats but failed to affect the procon vulsant action of NMDA. This augmentative effect was inhibited by MK-80 I. Conclusion: These results suggest that both NMDA and AMPA receptor activation arc ncccssary to induce RF. In audiogcnic scizurcs, thc auditory stimulation probably is equivalent to the activation of NMDA receptors, and thc relay mcchanism from RF to GTCS is presumably related to NMDA receptors.