[Epilepsy and dementia].

Japan is experiencing an increase in the number of dementia patients, and the incidence of epilepsy is high among the elderly. A survey, from 2007 to 2012, of 279 epilepsy patients admitted to our hospital's neurology department showed that newly-onset epilepsy occurred more frequently in elderly patients. Of 153 elderly patients with epilepsy, aged 65 years and older, 31(20.2%) had dementia as an underlying disease. Although the prevalence of epilepsy in dementia is varied, higher brain dysfunctions are known to occur as a result of epilepsy. Considering such symptoms as epilepsy with higher brain dysfunction (E-HBD) would enable clinical investigation without overlooking higher brain dysfunctions that have effective treatments.

Self-rated anosognosia score may be a sensitive and predictive indicator for progressive brain atrophy in amyotrophic lateral sclerosis: an X-ray computed tomographic study.

We investigated whether a self-rated anosognosia score can be an indicator for progression of brain atrophy in patients with amyotrophic lateral sclerosis (ALS). Scores for 16 patients were compared with the ventricular areas of the bilateral anterior and inferior horns measured on x-ray computed tomography. Longitudinal enlargement was expressed as a monthly increase in size: (ventricular size at the initial scan - ventricular size at the follow-up scan)/scan interval (months). The anosognosia scores ranged from -4 to 3 and 3-18 in patients with and without frontotemporal lobar degeneration (FTLD), respectively (p = 0.0011). Anosognosia scores were significantly correlated with sizes of anterior (r = 0.704, p = 0.0016) and inferior (r = 0.898, p < 0.0001) horns. In non-demented patients for whom follow-up CT scans were available (n = 7), the scores were significantly correlated with the longitudinal increase in inferior horn size (r = 0.754, p = 0.0496), but not with that of anterior horn size (r = -0.166, p = 0.7111). In conclusion, anosognosia in ALS is associated with greater anterior and inferior horn sizes, reflecting frontotemporal lobar atrophy. Moreover, mild anosognosia in ALS patients without FTLD may predict impending inferior horn enlargement, reflecting medial temporal atrophy.

High serum high-density lipoprotein-cholesterol is associated with memory function and gyrification of insular and frontal opercular cortex in an elderly memory-clinic population.

The issue of whether serum lipid marker values are cognitively and neurologically significant for elderly individuals attending a memory clinic has been controversial. We investigated the associations of serum lipid markers with the memory function and cortical structure in 52 patients aged ≥75 years who had attended our memory clinic based on their subjective memory complaints. None had a history of medication for hyperlipidemia. The Wechsler Memory Scale-Revised (WMS-R) was administered to all patients for the assessment of their memory function. Serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDLC), and triglyceride (TG) were measured for each patient. Surface-based morphometry (SBM) was performed for the calculation of each patient's cortical thickness and gyrification index based on structural MRI data. Our analyses revealed that the serum HDLC level was positively and significantly correlated with the WMS-R subtests of visual paired associates I/II and logical memory I (p < 0.05). The serum TG level was negatively correlated with the logical memory I subtest. The SBM results showed positive correlations between the serum HDLC level and the gyrification indices of the bilateral insular and frontal opercular cortices, and those two gyrification indices were positively correlated with the logical memory I and visual paired associates I/II. These results suggest that in these elderly patients, a high serum HDLC level was associated with not only preserved memory function but also gyrification of the insular and frontal opercular cortex. We conclude that elderly individuals' serum lipid markers should be carefully assessed in memory clinic settings, because serum HDLC may be a biomarker for memory function and cortical structure.

[Characteristics of Geriatric Epilepsy Can Include Dementia].

Japan has become a "super-aged" society, in which more than 20% of the population is over the age of 65 years. As the incidence rates of both dementia and epilepsy are high in elderly individuals, the prevalence rates of dementia and epilepsy have both increased in recent years. Dementia and epilepsy are often characterized by ambiguous symptoms, with numerous concomitant symptoms observed in these patients. Moreover, many reports indicate that the forgetfulness observed in dementia patients was actually due to the occurrence of epileptic seizures. Because Japan is currently a super-aged society, it is important to understand the characteristics of and relationships between dementia and epilepsy.

Accumulation of 123I-Ioflupane Is a Useful Marker of the Efficacy of Selegiline Monotherapy in Drug-Naïve Parkinson's Disease.

Background: Selegiline enhances the patient's endogenous dopamine by inhibiting dopamine metabolism. The efficacy of selegiline monotherapy for drug-naïve Parkinson's disease (PD) patients may depend on the degree of dopaminergic neuronal degeneration. 123I-Ioflupane single photon emission computed tomography (SPECT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy are diagnostic methods to assess the pharmacological and pathological changes in PD. Objective: We examined the utility of these imaging methods to predict the efficacy of selegiline monotherapy for motor symptoms in drug-naïve PD patients. Methods: We observed the efficacy of selegiline monotherapy in 28 drug-naïve PD patients and compared the improvement in motor function and the imaging findings. These patients received selegiline monotherapy, and the amount was increased to the optimal dose in clinical practice. Motor function was assessed using the Unified Parkinson's Rating Scale (UPDRS) at baseline and at the stable dose. Imaging was performed before treatment, and the striatal Specific Binding Ratio (SBR) of the 123I-Ioflupane SPECT and the Heart-to-Mediastinum (H/M) ratio of the 123I-MIBG myocardial scintigraphy were calculated. Both ratios were compared with improvements in scores for motor assessment using Pearson's correlation coefficient. Results: The mean UPDRS part III score significantly improved with at least 5.0 mg/day of selegiline. Further dose escalation did not improve the mean motor score. The percent improvement in the motor score from baseline showed a significant negative correlation with the SBR of average of the right and left striatum, but not with the H/M ratio. Multiple regression analysis using patient's background factors showed that percent improvement in the UPDRS part III score directly correlate with the SBR (p = 0.04), but not with the age (p = 0.72), disease duration (p = 0.31), baseline UPDRS part III (p = 0.77) and the drug dose (p = 0.26). Conclusion: PD patients with a lower accumulation of 123I-Ioflupane in the striatum can have greater improvement with selegiline monotherapy.

Efficacy of levetiracetam in primary hemifacial spasm.

Hemifacial spasm (HFS) is a peripherally-induced movement disorder characterized by the involuntary, unilateral, intermittent, irregular, tonic or clonic contractions of muscles innervated by the ipsilateral facial nerve. Kindling-like hyperactivity of the facial nucleus induced by constant stimulation of compressing artery is considered as the predominant mechanism underlying the pathogenesis of HFS. As a treatment for HFS, microsurgical decompression and botulinum toxin injection have been shown to be highly successful. Anticonvulsant drugs relieve HFS in some patients; however, the use of such drugs is limited owing to their side effects, predominantly in elderly patients. We experienced two elderly HFS patients who exhibited a marked response to levetiracetam (LEV) without side effects. Although the exact underlying pharmacological mechanism remains unknown, we assume anti-kindling effect as one of the important pharmacological mechanism underlying the effect of LEV against HFS. Moreover, LEV is considered to be suitable for use in elderly patients because of its good tolerability. In addition, the lack of hepatic induction or inhibition makes it an easy and safe drug when used in addition to other anticonvulsants. Although the long-term benefit remains unknown, LEV may represent an alternative treatment for elderly HFS patients who are unable to undergo or decline surgical intervention and/or botulinum toxin injections or are intolerant to other anticonvulsants.

Improvement in Language Function Correlates with Gait Improvement in Drug-naïve Parkinson's Disease Patients Taking Dopaminergic Medication.

BACKGROUND: Dopaminergic drugs, the gold standard for motor symptoms, are known to affect cognitive function in Parkinson's disease (PD) patients. OBJECTIVE: We compared the effects of dopaminergic treatment on motor and cognitive function in drug-naïve patients. METHODS: Dopaminergic medication (levodopa, dopamine agonist, selegiline) was given to 27 drug-naïve PD patients and increased to a dose optimal for improved motor symptoms. Patients were tested prior to, and 4-7 months after, drug initiation. Motor function was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Cognitive function was assessed using both the Japanese version of the Montreal Cognitive Assessment (MoCA-J) and the Neurobehavioral Cognitive Status Examination (COGNISTAT-J). Improvements from baseline for both motor and cognitive assessment were compared. RESULTS: Mean score of all motor assessments (UPDRS total score of Parts II and III, and sub-scores of tremor, rigidity, bradykinesia, gait, and postural instability) and certain cognitive assessments (MoCA-J total score and subscore of delayed recall) significantly improved with dopaminergic medication. Gait score improvement showed significant positive correlation with improvement in MoCA-J language domain and in language-comprehension subtests of COGNISTAT-J using Spearman's correlation coefficients. Furthermore, multiple regression analysis showed gait score improvement significantly correlated with improvements in the subtests of language-comprehension in COGNISTAT-J. CONCLUSION: There is correlated improvement in both gait and language function in de novo PD patients in response to dopaminergic drugs. Gait and language dysfunction in these patients may share a common pathophysiology linked to dopamine deficits.

[Association between Elderly Onset Epilepsy and Dementia].

Japan is experiencing an increase in the number of patients with dementia, and the incidence of epilepsy is high among the elderly. A survey of patients with epilepsy who were admitted to our hospital's neurology department showed that new onset epilepsy occurred more frequently in elderly patients. In addition, a greater proportion of elderly patients had dementia as an underlying disease. Although the prevalence of epilepsy in dementia varies, higher brain dysfunctions are known to be related to epilepsy. Because a symptom of epilepsy may be mistaken for dementia, it is important to understand the association between epilepsy and dementia, including their tendencies and characteristics.

[Epilepsy with higher brain dysfunction].

Acquired higher brain dysfunction is for the most part due to cerebral vascular disease, but epilepsy may also be a cause. In this study with five patients, we discuss the advantages of anti-epileptic drugs (AEDs) for persistent higher brain dysfunction. The patients showed chronic amnesia or acute aphasia, with associated symptoms like personality change. All five cases affected automatism or convulsive attack, though only after the emergence of higher brain dysfunction and administration of AEDs. There were underlying diseases like cerebral arteriovenous malformation in four cases, but the other patient had none. Electroencephalogram and single photon emission computed tomography revealed one case of aphasia epilepsy with higher brain dysfunction. These results suggest the potential therapeutic efficacy of AEDs for persistent higher brain dysfunction, and we must differentiate epilepsy with higher brain dysfunction from dementia or cerebral vascular disease.

Programmable shunt valves: in vitro assessment of safety of the magnetic field generated by a portable game machine.

Cerebrospinal fluid (CSF) shunts are frequently used to treat hydrocephalus. The use of a programmable shunt valve allows physicians to easily change the opening pressure. Since patients with adjustable CSF shunt valves may use portable game machines, the permanent magnets in these machines may alter the shunt valve programmed settings or permanently damage the device. This study investigated the risk of unintentional valve adjustment associated with the use of game machines in patients with programmable CSF shunt valves. Four adjustable valves from 4 different manufacturers, Sophysa Polaris model SPV (Polaris valve), Miethke proGAV (proGAV), Codman Hakim programmable valve (CHPV), and Strata II small valve (Strata valve), were evaluated. Magnetic field interactions were determined using the portable game machine, Nintendo DS Lite (DS). The maximum distance between the valve and the DS that affected the valve pressure setting was measured by x-ray cinematography. The Polaris valve and proGAV were immune to unintentional reprogramming by the DS. However, the settings of the CHPV and Strata valves were randomly altered by the DS. Patients with an implanted shunt valve should be made aware of the risks posed by the magnetic fields associated with portable game machines and commonly used home electronics.

Central administration of p-hydroxyamphetamine produces a behavioral stimulant effect in rodents: evidence for the involvement of dopaminergic systems.

RATIONALE AND OBJECTIVES: It is well-known that amphetamine induces increased locomotor activity in rodents. We previously found that intracerebroventricular (i.c.v.) administration of p-hydroxyamphetamine (p-OHA), an amphetamine metabolite, increases synaptic dopamine (DA) levels in the striatum. In the present study, we investigated the effect of p-OHA on locomotor activity in rodents. RESULTS: In mice, i.c.v. administration of p-OHA significantly increased locomotor activity in a dose-dependent manner. p-Hydroxynorephedrine, another amphetamine metabolite, did not increase locomotor activity. This effect of p-OHA was inhibited by pretreatment with nomifensine, a dopamine-uptake inhibitor, but not by fluoxetine, a serotonin-uptake inhibitor, or diethyldithiocarbamate, a dopamine-beta-hydroxylase inhibitor. Furthermore, we tested the effects of microinjections of p-OHA into the rat nucleus accumbens (NAc) on locomotor activity. Local infusion of p-OHA into the NAc significantly increased locomotor activity. As in mice, the increased locomotor activity induced by p-OHA microinjection into the NAc in rats was inhibited by nomifensine. CONCLUSIONS: These data suggest that dopaminergic systems in the NAc may play important roles in p-OHA-induced locomotor activity in rodents.

Influence of memantine on brain monoaminergic neurotransmission parameters in mice: neurochemical and behavioral study.

Memantine, a non-competitive antagonist of NMDA receptors, has recently been used in Alzheimer's disease. The influences of memantine on behavioral changes, monoamine oxidase (MAO) activity and reuptake of both serotonin (5-HT) and dopamine in mice were examined in the present study. Memantine dose-dependently increased locomotor activity. This effect was inhibited by intraperitoneal (i.p.) administration of haloperidol. Furthermore, administration [intracerebroventricular (i.c.v.)] of memantine did not induce the head-twitch response (HTR). However, the 5-HT-induced HTR was potentiated by the combined administration of memantine. The enhanced HTR was inhibited by i.p. administration of haloperidol or 5-HT(2A) antagonist ketanserin. Memantine at 1 mM inhibited both MAO-A and MAO-B activities in mouse forebrain homogenates to 37% and 64% of controls, respectively. Lineweaver-Burk plots analysis revealed competitive inhibition with both MAO-A and MAO-B. The inhibitions were also reversible. Memantine inhibited the reuptake of both 5-HT and dopamine into mouse forebrain synaptosomes. 5-HT and dopamine reuptakes were inhibited to 2% and 16% of controls, respectively, with 1 mM memantine. These findings suggest that the increased locomotor activity and enhanced 5-HT-induced HTR by memantine may result from the reuptake and turnover inhibitions of 5-HT and dopamine.