Stiripentol for the treatment of super-refractory status epilepticus with cross-sensitivity.

BACKGROUND: Cross-sensitivity of rash has been reported between various antiepileptic drugs (AEDs). However, few studies have determined the frequency and management of cross-sensitivity in patients with super-refractory status epilepticus (SRSE). AIMS OF THE STUDY: To examine the optimal AED for treating SRSE with cross-sensitivity. METHODS: We performed a retrospective review of adult patients with SRSE treated at Nagoya City University Hospital, in which we investigated the frequency of cross-sensitivity among patients with SRSE and their clinical and medical profiles. RESULTS: We identified 10 adult patients with SRSE, 5 of whom had cross-sensitivity. Stiripentol (STP) was administered when previously used AEDs had demonstrated cross-sensitivity and failed to control seizures. After initiation of STP, the dose of general anaesthetics was reduced, and status epilepticus (SE) eventually ceased with co-administered AEDs without additional adverse effects. The mean time to SE cessation after initiation of STP was 30.8 days (range, 18-46 days), mean duration of general anaesthesia was 101.2 days (range, 74-128 days), and mean number of AEDs was 9.0 (range, 6-11). CONCLUSIONS: This study suggests that cross-sensitivity between AEDs is common in adults with SRSE and that STP may be useful for treating SRSE with cross-sensitivity.

Clinico-radiological features of subarachnoid hyperintensity on diffusion-weighted images in patients with meningitis.

AIM: To investigate the clinical and radiological features of meningitis with subarachnoid diffusion-weighted imaging (DWI) hyperintensity. MATERIALS AND METHODS: The clinical features, laboratory data, and radiological findings, including the number and distribution of subarachnoid DWI hyperintense lesions and other radiological abnormalities, of 18 patients seen at five institutions were evaluated. RESULTS: The patients consisted of eight males and 10 females, whose ages ranged from 4 months to 82 years (median 65 years). Causative organisms were bacteria in 15 patients, including Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Klebsiella pneumoniae, and Listeria monocytogenes. The remaining three were fungal meningitis caused by Cryptococcus neoformans. Subarachnoid DWI hyperintense lesions were multiple in 16 of the 18 cases (89%) and predominantly distributed around the frontal lobe in 16 of the 18 cases (89%). In addition to subarachnoid abnormality, subdural empyema, cerebral infarction, and intraventricular empyema were found in 50, 39, and 39%, respectively. Compared with paediatric patients, adult patients with bacterial meningitis tended to have poor prognoses (7/10 versus 1/5; p = 0.1). CONCLUSION: Both bacterial and fungal meningitis could cause subarachnoid hyperintensity on DWI, predominantly around the frontal lobe. This finding is often associated with poor prognosis in adult bacterial meningitis.

Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxic-ischaemic rats with human umbilical cord blood grafts.

We recently demonstrated that blood-brain barrier permeabilization using mannitol enhances the therapeutic efficacy of systemically administered human umbilical cord blood (HUCB) by facilitating the entry of neurotrophic factors from the periphery into the adult stroke brain. Here, we examined whether the same blood-brain barrier manipulation approach increases the therapeutic effects of intravenously delivered HUCB in a neonatal hypoxic-ischaemic (HI) injury model. Seven-day-old Sprague-Dawley rats were subjected to unilateral HI injury and then at day 7 after the insult, animals intravenously received vehicle alone, mannitol alone, HUCB cells (15k mononuclear fraction) alone or a combination of mannitol and HUCB cells. Behavioural tests at post-transplantation days 7 and 14 showed that HI animals that received HUCB cells alone or when combined with mannitol were significantly less impaired in motor asymmetry and motor coordination compared with those that received vehicle alone or mannitol alone. Brain tissues from a separate animal cohort from the four treatment conditions were processed for enzyme-linked immunosorbent assay at day 3 post-transplantation, and revealed elevated levels of GDNF, NGF and BDNF in those that received HUCB cells alone or when combined with mannitol compared with those that received vehicle or mannitol alone, with the combined HUCB cells and mannitol exhibiting the most robust neurotropic factor up-regulation. Histological assays revealed only sporadic detection of HUCB cells, suggesting that the trophic factor-mediated mechanism, rather than cell replacement per se, principally contributed to the behavioural improvement. These findings extend the utility of blood-brain barrier permeabilization in facilitating cell therapy for treating neonatal HI injury.

Hexagonal close-packed array formed by selective adsorption onto hexagonal patterns.

A patterned two-dimensional hexagonally ordered array of ferritin molecules, the outer surfaces of which had been genetically modified by titanium (Ti) specific binding peptides (minT1-LF), was realized in a self-assembling manner on a hexagonal Ti thin film island made on a silicon substrate. The optimum degree of order was realized at the pH with the maximum selectivity of minT1-LF adsorption on the Ti surface with respect to the silicon dioxide (SiO2) surface. Quartz crystal microbalance (QCM) measurement revealed that minT1-LF adsorbed onto the Ti surface strongly and irreversibly, but adsorbed onto the silicon dioxide surface weakly and reversibly. It was suggested that the concentration of minT1-LF on the Ti pattern promotes hexagonal close-packed ordering and axis aligning.

Lack of exercise, via hindlimb suspension, impedes endogenous neurogenesis.

Bedridden patients who receive good physical rehabilitation are able to exhibit clinical improvement. Accumulating evidence demonstrates that exercise increases endogenous neurogenesis and may even protect against central nervous system (CNS) disorders. Here, we explored the effects of lack of exercise on neurogenesis in rats by employing a routine hindlimb suspension (HS) model over a 2-week period, which consists of elevating their tails, thereby raising their hindlimbs above the ground and unloading the weights in these extremities. In addition, the effects of exercise and recovery time with normal caging after HS were also explored. BrdU (50 mg/kg, i.p.) was injected every 8 h over the last 4 days of each paradigm to label proliferative cells. Immunohistochemical results revealed that HS significantly reduced the number of BrdU/Doublecortin double-positive cells in the subventricular zone and dentate gyrus. Exercise and recovery time significantly improved atrophy of the soleus muscle, but did not attenuate the HS-induced decrement in BrdU/Dcx-positive cells. A separate cohort of animals was exposed to the same HS paradigm and enzyme-linked immunosorbent assay (ELISA) of neurotrophic factors was performed on brain tissue samples harvested at the end of the HS period, as well as plasma samples from all animals. ELISA results revealed that HS reduced the levels of brain-derived neurotrophic factor in the hippocampus and vascular endothelial growth factor plasma levels. This study revealed that lack of exercise reduced neurogenesis with downregulation of neurotrophic factors. The use of the HS model in conjunction with CNS disease models should further elucidate the role of exercise in neurogenesis and neurotrophic factors in neurologic disorders.

Overexpression of D2/D3 receptors increases efficacy of ropinirole in chronically 6-OHDA-lesioned Parkinsonian rats.

Ropinirole, which is a non-ergot dopamine agonist derivative, exerts therapeutic benefits in Parkinson's disease (PD). Based on recent studies implicating dopamine receptors 2 and 3 (D2R and D3R) as possible targets of ropinirole, we over-expressed these dopamine receptor genes in the dopamine-denervated striatum of rodents to reveal whether their over-expression modulated ropinirole activity. Adult Sprague-Dawley rats initially received unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. At 1 month after surgery, successfully lesioned animals (3 or less forelimb akinesia score, and 8 or more apomorphine-induced rotations/min over 1 h) were randomly assigned to intrastriatal injection (ipsilateral to the lesion) of blank lentiviral vector, D2R, D3R or both genes. At about 5 months post-lesion, ropinirole (0.2 mg/kg, i.p.) was administered daily for 9 consecutive days. The subtherapeutic dose of ropinirole improved the use of previously akinetic forelimb and produced robust circling behavior in lesioned animals with striatal over-expression of both D2R and D3R compared to lesioned animals that received blank vector. In contrast, the subtherapeutic dose of ropinirole generated only modest motor effects in lesioned animals with sole over-expression of D2R or D3R. Western immunoblot and autoradiographic assays showed enhanced D2R and D3R protein levels coupled with normalized D2R and D3R binding in the ventral striatum of lesioned animals with lentiviral over-expression of both D2R and D3R relative to vehicle-treated lesioned animals. Immunohistochemical analyses showed that D2R and D3R GFP fluorescent cells colocalized with enkephalin and substance P immunoreactive medium spiny neurons. These data support the use of the subtherapeutic dose of ropinirole in a chronic model of PD.

Brain malformations caused by retroviral vector-mediated gene transfer of hippocampal cholinergic neurostimulating peptide precursor protein into the CNS via embryonic mice ventricles.

Hippocampal cholinergic neurostimulating peptide precursor protein (HCNP-pp) is a unique multifunctional protein, being not only the precursor of HCNP, which promotes the phenotype development of septo-hippocampal cholinergic neurons, but also the binding protein of phosphatidylethanolamine, ATP, Raf-1 kinase (known as "Raf-1 kinase inhibitory factor" in peripheral organs), and serine protease. We obtained a high-titer retroviral vector harboring HCNP-pp cDNA by the use of a modified packaging cell line and centrifugation, and by injecting it into embryonic mouse ventricles, we investigated the function of its gene product within the central nervous system (CNS). We found that efficient transduction into hippocampal pyramidal neurons can be achieved by injecting the vector into embryonic brain ventricles on embryonic day 14 (E14). Three days after receiving the intraventricular injection of the high-titer HCNP-pp retrovirus vector on E14, the tissues around the ventricles showed an overexpression of HCNP-pp. This was accompanied by a reduced amount of activated MEK and Erk (as analyzed by histochemical and Western blot methods), suggesting that HCNP-pp also regulates the MAP-kinase cascade within the CNS. Surprisingly, mouse brains that received the HCNP-pp retroviral vector showed massive malformation of the hippocampus and cerebellum when examined 30 days after birth. This shows that strictly regulated HCNP-pp gene expression is necessary for the normal development of the mouse brain, and that the moderate overexpression achieved by retroviral vector-mediated gene transfer is sufficient to cause severe abnormality of entire brain structures.

Anti-atherogenic antioxidants regulate the expression and function of proteasome alpha-type subunits in human endothelial cells.

It has been proposed that phenolic antioxidants such as probucol exert their anti-atherogenic effects through scavenging lipid-derived radicals. In this study the potential for genomics to reveal unanticipated pharmacological properties of phenolic antioxidants is explored. It was found that two anti-atherogenic compounds, BO-653 and probucol, inhibited the expression of three alpha-type proteasome subunits, PMSA2, PMSA3, and PMSA4 in human umbilical vein endothelial cells. Here we report that both BO-653 and probucol caused not only inhibition of the mRNA levels of these three subunits but also inhibition of both the gene expression and protein synthesis of the alpha-type subunit, PMSA1. Other subunit components of the proteasome such as the beta-type subunits (PMSB1, PMSB7), the ATPase subunit of 19 S (PMSC6), the non-ATPase subunit of 19 S (PMSD1), and PA28 (PMSE2) were not significantly affected by treatment with these compounds. The specific inhibition of alpha-type subunit expression in response to these antioxidants resulted in functional alterations of the proteasome with suppression of degradation of multiubiquitinated proteins and IkappaBalpha. These results suggest that certain compounds previously classified solely as antioxidants are able to exert potentially important modulatory effects on proteasome function.

Age-dependent changes in HCNP-related antigen expression in the human hippocampus.

Hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from the young rat hippocampus, enhances the cholinergic phenotype development of the medial septal nucleus in vitro. In this study, we examined the HCNP-antigen distribution and the age-related changes in the number of positive cells in the hippocampus (obtained at autopsy from 74 subjects with no known neurological disorders). Immunohistochemical assay revealed that the immunopositive cells were GABAergic neurons and oligodendrocytes. They were first identified in the fetus at around 25 to 30 weeks and their number increased rapidly with advancing postconceptional age to reach maximal at the perinatal stage and in early postnatal life; it then decreased to the adult level by 10 years old. These results suggest that HCNP-related antigen may play important roles in the development and/or differentiation of the human hippocampus.

Muscarinic cholinergic and glutamatergic reciprocal regulation of expression of hippocampal cholinergic neurostimulating peptide precursor protein gene in rat hippocampus.

Hippocampal cholinergic neurostimulating peptide, an undecapeptide originally isolated from the hippocampus of young rats, enhances acetylcholine synthesis in rat medial septal nucleus in vitro. Hippocampal cholinergic neurostimulating peptide is derived from the N-terminal region of its 21-kmol.wt precursor protein. The highest expression of the hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA is in hippocampal pyramidal neurons. In an in vitro rat hippocampal slice, preparation in which electrical stimulation could be delivered to the Schaffer collateral-CA1 pyramidal cell synapse, semi-quantitative non-radioisotopic in situ hybridization, demonstrated that expression of the hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA is regulated by neuronal activity. Selective inhibition with pharmacological agents revealed that the constitutive hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA level can be up-regulated by D-(-)-2-amino-5-phosphono-valeric acid, and that activity-dependent transcription can be inhibited by tetrodotoxin, nifedipine, 6-cyano-7-nitroquinoxaline-2,3-dione, and scopolamine, but not by mecamylamine. These results indicate that septal cholinergic neurons and hippocampal glutamatergic neurons exert a reciprocal influence over the expression of hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA in the hippocampus, and that the activity-dependent and constitutive expressions of hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA may be regulated by different routes, involving calcium influx via L-type Ca(2+) channels and N-methyl-D-aspartate receptors.

Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not.

Carboxypeptidase R (EC 3.4.17.20; CPR) and carboxypeptidase N (EC 3. 4.17.3; CPN) cleave carboxyl-terminal arginine and lysine residues from biologically active peptides such as kinins and anaphylatoxins, resulting in regulation of their biological activity. Human proCPR, also known as thrombin-activatable fibrinolysis inhibitor, plasma pro-carboxypeptidase B, and pro-carboxypeptidase U, is a plasma zymogen activated during coagulation. CPN, however, previously termed kininase I and anaphylatoxin inactivator, is present in a stable active form in plasma. We report here the isolation of mouse proCPR and CPN cDNA clones that can induce their respective enzymatic activities in culture supernatants of transiently transfected cells. Potato carboxypeptidase inhibitor can inhibit carboxypeptidase activity in culture medium of mouse proCPR-transfected cells. The expression of proCPR mRNA in murine liver is greatly enhanced following LPS injection, whereas CPN mRNA expression remains unaffected. Furthermore, the CPR activity in plasma increased 2-fold at 24 h after LPS treatment. Therefore, proCPR can be considered a type of acute phase protein, whereas CPN is not. An increase in CPR activity may facilitate rapid inactivation of inflammatory mediators generated at the site of Gram-negative bacterial infection and may consequently prevent septic shock. In view of the ability of proCPR to also inhibit fibrinolysis, an excess of proCPR induced by LPS may contribute to hypofibrinolysis in patients suffering from disseminated intravascular coagulation caused by sepsis.

Hippocampal cholinergic neurostimulating peptides (HCNP).

Neuronal development and differentiation require a variety of cell interactions. Diffusible molecules from target neurons play an important part in mediating such interactions. Our early studies used explant culture technique to examine the factors that enhance the differentiation of septo-hippocampal cholinergic neurons, and they revealed that several components resident in the hippocampus are involved in the differentiation of presynaptic cholinergic neurons in the medial septal nucleus. One of these components, originally purified from young rat hippocampus, is a novel undecapeptide (hippocampal cholinergic neurostimulating peptide; HCNP); this enhances the production of ChAT, but not of AchE. Later experiments revealed that: (1) a specific receptor appears to mediate this effect; (2) NGF and HCNP act cooperatively to regulate cholinergic phenotype development in the medial septal nucleus in culture; and (3) these two molecules differ both in their mechanism of release from the hippocampus and their mechanism of action on cholinergic neurons. The amino acid sequence deduced from base sequence analysis of cloned HCNP-precursor protein cDNA shows that HCNP is located at the N-terminal domain of its precursor protein. The 21 kDa HCNP precursor protein shows homology with other proteins, and it functions not only as an HCNP precursor, but also as a binding protein for ATP, opioids and phosphatidylethanolamine. The distribution and localization of HCNP-related components and the expression of their mRNAs support the notion that the precursor protein is multifunctional. In keeping with its multiple functions, the multiple enhancers and promoters found in the genomic DNA for HCNP precursor protein may be involved in the regulation of its gene in a variety of cells and at different stages of development. Furthermore, several lines of evidence obtained from studies of humans and animal models suggest that certain types of memory and learning disorders are associated with abnormal accumulation and expression of HCNP analogue peptide and/or its precursor protein mRNA in the hippocampus.

Decay-accelerating factor in guinea pig stomachs following ischemia reperfusion stress.

A complement regulatory protein, decay-accelerating factor (DAF, CD55), is known to protect host tissues from autologous complement activation. DAF is present on the apical side of human gastric epithelial cells, and its expression increases during gastritis. To develop an animal model for analysis of DAF expression on gastric cells, a mAb to guinea pig DAF was successfully used. Although DAF expression in the mucosal epithelium of the stomach is weak, as judged by immunohistochemical staining with the mAb, it was temporarily up-regulated at 12 and 24 h, and at 3 days after ischemia reperfusion (I/R) (p < 0.05). The DAF mRNA level in gastric tissues was determined by Northern blot analysis and found to be highest at 6 h after I/R, returning to the baseline at 24 h. Strong DAF mRNA expression was observed in the cytoplasm of cells beneath the eroded tissues 6 h after I/R. In guinea pigs, alternative splicing of DAF mRNA generates both GPI-anchored types and transmembrane types of DAF. RT-PCR analysis revealed that mRNAs of the transmembrane types had become significantly dominant by 6 h after I/R, whereas levels for the GPI-anchored types remained unchanged. In guinea pigs depleted of complement by cobra venom factor treatment, the area of erosion and the up-regulation of DAF expression in gastric epithelial cells after I/R were significantly limited compared with the normocomplementemic group, indicating that DAF may be up-regulated by an inflammatory stress.

[A case of sarcoid meningoencephalitis with an isolated supratentorial lesion].

A rare case of sarcoid meningoencephalitis with no systemic lesion is reported here. A 58-year old man was admitted experiencing dull headache and speech disturbance. He had never received a diagnosis of systemic sarcoidosis. On admission, neurological examination revealed dysarthria, a defect of the right-side visual field and accelerated right Achilles tendon reflex. A T2-weighted MRI showed a high-intensity signal in the white matter of the left parieto-occipital lobe surrounded by severe brain edema with a mass effect. The meninges around the lesion were enhanced by gadolinium, but no enhancement was observed in the basal portion. Angiotensin-converting enzyme (ACE) activities of cerebrospinal fluid (CSF) and serum were within normal range. The level of interleukin-6 in the CSF was slightly elevated. Chest X ray films and chest CT revealed no abnormal lesions. Whole body gallium scanning showed a hot region only in the intracranial lesion. A brain biopsy was performed. Histological examination revealed typical granuloma of sarcoidosis accompanied by microvasculitis and epithelioid cell granuloma without caseous necrosis. Oral administration of prednisolone improved all symptoms and MRI findings. These observations suggest that release of cytokines from macrophages and epithelioid cells, as well as disruption of the blood-brain barrier due to microvasculitis, are involved in the mechanism responsible for producing lesions of sarcoid meningoencephalitis.

The natriuretic peptide clearance receptor locally modulates the physiological effects of the natriuretic peptide system.

Natriuretic peptides (NPs), mainly produced in heart [atrial (ANP) and B-type (BNP)], brain (CNP), and kidney (urodilatin), decrease blood pressure and increase salt excretion. These functions are mediated by natriuretic peptide receptors A and B (NPRA and NPRB) having cytoplasmic guanylyl cyclase domains that are stimulated when the receptors bind ligand. A more abundantly expressed receptor (NPRC or C-type) has a short cytoplasmic domain without guanylyl cyclase activity. NPRC is thought to act as a clearance receptor, although it may have additional functions. To test how NPRC affects the cardiovascular and renal systems, we inactivated its gene (Npr3) in mice by homologous recombination. The half life of [125I]ANP in the circulation of homozygotes lacking NPRC is two-thirds longer than in the wild type, although plasma levels of ANP and BNP in heterozygotes and homozygotes are close to the wild type. Heterozygotes and homozygotes have a progressively reduced ability to concentrate urine, exhibit mild diuresis, and tend to be blood volume depleted. Blood pressure in the homozygotes is 8 mmHg (1 mmHg = 133 Pa) below normal. These results are consistent with the sole cardiovascular/renal function of NPRC being to clear natriuretic peptides, thereby modulating local effects of the natriuretic peptide system. Unexpectedly, Npr3 -/- homozygotes have skeletal deformities associated with a considerable increase in bone turnover. The phenotype is consistent with the bone function of NPRC being to clear locally synthesized CNP and modulate its effects. We conclude that NPRC modulates the availability of the natriuretic peptides at their target organs, thereby allowing the activity of the natriuretic peptide system to be tailored to specific local needs.

Increased expression of hippocampal cholinergic neurostimulating peptide-related components and their messenger RNAs in the hippocampus of aged senescence-accelerated mice.

Hippocampal cholinergic neurostimulating peptide stimulates cholinergic phenotype development by inducing choline acetyltransferase in the rat medial septal nucleus in vitro. Adult senescence-accelerated-prone mice/8, a substrain of the senescence-accelerated-prone mouse, show a remarkable age-accelerated deterioration in learning and memory. We cloned mouse hippocampal cholinergic neurostimulating peptide precursor protein complementary DNA. The deduced amino acid sequence showed that the neurostimulating peptide itself is the same as that found in the rat. In situ hybridization revealed that the highest expression of the precursor protein messenger RNA was in hippocampal pyramidal neurons. Compared with a strain of senescence-accelerated-resistant mouse (control mouse), adult senescence-accelerated-prone mice/8 showed increased expression of both the precursor messenger RNA and the neurostimulating peptide-related immunodeposits in the hippocampal CA1 field. The deposits were intensely and diffusely precipitated in neuropils throughout the strata oriens and radiatum in senescence-accelerated-prone mice/8, but not in control mice. The neurostimulating peptide content in the hippocampus was higher in senescence-accelerated-prone mice/8 than in control mice, while its precursor protein itself was not different between the two strains. Furthermore, our previous and present data show that the medial septal and hippocampal choline acetyltransferase activity was significantly lower in senescence-accelerated-prone mice/8 than in control mice. The data suggest that, in hippocampal neurons in adult senescence-accelerated-prone mice/8, the production of hippocampal cholinergic neurostimulating peptide precursor protein in neuronal somata, which is associated with an increased expression of its messenger RNA in the CA1 field, occurs as a consequence of low activity in their presynaptic cholinergic neurons. This is followed by accelerated processing to generate bioactive peptide and transport to its functional fields. However, certain mechanisms reduce the release of the peptide and lead to its accumulation in the neuropil. These disturbances of the septohippocampal cholinergic system might be the biochemical mechanism underlying the characteristic deterioration of senescence-accelerated-prone mice/8.

An unusual course of progressive multifocal leukoencephalopathy in a patient with idiopathic CD4+ T lymphocytopenia.

A case is reported of idiopathic CD4+T lymphocytopenia with progressive multifocal leukoencephalopathy and cervical lymph node tuberculosis. A 57 year old Japanese man presented with cervical lymphadenopathy and progressive neurological deficits, and six months later he developed akinetic mutism. He had a persistent severely depressed number of circulating CD4+T lymphocytes in the absence of human immunodeficiency virus infection. T1 weighted MRI showed a diffuse decreased signal intensity limited to the white matter without mass effect. A brain biopsy specimen had a morphology similar to that of progressive multifocal leukoencephalopathy. Polyomavirus antigen was detected in the brain lesion, and viral DNA was identified in nucleated blood cells and urine. Unusually this serious medical condition has lasted for more than three years without remission. To our knowledge this is the first patient with CD4+T lymphocytopenia with progressive multifocal leukoencephalopathy, suggesting that similar opportunistic infections should be considered even in previously normal people.

[A case of clinically diagnosed Creutzfeldt-Jakob disease with serial MRI diffusion weighted images].

We reported MRI findings in a 49-year-old woman with clinically diagnosed Creutzfeldt-Jakob disease (CJD). She was admitted to our hospital because of confusion, which initially appeared 5 weeks prior and was rapidly worsened. Two weeks later, she developed myoclonic jerks in her extremities with periodic synchronous discharges on EEG. Six months later, she became mutic. Brain MRI at 3 weeks after the admission demonstrated high signal intensities in the bilateral caudate nuclei and putamina on T2 weighted images (T2WIs). Diffusion weighted images (DWIs) showed hyperintensities in the basal ganglia and in the parietal and occipital cortices. Five weeks later, the abnormal intensities in the basal ganglia were still observed on T2WIs but decreased on DWIs. Five months later, the increased signal intensities in the basal ganglia had disappeared both on T2WIs and DWIs, but new hyperintensities appeared in the insula and the temporal area on DWIs. We concluded that DWIs may be useful for the demonstrations of a lesion in the cerebral cortex and the spread of lesions.

High levels of hippocampal cholinergic neurostimulating peptide (HCNP) in the CSF of some patients with Alzheimer's disease.

Hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from the hippocampus of young rats, enhances the cholinergic development of rat medial septal nuclei in vitro. This report concerns the determination of the HCNP content of the cerebrospinal fluid (CSF) of 173 clinically, and of 22 clinico-pathologically defined patients. A radioimmunoassay was used throughout. The HCNP level was relatively uniform among the clinically defined patients; for almost all non-Alzheimer's patients, the level fell within the range delimited by +/- 2 SD of the mean for all patients taken together, and none of them had a level above this range. By contrast, the early-onset Alzheimer's disease patients could be divided on the basis of their HCNP level into two groups, one with high levels (markedly above the mean +/- 2SD range), and the other with levels similar to those of the other patients. The analysis of the CSF samples obtained postmortem revealed that Group I Alzheimer-type dementia (ATD) patients with clinico-pathologically established diagnoses had a strikingly higher level of HCNP than patients with either Group II ATD or cerebral vascular disease. These results suggest that HCNP is involved in certain pathophysiological alterations associated with dementia, and that its determination may be useful in patient evaluation. Copyright 1998 Lippincott Williams & Wilkins