Changes in cerebral venous sinuses diameter after lumbar puncture in idiopathic intracranial hypertension: a prospective MRI study.

BACKGROUND: Idiopathic intracranial hypertension (IIH), is characterized by elevated intracranial pressure (ICP) without a clear cause. Recently it was shown that in more than 90% of the IIH patients there is stenosis of the transverse dural sinuses. In this study we assessed the changes in diameter of cerebral veins after lumbar puncture, in order to have some more insight regarding the volume and pressure influence on cerebral veins. METHODS: We prospectively included 13 patients suspected with IIH, admitted for investigation in the Soroka medical center. All the patients had a lumbar puncture (LP) with opening pressure measurement and CSF analysis, and two MRI-MRV studies: one before the LP and one after it. Measurements of the cerebral venous sinuses diameter were performed. RESULTS: Significant stenosis of both transverse sinuses was found before LP in IIH patients with an average diameter of 1.77 mm of the right TS, and 1.57 mm of the left TS. After the LP, there was a significant increase in all venous sinuses diameters (P < .05). There was no correlation between the changes in diameter of the venous sinuses after LP and opening pressure measured or BMI. CONCLUSIONS: Our results support other studies and demonstrated narrowing of the transverse sinuses in IIH patients. The main finding of this study is the increase in cerebral sinuses diameter after LP. This observation should be considered when evaluating cerebral venous sinuses after LP. A larger scale study is warranted to validate our findings.

Glycans in sera of amyotrophic lateral sclerosis patients and their role in killing neuronal cells.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by degeneration of upper and lower motor neurons. To date, glycosylation patterns of glycoproteins in fluids of ALS patients have not been described. Moreover, the aberrant glycosylation related to the pathogenesis of other neurodegenerative diseases encouraged us to explore the glycome of ALS patient sera. We found high levels of sialylated glycans and low levels of core fucosylated glycans in serum-derived N-glycans of patients with ALS, compared to healthy volunteer sera. Based on these results, we analyzed the IgG Fc N(297)-glycans, as IgG are major serum glycoproteins affected by sialylation or core fucosylation and are found in the motor cortex of ALS patients. The analyses revealed a distinct glycan, A2BG2, in IgG derived from ALS patient sera (ALS-IgG). This glycan increases the affinity of IgG to CD16 on effector cells, consequently enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). Therefore, we explore whether the Fc-N(297)-glycans of IgG may be involved in ALS disease. Immunostaining of brain and spinal cord tissues revealed over-expression of CD16 and co-localization of intact ALS-IgG with CD16 and in brain with activated microglia of G93A-SOD1 mice. Intact ALS-IgG enhanced effector cell activation and ADCC reaction in comparison to sugar-depleted or control IgG. ALS-IgG were localized in the synapse between brain microglia and neurons of G93A-SOD1 mice, manifesting a promising in vivo ADCC reaction. Therefore, glycans of ALS-IgG may serve as a biomarker for the disease and may be involved in neuronal damage.

miRNA malfunction causes spinal motor neuron disease.

Defective RNA metabolism is an emerging mechanism involved in ALS pathogenesis and possibly in other neurodegenerative disorders. Here, we show that microRNA (miRNA) activity is essential for long-term survival of postmitotic spinal motor neurons (SMNs) in vivo. Thus, mice that do not process miRNA in SMNs exhibit hallmarks of spinal muscular atrophy (SMA), including sclerosis of the spinal cord ventral horns, aberrant end plate architecture, and myofiber atrophy with signs of denervation. Furthermore, a neurofilament heavy subunit previously implicated in motor neuron degeneration is specifically up-regulated in miRNA-deficient SMNs. We demonstrate that the heavy neurofilament subunit is a target of miR-9, a miRNA that is specifically down-regulated in a genetic model of SMA. These data provide evidence for miRNA function in SMN diseases and emphasize the potential role of miR-9-based regulatory mechanisms in adult neurons and neurodegenerative states.

Acetylcholinesterase inhibitors and cholinergic modulation in Myasthenia Gravis and neuroinflammation.

The cholinergic network affects various cellular functions including neurotransmission, and immune reactions. In Myasthenia Gravis (MG), diagnosis and symptomatic therapy are based on cholinergic modulation by acetylcholinesterase inhibitors (AChEI). In Alzheimer's disease (AD) a neurodegenerative disorder associated with inflammatory pathology, cholinergic systems cell loss occurs early. Treatments with special AChEI enhance cholinergic transmission and may act as anti-inflammatory agent via immunocompetent cells expressing alpha-7 acetylcholine receptor (AChR). In Multiple Sclerosis (MS) an inflammatory T-cell-mediated disease, demyelination and neurodegeneration follow neuroinflammation. MS treatment includes anti-inflammatory and immunomodulatory drugs. AChEI can induce cholinergic up-regulation with subsequent effect on neuroinflammation via alpha-7-AChR expressing cells. These effects are additional to the cognitive benefit induced by AChEI.

Not only headache: higher degree of sexual pain symptoms among migraine sufferers.

Chronic illness and chronic pain can have profound negative effects on relationship and sexual satisfaction, yet the influence of migraine on sexuality has not been previously evaluated. To assess sexual functions in subjects with migraine compared to those with no migraine. We evaluated female university students using the Israeli sexual behavior inventory (ISBI). Migraine was diagnosed according to self-reported symptoms according to the IHS criteria. Several dimensions of female sexuality--desire, orgasm, sexual avoidance, interpersonal sexual relationship, health influence, satisfaction and pain were evaluated using a structured questionnaire. Thirty-three (23.9%) of the participants met the IHS criteria for episodic migraine with and without aura. Sexual activity, desire, orgasm and satisfaction from sexual life did not differ significantly between migraine sufferers and non-sufferers. Migraine patients reported lower ISBI scores, higher health influence on sexual life, higher levels of sexual pain and lower sexual satisfaction. Migraine negatively affected the sexual life of sufferers. Sexual pain disorder is more common among migraine sufferers compared to non-migraineurs.

The role of cholinergic balance perturbation in neurological diseases.

The maintenance of a balanced cholinergic homeostasis is crucial for the function of the central nervous system, peripheral nervous system and the neuromuscular junction. However, it appears that the cholinergic system is not restricted to neurons and synapses but may also involve immune reactions. In the present review we reassess the role of the cholinergic balance in myasthenia gravis and Alzheimer's disease which for a long time are known to be associated with cholinergic transmission perturbation. We have included neuroinflammation, particularly multiple sclerosis in this group of neurological disorders in light of the relatively new studies involving the immune cholinergic system. In all the aforementioned disorders, treatment with acetylcholinesterase inhibitors can attenuate inflammation. This is performed by increasing the acetylcholine (ACh) concentration near immune cells and making it available for interaction with alpha(7) nicotinic ACh receptor, expressed on these cells. This outcome is additional to the effect of acetylcholinesterase inhibitors on neurons and synapses.

Readthrough acetylcholinesterase in inflammation-associated neuropathies.

The cholinergic control over inflammatory reactions calls for deciphering the corresponding protein partners. An example is blood-nerve barrier disruption allowing penetration of inflammatory factors, which is notably involved in various neuropathies due to yet unknown molecular mechanism(s). In rats, lipopolysaccharide (LPS) administration followed by intra-neural (i.n.) saline injection inducing a focal blood-nerve disruption leads to systemic inflammatory reaction accompanied by transient conduction impairment in the sciatic nerve. Here, we provide evidence compatible with the hypothesis that ARP, the naturally cleavable C-terminal peptide of the stress-induced "readthrough" acetylcholinesterase variant (AChE-R), is causally involved in the emergence of this LPS-induced conduction impairment. Intra-neural injection to naïve rats of conditioned medium from cultured splenocytes exposed to LPS in vitro (reactive splenocyte medium) induced a transient conduction impairment that was accompanied by facilitated accumulation of cleaved intra-neural ARP. Protein kinase C (PKC) betaII, known to interact with ARP, was significantly elevated in the LPS-exposed sciatic nerve preparations. Moreover, direct i.n. injection of synthetic ARP30, bearing the mouse AChE-R C-terminal sequence, similarly induced PKCbetaII expression and conduction impairment. The induction of neural conduction impairment by ARP, possibly through its interaction with PKCbetaII, suggests a role for AChE-R expression in inflammation-associated neuropathies.

Triptans--why once?

OBJECTIVE: To evaluate triptan use patterns in a large Israeli HMO district. BACKGROUND: Triptans, 5HT(1B/1D) agonists, provide an effective and safe relief of headache and accompanying symptoms during an acute migraine attack. METHOD: We retrospectively reviewed the computerized prescription filling data of 1498 patients who filled a first triptan prescription between July 2003 and June 2004. RESULTS: During a 1-year follow-up period, 841 patients (56.1%) purchased triptans only once. Single-time users were significantly more prevalent among men and in patients younger than 30 or older than 70 years. CONCLUSIONS: It seems that many migraine patients choose not to use triptans after their first experience with the drug.

Stimulated-single fiber electromyography monitoring of anti-sense induced changes in experimental autoimmune myasthenia gravis.

The neuromuscular weakness associated with myasthenia gravis (MG) can be transiently relieved by pharmacological inhibitors of acetylcholinesterase (AChE). Here, we expand the anticholinesterase repertoire to include 2'-O-methyl-protected antisense oligonucleotides targeted to AChE mRNA (EN101). Using stimulated-single fiber electromyography, we show that EN101 treatment of rats with experimental autoimmune myasthenia gravis (EAMG), improved the mean consecutive difference (MCD) and blocking for 24h. This treatment was more efficient than pyridostigmine and was accompanied by marked improvement in stamina and clinical profile.

Traumatic intracranial hemorrhage in patients with seizures: descriptive characteristics.

We reviewed the records of all patients with recurrent seizures and severe head injury-induced traumatic intracranial hemorrhage (TIH) between 1989 and 2003 in three Israeli medical centers. We identified 52 cases (44 males, mean age=43+/-19 years, range=8-84; 8 females; mean age=74+/-12 years, range=48-85). Twenty-seven (52%) had additional known risk factors for TIH, e.g., older age, alcohol abuse, and anticoagulant use. All five children and adolescents had mental retardation. Approximately one-half of patients with seizures and TIH have additional risk factors for TIH. Non-mentally retarded children and adolescents with seizures are probably at low risk of developing TIH. Women less than 70 years old with seizures are much less prone to TIH than men. In young "otherwise healthy" patients with epilepsy, suboptimal treatment seems to be an important factor in the occurrence of TIH.

Inhibition of Ras attenuates the course of experimental autoimmune neuritis.

EAN induced in Lewis rats by immunization with peripheral bovine myelin was treated by the Ras inhibitor farnesylthiosalicylate (FTS). Treatment from day 0 with FTS (5 mg/kg intraperitoneally twice daily) attenuated peak clinical scores (mean+/-S.E., 2.5+/-0.5 compared to 4.1+/-0.5 in saline treated controls, p=0.018, t-test) but not recovery. Treatment from day 10 with FTS attenuated peak disability (2.5+/-0.6, p=0.032 compared to saline treated controls) and improved recovery (0.84+/-0.42, untreated controls 2.4+/-0.6, p=0.028 by repeated measures ANOVA). Effects were confirmed by rotarod and nerve conduction studies. An inactive analogue, geranylthiosalicylate, had no clinical effect. Inhibition of Ras is of potential use in the treatment of inflammatory neuropathies.

A high incidence of migraine with aura among morbidly obese women.

INTRODUCTION: Nearly two-thirds of adults in the United States and an increasing percentage of the population worldwide are overweight or obese. The relationship of obesity to headache has received inadequate attention. We evaluated the incidence of headache in a sample of morbidly obese women. METHODS: Morbidly obese women, attending the surgical preoperative clinic of Soroka University Medical Center for preoperative assessment for laparoscopic gastric banding were evaluated using a structured interview and their medical charts were reviewed. RESULTS: During a 2-month period, 27 morbidly obese women were interviewed, with a mean BMI of 41.07. Ten patients suffered from migraine with aura, three from migraine without aura, and four from tension headache. CONCLUSION: The unusually high incidence of migraine with aura can be attributed to extraovarian production of estrogen and estradiol in the adipose tissue. Further study is indicated to explore the therapeutic role of weight loss in headache care.

Induction of conduction block by Campylobacter jejuni lipopolysaccharides and focal neural insult.

A systemic exposure to gram negative LPS have caused transient conduction abnormalities in a certain strain of rats probably associated with the action of cytokines secreted by macrophages. Our previous studies demonstrated that anti-GM1 antibodies induced in rats by the cross-reactive Cj-LPS, caused no conduction abnormalities. We designed the present study to evaluate the effect of systemic exposure to Cj-LPS on nerve conduction after a focal minor neural trauma. Female Lewis rats were sensitized against KLH by repetitive subcutaneous injections. After 28 days rats were intraneurally injected with saline in the right sciatic nerve and concomitantly with intraperitoneal Cj-LPS. Sciatic nerve conduction studies were performed on days 0, 1, 2, 3, and 7 after injections. Nerve conduction blocks developed in all the rats (n=10) which received an intraneural injection of saline concomitantly with the systemic Cj-LPS exposure, before titers of anti-ganglioside antibodies were detected. We conclude that humoral factors (possibly cytokines), other than antibodies are secreted by lymphocytes and macrophages stimulated by gram negative LPS, and cause functional conduction abnormalities when the blood-nerve barrier is disrupted.

Anti-heparan sulfate antibodies in neurological disease.

Antibodies to heparan sulfate (HS) have previously been found in association with peripheral neuropathy. We tested sera from patients with neuropathies and with other neurological diseases for antibodies to HS using an avidin-biotin enzyme-linked immunosorbent assay (ELISA) system. Increased titers of anti-HS antibodies were found in 3.4% of patients with neuropathy, and in 3% of patients with other neurological diseases. In all cases, however, an inflammatory disease was present, including chronic inflammatory neuropathy, cerebral vasculitis, or multiple sclerosis. Antibodies to HS appear not to be specific for neuropathy, as they occur in several inflammatory diseases. They might contribute to the associated breakdown of the blood-brain or blood-nerve barrier.

Detection of anti-ganglioside antibodies in Guillain-Barré syndrome and its variants by the agglutination assay.

Sera from 40 patients with Guillain-Barré syndrome (GBS), including the subtypes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS) were examined for the presence of anti-ganglioside antibodies using the ganglioside agglutination assay, and the enzyme-linked immunosorbent assay (ELISA). In the ELISA system, sera were tested for IgM and IgG antibodies to GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides. Antibodies to gangliosides were detected in 21 (53%) of the GBS patients by agglutination assay and in 17 (43%) of the patients by ELISA. Some of the sera reacted with more than one ganglioside. Antibodies were not found in the control sera that were studied. The agglutination assay may be useful for rapid screening of GBS sera for antibodies to multiple gangliosides.