Histamine has a long history of therapeutic use in many diseases, including Multiple Sclerosis (MS). Recently, transdermal Histamine has been successfully employed for the amelioration of symptoms of both Relapsing/Remitting And Progressive Multiple Sclerosis.

This paper summarizes preliminary experiences with transdermal Histamine for MS at the Tahoma Clinic: 67 percent of 55 patients using Histamine transdermal cream had improvements in one or more areas including: Extremity Strength, Balance, Bladder Control, Fatigue, Activities Of Daily Living, and Cognitive Functioning, sustained for periods of up to three months.

One-third of patients had improvements in three or more areas of functioning. Five possible mechanisms of action are postulated:

1. Augmentation of subnormal Cerebral tissue levels of Histamine
2. Improved electrical function of DeMyelinated fibers
3. Increased Cerebral blood flow
4. Suppression of AutoImmune Responses
5. Stimulation of ReMyelination.

These will be discussed in detail in Part II of this article.

The presence of terminally differentiated slow- and non-dividing cells in the Central Nervous System (CNS) provides a safe harbor for Viral persistence and latency and constitutes a unique Immunologic environment for Viral Infections.

Studies of experimental model systems of Viral infections of the CNS provide insight into mechanisms of Viral persistence and Immune-Mediated Pathology.

NidoViruses are comprised of 2 families of Viruses, CoronaViruses and ArteriViruses, and are common Pathogens of humans and a variety of animal species.

Both families of Viruses contain NeuroTropic strains that produce experimental Neurologic Diseases in rodents. These include acute Meningitis and EncCphalitis; Acute PolioMyelitis; and Chronic Inflammatory, Immune-mediated, DeMyelination.

CoronaVirus-induced DeMyelinating Disease mimics many of the pathologic features of Multiple Sclerosis (MS).

Objectives
Incontinent IleoVesicoStomy is an alternative form of Urinary management applied to patients with NeuroGenic Vesical Dysfunction, who are either unable or unwilling to perform clean intermittent Self-Catheterization or assisted Catheterization.

We review our operative results, Urodynamic data, and complications observed in patients who underwent creation of Incontinent IleoVesicoStomy at our institution.

Methods
Thirteen patients (mean age 43.2 years) with Neurogenic Bladder Dysfunction underwent an Incontinent IleoVesicoStomy between 1994 and 1998.

The etiologies of the Neurogenic Bladder Dysfunction were

1. Spinal Cord Injury in 8 patients
2. Multiple Sclerosis in 4 patients
3. Tuberculous Meningitis in 1 patient

The preoperative data, surgical records, Urodynamic findings, and postoperative complications were assessed.

Results
All patients experienced complications of their pretreatment Bladder management. The mean operating room time was 242 minutes (range 170 to 395), including 14 additional procedures in 11 patients.

The mean estimated blood loss was 403.8 mL (range 50 to 2000). No patient required blood transfusion. There were no intraoperative complications. Only 1 patient required reoperation for Stomal revision.

One patient had a Ureteral stone 2 years after surgery; 1 patient has continued to have Urinary Tract Infections despite a negative workup. The mean follow-up was 23 months (range 6 to 57). The mean Bladder leak point pressure through the Stoma was 8.2 cm H2O.

Conclusions
The Incontinent IleoVesicoStomy is a useful technique in the treatment of patients with Neurogenic Bladder unable to perform clean intermittent Catheterization. It provides patients with a low-pressure Urinary conduit that empties readily without an Indwelling Catheter.

The Blood-Brain Barrier (BBB) plays a crucial role in Central Nervous System (CNS) HomeoStasis. Serving as the Brain's protective shield, it regulates soluble factor and Cellular exchanges from blood to Brain.

Critical to its function, the BBB is composed of Brain MicroVascular Endothelial Cells (BMVEC), a Collagen matrix, and Astrocytes. Astrocytic endfeet surround the BMVEC abluminal surface and influence the 'tightness' and trafficking role of the Barrier.

In NeuroDegenerative disorders (for example Stroke, Multiple Sclerosis and HIV EnCephalitis) the BBB becomes compromized. This is, in part, Immune mediated.

An accumulating body of evidence demonstrates that the Cellular components of the BBB are themselves ImmunoCompetent. PeriVascular Cells (Astrocytes, Macrophages and Microglial Cells) and BMVEC produce inflammatory factors that affect BBB permeability and expression of Adhesion Molecules.

These affect cell trafficking into the CNS. Leukocyte BBB migration can be influenced by Cytokines and Chemokines produced by Glia. Astrocytes and Macrophages secrete a multitude of factors that affect Brain Immune Responses.

Interactions between BMVEC, Leukocytes and/or Glia, Immunological activation and noxious (infectious, toxic and Immune-mediated) Brain insults all appear to play important roles in this BBB cell trafficking.

New information gained into the mechanisms of Leukocyte-Brain penetration may provide novel insights in the PathoGenesis and treatment strategies of NeuroDegenerative Disorders.

The Blood-Brain Barrier (BBB) regulates the passage of solutes between the CNS and the blood.

The BBB not only restricts the entry of Serum proteins into the CNS, but it also controls the passage of Nutrients, Electrolytes, Vitamins, Minerals, Free Fatty Acids, Peptides, and regulatory proteins in both the Brain to blood and blood to Brain direction.

The BBB performs these functions through a number of saturable and non-saturable mechanisms. For example:
• Efflux (CNS to blood) mechanisms regulate the levels of nutrients and minerals in the CSF
• Detoxify the CNS
• Reinforce the impermeability of the BBB against circulating toxins and many drugs
• Secrete CNS-originating substances into the blood
• Drain substances directly into the Cervical Lymphatic Nodes

Influx mechanisms control the HomeoStatic environment of the CNS, supply the Brain with nutrients, and help to integrate CNS and peripheral functions. These mechanisms are altered in and can be the basis for disease and many of these systems are altered in NeuroAIDS.

We review here examples of several diseases in which the functions of the BBB are altered, and some conditions, such as Alcoholism, Multiple Sclerosis, Obesity, and a subtype of Mental Retardation, where those altered functions may underlie the PathoPhysiology.

Finally, we consider some of the ways in which these aspects of the BBB could be active in NeuroAIDS, including the efflux of Anti-Virals, the transport of Virus by adsorptive Endocytosis, egress routes for HIV-1 via Brain Lymphatics, and the release of neurotoxins from Brain Endothelial Cells.

In order to characterize antigenic Epitopes specifically targeted by the Immune response of patients with Multiple Sclerosis (MS), the AntiBody specificities of CerebroSpinal Fluids (CSF) and Sera from the same MS patients have been analyzed using a random pentadecapeptide library displayed on phage.

The 3 peptides (mimotopes) selected with MS Sera were not disease-specific. In contrast, the combination of 4 MS CSF selected mimotopes, allowed the detection of specific AntiBodies in 21 of 60 MS CSF whereas only 2 of 27 CSF from patients with Other Neurological Diseases equally recognized the 4 mimotopes.

Some Amino Acid similarities were found between two MS CSF selected mimotopes and two envelope regions (319-329 and 433-443, respectively) of MSRV (Multiple-Sclerosis-Associated RetroVirus) and the related endogenous RetroVirus HERV-W.

Copyright 1999 Academic Press.

Background
Lesion development in MS is initiated by migration of inflammatory cells into the Central Nervous System, a process dependent on Endothelial Cell-Lymphocyte interaction.

Bradykinin B1 Receptor is a membrane-bound G protein-coupled receptor shown to be upregulated on the surface of various cells types during inflammation.

Objective & Methods
To assess the expression and function of the Bradykinin B1 receptor on T-Lymphocytes from MS patients. The authors used multiplex polymerase chain reaction amplification and Western blot techniques to demonstrate B1 receptor expression by T-Cells.

A modified Boyden chamber assay also was used to assess the effect of B1 agonist and antagonist on T-Cell migration.

Results
The authors demonstrated that the expression of B1 receptor was upregulated on T-Cells derived from peripheral blood of MS patients.

Expression of this receptor was upregulated on T-Cells from patients with Secondary/Progressive MS and Relapsing/Remitting patients in active relapse.

Expression was lower in Relapsing/Remitting patients in remission and least in control subjects, including patients with Epilepsy, Chronic Inflammatory DeMyelinating PolyNeuritis, and Systemic Lupus Erythematosus.

In vitro treatment of cells from healthy control subjects with Tumor Necrosis Factor- and Interferon- also induced the expression of B1 receptors.

The authors also found that the significantly higher rate of migration of MS T-Lymphocytes, compared with control subjects in the Boyden chamber assay, could be prevented by the addition of the selective and stable B1 agonist Sar (D-Phe8) desArg9-BK.

Conclusion
The authors demonstrate that B1 receptors are upregulated by T-Lymphocytes during the course of MS and that signaling through this receptor with a B1 agonist can negatively regulate T-Cell migration in vitro.

Objective
To assess the clinical effectiveness of the Odstock Dropped Foot Stimulator by analysis of its effect on Physiological Cost Index (PCI) and speed of walking.

This Functional Electrical Stimulation (FES) device stimulates the common Peroneal Nerve during the swing phase of Gait.

Design & Subjects
A retrospective study of patients who had used the device for 4 1/2 months. One hundred fifty-one patients with a Dropped Foot resulting from an Upper Motor Neuron lesion.

Setting
A medical physics and biomedical engineering department of a district general hospital specializing in the clinical application of FES and a NeuroPhysiotherapy department at a separate hospital.

Main Outcome Measures
Changes in walking speed and effort of walking, as measured by PCI over a 10-meter course.

Results
There was a 92.7% compliance with treatment. Stroke patients showed a mean increase in walking speed of 27% (p<.01) and reduction in PCI of 31% (p<.01) with stimulation, and changes of 14% (p<.01) and 19% (p<.01), respectively, while not using the stimulator. Multiple Sclerosis patients gained similar Orthotic benefit, but no "carry-over."

Conclusions
The measured differences in walking with and without stimulation were statistically significant in the Stroke and Multiple Sclerosis groups.