Daytona Casual Test- Lotus Exige S Honda Powered

Driver : Christopher Prusinski

Engineer : Steve Mason

Event : PBOC Daytona  October 2012

http://www.youtube.com/watch?v=7Gd1nHrNv4g&feature=youtu.be

Uncontrolled Hypertension Treated with Renal Denervation

   Renal denervation, an intravascular procedure that employs radiofrequency pulses induces denervation of the sympathetic innervation of a patient's renal arteries. Approximately 10,000 patients have been treated worldwide resulting in a drop in blood pressure of 28/10 mm Hg in patients that began their treatment with pressures of approximately 180/100 mm Hg, with a response rate of over 90% and a duration of over 36 months of follow-up.
   Additionally, RD was applied to normotensive patients with heart failure resulting in a 25% improvement in left ventricular ejection fraction 12 months after RD.
   RD is investigational in the US.
Annual Congress of the European Society of Cardiology (Munich)

Intranasal Stem cell Delivery in PD Rat model

  Mesenchymal stem cells (MSC) were delivered into the nose preferentially migrated to the brain and survived up to six months improving motor function significantly (up 68%) in the rat model of Parkinson's disease. Levels of dopamine were much higher in the treated rats.
Rejuvenation Research Volume: 14 Issue 1: February 17, 2011

Potential Universal Treatment of Neurodegenerative Disorders

Researchers at MRC toxicology unit in the UK, lead by Giovanna R. Mallucci,MD,PhD have associated the activation of a protein called eIF2 (the alpha subunit of eukaryotic translation initiation factor 2) with the cell death and synaptic damage seen in prion neurodegeneration. Even more importantly, they blocked eIF2alpha phosphorylation and reversed the disease process !

The buildup of prion protein as it replicates induces "persistent translational repression" of general protein synthesis by eIF2alpha, which in turn was associated with synaptic failure and cell death. According to NEUROLOGY TODAY, the normally protective mechanism is over-activated with fatal prolonged failure of protein synthesis.

Researchers then used viral vectors to overexpress an enzyme specific eIF2alpha-P phosphatase called GADD34 to reduce prion protein levels, protecting brain hippocampal cells which are commonly targeted in the sick with memory disorders.

Researchers are now looking for drugs that could work on this pathway in humans to provide a unified treatment approach for these incurable diseases.

Nature 2012;E-pub 2012 May 6

Unifying Theory of a Prion-like Process in Neurodegenerative Disease

Researchers at UCSF are the first to demonstrate that amyloid beta (Abeta) deposition can be planted in the brain by synthetic amyloid beta alone, fortifying the conclusion that a prion-like process of corruptive protein templating is involved.

Transgenic mice were inoculated with brain derived Abeta or synthetic Abeta peptide protein. Inoculated mice showed significant Abeta deposition over time.

These findings further support an enlarging body of evidence that abnormal protein accumulations seen in Alzheimer's disease, Parkinson's disease,and ALS/Frototemporal degeneration follow the same pathologic process.....an abnormal protein creates a template and seeds other proteins to self-propagate, misfold, build up, and eventually damage brain tissue inducing cell death.

Using this knowledge, treatment would be started decades before symptom declaration, targeting the initial seed and preventing the deluge of misfolded toxic proteins that follows.

Science 2012:336,1511-1513

Robotic Arm Used by Longstanding Tetraplegics

Employing a 96-channel microelectrode array implanted in the motor cortex of tetraplegics, without rigorous training , two patients were able to control a robotic arm over a broad space performing reach and grasp movements . One patient was even able to drink coffee ! This neural interface system-based control transmitted signals from a small population of cerebral cortical motor neurons to manipulate the robotic arm. This study shows that years after injury to the CNS that such a system may be employed to recreate useful multidimensional control of complex devices directly from a small sample of neural signals.

Nature may 16,2012

Possible New Predictive Test for PD

Tissue obtained during colonoscopy showed immunostaining for alpha-synuclein years before the declaration of first motor symtoms consistent with disease onset. Additional study is required to determine if this will be a useful biomarker of pre-motor Parkinson's disease.

Movement Disorders May 1,2012

Alemtuzumab in MS

In patients with relapsing-remitting MS, alemtuzumab was found to be superior to interferon beta 1-a . Patients were randomized to 12 mg of alemtuzumab for 5 days at month 0 and 3 days at month 12 by infusion or 44 mcg qod with interferon beta 1-a.

Neurology 2012;78:(14):1069-1078

Lancet Neurology 2011;10(4):338-348

Rest in Peace Dad..We'll Miss You Pop

Chester Joseph Prusinski, DO 
October 5, 1938 - August 6, 2012

Donations to the American Brain Foundation
www.curebraindisease.org

Coffee To Improve Movement In Parkinson's Disease

Coffee ingestion has been shown to decrease risk of Parkinson's disease and now a new study from McGill University in Montreal suggests it actually improves movement of those with the disease.

Neurology August 1,2012

Watch You Tube For Treatment of Vertigo

A very successful treatment for "Benign" paroxysmal positional vertigo ( a common cause of dizziness ) called the Epley maneuver can be found on You Tube for physicians and the afflicted alike.

Neurology July 24,2012

New Blood Biomarker May Help Predict Alzheimer's

A fat called ceramide at high levels may increase a person's risk of developing Alzheimer's.

Neurology July 18,2012

Implantable Fuel Cell To Power Prosthetics

An implantable fuel cell that generates power through glucose oxidation has been developed that may be used to power future neural prosthetics.

The fuel cell was created employing semiconductor fabrication techniques that allow it to exist with integrated circuits on a single silicon wafer.

An activated platinum anode facilitates glucose oxidation. Half-open geometry is used in the fuel cell's configuration that shields the anode and exposes the cathode.

It is theorized that the CNS recirculation of CSF around the brain will provide adequate glucose energy harvesting without adverse effects.

Thus, low-power brain-machine interfaces can be powered or re-charged by glucose fuel cells.

PLoS ONE June 12 2012

New Oral MS drug Reduces Brain Lesions

From the 2012 AAN annual meeting, ONO-4641, a potent selective sphingosine-1-phosphate (S1P) receptor agonist (two other similar drugs are Fingolimod...already FDA approved... and BAF), was found to reduce the number of lesions on MRI in patients with the relapsing remitting form of MS.The drug was well tolerated with no unexpected adverse events. Those adverse events were dose related cardiovascular ones. The phase 2b study of ONO-4641 shows that lower doses will be safer.

Impaired Cognitive Function in Asymptomatic Carotid artery Disease

From the International Stroke Conference, Dr. C. Balucani enrolled 330 patients from 2005-10. In each of four evaluations, patients with bilateral internal carotid artery stenosis showed significant impairments in both brain hemispheres compared to controls.Patients with unilateral stenosis showed significant impairment only in the brain hemisphere connected to the embarrassed vascular supply.

Memories Blocked..but Recall Restored

HDAC2 ( histone deacetylase 2 ) regulates the expression of genes involved in learning and memory. MIT scientists led by Li-Huei Tsai,PhD blocked the buildup of HDAC2 in a mouse model of Alzheimer's disease and it restored structural and synaptic plasticity allowing mice with symptoms of AD to restore and access memory. This experiment suggests that memories of things learned may still be stored in the brain but overproduction of HDAC2 blocks access to those memories. This finding has already been experimentally replicated.

In another epigenetic part of their study, these researchers found that glucocorticoid receptor 1normally turned on by stress was in fact switched on/activated from the accumulation of Abeta amyloid causing an increase in HDAC2 and chronic blockage of the genes necessary for memory.

For alzheimer's patients , these MIT researchers have developed a potent HDCA2 inhibitor and are preparing to submit papers to the FDA to begin experimental testing.

NATURE 2012 ; 483 (7388):222-226

Also see Science 2012;335(6075):1513-1516 "Generation of a synthetic memory trace"

Potential Treatment for Alzheimer's Disease :Bexarotene

I have been in email communication with the lead investigator Gary Landreth,Ph.D. of Case Western Reserve University ( my father's alma mater ) in my home town of Cleveland, OH as I am very excited about his preliminary findings in using bexarotene ( Targretin ) in mouse models of Alzheimer's disease. This drug has been FDA approved for the treatment of cutaneous T-cell lymphoma, has been in use in humans in this capacity for 10 years and has a favorable safety profile.

In this experiment led by Paige E. Cramer, after a 14 day treatment period, there was a sustained 30% reduction in soluble amyloid-beta levels and a 75% reduction in amyloid-beta plaques ! More to come.....

( Science 2012 Feb 9 )

Double Edged Sword: AMYVID

Amyvid ( florbetapir F18 Injection) was approved by the FDA on April 10th for the imaging of amyloid using positron emission tomography (PET) in adults being evaluated for Alzheimer's disease. The problems : what constitutes a definitively abnormal scan ? If a scan reveals significant amyloid burden, then what ? CSF biomarkers can aid the neurological exam and establish a diagnosis with better than ever sensitivity, but then what ? As we have no definitive cure for the disease......stay tuned as hope is on the horizon !

PS. This test is not currently covered by Medicare...cost to consumer $3000.00

A WORLD'S FIRST: A Parkinson's Vaccine

Phase I study of the AFFIRIS AG Parkinson's candidate PD01A has begun.PD01A targets alpha-synuclein and induces antibodies to neutralize its toxic impact potentially modifying the diseases course. This is a "First-in-man""First-in kind"trial that will enroll 32 patients to be the pioneers of this immunotherapy of Parkinson's disease.

www.affiris.com

Dizziness Update

DIZZINESS
HC-BPPV ( apogeotropic horizontal canal benign paroxysmal positional vertigo ) Tx=Gufoni maneuver
Neurology 2011; E-pub Dec 14

MS Update in Pregnancy

Multiple Sclerosis
Glatiramer acetate = in pregnancy
Continuum 2010;16(5):193-210
Rebif 22 mcg sc qod then 44mcg
(Interferon beta 1-a)
REFLEXION study sc beta I nterferon-1a 44mcg 3X/wk ...early(AAN2012)

Dementia Update Cliffnotes

DEMENTIA
Dementia with Lewy body DLB=Decreased CSF alpha- synuclein
AD=Decreased CSF amyloid-beta 42 (earlier bio-mkr) ⬆total-tau and phospho-tau
Increased soluble amyloid precursor protein beta (sAPP) (Neuro 77;1:7/11)
DLB and AD = 80 % Diagnostic sensitivity
AD with Lewy body pathology 35-40% Diagnostic sensitivity

Brain 2010 Sept 7 2011.......
P300 < 323ms ,>5.0 mV = nml
E. Braverman, Cornell/Harvard

DRUG Treatment of Psychiatric consequences of DementingIllness
1. Impulsive Tx (stealing, sexual) : (Zoloft) sertraline 200mg/d, lamictal, VPA,divalproex,Inderal
2. Agitation /Paranoia : trazodone
3. Delusional : risperidone (ie. delusion of theft)

Mild Cognitive Impairment Treatment
MCI (Neurology 1/10/12 Vanderbilt nicotine patch 15 mg/d...cotinine is the active ingredient (from tobaccoJrnlAD) 2/14/11

CDR ( Clin. Dementia rating scale ) www.wustl.edu Wash U. St. Louis
CDR 3=severe,CDR2=mod, 1=mild,0.5 very mild

PET in diff dementia PLoS One 2011;6(3):e18111

DBS of entorhinal cortex enhances memory in MCI --( NEJM 2012;366:502-510)

✳FTD ( frontotemporal degeneration )
1. Progranulin Blood Test (A@G Pharma) ⬇Progranulin in blood dt Progranulin gene (PGRN) mutation ( Nature 2006)
2.C9ORF72 mutation(Neuron2011;72:245-56;257-68)(Lancet Neurol.3/9/12)

Alzheimer's Disease ⬆plasma Adiponectin (ArchNeurol2012Jan1)

Parkininson's Treatment Breakthrough

Ucla--Synucleinopathies:PD,DLB,MSA
CLR01....a C-shaped complex molecular compound that wrap around the chains of lysine of alpha-Synuclein aggregates removing them. A process-specific mechanism employing transgenic zebra fish model of PD ( A tropical freshwater fish )