Immediately following the CHMP BROAD LABEL recommendation set to be delivered at the end of this month we'll be serving coffee and donuts in the church basement. You're all welcome to attend that as well as the mass for Ray following that event. Because let's face it friends...when you're down to having your brain parts being relocated inside your head as your primary argument..... you're dead meat.
You see folks...the ONLY thing IMO that would stop a broad label approval would be drug interactions between various primary illness patients. And as we've seen with N here in the U.S., that will be handled with a package labeling and insert. PBA..is PBA..in whatever the patient AND whatever the primary neurological condition is that caused it. N is not trying to treat the neurological condition as Ray is so humorously attempting to point out in his flapping around helplessly argument about where in the brain the primary illness might be originating or most impacting...the fact is they are ALL THEN impacting the emotional response cause and effect center of the brain which DOESN'T magically shift around inside your head.
PBA is caused..in ALL cases...by lesions in that area of the brain causing an emotional disconnect.
This is why it's really so easy to identify with a survey for instance that asks the question...do you REALLY feel the way your emotions are acting out? In other words..if you're laughing and ACTING depressed...do you really FEEL depressed? Is anything happening in your life at that moment that would have otherwise brought that episode on? My friends..there is an ALARMING number of survey patients who say ........NO. There's not.
And i say ALARMING because the FACT of the matter is...upwards of HALF OR MORE OF ALL STROKE patients ALSO have PBA with some of them having PBA as the ONLY remaining issue of their stroke causing in some cases their lives to be RUINED because of it. Chmp will never allow that to stand. Expect a broad label approval TS /jmho
Sentiment: Strong Buy
Ray is spending countless hours it seems making the same tired point but in doing so apparently misses the only real point altogether. Nuedexta is a drug that treats PBA regardless of whatever primary illness triggered it or what area of the brain that originated in. If PBA were a broken leg instead...Nuedexta is treating the broken leg....not the Activity that CAUSED the broken leg as you continually and repetitively attempt to associate as being the reason more testing is needed. What you are saying is that just because someone playing baseball might sometimes get a broken leg and THAT was the subject of Avnr's studies..and Football was found to sometimes cause broken legs and THAT was the subject of Avnrs studies....then ONLY PEOPLE who play baseball and football who wind up with a broken leg should then be entitled to be approved for this drug and that anyone else should have been the subject of a study as well. The fact of the matter is LOTS of things cause broken legs...and LOTS of things cause PBA. And nuedexta is on the market to treat PBA....not the primary illness that caused it. BUT..what Avnr has ALSO done is to provide the regulators with a LOT of evidence about ALL kinds of other things that CAUSE PBA and a lot of evidence to show that N is effective in ALL those cases as well. And furthermore....we are talking about two ingredients that are about as safe and effective as you're going to get in the world of drugs. AND, we're talking about a drug that works VERY quickly and so doctors can know whether this treatment is effective or not in treating the patients condition. Thereby reducing the risks even further regarding any prolonged use.
Ray....you need to give it UP. Because you and I BOTH know that the chances of the EU not approving a broad label is VERY slim indeed. You're posts have gone from bad to desperate and like another poster described..you sound like you're drowning and trying to cling to anything now to save you. ~TS
Sentiment: Strong Buy
No Trade, you either just refuse to admit that you get my point, or you really don't get it.
The point is that PBA may be caused by different diseases in different sites of the brain, with different neurotransmitters and actually, IT IS NOT KNOWN that PBA due to different neurologic illnesses is effectively treated by dex/quin.
Now you want to believe that PBA from different neurologic illnesses is effectively treated by dex/quin, but the fact is, since there has been no drug study in these non-MS and non-ALS neurologic conditions,
IT IS NOT KNOWN that PBA due to those other neurologic illnesses is effectively treated by dex/quin.
And you can not expect European scientists to ignore these salient facts like you ignore them.
The European scientists may make the same leap of faith that the FDA made, or they may not.
"Parvizi et al. have recently proposed an alternate mechanism for uncontrollable laughing and crying.27 They suggest that pathways from higher cortical association areas to the cerebellum are involved in the adjustment of laughing and crying responses to appropriate environmental cues. They propose that lesions that interrupt either cortico-cerebellar communication or cerebellar communication with effector sites that produce emotional responses (e.g., the motor cortex or brainstem) can disrupt cerebellar modulation of affective displays, and produce the PBA syndrome."
From a 2005 article by Avanir employee Laura Pope and another author: Note that theories of where in the brain PBA originates is all over the map:
The neuropathological and neurophysiological substrates of the PBA syndrome are not completely understood. Kinnier Wilson hypothesized that the syndrome was caused by bilateral corticobulbar motor tract lesions, which uncoupled cranial motor nerve nuclei and supranuclear integrative centers from their cortical control.5,13—16 Subsequent authors have emphasized regulatory functions attributable to temporal and infratemporal limbic system centers for emotional expression and emotional experience.3,4,14,17 The PBA syndrome has been reported in a variety of neurological diseases, including ischemic stroke, brain trauma, motor neuron disease, multiple sclerosis, and the dementias.18 Diminished serotonin metabolism by single photon emission computed tomography (SPECT) has been reported in some patients with PBA.82 Low cerebral spinal fluid (CSF) homovanillic acid has been reported in a cohort of stroke patients with PBA.19 A summary of anatomic findings in 30 cases indicated that the lesions always involved systems with motor functions, and that the lesions were always multifocal, or bilateral.84 The most common neuroanatomic structures involved were the internal capsules, the substantia nigra, the cerebral peduncles, and the pyramidal tracts. Imaging studies suggest that, occasionally, single lesions in the brainstem or posterior fossa can generate the PBA syndrome.20—26
"...the ONLY thing IMO that would stop a broad label approval would be drug interactions between various primary illness patients"
Wrong. Drug interactions don't prevent a drug from getting approved. Drug interactions are warned about in the label but have virtually nothing to do with a drug getting approved or not.
Can you name one drug that was not approved or taken off the market because of drug interactions? I can't think of any.
" N is not trying to treat the neurological condition -------- helpless argument about where in the brain the primary illness might be originating or most impacting..."
Wrong again. The primary illness has to be affecting a part of the brain whose dysfunction causes PBA---or else the primary illness would not be causing PBA. When dex/quin treats PBA, it is treating the neurons that cause PBA that are affected by the underlying neurologic disease. The underlying neurologic disease has to be affecting an area of the brain that causes PBA to cause PBA. It does not get more basic than this.
"the fact is they are ALL THEN impacting the emotional response cause and effect center of the brain which DOESN'T magically shift around inside your head."
Wrong for a third time. The "emotional response cause and effect center" isn't a center at all.
Emotions require cognitive thought and originate in the cerebral cortex. Those emotions lead eventually to motor neurons which innervate the muscles that express laughter and crying.
The motor response to emotion is normally inhibited and under some voluntary control but can not be entirely controlled voluntarily. So I guess the voluntary control of emotions is in the cerebral cortex which may explain how conditions like dementia, stroke and traumatic brain injury lead to PBA. But PBA from what I recall reading is mainly thought to be mediated around the brainstem which is quite far away from the cerebral cortex.
I believe MS can cause problems with neurons around the brainstem.
ALS, being predominantly a motor neuron disease, is probably causing PBA by a direct effect on the motor neurons that cause laughing and crying.
Parkinson's would not be affecting the brainstem, it would be mainly affecting the striatum and through dopamine, not glutamate. A different neurotransmitter, glutamate, is affected by dextromethorphan. One can get dementia from Parkinson's. I imagine that is Parkinson's affecting the cerebral cortex so maybe that is how Parkinson's causes PBA.
The point again is that PBA can be caused by lesions in different parts of the brain, and probably by different neurotransmitters so it is not a given that a drug that treats PBA due to one or two underlying neurologic illness treats PBA due to any underlying neurologic condition effectively. This should be shown by clinical study, and definitely not only by anecdotal reports.