Hello Carla, the best way to see neurodegenerative conditions are, rather, to view them as a continuum of cognitive impairment. None of it is normal or "old-age memory loss" as a differential. So on, one end of the spectrum, you have no cognitive abnormalities and on the other end of the spectrum you have Major Neurocognitive Disorder. So on this continuum of disorders (between a normal individual and MNCD) you can have the following: 1. you can a person with subjective cognitive loss, but objectively the neurobehavioral tests or screens like MMSE/MOCA are normal; eg, Einstein starts with a high baseline and then subjectively develops cogntivie problems - no test will pick the cognitive problems up at this stage. 2. you can have a person recorded cognitive deficits on the neurobehavioral tests or screens but doesn't influence his activities of daily living / social functioning status, this would be referred as Minor Neurocognitive Disorder. 3. Then you have a person with deficits on the neurobehavioral tests or screens as well as interference with ADL/social functioning status, and that would be classified as Major Neurocognitive Disorder. Each of these levels has its own differentials, depending on the diagnosis. eg Alzheimer's disease patients will start with point 1 - but will then eventually progress to point 3. Being in point one doesn't necessarily mean that you will end up in point 3 - there is a list of differentials for point 1 eg Vascular diseases, Hippocampal Sclerosis, Argyrophilic Grain Disease, and Primary Age-Related Tauopathy (these are beyond the scope for your level) so that means you might just stagnate at point 1. The risk of having something that will eventually cause progression is +/- 10% per year - which I mentioned in the presentation, this gets compounded by a multi-modal system. Vascular risk factors/lifestyle/diet etc. Therefore trying to make the diagnosis at point 1 will help you to calculate the risk of progression to point 3 in the future eg FTD, Alzheimer's, CBS etc etc. but will it necessarily help the patient? Irrespectively treatment at this stage (stage1 ) will be aimed to delay progression to stage 2/3 etc. and this will be aimed at minimizing risk factors; exercise etc. These risk factors, like I mentioned, compound this whole degenerative process, irrespective if you have amyloid/tau built up in the brain.

Acetylcholine also acts at various sites within the CNS, where it functions as a neurotransmitter and as a neuromodulator. It plays a role in various higher functioning processes like motivation, arousal, attention, learning, and memory, and is also involved in promoting REM sleep. Disrupted levels of acetylcholine, is believed to be one of the underlying pathophysiological mechanisms in cognitive disorders. Therefore, if you inhibit acetylcholine, you might cause further disruption of the underlying cognitive processes

Hello Luke. The condition in the presentation that I referred to, was called Normal Pressure Hydrocephalus aka NPH. This is a special condition which is characterized by a constellation of clinical findings referred to as the Wet (incontinence), Wacky (Dementia) & Wobbly (gait apraxia/bruns apraxia/lower half Parkinson's). This is a rapid form of dementia with early gait involvement, characterized by in increase in CSF production & decrease in CSF absorption. This creates features of hydrocephalus on neuro-imaging but it is not really hydrocephalus as the intracranial pressures are still normal when we perform manometry assessments. The csf then accumulates in the brain and ventricles creating pockets, hence the term DESH has been coined. There are numerous other diagnostic criteria that we look at for these patients, but that falls beyond the scope of 4th year level. If you do want the information I will be glad to share it with you. In patients with significant cerebral atrophy, you can get enlargement of the ventricles as well as subarachnoid spaces, this is referred to as ex-vacuole dilation If an unfortunate patient with significant cerebral atrophy do develop hydrocephalus, it will mask the atrophy by the cerebral swelling.

Are you referring to the case study of the 3rd CN or 4th. The 3rd CN had a lesion in the ventral medial pons. The pictures that I showed at 33:52 for the trochlear nerve should have had a lesion on the left dorsal midbrain at the level of the inferior colliculus if you wanted to place the lesion in the midbrain (remember, Trochlear nerve is the only one that exists dorsally and decussates to the opposite side)

Yes, is the simple answer to the question. It does become much more complicated esp when we delve into the brain architecture. This has a lot to do with the way in which association fibers cross each other. A lot of people actually have crossed language centers where the language areas are situated in both hemispheres, this typically occurs when you are multilingual. In these cases, the second language typically sits in the non-dominant lobe. So what do you think will happen in these patients when you have a dominant lobe stroke when you have a non-dominant lobe second language center? There is also a phenomenon called diaschisis which was first coined more than a 100 years ago by von Monakow. Where gradually over time afferent neurons acquire inputs from numerous sources in the brain as a result of synaptic modification. In other words, the neurons start to act like mirrors to each other. So information that was initially covered by one neuron, can be projected over to another. So when a neuron becomes injured, its information can be projected by its mirror neurons. Therefore, language can, henceforth, have many "back-up" areas in the brain.

The seat for near reflex is situated in the midbrain. In a deafferented pupil, only the optic nerves are affected, in other words, no light is coming from the afferent's side, therefore it won't trigger and efferent response (pupillary constriction). all of the somatic motor functioning as well as visceral motor function in the midbrain is still preserved though e.g. if the near reflex is tested, the pupils will still constrict

Strokes are typically very hyper-acute; defined as being: Acute focal neurological with maximum intensity on onset , with a vascular etiology resulting in damage to the brain, spinal cord or optic nerves. The clue here is maximum intensity from the time of onset, demyelinating conditions also have an acute onset, but typically evolving hours to days, but not the typical hyper-acute, seconds in onset picture. Either case, a further work-up in both cases are warranted characterized by MRI and possible LP

Yes you are correct. The ipsilateral part is due to the lesion sitting in the MLF ipsilateral to the lesion in the brainstem. 52:21 shows the picture nicely (lightning strike is the lesion). therefore the 3rd CN nerve won't know that the 6th CN nerve is working therefore it won't adduct, but the 6th CN nerve will be the one that is still doing all of the work - abduction, but the 6th CN will now be on the opposite side of the lesion.

If you recall the picture at 1:00:00, you can see the spinal nucleus carries general somatic afferent input fibers from the ipsilateral part of the face. They haven't crossed over, to the trigeminothalamic tract that runs on the opposite side of the brainstem, yet. Therefore you will knock out the fibers on the ipsilateral side of the face, but also the contralateral spinothalamic fibers on the opposite side of the body (remember the spinothalamic tracts already decussated at the level of the spinal cord), these fibers run just next to the spinal nucleus in the medulla coming in from the opposite side of the body, hence a checkerboard fallout of sensation will occur.

There are no ascending, or afferent tracts, responsible for spatial recognition. Remember what I mentioned. You have, to have intact afferent fibres, to be able to assess higher functioning. The definition in visuospatial disorders stipulate that an agnosia is a disorder in recognizing sensory stimuli despite having intact sensation. So higher functioning (e.g Visuospatial recognition) should rather be seen as, interpreting centres, for touch, vision, hearing as well as speech, reasoning, emotions, learning and learned motor behaviours. In other words it refers to conscious mental activity, such as thinking, remembering, and reasoning that arise from our lower processing input pathways e.g. spinothalamic tracts. An analogy: Seeing a spider, or feeling a spider crawling on your skin is merely afferent input signals arising from your Pacinian corpuscles in the dermis transmitted via the afferent pathways to reach the brain. If you have an associated higher mental activity related to spiders: eg it is a spider crawling on you, a spider is an arachnid, if they bite you, then you will die. You might even have a friend that was bitten by a spider, and they died (these are all higher input functioning governing what a spider is, looks like, feels and consequences of a spider when it bites you) - and then in that instant, you will be tempted to react and slap the spider from your arm. If you a problem in the sensory pathway e.g. peripheral neuropathy where you cannot feel the spider, none of the higher functioning will take place.

In most cases the patients are completely unware of that side of their visuospatial area. They are definitely NOT confused. To use an analogy: similar to Schrödinger can theory which states that if you place a cat and something that could kill the cat (a radioactive atom) in a box and sealed it, you would not know if the cat was dead or alive until you opened the box, so until the box was opened, the cat was (in a sense) both "dead and alive". This is similar to what a patient with visuospatial neglect have. They are unware of that side of their body, until you make them aware of that side.

The seat for near reflex is situated in the midbrain. In a deafferented pupil, only the optic nerves are affected, in other words, no light is coming from the afferent's side, therefore it won't trigger and efferent response (pupillary constriction). all of the somatic motor functioning as well as visceral motor function in the midbrain is still preserved though e.g. if the near reflex is tested, the pupils will still constrict

That is correct, NE re-uptake gets blocked therefore causing the dilated pupil eg sympathetic response

So speech content is the subject and the ideas expressed in it. In other words, they talk a lot - more than 100words / minute, have a lot of paraphasia's, coin their own words, creating new words - also known as a word salad. - but the ideas expressed in the content of their language is empty; it is merely just jargon.

Cranial nerves always have ipsilateral fallout (except for the pesky trochlear nerve), therefore if you have a patient with cranial nerve dysfunction you have to think the dysfunction is ipsilateral to the nucleus, fascicle or nerve itself. So if the patient has ipsilateral facial weakness but opposite arm and leg weakness then the lesion has to be in the pons because you have that checker-board pattern (ipsilateral face, contralateral body)