 Okay, our next case is a 58-year-old female with speech disturbance, forgetfulness, malaise, and fatigue. Let's focus on the speech disturbance for a moment. We are looking for an infarct in the speech area. More often in the left temporal region, see none on the flare. Although there are scattered areas of periventricular white matter disease, not uncommon in middle-aged adults, probably a few more volumetrically than we would expect, but not a macro-infarction. On the coronal T2 water-weighted image, you might have noticed that the left temporal horn is a little larger than the right temporal horn, and for age 58 there is generalized atrophy. Let's go back over to the axial flare image and look at the prominence of the sulci of the olfactory gyri and orbitofrontal gyri. Now let's take on our questions with that information. The most conspicuous finding on the MR study is A. unilateral valerian degeneration B. asymmetric hippocampo and cerebral atrophy C. unilateral infarction D. white matter gliosis E. cerebellar atrophy And if you said, as we clued you in and pointed out, that it's asymmetric hippocampal and cerebral atrophy, that being on the left greater than right, you would be correct. We didn't find a unilateral infarction. We didn't find any large areas of confluent gliosis, although there was some scattered ones. And in terms of the cerebellum, there really wasn't much cerebellar atrophy at all. Let's look at the sagittal midline cut to reaffirm that. Indeed, there's very little to know cerebellar atrophy. Let's go on to the next question. Given the history, the most likely diagnosis is A. amyloid angiopathy B. vascular dementia C. multi-system atrophy D. semantic dementia and E. wernicke's encephalopathy. Well, in amyloid angiopathy you expect to see a bleed within a bleed or multiple foci of hemorrhage or ciderosis, we see none. Vascular dementia, you would expect either multiple infarcts or more severe gliosis. Multi-system atrophy is not associated with the initiation of a speech disturbance. Wernicke's encephalopathy usually has a history of alcohol use. The patients may have seizures and the mammillary body may be hemorrhagic or severely atrophic. I must admit this mammillary body is small. Let's blow it up. But it is not hemorrhagic. Wernicke's encephalopathy may be associated with bilateral basal ganglia and more frequently bilateral thalamic hyperintensities, not present here. The history also doesn't support the diagnosis. Wernicke's is a more acute phenomenon. So the most likely diagnosis is semantic dementia. We're going to go through that in a few minutes, but most likely is a variant of Alzheimer's disease with a left-sided cerebral predominance affecting the entorhinal cortex and the temporal lobes, as in this case, left greater than right. More on that in a few moments. Let's go to question number three. Anterior but not posterior hippocampal atrophy is typical of A, dementia with Lewy bodies. B, frontotemporal lobar dementia. C, ALZ or Alzheimer's disease. D, mild cognitive impairment syndrome. E, Parkinsonian dementia. First, dementia with Lewy bodies. The pattern of atrophy in this disorder is very nonspecific. Although it's said bilateral putaminal involvement or signal alteration suggests the diagnosis. Lewy body patients have visual hallucinations, not present here. Frontotemporal lobar dementia does have an anterior hippocampal pattern of atrophy, and that is the correct answer. Whereas Alzheimer's disease has a more temporal parietal pattern of atrophy, but also involves the hippocampus and entorhinal cortex. Mild cognitive impairment syndrome should have little to no atrophy and the patient certainly should be able to speak. That's why it's mild. And Parkinsonian dementia has a diffuse pattern of atrophy, but one should see the typical changes in iron distribution in the brainstem, where the substantia nigra is almost inseparable from the adjacent red nucleus. They essentially bleed together as one structure. Let's go to question number four. All of the following are associated with extreme hippocampal atrophy, except A, a gyrophilic grain disease. That's right, grain disease. B, frontotemporal lobar dementia. C, semantic dementia. D, tau mutation abnormalities. E, Huntington's disease. Well, the answer to this question, the one that is not associated with extreme, although there is some hippocampal atrophy, is Huntington's disease. We're going to get into the tautopathy just briefly at the end, so I won't touch on that now. Semantic dementia may well be a variant of Alzheimer's disease. So Alzheimer's disease typically involves the hippocampus, so does semantic dementia, although left greater than right, PICS disease or frontotemporal lobar dementia involves the enterinal cortex, but more anterior than posterior, and you'll see that these areas are involved in a gyrophilic grain disease as well, and we'll explain what that disorder is. So just a few words about this case. Three important primary neurodegenerative dementias include Alzheimer's disease or ALZ, Lewy body dementia or LBD, and frontotemporal degeneration, PICS disease, which goes under various other names as well. Let's talk about PICS disease or frontotemporal lobar dementia. It's associated with atrophy of the frontal and anterior temporal lobes, but the posterior aspect of the second temporal gyrus and parietal lobes are typically spared. Therefore ventricular enlargement is prominent in the frontal and temporal regions. These patients may develop what's known as PICS bodies. Atrophy is asymmetric in 60% of patients, so there may be some visual overlap with the condition known as semantic dementia to be discussed. Because this is a frontal lobe disorder, the patients often have loss of their inhibitions. They may behave very aggressively. They may eat their dinner at the dinner table with their feet. They may demonstrate dis-executive syndrome. They may exhibit frontal lobe signs such as sucking. The onset of aphasia and behavioral disturbance occurring around 60 years of age is a little earlier than you typically see with Alzheimer's, which is somewhere in the 65 to 75-year-old age range. As far as aphasia goes, there are two types of progressive aphasia. There's non-fluent progressive aphasia and there is fluent progressive aphasia, also known as semantic aphasia. Let's talk about semantic aphasia. This falls within the clinical spectrum of frontal temporal dementia and a newer entity called semantic aphasia with dementia. It's a syndrome of progressive deterioration in semantic memory. What's semantic memory? It's the knowledge of objects, people, concepts, and words, resulting in the inability to name objects, impaired comprehension, and speech that is fluent but empty of content, so-called gobbledygook. In other words, it's the kind of speech you see coming out of U.S. Congress. In the latter stages, the patients may develop other behavioral and cognitive disorders. In CT and MR, the atrophy is seen in the perisilvian region of the frontal and temporal region, and abnormalities are asymmetric, more severe on the left side, and here we have that left-sided severity. A little prominence of the sulcus here in the inferior temporal region, prominence of the silvian fissure, and then we go back to the temporal horn, which is more dilated on the left than the right. Diffusion on nuclear medicine and other studies is reduced in the left side of the head in patients with semantic aphasia with dementia. Lewy body dementia, or LBD, presents with extra-paraminal symptoms, thus the explanation in part for the putamenal involvement, which is not seen in many of these other conditions. They have fluctuating cognitive deficit, and it's often considered a disease of Parkinson's syndrome with visual hallucinations. When those two go together, LBD should be your first choice. Depression and agitation are common. The differential diagnosis visually on the imaging from Alzheimer's disease is crucial, but very difficult, because anti-psychotic medications, anti-dopaminergic and anti-cholinergic neuroleptic therapies that are used for the treatment of dementia associated with psychosis may lead to irreversible extra-paraminal symptoms in the Lewy body dementia patient. So in other words, you can give them a permanent movement disorder and make them worse, which is a tragedy. The MR features for Lewy body dementia, once again, are not specific. You really must have that clinical information of visual, more common, then auditory hallucinations. But if you have bilateral putamenal involvement, that's a tip-off. Huntington's disease or Huntington's career major. That wasn't one of our main dementias we started with, but it is inherited as an autosomal dominant, and there are sporadic forms. It occurs in mid-adulthood, but the more severe the genetic abnormality in the imprint of the cytosine, adenosine, guanine repeats the earlier the onset. So you can genetically plan when this disease is going to come on. It's one of the most common hereditary neurodegenerative diseases and demonstrates a progressive course, unfortunately leading to death within 10 years. Genetic testing is now readily available. The progressive movement disorder, usually not pure Korea, but rather choreoathetosis, involves the entire musculature and is followed eventually by cognitive deficit, agitation and dementia. Psychiatric disorders such as depression and psychosis may precede the development of Korea and produce a profound quagmire of a diagnosis. In other words, the patients are treated as somebody that has an emotional or mental issue rather than one that is genetic and neurodegenerative in character. Atrophy of the head of the caudate and putamina, even necrosis of these two, with holes in each demonstrating increased relaxivity, can occur with this disease. The caudate atrophy allows the frontal horns to bow out and they appear somewhat box-like and more rounded in shape. We'll see later on that the white matter is normal, but the gray matter around the apriculum is fuzzy, ill-defined and thin. Sometimes the paracentral, lobular and hypothalamus are involved. The atrophy is more pronounced in the frontal lobes and while the enterital cortex can be involved, it is nominal to mild in severity. As an aside, in case you are wondering, and maybe you weren't, a gyrophilic-grain disease of old age is a tauopathy with Alzheimer's disease, progressive super nuclear palsy, corticobasal degeneration, and frontal temporal dementia, all examples of tauopathies. A gyrophilic-grain disease is associated with severe atrophy in the enterinal cortex, the hippocampus, and the amygdala, which is true for all of these tauopathy disorders mentioned. By the way, you have tauopathies and you'll hear now and later on that there are syn-nucleinopathies. This refers to impairment of the alpha-syn-nuclein metabolism and includes multi-system atrophy, already discussed, and LBD, Lewy body dementia. Thanks, this concludes our discussion of a difficult neurodegenerative case, semantic aphasia with dementia, in which there is asymmetric atrophy, especially in the frontal region, especially in the enterinal cortex, left greater than right, rendering this patient speechless. Eventually, this inability to speak turns into a full-blown dementia. Let's take a look at the next case, shall we?