CASE 32-1
A 64-year-old man presented with rapidly progressive, subacute, nonfluctuating dementia, and recurrent unprovoked falls. He had been well 8 months previously. At that point, the family noted the onset of apathy and problems with sleep. Two months later, the patient was noted to have problems with balance and gait, and had a number of unprovoked falls with gait unsteadiness and “dizziness.” He then developed jerky movements, especially in the arms. In the ensuing months, he had worsening disorientation and cognitive decline. He started having difficulties with recognizing relatives. He became withdrawn, akinetic, and mute. He was conscious, but did not have any meaningful reactions to voice commands.
Rapidly progressive progressive dementia (RPD) is a clinical diagnosis that has the following characteristics:
Rapidly progressive dementia (RPD) refers to a dementing process that develops over a period of less than 2 years.1
RPDs are a category of disease processes characterized by being diagnostic conundrums at presentation.
There are certain characteristics that are common but not universal in RPDs:
Rapid progression of cognitive decline
Presence of movement disorders, in particular ataxia, gait disorders, or myoclonus
Concomitant behavioral or psychiatric symptoms
Epileptiform or periodic waveforms on EEG
In the aforementioned vignette, the time course, the presence of ataxia, gait problems, myoclonus, and akinetic mutism point the clinician toward a diagnosis of RPD.
Many conditions presenting as RPD are associated with high levels of morbidity and mortality. Early recognition allows prognostication and gives the family time to plan for eventualities.
Some of these conditions are treatable if detected early.
The general approach to evaluating these patients is different in RPDs and chronic dementias.
A study conducted at the University of California San Francisco (UCSF) evaluated 178 patients with RPD and found 62% to be due to prion diseases. Of the remaining cases, 39% were neurodegenerative, 22% were autoimmune, 6% were infectious, another 6% were psychiatric, 14% were due to other causes, and 12% did not have a definitive diagnosis. It is likely that these data reflect a referral bias to UCSF given its reputation in the field of prion disease.2
In other tertiary settings, prion diseases may contribute less to the overall case mix. For example, a study of 68 consecutive patients referred for RPD to an Athens clinic consisted of 21 patients with neurodegenerative dementias (AD followed by frontotemporal dementias and Lewy body disease), 9 with vascular dementia, another 9 with Creutzfeldt-Jakob disease (CJD), 4 people with normal-pressure hydrocephalus (NPH) (Figure 32-1), 4 with infections (syphilis, HIV, and Q fever), 3 with auto-immune problems (multiple sclerosis, limbic encephalitis, and scleroderma), 2 with toxic-metabolic causes (B12 deficiency, drugs), and the last two with psychiatric and illicit drug-related causes.3
In non-tertiary settings, some of the referred patients may have delirium on a background of dementia, which can cause a rapid decline in their cognitive and functional status and thus be mistaken for RPD.
The semiology of subacute delirium resembles that of RPD. In both cases, fluctuations may occur in the course of the disease, there may be changes in circadian rhythms, tremors and myoclonus may occur, and there are often behavioral changes complete with hallucinations. Hypervigilance and sympathetic arousal seem to be more common in subacute delirium, and it is more likely for a delirious patient to reverse their night-day cycle completely, but even this is unreliable for making definite distinctions between the two entities.4
Given these vagaries, screening for common causes of delirium (“I WATCH DEATH”) should be part of the workup for RPDs. The depth of inquiry and testing should depend on the premorbid risk of delirium.
A patient may reasonably be considered to have an increased risk of delirium if he/she has one of the following:
Age >60 years
History of baseline cognitive impairment
Malnutrition or dehydration
Psychiatric comorbidities, especially depression, chronic psychosis, and/or substance abuse
Medical conditions, especially organ failure and hyponatremia.5
The causes of acute delirium and subacute delirium are largely identical. Attention should be paid not to miss the following causes of subacute delirium:
Sleep: Sleep disorders including obstructive sleep apnea (OSA), periodic limb movement of sleep (PLMS), restless leg syndrome (RLS), and sleep deprivation may present with a rapid decline in cognition, especially in the elderly.
Medications: Anticholinergic and psychoactive drugs may cause confusion and cognitive decline.
Depression: This condition is the leading cause of pseudo-dementia. As such we recommend screening for depression with Geriatric Depression Scale for elderly patients who present with a “hypoactive” form of cognitive decline.
Unmasking of cognitive deficits: Sometimes the seemingly rapid decline in cognition is merely the unmasking of pre-existing cognitive deficiencies. For example, a widower may now be unable to function properly because their late spouse was doing all their finances and so on.6
The approach will depend on three sets of factors:
Disease factors: The rapidity of progression will affect the approach to the patient. With a particularly rapid progressive course, one might eschew the stepped approach and do all the testing at once and gamble with empiric treatments.
Physician factors: With clinical experience, approach to diseases becomes less systematic and reliance on pattern recognition increases. A neurologist who has extensive experience with limbic encephalitis, for example, may elect a more limited approach to a patient with a highly suggestive presentation.
Patient factors: The wishes of the patient and their willingness to bear the burden of testing are also determining factors in the approach.
So, for example, a rapid course in a young patient who, we surmise, might want an aggressive approach to investigation might prompt one to order all required testing at the outset, with empiric therapies being started based on clinical risk and suspicion. On the other hand, an Alzheimer-like presentation in an older patient, with significant comorbidities and a living will consistent with a more gentle approach, may prompt an experienced physician to take a more conservative approach.
Laboratory studies:2
Blood, urine, and stool: CMP, blood osmolality, serum glucose, B12, folate, thyroid function test, antithyroglobulin, antithyroid peroxidase antibodies, CBC, PT (INR), ANA, ESR, CRP, ACE, blood cultures, urinalysis, syphilis serology, HIV, Lyme, urine drug screen, ABG, LDH, fecal occult blood testing, PSA, and paraneoplastic panel should be included.
CSF studies: Large volumes would be needed—Cell count, protein, lactate, glucose, oligoclonal bands, IgG index, 14-3-3 protein, bacterial, fungal, and AFB cultures, Whipple disease testing, VDRL, viral PCR and antibodies (CMV, JC, HSV, West Nile disease, and HHV-6), cytology, flow cytometry, beta-amyloid, and phosphorylated tau should be sent; 5–10 mL of CSF should be frozen and set aside.
Imaging:
Chest x-ray—Look for neoplastic and granulomatous disease.
MRI—As to reduce the number of times the patient needs to be sedated, we recommend MRI with and without contrast of the brain, as well as MRA and MRS done during the same session.
EEG:
Look for focal and generalized slowing. A number of RPDs are associated with rhythmic patterns including frontal intermittent rhythmic delta activity (FIRDA), temporal intermittent rhythmic delta activity (TIRDA), and periodic sharp waves.
“De novo” absence status of the elderly may present with bifrontal rhythmic activity and is associated with withdrawal of medications.
The EEG during sleep may also be useful. In frontotemporal dementia, the amount of deep sleep is reduced greatly. In corticobasal degeneration and Huntington’s disease, there is an increased risk of periodic limb movement of sleep.
If a patient was suspected of having an atypical presentation of a neurodegenerative disease, what additional tests may be considered?
A detailed neuropsychological assessment may be useful in cases of suspected neurodegenerative disorder, but often the patient may not have the minimum set of cognitive skills to participate in the testing if RPD is suspected. The use of brain PET or SPECT can also provide additional information that can then be correlated with the neuropsychological testing to see if the overall picture fits a particular neurodegenerative condition. In selected individuals with a family history of degenerative disease, genetic testing can also be of use.
If the result of a test in the paraneoplastic panel is positive, which additional testing is recommended?
If there is evidence of a paraneoplastic syndrome, then a concerted effort to find a possible malignancy should be made. The workup typically will include contrasted CT of chest, abdomen and pelvis, tumor markers (AFP, HCG, Ca15-3, Ca125, CEA, Ca19-9, PSA, and others depending on suspicion), and stool occult blood test as a basic workup for malignancy. Then, depending on the type of autoantibodies, further testing such as mammography, transrectal ultrasound, or endoscopy may be performed. If no malignancy is found then a whole-body PET scan, which has a high negative predictive value, should be used as a final confirmatory test.
For patients with paraneoplastic antibodies in whom no cancer is found, periodic surveillance with nuclear or radiological imaging should be performed. The time interval between episodes of surveillance should be determined in consultation with the oncologist and depends on the suspected origin of the carcinoma, but is commonly yearly for a period of 5 years.7
If the MRI imaging during the workup shows extensive white matter disease, what additional testing may be considered?
When widespread white matter disease is present, a subset of the following may be appropriate based on clinical suspicion: urine sulfatide levels, serum very long chain fatty acids, galactosylceramide beta-galactosidase (GALC) activity, multiple sclerosis workup (contrasted MRI, lumbar puncture for oligoclonal bands and evoked potentials as needed), and NOTCH-3 genetic testing.8
If the MRI imaging during the workup shows signal change in the basal ganglia, what conditions should be considered?
Bilateral changes to the basal ganglia should alert the clinician to the possibility of carbon monoxide, cyanide, hydrogen sulfide, toluene, or disulfiram toxicity. Accumulation of divalent cations can similarly cause signal changes in the basal ganglia, examples including iron (PKAN), copper (Wilson disease), manganese, and calcium (Fahr disease and pseudohypoparathyroidism). Atrophy of the head of the caudate nucleus can point toward Huntington’s disease.9–11
24-hour urine for heavy metals and porphyrins.
Cerebral angiogram—mainly to rule out vasculitis or multiple intercranial dural arteriovenous fistulas (DAVFs).
These are ultimately tests with low yield that may be considered in selected cases.
The ultimate tool of diagnosis is, in fact, brain biopsy. Brain biopsy should be performed if diagnosis cannot be made by less invasive techniques and especially if there are potentially treatable causes of dementia being considered.12
CASE 32-1 (continued)
The patient was admitted to hospital for further investigations of RPD. Routine blood tests, vasculitic, autoimmune, tumor marker, drug screen, and serologies were negative. The CSF sample was found to have normal protein and glucose content, and a cell count of 5/microliter, mostly monocytes. The 14-3-3 was reported as positive. Other microbiological studies on the CSF were negative.
Figure 32-2 represents our algorithm for an overall diagnostic approach to RPD. The initial workup was not consistent with delirium or a paraneoplastic syndrome. Clinically, the presentation resembled sporadic CJD and not vCJD. At this advanced stage of dementia, neuropsychological assessment was not practical and it was thought a PET scan was unlikely to be of diagnostic utility. The EEG and the MRI were typical for prion disease, and the CSF results were consistent with this diagnosis. A brain biopsy was performed at the request of the family, which showed spongiform encephalopathy, confirming the diagnosis of sporadic Creutzfeldt-Jacob disease.
Some of the common presentations of RPDs, for the purposes of simplification, are as follows:
Prion-like presentation—In addition to rapid dementia, this presentation is associated with psychiatric comorbidities including hallucination or apathy, EEG changes, myoclonus, and sometimes motor, extrapyramidal, or cerebellar signs. With this presentation, the most likely diagnosis is prion disease, especially sporadic CJD. When classic neurodegenerative diseases present with rapid decline, they can be accompanied by behavioral issues, myoclonus, and pyramidal and extra-pyramidal symptoms, and thus be mistaken for prion disease. With rapidly progressive Alzheimer disease, the risk of epileptiform activity is increased, which can resemble periodic discharges. Less commonly, a patient may present with subacute sclerosing panencephalitis (SSPE) or delayed rubella infection, which is also associated with myoclonus, pyramidal signs, and RPD. The EEG is characterized by bursts every 3–20 seconds.
Limbic encephalitis-like presentation—Limbic encephalitis presents with amnesia, confusion, psychiatric disorders, and seizures. There are often MRI signal changes in mesial temporal lobes, and EEG shows temporal epileptiform discharges. Classically limbic encephalitis is caused by paraneoplastic diseases. Paraneoplastic syndromes can also include neuropathies and some degree of encephalomyelitis. There are two kinds of “paraneoplastic” syndromes: one type (classic paraneoplastic syndromes) is almost always due to coexistence of malignancy, with autoantibodies directed toward intracellular antigens, and has poor prognosis. The other is idiopathic in about half the cases, with autoantibodies against surface antigens, and has a relatively good prognosis if treated aggressively with immunosuppressants. Steroid-sensitive encephalopathies, of which Hashimoto encephalopathy is a prototype, can be treated with steroids alone. Two other conditions can have a similar presentation, at least initially: herpes simplex encephalitis, which quickly escalates to become a severe encephalitis, and partial complex status epilepticus.
Rapidly progressive or fulminant white matter disease—Genetic, infectious, vascular, and autoimmune causes may cause extensive white matter dysfunction and pathology. These commonly present with a subcortical dementia, sometime also affecting the long tracts. The presence of white matter disease is somewhat obvious after the initial investigations, which include an MRI of the brain.
What are some potentially reversible causes of RPD, and how do they present? How are these different from the causes of subacute delirium?
Causes of delirium do not often cause significant damage to the brain unless complications occur. For example, low-serum sodium or hepatic encephalopathy, if treated well and in a timely manner, will likely lead to full recovery, if the underlying causes of delirium are removed. The causes of subacute delirium affect the central nervous system (CNS) indirectly through their influence on circulation, hormonal, and cytokine milieu. The “potentially reversible” causes of RPD damage the brain tissue directly. The resulting deficits may not be reversed if the treatment is delayed. As such potentially reversible causes of RPD stand in a separate class in diagnostic logic.
Chronic meningitis: Chronic meningitis may occur due to infectious agents, neoplasm, or autoimmune causes. The presentation is often stereotypical with rapidly progressive dementia, chronic headache, neck or back pain, cranial neuropathies, and possible hydrocephalus. These are often difficult to diagnose and require quite extensive workup when suspected.
Subacute encephalitis: These are often more rapidly progressive than chronic meningitides. They may rarely present similar in tempo to chronic meningitides, in which case cranial neuropathies and hydrocephalus are rarer. Focal neurological signs are seen in the context of strokes caused by viral encephalitis. The two categories may often be distinguished based on their CSF profile.
Intracranial malignancies: These have two modes of presentation: as space-occupying lesions or as malignant meningitides. In the latter case, the symptoms are similar to chronic meningitides.
Nutritional deficiency: Several classic neurological conditions are caused by vitamin B deficiencies. Typically an encephalopathy may be accompanied by dysfunction of other systems such hemopoietic, integumentary, gastrointestinal, or cardiovascular.
Heavy metal toxicity: Heavy metal toxicity (such as lead or arsenic) is associated with cognitive changes, peripheral neuropathy, and abdominal pain. Toxicity caused by divalent cations (copper in Wilson’s disease or calcium in Fahr disease) causes neuropsychiatric problems, a subcortical dementia, and extrapyramidal symptoms.
Systemic autoimmune conditions: These are extremely rare causes of RPDs.
What is the pathophysiology of CJD and vCJD?
Prions are misfolded proteins PrPsc (derived from normal cell surface proteins PrPc), which are infectious and cause degeneration of the CNS.
Approximately what proportion of CJD is familial or due to vCJD?
85% of cases are sporadic where there is either an in vivo mutation or spontaneous conversion of PrPc to PrPsc.
15% are familial and inherited in an autosomal dominant manner.
A small minority is variant CJD, also known as bovine spongiform encephalopathy.
What are the risk factors for CJD and vCJD, respectively?
Age: Most cases are sporadic where age is the only risk factor.
Classic CJD presents between the ages of 50 and 70 years, but it is seen even in teenagers and octogenarians.
Variant CJD presents in teenagers and young adults.
Exposure:
Classic CJD was transmitted traditionally by hormones and tissue transplantation from cadaveric sources. There are also reports of transmission via surgical instrumentation.
Variant CJD is associated with consumption of tainted meat from meat supply contaminated with bovine spongiform encephalopathy.
Heredity:
There are familial forms of CJD transmitted by PRNP gene on chromosome 20. The most common mutation is E200K.
The polymorphism on codon 129 on the PRNP gene, which codes for either methionine (M) or valine (V), can be of clinical significance: 90% sCJD are MM or VV. 100% with vCJD are MM. MM also increases the risk for iatrogenic CJD.
Codon 129 also interacts with other mutations; for example, D178N with V on codon 129 causes a CJD phenotype whereas, when present alongside M, it causes fatal familial insomnia.
What are the classic phases of CJD progression? How does CJD present?
Incubation:
An incubation period of 1.5–2 years has been postulated; however, there are case reports with presumed incubation periods of up to 40 years.
Prodrome:
Prodrome is seen in a third of all cases: fatigue, sleep disturbance, weight changes, anxiety, vague pain, and dizziness.
Presentation:
In classic CJD, the symptoms are dementia (deficits in all cognitive modalities including executive and memory functions) plus 2 of the following:
Myoclonus
Visual or cerebellar symptoms—once cerebellar symptoms appear, the rate of cognitive decline is often increased.
Upper motor neuron or extrapyramidal signs
Akinetic mutism
The presence of dementia and two of the aforementioned symptoms is designated possible CJD by the WHO diagnostic criteria if no other explanations for the symptoms exist. It is designated probable CJD if the results of testing on CSF, EEG, or MRI are consistent with CJD. Definite CJD is a tissue diagnosis.
How does vCJD present? Are there other common clinical presentations of CJD?
In variant CJD, the presenting symptoms are psychiatric, which may predate the other symptoms by a few months. Dementia, extrapyramidal, and cerebellar signs are often present. There is also the characteristic absence of myoclonus and the presence of dysesthesias.
Clinical variants, based on additional early signs, include:
Heidenhain variant: cortical blindness
Amyotrophic variant: LMN signs
Brownell-Oppenheimer variant: ataxia
Stern-Garcia variant: extrapyramidal
What are the CSF findings in CJD? When should 14-3-3 be used in aid of diagnosis?
The CSF shows normal routine tests except for occasional mild pleocytosis.
14-3-3 is a nonspecific marker of neuronal damage, which is raised in CJD. The recent AAN guideline suggests that it should only be used in cases where the pretest probability is neither too high nor too low.17
What are the EEG findings in CJD?
Periodic sharp wave discharges (PSWD) are seen in classic CJD. These are periodic discharges with a frequency of 1–1.5 Hz, which disappear during sleep. They are also rarely seen in vCJD.
Giant spikes waves are seen with photic stimulation, which suppresses PSWD.
FIRDA appears when the patient is akinetic mute.
What are the imaging signatures of CJD and vCJD?
MRI is an essential part of making the diagnosis of prion disease. The main changes occur in the gray matter. When affecting the cortex, there is restriction on high-b-value DWI. This is termed ribboning. In addition, there is involvement of the deep gray matter.
In classic CJD, there is restriction in basal ganglia, thalamus, and cortex (see Figure 32-3).
In variant CJD, there is restriction of posterior thalamus (pulvinar sign) and the dorsomedial thalamus in an arch resembling a hockey stick (hockey stick sign).
Are there any effective treatments for CJD?
There are no treatments proven to slow the progression of CJD in vivo. Great care should be taken not to reuse equipment used on patients with suspected CJD. If utensils are to be reused, then they need to be sterilized by heating at a high temperature or sterilizing with high concentrations of sodium hydroxide.
What is the role of brain biopsy in the diagnosis of CJD?
Brain tissue is obtained by biopsy. The diagnosis of classic CJD is made in the presence of typical histopathological changes of spongiform encephalopathy and staining for the prion protein on immunohistochemistry. The presence of scrapie-associated fibrils on electron microscopy in the synaptosome and the Western blot confirmation of protease resistance PrP are diagnostic. An alternative source of tissue for the diagnosis of vCJD is the pharyngeal tonsil.
What is the prognosis of CJD?
Classic CJD is fatal within 6 months of the onset of symptoms.
Variant CJD is fatal within 1–2 years.
What are some of the other prion diseases?
Gerstmann-Straussler-Scheinker disease
This is an autosomal dominant (AD) condition presenting at around 40 years of age and is associated with dementia and ataxia but not myoclonus. It progresses to death in 2–10 years. There are four clinical subtypes based on the mutation in PRNP gene: ataxic, telencephalic, progressive spastic paraparesis, and slowly progressive dementia (called slow because it may take as long as 20 years before death).
Fatal familial insomnia:
This condition may be sporadic or hereditary. It causes insomnia and delirium characterized by overactive sympathetic nervous system. It is fatal within 1–2 years.
Originally prion diseases were erroneously thought to be “slow virus diseases” because of the similarity of presentation between prion disease and a number of diseases due to reactivation of viruses in the brain. The archetypic slow virus disease is SSPE, which, due to increased rates of vaccination, is now exceedingly rare but does occasionally present in the clinic.
What is SSPE?
This is an invariably fatal neurodegenerative condition related to measles infection, which presents some 7–10 years after the episode of natural infection often before the age of two. The risk of SSPE after vaccination is lower by an order of magnitude. SSPE rates have declined with the introduction of vaccination but may make a comeback due to return of the culture of nonvaccination in the United States.
How does SSPE present?
Four clinical stages have been described:
Stage I: There is a prodromal phase of weeks to years where nonspecific behavioral and learning difficulties may manifest.
Stage II: In this stage, the patient presents with myoclonus, RPD, and pyramidal symptoms, which may last up to a year.
Stage III: There is flaccidity, decorticate rigidity, and autonomic failure.
Stage IV: Persistent vegetative state.
Are there any useful laboratory tests in the diagnosis of SSPE?
Not really; measles serology shows previous exposure or vaccination.
What are some of the EEG findings in SSPE?
The EEG findings from later stage II are characteristic. There are high-voltage bursts every 3–20 seconds corresponding to myoclonic jerks, which disappear with sleep.
What is seen on the MRI in SSPE?
Findings are relatively nonspecific. In the acute stage, there are hyperintensities on T2 imaging, especially in the parietal and temporal lobes. In the chronic stage, there is generalized atrophy and involvement of the deep gray matter.
Are there effective treatments for SSPE?
Treatments have not been shown to be useful in SSPE.
Can other viruses cause similar presentation?
Delayed rubella encephalitis is similar to SSPE, but the rubella virus appears to be the etiologic factor.
The diagnosis, treatment, and approach to these conditions have been discussed elsewhere in the book. We will reiterate some facts as they pertain to RPDs. In atypical presentations of neurodegenerative diseases, EEG and neuroimaging play a greater role in the diagnosis of such conditions. As a rule, the CSF and laboratory findings are normal in these conditions, the exception being CSF finding of low Aβ42 and increased phosphorylated tau in Alzheimer disease. The presentation of neurodegenerative disease as RPD is very atypical, but given the much greater prevalence of these conditions compared to some of the other causes, in most series neurodegenerative causes are among the leading differentials of rapidly progressive dementia.
How can FTD mimic prion disease?
There are a number of reasons why FTD, especially FTD-ALS, may be a mimic for prion disease.
First, changes in behavior are relatively early in the course of the disease and, at times, the progression of dementia may be relatively rapid or may be unmasked by changing circumstances.
Second, there are associated pyramidal, gait abnormalities, and myoclonus, which are also seen in prion diseases.
What are the EEG findings in FTD?
Waking EEG is often not very helpful in FTD, but a sleep EEG or a sleep study may show a significant reduction in stage III sleep and, to a lesser extent, REM sleep. Overall, there is fragmentation of sleep.
How can imaging help distinguish between FTD and other causes of RPD?
Atrophy is found predominantly in the frontal lobes and anterior aspects of the temporal lobes. In severe cases of atrophy, there is the “knife edge sign” where the temporal poles look like knife blades (see chapter on dementias).
How does CBD mimic prion disease?
Corticobasal degeneration is associated with dementia and loss of cortical functions, most notably praxis. Myoclonus is common, as are parkinsonian symptoms.
How can EEG help with the diagnosis of CBD?
The findings are relatively nonspecific. Early in the disease, there is slowing and FIRDAs. Periodic leg movement and restless leg are also very common in this condition.
What are the imaging findings in CBD?
CBD is associated with the atrophy of the caudate nucleus, the putamen, premotor, and superior parietal gyri (see chapter on dementias).
How does PSP present as an RPD?
PSP may present with rapidly progressive dementia, gait dysfunction, and movement disorders.
What are the typical EEG findings?
Slowing and FIRDAs correlate with frontal dysfunction and appear late in the course of the disease.
What are the typical imaging findings?
PSP is classically associated with midbrain atrophy. When viewed in sagittal plane, the brainstem appears like a humming bird with the belly being the pons, the wings being the vermis, and the head being the atrophied midbrain.
In cross section, there are T2 changes in the tegmentum of the midbrain (see chapter on dementia).
How can DLBD mimic prion disease?
Lewy body disease can show rapid deterioration especially in response to ill-advised medication choices. The presence of myoclonus and extrapyramidal symptoms are not uncommon.
What are some of the common EEG findings?
There is significant early slowing of background rhythm with transient slowing in the temporal lobes corresponding to a history of loss of consciousness.
What is often seen on imaging?
There is frontal and parieto-temporal atrophy on MR imaging, but this is much less than expected from the degree of dementia.
In contrast to other neurodegenerative diseases, the MRS NAA/Cr ratio is preserved in DLB and there is usually no atrophy of the mesial temporal area.
PET scanning shows hypoperfusion in the occipital lobes.
What are some of the types of AD that may mimic prion diseases?
AD is a heterogeneous condition. Most AD presenting as RPD falls into two categories:
Early onset AD—It is sometimes associated with white matter changes, and there is less mesial temporal lobe atrophy compared with classic AD.
Rapidly progressive AD—It presents in mid-seventies; it is often fatal within 2 or 3 years and is associated with early focal neurological signs.23
What are the CSF findings in AD?
There may often be very high levels of phosphorylated tau and very low levels of Aβ1-42. 14-3-3 may also be present in the rapidly progressive type of AD.
What are the EEG findings in AD which presents as RPD?
There is increased delta and theta and reduced alpha and beta activities. There is increased epileptiform activity, and generalized slowing is best seen in the frontal lobe. This slowing is seen more in young-onset AD. Myoclonus, when seen, resembles cortical reflex myoclonus.
What can be seen on imaging?
Classically AD is associated with atrophy of the mesial temporal lobes followed by occipital and parietal lobes and ultimately the brain as a whole. However, early-onset AD has less mesial temporal atrophy compared with classic AD.
When there is concomitant amyloid angiopathy, it may be seen on susceptibility weighted imaging.
Presenilin 1, one of the causes of presenile AD, may be associated with white matter changes on FLAIR imaging.
Use of metabolic or amyloid PET may be useful but not widely available. Classically, PET scan shows hypometabolism in the parietal and temporal lobes.
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