Personality Change Flashcards
Assessing level of consciousness in a patient assesses the function of. . .
. . . the reticular activating system and ascending projections. BUT, can also indicate bilateral thalamic involvement or diffuse involvement (such as in intracranial hypertension or subdural hemorrhage)
“Lethargic” patient
Falls asleep without repeated stimulation
“Stuporous” patient
Requires vigorous and/or painful physical stimulation to be awakened
Think Prince Ivan
“Obtunded” patient
Somewhere between lethargic and stuporous
Differences between different clinical tests for attention
Note that the spelling task requires language ability and the subtraction task requires calculation, so forward and backward repetition of a string of numbers of increasing length provided by the examiner or recitation of the days of the week (or months of the year) backward may be simpler and less confounded ways of testing attention.
Even patients with the most profound deficits in memory due to neurologic conditions should never forget ___
Even patients with the most profound deficits in memory due to neurologic conditions should never forget their own names
Time course of dementia vs “rapidly progressive” dementia
Dementia is a chronic disease that develops over years
Rapidly progressive dementia develops over weeks to months
Frontal release signs (list)
- Snout reflex: the patient purses the lips when the examiner taps at the center of the lips.
- Grasp reflex: the patient cannot inhibit grasping the examiner’s hand or an object when placed into the patient’s hand.
- Suck reflex: the patient will attempt to suck any object (such as a pen) moved toward the mouth.
- Rooting reflex: lightly touching the patient’s cheek causes the patient to turn the head toward that side.
- Palmomental reflex: briskly scratching the patient’s palm causes a twitch of the ipsilateral chin.
Laboratory evaluation for dementia
- B12
- TSH
- MRI
Alzheimer’s disease
- Most common neurodegenerative cause of dementia
- Most cases sporadic, some familial
- Heritable form due to amyloid precursor protein, presenilin 1, presenilin 2 variants that predispose to amyloid plaque buildup - younger age of onset
- APP is on chromosome 21, so Down’s patients also at increased risk
- Episodic memory first and most prominently affected
- Other common traits at presentation include getting lost, decreased performance at work, and word retrieval difficulty.
*
Posterior cortical atrophy
- A variant of Alzheimer’s disease where neurodegeneration occurs specifically in parieto-occipital regions
- Leads to visual cognitive deficits, specifically Balint’s syndrome
- Can also occur with other neurodegenerative diseases, but most commonly we see it in AD.
Neuroimaging Features of Alzheimer’s Disease
- MRI in AD usually demonstrates bilateral atrophy in medial temporal regions (hippocampus and entorhinal cortex) and the superior parietal lobe
- Image: Axial MRI images showing marked bilateral hippocampal atrophy (A) and bilateral parietal more so than frontal cortical atrophy (B) in a patient with Alzheimer’s disease.
ABSEPTIC mnemonic
Entorhinal cortex
An area of the brain located in the medial temporal lobe and functions as a hub in a widespread network for memory, navigation and the perception of time. The EC is the main interface between the hippocampus and neocortex.
Laboratory Features of Alzheimer’s Disease
- In the cerebrospinal fluid (CSF), low Aβ42 and increased tau (leading to decreased Aβ42/tau ratio) can predict underlying Alzheimer pathology in the appropriate clinical setting.
- Amyloid is presumably low in the CSF because it has accumulated in plaques in the brain.
Treatment of Alzheimer’s disease
-
Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the N-methyl-d-aspartate (NMDA) antagonist memantine may provide modest symptomatic benefit in cognition in patients with AD.
- Gastrointestinal side effects can occur with the cholinesterase inhibitors.
- A common treatment strategy in patients with AD is to use a cholinesterase inhibitor initially (if tolerated), and to add memantine as patients progress to moderate/severe dementia.
- Otherwise, care of patients with AD is supportive.
Dementia With Lewy Bodies
- One of the Parkinson’s Plus syndromes
- Parkinsonian symptoms go along with dementia
- Dementia characterized by initial deficits in visuospatial and executive function, in tandem with parkinsonian hypokinesia and REM sleep abnormalities
- Later may develop visual hallucinations, fluctuations in attention and level of arousal
- Neuroleptic sensitivity (worsened parkinsonism and/or cognition with administration of neuroleptics) and autonomic dysfunction (orthostasis, constipation, incontinence, sexual dysfunction) are frequently present
Distinguishing Dementia with Lewy Bodies from pure Parkinson’s with dementia
- Patients with DLB develop symptoms and signs of dementia before or simultaneously with features of parkinsonism
- In Parkinson’s disease dementia, parkinsonism usually precedes dementia by years
- Parkinsonism in DLB is usually symmetric (in Parkinson’s disease, parkinsonism usually begins asymmetrically)
- Parkinsonism in DLB is usually less responsive to levodopa (or may not respond at all) compared to patients with Parkinson’s disease (whose parkinsonism generally responds to levodopa).
Neuroimaging Features of Dementia With Lewy Bodies
There is no characteristic pattern of atrophy on structural imaging in DLB, but nuclear imaging may show hypometabolism/hypoperfusion in occipital and temporoparietal regions (especially along the sylvian fissure) (compared to just temporoparietal hypometabolism/hypoperfusion in AD).
DLB vs AB on MRI (with a normal control)
Treatment of Dementia With Lewy Bodies
- As in AD, cholinesterase inhibitors and memantine may be useful in symptomatic management of cognitive dysfunction in DLB.
- As in the other Parkinson-plus syndromes, there is usually little or no response to dopaminergic therapies (in contrast to Parkinson’s disease), but if parkinsonism is a prominent disabling feature in a patient with DLB, a trial of levodopa can be considered.
- Symptomatic treatment can be considered for mood, REM sleep behavior disorder (clonazepam), and autonomic dysfunction.
Drug of choice for treating REM sleep dysfunction in Parkinson’s and Parkinson’s-Plus syndromes
Clonazepam
A benzodiazepine highly effective for RBD
Frontotemporal Dementia
-
Includes two categories of dementia syndromes: behavioral variant FTD (bvFTD) and primary progressive aphasia (PPA).
- bvFTD is characterized by personality changes and neuropsychiatric dysfunction (might be apathy, disinhibition, social withdrawal, social deviant behavior, etc. Very broad range)
- Clinical insight typically poor
- Other common features include loss of empathy, obsessive compulsive or perseverative behaviors, and executive dysfunction
- PPA is characterized by language deficits
- three variants with particular language deficits: nonfluent/agrammatic, semantic, and logopenic
- bvFTD is characterized by personality changes and neuropsychiatric dysfunction (might be apathy, disinhibition, social withdrawal, social deviant behavior, etc. Very broad range)
Neuroimaging in frontotemporal dementia
- Neuroimaging in FTD shows selective frontotemporal atrophy that may be very focal within language areas in PPA.
- Images: Sagittal (A) and axial (B) T1-weighted images demonstrating marked left frontotemporal atrophy. Note the widening of the insula (A) and the “knife edge” atrophy of the left temporal lobe (B).
Unlike focal tumors of the brain, diffuse infiltrative lesions or diffuse metastases can present with . . .
. . . global cognitive dysfunction and/or personality changes without obvious focal deficits
Syndrome of hearing loss, tinnitus, imbalance. Where is the tumor and what type of tumor is it likely to be?
cerebellopontine angle tumor
most commonly vestibular schwannoma or meningioma
Syndrome of bitemporal hemianopia. Where is the tumor and what type of tumor is it likely to be?
At the optic chiasm
Pituitary tumors or craniopharyngioma are most common
Syndrome of visual disturbance. Where is the tumor and what type of tumor is it likely to be?
Anterior to the optic chiasm
optic glioma, optic nerve sheath meningioma, or olfactory groove meningioma(olfactory groove meningioma may also cause unilateral loss of smell)
Syndrome of multiple cranial neuropathies. Where is the tumor and what type of tumor is it likely to be?
skull base lesion, brainstem lesion, or leptomeningeal metastases
Can be caused by wide variety of tumors, often metastatic in origin
In general, ___ are often used for the treatment of peritumoral vasogenic edema in patients whose brain tumors are symptomatic (e.g., headache and/or focal deficits) as a result of the location and size of the mass and its surrounding edema.
In general, steroids are often used for the treatment of peritumoral vasogenic edema in patients whose brain tumors are symptomatic (e.g., headache and/or focal deficits) as a result of the location and size of the mass and its surrounding edema.
Steroids are part of the treatment for ___ and can alter biopsy results if administered prior to biopsy
Steroids are part of the treatment for primary nervous system lymphoma and can alter biopsy results if administered prior to biopsy
So, wait and biopsy first before you give steroids, since some lymphomas that may be distinguished on biopsy have a VERY good prognosis if detected and treated with targeted therapy.
Most brain metastases come from disease that is primary to:
- Lung cancer
- Breast cancer
- Colon cancer
- Melanoma
How metastatic cancer appears on MRI
- Usually found at the gray-white matter junction
- Ring-enhancing lesions on contrast
- May be associated with intratumor hemorrhage (especially lung cancer)
Gastrointestinal cancer metastases have a predilection for metastasizing to ___
Gastrointestinal cancer metastases have a predilection for metastasizing to the posterior fossa
Metastatic prostate cancer of the brain
Prostate cancer only very rarely metastasizes to the brain, but can metastasize to the skull and/or dura mater, causing neurologic symptoms by impinging upon the brain and/or cranial nerevs.
Treatment of brain metastases
Involves surgical resection (for large, symptomatic metastases), stereotactic radiosurgery, and/or whole brain radiation
Leptomeningeal metastases
- Can cause headache, nausea/vomiting, cranial nerve involvement, and/or confusion
- If spinal leptomeningeal involvement, back and radicular pain due to involvement of nerve roots
- Most commonly breast cancer, lung cancer, hematologic malignancies, and melanoma
- Usually unaccompanied by brain metastases
- Treatment of leptomeningeal metastases is directed at the primary underlying cancer, but prognosis is generally poor.
MRI of leptomeningeal metastasis
- Contrast-enhanced brain imaging reveals enhancement of the leptomeninges, which can be noted in the cerebellar folia, surrounding the brainstem, and invaginating the cerebral sulci
- Hydrocephalus may also be present.
- Normal MRI does not exclude the possibility of leptomeningeal metastases! Definitive diagnosis is made by CSF cytology and flow
___ are the most common primary intracranial tumors, although both are less common than ___
Meningiomas and glial tumors are the most common primary intracranial tumors, although both are less common than metastases.
Meningiomas
- Dural based lesions that enhance uniformly on contrast-enhanced neuroimaging and often have a dural tail of enhancement at the margins of the tumor
- Treatment of meningiomas is surgical.
- Postoperative radiation therapy is used for grade 3 (anaplastic) meningiomas and incompletely resected grade 2 (atypical) meningiomas
- Radiation therapy without surgery may be considered for patients whose meningiomas are inoperable, or in patients who are not good surgical candidates.
- Incidentally discovered meningiomas can generally be followed with serial imaging if they are small and asymptomatic.
Gliomas
- Gliomas range from low grade (grades 1–2) to high grade (grades 3–4).
- Grade 4 (glioblastoma) is associated with the worst prognosis (usually just over 1 year survival even with treatment), although patients with lower grade tumors can survive for over a decade with treatment.
- On neuroimaging, low-grade gliomas are typically T2/FLAIR hyperintense lesions with little or no contrast enhancement
- Glioblastoma appears as a contrast-enhancing mass with a necrotic appearing center, and often progresses along white matter tracts such as across the corpus callosum (“butterfly glioma”)
- Treatment regimens for gliomas involve maximal surgical resection (when feasible), fractionated focal radiation therapy, and chemotherapy (with temozolomide).
What type of tumor is shown?
Glioma, low grade
What type of tumor is shown?
Glioma, specifically gliomatosis cerebri
What type of tumor is shown?
Glioblastoma, high grade
Gliomatosis cerebri
An infiltrating, usually high-grade, glial cell tumor that appears as diffuse and confluent on neuroimaging studies but generally does not enhance (Fig. 24–6).
Given its inoperability, prognosis is poor.
Primary CNS lymphoma
- Most commonly a diffuse large B-cell lymphoma
- Can occur in normal healthy patients as well as in immunocompromised patients
- Especially common in HIV and EBV co-infected patients
- Neuroimaging demonstrates one or more contrast-enhancing lesions in the supratentorial or infratentorial white matter that may show central diffusion restriction due to high cellularity
- This appearance is not specific, so biopsy is necessary for diagnosis
- CSF cytology and flow cytometry, some special stainings
- Remember, if lymphoma is under consideration, steroids should be avoided prior to biopsy as they may alter biopsy results
- Treatment is with chemotherapy, and radiation is used in some cases; surgery is not indicated..
What type of tumor is shown?
Primary CNS lymphoma, likely diffuse large B cell lymphoma
Most common benign and malignant tumors in adult and pediatric cases of brain cancer
Some astrocytomas will progress to . . .
. . . become glioblastomas
Pediatric medulloblastomas will often affect ____
Pediatric medulloblastomas will often affect the 4th ventricle, cerebellum, and pons
A brain tumor within the cerebral cortex is biopsied. Based on histologic appearance and location, what type of tumor is this?
Oligodendroglioma
Has a characteristic “fried egg” appearance
A brain tumor pressing up against the posterior cerebellum, in the posterior fossa, is biopsied from a 7 year old child with cerebellar symptoms. Based on histologic appearance and location, what type of tumor is this?
Medulloblastoma
You can tell by the characteristic “Homer-Wright Rosettes” made by the nuclei and bare cytoplasmic spaces.
“Drop” metastasis
When a brain tumor metastasizes to the spinal cord by following the flow of the CSF downward.
Commonly happens with medulloblastomas and ependymomas in the posterior fossa
Two most common pediatric brain cancers
- Medulloblastoma
- Ependymoma
Both tend to affect the cerebellum/brainstem area and both may cause drop metastases
A brain tumor pressing up against the posterior cerebellum, in the posterior fossa, is biopsied from a 7 year old child with cerebellar symptoms. Based on histologic appearance and location, what type of tumor is this?
Ependymoma
You can tell by the perivascular rosettes, surrounding the blood vessels.
Pineal gland tumors and Parinaud syndrome
- Parinaud syndrome is caused by pineal tumors or other tumors that compress the dorsal midbrain and superior colliculus
- Parinaud syndrome is characterized by: Impaired vertical gaze, impaired pupillary light reflex, and convervence retraction nystagmus (in other words, the eyes appear to jerk backwards into the orbit when the patient attempts to look up)
Tumors of the cerebellar-pontine angle
- Basically in the area of the 4th ventricle
- Most commonly Schwannomas (vestibular schwannomas to be specific)
- Often compress the vestibular nerve
- Bilateral vestibular schwannomas may occur in the heritable cancer syndrome of neurofibromatosis type II
- Mnemonic: 2 schwannomas, NF2, chromosome 22
- Bilateral vestibular schwannomas may occur in the heritable cancer syndrome of neurofibromatosis type II
Most common tumors of the spine
- Astrocytoma and Ependymoma (in spinal cord proper)
- Schwannoma and Meningioma (outside the spinal cord proper in the epidural space, but may compress the spine)
Leptomeningeal lymphoma will often present as. . .
. . . numerous cranial nerve deficits
Since the leptomeninges surround the cranial nerves as they transit out of the CNS.
Glioblastoma metastasis
Glioblastoma’s rarely metastasize outside of the brain and spine for unclear reasons. We do not due periodic screening of other organs once this diagnosis occurs given rarity of metastasis. They are aggressive tumors.
Extra-axial
Not within the brain parenchyma, but compressing it/in the area.
Often meningiomas
Area Postrema
Emetic center of the brain
Whenever there is a process that involves compression of this area, nausea and vomiting will be triggered. This is why elevated intracranial pressure induces N/V.
Cranial nerve 6 palsies with increased intracranial pressure
- At bottom of cranial space
- Can easily be compressed against the skull whenever there is increased intracranial pressure
- Common unilateral or bilateral injury with elevated ICP
What is going on in this MRI?
Sagittal (A) and axial (B) T1-weighted images demonstrating marked left frontotemporal atrophy. Note the widening of the insula (A) and the “knife edge” atrophy of the left temporal lobe (B).
Vascular dementia
- Refers to impaired cognitive function due to cerebral infarction
- May be due to accumulation of deficits from serial strokes, more insidious with chronic accumulation of subcortical microvascular disease, or some combination
- Clinical signs depend upon sites of prior infarction, but executive dysfunction and cognitive slowing are common
- Focal features, upper motor neuron signs, and/or pseudobulbar affect may be present.
Treatment of vascular dementia
-
Secondary stroke prevention
- Risk factor management (BP, glucose, lipids)
- Anticoagulation
- Cholinesterase inhibitors and memantine also useful for VD
- Some overlap between VD and AD as well
Anton syndrome
When patients with cortical blindness are unaware that they are blind.
This occurs with cortical blindness, where the patient’s eyes and optic nerves are working fine and reflexes are intact, but the patient cannot decode any visual information.
Charles Bonnet Syndrome
In patients with bilateral visual loss of any cause (most commonly ocular in older adults), patients may develop “release” hallucinations (Charles Bonnet syndrome).
These hallucinations are generally of small people, are not threatening to the patient, and the patient usually knows they are not real (good clinical insight)
Pathological hallmarks of alzheimer’s disease
- Amyloid plaques extracellularly
- “Tangles” of tau protein intracellularly
Dementia summary table
