NINCDS-ADRDA Criteria for Diagnosis of AD

Summary of NINCDS-ADRDA Criteria for Diagnosis of AD

Probable AD

Deficits in two or more domains of cognition

Progressive decline of memory and other cognitive functions

Preserved consciousness

Onset between ages 40 and 90

Absence of systemic or other brain disease that could account for symptoms

Possible AD

Atypical onset, presentation, or clinical course of dementia

Presence of another illness capable of producing dementia

Definite AD

Clinical criteria for probable AD

Tissue diagnosis by autopsy or biopsy

NINCDS-ADRDA Criteria for the Diagnosis of Alzheimer's Disease *

I. Clinical Diagnosis of Probable Alzheimer's Disease

1. Dementia established by clinical examination and mental status testing and confirmed by neuropsychological testing
2. Deficits in at least two cognitive domains
3. Progressive cognitive decline, including memory
4. Normal level of consciousness
5. Onset between ages 40 and 90 (most common after 65) years
6. No other possible medical or neurological explanation

II. Probable Alzheimer's Disease Diagnosis Supported by

1. Progressive aphasia, apraxia, and agnosia
2. Impaired activities of daily living
3. Family history of similar disorder
4. Brain atrophy on CT/MRI, especially if progressive
5. Normal CSF, EEG (or nonspecifically abnormal)

III. Other Clinical Features Consistent with Probable Alzheimer's Disease

1. Plateau in course
2. Associated symptoms: depression; insomnia; incontinence; illusions; hallucinations; catastrophic verbal, emotional, or physical outbursts; sexual disorders; weight loss; during more advanced stages increased muscle tone, myoclonus, and abnormal gait
3. Seizures in advanced disease
4. CT normal for age

IV. Features That Make Alzheimer's Disease Uncertain or Unlikely

1. Acute onset
2. Focal sensorimotor signs
3. Seizures or gait disorder early in course

V. Clinical Diagnosis of Possible Alzheimer's Disease

1. Dementia with atypical onset or course in the absence of another medical/neuropsychiatric explanation
2. Dementia with another disease not felt otherwise to be the cause of dementia
3. For research purposes, a progressive focal cognitive deficit

VI. Definite Alzheimer's Disease

1. Meets clinical criteria for probable Alzheimer's disease
2. Tissue confirmation (autopsy or brain biopsy)

VII. Research Classification of Alzheimer's disease should specify

1. Familial?
2. Early onset (before age 65)?
3. Down's syndrome (trisomy 21)?
4. Coexistent other neurodegenerative disease (e.g., Parkinson's disease)?

McKhann G, Drachman D, Folstein M, et al: Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939–944

DSM-IV criteria for the diagnosis of AD

1.       The development of multiple cognitive deficits manifested by both:

(a)     Memory impairment (impaired ability to learn new information or to recall previously learned information)

(b)     One or more of the following cognitive disturbances:

                                                   i.      Aphasia (language disturbance)

                                                  ii.      Apraxia (impaired ability to carry out motor activities despite intact motor function)

                                                iii.      Agnosia (failure to recognize or identify objects despite intact sensory function)

                                                iv.      Disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting)

2.       The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning.

3.       The course is characterized by gradual onset and continuing cognitive decline.

4.       The cognitive deficits in Criteria A1 and A2 are not due to any of the following:

(a)     Other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson’s disease, Huntington’s disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor)

(b)     Systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)

(c)     Substance-induced conditions

5.       The deficits do not occur exclusively during the course of a delirium.

6.       The disturbance is not better accounted for by another Axis I disorder (e.g., Major Depressive Disorder, Schizophrenia).

Brain imaging of vascular dementia

I. Topography

Radiologic lesions associated with dementia include ANY of the following or combinations thereof:

1. Large-vessel strokes in the following territories:

Bilateral anterior cerebral artery

Posterior cerebral artery, including paramedian thalamic infarctions, inferior medial temporal lobe lesions

Association areas: parietotemporal, temporo-occipital territories (including angular gyrus)

Watershed carotid territories: superior frontal, parietal regions

2. Small-vessel disease:

Basal ganglia and frontal white matter lacunes

Extensive periventricular white matter lesions

Bilateral thalamic lesions

II. Severity

In addition to the above, relevant radiologic lesions associated with dementia include:

Large-vessel lesions of the dominant hemisphere

Bilateral large-vessel hemispheric strokes

Leukoencephalopathy involving at least ?4 of the total white matter

Although volume of lesion is weakly related to dementia, an additive effect may be present. White matter changes observed only on T, MRI but not on T, MRI or CT may not be significant.

Absence of vascular lesions on brain CT/MRI rules out probable vascular dementia.

NINDS - AIREN criteria for the diagnosis of vascular dementia

I. The criteria for the clinical diagnosis of probable vascular dementia include all of the following:

1. Dementia:  

• Defined by cognitive decline from a previously higher level of functioning and
• Manifested by impairment of memory and of two or more cognitive domains (orientation, attention, language, visuospatial functions, executive functions, motor control, and praxis), preferable established by clinical examination and documented by neuropsychological testing;
• Deficits should be severe enough to interfere with activities of daily living not due to physical effects of stroke alone.
• Exclusion criteria: cases with disturbance of consciousness, delirium, psychosis, severe aphasia, or major sensorimotor impairment precluding neuropsychological testing. Also excluded are systemic disorders or other brain diseases (such as AD) that in and of themselves could account for deficits in memory and cognition.

2. Cerebrovascular disease:

·         Defined by the presence of focal signs on neurologic examination, such as hemiparesis, lower facial weakness, Babinski sign, sensory deficit, hemianopia, and dysarthria consistent with stroke (with or without history of stroke), and

·         Evidence of relevant CVD by brain imaging (CT or MRI) including multiple large vessel infarcts or a single strategically placed infarct (angular gyrus, thalamus, basal forebrain, or PCA or ACA territories), as well as multiple basal ganglia and white matter lacunes, or extensive periventricular white matter lesions, or combinations there of.

3. A relationship between the above two disorders: manifested or inferred by the presence of ≥ 1 of the following:
1. Onset of dementia within 3 months following a recognized stroke
2. Abrupt deterioration in cognitive functions; or fluctuating, stepwise progression of cognitive deficits.

II. Clinical features consistent with the diagnosis of probable vascular dementia include the following:

1.       Early presence of gait disturbance (small-step gait or marche a petits pas, or magnetic, apraxic-ataxic or parkinsonian gait);

2.       History of unsteadiness and frequent, unprovoked falls;

3.       Early urinary frequency, urgency, and other urinary symptoms not explained by urologic disease;

4.       Pseudobulbar palsy;

5.       Personality and mood changes, abulia, depression, emotional incontinence, or other subcortical deficits including psychomotor retardation and abnormal executive function.

III. Features that make the diagnosis of vascular dementia uncertain or unlikely include

1.       Early onset of  memory deficit and progressive worsening of memory deficit and progressive worsening of memory and other cognitive functions such as language (transcortical sensory aphasia), motor skills (apraxia), and perception (agnosia), in the absence of corresponding focal lesions on brain imaging;

2.       Absence of focal neurological signs, other than cognitive disturbance; and

3.       Absence of cerebrovascular lesions on brain CT or MRI

IV. Clinical diagnosis of possible vascular dementia may be made in the presence of dementia (section I-1) with focal neurologic signs in patients in whom brain imaging studies to confirm definite CVD are missing; or in the absence of clear temporal relationship between dementia and stroke; or in patients with subtle onset and variable course (plateau or improvement) of cognitive deficits and evidence of relevant CVD.

V. Criteria for diagnosis of definite vascular dementia are

1.       Clinical criteria for probable vascular dementia;

2.  Histopathologic evidence of CVD obtained from biopsy or autopsy;
Absence of neurofibrillary tangles and neuritic plaques exceeding those expected for age; and
Absence of other clinical or pathological disorder capable of producing dementia.

VI. Classification of vascular dementia for research purposes may be made on the basis of clinical, radiologic, and neuropathologic features, for subcategories or defined conditions such as cortical vascular dementia, subcortical vascular dementia, BD, and thalamic dementia.

The term "AD with CVD" should be reserved to classify patients fulfilling the clinical criteria for possible AD and who also present clinical or brain imaging evidence of relevant CVD. Traditionally, these patients have been included with VaD in epidemiologic studies. The term "mixed dementia," used hitherto, should be avoided.

DSM-IV criteria for the diagnosis of vascular dementia

DSM-IV criteria for the diagnosis of vascular dementia

A. The development of multiple cognitive deficits manifested by both:

1. Memory impairment (impaired ability to learn new information or to recall previously learned information)
2. One or more of the following cognitive disturbances:

(a) Aphasia (language disturbance)

(b) Apraxia (impaired ability to carry out motor activities despite intact motor function)

(c) Agnosia (failure to recognize or identify objects despite intact sensory function)

(d) Disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting)

B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning.

C. Focal neurological signs and symptoms (e.g., exggeration of deep tendon reflexes, extensor plantar response, psuedobulbar palsy, gait abnormalities, weakness of an extremity) or laboratory evidence indicative of cerebrovascular disease (e.g., multiple infarctions involving cortex and underlyig white matter) that are judged to be etiologically related to the disturbance.

D. The deficits do not occur exclusively during the course of a delirium

Vascular supply of brain

BRANCHES OF INTERNAL CAROTID

Meningohypophyseal trunk (that “Italian artery” Bernasconi-Casanari)

Ophthalmic

Superior hypophyseal

Posterior communicating (infundibulum, connects to PCA)

Anterior choroidal (AChoA – marker for temporal lobe herniation)

Anterior cerebral (ACA)

- Frontopolar

- Callosomarginal

- Pericallosal

Middle cerebral (MCA)

- Lenticulostriate (perforators to basal ganglia)

Internal Carotid (ICA)

- Cervical-Petrous-Cavernous-Supraclinoidsegments

POSTERIOR CIRCULATION BRANCHES

Vertebral

- Muscular (occipital) branches

- Meningeal branch

- PICA

Basilar

- AICA

- Superior cerebellar (SCA)

- Posterior cerebral (PCA)

- Posterior communicating

- Posterior choroidal (medial/ and lateral branches)

- Parietoccipital

- Posterior temporal

- Calcarine

EXTERNAL CAROTID BRANCHES

Superior thyroid

Lingual

Facial

Ascending pharyngeal

Occipital

Posterior auricular

Superficial temporal

Internal maxillary

- Middle meningeal (f. spinosum)

DEEP VENOUS DRAINAGE

Anterior septal

Thalamostriate

Internal cerebral veins (paired)

Basal vein(s) of Rosenthal (medial temporal lobe)

Great vein of Galen

Inferior sagittal sinus (free edge of Falx)

Straight sinus

Superior sagittal sinus (don’t forget the “Torcular Herophilus”)

Transverse sinus

Sigmoid sinus

Internal jugular

COMMENT: Superficial drainage is superficial middle cerebral vein, vein of Trolard and vein of Labbe to superior sagittal sinus

Thalamic Regions and Nuclei

Thalamic Regions and Nuclei
• Anterior

o Anterior nucleus

• Medial
o Medial (or dorsal) nucleus
o Midline nuclei
• Lateral
o Dorsal
 Lateral dorsal nucleus
o Ventral
 Ventral anterior nucleus
 Ventral lateral nucleus
 Ventral posterior lateral nucleus
 Ventral posterior medial nucleus
• Posterior
o Dorsal
 Lateral posterior nucleus
 Pulvinar
• Medial
• Lateral
• Inferior
o Ventral
 Posterior thalamic zone
 Medial geniculate body
 Lateral geniculate body
• Intralaminar
o Centromedian and parafascicular nuclei
o Smaller intralaminar nuclei
• Reticular nucleus

Pathology of AD

Pathology of AD

The most severe pathology is usually seen in the hippocampus, temporal cortex, and nucleus basalis.
The most important microscopic findings are neuritic "senile" plaques and cytoplasmic neurofibrillary tangles (NFTs). These two lesions accumulate in small numbers during normal aging of the brain but occur in quantitative excess in the dementia of AD.

Neuritic plaques contain
• A central core that includes Ab amyloid, proteoglycans, Apo E, a1 antichymotrypsin, and other proteins.
• The plaque core is surrounded by the debris of degenerating neurons, microglia, and macrophages

Ab amyloid
• 4.2-kDa protein of 39 to 42 amino acids
• Proteolytically from a larger transmembrane protein (amyloid precursor protein, APP) through cleavage by two enzymes termed b and g secretase
• Normal function of Ab amyloid is unknown.
• APP has been shown to have neurotrophic and neuroprotective activities.

The accumulation of Ab amyloid in cerebral arterioles is termed amyloid angiopathy.

NFTs
• silver-staining,
• twisted neurofilaments in neuronal cytoplasm that represent abnormally phosphorylated tau (t) protein and
• Appear as paired helical filaments by electron microscopy.

Tau is a microtubule-associated protein that may function to assemble and stabilize the microtubules that convey cell organelles, glycoproteins, and other important materials through the neuron. The ability of tau protein to bind to microtubule segments is determined partly by the number of phosphate groups attached to it. Increased phosphorylation of tau protein may disturb this normal process.

Ring enhancing lesions

RING ENHANCING LESIONS

1. Neurocysticercosis

2. Tuberculoma

3. Toxoplasma

4. Crytococcus

5. Resolving hematoma (10-21 days)/ Subacute infarct/contusion

6. Abscess – ring is smooth and regular and usually thinner on the medial side

7. Primary brain tumor (glioblastoma)

8. Metastasis (especially post chemotherapy)

9. Multiple sclerosis

10. Radiation necrosis

11. Postoperative change

12. Aneurysm

HIV most common are toxoplasma, crytococcus, and TB (Toxoplasmosis is most common)

No single feature is pathognomonic, although a cystic lesion that markedly restricts centrally (the fluid component) on DWI should be considered an abscess until proven otherwise

Distinctive radiologic characteristics of ring-enhancing lesions

· Abscesses: thin, uniform ring, thinner on medial border, smoother outer margin; satellite lesions are often present

· Neoplasms: thicker, more irregular rims.

· Demyelinating disease: incomplete rings, "open-ring sign.

· Enhancing wall characteristics

o thick and nodular and irregular rims favours neoplasm

o thin and regular favours abscess

o incomplete ring favours demyelination (the "open ring" or "incomplete ring" sign)

o low T2 signal favours abscess

o restricted diffusion of enhancing wall favours GBM or demyelination

o Cerebrovascular disease: either partially cortical and partially deep - where the surface enhancement is serpentine in gray matter or, there is "ring enhancement" around basal ganglia (e.g. the caudate head).

· Surrounding edema

o extensive oedema relative to lesion size favours abscess

o increased perfusion favours neoplasm (metastases or primary cerebral malignancy)

o Demyelinating lesions usually do not have much mass effect

· Central fluid / content

o restricted diffusion (bright on DWI and low ADC values) favours abscess

o necrotic neoplasms have more liquid centers and are dark on DWI

· Number of lesions

o similar sized rounded lesions at grey white matter junction favours metastases or abscesses

o irregular mass with adjacent secondary lesions embedded in the same region of 'oedema' favours GBM

o Small (<1 to 2cm)> neurocysticercosis.

Diffusion-weighted MRI imaging (DWI)

DWI is based on the random movement of water known as Brownian motion.

Stationary water, unlike freely moving water, is depicted as high signal intensity on DWI, with a decreased signal on the corresponding apparent diffusion coefficient (ADC) maps. The more restricted the water motion is, the less is the value of the ADC.

· Abscesses: DWI bright/ADC dark

· Tumor cavities: DWI dark/ADC bright

· An abscess cavity usually demonstrates high signal on DWI with decreased ADC values, unlike necrotic tumor cavities, which demonstrate the opposite. The restricted diffusion is directly related to the presence of pus in the abscess cavity, likely associated with high cellularity and viscosity.

Metastases

• Marked vasogenic edema and mass effect
• Isointense to mildly hypointense on T1-weighted images
• Hyperintense on T2-weighted images or with FLAIR.
• Surrounding edema is relatively hypointense on FLAIR and on T1-weighted images; they are hyperintense on T2-weighted images.
• Hemorrhagic metastases or melanoma lesions are hyperintense on T1-weighted images.
• On T2-weighted images, mucinous adenocarcinoma may be hypointense, owing to calcification; hemorrhagic metastases may be hypointense, owing to the chronic breakdown of blood products.
• Following administration of a contrast agent, solid, nodular or irregular ring patterns of enhancement are seen. Nonenhancing lesions are less likely to be metastases.
• Contrast-enhanced MRI is the best method for detection of meningeal tumor seeding, which appears as abnormal dural enhancement. This is a nonspecific finding; however, in the correct clinical setting, it correlates with the presence of sheets of tumor cells affecting the meninges.

· On imaging, dural-based metastases may resemble meningioma.

· Leptomeningeal carcinomatosis may resemble chronic meningitis;

· Leptomeningeal enhancement may occur after the administration of radiation or following extra-axial hemorrhage; it may also occur below a craniotomy site.

· Single or multiple ring-enhancing lesions with edema may resemble infectious processes.

· Solitary lesions resemble primary brain tumors.

Abscess

MRI findings of brain abscess vary with time.

Early cerebritis stage

• Ill-defined subcortical hyperintense zone that can be noted on T2-weighted imaging.
• Hyperintense on DWI with ADC values of <0.9> 2 are more likely nonabscess cystic lesions.
• Contrast-enhanced T1W: poorly delineated enhancing areas within the isointense to mildly hypointense edematous region.

Late cerebritis stage

• Central necrotic area is hyperintense to brain tissue on proton-density and T2-weighted sequences.
• Thick & irregularly marginated rim appears isointense to mildly hyperintense on spin-echo T1-weighted images and isointense to relatively hypointense on proton-density and T2-weighted scans.
• Peripheral edema is common. The rim enhances intensely following contrast administration.
• Satellite lesions may be demonstrated.
• Early and late capsule stages
• Collagenous abscess capsule is visible prior to contrast as a comparatively thin-walled isointense to slightly hyperintense ring that becomes hypointense on T2-weighted MRIs.
• DWI aids in depiction of specific features of a brain abscess. If a cerebral abscess ruptures into the ventricular system, DWI demonstrate specific patterns.
• Purulent material within the ventricle appears similar to that of the central abscess cavity, with a strongly hyperintense signal on diffusion-weighted images.

MRS may be helpful in the differential diagnosis of toxoplasmosis versus CNS lymphoma. CNS lymphoma generally shows a mild pattern of elevated lipid and lactate peaks, with a prominent choline peak with some other normal metabolites. In toxoplasmosis, there are elevated lipid and lactate peaks, while other normal brain metabolites are nearly absent.

Diffusion-weighted MR may be useful in differentiating abscess from necrotic tumor. Diffusion-weighted echo planar images demonstrate an abscess as a high signal intensity with a corresponding reduction in the apparent diffusion coefficient. The brightness on DWI is related to the cellularity and viscosity of the contents within the abscess cavity. Tumors with central necrosis have marked hypointensity on diffusion-weighted images and much higher apparent diffusion coefficient values. The pattern described above for an abscess has also been noted for acute cerebral infarction.

Lymphoma

The classic appearance of CNS lymphoma on MRI

· T1-weighted: isointense to isointense-to-hypointense nodule or mass.

· T2-weighted: isointense-to-hyperintense mass.

· Gadolinium-enhanced T1-weighted: enhance intensely and diffusely.

In patients with AIDS-related immunosuppression, a ringlike enhancing pattern is seen most often. Often, little or no surrounding vasogenic edema is demonstrated.

· Tumor lesions may cross the midline and may appear as a butterfly tumor involving both cerebral hemispheres.
· In 30% of patients, leptomeningeal involvement is encountered, usually in secondary systemic lymphoma; in such cases, meningeal involvement is typical.
· Involvement of the perivascular spaces with contrast enhancement is strongly suggestive of CNS lymphoma (in such cases, lymphoma must be differentiated from sarcoidosis and CNS tuberculosis);
· Involvement of the corpus callosum is also strongly suggestive of CNS lymphoma (in such cases, lymphoma must be differentiated from glioma and metastatic neoplasm).
· Contrast-enhancing, thickened ependyma may be seen (cytomegalovirus ependymitis in AIDS or metastatic neoplasm such as carcinoma of lung or breast, and ependymal spread of anaplastic glioma must be differentiated).
· Contrast-enhancing, thickened ependyma may be seen. If such findings are seen in patients with AIDS, lymphoma must be differentiated from cytomegalovirus ependymitis; if such findings are encountered in patients who do not have AIDS, lymphoma must be differentiated from metastatic neoplasm, such as carcinoma of the lung or breast.
· In addition, in patients with these findings, lymphoma must be differentiated from ependymal spread of anaplastic glioma.

Meningioma

· Homogeneous, extraaxial mass, it may show meningeal cysts, ring enhancement, fatty transformation, and en plaque morphology
· Nonenhanced T1-weighted: most are isointense. Fibromatous meningiomas may be more hypointense than the cerebral cortex.
· T2-weighted: hyperintense, also show the extent of edema.
· Multiple meningioma occurred between 5-40%
· Intense enhancement is seen in 85% of tumors, A ring appearance may represent a capsule
· Dural tail: collar of thickened, enhancing tissue that surrounds their dural attachment, represents thickened dura which may be either reactive or neoplastic. A dural tail occurs in approximately 65% of meningiomas and 15% of other peripheral tumors; not specific for meningiomas, it is highly suggestive of the diagnosis.

Hyperintensity on T2-weighted images indicates soft tumor consistency and microhypervascularity. This is seen more often in aggressive, angioblastic, or meningothelial tumors. T2-weighted signal intensity is best correlated with both the histology and consistency of the meningioma. Generally, low-intensity portions of the tumor on T2-weighted images indicate a more fibrous and harder character (eg, fibroblastic meningiomas), whereas higher-intensity portions indicate a softer character (eg, angioblastic tumor).

Malignant meningioma may invade the calvarium and cerebral parenchyma 1%

MRS reveals lactate in embolized areas of the meningioma immediately after embolization. Lipids are not observed before the 3rd day after embolization and are always associated with avascular and soft tissue at the time of surgery.

Tuberculosis

Contrast-enhanced CT scanning of the brain

· Prominent leptomeningeal and basal cistern enhancement

· With ependymitis, linear periventricular enhancement is present.

· Ventricular dilatation (eg, dilatation of the third and fourth ventricles) due to hydrocephalus is usually seen.

· Often, low-attenuating focal infarcts are seen in the deep gray-matter nuclei, deep white matter, and pons; these infarcts result from associated vasculitis.

· Caseating granulomas are rim enhancing; if these have a central calcific focus, they may form a targetlike lesion.

· All lesions are surrounded by hypoattenuating edema.

Primary differential diagnoses are fungal meningitis, bacterial meningitis, carcinomatous meningitis, and neurosarcoidosis.

MRI

· Gadolinium-enhanced T1-weighted images

o Prominent leptomeningeal and basal cistern enhancement

o With ependymitis, linear periventricular enhancement is present.

· Ventricular dilatation due to hydrocephalus is usually seen.

· Deep gray-matter nuclei, deep white matter, and pontine infarctions resulting from vasculitis are hyperintense on T2-weighted images.

· Diffusion-weighted MRI is especially sensitive in depicting early ischemic lesions when findings on the T2-weighted MRIs are normal.

Parenchymal cerebritis may show hyperintensity with little or no enhancement on T2-weighted images.

Parenchymal tuberculomas demonstrate various patterns

· Typically hypointense on T2-weighted images, but they may be hyperintense as well.

· Hypointense walls or rims on T2-weighted MRIs.

· Noncaseating granulomas are homogeneously enhancing lesions.

· Caseating granulomas are rim enhancing.

· Granulomas may also form a miliary pattern with multiple tiny, enhancing nodules scattered throughout the brain.

· Lesions are typically surrounded by hyperintense edema on T2-weighted images.

MRS: To differentiate from neoplasms

· Elevated fatty-acid spectra that are best seen by using the stimulated-echo acquisition mode technique and a short echo time.

· Necrosis of the waxy walls of mycobacteria within the granuloma is believed to cause the elevation of fatty-acid peaks.

· Lactate peak is caused by anaerobic glycolysis and is found in inflammatory, ischemic, and neoplastic lesions of the brain; this finding is nonspecific

MULTIPLE ENHANCING LESIONS

Hematogenous:

1. Metastases

2. Lymphoma

3. AIDS Disseminated infection (multiple abscesses)

4. Multifocal infarction

5. Inflammatory/Unknown Etiology:

6. Multiple Sclerosis (white matter lesions)

7. Vasculitis

8. Hypertensive Crisis/Ecclampsia

Inherited Mass Lesions/Neoplasms:

1. Hemangioblastoma (von Hippel-Lindau)

2. Arteriovenous malformations (cavernous hemangioma >> AVM)

3. Meningiomas – 4% are multiple (some with NF-2, most without)

4. Multicentric gliomas – 5% of all gliomas

5. Tuberous sclerosis

6. Neurofibromatosis (both types – NF1 (von Recklinhausen) and NF2 (MISME)