Neurodegenerative disorders of brain

Neurodegenerative disorders of brain Dr. U Sinharoy Most common neurodegenerative disorders of the brain can be divided into 4 groups consisting as follows:

DementiaParkinsonism and other extrapyramidal disordersMotor neuron diseases andDiseases of the cerebellar system

73-year-old male patient AC: On FLAIR images obtained in axial plane, asymmetric atrophy is found with dilatation of the temporal horns and atrophy of the temporal lobes(A+B). In contrast to the relatively widened outer liquor spaces at the temporal region due to the atrophy (arrows, A+B), the parietal and frontal sulci are normal and small (arrowheads, C). Additionally, some leucencephalopathic lesions are present. D: On T2-weighted Spin-Echo-sequence in coronal plane, an atrophy of the hippocampal region on both sides (arrow).ALZHEIMERS DISEASE (ad)73-year-old male patient AC: On FLAIR images obtained in axial plane, asymmetric atrophy is found with dilatation of the temporal horns and atrophy of the temporal lobes(A+B). In contrast to the relatively widened outer liquor spaces at the temporal region due to the atrophy (arrows, A+B), the parietal and frontal sulci are normal and small (arrowheads, C). Additionally, some leucencephalopathic lesions are present. D: On T2-weighted Spin-Echo-sequence in coronal plane, an atrophy of the hippocampal region on both sides (arrow).

AD: short diagnosisMedial lobe atrophy microangiopathic lesions, hemorrhageatrophy of innominate substance

This series of three coronal T1-weighted studies, from an individual with autopsy-proven Alzheimer disease (AD), were each acquired 1 yr apart and show progressive hippocampal (H) atrophy

score 0: no atrophyscore 1: only widening of choroid fissurescore 2: also widening of temporal horn of lateral ventricle

score 3: moderate loss of hippocampal volume (decrease in height)

score 4: severe volume loss of hippocampus

< 75 years: score 2 or more is abnormal.> 75 years: score 3 or more is abnormal.

PiB PET Images of normal control, MCI, and AD subjects showing a range of amyloid- deposition. Most controls show no evidence of amyloid- deposition (NC), but a substantial portion (25%) do (NC+). Most patients with MCI show moderate (MCI+) or severe amyloid- deposition (MCI++), but as many as 40%50% show no evidence of amyloid- pathology (MCI). The vast majority of clinically diagnosed AD patients show heavy amyloid- deposition (AD).

Transaxial FDG-PET images of a normal control subject and a patient with mild AD. Note severe hypometabolism (yellow and blue cortical regions) in association and limbic cortex. They include posteriomedial parietal (precuneus), lateral parietal, lateral temporal, and medial temporal lobes. This pattern slowly worsens in parallel with symptoms and is well correlated at autopsy with AD pathologic diagnosis.the combination of atrophy in the left anterior cingulate (LAC) and the left anterior temporal pole (LAT) can distinguish FTD from controls with age-associated frontal atrophy with 90% accuracy.

the LAC [axial (a) and mid-sagittal (b)]

the LAT [coronal (c), axial (d) and sagittal (e)].

the combination of atrophy in the left anterior cingulate (LAC) and the left anterior temporal pole (LAT) can distinguish FTD from controls with age-associated frontal atrophy with 90% accuracy.

the LAC [axial (a) and mid-sagittal (b)]

the LAT [coronal (c), axial (d) and sagittal (e)].

Frontotemporal Dementia

(formerly Picks disease): short diagnosisknife blade atrophy (frontal, temporal lobe) enlargement of the frontal and inferior horn of the ventriclesenlargement of the interpeduncular cistern increased signal intensity (T2, PD) in atrophic areas

AD causes hypometabolism predominantly in posterior regions: the posterior temporoparietal association cortex and posterior cingulate cortex (Minoshimaet al.,1997). FTD causes hypometabolism predominantly in anterior regions: the frontal lobes, anterior temporal cortex and anterior cingulate cortex (Ishiiet al.,1998)

12Dementia with Lewy bodies: short diagnosis microangiopathic lesions focal or generalized atrophy white matter involvement (parieto-occipital)

Voxel-based morphometry (VBM) was used to assess patterns of grey matter (GM)

Region-of-interest (ROI) analyses were also performed comparing loss of the midbrain, substantia innominata (SI), temporoparietal cortex and hippocampus between the groups.

The DLB group showed very little cortical involvement on VBM with regional GM loss observed primarily in the dorsal midbrain, SI and hypothalamus.

the Alzheimer's disease group showed a widespread pattern of GM loss involving the temporoparietal association cortices and the medial temporal lobes.

Schematic diagram showing the location of cholinergic, serotonergic and noradrenergic neurons in the brainstem and basal forebrain. The inset shows the patterns of GM loss identified in the DLB group (seeFig. 3), and illustrates how the locations of the neurotransmitter nuclei correspond with the regions of loss in DLB. The cholinergic neurons in the nucleus basalis of Meynert project widely through the cingulum to the medial cerebral cortex with some lesser connections to the thalamus; neurons in the septal nuclei of the hypothalamus connect to the fornix and hippocampus (structure not shown); and neurons in the dorsal midbrain project to the thalamus. The serotonergic neurons in the dorsal raphe nucleus project to the basal ganglia and the basal forebrain, from which they distribute widely to the cerebral cortex. The noradrenergic neurons in the locus coeruleus innervate the brainstem and cerebellum, and also project to the basal forebrain, hypothalamus, temporal lobe (structure not shown) and the entire coerebral cortex (Mesulamet al.,1983; Mesulam and Geula,1988; Woolseyet al.,2003; Benarroch,2006).15Parkinsonism and other extrapyramidaldisorders :

Parkinsons diseaseMultisystem atrophy (MSA)Progressive supranuclear palsy (PSP)Corticobasal degeneration (CBD)Huntingtons diseaseWilsons disease

Overincreased R2* indicating increased iron load and more recently susceptibility-weighted imaging), magnetization transfer ratio (MTR reduced) and spectroscopy. Basal ganglia: studies showed no or mild changes in FA, R2* or MTR. Locus coeruleus area (white arroxw head): reduced signal intensity was detected using neuromelanin imaging.view of MRI methods used to study PD. Cortex: changes were detected using voxel-based techniques, cortical thickness measurements and perfusion imaging. Brain connectivity was investigated using resting-state functional MRI (rs-fMRI) for functional connectivity and tractography for structural connectivity. Substantia nigra (yellow contour): changes were detected using diffusion imaging (reduced fractional anisotropy - FA), relaxometry (

17Conventional T1- and T2-weighted MRI shows normal nigral structure in idiopathic PD and so is not diagnostically helpful.

Volumetric T1-weighted MRI studies have also failed to detect a reduction in nigral volume in PD, possibly because of difficulties in accurately defining the border of the nigra compactaA potential advance involves the use of diffusion tensor imaging to determine regional fractional anisotropy within the nigra.Nigral fractional anisotropy values were reduced in all PD patients, compared with the control

the swallow tail appearance as an easy recognizable sign of the healthy appearing substantia nigra which is lost in Parkinsons diseasePSP: Presence of any of the following: midbrain diameter < 17 mm, signal increase of midbrain, dilatation of the third ventricle, frontal or temporal lobe atrophy, signal increase of globus pallidus on 0.5-T scan, or atrophy of the red nucleus. MSA-P: Presence of any of the following: hyperintense putaminal rim or putaminal hyperintensity; signal increase in the cerebellum, middle cerebellar peduncles, or pons (hot cross bun); atrophy of the dentate nucleus; or dilatation of the fourth ventricle. MSA-C: Presence of any of the following: signal increase or atrophy in the cerebellum, middle cerebellar peduncles, pons (hot-cross bun), or inferior olives; atrophy of the medulla or dentate nucleus; or dilatation of the fourth ventricle.

Mickey mouse sign is referring to the axial MRI view of the brainstem, showing a selective atrophy of the midbrain tegmentum, with relative sparing of the midbrain tectum and cerebral peduncles

hummingbird sign. This is caused by the atrophy of the midbrain tegmentum and a relative increase in the length of the interpeduncular fossa over the anteroposterior diameter of the midbrain tegmentum. This sign has nearly 100% sensitivity

ical for MSA-C.

Brain MRI (1.5 T)

Axial T2 image showing the classic hot cross bun sign in the pons; axial (B) and coronal (C) T2 images depicting a hyperintense rim bordering the lateral margin of both putamina (white arrows);

(D) sagittal T2 sequence disclosing pontine and cerebellar atrophyThis sign is probably related to degeneration of transverse pontocerebellar fibers, whereas the hyperintense rim bordering the putamina has been associated with neuronal loss, reactive microgliosis, and astrogliosis.

A, Normal iron distribution, ie, globus pallidum hypointensity relative to the putamen in a patient with Parkinson disease (axial section, 1.5 T, T2 weighting).

B, Reversal of normal iron distribution with severe putaminal hypointensity relative to the globus pallidum (inset) in a patient with multiple-system atrophy with predominant parkinsonism.

C, Normal iron distribution in the globus pallidum relative to the putamen in a patient with Parkinson disease (coronal section, 1.5 T, T2 weighting).

D, Reversal of normal iron distribution with mild putaminal hypointensity relative to the globus pallidum (arrow) in a patient with multiple-system atrophy with predominant parkinsonism.

Normal posterolateral putaminal margin in a patient with a clinical diagnosis of Parkinson disease (axial section, 1.5 T, T2 weighting). B, Mild slitlike hyperintensity of the posterolateral putaminal rim (inset, arrow) in a patient with a clinical diagnosis of multiple-system atrophy with predominant parkinsonism (axial section, 1.5 T, T2 weighting). C, Moderate slitlike hyperintensity of the posterolateral putaminal rim (inset, arrow) in a patient with a clinical diagnosis of multiple-system atrophy with predominant parkinsonism (axial section, 1.5 T, T2 weighting).

A, Normal brainstem and cerebellum in a patient with Parkinson disease (sagittal section, 1.5 T, T1 weighting).

B, Mild brainstem and cerebellar atrophy in a patient with multiple-system atrophy with predominant parkinsonism (sagittal section, 1.5 T, T1 weighting).

C, Severe brainstem and cerebellar atrophy in a patient with multiple-system atrophy with predominant parkinsonism (sagittal section, 1.5 T, T1 weighting).

A: On axial FLAIR images dilated interpeduncular cistern is visualized. B: Axial T2-weighted images show signal decrease of the putamen with exceptionof a small lateral margin, known as the putaminal rim sign, underlining the diagnosis of MSA-P.

CBDG might be unique in showing hyperintensity in the subcortical white matter in the rolandic region on FLAIR images asymmetric atrophy predominantly contralateral to the side clinically more severely affected. Asymmetric atrophy in the cerebral peduncle without signal abnormalities was also characteristic of CBD. Atrophy in the midbrain tegmentum was also seen in patients with CBDS.

In CBD, midbrain tegmentum atrophy is severe, and degeneration in this area is correlated with the severity. However, this finding do not help in the differential diagnosis distinguishing CBD from PSP. T1-weighted imaging showed symmetric high-intensity signals in the subthalamic nucleus, but a large proportion of patients with PSP has a similar finding.

Wilsons disease:Magnetic resonance imaging (MRI) of brain :

Diffuse hyperintensities in pons with trident sign .Symmetrical hyperintensities in both halves of midbrain and periaqueductal gray matter with hypointense red nuclei and subtantia nigra forming face of giant panda sign and hyperintensities in bilateral thalami.abnormal hypointensities seen in bilateral globus pallidus.Hyperintesities in the claustrum and external capsule bilaterally.Cerebral and cerebellar atrophy.

T2-weighted axial MRI demonstrates hyperintense signal in the bilateral thalami and putamen

T2-weighted axial MRI demonstrates the face of the giant panda in the midbrain with high signal in tegmentum and normal red nuclei (arrow)

T2-weighted axial MRI reveals the face of the miniature panda in pons with hypointensity of central tegmental tracts (arrow) with hyperintensity of aqueductal opening to fourth ventricle

MRI brain T2-weighted image shows abnormal hyperintensity in pons with characteristic hypointense trident sign (A) and characteristic face of giant panda sign in midbrain (B).

:(a) T2 FLAIR axial image shows the bilateral putaminal (arrowhead) and thalamic involvement. (b) T2-weighted axial image shows the curvilinear hyperintense internal medullary lamina (arrowhead) between the medial and lateral thalamic groups of nuclei with a "split thalamus" appearance.

(c) Medial and lateral nuclear groups of the thalamus on either side of the hyperintense internal medullary lamina (arrowhead) seen on the coronal T2 image. Hyperintensity in the fields of florel is also seen (arrow)

:(a) T2 FLAIR axial image shows the bilateral putaminal (arrowhead) and thalamic involvement. (b) T2-weighted axial image shows the curvilinear hyperintense internal medullary lamina (arrowhead) between the medial and lateral thalamic groups of nuclei with a "split thalamus" appearance.

(c) Medial and lateral nuclear groups of the thalamus on either side of the hyperintense internal medullary lamina (arrowhead) seen on the coronal T2 image. Hyperintensity in the fields of florel is also seen (arrow)

NEUROIMAGEYear: 2010 |Volume: 58 |Issue: 4 |Page: 680"Split thalamus": Internal medullary involvement in Wilson's disease

Uttam George1,Nunenga Varte1,Shubhra Rathore1,Vishesh Jain1,Sandeep Goyal21Department of Radiodiagnosis, Christian Medical College and Hospital, Ludhiana, Punjab, India2Department of Psychiatry, Christian Medical College and Hospital, Ludhiana, Punjab, India

Huntington diseaseThe most striking, and best known, feature is that of caudate head atrophy resulting in enlargement of the frontal horns,often giving them a "box" like configuration. This can be quantified by an number of measurements:frontal horn width to intercaudate distance ratio (FH/CC)intercaudate distance to inner table width ratio (CC/IT)

The normal CC/IT ratio range 0.09 to 0.12. As the caudate heads reduce in size, the CC distance will increase and as such the the CC/IT ratio will increase.The normal mean FH/CC ratio range is 2.2 to 2.6. As the caudate heads reduce in volume the CC distance will approach the FH distance, and the ratio will approach 1.In ALS, signal-intensity changes on conventional MR imaging (ie, T2-weighted, PD-weighted, and FLAIR sequences) can be observed along the CST.

Typically, CST changes, which are best followed on coronal scans, appear as areas of bilateral increased signal intensity from the centrum semiovale to the brain stem.

However, the frequency of CST hyperintensities in patients with ALS varies significantly in the different studies (ranging from 15% to 76%), and it is not clear yet which may be the most sensitive MR image to detect them.

The combined application of T2-weighted, PD-weighted, and FLAIR images has recently reached a sensitivity of approximately 62%.In addition, CST signal-intensity changes do not correlate with clinical scores.

More remarkably, CST hyperintensities have also been described in healthy subjects,and in patients with other conditions, such as Krabbe disease,X-linked Charcot-Marie Tooth neuropathies,and adrenomyeloneuropathy.27

symmetric hyperintensity in the anterior temporal subcortical WMhypointensity along the precentral corticesAD, Hyperintensity at the subcortical precentral gyrus and the centrum semiovale