HUNTINGTON’S DISEASE patient 2 patient 1 IRREVERSIBLE SUBCORTICAL HUNTINGTON’S DISEASE patient 2 patient 1 Fig. Huntington’s disease: CT & MRI images of two different patients show bilateral caudate head atrophy. Also note cerebellar atrophy in patient 2 on MRI. HUNTINGTON’S DISEASE: Occurs in ~ 4-5 persons per million with age of onset around 4/5th decades. It is inherited in an autosomal dominant fashion with complete penetrance. A marker linked to Huntington gene is localized to the short arm of chromosome 4. C/F: choreo-athetosis, rigidity, dementia, and emotional disturbance. Disease progresses relentlessly. Neuroimaging show characteristic atrophy of the caudate and putamen. T2WI may also show signal changes of the striatum, either hyperintensity (due to loss of myelinated fibers & gliosis)or hypointensity on T2WI (from iron accumulation). Cerebellar and brainstem; along with cortical and subcortical atrophy may also be seen.

Cerebrovascular disease and dementia (vascular cognitive impairment) IRREVERSIBLE SUBCORTICAL Cerebrovascular disease and dementia (vascular cognitive impairment) Cerebrovascular disease accounts for second largest group of dementia either alone or in combination with AD. VCI (vascular cognitive impairment) is attributed to CVD. Latest clinical criterias are given by NINDS-AIREN 1) evidence of impairment in memory + two other cognitive domains. 2) evidence of CVD ie focal deficites 3) onset of dementia within 3 months of stroke. Stroke dementia CADASIL Amyloid angiopathy Subcortical vascular dementia Silent infarct & white matter hyperintensities Incidence rate of VaD are generally 5-10 folds less than those of AD. VaD is often seen in combination with Alzheimer disease and there is no good criteria to distinguish mixed from the vascular alone. Imaging plays important role in identifying silent strokes, small lacunes, or tiny microhemorrhgaes which may be responsible for cognitive decline or cortical or subcortical deficits.

MULTI-INFARCT DEMENTIA IRREVERSIBLE SUBCORTICAL MULTI-INFARCT DEMENTIA Fig Pick’s disease: Axial CT & Coronal MRI images show striking atrophy of the frontal lobes bilaterally with normal parieto-occipital lobes. MULTI-INFARCT DEMENTIA (MID) accounts for ~10% & is the 2nd most common cause of dementia and occurs more often in patients with hypertension, diabetes mellitus, hyperlipidemia, smoking and those who with several strokes. On imaging: MID appears as multiple areas of infarction involving the cerebral cortex, deep white matter, and/or basal ganglia. MID occurs when multiple small infarcts or hemorrhages cause enough neuronal or axonal loss to impair brain function. Because infarction is the cause, vascular dementia tends to progress in discrete steps; each episode is accompanied by intellectual decline.

BINSWANGER SUBCORTICAL ARTERIOSCLEROTIC ENCEPHALOPATHY The exact etiology of BD is unclear. Alterations in vascular permeability and the blood-brain barrier with diabetes, cardiac disease, CVA and, hypertension (75%) have been associated. Histopathology: Diffuse and patchy loss of myelin in the cerebral white matter, with areas of reactive gliosis with decrease in nerve fibers. LUDWIG BINSWANGER (1881 - 1966) Imaging: shows areas of hypodensities (nearly symmetric) in the periventricular white matter called “leukoaraiosis”. Lacunae are often apparent in the basal ganglia and thalamus. Ventricular enlargement due to volume loss of periventricular white matter and cerebrospinal fluid absorption into the surrounding tissue.

DECREASED COGNITIVE FUNCTION IRREVERSIBLE SUBCORTICAL SILENT CEREBRAL INFARCTS DECREASED COGNITIVE FUNCTION SILENT INFARCTIONS are defined as absence of clinical symptoms with MR imaging of findings of infarct. In sickel cell disease they are twice as common as clinical infarctions and may occur in up to 22% of children by first decade. C/F: increasingly recognized as a major cause of school problems, lower intelligence quotient (IQ) and other neurocognitive deficits. Elevated velocity of distal ICA and proximal MCA (> 170-200 cm/sec) is shown to be associated with increased incidence of stroke. Transcranial doppler has emerged as valuable predictive tool for assessing the velocity in pediatric patients.

IRREVERSIBLE SUBCORTICAL AMYLOIDOSIS Diagnostic clue- Normotensive demented patient with lobar hemorrhages and multifocal black dots on T2 and GRE CEREBRAL AMYLOID ANGIOPATHY (CAA): is characterized by the presence of homogenous eosinophilic deposits in the cortical and meningeal vessels which leads to luminal stenosis and fibrinoid necrosis. This makes vessels fragile and increases the tendency to bleed. CAA has no correlation with hypertension, diabetes or atherosclerosis. Imaging: may show superficial lobar hematomas, commonly with subcortical or subarachnoid extension. Focal or patchy/ confluent WM disease (70%),and/or nonhemorrhagic diffuse encephalopathy. GRE and T2WI may show multifocal black dots.

NEURONAL CEROID LIPOFUSCINOSES (NCL) IRREVERSIBLE SUBCORTICAL METABOLIC Introduction Any metabolic disorder which causes chronic or acute destruction of the brain parenchymal cells may over a period of time present with signs and symptoms of dementia depending on the area of involvement and severity of the disease. NEURONAL CEROID LIPOFUSCINOSES (NCL) General: NCL are common progressive encephalopathies of childhood. Metabolic defect is due to palmitoyl-protein thioesterase deficiency which leads to progressive accumulation of lipofuscins (lipopigments) in cells of the brain and other tissues. There are at least 6 types identified and they have different presentations. Juvenile NCL is called as Batten disease.. Clinical features- Failure of vision, progressive dementia, seizures, progressive impairment of speech and motor function. Definitive diagnosis is by electron microscopic analysis of lymphocytes from peripheral blood. Infantile form: Deposition of lipopigments in rods and cones leads to mental deterioration, seizures, retinal blindness, and abnormal electroretinogram. Onset is from 9 to 19 months of age with rapid, progressive mental deterioration. Death generally occurs between 8 and 11 years of age.

NEURONAL CEROID LIPOFUSCINOSES IRREVERSIBLE SUBCORTICAL NEURONAL CEROID LIPOFUSCINOSES Imaging: MR of brain shows variable cerebral plus cerebellar atrophy associated with high signal rim around ventricles and low signal intensity in the thalami and globus pallidus on T2WI. Infantile form shows pronounced cerebellar atrophy. MRS- shows complete loss of the NAA peak with marked reduction of creatine plus choline and elevation of myo–inositol and lactate in gray and white matter. SPECT/ PET 18 F- FDG studies show severe reduction in metabolism in all the cortical and subcortical structures. Similar changes are also noted in the cerebellum.

GANGLIOSIDOSIS: TAY SACHS DISEASE IRREVERSIBLE SUBCORTICAL GANGLIOSIDOSIS: TAY SACHS DISEASE Fig. GM2 Gangliosidosis: T2W images show diffuse hyper intensity of the white matter and lentiform nuclei. Thalami show hypointensity bilaterally. TAY SACHS DISEASE is found mainly in Jewish population and is due to deficiency of - N- acetylhexosaminidase - A- isoenzyme. Clinical features- infant presents with hyperacusis, irritability, hypotonia, psychomotor retardation and cherry red spot on macula and later stages with dementia. Imaging- In early phase there is high signal intensity within the bilateral basal ganglia on T2WI. In later phases due to calcification in the basal ganglia, it may show high signal intensity on T1 and low T2WI. In late phase, there is extensive gliosis, demyelination and cavitation. Classical imaging findings at this time include bilateral symmetrical thalamic calcification on CT and hypointensity on T2WI & hyperintensity on T1WI. β