2. • Age onset 17-45 years
• YOD often presents in its early stages as
behavioral changes, depression, and
psychosis, and patients may not develop
cognitive deficits until later in the disease
process.
3. • includes early-onset forms of adult
neurodegenerative conditions including
• Alzheimer's disease
• Vascular dementia
• Frontotemporal dementia
• Lewy body dementias
• Huntington's disease
• Prion disease
4. Alzheimer s dementia
• Sporadic AD mutation of APP, PSEN1, or PSEN2
• Age of onset – 40-50 yrs
• In addition to dementia has behavioural
features:
• (agitation, withdrawal, hallucinations), motor
symptoms, myoclonus)
5. • CT or MRI (cerebral cortical atrophy)
• FDG-PET (cerebral hypometabolism
posterior> anterior)
• CSF (low Aβ 42 and high tau)
• Genetic testing
6. Vascular dementia
CADASIL
• AD mutation of NOTCH3 on Chr19
• Age of onset – 30-60 yrs
• Psychiatric features (mood disturbance,
apathy), migraine with aura, cerebrovascular
disease, seizures.
7. • MRI brain - begin asT2 hyperintensities in
temporal lobe/external capsule and
subcortical infarcts, progress to diffuse white
matter changes.
• skin biopsy (granular osmophilic material in
media of arterioles on EM)
8. Cerebral amyloid angiopathy
• Sporadic AD mutations in the APP,
CST3, or ITM2B genes
• Age of onset – 40-70 yrs
• Lobar intracerebral hemorrhage, headache,
focal neurological deficits
9. Frontotemporal dementia
• Sporadic AD mutation of MAPT or GRN on
Chr17 or hexanucleotide repeat C9ORF72
• Age of onset -35-87 years
• Behavior and personality change, aphasia,
dysarthria, dysphagia, associated
parkinsonism or motor neuron disease
10. • CT or MRI (regionally specific frontal and
temporal atrophy)
• FDG-PET (anterior> posterior
hypometabolism)
• genetic testing
11. Lewy body dementia
• Sporadic Rare mutations in SNCA, SNCB50-83
age of onset 10-15 years
• Fluctuating alertness, visual hallucinations,
parkinsonism, REM sleep behavior disorder
12. Multiple system atrophy
• Sporadic Rare associations with SNCA gene
• age of onset 54-60 years
• Parkinsonism with anterocollis, autonomic
failure, ataxia, pyramidal signs, REM sleep
behavior disorder, nocturnal stridor
13. • MRI (brainstem “hot cross bun” sign or
hypointensity of extreme capsule)
• polysomnography for loss of muscle atonia in
REM sleep; autonomic testing
• genetic testing
14. Huntingtons disease
• AD mutation of CAG repeats in HTT gene on
Chr4
• AGE of onset -35-44 years
• Chorea, prominent behavioral features and
personality change
• MRI (atrophy of caudate and putamen);
genetic testing
15. CJD
• Sporadic (sCJD)
Acquired (vCJD)
Iatrogenic (iCJD)
Genetic (gCJD)
AD mutation of PRNP on Chr20
AGE of onset 30-50 yrs
Ataxia, myoclonus, personality change
16. • MRI (DWI and FLAIR sequences with cortical
ribboning, hyperintense basal ganglia and
thalamus)
• CSF (incr 14-3-3 protein)
• EEG (triphasic or sharp wave bursts every 0.5
to 2 sec)
• genetic testing
17. MELAS
Mutation in mitochondrial DNA gene MT-
TL1 and MT-ND5 2-10 years
Normal early development, short stature,
generalized tonic-clonic seizures, headache,
anorexia, vomiting, exercise intolerance,
proximal limb weakness, stroke-like episodes,
lactic acidosis, sensorineural hearing loss
18. INVESTIGATIONS
• MRI - T2 hyperintensity in posterior cerebrum,
DWI signal changes in stroke-like regions
• Blood tests -elevated lactate
• CSF -elevated lactate, elevated protein but
<100 mg/dl
19. MERRF
• Mutation in mitochondrial DNA gene MT-
TKChildhood-
• Normal early development, myoclonus,
generalized epilepsy, ataxia, weakness,
hearing loss, short stature, optic atrophy,
Wolff-Parkinson-White syndrome
20. • MRI (basal ganglia calcification, bilateral
putaminal necrosis, atrophy of brain stem and
cerebellum)
• Blood tests (elevated lactate and pyruvate);
CSF (elevatedlactate and pyruvate, elevated
protein but <100 mg/dL)
• EEG (generalized spike and wave discharge
21. • EMG & muscle biopsy - (ragged red fibers that
do not stain for cytochrome c oxidase but
stain for succinate dehydrogenase)
22. Classic muscle biopsy features of MERRF: (A) ragged-red fibers (RRF) stained
with modified Gomori-trichrome; (B) RRF stained with succinate dehydrogenase
(SDH); and (C) deficient muscle fiber activity using a cytochrome c oxidase (COX)
stain
23. Kearne sayre syndrome
• Deletion of mitochondrial DNA
• Before 20 years
• Pigmentary retinopathy, progressive external
ophthalmoplegia, cardiac conduction block,
ataxia, deafness, diabetes mellitus and other
endocrinopathies
24. • MRI (hyperintensity of basal ganglia,
brainstem, cerebral/cerebellar white matter)
• Blood tests (elevated lactate and pyruvate)
25. Lysosomal storage disorders
• Tay sachs disease- Weakness, dystonia, ataxia,
motor neuron disease, psychiatric symptoms
• Absent hexosaminidase A activity with normal
or increased hexosaminidase B.
26. NEIMANN PICKS DISEASE
• Neimann pick disease type c- Psychiatric
symptoms, ataxia, vertical supranuclear gaze
palsy, dystonia, seizures, dysarthria, dysphagia
• MRI (atrophy of white matter tracts and
bilateral hippocampus, thalamus, superior
cerebellum, insula)
27. GAUCHER S DISEASE
• Gauchers disease type2 &3 -
Hepatosplenomegaly, pancytopenia, lung
disease
• Type 2: bulbar signs, pyramidal signs.
• Type 3: oculomotor apraxia, seizures,
myoclonus, bone diseas
28. Fabry s disease
• Acroparesthesia, angiokeratoma,
hypohidrosis, corneal and lenticular opacities,
proteinuria, renal disease, cardio- and
cerebrovascular disease.
• decreased alpha galactosidase activity
33. HEAVY METAL POISONING
• Mercury poisoning: psychiatric symptoms,
distal sensory and motor neuropathy, GI
symptoms, weakness, developmental delay,
inflammation of gums, constricted visual
fields, deafness, ataxia.
Arsenic poisoning: arrhythmia and ARDS.
Lead poisoning: anemia
35. ALCOHOL
• Ingestion with neurotoxic effects
Alcohol-related dementias include thiamine
deficiency, hepatic encephalopathy, and
Marchiafava-Bignami disease
36. NPH
• Impaired CSF flow
• more common after head trauma, CNS
infection, CNS hemorrhage
• Gait disturbance (“magnetic”), urinary
incontinence
• MRI -ventriculomegaly,
37. • periventricular white matter hyperintensity,
no evidence of CSF flow obstruction)
• high volume LP or CSF drain to identify
• patients that may respond to shunt placement
38. Chronic traumatic encephalopathy
• Repetitive injury to brain
e.g. professional athletes ,blast,injury
Depression, apathy, poor impulse control,
multi-domain cognitive decline, variable
parkinsonism.
MRI (generalized and medial temporal lobe
atrophy or ventriculomegaly
