1. Small Vessel Diseases of the Brain
Hereditary causes of Hemiparesis

2. Background
Hereditary, unrelated to arteriosclerosis or hypertensive disease
Cerebral autosomal dominant ateriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form
Leads to cognitive decline and dementia from multiple small ischaemic lesions and lacunar infarcts
Yamamoto Y, Craggs L, Baumannt M, Kalimo H, Kalaria RN. Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain. Neuropathology and Applied Neurobiology. 2011;37:

3. Pathophysiology
Mutation in one of 4 different genes: NOTCH3, HTRA1, TREX1, COL4A1
Sucortical lesions
Diffuse white matter changes
Lacunes
Microinfarction
Yamamoto Y, Craggs L, Baumannt M, Kalimo H, Kalaria RN. Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain. Neuropathology and Applied Neurobiology. 2011;37:

4. Pathophysiology continued…
Affects intracerebral small vessels including: arteries, arterioles, capillaries, and small veins
Arteriolar narrowing
Thickened arterial walls with fibrosis
Accumulation of eosinophilic material
Pericyte degeneration
Loss of vascular smooth muscle cells
Arterial changes lead to reduction in cerebral blood flow and blood volume in affected areas
Yamamoto Y, Craggs L, Baumannt M, Kalimo H, Kalaria RN. Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain. Neuropathology and Applied Neurobiology. 2011;37:

5. Signs & Symptoms Mean age of onset (first stroke) is 46 y/o
May be preceded by migraines
Cognitive changes: deficits in attention, processing speed, and executive function
Dementia by the sixth decade of life
Prognosis for disability and death worse for men > women by 6 years
Yamamoto Y, Craggs L, Baumannt M, Kalimo H, Kalaria RN. Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain. Neuropathology and Applied Neurobiology. 2011;37:

6. Diagnostic tests and Imaging
T2 weighted MRI
Neuroimaging
Yamamoto Y, Craggs L, Baumannt M, Kalimo H, Kalaria RN. Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain. Neuropathology and Applied Neurobiology. 2011;37:

7. Small vessel disease compared to large vessel disease Reference: Yamamoto Y, Craggs L, Baumannt M, Kalimo H, Kalaria RN. Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain. Neuropathology and Applied Neurobiology. 2011;37:

8. Types of Small Vessel Disease with hemiplegia
Hereditary Small Vessel Disease of the Brain (SVDB) – Autosomal Dominant
- Age of onset: y/o
- Duration of disease: > 5 years
- Key clinical features: Hemiplegia, motor and sensory deficits, memory impairments
- Neuroimaging findings: diffuse white matter changes, deep cerebral infarcts, degeneration of pyramidal tract, and multiple micro bleeds
Reference: Yamamoto Y, Craggs L, Baumannt M, Kalimo H, Kalaria RN. Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain. Neuropathology and Applied Neurobiology. 2011;37:

9. Types of Small Vessel Disease with hemiplegia
COL4A1-related disorder (stroke syndrome) – Autosomal dominant
- Age of onset: y/o
- Duration of disease: > 8 years
- Key clinical features: infantile hemiparesis, migraines, intracerebral hemorrhages, seizures, Raynaud phenomenon, dementia
- Neuroimaging findings: diffuse white matter changes, dilated perivasular changes, subcortical infarcts, microbleeds, and absence of porencephaly cavities
Reference: Yamamoto Y, Craggs L, Baumannt M, Kalimo H, Kalaria RN. Review: Molecular genetics and pathology of hereditary small vessel diseases of the brain. Neuropathology and Applied Neurobiology. 2011;37: