Neuropathology Flashcards

Question

Intracerebral haemorrhage: definition, causes and related pathology, common sites

Answer 1

Definition = haemorrhage within the brain due to rupture of a small intra-parenchymal vessel --> HYPERDENSE SOL on CT * *Causes - HT - -> MC factor a/w DEEP BRAIN parenchymal haemorrhage (basal ganglia, thalamus) - -> pathology: hyaline arteriosclerosis, Charcot-Bouchard aneurysms (microaneurysmal outpouchings) - Cerebral amyloid angiopathy - -> MC factor a/w LOBAR haemorrhage - -> commonly involving superficial cortical vessels of occipital and parietal lobes - -> a/w Alzheimer's disease - -> pathology: brittle vessels with palely eosinophilic material impregnated on vessel wall - Haematological: thrombocytopenia, leukaemia (too many WBC makes vessels bleed easily) - Tumours: glioma (high grade), metastasis (melanoma, RCC) -- also lobar haemorrhage - Vascular: AVM - "Congenital": ruptured berry aneurysm - Drug: thrombolytics Common sites: - BASAL GANGLIA (most common) - thalamus - cerebellum - lobes of brain, brainstem

Answer 2

Bleeding into subarachnoid space (basal cisterns) Causes - ANEURYSM - AV malformation - -> BERRY aneurysm most common: due to HT; structural defects of media and elastica develop over time; connective tissue disease e.g. Marfan's - -> 90% found in arterial branch points of anterior circulation in Circle of Willis - AComm branch MC (note: if aneurysm is very large, it can bury into cerebral parenchyma and burst --> cerebral haemorrhage instead of SAH) - -> Fusiform atherosclerotic aneurysm (basilar artery) - -> Infective mycotic aneurysm (SBE) Complications: - Early phase = vasospasm cause irritation to basal cisterns --> additional ischaemic injury (1/3 mortality) = cardiac arrhythmia due to brainstem hypoxia - Healing phase = rebleeding = hydrocephalus (organisation of haematoma occluded CSF outflow) Clinical presentations: - Sudden onset of severe occipital headache ("worst headache ever") - nuchal rigidity due to irritation of meningeal membranes

Answer 3

Group of diseases characterised by DECLINE IN COGNITION involving one more cognitive domains. causing ADL impairment Memory --> early presentation of Alzheimer's disease Language, Behavioural --> early presentation of Fronto-temporal dementia Behavioural, Executive function --> early presentation in vascular dementia Visual spatial Late presentations: depression, hallucination, delusion, agitation, withdrawal Mild cognitive impairment (MCI) = between cognitive changes of aging and early dementia -- ADL not substantially interfered

Answer 4

Primary causes: * **Common - Alzheimer's disease (70%) - Vascular dementia (20%) - Parkinson's disease (small proportion) - Fronto-temporal dementia Less common - MS, ALS, Creutzfeldt-Jakob disease, Parkinson-plus syndrome Secondary causes: - CNS - chronic subdural haematoma, brain tumours, normal pressure hydrocephalus - Iatrogenic - drugs, alcoholism, Vit B12 deficiency - Hypothyroidism - Psychiatric disorders - HIV infection

Answer 5

Most common cause of dementia Risk factors: - Sporadic type - -> age (>80) - -> apoE allele (epsilon 4; higher risk than 3 or 2) - Familial early onset type(<1% cases; AD inheritance, a/w Down's syndrome) - -> amyloid precursor protein (APP) mutations on chr 21 - -> presenilin (PS1 & PS2) mutations on chr 14 and 1

Answer 6

Gross morphology (non-specific) - cerebral ATROPHY: narrowed gyri, widened sulci, decreased brain weight - VENTRICULAR DILATION secondary to decrease in brain volume Histology - NEURITIC PLAQUES and NEUROFIBRILLARY TANGLES - -> normally seen in the brains of elderly but exaggerated in AD - -> HIPPOCAMPUS most commonly affected Neuritic plaque - EXTRACELLULAR amyloid core surrounded by dystrophic neurites (dilated, tortuous) - pathogenesis --> abnormal cleavage of APP at cell membrane = POLYMERISATION OF A-BETA PEPTIDES (aggreggation) - staining: silver stain, congo red stain, Ab against A-beta Neurofibrillary tangles - INTRACELLULAR tau-containing irregular twisted filaments in cytoplasm - pathogenesis: HYPERPHOSPHORYLATION OF TAU protein (alters cytoskeleton microtubules in neuron = cells die) - staining: silver stain, Ab against tau CEREBRAL AMYLOID ANGIOPATHY - amyloid (almost identical to A-beta in neuritic plaques) present in cerebral vessels - weakening of vessels increases risk of haemorrhage - staining: Ab against A-beta, congo red

Answer 7

Clinical: - early: loss of smell, NO focal neurological deficits - late: changes in behaviour, judgement, language Treatment: - cholinesterase inhibitors improve memory and reduce hallucination; S/E bradycardia e.g. donepezil - NMDA inhibitor for moderate to severe diseases e.g. memantine

Answer 8

Group of syndromes including - multi-infarct dementia i.e. repeated strokes (especially if sub temporal gyrus affected) -- stroke increases risk of mental impairment by 4-5x - subcortical infarcts (damage white matter) - Binswanger disease: diffuse white matter disease (due to chronic arteriosclerosis and poor perfusion of small vessels) - -> leukoaraiosis: demyelination of white matter particularly in periventricular region (shrinking and scarring seen as radiolucency on imaging) Clinical presentation - STEPWISE DECLINE in cognition in multi-infarct dementia (symptoms stay same for a while then suddenly decline)

Answer 9

Not primary related to dementia!! Hypokinetic movement disorder due to degeneration of dopaminergic neurons in substantia nigra (depigementation) Pathology: LEWY BODY (alpha-synuclein inclusion in neurons; lewy neurites), TAU PROTEIN Dementia in 10-15% patients due to: - Alzheimer's disease - Dementia with Lewy body (DLB) --> Lewy body spreading from brainstem to cerebral cortex ==> core features: PARKINSONIAN features, fluctuating levels of ALERTNESS, visual HALLUCINATIONS Clinical presentations - cogwheel rigidity - bradykinesia: masked face - resting tremor (pill rolling) - postural instability, stooped posture - gait: difficulty in initiating first step, shuffling gait

Answer 10

50-70 yrs old Heterogenous set of disorders a/w focal degeneration of frontal and/or temporal lobes Distinguished from AD: - alterations in personality, behaviour and language PRECEDE MEMORY LOSS - no focal neurological deficits (same as AD) Pathogenesis and associations: - C9ORF72 (chr9) mutation -- accumulation of TDP-43; a/w ALS - MAPT (ch17) mutation -- accumulation of TAU (PICK BODIES); a/w Parkinsonism

Answer 11

Rare Prions = infectious proteins without nucleic acids -- "infectious": protease-resistant misfolded PrP promotes conversion of normal PrP to protease-resistant PrP -- can't be killed with standard sterilisation techniques -- can stain with Ab (IHC), western blot Transmissible spongiform encephalopathy/ Creutzfeldt-Jakob disease - early old age - TRANSMISSION through electrodes, dura mater graft (direct inoculation to brain), ingestion from infected cattle (bovine spongiform encephalopathy/ mad cow disease) - SPONGIFORM -- "bubble and holes" change in cerebral cortex and deep gray matter structures (microscopic vacuoles - ENCEPHALOPATHY -- subacute dementia, myoclonic jerks, characteristic EEG changes with periodic spikes, death <1 yr

Answer 12

MMSE and AMT for late stage dementia HKMoCA for early stage dementia Modified Barthel index for assessing ADL impairment

Answer 13

Main causes in adults - usually inflammatory (part of autoimmunity) - neurogenic diseases - dystrophy - metabolic disease Characteristics - no obvious neurological causes - symmetrical and diffuse - no associated sensory loss (presence of sensory loss = peripheral neuropathy) - adult vs paediatric: early onset - patterns of muscle weakness - - proximal weaker than distal - - face-sparing e.g. LGMD, DMD/BMD - - face involvement e.g. FSHD

Answer 14

Inflammatory/auto-immune markers: ESR, antibodies CK-MM isoenzyme: specific to skeletal muscle Electromyography (EMG) Muscle biopsy: definitive diagnosis for difficult cases; examined in transverse section (need snap freezing) DNA studies

Answer 15

Polymyositis, dermatomyositis, necrotising autoimmune myopathy Acquired, most common in adult/middle age Pathology: large number of inflammatory cells migrating and damaging muscles Clinical presentation: proximal muscle weakness and tenderness (symmetrical) Associations: - systemic autoimmune disease - STATINS - HIV - paraneoplastic disease (especially dermatomyositis) Investigations - high ESR, CK - **EMG: polyphasic units - autoimmune Ab Treatment: steroids, cancer surveillance (especially dermatomyositis)

Answer 16

Amyotrophic lateral sclerosis/ motor neuron disease - insidious onset - neuronal loss at ALL LEVELS OF MOTOR SYSTEM (cortex, brainstem and anterior horn cells) - -> usually LMN first then UMN Clinical presentations: - LMN signs - -> skeletal muscle weakness (asymmetric) and atrophy (extensors more affected) - -> bulbar palsy: dysphagia, dysphasia - -> respiratory muscle paralysis: death in 3-5 yrs - UMN signs - -> spasticity, Babinski sign - Extraocular muscles, bowel/bladder muscles and sensory functions spared (parasympathetic system preserved) - some familial cases associated with fronto-temporal dementia (TDF-43 accumulation) but otherwise cognition is normal Pathology: - no inflammation, reduction in number of anterior horn cells neurons Treatment: - Riluzole (glutamate release inhibitor)

Answer 17

Primary muscle diseases Duchenne/Becker muscular dystrophy Limb-girdle muscular dystrophy Facioscapulohumeral dystrophy

Answer 18

Pathogenesis: - Deletions (MC) or duplications of Dystrophin gene (Xp21 - X-linked disease) - dystrophin acts as anchor for actin to adhere to plasma membrane allowing efficient transmission of signals ``` Duchenne = out-of-frame mutations ==> total truncation of protein Becker = in-frame mutations ==> milder disease ``` Diagnosis: - muscle biopsy: dystrophin IMMUNOSTAINING (nothing on DMD, little on BMD) - DNA studies: western blot - other labs: CK very high at birth and decreases as muscles degenerate; also higher in female carriers Clinical presentations: (male) - symptoms occur before 5yrs old (delayed motor milestones e.g. difficulty in running/rising) - weakness and wasting of PELVIC muscles: GOWER's SIGN, waddling gait, toe-walking, lumbar lordosis - CALF pseudohypertrophy due to FIBROSIS AND INFILTRATION OF MUSCLE TISSUE BY FATTY TISSUE (thigh muscles not strong enough) - CARDIOMYOPATHY: heart failure, arrhythmia - intellectual impairment (30%) Pathology: increase connective tissue replacing myofibres Prognosis: DMD death by 20s, BMD by 40-50s

Answer 19

AD or AR Facial sparing, involving limb girdle (scapula/arms + pelvic/thighs) Early or adult onset

Answer 20

>1 form of disease - one of which is AD deletion of repeat DNA sequences at chromosome 4q Muscle involvement - facial muscles - upper and distal limbs: scapular winging - pelvic girdles preserved

Answer 21

Generalised hypotonia in newborn Spinal muscular atrophy (SMA) - AR deletions of SMN1 gene --> atrophic fibre GROUPS (failed development) - type I (infantile) most common: floppy baby syndrome, CANNOT SIT UNSUPPORTED (Werdnig-Hoffman disease) - type II (intermediate) and type III (juvenile) Mitochondrial myopathy - maternally transmitted diseases, gene deletions most common - usually a/w brain degeneration - examples: MELAS, progressive external ophthalmoplegia - pathology: RAGGED RED FIBRES using special stain (at rim of myofibres); EM accumulation under sarcolemma Metabolic myopathy - symptomatic only with exercise or fasting - glycogen storage disease, lipid storage disease (myofibres stained with lipids which can't be metabolised) Other causes: congenital muscular dystrophy/myopathies, perinatal asphyxia

Neuropathology Flashcards

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