Neurodegenerative diseases

• parkinsons due to loss of dopaminergic neurons in substansia nigra pars compacta ( depigmentation)

  presents with

  dyskinesia akinesia pill rolling tremor shuffling gait tremor at rest cogwheel or lead pipe rigidity posturial instability dementia is a late finding

  neurons contained intracellular eosinophilic inclusions composed of alpha synuclein
• huntingotn disease is autosomal dominant due to repeated cag units in htt gene on chromosome 4 causes chorea athetosis astrexsis dementia agression depression mistaken for substance use presents age 30-40 atrophy of caudate and putamen and ex vacuo ventriculomegaly loss of ach and gaba

  neuronal damage via binding ndma receptors and glutamate exotoxicity increased dopamine
• Dementia is decline cognitive ability with conciousness reversible causes include depression hypothyroidism vitamin b12 deficiency neurosyphilis normal perssure hydrocephalus
• alzheimer dementia increased age is a risk factor down syndrome associated with earlies development of disease

  Apoe2 is protective against sporadic form

  Apoe4 increases risk

  App presenlin 2 presenilin 2 are for familial forms earlier onset

  narrowing of gyri widening of sulci in hippocampus beta amyloid cores may cause amyloid angiopathy and intracranial hemorrhage neurofibrillary tangles of hyperphosphated tau proteins number of tangles correlate with level of dementia

  hirano bodies intracellular eosinophilic proteinacious rods in hippocampus and cortical atrophy
• frontotemporal dementia picks disease presents early with personalit and behavioral changes and aphasia wide frontal and temporal atrophy associated with ubiquinated tdp 43 and hyperphosphorylated tau
• lewy dementia presents as visual hallucination dementia with alternating cognition and alertness rem sleep behaviour parkinsonism

  intracellular lewy inclusions in cortex ONLY IF COGNITIVE FUNCTION AND MOTOR ONSETS HAVE MORE THAN 1 YEAR APART

  otherwise it is dementia secondary to parkinson
• Vascular infarct is the 2nd most common cause of dementia stepwise decline in cognitive function and late onset memory loss due to chronic ishemia or multiple arterial infarcts ct or mri show multiple cortical or subcortical infarcts
• creutzfelt jacob disease spongiform encephalopathy without inflamation prpc becomes prpsc fatal causes beta pleated sheets resistant to proteases sporadic but may be via contaminated surgical equipment rapidly progressive dementia with myoclonus

  periodic Sharp waves on eeg and increased proteins 14-3-3 in csf
• Hiv encephalopathy late stage hiv subcortical dysfunction cognitive defects gait depression irritability diffuse gray matter and subcortical atrophy microglial nodules with multinucleated giant cells