1. Neurology MIRANDA – MOLINA – MONZON – MORALES – MUSNI – NALLAS - NAVAL Batch 2011 - Section C

3. History A 63 y/o woman was brought by her husband for consult because of increasing forgetfulness. The husband reports that his wife had completed a degree in BS Education. She has been teaching for the past 25 yrs. Confidentially, he reports that she has increasing difficulty remembering her class schedules and examinations as well as conversations with coworkers over the past year. He likewise noted reduced interest and withdrawal from many long-standing social activities. Recently, she left food cooking on the stove, which resulted in a small kitchen fire. 3

4. History The patient has no significant current medical problems and takes no medications. The patient's older brother has recently been diagnosed with the same illness. There were no significant PE findings. On mental status testing, the patient was noted to be disoriented to time and person. She had difficulty with calculation and had impaired short-term verbal memory. Visuospatial abilities, however, were intact. Cranial CT scan done revealed normal findings. 4

5. Salient Features Pertinent Positive 63 year old, female CC: Increasing forgetfulness over the past year –Difficulty remembering class schedules and exams and conversations with co- workers –Left food cooking on the stove  small kitchen fire Impaired short-term verbal memory Reduced interest ; withdrawal from social activities Disoriented to person and time Difficulty with calculation Brother: diagnosed with same illness 5

6. Salient Features Pertinent Negative No significant medical problems No medications taken No significant PE findings Visuospatial abilities intact Normal CT 6

7. Salient Features Pertinent Positive 63 year old, female CC: Increasing forgetfulness over the past year Impaired short-term verbal memory Reduced interest; withdrawal from social activities Disoriented to person and time Difficulty with calculation Brother: diagnosed with same illness 7

8. Memory Impairment DEMENTIADELIRIUMAMNESIA Stable level of consciousness Impairment in consciousness Stable level of consciousness Multiple cognitive defects Attention deficits Insidious onsetAbrupt onsetOnset depends on etiology Behavioral abnormality 8Reference

9. Salient Features Pertinent Positive 63 year old, female CC: Increasing forgetfulness over the past year Impaired short-term verbal memory Reduced interest; withdrawal from social activities Disoriented to person and time Difficulty with calculation Brother: diagnosed with same illness 9 Reference DEMENTIA Stable level of consciousness Multiple cognitive defects Insidious onset Behavioral abnormality Pseudodementia is a depression- related cognitive dysfunction

10. Clinical Impression

11. Dementia Syndrome of cognitive decline with variable non-cognitive features of behavioral and psychiatric symptoms and disturbance in activities of daily living 11Reference

12. Criteria for Dementia DSM –IV criteria Multiple Cognitive Deficits 1.Memory Impairment 2.One or more Aphasia Apraxia Agnosia Executive Impaired Social/Occupational function Gradual and progressive course Patient Increasing forgetfulness over the past year –Difficulty remembering –class schedules –exams – conversations with co-workers –Attention: Left food cooking on the stove  small kitchen fire Reduced interest ; withdrawal from social activities Disoriented to person and time Difficulty with calculation Impaired short-term verbal memory

13. Classification Disease in which Dementia is: Associated with clinical and laboratory signs of other medical diseases Associated with other neurological signs but not with other obvious medical disorders –Invariable associated with other neurologic signs –Often associated with other neurologic signs Usually the only evidence of neurologic or medical diseases 13Principles of Neurology, 8 th Edition Pertinent Negatives No significant medical problems No medications taken No significant PE findings Normal CT

14. Dementia Associated with clinical and laboratory signs of other medical diseases Aids-HIV infection Endocrine disorders: Hypothyroidism, Cushing syndrome Nutritional deficiency States: Wernicke Korsakoff syndrome Chronic meningoencephalitis Hepatoenticular degeneration Chronic Drug Intoxications (CO poisoning) Prolong Hypoglycemia or hypoxia Paraneoplastic “limbic”: encephalitis Heavy metal exposure Dialsis dementia (rare) 14Principles of Neurology, 8 th Edition

15. Dementia Associated with other neurological signs but not with other obvious medical disorders Invariable associated with other neurologic signs –Huntington Disease –Multiple sclerosis, Schilder disease, Adrenal Leukodystrophy and demyelinating disease (spastic Weakness, pseudobulbar palsy, blindness) –Lipid Storage disease (myoclonic siezures, blindness, spasticity, cerebellar ataxia) –Parkinson disease Often associated with other neurologic signs –Multiple thrombotic or embolic cerebral infarctions and Binswager disease –Brain tumor –Brain trauma (cerebral contusions, midbrain hemorrhages, chronic subdural hematoma) –Lewy body Disease (Parkinsonian Features) –Hydrocephalous usually with ataxia of gait 15Principles of Neurology, 8 th Edition

16. Dementia Dementia is usually the only evidence of neurologic or medical disease Alzheimers Disease Diffuse Lewy Body Dementia Pick Disease Frontotemporal and frontal lobe dementias 16Reference

17. Dementia Diffuse Cerebral Atrophy –Alzheimers Disease –Diffuse Lewy Body Dementia Circumscribed Cerebral Atrophy –Pick Disease –Frontotemporal and frontal lobe dementias 17Reference

18. 18Reference Alzheimer’s Disease Lewy Body Disease Pick’s Disease Frontotemporal Dementia ≥ 60 years old; 3x higher in women Memory impairment Aphasia, apraxia, agnosia, executive dysfunction Early aphasia; Dysexecutive syndrome Speech deterioration; Poor judgment and abstraction Impaired social or occupational function Marked psychiatric Sx Prominent alteration in personality behavior; Neglect of personal hygiene and grooming Early personality changes; Ritualistic & repetitive behavior; Disinhibition Fluctuating confusion Visual Hallucinations Paranoid delusions Hallucinations (+) Family History Insidious onset2-5 years course of illness Dementia: Usually the only evidence of neurologic or medical diseases Patient 63 year old woman Memory impairment Difficulty with calculation Withdrawal from social activities Disoriented to person and time Her brother diagnosed with same illness Symptoms noted over the past year

19. Alzheimer’s Disease

20. A. The development of multiple cognitive deficits manifested by both: -1.Memory impairment (impaired ability to learn new information or to recall previously learned information) -2.One or more of the following cognitive disturbances: (a) aphasia (language disturbance) (b) apraxia (impaired ability to carry out motor activities depite intact motor function) (c) agnosia (failure to recognize or identify objects despite intact sensory function) (d) disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting) B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning. C. The course is characterized by gradual onset and continuing cognitive decline. D. The cognitive deficits in Criteria A1 and A2 are not due to any of the following: (a) other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor) (b) systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection) (d) substance-induced conditions E. The deficits do not occur exclusively during the course of a delirium. F. The disturbance is not better accounted for by an Axis I disorder 20Reference Alzheimer’s Disease DSM IV Criteria

21. A. The development of multiple cognitive deficits manifested by both: -1.Memory impairment (impaired ability to learn new information or to recall previously learned information) -2.One or more of the following cognitive disturbances: (a) aphasia (language disturbance) (b) apraxia (impaired ability to carry out motor activities despite intact motor function) (c) agnosia (failure to recognize or identify objects despite intact sensory function) (d) disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting) B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning. C. The course is characterized by gradual onset and continuing cognitive decline. D. The cognitive deficits in Criteria A1 and A2 are not due to any of the following: (a) other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor) (b) systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection) (d) substance-induced conditions E. The deficits do not occur exclusively during the course of a delirium. F. The disturbance is not better accounted for by an Axis I disorder 21 Reference

22. Alzheimer’s Disease Most common cause of dementia Incidence increases with age –60 years and above 3x higher in women (+) Family History –Chromosome 21 – amyloid gene – senile plaques –Chromosome 19 – ApoE4 gene – inherited predisposition –Chromosome 1, 14 – Presenilins 1 and 2 22Reference

23. Alzheimer’s Disease Risk Factors Old age Family history Low education Head trauma High cholesterol Hypothyroidism Exposure to metals 23Reference

24. Alzheimer’s Disease Risk Factors Old age – 63 yrs old Family history – older brother Low education Head trauma High cholesterol Hypothyroidism Exposure to metals 24Reference

25. Alzheimer’s Disease Clinical Features Gradual development of forgetfulness Cognitive Dysfunctions –Language: expression, comprehension, reading, writing –Decline in arithmetic skills (acalculia/dyscalculia) –Visuospatial orientation 4 A’s: amnesia, aphasia, apraxia, agnosia 25Reference

26. Alzheimer’s Disease Clinical Features Gradual development of forgetfulness Cognitive Dysfunctions –Language: expression, comprehension, reading, writing –Decline in arithmetic skills (acalculia/dyscalculia) –Visuospatial orientation 4 A’s: amnesia, aphasia, apraxia, agnosia 26Reference

27. Alzheimer’s Disease Clinical Features Executive Dysfunction –Planning –Organizing –Sequencing –Abstract thinking Behavioral and personality change Decline in ADL 27Reference

28. Alzheimer’s Disease Clinical Features Executive Dysfunction –Planning –Organizing –Sequencing –Abstract thinking Behavioral and personality change –Withdrawal from social activities Decline in ADL –Disturbance in the household and workplace 28Reference

29. Alzheimer’s Disease Pathophysiology Generalized brain atrophy Loss of neurons Astrocytic proliferation - inflammation Microscopic changes - Neurofibrillary tangles Histological marker - Amyloid deposition Histological marker - Granulovacuolar degeneration 29Reference

30. Alzheimer’s Disease Diagnostic Procedures Cranial CT or MRI scan - Mild AD: normal or MTL atrophy - Advanced AD –Generalized atrophy EEG - Diffuse slowing (theta/delta range) in late disease CSF analysis - Normal, slight increase in total protein 30Reference

31. Alzheimer’s Disease Diagnostic Procedures Neuropsychological Tests - Poor memory, verbal skills in early to moderate stages Biologic Markers - CSF tau and β amyloid - Inflammatory markers –Isopostane (serum & CSF) 31Reference

32. Lewy Body Disease

33. Characterized by cortical neurons which contain Lewy Bodies –a-synuclein (related to Parkinson’s Disease) Marked psychiatric symptoms Differentiated from AD lack of prominent –neurofibrillary changes –senile plaques Clinical Features –Fluctuating confusion –Visual Hallucinations –Paranoid delusions –Neuroleptic sensitivity –Orthostatic hypotension 33Reference

34. Pick’s Disease

35. Also known as lobar atrophy Asymmetrical circumscribed atrophy (fronto- temporal) Paper thin gyri corpus callosum anterior commissure Loss of neurons in first 3 layers and swelling of neurons containing argentophilic (Pick) bodies in the cytoplasm Straight fibrils in MTL Ballooned cortical neurons in cortex Astrocytic gliosis in cortical and subcortical areas 35Reference

36. Pick’s Disease Clinical Features Difficult to diagnose clinically Prominent alteration in personality and behavior Dysexecutive syndrome Frontal release signs Early aphasia (dominant F-T dysfunction) Frontal type: taciturn, inert, dull emotionally, lack initiative Temporal type: talkative, lighthearted, cheerful or anxious, attentive to every incident Neglect of personal hygiene and grooming More hallucinations than AD Unknown causes 2-5 years course of illness 36Reference

37. Frontotemporal Dementia

38. Frontotemporal Frontal and temporal lobe degeneration Histology –Tau staining material in affected neurons Chromosome 17 Heritable and non-heritable –Pathology: cell loss, microvacuolation of frontal and temporal cortex, gliosis, tau protein deposition 38Reference

39. Frontotemporal Diffuse cortical degeneration of the frontal lobes –Early personality changes (apathy/disinhibition) –Euphoria –Perseveration –Ritualistic and repetitive behavior –Speech deterioration –Poor judgment and abstraction –Disinhibition Anterior temporal lobe involvement –Hyperorality and hyperphagia Lateral Temporal lobe –Aphasic and word-finding syndrome –Initial and predominant feature 39Reference

40. Diagnostic Procedures

41. Mini-Mental State Examination Blood tests Cranial CT scan or MRI Single-photon emission CT (SPECT) EEG CSF analysis 41Reference

42. Mini-Mental State Examination assesses cognitive abilities such as orientation to time and place, use of language, memory, attention, and abilities to carry out various tasks and follow instructions 42Reference

46. Blood tests check for infections or conditions such as vitamin deficiency, anemia, medication levels, disorders of the thyroid, kidneys or liver 46Reference

47. Cranial CT scan or MRI reveals reduction in the size of the brain (atrophy), widened indentations in the tissues, and enlargement of the cerebral ventricles 47Reference

48. Single-photon emission CT (SPECT) imaging detects blood flow in the brain used in some medical centers to distinguish Alzheimer’s disease from vascular dementia 48Reference

49. EEG diffuse slowing (theta/delta range) in late disease 49Reference

50. CSF analysis normal, slight increase in total protein biologic markers: amyloid beta or tau proteins 50Reference

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