1. Johns Hopkins University School of Medicine Clinico-Pathological Conference Benjamin M. Greenberg, M.D., M.H.S. Assistant Professor Department of Neurology Johns Hopkins School of Medicine

3. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

4. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

5. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex White Matter Deep Gray

6. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

7. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

8. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

9. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

10. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

11. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

12. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

13. Differential Diagnosis at This Point Cortex Brainstem Spinal Cord Nerve Root Plexus Nerve Neuromuscular Junction Muscle Cerebellum Subcortex

15. Time course is important for defining pathologic process, not localization.

16. Double vision = brainstem or cranial nerve

17. Personality changes = Frontal > Temporal Lobe

18. Parkinsonism = substantia nigra (deep gray)

19. ? opsoclonus

20. Associated symptoms are important for defining the pathology, not localization

21. OculomotorLimbic Extrapyramidal Midbrain Frontal LobeBasal Ganglia

24. Subacute Central Nervous System Degeneration with Parkinsonism, Eye Movement Abnormalities and Frontal Love Dysfunction “Degenerative” –Parkinson’s Disease –Progressive Supranuclear Palsy –Corticobasal Degeneration –Diffuse lewy body disease Toxic/Metabolic –Wilson’s –Manganeese –MPTP Infectious –Whipple’s –Prion Diseases –Flaviviruses Mitochondrial Disorders Nutritional –Deficiencies B12 ThiamineMedications/Drugs –Dopamine Antagonists Immune Mediatied –Paraneoplastic –ADEM –Multiple SclerosisNeoplastic –CNS lymphoma –Intravascular lymphoma –Glioma

29. Subacute Central Nervous System Degeneration with Parkinsonism, Eye Movement Abnormalities and Frontal Love Dysfunction “Degenerative” –Parkinson’s Disease –Progressive Supranuclear Palsy –Corticobasal Degeneration –Diffuse lewy body disease Toxic/Metabolic –Wilson’s –Manganeese –MPTP Infectious –Whipple’s –Prion Diseases –Flaviviruses Mitochondrial Disorders Nutritional –Deficiencies B12 ThiamineMedications/Drugs –Dopamine Antagonists Immune Mediatied –Paraneoplastic –ADEM –Multiple SclerosisNeoplastic –CNS lymphoma –Intravascular lymphoma –Glioma

30. Whipple’s Disease First described in 1907 by George Hoyt Whipple, a JHH pathologist –He developed recurring arthropathy, weight loss, and steatorrhoea, became worse, and died. At necropsy the intestine and mesenteric lymph glands were infiltrated by mononuclear cells and deposits of fat. Weakly gram positive rod, Actinomycetes Neurologically –Cognitive decline –Vertical Gaze difficulty –Oculomasticatory myorhythmia –Movement disorders

31. Paraneoplastic Subacute presentations Opsoclonus –small cell lung cancer –Neuroblastoma –Gynecologic malignancies Limbic Encephalitis –small cell lung cancer (anti-Hu) –Germ cell tumors –can have brainstem encephalitis. Can precede malignancy by years

33. Paraneoplastic Syndrome (Whipple’s is a close second)