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

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

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

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

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

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

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

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

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

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

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

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

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

Double vision = brainstem or cranial nerve

Personality changes = Frontal > Temporal Lobe

Parkinsonism = substantia nigra (deep gray)

? opsoclonus

Associated symptoms are important for defining the pathology, not localization

OculomotorLimbic Extrapyramidal Midbrain Frontal LobeBasal Ganglia

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

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

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

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

Paraneoplastic Syndrome (Whipple’s is a close second)