Johns Hopkins University Johns Hopkins University School of MedicineSchool of Medicine

Clinico-Pathological ConferenceClinico-Pathological Conference

Benjamin M. Greenberg, M.D., M.H.S.Benjamin M. Greenberg, M.D., M.H.S.

Assistant ProfessorAssistant Professor

Department of NeurologyDepartment of Neurology

Johns Hopkins School of MedicineJohns Hopkins School of Medicine

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

White Matter

Deep Gray

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Differential Diagnosis at This Differential Diagnosis at This PointPoint

Cortex

BrainstemSpinal CordNerve RootPlexusNerveNeuromuscular JunctionMuscle

CerebellumSubcortex

Time course is important for definingpathologic process, not localization.

Double vision = brainstem or cranial nerve

Personality changes = Frontal > Temporal Lobe

Parkinsonism = substantia nigra (deep gray)

? opsoclonus

Associated symptoms are important fordefining the pathology, not localization

Oculomotor Limbic Extrapyramidal

Midbrain Frontal Lobe Basal Ganglia

Subacute Central Nervous System Degeneration Subacute Central Nervous System Degeneration with Parkinsonism, Eye Movement Abnormalities with Parkinsonism, Eye Movement Abnormalities

and Frontal Love Dysfunctionand Frontal Love Dysfunction

““Degenerative”Degenerative”– Parkinson’s DiseaseParkinson’s Disease– Progressive Supranuclear Progressive Supranuclear

PalsyPalsy– Corticobasal DegenerationCorticobasal Degeneration– Diffuse lewy body diseaseDiffuse lewy body disease

Toxic/MetabolicToxic/Metabolic– Wilson’sWilson’s– ManganeeseManganeese– MPTPMPTP

InfectiousInfectious– Whipple’sWhipple’s– Prion DiseasesPrion Diseases– FlavivirusesFlaviviruses

Mitochondrial DisordersMitochondrial Disorders

NutritionalNutritional– DeficienciesDeficiencies

B12B12ThiamineThiamine

Medications/DrugsMedications/Drugs– Dopamine AntagonistsDopamine Antagonists

Immune MediatiedImmune Mediatied– ParaneoplasticParaneoplastic– ADEMADEM– Multiple SclerosisMultiple Sclerosis

NeoplasticNeoplastic– CNS lymphomaCNS lymphoma– Intravascular lymphomaIntravascular lymphoma– GliomaGlioma

Subacute Central Nervous System Degeneration Subacute Central Nervous System Degeneration with Parkinsonism, Eye Movement Abnormalities with Parkinsonism, Eye Movement Abnormalities

and Frontal Love Dysfunctionand Frontal Love Dysfunction

““Degenerative”Degenerative”– Parkinson’s DiseaseParkinson’s Disease– Progressive Supranuclear Progressive Supranuclear

PalsyPalsy– Corticobasal DegenerationCorticobasal Degeneration– Diffuse lewy body diseaseDiffuse lewy body disease

Toxic/MetabolicToxic/Metabolic– Wilson’sWilson’s– ManganeeseManganeese– MPTPMPTP

InfectiousInfectious– Whipple’sWhipple’s– Prion DiseasesPrion Diseases– FlavivirusesFlaviviruses

Mitochondrial DisordersMitochondrial Disorders

NutritionalNutritional– DeficienciesDeficiencies

B12B12ThiamineThiamine

Medications/DrugsMedications/Drugs– Dopamine AntagonistsDopamine Antagonists

Immune MediatiedImmune Mediatied– ParaneoplasticParaneoplastic– ADEMADEM– Multiple SclerosisMultiple Sclerosis

NeoplasticNeoplastic– CNS lymphomaCNS lymphoma– Intravascular lymphomaIntravascular lymphoma– GliomaGlioma

Whipple’s DiseaseWhipple’s Disease

First described in 1907 by George Hoyt Whipple, First described in 1907 by George Hoyt Whipple, a JHH pathologista JHH pathologist– He developed recurring arthropathy, weight loss, and He developed recurring arthropathy, weight loss, and

steatorrhoea, became worse, and died. At necropsy steatorrhoea, became worse, and died. At necropsy the intestine and mesenteric lymph glands were the intestine and mesenteric lymph glands were infiltrated by mononuclear cells and deposits of fat.infiltrated by mononuclear cells and deposits of fat.

Weakly gram positive rod, Weakly gram positive rod, ActinomycetesActinomycetes NeurologicallyNeurologically– Cognitive declineCognitive decline– Vertical Gaze difficultyVertical Gaze difficulty– Oculomasticatory myorhythmia Oculomasticatory myorhythmia – Movement disordersMovement disorders

ParaneoplasticParaneoplastic

Subacute presentationsSubacute presentationsOpsoclonus Opsoclonus – small cell lung cancersmall cell lung cancer– NeuroblastomaNeuroblastoma– Gynecologic malignanciesGynecologic malignancies

Limbic Encephalitis Limbic Encephalitis – small cell lung cancer (anti-Hu)small cell lung cancer (anti-Hu)– Germ cell tumorsGerm cell tumors– can have brainstem encephalitis.can have brainstem encephalitis.

Can precede malignancy by yearsCan precede malignancy by years

Paraneoplastic SyndromeParaneoplastic Syndrome

(Whipple’s is a close second)(Whipple’s is a close second)