DSS 2013-Case 2 Declan McGuone, Jeremy Schmahmann, E. Tessa Hedley-Whyte, Matthew P. Frosch...

DSS 2013-Case 2

Declan McGuone, Jeremy Schmahmann,

E. Tessa Hedley-Whyte, Matthew P. Frosch

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

Disclosures

NONE

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

Clinical History

• 69 yo pain & stiffness 2 days after neck lipectomy

• No sx of infection or neurologic symptoms

• Hydromorphone (1.5mg + 1mg) & diphenhydramine (25+25 mg)

• Admitted. Next AM unresponsive, hypotensive & hypoxic. Resuscitated and receives Narcan

• Discharged home at baseline 3 days later

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HARVARDMEDICAL SCHOOL

Clinical History, cont.• 3 WKS :

– Behavioral, memory & attention deficits appeared.

– Over next 72 hrs rapid decline in mental status with progressive akinesia, mutism & rigidity

• Lab investigations– Unremarkable

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

T2/FLAIR

Clinical History

• 3 MOS : she was alert, responsive, followed simple commands.

• 6-9 MOS: fluent speech, paranoid & delusional with impaired visuo-spatial, memory encoding, exec. & behavioral functions.

• Death 2 years following presentation

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

1300g

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

Discussion

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PATHOLOGY

HARVARDMEDICAL SCHOOL

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

Neurofilament GFAP

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

CD68 CD45

CD45

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PATHOLOGY

HARVARDMEDICAL SCHOOL

Diagnosis

Delayed post-hypoxic leukoencephalopathy

Delayed post-hypoxic leukoencephalopathy

• A rare complication of prolonged cerebral hypoxia

• The classic clinical presentation is biphasic – patients recover within 24hours of a prolonged hypoxic injury and return to baseline before developing a sudden onset neuropsychiatric syndrome within 1-3 weeks

• Exact incidence is not known

• Etiology of insults reported to cause DPHL is heterogeneous (e.g. anoxic anoxia, anemic anoxia and ischemic anoxia)

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

Delayed post-hypoxic leukoencephalopathy• Two clinical phenotypes:

– Parkinsonism• Rigidity, tremor, masked facies. dystonic posturing, agitation,

apathy, hallucinations, odd behavior, impaired cognition, emotional lability

– Akinetic mutism• Apathy, functional incontinence, pathologic laughter or crying,

• Examination:– Frontal release signs – CST signs (hyperreflexia, Babinski) – Frontal-executive dysfunction

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

Neuropathology

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PATHOLOGY

HARVARDMEDICAL SCHOOL

• Severe diffuse hemispheric demyelination (sparing of U-fibers)

• Morphologically normal oligodendroglia

• No vacuolar change (as sometimes seen with inhaled heroin)

• Preserved neocortical and hippocampal architecture

•Elevated CSF myelin basic protein (marker of acute widespread demyelination)

Plum and Posner, Archives internal medicine, 1962

Mechanism

• Unknown but likely multifactorial

• ? Mitochondrial dysfunction– DPHL can be reproduced in animals using potassium cyanide to

impair cytochrome c (Shprecher D, Mehta L, et al. Neurorehabilitation, 2010)

• ? Reduced cerebral blood flow (DPHL more prevalent and more severe in older patients with cerebrovascular disease)

• ? Pseudodeficiency of Arylsulfatase A (Gottfried JA, Mayer SA et al. Neurology 1997)

• ? Delayed oligodendroglial apoptosis (Chu K, Jung KH et al. Eur Neurol 2004)

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL

References[1] Plum F, Posner JB, et al. Delayed neurological deterioration after

anoxia. Arch Intern Med, 1962

[2] Shprecher D, Mehta L. The syndrome of delayed post-hypoxic leukoencephalopathy. Neurorehabilitation, 2010.

[3] Shprecher D, Flanigan K et al. Clinical and diagnostic features of delayed hypoxic leukeoncephalopathy. J Neuropsychitary Clin Neurosci, 2008

[4] Choi IS. Delayed neurologic sequelae in carbon monoxide intoxication. Arch Neurol, 1983

[5] Gottfried JA, et al. Delayed posthypoxic demyelination. Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy. Neurology 1997.

MASSACHUSETTSGENERAL HOSPITAL

PATHOLOGY

HARVARDMEDICAL SCHOOL