Clinicopathologic Conference (CPC) 02/05/16 Neurology Resident: Diana Mnatsakanova Pathologist: Ronald Hamilton

History HPI: AW is a 90 yo woman with hx of gait instability and falls who was followed by movement disorders clinic. Problems with balance started since MVA in 2007, after which she started experiencing gait instability and falls. She typically fell backwards. She also had noted weakness which was mostly related to slowness. She had noted left sided rest tremor in 2013 which progressed to the right side. No hx of hallucination, confusion, delusions, REM sleep abnormalities. She was started on a trial of Sinemet in 2014 up to 2 tabs QID with minimal improvement as she continued to have retropulsion. Tremors did not improve. Over time, her gait worsened, requiring use of a walker. She was bedridden by the end of 2015 at which point CT of chest/abdomen revealed numerous masses, pulmonary nodules and lymphadenopathy; Care was transitioned to comfort measures. ROS was positive for urinary incontinence and memory problems (mostly amnestic without fluctuations). PMH: MVA in 2007, concussion, migraine headaches, vertigo, TIAs Medications: Asa, Ritalin, Zoloft, Ca-VitD

Examination MENTAL STATUS: Alert , oriented x4, speech without dysarthria, language intact. Concentration and fund of knowledge appropriate. Present Glabellar sign. CN: EOMs with intact range, smooth pursuits slightly saccadic, saccades with normal speed and range, absent nystagmus, absent square wave jerks; otherwise unremarkable MOTOR: low amplitude low frequency rest tremor was present LUE>RUE; tone was increased mildly LUE>RUE, mild bradykinesia present more on LUE > RUE. Full strength throughout SENS: intact to light touch REFLEX: : 2+ throughout, plantar responses flexor, absent Hoffman’s sign COORD: no dysmetria on FTN, HTS, Negative Romberg GAIT: able to stand up with assistance slowly, shortened stride length, slow pace and intermittent hesitation, turns with multiple steps, some postural truncal swaying during ambulation, stance with normal base, pull test was positive, normal arm swing.

Radiology

Differential Diagnosis Atypical Parkinsonism – given early falls with retropulsion, poor response to levodopa. Did have urinary incontinence but this was noted immediately after MVA without signs of progression. Overall hx and exam do not fit any particular type of parkinsonian plus syndrome such as CBD, PSP, or MSA Dementia with Lewy bodies – memory difficulties, inattentive, although no hx of hallucination or fluctuating confusion Idiopathic Parkinson Disease – asymmetric presentation, gradual progression Vascular Parkinsonism- white matter changes, hydrocephalus ex vacuo on MRI

Predicted Pathology Parkinson’s Disease Predicted Gross pathology: Pallor of the substantia nigra (SN) and possibly locus ceruleous Cortical Atrophy and ventricular dilatation Predicted Micro pathology: Loss of neurons in the SN; presence of Lewy bodies in the SN, locus ceruleus, dorsal motor nuclear of vagus, nucleus basalis of Meynert Cortical Lewy bodies Immunohistochemical features: α-synuclein and ubiquitin glial inclusions; Lewy neurites with α-synuclein, ubiquitin, or neurofilaments Dementia with Lewy Bodies Cortical and brain stem Lewy bodies Three levels of involvement: brain stem, limbic, and neocortical Diffuse and neuritic plaques and neurofibrillary tangles

Predicted Pathology Multiple System Atrophy Predicted Gross pathology: MSA-P: atrophy and discoloration of the putamen, atrophy of caudate nucleus MSA-C: atrophy of cerebellum, middle cerebellar peduncle, and pons Pallor of the substantia nigra (SN) in both types Predicted Micro pathology: MSA-P: neuronal loss and astrocytosis in the striatonigral system MSA-C: cerebellar degeneration with Purkinje cell loss Immunohistochemical features: α -synuclein, ubiquitin, and tau glial cytoplasmic inclusions in the pyramidal, extrapyramidal, limbic, corticocerebellar, and supraspinal autonomic systems

Virtual microscopy Frontal CTX Slide A Midbrain Slide G H&E Abeta Tau Midbrain Slide G Hippocampus Slide E