The Brigham Department of Neurology

Martin A. Samuels, Chairman

Director, Brigham and Women’s Institute for the Neurosciences
Miriam Sydney Joseph Professor of Neurology
Harvard Medical School

Miriam Sydney
Joseph Samuels
Conflict of Interest Disclosure

NONE
 Update in Neurology
ACP 2017
Martin A. Samuels, MD, MACP
Chairman, Department of Neurology
Brigham and Women’s Hospital
Miriam Sydney Joseph Professor of Neurology
Harvard Medical School
 Update in Neurology 2017
• Stroke and Cerebrovascular Diseases
• Neuromuscular Diseases
• Movement Disorders
• Traumatic Brain Injury
• Nociception, Pain, Suffering and Opioids
• Autoimmune Neurology
• Neurocardiology
 Stroke and Cerebrovascular Diseases
• Since 2015 endovacular Rx is an option
• Some trials terminated early; small sample size
• Meta-analysis of five trials
– 1287 participants
– Primary outcome: disability at 3 months
– Mean age 67 year; 47% female
– Median time to trial entry = 196 minutes
– Median time to arterial puncture = 238 minutes
– Median time to reperfusion = 286 minutes
– 71% proximal MCA; 22% distal internal carotid
– Results
• Disability increased with Rx delay
• 3 hours: OR = 2.79; risk difference = 39.2%
• 6 hours: OR = 1.98; risk difference = 30.2%
• 8 hours: OR = 1.58; risk difference = 0
• Risk reduction persisted through 7 hours, 18 minutes
• Conclusions: benefit for about 6-7 hours post stroke

Badhiwala JH et al. Endovascular thrombectomy for acute ischemic stroke: a

meta-analysis. JAMA 2015; 314: 1832.
 Neuromuscular Diseases
• Acquired myasthenia gravis (MG) is caused by binding of
autoantibodies to acetylcholine receptors
• Thymectomy in non-thymomatous cases was controversial
• Randomized trial of 126 patients with generalized non-
thymomatous MG of less than 5 years duration
• All were class II-IV (generalized) with anti-receptor Abs
• Results: Thymecomy patients
– had lower MG score compared to prednisone alone
– Had lower average requirements for alternate-day prednisone
– Required less immunosupprsssion with azathioprine
– Were less likely to be admitted for exacerbations
• Conclusion: Thymectomy improves outcome in acquired
generalized MG, but is not a cure

Wolfe GI et al. Randomized trial of thymectomy in myasthenia gravis. N

Engl J Med 2016; 375: 511.
 Movement Disorders
• Braak hypothesis: abnormally folded protein (α-
synuclein) carried from the gut by nerves to CNS;
vagus a major pathway
• Swedish and Danish National Patient Registries
queried and results were similar
• Results: Up to 20 years post truncal vagotomy, there
is a lower risk of Parkinson disease; not true for
selective (gastric) vagotomy
• Conclusions: Data support the Braak hypothesis of
the pathogenesis of PD, but vagotomy is not
recommended as a treatement for PD
Svensson E et al. Vagotomy and subsequent risk of
Parkinson disease. Ann Neurol 2015; 78: 522-529
 Movement Disorders
• Braak hypothesis: abnormally folded protein (α-
synuclein) carried from the gut by nerves to CNS;
vagus a major pathway
• Swedish and Danish National Patient Registries
queried and results were similar
• Results: Up to 20 years post truncal vagotomy, there
is a lower risk of Parkinson disease; not true for
selective (gastric) vagotomy
• Conclusions: Data support the Braak hypothesis of
the pathogenesis of PD, but vagotomy is not
recommended as a treatement for PD
Svensson E et al. Vagotomy and subsequent risk of
Parkinson disease. Ann Neurol 2015; 78: 522-529
Mild Traumatic Brain Injury (Concussion)
• Concussion: a neurological deficit caused by
head injury (formerly loss of consciousness from
trauma).
• Chronic traumatic encephalopathy (CTE)
– Dementia pugilistica
– Tau (tangle) pathology
– ? Prion-like pathophysiology

McKee A et al. The neuropathology of chronic traumatic

encephalopathy. Brain Pathology 2015; 25: 350.
Can A Folded Protein Released By Head Injury Spread Like A Prion?
Frank L. Wiley Junior High School
Football Team 1959
Frank L. Wiley Junior High School
Football Team 1959
Frank L. Wiley Junior High School
Football Team 1959
Frank L. Wiley Junior High School
Football Team 1959
Tom Mack in High School
Marty Samuels in High School
Marty Samuels in High School
Tom Mack, University of Michigan
Tom Mack NFL Hall of Fame
184 Straight Games
Marty Samuels, Neurologist
40 Straight Years as a Doctor
 A Balanced View
• Protein aggregation may, in fact, be an important
mechanism in neurodegeneration (e.g. amyloid,
tau, prion, ubiquitin, synuclein)
• Genetics are probably the main determinant of
protein self-aggregation, but other factors (e.g.
infection, trauma, environmental exposures) are
possibly also important
• As in all of medicine (and in life) one must weigh
the relative benefits and risks of any activity (e.g.
sports, foods, sex)
 Nociception, Pain and Suffering
• Nociception: potentially tissue damaging
stimuli
• Pain: the unpleasant effects of nociception
• Suffering: A psychological state of dysphoria.
Causes include Pain, poverty, war and
numerous other social factors
• Opiods (endogenous and exogenous) are
useful for pain due to nociception
• Treating suffering with opioids can lead to
complications
Nociception Transmission System
Descending Nociception Modulation System
 Consequenses of Nociception
• Neurogenic inflammation is caused by innervation
of vessels and other structures by neurons that
mediate nociception (the inflammatory reflex), a
process that can be inhibited by serotonin Ib and
Id receptor activity
• The inflammatory reflex may result in a CSF
pleocytosis
• A slowly migrating negative wave may arise in the
cortex (spreading depression), which is probably
the cause of the aura of some migraines
• Pain only results when the afferent limb of the
reflex reaches the thalamus
• Chronic pain is one cause of suffering
• Opioids used to treat chronic pain causes
suffering rather than relieve it
 Autoimmune Neurology
• Paraneoplastic and now “benign” diseases

• Intracellular antigens
– Hu
– Ro
– Etc

• Cell surface antigens

– VGKC
• LGI1
• Caspr 2
– NMDA
 Neurocardiology
• Takotsubo-like cardiomyopathy
• Catecholamine toxicity
• Balance of autonomic innervation protects
 Patient Case History
(courtesy of Leonard Lilly, M.D.)
• 62 year old woman, previously healthy,
presented to hospital with chest
discomfort
• Symptoms began 6 hours earlier,
described as a diffuse anterior heaviness
with shortness of breath; started
minutes after being told that her son
was seriously injured in an automobile
accident
Laboratory Studies
Echocardiogram
LAD Coronary Angiogram
Right Coronary Angiogram
Left Ventriculogram
 Clinical Course
• Remained clinically stable: chest
discomfort resolved; no heart failure or
arrhythmias
• Maintained on aspirin, beta-blocker, ACE
inhibitor; No diuretic requirement
• Discharged on hospital day 3
• Returned for repeat echocardiogram
Repeat Echocardiogram
Two weeks later
Schematic Diagram of the Innervation of the Heart
(after Truax)
 Two Sisters

A woman in her 70’s collapses and is

brought to the emergency department by
her sister, who is told the the problem is a
lethal intracerebral hemorrhage. Upon
hearing the news the second sister also
collapses.
Sister 1

Sister 2
Debby Reynolds and Carrie Fisher
 Update in Neurology 2017
• Stroke and Cerebrovascular Diseases
• Neuromuscular Diseases
• Movement Disorders
• Traumatic Brain Injury
• Nociception, Pain, Suffering and Opioids
• Autoimmune Neurology
• Neurocardiology
 Martin A. Samuels
Chairman, Department of Neurology
Brigham and Women’s Hospital
Miriam Sydney Joseph Professor of Neurology
Harvard Medical School

Miriam Sydney
Joseph Samuels

1940 1980 2017

 The Brigham Department of Neurology
Martin A. Samuels, Chairman
Director, Brigham and Women’s Institute for the Neurosciences
Miriam Sydney Joseph Professor of Neurology
Harvard Medical School

Miriam Sydney
Joseph Samuels