Transcript May 3, 2013 - Kyle Carpenter

Neurology Case
Kyle Carpenter PGY III
History of Present Illness
 60 year old left handed male
 Chief complaint- difficult speaking, frequent falls
 On his first visit his wife noted that for past 2 years the
patient’s language and vocabulary had suffered
 He was having trouble recalling words that he wanted to say
 e.g. he was formerly a mechanic and was having trouble
remembering names of tools
 His short term memory had also progressively worsened
during this same time
 Also for about one year prior had been falling frequently (12 times per week)
 Difficulty swallowing and crying spells for no apparent
 He was no longer paying bills or driving
Past medical history
 Hypertension
 Diabetes (A1C of 8.9%)
 Hyperlipidemia
 GERD
 Depression
 Social
 Stopped smoking and
drinking 20 years prior
 Surgery
 CTS in 2011
 Kidney stone
Exam
 Mental status
 Can name correct city, and year but not month or day
 Naming intact.
 2/3 object at 5min recall
 Comprehension intact but perseverates
 Speech
 Fluent but with severe word finding difficulty
 Only 8 objects on “D” test (12 is normal)
 Decreased emotion in speech
 Cranial Nerves
 Intact
 Orbicularis oculi 5/5
 Tongue strength is normal
Exam
 Motor
•
•
Tone is normal
Atrophy of FDI
Right
NF
NE
 3+ Patella
 Downgoing toes
 Gait
5
44
5
5
5
5
HF
4+
4+
HE
KF
KE
DF
PF
4+
4+
5
5
4
5
 3+ in bilaterally UE
 0 Ankle
Left
5
SA
EF
EE
WF
WE
 Reflexes
 Wide based, slow, unable to
walk heel to toe
5
5
5
5
 Cerebellar
 FNF intact but slo
 Sensory
 Difficult to assess but likely
intact to all modalities
5
5
4
5
Second Visit
 CT head showed moderate cortical atrophy
 Seen in clinic three months later
 Almost completely anomic. 1-2 words at the most
 Unable to answer orientation questions
 Could follow 1 step commands but nothing more
complicated
 Confined to a wheelchair, diffuse weakness
 Further atrophy of hands, arms, legs
 Fasciculations seen in leg and arm muscles
 Further testing was done
 Where?
 What?
Frontotemporal Dementia and
Amyotrophic Lateral Sclerosis
FTD-ALS
 Each disease is typically
diagnosed separately
 15% of ALS patients have FTD
 10% of FTD patients
 Slightly more common in men
than women
 Cognitive symptoms typically
occur first but motor
symptoms can occur before or
simultaneously
 Interval is 3 months to 7
years with mean of 2 years
 Survival is worse in FTD-ALS
patients than ALS without
dementia
 A proposed classification
scheme
 ALSci (cognitively impaired)
 ALSbi (behaviorally
impaired)
 ALS-FTD (meet Neary
Criteria)
 FTD-MND (patients who
have motor neuron loss at
autopsy but no clinical
signs)
 ALS-dementia (Alzheimer's
or vascular)
M. J. Strong, G. M. Grace, M. Freedman, et al., “Consensus criteria for the
diagnosis of frontotemporal cognitive and behavioural syndromes in
amyotrophic lateral sclerosis,”Amyotrophic Lateral Sclerosis, vol. 10, no. 4,
pp. 131–146, 2009.
Amyotrophic Lateral Sclerosis
 ALS used interchangeably
with ‘Motor Neuron Disease’
and ‘Lou Gehrig's Disease’
 Diagnosed clinically with a
mixture of upper motor
neuron signs and lower motor
neuron signs

Progressive weakness that
can begin in legs, arms or
bulbar region
 Atrophy and fasciculation
(LMN)
 Hyperreflexia, upgoing toes,
jaw jerk (UMN)
 EMG shows active denervation
and reinnervation

First described in 1869 by Charcot

Marie in 1892 reported on behavioral changes in
ALS patients

Entrenched in Neurology that body wasted and
mind was spared

In late 80s Stan Appel and Forbes Norris
developed clinics devoted to ALS clinics

This concept spread to major centers allowing
Neurologists to develop large ALS patient
populations

Reports were generated linking ALS and dementia

Criteria for FTD were published in 1998 and ALS
and FTD were linked
FRONTOTEMPORAL DEMENTIA
Symptoms

Insidious onset with slow progression

Age 50-60
 Types
 Behavioral variant (bvFTD)
 Disinhibition, apathy, behavior
changes (next slide)
 Primary Progressive Aphasia
 Decreased expression of
language, anomia
 Relative preservation of
comprehension
 Semantic Dementia (now
considered a variant of PPA)
 Fluent grammatically correct
speech but empty of content
 Loss of executive function early
is seen in all three
 Typically preservation of
short term memory,
praxis and visualospatial
skills
 Diagnosed via Neary
Criteria (other criteria
have been suggested)
Table 1: Behavioral features in FTLD
Disinhibited type
Increased interest in sexual activity
Lack of judgment
Swearing
Violation of personal space
Impulsive buying
Paranoia
Criminal activity
Grandiose thinking
Ignoring social etiquette
Apathetic type
Blunted emotions
Disinterested and withdrawn
Lack of attention to personal hygiene
Lack of empathy
Stereotypical type
Hoarding
Food fads, overeating
Ritualistic/repetitive behavior
Testing FTD in ALS patients

Can be difficult to test for language disorders due to
 bulbar weakness (dysarthria),
 hand weakness impairs writing

Cognitive changes can be seen in patients follows in specialty clinics
 Comprehension in pulmonary testing
 Spelling and grammatical errors

Various studies and questionnaires have used to identify dementia in ALS
patients
CANTABCambridge
 CANTAB
Neuropsychological Test Automated
 Computer touch screen and Neurologist opinion
Battery
 Memory loss 7%, FTD
criteria 22%
NPI- Neuropsychiatric
Inventory
 Caregiver
questionnaire Inventory
FBIFrontal Behavioral
CBI- Cambridge
Behavioral
Inventory
 NPI, FBI, CBI,
FrSBe
FrSBe- Frontal
Systems Behavioral
Apathy 56%, stereotypical behaviors 20%, executive dysfunction
Scale
34-48%, disinhibition 18-27% 11% meet criteria for FTD
MMSE- Mini mental Status Exam
FTD In ALS

2003 study of 100 patients screened with verbal fluency and MMSE
 31 had abnormal fluency (“D” or animal test). 50% of bulbar onset
patients had abnormal exam, 25% of limb onset patients
 All had normal MMSE

2012 study of 160 patients with formal neuropsych testing
 14% met FTD-Neary criteria, 21% had cognitive impairment and 47%
were normal

2005 study of 279 patients
 15% with FTD, 49% normal cognition, 43% cognitive impairment

ALS patients over time 52 patients every 4 months showed abnormal at onset did not show
decline
FTD in ALS
 2009 AAN practice
parameter acknowledged
lack of consensus of
screening tool
 ALS Cognitive Behavioral
Screen- has been
validated
 15 caregiver questions
 8 item physician
assessment
 5 min
 Penn State Screen
Battery of Frontal and
Temporal Dysfunction
Syndrome
 20 minutes
 Not validated
 UCSF Screen Battery
 45 minutes, includes
ALS specific FBI and
depression screen
ALS in FTD patients
 Studies have had varied results
 2002 study of 36 FTD patients with detailed
neuromuscular exam and EMG
 5 had definite ALS, 5 had fasciculations on EMG and 1 of
these developed definite ALS 1 year later
 2008 retrospective study of FTDbv
 18 of 61 developed definite ALS
Genetics
 Various genetic mutations
have been linked to both
familial ALS and FTD
 Familial cases are far
outnumbered by sporadic
cases in both disorders
(10% of ALS and 40% of
FTD)
 Three most important
genes associated with FTD
are microtubule associated
protein tau (MAPT),
progranulin and C9ORF72
 Mutations in the SOD1
gene are most common in
familial ALS
 Two studies in 2012 found
a mutation in the
C9ORF72 gene that
occurred in both ALS and
FTD.
 This was the first genetic
link between the two
diseases
 Progranulin and C9ORF72
mutations can deposition
of TAR-DNA binding
protein 43 (TDP-43)
 TDP-43 is an ubiquinated
protein that has been
found to accumulate in
both ALS and FTD
Sources
 ALS and Frontotemporal Dysfunction: A Review. Eugene Y.
Achi and Stacy A. Rudnicki Neurology Research
International
Volume 2012 (2012), Article ID 806306, 9 pages
doi:10.1155/2012/806306

Renton AE, Majounie E, Waite A, et al. A hexanucleotide
repeat expansion in C9ORF72 is the cause of chromosome
9p21-linked ALS-FTD. Neuron 2011;72:257–268
 Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of
revised diagnostic criteria for the behavioural variant of
frontotemporal dementia. Brain 2011;134(pt 9):2456Y2477
 M. J. Strong, G. M. Grace, M. Freedman, et al., “Consensus
criteria for the diagnosis of frontotemporal cognitive and
behavioural syndromes in amyotrophic lateral
sclerosis,”Amyotrophic Lateral Sclerosis, vol. 10, no. 4, pp.
131–146, 2009.