European Journal of Neurology 2007, 14: 860–864 doi:10.1111/j.1468-1331.2007.01773.

Extrapyramidal signs, primitive reflexes and incontinence in fronto-temporal

dementia
J. Diehl-Schmida, J. Schu
lte-Overbergb, J. Hartmanna, H. Förstla, A. Kurza
and P. Häussermannb,c
Departments of aPsychiatry and bNeurology of Technische Universität München, München; and cDepartment of Psychiatry, University of
Kiel, Kiel, Germany

Keywords:
extrapyramidal signs,
fronto-temporal dementia,
incontinence, primitive
reflexes
Received 12 September 2006
Accepted 12 February 2007
According to the diagnostic consensus criteria [1] akinesia, rigidity and tremor as well
as primitive reflexes and incontinence support the diagnosis of fronto-temporal
dementia (FTD). However, the prevalence of extrapyramidal signs (EPMS), primitive
reflexes and incontinence in FTD has not yet been systematically studied. In the
present study, thirty-one patients with mild or moderate FTD without previous or
present antipsychotic medication underwent a detailed neurological exam including
the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS). The
average total score on the motor subscale of the UPDRS was 14.0 points. Akinesia
and Parkinsonian gait or posture were found frequently but were mild in most in-
stances. Rigidity was found in 36% of the patients. Resting tremor was a rare
symptom. The only primitive reflex that occurred was a positive palmomental that was
found in 7% of the patients. Urinary incontinence was present in 26%. The results
have to be confirmed with larger or pooled patient samples from different ascertain-
ment scenarios. If the results of the present study can be replicated, a revision of the
consensus criteria from 1998 might be considered.

ior, speech, and language the core and supportive

Introduction
For a long time dementia secondary to fronto-temporal
lobar degeneration (FTLD) has been considered a rare
condition and a difficult diagnosis. Since the introduc-
tion of detailed consensus criteria in 1998 [1], however,
it has become obvious that FTLD probably accounts
for 50% of presenile cases of dementia [2,3] and for
3–20% of all dementias [3–6]. The consensus criteria
divide FTLD into three major clinical subtypes: (i)
fronto-temporal dementia (FTD), a behavioral syn-
drome that results from selective involvement of the
frontal and/or temporal cortices; (ii) semantic dementia
defined as a disorder of language, semantics and
recognition of visual percepts caused by predominant
anterior temporal pathology; and (iii) progressive non-
fluent aphasia, a syndrome associated with asymmetric
degeneration of the fronto-temporal cortex in the
language-dominant hemisphere.
The consensus criteria, developed by the participants
of an international workshop on FTLD, specify core
and supportive features for each of the three proto-
typical syndromes and provide broad inclusion and
exclusion criteria. In addition to the aspects of behav-
Correspondence: Dr Janine Diehl-Schmid, Klinik und Poliklinik für
Psychiatrie und Psychotherapie der TU München, Ismaninger Str. 22,
81675 München, Germany (tel.: +49 89 4140 4279; fax:
+49 89 4140 4923; e-mail: janine.diehl@lrz.tum.de).
features include physical signs. Specifically, the presence
of extrapyramidal signs (EPMS), akinesia, rigidity,
tremor, or primitive reflexes is considered to make the
diagnosis of FTD more probably. Furthermore,
incontinence is listed as a supportive diagnostic feature
of FTD. However, no empirical evidence is provided in
the consensus paper to underpin the diagnostic role of
physical and neurological signs.
The neurological symptoms presented by patients
with FTD have been described in case studies [7], a few
studies have addressed the neurological signs associated
with FTLD [8–10], and the prevalence of EPMS has
been analyzed in histopathological subtypes of FTLD
[11]. To date, however, no study has systematically
looked at the prevalence of EPMS, primitive reflexes
and urinary/fecal incontinence in FTD. Therefore the
aim of the present study was to assess the prevalence of
these neurological features in FTD. A second objective
was to investigate, if frequency/severity of EPMS
correlates with demographic or clinical variables.
Patients and methods
Thirty one consecutively referred outpatients (eight
female, 23 male) received a comprehensive neurological,
neuropsychological and psychiatric work-up at a
university outpatient unit for cognitive disorders.
Patients were included in the study who fulfilled the

860 Ó 2007 EFNS


revised Lund-Manchester diagnostic criteria [1] for
FTD and who showed a significant fronto-temporal
reduction of glucose uptake on 18F-fluorodeoxy glu-
cose (FDG) positron emission tomography. The diag-
nosis was established by consensus of two experienced
geriatric psychiatrists (JD-S, AK). The diagnostic
evaluation included a history obtained from the patient
and the caregiver, a psychiatric assessment, and a
laboratory screen. All patients underwent neuropsy-
chological testing which included the Mini-Mental-
State-Examination (MMSE) as a measure of cognitive
impairment [12], the German version of the Consortium
to Establish a Registry of Alzheimer’s Disease Neuro-
psychological Assessment Battery [13], and a selection
of frontal executive tests. Neuropsychiatric symptoms
were ascertained using the Frontal Behavioral Inven-
tory (FBI) [14]. The overall severity of disease was rated
on the Clinical Dementia Rating (CDR) [15]. Cranial
computed tomography or magnetic resonance imaging
was performed to exclude other causes of focal brain
damage. All patients underwent 18F-FDG-positron
emission tomography. A thorough standardized neu-
rological examination was carried out by a neurologist
with special experience in movement disorders (PH).
EPMS were assessed using the motor part (PART III)
of the Unified Parkinson’s Disease Rating Scale (UP-
DRS) [16]. It contains 31 items designed to rate the
severity of motor symptoms that are typically found in
patients with Parkinson’s disease (PD), including
speech, facial expression, resting tremor (neck, right
arm, left arm, right leg, left leg), action tremor (right
arm, left arm), rigidity (neck, right arm, left arm, right
leg, left leg), finger taps (right, left), hand movements
(right, left), rapid alternating movements (right, left),
leg agility (right, left), arising from a chair, posture,
gait, postural stability, and body bradykinesia. Symp-
toms are rated on a scale of 0–4 (0 ¼ normal; 4 ¼
maximum impairment) which yields a maximum
(worst) score of 108. To assess the frequency of neu-
rological symptoms, we combined the UPDRS motor
items into four domains and transformed them to
dichotomous variables (symptom present or absent): (i)
resting tremor, (ii) rigidity, (iii) akinesia (including fa-
cial expression, finger tips, hand movements, leg agility
and body bradykinesia), and (iv) Parkinsonian posture/
gait. Primitive reflexes (grasp, suck, palmomental) were
assessed and the presence of urinary and fecal incon-
tinence was recorded.
With regard to the high rates of extrapyramidal ad-
verse effects of antipsychotic drugs in FTD [17] patients
with previous or present antipsychotic treatment were
excluded. Patients were also excluded who fulfilled
clinical diagnostic criteria for amyotrophic lateral
sclerosis [18], corticobasal degeneration (CBD) as de-
Ó 2007 EFNS European Journal of Neurology 14, 860–864
Physical signs in fronto-temporal dementia 861
fined by unilateral rigidity, prominent apraxia and alien
hand syndrome [19], or possible progressive supranu-
clear palsy (PSP), requiring either vertical supranuclear
gaze palsy or both slowing of vertical saccades and
prominent postural instability, and falls in the first year
of onset [20].
The study was approved by the ethics committee of
the medical faculty at Technische Universität München,
and informed consent was obtained from all patients
prior to their inclusion in the study in accordance with
the Declaration of Helsinki.
Statistical analysis
The correlation between the total score of the motor
part of the UPDRS and gender, age, age at onset,
duration of the disease, severity of dementia and total
score on the FBI was analyzed using Spearman’s cor-
relation coefficient.
Results
Demographic information, mean MMSE and FBI
scores, duration and severity of the disease are shown in
Table 1.
The severity of dementia was mild (CDR 0.5 or 1) in
24 patients and moderate (CDR ¼ 2) in seven. The
mean score on the motor subscale of the UPDRS was
14.0 points. The frequency of EPMS is presented on
Table 2. Akinesia was the most prevalent symptom
(84%). Parkinsonian gait or posture was found in 71%
of the patients, rigidity and postural instability in 36%.
Resting tremor was only observed in a few cases (7%).
Seven percent of the patients had a positive palmo-
mental reflex. Other types of primitive reflexes were
absent. Urinary incontinence was found in 26% of the
patients (five with mild dementia, three with moderate
dementia). Four of the patients with urinary incontin-
ence suffered from additional fecal incontinence.
Table 1 Patient characteristics
N 31
Female/male 8/23
Age at onset* 63.1 (9.1)
Age* 67.8 (9.5)
Disease duration* 4.8 (2.9)
MMSE* 23.1 (4.8)
FBI* 27 (9.8)
N (CDR ¼ 0.5) 11
N (CDR ¼ 1) 13
N (CDR ¼ 2) 7
*Mean (SD).
MMSE, Mini-Mental-State-Examination; FBI, Frontal Behavioral
Inventory; CDR, Clinical Dementia Rating.
862 J. Diehl-Schmid et al.

Table 2 UPDRS mean total score and prevalences of EPMS, primitive not rely on standardized assessment instruments very
reflexes and incontinence mild Parkinsonian signs may be overlooked. Another
N 31 study examined EPMS in a patient population with
UPDRS (mean (SD) (min–max) 14.0 (13.0) (0–56) FTLD in neuronal intermediate filament inclusion dis-
Akinesia 83.9% ease and found EPMS in eight of 10 patients [11]. These
Rigidity 35.5% results are very similar to what we found in our study.
Resting tremor 6.5%
Parkinsonian posture/gait 71.0%
In comparison, EPMS in AD seem to be less frequent
Postural instability 35.5% in mild to moderate stages. A number of studies have
Primitive reflexes 6.7% shown, that akinesia and Parkinsonian gait and posture
Urinary incontinence 25.8% were the most frequent EPMS in patients with AD,
Fecal incontinence 12.9% occurring in about up to 40% of patients free of neuro-
N, number of patients; SD, standard deviation; UPDRS, Unified leptic medication. Tremor was found to be the least
Parkinson’s Disease Rating Scale; EPMS, extrapyramidal signs. frequent symptom (up to 10%) [21–23].
In the current study, the UPDRS total score did not
correlate with the duration of the disease or the severity
Table 3 Associations between the total UPDRS score, demographic of cognitive or behavioral symptoms as assessed using
variables and total scores on the MMSE and FBI the MMSE and the FBI. However, a significant, pos-
Correlation itive correlation was found between motor symptoms
Variable coefficient P and the patientsÕ age and age of disease onset. This
finding is consistent with the repeated observation that
Age 0.39 0.03
Age at onset 0.40 0.03 the prevalence of EPMS increases with advancing age,
Sex 0.31 0.09 both in cognitively healthy individuals [24–26] and in
Duration of disease 0.02 0.92 patients with AD [21].
Cognitive impairment (MMSE) )0.23 0.24 The pathophysiologic basis of EPMS in FTLD re-
Neuropsychiatric symptoms (FBI) 0.24 0.19
mains unclear. EPMS may in part be related to atrophy
UPDRS, Unified Parkinson’s Disease Rating Scale; MMSE, of the basal ganglia found in FTLD [27]. Neuronal loss
Mini-Mental-State-Examination; FBI, Frontal Behavioral Inventory. within the substantia nigra has been found in several
patients with FTLD [28] and has extensively been des-
cribed in idiopathic PD. Furthermore, a similar
There were moderate but statistically significant impairment of the nigrostriatal dopaminergic pathways
positive associations between the UPDRS total score has been recently found in FTD as in idiopathic PD,
and age as well as age at onset. The UPDRS score was with the projections to the putamen and the caudate
unrelated to gender, duration of illness, global severity nuclei being particularly affected. In addition, there is a
of dementia, cognitive impairment, and neuropsychi- reduction of the presynaptic dopamine transporter in
atric symptoms (Table 3). the putamen and the caudate nuclei both in FTD and
PD [29].
A limitation of the current study is the lack of stan-
Discussion
dardized follow-up assessment. Meanwhile it is well
The present study suggests that EPMS, particularly known, that there is a pathological overlap between
akinesia and Parkinsonian gait or posture occur in the FTD, CBD and PSP [30]. Recent studies have shown,
majority of patients with FTD at mild and moderate that a number of the patients with FTD develop CBD
stages of the disease, whereas resting tremor is a very or PSP in the course of the disease [31,32]. It cannot be
rare symptom. Generally, the patients had a low score excluded, that some of the patients of our study have
on the motor subscale of the UPDRS and the range was developed CBD or PSP later in the course of the dis-
wide (0–56 points). This finding could reflect a selection ease, and that the EPMS objectified in these cases were
bias, as the patients of the present study were recruited related to early CBD or PSP.
in a psychiatric unit. We cannot exclude the possibility More than 25% of the patients suffered from urinary
that FTD patients with more marked neurological incontinence. It is noteworthy that in several patients
symptoms are preferentially referred to other institu- urinary incontinence already occurred at early stages of
tions. The prevalence of EPMS in the present study was the disease. Micturition involves a vast network of
higher than was found in a French study, which cortical and subcortical regions. Various animal and
reported Parkinsonism in 40% of 74 patients with neuroimaging studies have referred to the brainstem,
FTLD [10]. That study, however, did not focus on superior frontal lobe and premotor cortical regions
EPMS, and in a routine clinical examination that does as areas implicated in micturition control [33–35].

Ó 2007 EFNS European Journal of Neurology 14, 860–864


Tonically inhibitory efferences to the detrusor muscle
stem from the frontal cortical areas prevent the bladder
from contracting until a socially acceptable time and
place to urinate is available. Within the neurodegener-
ative process of FTD it is very probably, that patients
lose frontal cortical control resulting in an unstable, so
called ÔoveractiveÕ bladder (idiopathic detrusor insta-
bility). This condition is manifested by urinary urgency
and urgency incontinence.
In a proportion of patients with FTD frequent toi-
leting can be observed [36,37]. Mostly it is interpreted as
perseverative or ritualistic behavior but might in fact be
caused by an overactive bladder, at least in some cases.
This has important implications for patient manage-
ment. A treatment attempt with muscarinic M3-select-
ive receptor antagonists, that inhibit involuntary
bladder contractions and have been shown to be
successful in the treatment of urinary urgency [38],
should be undertaken in patients with FTD and urinary
incontinence.
According to the recent diagnostic criteria, akinesia,
rigidity and tremor support the diagnosis of FTD. The
results of our study confirm a high prevalence of aki-
nesia in patients with FTD. The motor abnormalities,
however, were mild in most of the cases, and may be
overlooked in a casual examination. Resting tremor
and primitive reflexes were rare symptoms in patients
with mild or moderate FTD.
Larger studies with patient samples from different
ascertainment scenarios are necessary, that also allow
analyses about the variation of neurological signs
depending on subtypes such as early versus late onset
FTD or genetic versus sporadic FTD. If the results of
our study were replicated, a revision of the diagnostic
criteria might be considered, that excludes tremor and
primitive reflexes as supportive diagnostic features for
FTD.
Acknowledgements
This work was supported by a grant from Kommission
für Klinische Forschung (No. 8765) and by the
Hochschul- und Wissenschaftsprogramm (HWP-II):
Fachprogramm ÔChancengleichheit für Frauen in Fors-
chung und LehreÕ of the Technische Universität Mün-
chen.
References
1. Neary D, Snowden JS, Gustafson L, et al. Frontotem-
poral lobar degeneration. A consensus on clinical diag-
nostic criteria. Neurology 1998; 51: 1546–1554.
2. Hodges J, Davies R, Xuereb J, Kril J, Halliday G. Sur-
vival in frontotemporal dementia. Neurology 2003; 61:
349–354.
Ó 2007 EFNS European Journal of Neurology 14, 860–864
Physical signs in fronto-temporal dementia 863
3. Ratnavalli E, Brayne C, Dawson K, Hodges J. The pre-
valence of frontotemporal dementia. Neurology 2002; 58:
1615–1621.
4. Barker W, Luis C, Kashuba A, et al. Relative frequencies
of Alzheimer’s disease, Lewy body, vascular and fronto-
temporal dementia, and hippocampal sclerosis in the State
of Florida Brain Bank. Alzheimer Disease and Associated
Disorders 2002; 16: 203–212.
5. Gislason T, Sjogren M, Larsson L, Skoog I. The preval-
ence of frontal variant frontotemporal dementia and
frontal lobe syndrome in a population based sample of 85
years old. Journal of Neurology, Neurosurgery, and Psy-
chiatry 2003; 74: 867–871.
6. Rosso S. Frontotemporal Dementia in the Netherlands:
Patient Characteristics and Prevalence Estimates from a
Population-Based Study. Rotterdam: Optima Grafische
Communicatie, 2003.
7. Boeve B, Tremont-Lukats I, Waclawik A, et al. Longi-
tudinal characterization of two siblings with frontotem-
poral dementia and parkinsonism linked to chromosome
17 associated with the S305N tau mutation. Brain 2005;
128: 752–772.
8. Davies R, Hodges J, Kril J, Patterson K, Halliday G,
Xuereb J. The pathological basis of semantic dementia.
Brain 2005; 128: 1984–1995.
9. Knopman D, Boeve B, Parisi J, et al. Antemortem diag-
nosis of frontotemporal lobar degeneration. Annals of
Neurology 2005; 57: 480–488.
10. Pasquier F, Lebert F, Lavenu I, Guillaume B. The clinical
picture of frontotemporal dementia: diagnosis and follow-
up. Dementia and Geriatric Cognitive Disorders 1999;
10(Suppl. 1): S10–S14.
11. Cairns N, Grossmann M, Arnold S, et al. Clinic and
neuropathologic variation in neuronal intermediate
filament inclusion disease. Neurology 2004; 63: 1346–1384.
12. Folstein M, Folstein S, McHugh P. ÔMini Mental StateÕ. A
practical method for grading the cognitive state of pa-
tients for the clinician. Journal of Psychiatric Research
1975; 12: 189–198.
13. Monsch A, Thalmann B. CERAD. The Consortium to
Establish a Registry for Alzheimer’s Disease. Neuropsych-
ologische Testbatterie. Basel: Memory Clinic Basel, 1997.
14. Kertesz A, Davidson W, Fox H. Frontal behavioral
inventory: diagnostic criteria for frontal lobe dementia.
Canadian Journal of Neurological Sciences 1997; 24: 29–36.
15. Hughes C, Berg L, Danziger W, Coben L, Martin R. A
new clinical scale for the staging of dementia. British
Journal of Psychiatry 1982; 140: 566–572.
16. Fahn S, Elton R, Members of the UPDRS Development
Committee. Unified Parkinson’s Disease Rating Scale. In:
Fahn S, Marsden C, Calne D, Goldstein M, eds. Recent
Development in ParkinsonÔs Disease. Florham Park (NJ):
Macmillan Healthcare Information, 1987; 153–163, 293–
304.
17. Pijnenburg Y, Sampson E, Harvey R, Fox N, Rossor M.
Vulnerability to neuroleptic side effects in frontotemporal
lobar degeneration. International Journal of Geriatric
Psychiatry 2003; 18: 67–72.
18. Brooks B, Miller R, Swash M, Munsat T for the World
Federation of Neurology Research Group on Motor
Neuron Diseases. El Escorial revisited: revised criteria for
the diagnosis of amyotrohic lateral sclerosis. Amyotrophic
Lateral Sclerosis and Other Motor Neuron Disorders 2000;
1(Suppl. 2): S293–S298.
864 J. Diehl-Schmid et al.
19. Gibb W, Luther P, Marsden C. Corticobasal degener-
ation. Brain 1989; 112: 1171–1192.
20. Litvan I, Agid Y, Calne D, et al. Clinical research criteria
for the diagnosis of progressive supranuclear palsy
(Steele-Richardson-Olszewski syndrome): report of the
NINDS-SPSP international workshop. Neurology 1996;
47: 1–9.
21. Lopez O, Wisnieski S, Becker J, Boller F, DeKosky S.
Extrapyramidal signs in patients with probable Alzheimer
disease. Archives of Neurology 1997; 54: 969–975.
22. Soininen H, Laulumaa V, Helkala E, Hartikainen P,
Riekkinen P. Extrapyramidal signs in Alzheimer’s disease:
a 3-year follow-up study. Journal of Neural Transmission.
Parkinson’s Disease and Dementia Section 1992; 4: 107–
119.
23. Scarmeas N, Hadjigeorgiou M, Papadimitriou A, et al.
Motor signs during the course of Alzheimer disease.
Neurology 2004; 63: 975–982.
24. Duncan G, Wilson J. Normal elderly have some signs of
PS. Lancet 1989; 2: 1392.
25. Teravaiinen H, Calne D. Motor system in normal aging
and Parkinson’s disease. In: Katzman R, Terry R, eds.
The Neurology of Aging. Philadelphia, PA: F.A. Davis,
1983: 85–109.
26. Wilson R, Schneider J, Beckett L, Evans D, Bennett D.
Progression of gait disorder and rigidity and risk of death
in older persons. Neurology 2002; 58: 1815–1819.
27. Brun A, Passant U. Frontal lobe degeneration of
non-Alzheimer type. Structural characteristics, diagnostic
criteria and relation to other frontotemporal dementias.
Acta Neurologica Scandinavica 1996; 168: 28–30.
28. Mann D, South P, Snowden J, Neary D. Dementia of
frontal lobe type: neuropathology and immuno-
histochemistry. Journal of Neurology, Neurosurgery, and
Psychiatry 1993; 56: 605–614.
29. Rinne J, Laine M, Kaasinen V, Norvasuo-Heilä M,
Nagren K, Helenius G. Striatal dopamine transporter and
extrapyramidal symptoms in frontotemporal dementia.
Neurology 2002; 58: 1489–1493.
30. McKhann G, Albert M, Grossman M, Miller B, Dickson
D, Trojanowski J. Clinical and pathological diagnosis of
frontotemporal dementia. Archives of Neurology 2001; 58:
1803–1809.
31. Kertesz A, Martinez-Lage P, Davidson W, Munoz D. The
corticobasal degeneration syndrome overlaps progressive
aphasia and frontotemporal dementia. Neurology 2000;
55: 1368–1375.
32. Kertesz A, McMonagle P, Blair M, Davidson W, Munoz
D. The evolution and pathology of frontotemporal
dementia. Brain 2005; 128: 1996–2005.
33. Griffiths D, Derbyshire S, Stenger A, Resnick N. Brain
control of normal and overactive bladder. Journal of
Urology 2005; 174: 1862–1867.
34. Kuhtz-Buschbeck J, Horst Cvd, Pott C, et al. Cortical
representation of the urge to void: a functional magnetic
resonance imaging study. Journal of Urology 2005; 174:
1477–1481.
35. Nour S, Svarer C, Kristensen J, Paulson O, Law I.
Cerebral activation during micturition in normal men.
Brain 2000; 123: 781–789.
36. Bathgate D, Snowden J, Varma A, Blackshaw A, Neary
D. Behaviour in frontotemporal dementia, Alzheimer’s
disease and vascular dementia. Acta Neurologica Scandi-
navica 2001; 103: 367–378.
37. Greck J, Lautenschlager N, Kurz A. Clinical aspects of
frontotemporal dementia. Fortschritte der Neurologie-
Psychiatrie 2000; 68: 447–457.
38. Staskin D. Overactive bladder in the elderly: a guide to
pharmacological management. Drugs Aging 2005; 22:
1013–1028.
Ó 2007 EFNS European Journal of Neurology 14, 860–864