Case Report
Multiple Sclerosis Manifesting with Cognitive and Neuropsychological
Symptoms – A Case Analysis
Krasimir R. GENOV*
Affiliation of the author:
Military Medical Academy, Clinic of Neurology, Sofia, Bulgaria
Corresponding author:
Assoc. Prof. Krasimir R. GENOV, M.D., Ph. D.
Clinic of nervous diseases- Military Medical Academy, Sofia, Bulgaria
3 Georgi Sofiiski str., 1000 Sofia, Bulgaria
Tel: (+359-2) 922 59 14
E-mail:
K.Genov@abv.bg
Abstract.
In the last years cognitive and
neuropsychological signs have been
noticed quite often early in the clinic of
multiple sclerosis patients. Nevertheless,
they have rarely been depicted in the
medical literature as isolated symptoms.
We present a case of multiple sclerosis
(MS) which manifested itself with
cognitive and neuropsychological signs 5
years before the final diagnosis.
We analyze the role of the white and the
gray matter lesions in the cognitive
deficit, neuropsychological and localized
neurological symptoms.
Key words: multiple sclerosis, cognitive
deficit, neuropsychological symptoms
Balkan Military Medical Review
Oct - Dec 2012; 15(4): 298 -304
Introduction
Cognitive and
neuropsychological
symptoms as part of MS disease have been
described in the first year of the 19
th
century by Charcot, but until recent times
were considered as rare and late
manifestation of the disease. The presented
results of several studies in the last 10
years show that they are early and common
manifestation of the disease
[3, 18, 20, 21].
Cognitive impairments of different degree
are found in approximately 85% of patients
with clinically proven MS (during the first
2 years since the onset of the disease) and
in 66% of patients presenting only with
retrobulbar
neuritis.
Swingler
and
Compston
found
neuropsychological
symptoms in 40% of 301 patients with
confirmed MS [29]. According to other
authors, about 60% of patients with early
MS suffer memory disorders, depression or
focal cortical syndromes [4, 9, 23].
Although a large percentage of patients
with
MS
develop
cognitive
and
neuropsychological
symptoms,
the
literature rarely describes cases of the
disease first presenting with isolated
cognitive
and
neuropsychological
symptoms. In a retrospective analysis,
Skegg (1993) described 29 patients with
neuropsychological symptoms of the
disease, as 18 (62%) of them had visited a
psychiatrist during the years before the
diagnosis of MS [25]. Cases of the disease
debuting with isolated cognitive or
neuropsychological symptoms are rarely
found in the specialized literature [1, 5, 12,
26, 33]. We present a patient with MS
presenting with progressive cognitive or
neuropsychological
symptoms
first
observed 5 years before the diagnosis.
Presentation of the case
A 48-year-old male repeatedly
consulted psychiatrists and was diagnosed
with
PTSD
(Posttraumatic
Stress
Disorder). His major complaints were:
changes in mood and behavior, serious
difficulties with official duties. According
to the patient’s parents, 10 years earlier he
had survived a car accident with minor
injuries (without head trauma). After the
accident some changes in the behavior had
developed – lethargy, apathy, isolation,
communication difficulties, difficulties
with official duties, changes in mood –
from depression to unreasonable laughter.
Later on, disturbances in attention,
concentration and memory were added.
Following the psychiatric treatment, for a
short period of time the patient became
more vivid, with higher spirits. The
treatment proved, however, ineffective and
was soon discontinued by the patient due
to the prescribed large amounts of
medications which he was unwilling to
take.
No established medical history.
Family history: mother suffering of Diabe
tes type 2, with no psychiatric disorders.
Social history: university degree, single,
good living standards and good family
relations.
During his hospitalization, the
patient complained of fatigue, concentra
tion and memory problems, mainly in
remembering recent events; he demonstra
ted wish for cure, although he had never
looked for neurological help in the past.
Initially we observed mental retardation,
changes in the mood (mainly euphoria)
and, rarely, depressed mood.
Neurological
status
(examination):
quadripyramidal syndrome, non-severe
discoordination syndrome, with intact
bowel and bladder functions.
EDSS (Expanded Disability Status Scale) –
1.5
299 Balkan Military Medical Review
Vol. 15, No 4, Oct –Dec 2012
Neuropsychological battery:
- PASAT (Paced Auditory Serial
Addition Test) – 12 points;
- MMSE
(Mini-Mental
State
Examination) – 15 points;
- STTPD (Simple Triple Test for
Psychoorganic Decline) – 6 points
- FMT (Feld-Markierungs test) –
Hentschel – SW 75;
- VRT (Visual Retention Test) –
Benton – 3 points
As a result from these tests we have
data for severe cognitive impairment
(deficit),
preserved
automental
and
particularly injured alomental orientation,
pathological decrease of concentration,
instability of attention, increased rate of
fatigue, severe impairment of fixating
auditory and visual memory of organic
type, mental retardation, lowered ability
for abstraction and for generalization, lack
of criticism, strongly limited abilities for
making decisions, damaged abilities for
construction, hypobulia, lack of initiative,
difficulties in adapting to changing
conditions.
Conclusion
A personality change of organic
type, characterized by asthenia, hypobulia,
lack of criticism, particularly impaired
orientation ability, severely damaged
ability of concentration and fixating
memory, injured normal rhythm day-night,
social isolation, permanently reduced
adaptation abilities was observed.
Due to the found bilateral pyramid
symptoms a MRI was performed. On axial
and sagittal T2W and TIRM images
multiple signal-intense focuses were found
in
cella
media,
corpus
callosum,
subcortical and periventricular, interpreted
as demyelination plaques of different age.
Figure No 1
Figure No 2
Discussion and literature review
Cognitive impairments in MS
patients may occur and could be observed
early in the disease, affecting 30-70% of
the patients [22]. It is assumed that they
appear as a result of subcortical type of
dementia, caused by axonal loss and
secondary cortical atrophy [30]. The
mechanism is related to the disturbance of
the connections between subcortical and
cortical structures, especially the limbic
cortex. The clinic is presented with
memory, attention, ability of abstract
Genov K: Multiple Sclerosis Manifesting with Cognitive and Neuropsychological
Symptoms
300
thinking, ability of information processing
and
executive
functions
disorders.
Typically, these disorders could not be
found using standard tests such as MMSE
[11]. They are more frequent and advanced
in patients with chronic progredient form
of MS and show correlation with
progression of the disease, but can remain
unchanged for many years.
The case described, the presence of
documented cases in literature of MS
patients
debuting
with
isolated
neuropsychological
and/or
cognitive
impairment, focal cortical syndromes
(aphasia,
epilepsy,
cortical
sensory
disorders) and the results of some
neuropathological
studies
and
neuroimaging data lead to the question: Is
it possible to have isolated or predominant
involvement of the cortex in MS patients?
In 2003 Zarei et al. expressed the
hypothesis of the existence of a cortical
variant of MS. They presented 6 patients
debuting with progressive demented
syndrome, combined with pure cortical
symptoms such as dysphasia, dysgraphia,
dyslexia and three of the patients were with
medical history of depression. All six
patients in the later period of clinical
studies developed classical symptoms of
MS and diagnosis was confirmed by MRI.
The
very
few
neuropathological
examinations focused on cortical lesions in
MS patients did not establish correlation
between the cortical lesions and the
cognitive deficit [2, 8, 10]. In the Brownell
and Hughes Study 5% of the lesions are
cortical, but all cortical lesions were
detected only in one patient of a total of 22
patients studied.
In opposite, Lumsden found
cortical lesions in 93% of the investigated
MS patients. The majority of cortical
lesions in these studies are located on the
border between white and grey brain
matter. Kidd et al. (1999) investigated
cortical lesions in MS patients and
categorized them in four groups depending
on their localization compared to cortical
blood vessels [6, 15, 17].
They found that cortical lesions are
localized around intracortical veins (V4),
in contrast to those localized on white and
grey matter border, associated with gyral
veins [14, 32]. Peterson et al. (2001)
studied 112 cortical lesions found in 110
tissue blocks of 50 MS patients and found
that cortical lesions contained 13 times
more CD3 positive lymphocytes and 6
times more CD68 positive macroglia
(macrophages of the subcortical lesions).
The results of these studies support the
hypothesis of the existence of a MS form
characterized by exclusive or predominant
cortical lesions.
It is assumed that cognitive
impairments are determined by the
location, number and size of the lesions,
identified by MRT. According to Fisher et
al. (2000) and Foong and Ron (2003) the
cognitive impairments are determined
mainly by the cortical atrophy, T1 and T2
lesions, localized in frontal lobes and
corpus callosum. Therefore, cognitive
impairment may occur in MS patients who
have reached certain levels of brain
atrophy and numbers of brain lesions with
such location [24, 29, 34]. Several studies
have tried to determine correlation between
neuropsychological
and
cognitive
symptoms and MRT identified lesions in
white and grey brain matter in MS patients.
The results are not significant. This may be
related to the limitations of the
neuroimaging methods used for the
detecting of cortical lesions in MS patients
and the variability of neuropsychological
tests used to detect cognitive deficit. The
MRT limitations come from the fact that
the cerebral cortex needs longer relaxation
time than white brain matter during MRT
examination [7, 16]. This reduces the
resolution and contrast of the lesions
compared to background grey matter in
conventional T2W MRT [13, 31]. Boggild
et al. found that invisible to conventional
301 Balkan Military Medical Review
Vol. 15, No 4, Oct –Dec 2012
T2W imaging cortical lesions can be
visualized by using FLAIR images with
prolonged inverse time [17].
Rovaris et al. (2000) using RARE
(rapid
acquisition
with
relaxation
enhancement) combined with fast FLAIR
found that cortical lesions are significantly
more in MS patients with cognitive
impairments.
Lazeron et al. (2000), using a
similar technique, found that the number of
cortical lesions significantly correlates
with index of cognitive impairment. Sokis
et al. (2001) also provide evidence of early
involvement of the cerebral cortex in MS
patients. They found cortical lesions in
such anatomical locations that may explain
clinical and electrophysiological symptoms
in MS patients debuting with epilepsy
seizures [17].
The results of these studies show
that with the advance of neuroimaging
methods the presence of cortical lesions
and its correlation to specific cortical
syndromes are increasingly determined.
The cortical atrophy, probably due to
axonal loss, is also commonly found in the
early stages at the disease and can be
visualized by using modern neuroimaging
methods [19, 27, 28].
At this stage, we could still not be
able to assess the role of lesions in white
and grey brain matter in the development
of cognitive impairment, neuropsycho
logical and focal cortical syndromes in MS
patients. It is possible, however, that in the
future we will be in the position to
distinguish a cortical form of MS with the
collection of clinical, pathoanatomical and
neuroimaging evidence.
References
1.
Bakashi, R., Dmochowski, J.,
Shaikh, Z., et al.: Gray matter T2
hypointensity is related to plaques and
atrophy in the brains of multiple sclerosis
patients. J. Neurol. Sci., 185: 19-26, 2001.
2.
Benedict, Ralph, H. B., Bakshi,
Rohit., et al: Frontal cortex atrophy
predicts cognitive impairment in multiple
sclerosis.
J.
Neuropsychiatry.
Clin.
Neurosci. 14(1): 44-51, 2002.
3.
Blinkenberg, M., Rune, K., Jensen,
C. V., et al: Reduced metabolism in
cerebral cortex correlates with MRI
changes and cognitive dysfunction in
patients with disseminated sclerosis.
Ugeskr. Laeger., 163(27): 3788-3792,
2001 July.
4.
Metzler, C.: Effects of left frontal
lesions on the selection of context –
appropriate meanings. Neuropsychology,
15(3): 315-328, 2001 July.
5.
Lazeron, R. H., Langdon, D. W.,
Filippi, M., et al: Neuropsychological
impairment in multiple sclerosis patients:
the role of (juxta) cortical lesion on
FLAIR. Mult. Scler., 6(4): 280-285, 2000
Aug.
6.
Blinkenberg, M., Rune, K., Jensen,
C. V., et al: Cortical cerebral metabolism
correlates with MRI lesion load and
cognitive dysfunction in MS. Neurology,
54(3): 558-564, 2000 Feb.
7.
Carmosino, M. J., Brousseau, K.
M., Arciniegas, D. B., et al: Initial
evaluations for multiple sclerosis in a
university
multiple
sclerosis
center:
outcomes and role of magnetic resonance
imaging in referral. Arch. Neurol., 62:
585-590, 2005.
8.
Dalton, C.M., Chard, D.T., Davies,
G.R., et al.: Early development of multiple
sclerosis is associated with progressive
grey matter atrophy in patients presenting
with clinically isolated syndromes. Brain,
127: 1101-1107, 2004.
9.
Ranjeva, J. P., Pelletier, J.,
Confort-Gouny, S., et al.: MRI/MRS of
corpus callosum in patients with clinically
isolated syndrome suggestive of multiple
sclerosis. Mult. Scler., 9: 554-565, 2003.
10.
Inglese M, Benedetti B, Filippi M.:
The relation between MRI measures of
inflammation and neurodegeneration in
Genov K: Multiple Sclerosis Manifesting with Cognitive and Neuropsychological
Symptoms
302
multiple
sclerosis.
Journal
of
the
neurological sciences, 233(1/2):15-19,
2005.
11.
Meier DS, Weiner HL, Khoury SJ,
et al.:. Magnetic resonance imaging
surrogates of multiple sclerosis pathology
and their relationship to central nervous
system atrophy. Journal of Neuroimaging,
14:46-53, 2004.
12.
M Rovaris and M Filippi. MRI and
cognition in MS. Journal of NeuroVi
rology. 175.
13.
Penner IK, Kappos L, Rausch M, et
al.: Therapy-induced plasticity of cognitive
functions in MS patients: insights from
fMRI. Journal of physiology, 99(4/6):455-
462, 2006.
14.
Truyen L, van Waesberghe JHTM,
van Walderveen MAA, et al.: Accumulation
of hypointense lesions (`black holes') on T1
spin-echo MRI correlates with disease
progression
in
multiple
sclerosis.
Neurology, 47: 1469 – 1476, 1997.
15.
van Buchem MA, Grossman RI,
Armstrong C, et al.: Correlation of
volumetric magnetization transfer imaging
with clinical data in MS. Neurology,
50:1609 – 1617, 1998.
16.
Zivadinov R, Bakshi R. Role of MRI
in multiple sclerosis II: brain and spinal
cord atrophy. Frontiers in bioscience,
9:647-664, 2004.
17.
Bermel RA, Sharma J, Tjoa CW, et
al.:
A
semiautomated
measure
of
whole/brain atrophy in multiple sclerosis.
Journal of the neurological sciences,
208(1/2):57-65, 2003.
18.
Bakshi R, Benedict RH, Bermel RA,
et al.: T2 hypointensity in the deep gray
matter of patients with multiple sclerosis: a
quantitative magnetic resonance imaging
study. Archives of Neurology, 59(1):62-68,
2002.
19.
Lazeron RH, Boringa JB, Schouten
M, et al.: Brain atrophy and lesion load as
explaining
parameters
for
cognitive
impairment in multiple sclerosis. Multiple
sclerosis, 11(5):524-531, 2005.
20.
Calabrese M, Agosta F, Rinaldi F,
et al.: Cortical lesions and atrophy
associated with cognitive impairment in
relapsing/remitting
multiple
sclerosis.
Archives of neurology, 66(9):1144-1150,
2009.
21.
Bermel
RA,
Bakshi
R.
The
measurement and clinical relevance of
brain atrophy in multiple sclerosis. Lancet
neurology, 5(2):158-170, 2006.
22.
Tartaglia MC, Arnold DL. The role
of MRS and fMRI in multiple sclerosis.
Advances in neurology, 98:185-202, 2006.
23.
Mainero C, Pantano P, Caramia F,
et al.: Brain reorganization during
attention and memory tasks in multiple
sclerosis: insights from functional MRI
studies. Journal of the neurological
sciences, 245:93-98, 2006.
24.
Benedict RH, Bruce JM, Dwyer
MG, et al.: Neocortical atrophy, third
ventricular
width,
and
cognitive
dysfunction in multiple sclerosis. Archives
of neurology, 63(9):1301-1306, 2006.
25.
Brass
SD,
Benedict
RH,
Weinstock/Guttman B, et al.: Cognitive
impairment is associated with subcortical
magnetic resonance imaging grey matter
T2 hypointensity in multiple sclerosis.
Multiple sclerosis, 12(4):437-444, 2006.
26.
Vrenken H., Geurts J.J. Gray and
normal-appearing white matter in multiple
sclerosis: an MRI perspective. Prog
Brain Res., 175: 465-482, 2009.
27.
Benedict R.H., Zivadinov R. Risk
factors for and management of cognitive
dysfunction inmultiple sclerosis. Nat Rev
Neurol, 7(6): 332-342, 2011.
28.
Till C., Ghassemi R., Aubert-
Broche B., et al.: MRI correlates of
cognitive impairment in childhood-onset
multiple
sclerosis.
Neuropsychology,
25(3): 319-332, 2011.
29.
Langdon
D.W.
Cognition
in
multiple sclerosis. Curr Opin Neurol,
24(3): 244-249, 2011.
30.
Ferraro D., Simone A.M., Merelli
E., et al.: Isolated progressive cognitive
303 Balkan Military Medical Review
Vol. 15, No 4, Oct –Dec 2012
impairment and depression in a patient
with neuroradiological features suggestive
of multiple sclerosis. Neurol Sci., 32(4):
695-697, 2011.
31.
Calabrese M., Rinaldini F., Grossi
P., et al.: Cortical pathology and cognitive
impairment in multiple sclerosis. Expert
Rev Neurother, 11(3): 425-432, 2011.
32.
Calabrese M., Filipi M., Gallo P.
Cortival lesions in multiple sclerosis. Nat
Rev Neurol, 6(8): 438-444, 2010.
33.
Dawe R.J., Bennett D.A., Schneider
J.A.,
Arfanakis
K.
Neuropathologic
correlates of hippocampal atrophy in the
elderly: a clinical pathologic, postmortem
MRI study. PLoS One. 6(10):26286, 2011.
34.
Schoonheim M.M., Geurts J.J.,
Landi D., et al.: Functional connectivity
changes in multiple sclerosis: a graph
analytical study of MEG resting state data.
Hum. Brain Mapp. 2011 sep 23.
Genov K: Multiple Sclerosis Manifesting with Cognitive and Neuropsychological
Symptoms
304
Dostları ilə paylaş: |