Case presentation
A 50-year-old Caucasian male, residing in an urban area, with right
laterality and no history of any chronic illnesses, was admitted to our
Neurology department with the complaint of weakness in the right limbs.
The patient’s symptoms had an acute onset 2 days prior to presentation.
Family history revealed that the patient’s mother suffered from an
ischemic stroke at the age of 87. The patient was an artist and a
painter, admitted to being a cigarette smoker (1 pack of cigarettes per
day for over 30 years) and to consuming alcohol daily (about 50 cmc of
spirits per day). There was no history of head trauma or any known
allergies.
The general examination revealed that the patient was conscious and
aware, had normal body temperature, no signs of recent trauma, a BMI
(Body Mass Index) of 21 kg/m2. The blood pressure was
234/146 mmHg, and the heart rate 104 beats per minute.
The neurological examination showed the following:
- Pyramidal tract signs characterized by hemiparesis regarding the right
limbs with a score of 4/5 (on the MRC – Modified Research Council
scale). Extensor plantar reflex was objectified in the right leg. The
patient also had central face palsy on the same side.
- Extrapyramidal signs characterized by slowness, left upper limb
rigidity, hypomimia and a low-volume, monotonous speech.
- Mild cognitive impairment on MMSE testing (a score of 27/30) and on
MOCA testing (25/30). The abilities affected in our patient were:
visuospatial/executive functions, short term memory and mathematical
functions.
Paraclinical investigations:On admission a head CT without contrast dye was performed (Figure 1.
A-E). The CT revealed a small hypodense lesion (Figure 1. B), with
ill-defined borders, located in the posterior limb of the left inner
capsule that was interpreted as an acute lacunar stroke.
Diffuse white matter hypodensity was observed, with symmetrical pattern,
regarding the periventricular region, the centrum semiovale and the
inner capsule. The juxtacortical arcuate fibers were spared. The
hypodense white matter lesions extended in the brainstem, cerebellar
peduncles and the cerebellum.
For a more precise evaluation of the white matter changes a native MRI
was performed (Figure 2. A-N).
MRI revealed an acute ischemic lesion (10/19 mm), hyperintense on the
DWI, FLAIR and T2WI sequences (Figure 2. B, 2. L), located in the
posterior limb of the inner capsule that extended to the lenticular
nucleus on the left. Diffuse hyperintense areas on T2WI and FLAIR
sequences were also observed in the white matter, with the same
distribution (supratentorial and infratentorial) as the hypodense areas
described on head CT (Figure 2. A-K), without abnormal restricted
diffusion (Figure 2. L). On the SWI sequences, conglomerate hypointense
lesions adjacent to the midline of the pons ware observed (Figure 2. N)
that were interpreted as old hemosiderin deposits. Similar lesions were
observed in the centrum semiovale (Figure 2. M).
Complete bloodwork was done. No notable laboratory changes regarding the
hematological profile, liver and kidney functions, coagulation
parameters were observed. No biological inflammatory syndrome was
present on admission and during hospitalization. Other notable bloodwork
parameters will be mentioned below in the differential diagnosis
subchapter. ECG was within normal range.
A carotid Doppler ultrasonography was performed which showed bilateral
non-stenotic atheromatous plaques, with heterogenous echogenicity;
irregular surface and a thickness ranging from 2.7 mm in the left common
carotid artery to 4.2 mm in the right common carotid artery were
observed.Differential diagnosis: Using the imaging aspects of the disease
on MRI we decided taking into account for the differential diagnosis
disorders which are compatible with the pattern of the white matter
lesions as presented in the article written by Schiffmann et al.10 These disorders where afterwards excluded using
clinical and biological findings.
- CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical
Infarcts and Leukoencephalopathy) usually has an earlier onset, during
the third decade. The lack of findings in the family history of our
patient, the absence of lesions on imaging anterior to the temporal
horns of the lateral ventricles and of the migraines makes this
diagnosis improbable. Also, the presence of vascular risk factors
(arterial hypertension and smoking) plead for an acquired
microangiopathy. 8,10.
- Multifocal Progressive Leukoencephalopathy may present itself with
similar imaging features to Binswanger’s Disease, but cerebral lacunes
should be absent 8. Characteristic lesions on MRI
are more often localized at the grey-white matter junction with damage
to the juxtacortical association fibres 11. On
clinical examination, motor coordination and gait disturbances are
frequently found alongside visual field deficits and language
abnormalities 11. A normal haematological and
immunological profile and the absence of opportunistic infections and
other infectious events in the past that would suggest an acquired or
intrinsic immunodeficiency are also favourable for excluding this
diagnosis 12.
- HIV-associated dementia is associated with a symmetrical,
periventricular pattern of changes to the white matter with sparing of
the juxtacortical and infra-tentorial white matter, atrophy of the
grey matter of the cerebral cortex, atrophy of the deep white matter
and volumetric changes of the basal ganglia 18,
changes that were not present in our patient. Also, the lack of
criteria that would suggest and acquired immunodeficiency as mentioned
in the previous paragraph makes this diagnostic much less probable
- Cerebral vasculitis as part of a systemic disorder may have various
features on MRI imaging, and the clinical and biological features of
the disease include: signs of a systemic disease, headaches, elevated
acute-phase reactants, inflammatory microcytic anemia, the presence of
auto-antibodies 13. None of these changes were found
in our patient. Antinuclear antibodies, anti-neutrophil cytoplasmic
antibodies, rheumatoid factor, circulating immune complexes where all
in normal range.
- Primary angiitis of the central nervous system (PACNS) is rare
disorder and should be suspected in younger patients with strokes,
without any known vascular risk factors. The major symptoms of this
disease include headaches (60% of cases), cognitive impairment (50%
of cases), neurological focal signs. Systemic and biological changes
that were described in the cases of systemic vasculitis are often
absent. On MRI, the lesions are typically multifocal, bilateral,
hyperintense on T2WI and FLAIR sequences, and can be found in the
superficial and deep white matter, and in the cortical grey matter and
basal ganglia 14. Of cardinal importance are the
bilateral stenosis and dilation of various sized blood vessels14 which were absent in our patient. The gold
standard for diagnosing or excluding PACNS is represented by cerebral
biopsy 14, which we preferred not to perform due to
lack of sufficient arguments that would justify the risk of the
investigation.
- Toxic leukoencephalopathy develops in the context of chronic exposure
to leukotoxic substances such as some illicit drugs (opioids, cocaine,
amphetamines). Leukoencephalopathy caused by use of heroin, also known
as ”chasing the dragon” syndrome, is one of the most studied of these
rare occurrences, and it usually presents on MRI with white matter
hyperintensities that are symmetrical, especially with changes in the
corticospinal tracts of the pons, perirolandic white matter,
cerebellar white matter with sparing of the juxtacortical white matter
and the grey matter 15, 16. These lesions are
similar to those seen in our case. The patient denied any use of
illicit substances, did not have any signs of chronic toxicity of the
substances mentioned above and did not develop any withdrawal events
during the 2-week hospitalization period. Toxic leukoencephalopathy
may also develop after chronic exposure to toluene. Our patient was a
painter and toluene can be found in many paints and solvents. and the
main neurological feature of chronic toluene toxicity is the cognitive
impairment 17. The patient refused to give any
information about the ingredients of the paints used by him.
Nevertheless, the presence of other lesions associated on MRI, other
than the white matter hyperintensities, are not typical in chronic
toluene toxicity. There were also no other systemic disturbances that
would suggest chronic toluene toxicity (altered kidney function,
respiratory, dermatological, gastrointestinal or musculoskeletal
abnormalities).
- Other illnesses that have a genetic etiology are usually detected
during childhood or adolescence and are frequently associated with
systemic abnormalities. Out of these pathologies, Fabry disease is
still worth mentioning. There are some rare cases described in
literature, in men, that had a late-onset at adult age and in which
only one or two organ systems were affected. The kidneys (chronic
kidney disease), and the cardiovascular system (hypertrophic
cardiomyopathy, valvular anomalies, conduction disorders) were most
frequently affected 19,20. Our patient had no
clinical or paraclinical evidence of a kidney or heart abnormalities.
When present, central nervous system affliction leads to frequent
ischemic strokes and cognitive impairment. On MRI, white matter
lesions are present in 80% of cases and can be heterogenous, ranging
from small, scattered and punctuate T2-weighted hyperintense foci to
bilateral diffuse, patchy and partly confluent white matter
hyperintensities. An important characteristic is that the lesions in
Fabry disease only present themselves in the supratentorial white
matter, which was not the case in our patient 19.
Outcome and follow-upThe therapeutic management targeted lowering of blood pressure in
accordance to the actual guidelines and secondary stroke prevention
using antiplatelet monotherapy and statins. Neurotrophic medication and
vitamins were administered. Blood pressure was especially difficult to
control requiring multiple associations of anti-hypertensive drugs. The
patient was also evaluated in the first 72 hours after admission by a
kinetotherapist, and daily sessions of active and passive mobilization
were performed. Regarding the clinical and neurological evolution, the
motor deficit, fine motor control and prehension improved during
admission and during the first month after discharge from hospital.