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:
  1. 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.
  2. Extrapyramidal signs characterized by slowness, left upper limb rigidity, hypomimia and a low-volume, monotonous speech.
  3. 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.
  1. 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.
  2. 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.
  3. 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
  4. 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.
  5. 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.
  6. 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).
  7. 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.