Cerebral small vessel disease (CSVD) is responsible for lacunar strokes and intracerebral hemorrhages and stands as the predominant cause of vascular cognitive impairment. The two prevailing pathologies associated with CSVD include arteriolosclerosis, typically induced by factors such as aging, hypertension, and other common vascular risk elements, and cerebral amyloid angiopathy (CAA), arising from the accumulation of β-amyloid within blood vessel walls. It is usually identified by various tissue changes observable on magnetic resonance imaging (MRI). These changes encompass a range of features, including but not limited to white matter hyperintensities (WMH), lacunar infarcts, cerebral microbleeds, and expanded perivascular spaces. These CSVD-related MRI findings are valuable tools in clinical practice for making diagnoses. There is substantial evidence supporting primary prevention efforts, and recent data underscores how rigorous blood pressure management can curtail the progression of WMH and postpone the onset of cognitive decline.

Cerebral small vessel disease, White matter hyperintensities, Lacunar stroke, Vascular cognitive impairment

As of 2018, cerebrovascular disease remains a leading cause of functional disability and death globally [1]. CSVD represents a group of pathologies with myriad etiologies and pathophysiology that mainly affect cerebral arteries, arterioles, capillaries, and venules [2]. Histologically, the vessel walls are thickened, the lumen is reduced, and thus, hypoperfusion of the target area leads to infarction and ischemia. CSVD accounts for approximately 20–30% of all ischemic strokes and is the leading cause of functional loss, cognitive decline, and disability in the elderly [3]. There have been many classifications of CSVD based on pathologic, histologic, or radiologic findings. However, it is broadly classified into two categories: amyloid and non-amyloid. A European brain small vascular disease expert group has classified it further into arteriosclerosis, cerebral amyloid angiopathy (CAA), non-amyloid CAA, inflammatory/ immunologically mediated small vessel disease, venule collagenosis, and others. Of these, type 1 arteriosclerosis is the most common, and hence, hypertension is one of the significant risk factors for CSVD.

Like most strokes, CSVD manifests as ischemia or hemorrhages depending on the etiology and underlying pathology, thus resulting in variations in neuroimaging from diffuse hyperintensities to micro-hyperintensities and hematomas [4]. On neuroimaging, the most common finding is WMH, with a prevalence of about 94%, and the greater the WMH, the higher the risk of incident stroke, dementia, and mortality than the general population [5].  Studies have suggested that there is a strong positive association between cognition and white matter lesions, which is thus used as an indicator for measuring cognitive decline [4].

Moreover, the literature says that small vessel disease is no longer a monodomain discipline but a multidomain, with effects extending beyond the commonly presented stroke and dementia to include balance, gait dysfunction, and neuropsychiatric disruptions [6]. Therefore, a comprehensive study of all clinical, radiological, and histological findings to make an accurate and elusive diagnosis of this disease is imperative. This article talks about one such case that was found challenging to diagnose.

The patient, a 30-year-old male known to have hypertension, sought medical attention in the outpatient department (OPD) due to a one-week history of troubling symptoms. His most prominent complaints included an abrupt onset of fever, chills, persistent nausea, constipation, and a notable decline in general physical strength. Additionally, the patient reported having trouble walking, necessitating external support for mobility.

Of medical significance, this individual had a documented history of hypertension, which was being effectively managed with antihypertensive medications. Pertinently, a thorough review of the patient’s family medical history did not uncover any significant hereditary medical conditions or predispositions. Comprehensive questioning regarding recent activities and exposures failed to reveal any apparent triggers or potential infectious sources, effectively ruling out recent travel or contact with individuals exhibiting similar symptoms.

The patient was transferred from the outpatient department (OPD) and was recommended to undergo various tests and investigations including complete blood cell count (CBC), erythrocyte sedimentation rate (ESR), echocardiography, abdominal ultrasound, urine examination, C-reactive protein (CRP), liver function tests (LFTs or LFs), renal function tests (RFTs), lipid profile, and serum electrolytes. The results of the tests were mostly normal. The CBC and ESR showed values that fell within the normal range. The Total Leukocyte Count (TLC) was 11300 per mm3, Hemoglobin was 14.1 g/dL, and the platelet count was 248000 per mm3. The ESR was 55 mm per hour, which is considered acceptable. CRP level measured 2.12 mg/dL. The lipid profile indicated a cholesterol level of 241 mg/dL and a low-density lipoprotein (LDL) level of 180 mg/dL. The serum electrolyte values were within the usual range. The results of the abdomen and pelvic ultrasonography indicated no abnormalities. The routine urine investigations revealed pale yellow, acidic urine with no presence of albumin or sugar. The urine sample was analyzed under a microscope and revealed the presence of 2 to 4 pus cells and 1 to 2 red blood cells. No other casts or abnormalities were observed. The echocardiography results were within normal limits; however, they revealed a small amount of mitral regurgitation.

On a detailed physical examination, the patient’s vital signs were observed to be well within the normal range. This encompassed blood pressure (130/80 mmHg), pulse (84 bpm), temperature (98 °F), and oxygen saturation (96%), providing initial reassurance regarding his overall health. His sleep increased, his appetite decreased, and his bowel habits were normal. A systemic examination did not elicit any overt abnormalities, suggesting that the origin of his symptoms might be more nuanced.

During the central nervous system (CNS) examination, his Glasgow Coma Scale (GCS) score was 15/15, indicating full consciousness. He appeared to be well-oriented, showed no signs of neck stiffness, and exhibited normal muscle strength, motor functions, and reflexes, including the plantar reflex. Two specific neurological assessments provided valuable insights into his condition. Romberg’s test yielded a positive result, suggesting compromised proprioceptive function and sensory ataxia, which can affect balance, particularly with closed eyes. Furthermore, the finger-nose test demonstrated a slight impairment, indicative of mild cerebellar dysfunction, impacting coordinated movements. These neurologically suggestive findings heightened suspicions regarding a potential underlying neurological disorder or pathology contributing to his presenting symptoms. And more than this, behavior changes were observed. He seemed apathetic, lethargic, and sometimes unaware of his surroundings. So, based on this temporal lobe, encephalopathy was suspected, and empirical treatment, which is acyclovir, was started. But MRI and lumbar puncture (LP) were advised for further investigations; the patient attendant refused LP; however, an MRI with and without contrast was performed, revealing the presence of WMH and enlarged perivascular spaces, which are indicative of CSVD.

Antihypertensive, aspirin, and antidiabetic drugs were recommended for the patient. Suggested dietary adjustments, limiting sodium intake and enhancing physical activity. Mentioned the essential elements that each meeting should assess, as well as the suggested frequency of these visits.

CSVD is the most common, chronic, and progressive vascular disease. The changes affect the arterioles, capillaries, and small veins supplying the white matter and deep structures of the brain [7]. The patient’s clinical presentation was slightly different from the classic symptoms associated with CSVD, which made it difficult to diagnose. Initially, it was thought the patient might have temporal lobe encephalopathy because cognitive functions were mostly unaffected or very slightly affected. After further examination (MRI), CSVD was diagnosed. Typically, cognitive decline, gait disturbances, and motor deficits are prominent features of such cases. It’s essential to emphasize that CSVD often leads to subcortical cognitive impairment, affecting executive functions, attention, and processing speed, which can significantly impact a patient’s quality of life. MRI remains the gold standard for diagnosing CSVD. In our case, MRI revealed characteristic findings, including white matter hyperintensities and periventricular hyperintensities. The white matter is the most vulnerable region to hypoxia or hypoperfusion due to the watershed effect [3]. Additionally, it is worth noting that MRI can identify periventricular and subcortical white matter lesions, providing valuable diagnostic insights. The patient’s history of hypertension and hyperlipidemia is a critical component of this case. Effective management of these vascular risk factors is not only essential for disease control but also paramount to preventing CSVD progression and further vascular events. Future studies may delve into the optimal blood pressure and lipid targets for CSVD management [8,9].

CSVD is managed by blood pressure control, antiplatelet therapy, cognitive rehabilitation, secondary stroke prevention, regular follow-up, and lifestyle changes. Adequate blood pressure control plays a pivotal role in CSVD management. Tailoring antihypertensive medications to individual patients’ needs is essential. However, specifying target blood pressure ranges or values would provide practical guidance [10]. The consideration of antiplatelet agents, such as aspirin, in certain cases of CSVD is crucial, especially for those at a high risk of recurrent lacunar infarcts. Patient-specific risk assessment should guide this decision [6]. Cognitive impairment in CSVD is a challenging aspect of patient care. Cognitive rehabilitation, encompassing cognitive training and lifestyle modifications, is a promising avenue for ameliorating these deficits. Future research may offer more insights into the most effective interventions [6]. Managing vascular risk factors like hyperlipidemia and diabetes is pivotal to preventing further vascular events. Elaborate on specific pharmacological and non-pharmacological strategies that can be employed in CSVD management. Stress the importance of regular follow-up visits to monitor disease progression, adjust medications, and address emerging symptoms [6]. Non-pharmacological interventions are equally significant and encompass dietary adjustments, limiting sodium intake, enhancing physical activity, and refraining from smoking [11].

It’s essential to note that there is no cure for CSVD, but these treatments and interventions aim to manage symptoms, slow down the progression of the disease, and reduce the risk of complications like stroke and cognitive decline. The specific treatment plan for an individual with CSVD should be determined by a healthcare professional based on their unique medical history and symptoms. Regular follow-up with a healthcare provider is crucial for monitoring the condition and adjusting the treatment plan as needed.

In conclusion, CSVD represents a prevalent yet often underdiagnosed condition with significant clinical implications. Recognizing its diverse clinical manifestations and risk factors is paramount for timely diagnosis and intervention. A multidisciplinary approach involving neurologists, physical therapists, dietitians, and other healthcare professionals is crucial for comprehensive CSVD management. Moreover, ongoing research holds promise for further refining our understanding of this condition and developing more effective therapeutic interventions. As we move forward, it is imperative to remain vigilant in our efforts to improve the quality of life for patients affected by CSVD.

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Corresponding Author:
Safeena Khan
Department of Basic Medical Sciences
Khyber Medical College, Peshawar, Pakistan
Email: safeenakhan00@gmail.com

Co-Authors:
Sehba Iqbal, Syed Mohammad Omair, Arshmaan Jawad, Waqas Inayat, DR Iqbal Haider
Department of Basic Medical Sciences
Khyber Medical College, Peshawar, Pakistan

All authors contributed to the conceptualization, investigation, and data curation by acquiring and critically reviewing the selected articles. They were collectively involved in the writing – original draft preparation, and writing – review & editing to refine the manuscript. Additionally, all authors participated in the supervision of the work, ensuring accuracy and completeness. The final manuscript was approved by all named authors for submission to the journal.

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https://doi.org/10.63096/medtigo3062232

Safeena K, Sehba I, Omair SM, Arshmaan J, Waqas I, Iqbal H. Isolated Cognitive Behavioral Changes with Distinctive MRI Findings in a Patient with Cerebral Small Vessel Disease. medtigo J Med. 2024;2(3):e3062232. doi:10.63096/medtigo3062232 Crossref