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When the white matter lies: A case series on Binswanger’s disease masquerading as paraphrenia
*Corresponding author: Siva Kumar Selvaraj, Department of Psychiatry, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu, India. siva.selvaraj98@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Selvaraj SK, Sudheer N, Rosalind R, Selvaraj V. When the white matter lies: A case series on Binswanger’s disease masquerading as paraphrenia. Arch Biol Psychiatry. 2025;3:30-4. doi: 10.25259/ABP_4_2025
Abstract
Binswanger’s disease (BD), also known as subcortical arteriosclerotic leucoencephalopathy, is a rare form of vascular dementia characterized by progressive white matter demyelination and lacunar infarctions. It commonly presents with cognitive decline, psychiatric symptoms, and motor impairments. However, in some cases, the initial presentation may mimic primary psychotic disorders, delaying diagnosis. This case series describes three elderly patients who initially presented with late-onset psychotic symptoms resembling paraphrenia, such as delusions and hallucinations. However, their diagnoses were later revised to subcortical vascular dementia with behavioral and psychological symptoms, after a history of cognitive decline and executive dysfunction was identified. Each had a history of hypertension and transient ischemic attacks, suggesting an underlying vascular etiology. Neuroimaging revealed extensive periventricular and subcortical white matter changes consistent with BD. Treatment with antipsychotics led to partial improvement in psychotic symptoms, while cognitive enhancers were introduced to address cognitive deficits. Despite symptomatic relief, cognitive impairment persisted, underscoring the irreversible nature of the disease. This case series highlights the importance of considering organic causes in elderly patients with new-onset psychotic symptoms. Late-onset psychosis, especially in the presence of vascular risk factors, warrants thorough neurological evaluation. Early recognition of Binswanger’s disease allows for targeted management of vascular risk factors, such as hypertension, which may help slow disease progression and improve quality of life. Recognizing this atypical presentation can prevent misdiagnosis and inappropriate treatment, ensuring a more comprehensive approach to patient care.
Keywords
BPSD
Binswanger’s disease
Cognitive dysfunction
Late onset psychosis
Paraphrenia
INTRODUCTION
Major neurocognitive disorder, previously called dementia, is a progressive, heterogenous condition caused by primary or secondary disease of the brain characterized by cognitive decline affecting multiple domains without clouding of consciousness.[1] It is defined by a decline in a previously acquired cognitive function, distinguishing it from other mental disorders such as schizophrenia and bipolar disorders, where the cognitive deficits are secondary. It is also associated with changes in behavior and personality that may coincide with disease progression.[2] Vascular dementia is the second most prevalent dementia after Alzheimer’s dementia,[3-5] results from chronic cerebrovascular pathology, and is often associated with hypertension and small vessel ischemic disease.[1] Binswanger’s disease (BD), also known as “subcortical arteriosclerotic encephalopathy,” is a form of subcortical vascular dementia and is characterized by stepwise cognitive decline, executive dysfunction, gait disturbances, and urinary incontinence, with neuroimaging showing diffuse white matter hyper-intensities and lacunar infarcts.[6,7] There is emerging evidence of behavioral and psychological symptoms that may precede overt cognitive deficits, leading to potential misdiagnosis as a primary psychiatric disorder.[8,9] This case series presents three elderly patients initially diagnosed with late-onset psychosis, later confirmed to have BD based on clinical history and neuroimaging. It highlights the role of early recognition, neuroimaging in distinguishing organic causes from primary psychiatric disorders in managing late-onset neuropsychiatric symptoms.
CASE SERIES
This case series describes three elderly patients with a history of uncontrolled systemic hypertension and multiple transient ischemic attacks, with no past or family history of mental illness. They were brought with symptoms of unprovoked agitation, emotional lability, delusions, and hallucinations in clear consciousness with corroborative mental status examination and were provisionally diagnosed as cases of late-onset psychosis and started on low-dose atypical antipsychotics. Further evaluation revealed a background of progressive cognitive decline in a stepwise manner, with intermittent periods of stable deficits, executive dysfunction, and increasing dependence on activities of daily living with new onset urinary incontinence. Neuroimaging showed cerebral atrophy, small vessel ischemic changes, and chronic lacunar infarcts consistent with BD [Figures 1-4]. Cognitive assessments demonstrated significant deficits, and all patients had high Hachinski ischemic index scores, supporting a vascular cause [Table 1]. Treatment with low doses of atypical antipsychotics and cognitive enhancers resulted in the resolution of behavioral and psychotic symptoms, while cognitive deficits remained stable. Secondary stroke prophylaxis was initiated in all cases [Table 2].
- Magnetic resonance imaging brain showing cerebral atrophic changes with prominent sulcal space (white arrows).
- Magnetic resonance imaging brain showing a chronic lacunar infarct in the left corona radiata and left gangliocapsular region (white arrow).
- Magnetic resonance imaging brain showing small-vessel ischemic changes (white arrows).
- Magnetic resonance imaging brain showing foci of microhemorrhage in bilateral thalami (white arrows).
| Assessments | Patient 1 | Patient 2 | Patient 3 |
|---|---|---|---|
| MMSE | 18 | 16 | 18 |
| MOCA | 14 | 12 | 14 |
| CDRS | 11.5 | 11.5 | 11 |
| Hachinski ischemic index | 10 | 6 | 8 |
| BPRS | 47 | 44 | 40 |
MMSE: Mini mental state examination, BPRS: Brief psychiatric rating scale, MOCA: Montreal cognitive assessment, CDRS: Clinical dementia rating (CDR) scale.
| Category | Case 1 | Case 2 | Case 3 |
|---|---|---|---|
| Demographic details | 70 years Female, Widow | 76 years Female, Married | 65 years Male, Married |
| Medical Comorbidities | Hypertension -13 years duration, hemorrhagic stroke with residual left hemiparesis, multiple TIAs | Hypertension and Diabetes Mellitus - 40 years duration, multiple TIAs | Hypertension -20 years duration, Diabetes Mellitus -10 years duration, multiple TIAs |
| Presenting complaints (Behavioural) |
Duration: 3 months; Onset: Insidious; Symptoms: unprovoked agitation, persecutory delusions, visual hallucinations; insomnia, bladder incontinence for 15 days. | Duration: 4 months; Onset: Insidious; Symptoms: agitation, violent behavior, persecutory & infidelity delusions, auditory & visual hallucinations, insomnia, bladder incontinence for 10 days. | Duration: 6 months; Onset: Insidious; Symptoms: agitation, inappropriate laughter, visual hallucinations, mood lability, insomnia, bladder incontinence for 15 days. |
| Cognitive Symptoms | 3 years history of stepwise cognitive decline and executive dysfunction interposed with periods of stable deficit, bedridden for 6 months | 2 years history of stepwise cognitive decline and executive dysfunction interposed with periods of stable deficit, assisted ADL | 3 years history of stepwise cognitive decline and executive dysfunction interposed with periods of stable deficit, supervised ADL |
| Mental status examination findings |
Disheveled, irritable, visual hallucinations, persecutory delusions, labile affect | Playful, disinhibited, cheerful, persecutory & infidelity delusions, hallucinations | Gait apraxia, tearful affect, visual hallucinations, fluctuating mood, partial insight |
| Rating Scale | MMSE: 18 MoCA: 14 CDRS: 11.5 Hachinski ischemic index : 10 BPRS: 47 |
MMSE: 16 MoCA: 12 CDRS: 11 Hachinski ischemic Index : 6 BPRS: 44 |
MMSE: 18 MoCA: 14 CDRS: 11 Hachinski ischemic Index: 8 BPRS: 40 |
| Neuroimaging findings | Cerebral atrophic changes [Figure 1], small vessel ischemic changes in bilateral frontoparietal white matter and periventricular region, Chronic lacunar infarct in Left Corona Radiata and Left ganglio-capsular region [Figure 2] with Foci of microhemorrhage in bilateral thalami | Moderate cerebral atrophy, chronic small vessel ischemic changes bilateral subcortical white matter [Figure 3]; multiple lacunar infarcts in periventricular white matter | Cerebral atrophic changes, small vessel ischemic changes in bilateral frontoparietal white matter and periventricular region, and Chronic lacunar infarct in Left Corona Radiata with Foci of microhemorrhage in bilateral thalami [Figure 4] |
| Pharmacological management | Risperidone 4mg —> changed to Quetiapine 50mg, Donepezil 10 mg, Memantine 5 mg |
Risperidone 4 mg, Donepezil 10 mg, Memantine 5 mg |
Quetiapine 50 mg, Memantine 5 mg |
| Secondary stroke prophylaxis with anti-platelets, statins and anti-hypertensive agents | |||
TIAs: Transient ischemic attacks, MOCA: Montreal Cognitive Assessment, CDRS: Clinical dementia rating scale, MMSE: Mini mental state examination, BPRS: Brief psychiatric rating scale, ADL: Activities of daily living.
DISCUSSION
BD is characterized by widespread demyelination of white matter, along with lacunar lesions in the basal ganglia and brainstem. The symptoms may be caused by structural damage and/or involvement of the neurotransmitter systems.[6] The initial presentation in all three cases suggested late-onset psychosis. Considering the metabolic comorbidity and addressing psychotic symptoms and agitation, tablet Risperidone was started in patients 1 and 2 while keeping the side effects under cautious watch. However, the presence of cognitive decline prompted further neuropsychological assessments confirming cognitive impairment and radiological evaluation, which confirmed diffuse white matter disease. Case 1 developed extrapyramidal side effects, hence was switched over to Tab Quetiapine 50 mg, to which she responded. Case 3 was started on Tab Quetiapine built up to 50 mg, as dementia with behavioral and psychotic symptoms was clarified in the index visit, and neuroimaging was available before initiation of medication, aiding earlier diagnosis and management. Each patient had at least one vascular risk factor, such as hypertension, along with signs of organic pathology, including urinary incontinence. Case 1 additionally exhibited residual right-sided hemiparesis, indicative of an upper motor neuron lesion. These findings, along with clinical symptoms, metabolic risk factors, and overall physical and neurological examination, supported the diagnosis of BD.[7] There were no features of delirium at the time of admission based on clinical examination and the confusion assessment method. Ultrasound abdomen and urine examination, including culture, ruled out urinary tract infection in all three cases. In addition to cognitive decline, the patients had emotional instability, visual hallucinations which were clear, well-formed, and not fluctuating in clear consciousness, more inclined to an organic cause than primary psychiatric disorder.[10] BD, also known as “subcortical arteriosclerotic encephalopathy,” is later in onset and has an abrupt or gradual progression with stepwise decline, characterized by white matter hyper-intensity and lacunar infarcts connected to circulatory and vascular issues, often leading to severe clinical outcomes commonly associated with high blood pressure, arteriosclerosis, and stroke.[6] Individuals with suspected vascular dementia have a history of temporary episodes of reduced blood flow to the brain caused by blockages in the brain’s blood vessels linked to a series of small strokes or, less commonly, a single major stroke, resulting in brief periods of confusion, vision loss, or motor weakness. These blockages, although small, can build up over time and have a cumulative impact on brain function. Symptoms of memory and cognitive decline gradually become noticeable, usually occurring later in life.[1] Caplan, in 1995, was the first to establish diagnostic criteria based on vascular risk factors, clinical presentation, and radiological features.[7] Nagaratnam and Nagaratnam described four symptom clusters, including late-onset paranoid psychosis, confusion, depression, and a behavioral syndrome resembling frontal lobe dysfunction.[8] Our review of literature revealed isolated case reports describing cases with psychiatric features such as psychosis and mood symptoms, later attributed to BD based on radiological investigation.[4,11-13] However, these reports had limitations such as a lack of longitudinal follow-up, minimal neuropsychological evaluation, and limited generalizability due to single-case designs. While there are no specific treatments, the American Heart Association recommends managing vascular risk factors, including controlling elevated blood pressure, using anti-platelets, statins, adopting a healthy lifestyle, and rehabilitation to slow the advancement of white matter lesions and improve functional outcome and quality of life.[14]
CONCLUSION
BD is a complex neuropsychiatric disease, and its pathophysiology is only partially understood. It can present with symptoms that mimic paraphrenia, leading to misdiagnosis and delayed treatment. This case series highlights that organicity should always be considered in elderly patients presenting with atypical and/or late onset psychiatric symptoms and new onset cognitive and behavioral changes, that can help improve outcomes and quality of life. Further research and awareness are needed to better understand and address the complexities of this condition.
Ethical approval:
The research/study approved by the Institutional Review Board at Velammal Medical College Hospital and Research Institute, number VMCIEC/126/2024, dated 27th September 2024.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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