Manju Mohanty

Study of factors determining caregiver burden among primary caregivers of patients with intracranial tumors.

Background: Caregivers of patients with intracranial tumors handle physical, cognitive, and behavioral impairments of patients. The purpose of this study was to assess the magnitude of burden experienced by primary caregivers of patients operated for intracranial tumors and evaluate factors influencing it. Methods: Descriptive cross-sectional design was used to assess home-care burden experienced by primary caregivers of patients operated for intracranial tumors. Using purposive sampling, 70 patient-caregiver pairs were enrolled. Modified caregiver strain index (MCSI) was used to assess the caregiver burden. Mini mental status examination (MMSE), Katz index of independence in activities of daily living (ADL), and neuropsychiatric inventory questionnaire (NPI-Q) were used to assess the status of patients. Results: Of 70 caregivers, 45 had mild, and 22 had moderate MCSI burden. A number of behavioral changes in NPI-Q had a significant correlation with MCSI burden (P < 0.001), whereas MMSE and Katz-ADL of patients did not show significant relation with caregiver burden. In NPI-Q, irritability, agitation, anxiety, depression, and sleep disturbances had a significant impact on MCSI. Among caregiver factors, unemployment, low per capita income, time spent, inability to meet household needs, quitting the job, and health problems had a significant impact on MCSI. In separate multivariate analyses, irritability component (P = 0.004) among behavioral changes of patients and caregivers’ inability to meet household needs (P < 0.001) had a significant association with caregiver burden independent of other factors. Conclusions: Behavioral changes in patients (especially irritability) and financial constraints had a significant independent impact on the burden experienced by primary caregivers of patients operated for intracranial tumors. Identifying and managing, these are essential for reducing caregiver burden.

The effect of cranioplasty following decompressive craniectomy on cerebral blood perfusion, neurological, and cognitive outcome

OBJECTIVE Decompressive craniectomy is an established therapy for refractory intracranial hypertension. Cranioplasty following decompressive craniectomy not only provides protection to the brain along with cosmetic benefits, but also enhances rehabilitation with meaningful functional recovery of potentially reversible cortical and subcortical damaged areas of the affected as well as the contralateral hemisphere. The aim of the study was to assess neurological and cognitive outcome as well as cerebral blood flow after cranioplasty. METHODS Thirty-four patients admitted for replacement cranioplasty after decompressive craniectomy for head injury were studied prospectively. Clinical, neurological, and cognitive outcomes were assessed by the Glasgow Outcome Scale (GOS), the Glasgow Coma Scale, and a battery of cognitive tests, respectively. Simultaneously, cerebral blood perfusion was assessed by technetium-99m ethyl cysteinate dimer (99mTc-ECD) brain SPECT imaging 7 days prior to and 3 months after cranioplasty. RESULTS Prior to cranioplasty 9 patients (26.5%) had GOS scores of 5 and 25 patients (73.5%) had GOS scores of 4, whereas postcranioplasty all 34 patients (100%) improved to GOS scores of 5. Approximately 35.3%-90.9% patients showed cognitive improvement postcranioplasty in various tests. Also, on comparison with brain SPECT, 94% of patients showed improvement in cerebral perfusion in different lobes. CONCLUSIONS Cranioplasty remarkably improves neurological and cognitive outcomes supported by improvement in cerebral blood perfusion.

Role of Plasma Clusterin in Alzheimer’s Disease—A Pilot Study in a Tertiary Hospital in Northern India

Objective To evaluate the role of plasma clusterin in Alzheimer’s disease (AD). Background Plasma clusterin is a promising biomarker as various studies have shown it to be associated with AD. But other studies have shown that plasma clusterin levels were not related to Alzheimer’s disease or presymptomatic AD. Hence the diagnostic value of plasma clusterin is still not conclusive. Methods Neuropsychological assessment, MRI brain, FDG-PET brain and CSF biomarkers of AD were used for establishing the diagnosis of MCI, AD or Vascular dementia. The CSF control group included patients who were having knee or hip surgery and plasma control group included the spouses of patients. Results Forty-six patients who gave consent for CSF examination and FDG PET brain were included in the study along with 19 control samples. Alzheimer’s group had 34 patients and Vascular group had 12 patients. Both had a significantly lower value of clusterin than the control samples (p<0.01). The median plasma clusterin level was 84.38 μg/ml in control group, 57.98μg/ml in Alzheimer’s group and 49.93μg/ml in the vascular group. Alzheimer and Vascular group did not differ in plasma clusterin levels. Moreover there was no correlation of plasma clusterin with AD severity. The sensitivity and specificity of plasma clusterin was low for any significance for clinical use. Conclusion Our pilot study shows that plasma clusterin is lower in Alzheimer’s disease with respect to control population. Plasma clusterin levels and severity of Alzheimer’s disease had no significant correlation. There was no difference in plasma clusterin between Alzheimer’s disease and Vascular Dementia. The sensitivity and specificity of plasma clusterin is low for any use in clinical practice. More studies are required to ascertain the utility of plasma clusterin as a biomarker in Alzheimer’s disease.

Dystrophin induced cognitive impairment: mechanisms, models and therapeutic strategies.

Existence of conserved domains in dystrophin and its associated complexes provide an opportunity to understand the role of dystrophin associated signalling and its association with neuronal metabolism in a variety of model organisms. We critically reviewed the studies till 2013 through established search engines and databases. Thus, we review the role of dystrophin and its isoforms in different animal models at developmental stages in the neuronal metabolism to enhance the therapeutic strategies. Dystrophin interacts with other proteins in such a way that, when affected, it results in co-morbidities including autism and other neuropsychiatric disorders. It is speculated that various signalling molecules may converge to disrupt neuronal metabolism not adequately studied. TGF-β, RhoGAP and CAM mediated signalling molecules are the chief cause of mortalities due to respiratory and cardiac involvement but remain underevaluated targets for cognitive impairment in DMD/BMD. Manipulation of these signalling pathways could be potent intervention in dystrophin induced cognitive impairment while complementary therapeutic approaches may also be helpful in the treatment of cognitive impairment associated with DMD/BMD.

Role of inflammatory and hemostatic biomarkers in Alzheimer’s and vascular dementia – A pilot study from a tertiary center in Northern India

INTRODUCTION A reliable plasma biomarker in differentiating between Alzheimers disease (AD) and Vascular dementia (VaD) is the need of the hour, in most memory clinics. Even though there is no disease modifying treatment, it is important to know the type of dementia for both symptomatic treatment and prognostication. METHODS Neuropsychological assessment, MRI brain, FDG-PET brain and CSF biomarkers of AD (Aβ42 and total tau) were used for establishing the diagnosis of Mild Cognitive Impairment (MCI), AD or VaD. RESULTS 68 diagnosed patients of AD/MCI/VaD were included. FDG PET brain, plasma fibrinogen, d dimer, IL6 and CRP were done in all 68 patients while 48 patients underwent CSF biomarker analysis. Sixteen patients had MCI, of which 11 were MCI-AD and 5 were MCI-VaSC. There were 41 patients with AD (Mild AD-9, Mod AD-23, Severe AD-9) and 11 patients with VaD. Alzheimer group (MCI-AD and AD) and Vascular group (MCI VaSC & VaD) consisted of 52 and 16 patients respectively. Alzheimer and Vascular groups did not exhibit significant difference in IL6 and CRP levels. Plasma fibrinogen levels were significantly higher in VaD and vascular group as compared to Alzheimer group. But MCI-VaSC was not significantly different from MCI-AD. Plasma d dimer levels were significantly higher in all vascular subgroups compared to Alzheimer subgroups except between MCI-VaSC and MCI-AD. CONCLUSION Hemostatic biomarkers were higher in Vascular group compared to Alzheimer group whereas there was no difference in inflammatory biomarkers. But the sensitivity and specificity of fibrinogen and d-dimer were not high enough for routine clinical use. Further studies in a larger sample are required to confirm these results.

Prevalence and Trends in the Neuropsychological Burden of Patients having Intracranial Tumors with Respect to Neurosurgical Intervention

Background: The burden of neuropsychological symptoms evidenced by behavioral changes among patients with intracranial tumors has not been studied in detail. Purpose: This study was conducted to prospectively assess the neuropsychological symptoms in patients with intracranial tumors undergoing treatment. Methods: A longitudinal study was conducted using purposive sampling to assess the neuropsychological symptoms in conscious and consenting patients with intracranial tumors who were availing treatment from a tertiary care center. Neuropsychiatric Inventory Questionnaire (NPI-Q), which identifies 12 behavioral disturbances, was assessed at baseline, and later at 1 month and 6 months after treatment, and scored as symptom severity as well as symptom scores. Results: Among the 34 patients studied, all had experienced at least one neuropsychological symptom. The commonest neuropsychological symptoms at baseline were anxiety (82%), agitation (75%), irritability (74%), depression (74%), and sleep disturbances (70%). The neuropsychiatric symptom and severity scores were 5.84 (SD ±2.7) and 11.8 (±7.1) at baseline, which reduced significantly to 4.3 (±3.1) and 5.6 (±3.2) at 1 month, and further to 2.3 (±2.9) and 3.6 (±3.2) at 6 months, respectively. The neuropsychological symptoms persistent at 6 months were anxiety (33%), depression (33%), sleep disturbances (33%), agitation (25%), irritability (25%), and disinhibition (25%). Conclusion: There is substantial neuropsychological burden among patients with intracranial tumors. The severity score improved immediately after surgery, while the symptom score improved gradually. The variable spectrum of improvement in neuropsychological symptoms at 6 months after surgical treatment needs further consideration. Addressing these symptoms should be one of the long-term goals of the neuro-oncology teams.

Trends in cognitive dysfunction following surgery for intracranial tumors.

Background: This study was conducted to prospectively assess the cognitive function of patients with intracranial tumors. Methods: The cognitive status of patients with intracranial tumors were prospectively studied before surgery, and later at 1 and 6 months following surgery, on purposive sampling, using validated post graduate institute (PGI) battery for brain dysfunction (score 0–30) with a higher dysfunction rating score indicating poor cognitive status. Results: Out of 23 patients enrolled, 20 could complete the study. They had substantial cognitive dysfunction before surgery (score 17.1 ± 9.4). Though there was no significant improvement (16.9 ± 9.0) at 1 month, the score improved significantly (10.3 ± 9.2) at 6 months following surgery (P = 0.008). The improvement was relatively subdued in intra-axial, malignant, and radiated tumors. Overall, there was a significant improvement in mental balance (P = 0.048), verbal retention of dissimilar pairs (P = 0.01), and recognition (P = 0.01), while dysfunction persisted in the domains of memory, verbal retention to similar pairs, and visual retention. Conclusion: Patients with intracranial tumors have substantial cognitive dysfunction, which tend to show significant improvement beyond 6 months following surgery, especially among tumors, which were extra-axial, benign, and nonirradiated.