Shyamal H. Mehta

Tamoxifen, a Selective Estrogen Receptor Modulator, Reduces Ischemic Damage Caused by Middle Cerebral Artery Occlusion in the Ovariectomized Female Rat

Previous work has demonstrated that physiological concentrations of 17β-estradiol can protect the female rat brain against middle cerebral artery occlusion (MCAO)-induced ischemic damage. The present study examined whether therapeutic doses of the clinically relevant selective estrogen receptor modulator (SERM), tamoxifen, can similarly protect the female rat brain against ischemic stroke damage. Adult female rats were bilaterally ovariectomized and implanted subcutaneously with either a placebo or tamoxifen time-release pellet (0.1, 0.8 or 2.4 mg/kg/day). One week later, the animals underwent permanent MCAO to assess the protective ability of the different tamoxifen doses on brain infarct size. As expected, MCAO produced a large infarct (∼53%) of the affected cerebral hemisphere in placebo (control) animals. The 0.1 mg/kg/day dose of tamoxifen did not exhibit any significant protective effects, however; the 0.8 and 2.4 mg/kg/day doses of tamoxifen, which are in the therapeutic range, dramatically reduced infarct of the affected cerebral hemisphere (∼70% reduction) as compared to the controls. The reduction of infarct size was primarily due to protection of two major structures, the cerebral cortex and striatum. Laser Doppler analysis further revealed that tamoxifen had no significant effect on cerebral blood flow either before or after MCAO, suggesting that tamoxifen protection is independent of cerebral blood flow changes. Further studies showed that tamoxifen pellets implanted at the time of MCAO did not reduce infarct size, suggesting that pretreatment with tamoxifen is necessary to observe a protective effect. These studies suggest that clinically important SERMs may have an additional unrecognized beneficial effect of protection of the female brain.

Nintendo Wii rehabilitation (“Wii-hab”) provides benefits in Parkinson's disease

Parkinsons disease (PD) impairs both activities of daily living (ADLs) and motor function and has adverse effects on mood in many patients. While dopaminergic medications are quite helpful for motor and ADLs impairments in PD, complementary therapies are also important in helping patients achieve maximum benefits and quality of life. We hypothesized that the Nintendo Wii (Wii) is a useful tool in improving motor and non-motor aspects in patients with PD, given its ability to drive functional movements and interactive nature. We enrolled twenty subjects with early to mid-stage PD in an open-label within-subjects study design where each subject was evaluated at baseline and then re-evaluated after playing the Wii three times per week for four weeks. Subjects were then re-evaluated one month later after not playing the Wii for a month to see if effects carried over. Subjects demonstrated significant improvements in the primary outcome measure (Nottingham Extended Activities of Daily Living Test (NEADL)), quality of life (PDQ-39) and motor function (UPDRS), and a trend toward improved mood (HAM-D) after four weeks of Wii therapy. Follow-up assessments one month later showed continued improvement for quality of life and UPDRS scores. The results demonstrate that Wii therapy provides short-term motor, non-motor, and quality of life benefits in PD. Further studies are needed to determine if there are long-term benefits of Wii therapy in PD.

Sleep disorders associated with Parkinson's disease: Role of dopamine, epidemiology, and clinical scales of assessment

Sleep dysfunction is common among patients with Parkinsons disease and occurs in approximately two thirds of patients. The problems range from nocturnal issues such as difficulty with sleep initiation, sleep fragmentation, disturbance of circadian rhythm, and rapid eye movement sleep behavior disorder, to daytime problems such as excessive daytime sleepiness. Frequent nighttime awakening and sleep disruption are the most common sleep problems in Parkinsons disease. Dopamine plays an important role in maintaining wakefulness. To improve sleep in Parkinsons disease, it is important to achieve the critical balance of adequate dopaminergic therapy and control of symptoms. Increased dopaminergic agents can cause dyskinesias and painful dystonia, and undertreatment can cause nighttime akinesia, rigidity, and worse quality of sleep. Other nondopaminergic drugs commonly used in Parkinsons disease can also affect sleep. In patients with advanced Parkinsons disease, deep brain stimulation of the subthalamic nucleus has a favorable impact on sleep quality and sleep architecture.

Drug-induced movement disorders

Movement disorders are frequently a result of prescription drugs or of illicit drug use. This article focuses on prescribed drugs but briefly mentions drugs of abuse. The main emphasis is on movement disorders caused by dopamine receptor-blocking agents. However, movement disorders caused by other drugs are also briefly discussed.

Peripheral Synucleinopathy in Early Parkinson's Disease: Submandibular Gland Needle Biopsy Findings

Finding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine whether needle biopsy of the submandibular gland reveals Lewy type alpha‐synucleinopathy in early PD.

Peripheral Synucleinopathy in Early Parkinson's Disease

Finding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine whether needle biopsy of the submandibular gland reveals Lewy type alpha‐synucleinopathy in early PD.

Advances in Biomarker Research in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and the numbers are projected to double in the next two decades with the increase in the aging population. An important focus of current research is to develop interventions to slow the progression of the disease. However, prerequisites to it include the development of reliable biomarkers for early diagnosis which would identify at-risk groups and disease progression. In this review, we present updated evidence of already known clinical biomarkers (such as hyposmia and rapid eye movement (REM) sleep behavior disorder (RBD)) and neuroimaging biomarkers, as well as newer possible markers in the blood, CSF, and other tissues. While several promising candidates and methods to assess these biomarkers are on the horizon, it is becoming increasingly clear that no one candidate will clearly fulfill all the roles as a single biomarker. A multimodal and combinatorial approach to develop a battery of biomarkers will likely be necessary in the future.

Graph theory network function in Parkinson’s disease assessed with electroencephalography

OBJECTIVES To determine what differences exist in graph theory network measures derived from electroencephalography (EEG), between Parkinsons disease (PD) patients who are cognitively normal (PD-CN) and matched healthy controls; and between PD-CN and PD dementia (PD-D). METHODS EEG recordings were analyzed via graph theory network analysis to quantify changes in global efficiency and local integration. This included minimal spanning tree analysis. T-tests and correlations were used to assess differences between groups and assess the relationship with cognitive performance. RESULTS Network measures showed increased local integration across all frequency bands between control and PD-CN; in contrast, decreased local integration occurred in PD-D when compared to PD-CN in the alpha1 frequency band. Differences found in PD-MCI mirrored PD-D. Correlations were found between network measures and assessments of global cognitive performance in PD. CONCLUSIONS Our results reveal distinct patterns of band and network measure type alteration and breakdown for PD, as well as with cognitive decline in PD. SIGNIFICANCE These patterns suggest specific ways that interaction between cortical areas becomes abnormal and contributes to PD symptoms at various stages. Graph theory analysis by EEG suggests that network alteration and breakdown are robust attributes of PD cortical dysfunction pathophysiology.

Simplified conversion method for unified Parkinson's disease rating scale motor examinations.

We evaluated a simplified method for converting Unified Parkinsons Disease Rating Scale Part III Motor Examination total scores (UPDRS III) to the International Parkinson and Movement Disorder Societys (MDS) revised version of the scores.

IgG4-related leptomeningitis: A reversible cause of rapidly progressive cognitive decline

Immunoglobulin G4–related diseases (IgG4-RD) are a newly recognized category of diseases. CNS involvement in IgG4-RD includes hypophysitis1 and intracranial or spinal manifestations of hypertrophic pachymeningitis.2,3 We present a unique case of rapid cognitive decline due to IgG4-related leptomeningitis.