Longitudinal Metabolite Changes in Progressive Multiple Sclerosis: A Study of 3 Potential Neuroprotective Treatments

BACKGROUND: 1 H-magnetic resonance spectroscopy (1 H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS). PURPOSE: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by 1 H-MRS and their association with clinical disability in SPMS. STUDY-TYPE: Longitudinal. POPULATION: 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%]. FIELD STRENGTH/SEQUENCE: 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1. ASSESSMENT: Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks. STATISTICAL TESTS: Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value<0.05 was considered statistically significant. RESULTS: In the placebo arm, tCho increased in GM (mean difference = -0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (β = -0.21); in the riluzole arm, GM Glx (β = -0.25) and Glx/tCr (β = -0.29) were reduced. Baseline tNAA(β = 0.22) and tNAA/tCr (β = 0.23) in NAWM were associated with 9HPT scores at 96-weeks. DATA CONCLUSION: 1 H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4

An International Survey of Deep Brain Stimulation Utilization in Asia and Oceania: The DBS Think Tank East.

Introduction: To evaluate the current utilization and challenges in fully implementing the use of deep brain stimulation (DBS) treatment in Asia and Oceania. Methods: We conducted a medical literature search to identify DBS research performed by investigators with a primary affiliation in Asian and Oceania countries between March 1, 2013, and March 1, 2019, followed by an international survey-based study. Additionally, we obtained added information regarding the DBS challenges and opportunities from the technology/industry perspective within China and Japan. We also described the current situation of DBS in India. Results: Most publications (390/494; 78.95%) in the English language originated from East Asia. In West Asia, Turkey, Israel, and Iran accounted for most DBS publications. We found no publications from the remaining 35 Asian countries. Lack of community referrals to tertiary centers was identified as the most common limitation for the widespread use of DBS in Asia (68.97%). In China, despite an increasing number of centers performing DBS surgeries, most of them accomplished less than 10 cases per year. In contrast, the number of DBS cases in Japan has been decreasing. Centers offering DBS surgeries as well as corresponding fellowship training in India are limited. Conclusion: Appropriate referrals, access, infrastructure, and the presence of full multidisciplinary DBS teams are common limitations of DBS in Asia. Most centers in China, Japan, and India performed less than 10 cases per year and a future study is expected to address the impact on quality in centers performing such few cases

Longitudinal metabolite changes in progressive multiple sclerosis:A study of 3 potential neuroprotective treatments

Background: 1 H-magnetic resonance spectroscopy (1 H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS). Purpose: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by 1 H-MRS and their association with clinical disability in SPMS. Study-type: Longitudinal. Population: 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%]. Field strength/sequence: 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1. Assessment: Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks. Statistical tests: Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value&lt;0.05 was considered statistically significant. Results: In the placebo arm, tCho increased in GM (mean difference = -0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (β = -0.21); in the riluzole arm, GM Glx (β = -0.25) and Glx/tCr (β = -0.29) were reduced. Baseline tNAA(β = 0.22) and tNAA/tCr (β = 0.23) in NAWM were associated with 9HPT scores at 96-weeks. Data conclusion: 1 H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function. Level of evidence: 1 TECHNICAL EFFICACY: Stage 4

A hospital-based cross-sectional study of clinical, wood's lamp, and dermoscopic findings in melasma

Background: Melasma is a common pigmentation disorder with female predominance. Depending on melanin depth, it can be epidermal, dermal, and mixed type. Assessment of this helps to chalk out a proper treatment plan. Dermoscopy is a device which helps to examine and assess pigment color and depth. Objective: Due to the relative dearth of literature on the correlation between clinical, dermoscopy, and Wood's lamp findings, we undertook this study to classify melasma and correlate dermoscopic features with clinical and Wood's lamp findings. Materials and Methods: Clinical, Wood's lamp, and dermoscopic examination with Dino-Lite Premier AM4113ZT were conducted in 160 patients of clinically diagnosed melasma. Findings of light-brown network and perifollicular sparing were considered for diagnosing epidermal melasma; gray-to-brown pigmentation, perifollicular or arciform pattern of hyperpigmentation for diagnosing dermal melasma. Patients with a combination of both were classified into mixed melasma. This was correlated with clinical and Wood's lamp findings. Results: Data analysis by statistical software R version 4.0.2 and Microsoft Excel showed female predominance (80%, n = 128). On clinical and Wood's lamp examination, the majority had mixed type of melasma; this was followed by epidermal and dermal melasma, respectively. Dermoscopic examination showed a mixed type of melasma in majority, followed by dermal and epidermal type. By Cohen's kappa, there was substantial agreement present between dermoscopic impression and Wood's lamp examination (K = 0.6112, P < 0.00001). Conclusion: Dermoscopic evaluation as a noninvasive tool provides a better insight on classifying the melasma patterns versus clinical and Wood's lamp examination and hence decides upon its further management

Palmar lichen planus mimicking tinea nigra

Lichen planus (LP) is a chronic inflammatory skin disease characterized by polygonal, violaceous papules commonly involving flexural areas of the wrists, legs, and oral and genital mucous membranes. This report describes a patient who presented with asymptomatic black colored patches on both palms simulating Tinea nigra, a superficial fungal infection. She was previously diagnosed as allergic contact dermatitis and was being treated with potent topical steroid i.e. clobetasol propionate 0.05% and white soft paraffin. Dermatoscopy of the lesion showed brownish pigmentation along ridges of the dermatoglyphics. A biopsy from the lesional skin showed findings of lichen planus. Our case highlights the potential diagnostic confusion that can occur with unusual variants of palmoplantar lichen planus and importance of histopathology in diagnosis of such unusual lesions

Hyperkeratotic palmoplantar lichen planus in a child

Lichen planus (LP) is a common idiopathic inflammatory disorder that affects the flexor aspect of the wrists, the legs, and the oral and genital mucosa. Depending upon the site of involvement, LP can be divided into mucosal, nail, scalp, or palmoplantar types. Palmoplantar LP can pose a diagnostic problem to the clinician as it resembles common dermatoses like psoriasis, verruca, corn, calluses, lichenoid drug eruption, and papular syphilide of secondary syphilis. In this case report, we describe a 4-year-old male child who presented with highly pruritic erythematous to violaceous hyperkeratotic papules and plaques on his palms and soles. Typical LP papules were noted on the upper back. Histopathology of the papular lesion showed features of LP. Dermatoscopy of a papule from the back showed the characteristic Wickham striae. We report this rare involvement of palm and soles in a case of childhood LP

Appearances in dermatopathology: The diagnostic and the deceptive

Dermatopathology involves study of the microscopic morphology of skin sections. It mirrors pathophysiologic changes occurring at the microscopic level in the skin and its appendages. Sometimes, we come across certain morphologic features that bear a close resemblance to our physical world. These close resemblances are referred to as "appearances" in parlance to dermatopathology. Sometimes, these "appearances" are unique to a certain skin disorder and thus help us to clinch to a definitive diagnosis (e.g., "tadpole" appearance in syringoma). However, frequently, these appearances are encountered in many other skin conditions and can be therefore be misleading. In this paper, we attempt to enlist such "appearances" commonly found in the dermatopathologic literature and also enumerate their differential diagnoses