Frequency-tuned electromagnetic field therapy improves post-stroke motor function: A pilot randomized controlled trial.

Background and purpose: Impaired upper extremity (UE) motor function is a common disability after ischemic stroke. Exposure to extremely low frequency and low intensity electromagnetic fields (ELF-EMF) in a frequency-specific manner (Electromagnetic Network Targeting Field therapy; ENTF therapy) is a non-invasive method available to a wide range of patients that may enhance neuroplasticity, potentially facilitating motor recovery. This study seeks to quantify the benefit of the ENTF therapy on UE motor function in a subacute ischemic stroke population. Methods: In a randomized, sham-controlled, double-blind trial, ischemic stroke patients in the subacute phase with moderately to severely impaired UE function were randomly allocated to active or sham treatment with a novel, non-invasive, brain computer interface-based, extremely low frequency and low intensity ENTF therapy (1-100 Hz, < 1 G). Participants received 40 min of active ENTF or sham treatment 5 days/week for 8 weeks; ~three out of the five treatments were accompanied by 10 min of concurrent physical/occupational therapy. Primary efficacy outcome was improvement on the Fugl-Meyer Assessment - Upper Extremity (FMA-UE) from baseline to end of treatment (8 weeks). Results: In the per protocol set (13 ENTF and 8 sham participants), mean age was 54.7 years (±15.0), 19% were female, baseline FMA-UE score was 23.7 (±11.0), and median time from stroke onset to first stimulation was 11 days (interquartile range (IQR) 8-15). Greater improvement on the FMA-UE from baseline to week 4 was seen with ENTF compared to sham stimulation, 23.2 ± 14.1 vs. 9.6 ± 9.0, p = 0.007; baseline to week 8 improvement was 31.5 ± 10.7 vs. 23.1 ± 14.1. Similar favorable effects at week 8 were observed for other UE and global disability assessments, including the Action Research Arm Test (Pinch, 13.4 ± 5.6 vs. 5.3 ± 6.5, p = 0.008), Box and Blocks Test (affected hand, 22.5 ± 12.4 vs. 8.5 ± 8.6, p < 0.0001), and modified Rankin Scale (-2.5 ± 0.7 vs. -1.3 ± 0.7, p = 0.0005). No treatment-related adverse events were reported. Conclusions: ENTF stimulation in subacute ischemic stroke patients was associated with improved UE motor function and reduced overall disability, and results support its safe use in the indicated population. These results should be confirmed in larger multicenter studies. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04039178, identifier: NCT04039178.

SARS-CoV-2-associated haemorrhagic encephalitis mimicking Herpes encephalitis.

Although acute encephalopathy is quite commonly seen in patients of SARS-CoV-2 infection, encephalitis characterised by brain inflammation is relatively rare. Encephalitis caused by Herpes simplex type 1 is the most common cause of identified sporadic encephalitis, and early diagnosis and prompt treatment can prevent the devastating outcome. In this brief communication, we report a case of SARS-CoV-2 associated haemorrhagic encephalitis mimicking herpes encephalitis. In today's pandemic era, it is especially important to distinguish herpes encephalitis from SARS-CoV-2-associated encephalitis as treatment and prognosis of both the conditions differ greatly. This case highlights the importance of suspecting SARS-CoV-2 infection in a patient presenting with clinical symptoms and brain imaging suggestive of Herpes encephalitis.

Curious case of steroid responsive diffuse anterior horn cell disease associated with COVID-19 infection.

Covid-19-associated neurological manifestations are being reported with increased frequency throughout the world. In a study from China, symptoms referable to peripheral nervous system (PNS) were described in approximately 9% of hospitalized Covid-19 patients. Common PNS symptoms reported in the study were loss of taste/smell and muscle pains. With this communication, we expand the spectrum of PNS manifestations of Covid-19 infection by reporting an association of steroid responsive diffuse anterior horn cell disease with Covid-19 infection from a tertiary care centre in India. Neurological manifestations of Covid-19 are diverse, and our case which to best of my knowledge is the first case in literature to report an occurrence of steroid responsive diffuse anterior horn cell disease associated with Covid-19 infection, adds to the ever-increasing spectrum of neurological manifestations associated with this pandemic causing virus. Good response to steroid in our case serves to provide an insight into the possible pathogenesis of this manifestation and also paves the way for future therapeutic decisions related to this association.

Paraneoplastic cerebellar degeneration as a presenting manifestation of non-Hodgkin's lymphoma.

BACKGROUND: Paraneoplastic Cerebellar degeneration (PCD) is one of the classical paraneoplastic syndromes (PNS) which is characterised by subacute onset, progressive cerebellar ataxia and is usually associated with small cell lung carcinoma, adeno carcinoma of breast and ovary followed by Hodgkin's lymphoma. OBJECTIVE: We herein report a case of subacute onset, progressive cerebellar ataxia in a 37-year-old female, who on evaluation was found to have non-Hodgkin's lymphoma and experienced good clinical response to treatment. DISCUSSION: As compared to solid tumours, chances of association of PNS with Lymphomas is quite low and there are only few case reports in the literature showing association of PCD with non-Hodgkin's lymphoma. As PCD is one of the classical PNS, it is very important to identify subtle cerebellar manifestations in an otherwise apparently normal individual, as early diagnosis and aggressive treatment can immensely improve the mortality and morbidity associated with this syndrome. CONCLUSION: This case signifies the importance of suspecting PNS as an important differential diagnosis in a young patient presenting with subacute onset progressive cerebellar ataxia and evaluating her extensively for malignancy in spite of no paraneoplastic antibody been detected as early diagnosis and treatment can lead to gratifying response. We do agree that 2 weeks follow up is a short time interval to determine whether the response was sustained or not, for which a long term follow up is required.

Covid-19 associated Guillain-Barre Syndrome: Contrasting tale of four patients from a tertiary care centre in India.

BACKGROUND: Globally, more than 12 million people have been infected with COVID -19 infection till date with more than 500,000 fatalities. Although, Covid-19 commonly presents with marked respiratory symptoms in the form of cough and dyspnoea, a neurotropic presentation has been described of late as well. OBJECTIVE: In this brief communication we report four cases of Covid-19 who presented to our hospital with features suggestive of Guillain-Barre Syndrome (GBS). DISCUSSION: The mechanisms by which SARS-CoV-2 causes neurologic damage are multifaceted, including direct damage to specific receptors, cytokine-related injury, secondary hypoxia, and retrograde travel along nerve fibres. The pathogenesis of GBS secondary to Covid-19 is not well understood. It is hypothesised that viral illnesses related GBS could be due to autoantibodies or direct neurotoxic effects of viruses. CONCLUSION: Nervous system involvement in Covid-19 may have been grossly underestimated. In this era of pandemic, it is very important for the physicians to be aware of association of GBS with Covid-19, as early diagnosis and treatment of this complication could have gratifying results. To the best of our knowledge, this is the first such case series of Guillain-Barre Syndrome associated with Covid-19 to be reported from India.

Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

Melatonergic drugs for therapeutic use in insomnia and sleep disturbances of mood disorders.

Insomnia is common among elderly people and nearly 30 to 40% of the adult population also suffer from insomnia. Pharmacological treatment of insomnia include the use of benzodiazepine and non-benzodiazepine drugs like zolpidem, zaleplon, Zopiclone. Although these drugs improve sleep, their usage is also associated with number of adverse effects, Melatonin, the hormone secreted by the pineal gland of all animals and human beings has been used for treatment of insomnias, since the timing of its secretion in humans as well as in most of the animals coincides with the increase of nocturnal sleep propensity. Because of its short half life, melatonin slow release preparations were introduced for treatment of insomnia. Recently ramelteon, a selective MT1, MT2 receptor agonist with greater efficacy of action in treating insomnia has been used clinically and has been found effective in improving sleep quality, sleep efficacy and also in reducing the sleep onset time when compared to melatonin or slow melatonin preparations. The mechanism of action of ramelteon in improving sleep is discussed in the paper. Another melatonergic drug agomelatine besides acting on MT1/MT2 receptors also displays 5-HT2c antagonism and this drug has been found effective as a novel antidepressant for treating major depressive disorders. Agomelatine besides causing remission of depressive symptoms also improves sleep quality and efficiency. Other antidepressants depressants that are in clinical use today do not improve sleep. There are other melatonergic drugs like tasimelteon, 6-chloromelatonin. But ramelteon and agomelatine deserve special attention for treatment of insomnia and sleep disturbances associated with depressive disorders and have promising role for treatment of sleep disorders.

Nerve conduction study of healthy Asian Malays: the influence of age on median, ulnar, and sural nerves.

BACKGROUND: Nerve conduction study is essential in the diagnosis of focal neuropathies and diffuse polyneuropathies. There are many factors that can affect nerve conduction velocity, and age is one of them. Most of the many studies of this effect, and the values from them, were on Caucasian subjects. Therefore, this study was designed to investigate the effect of age on conduction velocity among healthy Asian Malay subjects by analyzing its influence on the median, ulnar, and sural nerves. MATERIAL/METHODS: A total of 250 healthy subjects were recruited. The subjects were divided into four age groups. The nerves tested were the median, ulnar, and sural nerves. Surface electrodes were used and the temperature was kept constant. The nerves were stimulated and recorded at specific sites both for motor and sensory conduction velocities. RESULTS: The mean velocities for the median and ulnar nerves, both motor and sensory, were 54.71+/-5.69 m/s (motor) and 54.04+/-7.02 m/s for the median nerve and 60.57+/-5.00 m/s (motor) and 52.92+/-5.89 m/s for the ulnar nerve. The mean velocity for the sural nerve was 47.97+/-4.48 m/s. Only median motor conduction velocity showed a significant reduction with increasing age (p=0.000). CONCLUSIONS: This study did not show any significant effect of age on nerve conduction velocities except for median motor conduction velocity. For future research it is planned to extend the recruitment to subjects who are much older (over 60 years of age) and study the effect of other personal factors such as height and body mass index on NCV.

Botulinum toxin type A in prophylactic treatment of migraine.

Current migraine preventive therapies are often unsatisfactory because of their limited efficacy, adverse effects, and drug interactions. An open-label, non-controlled study of botulinum toxin type A (BTX-A) suggested some benefits for patients with migraine. To assess the efficacy and safety of BTX-A, a randomized, double-blind, vehicle-controlled, parallel group study was conducted in 32 patients with a history of 2 to 8 migraine attacks per month, with or without aura. The patients were randomized to receive single administrations of 50-U BTX-A or vehicle injected into multiple sites of pericranial muscles at the same visit. Patients kept daily diaries in which they recorded outcome measures like migraine frequency, migraine severity, and the occurrence of migraine-associated symptoms. Patients graded symptoms on a 4-point scale ranging from grades 0 to 3 before and up to 3-months after treatment. The assessments were made at 0, 1, and 3 months. The primary efficacy parameters included number of headaches resolved (grade 3/2 to grade 0) and alleviation of other accompanying symptoms of migraine. The supplementary end point included improvement in quality of life (QOL). About 75% of patients reported complete relief to mild headache (grade 0-1) by BTX-A and none by placebo group. Patient' QOL parameters like energy/vitality and feelings and concerns about the treatment had shown considerable improvement. However, normal day-to-day work functioning and social interactions deteriorated. No adverse effects were reported in any of the patients in either of the groups during the study. It is evident from the study that pericranial injection of 50-U BTX-A showed good efficacy and tolerability as a prophylactic agent. However, this therapy will be expensive to the patients, but it is far superior in providing relief to the patients compared with existing therapies.

Nerve conduction study among healthy malays. The influence of age, height and body mass index on median, ulnar, common peroneal and sural nerves.

Nerve conduction study is essential in the diagnosis of focal neuropathies and diffuse polyneuropathies. Age, height and body mass index (BMI) can affect nerve velocities as reported by previous studies. We studied the effect of these factors on median, ulnar, common peroneal and sural nerves among healthy Malay subjects. We observed slowing of nerve conduction velocities (NCVs) with increasing age and BMI (except ulnar sensory velocities). No demonstrable trend can be seen across different height groups except in common peroneal nerve.

Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine.

OBJECTIVES: To study the efficacy and tolerability of prochlorperazine (PCZ) management of acute migraine. DESIGN AND METHODS: A double blind comparative study was conducted to assess the efficacy of buccal PCZ 3 mg compared with oral ergotamine tartarate 1 mg plus caffeine 100 mg (ERG) or placebo (buccal or oral) for treatment of acute migraine. In all, 114 episodes of acute migraine were evaluated. Patients graded symptoms on a four-point scale before and up to 4 hours after treatment. The primary efficacy parameters included headache resolution within 2 hours (grade 3 or 2 to grade 0) and alleviation of other accompanying symptoms of migraine. The supplementary endpoints included improvement in quality of life (QOL). RESULTS: The percentage of patients reporting resolution of headache (to grade 0) was 51.4% for buccal PCZ and 21.7% for buccal placebo, 23.1% for oral ERG and 28.6% for oral placebo, headache tended to recur in both the placebo and ERG groups after initial improvement. Buccal PCZ was well tolerated; no signs of local irritation were evident, and patients found the formulation easy to use. Mild but transient sedation and drowsiness were observed in 41%. CONCLUSIONS: In the present study, PCZ 3 mg via the buccal route produced faster improvement and greater efficacy than placebo (oral as well as buccal) or oral ERG. The global QOL score 2 hours after treatment scores was higher in the PCZ group. Buccal PCZ may represent a particularly effective alternative for acute migraine treatment.

Effect of Yoga asanas on nerve conduction in type 2 diabetes.

Twenty Type 2 diabetic subjects between the age group of 30-60 years were studied to see the effect of 40 days of Yoga asanas on the nerve conduction velocity. The duration of diabetes ranged from 0-10 years. Subject suffering from cardiac, renal and proliferative retinal complications were excluded from the study Yoga asanas included Suryanamskar. Tadasan, Konasan, Padmasan Pranayam, Paschimottansan Ardhmatsyendrasan, Shavasan, Pavanmukthasan, Sarpasan and Shavasan. Subjects were called to the cardio-respiratory laboratory in the morning time and were given training by the Yoga expert. The Yoga exercises were performed for 30-40 minutes every day for 40 days in the above sequence. The subjects were prescribed certain medicines and diet. The basal blood glucose, nerve conduction velocity of the median nerve was measured and repeated after 40 days of Yogic regime. Another group of 20 Type 2 diabetes subjects of comparable age and severity, called the control group, were kept on prescribed medication and light physical exercises like walking. Their basal & post 40 days parameters were recorded for comparison. Right hand and left hand median nerve conduction velocity increased from 52.81 +/- 1.1 m/sec to 53.87 +/- 1.1 m/sec and 52.46 +/- 1.0 to 54.75 +/- 1/1 m/sec respectively. Control group nerve function parameters deteriorated over the period of study, indicating that diabetes is a slowly progressive disease involving the nerves. Yoga asanas have a beneficial effect on glycaemic control and improve nerve function in mild to moderate Type 2 diabetes with sub-clinical neuropathy.