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V. S. Ramachandran

Vilayanur Subramanian Ramachandran (born 10 August 1951) is an Indian-American neuroscientist Ramachandran is known for his wide-ranging experiments and theories in behavioral neurology, including the invention of the mirror box.

After early work on human vision, Ramachandran turned to work on wider aspects of neurology including phantom limbs and phantom pain.

Ramachandran invented mirror therapy which is now used to treat amputees with phantom limb pain and also to help restore motor control in stroke victims with weakened limbs.

Ramachandran's popular books Phantoms in the Brain (1998), The Tell-Tale Brain (2010), and others describe neurological and clinical studies of people with synesthesia, Capgras syndrome, and a wide range of other unusual conditions.

Ramachandran was one of the first researchers to recognize the potential of neuroimaging technology to demonstrate the plastic changes that take place in the human cortex after amputation.[12]

Ramachandran then began research on phantom limbs, but later moved on to study a wider range of neurological mysteries, including body integrity identity disorder and the Capgras delusion.

Ramachandran has responded, 'I have—for better or worse—roamed the whole landscape of visual perception, stereopsis, phantom limbs, denial of paralysis, Capgras syndrome, synaesthesia, and many others.'[16]

Ramachandran has served as a consultant to the Modius company which is developing weight reduction technology that relies on electrically stimulating parts of the brain that control weight loss.[18]

When an arm or leg is amputated, patients often continue to feel vividly the presence of the missing limb as a 'phantom limb' (an average of 80%).

Ramachandran thought that phantom pain might be caused by the mismatch between the amputee's different nerve systems: his visual system tells him the limb is missing, but nerve signals to the brain say the limb is still there.

The so-called mirror box was a simple apparatus that uses a mirror reflecting an amputee's good arm so that it appears to be the extension of the one missing:

They put their surviving arm through a hole in the side of a box with a mirror inside, so that, peering through the open top, they would see their arm and its mirror image, as if they had two arms.

Out of 115 publications between 2012 and 2017 about using mirror therapy to treat phantom limb pain, a 2018 review, found only 15 studies whose scientific results should be considered.

Similarly, a 2017 review that studied a wider range of uses for mirror therapy, concluded, 'Mirror therapy has been used to treat phantom limb pain, complex regional pain syndrome, neuropathy and low back pain.

According to Rizzolati, 'Mirror neurons are a specific type of visuomotor neuron that discharge both when a monkey executes a motor act and when it observes a similar motor act performed by another individual.'[39]

In 2000, Ramachandran made what he called some 'purely speculative conjectures' that 'mirror neurons [in humans] will do for psychology what DNA did for biology: they will provide a unifying framework and help explain a host of mental abilities that have hitherto remained mysterious and inaccessible to experiments.'[40]

Ramachandran has suggested that research into the role of mirror neurons could help explain a variety of human mental capacities such as empathy, imitation learning, and the evolution of language.

suggested that in addition to providing a neural substrate for figuring out another persons intentions...the emergence and subsequent sophistication of mirror neurons in hominids may have played a crucial role in many quintessentially human abilities such as empathy, learning through imitation (rather than trial and error), and the rapid transmission of what we call 'culture'.

In 1999, Ramachandran, in collaboration with then post-doctoral fellow Eric Altschuler and colleague Jaime Pineda, hypothesized that a dysfunction of mirror neuron activity might be responsible for some of the symptoms and signs of autism spectrum disorders.[46]

Ramachandran and his graduate student, Ed Hubbard, conducted research with functional magnetic resonance imaging that found increased activity in the color recognition areas of the brain in synesthetes compared to non-synesthetes.[57][58] Ramachandran

Building on medical case studies that linked brain damage to syndromes such as somatoparaphrenia (lack of limb ownership) the authors speculated that the desire for amputation could be related to changes in the right parietal lobe.

MEG scans demonstrated that their right superior parietal lobules were significantly less active in response to tactile stimulation of a limb that the subjects wished to have amputated, as compared to age/sex matched controls.

Retinopathy Telescreening Systems

Second, the new blood vessels of proliferative diabetic retinopathy and contraction of the accompanying fibrous tissue can distort the retina and lead to tractional retinal detachment, producing severe and often irreversible vision loss.

For patients under age 30 years, annual retinal examinations are recommended beginning within 3 to 5 years after diagnosis of diabetes once the patient is 10 years old or older.

Diabetic retinopathy telescreening systems involve taking digital pictures of the retina of diabetic patients in the primary care physician's office, and electronically transmitting these pictures to a reading center for evaluation for diabetic retinopathy and macular edema by trained non-physician technicians.

A cost-effectiveness analysis performed by the British National Health Service Centre for Reviews and Dissemination concluded that screening using a digital camera may be more accurate than screening by the general practitioner, and offers an opportunity to reduce costs of diabetic screening, especially as the costs of digital cameras come down.

The Inoveon System of retinopathy screening (iScore, Inoveon Corp., Oklahoma City, OK) involves 7-standard field stereoscopic 30° digital fundus photographs through dilated pupils obtained by a trained photographer located in or near the primary care physician's office, electronic transmission of these digital photographs, examination and grading of these images by non-physician technicians, and rereading of a selected sample of images for assessment of inter- and intra-rater reliability.

If images are not adequate to allow the technician readers to make an assessment of the patient's diabetic retinopathy or macular edema status, Inoveon recommends to the primary care physician that the patient be referred for further evaluation by an ophthalmologist or optometrist.

In a study comparing high-resolution digital stereoscopic fundus photographs (Inoveon System) to plain film stereoscopic fundus photographs (the gold standard), Fransen et al (2002) reported that the digital photographs provided highly accurate diabetic retinopathy referral decisions.

The primary endpoint was the detection of threshold events requiring referral, which was defined as an ETDRS retinopathy severity level greater than 52, questionable or definite clinically significant macular edema, or ungradable images.

The investigators found that the sensitivity of the digital photography system in detecting threshold events, compared to plain film photography, was 98.2% (confidence interval [CI]: 90.5 % to 100%) and the specificity was 89.7% (CI: 85.1 % to 93.3 %).

Agreement between digital photographs and contact lens biomicroscopy was 83.6 % for clinically significant macular edema (CSME), 83.6% for CSME type 1, 96.1% for CSME type 2, 88.5% for CSME type 3, 75% for macular edema, 77.9% for microaneurysms, 83.7% for intraretinal hemorrhage, and 73.1 %for hard exudates.

As referral on the basis of any retinopathy, no matter how mild, may result in an unnecessarily high number of referrals, the study evaluated a second threshold level of very mild non-proliferative diabetic retinopathy to reduce the number of unnecessary referrals.

Using this threshold, there was substantial agreement based on “microaneurysms or less retinopathy” (which includes no diabetic abnormalities and microaneurysms only) versus retinal hemorrhages or worse retinopathy' (Kappa stastistic 0.78 OD, 0.88 OS), with corresponding sensitivities (0.95 OD, 0.98 OS) and specificities (0.81 OD, 0.87 OS).

The investigators concluded that this image validation studyshowed that the DigiScope has excellent agreement, sensitivity, and specificity compared with the “gold-standard” 7-field color stereo photography for identifying patients with any or low levels of diabetic retinopathy who should be under the care of an ophthalmologist.

Although this may eventually permit undilated photographic retinopathy screening, no rigorous studies to date validate the equivalence of these photographs with 7-standard field stereoscopic 30° fundus photography for assessing diabetic retinopathy.

Compared with bedside binocular ophthalmoscopy, remote interpretation of RetCam II/III images had a sensitivity of 100 %, specificity of 99.8 %, positive predicative value (PPV) of 95.5 %, and negative predicative value (NPV) of 100 % for the detection of TW-ROP.

These investigators stated that telemedicine appeared to be a safe, reliable, and cost-effective complement to the efforts of ROP specialists, capable of increasing patient access to screening and focusing the resources of the current ophthalmic community on infants with potentially vision-threatening disease.

However, implementation of routine use of this screening method for at-risk premature infants has presented challenges within the existing care systems, including relative local scarcity of qualified ophthalmologist examiners in some locations and the remote location of some NICUs.

Modern technology, including the development of wide-angle ocular digital fundus photography, coupled with the ability to send digital images electronically to remote locations, has led to the development of telemedicine-based remote digital fundus imaging (RDFI-TM) evaluation techniques.

These wide-field imaging systems have the intended use of ophthalmic imaging of all newborn babies and meet the requirements for ROP screening, thereby serving as competition within the ROP screening market previously dominated by one camera imaging system.

Wongwai and associates (2018) evaluated the diagnostic accuracy of a digital fundus photographic system that consists of taking fundus photographs by a trained technician using a RetCam shuttle and interpreting fundus images by an expert to detect ROP requiring treatment (ROP-RT, which defined as type I ROP according to the Early Treatment for ROP study (ETROP).

sensitivity 100.0 % (66.4 to 100.0), specificity 97.8 % (92.1 to 99.7), PPV 81.8 % (48.2 to 97.7), NPV 100.0 % (95.8 to 100.0), LR+ 44.5 (11.3 to 175.2), and LR- 0.1 (0.0 to 0.8).

sensitivity 100.0 % (66.4 to 100.0), specificity 95.6 % (89.0 to 98.8), PPV 69.2 % (38.6 to 90.9), NPV 100.0 % (95.8 to 100.0), LR+ 22.5 (8.6 to 58.6), LR- 0.1 (0.0 to 0.8).

When a telemedicine screening approach is used, the AAP/AAO/AAPOS/AACO joint statement suggests that it follow the same schedule as ophthalmoscopic screening (as described above) and that infants at risk undergo indirect ophthalmoscopy by a qualified ophthalmologist at least once before initiating treatment or terminating screening”.

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