Browsing by Author "Kishore, A"

Now showing 1 - 20 of 37
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    A case of amyloid myopathy masquerading as inflammatory myopathy
    (NEUROLOGY INDIA, 2010) Das, A; Mahadevan, A; Kishore, A; Shankar, SK
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    Abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions in cervical dystonia.
    (Sci Rep. 2018, 2018-02) Popa, T; Hubsch, C; James, P; Richard, A; Russo, M; Pradeep, S; Krishan, S; Roze, E; Meunier, S; Kishore, A
    The cerebellum can influence the responsiveness of the primary motor cortex (M1) to undergo spike timing-dependent plastic changes through a complex mechanism involving multiple relays in the cerebello-thalamo-cortical pathway. Previous TMS studies showed that cerebellar cortex excitation can block the increase in M1 excitability induced by a paired-associative stimulation (PAS), while cerebellar cortex inhibition would enhance it. Since cerebellum is known to be affected in many types of dystonia, this bidirectional modulation was assessed in 22 patients with cervical dystonia and 23 healthy controls. Exactly opposite effects were found in patients: cerebellar inhibition suppressed the effects of PAS, while cerebellar excitation enhanced them. Another experiment comparing healthy subjects maintaining the head straight with subjects maintaining the head turned as the patients found that turning the head is enough to invert the cerebellar modulation of M1 plasticity. A third control experiment in healthy subjects showed that proprioceptive perturbation of the sterno-cleido-mastoid muscle had the same effects as turning the head. We discuss these finding in the light of the recent model of a mesencephalic head integrator. We also suggest that abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions of the integrator in cervical dystonia.
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    Acute dysautonomia following mumps
    (NEUROLOGY INDIA, 1999)
    Pure acute or subacute dysautonomia is a rare entity. Its etiology is as yet unknown. However, majority of these cases have a preceding viral infection such as herpes simplex, infectious mononucleosis, rubella or coxsackie B. A unique patient in whom acute dysautonomia followed mumps is reported.
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    Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation
    (Neurobiology of aging, 2014-11) Kishore, A; Popa, T; James, P; Yahia-Cherif, L; Backer, F; Varughese, CL; Govind, P; Pradeep, S; Meunier, S
    The plasticity of motor cortex is integral for motor memory and skills acquisition but it declines with aging. Forty healthy volunteers, across 6 decades, were tested to examine the (a) age-dependency of motor cortex responsiveness to plasticity induction, as measured from the response to paired associative stimulation (PAS) and the (b) effect of aging on the cerebellar modulation of motor cortex response to PAS. We examined if reduced dopaminergic transmission was involved in the age-related decline of response to PAS by retesting 10 of the older subjects after a single dose of levodopa. There was a substantial decline in the motor cortex response to PAS with aging, which was restored by levodopa in the older subjects. The cerebellar modulation of motor cortex response to PAS was less vulnerable to aging and a single session of cerebellar inhibition reinstated the cortical responsiveness in older subjects. Both levodopa and cerebellar inhibition can be tested for their ability to enhance motor skills acquisition and motor performance in the elderly individuals.
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    Autophagy enhancement is rendered ineffective in presence of α-synuclein in melanoma cells
    (J Cell Commun Signal., 2017-07) Nandakumar, S; Vijayan, B; Kishore, A; Thekkuveettil, A
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    Blindness, ophthalmoplegia and extensive radiculopathy: An unusual clinical syndrome in intracranial sino-venous thrombosis
    (NEUROLOGY INDIA, 2004)
    Isolated intracranial hypertension is a common manifestation of intracranial sino-venous thrombosis (ISVT). Markedly elevated intracranial tension presents with unusual features including cranial neuropathies and radiculopathy. We report two cases with ISVT, which presented with headache, papilledema, progressive visual loss, complete ophthalmoplegia and flaccid areflexic quadriparesis along with a normal sensorium. Magnetic resonance imaging (MRI) of the brain and cervical spinal cord showed no lesions that could account for the neurological deficits. Markedly elevated lumbar CSF pressure was noted in both cases. Nerve conduction study favored radiculopathy in one case and was normal in the other. Raised intracranial pressure was found to be the sole cause for the clinical manifestations. Visual impairment persisted in one patient despite lumbo-peritoneal shunting while the other died of septicemia. To our knowledge there are no previous reports of a syndrome comprising blindness, ophthalmoplegia and flaccid quadriplegia due to intracranial hypertension in ISVT.
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    Cerebellar influence on motor cortex plasticity: behavioral implications for Parkinson's disease
    (FRONTIERS IN NEUROLOGY, 2014) Kishore, A; Meunier, S; Popa, T
    Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration, and normal functioning of these networks. Strong topography-specific connections among the basal ganglia, cerebellum, and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other's plastic responses and functions. The defective striatal signaling in Parkinson's disease (PD) could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar, and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD.
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    Cerebellar Processing of Sensory Inputs Primes Motor Cortex Plasticity
    (CEREBRAL CORTEX, 2013) Popa, T; Velayudhan, B; Hubsch, C; Pradeep, S; Roze, E; Vidailhet, M; Meunier, S; Kishore, A
    Plasticity of the human primary motor cortex (M1) has a critical role in motor control and learning. The cerebellum facilitates these functions using sensory feedback. We investigated whether cerebellar processing of sensory afferent information influences the plasticity of the primary motor cortex (M1). Theta-burst stimulation protocols (TBS), both excitatory and inhibitory, were used to modulate the excitability of the posterior cerebellar cortex and to condition an ongoing M1 plasticity. M1 plasticity was subsequently induced in 2 different ways: by paired associative stimulation (PAS) involving sensory processing and TBS that exclusively involves intracortical circuits of M1. Cerebellar excitation attenuated the PAS-induced M1 plasticity, whereas cerebellar inhibition enhanced and prolonged it. Furthermore, cerebellar inhibition abolished the topography-specific response of PAS-induced M1 plasticity, with the effects spreading to adjacent motor maps. Conversely, cerebellar excitation had no effect on the TBS-induced M1 plasticity. This demonstrates the key role of the cerebellum in priming M1 plasticity, and we propose that it is likely to occur at the thalamic or olivo-dentate nuclear level by influencing the sensory processing. We suggest that such a cerebellar priming of M1 plasticity could shape the impending motor command by favoring or inhibiting the recruitment of several muscle representations.
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    Cerebellar Sensory Processing Alterations Impact Motor Cortical Plasticity in Parkinson's Disease: Clues from Dyskinetic Patients
    (Cereb. Cortex (2013), 2013-04) Kishore, A; Popa, T; Balachandran, A; Chandran, S; Pradeep, S; Backer, F; Krishnan, S; Meunier, S
    The plasticity of primary motor cortex (M1) in patients with Parkinson's disease (PD) and levodopa-induced dyskinesias (LIDs) is severely impaired. We recently reported in young healthy subjects that inhibitory cerebellar stimulation enhanced the sensorimotor plasticity of M1 that was induced by paired associative stimulation (PAS). This study demonstrates that the deficient sensorimotor M1 plasticity in 16 patients with LIDs could be reinstated by a single session of real inhibitory cerebellar stimulation but not sham stimulation. This was evident only when a sensory component was involved in the induction of plasticity, indicating that cerebellar sensory processing function is involved in the resurgence of M1 plasticity. The benefit of inhibitory cerebellar stimulation on LIDs is known. To explore whether this benefit is linked to the restoration of sensorimotor plasticity of M1, we conducted an additional study looking at changes in LIDs and PAS-induced plasticity after 10 sessions of either bilateral, real inhibitory cerebellar stimulation or sham stimulation. Only real and not sham stimulation had an antidyskinetic effect and it was paralleled by a resurgence in the sensorimotor plasticity of M1. These results suggest that alterations in cerebellar sensory processing function, occurring secondary to abnormal basal ganglia signals reaching it, may be an important element contributing to the maladaptive sensorimotor plasticity of M1 and the emergence of abnormal involuntary movements.
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    Cerebellum in levodopa-induced dyskinesias: the unusual suspect in the motor network
    (FRONTIERS IN NEUROLOGY, 2014) Kishore, A; Popa, T
    The exact mechanisms that generate levodopa-induced dyskinesias (LID) during chronic levodopa therapy for Parkinson's disease (PD) are not yet fully established. The most widely accepted theories incriminate the non-physiological synthesis, release and reuptake of dopamine generated by exogenously administered levodopa in the striatum, and the aberrant plasticity in the cortico-striatal loops. However, normal motor performance requires the correct recruitment of motor maps. This depends on a high level of synergy within the primary motor cortex (M1) as well as between M1 and other cortical and subcortical areas, for which dopamine is necessary. The plastic mechanisms within M1, which are crucial for the maintenance of this synergy, are disrupted both during "OFF" and dyskinetic states in PD. When tested without levodopa, dyskinetic patients show loss of treatment benefits on long-term potentiation and long-term depression-like plasticity of the intracortical circuits. When tested with the regular pulsatile levodopa doses, they show further impairment of the M1 plasticity, such as inability to depotentiate an already facilitated synapse and paradoxical facilitation in response to afferent input aimed at synaptic inhibition. Dyskinetic patients have also severe impairment of the associative, sensorimotor plasticity of M1 attributed to deficient cerebellar modulation of sensory afferents to M1. Here, we review the anatomical and functional studies, including the recently described bidirectional connections between the cerebellum and the basal ganglia that support a key role of the cerebellum in the generation of LID. This model stipulates that aberrant neuronal synchrony in PD with LID may propagate from the subthalamic nucleus to the cerebellum and "lock" the cerebellar cortex in a hyperactive state. This could affect critical cerebellar functions such as the dynamic and discrete modulation of M1 plasticity and the matching of motor commands with sensory information from the environment during motor performance. We propose that in dyskinesias, M1 neurons have lost the ability to depotentiate an activated synapse when exposed to acute pulsatile, non-physiological, dopaminergic surges and become abnormally receptive to unfiltered, aberrant, and non-salient afferent inputs from the environment. The motor program selection in response to such non-salient and behaviorally irrelevant afferent inputs would be abnormal and involuntary. The motor responses are worsened by the lack of normal subcortico cortical inputs from cerebellum and basal ganglia, because of the aberrant plasticity at their own synapses. Artificial cerebellar stimulation might help re-establish the cerebellar and basal ganglia control over the non-salient inputs to the motor areas during synaptic dopaminergic surges.
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    Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex
    (Cerebellum, 2017-02) Caligiore, D; Pezzulo, G; Baldassarre, G; Bostan, AC; Strick, PL; Doya, K; Helmich, RC; Dirkx, M; Houk, J; Jörntell, H; Lago-Rodriguez, A; Galea, JM; Miall, RC; Popa, T; Kishore, A; Verschure, PF; Zucca, R; Herreros, I
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    Cortical plasticity and levodopa-induced dyskinesias in Parkinson's disease: Connecting the dots in a multicomponent network
    (Clin Neurophysiol., 2017-06) Rajan, R; Popa, T; Quartarone, A; Ghilardi, MF; Kishore, A
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    Deep brain stimulation for Parkinson's disease
    (NEUROLOGY INDIA, 2003)
    Dopaminerigic replacement therapy with levodopa/carbidopa is still the cornerstone for the treatment of Parkinson's disease (PD). However, the medical management of PD is complicated by the appearance of disabling motor response fluctuations, levodopa-induced dyskinesias and psychosis. Since the early 1990s, surgical therapies have made a rapid reentry into the therapeutic armamentarium for PD and deep brain stimulation (DBS) of the globus pallidus interna or subthalamic nuclei is currently the most promising of such interventions. Recognition of the physiological changes in basal ganglia circuits in animal models of PD has provided the much-needed theoretic basis for targeting these areas. DBS of these areas has proven to be a safe procedure and effective against all the major motor symptoms of PD. Though not curative it can substantially reduce motor response fluctuations, levodopa-induced dyskinesias, and improve the quality of life of these patients. DBS is an expensive treatment and hardware-related complications are not rare. The results of the procedure are dependent on careful patient selection and the experience of the performing team. An update on the principles, methods and results of such procedures is essential to raise the awareness of this new therapeutic modality and to provide guidelines to the referring physicians.
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    Defective cerebellar control of cortical plasticity in writer's cramp
    (Brain., 2013-07) Hubsch, C; Roze, E; Popa, T; Russo, M; Balachandran, A; Pradeep, S; Mueller, F; Brochard, V; Quartarone, A; Degos, B; Vidailhet, M; Kishore, A; Meunier, S
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    Design and Evaluation of Chitra Swab Collection Booths for Health Professionals in COVID-19 Pandemic
    (Transactions of the Indian National Academy of Engineering, 2020-12) Prajapati, AK; Nair, SS; Venkatesan, RB; Muraleedharan, CV; Kishore, A
    The 2019 novel coronavirus (SARS-CoV-2), officially named as COVID-19 by the WHO, has spread to more than 180 countries and the confirmed coronavirus cases have reached around 10 million with 0.6 million deaths by end of June 2020. Moreover, there is no sign of a sustained decline in any country till date. Continuous rise of positive cases has instilled fear in people, society and even health professionals. According to WHO’s daily situation report, 22,073 COVID-19 cases of healthcare professionals have been reported to the WHO as of Wednesday, 8 April 2020 by Jin (Mil Med Res 7:24, 2020). Infection to health professionals is a serious concern not only because they are a valuable frontline worker but also because of the risk of spread to co-workers and non-Covid patients. This project was undertaken to develop a solution to minimize the chance of infection to the health care professionals by providing them isolation from a potential source of Covid-19 and similar highly contagious diseases. The two models of Chitra swab collection booth were developed to: (1) protect health professionals from the risk of infection (2) to provide technical know-how to manufacturers to produce booths using locally available materials while meeting international regulations and (3) reduce the consumption of personal protective equipment. The prototypes developed were tested for safety and efficacy in accordance with the guidelines of the Centers for Disease Control and Prevention, Atlanta, USA. The device received the registration for commercialisation from the Central Drugs Control Standard Organization, Ministry of Health, Government of India, as a non-notified medical device.
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    Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson's disease patients
    (Parkinsonism Relat Disord., 2016-12) Krishnamoorthy, S; Rajan, R; Banerjee, M; Kumar, H; Sarma, G; Krishnan, S; Sarma, S; Kishore, A
    Introduction: Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson’s disease (PD) patients. Methods: We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped. Results: Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR ¼ 2.22, 95% CI: 1.03e4.86, p ¼ 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR ¼ 1.14, 95% CI: 1.01e1.29, p ¼ 0.041), current dopamine agonist but not Levodopa use (OR ¼ 2.16, 95% CI: 1.03e4.55, p ¼ 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05e4.18, p ¼ 0.035) were independently associated with ICD. Conclusion: DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype.
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    Electrode Position and Current Amplitude Modulate Impulsivity after Subthalamic Stimulation in Parkinsons Disease-A Computational Study
    (FRONTIERS IN PHYSIOLOGY, 2016) Mandali, A; Chakravarthy, VS; Rajan, R; Sarma, S; Kishore, A
    Background: Subthalamic Nucleus Deep Brain Stimulation (SIN-DES) is highly effective in alleviating motor symptoms of Parkinson's disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD). Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation. We hypothesized that the position of electrode and stimulation current modulate impulsivity after STN-DBS. Methods: We built a computational spiking network model of basal ganglia (BG) and compared the model's STN output with STN activity in PD. Reinforcement learning methodology was applied to simulate IGT performance under various conditions of dopaminergic and STN stimulation where IGT total and bin scores were compared among various conditions. Results: The computational model reproduced neural activity observed in normal and PD conditions. Untreated and medically-treated PD conditions had lower total IGT scores (higher impulsivity) compared to HC (P < 0.0001). The electrode position that happens to selectively stimulate the part of the STN corresponding to an advantageous panel on IGT resulted in de-selection of that panel and worsening of performance (P < 0.0001). Supratherapeutic stimulation amplitudes also worsened IGT performance (P < 0.001). Conclusion(s): In our computational model, STN stimulation led to impulsive decision making in IGT in PD condition. Electrode position and stimulation current influenced impulsivity which may explain the variable effects of STN-DBS reported in patients.
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    Evidence of functional somatotopy in GPi from results of pallidotomy
    (BRAIN, 2000)
    The objective of this study was to explore the functional anatomy of the globus pallidus internus (GPi) by studying the effects of unilateral pallidotomy on parkinsonian 'off' signs and levodopa-induced dyskinesias (LID), We found significant positive! correlations between the preoperative levodopa responsiveness of motor signs and the levodopa responsiveness of scores in timed tests (Core Assessment Program for Intracerebral Transplantations) in the contralateral limbs and the improvement in these scores after surgery, whereas there was no correlation with the improvement in LID, We also found a highly significant correlation (P < 0,0001, p = 0.8) between the volume of the ventral lesion in the GPi and the improvement in LID in the contralateral limbs, whereas there was no correlation between the ventral volume and the improvement in parkinsonian 'off' signs. The volumes of the total Lesion cylinder and the dorsal lesion did not correlate with the outcome of either dyskinesias or parkinsonian 'off' signs. The differential predictive value of levodopa responsiveness for the outcome of parkinsonian 'off' signs and LID and the different correlations of ventral lesion volume with dyskinesias and parkinsonian 'off' signs indicate that different anatomical or pathophysiological substrates may be responsible for the generation of parkinsonian 'off' signs and dyskinesias, Whereas cells in a wider area of the GPi may be implicated in parkinsonism, the ventral GPi seems to be crucial for the manifestation of LID. We suggest that our observations are additional proof of the functional somatotopy of the systems within the GPi that mediate parkinsonism and dyskinesias, especially along the dorsoventral trajectory used in pallidotomy. The outcome of pallidotomy in which the lesion involves the ventral and dorsal GPI could be the net effect of alteration in the activity of pathways which mediate different symptoms, and hence could be variable.
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    Gender influence on selection and outcome of deep brain stimulation for Parkinsons disease
    (ANNALS OF INDIAN ACADEMY OF NEUROLOGY, 2014) Chandran, S; Krishnan, S; Rao, RM; Sarma, SG; Sarma, PS; Kishore, A
    Background: Gender differences exist in Parkinsons disease (PD), both in clinical manifestations and response to medical treatment. We investigated whether gender differences occur in the clinical characteristics of patients selected for bilateral subthalamic nucleus deep brain stimulation (STN DBS) or in the outcome when resource limits influence treatment choices made by patients. Materials and Methods: Fifty-one consecutive patients were evaluated 1 month before, and 12 months after bilateral STN DBS. All patients were rated using Unified Parkinsons Disease Rating Scale, Parkinsons Disease Quality of Life (PDQL) Scale, Addenbrookes Cognitive Examination and Beck Depression Inventory. Results: Pre-operative characteristics did not differ between the genders except for lower doses of drugs (P = 0.03), worse emotional scores in PDQL (P = 0.01) and worse depression (P = 0.03) in women. There was no gender difference in the surgical outcome, except a lesser reduction of dopaminergic drugs in women. Depression and quality of life (QOL) improved equally well in women and men. Conclusion: Bilateral STN DBS is equally efficacious in both genders as a treatment for motor complications of PD and for improving QOL. Women are likely to be undertreated because of more severe dyskinesia and may experience less emotional well-being, and could therefore potentially benefit from earlier surgical treatment.
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    Gender influence on selection and outcome of deep brain stimulation for Parkinson’s disease
    (Annals of Indian Academy of Neurology, 2014-12) Chandran, S; Syam, K; Rao, RM; Sarma, SG; Sarma, PS; Kishore, A
    BACKGROUND: Gender differences exist in Parkinson's disease (PD), both in clinical manifestations and response to medical treatment. We investigated whether gender differences occur in the clinical characteristics of patients selected for bilateral subthalamic nucleus deep brain stimulation (STN DBS) or in the outcome when resource limits influence treatment choices made by patients. MATERIALS AND METHODS: Fifty-one consecutive patients were evaluated 1 month before, and 12 months after bilateral STN DBS. All patients were rated using Unified Parkinson's Disease Rating Scale, Parkinson's Disease Quality of Life (PDQL) Scale, Addenbrooke's Cognitive Examination and Beck Depression Inventory. RESULTS: Pre-operative characteristics did not differ between the genders except for lower doses of drugs (P = 0.03), worse emotional scores in PDQL (P = 0.01) and worse depression (P = 0.03) in women. There was no gender difference in the surgical outcome, except a lesser reduction of dopaminergic drugs in women. Depression and quality of life (QOL) improved equally well in women and men. CONCLUSION: Bilateral STN DBS is equally efficacious in both genders as a treatment for motor complications of PD and for improving QOL. Women are likely to be undertreated because of more severe dyskinesia and may experience less emotional well-being, and could therefore potentially benefit from earlier surgical treatment.