A Report by Dr. Subbulakshmi Natarajan, MBBS, DCN (Lond), FRCP (Edin), Clinical Neuroscientist & Science Writer.
December brings the promise of pleasant, cool days to Chennai, south India, along with the annual Indian classical music and dance festivals and church choral music, to mark a month-long atmosphere of peace, joy and festivity. It was in this part of the year, in the serenity of the colonial era milieu of Madras Club, that an international cast of experts discussed the brain, mind and their rich interface, sharing the global trends in the field and their individual and team experiences at the exclusive closed door meeting (by invitation) of the International Neuropsychiatric Association. The theme of the INA Colloquium 2019 was “New Horizons in Neuropsychiatry’
Prof. Ennapadam S Krishnamoorthy, the INA President, extended a warm welcome. It was an honour to have the inaugural President of INA , Prof. Colin Shapiro (1998-2002) and INA’s third President , Prof. Perminder Sachdev (2004-2006) as colloquium faculty. Other eminent, senior members of INA also comprised the colloquium faculty.
Prof. Krishnamoorthy called upon faculty members to light the ‘Lamp of Knowledge’ , to the background chant to Saraswathi, the Goddess of Learning. “The overall theme ‘Brain and Behaviour’ belongs to all present,” he said and announced that those attending the colloquium could register free for a year to become members of INA, and receive ‘the INA pin’ In the hands of the experts and over several decades, the complexities of mind, brain and behaviour captured separately by the specialities of Neurology and Psychiatry, have been brought together in a holistic manner under the INA banner, much to the benefit of Neuroscience, the clinician and the patient. It was keenly felt that this knowledge deserved to be shared by a wider medical fraternity towards global excellence in brain and mind healthcare and research.
The colloquium was sponsored by the ever-flowing generosity of the TS Srinivasan family. The handsome endowment towards this was in honour of the philanthropist industrialist, TS Srinivasan.
Prof ES Krishnamoorthy opened the scientific session with ‘Innovation: An Integrated Care Model in Neuropsychiatry’ as practiced in the Buddhi Clinic, Chennai, founded by him in 2010. The Integrated Brain and Mind care at Buddhi Clinic , towards ‘Restoration, Rehabilitation and Rejuvenation ‘ has over the years developed protocols and procedures which make them sustainable, replicable and measurable. More gratifying is the qualitative measure of patient response. Here, CAM enjoys a common platform with Modern Neuropsychiatry and Neurorehabilitation.
Perminder Sachdev, Professor of Neuropsychiatry at UNSW, Co-Director of the Centre for Healthy Brain Ageing (CHeBA), UNSW, Australia, took us through the exciting present day ‘Biomarker Approach to the Diagnosis of Dementia’, and the dilemmas in this unrelenting quest for the Holy Grail. The heterogeneous presentation of person-specific contribution of neuropathologies to cognitive loss (more so in old age), makes the search for an AD biomarker elusive. It is only with pooling of multiple data that we can hope to arrive at a biomarker complex to detect at the pre-AD phase. NIA AA has proposed an effective Research Framework for AD biomarker grouping AT(N) (Jack C et al, 2018). He touched on the consensus study (VICCCS) on the vascular causes of dementia, for which he was an international collaborator along with two other speakers, Prof. Ingmar Skoog and Prof. Raj Kalaria.
Raj Kalaria , Professor of Neuropathology, Newcastle University, UK shared with us his twenty- year experience and heading the Neurovascular Group at the Institute of Neuroscience, Newcastle, in ‘the Cognitive Function after Stroke’ ( CogFAST) study. Being a strong proponent of the concept of cognitive decline due to vascular causes, he observed that the understanding of lifestyle diseases and the preventable nature of the risk factors led to a renewed interest in refinement and classification of vascular dementias (VaD). It resulted in ‘Vascular Impairment of Cognition Classification Consensus Study (VICCCS)’, with international collaborators, on sensitive and specific clinical and research criteria to diagnose the earliest phase of Vascular Cognitive Impairment (VCI). He went on to say that cerebral vessel disease may be an under-recognised risk factor for AD dementia-the vascular pathology in AD is arteriosclerosis and capillary degeneration. Changes in vessel wall causes chronic hypoperfusive state (oligaemia) and the white matter changes and may result in either stroke or degeneration (to AD) or in a mixed type which includes both.
Epilepsy and Behaviour – Learning through case studies
This session saw four interesting presentations by leading Indian experts.
The Many Ramifications of Post-ictal Psychosis
Bindu Menon, Professor and Head of Dept. of Neurology, Apollo Specialty Hospital, Nellore, south India, was a case based presentation. A 38 year lady, single, living with her parents, diagnosed as complex partial seizures with secondary generalization, based on clinical, EEG and imaging parameters. She was on optimum dose of levetiracetem, with a history of poor drug adherence and with recurrent episodes. She presented in a confused, agitated state, with auditory and visual hallucinations and with persecutory delusions and aggressive behaviour. Her mother reported a cluster of seizures two days prior to this admission and reported that she had had two similar bizarre episodes earlier. Dr. Menon took us through the differential diagnosis of such a presentation and elegantly argued her opting for Post-ictal Psychosis (PIP), based on Logsdail and Toone criteria.
Epilepsy and Neurodisability
Prof. Nirmal Surya, Consultant Neurophysician, Bombay Hospital Institute of Medical Sciences, shared his experience in neurorehabilitation of young patients with neurodevelopmental disabilities (NDD) with associated epilepsy at the Epilepsy Foundation Centre and his rural community-based outreach programmes. His multidisciplinary team offers management of the physical, cognitive, language, psychosocial and behavioural problems of these patients. He presented video clips of 4 cases, with various levels and types of disability. The lack of awareness, the continuing stigma attached to epilepsy and all forms of disability, poor availability and accessibility of rehabilitation centres, and the out-of-pocket expenditure are major concerns in India
Paediatric Psychogenic Non-epileptic Seizures
Dr. Praveen Kumar Jakati, Consultant Child and Adolescent Psychiatrist, Institute of Neuroscience, Kolkata, India-spoke on Paediatric Psychogenic Non-epileptic Seizures PNES, and showed video- EEGs of typical episodes in a few patients. Comprehensive psychiatric assessment points to a conversion disorder or occasionally a dissociative disorder. Gold standard for diagnosis is a prolonged video EEG. Early recognition of PNES and early intervention offers the best results
Epilepsy and Behaviour: the gentle overlap
Prof Manjari Tripati, Head of Dept. of Neurology, AIIMS, Delhi outlined the ‘Good, Bad and the Ugly’ in surgical intervention for intractable epilepsy in her study of over 200 cases in the dedicated epilepsy neurosurgical dept. of AIIMS, Delhi. The ‘good’ was the 10-fold improvement in the seizure episodes and significant improvement clinically and on the Child Behaviour Checklist, and Paediatric Quality of Life Measure The ‘ugly’ were two patients, both teenage boys, who underwent posterior temporo-parietal resections; one became seizure- free following surgery, the other continued to have about 4 seizures a month. In both cases, post operative ASD was diagnosed, with severe behavioural problems. There was little improvement after therapies over several years.
Why is ASD in such cases underreported in world literature? The posterior brain location of both these lesions could perhaps account for the post-op ASD, as the parieto-occipital region represents ‘autistic functionality’ and ‘theory of mind’.
‘If you have anything interesting to say, you must be able to convey it within eight minutes- these are what these stand ups are about, following which they will be open for discussion’. The 4 Buddhi team members were game for the challenge !
Mr. Vivek Misra, Neuroscientist & Neuromodulation consultant of the Buddhi team spoke on Integrating Neuromodulation in a Multidisciplinary Care Paradigm. He contributes to the neuromodulation with brain stimulation with repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS). He outlined the beneficial effects of rTMS on the Parkinson’s disease patients at Buddhi Clinic and discussed future plans for brain stimulation in the lab. rTMS not only improves the motor performance but also the cognitive and behavioural outcomes- 20 sessions bilateral motor area stimulated following the standard protocol showed benefit not only on the UPDRS scale but also showed progressive improvement on MoCA and NPI assessment at baseline, mid treatment and end of brain stimulation, WHOQOL BREF showed positive scores on the social domain. The audience suggested more cases in the series under controlled conditions are required to launch the study on a research basis.
Dr. VG Srivatsa, Neuropsychiatrist presented on intractable behavioural difficulties, anxiety, aggression, below average intelligence in a 14 year old treated with a multidisciplinary integrated approach including neurodevelopmental therapy, behavioural therapy , family focused therapy and rTMS. It was a diagnostic dilemma. The Buddhi clinic team came to a diagnosis of ASD with intellectual disability and severe anxiety state. Rapidly escalating anxiety and panic in the wake of below average intelligence, with the added effect of early life trauma was suggested by two experts reviewing the case who ruled out autism.
Indhu Rajagopal, Clinical Psychologist, Buddhi clinic
Case presentation was of a 17 year old girl Treatment-resistant depression following a single seizure – found with LOC, vomited once, aggressive on admission, EEG normal initially, subsequent prolonged EEG showed bilateral temporo-parietal and occipital epileptiform activity . CT brain normal, stressors at school and home with maladaptive responses. History of recurrent attacks of migraine.Patient was treated as a case of seizure disorder with Levetiracetam and Clobazam. Subsequently, Levetiracetam was tapered and Lamotrigine introduced, with some improvement all round. Paroxetime CR was continued.
The final diagnosis was AED –induced mood and anxiety disorder with accompanying insomnia.
Dr. Krishnaswamy Viswanathan, Senior Neurosurgeon – is Director of the Buddhi Clinic at Porur. He operates at Sri Ramachandra Medical College and Research Centre- He is an MRCS Edinburgh, and received special training in DBS at the Sai Baba Hospital at Whitefield, Bengaluru.
He explained the procedure for DBS electrode implantation in the brain, in some detail and the brain stimulation. The videograph, of his patient, an elderly male with dystonia, pre and post operative, and following three months of therapy, was impressive.
Clinical Neuropsychiatry- The Child
Prof. Valsa Eapen, Chair, Infant, Child and Adolescent Psychiatry, University of New South Wales, Australia elaborated on ‘The Burden of Neurodevelopmental Disability- Call for Action’ Globally NDD affects 52.9 million children, accounting for 29.3 million years lived in disability; and 23% of 2-9year olds. She outlined ‘A New- to- World Integrated Approach’ to Child Development covering the first 2000 days. Each stage of integrated service delivery needs to build on to the next a form of ‘cumulative buffering’ to counter cumulative risks. New South Wales Child Development Study is ‘A Longitudinal, Multiagency, Trans-generational Record Linkage Study’ in which 77, 062 children and their parents are under review- Carr et al 2019. The message of hope is that advances in Neuroscience, molecular biology, genomics and the Behavioural and Social Sciences could be leveraged to catalyse innovative policies and practices across sectors.
KP Vinayan Prof. and Head, Dept. of Paediatric Neurology, Amritha Advanced Centre for Epilepsy, Amrita Institute of Medical Sciences, Kochi, Kerala demystified ‘Developmental Encephalopathies: A New Terminology or a Conceptual Progress?’ He broke down the elements in the most recent International League Against Epilepsy (ILAE) Commission Report definition of Epileptic Encephalopathies. There is an underlying brain pathology, either congenital or acquired. The epileptic activity itself contributes to severe cognitive and behavioural deficits which is well beyond what might be expected from the underlying brain pathology and these impairments can worsen over time. Treatment of the seizures or EEG abnormalities, a herculean task in this group, would be expected to improve the cognitive and behavioural deficits and also reduce the seizures. He discussed Lennox- Gastaut syndrome and Davert syndrome as examples.
Mustafa M. Hussain, Prof. of Neurology, Psychiatry and Internal Medicine , Director Neuromodulation and Therapeutics, UT Southwestern Medical Centre, Dallas, USA, recounted his over twenty years experience in neuromodulation procedures in ‘Dawn of a New Era in Depression’ The remarkable value of ECT in depression cannot be underestimated, he said. However, the more modern Magnetic Seizure Therapy enters the brain unimpeded, the seizure is focal, mild and only on the targeted regions, there is better control over the induced seizure, it does not affect cortical regions responsible for cognitive side effects, and the recovery after a session is quick. The induced seizure modulates the neuronal activity within the brain to effect change. He confessed that Neuromodulation is expensive therapy, and if Fluoxetine could do the job, he would go for it.
Clinical Neuropsychiatry : The Adult
Colin Shapiro, Professor, Dept of Psychiatry and Ophthalmology, University of Toronto, Canada Director, International Sleep Clinic spoke on ‘Sleep and the Expansion of Neuropsychiatry’ with conviction that “Every psychiatrist must be doing a sleep study on every patient they see!” There may be an underlying history of sexual abuse or PTSD. Sleep deprivation can have its impact on many psychiatric conditions, depression in particular, and anxiety, and lead to excessive dependence on sleeping dose medication, and to drug and alcohol abuse. Sleep apnoea is more common than estimated. Non-communicable diseases may be exacerbated due to sleep deprivation. Polysomnography provides the critical information on sleep disorders. The factors to be studied in a sleep EEG record are
- 1. Sleep continuity disturbances
- 2. Slow wave sleep deficit
- 3. REM sleep disorder
- 4. Short sleep duration.
Prof Niruj Agrawal, Consultant Neuropsychiatrist and Hon. Senior Lecturer, St George’s Hospital, London, dealt with the topic Dementia following Traumatic Brain Injury (TBI) – a reality. After TBI or repetitive injury as in contact sports, a gap of several decades, may be followed by aggressive behaviour, cognitive decline and memory deficit. The inflammation following TBI, the white matter changes, brain atrophy and subsequent ‘immunotoxicity’, can trigger a progressive neurological degeneration, a condition called chronic traumatic encephalopathy. There is a progressive increase primarily of phosphorylated tau, and also of amyloid beta and alpha synuclein associated with a clinical presentation of Alzheimer’s disease, fronto-temporal dementia or Parkinson’s disease.
Neurotheology- A Thought Leadership Session
Dr Sudhir Shah, Neurologist, Ahmedabad, has a regular consulting clinic, but his unique research interest borders on Neurotheology, dipping into the neural correlates of religious and spiritual belief. He elaborated on ‘Happiness, Meditation and the Brain’ – the merits of positive emotions and the role of gratitude, compassion, forgiveness, appreciation of others and acceptance of what cannot be changed, the ancient day wisdom for physical, mental and psychological well-being. “We are our own enemies when negative emotions take over” he emphasized. The four paths of yoga of karma, gnana, bhakthi and the classical raja yoga help in control of the mind. He presented functional neuroimaging scans of studies (in some of which he was part of the study group) where meditation activates the neural structures involved in attention and control of the autonomic nervous system and emotions positive or negative show response in the limbic areas.
Prathima Murthy Prof. and Head, Dept.of Psychiatry- Chief of De-addiction Services, NIMHANS, Benguluru, when faced with the question Neurostimulation for Addictive Disorders, Fad or Fact? started her talk by confessing “I am a clinician and a ‘mechanistic agnostic’, but if it helps my patient, I am willing to go along with it”. She went on to describe the various stimulation modalities used on her patients, and the human research studies conducted in her lab on some newer modalities. Addictive drugs cause activation of reward pathways. Biological, sociological and psychological factors influence the vulnerable. Transcranial direct current stimulation (tDCS) is safe , employs low intensity current, is non-invasive, and achieves neuronal sensitivity through weak intensity current stimulation. Modulation of prefrontal cortical excitability with tDCS may reduce alcohol craving and cue-reactivity. Periodic follow up is required as the effect of the neuromodulation wanes over time.
Dr. Adith Mohan, CheBA, Sydney, Australia elaborated on the ‘Psychosis of Suspected Autoimmune Origin- proposed model for co-ordinated clinical care at the Neuropsychiatric Institute, Sydney’. He opened his talk quoting Susannah Cahalan who describes her experience of the condition and recovery in her book ‘Brain on Fire’ (2018) where she agonises on “How many people currently are in psychiatric wards and nursing homes denied the relatively simple cure of steroids, plasma exchange, (or) more intense immunotherapy?”. What is important is to pick these patients early clinically, and treat, the red flags being- 1st week of viral prodrome ;1-2 weeks of psychotic symptoms, delusions, hallucinations, mania, agitation, speech changes, disorganized thinking, catatonia , insomnia, and often seizures; weeks to months of neurological complications, movement abnormalities, dysautonomia, hypoventilation and seizures, coma. This is the inflammatory phase and tapers, followed by months to years of prolonged deficits- executive dysfunction, impulsivity, disinhibition, and sleep abnormalities. The pathomechanism: Antibodies of IgG class targeting NMDAR subunits on dendritic clusters. 40 % triggers are paraneoplastic (ovarian teratoma)- As NMS is a major risk, one must be wary of use of antipsychotics.
Prof.Krishnamoorthy quoted the example of the 13 year female patient in his Buddhi clinic in 2013, with bizarre, acquired, acute behavioural psychosis and cognitive deficit. Under the guidance of Prof. Angela Vincent, the patient tested positive for NMDA receptor antibodies and recovered well with a course of Methylprednisolone, with a relapse after a few years. It is important to create awareness among Psychiatrists when to suspect autoimmune psychosis, a reversible condition.
Dr Mohan suggested the latest article underlining the red flags – ‘Autoimmune Psychosis – an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin’ – Thomas Pollak, Lancet Psychiatry, Nov 2019 .
John P John, Prof of Psychiatry, NIMHANS , has a special research interest in ‘Multimodal brain imaging in Schizophrenia and Dementia’. The Multi- modal Brain Imaging Analytic Lab (MBIAL) of NIMHANS has state of the art equipment, funded by Department of Biotechnology, Government of India. The research is conducted with the collaboration of the DST-sponsored clinical group at NIMHANS. One test for the schizophrenia participant in the research was the semantic word fluency test (word generation) against repeating what is produced on the screen. In this task, activation is as important as is deactivation. In normal subject, anterior prefrontal activation is accompanied by posterior brain deactivation. In the patient of schizophrenia, there is less deactivation of posterior brain. There is hyperconnectivity in Default mode network (DMN) in schizophrenia and a positive relation between DMN connectivity and the psychotic symptoms. (Whitfield Gabrieli et al, PNAS, 2009). The reason why the DMN is of particular relevance in the study of dementia is because these areas are where AB amyloid is deposited even in early MCI. The DMN shows less connectivity.
Ingmar Skoog, Prof of Psychiatry, University of Gothenburg, Director, Centre for Health and Ageing and Leader for the Neuroepidemiology Unit, Gothenburg, Sweden stressed that the first biomarker appearance and preclinical AD can have a gap of 20 years, the order being CSF abeta , PET amyloid, CSF tau, PET tau, MRI atrophy, memory symptoms, MCI, Dementia – ( ‘Temporal ordering of the pathological processes of AD’. Jack et al, Lancet, 2013.) Prof. Skoog has a large series of CSF studies, as the study participants give consent for lumbar puncture and even for a follow up study. Other concomitant pathological markers in CSF he has studied in 85 year olds: total tau a biomarker for neuronal damage; neurogranin a marker for synaptic degeneration, a post synaptic protein, CSF levels of which increase significantly in MCI and AD; phospho tau 18, a marker for tangle pathology, phosphorylation of tau appearing to be specific to AD, showing a 2-3-fold increase in CSF; YKL -40, a marker for reactive astrocytosis, increase of which coccurs in the CSF in AD and FTD.
Mathew Varghese, Prof. of Psychiatry, Geriatric Dept., NIMHANS spoke on the ‘Psychosocial Interventions in Dementia’ with particular reference to the Indian scenario and as practiced in his department. He emphasised that in India it is mainly informal caregiving at home. Education of the caregivers with the ABC symptoms of dementia, namely problems with activities of daily living (ADL) and the behavioural and cognitive symptoms, which require attention is provided in the clinic through family counseling. The need for progressive coping is underlined. The care recommended is a whole -day structured activity schedule, simple, tasks, keeping the general health, nutrition and exercise of the patient in mind, in a safe environment, preserving the dignity of the patient and avoiding confrontation. Prof. Varghese has been involved in modules for dementia healthcare from 2003. Agencies and Societies providing service are ARDSI (the Indian chapter of ADI), HelpAge India and Senior Citizens Forum. The Mental Healthcare Act- has outlined some positive steps towards a national level preparedness. National Health Mission, the flagship programme of GoI, is in the process of preparing district clinic manuals for rehabilitation centres.
Amithaba Ghosh, Consultant Neurologist from Kolkata, spoke about Frontotemporal dementia in the Indian setting presenting unique biological, cognitive, behavioural and psychosocial data from this setting.
The impressive cast of Indian chairpersons for the colloquium included Professors :
- Lakshminarasimhan R, Chennai
- Mehndiratta MM, Delhi
- Bharat Srikala, Bangalore
- Bhattacharya Kalyan, Kolkata,
- Padmavathi R, Chennai,
- Lakshminarayanan R, Chennai,
- Sudhakar TP, Tirupathi,
- Thara R, Chennai,
- Vijayakumar Lakshmi, Chennai.
Chennai being a hub of Indian Neuroscience, it does not stop with the advantage of inviting local experts, but for opting for among the best in the field.
In all the INA Colloquium was a meeting of minds, Western & Eastern, modern scientific and ancient integrative, discussing many aspects of the brain and mind interface. Truly a feast for the brain, mind & soul, with the wonderful fusion cuisine of Madras Club satisfying also the palate.