Integrated Case-based Clinical Approach in Understanding Pathways, Complexities, Pitfalls and Challenges in Neurodegenerative Disorders
This is a pre publication personal draft copy for our own fair use to promote academic learning and pre publication peer review even before it is published formally in a journal. This was originally written by our team for the American Journal of neurodegenerative disorders and some of the cases have also been shared in our clinical problem solving conference on January 2022 that can be accessed here : https://ashiness92.blogspot.com/2022/01/clinical-problem-solving-2022.html?m=1
Please check out the draft article processing discussions at the bottom toward improving the English after the AJND editors asked for a revision. Again this blog post is being shared as fair use to disseminate science and art for global academic development.
ABSTRACT:
INTRODUCTION:
The current paper illustrates 5 clinical cases of neurodegenerative disorders presented at our tertiary care rural hospital of south India. We intended to integrate the case-based clinical understandings by thematic analysis of each single case data. In all our patients with neurodegenerative brain disorders, we identified common clinical ground in initial presentation with movement disorder(s) combined with psychiatric symptoms. These patients eventually developed different courses of events during their illness.
METHODOLOGY:
A series of patients with neurodegenerative disorder attending the Medicine or Psychiatry services of our rural medical college catering to a district population of 2,000,000 were evaluated.
CONCLUSION:
In this small case series, a clear association between Neurodegenerative Disorders and psychiatric symptoms could herald movement disorders as a clinical marker of organic psychopathology. The association can be confounded by substance abuse, stress, sleep disruption and even therapeutic interventions, and thus a thorough clinical history and a deep understanding of psychopathology enabled a clear identification of these associations.
Key Words: Neurodegenerative disorders; Organic psychopathology; Case-based blended learning ecosystem; Movement disorders.
INTRODUCTION:
In recent times, the distinction between organic and functional psychoses has become blurred and these are better described as primary and secondary psychoses, where “secondary” refers to there being an identifiable pathogenic substrate [1]. Neurodegenerative disorders can cause delusions and psychosis by extensive loss of acetylcholine and dopamine releasing basal forebrain projection neurons. Due to disrupted brain circuitry, with time the brain areas atrophy and psychosis can occur. In addition to structural alterations, faulty dopamine signals and the loss of receptor modulation can provoke delusions in both primary and secondary psychosis. [2] This hypothesis has produced some emergent findings to merit further research.
Application of our existing framework of Case-Based Blended Learning Ecosystem (CBBLE) [3] in psychiatry and neurology aims at reducing the burden of misdiagnosis and mistreatment. In this learning ecosystem, concerted team communication and collaborative learning between participants provide evidence-based, patient-centred inputs across an online platform so the learning outcome of participants can improve patient outcomes [3].
A better understanding of psychiatric symptoms particularly in neurodegenerative disorders can be gained from a detailed study of the accessible events or case studies. For this research, we evaluated the similarities and differences among the different cases of Neurodegenerative disorders who presented to our rural medical hospital. A better understanding of psychiatric symptoms particularly in neurodegenerative disorders can be gained from a detailed study of the accessible events or case studies.
CASE 1:
A 50-year-old man with a history of alcohol and nicotine dependence and type 2 DM had presented with the complaints of frequent falls, dropping eyelids, walking into objects, and involuntary coarse hand movements. He noted a progressive difficulty in keeping his eyes open, which was aggravated by blinking. His wife narrated that he withdrew emotionally and stopped conversing with others and instead for the last 6 months talked mainly to himself. He started avoiding people, talking, and smiling to himself and developed delusions of persecution. While walking, he would hardly look around or sideways and there was very minimal swaying and swings of arms. He noticed intermittent involuntary bilateral hand movements, while doing his fieldwork. The patient was thin built with no facial expression which was noted during our interaction with him. His mini-mental state examination score was normal (29/30). He had asymmetrical, small, rhythmic movements of his bilateral distal upper limbs, which increased with motor activity. On Central Nervous System Examination, his muscle tone was increased in all four limbs and his deep tendon reflexes (biceps, triceps, and knee) were exaggerated. His plantar reflex was normal. He was unable to perform upward and downward gaze movements pointing towards oculomotor nerve involvement. His routine blood work was normal, neuroimaging showed mild cerebral atrophy.
He was diagnosed with Parkinson’s disease with progressive supranuclear palsy and discharged with a prescription for a thrice-daily combination of levodopa and carbidopa along with once-daily quetiapine. A brief timeline of events for case 1 is illustrated in figure 1.
CASE 2:
A 66-year-old married male farmer from Telangana state with no significant past or family history of mental illness presented with his wife to our psychiatric inpatient services during the summer of 2018 for gross rigidity in the body, asymmetric tremors for 4 to 5 years. He also complained of visual hallucinations, memory deterioration, disinhibited behaviour, fearfulness, early and middle insomnias and episodes of aimless wandering over 2 years period. According to family members, his voice became muffled and lower in intensity, and he would answer only in one or two words, unlike his previous self. His family members noted that the pace of his gait and normal arm swings were remarkably reduced by the midwinter in 2015. He was started on a twice a day combination of 110 mg levodopa/carbidopa 3 years ago by his local district neurologist. However, there was a minimal response and shaky, pill-rolling movements of distal hands gradually increased in frequency, intensity and duration with a typical static pattern leaving him incapacitated and unable to hold any objects for the last 6 months.
For disinhibiting behaviour, he was prescribed 5 mg of haloperidol for a week by a private psychiatrist after which his rigidity and bradykinesia worsened. He further developed confusion when he was put on 6 mg/day of trihexyphenidyl. He stopped identifying people visiting his home and episodes of disinhibited behaviour, talking to himself, visual hallucinations, fearfulness, the delusion of persecution, and aimless wandering increased. He reported seeing unfamiliar people standing in front and observing him, or running in his veranda, at other times he would behave as if his relatives were sitting beside his bed and on several occasions, he screamed as if snakes were crawling around his bed/house. His self-care, social interactions with his friends and his usual activities like going to the vegetable market and attending social functions decreased. There was no history of headache, seizures, head injury, or vomiting in the morning (ruling out intracranial space-occupying lesions), neither there was a history of hyperorality and hypersexuality, repeated, over ritualistic activities (ruling out specific syndromes) or thought alienation or other SFRS (ruling out schizophrenia).
On examination, he did not have any signs of meningeal irritations, spine, or cranium deformity. He was conscious, oriented to time and place but was confused about the people around him. His mood was depressed and labile. His cognitions were impaired (MMSE 11/30), and memory registration and retrieval were poor and there were gross deficits in recent, remote and working memory. His speech was muffled, low volume, curtailed and monotonous without inflection or prosody. His judgement, praxis, simple calculations, object naming, logical thinking and insight were impaired. His posture was stooped, and his gait was festinating. He had symmetrical tremulousness of his distal upper limbs with typical 6 Hz frequency, coarse, pill-rolling tremors, predominant contraction and relaxation of flexor and extensor with less prominent rotatory components between finger and thumb. His tone in muscles and joints were increased as he showed a cog-wheel type of rigidity on clinical evaluation. His cranial nerves were normal. His vitals and other systemic examinations were essentially normal. He was hospitalized and comprehensive assessments were done.
An axial T2 weighted magnetic resonance imaging (MRI) brain showed asymmetric cerebral atrophy with mild, generalized enlargement of fronto-temporo-parietal sulci and mild decrease signal intensity of basal ganglia with apparently normal width of pars compacta in substantia nigra without any clear depigmentation or any blurring or thinning in contrast to what is typically seen in Parkinson's Disease. There was also evidence of mild thinning of the postcentral gyrus (left > right side) indicating the initial stage of cortico-basal degeneration. Midbrain tegmentum areas appeared smaller in size than normal; however, pons and cerebellar volumes were normal and there were no T2 hypo-intensities in either putamen or caudate nucleus ruling out multiple system atrophy.
He was diagnosed with Parkinson's plus syndrome (Idiopathic Parkinson’s disease with dementia and cortico-basal degeneration). He was started on quetiapine 50 mg HS, his levodopa/carbidopa combination (110 mg/day) dose was increased to thrice a day, 10 mg morning memantine was started for his dementia which gradually increased to 20 mg/day and 60 mg propranolol was added for his tremors. 2 mg of lorazepam was given in the initial first few days for his sleep disturbances along with quetiapine. A serial MMSE was implemented weekly showing an improvement of 3 to 4 points over 12 to 16 weeks. His ADS Cog Score improved from baseline 26 to 36. His hallucinations, delusions, disinhibitory and wandering behaviour showed marked improvement, as did his sleep and personal care. He responded positively to rehabilitation for routine and basic needs and use of directions, in addition, specific symbols and behavioural principles were taught to the family. His bradykinesia tremors were mildly reduced but his rigidity continued. After 6 months, he deteriorated markedly in cognitive functions (MMSE score in October 2019 was 10), developed apathy and worsened in his parkinsonian symptoms, especially rigidity and akinesia and he was not responsive to even QID levodopa (110 mg). Eventually, in January 2020, he developed difficulty in identifying relatives, upper limb myoclonic jerks and dystonia in the neck and upper limbs leading to dysphagia. His dose of memantine was increased to 30 mg/day and he was started on rivastigmine 3 mg/day, with lorazepam 6 mg/day. Lorazepam was withdrawn while he remained on the other prescribed interventions, however, this produced no specific improvements, and the patient became bedridden with deteriorating quality of life. A brief timeline of events for case 1 is illustrated in figure 2.
Case 3:
A right-handed 67-year-old married woman presented to our hospital with complaints of rhythmic, involuntary movements of her right forearm and her left index finger and thumb and intermittent stiffness for 4 to 5 months. Her husband started noticing these involuntary movements insidiously while she was taking her food plate and eating, it was even increased at rest and were present intermittently when she went for sleep. Over the next few days, her husband further noticed that tremors were more during rest rather than at work and resolves in deep sleep. She was not having control over those shaking movements, and she thought it might be because of her age. Gradually the tremors worsened, and intermittent stiffness commenced in her left hand as she noticed difficulty in initiating movements when trying to put on her clothes. In addition, whenever she had to hold anything with her left hand it would take more time than what she used to take before.
For 20 days, her husband says she has not involved herself in family conversation unlike her previous self and she stopped responding to people or would give only a delayed and curtailed response. On examination, she was conscious, oriented to time, place, and person. She had a mask-like face. She presented with asymmetrical rhythmic, oscillatory, small amplitude movements of distal muscles of her right forearm and pill-rolling tremors observed involving the left thumb and index finger. Her tremors were present at rest but were absent during motor activity. She had slow initiation of motor activity and a delayed verbal response on longer interviews. Her limbs had lead pipe rigidity present and all her reflexes were exaggerated. Her MMSE score was 25/30. On a cardiovascular system examination, a systolic murmur was heard in the aortic area till apex. Her laboratory investigations were within the normal range. Her 2D Echo revealed severe aortic stenosis, concentric left ventricular hypertrophy (LVH) with an ejection fraction of 55%. A magnetic resonance imaging of her brain showed mild cerebral atrophy, tiny calcifications without any oedema in the right lentiform nucleus and left temporal lobe, and a few small vessel ischaemic changes. She was diagnosed with Parkinson’s disease and was discharged on levodopa and carbidopa combination 110mg with vitamins B1, B6 and B12 combination thrice a day. A month later, she began having occasional, second person auditory hallucinations on follow-up at our hospital, however, her tremors were reduced.
Case 4:
A 49-years old right-handed male lecturer without any significant past medical or psychiatric history has presented to us with an insidious onset of progressive, asymmetric involuntary movements of the index and middle fingers of the right upper limb since November 2020. The patient reports that his movements worsened with rest and abated with voluntary activity. For the past 2 months, he has been unable to correct answer sheets or write properly because of to-and-fro oscillatory rhythmic movements of right thumb involvement resulting in an inability to maintain his hand stability. His handwriting was getting crowded and distorted with very small letters which at times were difficult to decipher. He started feeling stiffness in his both wrists (right>left) throughout the range of motion while lifting or wiping movements and could feel its accentuation to his elbows at times. His brother and wife reported that he has been speaking in a monotonous tone in the past 2 months or so. For about a month, the semiological features of involuntary movements of the right hand have appeared in his left extremity as well and his gait has become slow, difficult to begin spontaneously rather had to start with small, short steps and a forward stoop typically of Parkinson's disease. He has had difficulty climbing up the staircase and experiences episodic loss of balance at times. He further admitted that he had difficulty walking in the dark and felt he would all without support. On further explorations for vegetative symptoms, he reported that for a few weeks he had no morning erections and a loss of sexual desire, however, his sleep and appetite was normal. He does not report difficulty in his activities of daily life. There was no history of swaying movement of the trunk while walking, overshooting his hand while picking up objects or difficulty in descending stairs. He neither had dizziness, light headedness when waking up, stiffness in his lower limbs, cotton wool sensation of the floor, burning pain or discriminating hot or cold perceptual stimuli. Further, there was no history suggestive of mood or psychotic disorder, substance use disorders, head injury, epilepsy, urinary incontinence, or memory deficits.
On examination, all the vitals of the patient were stable and his baseline MMSE score was 29/30. Cogwheel rigidity was noted at his right wrist, coarse tongue tremors and micrographia were present. On a foot-tapping examination, movements of his right lower limb were found to be slower than his left lower limb. He had a postural blood pressure drop of about 20/10 mm of Hg after 3 minutes on standing to lying down/supine posture. The patient was diagnosed with Parkinson's disease and was started on oral syndopa (Levodopa plus carbidopa) 110mg 4 times a day. He showed significant improvement in his tremors and rigidity over the last few months.
Case 5
A 58-year-old, married man presented with a history of alcohol dependence currently in remission over 3 years had presented to our tertiary care rural hospital with a history of acute onset of slurring of speech, deviation of angle of mouth to the right, urinary incontinence and significant cognitive decline for 6 months leading to termination from employment. He was found to carry temple belongings without permission when visiting temples and he incurred the rages of priests and family members and therefore was forbidden to attend the nearby temples. He had significant forgetfulness for daily tasks, people he met or happenings around and he failed for retrieval of names or objects asked. He became reluctant to shave, shower or bathe independently and would need assistance from his son for these tasks. In the ensuing days, he began having difficulty recognizing friends and relatives but would recognize his son and his wife. He would smile while naming his family members as he could not get their names properly. He sometimes had transient visual and/or auditory hallucinations. He was unable to button or unbutton his shirt or fold the clothes, unlike his usual self. He repeated the same answer for every question asked (echolalia/ perseverations) and would get impulsive or aggressive about petty issues but also calms down within 5 to 10 minutes on his own as if nothing has happened as he would not remember if being distracted. He, however, stopped laughing at jokes. For the last few weeks, he had difficulty in swallowing solids and liquids and whatever he consumed would be partly drooled out from the left angle of his mouth. He showed a remarkable delay in responding to commands, persistent urinary incontinence accompanied by intermittent wandering spells and disinhibited behaviour.
On presentation, the patient was conscious and cooperative, his MMSE score was 9/30. His speech was slurred and poorly comprehended, his fluency was impaired, but repetitions were intact. On performing parietal lobe evaluation, his right to left discrimination, visuospatial orientation and construction abilities were significantly impaired and while on evaluation of the occipital lobe, we noted persistent prosopagnosia. On cranial nerves examination, there was clear evidence of left facial nerve palsy as we observed the loss of wrinkles over the left forehead and deviation of his mouth to the right. His biceps, triceps and supinator and knee reflexes were exaggerated. His metabolic profile was within the normal range. His MRI of the Brain showed supratentorial hydrocephalus, cerebral and cerebellar atrophy along with chronic ischaemic changes. He was diagnosed with probable Alzheimer’s dementia and was started on donepezil 10mg/ day which was increased to 20 mg/day after a week. His MMSE score improved from 9/30 to 11/30 by week 6 and we lost his follow-up there onwards.
DISCUSSION:
We performed this study within our existing framework of a CBBLE [3] when we received an invitation from the American Journal of Neurodegenerative Disorders (AJND). Psychoses can develop in patients with brain disorders secondary to neurodegenerative disorders, tumours, or cerebrovascular accidents. We explored the organic psychopathology of psychosis in neurodegenerative disorders. We postulate that movement disorder is an obvious logical bio-clinical marker toward organic psychopathology of psychiatric symptoms found in neurodegenerative disorders. A detailed thematic analysis of the accessible events in these patients offered newer insights into the organic nature of psychiatry.
ANATOMICAL LOCALIZATION OF PSYCHOSES:
Cummings was one of the first to correlate psychotic symptoms with the underlying pathobiology by focussing on delusions. He proposed that dysfunction of subcortical basal ganglia – limbic system interactions including abnormal dopamine neurotransmission leads to the formation of delusions [4]. Acute onset of delayed psychosis was observed after right temporoparietooccipital stroke or trauma in a study, in patients with no prior history of earlier psychiatric illness [5 - 7]. Kumral and Ozturk prospectively observed mental status of patients with acute stroke and found 5% of them with right hemispheric lesions developed delusions and were more common with right posterior temporoparietal lesions [6]. A meta-analysis revealed that there was a greater grey matter volume reduction in the right inferior frontal gyrus and superior temporal gyrus among the subjects at high risk to psychosis. These studies conclude that dysregulations in the right prefrontal cortex including the basal ganglia and the limbic system are associated with the development of delusions [7, 8].
Cummings was one of the first to correlate psychotic symptoms with the underlying pathobiology by focussing on delusions. He proposed that dysfunction of subcortical basal ganglia – limbic system interactions including abnormal dopamine neurotransmission leads to the formation of delusions [4]. Acute onset of delayed psychosis was observed after right temporoparietooccipital stroke or trauma in a study, in patients with no prior history of earlier psychiatric illness [5 - 7]. Kumral and Ozturk prospectively observed mental status of patients with acute stroke and found 5% of them with right hemispheric lesions developed delusions and were more common with right posterior temporoparietal lesions [6]. A meta-analysis revealed that there was a greater grey matter volume reduction in the right inferior frontal gyrus and superior temporal gyrus among the subjects at high risk to psychosis. These studies conclude that dysregulations in the right prefrontal cortex including the basal ganglia and the limbic system are associated with the development of delusions [7, 8].
CASE DISCUSSION
FIRST CASE - A MIDDLE-AGED MAN WITH PROGRESSIVE SUPRANUCLEAR PALSY
The case study of the first patient highlights the organic psychopathology that underlies the comorbidity of movement disorder, and motor and psychiatric manifestations in a neurodegenerative disorder.
Our patient was diagnosed with progressive supranuclear palsy (PSP). PSP is an atypical variant of Parkinson's disease, also known as the Steele-Richardson-Olszewski syndrome. This condition is characterized by supranuclear gaze palsy, progressive axial rigidity, pseudobulbar palsy, and mild dementia and dysphagia. Most of the patients with PSP present with moderate to severe apathy followed by disinhibition, depression, and sleep disorders [9]. Approximately 20% of PSP patients are noted to have impaired interpersonal functioning, communication problem, poor relationships and difficulty in active engagement with family and friends. Emotion expression in PSP is more impaired than in Parkinson's disease [10].
This neurodegenerative disorder is histopathologically recognized by a neuronal loss with globose neurofibrillary tangles, and the presence of tau-positive inclusions in tufted astrocytes, and gliosis in the basal ganglia, cerebellum, and brain stem [11]. Some treatments, for example, caffeine supplement or nicotine patches might also be trailed. There are tapping apps people can use to maintain motor skills.
The case study of the first patient highlights the organic psychopathology that underlies the comorbidity of movement disorder, and motor and psychiatric manifestations in a neurodegenerative disorder.
SECOND CASE - CORTICOBASAL DEGENERATION
Our second patient was diagnosed with corticobasal degeneration. The corticobasal syndrome is usually characterized by akinetic-rigid parkinsonism, dystonic and myoclonic movements, associated with cortical symptoms such as ideomotor apraxia, alien limb phenomena, aphasia, or sensory neglect. Our case has typical symptoms of Parkinson’s disease with gradually progressive cognitive decline and complex amalgamation of neuropsychiatric symptoms with clear functional deterioration. Index patient received undocumented antipsychotics which worsened his parkinsonism features. The usual confusion of onset of independent Lewi body dementia in Parkinson’s disease always showed a great deal of controversy as few expert consensuses believe that it should occur within the first year after the onset of Parkinson's to call it as an independent entity since Alzheimer's Dementia (AD) like dementia can also occur in the progressive brain degeneration. McKeith et al described the spectrum of clinical features in comparison between 21 cases of DLB and 37 cases of AD proven histologically [12]. The DLB patients tended to show mild cognitive impairment at presentation and more often showed depression as well as marked fluctuation. Almost half of the patients with DLB had falls or transient and unexplained losses of consciousness, which were rare in those with AD.
THIRD CASE - PARKINSON’S DISEASE
Our third patient’s clinical presentation was consistent with Parkinson’s disease. She had no symptoms suggestive of dementia but developed drug-induced auditory hallucinations. The presence of psychosis or dementia-like presentation is not uncommon in Parkinson’s disease, since the nigrostriatal pathway is commonly involved in Parkinson’s disease, with gradual impairment in mesolimbic and mesocortical pathways which may lead to some of the psychiatric manifestations. Studies have reported common presentation of hallucinations (15%-40%) and delusions (10%) in treated PD patients [13,14].
FOURTH CASE – MULTISYSTEM ATROPHY
Our fourth patient’s clinical presentation was consistent with multisystem atrophy. Multi-system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movements, muscle rigidity, postural instability. In a study conducted with 30 patients it was found that in 73% of patients with MSA, the first symptom was autonomic followed by motor symptom in 10% [15]. Erectile dysfunction was found to be the most common symptom among these patients followed by postural instability, urinary hesitancy, and sleep disorders [16]
FIFTH CASE – ALZHEIMER’S DEMENTIA
Our patient presented with slurred speech, mouth deviation to the right, smacking of lips, urinary incontinence, visual hallucinations for 6 months and progressive dementia for 5 months. Alzheimer's disease (AD) is characterized by progressive dementia and is the most common cause of dementia. In patients with probable AD, higher incidence (51.3%) of hallucinations and delusions were reported at 4 years. The accelerated cognitive decline may also be a predictive marker for their occurrence [17]. studies have found that psychosis in AD was associated with more rapid cognitive decline and increased mortality rate [18,19].
DIAGNOSTIC UNCERTAINTY AND ROLE OF CLINICAL AUTOPSY
Most of our cases had neuroimaging scans without dopaminergic deficit, the definitive diagnosis can be achieved in these patients only after a clinical brain autopsy. Here’s a report of a 50-year-old man, a doctor who was initially diagnosed with Parkinson's disease and later with multi-system atrophy but after his death, the brain autopsy revealed parkinsonism with Lewy body disease with brainstem predominance [20]. Accuracy of the aetiology of diagnosis is paramount for the family as well as for the population at-large for healthcare planning and research.
Clinical autopsy, also known as a pathological autopsy, is regarded as the gold standard for confirmation of the cause of death, which may be unknown to treating clinicians and relatives of the deceased. Studies have found significant discrepancies between premortal clinical diagnoses and autopsy findings in over 30% of patients [21]. For example, 16% of the cancers diagnosed at autopsy were unknown earlier. Similarly, a significant portion of deaths with uncertainty was found to have a myocardial infarction at autopsy, which can be presumed as the prevalence of atherosclerotic heart disease is also higher [22]. Despite that, it has been underutilized in rural medical institutions in India and even declining throughout the healthcare systems of the developed countries. Several factors might be contributory to the barriers to this global health thanatology implementation problem in India such as overlooking the potential benefits of clinical autopsy among the clinicians and public, religious views and stigma attached to body dissection of close ones [23]. Clinicians assume that the cause of death is already known or will not yield any additional information or that the relatives will oppose autopsy. In addition, financial reasons and advancing diagnostics may also depreciate the need for a clinical autopsy.
In our series of cases with neurodegenerative disorders, clinical autopsy might reveal some insight into the pathophysiology of their illness events, but this does not reveal the dynamic functional information needed for daily life. Clinical autopsy procedures can increase knowledge of the disease systems, biological underpinnings and frailties that exacerbate the disease.
To increase the utilization of clinical autopsy procedures in India, facilities need to be expanded and all the stakeholders will need to get involved including the clinicians, policymakers, and lay public. Clinicians and policymakers need to understand the values of clinical autopsy in education, research, healthcare quality control and declare it as a useful investigative tool. The lay public, being an essential decision-maker, should be made aware of the potential benefits of the procedure. The medical institutions, particularly in rural areas, should build the infrastructure including forensic-pathology laboratories, equipment, and forensic experts within a well-defined policy framework. Autopsies are also one of the best ways to train pathologists and therefore, postgraduate institutions can also make an effort to implement a clinical autopsy training program involving a multidisciplinary clinical team. Undergraduate medical students should be well-taught about the clinical autopsy.
THERAPEUTIC UNCERTAINTY AND CHALLENGES
In our patients with a neurodegenerative brain disorder, we found common ground in their presentation as a movement disorder along with psychiatric symptoms and later development of different courses of illness events. In a visual representation of event timeline in neurodegenerative disorders, one notices progression in a downward spiral while with other brain injuries such as stroke it is much more rewarding as it is more about recovery. However, such therapeutic uncertainty in our cases could be minimized if regularly supported by a CBBLE that can not only offer evidence-based decision tools, but also a regular connection with global experts to improve documentation, transparency, and newer learning insights as well as innovation toward optimizing solutions [3]. Once the neurodegeneration begins like in dementia, there is no cure for it nor does any treatment exists to modify or reverse its eventual progression. Available therapeutic interventions, therefore, target to improve cognitive functions.
NEUROCOGNITIVE REHABILITATION:
Cognitive impairment is a very prevalent non-motor symptom in Parkinson's disease and may present in the early stages of the disease. Cognitive impairment deteriorates with the progression of the disease until dementia develops after 10-20 years [24,25]. Studies found that mild cognitive impairment (MCI) is contributory to developing dementia and may be a prodromal stage for dementia in Parkinson’s disease [25,26]. Both cognitive decline and dementia can reduce the quality of life and functional disability of patients with Parkinson’s disease [27]. Therefore, patients with Parkinson’s disease require therapeutic strategies that treat cognitive impairment.
Cognitive rehabilitation programs have been found efficacious in improving cognitive declines and may improve functional disability and make brain changes in patients with Parkinson's disease [28]. Cognitive rehabilitation of fewer than 3 months has demonstrated brain connectivity and activation improvements [28]. In addition, the involvement of caregivers in cognitive rehabilitation is important [29]. However, the data on long-term maintenance of cognitive changes post-rehabilitation is still less known. In our series of cases, neurocognitive rehabilitation could not be performed, which is again a barrier to implementation in Indian rural medical institutions where hospitals often do not have a good neurorehabilitation center with enough cognitive rehabilitation experts. Chronic, progressive, incurable disorders like Parkinson's disease may also become a barrier to offering these non-pharmacological therapeutics. Patients with neurological disorders are mostly concentrated in rural India. A study conducted in rural areas in Uttar Pradesh found that economical constraints, lack of awareness, family negligence and transportation problems are majors for neurocognitive rehabilitation [30]. To remove these barriers, the researchers need to identify the potential barriers to implementation. The policymakers should help institute cost-effective, accessible rehabilitation centers for under-served populations and take appropriate measures to remove those barriers. The public should be well-educated about the potential benefits of neurocognitive rehabilitation. Facilities should build a good infrastructure for neurorehabilitation.
CONCLUSION AND FUTURE DIRECTIONS:
A rural medical college receives few neurodegenerative disorder patients. The diagnostic and therapeutic challenges identified in the study need to be addressed toward the improvement of diagnostic and therapeutic outcomes in this population. Scholarly integration of medical education and research through a global CBBLE model in psychiatry and neurology may help to address those challenges in the missing Indian setting as reflected in the discussion. A current functioning prototype is available and accessible to our institution although it needs better active participation toward scaling and sustainability.
Given the composite nature of neuropsychiatric disorders that have a vigorous and complementary base, the organic and functional discrimination of these disorders appears to be a valuable tool that aids in deciding and prioritizing the treatment plan. One of the vital purposes of the discrimination between organic and functional disorders seem to dispense a valid rationale and vernacular to empower the clinicians in prioritizing the medical interference. The functional-organic discrimination strives to distinguish clinical features which could be possibly elucidated by well remarkable biological changes, still prevailing as one of the pivotal diagnostic bases in present-day neuroscience.
ETHICS STATEMENT & INFORMED CONSENT:
The Institutional Ethics Committee approved this study with Ref. No. ETHICS COMMITTEE/KIMS/NKP/2021/55.
Consents were taken from both the patient and the attendants and there is no disclosure of (identifiable) patient information in our paper.
CONFLICTS OF INTEREST:
The authors declare no conflicts of interest. Dr Amy Price is a research editor with the BMJ, she has no relevant conflicts of interest to declare in this manuscript.
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Post first editorial review processing:
[12/22/2021, 9:11 AM] Aashita KIMS PG: Dear Dr. Kashy,
Many thanks for your letter. We’ve received your Ethics Certificate. Besides, we’ve just received the comments from reviewers and will process your paper (AJND0136991R2) as soon as possible.
We appreciate your kind cooperation.
Best regards,
Editorial Office
American Journal of Neurodegenerative Disease
[12/22/2021, 9:12 AM] Aashita KIMS PG: However, i don't know who is Kashy 😂
[12/22/2021, 9:12 AM] Vivek Poddar 3: Kashyap to Kashy I think
[12/22/2021, 9:25 AM] Aashita KIMS PG: Yeah 😅
[12/24/2021, 6:55 PM] Amy Price: They are asking for a certificate, I can't supply this so I suggest you supply from one of your institutions or share your plan along with the corrections. Take it through the free Grammarly program and use the edits that make sense. I suggest you have 4 non medical friends read this and suggest where clarity is needed. Vivek knows how to remove the medical jargon and make this understandable so any reader can comprehend and enjoy the paper. Have the same friends reread the paper and approve it. Acknowledge these 4 individual in the acknowledgements.
[12/24/2021, 6:56 PM] Rakesh Biswas: Alright. Good idea about grammerly. I guess then we can try that.
[12/24/2021, 7:43 PM] Vivek Poddar 3: I will try to edit it. I will also run through grammarly. We need to convey that we don't have a fund for this to check with professional editing service.
[12/24/2021, 7:44 PM] Aashita KIMS PG: Yes I just checked a few editing services and they are charging alot 😳 especially since are paper has around 8400 words
[12/24/2021, 7:45 PM] Aashita KIMS PG: I'll go through it once again and will take the help of some of my friends as well.
[12/24/2021, 7:58 PM] Vivek Poddar 3: Madam, send me the final version after the edits. I will final edit it
[12/24/2021, 7:58 PM] Aashita KIMS PG: Alright
[12/24/2021, 8:01 PM] Amy Price: I edited slightly to give you an idea please look at the way this is done for NEJM CME, this is the interest you want to create and the level of complexity to share.
[5/1, 10:40 AM] Rakesh Biswas: Thanks @Vivek Poddar 3 .
@Aashita KIMS PG Lets submit this revision if there are no further inputs from the other authors here?
[5/1, 11:07 AM] Rakesh Biswas: Few typos :
"dropping eyelids" sounds quaint but I think we meant "drooping"?
[5/1, 11:17 AM] Rakesh Biswas: Grammar 👇
"For disinhibiting behaviour,"
Will be
"For disinhibited behaviour,"
[5/1, 11:19 AM] Rakesh Biswas: Abbreviation 🤔
" other SFRS (ruling out schizophrenia)."
What is SFRS?
[5/1, 11:25 AM] Rakesh Biswas: This sentence doesn't make sense 👇
"repeated, over ritualistic activities (ruling out specific syndromes)"
Either correct it or remove it
[5/1, 12:04 PM] Aashita KIMS PG: Yes sir
I noticed that one yesterday sir
Will change it
[5/1, 12:04 PM] Aashita KIMS PG: Okay sir
[5/1, 7:21 PM] Rakesh Biswas: On examination, he did not have any signs of meningeal irritation,
And not
On examination, he did not have any signs of meningeal irritations,
[5/1, 7:23 PM] Rakesh Biswas: His cognition was impaired
And not
His cognitions were impaired
[5/1, 8:43 PM] Rakesh Biswas: Instead of
"Her husband started noticing these involuntary movements insidiously while she was taking her food plate and eating, it was even increased at rest and were present intermittently when she went for sleep"
It will be two sentences :
Her husband started noticing these involuntary movements insidiously while she was taking her food plate and eating. It was even increased at rest and was present intermittently when she went to sleep.
Also note the changes in the prepositions in the second sentence above
[5/1, 11:24 PM] Rakesh Biswas: Typo :
felt he would all without support
felt he would fall without support
[5/1, 11:26 PM] Vivek Poddar 3: Thank you sir. I am incorporating your corrections.
[5/1, 11:27 PM] Rakesh Biswas: On further explorations for vegetative symptoms, he reported that for a few weeks he had no morning erections and a loss of sexual desire, however, his sleep and appetite was normal.
Change to
On inquiry, he reported that for a few weeks he had no morning erections and a loss of sexual desire, however, his sleep and appetite was normal.
[5/1, 11:31 PM] Rakesh Biswas: Instead of
He was found to carry temple belongings without permission when visiting temples and he incurred the rages of priests and family members and therefore was forbidden to attend the nearby temples.
Change to
He was found to carry temple belongings without permission when visiting temples for which he incurred the wrath of priests and family members and was forbidden further to attend nearby temples.
[5/1, 11:38 PM] Rakesh Biswas: He had significant forgetfulness for daily tasks, people he met or happenings around and he failed for retrieval of names or objects asked.
Change to
He had significant forgetfulness for daily tasks, people he met or happenings around and he failed to recall names of objects asked.
[5/1, 11:45 PM] Rakesh Biswas: would get impulsive or aggressive about petty issues but also calms down within 5 to 10 minutes on his own as if nothing has happened as he would not remember if being distracted.
Change to
would get impulsive or aggressive about petty issues but also calmed down within 5 to 10 minutes on his own as if nothing had happened.
[5/2, 12:03 AM] Kims Aditya Samitinjay: Erections can be changed to tumescence?
[5/2, 8:03 AM] Rakesh Biswas: One idea central to good practices in writing is to use words that people globally understand in an easier manner
A writer always needs to increase his global audience rather than restrict it to an elite few who can understand medical terms?
[5/2, 8:06 AM] Rakesh Biswas: Now in the next sentence :
He, however, stopped laughing at jokes.
However would have been great to use if the preceding sentence created a joke such as the patient doing something funny but here it would be perhaps more appropriate to say,
He also stopped laughing at jokes.
[5/2, 8:24 AM] Rakesh Biswas: The sentence below viewed from a global writer's lens :
On presentation, the patient was conscious and cooperative, his MMSE score was 9/30.
Duh! What's MMSE 9/30. I'm tired of googling these authors. Might as well ask them to hire a proper writer who knows English!
So,
On presentation, the patient was conscious and cooperative, his MMSE score was 9/30. "The Mini-Mental State Exam (MMSE) is a widely used test of cognitive function among the elderly; it includes tests of orientation, attention, memory, language and visual-spatial skills." (add ref)
[5/2, 8:27 AM] Rakesh Biswas: His speech was slurred and poorly comprehended,
Change to
His speech was slurred and incomprehensible
[5/2, 8:32 AM] Rakesh Biswas: On performing parietal lobe evaluation, his right to left discrimination, visuospatial orientation and construction abilities were significantly impaired and while on evaluation of the occipital lobe, we noted persistent prosopagnosia
Maybe the other coauthors who may have picked the thread on what is wrong (English wise) with our write up can have a go at this and subsequent sentences sharing it here as above and then hopefully it will be word perfect for our English reviewers who I suspect are not as medically trained as we are (medical training may hamper English training unless you have a good English background before entering medicine, (my personal biased opinion at the moment).
Figures :
